Reply to S. Alanee et al

Abstract

In their letter, Alanee and Dynda 1 point out the lack of inclusion of patients with extragonadal germ cell tumors (GCT) in our study. 2 We quantified cardiovascular disease (CVD) mortality among men with testicular nonseminoma whose initial course of treatment included either chemotherapy without radiation or surgery without radiation and who were reported to the population-based SEER program (1980 to 2010). 2 Alanee et al 3 previously examined the risk of CVD mortality in 5-year survivors of extragonadal GCT in the SEER program, including those diagnosed in the 1970s before the widespread use of cisplatin-based chemotherapy (1973 to 2008). Compared with patients with gonadal GCT (n 5 34,990; median follow-up, 88 months), Alanee et al 3 found that patients with primary mediastinal GCT (n 5 824; median follow-up, 26 months) and nonmediastinal extragonadal GCT (n 5 1,469; median followup, 46 months) had significantly increased risks (4.5-fold; 95% CI, 2.5 to 8.0; number not specified v 2.8-fold; 95% CI, 1.7 to 4.5; number not specified) for total CVD mortality, although numbers of deaths by latency period were not reported. Alanee et al 3 did not examine CVD mortality within one year of extragonadal GCT diagnosis, because the cohort was restricted to 5-year survivors. As reviewed previously, 2 Alanee et al 3 postulated that their findings were a result of the typically larger amounts of primary cisplatin-based chemotherapy and additional salvage chemotherapy needed to treat extragonadal GCT, although treatment data were unavailable to confirm this hypothesis. Nonetheless, their results support our tenet that cisplatin-based chemotherapy may, in part, explain the significantly increased CVD mortality we observed in the first year after testicular cancer (TC) diagnosis among patients who were administered chemotherapy (standardized mortality ratio, 5.31; 95% CI, 2.65 to 9.51; n 5 11), but not after surgery alone (standardized mortality ratio, 0.75; 95% CI, 0.09 to 2.72; n 5 2). In addition, it is important to recognize that, as we have reviewed, 2 a number of other factors likely contributed to early CVD mortality among our chemotherapy-treated patients, including the Khorana categorization of TC as a high-risk cancer for chemotherapy-associated venous thromboembolism, more advanced stage, direct vascular effects of cisplatin-based chemotherapy, and other influences.As reviewed by Feldman et al, 4 direct vascular injury and endothelial dysfunction likely play important roles in the pathophysiology of cardiovascular effects of cisplatin-based chemotherapy. Survivors of TC display increased levels of biomarkers for endothelial dysfunction and inflammation after cisplatin-based chemotherapy, including von Willebrand factor, fibrinogen, tissue-type plasminogen activator, and high-sensitivity C-reactive protein. 4,5 Compared with prechemotherapy measurements, carotid intimal medial thickness was significantly increased among survivors of TC (n 5 57) within 10 weeks of completing four courses of bleomycin, etoposide, and ...

Clinical Characteristics of Testicular Nonseminomatous Germ Cell Tumor from West China: A 10-Year Experience of a Super regional Center

“…Other chemotherapyrelated multi-system side effects like cardiovascular disease, leukyemia, etc. were also reported by some researchers (8)(9)(10)(11). Every sword has its two sides, advantages and disadvantages of chemotherapy should be evaluated comprehensively.…”