Intrinsic Radiosensitivity Index Differences of Sarcoma and the Potential for Genome-Adjusted Radiation Dosing

Abstract

Purpose/Objective(s): Sarcomas are a rare and heterogeneous disease with wide variation in histopathological features and response to radiation therapy (RT). We have previously developed and validated a gene expression signature to measure intrinsic tumor radiosensitivity, the radiosensitivity index (RSI). In this study, we assessed the RSI of multiple subtypes of sarcomas using a cohort of surgically resected lesions. Materials/Methods: A cohort of 232 resected sarcoma samples including angiosarcoma (nZ14), chondrosarcoma (nZ11), Ewing sarcoma (nZ3), fibrosarcoma (nZ7), leiomyosarcoma (nZ53), liposarcoma (nZ58), MPNST (nZ3), osteosarcoma (nZ7), pleomorphic sarcoma (nZ29), and synovial sarcoma (nZ11) were identified from our prospective, observational protocol. RSI was analyzed using the previously published algorithm. Differences in RSI were analyzed with ANOVA testing and differences in specific RSI histologies evaluated using Tukey Honest Significant Differences with two-sided p-values <0.05 considered significant. Results: The median RSI across the 232 sarcoma tissue samples was 0.52 (range 0.09-1.01). Using a previously identified cut-point, the majority of sarcoma samples (nZ195, 84%) were noted to be radioresistant. The median RSIs for the sarcoma subtypes in increasing order of radioresistance were: angiosarcoma (0.44, range 0.20-0.64), Ewing sarcoma (0.47, range 0.41-0.50), chondrosarcoma (0.48, range 0.19-0.64), , fibrosarcoma (0.49, range 0.38-0.87), MPNST (0.49, range 0.23-0.71), leiomyosarcoma (0.52, range 0.09-0.70), pleomorphic sarcoma (0.53, range 0.25-0.76), osteosarcoma (0.54, range 0.43-0.64), synovial sarcoma (0.55, range 0.29-0.85) and liposarcoma (0.60, range 0.25-1.01). There is an overall significant ANOVA test comparing these histologies (pZ 0.0113), suggesting heterogeneous radiation therapeutic effects if treated with a uniform dose. There are significant differences for liposarcoma vs. angiosarcoma (95% Tukey CI 0.16, 0.01-0.31 pZ0.011) and liposarcoma vs. leiomyosarcoma (95% Tukey CI 0.10, 0.01-0.20) (pZ0.011). Conclusion: Sarcomas have a high degree of heterogeneity which results in varied clinical and pathological outcomes following treatment with preoperative RT. There are significant difference in the intrinsic radiosensitivity among and within sarcoma subtypes. Subtype specific genome-based radiation therapy could potentially improve clinical outcome/toxicity for this disease in the era of precision medicine.

Primary Leiomyosarcoma of the Glans

“…The extension of the procedure (amputation vs partial penectomy) depends on the location and extension of the lesion on the penis an invasion of adjacent tissues and structures. Radiotherapy would be reserved to palliation in inoperable tumors, since leiomyosarcomas are not listed at as the most sensitives sarcomas to radiation therapy ( 13 ).…”

Current advances in radiotherapy for soft tissue sarcomas

“…To predict the response to treatment, scientists created a model of radiosensitivity as a function of gene expression and other factors in a form of a rank-based linear regression algorithm to establish the radiosensitivity index (RSI). This model was used in further research to calculate the RSI of 113 resected STS samples [41]. The study investigated a predictive value of RSI for locoregional control with preoperative RT in STS.…”

Stereotactic radiotherapy for soft tissue and bone sarcomas: real-world evidence

“…Interestingly, new studies on their radiosensitivity gave surprising results. 6,7 For example, myxoid liposarcomas present excellent pathological response to low-dose preoperative radiotherapy with 100% of 2-year local control rate in two phase II clinical trials. 8,9 Moreover, even within the same STBS pathological subtype, the radiosensitivity may vary.…”

“…8,9 Moreover, even within the same STBS pathological subtype, the radiosensitivity may vary. 7 The analysis of real-world evidence could provide valuable insights into outcomes of SRT in routine practice and help to optimize the treatment. 10 The objectives of this study were to summarize the utilization and outcomes of SRT in the management of advanced STBS, identify the patients who benefit the most, and check whether the given dose matters.…”