Effect of pretreatment central adiposity on the cardiometabolic risk of male germ cell tumor survivors after cisplatin-based chemotherapy.

5019 Background: Preferential fat accumulation in the visceral compartment (i.e. central adiposity) increases cardiovascular risk in the general population independent of body mass index (BMI). We investigated how body fat distribution modulates the cardiometabolic risk of male germ cell tumor (GCT) survivors after cisplatin-based chemotherapy. Methods: For 456 patients in The Platinum Study enrolled at Memorial Sloan Kettering Cancer Center, visceral (VAT) and subcutaneous (SAT) adipose tissue compartments were quantified on pre-chemotherapy computed tomography (CT) scans (median time between CT and chemotherapy: 13 days, range: 0-56). The VAT/SAT ratio was calculated as a quantitative indicator of central adiposity. Endpoints were (I) post-chemotherapy cardiovascular risk as per the office-based Framingham risk calculator, and (II) incidence of post-chemotherapy cardiometabolic disease defined as need for new anti-hypertensive drugs, or lipid-lowering drugs, or medication used to treat diabetes. Changes in fat distribution after chemotherapy were analyzed in a subgroup with post-chemotherapy CTs (n = 108; median interval from chemotherapy start: 18 months, range: 7-185). Linear regression with interaction terms (endpoint 1, subgroup analysis) and Cox proportional hazard regression (endpoint 2) were applied. Results: For all 456 patients, median age at chemotherapy initiation was 31 years and median follow-up was 27 months (range: 7, 207). At baseline (pre-chemotherapy), the median BMI was 26.2 kg/m2, and 102 patients (22.4%) had a BMI of ≥30 kg/m2. The median VAT/SAT ratio at baseline CT was 0.49, and positively associated with higher post-chemotherapy Framingham risk scores after adjustment for age, BMI, and blood pressure measurements at chemotherapy start, as well as post-therapy follow-up time (adjusted β-estimate: 1.36, 95% CI: 1.15, 1.59, p < 0.001). A higher VAT/SAT ratio also inferred a higher likelihood of new onset cardiometabolic disease in patients with BMI ≥30 kg/m2 (age-adjusted HR: 3.11, 95%CI: 1.01, 9.62, p = 0.048), but not in those with BMI < 30 kg/m2. In the subgroup analysis, we observed a significant increase of BMI after chemotherapy (mean: +1.1 kg/m2, 95% CI: +0.58, +1.54; p < 0.001). Changes in BMI were positively associated with changes of the VAT/SAT ratio (β-estimate: 3.0, 95% CI: 2.23, 4.04; p < 0.001), meaning that weight gain occurred preferentially in the VAT compartment, while weight loss tended to be paralleled by an improved body fat distribution. Conclusions: In male GCT patients, central adiposity at baseline increases cardiometabolic risk after cisplatin-based chemotherapy, particularly for obese individuals. Quantification of an individual’s body fat distribution on pre-chemotherapy CT could potentially help to identify high risk individuals who may benefit from intensified risk-modulating interventions.

Bleomycin-Induced Pneumonitis in the Treatment of Ovarian Sex Cord–Stromal Tumors: A Systematic Review and Meta-analysis

ObjectiveAdult ovarian sex cord–stromal tumors (SCSTs) are a rare histological subtype of ovarian cancer associated with a favorable prognosis. Bleomycin-containing regimens are standards of care, although pneumonitis may cause potentially fatal dose-limiting toxicity. We aimed to evaluate the safety of bleomycin in SCST treatment.MethodsWe performed a systematic literature review of all studies of bleomycin therapy for SCSTs that were referenced in MEDLINE (PubMed), EMBASE, and Cochrane Central Register of Controlled Trials and published from 1986 to 2014.ResultsEight studies totaling 221 patients were included. Rates of pneumonitis (7.7%; 95% confidence interval, 4.2–11.2) and mortality (1.8%; 95% confidence interval, 0.1–3.6) related to bleomycin were significant. However, these results were very similar to those reported for men who were treated with bleomycin for a male germ cell tumor, suggesting that women with ovarian SCSTs are not particularly vulnerable to bleomycin lung toxicity. The main risk factors of bleomycin-induced pneumonitis are high cumulative bleomycin dose (>400 U or mg), age older than 40 years, and impaired renal function. Whether granulocyte colony-stimulating factor is a risk factor remains controversial.ConclusionsBleomycin-induced pneumonitis frequently occurs in patients with SCSTs and lacks effective treatment. Prevention lies in limiting cumulative bleomycin dose, monitoring pulmonary function during treatment, discontinuing bleomycin at the onset of pulmonary symptoms or if pulmonary function is impaired, and avoiding bleomycin in older patients.