Harmke J. Groot, Jan Martijn Kerst, Katarzyna Jóźwiak, Alexandra W. van den Belt-Dusebout, Simon Horenblas, Flora E. van Leeuwen, and Michael Schaapveld, Netherlands Cancer Institute; Alfons J.M. van den Eertwegh, Vrije Universiteit Medical Center; Heinz-Josef Klümpen, Academic Medical Center, Amsterdam; Sjoukje Lubberts, Igle J. de Jong, Alfons C.M. van den Bergh, and Jourik A. Gietema, University Medical Center Groningen, University of Groningen, Groningen; Ronald de Wit and Luca Incrocci, Erasmus Medical Center Cancer Institute, Rotterdam; Johannes A. Witjes, Radboud University Medical Center, Nijmegen; Gerard Groenewegen, University Medical Center Utrecht Cancer Center, Utrecht; Philip M. Poortmans, Instituut Verbeeten, Tilburg; Hetty A. van den Berg, Catharina Hospital, Eindhoven; Tineke J. Smilde, Jeroen Bosch Hospital, 's-Hertogenbosch; Ben G.L. Vanneste, MAASTRO Clinic; Maureen J. Aarts, Maastricht University Medical Center, Maastricht, the Netherlands; and Philip M. Poortmans, Institut Curie, Paris, France.
J Clin Oncol. 2018 Aug 20;36(24):2504-2513. doi: 10.1200/JCO.2017.77.4174. Epub 2018 Jul 10.
Purpose Testicular cancer (TC) treatment increases risk of subsequent malignant neoplasms (SMNs). It is unknown whether changes in TC treatment over time have affected SMN risk. Methods Solid SMN risk was evaluated in a multicenter cohort comprising 5,848 1-year survivors treated for TC before age 50 years between 1976 and 2007. SMN incidence was compared with cancer incidence in the general population. Treatment-specific risks were assessed using multivariable regression in a case-cohort design. Results After a median follow-up of 14.1 years, 350 solid SMNs were observed, translating into a 1.8-fold (95% CI, 1.6-2.0) increased risk compared with general population rates. Solid SMN risk was increased in patients with seminoma and those with nonseminoma (standardized incidence ratio, 1.52 and 2.21, respectively). Patients with nonseminoma experienced increased risk of SMNs of the thyroid, lung, stomach, pancreas, colon, and bladder and of melanoma and soft tissue sarcoma, whereas those with seminoma experienced increased risk of SMNs of the small intestine, pancreas, and urinary bladder. The 25-year cumulative incidence of solid SMNs was 10.3% (95% CI, 9.0% to 11.6%). In multivariable analysis, platinum-based chemotherapy was associated with increased risk of a solid SMN (hazard ratio [HR], 2.40; 95% CI, 1.58 to 3.62), colorectal SMN (HR, 3.85; 95% CI, 1.67 to 8.92), and noncolorectal GI SMN (HR, 5.00; 95% CI, 2.28 to 10.95). Receipt of platinum 400 to 499 and ≥ 500 mg/m increased solid SMN risk compared with surgery only (HR, 2.43; 95% CI, 1.40 to 4.23 and HR, 2.42; 95% CI, 1.50 to 3.90, respectively), whereas risk was not significantly increased with lower doses (HR, 1.75; 95% CI, 0.90 to 3.43). The HR of a GI SMN increased by 53% (95% CI, 26% to 80%) per 100 mg/m of platinum-containing chemotherapy. The HR of an infradiaphragmatic SMN increased by 8% per Gray of radiation dose administered (95% CI, 6% to 9%; P < .001). Conclusion Radiotherapy and platinum-containing chemotherapy are associated with increased solid SMN risk, specifically with GI SMNs.
目的 睾丸癌（TC）的治疗会增加随后发生恶性肿瘤（SMN）的风险。目前尚不清楚随着时间的推移，TC 治疗方法的改变是否会影响 SMN 的风险。
方法 本研究纳入了一个多中心队列，共包括 5848 名年龄在 50 岁以下、1976 年至 2007 年期间接受 TC 治疗的 1 年幸存者。通过比较队列中癌症的发病率，评估了实体性 SMN 的风险。采用病例对照设计中的多变量回归来评估特定治疗方法的风险。
结果 中位随访 14.1 年后，观察到 350 例实体性 SMN，与一般人群相比，风险增加了 1.8 倍（95%CI，1.6-2.0）。精原细胞瘤和非精原细胞瘤患者的实体性 SMN 风险增加（标准化发病比分别为 1.52 和 2.21）。非精原细胞瘤患者发生甲状腺癌、肺癌、胃癌、胰腺癌、结肠癌和膀胱癌以及黑色素瘤和软组织肉瘤的风险增加，而精原细胞瘤患者发生小肠癌、胰腺癌和膀胱癌的风险增加。25 年的实体性 SMN 累积发病率为 10.3%（95%CI，9.0%至 11.6%）。多变量分析显示，铂类化疗与实体性 SMN（风险比 [HR]，2.40；95%CI，1.58 至 3.62）、结直肠癌 SMN（HR，3.85；95%CI，1.67 至 8.92）和非结直肠癌胃肠道 SMN（HR，5.00；95%CI，2.28 至 10.95）的风险增加相关。与仅手术治疗相比，接受铂类药物 400 至 499 毫克/平方米和≥500 毫克/平方米的治疗与实体性 SMN 风险增加相关（HR，2.43；95%CI，1.40 至 4.23 和 HR，2.42；95%CI，1.50 至 3.90），而较低剂量的铂类药物治疗与风险增加无关（HR，1.75；95%CI，0.90 至 3.43）。每增加 100 毫克/平方米的铂类化疗药物，胃肠道 SMN 的 HR 增加 53%（95%CI，26%至 80%）。每增加 1 Gray 的放射剂量，膈下 SMN 的 HR 增加 8%（95%CI，6%至 9%；P<0.001）。
结论 放疗和含铂化疗与实体性 SMN 风险增加相关，特别是胃肠道 SMN。
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