Person:

Tishler, Roy

Background: Preclinical studies suggest a synergistic effect between radiation, immunotherapy and anti-angiogenic therapy, although the mechanisms are unclear. Angiogenic cytokines are known to affect the immune system, and their levels may be associated with response to immunotherapy. Here, we assess changes in circulating VEGF, as well as angiogenic cytokines angiopoietin-1 and -2 (Ang1, Ang2), and placental growth factor (PLGF) that occur during definitive chemo-radiotherapy in HNSCC patients. Methods: We prospectively collected blood samples from patients receiving definitive radiation with or without chemotherapy. Serum Ang1, Ang2, VEGF, and PLGF were measured via cytokine assays. Results: The majority of patients had advanced stage, node positive HPV-associated oropharyngeal cancer, and received radiation to a median dose of 70 Gy with concurrent cisplatin. Over the course of treatment, serum VEGF and Ang1 levels decreased in 20/24 (84 %, p < 0.0001) and 21/24 (88 %, p < 0.0001) patients, respectively, and Ang2 and PLGF levels increased in 20/24 (83 %, p < 0.0001) patients. Conclusions: We find significant changes in angiogenic cytokines in the majority of HNSCC patients over the course of chemoradiation. Decreases in VEGF caused by radiation may represent one mechanism of potential synergy with immunotherapy. Increases in Ang2 and PLGF are interesting given their link to tumor associated angiogenesis and poor prognosis. Additional studies are needed to explore synergies between anti-angiogenic treatments, immunotherapy, and chemoradiation in HNSCC. Electronic supplementary material The online version of this article (doi:10.1186/s40425-016-0138-9) contains supplementary material, which is available to authorized users.

Dental restorations, fixed prosthodontics, and implants affect dose distribution in head and neck radiation therapy due to the high atomic number of the materials utilized. The backscatter of electrons from metallic materials due to the impinging treatment x‐ray results in localized dose enhancements. These dose enhancements cause localized mucositis in patients who have dental work, a significant clinical complication. We investigated the backscatter effect of 23 configurations of dental work using the EGS4nrc Monte Carlo (MC) simulation system. We found that all‐metal fixed partial dentures caused the highest amount of dose enhancement – up to 33% – while amalgam restorations did not cause a significant amount. Restorations with a ceramic veneer caused up to 8% enhancement. Between 3 mm and 5 mm of water‐equivalent material almost completely absorbed the backscatter. MC simulations provide an accurate estimate of backscatter dose, and may provide patient‐specific estimates in future.