Development and Validation of a Gene Signature for Patients with Head and Neck Carcinomas Treated by Postoperative Radio(chemo)therapy
Schmidt, S., Linge, A., Zwanenburg, A., Leger, S., Lohaus, F., Krenn, C., Appold, S., Gudziol, V., Nowak, A., von Neubeck, C., Tinhofer, I., Budach, V., Sak, A., Stuschke, M., Balermpas, P., Rödel, C., Bunea, H., Grosu, A.-L., Abdollahi, A., Debus, J., Ganswindt, U., Belka, C., Pigorsch, S., Combs, S. E., Mönnich, D., Zips, D., Baretton, G. B., Buchholz, F., Baumann, M., Krause, M., Löck, S., for the DKTK-ROG
The American Association for Cancer Research (AACR)
Published 2018
The American Association for Cancer Research (AACR)
Published 2018
| Publication Date: |
2018-03-16
|
|---|---|
| Publisher: |
The American Association for Cancer Research (AACR)
|
| Print ISSN: |
1078-0432
|
| Electronic ISSN: |
1557-3265
|
| Topics: |
Medicine
|
| Published by: |
| _version_ | 1836398847818989568 |
|---|---|
| autor | Schmidt, S., Linge, A., Zwanenburg, A., Leger, S., Lohaus, F., Krenn, C., Appold, S., Gudziol, V., Nowak, A., von Neubeck, C., Tinhofer, I., Budach, V., Sak, A., Stuschke, M., Balermpas, P., Rödel, C., Bunea, H., Grosu, A.-L., Abdollahi, A., Debus, J., Ganswindt, U., Belka, C., Pigorsch, S., Combs, S. E., Mönnich, D., Zips, D., Baretton, G. B., Buchholz, F., Baumann, M., Krause, M., Löck, S., for the DKTK-ROG |
| beschreibung | Purpose: The aim of this study was to identify and independently validate a novel gene signature predicting locoregional tumor control (LRC) for treatment individualization of patients with locally advanced HPV-negative head and neck squamous cell carcinomas (HNSCC) who are treated with postoperative radio(chemo)therapy (PORT-C). Experimental Design: Gene expression analyses were performed using NanoString technology on a multicenter training cohort of 130 patients and an independent validation cohort of 121 patients. The analyzed gene set was composed of genes with a previously reported association with radio(chemo)sensitivity or resistance to radio(chemo)therapy. Gene selection and model building were performed comparing several machine-learning algorithms. Results: We identified a 7-gene signature consisting of the three individual genes HILPDA, CD24, TCF3 , and one metagene combining the highly correlated genes SERPINE1, INHBA, P4HA2 , and ACTN1 . The 7-gene signature was used, in combination with clinical parameters, to fit a multivariable Cox model to the training data (concordance index, ci = 0.82), which was successfully validated (ci = 0.71). The signature showed improved performance compared with clinical parameters alone (ci = 0.66) and with a previously published model including hypoxia-associated genes and cancer stem cell markers (ci = 0.65). It was used to stratify patients into groups with low and high risk of recurrence, leading to significant differences in LRC in training and validation ( P 〈 0.001). Conclusions: We have identified and validated the first hypothesis-based gene signature for HPV-negative HNSCC treated by PORT-C including genes related to several radiobiological aspects. A prospective validation is planned in an ongoing prospective clinical trial before potential application in clinical trials for patient stratification. Clin Cancer Res; 24(6); 1364–74. ©2018 AACR . |
| citation_standardnr | 6208032 |
| datenlieferant | ipn_articles |
| feed_id | 9363 |
| feed_publisher | The American Association for Cancer Research (AACR) |
| feed_publisher_url | http://www.aacr.org/ |
| insertion_date | 2018-03-16 |
| journaleissn | 1557-3265 |
| journalissn | 1078-0432 |
| publikationsjahr_anzeige | 2018 |
| publikationsjahr_facette | 2018 |
| publikationsjahr_intervall | 7984:2015-2019 |
| publikationsjahr_sort | 2018 |
| publisher | The American Association for Cancer Research (AACR) |
| quelle | Clinical Cancer Research |
| relation | http://clincancerres.aacrjournals.org/cgi/content/short/24/6/1364?rss=1 |
| search_space | articles |
| shingle_author_1 | Schmidt, S., Linge, A., Zwanenburg, A., Leger, S., Lohaus, F., Krenn, C., Appold, S., Gudziol, V., Nowak, A., von Neubeck, C., Tinhofer, I., Budach, V., Sak, A., Stuschke, M., Balermpas, P., Rödel, C., Bunea, H., Grosu, A.-L., Abdollahi, A., Debus, J., Ganswindt, U., Belka, C., Pigorsch, S., Combs, S. E., Mönnich, D., Zips, D., Baretton, G. B., Buchholz, F., Baumann, M., Krause, M., Löck, S., for the DKTK-ROG |
| shingle_author_2 | Schmidt, S., Linge, A., Zwanenburg, A., Leger, S., Lohaus, F., Krenn, C., Appold, S., Gudziol, V., Nowak, A., von Neubeck, C., Tinhofer, I., Budach, V., Sak, A., Stuschke, M., Balermpas, P., Rödel, C., Bunea, H., Grosu, A.-L., Abdollahi, A., Debus, J., Ganswindt, U., Belka, C., Pigorsch, S., Combs, S. E., Mönnich, D., Zips, D., Baretton, G. B., Buchholz, F., Baumann, M., Krause, M., Löck, S., for the DKTK-ROG |
| shingle_author_3 | Schmidt, S., Linge, A., Zwanenburg, A., Leger, S., Lohaus, F., Krenn, C., Appold, S., Gudziol, V., Nowak, A., von Neubeck, C., Tinhofer, I., Budach, V., Sak, A., Stuschke, M., Balermpas, P., Rödel, C., Bunea, H., Grosu, A.-L., Abdollahi, A., Debus, J., Ganswindt, U., Belka, C., Pigorsch, S., Combs, S. E., Mönnich, D., Zips, D., Baretton, G. B., Buchholz, F., Baumann, M., Krause, M., Löck, S., for the DKTK-ROG |
| shingle_author_4 | Schmidt, S., Linge, A., Zwanenburg, A., Leger, S., Lohaus, F., Krenn, C., Appold, S., Gudziol, V., Nowak, A., von Neubeck, C., Tinhofer, I., Budach, V., Sak, A., Stuschke, M., Balermpas, P., Rödel, C., Bunea, H., Grosu, A.-L., Abdollahi, A., Debus, J., Ganswindt, U., Belka, C., Pigorsch, S., Combs, S. E., Mönnich, D., Zips, D., Baretton, G. B., Buchholz, F., Baumann, M., Krause, M., Löck, S., for the DKTK-ROG |
| shingle_catch_all_1 | Development and Validation of a Gene Signature for Patients with Head and Neck Carcinomas Treated by Postoperative Radio(chemo)therapy Purpose: The aim of this study was to identify and independently validate a novel gene signature predicting locoregional tumor control (LRC) for treatment individualization of patients with locally advanced HPV-negative head and neck squamous cell carcinomas (HNSCC) who are treated with postoperative radio(chemo)therapy (PORT-C). Experimental Design: Gene expression analyses were performed using NanoString technology on a multicenter training cohort of 130 patients and an independent validation cohort of 121 patients. The analyzed gene set was composed of genes with a previously reported association with radio(chemo)sensitivity or resistance to radio(chemo)therapy. Gene selection and model building were performed comparing several machine-learning algorithms. Results: We identified a 7-gene signature consisting of the three individual genes HILPDA, CD24, TCF3 , and one metagene combining the highly correlated genes SERPINE1, INHBA, P4HA2 , and ACTN1 . The 7-gene signature was used, in combination with clinical parameters, to fit a multivariable Cox model to the training data (concordance index, ci = 0.82), which was successfully validated (ci = 0.71). The signature showed improved performance compared with clinical parameters alone (ci = 0.66) and with a previously published model including hypoxia-associated genes and cancer stem cell markers (ci = 0.65). It was used to stratify patients into groups with low and high risk of recurrence, leading to significant differences in LRC in training and validation ( P < 0.001). Conclusions: We have identified and validated the first hypothesis-based gene signature for HPV-negative HNSCC treated by PORT-C including genes related to several radiobiological aspects. A prospective validation is planned in an ongoing prospective clinical trial before potential application in clinical trials for patient stratification. Clin Cancer Res; 24(6); 1364–74. ©2018 AACR . Schmidt, S., Linge, A., Zwanenburg, A., Leger, S., Lohaus, F., Krenn, C., Appold, S., Gudziol, V., Nowak, A., von Neubeck, C., Tinhofer, I., Budach, V., Sak, A., Stuschke, M., Balermpas, P., Rödel, C., Bunea, H., Grosu, A.-L., Abdollahi, A., Debus, J., Ganswindt, U., Belka, C., Pigorsch, S., Combs, S. E., Mönnich, D., Zips, D., Baretton, G. B., Buchholz, F., Baumann, M., Krause, M., Löck, S., for the DKTK-ROG The American Association for Cancer Research (AACR) 1078-0432 10780432 1557-3265 15573265 |
| shingle_catch_all_2 | Development and Validation of a Gene Signature for Patients with Head and Neck Carcinomas Treated by Postoperative Radio(chemo)therapy Purpose: The aim of this study was to identify and independently validate a novel gene signature predicting locoregional tumor control (LRC) for treatment individualization of patients with locally advanced HPV-negative head and neck squamous cell carcinomas (HNSCC) who are treated with postoperative radio(chemo)therapy (PORT-C). Experimental Design: Gene expression analyses were performed using NanoString technology on a multicenter training cohort of 130 patients and an independent validation cohort of 121 patients. The analyzed gene set was composed of genes with a previously reported association with radio(chemo)sensitivity or resistance to radio(chemo)therapy. Gene selection and model building were performed comparing several machine-learning algorithms. Results: We identified a 7-gene signature consisting of the three individual genes HILPDA, CD24, TCF3 , and one metagene combining the highly correlated genes SERPINE1, INHBA, P4HA2 , and ACTN1 . The 7-gene signature was used, in combination with clinical parameters, to fit a multivariable Cox model to the training data (concordance index, ci = 0.82), which was successfully validated (ci = 0.71). The signature showed improved performance compared with clinical parameters alone (ci = 0.66) and with a previously published model including hypoxia-associated genes and cancer stem cell markers (ci = 0.65). It was used to stratify patients into groups with low and high risk of recurrence, leading to significant differences in LRC in training and validation ( P < 0.001). Conclusions: We have identified and validated the first hypothesis-based gene signature for HPV-negative HNSCC treated by PORT-C including genes related to several radiobiological aspects. A prospective validation is planned in an ongoing prospective clinical trial before potential application in clinical trials for patient stratification. Clin Cancer Res; 24(6); 1364–74. ©2018 AACR . Schmidt, S., Linge, A., Zwanenburg, A., Leger, S., Lohaus, F., Krenn, C., Appold, S., Gudziol, V., Nowak, A., von Neubeck, C., Tinhofer, I., Budach, V., Sak, A., Stuschke, M., Balermpas, P., Rödel, C., Bunea, H., Grosu, A.-L., Abdollahi, A., Debus, J., Ganswindt, U., Belka, C., Pigorsch, S., Combs, S. E., Mönnich, D., Zips, D., Baretton, G. B., Buchholz, F., Baumann, M., Krause, M., Löck, S., for the DKTK-ROG The American Association for Cancer Research (AACR) 1078-0432 10780432 1557-3265 15573265 |
| shingle_catch_all_3 | Development and Validation of a Gene Signature for Patients with Head and Neck Carcinomas Treated by Postoperative Radio(chemo)therapy Purpose: The aim of this study was to identify and independently validate a novel gene signature predicting locoregional tumor control (LRC) for treatment individualization of patients with locally advanced HPV-negative head and neck squamous cell carcinomas (HNSCC) who are treated with postoperative radio(chemo)therapy (PORT-C). Experimental Design: Gene expression analyses were performed using NanoString technology on a multicenter training cohort of 130 patients and an independent validation cohort of 121 patients. The analyzed gene set was composed of genes with a previously reported association with radio(chemo)sensitivity or resistance to radio(chemo)therapy. Gene selection and model building were performed comparing several machine-learning algorithms. Results: We identified a 7-gene signature consisting of the three individual genes HILPDA, CD24, TCF3 , and one metagene combining the highly correlated genes SERPINE1, INHBA, P4HA2 , and ACTN1 . The 7-gene signature was used, in combination with clinical parameters, to fit a multivariable Cox model to the training data (concordance index, ci = 0.82), which was successfully validated (ci = 0.71). The signature showed improved performance compared with clinical parameters alone (ci = 0.66) and with a previously published model including hypoxia-associated genes and cancer stem cell markers (ci = 0.65). It was used to stratify patients into groups with low and high risk of recurrence, leading to significant differences in LRC in training and validation ( P < 0.001). Conclusions: We have identified and validated the first hypothesis-based gene signature for HPV-negative HNSCC treated by PORT-C including genes related to several radiobiological aspects. A prospective validation is planned in an ongoing prospective clinical trial before potential application in clinical trials for patient stratification. Clin Cancer Res; 24(6); 1364–74. ©2018 AACR . Schmidt, S., Linge, A., Zwanenburg, A., Leger, S., Lohaus, F., Krenn, C., Appold, S., Gudziol, V., Nowak, A., von Neubeck, C., Tinhofer, I., Budach, V., Sak, A., Stuschke, M., Balermpas, P., Rödel, C., Bunea, H., Grosu, A.-L., Abdollahi, A., Debus, J., Ganswindt, U., Belka, C., Pigorsch, S., Combs, S. E., Mönnich, D., Zips, D., Baretton, G. B., Buchholz, F., Baumann, M., Krause, M., Löck, S., for the DKTK-ROG The American Association for Cancer Research (AACR) 1078-0432 10780432 1557-3265 15573265 |
| shingle_catch_all_4 | Development and Validation of a Gene Signature for Patients with Head and Neck Carcinomas Treated by Postoperative Radio(chemo)therapy Purpose: The aim of this study was to identify and independently validate a novel gene signature predicting locoregional tumor control (LRC) for treatment individualization of patients with locally advanced HPV-negative head and neck squamous cell carcinomas (HNSCC) who are treated with postoperative radio(chemo)therapy (PORT-C). Experimental Design: Gene expression analyses were performed using NanoString technology on a multicenter training cohort of 130 patients and an independent validation cohort of 121 patients. The analyzed gene set was composed of genes with a previously reported association with radio(chemo)sensitivity or resistance to radio(chemo)therapy. Gene selection and model building were performed comparing several machine-learning algorithms. Results: We identified a 7-gene signature consisting of the three individual genes HILPDA, CD24, TCF3 , and one metagene combining the highly correlated genes SERPINE1, INHBA, P4HA2 , and ACTN1 . The 7-gene signature was used, in combination with clinical parameters, to fit a multivariable Cox model to the training data (concordance index, ci = 0.82), which was successfully validated (ci = 0.71). The signature showed improved performance compared with clinical parameters alone (ci = 0.66) and with a previously published model including hypoxia-associated genes and cancer stem cell markers (ci = 0.65). It was used to stratify patients into groups with low and high risk of recurrence, leading to significant differences in LRC in training and validation ( P < 0.001). Conclusions: We have identified and validated the first hypothesis-based gene signature for HPV-negative HNSCC treated by PORT-C including genes related to several radiobiological aspects. A prospective validation is planned in an ongoing prospective clinical trial before potential application in clinical trials for patient stratification. Clin Cancer Res; 24(6); 1364–74. ©2018 AACR . Schmidt, S., Linge, A., Zwanenburg, A., Leger, S., Lohaus, F., Krenn, C., Appold, S., Gudziol, V., Nowak, A., von Neubeck, C., Tinhofer, I., Budach, V., Sak, A., Stuschke, M., Balermpas, P., Rödel, C., Bunea, H., Grosu, A.-L., Abdollahi, A., Debus, J., Ganswindt, U., Belka, C., Pigorsch, S., Combs, S. E., Mönnich, D., Zips, D., Baretton, G. B., Buchholz, F., Baumann, M., Krause, M., Löck, S., for the DKTK-ROG The American Association for Cancer Research (AACR) 1078-0432 10780432 1557-3265 15573265 |
| shingle_title_1 | Development and Validation of a Gene Signature for Patients with Head and Neck Carcinomas Treated by Postoperative Radio(chemo)therapy |
| shingle_title_2 | Development and Validation of a Gene Signature for Patients with Head and Neck Carcinomas Treated by Postoperative Radio(chemo)therapy |
| shingle_title_3 | Development and Validation of a Gene Signature for Patients with Head and Neck Carcinomas Treated by Postoperative Radio(chemo)therapy |
| shingle_title_4 | Development and Validation of a Gene Signature for Patients with Head and Neck Carcinomas Treated by Postoperative Radio(chemo)therapy |
| timestamp | 2025-06-30T23:33:35.037Z |
| titel | Development and Validation of a Gene Signature for Patients with Head and Neck Carcinomas Treated by Postoperative Radio(chemo)therapy |
| titel_suche | Development and Validation of a Gene Signature for Patients with Head and Neck Carcinomas Treated by Postoperative Radio(chemo)therapy |
| topic | WW-YZ |
| uid | ipn_articles_6208032 |