Genomic identification of sarcoma radiosensitivity and the clinical implications for radiation dose personalization
Background: Soft-tissue sarcomas (STS) are heterogeneous with variable response to radiation therapy (RT). Utilizing the radiosensitivity index (RSI) we estimated the radiobiologic ratio of lethal to sublethal damage (α/β), genomic-adjusted radiation dose(GARD), and in-turn a biological effective ra...
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| Format: | Article |
| Language: | English |
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Elsevier
2021-10-01
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| Series: | Translational Oncology |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1936523321001571 |
| _version_ | 1818883126605119488 |
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| author | George Yang Zhigang Yuan Kamran Ahmed Eric A. Welsh William J. Fulp Ricardo J. Gonzalez John E. Mullinax Douglas Letson Marilyn Bui Louis B. Harrison Jacob G. Scott Javier F. Torres-Roca Arash O. Naghavi |
| author_facet | George Yang Zhigang Yuan Kamran Ahmed Eric A. Welsh William J. Fulp Ricardo J. Gonzalez John E. Mullinax Douglas Letson Marilyn Bui Louis B. Harrison Jacob G. Scott Javier F. Torres-Roca Arash O. Naghavi |
| author_sort | George Yang |
| collection | DOAJ |
| description | Background: Soft-tissue sarcomas (STS) are heterogeneous with variable response to radiation therapy (RT). Utilizing the radiosensitivity index (RSI) we estimated the radiobiologic ratio of lethal to sublethal damage (α/β), genomic-adjusted radiation dose(GARD), and in-turn a biological effective radiation dose (BED). Methods: Two independent cohorts of patients with soft-tissue sarcoma were identified. The first cohort included 217 genomically-profiled samples from our institutional prospective tissue collection protocol; RSI was calculated for these samples, which were then used to dichotomize the population as either highly radioresistant (HRR) or conventionally radioresistant (CRR). In addition, RSI was used to calculate α/β ratio and GARD, providing ideal dosing based on sarcoma genomic radiosensitivity. A second cohort comprising 399 non-metastatic-STS patients treated with neoadjuvant RT and surgery was used to validate our findings. Results: Based on the RSI of the sample cohort, 84% would historically be considered radioresistant. We identified a HRR subset that had a significant difference in the RSI, and clinically a lower tumor response to radiation (2.4% vs. 19.4%), 5-year locoregional-control (76.5% vs. 90.8%), and lower estimated α/β (3.29 vs. 5.98), when compared to CRR sarcoma. Using GARD, the dose required to optimize outcome in the HRR subset is a BEDα/β=3.29 of 97 Gy. Conclusions: We demonstrate that on a genomic scale, that although STS is radioresistant overall, they are heterogeneous in terms of radiosensitivity. We validated this clinically and estimated an α/β ratio and dosing that would optimize outcome, personalizing dose. |
| first_indexed | 2024-12-19T15:28:42Z |
| format | Article |
| id | doaj.art-ddb740cb8b0b41ac990b8c196e3698d1 |
| institution | Directory Open Access Journal |
| issn | 1936-5233 |
| language | English |
| last_indexed | 2024-12-19T15:28:42Z |
| publishDate | 2021-10-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Translational Oncology |
| spelling | doaj.art-ddb740cb8b0b41ac990b8c196e3698d12022-12-21T20:15:48ZengElsevierTranslational Oncology1936-52332021-10-011410101165Genomic identification of sarcoma radiosensitivity and the clinical implications for radiation dose personalizationGeorge Yang0Zhigang Yuan1Kamran Ahmed2Eric A. Welsh3William J. Fulp4Ricardo J. Gonzalez5John E. Mullinax6Douglas Letson7Marilyn Bui8Louis B. Harrison9Jacob G. Scott10Javier F. Torres-Roca11Arash O. Naghavi12H. Lee Moffitt Cancer Center and Research Institute, Department of Radiation Oncology, United StatesH. Lee Moffitt Cancer Center and Research Institute, Department of Radiation Oncology, United StatesH. Lee Moffitt Cancer Center and Research Institute, Department of Radiation Oncology, United StatesBiostatistics, United StatesFred Hutchinson Research Institute, United StatesSarcoma, United StatesSarcoma, United StatesSarcoma, United StatesSarcoma, United States; Pathology, United StatesH. Lee Moffitt Cancer Center and Research Institute, Department of Radiation Oncology, United StatesCleveland Clinic, Translational Hematology and Oncology Research, United StatesH. Lee Moffitt Cancer Center and Research Institute, Department of Radiation Oncology, United StatesH. Lee Moffitt Cancer Center and Research Institute, Department of Radiation Oncology, United States; Corresponding author.Background: Soft-tissue sarcomas (STS) are heterogeneous with variable response to radiation therapy (RT). Utilizing the radiosensitivity index (RSI) we estimated the radiobiologic ratio of lethal to sublethal damage (α/β), genomic-adjusted radiation dose(GARD), and in-turn a biological effective radiation dose (BED). Methods: Two independent cohorts of patients with soft-tissue sarcoma were identified. The first cohort included 217 genomically-profiled samples from our institutional prospective tissue collection protocol; RSI was calculated for these samples, which were then used to dichotomize the population as either highly radioresistant (HRR) or conventionally radioresistant (CRR). In addition, RSI was used to calculate α/β ratio and GARD, providing ideal dosing based on sarcoma genomic radiosensitivity. A second cohort comprising 399 non-metastatic-STS patients treated with neoadjuvant RT and surgery was used to validate our findings. Results: Based on the RSI of the sample cohort, 84% would historically be considered radioresistant. We identified a HRR subset that had a significant difference in the RSI, and clinically a lower tumor response to radiation (2.4% vs. 19.4%), 5-year locoregional-control (76.5% vs. 90.8%), and lower estimated α/β (3.29 vs. 5.98), when compared to CRR sarcoma. Using GARD, the dose required to optimize outcome in the HRR subset is a BEDα/β=3.29 of 97 Gy. Conclusions: We demonstrate that on a genomic scale, that although STS is radioresistant overall, they are heterogeneous in terms of radiosensitivity. We validated this clinically and estimated an α/β ratio and dosing that would optimize outcome, personalizing dose.http://www.sciencedirect.com/science/article/pii/S1936523321001571Radiation therapyRadiosensitivityGenomic-adjusted radiation dose |
| spellingShingle | George Yang Zhigang Yuan Kamran Ahmed Eric A. Welsh William J. Fulp Ricardo J. Gonzalez John E. Mullinax Douglas Letson Marilyn Bui Louis B. Harrison Jacob G. Scott Javier F. Torres-Roca Arash O. Naghavi Genomic identification of sarcoma radiosensitivity and the clinical implications for radiation dose personalization Translational Oncology Radiation therapy Radiosensitivity Genomic-adjusted radiation dose |
| title | Genomic identification of sarcoma radiosensitivity and the clinical implications for radiation dose personalization |
| title_full | Genomic identification of sarcoma radiosensitivity and the clinical implications for radiation dose personalization |
| title_fullStr | Genomic identification of sarcoma radiosensitivity and the clinical implications for radiation dose personalization |
| title_full_unstemmed | Genomic identification of sarcoma radiosensitivity and the clinical implications for radiation dose personalization |
| title_short | Genomic identification of sarcoma radiosensitivity and the clinical implications for radiation dose personalization |
| title_sort | genomic identification of sarcoma radiosensitivity and the clinical implications for radiation dose personalization |
| topic | Radiation therapy Radiosensitivity Genomic-adjusted radiation dose |
| url | http://www.sciencedirect.com/science/article/pii/S1936523321001571 |
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