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Intraoperative radiotherapy: review of techniques and results

Identifieur interne : 000225 ( Pmc/Checkpoint ); précédent : 000224; suivant : 000226

Intraoperative radiotherapy: review of techniques and results

Auteurs : Avinash Pilar ; Meetakshi Gupta ; Sarbani Ghosh Laskar ; Siddhartha Laskar

Source :

RBID : PMC:5493441

Abstract

Intraoperative radiotherapy (IORT) is a technique that involves precise delivery of a large dose of ionising radiation to the tumour or tumour bed during surgery. Direct visualisation of the tumour bed and ability to space out the normal tissues from the tumour bed allows maximisation of the dose to the tumour while minimising the dose to normal tissues. This results in an improved therapeutic ratio with IORT. Although it was introduced in the 1960s, it has seen a resurgence of popularity with the introduction of self-shielding mobile linear accelerators and low-kV IORT devices, which by eliminating the logistical issues of transport of the patient during surgery for radiotherapy or building a shielded operating room, has enabled its wider use in the community.

Electrons, low-kV X-rays and HDR brachytherapy are all different methods of IORT in current clinical use. Each method has its own unique set of advantages and disadvantages, its own set of indications where one may be better suited than the other, and each requires a specific kind of expertise.

IORT has demonstrated its efficacy in a wide variety of intra-abdominal tumours, recurrent colorectal cancers, recurrent gynaecological cancers, and soft-tissue tumours. Recently, it has emerged as an attractive treatment option for selected, early-stage breast cancer, owing to the ability to complete the entire course of radiotherapy during surgery. IORT has been used in a multitude of roles across these sites, for dose escalation (retroperitoneal sarcoma), EBRT dose de-escalation (paediatric tumours), as sole radiation modality (early breast cancers) and as a re-irradiation modality (recurrent rectal and gynaecological cancers).

This article aims to provide a review of the rationale, techniques, and outcomes for IORT across different sites relevant to current clinical practice.


Url:
DOI: 10.3332/ecancer.2017.750
PubMed: 28717396
PubMed Central: 5493441


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PMC:5493441

Le document en format XML

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<p>Intraoperative radiotherapy (IORT) is a technique that involves precise delivery of a large dose of ionising radiation to the tumour or tumour bed during surgery. Direct visualisation of the tumour bed and ability to space out the normal tissues from the tumour bed allows maximisation of the dose to the tumour while minimising the dose to normal tissues. This results in an improved therapeutic ratio with IORT. Although it was introduced in the 1960s, it has seen a resurgence of popularity with the introduction of self-shielding mobile linear accelerators and low-kV IORT devices, which by eliminating the logistical issues of transport of the patient during surgery for radiotherapy or building a shielded operating room, has enabled its wider use in the community.</p>
<p>Electrons, low-kV X-rays and HDR brachytherapy are all different methods of IORT in current clinical use. Each method has its own unique set of advantages and disadvantages, its own set of indications where one may be better suited than the other, and each requires a specific kind of expertise.</p>
<p>IORT has demonstrated its efficacy in a wide variety of intra-abdominal tumours, recurrent colorectal cancers, recurrent gynaecological cancers, and soft-tissue tumours. Recently, it has emerged as an attractive treatment option for selected, early-stage breast cancer, owing to the ability to complete the entire course of radiotherapy during surgery. IORT has been used in a multitude of roles across these sites, for dose escalation (retroperitoneal sarcoma), EBRT dose de-escalation (paediatric tumours), as sole radiation modality (early breast cancers) and as a re-irradiation modality (recurrent rectal and gynaecological cancers).</p>
<p>This article aims to provide a review of the rationale, techniques, and outcomes for IORT across different sites relevant to current clinical practice.</p>
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</TEI>
<pmc article-type="review-article">
<pmc-dir>properties open_access</pmc-dir>
<front>
<journal-meta>
<journal-id journal-id-type="nlm-ta">Ecancermedicalscience</journal-id>
<journal-id journal-id-type="iso-abbrev">Ecancermedicalscience</journal-id>
<journal-id journal-id-type="publisher-id">ecancermedicalscience</journal-id>
<journal-title-group>
<journal-title>ecancermedicalscience</journal-title>
</journal-title-group>
<issn pub-type="epub">1754-6605</issn>
<publisher>
<publisher-name>Cancer Intelligence</publisher-name>
</publisher>
</journal-meta>
<article-meta>
<article-id pub-id-type="pmid">28717396</article-id>
<article-id pub-id-type="pmc">5493441</article-id>
<article-id pub-id-type="doi">10.3332/ecancer.2017.750</article-id>
<article-id pub-id-type="publisher-id">can-11-750</article-id>
<article-categories>
<subj-group subj-group-type="heading">
<subject>Review</subject>
</subj-group>
</article-categories>
<title-group>
<article-title>Intraoperative radiotherapy: review of techniques and results</article-title>
</title-group>
<contrib-group>
<contrib contrib-type="author">
<name>
<surname>Pilar</surname>
<given-names>Avinash</given-names>
</name>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Gupta</surname>
<given-names>Meetakshi</given-names>
</name>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Ghosh Laskar</surname>
<given-names>Sarbani</given-names>
</name>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Laskar</surname>
<given-names>Siddhartha</given-names>
</name>
</contrib>
<aff>Department of Radiation Oncology, Tata Memorial Hospital, Dr Ernest Borges’ Marg, Parel, Mumbai, MS, India 400012</aff>
</contrib-group>
<author-notes>
<corresp id="c1-can-11-750">
<bold>Correspondence to:</bold>
Siddhartha Laskar.
<email>laskars2000@yahoo.com</email>
</corresp>
</author-notes>
<pub-date pub-type="collection">
<year>2017</year>
</pub-date>
<pub-date pub-type="epub">
<day>29</day>
<month>6</month>
<year>2017</year>
</pub-date>
<volume>11</volume>
<elocation-id>750</elocation-id>
<history>
<date date-type="received">
<day>18</day>
<month>1</month>
<year>2017</year>
</date>
</history>
<permissions>
<copyright-statement>© the authors; licensee ecancermedicalscience.</copyright-statement>
<copyright-year>2017</copyright-year>
<license license-type="open-access" xlink:href="http://creativecommons.org/licenses/by/3.0">
<license-p>
<pmc-comment>CREATIVE COMMONS</pmc-comment>
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (
<ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/licenses/by/3.0">http://creativecommons.org/licenses/by/3.0</ext-link>
), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.</license-p>
</license>
</permissions>
<abstract>
<p>Intraoperative radiotherapy (IORT) is a technique that involves precise delivery of a large dose of ionising radiation to the tumour or tumour bed during surgery. Direct visualisation of the tumour bed and ability to space out the normal tissues from the tumour bed allows maximisation of the dose to the tumour while minimising the dose to normal tissues. This results in an improved therapeutic ratio with IORT. Although it was introduced in the 1960s, it has seen a resurgence of popularity with the introduction of self-shielding mobile linear accelerators and low-kV IORT devices, which by eliminating the logistical issues of transport of the patient during surgery for radiotherapy or building a shielded operating room, has enabled its wider use in the community.</p>
<p>Electrons, low-kV X-rays and HDR brachytherapy are all different methods of IORT in current clinical use. Each method has its own unique set of advantages and disadvantages, its own set of indications where one may be better suited than the other, and each requires a specific kind of expertise.</p>
<p>IORT has demonstrated its efficacy in a wide variety of intra-abdominal tumours, recurrent colorectal cancers, recurrent gynaecological cancers, and soft-tissue tumours. Recently, it has emerged as an attractive treatment option for selected, early-stage breast cancer, owing to the ability to complete the entire course of radiotherapy during surgery. IORT has been used in a multitude of roles across these sites, for dose escalation (retroperitoneal sarcoma), EBRT dose de-escalation (paediatric tumours), as sole radiation modality (early breast cancers) and as a re-irradiation modality (recurrent rectal and gynaecological cancers).</p>
<p>This article aims to provide a review of the rationale, techniques, and outcomes for IORT across different sites relevant to current clinical practice.</p>
</abstract>
<kwd-group>
<kwd>IORT</kwd>
<kwd>techniques</kwd>
<kwd>indications</kwd>
<kwd>outcomes</kwd>
<kwd>complications</kwd>
</kwd-group>
</article-meta>
</front>
<floats-group>
<table-wrap id="table1" position="float">
<label>Table 1.</label>
<caption>
<title>Studies of IORT in recurrent head and neck cancer after gross total resection.</title>
</caption>
<table frame="border" rules="all">
<thead>
<tr>
<th align="center" valign="top" rowspan="1" colspan="1">Author/Year</th>
<th align="center" valign="top" rowspan="1" colspan="1">Sample size</th>
<th align="center" valign="top" rowspan="1" colspan="1">Study design</th>
<th align="center" valign="top" rowspan="1" colspan="1">IORT type</th>
<th align="center" valign="top" rowspan="1" colspan="1">IORT dose (Gy)</th>
<th align="center" valign="top" rowspan="1" colspan="1">Prior RT (%)</th>
<th align="center" valign="top" rowspan="1" colspan="1">Adj. RT (%)</th>
<th align="center" valign="top" rowspan="1" colspan="1">Median follow-up</th>
<th align="center" valign="top" rowspan="1" colspan="1">LC (%)</th>
<th align="center" valign="top" rowspan="1" colspan="1">OS (%)</th>
<th align="center" valign="top" rowspan="1" colspan="1">Toxicity grade 3 or ></th>
</tr>
</thead>
<tbody>
<tr>
<td align="left" valign="top" rowspan="1" colspan="1">Scala
<italic>et al</italic>
2013 [
<xref rid="ref20" ref-type="bibr">20</xref>
]</td>
<td align="left" valign="top" rowspan="1" colspan="1">76 (100% recurrent)</td>
<td align="left" valign="top" rowspan="1" colspan="1">Retrospective</td>
<td align="left" valign="top" rowspan="1" colspan="1">HDR IORT</td>
<td align="left" valign="top" rowspan="1" colspan="1">10–17.5</td>
<td align="left" valign="top" rowspan="1" colspan="1">71</td>
<td align="left" valign="top" rowspan="1" colspan="1">24</td>
<td align="left" valign="top" rowspan="1" colspan="1">11</td>
<td align="left" valign="top" rowspan="1" colspan="1">62 (2yr)</td>
<td align="left" valign="top" rowspan="1" colspan="1">42 (2yr)</td>
<td align="left" valign="top" rowspan="1" colspan="1">Total -6%
<break></break>
Neuropathy-1
<xref ref-type="table-fn" rid="table1-fn1">
<sup>*</sup>
</xref>
<break></break>
Wound-1
<xref ref-type="table-fn" rid="table1-fn1">
<sup>*</sup>
</xref>
</td>
</tr>
<tr>
<td align="left" valign="top" rowspan="1" colspan="1">Ziedan
<italic>et al</italic>
2012 [
<xref rid="ref21" ref-type="bibr">21</xref>
]</td>
<td align="left" valign="top" rowspan="1" colspan="1">96 (48% recurrent)</td>
<td align="left" valign="top" rowspan="1" colspan="1">Retrospective (parotid cancers)</td>
<td align="left" valign="top" rowspan="1" colspan="1">IOERT</td>
<td align="left" valign="top" rowspan="1" colspan="1">15–20</td>
<td align="left" valign="top" rowspan="1" colspan="1">55</td>
<td align="left" valign="top" rowspan="1" colspan="1">57</td>
<td align="left" valign="top" rowspan="1" colspan="1">67</td>
<td align="left" valign="top" rowspan="1" colspan="1">68.5 (3yr)</td>
<td align="left" valign="top" rowspan="1" colspan="1">66.1 (3yr)</td>
<td align="left" valign="top" rowspan="1" colspan="1">Total -27%
<break></break>
Fistula-4
<xref ref-type="table-fn" rid="table1-fn1">
<sup>*</sup>
</xref>
<break></break>
ORN-4
<xref ref-type="table-fn" rid="table1-fn1">
<sup>*</sup>
</xref>
<break></break>
Neuropathy-1
<xref ref-type="table-fn" rid="table1-fn1">
<sup>*</sup>
</xref>
</td>
</tr>
<tr>
<td align="left" valign="top" rowspan="1" colspan="1">Ziedan
<italic>et al</italic>
2011 [
<xref rid="ref22" ref-type="bibr">22</xref>
]</td>
<td align="left" valign="top" rowspan="1" colspan="1">231 (89% recurrent)</td>
<td align="left" valign="top" rowspan="1" colspan="1">Retrospective</td>
<td align="left" valign="top" rowspan="1" colspan="1">IOERT</td>
<td align="left" valign="top" rowspan="1" colspan="1">15–20</td>
<td align="left" valign="top" rowspan="1" colspan="1">81</td>
<td align="left" valign="top" rowspan="1" colspan="1">21</td>
<td align="left" valign="top" rowspan="1" colspan="1">12</td>
<td align="left" valign="top" rowspan="1" colspan="1">55 (3yr)</td>
<td align="left" valign="top" rowspan="1" colspan="1">34 (3yr)</td>
<td align="left" valign="top" rowspan="1" colspan="1">Total-27%
<break></break>
ORN-8
<xref ref-type="table-fn" rid="table1-fn1">
<sup>*</sup>
</xref>
<break></break>
Neuropathy-8
<xref ref-type="table-fn" rid="table1-fn1">
<sup>*</sup>
</xref>
<break></break>
Fistulas-20
<xref ref-type="table-fn" rid="table1-fn1">
<sup>*</sup>
</xref>
</td>
</tr>
<tr>
<td align="left" valign="top" rowspan="1" colspan="1">Perry
<italic>et al</italic>
2010 [
<xref rid="ref19" ref-type="bibr">19</xref>
]</td>
<td align="left" valign="top" rowspan="1" colspan="1">34(100% recurrent)</td>
<td align="left" valign="top" rowspan="1" colspan="1">Retrospective</td>
<td align="left" valign="top" rowspan="1" colspan="1">HDR IORT</td>
<td align="left" valign="top" rowspan="1" colspan="1">10–20</td>
<td align="left" valign="top" rowspan="1" colspan="1">100</td>
<td align="left" valign="top" rowspan="1" colspan="1">15</td>
<td align="left" valign="top" rowspan="1" colspan="1">23</td>
<td align="left" valign="top" rowspan="1" colspan="1">56 (2yr)</td>
<td align="left" valign="top" rowspan="1" colspan="1">55 (2yr)</td>
<td align="left" valign="top" rowspan="1" colspan="1">Total-29%
<break></break>
Wound-3
<xref ref-type="table-fn" rid="table1-fn1">
<sup>*</sup>
</xref>
<break></break>
ORN-1
<xref ref-type="table-fn" rid="table1-fn1">
<sup>*</sup>
</xref>
<break></break>
Neuropathy-1
<xref ref-type="table-fn" rid="table1-fn1">
<sup>*</sup>
</xref>
</td>
</tr>
<tr>
<td align="left" valign="top" rowspan="1" colspan="1">Chen
<italic>et al</italic>
2007 [
<xref rid="ref17" ref-type="bibr">17</xref>
]</td>
<td align="left" valign="top" rowspan="1" colspan="1">137 (100% recurrent)</td>
<td align="left" valign="top" rowspan="1" colspan="1">Retrospective</td>
<td align="left" valign="top" rowspan="1" colspan="1">IOERT</td>
<td align="left" valign="top" rowspan="1" colspan="1">10–18</td>
<td align="left" valign="top" rowspan="1" colspan="1">83</td>
<td align="left" valign="top" rowspan="1" colspan="1">26</td>
<td align="left" valign="top" rowspan="1" colspan="1">41</td>
<td align="left" valign="top" rowspan="1" colspan="1">61 (3yr)</td>
<td align="left" valign="top" rowspan="1" colspan="1">36 (3yr)</td>
<td align="left" valign="top" rowspan="1" colspan="1">Total-6%
<break></break>
Wound-4
<xref ref-type="table-fn" rid="table1-fn1">
<sup>*</sup>
</xref>
<break></break>
Fistula-2
<xref ref-type="table-fn" rid="table1-fn1">
<sup>*</sup>
</xref>
<break></break>
Neuropathy-1
<xref ref-type="table-fn" rid="table1-fn1">
<sup>*</sup>
</xref>
</td>
</tr>
<tr>
<td align="left" valign="top" rowspan="1" colspan="1">Pinheiro
<italic>et al</italic>
2002 [
<xref rid="ref23" ref-type="bibr">23</xref>
]</td>
<td align="left" valign="top" rowspan="1" colspan="1">34- SCC 10- non-SCC</td>
<td align="left" valign="top" rowspan="1" colspan="1">Retrospective</td>
<td align="left" valign="top" rowspan="1" colspan="1">IOERT</td>
<td align="left" valign="top" rowspan="1" colspan="1">12.5–22.5</td>
<td align="left" valign="top" rowspan="1" colspan="1">64</td>
<td align="left" valign="top" rowspan="1" colspan="1">36</td>
<td align="left" valign="top" rowspan="1" colspan="1">75.6 for living
<break></break>
patients</td>
<td align="left" valign="top" rowspan="1" colspan="1">46 52 (2yr)</td>
<td align="left" valign="top" rowspan="1" colspan="1">32 50 (2yr)</td>
<td align="left" valign="top" rowspan="1" colspan="1">Total-7%
<break></break>
Fistula-1
<xref ref-type="table-fn" rid="table1-fn1">
<sup>*</sup>
</xref>
<break></break>
Neuropathy-1
<xref ref-type="table-fn" rid="table1-fn1">
<sup>*</sup>
</xref>
<break></break>
Carotid blowout-1
<xref ref-type="table-fn" rid="table1-fn1">
<sup>*</sup>
</xref>
</td>
</tr>
<tr>
<td align="left" valign="top" rowspan="1" colspan="1">Nag
<italic>et al</italic>
1998 [
<xref rid="ref18" ref-type="bibr">18</xref>
]</td>
<td align="left" valign="top" rowspan="1" colspan="1">38 (100% recurrent)</td>
<td align="left" valign="top" rowspan="1" colspan="1">Retrospective</td>
<td align="left" valign="top" rowspan="1" colspan="1">IOERT</td>
<td align="left" valign="top" rowspan="1" colspan="1">15–20</td>
<td align="left" valign="top" rowspan="1" colspan="1">100</td>
<td align="left" valign="top" rowspan="1" colspan="1">0</td>
<td align="left" valign="top" rowspan="1" colspan="1">30</td>
<td align="left" valign="top" rowspan="1" colspan="1">19 (1yr)</td>
<td align="left" valign="top" rowspan="1" colspan="1">21% (1yr)</td>
<td align="left" valign="top" rowspan="1" colspan="1">Total -16%
<break></break>
Fistula-2
<xref ref-type="table-fn" rid="table1-fn1">
<sup>*</sup>
</xref>
</td>
</tr>
</tbody>
</table>
<table-wrap-foot>
<p>Adj. RT: Adjuvant post-IORT RT, LC: local control, OS: overall Survival,</p>
<fn id="table1-fn1">
<label>*</label>
<p>Number of patients.</p>
</fn>
</table-wrap-foot>
</table-wrap>
<table-wrap id="table2" position="float">
<label>Table 2.</label>
<caption>
<title>Randomised control trials of IORT versus WBI in early-breast cancer.</title>
</caption>
<table frame="border" rules="all">
<thead>
<tr>
<th align="center" valign="top" rowspan="1" colspan="1">Trial name</th>
<th align="center" valign="top" rowspan="1" colspan="1">Sample size</th>
<th align="center" valign="top" rowspan="1" colspan="1">Age</th>
<th align="center" valign="top" rowspan="1" colspan="1">Inclusion criteria</th>
<th align="center" valign="top" rowspan="1" colspan="1">IORT type</th>
<th align="center" valign="top" rowspan="1" colspan="1">IORT dose</th>
<th align="center" valign="top" rowspan="1" colspan="1">Trial design</th>
<th align="center" valign="top" rowspan="1" colspan="1">Local recurrence (5yr)</th>
<th align="center" valign="top" rowspan="1" colspan="1">Overall survival/mortality (5yr)</th>
</tr>
</thead>
<tbody>
<tr>
<td align="left" valign="top" rowspan="1" colspan="1">ELIOT [
<xref rid="ref28" ref-type="bibr">28</xref>
]</td>
<td align="left" valign="top" rowspan="1" colspan="1">1305 median follow-up: 5.8 years</td>
<td align="left" valign="top" rowspan="1" colspan="1">> 48 years</td>
<td align="left" valign="top" rowspan="1" colspan="1">any invasive cancer < 2.5 cm</td>
<td align="left" valign="top" rowspan="1" colspan="1">IOERT</td>
<td align="left" valign="top" rowspan="1" colspan="1">ELIOT:21 Gy/1# to tumour bed with 6–9 MeV electrons
<break></break>
WBI:50 Gy/25# + 10 Gy/5# boost</td>
<td align="left" valign="top" rowspan="1" colspan="1">Equivalence trial:
<break></break>
Statistical margin was local recurrence of 7.5% in the IORT group</td>
<td align="left" valign="top" rowspan="1" colspan="1">ELIOT:4.4% (95% C.I: 2.7–6.1)
<break></break>
WBI: 0.4%
<break></break>
<italic>p</italic>
< 0.0001</td>
<td align="left" valign="top" rowspan="1" colspan="1">ELIOT:96.8%
<break></break>
WBI: 96.9%
<break></break>
</td>
</tr>
<tr>
<td align="left" valign="top" rowspan="1" colspan="1">TARGIT-A [
<xref rid="ref27" ref-type="bibr">27</xref>
]
<break></break>
</td>
<td align="left" valign="top" rowspan="1" colspan="1">3451 Median follow-up:
<break></break>
2.5 years</td>
<td align="left" valign="top" rowspan="1" colspan="1">> 45years</td>
<td align="left" valign="top" rowspan="1" colspan="1">T1-2, N0, 1 IDC < 3.5 cm
<break></break>
(If EIC or ILC on final histology,
<break></break>
add whole breast RT)</td>
<td align="left" valign="top" rowspan="1" colspan="1">X-ray IORT (50 kv X-ray)</td>
<td align="left" valign="top" rowspan="1" colspan="1">TARGIT: 20 Gy to tumour bed
<break></break>
5–7 Gy at 1 cm depth
<break></break>
WBI: 40–56 Gy with or without boost 10–16 Gy</td>
<td align="left" valign="top" rowspan="1" colspan="1">Non-inferiority trial:
<break></break>
Statistical margin was 2.5% difference in local recurrence at 5 years</td>
<td align="left" valign="top" rowspan="1" colspan="1">TARGIT:3.3% (95% CI: 2.1–5.1)
<break></break>
WBI:1.3%
<break></break>
(95% CI: 0.7–2.5)
<break></break>
<italic>p</italic>
= 0.042</td>
<td align="left" valign="top" rowspan="1" colspan="1">TARGIT:3.9%
<break></break>
WBI: 5.3
<break></break>
<italic>p</italic>
= 0.009
<break></break>
</td>
</tr>
</tbody>
</table>
<table-wrap-foot>
<p>EIC: extensive intraductal component, ILC: invasive lobular cancer, WBI: whole breast RT.</p>
</table-wrap-foot>
</table-wrap>
<table-wrap id="table3" position="float">
<label>Table 3.</label>
<caption>
<title>Studies of IORT in locally advanced colorectal cancer after gross total resection.</title>
</caption>
<table frame="border" rules="all">
<thead>
<tr>
<th align="center" valign="top" rowspan="1" colspan="1">Author/Year</th>
<th align="center" valign="top" rowspan="1" colspan="1">Sample size</th>
<th align="center" valign="top" rowspan="1" colspan="1">Study design</th>
<th align="center" valign="top" rowspan="1" colspan="1">T4 %</th>
<th align="center" valign="top" rowspan="1" colspan="1">IORT type</th>
<th align="center" valign="top" rowspan="1" colspan="1">IORT dose (Gy)</th>
<th align="center" valign="top" rowspan="1" colspan="1">EBRT %</th>
<th align="center" valign="top" rowspan="1" colspan="1">Median F/U</th>
<th align="center" valign="top" rowspan="1" colspan="1">LC 5 year (%)</th>
<th align="center" valign="top" rowspan="1" colspan="1">OS 5 year (%)</th>
<th align="center" valign="top" rowspan="1" colspan="1">Toxicity grade 3 or ></th>
</tr>
</thead>
<tbody>
<tr>
<td align="left" valign="top" rowspan="1" colspan="1">Ratto
<italic>et al</italic>
. [
<xref rid="ref52" ref-type="bibr">52</xref>
] 2003</td>
<td align="left" valign="top" rowspan="1" colspan="1">43
<break></break>
IORT-19
<break></break>
No IORT-24</td>
<td align="left" valign="top" rowspan="1" colspan="1">NRC</td>
<td align="left" valign="top" rowspan="1" colspan="1">93</td>
<td align="left" valign="top" rowspan="1" colspan="1">IOERT</td>
<td align="left" valign="top" rowspan="1" colspan="1">10–15</td>
<td align="left" valign="top" rowspan="1" colspan="1">100</td>
<td align="left" valign="top" rowspan="1" colspan="1">74</td>
<td align="left" valign="top" rowspan="1" colspan="1">Sx + IORT: 91
<break></break>
Sx − 57
<break></break>
<italic>p</italic>
= 0.035</td>
<td align="left" valign="top" rowspan="1" colspan="1">61</td>
<td align="left" valign="top" rowspan="1" colspan="1">NR for IORT patients</td>
</tr>
<tr>
<td align="left" valign="top" rowspan="1" colspan="1">Sadahiro
<italic>et al</italic>
. [
<xref rid="ref53" ref-type="bibr">53</xref>
] 2004</td>
<td align="left" valign="top" rowspan="1" colspan="1">IORT-99
<break></break>
No IORT-68</td>
<td align="left" valign="top" rowspan="1" colspan="1">NRC</td>
<td align="left" valign="top" rowspan="1" colspan="1">12</td>
<td align="left" valign="top" rowspan="1" colspan="1">IOERT</td>
<td align="left" valign="top" rowspan="1" colspan="1">15–25</td>
<td align="left" valign="top" rowspan="1" colspan="1">100 (20 Gy only)</td>
<td align="left" valign="top" rowspan="1" colspan="1">67
<break></break>
83</td>
<td align="left" valign="top" rowspan="1" colspan="1">Sx + IORT-98
<break></break>
Sx- 84
<break></break>
<italic>p</italic>
= 0.002</td>
<td align="left" valign="top" rowspan="1" colspan="1">Sx + IORT- 79
<break></break>
Sx- 58
<break></break>
<italic>p</italic>
= 0.002</td>
<td align="left" valign="top" rowspan="1" colspan="1">NR for IORT patients</td>
</tr>
<tr>
<td align="left" valign="top" rowspan="1" colspan="1">Ferenschild
<italic>et al</italic>
. [
<xref rid="ref54" ref-type="bibr">54</xref>
] 2006</td>
<td align="left" valign="top" rowspan="1" colspan="1">123
<break></break>
IORT-30
<break></break>
No IORT-93</td>
<td align="left" valign="top" rowspan="1" colspan="1">NRC</td>
<td align="left" valign="top" rowspan="1" colspan="1">25</td>
<td align="left" valign="top" rowspan="1" colspan="1">HDR-IORT</td>
<td align="left" valign="top" rowspan="1" colspan="1">10</td>
<td align="left" valign="top" rowspan="1" colspan="1">100</td>
<td align="left" valign="top" rowspan="1" colspan="1">25</td>
<td align="left" valign="top" rowspan="1" colspan="1">R0+IORT:72
<break></break>
R0:71 (N.S diff)
<break></break>
<italic>R</italic>
<sup>(+)</sup>
+ IORT:58
<break></break>
<italic>R</italic>
<sup>(+)</sup>
:0 (
<italic>p</italic>
= 0.016)</td>
<td align="left" valign="top" rowspan="1" colspan="1">R0+IORT:56
<break></break>
R0:66 (N.s diff)
<break></break>
<italic>R</italic>
+ ( + ) IORT:38
<break></break>
<italic>R</italic>
+:0 (
<italic>p=</italic>
0.026)</td>
<td align="left" valign="top" rowspan="1" colspan="1">NR for IORT patients</td>
</tr>
<tr>
<td align="left" valign="top" rowspan="1" colspan="1">Roeder
<italic>et al</italic>
. [
<xref rid="ref55" ref-type="bibr">55</xref>
] 2007</td>
<td align="left" valign="top" rowspan="1" colspan="1">243</td>
<td align="left" valign="top" rowspan="1" colspan="1">RC</td>
<td align="left" valign="top" rowspan="1" colspan="1">20</td>
<td align="left" valign="top" rowspan="1" colspan="1">IOERT</td>
<td align="left" valign="top" rowspan="1" colspan="1">10–15</td>
<td align="left" valign="top" rowspan="1" colspan="1">86</td>
<td align="left" valign="top" rowspan="1" colspan="1">59</td>
<td align="left" valign="top" rowspan="1" colspan="1">R0 + IORT- 94
<break></break>
<italic>R</italic>
<sup>(+)</sup>
+ IORT-72</td>
<td align="left" valign="top" rowspan="1" colspan="1">NR</td>
<td align="left" valign="top" rowspan="1" colspan="1">Total-10%
<break></break>
Proctitis-8
<break></break>
Fistula-7
<break></break>
Bowel stenosis-8</td>
</tr>
<tr>
<td align="left" valign="top" rowspan="1" colspan="1">Mathis
<italic>et al</italic>
. [
<xref rid="ref50" ref-type="bibr">50</xref>
] 2008</td>
<td align="left" valign="top" rowspan="1" colspan="1">146</td>
<td align="left" valign="top" rowspan="1" colspan="1">PC</td>
<td align="left" valign="top" rowspan="1" colspan="1">64</td>
<td align="left" valign="top" rowspan="1" colspan="1">IOERT</td>
<td align="left" valign="top" rowspan="1" colspan="1">7.5–25</td>
<td align="left" valign="top" rowspan="1" colspan="1">100</td>
<td align="left" valign="top" rowspan="1" colspan="1">44</td>
<td align="left" valign="top" rowspan="1" colspan="1">86</td>
<td align="left" valign="top" rowspan="1" colspan="1">52</td>
<td align="left" valign="top" rowspan="1" colspan="1">Total- 22%
<break></break>
Neuropathy-3
<xref ref-type="table-fn" rid="table3-fn1">
<sup>*</sup>
</xref>
<break></break>
GI/GU-23
<xref ref-type="table-fn" rid="table3-fn1">
<sup>*</sup>
</xref>
</td>
</tr>
<tr>
<td align="left" valign="top" rowspan="1" colspan="1">Masaki
<italic>et al</italic>
. [
<xref rid="ref56" ref-type="bibr">56</xref>
] 2008</td>
<td align="left" valign="top" rowspan="1" colspan="1">44
<break></break>
IORT-19
<break></break>
No IORT-25</td>
<td align="left" valign="top" rowspan="1" colspan="1">RCT</td>
<td align="left" valign="top" rowspan="1" colspan="1">0</td>
<td align="left" valign="top" rowspan="1" colspan="1">IOERT</td>
<td align="left" valign="top" rowspan="1" colspan="1">18–20</td>
<td align="left" valign="top" rowspan="1" colspan="1">No</td>
<td align="left" valign="top" rowspan="1" colspan="1">34</td>
<td align="left" valign="top" rowspan="1" colspan="1">Sx+IORT-94.7
<break></break>
Sx-95.5%</td>
<td align="left" valign="top" rowspan="1" colspan="1">
<italic>p =</italic>
0.344
<break></break>
N.s diff</td>
<td align="left" valign="top" rowspan="1" colspan="1">Urinary catheter indwelling 29% vs. 3%,
<break></break>
Rest- N.s diff</td>
</tr>
<tr>
<td align="left" valign="top" rowspan="1" colspan="1">Valentini
<italic>et al</italic>
. [
<xref rid="ref57" ref-type="bibr">57</xref>
] 2009</td>
<td align="left" valign="top" rowspan="1" colspan="1">100
<break></break>
IORT-29
<break></break>
No IORT-71</td>
<td align="left" valign="top" rowspan="1" colspan="1">NRC</td>
<td align="left" valign="top" rowspan="1" colspan="1">100</td>
<td align="left" valign="top" rowspan="1" colspan="1">IOERT</td>
<td align="left" valign="top" rowspan="1" colspan="1">10–15</td>
<td align="left" valign="top" rowspan="1" colspan="1">100</td>
<td align="left" valign="top" rowspan="1" colspan="1">31</td>
<td align="left" valign="top" rowspan="1" colspan="1">R0+IORT:100
<break></break>
R0:81
<break></break>
<italic>p</italic>
= 0.014</td>
<td align="left" valign="top" rowspan="1" colspan="1">NR</td>
<td align="left" valign="top" rowspan="1" colspan="1">NR for IORT patients</td>
</tr>
<tr>
<td align="left" valign="top" rowspan="1" colspan="1">Dubois
<italic>et al</italic>
[
<xref rid="ref58" ref-type="bibr">58</xref>
] 2008</td>
<td align="left" valign="top" rowspan="1" colspan="1">142
<break></break>
IORT-73
<break></break>
No IORT-69</td>
<td align="left" valign="top" rowspan="1" colspan="1">RCT</td>
<td align="left" valign="top" rowspan="1" colspan="1">100</td>
<td align="left" valign="top" rowspan="1" colspan="1">IOERT</td>
<td align="left" valign="top" rowspan="1" colspan="1">15–18</td>
<td align="left" valign="top" rowspan="1" colspan="1">100</td>
<td align="left" valign="top" rowspan="1" colspan="1">60</td>
<td align="left" valign="top" rowspan="1" colspan="1">Sx + IORT- 91.8
<break></break>
Sx- 92.8
<break></break>
<italic>p</italic>
= 0.6018</td>
<td align="left" valign="top" rowspan="1" colspan="1">Sx + IORT - 69.8
<break></break>
Sx- 74.8
<break></break>
<italic>p</italic>
=0.25</td>
<td align="left" valign="top" rowspan="1" colspan="1">No difference in toxicity
<italic>p</italic>
=0.15</td>
</tr>
<tr>
<td align="left" valign="top" rowspan="1" colspan="1">Kusters
<italic>et al</italic>
[
<xref rid="ref59" ref-type="bibr">59</xref>
] 2010</td>
<td align="left" valign="top" rowspan="1" colspan="1">605</td>
<td align="left" valign="top" rowspan="1" colspan="1">PC
<break></break>
Pooled analysis</td>
<td align="left" valign="top" rowspan="1" colspan="1">29</td>
<td align="left" valign="top" rowspan="1" colspan="1">IOERT</td>
<td align="left" valign="top" rowspan="1" colspan="1">10–12.5</td>
<td align="left" valign="top" rowspan="1" colspan="1">100</td>
<td align="left" valign="top" rowspan="1" colspan="1"></td>
<td align="left" valign="top" rowspan="1" colspan="1">R0+IORT- 90.5
<break></break>
<italic>R</italic>
<sup>(+)</sup>
+ IORT-55
<break></break>
<italic>p</italic>
< 0.001</td>
<td align="left" valign="top" rowspan="1" colspan="1">67</td>
<td align="left" valign="top" rowspan="1" colspan="1">NR</td>
</tr>
<tr>
<td align="left" valign="top" rowspan="1" colspan="1">Sole
<italic>et al</italic>
. [
<xref rid="ref60" ref-type="bibr">60</xref>
] 2014</td>
<td align="left" valign="top" rowspan="1" colspan="1">335</td>
<td align="left" valign="top" rowspan="1" colspan="1">PC</td>
<td align="left" valign="top" rowspan="1" colspan="1">16</td>
<td align="left" valign="top" rowspan="1" colspan="1">IOERT</td>
<td align="left" valign="top" rowspan="1" colspan="1">10–15</td>
<td align="left" valign="top" rowspan="1" colspan="1">100</td>
<td align="left" valign="top" rowspan="1" colspan="1">72.6</td>
<td align="left" valign="top" rowspan="1" colspan="1">92</td>
<td align="left" valign="top" rowspan="1" colspan="1">75</td>
<td align="left" valign="top" rowspan="1" colspan="1">Total-10%
<break></break>
GI-19
<xref ref-type="table-fn" rid="table3-fn1">
<sup>*</sup>
</xref>
<break></break>
GU-8
<xref ref-type="table-fn" rid="table3-fn1">
<sup>*</sup>
</xref>
<break></break>
Neuropathy-7
<xref ref-type="table-fn" rid="table3-fn1">
<sup>*</sup>
</xref>
</td>
</tr>
<tr>
<td align="left" valign="top" rowspan="1" colspan="1">Holman
<italic>et al</italic>
[
<xref rid="ref61" ref-type="bibr">61</xref>
] 2016</td>
<td align="left" valign="top" rowspan="1" colspan="1">417</td>
<td align="left" valign="top" rowspan="1" colspan="1">PC
<break></break>
Pooled analysis</td>
<td align="left" valign="top" rowspan="1" colspan="1">100%
<break></break>
T4</td>
<td align="left" valign="top" rowspan="1" colspan="1">IOERT</td>
<td align="left" valign="top" rowspan="1" colspan="1">10–12.5</td>
<td align="left" valign="top" rowspan="1" colspan="1">97</td>
<td align="left" valign="top" rowspan="1" colspan="1">52</td>
<td align="left" valign="top" rowspan="1" colspan="1">
<italic>R</italic>
0 + IORT- 87
<break></break>
<italic>R</italic>
1 + IORT- 60
<break></break>
<italic>R</italic>
2 + IORT- 57
<break></break>
<italic>p</italic>
< 0.001</td>
<td align="left" valign="top" rowspan="1" colspan="1">
<italic>R</italic>
0 + IORT-65
<break></break>
<italic>R</italic>
1 + IORT- 34
<break></break>
<italic>R</italic>
2 + IORT- 14
<break></break>
<italic>p</italic>
< 0.001</td>
<td align="left" valign="top" rowspan="1" colspan="1">NR</td>
</tr>
</tbody>
</table>
<table-wrap-foot>
<p>NRC: non randomised comparison, RCT: randomised controlled trial, PC: prospective cohort, RC: retrospective cohort, F/U: follow-up, Sx: surgery,
<italic>R</italic>
<sup>(+)</sup>
: residual after surgery, LC:-local control, OS:-overall Survival, NR: not reported,</p>
<fn id="table3-fn1">
<label>*</label>
<p>Number of patients,</p>
</fn>
<p>N.s diff: Non significant difference.</p>
</table-wrap-foot>
</table-wrap>
<table-wrap id="table4" position="float">
<label>Table 4.</label>
<caption>
<title>studies of IORT in locally recurrent colorectal cancers.</title>
</caption>
<table frame="border" rules="all">
<thead>
<tr>
<th align="center" valign="top" rowspan="1" colspan="1">Author/Year</th>
<th align="center" valign="top" rowspan="1" colspan="1">Sample size</th>
<th align="center" valign="top" rowspan="1" colspan="1">Study design</th>
<th align="center" valign="top" rowspan="1" colspan="1">IORT type</th>
<th align="center" valign="top" rowspan="1" colspan="1">IORT dose (Gy)</th>
<th align="center" valign="top" rowspan="1" colspan="1">Prior EBRT %</th>
<th align="center" valign="top" rowspan="1" colspan="1">Adj. EBRT %</th>
<th align="center" valign="top" rowspan="1" colspan="1">Median Follow up</th>
<th align="center" valign="top" rowspan="1" colspan="1">LC 5year (%)</th>
<th align="center" valign="top" rowspan="1" colspan="1">OS 5year (%)</th>
<th align="center" valign="top" rowspan="1" colspan="1">Toxicity grade 3 or ></th>
</tr>
</thead>
<tbody>
<tr>
<td align="left" valign="top" rowspan="1" colspan="1">Suzuki
<italic>et al</italic>
. [
<xref rid="ref63" ref-type="bibr">63</xref>
] 1995</td>
<td align="left" valign="top" rowspan="1" colspan="1">106
<break></break>
Sx+IORT:42
<break></break>
Sx:64</td>
<td align="left" valign="top" rowspan="1" colspan="1">NRC</td>
<td align="left" valign="top" rowspan="1" colspan="1">IOERT</td>
<td align="left" valign="top" rowspan="1" colspan="1">10–30</td>
<td align="left" valign="top" rowspan="1" colspan="1">25</td>
<td align="left" valign="top" rowspan="1" colspan="1">98</td>
<td align="left" valign="top" rowspan="1" colspan="1">44</td>
<td align="left" valign="top" rowspan="1" colspan="1">Sx+IORT:60%
<break></break>
Sx:7%
<break></break>
at 3years</td>
<td align="left" valign="top" rowspan="1" colspan="1">Sx+IORT:19
<break></break>
Sx: 7%
<break></break>
P=0.0006</td>
<td align="left" valign="top" rowspan="1" colspan="1">Total-36%
<break></break>
Abcess-5
<break></break>
GI/GU-9
<break></break>
wound-3</td>
</tr>
<tr>
<td align="left" valign="top" rowspan="1" colspan="1">Valentini
<italic>et al</italic>
. [
<xref rid="ref66" ref-type="bibr">66</xref>
] 1999</td>
<td align="left" valign="top" rowspan="1" colspan="1">47
<break></break>
Sx+IORT:11
<break></break>
Sx:14</td>
<td align="left" valign="top" rowspan="1" colspan="1">NRC</td>
<td align="left" valign="top" rowspan="1" colspan="1">IOERT</td>
<td align="left" valign="top" rowspan="1" colspan="1">10–15</td>
<td align="left" valign="top" rowspan="1" colspan="1">28</td>
<td align="left" valign="top" rowspan="1" colspan="1">100</td>
<td align="left" valign="top" rowspan="1" colspan="1">80</td>
<td align="left" valign="top" rowspan="1" colspan="1">Sx+IORT:80
<break></break>
Sx:24
<break></break>
<italic>p</italic>
< 0.05</td>
<td align="left" valign="top" rowspan="1" colspan="1">Sx+IORT:41
<break></break>
Sx:16
<break></break>
N.S diff</td>
<td align="left" valign="top" rowspan="1" colspan="1">Hydronephrosis-1
<break></break>
Neuropathy-0
<xref ref-type="table-fn" rid="table4-fn1">
<sup>*</sup>
</xref>
</td>
</tr>
<tr>
<td align="left" valign="top" rowspan="1" colspan="1">Alektiar
<italic>et al</italic>
. [
<xref rid="ref75" ref-type="bibr">75</xref>
] 2000</td>
<td align="left" valign="top" rowspan="1" colspan="1">74</td>
<td align="left" valign="top" rowspan="1" colspan="1">RC</td>
<td align="left" valign="top" rowspan="1" colspan="1">HDR-IORT</td>
<td align="left" valign="top" rowspan="1" colspan="1">10–18</td>
<td align="left" valign="top" rowspan="1" colspan="1">53</td>
<td align="left" valign="top" rowspan="1" colspan="1">39</td>
<td align="left" valign="top" rowspan="1" colspan="1">22</td>
<td align="left" valign="top" rowspan="1" colspan="1">
<italic>R</italic>
0+IORT- 43
<break></break>
<italic>R</italic>
<sup>(+)</sup>
+IORT-26
<break></break>
<italic>p</italic>
= 0.02</td>
<td align="left" valign="top" rowspan="1" colspan="1">
<italic>R</italic>
0+IORT-36
<break></break>
<italic>R</italic>
<sup>(+)</sup>
+IORT-11
<break></break>
<italic>p</italic>
= 0.04</td>
<td align="left" valign="top" rowspan="1" colspan="1">Fistula-8
<xref ref-type="table-fn" rid="table4-fn1">
<sup>*</sup>
</xref>
<break></break>
Neuropathy-1
<xref ref-type="table-fn" rid="table4-fn1">
<sup>*</sup>
</xref>
<break></break>
Ureter-10
<xref ref-type="table-fn" rid="table4-fn1">
<sup>*</sup>
</xref>
<break></break>
Wound-5
<xref ref-type="table-fn" rid="table4-fn1">
<sup>*</sup>
</xref>
</td>
</tr>
<tr>
<td align="left" valign="top" rowspan="1" colspan="1">Lindel
<italic>et al</italic>
. [
<xref rid="ref76" ref-type="bibr">76</xref>
] 2001</td>
<td align="left" valign="top" rowspan="1" colspan="1">IORT-49
<break></break>
No IORT-20</td>
<td align="left" valign="top" rowspan="1" colspan="1">NRC</td>
<td align="left" valign="top" rowspan="1" colspan="1">IOERT</td>
<td align="left" valign="top" rowspan="1" colspan="1">10–20</td>
<td align="left" valign="top" rowspan="1" colspan="1">14</td>
<td align="left" valign="top" rowspan="1" colspan="1">94</td>
<td align="left" valign="top" rowspan="1" colspan="1">NR</td>
<td align="left" valign="top" rowspan="1" colspan="1">
<italic>R</italic>
0 + IORT-56
<break></break>
<italic>R</italic>
<sup>(+)</sup>
+IORT-14
<break></break>
</td>
<td align="left" valign="top" rowspan="1" colspan="1">
<italic>R</italic>
0 + IORT-40
<break></break>
<italic>R</italic>
<sup>(+)</sup>
+IORT-17
<break></break>
</td>
<td align="left" valign="top" rowspan="1" colspan="1">Wound complication-4
<xref ref-type="table-fn" rid="table4-fn1">
<sup>*</sup>
</xref>
<break></break>
Neuropathy-4
<xref ref-type="table-fn" rid="table4-fn1">
<sup>*</sup>
</xref>
</td>
</tr>
<tr>
<td align="left" valign="top" rowspan="1" colspan="1">Wiig
<italic>et al</italic>
. [
<xref rid="ref67" ref-type="bibr">67</xref>
] 2002</td>
<td align="left" valign="top" rowspan="1" colspan="1">107
<break></break>
Sx+IORT:59
<break></break>
Sx:48</td>
<td align="left" valign="top" rowspan="1" colspan="1">NRC</td>
<td align="left" valign="top" rowspan="1" colspan="1">IOERT</td>
<td align="left" valign="top" rowspan="1" colspan="1">15–20</td>
<td align="left" valign="top" rowspan="1" colspan="1">0</td>
<td align="left" valign="top" rowspan="1" colspan="1">100</td>
<td align="left" valign="top" rowspan="1" colspan="1">NR</td>
<td align="left" valign="top" rowspan="1" colspan="1">Sx+IORT:50
<break></break>
Sx: 30
<break></break>
N.S diff</td>
<td align="left" valign="top" rowspan="1" colspan="1">Sx+IORT:30
<break></break>
Sx: 30%
<break></break>
N.S diff</td>
<td align="left" valign="top" rowspan="1" colspan="1">late toxicity: NR
<break></break>
Acute complication: N.s diff</td>
</tr>
<tr>
<td align="left" valign="top" rowspan="1" colspan="1">Dresen
<italic>et al</italic>
[
<xref rid="ref69" ref-type="bibr">69</xref>
]. 2008</td>
<td align="left" valign="top" rowspan="1" colspan="1">147</td>
<td align="left" valign="top" rowspan="1" colspan="1">RC</td>
<td align="left" valign="top" rowspan="1" colspan="1">IOERT</td>
<td align="left" valign="top" rowspan="1" colspan="1">10.–17.5</td>
<td align="left" valign="top" rowspan="1" colspan="1">53</td>
<td align="left" valign="top" rowspan="1" colspan="1">84</td>
<td align="left" valign="top" rowspan="1" colspan="1">NR</td>
<td align="left" valign="top" rowspan="1" colspan="1">
<italic>R</italic>
0 + IORT-69
<break></break>
<italic>R</italic>
1 + IORT-29
<break></break>
<italic>R</italic>
2 + IORT-28
<italic>p</italic>
< 0.001(3yr)</td>
<td align="left" valign="top" rowspan="1" colspan="1">
<italic>R</italic>
0 + IORT-59
<break></break>
<italic>R</italic>
1 + IORT-27
<break></break>
<italic>R</italic>
2 + IORT-24
<break></break>
<italic>p</italic>
< 0.001(3yr)</td>
<td align="left" valign="top" rowspan="1" colspan="1">Neuropathy-16
<xref ref-type="table-fn" rid="table4-fn1">
<sup>*</sup>
</xref>
<break></break>
Ureter stenosis-4
<xref ref-type="table-fn" rid="table4-fn1">
<sup>*</sup>
</xref>
</td>
</tr>
<tr>
<td align="left" valign="top" rowspan="1" colspan="1">Haddock
<italic>et al</italic>
. [
<xref rid="ref65" ref-type="bibr">65</xref>
] 2011</td>
<td align="left" valign="top" rowspan="1" colspan="1">607</td>
<td align="left" valign="top" rowspan="1" colspan="1">PC</td>
<td align="left" valign="top" rowspan="1" colspan="1">IOERT</td>
<td align="left" valign="top" rowspan="1" colspan="1">7.5–30</td>
<td align="left" valign="top" rowspan="1" colspan="1">45</td>
<td align="left" valign="top" rowspan="1" colspan="1">96</td>
<td align="left" valign="top" rowspan="1" colspan="1">44</td>
<td align="left" valign="top" rowspan="1" colspan="1">
<italic>R</italic>
0 + IORT-79
<break></break>
<italic>R</italic>
1 + IORT-56
<break></break>
<italic>R</italic>
2 + IORT-49
<break></break>
<italic>p</italic>
< 0.001</td>
<td align="left" valign="top" rowspan="1" colspan="1">
<italic>R</italic>
0 + IORT-46
<break></break>
<italic>R</italic>
1 + IORT-27
<break></break>
<italic>R</italic>
2 + IORT-16
<break></break>
<italic>p</italic>
< 0.001</td>
<td align="left" valign="top" rowspan="1" colspan="1">Total-11%
<break></break>
Wound-42
<xref ref-type="table-fn" rid="table4-fn1">
<sup>*</sup>
</xref>
<break></break>
Neropathy-18
<xref ref-type="table-fn" rid="table4-fn1">
<sup>*</sup>
</xref>
</td>
</tr>
<tr>
<td align="left" valign="top" rowspan="1" colspan="1">Roeder
<italic>et al</italic>
.[
<xref rid="ref70" ref-type="bibr">70</xref>
] 2012</td>
<td align="left" valign="top" rowspan="1" colspan="1">97</td>
<td align="left" valign="top" rowspan="1" colspan="1">PC</td>
<td align="left" valign="top" rowspan="1" colspan="1">IOERT</td>
<td align="left" valign="top" rowspan="1" colspan="1">10–20</td>
<td align="left" valign="top" rowspan="1" colspan="1">44</td>
<td align="left" valign="top" rowspan="1" colspan="1">52</td>
<td align="left" valign="top" rowspan="1" colspan="1">33</td>
<td align="left" valign="top" rowspan="1" colspan="1">
<italic>R</italic>
0 + IORT-82
<break></break>
<italic>R</italic>
1 + IORT-41
<break></break>
<italic>R</italic>
2 + IORT-18
<break></break>
<italic>p</italic>
< 0.001(3yr)</td>
<td align="left" valign="top" rowspan="1" colspan="1">
<italic>R</italic>
0 + IORT-80
<break></break>
<italic>R</italic>
1 + IORT-37
<break></break>
<italic>R</italic>
2 + IORT-35
<break></break>
<italic>p</italic>
< 0.001(3yr)</td>
<td align="left" valign="top" rowspan="1" colspan="1">Acute:
<break></break>
Abscess /fistula-16
<break></break>
Late:
<break></break>
Neuropathy-8
<xref ref-type="table-fn" rid="table4-fn1">
<sup>*</sup>
</xref>
<break></break>
Ureter stenosis-3
<xref ref-type="table-fn" rid="table4-fn1">
<sup>*</sup>
</xref>
</td>
</tr>
<tr>
<td align="left" valign="top" rowspan="1" colspan="1">Calvo
<italic>et al</italic>
. [
<xref rid="ref68" ref-type="bibr">68</xref>
] 2013</td>
<td align="left" valign="top" rowspan="1" colspan="1">60</td>
<td align="left" valign="top" rowspan="1" colspan="1">RC</td>
<td align="left" valign="top" rowspan="1" colspan="1">IOERT</td>
<td align="left" valign="top" rowspan="1" colspan="1">10–15</td>
<td align="left" valign="top" rowspan="1" colspan="1">50</td>
<td align="left" valign="top" rowspan="1" colspan="1">47</td>
<td align="left" valign="top" rowspan="1" colspan="1">36</td>
<td align="left" valign="top" rowspan="1" colspan="1">44
<break></break>
<italic>R</italic>
0 vs
<italic>R</italic>
1: HR-2.09,
<italic>p</italic>
= 0.05</td>
<td align="left" valign="top" rowspan="1" colspan="1">43
<break></break>
<italic>R</italic>
0 vs R1:HR-2.9,
<italic>p</italic>
= 0.05</td>
<td align="left" valign="top" rowspan="1" colspan="1">Total:42%
<break></break>
Fistula-4
<xref ref-type="table-fn" rid="table4-fn1">
<sup>*</sup>
</xref>
<break></break>
Neuropathy-4
<xref ref-type="table-fn" rid="table4-fn1">
<sup>*</sup>
</xref>
<break></break>
GI-4
<xref ref-type="table-fn" rid="table4-fn1">
<sup>*</sup>
</xref>
</td>
</tr>
<tr>
<td align="left" valign="top" rowspan="1" colspan="1">Holman
<italic>et al</italic>
. [
<xref rid="ref71" ref-type="bibr">71</xref>
] 2017</td>
<td align="left" valign="top" rowspan="1" colspan="1">565</td>
<td align="left" valign="top" rowspan="1" colspan="1">PC pooled analysis</td>
<td align="left" valign="top" rowspan="1" colspan="1">IOERT</td>
<td align="left" valign="top" rowspan="1" colspan="1">10–20</td>
<td align="left" valign="top" rowspan="1" colspan="1">46</td>
<td align="left" valign="top" rowspan="1" colspan="1">95</td>
<td align="left" valign="top" rowspan="1" colspan="1">40 months
<break></break>
In survivors</td>
<td align="left" valign="top" rowspan="1" colspan="1">
<italic>R</italic>
0 + IORT-72
<break></break>
<italic>R</italic>
1 + IORT-36
<break></break>
<italic>R</italic>
2 + IORT-39
<break></break>
<italic>p</italic>
< 0.0001</td>
<td align="left" valign="top" rowspan="1" colspan="1">
<italic>R</italic>
0 + IORT-48
<break></break>
<italic>R</italic>
1 + IORT-25
<break></break>
<italic>R</italic>
2 + IORT-17
<break></break>
<italic>p</italic>
< 0.0001</td>
<td align="left" valign="top" rowspan="1" colspan="1"></td>
</tr>
</tbody>
</table>
<table-wrap-foot>
<p>NRC: non randomised comparison, RCT: randomised controlled trial, PC: prospective cohort, RC: retrospective cohort, Sx: surgery,
<italic>R</italic>
<sup>(+)</sup>
: residual after surgery,
<italic>R</italic>
0: no residual after surgery, LC: local control, OS: overall survival, NR: not reported,</p>
<fn id="table4-fn1">
<label>*</label>
<p>Number of patients,</p>
</fn>
<p>N.s diff: non-significant difference.</p>
</table-wrap-foot>
</table-wrap>
<table-wrap id="table5" position="float">
<label>Table 5.</label>
<caption>
<title>Studies of IORT in extremity soft tissue sarcoma in combination with function preserving surgery and moderate doses of EBRT (40-50Gy).</title>
</caption>
<table frame="border" rules="all">
<thead>
<tr>
<th align="center" valign="top" rowspan="1" colspan="1">Author/Year</th>
<th align="center" valign="top" rowspan="1" colspan="1">Sample size</th>
<th align="center" valign="top" rowspan="1" colspan="1">Study design</th>
<th align="center" valign="top" rowspan="1" colspan="1">IORT type</th>
<th align="center" valign="top" rowspan="1" colspan="1">IORT dose Gy</th>
<th align="center" valign="top" rowspan="1" colspan="1">EBRT %</th>
<th align="center" valign="top" rowspan="1" colspan="1">Median follow-up</th>
<th align="center" valign="top" rowspan="1" colspan="1">LC 5 year</th>
<th align="center" valign="top" rowspan="1" colspan="1">DFS 5 year</th>
<th align="center" valign="top" rowspan="1" colspan="1">OS 5 year</th>
<th align="center" valign="top" rowspan="1" colspan="1">Complications</th>
</tr>
</thead>
<tbody>
<tr>
<td align="left" valign="top" rowspan="1" colspan="1">Edmonson
<italic>et al</italic>
. [
<xref rid="ref77" ref-type="bibr">77</xref>
] 2001</td>
<td align="left" valign="top" rowspan="1" colspan="1">39 (Recurrent-3%,
<italic>R</italic>
+:38%)</td>
<td align="left" valign="top" rowspan="1" colspan="1">Retrospective</td>
<td align="left" valign="top" rowspan="1" colspan="1">IOERT/HDR IORT</td>
<td align="left" valign="top" rowspan="1" colspan="1">10–20</td>
<td align="left" valign="top" rowspan="1" colspan="1">100</td>
<td align="left" valign="top" rowspan="1" colspan="1">70</td>
<td align="left" valign="top" rowspan="1" colspan="1">90
<xref ref-type="table-fn" rid="table5-fn3">
<sup>α</sup>
</xref>
</td>
<td align="left" valign="top" rowspan="1" colspan="1">NR</td>
<td align="left" valign="top" rowspan="1" colspan="1">80</td>
<td align="left" valign="top" rowspan="1" colspan="1">NR for IORT</td>
</tr>
<tr>
<td align="left" valign="top" rowspan="1" colspan="1">Azinovic
<italic>et al</italic>
. [
<xref rid="ref78" ref-type="bibr">78</xref>
] 2003</td>
<td align="left" valign="top" rowspan="1" colspan="1">45 (Recurrent-42%,
<italic>R</italic>
+:33%)</td>
<td align="left" valign="top" rowspan="1" colspan="1">Retrospective</td>
<td align="left" valign="top" rowspan="1" colspan="1">IOERT</td>
<td align="left" valign="top" rowspan="1" colspan="1">10–20</td>
<td align="left" valign="top" rowspan="1" colspan="1">80</td>
<td align="left" valign="top" rowspan="1" colspan="1">93</td>
<td align="left" valign="top" rowspan="1" colspan="1">80
<break></break>
<italic>R</italic>
0 vs
<italic>R</italic>
1:
<break></break>
88 vs 57
<break></break>
<italic>p</italic>
= 0.04</td>
<td align="left" valign="top" rowspan="1" colspan="1">NR</td>
<td align="left" valign="top" rowspan="1" colspan="1">64</td>
<td align="left" valign="top" rowspan="1" colspan="1">Wound complication -4
<xref ref-type="table-fn" rid="table5-fn1">
<sup>*</sup>
</xref>
<break></break>
Neuropathy-5
<xref ref-type="table-fn" rid="table5-fn1">
<sup>*</sup>
</xref>
<break></break>
Fracture-2
<xref ref-type="table-fn" rid="table5-fn1">
<sup>*</sup>
</xref>
</td>
</tr>
<tr>
<td align="left" valign="top" rowspan="1" colspan="1">Kretzler
<italic>et al</italic>
. [
<xref rid="ref79" ref-type="bibr">79</xref>
] 2004</td>
<td align="left" valign="top" rowspan="1" colspan="1">28
<break></break>
(Recurrent -57%,
<italic>R</italic>
+:39%)</td>
<td align="left" valign="top" rowspan="1" colspan="1">Retrospective</td>
<td align="left" valign="top" rowspan="1" colspan="1">HDR/IOERT</td>
<td align="left" valign="top" rowspan="1" colspan="1">12–15</td>
<td align="left" valign="top" rowspan="1" colspan="1">90</td>
<td align="left" valign="top" rowspan="1" colspan="1">55</td>
<td align="left" valign="top" rowspan="1" colspan="1">84</td>
<td align="left" valign="top" rowspan="1" colspan="1">54</td>
<td align="left" valign="top" rowspan="1" colspan="1">66</td>
<td align="left" valign="top" rowspan="1" colspan="1">Total-24%
<break></break>
Neuropathy-1
<xref ref-type="table-fn" rid="table5-fn1">
<sup>*</sup>
</xref>
<break></break>
Fractures-2
<xref ref-type="table-fn" rid="table5-fn1">
<sup>*</sup>
</xref>
<break></break>
Contracture-2
<xref ref-type="table-fn" rid="table5-fn1">
<sup>*</sup>
</xref>
</td>
</tr>
<tr>
<td align="left" valign="top" rowspan="1" colspan="1">Oertel
<italic>et al</italic>
. [
<xref rid="ref80" ref-type="bibr">80</xref>
] 2006</td>
<td align="left" valign="top" rowspan="1" colspan="1">153
<break></break>
(Recurrent - 38%,
<italic>R</italic>
+: 30%)</td>
<td align="left" valign="top" rowspan="1" colspan="1">Retrospective</td>
<td align="left" valign="top" rowspan="1" colspan="1">IOERT</td>
<td align="left" valign="top" rowspan="1" colspan="1">10–20</td>
<td align="left" valign="top" rowspan="1" colspan="1">100</td>
<td align="left" valign="top" rowspan="1" colspan="1">33</td>
<td align="left" valign="top" rowspan="1" colspan="1">78</td>
<td align="left" valign="top" rowspan="1" colspan="1">NR</td>
<td align="left" valign="top" rowspan="1" colspan="1">77</td>
<td align="left" valign="top" rowspan="1" colspan="1">Wound-17%
<break></break>
Neuropathy-7
<xref ref-type="table-fn" rid="table5-fn1">
<sup>*</sup>
</xref>
<break></break>
Lymphededma-6
<xref ref-type="table-fn" rid="table5-fn1">
<sup>*</sup>
</xref>
</td>
</tr>
<tr>
<td align="left" valign="top" rowspan="1" colspan="1">Niewald
<italic>et al</italic>
. [
<xref rid="ref81" ref-type="bibr">81</xref>
] 2009</td>
<td align="left" valign="top" rowspan="1" colspan="1">38
<break></break>
(Recurrent -24%,)</td>
<td align="left" valign="top" rowspan="1" colspan="1">Retrospective</td>
<td align="left" valign="top" rowspan="1" colspan="1">HDR-IORT</td>
<td align="left" valign="top" rowspan="1" colspan="1">8–15</td>
<td align="left" valign="top" rowspan="1" colspan="1">100</td>
<td align="left" valign="top" rowspan="1" colspan="1">27</td>
<td align="left" valign="top" rowspan="1" colspan="1">63</td>
<td align="left" valign="top" rowspan="1" colspan="1">NR</td>
<td align="left" valign="top" rowspan="1" colspan="1">57</td>
<td align="left" valign="top" rowspan="1" colspan="1">Skin-42%
<break></break>
Neuropathy-0</td>
</tr>
<tr>
<td align="left" valign="top" rowspan="1" colspan="1">Call
<italic>et al</italic>
. [
<xref rid="ref82" ref-type="bibr">82</xref>
] 2012
<xref ref-type="table-fn" rid="table5-fn2">¥</xref>
</td>
<td align="left" valign="top" rowspan="1" colspan="1">61
<break></break>
(Recurrent -21%,
<italic>R</italic>
+:18%)</td>
<td align="left" valign="top" rowspan="1" colspan="1">Retrospective</td>
<td align="left" valign="top" rowspan="1" colspan="1">IOERT</td>
<td align="left" valign="top" rowspan="1" colspan="1">7.5–20</td>
<td align="left" valign="top" rowspan="1" colspan="1">100</td>
<td align="left" valign="top" rowspan="1" colspan="1">70</td>
<td align="left" valign="top" rowspan="1" colspan="1">91</td>
<td align="left" valign="top" rowspan="1" colspan="1">80</td>
<td align="left" valign="top" rowspan="1" colspan="1">72</td>
<td align="left" valign="top" rowspan="1" colspan="1">Wound-3.2%
<break></break>
Neuropathy-1
<xref ref-type="table-fn" rid="table5-fn1">
<sup>*</sup>
</xref>
</td>
</tr>
<tr>
<td align="left" valign="top" rowspan="1" colspan="1">Calvo
<italic>et al</italic>
. [
<xref rid="ref83" ref-type="bibr">83</xref>
] 2014</td>
<td align="left" valign="top" rowspan="1" colspan="1">159
<break></break>
(
<italic>R</italic>
1-16%)</td>
<td align="left" valign="top" rowspan="1" colspan="1">Retrospective pooled</td>
<td align="left" valign="top" rowspan="1" colspan="1">IOERT</td>
<td align="left" valign="top" rowspan="1" colspan="1">10–20</td>
<td align="left" valign="top" rowspan="1" colspan="1">100</td>
<td align="left" valign="top" rowspan="1" colspan="1">53</td>
<td align="left" valign="top" rowspan="1" colspan="1">82
<break></break>
<italic>R</italic>
0 vs
<italic>R</italic>
1:
<break></break>
<italic>p</italic>
= 0.009</td>
<td align="left" valign="top" rowspan="1" colspan="1">62</td>
<td align="left" valign="top" rowspan="1" colspan="1">72</td>
<td align="left" valign="top" rowspan="1" colspan="1">Acute skin/wound- 16%
<break></break>
Neuropathy-6
<xref ref-type="table-fn" rid="table5-fn1">
<sup>*</sup>
</xref>
<break></break>
Lympedema-7
<xref ref-type="table-fn" rid="table5-fn1">
<sup>*</sup>
</xref>
</td>
</tr>
<tr>
<td align="left" valign="top" rowspan="1" colspan="1">Roeder
<italic>et al</italic>
. [
<xref rid="ref84" ref-type="bibr">84</xref>
] 2014</td>
<td align="left" valign="top" rowspan="1" colspan="1">34
<break></break>
(
<italic>R</italic>
1-12%)</td>
<td align="left" valign="top" rowspan="1" colspan="1">Prospective</td>
<td align="left" valign="top" rowspan="1" colspan="1">IOERT</td>
<td align="left" valign="top" rowspan="1" colspan="1">10–15</td>
<td align="left" valign="top" rowspan="1" colspan="1">100</td>
<td align="left" valign="top" rowspan="1" colspan="1">43</td>
<td align="left" valign="top" rowspan="1" colspan="1">97
<break></break>
</td>
<td align="left" valign="top" rowspan="1" colspan="1">66</td>
<td align="left" valign="top" rowspan="1" colspan="1">79</td>
<td align="left" valign="top" rowspan="1" colspan="1">Neuropathy-1
<xref ref-type="table-fn" rid="table5-fn1">
<sup>*</sup>
</xref>
<break></break>
osteonecrosis-1
<xref ref-type="table-fn" rid="table5-fn1">
<sup>*</sup>
</xref>
<break></break>
Joint dysfunction-1
<xref ref-type="table-fn" rid="table5-fn1">
<sup>*</sup>
</xref>
</td>
</tr>
<tr>
<td align="left" valign="top" rowspan="1" colspan="1">Roeder
<italic>et al</italic>
. [
<xref rid="ref85" ref-type="bibr">85</xref>
] 2016</td>
<td align="left" valign="top" rowspan="1" colspan="1">183
<break></break>
(Recurrent -22%,
<italic>R</italic>
1 - 32%)</td>
<td align="left" valign="top" rowspan="1" colspan="1">Retrospective</td>
<td align="left" valign="top" rowspan="1" colspan="1">IOERT</td>
<td align="left" valign="top" rowspan="1" colspan="1">8–20</td>
<td align="left" valign="top" rowspan="1" colspan="1">100</td>
<td align="left" valign="top" rowspan="1" colspan="1">64</td>
<td align="left" valign="top" rowspan="1" colspan="1">86
<break></break>
<italic>R</italic>
0 vs
<italic>R</italic>
1: 92 vs 75
<italic>p</italic>
= 0.019</td>
<td align="left" valign="top" rowspan="1" colspan="1">61</td>
<td align="left" valign="top" rowspan="1" colspan="1">77</td>
<td align="left" valign="top" rowspan="1" colspan="1">Total-19%
<break></break>
Wound-15
<xref ref-type="table-fn" rid="table5-fn1">
<sup>*</sup>
</xref>
<break></break>
Neuropathy-14
<xref ref-type="table-fn" rid="table5-fn1">
<sup>*</sup>
</xref>
<break></break>
osteonecrosis-11
<xref ref-type="table-fn" rid="table5-fn1">
<sup>*</sup>
</xref>
</td>
</tr>
</tbody>
</table>
<table-wrap-foot>
<p>
<italic>R</italic>
+: Residual after surgery,
<italic>R</italic>
0: no residual after surgery, LC: local control, OS: overall Survival, DFS: disease-free survival, NR: not reported,</p>
<fn id="table5-fn1">
<label>
<sup>*</sup>
</label>
<p>Number of patients,</p>
</fn>
<fn id="table5-fn2">
<label>¥</label>
<p>call
<italic>et al</italic>
included only upper extremity tumours,</p>
</fn>
<fn id="table5-fn3">
<label>α</label>
<p>-crude rate</p>
</fn>
</table-wrap-foot>
</table-wrap>
<table-wrap id="table6" position="float">
<label>Table 6.</label>
<caption>
<title>Studies of IORT in Retroperitoneal sarcoma.</title>
</caption>
<table frame="border" rules="all">
<thead>
<tr>
<th align="center" valign="top" rowspan="1" colspan="1">Author/Year</th>
<th align="center" valign="top" rowspan="1" colspan="1">Sample size</th>
<th align="center" valign="top" rowspan="1" colspan="1">Study design</th>
<th align="center" valign="top" rowspan="1" colspan="1">IORT type</th>
<th align="center" valign="top" rowspan="1" colspan="1">IORT dose (Gy)</th>
<th align="center" valign="top" rowspan="1" colspan="1">EBRT %</th>
<th align="center" valign="top" rowspan="1" colspan="1">Median follow-up</th>
<th align="center" valign="top" rowspan="1" colspan="1">LC 5 year (%)</th>
<th align="center" valign="top" rowspan="1" colspan="1">OS 5 year (%)</th>
<th align="center" valign="top" rowspan="1" colspan="1">Toxicity grade 3 or ></th>
</tr>
</thead>
<tbody>
<tr>
<td align="left" valign="top" rowspan="1" colspan="1">Sindelar
<italic>et al</italic>
. [
<xref rid="ref86" ref-type="bibr">86</xref>
] 1993</td>
<td align="left" valign="top" rowspan="1" colspan="1">35
<break></break>
GTR-100%</td>
<td align="left" valign="top" rowspan="1" colspan="1">RCT
<break></break>
Sx + IORT + low-dose PORT
<break></break>
Vs Sx + high-dose PORT</td>
<td align="left" valign="top" rowspan="1" colspan="1">IOERT</td>
<td align="left" valign="top" rowspan="1" colspan="1">20</td>
<td align="left" valign="top" rowspan="1" colspan="1">100</td>
<td align="left" valign="top" rowspan="1" colspan="1">96</td>
<td align="left" valign="top" rowspan="1" colspan="1">IORT + PORT- 60%’
<break></break>
PORT-20%</td>
<td align="left" valign="top" rowspan="1" colspan="1">-</td>
<td align="left" valign="top" rowspan="1" colspan="1">Neuropathy
<break></break>
IORT + PORT-60%
<break></break>
PORT-5%
<break></break>
Enteritis
<break></break>
IORT + PORT-13%
<break></break>
PORT-50%</td>
</tr>
<tr>
<td align="left" valign="top" rowspan="1" colspan="1">Alektiar
<italic>et al</italic>
. [
<xref rid="ref87" ref-type="bibr">87</xref>
] 2000</td>
<td align="left" valign="top" rowspan="1" colspan="1">32
<break></break>
Recurrent -62%, GTR-94%</td>
<td align="left" valign="top" rowspan="1" colspan="1">Retrospective cohort</td>
<td align="left" valign="top" rowspan="1" colspan="1">HDR-IORT</td>
<td align="left" valign="top" rowspan="1" colspan="1">12–15</td>
<td align="left" valign="top" rowspan="1" colspan="1">78</td>
<td align="left" valign="top" rowspan="1" colspan="1">33</td>
<td align="left" valign="top" rowspan="1" colspan="1">62</td>
<td align="left" valign="top" rowspan="1" colspan="1">45</td>
<td align="left" valign="top" rowspan="1" colspan="1">GI -18%
<break></break>
Neuropathy-0%</td>
</tr>
<tr>
<td align="left" valign="top" rowspan="1" colspan="1">Gieschen
<italic>et al</italic>
. [
<xref rid="ref88" ref-type="bibr">88</xref>
] 2001</td>
<td align="left" valign="top" rowspan="1" colspan="1">37
<break></break>
IORT-20
<break></break>
No IORT-17
<break></break>
Recurrent-22%
<break></break>
GTR-78%</td>
<td align="left" valign="top" rowspan="1" colspan="1">Retrospective cohort</td>
<td align="left" valign="top" rowspan="1" colspan="1">IOERT</td>
<td align="left" valign="top" rowspan="1" colspan="1">10–20</td>
<td align="left" valign="top" rowspan="1" colspan="1">
<break></break>
100
<break></break>
100</td>
<td align="left" valign="top" rowspan="1" colspan="1">38</td>
<td align="left" valign="top" rowspan="1" colspan="1">
<break></break>
IORT-83
<break></break>
No IORT-61
<break></break>
p = 0.197
<xref ref-type="table-fn" rid="table6-fn2">¥</xref>
</td>
<td align="left" valign="top" rowspan="1" colspan="1">
<break></break>
IORT-74
<break></break>
No IORT-30
<break></break>
p = 0.044
<xref ref-type="table-fn" rid="table6-fn2">¥</xref>
</td>
<td align="left" valign="top" rowspan="1" colspan="1">Total-20%
<break></break>
Neuropathy-1
<xref ref-type="table-fn" rid="table6-fn1">
<sup>*</sup>
</xref>
<break></break>
Fistula-2
<xref ref-type="table-fn" rid="table6-fn1">
<sup>*</sup>
</xref>
</td>
</tr>
<tr>
<td align="left" valign="top" rowspan="1" colspan="1">Peterson
<italic>et al</italic>
[
<xref rid="ref89" ref-type="bibr">89</xref>
] 2002</td>
<td align="left" valign="top" rowspan="1" colspan="1">87
<break></break>
Recurrent-50%, GTR-84%</td>
<td align="left" valign="top" rowspan="1" colspan="1">Retrospective cohort</td>
<td align="left" valign="top" rowspan="1" colspan="1">IOERT</td>
<td align="left" valign="top" rowspan="1" colspan="1">8.75–30</td>
<td align="left" valign="top" rowspan="1" colspan="1">89</td>
<td align="left" valign="top" rowspan="1" colspan="1">42</td>
<td align="left" valign="top" rowspan="1" colspan="1">59</td>
<td align="left" valign="top" rowspan="1" colspan="1">47</td>
<td align="left" valign="top" rowspan="1" colspan="1">GI-14%
<break></break>
Neuropathy- 10%</td>
</tr>
<tr>
<td align="left" valign="top" rowspan="1" colspan="1">Bobin
<italic>et al</italic>
. [
<xref rid="ref90" ref-type="bibr">90</xref>
] 2003</td>
<td align="left" valign="top" rowspan="1" colspan="1">24
<break></break>
Recurrent-79%
<break></break>
GTR-92</td>
<td align="left" valign="top" rowspan="1" colspan="1">Retrospective cohort</td>
<td align="left" valign="top" rowspan="1" colspan="1">IOERT</td>
<td align="left" valign="top" rowspan="1" colspan="1">8–22</td>
<td align="left" valign="top" rowspan="1" colspan="1">92</td>
<td align="left" valign="top" rowspan="1" colspan="1">53</td>
<td align="left" valign="top" rowspan="1" colspan="1">46</td>
<td align="left" valign="top" rowspan="1" colspan="1">56</td>
<td align="left" valign="top" rowspan="1" colspan="1">Total-8%
<break></break>
Neuropathy-2
<xref ref-type="table-fn" rid="table6-fn1">
<sup>*</sup>
</xref>
</td>
</tr>
<tr>
<td align="left" valign="top" rowspan="1" colspan="1">Pierie
<italic>et al</italic>
. [
<xref rid="ref91" ref-type="bibr">91</xref>
] 2006</td>
<td align="left" valign="top" rowspan="1" colspan="1">IORT-14
<break></break>
No IORT-27
<break></break>
Recurrent-0%
<break></break>
GTR-100%</td>
<td align="left" valign="top" rowspan="1" colspan="1">Retrospective cohort</td>
<td align="left" valign="top" rowspan="1" colspan="1">IOERT</td>
<td align="left" valign="top" rowspan="1" colspan="1">10–20</td>
<td align="left" valign="top" rowspan="1" colspan="1">100
<break></break>
100</td>
<td align="left" valign="top" rowspan="1" colspan="1">27</td>
<td align="left" valign="top" rowspan="1" colspan="1">NR</td>
<td align="left" valign="top" rowspan="1" colspan="1">IORT-77
<break></break>
No IORT-45
<break></break>
<italic>p</italic>
= 0.38</td>
<td align="left" valign="top" rowspan="1" colspan="1">GI-1%
<break></break>
Neuropathy-3%</td>
</tr>
<tr>
<td align="left" valign="top" rowspan="1" colspan="1">Krempien
<italic>et al</italic>
. [
<xref rid="ref92" ref-type="bibr">92</xref>
] 2006</td>
<td align="left" valign="top" rowspan="1" colspan="1">67
<break></break>
Recurrent-61%, GTR-82%</td>
<td align="left" valign="top" rowspan="1" colspan="1">Retrospective cohort</td>
<td align="left" valign="top" rowspan="1" colspan="1">IOERT</td>
<td align="left" valign="top" rowspan="1" colspan="1">12–20</td>
<td align="left" valign="top" rowspan="1" colspan="1">67</td>
<td align="left" valign="top" rowspan="1" colspan="1">30</td>
<td align="left" valign="top" rowspan="1" colspan="1">40</td>
<td align="left" valign="top" rowspan="1" colspan="1">64
<break></break>
<italic>R</italic>
0:87
<break></break>
<italic>R</italic>
+:50
<break></break>
<italic>p</italic>
< 0.01</td>
<td align="left" valign="top" rowspan="1" colspan="1">Fistula-3
<xref ref-type="table-fn" rid="table6-fn1">
<sup>*</sup>
</xref>
<break></break>
Neuropathy-5
<xref ref-type="table-fn" rid="table6-fn1">
<sup>*</sup>
</xref>
<break></break>
Urethral stenosis-2
<xref ref-type="table-fn" rid="table6-fn1">
<sup>*</sup>
</xref>
</td>
</tr>
<tr>
<td align="left" valign="top" rowspan="1" colspan="1">Pawlik
<italic>et al</italic>
. [
<xref rid="ref93" ref-type="bibr">93</xref>
] 2006</td>
<td align="left" valign="top" rowspan="1" colspan="1">72
<break></break>
IORT-22
<break></break>
No IORT-50
<break></break>
Recurrent-25%, GTR-75%</td>
<td align="left" valign="top" rowspan="1" colspan="1">Prospective cohort</td>
<td align="left" valign="top" rowspan="1" colspan="1">IOERT</td>
<td align="left" valign="top" rowspan="1" colspan="1">15</td>
<td align="left" valign="top" rowspan="1" colspan="1">100</td>
<td align="left" valign="top" rowspan="1" colspan="1">40</td>
<td align="left" valign="top" rowspan="1" colspan="1">60
<xref ref-type="table-fn" rid="table6-fn2">¥</xref>
</td>
<td align="left" valign="top" rowspan="1" colspan="1">50</td>
<td align="left" valign="top" rowspan="1" colspan="1">NR</td>
</tr>
<tr>
<td align="left" valign="top" rowspan="1" colspan="1">Ballo
<italic>et al</italic>
. [
<xref rid="ref94" ref-type="bibr">94</xref>
] 2007</td>
<td align="left" valign="top" rowspan="1" colspan="1">83
<break></break>
IORT-18
<break></break>
No IORT-63
<break></break>
Recurrent-28%,
<italic>R</italic>
+-47%</td>
<td align="left" valign="top" rowspan="1" colspan="1">Retrospective cohort</td>
<td align="left" valign="top" rowspan="1" colspan="1">IOERT</td>
<td align="left" valign="top" rowspan="1" colspan="1">10–15</td>
<td align="left" valign="top" rowspan="1" colspan="1">100</td>
<td align="left" valign="top" rowspan="1" colspan="1">47</td>
<td align="left" valign="top" rowspan="1" colspan="1">
<break></break>
IORT-46
<break></break>
No IORT-51
<break></break>
<italic>p</italic>
= 0.9</td>
<td align="left" valign="top" rowspan="1" colspan="1">NR</td>
<td align="left" valign="top" rowspan="1" colspan="1">NR</td>
</tr>
<tr>
<td align="left" valign="top" rowspan="1" colspan="1">Dziewirski
<italic>et al</italic>
. [
<xref rid="ref95" ref-type="bibr">95</xref>
] 2010</td>
<td align="left" valign="top" rowspan="1" colspan="1">57
<break></break>
Recurrent -74%, GTR-85%</td>
<td align="left" valign="top" rowspan="1" colspan="1">Prospective cohort</td>
<td align="left" valign="top" rowspan="1" colspan="1">HDR-IORT</td>
<td align="left" valign="top" rowspan="1" colspan="1">20</td>
<td align="left" valign="top" rowspan="1" colspan="1">60</td>
<td align="left" valign="top" rowspan="1" colspan="1">20</td>
<td align="left" valign="top" rowspan="1" colspan="1">51</td>
<td align="left" valign="top" rowspan="1" colspan="1">55</td>
<td align="left" valign="top" rowspan="1" colspan="1">NR</td>
</tr>
<tr>
<td align="left" valign="top" rowspan="1" colspan="1">Sweeting
<italic>et al</italic>
. [
<xref rid="ref96" ref-type="bibr">96</xref>
] 2013</td>
<td align="left" valign="top" rowspan="1" colspan="1">18
<break></break>
Recurrent-28%, GTR-100%</td>
<td align="left" valign="top" rowspan="1" colspan="1">Retrospective cohort</td>
<td align="left" valign="top" rowspan="1" colspan="1">IOERT</td>
<td align="left" valign="top" rowspan="1" colspan="1">10–20</td>
<td align="left" valign="top" rowspan="1" colspan="1">94</td>
<td align="left" valign="top" rowspan="1" colspan="1">43</td>
<td align="left" valign="top" rowspan="1" colspan="1">64</td>
<td align="left" valign="top" rowspan="1" colspan="1">72</td>
<td align="left" valign="top" rowspan="1" colspan="1">NR</td>
</tr>
<tr>
<td align="left" valign="top" rowspan="1" colspan="1">Roeder
<italic>et al</italic>
. [
<xref rid="ref97" ref-type="bibr">97</xref>
] 2014</td>
<td align="left" valign="top" rowspan="1" colspan="1">27
<break></break>
Recurrent-15%, GTR-100%</td>
<td align="left" valign="top" rowspan="1" colspan="1">Prospective cohort</td>
<td align="left" valign="top" rowspan="1" colspan="1">IOERT</td>
<td align="left" valign="top" rowspan="1" colspan="1">10–20</td>
<td align="left" valign="top" rowspan="1" colspan="1">100</td>
<td align="left" valign="top" rowspan="1" colspan="1">33</td>
<td align="left" valign="top" rowspan="1" colspan="1">72</td>
<td align="left" valign="top" rowspan="1" colspan="1">74</td>
<td align="left" valign="top" rowspan="1" colspan="1">Total-6% late toxicity</td>
</tr>
<tr>
<td align="left" valign="top" rowspan="1" colspan="1">Stucky
<italic>et al</italic>
. [
<xref rid="ref98" ref-type="bibr">98</xref>
] 2014</td>
<td align="left" valign="top" rowspan="1" colspan="1">63
<break></break>
IORT-37
<break></break>
Sx only-26
<break></break>
Recurrent-36%,GTR-89%</td>
<td align="left" valign="top" rowspan="1" colspan="1">Retrospective cohort</td>
<td align="left" valign="top" rowspan="1" colspan="1">IOERT</td>
<td align="left" valign="top" rowspan="1" colspan="1">10–20</td>
<td align="left" valign="top" rowspan="1" colspan="1">
<break></break>
100
<break></break>
0</td>
<td align="left" valign="top" rowspan="1" colspan="1">45</td>
<td align="left" valign="top" rowspan="1" colspan="1">
<break></break>
IORT-89
<break></break>
Sx-46
<break></break>
<italic>p</italic>
= 0.03</td>
<td align="left" valign="top" rowspan="1" colspan="1">
<break></break>
IORT-60
<break></break>
No IORT-60</td>
<td align="left" valign="top" rowspan="1" colspan="1">Ureteral stricture-1
<break></break>
No grade-3 neuropathy</td>
</tr>
<tr>
<td align="left" valign="top" rowspan="1" colspan="1">Gronchi
<italic>et al</italic>
. [
<xref rid="ref99" ref-type="bibr">99</xref>
] 2014</td>
<td align="left" valign="top" rowspan="1" colspan="1">83
<break></break>
IORT-14pts only
<break></break>
Recurrent-24%
<break></break>
GTR-84%</td>
<td align="left" valign="top" rowspan="1" colspan="1">Prospective cohort</td>
<td align="left" valign="top" rowspan="1" colspan="1">IOERT</td>
<td align="left" valign="top" rowspan="1" colspan="1">10–12</td>
<td align="left" valign="top" rowspan="1" colspan="1">88</td>
<td align="left" valign="top" rowspan="1" colspan="1">58</td>
<td align="left" valign="top" rowspan="1" colspan="1">63</td>
<td align="left" valign="top" rowspan="1" colspan="1">59</td>
<td align="left" valign="top" rowspan="1" colspan="1">NR</td>
</tr>
</tbody>
</table>
<table-wrap-foot>
<p>RCT: randomised control trial, PORT: post-operative RT, Sx: surgery, LC: local control, OS: overall survival, DFS: disease-free survival, NR: not reported,</p>
<fn id="table6-fn1">
<label>*</label>
<p>Number of patients</p>
</fn>
<fn id="table6-fn2">
<label>
<sup>¥</sup>
</label>
<p>In GTR patients,</p>
</fn>
<p>α-crude rate</p>
</table-wrap-foot>
</table-wrap>
<table-wrap id="table7" position="float">
<label>Table 7.</label>
<caption>
<title>Studies of IORT in various paediatric tumours.</title>
</caption>
<table frame="border" rules="all">
<thead>
<tr>
<th align="center" valign="top" rowspan="1" colspan="1">Author/Year</th>
<th align="center" valign="top" rowspan="1" colspan="1">Sample size</th>
<th align="center" valign="top" rowspan="1" colspan="1">Study design</th>
<th align="center" valign="top" rowspan="1" colspan="1">IORT type</th>
<th align="center" valign="top" rowspan="1" colspan="1">IORT dose (Gy)</th>
<th align="center" valign="top" rowspan="1" colspan="1">EBRT %</th>
<th align="center" valign="top" rowspan="1" colspan="1">Median Follow-up</th>
<th align="center" valign="top" rowspan="1" colspan="1">LC 5 year (%)</th>
<th align="center" valign="top" rowspan="1" colspan="1">OS 5 year (%)</th>
<th align="center" valign="top" rowspan="1" colspan="1">Toxicity grade 3 or ></th>
</tr>
</thead>
<tbody>
<tr>
<td align="left" valign="top" rowspan="1" colspan="1">Haase
<italic>et al</italic>
[
<xref rid="ref102" ref-type="bibr">102</xref>
] 1994</td>
<td align="left" valign="top" rowspan="1" colspan="1">25 (neuroblastoma)</td>
<td align="left" valign="top" rowspan="1" colspan="1">Prospective, single arm</td>
<td align="left" valign="top" rowspan="1" colspan="1">IOERT</td>
<td align="left" valign="top" rowspan="1" colspan="1">10–17</td>
<td align="left" valign="top" rowspan="1" colspan="1">NR</td>
<td align="left" valign="top" rowspan="1" colspan="1">51 (mean)</td>
<td align="left" valign="top" rowspan="1" colspan="1">75</td>
<td align="left" valign="top" rowspan="1" colspan="1">63</td>
<td align="left" valign="top" rowspan="1" colspan="1">No late effects at 5-year follow-up</td>
</tr>
<tr>
<td align="left" valign="top" rowspan="1" colspan="1">Nag
<italic>et al</italic>
[
<xref rid="ref106" ref-type="bibr">106</xref>
] 2003</td>
<td align="left" valign="top" rowspan="1" colspan="1">13 (5 metastatic)</td>
<td align="left" valign="top" rowspan="1" colspan="1">Retrospective</td>
<td align="left" valign="top" rowspan="1" colspan="1">IOERT</td>
<td align="left" valign="top" rowspan="1" colspan="1">10–15</td>
<td align="left" valign="top" rowspan="1" colspan="1">38</td>
<td align="left" valign="top" rowspan="1" colspan="1">42</td>
<td align="left" valign="top" rowspan="1" colspan="1">72
<break></break>
(3yr)</td>
<td align="left" valign="top" rowspan="1" colspan="1">31
<break></break>
(3yr)</td>
<td align="left" valign="top" rowspan="1" colspan="1">late morbidity-30%</td>
</tr>
<tr>
<td align="left" valign="top" rowspan="1" colspan="1">Goodman
<italic>et al</italic>
[
<xref rid="ref104" ref-type="bibr">104</xref>
] 2003</td>
<td align="left" valign="top" rowspan="1" colspan="1">66 (35% recurrent)</td>
<td align="left" valign="top" rowspan="1" colspan="1">Retrospective</td>
<td align="left" valign="top" rowspan="1" colspan="1">HDR-IORT</td>
<td align="left" valign="top" rowspan="1" colspan="1">12–15</td>
<td align="left" valign="top" rowspan="1" colspan="1">44</td>
<td align="left" valign="top" rowspan="1" colspan="1">12</td>
<td align="left" valign="top" rowspan="1" colspan="1">56
<break></break>
(2yr)</td>
<td align="left" valign="top" rowspan="1" colspan="1">54
<break></break>
(2yr)</td>
<td align="left" valign="top" rowspan="1" colspan="1">Late morbidity-12%</td>
</tr>
<tr>
<td align="left" valign="top" rowspan="1" colspan="1">Oertel
<italic>et al</italic>
<break></break>
[
<xref rid="ref103" ref-type="bibr">103</xref>
] 2005</td>
<td align="left" valign="top" rowspan="1" colspan="1">18 (17% recurrent)</td>
<td align="left" valign="top" rowspan="1" colspan="1">Retrospective</td>
<td align="left" valign="top" rowspan="1" colspan="1">IOERT</td>
<td align="left" valign="top" rowspan="1" colspan="1">8–15</td>
<td align="left" valign="top" rowspan="1" colspan="1">100</td>
<td align="left" valign="top" rowspan="1" colspan="1">54.5</td>
<td align="left" valign="top" rowspan="1" colspan="1">95
<break></break>
(3yr)</td>
<td align="left" valign="top" rowspan="1" colspan="1">83
<break></break>
(3yr)</td>
<td align="left" valign="top" rowspan="1" colspan="1">late morbidity-33%
<break></break>
Loss of Limb-1
<xref ref-type="table-fn" rid="table7-fn1">
<sup>*</sup>
</xref>
<break></break>
Neuropathy-1
<xref ref-type="table-fn" rid="table7-fn1">
<sup>*</sup>
</xref>
</td>
</tr>
<tr>
<td align="left" valign="top" rowspan="1" colspan="1">Stauder
<italic>et al</italic>
[
<xref rid="ref107" ref-type="bibr">107</xref>
] 2011</td>
<td align="left" valign="top" rowspan="1" colspan="1">20</td>
<td align="left" valign="top" rowspan="1" colspan="1">Retrospective</td>
<td align="left" valign="top" rowspan="1" colspan="1">IOERT</td>
<td align="left" valign="top" rowspan="1" colspan="1">7.5–25</td>
<td align="left" valign="top" rowspan="1" colspan="1">100</td>
<td align="left" valign="top" rowspan="1" colspan="1">139</td>
<td align="left" valign="top" rowspan="1" colspan="1">77
<break></break>
(10yr)</td>
<td align="left" valign="top" rowspan="1" colspan="1">65
<break></break>
(10yr)</td>
<td align="left" valign="top" rowspan="1" colspan="1">No grade 3 or more late effects or second primary</td>
</tr>
<tr>
<td align="left" valign="top" rowspan="1" colspan="1">Sole
<italic>et al</italic>
[
<xref rid="ref105" ref-type="bibr">105</xref>
] 2015</td>
<td align="left" valign="top" rowspan="1" colspan="1">71 (35% recurrent)</td>
<td align="left" valign="top" rowspan="1" colspan="1">Retrospective</td>
<td align="left" valign="top" rowspan="1" colspan="1">IOERT</td>
<td align="left" valign="top" rowspan="1" colspan="1">7.5–20</td>
<td align="left" valign="top" rowspan="1" colspan="1">100</td>
<td align="left" valign="top" rowspan="1" colspan="1">72</td>
<td align="left" valign="top" rowspan="1" colspan="1">68
<break></break>
(10yr)</td>
<td align="left" valign="top" rowspan="1" colspan="1">74
<break></break>
(10yr)</td>
<td align="left" valign="top" rowspan="1" colspan="1">Late morbidity-13%
<break></break>
Neuropathy-4
<xref ref-type="table-fn" rid="table7-fn1">
<sup>*</sup>
</xref>
<break></break>
Necrosis-2
<xref ref-type="table-fn" rid="table7-fn1">
<sup>*</sup>
</xref>
<break></break>
Lymphedema-2
<xref ref-type="table-fn" rid="table7-fn1">
<sup>*</sup>
</xref>
</td>
</tr>
</tbody>
</table>
<table-wrap-foot>
<p>LC: local control, OS: overall survival, DFS: disease-free survival, NR: not reported,</p>
<fn id="table7-fn1">
<label>
<sup>*</sup>
</label>
<p>Number of patients.</p>
</fn>
</table-wrap-foot>
</table-wrap>
<table-wrap id="table8" position="float">
<label>Table 8.</label>
<caption>
<title>Studies of IORT in recurrent gynaecological malignancies after gross total resection.</title>
</caption>
<table frame="border" rules="all">
<thead>
<tr>
<th align="center" valign="top" rowspan="1" colspan="1">Author/Year</th>
<th align="center" valign="top" rowspan="1" colspan="1">Sample size</th>
<th align="center" valign="top" rowspan="1" colspan="1">Site</th>
<th align="center" valign="top" rowspan="1" colspan="1">Primary/Recurrent</th>
<th align="center" valign="top" rowspan="1" colspan="1">IORT type</th>
<th align="center" valign="top" rowspan="1" colspan="1">IORT dose (Gy)</th>
<th align="center" valign="top" rowspan="1" colspan="1">Prior EBRT %</th>
<th align="center" valign="top" rowspan="1" colspan="1">Present EBRT %</th>
<th align="center" valign="top" rowspan="1" colspan="1">Median follow-up</th>
<th align="center" valign="top" rowspan="1" colspan="1">LC 5yr (%)</th>
<th align="center" valign="top" rowspan="1" colspan="1">OS 5yr (%)</th>
<th align="center" valign="top" rowspan="1" colspan="1">Toxicity grade 3 or ></th>
</tr>
</thead>
<tbody>
<tr>
<td align="left" valign="top" rowspan="1" colspan="1">Haddock
<italic>et al</italic>
. [
<xref rid="ref113" ref-type="bibr">113</xref>
,
<xref rid="ref115" ref-type="bibr">115</xref>
] 1996</td>
<td align="left" valign="top" rowspan="1" colspan="1">63</td>
<td align="left" valign="top" rowspan="1" colspan="1">Cervix-40
<break></break>
Endometrium-16
<break></break>
Others-8</td>
<td align="left" valign="top" rowspan="1" colspan="1">Primary-16%
<break></break>
Recurrent-84%</td>
<td align="left" valign="top" rowspan="1" colspan="1">IOERT</td>
<td align="left" valign="top" rowspan="1" colspan="1">8–25</td>
<td align="left" valign="top" rowspan="1" colspan="1">0
<break></break>
70</td>
<td align="left" valign="top" rowspan="1" colspan="1">100
<break></break>
63</td>
<td align="left" valign="top" rowspan="1" colspan="1">NR</td>
<td align="left" valign="top" rowspan="1" colspan="1">61</td>
<td align="left" valign="top" rowspan="1" colspan="1">27</td>
<td align="left" valign="top" rowspan="1" colspan="1">Total-17%
<break></break>
GI-5
<xref ref-type="table-fn" rid="table8-fn1">
<sup>*</sup>
</xref>
<break></break>
Neuropathy-2
<xref ref-type="table-fn" rid="table8-fn1">
<sup>*</sup>
</xref>
</td>
</tr>
<tr>
<td align="left" valign="top" rowspan="1" colspan="1">Mahe
<italic>et al</italic>
. [
<xref rid="ref124" ref-type="bibr">124</xref>
,
<xref rid="ref125" ref-type="bibr">125</xref>
] 1996</td>
<td align="left" valign="top" rowspan="1" colspan="1">70</td>
<td align="left" valign="top" rowspan="1" colspan="1">Cervix</td>
<td align="left" valign="top" rowspan="1" colspan="1">Recurrent-100%</td>
<td align="left" valign="top" rowspan="1" colspan="1">IOERT
<break></break>
X ray IORT</td>
<td align="left" valign="top" rowspan="1" colspan="1">10–30</td>
<td align="left" valign="top" rowspan="1" colspan="1">97</td>
<td align="left" valign="top" rowspan="1" colspan="1">42</td>
<td align="left" valign="top" rowspan="1" colspan="1">15</td>
<td align="left" valign="top" rowspan="1" colspan="1">21 (3yr)</td>
<td align="left" valign="top" rowspan="1" colspan="1">8 (3yr)</td>
<td align="left" valign="top" rowspan="1" colspan="1">Total-14%Neuropathy-5
<xref ref-type="table-fn" rid="table8-fn1">
<sup>*</sup>
</xref>
<break></break>
Ureteral obstruction-4
<xref ref-type="table-fn" rid="table8-fn1">
<sup>*</sup>
</xref>
</td>
</tr>
<tr>
<td align="left" valign="top" rowspan="1" colspan="1">Del carmen
<italic>et al</italic>
. [
<xref rid="ref126" ref-type="bibr">126</xref>
] 2000</td>
<td align="left" valign="top" rowspan="1" colspan="1">15</td>
<td align="left" valign="top" rowspan="1" colspan="1">Cervix-5Endometrium-3
<break></break>
Vagina-7</td>
<td align="left" valign="top" rowspan="1" colspan="1">Recurrent-93%</td>
<td align="left" valign="top" rowspan="1" colspan="1">IOERT</td>
<td align="left" valign="top" rowspan="1" colspan="1">10–22.5</td>
<td align="left" valign="top" rowspan="1" colspan="1">60</td>
<td align="left" valign="top" rowspan="1" colspan="1">6</td>
<td align="left" valign="top" rowspan="1" colspan="1">NR</td>
<td align="left" valign="top" rowspan="1" colspan="1">NR</td>
<td align="left" valign="top" rowspan="1" colspan="1">74</td>
<td align="left" valign="top" rowspan="1" colspan="1">Neuropathy-4
<xref ref-type="table-fn" rid="table8-fn1">
<sup>*</sup>
</xref>
<break></break>
GU-3
<xref ref-type="table-fn" rid="table8-fn1">
<sup>*</sup>
</xref>
<break></break>
Lymphedema-2
<xref ref-type="table-fn" rid="table8-fn1">
<sup>*</sup>
</xref>
</td>
</tr>
<tr>
<td align="left" valign="top" rowspan="1" colspan="1">Martinez-monge
<italic>et al</italic>
.[
<xref rid="ref116" ref-type="bibr">116</xref>
] 2001</td>
<td align="left" valign="top" rowspan="1" colspan="1">67</td>
<td align="left" valign="top" rowspan="1" colspan="1">Cervix</td>
<td align="left" valign="top" rowspan="1" colspan="1">Primary-46%
<break></break>
Recurrent-54%</td>
<td align="left" valign="top" rowspan="1" colspan="1">IOERT</td>
<td align="left" valign="top" rowspan="1" colspan="1">10–25
<break></break>
10–20</td>
<td align="left" valign="top" rowspan="1" colspan="1">
<break></break>
86</td>
<td align="left" valign="top" rowspan="1" colspan="1">97
<break></break>
14</td>
<td align="left" valign="top" rowspan="1" colspan="1">58
<break></break>
19</td>
<td align="left" valign="top" rowspan="1" colspan="1">80.5
<break></break>
49</td>
<td align="left" valign="top" rowspan="1" colspan="1">58 (10yr)
<break></break>
14 (10yr)</td>
<td align="left" valign="top" rowspan="1" colspan="1">Total-14.9%
<break></break>
Neuropathy-1
<xref ref-type="table-fn" rid="table8-fn1">
<sup>*</sup>
</xref>
<break></break>
Chronic pain-8
<xref ref-type="table-fn" rid="table8-fn1">
<sup>*</sup>
</xref>
</td>
</tr>
<tr>
<td align="left" valign="top" rowspan="1" colspan="1">Gemignani
<italic>et al</italic>
. [
<xref rid="ref114" ref-type="bibr">114</xref>
] 2001</td>
<td align="left" valign="top" rowspan="1" colspan="1">17</td>
<td align="left" valign="top" rowspan="1" colspan="1">Cervix-9
<break></break>
Endometrium-7
<break></break>
Vagina-1</td>
<td align="left" valign="top" rowspan="1" colspan="1">Recurrent-
<break></break>
100%</td>
<td align="left" valign="top" rowspan="1" colspan="1">HDR-IORT</td>
<td align="left" valign="top" rowspan="1" colspan="1">12–15</td>
<td align="left" valign="top" rowspan="1" colspan="1">82</td>
<td align="left" valign="top" rowspan="1" colspan="1">12</td>
<td align="left" valign="top" rowspan="1" colspan="1">20</td>
<td align="left" valign="top" rowspan="1" colspan="1">67 (3yr)</td>
<td align="left" valign="top" rowspan="1" colspan="1">54 (3yr)</td>
<td align="left" valign="top" rowspan="1" colspan="1">GI-4
<xref ref-type="table-fn" rid="table8-fn1">
<sup>*</sup>
</xref>
<break></break>
Neuropathy-3
<xref ref-type="table-fn" rid="table8-fn1">
<sup>*</sup>
</xref>
<break></break>
Wound-4
<xref ref-type="table-fn" rid="table8-fn1">
<sup>*</sup>
</xref>
</td>
</tr>
<tr>
<td align="left" valign="top" rowspan="1" colspan="1">Dowdy
<italic>et al</italic>
. [
<xref rid="ref126" ref-type="bibr">126</xref>
] 2006</td>
<td align="left" valign="top" rowspan="1" colspan="1">25</td>
<td align="left" valign="top" rowspan="1" colspan="1">Endometrium</td>
<td align="left" valign="top" rowspan="1" colspan="1">Recurrent-
<break></break>
100%</td>
<td align="left" valign="top" rowspan="1" colspan="1">IOERT</td>
<td align="left" valign="top" rowspan="1" colspan="1">10–25</td>
<td align="left" valign="top" rowspan="1" colspan="1">56</td>
<td align="left" valign="top" rowspan="1" colspan="1">84</td>
<td align="left" valign="top" rowspan="1" colspan="1">34</td>
<td align="left" valign="top" rowspan="1" colspan="1">84</td>
<td align="left" valign="top" rowspan="1" colspan="1">
<italic>R</italic>
0-71
<break></break>
<italic>R</italic>
1-47
<break></break>
<italic>R</italic>
2-0</td>
<td align="left" valign="top" rowspan="1" colspan="1">Neuropathy-8
<xref ref-type="table-fn" rid="table8-fn1">
<sup>*</sup>
</xref>
<break></break>
GU-5
<xref ref-type="table-fn" rid="table8-fn1">
<sup>*</sup>
</xref>
<break></break>
Fitula-5
<xref ref-type="table-fn" rid="table8-fn1">
<sup>*</sup>
</xref>
</td>
</tr>
<tr>
<td align="left" valign="top" rowspan="1" colspan="1">Tran
<italic>et al</italic>
. [
<xref rid="ref118" ref-type="bibr">118</xref>
]
<break></break>
2007</td>
<td align="left" valign="top" rowspan="1" colspan="1">36</td>
<td align="left" valign="top" rowspan="1" colspan="1">Cervix-17
<break></break>
Endometrium-11
<break></break>
Others-8</td>
<td align="left" valign="top" rowspan="1" colspan="1">Recurrent-89%</td>
<td align="left" valign="top" rowspan="1" colspan="1">X-ray IORT</td>
<td align="left" valign="top" rowspan="1" colspan="1">6–17.5</td>
<td align="left" valign="top" rowspan="1" colspan="1">72</td>
<td align="left" valign="top" rowspan="1" colspan="1">53</td>
<td align="left" valign="top" rowspan="1" colspan="1">50</td>
<td align="left" valign="top" rowspan="1" colspan="1">44</td>
<td align="left" valign="top" rowspan="1" colspan="1">47</td>
<td align="left" valign="top" rowspan="1" colspan="1">Total-27%
<break></break>
Wound-4
<xref ref-type="table-fn" rid="table8-fn1">
<sup>*</sup>
</xref>
<break></break>
GI-1
<xref ref-type="table-fn" rid="table8-fn1">
<sup>*</sup>
</xref>
</td>
</tr>
<tr>
<td align="left" valign="top" rowspan="1" colspan="1">Barney
<italic>et al</italic>
[
<xref rid="ref119" ref-type="bibr">119</xref>
].2013</td>
<td align="left" valign="top" rowspan="1" colspan="1">86</td>
<td align="left" valign="top" rowspan="1" colspan="1">Cervix-100</td>
<td align="left" valign="top" rowspan="1" colspan="1">Recurrent-85%</td>
<td align="left" valign="top" rowspan="1" colspan="1">IOERT</td>
<td align="left" valign="top" rowspan="1" colspan="1">6–25</td>
<td align="left" valign="top" rowspan="1" colspan="1">81</td>
<td align="left" valign="top" rowspan="1" colspan="1">71</td>
<td align="left" valign="top" rowspan="1" colspan="1">32</td>
<td align="left" valign="top" rowspan="1" colspan="1">Primary-70
<break></break>
Recurrent-61%
<break></break>
(3yr)</td>
<td align="left" valign="top" rowspan="1" colspan="1">25
<break></break>
(3yr)</td>
<td align="left" valign="top" rowspan="1" colspan="1">GI-4
<xref ref-type="table-fn" rid="table8-fn1">
<sup>*</sup>
</xref>
<break></break>
GU-4
<xref ref-type="table-fn" rid="table8-fn1">
<sup>*</sup>
</xref>
<break></break>
Neuropathy-1
<xref ref-type="table-fn" rid="table8-fn1">
<sup>*</sup>
</xref>
</td>
</tr>
<tr>
<td align="left" valign="top" rowspan="1" colspan="1">Calvo
<italic>et al</italic>
.[
<xref rid="ref120" ref-type="bibr">120</xref>
] 2013</td>
<td align="left" valign="top" rowspan="1" colspan="1">35</td>
<td align="left" valign="top" rowspan="1" colspan="1">Cervix-20 Endometrium-7 Others-8</td>
<td align="left" valign="top" rowspan="1" colspan="1">Recurrent-
<break></break>
100%</td>
<td align="left" valign="top" rowspan="1" colspan="1">IOERT</td>
<td align="left" valign="top" rowspan="1" colspan="1">10–15</td>
<td align="left" valign="top" rowspan="1" colspan="1">71</td>
<td align="left" valign="top" rowspan="1" colspan="1">46</td>
<td align="left" valign="top" rowspan="1" colspan="1">46</td>
<td align="left" valign="top" rowspan="1" colspan="1">58</td>
<td align="left" valign="top" rowspan="1" colspan="1">42</td>
<td align="left" valign="top" rowspan="1" colspan="1">Fistula-5
<xref ref-type="table-fn" rid="table8-fn1">
<sup>*</sup>
</xref>
<break></break>
Ureter stenosi-2
<xref ref-type="table-fn" rid="table8-fn1">
<sup>*</sup>
</xref>
<break></break>
Neuropathy-1
<xref ref-type="table-fn" rid="table8-fn1">
<sup>*</sup>
</xref>
</td>
</tr>
<tr>
<td align="left" valign="top" rowspan="1" colspan="1">Backes
<italic>et al</italic>
.[
<xref rid="ref127" ref-type="bibr">127</xref>
] 2014</td>
<td align="left" valign="top" rowspan="1" colspan="1">32</td>
<td align="left" valign="top" rowspan="1" colspan="1">Cervix-21
<break></break>
Others-11
<break></break>
IORT in 66% only</td>
<td align="left" valign="top" rowspan="1" colspan="1">Recurrent-
<break></break>
100%</td>
<td align="left" valign="top" rowspan="1" colspan="1">IOERT/HDR-IORT</td>
<td align="left" valign="top" rowspan="1" colspan="1">10–20</td>
<td align="left" valign="top" rowspan="1" colspan="1">100</td>
<td align="left" valign="top" rowspan="1" colspan="1">0</td>
<td align="left" valign="top" rowspan="1" colspan="1">NR</td>
<td align="left" valign="top" rowspan="1" colspan="1">PE+IORT-10Mon
<break></break>
LEER+IORT-9Mon
<break></break>
PE-33Mon</td>
<td align="left" valign="top" rowspan="1" colspan="1">PE+IORT-10Mon
<break></break>
LEER+IORT-10Mon
<break></break>
PE-41Mon</td>
<td align="left" valign="top" rowspan="1" colspan="1">NR</td>
</tr>
<tr>
<td align="left" valign="top" rowspan="1" colspan="1">Foley
<italic>et al</italic>
.[
<xref rid="ref121" ref-type="bibr">121</xref>
] 2014</td>
<td align="left" valign="top" rowspan="1" colspan="1">32</td>
<td align="left" valign="top" rowspan="1" colspan="1">Cervix-21
<break></break>
Endometrium-6
<break></break>
Others-5</td>
<td align="left" valign="top" rowspan="1" colspan="1">Rccurent-81%</td>
<td align="left" valign="top" rowspan="1" colspan="1">IOERT</td>
<td align="left" valign="top" rowspan="1" colspan="1">10–22.5</td>
<td align="left" valign="top" rowspan="1" colspan="1">88</td>
<td align="left" valign="top" rowspan="1" colspan="1">20</td>
<td align="left" valign="top" rowspan="1" colspan="1">26</td>
<td align="left" valign="top" rowspan="1" colspan="1">
<italic>R</italic>
1-73
<break></break>
<italic>R</italic>
2-71</td>
<td align="left" valign="top" rowspan="1" colspan="1">
<italic>R</italic>
1-77
<break></break>
<italic>R</italic>
2-55
<italic>p</italic>
= 0.001</td>
<td align="left" valign="top" rowspan="1" colspan="1">Total-47%
<break></break>
GU-2
<break></break>
Lymphedema-2</td>
</tr>
<tr>
<td align="left" valign="top" rowspan="1" colspan="1">Sole
<italic>et al</italic>
. [
<xref rid="ref117" ref-type="bibr">117</xref>
] 2014</td>
<td align="left" valign="top" rowspan="1" colspan="1">61</td>
<td align="left" valign="top" rowspan="1" colspan="1">Cervix-18
<break></break>
Endometrium-32
<break></break>
Ovarian-9
<break></break>
Vagina-2</td>
<td align="left" valign="top" rowspan="1" colspan="1">Recurrent
<break></break>
Pelvic-57%
<break></break>
Para-aortic-
<break></break>
43%</td>
<td align="left" valign="top" rowspan="1" colspan="1">IOERT</td>
<td align="left" valign="top" rowspan="1" colspan="1">10–15</td>
<td align="left" valign="top" rowspan="1" colspan="1">66</td>
<td align="left" valign="top" rowspan="1" colspan="1">48</td>
<td align="left" valign="top" rowspan="1" colspan="1">42</td>
<td align="left" valign="top" rowspan="1" colspan="1">65</td>
<td align="left" valign="top" rowspan="1" colspan="1">45</td>
<td align="left" valign="top" rowspan="1" colspan="1">Total-20%
<break></break>
Fistula-5
<xref ref-type="table-fn" rid="table8-fn1">
<sup>*</sup>
</xref>
<break></break>
Neuropathy-1
<xref ref-type="table-fn" rid="table8-fn1">
<sup>*</sup>
</xref>
<break></break>
Wound-3
<xref ref-type="table-fn" rid="table8-fn1">
<sup>*</sup>
</xref>
</td>
</tr>
<tr>
<td align="left" valign="top" rowspan="1" colspan="1">Arians
<italic>et al</italic>
.[
<xref rid="ref122" ref-type="bibr">122</xref>
] 2016</td>
<td align="left" valign="top" rowspan="1" colspan="1">36</td>
<td align="left" valign="top" rowspan="1" colspan="1">Cervix-18
<break></break>
Endometrium-12
<break></break>
Vulva-6</td>
<td align="left" valign="top" rowspan="1" colspan="1">Recurrent-
<break></break>
100%</td>
<td align="left" valign="top" rowspan="1" colspan="1">IOERT</td>
<td align="left" valign="top" rowspan="1" colspan="1">10–18</td>
<td align="left" valign="top" rowspan="1" colspan="1">76
<break></break>
25
<break></break>
100</td>
<td align="left" valign="top" rowspan="1" colspan="1">11
<break></break>
17
<break></break>
17</td>
<td align="left" valign="top" rowspan="1" colspan="1">14</td>
<td align="left" valign="top" rowspan="1" colspan="1">Cervix-0
<break></break>
Endometrium-40
<break></break>
Vulva-20
<break></break>
<italic>p</italic>
= 0.017</td>
<td align="left" valign="top" rowspan="1" colspan="1">Cervix-6
<break></break>
Endometrium-50
<break></break>
Vulva-17
<break></break>
<italic>P</italic>
= 0.038</td>
<td align="left" valign="top" rowspan="1" colspan="1">Wound complications-5
<xref ref-type="table-fn" rid="table8-fn1">
<sup>*</sup>
</xref>
<break></break>
Neuropathy-4
<xref ref-type="table-fn" rid="table8-fn1">
<sup>*</sup>
</xref>
<break></break>
Lymphedema-3
<xref ref-type="table-fn" rid="table8-fn1">
<sup>*</sup>
</xref>
</td>
</tr>
</tbody>
</table>
<table-wrap-foot>
<p>Sx: surgery, LC: local control, OS: overall survival, NR: not reported,</p>
<fn id="table8-fn1">
<label>
<sup>*</sup>
</label>
<p>Number of patients</p>
</fn>
<p>PE: pelvic exenteration, LEER: laterally extended endopelvic resection, Mon: median survival in months.</p>
</table-wrap-foot>
</table-wrap>
<table-wrap id="table9" position="float">
<label>Table 9.</label>
<caption>
<title>Studies of IORT in bladder and renal cancers.</title>
</caption>
<table frame="border" rules="all">
<thead>
<tr>
<th align="center" valign="top" rowspan="1" colspan="1">Author/Year</th>
<th align="center" valign="top" rowspan="1" colspan="1">Sample size</th>
<th align="center" valign="top" rowspan="1" colspan="1">Study design</th>
<th align="center" valign="top" rowspan="1" colspan="1">IORT type</th>
<th align="center" valign="top" rowspan="1" colspan="1">IORT dose (Gy)</th>
<th align="center" valign="top" rowspan="1" colspan="1">Prior EBRT %</th>
<th align="center" valign="top" rowspan="1" colspan="1">Present EBRT %</th>
<th align="center" valign="top" rowspan="1" colspan="1">Median follow-up months</th>
<th align="center" valign="top" rowspan="1" colspan="1">LC 5 year %</th>
<th align="center" valign="top" rowspan="1" colspan="1">OS 5 year %</th>
<th align="center" valign="top" rowspan="1" colspan="1">Toxicity grade 3 or ></th>
</tr>
</thead>
<tbody>
<tr>
<td align="left" valign="top" rowspan="1" colspan="1">Hallemeier
<italic>et al</italic>
. [
<xref rid="ref128" ref-type="bibr">128</xref>
] 2013</td>
<td align="left" valign="top" rowspan="1" colspan="1">Bladder-13, Ureter-4
<break></break>
Recurrent-88%</td>
<td align="left" valign="top" rowspan="1" colspan="1">Retrospective cohort</td>
<td align="left" valign="top" rowspan="1" colspan="1">IOERT</td>
<td align="left" valign="top" rowspan="1" colspan="1">10–20</td>
<td align="left" valign="top" rowspan="1" colspan="1">24</td>
<td align="left" valign="top" rowspan="1" colspan="1">94</td>
<td align="left" valign="top" rowspan="1" colspan="1">43.2
<break></break>
In survivors</td>
<td align="left" valign="top" rowspan="1" colspan="1">51
<break></break>
(2 yr)</td>
<td align="left" valign="top" rowspan="1" colspan="1">16 (5 yr)
<break></break>
<italic>R</italic>
0+
<italic>R</italic>
1: 56
<break></break>
<italic>R</italic>
2-11
<break></break>
<italic>p</italic>
= 0.03 (2 yr)</td>
<td align="left" valign="top" rowspan="1" colspan="1">Total-12%
<break></break>
Ureter stricture-4
<break></break>
Fistula-1</td>
</tr>
<tr>
<td align="left" valign="top" rowspan="1" colspan="1">Paly
<italic>et al</italic>
. [
<xref rid="ref134" ref-type="bibr">134</xref>
] 2014</td>
<td align="left" valign="top" rowspan="1" colspan="1">98-RCC
<break></break>
Recurrent-72%</td>
<td align="left" valign="top" rowspan="1" colspan="1">Retrospective</td>
<td align="left" valign="top" rowspan="1" colspan="1">IOERT</td>
<td align="left" valign="top" rowspan="1" colspan="1">9.5–20</td>
<td align="left" valign="top" rowspan="1" colspan="1"></td>
<td align="left" valign="top" rowspan="1" colspan="1">63</td>
<td align="left" valign="top" rowspan="1" colspan="1">42
<break></break>
In survivors</td>
<td align="left" valign="top" rowspan="1" colspan="1">76</td>
<td align="left" valign="top" rowspan="1" colspan="1">Advanced-37
<break></break>
Recurrent-55</td>
<td align="left" valign="top" rowspan="1" colspan="1">Total-5%
<break></break>
Pancreatic leak-3
<xref ref-type="table-fn" rid="table9-fn1">
<sup>*</sup>
</xref>
<break></break>
gastritis-1
<xref ref-type="table-fn" rid="table9-fn1">
<sup>*</sup>
</xref>
<break></break>
ARDS-1
<xref ref-type="table-fn" rid="table9-fn1">
<sup>*</sup>
</xref>
</td>
</tr>
<tr>
<td align="left" valign="top" rowspan="1" colspan="1">Calvo
<italic>et al</italic>
. [
<xref rid="ref130" ref-type="bibr">130</xref>
] 2013</td>
<td align="left" valign="top" rowspan="1" colspan="1">25-RCC
<break></break>
Recurrent-40%</td>
<td align="left" valign="top" rowspan="1" colspan="1">Retrospective</td>
<td align="left" valign="top" rowspan="1" colspan="1">IOERT</td>
<td align="left" valign="top" rowspan="1" colspan="1">9–15</td>
<td align="left" valign="top" rowspan="1" colspan="1">-</td>
<td align="left" valign="top" rowspan="1" colspan="1">60</td>
<td align="left" valign="top" rowspan="1" colspan="1">266</td>
<td align="left" valign="top" rowspan="1" colspan="1">80</td>
<td align="left" valign="top" rowspan="1" colspan="1">38</td>
<td align="left" valign="top" rowspan="1" colspan="1">Total-24%</td>
</tr>
<tr>
<td align="left" valign="top" rowspan="1" colspan="1">Habl
<italic>et al</italic>
. [
<xref rid="ref132" ref-type="bibr">132</xref>
] 2013</td>
<td align="left" valign="top" rowspan="1" colspan="1">17-RCC
<break></break>
Recurrent-100%</td>
<td align="left" valign="top" rowspan="1" colspan="1">Retrospective</td>
<td align="left" valign="top" rowspan="1" colspan="1">IOERT</td>
<td align="left" valign="top" rowspan="1" colspan="1">10–20</td>
<td align="left" valign="top" rowspan="1" colspan="1"></td>
<td align="left" valign="top" rowspan="1" colspan="1">65</td>
<td align="left" valign="top" rowspan="1" colspan="1">18</td>
<td align="left" valign="top" rowspan="1" colspan="1">91 (2 yr)</td>
<td align="left" valign="top" rowspan="1" colspan="1">73
<break></break>
(2 yr)</td>
<td align="left" valign="top" rowspan="1" colspan="1">None</td>
</tr>
<tr>
<td align="left" valign="top" rowspan="1" colspan="1">Hallemeier
<italic>et al</italic>
. [
<xref rid="ref129" ref-type="bibr">129</xref>
] 2012</td>
<td align="left" valign="top" rowspan="1" colspan="1">22-RCC
<break></break>
Recurrent-86%</td>
<td align="left" valign="top" rowspan="1" colspan="1">Retrospective</td>
<td align="left" valign="top" rowspan="1" colspan="1">IOERT</td>
<td align="left" valign="top" rowspan="1" colspan="1">10–20</td>
<td align="left" valign="top" rowspan="1" colspan="1">-</td>
<td align="left" valign="top" rowspan="1" colspan="1">95</td>
<td align="left" valign="top" rowspan="1" colspan="1">119
<break></break>
In survivors</td>
<td align="left" valign="top" rowspan="1" colspan="1">73</td>
<td align="left" valign="top" rowspan="1" colspan="1">40
<break></break>
<italic>R</italic>
0-80
<break></break>
<italic>R</italic>
1-29
<break></break>
<italic>p</italic>
= 0.057</td>
<td align="left" valign="top" rowspan="1" colspan="1">Total-23%
<break></break>
ARDS-1
<xref ref-type="table-fn" rid="table9-fn1">
<sup>*</sup>
</xref>
Pancreatic pseudocyst-1
<xref ref-type="table-fn" rid="table9-fn1">
<sup>*</sup>
</xref>
<break></break>
Perforated ulcer-2
<xref ref-type="table-fn" rid="table9-fn1">
<sup>*</sup>
</xref>
</td>
</tr>
<tr>
<td align="left" valign="top" rowspan="1" colspan="1">Master
<italic>et al</italic>
. [
<xref rid="ref133" ref-type="bibr">133</xref>
] 2005</td>
<td align="left" valign="top" rowspan="1" colspan="1">14-RCC
<break></break>
Recurrent-100%</td>
<td align="left" valign="top" rowspan="1" colspan="1">Retrospective</td>
<td align="left" valign="top" rowspan="1" colspan="1">IOERT</td>
<td align="left" valign="top" rowspan="1" colspan="1">12–20</td>
<td align="left" valign="top" rowspan="1" colspan="1"></td>
<td align="left" valign="top" rowspan="1" colspan="1">NR</td>
<td align="left" valign="top" rowspan="1" colspan="1">66
<break></break>
(mean in survivors)</td>
<td align="left" valign="top" rowspan="1" colspan="1">85
<break></break>
(crude rate)</td>
<td align="left" valign="top" rowspan="1" colspan="1">30</td>
<td align="left" valign="top" rowspan="1" colspan="1">NR</td>
</tr>
<tr>
<td align="left" valign="top" rowspan="1" colspan="1">Eble
<italic>et al</italic>
. [
<xref rid="ref131" ref-type="bibr">131</xref>
] 1998</td>
<td align="left" valign="top" rowspan="1" colspan="1">11-RCC
<break></break>
Recurrent-73%</td>
<td align="left" valign="top" rowspan="1" colspan="1">Retrospective</td>
<td align="left" valign="top" rowspan="1" colspan="1">IOERT</td>
<td align="left" valign="top" rowspan="1" colspan="1">15–20</td>
<td align="left" valign="top" rowspan="1" colspan="1">-</td>
<td align="left" valign="top" rowspan="1" colspan="1">100</td>
<td align="left" valign="top" rowspan="1" colspan="1">24</td>
<td align="left" valign="top" rowspan="1" colspan="1">100</td>
<td align="left" valign="top" rowspan="1" colspan="1">47
<break></break>
(4 yr)</td>
<td align="left" valign="top" rowspan="1" colspan="1">Wound-2
<xref ref-type="table-fn" rid="table9-fn1">
<sup>*</sup>
</xref>
<break></break>
None IORT related</td>
</tr>
</tbody>
</table>
<table-wrap-foot>
<p>RCT: randomised control trial, Sx: surgery, LC: local control, OS: overall survival, DFS: disease-free survival, NR:-not reported,</p>
<fn id="table9-fn1">
<label>
<sup>*</sup>
</label>
<p>Number of patients</p>
</fn>
<p>ARDS: acute respiratory distress syndrome.</p>
</table-wrap-foot>
</table-wrap>
<table-wrap id="table10" position="float">
<label>Table 10.</label>
<caption>
<title>IORT studies for prostate cancers.</title>
</caption>
<table frame="border" rules="all">
<thead>
<tr>
<th align="center" valign="top" rowspan="1" colspan="1">Author/Year</th>
<th align="center" valign="top" rowspan="1" colspan="1">Sample size</th>
<th align="center" valign="top" rowspan="1" colspan="1">Study design</th>
<th align="center" valign="top" rowspan="1" colspan="1">IORT type</th>
<th align="center" valign="top" rowspan="1" colspan="1">IORT dose (Gy)</th>
<th align="center" valign="top" rowspan="1" colspan="1">Present EBRT %</th>
<th align="center" valign="top" rowspan="1" colspan="1">Median follow-up months</th>
<th align="center" valign="top" rowspan="1" colspan="1">LC 5 year %</th>
<th align="center" valign="top" rowspan="1" colspan="1">OS 5 year %</th>
<th align="center" valign="top" rowspan="1" colspan="1">Toxicity grade 3 or ></th>
</tr>
</thead>
<tbody>
<tr>
<td align="left" valign="top" rowspan="1" colspan="1">Krengli
<italic>et al</italic>
. [
<xref rid="ref139" ref-type="bibr">139</xref>
] 2010</td>
<td align="left" valign="top" rowspan="1" colspan="1">38 (intermediate–
<break></break>
high-risk Pca,
<break></break>
Margin +ve: 71%)</td>
<td align="left" valign="top" rowspan="1" colspan="1">Prospective</td>
<td align="left" valign="top" rowspan="1" colspan="1">IOERT</td>
<td align="left" valign="top" rowspan="1" colspan="1">10–12</td>
<td align="left" valign="top" rowspan="1" colspan="1">Margin +ve and/or ECE</td>
<td align="left" valign="top" rowspan="1" colspan="1">18.2</td>
<td align="left" valign="top" rowspan="1" colspan="1">NR</td>
<td align="left" valign="top" rowspan="1" colspan="1">NR
<break></break>
</td>
<td align="left" valign="top" rowspan="1" colspan="1">No grade 3
<break></break>
complications</td>
</tr>
<tr>
<td align="left" valign="top" rowspan="1" colspan="1">Rocco
<italic>et al</italic>
. [
<xref rid="ref136" ref-type="bibr">136</xref>
] 2009</td>
<td align="left" valign="top" rowspan="1" colspan="1">IORT-33
<break></break>
(intermediate–
<break></break>
high-risk Pca,
<break></break>
Margin +ve: 24%)
<break></break>
RP-100</td>
<td align="left" valign="top" rowspan="1" colspan="1">Matched pair analysis</td>
<td align="left" valign="top" rowspan="1" colspan="1">IOERT</td>
<td align="left" valign="top" rowspan="1" colspan="1">12</td>
<td align="left" valign="top" rowspan="1" colspan="1">IORT-88
<break></break>
<italic>R</italic>
1, pT4, N+
<break></break>
RP-44</td>
<td align="left" valign="top" rowspan="1" colspan="1">16</td>
<td align="left" valign="top" rowspan="1" colspan="1">IORT-97
<break></break>
RP-86 (bRFS)</td>
<td align="left" valign="top" rowspan="1" colspan="1">100
<break></break>
( 2yr)</td>
<td align="left" valign="top" rowspan="1" colspan="1">Acute grade ≥ 2
<break></break>
IORT vs. RP
<break></break>
GU-7% vs. 5%
<break></break>
GI-3% vs. 4%
<break></break>
Lategrade ≥ 2
<break></break>
IORT vs. RP
<break></break>
GU-3% vs. 1%
<break></break>
GI-0% vs. 1%</td>
</tr>
<tr>
<td align="left" valign="top" rowspan="1" colspan="1">Saracino
<italic>et al</italic>
[
<xref rid="ref141" ref-type="bibr">141</xref>
] 2007</td>
<td align="left" valign="top" rowspan="1" colspan="1">34
<break></break>
(intermediate-risk Pca, Margin +ve: 41%)</td>
<td align="left" valign="top" rowspan="1" colspan="1">Prospective</td>
<td align="left" valign="top" rowspan="1" colspan="1">IOERT</td>
<td align="left" valign="top" rowspan="1" colspan="1">16–22</td>
<td align="left" valign="top" rowspan="1" colspan="1">None</td>
<td align="left" valign="top" rowspan="1" colspan="1">41</td>
<td align="left" valign="top" rowspan="1" colspan="1">77.3
<break></break>
(3-yr bRFS)</td>
<td align="left" valign="top" rowspan="1" colspan="1">71
<break></break>
(3-yr)</td>
<td align="left" valign="top" rowspan="1" colspan="1">None</td>
</tr>
<tr>
<td align="left" valign="top" rowspan="1" colspan="1">Orrechia
<italic>et al</italic>
. [
<xref rid="ref140" ref-type="bibr">140</xref>
] 2007</td>
<td align="left" valign="top" rowspan="1" colspan="1">11
<break></break>
(high-risk Pca)</td>
<td align="left" valign="top" rowspan="1" colspan="1">Prospective</td>
<td align="left" valign="top" rowspan="1" colspan="1">IOERT</td>
<td align="left" valign="top" rowspan="1" colspan="1">12</td>
<td align="left" valign="top" rowspan="1" colspan="1">67</td>
<td align="left" valign="top" rowspan="1" colspan="1">NR</td>
<td align="left" valign="top" rowspan="1" colspan="1">NR</td>
<td align="left" valign="top" rowspan="1" colspan="1">NR</td>
<td align="left" valign="top" rowspan="1" colspan="1">1 had acute symptomatic lymphocele</td>
</tr>
<tr>
<td align="left" valign="top" rowspan="1" colspan="1">Kato
<italic>et al</italic>
. [
<xref rid="ref138" ref-type="bibr">138</xref>
] 1998</td>
<td align="left" valign="top" rowspan="1" colspan="1">54
<break></break>
Stage B2-D1
<xref ref-type="table-fn" rid="table10-fn1">
<sup>α</sup>
</xref>
<break></break>
No RP</td>
<td align="left" valign="top" rowspan="1" colspan="1">Prospective</td>
<td align="left" valign="top" rowspan="1" colspan="1">IOERT</td>
<td align="left" valign="top" rowspan="1" colspan="1">25–30</td>
<td align="left" valign="top" rowspan="1" colspan="1">100
<break></break>
(30 Gy)</td>
<td align="left" valign="top" rowspan="1" colspan="1">54</td>
<td align="left" valign="top" rowspan="1" colspan="1">83 (LC)
<break></break>
75
<break></break>
(bRFS)</td>
<td align="left" valign="top" rowspan="1" colspan="1">NR</td>
<td align="left" valign="top" rowspan="1" colspan="1">Late rectal toxicity-7%
<break></break>
(No toxicity with IORT of 25 Gy)</td>
</tr>
<tr>
<td align="left" valign="top" rowspan="1" colspan="1">Higashi
<italic>et al</italic>
. [
<xref rid="ref137" ref-type="bibr">137</xref>
] 1998</td>
<td align="left" valign="top" rowspan="1" colspan="1">35
<break></break>
Stage B-C
<xref ref-type="table-fn" rid="table10-fn1">
<sup>α</sup>
</xref>
<break></break>
No RP</td>
<td align="left" valign="top" rowspan="1" colspan="1">Prospective</td>
<td align="left" valign="top" rowspan="1" colspan="1">IOERT</td>
<td align="left" valign="top" rowspan="1" colspan="1">25–30</td>
<td align="left" valign="top" rowspan="1" colspan="1">100
<break></break>
(30 Gy)</td>
<td align="left" valign="top" rowspan="1" colspan="1">NR</td>
<td align="left" valign="top" rowspan="1" colspan="1">NR</td>
<td align="left" valign="top" rowspan="1" colspan="1">Stage B-92
<break></break>
Stage C-87</td>
<td align="left" valign="top" rowspan="1" colspan="1">NR</td>
</tr>
</tbody>
</table>
<table-wrap-foot>
<p>RCT: randomised control trial, Sx: surgery, LC: local control, OS: overall survival, DFS: disease-free survival, NR: not reported, *Number of patients, RP: radical prostatectomy, Pca: prostate cancer, ECE: extra capsular extension,
<italic>R</italic>
1: margin +ve,
<italic>N</italic>
+: node-positive disease, bRFS: biochemical relapse-free survival,</p>
<fn id="table10-fn1">
<label>
<sup>α</sup>
</label>
<p>Whitmore-Jewett staging system [Whitmore 1956, Jewett 1975].</p>
</fn>
</table-wrap-foot>
</table-wrap>
<table-wrap id="table11" position="float">
<label>Table 11.</label>
<caption>
<title>IORT studies for gastric cancers.</title>
</caption>
<table frame="border" rules="all">
<thead>
<tr>
<th align="center" valign="top" rowspan="1" colspan="1">Author/Year</th>
<th align="center" valign="top" rowspan="1" colspan="1">Sample size</th>
<th align="center" valign="top" rowspan="1" colspan="1">Study design</th>
<th align="center" valign="top" rowspan="1" colspan="1">IORT type</th>
<th align="center" valign="top" rowspan="1" colspan="1">IORT dose (Gy)</th>
<th align="center" valign="top" rowspan="1" colspan="1">EBRT (%)</th>
<th align="center" valign="top" rowspan="1" colspan="1">Type of nodal dissection</th>
<th align="center" valign="top" rowspan="1" colspan="1">Median follow-up (months)</th>
<th align="center" valign="top" rowspan="1" colspan="1">LRC</th>
<th align="center" valign="top" rowspan="1" colspan="1">OS 5 year (%)</th>
<th align="center" valign="top" rowspan="1" colspan="1">Toxicity grade 3 or ></th>
</tr>
</thead>
<tbody>
<tr>
<td align="left" valign="top" rowspan="1" colspan="1">Sindelar
<italic>et al</italic>
. [
<xref rid="ref149" ref-type="bibr">149</xref>
] 1993</td>
<td align="left" valign="top" rowspan="1" colspan="1">Sx+IORT-27
<break></break>
Sx+/-EBRT-33</td>
<td align="left" valign="top" rowspan="1" colspan="1">RCT</td>
<td align="left" valign="top" rowspan="1" colspan="1">IOERT</td>
<td align="left" valign="top" rowspan="1" colspan="1">20</td>
<td align="left" valign="top" rowspan="1" colspan="1">0
<break></break>
72</td>
<td align="left" valign="top" rowspan="1" colspan="1">NR</td>
<td align="left" valign="top" rowspan="1" colspan="1">84</td>
<td align="left" valign="top" rowspan="1" colspan="1">37
<break></break>
8
<break></break>
<italic>p</italic>
< 0.001</td>
<td align="left" valign="top" rowspan="1" colspan="1">25 months (M.S)
<break></break>
21 months (M.S)
<break></break>
<italic>p</italic>
= 0.99</td>
<td align="left" valign="top" rowspan="1" colspan="1">Fistula:
<break></break>
IORT-4 vs. Sx-5
<xref ref-type="table-fn" rid="table11-fn1">
<sup>*</sup>
</xref>
<break></break>
Enteritis:
<break></break>
IORT-0 vs. Sx-2
<xref ref-type="table-fn" rid="table11-fn1">
<sup>*</sup>
</xref>
</td>
</tr>
<tr>
<td align="left" valign="top" rowspan="1" colspan="1">Abe
<italic>et al</italic>
[
<xref rid="ref1" ref-type="bibr">1</xref>
] 1995</td>
<td align="left" valign="top" rowspan="1" colspan="1">IORT-94
<break></break>
No IORT-127</td>
<td align="left" valign="top" rowspan="1" colspan="1">NRC</td>
<td align="left" valign="top" rowspan="1" colspan="1">IOERT</td>
<td align="left" valign="top" rowspan="1" colspan="1">28–35</td>
<td align="left" valign="top" rowspan="1" colspan="1">none</td>
<td align="left" valign="top" rowspan="1" colspan="1">NR</td>
<td align="left" valign="top" rowspan="1" colspan="1">NR</td>
<td align="left" valign="top" rowspan="1" colspan="1">NR</td>
<td align="left" valign="top" rowspan="1" colspan="1">Stage II:
<break></break>
IORT-78
<break></break>
No IORT-66
<break></break>
Stage III:
<break></break>
IORT-60
<break></break>
No IORT-51
<break></break>
Stage IV:
<break></break>
IORT-33
<break></break>
No IORT-14 (all N.S)</td>
<td align="left" valign="top" rowspan="1" colspan="1">NR</td>
</tr>
<tr>
<td align="left" valign="top" rowspan="1" colspan="1">Avizonis
<italic>et al</italic>
.[
<xref rid="ref158" ref-type="bibr">158</xref>
] 1995</td>
<td align="left" valign="top" rowspan="1" colspan="1">27</td>
<td align="left" valign="top" rowspan="1" colspan="1">Prospective phase II</td>
<td align="left" valign="top" rowspan="1" colspan="1">IOERT</td>
<td align="left" valign="top" rowspan="1" colspan="1">12.5–16.5</td>
<td align="left" valign="top" rowspan="1" colspan="1">79</td>
<td align="left" valign="top" rowspan="1" colspan="1">NR</td>
<td align="left" valign="top" rowspan="1" colspan="1">NR</td>
<td align="left" valign="top" rowspan="1" colspan="1">85</td>
<td align="left" valign="top" rowspan="1" colspan="1">47
<break></break>
(2yr)</td>
<td align="left" valign="top" rowspan="1" colspan="1">Acute
<break></break>
toxicity-14%
<break></break>
Late-7%</td>
</tr>
<tr>
<td align="left" valign="top" rowspan="1" colspan="1">Ogata
<italic>et al</italic>
. [
<xref rid="ref152" ref-type="bibr">152</xref>
] 1995</td>
<td align="left" valign="top" rowspan="1" colspan="1">IORT-58
<break></break>
No IORT-120</td>
<td align="left" valign="top" rowspan="1" colspan="1">Retrospective</td>
<td align="left" valign="top" rowspan="1" colspan="1">IOERT</td>
<td align="left" valign="top" rowspan="1" colspan="1">12</td>
<td align="left" valign="top" rowspan="1" colspan="1">None</td>
<td align="left" valign="top" rowspan="1" colspan="1">D2</td>
<td align="left" valign="top" rowspan="1" colspan="1">NR</td>
<td align="left" valign="top" rowspan="1" colspan="1">NR</td>
<td align="left" valign="top" rowspan="1" colspan="1">Stage II:
<break></break>
IORT-100,
<break></break>
No IORT-63 (4yr)
<break></break>
Stage III:
<break></break>
IORT-55
<break></break>
No IORT-35 (8yr)
<break></break>
Stage IV:
<break></break>
IORT-12
<break></break>
No IORT-13 (5yr)</td>
<td align="left" valign="top" rowspan="1" colspan="1">None</td>
</tr>
<tr>
<td align="left" valign="top" rowspan="1" colspan="1">Coquard
<italic>et al</italic>
. [
<xref rid="ref156" ref-type="bibr">156</xref>
] 1997</td>
<td align="left" valign="top" rowspan="1" colspan="1">63
<break></break>
(
<italic>R</italic>
0-92%)</td>
<td align="left" valign="top" rowspan="1" colspan="1">Retrospective</td>
<td align="left" valign="top" rowspan="1" colspan="1">IOERT</td>
<td align="left" valign="top" rowspan="1" colspan="1">12–23</td>
<td align="left" valign="top" rowspan="1" colspan="1">48</td>
<td align="left" valign="top" rowspan="1" colspan="1">D1-89%</td>
<td align="left" valign="top" rowspan="1" colspan="1">61 in survivors</td>
<td align="left" valign="top" rowspan="1" colspan="1">76 (crude rate)</td>
<td align="left" valign="top" rowspan="1" colspan="1">47</td>
<td align="left" valign="top" rowspan="1" colspan="1">None attributed to IORT</td>
</tr>
<tr>
<td align="left" valign="top" rowspan="1" colspan="1">Skoropad
<italic>et al</italic>
. [
<xref rid="ref154" ref-type="bibr">154</xref>
] 2000</td>
<td align="left" valign="top" rowspan="1" colspan="1">78
<break></break>
Pre-op RT+IORT+ Sx vs. Sx alone</td>
<td align="left" valign="top" rowspan="1" colspan="1">RCT</td>
<td align="left" valign="top" rowspan="1" colspan="1">IOERT</td>
<td align="left" valign="top" rowspan="1" colspan="1">20</td>
<td align="left" valign="top" rowspan="1" colspan="1">100
<break></break>
(Pre-op RT-20 Gy/5
<xref ref-type="table-fn" rid="table11-fn2">
<sup>#</sup>
</xref>
)</td>
<td align="left" valign="top" rowspan="1" colspan="1">D1</td>
<td align="left" valign="top" rowspan="1" colspan="1">NR</td>
<td align="left" valign="top" rowspan="1" colspan="1">NR</td>
<td align="left" valign="top" rowspan="1" colspan="1">Entire cohort:
<break></break>
IORT:21months
<break></break>
No IORT: 9months
<break></break>
(
<italic>P</italic>
= 0.311)
<break></break>
Node +ve and
<break></break>
Advanced stage: IORT vs. No IORT:
<break></break>
<italic>p</italic>
< 0.05</td>
<td align="left" valign="top" rowspan="1" colspan="1">Similar acute toxicity in both arms
<break></break>
Higher pancreatitis surgery alone.
<break></break>
No RT late toxicity</td>
</tr>
<tr>
<td align="left" valign="top" rowspan="1" colspan="1">Weese
<italic>et al</italic>
. [
<xref rid="ref159" ref-type="bibr">159</xref>
] 2000</td>
<td align="left" valign="top" rowspan="1" colspan="1">16
<break></break>
(IORT-56%)</td>
<td align="left" valign="top" rowspan="1" colspan="1">Prospective</td>
<td align="left" valign="top" rowspan="1" colspan="1">IOERT</td>
<td align="left" valign="top" rowspan="1" colspan="1">10</td>
<td align="left" valign="top" rowspan="1" colspan="1">88</td>
<td align="left" valign="top" rowspan="1" colspan="1">D2</td>
<td align="left" valign="top" rowspan="1" colspan="1">27</td>
<td align="left" valign="top" rowspan="1" colspan="1">93 (crude rate)</td>
<td align="left" valign="top" rowspan="1" colspan="1">66 (crude rate at 3yr)</td>
<td align="left" valign="top" rowspan="1" colspan="1">NR</td>
</tr>
<tr>
<td align="left" valign="top" rowspan="1" colspan="1">Glehen
<italic>et al</italic>
. [
<xref rid="ref160" ref-type="bibr">160</xref>
] 2003</td>
<td align="left" valign="top" rowspan="1" colspan="1">42
<break></break>
(All Node +ve,
<italic>R</italic>
0-93%)</td>
<td align="left" valign="top" rowspan="1" colspan="1">Retrospective</td>
<td align="left" valign="top" rowspan="1" colspan="1">IOERT</td>
<td align="left" valign="top" rowspan="1" colspan="1">12–15</td>
<td align="left" valign="top" rowspan="1" colspan="1">97</td>
<td align="left" valign="top" rowspan="1" colspan="1">NR</td>
<td align="left" valign="top" rowspan="1" colspan="1">131</td>
<td align="left" valign="top" rowspan="1" colspan="1">79</td>
<td align="left" valign="top" rowspan="1" colspan="1">45</td>
<td align="left" valign="top" rowspan="1" colspan="1">NR</td>
</tr>
<tr>
<td align="left" valign="top" rowspan="1" colspan="1">Miller
<italic>et al</italic>
. [
<xref rid="ref161" ref-type="bibr">161</xref>
] 2006</td>
<td align="left" valign="top" rowspan="1" colspan="1">50
<break></break>
(
<italic>R</italic>
0-42%, recurrent-26%, oesophagus-14%)</td>
<td align="left" valign="top" rowspan="1" colspan="1">Retrospective</td>
<td align="left" valign="top" rowspan="1" colspan="1">IOERT</td>
<td align="left" valign="top" rowspan="1" colspan="1">10–25</td>
<td align="left" valign="top" rowspan="1" colspan="1">96</td>
<td align="left" valign="top" rowspan="1" colspan="1">NR</td>
<td align="left" valign="top" rowspan="1" colspan="1">19</td>
<td align="left" valign="top" rowspan="1" colspan="1">75</td>
<td align="left" valign="top" rowspan="1" colspan="1">15 (5 yr)</td>
<td align="left" valign="top" rowspan="1" colspan="1">Acute-48%
<break></break>
Chronic-26%
<break></break>
GI-6
<xref ref-type="table-fn" rid="table11-fn1">
<sup>*</sup>
</xref>
<break></break>
Overall treatment-related mortality-6%</td>
</tr>
<tr>
<td align="left" valign="top" rowspan="1" colspan="1">Qin
<italic>et al</italic>
. [
<xref rid="ref153" ref-type="bibr">153</xref>
] 2006</td>
<td align="left" valign="top" rowspan="1" colspan="1">IORT-106
<break></break>
No IORT-441</td>
<td align="left" valign="top" rowspan="1" colspan="1">NRC</td>
<td align="left" valign="top" rowspan="1" colspan="1">IOERT</td>
<td align="left" valign="top" rowspan="1" colspan="1">10–30</td>
<td align="left" valign="top" rowspan="1" colspan="1">None</td>
<td align="left" valign="top" rowspan="1" colspan="1">D2/3</td>
<td align="left" valign="top" rowspan="1" colspan="1">NR</td>
<td align="left" valign="top" rowspan="1" colspan="1">NR</td>
<td align="left" valign="top" rowspan="1" colspan="1">Stage III D2:
<break></break>
IORT- 60%
<break></break>
No IORT-36%
<break></break>
<italic>p</italic>
< 0.005
<break></break>
Stage III D3:
<break></break>
IORT-61%
<break></break>
No IORT-56%
<break></break>
<italic>p</italic>
> 0.05</td>
<td align="left" valign="top" rowspan="1" colspan="1">NR</td>
</tr>
<tr>
<td align="left" valign="top" rowspan="1" colspan="1">Drognitz
<italic>et al</italic>
. [
<xref rid="ref151" ref-type="bibr">151</xref>
] 2007</td>
<td align="left" valign="top" rowspan="1" colspan="1">IORT-61
<break></break>
No IORT-61
<break></break>
(
<italic>R</italic>
0-100%)</td>
<td align="left" valign="top" rowspan="1" colspan="1">NRC</td>
<td align="left" valign="top" rowspan="1" colspan="1">IOERT</td>
<td align="left" valign="top" rowspan="1" colspan="1">15–25</td>
<td align="left" valign="top" rowspan="1" colspan="1">None</td>
<td align="left" valign="top" rowspan="1" colspan="1">D2</td>
<td align="left" valign="top" rowspan="1" colspan="1">56</td>
<td align="left" valign="top" rowspan="1" colspan="1">90</td>
<td align="left" valign="top" rowspan="1" colspan="1">IORT-58%
<break></break>
No IORT-59%
<break></break>
<italic>p</italic>
= 0.99</td>
<td align="left" valign="top" rowspan="1" colspan="1">Perioperative mortality-4.9% both groups
<break></break>
Surgical morbidity:
<break></break>
IORT:44%
<break></break>
No IORT: 20%</td>
</tr>
<tr>
<td align="left" valign="top" rowspan="1" colspan="1">Fu
<italic>et al</italic>
. [
<xref rid="ref148" ref-type="bibr">148</xref>
] 2008</td>
<td align="left" valign="top" rowspan="1" colspan="1">97
<break></break>
IORT-46
<break></break>
No IORT-51
<break></break>
(
<italic>R</italic>
0-90%)</td>
<td align="left" valign="top" rowspan="1" colspan="1">Prospective</td>
<td align="left" valign="top" rowspan="1" colspan="1">IOERT</td>
<td align="left" valign="top" rowspan="1" colspan="1">12–15</td>
<td align="left" valign="top" rowspan="1" colspan="1">100%
<break></break>
CTRT</td>
<td align="left" valign="top" rowspan="1" colspan="1">D2</td>
<td align="left" valign="top" rowspan="1" colspan="1">24</td>
<td align="left" valign="top" rowspan="1" colspan="1">77
<break></break>
IORT- 77
<break></break>
No IORT- 63
<break></break>
<italic>p</italic>
= 0.05, (3Yr)</td>
<td align="left" valign="top" rowspan="1" colspan="1">44
<break></break>
IORT-56
<break></break>
No IORT-47
<break></break>
<italic>p</italic>
= 0.20, (3Yr)</td>
<td align="left" valign="top" rowspan="1" colspan="1">Late toxicity-3
<xref ref-type="table-fn" rid="table11-fn1">
<sup>*</sup>
</xref>
<break></break>
No difference among groups</td>
</tr>
<tr>
<td align="left" valign="top" rowspan="1" colspan="1">Zhang
<italic>et al</italic>
. [
<xref rid="ref150" ref-type="bibr">150</xref>
] 2012</td>
<td align="left" valign="top" rowspan="1" colspan="1">97
<break></break>
IORT-46
<break></break>
No IORT-51
<break></break>
(
<italic>R</italic>
0-90%)</td>
<td align="left" valign="top" rowspan="1" colspan="1">Prospective</td>
<td align="left" valign="top" rowspan="1" colspan="1">IOERT</td>
<td align="left" valign="top" rowspan="1" colspan="1">12–15</td>
<td align="left" valign="top" rowspan="1" colspan="1">100% CTRT</td>
<td align="left" valign="top" rowspan="1" colspan="1">D2</td>
<td align="left" valign="top" rowspan="1" colspan="1">37</td>
<td align="left" valign="top" rowspan="1" colspan="1">50
<break></break>
IORT-50
<break></break>
No IORT-35
<break></break>
<italic>p</italic>
= 0.04</td>
<td align="left" valign="top" rowspan="1" colspan="1">26
<break></break>
IORT-28
<break></break>
No IORT-26
<break></break>
<italic>p</italic>
= 0.4</td>
<td align="left" valign="top" rowspan="1" colspan="1">IORT vs. No IORT
<break></break>
Acute-39% vs. 37%
<break></break>
Late-.10% vs. 0%,
<italic>p</italic>
= 0.02
<break></break>
Enteritis-1
<xref ref-type="table-fn" rid="table11-fn1">
<sup>*</sup>
</xref>
<break></break>
Haemorrhage-4
<xref ref-type="table-fn" rid="table11-fn1">
<sup>*</sup>
</xref>
</td>
</tr>
<tr>
<td align="left" valign="top" rowspan="1" colspan="1">Calvo
<italic>et al</italic>
. [
<xref rid="ref155" ref-type="bibr">155</xref>
] 2012</td>
<td align="left" valign="top" rowspan="1" colspan="1">32
<break></break>
(
<italic>R</italic>
0-100%)</td>
<td align="left" valign="top" rowspan="1" colspan="1">Retrospective</td>
<td align="left" valign="top" rowspan="1" colspan="1">IOERT</td>
<td align="left" valign="top" rowspan="1" colspan="1">10–15</td>
<td align="left" valign="top" rowspan="1" colspan="1">47</td>
<td align="left" valign="top" rowspan="1" colspan="1">D2</td>
<td align="left" valign="top" rowspan="1" colspan="1">40</td>
<td align="left" valign="top" rowspan="1" colspan="1">84</td>
<td align="left" valign="top" rowspan="1" colspan="1">55</td>
<td align="left" valign="top" rowspan="1" colspan="1">Acute GI-5
<xref ref-type="table-fn" rid="table11-fn1">
<sup>*</sup>
</xref>
</td>
</tr>
</tbody>
</table>
<table-wrap-foot>
<p>RCT: randomised control trial, NRC: non-randomised comparison, Sx: surgery, LC: local control, OS: overall survival, DFS: disease-free survival, NR: not reported,</p>
<fn id="table11-fn1">
<label>
<sup>*</sup>
</label>
<p>Number of patients,</p>
</fn>
<fn id="table11-fn2">
<label>
<sup>#</sup>
</label>
<p>fractions,</p>
</fn>
<p>Pre-op: pre-operative, M.S: median survival, N.S: non-significant.</p>
</table-wrap-foot>
</table-wrap>
<table-wrap id="table12" position="float">
<label>Table 12.</label>
<caption>
<title>Studies of IORT in the management of pancreatic cancers.</title>
</caption>
<table frame="border" rules="all">
<thead>
<tr>
<th align="center" valign="top" rowspan="1" colspan="1">Author/Year</th>
<th align="center" valign="top" rowspan="1" colspan="1">Sample size</th>
<th align="center" valign="top" rowspan="1" colspan="1">Study design</th>
<th align="center" valign="top" rowspan="1" colspan="1">IORT type</th>
<th align="center" valign="top" rowspan="1" colspan="1">IORT dose (Gy)</th>
<th align="center" valign="top" rowspan="1" colspan="1">EBRT %</th>
<th align="center" valign="top" rowspan="1" colspan="1">Median follow-up</th>
<th align="center" valign="top" rowspan="1" colspan="1">LC 5 year (%)</th>
<th align="center" valign="top" rowspan="1" colspan="1">OS 5 year (%)</th>
<th align="center" valign="top" rowspan="1" colspan="1">Toxicity grade 3 or ></th>
</tr>
</thead>
<tbody>
<tr>
<td align="left" valign="top" rowspan="1" colspan="1">Mohiuddin
<italic>et al</italic>
. [
<xref rid="ref178" ref-type="bibr">178</xref>
] 1995</td>
<td align="left" valign="top" rowspan="1" colspan="1">49 UR-PC
<break></break>
(Resected-0%)</td>
<td align="left" valign="top" rowspan="1" colspan="1">Retrospective</td>
<td align="left" valign="top" rowspan="1" colspan="1">IOERT</td>
<td align="left" valign="top" rowspan="1" colspan="1">10–20</td>
<td align="left" valign="top" rowspan="1" colspan="1">100
<break></break>
(Post-op)</td>
<td align="left" valign="top" rowspan="1" colspan="1">28</td>
<td align="left" valign="top" rowspan="1" colspan="1">69</td>
<td align="left" valign="top" rowspan="1" colspan="1">7 (4yr)</td>
<td align="left" valign="top" rowspan="1" colspan="1">Acute toxicity-14%
<break></break>
GI bleeding-2
<xref ref-type="table-fn" rid="table12-fn1">
<sup>*</sup>
</xref>
<break></break>
Late toxicity-19%
<break></break>
GI bleeding-3
<xref ref-type="table-fn" rid="table12-fn1">
<sup>*</sup>
</xref>
<break></break>
Obstruction-2
<xref ref-type="table-fn" rid="table12-fn1">
<sup>*</sup>
</xref>
</td>
</tr>
<tr>
<td align="left" valign="top" rowspan="1" colspan="1">Nishimura
<italic>et al</italic>
. [
<xref rid="ref179" ref-type="bibr">179</xref>
] 1997</td>
<td align="left" valign="top" rowspan="1" colspan="1">Resected-157
<break></break>
IORT- 55
<break></break>
No IORT-102
<break></break>
Unresectable-175
<break></break>
IORT-71
<break></break>
No IORT-104</td>
<td align="left" valign="top" rowspan="1" colspan="1">Retrospective</td>
<td align="left" valign="top" rowspan="1" colspan="1">IOERT</td>
<td align="left" valign="top" rowspan="1" colspan="1">12–33 Gy</td>
<td align="left" valign="top" rowspan="1" colspan="1">Resected-
<break></break>
70
<break></break>
Unresectable-87
<break></break>
(Pre-op or post-op)</td>
<td align="left" valign="top" rowspan="1" colspan="1">NR</td>
<td align="left" valign="top" rowspan="1" colspan="1">NR</td>
<td align="left" valign="top" rowspan="1" colspan="1">Resected:
<break></break>
IORT-16
<break></break>
No IORT-0 (2yr)
<break></break>
Unresectable:
<break></break>
IORT-14
<break></break>
No IORT-0
<break></break>
<italic>p</italic>
< 0.05 (2yr)</td>
<td align="left" valign="top" rowspan="1" colspan="1">IORT:
<break></break>
Late toxicity:
<break></break>
gastric ulcer-18
<xref ref-type="table-fn" rid="table12-fn1">
<sup>*</sup>
</xref>
<break></break>
Intestinal perforation-4
<xref ref-type="table-fn" rid="table12-fn1">
<sup>*</sup>
</xref>
</td>
</tr>
<tr>
<td align="left" valign="top" rowspan="1" colspan="1">Ma
<italic>et al</italic>
. [
<xref rid="ref177" ref-type="bibr">177</xref>
] 2004</td>
<td align="left" valign="top" rowspan="1" colspan="1">81 UR-PC
<break></break>
(Resected-0%)
<break></break>
IORT-18
<break></break>
IORT+EBRT-25
<break></break>
EBRT-16
<break></break>
Palliative Sx-22</td>
<td align="left" valign="top" rowspan="1" colspan="1">Retrospective</td>
<td align="left" valign="top" rowspan="1" colspan="1">IOERT</td>
<td align="left" valign="top" rowspan="1" colspan="1">15–25</td>
<td align="left" valign="top" rowspan="1" colspan="1">80
<break></break>
(Post-op)</td>
<td align="left" valign="top" rowspan="1" colspan="1">NR</td>
<td align="left" valign="top" rowspan="1" colspan="1">NR
<break></break>
(60% complete pain relief with IORT)</td>
<td align="left" valign="top" rowspan="1" colspan="1">
<break></break>
10.7 (M.S)
<break></break>
12.2 (M.S)
<break></break>
5.1 (M.S)
<break></break>
7 (M.S)</td>
<td align="left" valign="top" rowspan="1" colspan="1">IORT vs IORT+EBRT:
<break></break>
Delayed gastric
<break></break>
emptying: 3 vs 2
<xref ref-type="table-fn" rid="table12-fn1">
<sup>*</sup>
</xref>
</td>
</tr>
<tr>
<td align="left" valign="top" rowspan="1" colspan="1">Willet
<italic>et al</italic>
. [
<xref rid="ref180" ref-type="bibr">180</xref>
] 2005</td>
<td align="left" valign="top" rowspan="1" colspan="1">150 UR-PC
<break></break>
(Resected-0%)
<break></break>
</td>
<td align="left" valign="top" rowspan="1" colspan="1">Retrospective</td>
<td align="left" valign="top" rowspan="1" colspan="1">IOERT</td>
<td align="left" valign="top" rowspan="1" colspan="1">15–20 Gy</td>
<td align="left" valign="top" rowspan="1" colspan="1">100 (Pre/post-op RT)</td>
<td align="left" valign="top" rowspan="1" colspan="1">NR</td>
<td align="left" valign="top" rowspan="1" colspan="1">NR</td>
<td align="left" valign="top" rowspan="1" colspan="1">7 (3Yr)</td>
<td align="left" valign="top" rowspan="1" colspan="1">Post-operative complications- 20%
<break></break>
Late toxicity- 15%
<break></break>
Upper GI bleed-16
<xref ref-type="table-fn" rid="table12-fn1">
<sup>*</sup>
</xref>
</td>
</tr>
<tr>
<td align="left" valign="top" rowspan="1" colspan="1">Jingu
<italic>et al</italic>
. [
<xref rid="ref176" ref-type="bibr">176</xref>
] 2012</td>
<td align="left" valign="top" rowspan="1" colspan="1">322
<break></break>
Resected-83
<break></break>
Unresectable- 109
<break></break>
Metastatic-130 (exclude)</td>
<td align="left" valign="top" rowspan="1" colspan="1">Retrospective</td>
<td align="left" valign="top" rowspan="1" colspan="1">IOERT</td>
<td align="left" valign="top" rowspan="1" colspan="1">20–30</td>
<td align="left" valign="top" rowspan="1" colspan="1">29 (post-op RT)</td>
<td align="left" valign="top" rowspan="1" colspan="1">38</td>
<td align="left" valign="top" rowspan="1" colspan="1">64</td>
<td align="left" valign="top" rowspan="1" colspan="1">9
<break></break>
<italic>R</italic>
2:HR-2.03,
<break></break>
<italic>p</italic>
< 0.001</td>
<td align="left" valign="top" rowspan="1" colspan="1">Late toxicity
<break></break>
GI-4
<xref ref-type="table-fn" rid="table12-fn1">
<sup>*</sup>
</xref>
</td>
</tr>
<tr>
<td align="left" valign="top" rowspan="1" colspan="1">Cai
<italic>et al</italic>
. [
<xref rid="ref174" ref-type="bibr">174</xref>
] 2013</td>
<td align="left" valign="top" rowspan="1" colspan="1">194 UR-PC
<break></break>
(Resected-0%)</td>
<td align="left" valign="top" rowspan="1" colspan="1">Retrospective</td>
<td align="left" valign="top" rowspan="1" colspan="1">IOERT</td>
<td align="left" valign="top" rowspan="1" colspan="1">10–25</td>
<td align="left" valign="top" rowspan="1" colspan="1">97% (Pre-op CTRT)</td>
<td align="left" valign="top" rowspan="1" colspan="1">12</td>
<td align="left" valign="top" rowspan="1" colspan="1">38 (3yr)</td>
<td align="left" valign="top" rowspan="1" colspan="1">6 (3yr)</td>
<td align="left" valign="top" rowspan="1" colspan="1">Acute toxicity- 21%
<break></break>
Late toxicity-14%
<break></break>
Haemorrhage-23
<xref ref-type="table-fn" rid="table12-fn1">
<sup>*</sup>
</xref>
</td>
</tr>
<tr>
<td align="left" valign="top" rowspan="1" colspan="1">Chen
<italic>et al</italic>
. [
<xref rid="ref175" ref-type="bibr">175</xref>
]
<break></break>
2016</td>
<td align="left" valign="top" rowspan="1" colspan="1">247 UR-PC
<break></break>
(Resected-0%)</td>
<td align="left" valign="top" rowspan="1" colspan="1">Retrospective</td>
<td align="left" valign="top" rowspan="1" colspan="1">IOERT</td>
<td align="left" valign="top" rowspan="1" colspan="1">10–20</td>
<td align="left" valign="top" rowspan="1" colspan="1">51% (Post-op CTRT)</td>
<td align="left" valign="top" rowspan="1" colspan="1">10</td>
<td align="left" valign="top" rowspan="1" colspan="1">35 (3yr)
<break></break>
Complete pain relief-70%</td>
<td align="left" valign="top" rowspan="1" colspan="1">7.2 (3yr)</td>
<td align="left" valign="top" rowspan="1" colspan="1">Post-operative complications-14%
<break></break>
Fistula-11
<xref ref-type="table-fn" rid="table12-fn1">
<sup>*</sup>
</xref>
<break></break>
Haemorrhage- 7
<xref ref-type="table-fn" rid="table12-fn1">
<sup>*</sup>
</xref>
</td>
</tr>
<tr>
<td align="left" valign="top" rowspan="1" colspan="1">Keane
<italic>et al</italic>
. [
<xref rid="ref181" ref-type="bibr">181</xref>
] 2016
<break></break>
</td>
<td align="left" valign="top" rowspan="1" colspan="1">68 UR-PC
<break></break>
After NACTRT
<break></break>
Resected-41 IORT-22 (R1-73%)
<break></break>
No IORT-19
<break></break>
Unresectable-18 (IORT-17)</td>
<td align="left" valign="top" rowspan="1" colspan="1">Retrospective</td>
<td align="left" valign="top" rowspan="1" colspan="1">IOERT</td>
<td align="left" valign="top" rowspan="1" colspan="1">
<break></break>
8–13
<break></break>
15–17</td>
<td align="left" valign="top" rowspan="1" colspan="1">100 % (NACTRT)</td>
<td align="left" valign="top" rowspan="1" colspan="1">21</td>
<td align="left" valign="top" rowspan="1" colspan="1">NR</td>
<td align="left" valign="top" rowspan="1" colspan="1">
<break></break>
35.1 (M.S)
<break></break>
24.5 (M.S)
<break></break>
24.8 (M.S)</td>
<td align="left" valign="top" rowspan="1" colspan="1">No significant difference in post-operative complications</td>
</tr>
<tr>
<td align="left" valign="top" rowspan="1" colspan="1">Kokubo
<italic>et al</italic>
. [
<xref rid="ref172" ref-type="bibr">172</xref>
] 2000</td>
<td align="left" valign="top" rowspan="1" colspan="1">138 R/BR-PC
<break></break>
(Resected-100%,
<italic>R</italic>
1-29%)</td>
<td align="left" valign="top" rowspan="1" colspan="1">Retrospective</td>
<td align="left" valign="top" rowspan="1" colspan="1">IOERT</td>
<td align="left" valign="top" rowspan="1" colspan="1">20–30</td>
<td align="left" valign="top" rowspan="1" colspan="1">45
<break></break>
(Pre-op:13%
<break></break>
Post op-47%
<break></break>
Both-40%)</td>
<td align="left" valign="top" rowspan="1" colspan="1">NR</td>
<td align="left" valign="top" rowspan="1" colspan="1">NR</td>
<td align="left" valign="top" rowspan="1" colspan="1">
<italic>R</italic>
0:19
<break></break>
<italic>R</italic>
1:4
<break></break>
<italic>p</italic>
< 0.005
<break></break>
(2-yr cause specific survival)</td>
<td align="left" valign="top" rowspan="1" colspan="1">Acute toxicity- none
<break></break>
Late toxicity-
<break></break>
GI ulcers-20%
<break></break>
Perforation-2
<xref ref-type="table-fn" rid="table12-fn1">
<sup>*</sup>
</xref>
</td>
</tr>
<tr>
<td align="left" valign="top" rowspan="1" colspan="1">Alfieri
<italic>et al</italic>
. [
<xref rid="ref165" ref-type="bibr">165</xref>
] 2001</td>
<td align="left" valign="top" rowspan="1" colspan="1">46 R/BR-PC (Resected-100%)
<break></break>
IORT-26 (R1-10%)
<break></break>
No IORT-20 (R1-13%)</td>
<td align="left" valign="top" rowspan="1" colspan="1">NRC</td>
<td align="left" valign="top" rowspan="1" colspan="1">IOERT</td>
<td align="left" valign="top" rowspan="1" colspan="1">10</td>
<td align="left" valign="top" rowspan="1" colspan="1">
<break></break>
100
<break></break>
0
<break></break>
(Post-op)</td>
<td align="left" valign="top" rowspan="1" colspan="1">82</td>
<td align="left" valign="top" rowspan="1" colspan="1">
<break></break>
IORT-58
<break></break>
No IORT-30
<break></break>
<italic>p</italic>
< 0.001</td>
<td align="left" valign="top" rowspan="1" colspan="1">
<break></break>
IORT-16
<break></break>
No IORT-6
<break></break>
<italic>p</italic>
= 0.06</td>
<td align="left" valign="top" rowspan="1" colspan="1">IORT vs. No IORT
<break></break>
Acute morbidity-
<break></break>
57% vs. 43% (
<italic>p</italic>
= 0.1)
<break></break>
Perioperative mortality-
<break></break>
8% vs. 9%</td>
</tr>
<tr>
<td align="left" valign="top" rowspan="1" colspan="1">Reni
<italic>et al</italic>
. [
<xref rid="ref173" ref-type="bibr">173</xref>
] 2001</td>
<td align="left" valign="top" rowspan="1" colspan="1">127 R/BR-PC
<break></break>
(Resected-82%)
<break></break>
IORT- 127
<break></break>
(
<italic>R</italic>
0-1:104,
<italic>R</italic>
2-23)
<break></break>
No IORT- 76 (
<italic>R</italic>
0-1:62,
<italic>R</italic>
2-14)</td>
<td align="left" valign="top" rowspan="1" colspan="1">Retrospective</td>
<td align="left" valign="top" rowspan="1" colspan="1">IOERT</td>
<td align="left" valign="top" rowspan="1" colspan="1">10–25</td>
<td align="left" valign="top" rowspan="1" colspan="1">
<break></break>
32
<break></break>
20
<break></break>
(Post-op)</td>
<td align="left" valign="top" rowspan="1" colspan="1">21 (in
<break></break>
survivors)</td>
<td align="left" valign="top" rowspan="1" colspan="1">Stage I-II:
<break></break>
IORT-73
<break></break>
No IORT-40
<break></break>
Stage III-IVA:
<break></break>
IORT-50
<break></break>
No IORT-45</td>
<td align="left" valign="top" rowspan="1" colspan="1">Stage I–II:
<break></break>
IORT-22
<break></break>
No IORT-6
<break></break>
Stage III-IVA:
<break></break>
IORT-3
<break></break>
No IORT-5</td>
<td align="left" valign="top" rowspan="1" colspan="1">IORT vs. No IORT: Acute toxicity: N.S difference
<break></break>
Chronic toxicity:
<break></break>
Abdominal pain 15 vs. 22%
<break></break>
Late GI bleed-6 vs. 3%
<break></break>
Stenosis-3% vs. 0%</td>
</tr>
<tr>
<td align="left" valign="top" rowspan="1" colspan="1">Messick
<italic>et al</italic>
. [
<xref rid="ref169" ref-type="bibr">169</xref>
] 2008</td>
<td align="left" valign="top" rowspan="1" colspan="1">49 R/BR-PC (Resected-100%, R1-74%)
<break></break>
IORT-22
<break></break>
No IORT-27
<break></break>
</td>
<td align="left" valign="top" rowspan="1" colspan="1">NRC</td>
<td align="left" valign="top" rowspan="1" colspan="1">IOERT</td>
<td align="left" valign="top" rowspan="1" colspan="1">10–12</td>
<td align="left" valign="top" rowspan="1" colspan="1">
<break></break>
76
<break></break>
64</td>
<td align="left" valign="top" rowspan="1" colspan="1">
<break></break>
10.1
<break></break>
13.3</td>
<td align="left" valign="top" rowspan="1" colspan="1">
<break></break>
IORT-82
<break></break>
No IORT-88
<break></break>
(N.S)</td>
<td align="left" valign="top" rowspan="1" colspan="1">
<break></break>
IORT-20 (M.S)
<break></break>
No IORT-13 (M.S)
<break></break>
(N.S)</td>
<td align="left" valign="top" rowspan="1" colspan="1">IORT vs. No IORT: Delayed gastric emptying-6.7 vs. 4.2%
<break></break>
Wound infection-4.5 vs. 22%
<break></break>
Pancreatic fistula 10 vs. 4.8% (N.S)</td>
</tr>
<tr>
<td align="left" valign="top" rowspan="1" colspan="1">Valentini
<italic>et al</italic>
. [
<xref rid="ref171" ref-type="bibr">171</xref>
] 2008</td>
<td align="left" valign="top" rowspan="1" colspan="1">26 R/BR-PC
<break></break>
Resected-100%,
<italic>R</italic>
1-4%
<break></break>
</td>
<td align="left" valign="top" rowspan="1" colspan="1">Retrospective</td>
<td align="left" valign="top" rowspan="1" colspan="1">IOERT</td>
<td align="left" valign="top" rowspan="1" colspan="1">10</td>
<td align="left" valign="top" rowspan="1" colspan="1">100
<break></break>
(Post-op: 65%)</td>
<td align="left" valign="top" rowspan="1" colspan="1">102 in survivors</td>
<td align="left" valign="top" rowspan="1" colspan="1">57</td>
<td align="left" valign="top" rowspan="1" colspan="1">15</td>
<td align="left" valign="top" rowspan="1" colspan="1">Perioperative
<break></break>
complications-11%</td>
</tr>
<tr>
<td align="left" valign="top" rowspan="1" colspan="1">Showalter
<italic>et al</italic>
. [
<xref rid="ref167" ref-type="bibr">167</xref>
] 2009</td>
<td align="left" valign="top" rowspan="1" colspan="1">R/BR-PC
<break></break>
IORT-37 (
<italic>R</italic>
1-2:43%)
<break></break>
No IORT-46 (
<italic>R</italic>
1-2: 30%)</td>
<td align="left" valign="top" rowspan="1" colspan="1">Retrospective</td>
<td align="left" valign="top" rowspan="1" colspan="1">IOERT</td>
<td align="left" valign="top" rowspan="1" colspan="1">10–20</td>
<td align="left" valign="top" rowspan="1" colspan="1">74
<break></break>
66
<break></break>
(Post-op RT)</td>
<td align="left" valign="top" rowspan="1" colspan="1">NR</td>
<td align="left" valign="top" rowspan="1" colspan="1">IORT-79
<break></break>
No IORT-61
<break></break>
<italic>p</italic>
= 0.19</td>
<td align="left" valign="top" rowspan="1" colspan="1">IORT-21 (M.S)
<break></break>
No IORT-19 (M.S)</td>
<td align="left" valign="top" rowspan="1" colspan="1">Perioperative
<break></break>
complications-46% vs. 40% (N.S)</td>
</tr>
<tr>
<td align="left" valign="top" rowspan="1" colspan="1">Valentini
<italic>et al</italic>
. [
<xref rid="ref168" ref-type="bibr">168</xref>
] 2009</td>
<td align="left" valign="top" rowspan="1" colspan="1">270
<break></break>
Resected-81%
<break></break>
(
<italic>R</italic>
1-27%)</td>
<td align="left" valign="top" rowspan="1" colspan="1">ISIORT Pooled analysis</td>
<td align="left" valign="top" rowspan="1" colspan="1">IOERT</td>
<td align="left" valign="top" rowspan="1" colspan="1">7.5–25</td>
<td align="left" valign="top" rowspan="1" colspan="1">64
<break></break>
(pre-op:24
<break></break>
Post-op:40)</td>
<td align="left" valign="top" rowspan="1" colspan="1">96</td>
<td align="left" valign="top" rowspan="1" colspan="1">23
<break></break>
Pre-op RT vs. post-op RT vs. IORT alone
<break></break>
<italic>p</italic>
< 0.0001</td>
<td align="left" valign="top" rowspan="1" colspan="1">18
<break></break>
IORT + Pre-op RT vs. IORT + post-op RT vs. IORT alone
<break></break>
<italic>p</italic>
< 0.0001</td>
<td align="left" valign="top" rowspan="1" colspan="1">Acute toxicity- None > G2
<break></break>
Late-NS</td>
</tr>
<tr>
<td align="left" valign="top" rowspan="1" colspan="1">Ogawa
<italic>et al</italic>
. [
<xref rid="ref170" ref-type="bibr">170</xref>
] 2010</td>
<td align="left" valign="top" rowspan="1" colspan="1">210 R/BR-PC
<break></break>
Resected-100%, R1-32%</td>
<td align="left" valign="top" rowspan="1" colspan="1">Retrospective</td>
<td align="left" valign="top" rowspan="1" colspan="1">IOERT</td>
<td align="left" valign="top" rowspan="1" colspan="1">20–30</td>
<td align="left" valign="top" rowspan="1" colspan="1">30</td>
<td align="left" valign="top" rowspan="1" colspan="1">26</td>
<td align="left" valign="top" rowspan="1" colspan="1">84 (2yr)</td>
<td align="left" valign="top" rowspan="1" colspan="1">42 (2yr)</td>
<td align="left" valign="top" rowspan="1" colspan="1">Late toxicity
<break></break>
GI-7
<xref ref-type="table-fn" rid="table12-fn1">
<sup>*</sup>
</xref>
</td>
</tr>
<tr>
<td align="left" valign="top" rowspan="1" colspan="1">Calvo
<italic>et al</italic>
. [
<xref rid="ref166" ref-type="bibr">166</xref>
]
<break></break>
2013</td>
<td align="left" valign="top" rowspan="1" colspan="1">60 R/BR-PC
<break></break>
(Resected-83%,
<break></break>
<italic>R</italic>
1-43%)
<break></break>
IORT-29
<break></break>
No IORT-31</td>
<td align="left" valign="top" rowspan="1" colspan="1">Prospective</td>
<td align="left" valign="top" rowspan="1" colspan="1">IOERT</td>
<td align="left" valign="top" rowspan="1" colspan="1">10–15</td>
<td align="left" valign="top" rowspan="1" colspan="1">100%
<break></break>
(Pre-op CTRT-32%)</td>
<td align="left" valign="top" rowspan="1" colspan="1">16</td>
<td align="left" valign="top" rowspan="1" colspan="1">58
<break></break>
No IORT:
<break></break>
HR-6.75,
<break></break>
<italic>p</italic>
= 0.01</td>
<td align="left" valign="top" rowspan="1" colspan="1">20
<break></break>
</td>
<td align="left" valign="top" rowspan="1" colspan="1">Perioperative complications-43% (N.S)
<break></break>
Chronic-17%
<break></break>
Neuropathy-4
<xref ref-type="table-fn" rid="table12-fn1">
<sup>*</sup>
</xref>
<break></break>
GI-3
<xref ref-type="table-fn" rid="table12-fn1">
<sup>*</sup>
</xref>
</td>
</tr>
</tbody>
</table>
<table-wrap-foot>
<p>RCT: randomised control trial, NRC: non-randomised comparison, Sx: surgery, LC: local control, OS: overall survival, DFS: disease-free survival, NR: not reported,</p>
<fn id="table12-fn1">
<label>
<sup>*</sup>
</label>
<p>Number of patients,</p>
</fn>
<p>
<sup>#</sup>
fractions, Pre-op: pre-operative, Post-op: post-operative, M.S: median survival in months, N.S: non-significant, R/BR-PC: resectable/borderline resectable pancreatic cancer, UR-PC: unresectable pancreatic cancer, NACTRT: neoadjuvant chemoradiotherapy, Resected: complete resections (R0/R1), Unresectable: R2/palliative resections.</p>
</table-wrap-foot>
</table-wrap>
</floats-group>
</pmc>
<affiliations>
<list></list>
<tree>
<noCountry>
<name sortKey="Ghosh Laskar, Sarbani" sort="Ghosh Laskar, Sarbani" uniqKey="Ghosh Laskar S" first="Sarbani" last="Ghosh Laskar">Sarbani Ghosh Laskar</name>
<name sortKey="Gupta, Meetakshi" sort="Gupta, Meetakshi" uniqKey="Gupta M" first="Meetakshi" last="Gupta">Meetakshi Gupta</name>
<name sortKey="Laskar, Siddhartha" sort="Laskar, Siddhartha" uniqKey="Laskar S" first="Siddhartha" last="Laskar">Siddhartha Laskar</name>
<name sortKey="Pilar, Avinash" sort="Pilar, Avinash" uniqKey="Pilar A" first="Avinash" last="Pilar">Avinash Pilar</name>
</noCountry>
</tree>
</affiliations>
</record>

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