Soft tissue sarcomas have traditionally been treated with a one-size fits all approach, despite a wide range of histologies and clinical outcomes.
The radiosensitivity index has demonstrated that soft tissue sarcomas are in general radioresistant, however exhibit a wide range of radiosensitivity.
These differences in radiosensitivity are associated with decreased locoregional control in patients with radioresistant histologies.
Using the radiosensitivity index we identify specific histologies of soft tissue sarcoma that may be more radioresistant, and suggest a genomic-based radiation dosing framework.
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 BED α/β= 3.29 of 97 Gy.