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.

Background: Immunotherapy with programmed cell death protein-1 (PD-1)/programmed cell death ligand-1 (PD-L1) inhibitors has been widely used in the treatment of solid tumors and Hodgkin lymphoma, demonstrating powerful efficacy and good safety. However, there is no systematic review and meta-analysis to fully investigate the efficacy and safety of PD-1/PD-L1 inhibitors in treating non-Hodgkin lymphoma (NHL). Methods: We searched PubMed, EMBASE, The Cochrane Library, China National Knowledge Infrastructure, Wanfang database, and abstracts of conference proceedings of annual meetings up to January 23, 2022, to identify eligible clinical trials. To evaluate the efficacy of PD-1/PD-L1 inhibitors, objective response rate (ORR), complete response rate (CRR), 1-year overall survival rate, and 1-year progression-free survival rate were analyzed. For safety analysis, we calculated rates of any grade and grade ≥3 treatment-related adverse events. Results: Overall 22 studies and 1150 participants were enrolled in this meta-analysis. The pooled ORR, CRR, 1-year overall survival, and 1-year progression-free survival rates were 0.43 (95% confidence interval [CI], 0.33–0.54), 0.21 (95% CI, 0.13–0.31), 0.72 (95% CI, 0.58–0.89), and 0.42 (95% CI, 0.29–0.62), respectively. The ORR and CRR in the combination immunochemotherapy subgroup (0.65 and 0.41) were higher than those in the monotherapy (0.27 and 0.09) and combination chemotherapy (0.39 and 0.19) subgroups. This study was registered with PROSPERO (#CRD 42022316805). Conclusion: Given that there were limited clinical trials and relatively few relevant studies, we conducted this meta-analysis to fully elucidate the efficacy and safety of PD-1/PD-L1 inhibitors in NHL. Our results suggested that PD-1/PD-L1 inhibitors improved outcomes of responses as well as survival rates in NHL patients with tolerable adverse events. More well-designed randomized clinical trials are still needed to further confirm our findings.

As a highly heterogeneous disease, diffuse large B-cell lymphoma shows different clinical presentations, molecular and immunophenotypic characteristics, International Prognostic Index (IPI score) and response to therapy, which consequently brings about different prognoses and survival results. In addition to surgery and chemotherapy, radiation is also one important modality to treat diffuse large B-cell lymphoma. Over the past few decades, radiation therapy has stepped forward because of technological revolutions. The role of radiation in treating diffuse large B-cell lymphoma is discussed, including: i) advances in modern-day radiation technology ii) potential toxicity from radiation, iii) indications for radiation, and iv) available studies about the efficacy of radiation.

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