Increased stomach cancer risk following radiotherapy for testicular cancer

The incidence of testicular cancer (TC), the most common malignancy affecting males aged 15–34 years in the United States and Europe (McGlynn et al, 2003; Garner et al, 2005), has continuously increased over the past 30 years (Chia et al, 2010). As a result of the introduction of radiotherapy in the 1950s and cisplatin-containing combination chemotherapy in 1978 (Einhorn and Donohue, 1977), TC is currently among the most curable solid tumours, with 10-year relative survival reaching 95% (Biggs and Schwartz, 2007; Verdecchia et al, 2007). Previous studies of TC survivors have demonstrated increased risks for treatment-related second solid malignancies, beginning 10–15 years after initial diagnosis, with stomach cancer being of particular concern among TC survivors, given reported standardised incidence ratios ranging from 2.0 to 9.2 (Van Leeuwen et al, 1993; Travis et al, 1997; Kollmannsberger et al, 1999; Travis et al, 2005; Robinson et al, 2007; Van den Belt-Dusebout et al, 2007; Horwich et al, 2014). Although excess cases have been most often attributed to radiotherapy, the effects of radiation dose to the stomach have not been assessed in large studies. Furthermore, although some investigations among Hodgkin's lymphoma survivors reported especially high risks after combined radiotherapy and chemotherapy (Mauch et al, 1996; Birdwell et al, 1997; Swerdlow et al, 2000; Van Leeuwen et al, 2000; Foss Abrahamsen et al, 2002; Morton et al, 2013), the effects of specific chemotherapy agents and doses on stomach cancer risk after TC have not been examined. Therefore, in an international cohort of 22 269 5-year survivors of TC, we evaluated treatment-related stomach cancer risk based on estimated radiation dose to the stomach and dose of chemotherapeutic agents for 92 stomach cancer patients and 180 individually matched controls.