Aims: This observational study characterized cardiovascular disease (CVD) mortality risk for multiple cancer sites, with respect to the following: (i) continuous calendar year, (ii) age at diagnosis, and (iii) follow-up time after diagnosis. Methods and results: The Surveillance, Epidemiology, and End Results program was used to compare the US general population to 3 234 256 US cancer survivors (1973–2012). Standardized mortality ratios (SMRs) were calculated using coded cause of death from CVDs (heart disease, hypertension, cerebrovascular disease, atherosclerosis, and aortic aneurysm/dissection). Analyses were adjusted by age, race, and sex. Among 28 cancer types, 1 228 328 patients (38.0%) died from cancer and 365 689 patients (11.3%) died from CVDs. Among CVDs, 76.3% of deaths were due to heart disease. In eight cancer sites, CVD mortality risk surpassed index-cancer mortality risk in at least one calendar year. Cardiovascular disease mortality risk was highest in survivors diagnosed at <35 years of age. Further, CVD mortality risk is highest (SMR 3.93, 95% confidence interval 3.89–3.97) within the first year after cancer diagnosis, and CVD mortality risk remains elevated throughout follow-up compared to the general population. Conclusion: The majority of deaths from CVD occur in patients diagnosed with breast, prostate, or bladder cancer. We observed that from the point of cancer diagnosis forward into survivorship cancer patients (all sites) are at elevated risk of dying from CVDs compared to the general US population. In endometrial cancer, the first year after diagnosis poses a very high risk of dying from CVDs, supporting early involvement of cardiologists in such patients.

Glioblastoma (GBM) may initially respond to treatment with ionizing radiation (IR), but the prognosis remains extremely poor because the tumors invariably recur. Using animal models, we previously showed that inhibiting stromal cell–derived factor 1 signaling can prevent or delay GBM recurrence by blocking IR-induced recruitment of myeloid cells, specifically monocytes that give rise to tumor-associated macrophages. The present study was aimed at determining if inhibiting colony stimulating factor 1 (CSF-1) signaling could be used as an alternative strategy to target pro-tumorigenic myeloid cells recruited to irradiated GBM. To inhibit CSF-1 signaling in myeloid cells, we used PLX3397, a small molecule that potently inhibits the tyrosine kinase activity of the CSF-1 receptor (CSF-1R). Combined IR and PLX3397 therapy was compared with IR alone using 2 different human GBM intracranial xenograft models. GBM xenografts treated with IR upregulated CSF-1R ligand expression and increased the number of CD11b+ myeloid-derived cells in the tumors. Treatment with PLX3397 both depleted CD11b+ cells and potentiated the response of the intracranial tumors to IR. Median survival was significantly longer for mice receiving combined therapy versus IR alone. Analysis of myeloid cell differentiation markers indicated that CSF-1R inhibition prevented IR-recruited monocyte cells from differentiating into immunosuppressive, pro-angiogenic tumor-associated macrophages. CSF-1R inhibition may be a promising strategy to improve GBM response to radiotherapy.

The 2-[18F]-Fluorodeoxyglucose (FDG) positron emission tomography (PET/CT) has become an imaging tool for clinical assessment of tumor, node, metastasis in non-small-cell lung cancer (NSCLC). Primary tumor maximum standardized uptake value (SUV(max)) on (18)F-FDG PET/CT before and after radiation therapy (RT) has been studied as a potential prognostic factor for NSCLC patients receiving radiotherapy. However, the sample sizes of most studies were small, and the results of the prediction value of SUV(max) remained undetermined, which lead us to perform a meta-analysis to improve the precision in estimating its effect. We performed a meta-analysis of published literature for primary tumor SUV(max)-based biomarkers of the outcome of NSCLC receiving radiotherapy. The required data for estimation of individual hazard ratios (HRs) to compare patients with a low and a high SUV(max) were extracted from each publication. A combined HR was calculated by Stata statistical software (Version 11). All of the results were verified by two persons to ensure its accuracy. Thirteen studies were finally included into this meta-analysis; data are available in 13 studies for pre-RT primary tumor SUV(max) and in five studies for post-RT. For overall survival, the combined HR estimate was 1.05 (95% confidence interval [CI], 1.02-1.08) and 1.32 (95% CI, 1.15-1.51) for pre-RT SUV(max) and post-RT SUV(max), respectively; 1.26 (95% CI, 1.05-1.52) and 2.01 (95% CI, 1.16-3.46) for local control (LC). In stereotactic body radiotherapy (SBRT) group, HR for LC was 1.11 (95% CI, 1.06-1.18) and 2.19 (95% CI, 1.34-3.60) for pre-SBRT SUV(max) and post-SBRT SUV(max), respectively. Both pre-RT and post-RT primary tumor SUV(max) can predict the outcome of patients with NSCLC treated with radiotherapy. Patients with high levels of pre-RT SUV(max) seemed to have poorer overall survival and LC.