Abstract. There is considerable interest in deploying stereotactic body radiotherapy in combination with immune therapy for patients with extracranial oligometastases. In addition to angiogenesis inhibition, sunitinib appears to mediate antitumor immunity through effects on circulating monocytic cells. The current study investigated the effects of combined sunitinib and stereotactic radiotherapy on hematopoiesis. As part of a phase I/II clinical trial utilizing concurrent sunitinib (25-50 mg on days 1-28) and image-guided radiation therapy (40-50 Gy in 10 fractions starting on days 8-19) for patients with metastatic cancer, the complete blood count, platelet count and automatic differential were performed pretreatment and on days 8 and 19. On average, sunitinib monotherapy for 7 days resulted in a 33% decrease in monocytes and an 18% decrease in neutrophils (P<0.01 for all). Compared to sunitinib alone, combined sunitinib and radiation resulted in a further decrease in neutrophils, lymphocytes and platelets (P<0.05). Following sunitinib and radiation treatment, a greater than average decrease in monocytes (≥200/µl) was associated with a significant increase in progression-free and overall survival times. This exploratory study provides further evidence that monocytes represent a potential biomarker in patients with solid tumors treated with sunitinib.

Abstract.Radiation technique for prostate cancer has continuously evolved over the past several decades. The aim of the present study was to describe the effects of implementing modern prostate intensity-modulated radiation therapy (M-IMRT) on dosimetry and outcome. Between January 2010 and April 2012, 48 consecutive patients were treated with conventional prostate IMRT (C-IMRT) to a dose of 81 Gy. Between May 2012 and April 2015, 50 consecutive patients were treated with M-IMRT to the entire prostate to a dose of 75.6-79.2 Gy, while using prostate magnetic resonance imaging fusion, dose-volume constraints prioritizing normal tissue avoidance above planning target volume coverage, and boosting any dominant intraprostatic masses to 79.2-81 Gy. Rectal Dmax, V75, V60, V65 and V50, bladder Dmax, V75, V70 and V65, and acute and late toxicities were compared between the C-IMRT and M-IMRT groups. The median follow-up for the C-IMRT and M-IMRT groups was 61 vs. 26 months, respectively (P<0.001). M-IMRT resulted in a significant reduction in median rectal Dmax, rectal V75, rectal V70, rectal V65, bladder Dmax, bladder V75, bladder V70 and bladder V65 (P<0.01 for all). There was no significant difference in rectal V50. The 2-year rate of late grade ≥2 rectal bleeding was 13% with C-IMRT vs. 3% with M-IMRT (P=0.03). The 2-year rate of late grade ≥2 genitourinary toxicity was 11% for C-IMRT vs. 5% for M-IMRT (P= 0.21). There were no significant differences in acute toxicity, biochemical control or overall survival.Therefore, compared with C-IMRT, M-IMRT was associated with reduced rectal toxicity without compromising disease control.

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