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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Frequency of Certain Established Risk Factors in Soft Tissue Sarcomas in Adults: A Prospective Descriptive Study of 658 Cases</title><author><name sortKey="Penel, Nicolas" sort="Penel, Nicolas" uniqKey="Penel N" first="Nicolas" last="Penel">Nicolas Penel</name><affiliation><nlm:aff id="I1">Département de Cancérologie Générale, Centre Oscar Lambret, 59020 Lille, France</nlm:aff></affiliation></author><author><name sortKey="Grosjean, Jessica" sort="Grosjean, Jessica" uniqKey="Grosjean J" first="Jessica" last="Grosjean">Jessica Grosjean</name><affiliation><nlm:aff id="I1">Département de Cancérologie Générale, Centre Oscar Lambret, 59020 Lille, France</nlm:aff></affiliation></author><author><name sortKey="Robin, Yves Marie" sort="Robin, Yves Marie" uniqKey="Robin Y" first="Yves Marie" last="Robin">Yves Marie Robin</name><affiliation><nlm:aff id="I2">Laboratoire d'Anatomopathologie, Centre Oscar Lambret, 59020 Lille, France</nlm:aff></affiliation></author><author><name sortKey="Vanseymortier, Luc" sort="Vanseymortier, Luc" uniqKey="Vanseymortier L" first="Luc" last="Vanseymortier">Luc Vanseymortier</name><affiliation><nlm:aff>NONE</nlm:aff></affiliation><affiliation><nlm:aff>NONE</nlm:aff></affiliation></author><author><name sortKey="Clisant, Stephanie" sort="Clisant, Stephanie" uniqKey="Clisant S" first="Stéphanie" last="Clisant">Stéphanie Clisant</name><affiliation><nlm:aff id="I4">Unité de Recherche Clinique, Centre Oscar Lambret, 59020 Lille, France</nlm:aff></affiliation></author><author><name sortKey="Adenis, Antoine" sort="Adenis, Antoine" uniqKey="Adenis A" first="Antoine" last="Adenis">Antoine Adenis</name><affiliation><nlm:aff id="I3">Département de Cancérologie Digestive et Urologique, Centre Oscar Lambret, 59020 Lille, France</nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">18497869</idno><idno type="pmc">2386887</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2386887</idno><idno type="RBID">PMC:2386887</idno><idno type="doi">10.1155/2008/459386</idno><date when="2008">2008</date><idno type="wicri:Area/Pmc/Corpus">002698</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">002698</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Frequency of Certain Established Risk Factors in Soft Tissue Sarcomas in Adults: A Prospective Descriptive Study of 658 Cases</title><author><name sortKey="Penel, Nicolas" sort="Penel, Nicolas" uniqKey="Penel N" first="Nicolas" last="Penel">Nicolas Penel</name><affiliation><nlm:aff id="I1">Département de Cancérologie Générale, Centre Oscar Lambret, 59020 Lille, France</nlm:aff></affiliation></author><author><name sortKey="Grosjean, Jessica" sort="Grosjean, Jessica" uniqKey="Grosjean J" first="Jessica" last="Grosjean">Jessica Grosjean</name><affiliation><nlm:aff id="I1">Département de Cancérologie Générale, Centre Oscar Lambret, 59020 Lille, France</nlm:aff></affiliation></author><author><name sortKey="Robin, Yves Marie" sort="Robin, Yves Marie" uniqKey="Robin Y" first="Yves Marie" last="Robin">Yves Marie Robin</name><affiliation><nlm:aff id="I2">Laboratoire d'Anatomopathologie, Centre Oscar Lambret, 59020 Lille, France</nlm:aff></affiliation></author><author><name sortKey="Vanseymortier, Luc" sort="Vanseymortier, Luc" uniqKey="Vanseymortier L" first="Luc" last="Vanseymortier">Luc Vanseymortier</name><affiliation><nlm:aff>NONE</nlm:aff></affiliation><affiliation><nlm:aff>NONE</nlm:aff></affiliation></author><author><name sortKey="Clisant, Stephanie" sort="Clisant, Stephanie" uniqKey="Clisant S" first="Stéphanie" last="Clisant">Stéphanie Clisant</name><affiliation><nlm:aff id="I4">Unité de Recherche Clinique, Centre Oscar Lambret, 59020 Lille, France</nlm:aff></affiliation></author><author><name sortKey="Adenis, Antoine" sort="Adenis, Antoine" uniqKey="Adenis A" first="Antoine" last="Adenis">Antoine Adenis</name><affiliation><nlm:aff id="I3">Département de Cancérologie Digestive et Urologique, Centre Oscar Lambret, 59020 Lille, France</nlm:aff></affiliation></author></analytic><series><title level="j">Sarcoma</title><idno type="ISSN">1357-714X</idno><idno type="eISSN">1369-1643</idno><imprint><date when="2008">2008</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>Soft tissue sarcomas are rare tumours with infrequent identified aetiological factors. Several genetic syndromes as well as previous radiation therapy and/or chronic lymphoedema have been suspected to predispose to some soft tissue sarcomas.
Between January 1997 and September 2005, we carried out a prospective descriptive study to estimate the frequency of some particular etiological factors among 658 patients with soft tissue sarcomas.
Sarcomas associated with a clinically identified genetic disease represent 2.8% out of all cases (95%CI: 1.5–3.8%). Most of these cases (14/19) are related to Recklinghausen neurofibromatosis. Radiation-induced sarcomas represent 3.3% out of all cases (95%CI: 1.7–5.1%). Most of these cases (9/22) are related to prior breast cancer treatment. We had observed only 1 case of Stewart-Treves syndrome. Liposarcoma, the most frequent histological subtype observed, is not associated with any particular aetiological entity.
Finally, most of the adult soft tissue sarcomas are not related to any classical clinically identified genetic disease or previous radiation therapy and/or chronic lymphoedema risk factors. Frequency of underlying genetic syndrome which may predispose to soft tissue sarcomas could be higher than previously reported.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Zahm, Sh" uniqKey="Zahm S">SH Zahm</name></author><author><name sortKey="Fraumeni, Jf" uniqKey="Fraumeni J">JF Fraumeni</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Levi, F" uniqKey="Levi F">F Levi</name></author><author><name sortKey="La Vecchia, C" uniqKey="La Vecchia C">C La Vecchia</name></author><author><name sortKey="Randimbison, L" uniqKey="Randimbison L">L Randimbison</name></author><author><name sortKey="Te, V C" uniqKey="Te V">V-C Te</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Coindre, J M" uniqKey="Coindre J">J-M Coindre</name></author><author><name sortKey="Terrier, P" uniqKey="Terrier P">P Terrier</name></author><author><name sortKey="Guillou, L" uniqKey="Guillou L">L 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<front><journal-meta><journal-id journal-id-type="nlm-ta">Sarcoma</journal-id><journal-id journal-id-type="iso-abbrev">Sarcoma</journal-id><journal-id journal-id-type="publisher-id">SRCM</journal-id><journal-title-group><journal-title>Sarcoma</journal-title></journal-title-group><issn pub-type="ppub">1357-714X</issn><issn pub-type="epub">1369-1643</issn><publisher><publisher-name>Hindawi Publishing Corporation</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">18497869</article-id><article-id pub-id-type="pmc">2386887</article-id><article-id pub-id-type="doi">10.1155/2008/459386</article-id><article-categories><subj-group subj-group-type="heading"><subject>Clinical Study</subject></subj-group></article-categories><title-group><article-title>Frequency of Certain Established Risk Factors in Soft Tissue Sarcomas in Adults: A Prospective Descriptive Study of 658 Cases</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Penel</surname><given-names>Nicolas</given-names></name><xref ref-type="aff" rid="I1"><sup>1</sup></xref><xref ref-type="corresp" rid="cor1">*</xref></contrib><contrib contrib-type="author"><name><surname>Grosjean</surname><given-names>Jessica</given-names></name><xref ref-type="aff" rid="I1"><sup>1</sup></xref></contrib><contrib contrib-type="author"><name><surname>Robin</surname><given-names>Yves Marie</given-names></name><xref ref-type="aff" rid="I2"><sup>2</sup></xref></contrib><contrib contrib-type="author"><name><surname>Vanseymortier</surname><given-names>Luc</given-names></name><xref ref-type="aff" rid="I1"><sup>1, 3</sup></xref><xref ref-type="aff" rid="I3"></xref></contrib><contrib contrib-type="author"><name><surname>Clisant</surname><given-names>Stéphanie</given-names></name><xref ref-type="aff" rid="I4"><sup>4</sup></xref></contrib><contrib contrib-type="author"><name><surname>Adenis</surname><given-names>Antoine</given-names></name><xref ref-type="aff" rid="I3"><sup>3</sup></xref></contrib></contrib-group><aff id="I1"><sup>1</sup>Département de Cancérologie Générale, Centre Oscar Lambret, 59020 Lille, France</aff><aff id="I2"><sup>2</sup>Laboratoire d'Anatomopathologie, Centre Oscar Lambret, 59020 Lille, France</aff><aff id="I3"><sup>3</sup>Département de Cancérologie Digestive et Urologique, Centre Oscar Lambret, 59020 Lille, France</aff><aff id="I4"><sup>4</sup>Unité de Recherche Clinique, Centre Oscar Lambret, 59020 Lille, France</aff><author-notes><corresp id="cor1">*Nicolas Penel: <email>n-penel@o-lambret.fr</email></corresp><fn fn-type="other"><p>Recommended by Ole Nielsen</p></fn></author-notes><pub-date pub-type="ppub"><year>2008</year></pub-date><pub-date pub-type="epub"><day>11</day><month>5</month><year>2008</year></pub-date><volume>2008</volume><elocation-id>459386</elocation-id><history><date date-type="received"><day>19</day><month>6</month><year>2007</year></date><date date-type="rev-recd"><day>20</day><month>1</month><year>2008</year></date><date date-type="accepted"><day>6</day><month>3</month><year>2008</year></date></history><permissions><copyright-statement>Copyright © 2008 Nicolas Penel et al.</copyright-statement><copyright-year>2008</copyright-year><license xlink:href="https://creativecommons.org/licenses/by/3.0/"><license-p>This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.</license-p></license></permissions><abstract><p>Soft tissue sarcomas are rare tumours with infrequent identified aetiological factors. Several genetic syndromes as well as previous radiation therapy and/or chronic lymphoedema have been suspected to predispose to some soft tissue sarcomas.
Between January 1997 and September 2005, we carried out a prospective descriptive study to estimate the frequency of some particular etiological factors among 658 patients with soft tissue sarcomas.
Sarcomas associated with a clinically identified genetic disease represent 2.8% out of all cases (95%CI: 1.5–3.8%). Most of these cases (14/19) are related to Recklinghausen neurofibromatosis. Radiation-induced sarcomas represent 3.3% out of all cases (95%CI: 1.7–5.1%). Most of these cases (9/22) are related to prior breast cancer treatment. We had observed only 1 case of Stewart-Treves syndrome. Liposarcoma, the most frequent histological subtype observed, is not associated with any particular aetiological entity.
Finally, most of the adult soft tissue sarcomas are not related to any classical clinically identified genetic disease or previous radiation therapy and/or chronic lymphoedema risk factors. Frequency of underlying genetic syndrome which may predispose to soft tissue sarcomas could be higher than previously reported.</p></abstract></article-meta></front><body><sec id="sec1"><title>1. INTRODUCTION</title><p>Soft tissue sarcomas (STS) are rare tumours. Their estimated incidence is close
to 3–4.5/100 000 [<xref rid="B1" ref-type="bibr">1</xref>, <xref rid="B2" ref-type="bibr">2</xref>]. Most of these cancers had no clearly defined cause but
several infrequent predisposing factors have been described, such as genetic
predisposition (including mainly Recklinghausen disease and bilateral
retinoblastoma) and iatrogenic factors (postirradiation sarcoma and
postoperative chronic lymphoedema) [<xref rid="B1" ref-type="bibr">1</xref>, <xref rid="B2" ref-type="bibr">2</xref>]. Several
previous studies have been conducted on this topic, but have been focused on
only one of these particular risk factors. There is no recent study analyzing
the frequency of all these risk factors on the same cohort of patients. In order to estimate the frequency
of these specific factors in adults with STS, we carried out along a 105-month period a prospective study on all new
consecutive cases treated in a single institution located in Northern
France area (4 millions inhabitants).</p></sec><sec id="sec2"><title>2. PATIENTS AND METHODS</title><sec sec-type="subsection" id="subsec2.1"><title>2.1. Patients</title><p>We have prospectively collected some clinical characteristics of
all new consecutive cases of adult (over 18 years old) (STS) treated at the Northern France Comprehensive Cancer centre
(namely, Centre Oscar Lambret) between January 1997 and September 2005. Three
kinds of tumours were excluded from this study, because
these cases were not (Kaposi tumours, mixed mullerian tumours of uterus) or
very recently (GIST) treated in our institution.</p></sec><sec sec-type="subsection" id="subsec2.2"><title>2.2. Data collection</title><p>The database included age at diagnosis, gender, tumour
location, histological subtype, grade (according to the Fédération Nationale
des Centres de Lutte Contre le Cancer System [<xref rid="B3" ref-type="bibr">3</xref>]), association with genetic
syndrome, previous or synchronous other malignancy, postoperative lymphoedema
(Stewart-Treves Syndrome), or postirradiation sarcoma. </p><p>A pathological review or a histological diagnosis
established in a reference centre is available in all cases (658). The grade is
available in 384 cases (58%).</p></sec><sec sec-type="subsection" id="subsec2.3"><title>2.3. Definitions</title><p>The diagnosis of genetic syndrome was based on
familial history criteria and clinical and phenotypic criteria [<xref rid="B4" ref-type="bibr">4</xref>–<xref rid="B9" ref-type="bibr">9</xref>]. For
example, a patient meeting two or more of the following criteria can be
diagnosed as suffering from Recklinghausen's neurofibromatosis: (i)
neurofibromas (two or more, or one plexiform neurofibroma), (ii) “café-au-lait”
macules (six or more measuring 1.5 cm in their greatest dimension), (iii)
freckling in the axillary's or inguinal
areas, (iv) optic glioma, (v) iris hamartomas (two or more), (vi) sphenoid
dysplasia (or thinning of the cortex of the long bones), and (vii)
first-degree relative [<xref rid="B4" ref-type="bibr">4</xref>]. The other
syndromes expected were: Li-Fraumeni syndrome [<xref rid="B5" ref-type="bibr">5</xref>], bilateral retinoblastoma
syndrome [<xref rid="B6" ref-type="bibr">6</xref>], Gardner
syndrome or familial polyposis adenomatous [<xref rid="B7" ref-type="bibr">7</xref>], adult progeria [<xref rid="B8" ref-type="bibr">8</xref>], and Gorlin
syndrome [<xref rid="B9" ref-type="bibr">9</xref>].</p><p>The diagnosis of radiation-induced sarcoma was based
on Arlen et al. [<xref rid="B10" ref-type="bibr">10</xref>] criteria: (i) histological diagnosis of sarcoma, (ii)
different histological diagnosis of the previous cancer, (iii) tumour in the border of radiation field, and (iv) a minimal
time interval of 3 years.</p></sec><sec sec-type="subsection" id="subsec2.4"><title>2.4. Statistical analysis</title><p>The description of population is based on crude
incidence with 95%-confidence interval for categorical parameters, median and
extreme values, or mean and standard deviation for continuous parameters. The
comparisons are based on Fisher exact test for categorical data and
Mann-Whitney test for continuous parameters. The significance was set up at 5%.</p></sec></sec><sec id="sec3"><title>3. RESULTS</title><sec sec-type="subsection" id="subsec3.1"><title>3.1. All new cases
treated between January 1997 and October 2005</title><p>The entire population included 658 cases. The sex
ratio male/female was 309/349 (excluding uterus sarcoma, the sex ratio was
309/308). At diagnosis, the median age was 52 (range, 18–99). The most common
histological subtypes were liposarcomas (20%),
leiomyosarcomas (17%), malignant fibrous histiocytofibromas (11%), and undifferentiated sarcomas (10%). The grade was 1 in 25% of cases, 2 in 26%, and 3 in 48%. The
tumour locations are listed in <xref ref-type="table" rid="tab1">Table 1</xref>. The main locations were lower limbs (34%), chest wall (15%), upper limbs (13%),
and retroperitoneum (10%).</p></sec><sec sec-type="subsection" id="subsec3.2"><title>3.2. STS associated
with genetic syndrome</title><p>Nineteen patients suffered from a genetic syndrome and
represented 2.8% out of all cases (IC95%: 1.5–3.8%). Most common genetic
syndromes were Recklinghausen
neurofibromatosis (14 cases) and bilateral retinoblastoma (2 cases). In this
subpopulation, the sex ratio was 13/6 and the median age at diagnosis was 37.5
(range, 18–64). Locations,
histological subtype, and grade are listed in <xref ref-type="table" rid="tab2">Table 2</xref>.</p><p> At diagnosis, these STS
associated with genetic syndrome were significantly younger than the entire
cohort (Median age 37.5 versus 53 years, <italic>P</italic> = .0016). In comparison with
other cases, these patients were more frequently located on trunk (<italic>P</italic> = .002) and
were more frequently peripheral malignant nerve sheath tumours (<italic>P</italic> = .005).
On the contrary, liposarcomas were significantly less frequent in STS associated with genetic syndrome (<italic>P</italic> = .04).</p></sec><sec sec-type="subsection" id="subsec3.3"><title>3.3. Stewart-Treves
syndrome</title><p>We had observed only one case of angiosarcoma
associated with previous lymphoedema as a consequence of surgical treatment of
a previous breast cancer.</p></sec><sec sec-type="subsection" id="subsec3.4"><title>3.4. Radiation-induced
soft tissue sarcomas</title><p>Twenty two radiation-induced STSs were observed. Location, histological subtypes, and grade
are listed in <xref ref-type="table" rid="tab3">Table 3</xref>. The mean
interval from the first cancer was 10 years (range, 3–45 years). The
most common previous cancers were breast cancers (10 cases) and non-Hodgkin
lymphomas (4 cases). At diagnosis, the patients were significantly older than
the entire cohort (median age 66 versus 53 years, <italic>P</italic> = .04). In comparison
with other cases, the radiation-induced were more frequently located on chest
wall (<italic>P</italic> = .002) and were more frequently undifferentiated spindle cell
sarcoma (<italic>P</italic> = .003) or angiosarcoma (<italic>P</italic> = .005). On the contrary,
liposarcomas were significantly less frequent in radiation-induced sarcoma
group (<italic>P</italic> < .001).</p></sec></sec><sec id="sec4"><title>4. DISCUSSION</title><p>In this prospective study of 658 adult STS, about 6% of patients present a
well-established risk factor: a genetic syndrome (2.8%) or an iatrogenic factor
such as previous radiation therapy (3.3%) or a postoperative chronic
lymphoedema (1 case). The characteristics of our entire group of patients
are consistent literature; the sex ratio is closed to 1 [<xref rid="B1" ref-type="bibr">1</xref>, <xref rid="B2" ref-type="bibr">2</xref>], the median age
is 55 years [<xref rid="B1" ref-type="bibr">1</xref>], lower and upper limbs locations are the most frequent,
liposarcomas and leiomyosarcoma are the most common histological subtypes
(after excluding malignant fibrous histiocytofibroma),
and grade 3 tumours are the most frequent [<xref rid="B11" ref-type="bibr">11</xref>, <xref rid="B12" ref-type="bibr">12</xref>].</p><p>Twenty two cases out of 658 (3.3%, 95% CsI: 1.7–5.1%)
present a radiation-induced STS. In
longitudinal studies, the prevalence of radiation-induced sarcomas is very low,
close to 0.14–0.20% [<xref rid="B13" ref-type="bibr">13</xref>–<xref rid="B15" ref-type="bibr">15</xref>]. After treatment by radiotherapy, the relative risk
for development of STS is comprised
between 8 and 50 [<xref rid="B10" ref-type="bibr">10</xref>, <xref rid="B13" ref-type="bibr">13</xref>, <xref rid="B14" ref-type="bibr">14</xref>]. As previously published [<xref rid="B16" ref-type="bibr">16</xref>], in our series,
breast cancers and lymphomas were the most frequent previous primaries treated
with radiation therapy. Radiation-induced sarcomas are more frequently STS (70%) than osseous sarcomas (30%) [<xref rid="B16" ref-type="bibr">16</xref>]. Malignant fibrous histiocytofibromas (16% in
the Brady et al. series) and angiosarcomas (15%) are the most common
histological subtype of radiation-induced STS.
The liposarcomas are exceptional [<xref rid="B16" ref-type="bibr">16</xref>]. In the Weiss and Enzinger series, about
10% of angiosarcomas
are radio-induced [<xref rid="B17" ref-type="bibr">17</xref>]. Radiation-induced STS
are usually high-grade tumours, for example, in the Brady's series, less than
6% of radio-induced sarcomas are grade 1 [<xref rid="B18" ref-type="bibr">18</xref>]. The radiation-induced sarcomas
are usually developed at the peripheral borders
of radiation fields. The mean interval from the first cancer treatment is about
10 years (range, 2 and 67 years) [<xref rid="B10" ref-type="bibr">10</xref>, <xref rid="B13" ref-type="bibr">13</xref>–<xref rid="B16" ref-type="bibr">16</xref>]. Angiosarcomas seem occur after a
shorter interval (about 5 years) [<xref rid="B10" ref-type="bibr">10</xref>, <xref rid="B13" ref-type="bibr">13</xref>–<xref rid="B15" ref-type="bibr">15</xref>]. The interval is also shorter in
cases associated with Bilateral Retinoblastoma [<xref rid="B6" ref-type="bibr">6</xref>].</p><p>The Stewart-Treves syndrome is defined as the
development of angiosarcoma or lymphangiosarcoma on chronic lymphoedema
whatever its cause (congenital,
postsurgical, or caused by filariosis,…) [<xref rid="B18" ref-type="bibr">18</xref>]. The
Stewart-Treves syndrome is exceptional and about 300 cases are known in
literature. Most of cases (168/186) are observed after axillary's clearance for
breast cancer [<xref rid="B19" ref-type="bibr">19</xref>]. In the Connecticut Registry, 8 cases are diagnosed after
the treatment of more than 41000 breast cancers [<xref rid="B21" ref-type="bibr">20</xref>]. The mean interval is
about 10 years (4–27) for cases secondary to breast cancer treatment [<xref rid="B18" ref-type="bibr">18</xref>, <xref rid="B19" ref-type="bibr">19</xref>, <xref rid="B20" ref-type="bibr">21</xref>].
The Stewart-Treves syndrome represents about 5% of all angiosarcomas [<xref rid="B18" ref-type="bibr">18</xref>, <xref rid="B19" ref-type="bibr">19</xref>, <xref rid="B20" ref-type="bibr">21</xref>].</p><p> In contrast to literature that
describes STS are classically related to genetic syndromes in less than 1% [<xref rid="B1" ref-type="bibr">1</xref>]
this study shows that 2.8% [1.5–3.8] of our patients suffered from a
clinically-diagnosed genetic syndrome. Recklinghausen
neurofibromatosis and bilateral retinoblastoma predominate. Other genetic
syndromes (Li-Fraumeni syndrome, Gardner
syndrome, ataxia-telangiectasia, and progeria) appear exceptional. We had no clear explanation to the present higher
than previously described frequency of genetic syndrome.</p><p> The estimated incidence of Recklinghausen
Neurofibromatosis is about 1/3,000–1/5,000. Fifty percent of cases are
sporadic [<xref rid="B4" ref-type="bibr">4</xref>, <xref rid="B21" ref-type="bibr">20</xref>]. These patients had a relative risk of cancers (including STS
and other sarcomas) about 4 in comparison with general population [<xref rid="B4" ref-type="bibr">4</xref>, <xref rid="B21" ref-type="bibr">20</xref>].
Cancers are the first cause of precocious deaths in such population. About 5%
of patients affected by Recklinghausen Neurofibromatosis develop malignant
peripheral nerve sheath tumour (MPNST). The MPNST are usually developed on a
neurofibroma [<xref rid="B4" ref-type="bibr">4</xref>, <xref rid="B22" ref-type="bibr">22</xref>] and can be multiple [<xref rid="B4" ref-type="bibr">4</xref>, <xref rid="B22" ref-type="bibr">22</xref>]. The male predominance is well
established (sex ratio 4/1 [<xref rid="B23" ref-type="bibr">23</xref>]). The median age at diagnosis of STS is about 32–36, clearly inferior to age
diagnosis in general population [<xref rid="B22" ref-type="bibr">22</xref>, <xref rid="B23" ref-type="bibr">23</xref>]. Classically, about 40% of MPNST is
associated with Recklinghausen Neurofibromatosis [<xref rid="B23" ref-type="bibr">23</xref>]. In our experience, 8 out
of 24 MPNST are associated with Recklinghausen Neurofibromatosis. The prognosis
of MPNST is not influenced by the presence of Recklinghausen Neurofibromatosis;
the 5-year overall survival is about 40% [<xref rid="B23" ref-type="bibr">23</xref>]. In our study, all findings are
consistent with the literature data (male predominance, young age, mainly
MPNST).</p><p> The present study presents several limitations.
Firstly, our study is not exhaustive; because according to estimated incidence
(3–4.4/100 000) [<xref rid="B1" ref-type="bibr">1</xref>, <xref rid="B2" ref-type="bibr">2</xref>] of adult STS in
Western countries, a total number comprised between 1140 and 1670 cases are
expected in our region in the same period. In consequence, we estimate that our
cohort represent between 44% and 65% of all cases. Secondly, it is a
single-centre study and our results may not be directly applicable to other
areas in France
or abroad. The malignant nature of
aggressive fibromatosis is still debated, but more recent reports suggest that
a part of these tumours must be considered as a particular form of low-grade
fibrosarcoma [<xref rid="B25" ref-type="bibr">24</xref>, <xref rid="B26" ref-type="bibr">25</xref>]. Because of recent
progress in histology, the proportion of the different histological subtypes
must be considered with caution. For example, the “malignant fibrous histiocytofibroma” actually disappears and
this diagnosis is modified into dedifferentiated liposarcoma and
dedifferentiated leiomyosarcoma [<xref rid="B24" ref-type="bibr">26</xref>]. Moreover, the diagnosis of genetic
syndromes were based on clinical criteria, a systematic genetic testing can
possibly modify those results.</p><sec sec-type="subsection" id="subsec4.1"><title>4.1. Conclusion</title><p>Most cases of adult STS
(94% in our experience) are not related to well-established risk factors
(radiation, genetic disease, and chronic lymphedema). Liposarcoma is the most
frequent histological subtype, but it is rarely associated with genetic disease
or postirradiation. New epidemiological explorations are necessary to analyze,
for example, the environmental and occupational risk factors (such as arsenic,
phenoxy-herbicides) and new iatrogenic factors (such as new chemotherapy agents
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of 658 patients with visceral and soft
tissue sarcomas treated at Oscar Lambret Cancer Centre between January 1997 and
September 2005. MPNST: malignant peripheral nerve sheath tumour.</p></caption><table frame="hsides" rules="groups"><thead><tr><th align="left" rowspan="1" colspan="1">Sex ratio</th><th align="center" colspan="3" rowspan="1">309 males/349 females</th></tr></thead><tbody><tr><td rowspan="2" colspan="1">Age</td><td align="center" colspan="3" rowspan="1">Median: 52 (18–99)</td></tr><tr><td align="center" colspan="3" rowspan="1">Mean: 52.4 (+/− 17.5)</td></tr><tr><td align="center" colspan="4" rowspan="1"><hr></hr></td></tr><tr><td rowspan="1" colspan="1">Parameter</td><td align="center" rowspan="1" colspan="1">Number
of cases</td><td align="center" rowspan="1" colspan="1">Percentage</td><td align="center" rowspan="1" colspan="1">95%-CI</td></tr><tr><td align="center" colspan="4" rowspan="1"><hr></hr></td></tr><tr><td rowspan="1" colspan="1">Liposarcoma</td><td align="center" rowspan="1" colspan="1">132</td><td align="center" rowspan="1" colspan="1">20.0</td><td align="center" rowspan="1" colspan="1">17–23</td></tr><tr><td rowspan="1" colspan="1">Leiomyosarcoma</td><td align="center" rowspan="1" colspan="1">113</td><td align="center" rowspan="1" colspan="1">17.0</td><td align="center" rowspan="1" colspan="1">14–20</td></tr><tr><td rowspan="1" colspan="1">Malignant histiocytofibroma</td><td align="center" rowspan="1" colspan="1">77</td><td align="center" rowspan="1" colspan="1">12.0</td><td align="center" rowspan="1" colspan="1">9–14</td></tr><tr><td rowspan="1" colspan="1">Undifferentiated sarcoma</td><td align="center" rowspan="1" colspan="1">65</td><td align="center" rowspan="1" colspan="1">9.8</td><td align="center" rowspan="1" colspan="1">7–12</td></tr><tr><td rowspan="1" colspan="1">Synovialosarcoma</td><td align="center" rowspan="1" colspan="1">43</td><td align="center" rowspan="1" colspan="1">6.5</td><td align="center" rowspan="1" colspan="1">4–8</td></tr><tr><td rowspan="1" colspan="1">Aggressive fibromatosis</td><td align="center" rowspan="1" colspan="1">32</td><td align="center" rowspan="1" colspan="1">4.8</td><td align="center" rowspan="1" colspan="1">3–6</td></tr><tr><td rowspan="1" colspan="1"> Angiosarcoma</td><td align="center" rowspan="1" colspan="1">28</td><td align="center" rowspan="1" colspan="1">4.2</td><td align="center" rowspan="1" colspan="1">3–6</td></tr><tr><td rowspan="1" colspan="1">Rhabdomyosarcoma</td><td align="center" rowspan="1" colspan="1">26</td><td align="center" rowspan="1" colspan="1">4.0</td><td align="center" rowspan="1" colspan="1">2–5</td></tr><tr><td rowspan="1" colspan="1">MPNST</td><td align="center" rowspan="1" colspan="1">24</td><td align="center" rowspan="1" colspan="1">3.6</td><td align="center" rowspan="1" colspan="1">2–5</td></tr><tr><td rowspan="1" colspan="1">Others</td><td align="center" rowspan="1" colspan="1">118</td><td align="center" rowspan="1" colspan="1">18.0</td><td align="center" rowspan="1" colspan="1">15–20</td></tr><tr><td align="center" colspan="4" rowspan="1"><hr></hr></td></tr><tr><td rowspan="1" colspan="1">Grade 1</td><td align="center" rowspan="1" colspan="1">97</td><td align="center" rowspan="1" colspan="1">25.2</td><td align="center" rowspan="1" colspan="1">21–30</td></tr><tr><td rowspan="1" colspan="1">Grade 2</td><td align="center" rowspan="1" colspan="1">101</td><td align="center" rowspan="1" colspan="1">26.3</td><td align="center" rowspan="1" colspan="1">22–30</td></tr><tr><td rowspan="1" colspan="1">Grade 3</td><td align="center" rowspan="1" colspan="1">186</td><td align="center" rowspan="1" colspan="1">48.4</td><td align="center" rowspan="1" colspan="1">43–53</td></tr><tr><td align="center" colspan="4" rowspan="1"><hr></hr></td></tr><tr><td rowspan="1" colspan="1">Lower limbs</td><td align="center" rowspan="1" colspan="1">225</td><td align="center" rowspan="1" colspan="1">34.2</td><td align="center" rowspan="1" colspan="1">30–38</td></tr><tr><td rowspan="1" colspan="1">Chest wall</td><td align="center" rowspan="1" colspan="1">99</td><td align="center" rowspan="1" colspan="1">15.0</td><td align="center" rowspan="1" colspan="1">12–17</td></tr><tr><td rowspan="1" colspan="1">Upper limbs</td><td align="center" rowspan="1" colspan="1">86</td><td align="center" rowspan="1" colspan="1">13.0</td><td align="center" rowspan="1" colspan="1">9–14</td></tr><tr><td rowspan="1" colspan="1">Retroperitoneum</td><td align="center" rowspan="1" colspan="1">69</td><td align="center" rowspan="1" colspan="1">10.4</td><td align="center" rowspan="1" colspan="1">8–12</td></tr><tr><td rowspan="1" colspan="1">Head and neck</td><td align="center" rowspan="1" colspan="1">48</td><td align="center" rowspan="1" colspan="1">7.2</td><td align="center" rowspan="1" colspan="1">5–9</td></tr><tr><td rowspan="1" colspan="1">Uterus</td><td align="center" rowspan="1" colspan="1">41</td><td align="center" rowspan="1" colspan="1">6.2</td><td align="center" rowspan="1" colspan="1">4–8</td></tr><tr><td rowspan="1" colspan="1">Abdominal wall</td><td align="center" rowspan="1" colspan="1">40</td><td align="center" rowspan="1" colspan="1">6.0</td><td align="center" rowspan="1" colspan="1">4–8</td></tr><tr><td rowspan="1" colspan="1">Breast</td><td align="center" rowspan="1" colspan="1">30</td><td align="center" rowspan="1" colspan="1">4.5</td><td align="center" rowspan="1" colspan="1">3–6</td></tr><tr><td rowspan="1" colspan="1">Pelvis</td><td align="center" rowspan="1" colspan="1">13</td><td align="center" rowspan="1" colspan="1">1.9</td><td align="center" rowspan="1" colspan="1">1–3</td></tr><tr><td rowspan="1" colspan="1">Others</td><td align="center" rowspan="1" colspan="1">7</td><td align="center" rowspan="1" colspan="1">1.0</td><td align="center" rowspan="1" colspan="1">3–6</td></tr></tbody></table></table-wrap><table-wrap id="tab2" position="float"><label>Table 2</label><caption><p>Sarcomas
associated with genetic syndromes.</p></caption><table frame="hsides" rules="groups"><thead><tr><th align="left" rowspan="1" colspan="1">Sex ratio</th><th align="center" colspan="3" rowspan="1">13 males/6 females</th></tr></thead><tbody><tr><td rowspan="2" colspan="1">Age</td><td align="center" colspan="3" rowspan="1">Median: 37.5 (18–64)</td></tr><tr><td align="center" colspan="3" rowspan="1">Mean: 37.5 (+/− 14)</td></tr><tr><td align="center" colspan="4" rowspan="1"><hr></hr></td></tr><tr><td rowspan="1" colspan="1">Parameter</td><td align="center" rowspan="1" colspan="1">Number of cases</td><td align="center" rowspan="1" colspan="1">Percentage</td><td align="center" rowspan="1" colspan="1">95%-CI</td></tr><tr><td align="center" colspan="4" rowspan="1"><hr></hr></td></tr><tr><td rowspan="1" colspan="1">Recklinghausen disease</td><td align="center" rowspan="1" colspan="1">14</td><td align="center" rowspan="1" colspan="1">73.6</td><td align="center" rowspan="1" colspan="1">56–95</td></tr><tr><td rowspan="1" colspan="1">Bilateral retinoblastoma</td><td align="center" rowspan="1" colspan="1">2</td><td align="center" rowspan="1" colspan="1">10.5</td><td align="center" rowspan="1" colspan="1">0–23</td></tr><tr><td rowspan="1" colspan="1">Familial polypadenomatosis</td><td align="center" rowspan="1" colspan="1">1</td><td align="center" rowspan="1" colspan="1">5.2</td><td align="center" rowspan="1" colspan="1">0–14</td></tr><tr><td rowspan="1" colspan="1">Gorlin
syndrome</td><td align="center" rowspan="1" colspan="1">1</td><td align="center" rowspan="1" colspan="1">5.2</td><td align="center" rowspan="1" colspan="1">0–14</td></tr><tr><td rowspan="1" colspan="1">Li-Fraumeni
syndrome</td><td align="center" rowspan="1" colspan="1">1</td><td align="center" rowspan="1" colspan="1">5.2</td><td align="center" rowspan="1" colspan="1">0–14</td></tr><tr><td align="center" colspan="4" rowspan="1"><hr></hr></td></tr><tr><td rowspan="1" colspan="1">MPNST</td><td align="center" rowspan="1" colspan="1">7</td><td align="center" rowspan="1" colspan="1">36.8</td><td align="center" rowspan="1" colspan="1">18–61</td></tr><tr><td rowspan="1" colspan="1">Undifferentiated sarcoma</td><td align="center" rowspan="1" colspan="1">4</td><td align="center" rowspan="1" colspan="1">15.7</td><td align="center" rowspan="1" colspan="1">2–37</td></tr><tr><td rowspan="1" colspan="1">Leiomyosarcoma</td><td align="center" rowspan="1" colspan="1">2</td><td align="center" rowspan="1" colspan="1">10.5</td><td align="center" rowspan="1" colspan="1">6–30</td></tr><tr><td rowspan="1" colspan="1">Synovialosarcoma</td><td align="center" rowspan="1" colspan="1">2</td><td align="center" rowspan="1" colspan="1">10.5</td><td align="center" rowspan="1" colspan="1">6–30</td></tr><tr><td rowspan="1" colspan="1">Angiosarcoma</td><td align="center" rowspan="1" colspan="1">1</td><td align="center" rowspan="1" colspan="1">5.2</td><td align="center" rowspan="1" colspan="1">0–14</td></tr><tr><td rowspan="1" colspan="1">Fibrosarcoma</td><td align="center" rowspan="1" colspan="1">1</td><td align="center" rowspan="1" colspan="1">5.2</td><td align="center" rowspan="1" colspan="1">0–14</td></tr><tr><td rowspan="1" colspan="1">Aggressive fibromatosis</td><td align="center" rowspan="1" colspan="1">1</td><td align="center" rowspan="1" colspan="1">5.2</td><td align="center" rowspan="1" colspan="1">0–14</td></tr><tr><td rowspan="1" colspan="1">Rhabdomyosarcoma</td><td align="center" rowspan="1" colspan="1">1</td><td align="center" rowspan="1" colspan="1">5.2</td><td align="center" rowspan="1" colspan="1">0–14</td></tr><tr><td align="center" colspan="4" rowspan="1"><hr></hr></td></tr><tr><td rowspan="1" colspan="1">Grade 1</td><td align="center" rowspan="1" colspan="1">0</td><td align="center" rowspan="1" colspan="1">0</td><td align="center" rowspan="1" colspan="1">0–0</td></tr><tr><td rowspan="1" colspan="1">Grade 2</td><td align="center" rowspan="1" colspan="1">3</td><td align="center" rowspan="1" colspan="1">27.2</td><td align="center" rowspan="1" colspan="1">5–49</td></tr><tr><td rowspan="1" colspan="1">Grade 3</td><td align="center" rowspan="1" colspan="1">8</td><td align="center" rowspan="1" colspan="1">72.8</td><td align="center" rowspan="1" colspan="1">50–99</td></tr><tr><td align="center" colspan="4" rowspan="1"><hr></hr></td></tr><tr><td rowspan="1" colspan="1">Chest wall</td><td align="center" rowspan="1" colspan="1">8</td><td align="center" rowspan="1" colspan="1">42.1</td><td align="center" rowspan="1" colspan="1">14–56</td></tr><tr><td rowspan="1" colspan="1">Lower limb</td><td align="center" rowspan="1" colspan="1">5</td><td align="center" rowspan="1" colspan="1">26.3</td><td align="center" rowspan="1" colspan="1">10–50</td></tr><tr><td rowspan="1" colspan="1">Head and neck</td><td align="center" rowspan="1" colspan="1">3</td><td align="center" rowspan="1" colspan="1">15.8</td><td align="center" rowspan="1" colspan="1">0–30</td></tr><tr><td rowspan="1" colspan="1">Abdominal wall</td><td align="center" rowspan="1" colspan="1">2</td><td align="center" rowspan="1" colspan="1">10.5</td><td align="center" rowspan="1" colspan="1">0–30</td></tr><tr><td rowspan="1" colspan="1">Pulmonary artery</td><td align="center" rowspan="1" colspan="1">1</td><td align="center" rowspan="1" colspan="1">5.2</td><td align="center" rowspan="1" colspan="1">0–14</td></tr></tbody></table></table-wrap><table-wrap id="tab3" position="float"><label>Table 3</label><caption><p>Radiation-induced
sarcomas.</p></caption><table frame="hsides" rules="groups"><thead><tr><th align="left" rowspan="1" colspan="1">Sex ratio</th><th align="center" colspan="3" rowspan="1">5 males /17 females</th></tr></thead><tbody><tr><td rowspan="2" colspan="1">Age</td><td align="center" colspan="3" rowspan="1">Median: 66<italic></italic>(27–83)</td></tr><tr><td align="center" colspan="3" rowspan="1">Mean: 57 (+/− 17)</td></tr><tr><td align="center" colspan="4" rowspan="1"><hr></hr></td></tr><tr><td rowspan="1" colspan="1">Parameter</td><td align="center" rowspan="1" colspan="1">Number of cases</td><td align="center" rowspan="1" colspan="1">Percentage</td><td align="center" rowspan="1" colspan="1">95%-CI</td></tr><tr><td align="center" colspan="4" rowspan="1"><hr></hr></td></tr><tr><td rowspan="1" colspan="1">Previous cancer</td><td align="center" rowspan="1" colspan="1">—</td><td align="center" rowspan="1" colspan="1">—</td><td align="center" rowspan="1" colspan="1">—</td></tr><tr><td rowspan="1" colspan="1">Breast cancer</td><td align="center" rowspan="1" colspan="1">10</td><td align="center" rowspan="1" colspan="1">45.0</td><td align="center" rowspan="1" colspan="1">24–66</td></tr><tr><td rowspan="1" colspan="1">Lymphoma</td><td align="center" rowspan="1" colspan="1">4</td><td align="center" rowspan="1" colspan="1">18.2</td><td align="center" rowspan="1" colspan="1">0–28</td></tr><tr><td rowspan="1" colspan="1">Cervix cancer</td><td align="center" rowspan="1" colspan="1">2</td><td align="center" rowspan="1" colspan="1">9.0</td><td align="center" rowspan="1" colspan="1">0–20</td></tr><tr><td rowspan="1" colspan="1">Prostate cancer</td><td align="center" rowspan="1" colspan="1">1</td><td align="center" rowspan="1" colspan="1">4.5</td><td align="center" rowspan="1" colspan="1">0–13</td></tr><tr><td rowspan="1" colspan="1">Bilateral retinoblastoma</td><td align="center" rowspan="1" colspan="1">1</td><td align="center" rowspan="1" colspan="1">3.5</td><td align="center" rowspan="1" colspan="1">0–13</td></tr><tr><td rowspan="1" colspan="1">Uterus cancer</td><td align="center" rowspan="1" colspan="1">1</td><td align="center" rowspan="1" colspan="1">4.5</td><td align="center" rowspan="1" colspan="1">0–13</td></tr><tr><td rowspan="1" colspan="1">Meningioma</td><td align="center" rowspan="1" colspan="1">1</td><td align="center" rowspan="1" colspan="1">4.5</td><td align="center" rowspan="1" colspan="1">0–13</td></tr><tr><td rowspan="1" colspan="1">Lymphoblastic acutate leukemia</td><td align="center" rowspan="1" colspan="1">1</td><td align="center" rowspan="1" colspan="1">4.5</td><td align="center" rowspan="1" colspan="1">0–13</td></tr><tr><td rowspan="1" colspan="1">Head and neck</td><td align="center" rowspan="1" colspan="1">1</td><td align="center" rowspan="1" colspan="1">4.5</td><td align="center" rowspan="1" colspan="1">0–13</td></tr><tr><td align="center" colspan="4" rowspan="1"><hr></hr></td></tr><tr><td rowspan="1" colspan="1">Undifferentiated spindle cell sarcoma</td><td align="center" rowspan="1" colspan="1">11</td><td align="center" rowspan="1" colspan="1">50.0</td><td align="center" rowspan="1" colspan="1">24–66</td></tr><tr><td rowspan="1" colspan="1">Angiosarcoma</td><td align="center" rowspan="1" colspan="1">4</td><td align="center" rowspan="1" colspan="1">18.2</td><td align="center" rowspan="1" colspan="1">2–34</td></tr><tr><td rowspan="1" colspan="1">Leiomyosarcoma</td><td align="center" rowspan="1" colspan="1">2</td><td align="center" rowspan="1" colspan="1">9.0</td><td align="center" rowspan="1" colspan="1">0–20</td></tr><tr><td rowspan="1" colspan="1">Osteosarcoma</td><td align="center" rowspan="1" colspan="1">1</td><td align="center" rowspan="1" colspan="1">4.5</td><td align="center" rowspan="1" colspan="1">0–13</td></tr><tr><td rowspan="1" colspan="1">Chondrosarcoma</td><td align="center" rowspan="1" colspan="1">1</td><td align="center" rowspan="1" colspan="1">4.5</td><td align="center" rowspan="1" colspan="1">0–13</td></tr><tr><td rowspan="1" colspan="1">Liposarcoma</td><td align="center" rowspan="1" colspan="1">1</td><td align="center" rowspan="1" colspan="1">4.5</td><td align="center" rowspan="1" colspan="1">0–13</td></tr><tr><td rowspan="1" colspan="1">PNET</td><td align="center" rowspan="1" colspan="1">1</td><td align="center" rowspan="1" colspan="1">4.5</td><td align="center" rowspan="1" colspan="1">0–13</td></tr><tr><td rowspan="1" colspan="1">Malignant
hemangioendothelioma</td><td align="center" rowspan="1" colspan="1">1</td><td align="center" rowspan="1" colspan="1">4.5</td><td align="center" rowspan="1" colspan="1">0–13</td></tr><tr><td align="center" colspan="4" rowspan="1"><hr></hr></td></tr><tr><td rowspan="1" colspan="1">Grade 1</td><td align="center" rowspan="1" colspan="1">1</td><td align="center" rowspan="1" colspan="1">5.5</td><td align="center" rowspan="1" colspan="1">0–13</td></tr><tr><td rowspan="1" colspan="1">Grade 2</td><td align="center" rowspan="1" colspan="1">2</td><td align="center" rowspan="1" colspan="1">11.1</td><td align="center" rowspan="1" colspan="1">0–29</td></tr><tr><td rowspan="1" colspan="1">Grade 3</td><td align="center" rowspan="1" colspan="1">15</td><td align="center" rowspan="1" colspan="1">83.3</td><td align="center" rowspan="1" colspan="1">72–100</td></tr><tr><td align="center" colspan="4" rowspan="1"><hr></hr></td></tr><tr><td rowspan="1" colspan="1">Chest wall</td><td align="center" rowspan="1" colspan="1">10</td><td align="center" rowspan="1" colspan="1">45.4</td><td align="center" rowspan="1" colspan="1">14–66</td></tr><tr><td rowspan="1" colspan="1">Head and neck</td><td align="center" rowspan="1" colspan="1">4</td><td align="center" rowspan="1" colspan="1">18.2</td><td align="center" rowspan="1" colspan="1">5–40</td></tr><tr><td rowspan="1" colspan="1">Lower limb</td><td align="center" rowspan="1" colspan="1">2</td><td align="center" rowspan="1" colspan="1">9.0</td><td align="center" rowspan="1" colspan="1">0–20</td></tr><tr><td rowspan="1" colspan="1">Upper limb</td><td align="center" rowspan="1" colspan="1">2</td><td align="center" rowspan="1" colspan="1">9.0</td><td align="center" rowspan="1" colspan="1">0–20</td></tr><tr><td rowspan="1" colspan="1">Pelvis</td><td align="center" rowspan="1" colspan="1">2</td><td align="center" rowspan="1" colspan="1">9.0</td><td align="center" rowspan="1" colspan="1">0–20</td></tr><tr><td rowspan="1" colspan="1">Retroperitoneum</td><td align="center" rowspan="1" colspan="1">1</td><td align="center" rowspan="1" colspan="1">4.5</td><td align="center" rowspan="1" colspan="1">0–20</td></tr><tr><td rowspan="1" colspan="1">Uterus</td><td align="center" rowspan="1" colspan="1">1</td><td align="center" rowspan="1" colspan="1">4.5</td><td align="center" rowspan="1" colspan="1">0–13</td></tr></tbody></table></table-wrap></floats-group></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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