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Purpose: Radiation-induced cardiotoxicity is a significant concern in thoracic oncology patients. However, the basis for this disease pathology is not well characterized. We developed a novel mouse model of radiation-induced cardiotoxicity to investigate pathophysiologic mechanisms and identify clinically targetable biomarkers of cardiac injury. Experimental Design: Single radiation doses of 20, 40, or 60 Gy were delivered to the cardiac apex of female C57BL/6 mice ages 9-11 weeks, with or without adjacent lung tissue, using conformal radiotherapy. Cardiac tissue was harvested up to 24 weeks postradiotherapy for histologic analysis. Echocardiography and Technetium-99m sestamibi single photon emission computed tomography (SPECT) at 8 and 16 weeks post-radiotherapy were implemented to evaluate myocardial function and perfusion. Mouse cardiac tissue and mouse and human plasma were harvested for biochemical studies. Results: Histopathologically, radiotherapy resulted in perivascular fibrosis 8 and 24 (P < 0.05) weeks post-radiotherapy. Apical perfusion deficits on SPECT and systolic and diastolic dysfunction on echocardiography 8 and 16 weeks postradiotherapy were also observed (P < 0.05). Irradiated cardiac tissue and plasma showed significant increases in placental growth factor (PlGF), IL6, and TNFa compared with nonradiated matched controls, with greater increases in cardiac cytokine levels when radiotherapy involved lung. Human plasma showed increased PlGF (P ¼ 0.021) and TNFa (P ¼ 0.036) levels after thoracic radiotherapy. PlGF levels demonstrated a strong correlation (r ¼ 0.89, P ¼ 0.0001) with mean heart dose. Conclusions: We developed and characterized a pathophysiologically relevant mouse model of radiation-induced cardiotoxicity involving in situ irradiation of the cardiac apex. The model can be used to integrate radiomic and biochemical markers of cardiotoxicity to inform early therapeutic intervention and human translational studies.

Background/Objectives Proton therapy (PRT) has emerged as a treatment option for chordomas/chondrosarcomas to escalate radiation dose more safely. We report results of a phase I/II trial of PRT in patients with chordoma/chondrosarcoma. Methods Twenty adult patients with pathologically confirmed, nonmetastatic chordoma or chondrosarcoma were enrolled in a single‐institution prospective trial of PRT from 2010 to 2014. Seventeen patients received adjuvant PRT and three received definitive PRT. Median dose was 73.8 Gy(RBE; range 68.4‐79.2 Gy) using PRT‐only (n = 6) or combination PRT/intensity‐modulated radiotherapy (IMRT) (n = 14). Quality‐of‐life (QOL) and fatigue were assessed weekly and every 3 months posttreatment with the Functional Assessment of Cancer Therapy ‐ Brain (FACTBr) and Brief Fatigue Inventory. Primary endpoint was feasibility (90% completing treatment with < 10 day treatment delay and ≤ 20% unexpected acute grade ≥ 3 toxicity). Results Tumors included chordomas of the skull base (n = 10), sacrum (n = 5), and cervical spine (n = 3), and skull base chondrosarcomas (n = 2). Median age was 57. The 80% had positive margins/gross disease. Median follow‐up was 37 months. Feasibility endpoints were met. The 3‐year local control and progression‐free survival was 86% and 81%. There were no deaths. Two patients had acute grade 3 toxicity (both fatigue). One had late grade 3 toxicity (epistaxis and osteoradionecrosis). There were no significant differences in patient reported fatigue or QOL from baseline to the end‐of‐treatment. Conclusions We report favorable local control, survival, and toxicity following PRT.

OBJECTIVETo define the prevalence and patterns of selfinitiated herbal and vitamin supplementation among men at high risk of developing prostate cancer, as there is increasing public awareness of prostate cancer screening, riskfactor assessment and prevention, leading to increasing interest in the use and systematic study of nutritional therapies for prostate cancer prevention. SUBJECTS AND METHODSSince 1996 our institution has prospectively maintained a prostate cancer-risk registry through its Prostate Cancer Risk Assessment Program (PRAP). Eligibility includes AfricanAmerican men, any man with at least one first-degree relative or two or more seconddegree relatives with prostate cancer, or men who tested positively for the BRCA1 gene mutation. A 420-item self-administered questionnaire was completed and included the use of nutritional supplements and complementary therapies. We divided men into groups who used supplements to lessen their cancer risk and those who did not. The prevalence and patterns of use were evaluated and the two groups then compared for differences in demographic, socioeconomic and risk-perception variables. RESULTSIn all, 345 high-risk men were enrolled in the PRAP over a 5-year period. Data on the use of dietary or herbal supplements were available on 333 men (97%), of whom over half (170) reported taking one or more supplements to prevent prostate cancer. Supplement use was divided into eight categories, including vitamins, minerals, extracts from fruits/seeds, organic compounds, flowers/bulbs, leaves/ bark, roots, or animal products. Most commonly used for self-initiated chemoprevention were vitamins (95%), minerals (28%), and fruit/seed extracts (18%). More than a quarter of men (27%) took three or more agents. Men taking proactive preventative measures were statistically more likely to be Caucasian and aged > 60 years ( P < 0.05). African-Americans were less likely to self-initiate preventative steps. Men taking supplements tended to return more often for follow-up and participate in PRAP longer, while those not taking supplements tended to earn less and report less self-perceived risk. CONCLUSIONS