High tumor mutational burden predicts worse prognosis for cervical cancer treated with radiotherapy

Purpose Tumor mutational burden (TMB) is a surrogate biomarker of neo-antigens and high TMB status is associated with favorable response to immune-checkpoint inhibitors (ICIs). This study aimed to elucidate the association between TMB and the outcome of definitive radiotherapy in patients with cervi...
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Autor*in:	Ota, Norichika [verfasserIn] Yoshimoto, Yuya Darwis, Narisa Dewi Maulany Sato, Hiro Ando, Ken Oike, Takahiro Ohno, Tatsuya

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2021

Schlagwörter:	Cervical cancer Radiotherapy Tumor mutational burden Prognosis

Anmerkung:	© The Author(s) 2021

Übergeordnetes Werk:	Enthalten in: Radiation medicine - Tokyo : Springer, 1999, 40(2021), 5 vom: 03. Dez., Seite 534-541
Übergeordnetes Werk:	volume:40 ; year:2021 ; number:5 ; day:03 ; month:12 ; pages:534-541

Links:	Volltext

DOI / URN:	10.1007/s11604-021-01230-5

Katalog-ID:	SPR04690445X

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245	1	0	\|a High tumor mutational burden predicts worse prognosis for cervical cancer treated with radiotherapy
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520			\|a Purpose Tumor mutational burden (TMB) is a surrogate biomarker of neo-antigens and high TMB status is associated with favorable response to immune-checkpoint inhibitors (ICIs). This study aimed to elucidate the association between TMB and the outcome of definitive radiotherapy in patients with cervical cancer. Materials and methods TMB and treatment outcome were retrospectively analyzed in patients with newly diagnosed cervical cancer treated with definitive radiotherapy available with somatic mutation data of pre-treatment tumors obtained using a commercially available gene panel. Results The study enrolled 98 patients (median follow-up period, 61 months). The median TMB was 9.5 mutations per megabase (range, 3.0–35.5 mutations per megabase). After dichotomization based on this median value, the 5-year overall survival (OS) for TMB-high patients was significantly worse than that of TMB-low patients (61.1% vs. 82.2%). Multivariate analysis identified high TMB status as a significant prognostic factor for worse OS, along with advanced stage, para-aortic lymph node involvement, and absence of concurrent chemotherapy. Conclusion These data indicate that TMB is a potential prognostic factor for worse survival in patients with cervical cancer treated with definitive radiotherapy, thereby providing a rationale for treatment of TMB-high cervical cancers with a combination of ICIs plus radiotherapy. Secondary abstract This retrospective study of 98 patients demonstrates for the first time that tumor mutational burden (TMB) is an independent prognostic factor for worse overall survival of patients treated with definitive radiotherapy, providing a rationale for treatment of TMB-high cervical cancers with a combination of immune-checkpoint inhibitors plus radiotherapy.
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700	1		\|a Ohno, Tatsuya \|4 aut
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allfields	10.1007/s11604-021-01230-5 doi (DE-627)SPR04690445X (SPR)s11604-021-01230-5-e DE-627 ger DE-627 rakwb eng Ota, Norichika verfasserin aut High tumor mutational burden predicts worse prognosis for cervical cancer treated with radiotherapy 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2021 Purpose Tumor mutational burden (TMB) is a surrogate biomarker of neo-antigens and high TMB status is associated with favorable response to immune-checkpoint inhibitors (ICIs). This study aimed to elucidate the association between TMB and the outcome of definitive radiotherapy in patients with cervical cancer. Materials and methods TMB and treatment outcome were retrospectively analyzed in patients with newly diagnosed cervical cancer treated with definitive radiotherapy available with somatic mutation data of pre-treatment tumors obtained using a commercially available gene panel. Results The study enrolled 98 patients (median follow-up period, 61 months). The median TMB was 9.5 mutations per megabase (range, 3.0–35.5 mutations per megabase). After dichotomization based on this median value, the 5-year overall survival (OS) for TMB-high patients was significantly worse than that of TMB-low patients (61.1% vs. 82.2%). Multivariate analysis identified high TMB status as a significant prognostic factor for worse OS, along with advanced stage, para-aortic lymph node involvement, and absence of concurrent chemotherapy. Conclusion These data indicate that TMB is a potential prognostic factor for worse survival in patients with cervical cancer treated with definitive radiotherapy, thereby providing a rationale for treatment of TMB-high cervical cancers with a combination of ICIs plus radiotherapy. Secondary abstract This retrospective study of 98 patients demonstrates for the first time that tumor mutational burden (TMB) is an independent prognostic factor for worse overall survival of patients treated with definitive radiotherapy, providing a rationale for treatment of TMB-high cervical cancers with a combination of immune-checkpoint inhibitors plus radiotherapy. Cervical cancer (dpeaa)DE-He213 Radiotherapy (dpeaa)DE-He213 Tumor mutational burden (dpeaa)DE-He213 Prognosis (dpeaa)DE-He213 Yoshimoto, Yuya aut Darwis, Narisa Dewi Maulany aut Sato, Hiro aut Ando, Ken aut Oike, Takahiro aut Ohno, Tatsuya aut Enthalten in Radiation medicine Tokyo : Springer, 1999 40(2021), 5 vom: 03. Dez., Seite 534-541 (DE-627)368312305 (DE-600)2117284-5 1862-5274 nnns volume:40 year:2021 number:5 day:03 month:12 pages:534-541 https://dx.doi.org/10.1007/s11604-021-01230-5 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_105 GBV_ILN_120 GBV_ILN_138 GBV_ILN_152 GBV_ILN_161 GBV_ILN_171 GBV_ILN_187 GBV_ILN_224 GBV_ILN_250 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_702 AR 40 2021 5 03 12 534-541
spelling	10.1007/s11604-021-01230-5 doi (DE-627)SPR04690445X (SPR)s11604-021-01230-5-e DE-627 ger DE-627 rakwb eng Ota, Norichika verfasserin aut High tumor mutational burden predicts worse prognosis for cervical cancer treated with radiotherapy 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2021 Purpose Tumor mutational burden (TMB) is a surrogate biomarker of neo-antigens and high TMB status is associated with favorable response to immune-checkpoint inhibitors (ICIs). This study aimed to elucidate the association between TMB and the outcome of definitive radiotherapy in patients with cervical cancer. Materials and methods TMB and treatment outcome were retrospectively analyzed in patients with newly diagnosed cervical cancer treated with definitive radiotherapy available with somatic mutation data of pre-treatment tumors obtained using a commercially available gene panel. Results The study enrolled 98 patients (median follow-up period, 61 months). The median TMB was 9.5 mutations per megabase (range, 3.0–35.5 mutations per megabase). After dichotomization based on this median value, the 5-year overall survival (OS) for TMB-high patients was significantly worse than that of TMB-low patients (61.1% vs. 82.2%). Multivariate analysis identified high TMB status as a significant prognostic factor for worse OS, along with advanced stage, para-aortic lymph node involvement, and absence of concurrent chemotherapy. Conclusion These data indicate that TMB is a potential prognostic factor for worse survival in patients with cervical cancer treated with definitive radiotherapy, thereby providing a rationale for treatment of TMB-high cervical cancers with a combination of ICIs plus radiotherapy. Secondary abstract This retrospective study of 98 patients demonstrates for the first time that tumor mutational burden (TMB) is an independent prognostic factor for worse overall survival of patients treated with definitive radiotherapy, providing a rationale for treatment of TMB-high cervical cancers with a combination of immune-checkpoint inhibitors plus radiotherapy. Cervical cancer (dpeaa)DE-He213 Radiotherapy (dpeaa)DE-He213 Tumor mutational burden (dpeaa)DE-He213 Prognosis (dpeaa)DE-He213 Yoshimoto, Yuya aut Darwis, Narisa Dewi Maulany aut Sato, Hiro aut Ando, Ken aut Oike, Takahiro aut Ohno, Tatsuya aut Enthalten in Radiation medicine Tokyo : Springer, 1999 40(2021), 5 vom: 03. Dez., Seite 534-541 (DE-627)368312305 (DE-600)2117284-5 1862-5274 nnns volume:40 year:2021 number:5 day:03 month:12 pages:534-541 https://dx.doi.org/10.1007/s11604-021-01230-5 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_105 GBV_ILN_120 GBV_ILN_138 GBV_ILN_152 GBV_ILN_161 GBV_ILN_171 GBV_ILN_187 GBV_ILN_224 GBV_ILN_250 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_702 AR 40 2021 5 03 12 534-541
allfields_unstemmed	10.1007/s11604-021-01230-5 doi (DE-627)SPR04690445X (SPR)s11604-021-01230-5-e DE-627 ger DE-627 rakwb eng Ota, Norichika verfasserin aut High tumor mutational burden predicts worse prognosis for cervical cancer treated with radiotherapy 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2021 Purpose Tumor mutational burden (TMB) is a surrogate biomarker of neo-antigens and high TMB status is associated with favorable response to immune-checkpoint inhibitors (ICIs). This study aimed to elucidate the association between TMB and the outcome of definitive radiotherapy in patients with cervical cancer. Materials and methods TMB and treatment outcome were retrospectively analyzed in patients with newly diagnosed cervical cancer treated with definitive radiotherapy available with somatic mutation data of pre-treatment tumors obtained using a commercially available gene panel. Results The study enrolled 98 patients (median follow-up period, 61 months). The median TMB was 9.5 mutations per megabase (range, 3.0–35.5 mutations per megabase). After dichotomization based on this median value, the 5-year overall survival (OS) for TMB-high patients was significantly worse than that of TMB-low patients (61.1% vs. 82.2%). Multivariate analysis identified high TMB status as a significant prognostic factor for worse OS, along with advanced stage, para-aortic lymph node involvement, and absence of concurrent chemotherapy. Conclusion These data indicate that TMB is a potential prognostic factor for worse survival in patients with cervical cancer treated with definitive radiotherapy, thereby providing a rationale for treatment of TMB-high cervical cancers with a combination of ICIs plus radiotherapy. Secondary abstract This retrospective study of 98 patients demonstrates for the first time that tumor mutational burden (TMB) is an independent prognostic factor for worse overall survival of patients treated with definitive radiotherapy, providing a rationale for treatment of TMB-high cervical cancers with a combination of immune-checkpoint inhibitors plus radiotherapy. Cervical cancer (dpeaa)DE-He213 Radiotherapy (dpeaa)DE-He213 Tumor mutational burden (dpeaa)DE-He213 Prognosis (dpeaa)DE-He213 Yoshimoto, Yuya aut Darwis, Narisa Dewi Maulany aut Sato, Hiro aut Ando, Ken aut Oike, Takahiro aut Ohno, Tatsuya aut Enthalten in Radiation medicine Tokyo : Springer, 1999 40(2021), 5 vom: 03. Dez., Seite 534-541 (DE-627)368312305 (DE-600)2117284-5 1862-5274 nnns volume:40 year:2021 number:5 day:03 month:12 pages:534-541 https://dx.doi.org/10.1007/s11604-021-01230-5 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_105 GBV_ILN_120 GBV_ILN_138 GBV_ILN_152 GBV_ILN_161 GBV_ILN_171 GBV_ILN_187 GBV_ILN_224 GBV_ILN_250 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_702 AR 40 2021 5 03 12 534-541
allfieldsGer	10.1007/s11604-021-01230-5 doi (DE-627)SPR04690445X (SPR)s11604-021-01230-5-e DE-627 ger DE-627 rakwb eng Ota, Norichika verfasserin aut High tumor mutational burden predicts worse prognosis for cervical cancer treated with radiotherapy 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2021 Purpose Tumor mutational burden (TMB) is a surrogate biomarker of neo-antigens and high TMB status is associated with favorable response to immune-checkpoint inhibitors (ICIs). This study aimed to elucidate the association between TMB and the outcome of definitive radiotherapy in patients with cervical cancer. Materials and methods TMB and treatment outcome were retrospectively analyzed in patients with newly diagnosed cervical cancer treated with definitive radiotherapy available with somatic mutation data of pre-treatment tumors obtained using a commercially available gene panel. Results The study enrolled 98 patients (median follow-up period, 61 months). The median TMB was 9.5 mutations per megabase (range, 3.0–35.5 mutations per megabase). After dichotomization based on this median value, the 5-year overall survival (OS) for TMB-high patients was significantly worse than that of TMB-low patients (61.1% vs. 82.2%). Multivariate analysis identified high TMB status as a significant prognostic factor for worse OS, along with advanced stage, para-aortic lymph node involvement, and absence of concurrent chemotherapy. Conclusion These data indicate that TMB is a potential prognostic factor for worse survival in patients with cervical cancer treated with definitive radiotherapy, thereby providing a rationale for treatment of TMB-high cervical cancers with a combination of ICIs plus radiotherapy. Secondary abstract This retrospective study of 98 patients demonstrates for the first time that tumor mutational burden (TMB) is an independent prognostic factor for worse overall survival of patients treated with definitive radiotherapy, providing a rationale for treatment of TMB-high cervical cancers with a combination of immune-checkpoint inhibitors plus radiotherapy. Cervical cancer (dpeaa)DE-He213 Radiotherapy (dpeaa)DE-He213 Tumor mutational burden (dpeaa)DE-He213 Prognosis (dpeaa)DE-He213 Yoshimoto, Yuya aut Darwis, Narisa Dewi Maulany aut Sato, Hiro aut Ando, Ken aut Oike, Takahiro aut Ohno, Tatsuya aut Enthalten in Radiation medicine Tokyo : Springer, 1999 40(2021), 5 vom: 03. Dez., Seite 534-541 (DE-627)368312305 (DE-600)2117284-5 1862-5274 nnns volume:40 year:2021 number:5 day:03 month:12 pages:534-541 https://dx.doi.org/10.1007/s11604-021-01230-5 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_105 GBV_ILN_120 GBV_ILN_138 GBV_ILN_152 GBV_ILN_161 GBV_ILN_171 GBV_ILN_187 GBV_ILN_224 GBV_ILN_250 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_702 AR 40 2021 5 03 12 534-541
allfieldsSound	10.1007/s11604-021-01230-5 doi (DE-627)SPR04690445X (SPR)s11604-021-01230-5-e DE-627 ger DE-627 rakwb eng Ota, Norichika verfasserin aut High tumor mutational burden predicts worse prognosis for cervical cancer treated with radiotherapy 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2021 Purpose Tumor mutational burden (TMB) is a surrogate biomarker of neo-antigens and high TMB status is associated with favorable response to immune-checkpoint inhibitors (ICIs). This study aimed to elucidate the association between TMB and the outcome of definitive radiotherapy in patients with cervical cancer. Materials and methods TMB and treatment outcome were retrospectively analyzed in patients with newly diagnosed cervical cancer treated with definitive radiotherapy available with somatic mutation data of pre-treatment tumors obtained using a commercially available gene panel. Results The study enrolled 98 patients (median follow-up period, 61 months). The median TMB was 9.5 mutations per megabase (range, 3.0–35.5 mutations per megabase). After dichotomization based on this median value, the 5-year overall survival (OS) for TMB-high patients was significantly worse than that of TMB-low patients (61.1% vs. 82.2%). Multivariate analysis identified high TMB status as a significant prognostic factor for worse OS, along with advanced stage, para-aortic lymph node involvement, and absence of concurrent chemotherapy. Conclusion These data indicate that TMB is a potential prognostic factor for worse survival in patients with cervical cancer treated with definitive radiotherapy, thereby providing a rationale for treatment of TMB-high cervical cancers with a combination of ICIs plus radiotherapy. Secondary abstract This retrospective study of 98 patients demonstrates for the first time that tumor mutational burden (TMB) is an independent prognostic factor for worse overall survival of patients treated with definitive radiotherapy, providing a rationale for treatment of TMB-high cervical cancers with a combination of immune-checkpoint inhibitors plus radiotherapy. Cervical cancer (dpeaa)DE-He213 Radiotherapy (dpeaa)DE-He213 Tumor mutational burden (dpeaa)DE-He213 Prognosis (dpeaa)DE-He213 Yoshimoto, Yuya aut Darwis, Narisa Dewi Maulany aut Sato, Hiro aut Ando, Ken aut Oike, Takahiro aut Ohno, Tatsuya aut Enthalten in Radiation medicine Tokyo : Springer, 1999 40(2021), 5 vom: 03. Dez., Seite 534-541 (DE-627)368312305 (DE-600)2117284-5 1862-5274 nnns volume:40 year:2021 number:5 day:03 month:12 pages:534-541 https://dx.doi.org/10.1007/s11604-021-01230-5 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_105 GBV_ILN_120 GBV_ILN_138 GBV_ILN_152 GBV_ILN_161 GBV_ILN_171 GBV_ILN_187 GBV_ILN_224 GBV_ILN_250 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_702 AR 40 2021 5 03 12 534-541
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source	Enthalten in Radiation medicine 40(2021), 5 vom: 03. Dez., Seite 534-541 volume:40 year:2021 number:5 day:03 month:12 pages:534-541
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topic_facet	Cervical cancer Radiotherapy Tumor mutational burden Prognosis
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authorswithroles_txt_mv	Ota, Norichika @@aut@@ Yoshimoto, Yuya @@aut@@ Darwis, Narisa Dewi Maulany @@aut@@ Sato, Hiro @@aut@@ Ando, Ken @@aut@@ Oike, Takahiro @@aut@@ Ohno, Tatsuya @@aut@@
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This study aimed to elucidate the association between TMB and the outcome of definitive radiotherapy in patients with cervical cancer. Materials and methods TMB and treatment outcome were retrospectively analyzed in patients with newly diagnosed cervical cancer treated with definitive radiotherapy available with somatic mutation data of pre-treatment tumors obtained using a commercially available gene panel. Results The study enrolled 98 patients (median follow-up period, 61 months). The median TMB was 9.5 mutations per megabase (range, 3.0–35.5 mutations per megabase). After dichotomization based on this median value, the 5-year overall survival (OS) for TMB-high patients was significantly worse than that of TMB-low patients (61.1% vs. 82.2%). Multivariate analysis identified high TMB status as a significant prognostic factor for worse OS, along with advanced stage, para-aortic lymph node involvement, and absence of concurrent chemotherapy. Conclusion These data indicate that TMB is a potential prognostic factor for worse survival in patients with cervical cancer treated with definitive radiotherapy, thereby providing a rationale for treatment of TMB-high cervical cancers with a combination of ICIs plus radiotherapy. 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author	Ota, Norichika
spellingShingle	Ota, Norichika misc Cervical cancer misc Radiotherapy misc Tumor mutational burden misc Prognosis High tumor mutational burden predicts worse prognosis for cervical cancer treated with radiotherapy
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topic_title	High tumor mutational burden predicts worse prognosis for cervical cancer treated with radiotherapy Cervical cancer (dpeaa)DE-He213 Radiotherapy (dpeaa)DE-He213 Tumor mutational burden (dpeaa)DE-He213 Prognosis (dpeaa)DE-He213
topic	misc Cervical cancer misc Radiotherapy misc Tumor mutational burden misc Prognosis
topic_unstemmed	misc Cervical cancer misc Radiotherapy misc Tumor mutational burden misc Prognosis
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title	High tumor mutational burden predicts worse prognosis for cervical cancer treated with radiotherapy
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title_full	High tumor mutational burden predicts worse prognosis for cervical cancer treated with radiotherapy
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author_browse	Ota, Norichika Yoshimoto, Yuya Darwis, Narisa Dewi Maulany Sato, Hiro Ando, Ken Oike, Takahiro Ohno, Tatsuya
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title_sort	high tumor mutational burden predicts worse prognosis for cervical cancer treated with radiotherapy
title_auth	High tumor mutational burden predicts worse prognosis for cervical cancer treated with radiotherapy
abstract	Purpose Tumor mutational burden (TMB) is a surrogate biomarker of neo-antigens and high TMB status is associated with favorable response to immune-checkpoint inhibitors (ICIs). This study aimed to elucidate the association between TMB and the outcome of definitive radiotherapy in patients with cervical cancer. Materials and methods TMB and treatment outcome were retrospectively analyzed in patients with newly diagnosed cervical cancer treated with definitive radiotherapy available with somatic mutation data of pre-treatment tumors obtained using a commercially available gene panel. Results The study enrolled 98 patients (median follow-up period, 61 months). The median TMB was 9.5 mutations per megabase (range, 3.0–35.5 mutations per megabase). After dichotomization based on this median value, the 5-year overall survival (OS) for TMB-high patients was significantly worse than that of TMB-low patients (61.1% vs. 82.2%). Multivariate analysis identified high TMB status as a significant prognostic factor for worse OS, along with advanced stage, para-aortic lymph node involvement, and absence of concurrent chemotherapy. Conclusion These data indicate that TMB is a potential prognostic factor for worse survival in patients with cervical cancer treated with definitive radiotherapy, thereby providing a rationale for treatment of TMB-high cervical cancers with a combination of ICIs plus radiotherapy. Secondary abstract This retrospective study of 98 patients demonstrates for the first time that tumor mutational burden (TMB) is an independent prognostic factor for worse overall survival of patients treated with definitive radiotherapy, providing a rationale for treatment of TMB-high cervical cancers with a combination of immune-checkpoint inhibitors plus radiotherapy. © The Author(s) 2021
abstractGer	Purpose Tumor mutational burden (TMB) is a surrogate biomarker of neo-antigens and high TMB status is associated with favorable response to immune-checkpoint inhibitors (ICIs). This study aimed to elucidate the association between TMB and the outcome of definitive radiotherapy in patients with cervical cancer. Materials and methods TMB and treatment outcome were retrospectively analyzed in patients with newly diagnosed cervical cancer treated with definitive radiotherapy available with somatic mutation data of pre-treatment tumors obtained using a commercially available gene panel. Results The study enrolled 98 patients (median follow-up period, 61 months). The median TMB was 9.5 mutations per megabase (range, 3.0–35.5 mutations per megabase). After dichotomization based on this median value, the 5-year overall survival (OS) for TMB-high patients was significantly worse than that of TMB-low patients (61.1% vs. 82.2%). Multivariate analysis identified high TMB status as a significant prognostic factor for worse OS, along with advanced stage, para-aortic lymph node involvement, and absence of concurrent chemotherapy. Conclusion These data indicate that TMB is a potential prognostic factor for worse survival in patients with cervical cancer treated with definitive radiotherapy, thereby providing a rationale for treatment of TMB-high cervical cancers with a combination of ICIs plus radiotherapy. Secondary abstract This retrospective study of 98 patients demonstrates for the first time that tumor mutational burden (TMB) is an independent prognostic factor for worse overall survival of patients treated with definitive radiotherapy, providing a rationale for treatment of TMB-high cervical cancers with a combination of immune-checkpoint inhibitors plus radiotherapy. © The Author(s) 2021
abstract_unstemmed	Purpose Tumor mutational burden (TMB) is a surrogate biomarker of neo-antigens and high TMB status is associated with favorable response to immune-checkpoint inhibitors (ICIs). This study aimed to elucidate the association between TMB and the outcome of definitive radiotherapy in patients with cervical cancer. Materials and methods TMB and treatment outcome were retrospectively analyzed in patients with newly diagnosed cervical cancer treated with definitive radiotherapy available with somatic mutation data of pre-treatment tumors obtained using a commercially available gene panel. Results The study enrolled 98 patients (median follow-up period, 61 months). The median TMB was 9.5 mutations per megabase (range, 3.0–35.5 mutations per megabase). After dichotomization based on this median value, the 5-year overall survival (OS) for TMB-high patients was significantly worse than that of TMB-low patients (61.1% vs. 82.2%). Multivariate analysis identified high TMB status as a significant prognostic factor for worse OS, along with advanced stage, para-aortic lymph node involvement, and absence of concurrent chemotherapy. Conclusion These data indicate that TMB is a potential prognostic factor for worse survival in patients with cervical cancer treated with definitive radiotherapy, thereby providing a rationale for treatment of TMB-high cervical cancers with a combination of ICIs plus radiotherapy. Secondary abstract This retrospective study of 98 patients demonstrates for the first time that tumor mutational burden (TMB) is an independent prognostic factor for worse overall survival of patients treated with definitive radiotherapy, providing a rationale for treatment of TMB-high cervical cancers with a combination of immune-checkpoint inhibitors plus radiotherapy. © The Author(s) 2021
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title_short	High tumor mutational burden predicts worse prognosis for cervical cancer treated with radiotherapy
url	https://dx.doi.org/10.1007/s11604-021-01230-5
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author2	Yoshimoto, Yuya Darwis, Narisa Dewi Maulany Sato, Hiro Ando, Ken Oike, Takahiro Ohno, Tatsuya
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High tumor mutational burden predicts worse prognosis for cervical cancer treated with radiotherapy

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