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In vitro parameters and treatment outcome in head and neck cancers treated with surgery and/or radiation: Cell characterization and correlations with local control and overall survival

Identifieur interne : 000460 ( Istex/Corpus ); précédent : 000459; suivant : 000461

In vitro parameters and treatment outcome in head and neck cancers treated with surgery and/or radiation: Cell characterization and correlations with local control and overall survival

Auteurs : Theodore Girinsky ; Alain Bernheim ; Richard Lubin ; Tahere Tavakoli-Razavi ; Frazer Baker ; François Janot ; Pierre Wibault ; Jean-Marc Cosset ; Pierre Duvillard ; Annie Duverger ; Bernard Fertil

Source :

RBID : ISTEX:32AAA4BD0B2DEA9283FD0F33A761297A3CF5676B

English descriptors

Abstract

Abstract: Purpose: To determine whether in vitro parameters (surviving fraction at 2 Gy, alpha values, and calculated cell growth fraction) were predictive of the treatment outcome.Methods and Materials:Biopsies were obtained from patients with a head and neck tumor. In vitro parameters were determined using the CAM plate assay. Cell characterization by cytogenetic analysis was performed on 19 different cell cultures. In 25 additional cell cultures, cell clonogenicity was tested using the Courtenay Mills assay.Results:Biopsies were obtained from 156 patients with a head and neck tumor and the oropharynx was the predominant primary site. In vitro parameters were obtained in 113 cases (72%) (SF2 in 93 cases and calculated cell growth fraction in 103 cases). Cell characterization showed that cells in CAM plates were diploid with no clonal chromosome abnormalities and gave colonies in soft agar with a mean cloning efficiency of 1.610−3. Only patients treated with surgery and/or radiation (76), were considered eligible for in vitro parameters and treatment outcome correlation studies. The mean follow-up is over 2 years (range 9–47 months). The local control rate was significantly higher (p = 0.04) for patients with alpha values above the cut-off point of 0.07 Gy−1 (69% vs. 38% at 2 years). The local control rate was also significantly higher (p = 0.04) for patients with calculated cell growth fraction values above the cut-off point of 0.06% (70% vs. 48% at 2 years). Moreover for these latter patients the overall survival rate was also significantly higher (p = 0.004) (54% vs. 26% at 2 years). It is worth noting that alpha and calculated cell growth fraction values below the cut-off points identified a small group of patients (about 20%) who were at a significantly high risk of local failure. From a pragmatic point of view, as only radiosensitivity or calculated cell growth fraction values could be obtained in a certain number of experiments due to technical reasons, the treatment outcome of patients who had either alpha and/or calculated cell growth fraction values below the cut-off levels (about 30% of all patients) was analyzed. This group of patients fared significantly worse (p = 0.02) in terms of local control (50% vs. 68% at 2 years) and (p = 0.04) overall survival (36% vs. 50% at 2 years).Conclusion:These results suggest that in vitro parameters using the CAM plate assay, might be useful in predicting the treatment outcome of patients with a head and neck tumor treated with surgery and postoperative radiation, or radiation alone. However, they must be considered as preliminary because the cut offs used in the study were chosen for exploratory purposes. Only a multivariate analysis including all clinical and biologic factors will allow us to draw any firm conclusions.

Url:
DOI: 10.1016/0360-3016(94)90350-6

Links to Exploration step

ISTEX:32AAA4BD0B2DEA9283FD0F33A761297A3CF5676B

Le document en format XML

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<div type="abstract" xml:lang="en">Abstract: Purpose: To determine whether in vitro parameters (surviving fraction at 2 Gy, alpha values, and calculated cell growth fraction) were predictive of the treatment outcome.Methods and Materials:Biopsies were obtained from patients with a head and neck tumor. In vitro parameters were determined using the CAM plate assay. Cell characterization by cytogenetic analysis was performed on 19 different cell cultures. In 25 additional cell cultures, cell clonogenicity was tested using the Courtenay Mills assay.Results:Biopsies were obtained from 156 patients with a head and neck tumor and the oropharynx was the predominant primary site. In vitro parameters were obtained in 113 cases (72%) (SF2 in 93 cases and calculated cell growth fraction in 103 cases). Cell characterization showed that cells in CAM plates were diploid with no clonal chromosome abnormalities and gave colonies in soft agar with a mean cloning efficiency of 1.610−3. Only patients treated with surgery and/or radiation (76), were considered eligible for in vitro parameters and treatment outcome correlation studies. The mean follow-up is over 2 years (range 9–47 months). The local control rate was significantly higher (p = 0.04) for patients with alpha values above the cut-off point of 0.07 Gy−1 (69% vs. 38% at 2 years). The local control rate was also significantly higher (p = 0.04) for patients with calculated cell growth fraction values above the cut-off point of 0.06% (70% vs. 48% at 2 years). Moreover for these latter patients the overall survival rate was also significantly higher (p = 0.004) (54% vs. 26% at 2 years). It is worth noting that alpha and calculated cell growth fraction values below the cut-off points identified a small group of patients (about 20%) who were at a significantly high risk of local failure. From a pragmatic point of view, as only radiosensitivity or calculated cell growth fraction values could be obtained in a certain number of experiments due to technical reasons, the treatment outcome of patients who had either alpha and/or calculated cell growth fraction values below the cut-off levels (about 30% of all patients) was analyzed. This group of patients fared significantly worse (p = 0.02) in terms of local control (50% vs. 68% at 2 years) and (p = 0.04) overall survival (36% vs. 50% at 2 years).Conclusion:These results suggest that in vitro parameters using the CAM plate assay, might be useful in predicting the treatment outcome of patients with a head and neck tumor treated with surgery and postoperative radiation, or radiation alone. However, they must be considered as preliminary because the cut offs used in the study were chosen for exploratory purposes. Only a multivariate analysis including all clinical and biologic factors will allow us to draw any firm conclusions.</div>
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<abstract>Abstract: Purpose: To determine whether in vitro parameters (surviving fraction at 2 Gy, alpha values, and calculated cell growth fraction) were predictive of the treatment outcome.Methods and Materials:Biopsies were obtained from patients with a head and neck tumor. In vitro parameters were determined using the CAM plate assay. Cell characterization by cytogenetic analysis was performed on 19 different cell cultures. In 25 additional cell cultures, cell clonogenicity was tested using the Courtenay Mills assay.Results:Biopsies were obtained from 156 patients with a head and neck tumor and the oropharynx was the predominant primary site. In vitro parameters were obtained in 113 cases (72%) (SF2 in 93 cases and calculated cell growth fraction in 103 cases). Cell characterization showed that cells in CAM plates were diploid with no clonal chromosome abnormalities and gave colonies in soft agar with a mean cloning efficiency of 1.610−3. Only patients treated with surgery and/or radiation (76), were considered eligible for in vitro parameters and treatment outcome correlation studies. The mean follow-up is over 2 years (range 9–47 months). The local control rate was significantly higher (p = 0.04) for patients with alpha values above the cut-off point of 0.07 Gy−1 (69% vs. 38% at 2 years). The local control rate was also significantly higher (p = 0.04) for patients with calculated cell growth fraction values above the cut-off point of 0.06% (70% vs. 48% at 2 years). Moreover for these latter patients the overall survival rate was also significantly higher (p = 0.004) (54% vs. 26% at 2 years). It is worth noting that alpha and calculated cell growth fraction values below the cut-off points identified a small group of patients (about 20%) who were at a significantly high risk of local failure. From a pragmatic point of view, as only radiosensitivity or calculated cell growth fraction values could be obtained in a certain number of experiments due to technical reasons, the treatment outcome of patients who had either alpha and/or calculated cell growth fraction values below the cut-off levels (about 30% of all patients) was analyzed. This group of patients fared significantly worse (p = 0.02) in terms of local control (50% vs. 68% at 2 years) and (p = 0.04) overall survival (36% vs. 50% at 2 years).Conclusion:These results suggest that in vitro parameters using the CAM plate assay, might be useful in predicting the treatment outcome of patients with a head and neck tumor treated with surgery and postoperative radiation, or radiation alone. However, they must be considered as preliminary because the cut offs used in the study were chosen for exploratory purposes. Only a multivariate analysis including all clinical and biologic factors will allow us to draw any firm conclusions.</abstract>
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<p>Purpose: To determine whether in vitro parameters (surviving fraction at 2 Gy, alpha values, and calculated cell growth fraction) were predictive of the treatment outcome.Methods and Materials:Biopsies were obtained from patients with a head and neck tumor. In vitro parameters were determined using the CAM plate assay. Cell characterization by cytogenetic analysis was performed on 19 different cell cultures. In 25 additional cell cultures, cell clonogenicity was tested using the Courtenay Mills assay.Results:Biopsies were obtained from 156 patients with a head and neck tumor and the oropharynx was the predominant primary site. In vitro parameters were obtained in 113 cases (72%) (SF2 in 93 cases and calculated cell growth fraction in 103 cases). Cell characterization showed that cells in CAM plates were diploid with no clonal chromosome abnormalities and gave colonies in soft agar with a mean cloning efficiency of 1.610−3. Only patients treated with surgery and/or radiation (76), were considered eligible for in vitro parameters and treatment outcome correlation studies. The mean follow-up is over 2 years (range 9–47 months). The local control rate was significantly higher (p = 0.04) for patients with alpha values above the cut-off point of 0.07 Gy−1 (69% vs. 38% at 2 years). The local control rate was also significantly higher (p = 0.04) for patients with calculated cell growth fraction values above the cut-off point of 0.06% (70% vs. 48% at 2 years). Moreover for these latter patients the overall survival rate was also significantly higher (p = 0.004) (54% vs. 26% at 2 years). It is worth noting that alpha and calculated cell growth fraction values below the cut-off points identified a small group of patients (about 20%) who were at a significantly high risk of local failure. From a pragmatic point of view, as only radiosensitivity or calculated cell growth fraction values could be obtained in a certain number of experiments due to technical reasons, the treatment outcome of patients who had either alpha and/or calculated cell growth fraction values below the cut-off levels (about 30% of all patients) was analyzed. This group of patients fared significantly worse (p = 0.02) in terms of local control (50% vs. 68% at 2 years) and (p = 0.04) overall survival (36% vs. 50% at 2 years).Conclusion:These results suggest that in vitro parameters using the CAM plate assay, might be useful in predicting the treatment outcome of patients with a head and neck tumor treated with surgery and postoperative radiation, or radiation alone. However, they must be considered as preliminary because the cut offs used in the study were chosen for exploratory purposes. Only a multivariate analysis including all clinical and biologic factors will allow us to draw any firm conclusions.</p>
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<ce:given-name>Tahere</ce:given-name>
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<ce:given-name>Jean-Marc</ce:given-name>
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To determine whether
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Biopsies were obtained from patients with a head and neck tumor.
<ce:italic>In vitro</ce:italic>
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Biopsies were obtained from 156 patients with a head and neck tumor and the oropharynx was the predominant primary site.
<ce:italic>In vitro</ce:italic>
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<ce:sup>−3</ce:sup>
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<ce:italic>in vitro</ce:italic>
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<ce:italic>p</ce:italic>
= 0.04) for patients with alpha values above the cut-off point of 0.07 Gy
<ce:sup>−1</ce:sup>
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<ce:italic>p</ce:italic>
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<ce:italic>p</ce:italic>
= 0.004) (54% vs. 26% at 2 years). It is worth noting that alpha and calculated cell growth fraction values below the cut-off points identified a small group of patients (about 20%) who were at a significantly high risk of local failure. From a pragmatic point of view, as only radiosensitivity or calculated cell growth fraction values could be obtained in a certain number of experiments due to technical reasons, the treatment outcome of patients who had either alpha and/or calculated cell growth fraction values below the cut-off levels (about 30% of all patients) was analyzed. This group of patients fared significantly worse (
<ce:italic>p</ce:italic>
= 0.02) in terms of local control (50% vs. 68% at 2 years) and (
<ce:italic>p</ce:italic>
= 0.04) overall survival (36% vs. 50% at 2 years).</ce:simple-para>
<ce:simple-para>
<math altimg="si4.gif">
<rm>
<unl type="bar">Conclusion:</unl>
</rm>
</math>
These results suggest that
<ce:italic>in vitro</ce:italic>
parameters using the CAM plate assay, might be useful in predicting the treatment outcome of patients with a head and neck tumor treated with surgery and postoperative radiation, or radiation alone. However, they must be considered as preliminary because the cut offs used in the study were chosen for exploratory purposes. Only a multivariate analysis including all clinical and biologic factors will allow us to draw any firm conclusions.</ce:simple-para>
</ce:abstract-sec>
</ce:abstract>
<ce:keywords>
<ce:section-title>Keywords</ce:section-title>
<ce:keyword>
<ce:text>Predictive assay</ce:text>
</ce:keyword>
<ce:keyword>
<ce:text>Tumor radiosensitivity</ce:text>
</ce:keyword>
<ce:keyword>
<ce:text>Head and neck cancers</ce:text>
</ce:keyword>
<ce:keyword>
<ce:text>Cell characterization</ce:text>
</ce:keyword>
<ce:keyword>
<ce:text>Cell growth fraction</ce:text>
</ce:keyword>
<ce:keyword>
<ce:text>Treatment outcome</ce:text>
</ce:keyword>
</ce:keywords>
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<title>In vitro parameters and treatment outcome in head and neck cancers treated with surgery and/or radiation: Cell characterization and correlations with local control and overall survival</title>
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<title>parameters and treatment outcome in head and neck cancers treated with surgery and/or radiation: Cell characterization and correlations with local control and overall survival</title>
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<name type="personal">
<namePart type="given">Theodore</namePart>
<namePart type="family">Girinsky</namePart>
<namePart type="termsOfAddress">M.D.</namePart>
<affiliation>Department of Radiation Oncology, Institut Gustave-Roussy, 94805 Villejuif, France</affiliation>
<description>Reprint requests to: Theodore Girinsky, Department of Radiation Oncology, Institut Gustave-Roussy, 94805 Villejuif, France.</description>
<role>
<roleTerm type="text">author</roleTerm>
</role>
</name>
<name type="personal">
<namePart type="given">Alain</namePart>
<namePart type="family">Bernheim</namePart>
<namePart type="termsOfAddress">M.D.</namePart>
<affiliation>Laboratory of Cytogenetics, CNRS UA 1158, Institut Gustave-Roussy, 94805 Villejuif, France</affiliation>
<role>
<roleTerm type="text">author</roleTerm>
</role>
</name>
<name type="personal">
<namePart type="given">Richard</namePart>
<namePart type="family">Lubin</namePart>
<namePart type="termsOfAddress">B.Sc.</namePart>
<affiliation>Laboratory of Cytogenetics, CNRS UA 1158, Institut Gustave-Roussy, 94805 Villejuif, France</affiliation>
<role>
<roleTerm type="text">author</roleTerm>
</role>
</name>
<name type="personal">
<namePart type="given">Tahere</namePart>
<namePart type="family">Tavakoli-Razavi</namePart>
<namePart type="termsOfAddress">Ph.D.</namePart>
<affiliation>Department of Biostatistics, Institut Gustave-Roussy, 94805 Villejuif, France</affiliation>
<role>
<roleTerm type="text">author</roleTerm>
</role>
</name>
<name type="personal">
<namePart type="given">Frazer</namePart>
<namePart type="family">Baker</namePart>
<namePart type="termsOfAddress">Ph.D., M.Sc.</namePart>
<affiliation>Baker Sanger, Inc., 8052 El Rio, Houston, TX 77054, USA</affiliation>
<role>
<roleTerm type="text">author</roleTerm>
</role>
</name>
<name type="personal">
<namePart type="given">François</namePart>
<namePart type="family">Janot</namePart>
<namePart type="termsOfAddress">M.D.</namePart>
<affiliation>Department of Head and Neck Surgery, Institut Gustave-Roussy, 94805 Villejuif, France</affiliation>
<role>
<roleTerm type="text">author</roleTerm>
</role>
</name>
<name type="personal">
<namePart type="given">Pierre</namePart>
<namePart type="family">Wibault</namePart>
<namePart type="termsOfAddress">M.D.</namePart>
<affiliation>Department of Radiation Oncology, Institut Gustave-Roussy, 94805 Villejuif, France</affiliation>
<role>
<roleTerm type="text">author</roleTerm>
</role>
</name>
<name type="personal">
<namePart type="given">Jean-Marc</namePart>
<namePart type="family">Cosset</namePart>
<namePart type="termsOfAddress">M.D.</namePart>
<affiliation>Department of Radiation Oncology, Institut Gustave-Roussy, 94805 Villejuif, France</affiliation>
<role>
<roleTerm type="text">author</roleTerm>
</role>
</name>
<name type="personal">
<namePart type="given">Pierre</namePart>
<namePart type="family">Duvillard</namePart>
<namePart type="termsOfAddress">M.D.</namePart>
<affiliation>Department of Pathology, Institut Gustave-Roussy, 94805 Villejuif, France</affiliation>
<role>
<roleTerm type="text">author</roleTerm>
</role>
</name>
<name type="personal">
<namePart type="given">Annie</namePart>
<namePart type="family">Duverger</namePart>
<namePart type="termsOfAddress">B.Sc.</namePart>
<affiliation>Laboratory of Cytogenetics, CNRS UA 1158, Institut Gustave-Roussy, 94805 Villejuif, France</affiliation>
<role>
<roleTerm type="text">author</roleTerm>
</role>
</name>
<name type="personal">
<namePart type="given">Bernard</namePart>
<namePart type="family">Fertil</namePart>
<namePart type="termsOfAddress">Ph.D.</namePart>
<affiliation>Unité INSERM 194, Hôpital Salpétrière, Paris, France</affiliation>
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<roleTerm type="text">author</roleTerm>
</role>
</name>
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<publisher>ELSEVIER</publisher>
<dateIssued encoding="w3cdtf">1994</dateIssued>
<copyrightDate encoding="w3cdtf">1994</copyrightDate>
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<abstract lang="en">Abstract: Purpose: To determine whether in vitro parameters (surviving fraction at 2 Gy, alpha values, and calculated cell growth fraction) were predictive of the treatment outcome.Methods and Materials:Biopsies were obtained from patients with a head and neck tumor. In vitro parameters were determined using the CAM plate assay. Cell characterization by cytogenetic analysis was performed on 19 different cell cultures. In 25 additional cell cultures, cell clonogenicity was tested using the Courtenay Mills assay.Results:Biopsies were obtained from 156 patients with a head and neck tumor and the oropharynx was the predominant primary site. In vitro parameters were obtained in 113 cases (72%) (SF2 in 93 cases and calculated cell growth fraction in 103 cases). Cell characterization showed that cells in CAM plates were diploid with no clonal chromosome abnormalities and gave colonies in soft agar with a mean cloning efficiency of 1.610−3. Only patients treated with surgery and/or radiation (76), were considered eligible for in vitro parameters and treatment outcome correlation studies. The mean follow-up is over 2 years (range 9–47 months). The local control rate was significantly higher (p = 0.04) for patients with alpha values above the cut-off point of 0.07 Gy−1 (69% vs. 38% at 2 years). The local control rate was also significantly higher (p = 0.04) for patients with calculated cell growth fraction values above the cut-off point of 0.06% (70% vs. 48% at 2 years). Moreover for these latter patients the overall survival rate was also significantly higher (p = 0.004) (54% vs. 26% at 2 years). It is worth noting that alpha and calculated cell growth fraction values below the cut-off points identified a small group of patients (about 20%) who were at a significantly high risk of local failure. From a pragmatic point of view, as only radiosensitivity or calculated cell growth fraction values could be obtained in a certain number of experiments due to technical reasons, the treatment outcome of patients who had either alpha and/or calculated cell growth fraction values below the cut-off levels (about 30% of all patients) was analyzed. This group of patients fared significantly worse (p = 0.02) in terms of local control (50% vs. 68% at 2 years) and (p = 0.04) overall survival (36% vs. 50% at 2 years).Conclusion:These results suggest that in vitro parameters using the CAM plate assay, might be useful in predicting the treatment outcome of patients with a head and neck tumor treated with surgery and postoperative radiation, or radiation alone. However, they must be considered as preliminary because the cut offs used in the study were chosen for exploratory purposes. Only a multivariate analysis including all clinical and biologic factors will allow us to draw any firm conclusions.</abstract>
<note type="content">Section title: Clinical original contribution</note>
<subject>
<genre>Keywords</genre>
<topic>Predictive assay</topic>
<topic>Tumor radiosensitivity</topic>
<topic>Head and neck cancers</topic>
<topic>Cell characterization</topic>
<topic>Cell growth fraction</topic>
<topic>Treatment outcome</topic>
</subject>
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<title>International Journal of Radiation Oncology, Biology, Physics</title>
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<publisher>ELSEVIER</publisher>
<dateIssued encoding="w3cdtf">19941115</dateIssued>
</originInfo>
<identifier type="ISSN">0360-3016</identifier>
<identifier type="PII">S0360-3016(00)X0308-2</identifier>
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<date>19941115</date>
<detail type="volume">
<number>30</number>
<caption>vol.</caption>
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<detail type="issue">
<number>4</number>
<caption>no.</caption>
</detail>
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<start>753</start>
<end>1015</end>
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