In addition to inducing lethal DNA damage in tumor and stromal cells, radiation can alter the interactions of tumor cells with their microenvironment. Recent technological advances in planning and delivery of external beam radiotherapy have allowed delivery of larger doses per fraction (hypofractionation) while minimizing dose to normal tissues with higher precision. The effects of radiation on the tumor microenvironment vary with dose and fractionation schedule. In this review, we summarize the effects of conventional and hypofractionated radiation regimens on the immune system and tumor stroma. We discuss how these interactions may provide therapeutic benefit in combination with targeted therapies. Understanding the differential effects of radiation dose and fractionation can have implications for choice of combination therapies.

Purpose To review outcomes of patients with oligometastatic prostate cancer (PCa) treated with stereotactic body radiation therapy (SBRT) and to identify variables associated with local failure. Methods and Materials We retrospectively reviewed records of patients treated with SBRT for oligometastatic PCa. Metastasis control (ie, control of the treated lesion, MC), biochemical progression-free survival, distant progression-free survival, and overall survival were estimated with the Kaplan-Meier method. Results Sixty-six men with 81 metastatic PCa lesions, 50 of which were castrate-resistant, were included in the analysis. Lesions were in bone (n=74), lymph nodes (n=6), or liver (n=1). Stereotactic body radiation therapy was delivered in 1 fraction to 71 lesions (88%), at a median dose of 16 Gy (range, 16–24 Gy). The remaining lesions received 30 Gy in 3 fractions (n=6) or 50 Gy in 5 fractions (n=4). Median follow-up was 16 months (range, 3–49 months). Estimated MC at 2 years was 82%. Biochemical progression-free survival, distant progression-free survival, and overall survival were 54%, 45%, and 83%, respectively. On multivariate analysis, only the dose of SBRT was significantly associated with MC; lesions treated with 16 Gy had 58% MC, and those treated with ≥18 Gy had 95% MC at 2 years (P≤.001). At 2 years, MC for lesions treated with ≥18 Gy (n=21) was 88%. No patient treated with ≥18 Gy in a single fraction or with any multifraction regimen had local failure. Six patients (9%) had grade 1 pain flare, and 2 (3%) had grade 2 pain flare. No grade 2 or greater late toxicities were reported. Conclusions Stereotactic body radiation therapy for patients with oligometastatic prostate cancer provided optimal metastasis control and acceptable toxicity with doses ≥18 Gy. Biochemical progression-free survival was 54% at 16 months with the inclusion of SBRT in the treatment regimen. Stereotactic body radiation therapy should be considered in patients with castration-refractory, oligometastatic prostate cancer who have limited options for systemic therapy.

Background: Although neoadjuvant radiotherapy is typically administered for locally-advanced rectal cancer to reduce local recurrence (LR), its role for patients who present with synchronous resectable liver and/or lung metastasis is not well defined. The aim of this study was to evaluate the role of neoadjuvant radiotherapy for patients with stage IV rectal cancer undergoing curative-intent surgery. Methods: This study is a retrospective review of a prospectively maintained surgical registry of all consecutive adult patients who underwent curative-intent resection at Mayo Clinic in Rochester, MN, from January 1990 until December 2014 with a median follow-up time of 43 (IQR 16-67) months. Eligible patients had locally-advanced rectal cancer (T3, T4 and/or nodal involvement) with synchronous resectable liver and/or lung metastasis. Exclusion criteria were as follows: patients with primary tumor stage of T1N0 or T2N0, patients with metastasis to organs other than the liver or lung, patients who had palliative resection, patients who had non-surgical treatment of synchronous metastasis (e.g., radiofrequency ablation), patients who received postoperative radiotherapy, or absence of research authorization. Ninety three patients were included of which 47 received neoadjuvant radiotherapy and 46 did not. All patients received neoadjuvant chemotherapy +/− radiotherapy followed by curative-intent surgery with metastasectomy performed either simultaneously with resection of the primary tumor or as a planned staged resection. The primary outcomes of this study are LR, distant metastasis, overall and disease-specific survival (DSS).Results: LR was observed in 12 patients (26%) who did not receive radiotherapy, while no LR developed in those who received neoadjuvant radiotherapy, P<0.001. Univariate analysis showed that neither age, sex, ASA class, BMI, tumor location, procedure performed, or neoadjuvant chemotherapy were associated with subsequent LR. The 5-year overall survival (OS) rates were: 43.3% (95% CI: 30.1, 62.3) for no radiotherapy vs. 58.3% (95% CI: 43.4, 78.2) with radiotherapy.Conclusions: Neoadjuvant radiotherapy should be considered in patients with locally-advanced stage IV rectal cancer. These data add to the evidence supporting neoadjuvant radiotherapy in the setting of resectable metastatic disease.

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