{"doi":"10.1016/j.tranon.2021.101165","title":"Genomic identification of sarcoma radiosensitivity and the clinical implications for radiation dose personalization","abstract":"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). 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. 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. 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.","journal":"Translational Oncology","year":2021,"id":152783,"datarank":1.6926430862960304,"base_score":4.304065093204169,"endowment":4.304065093204169,"self_citation_contribution":0.6456097639806255,"citation_network_contribution":1.047033322315405,"self_endowment_contribution":0.6456097639806255,"citer_contribution":1.047033322315405,"corpus_percentile":87.62280498182099,"corpus_rank":1601,"citation_count":73,"citer_count":41,"citers_with_citation_signal":29,"citers_with_endowment":29,"datacite_reuse_total":0,"is_dataset":true,"is_dataset_confidence":0.6785,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":648346,"name":"Zhigang Yuan","orcid":"0000-0002-6060-4004","position":1,"is_corresponding":false},{"id":325113,"name":"Kamran A. Ahmed","orcid":"0000-0003-3331-1529","position":2,"is_corresponding":false},{"id":341885,"name":"Eric A. Welsh","orcid":"0000-0002-9302-3855","position":3,"is_corresponding":false},{"id":258346,"name":"William J. Fulp","orcid":"0000-0001-6888-0794","position":4,"is_corresponding":false},{"id":648347,"name":"Ricardo González","orcid":"0000-0003-3853-2582","position":5,"is_corresponding":false},{"id":514597,"name":"John E. Mullinax","orcid":"0000-0002-9596-6785","position":6,"is_corresponding":false},{"id":649081,"name":"Douglas Letson","orcid":null,"position":7,"is_corresponding":false},{"id":576286,"name":"Marilyn M. Bui","orcid":"0000-0003-4963-2255","position":8,"is_corresponding":false},{"id":319302,"name":"Louis B. Harrison","orcid":null,"position":9,"is_corresponding":false},{"id":261754,"name":"Jacob G. Scott","orcid":"0000-0003-2971-7673","position":10,"is_corresponding":false},{"id":318020,"name":"Javier F. Torres–Roca","orcid":"0000-0001-5169-2121","position":11,"is_corresponding":false},{"id":648348,"name":"A.O. Naghavi","orcid":"0000-0002-0884-1942","position":12,"is_corresponding":false},{"id":648345,"name":"G.Q. Yang","orcid":"0000-0003-4745-2592","position":0,"is_corresponding":true}],"reference_count":51,"raw_metadata":null,"created_at":"2026-07-18T23:43:34.972031Z","pmid":"34246048","pmcid":"PMC8274330","fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}