TY - JOUR
T1 - Risk of Solid Cancer After Treatment of Testicular Germ Cell Cancer in the Platinum Era
AU - Groot, Harmke J.
AU - Lubberts, Sjoukje
AU - de Wit, Ronald
AU - Witjes, Johannes A.
AU - Kerst, Jan Martijn
AU - de Jong, Igle J.
AU - Groenewegen, Gerard
AU - van den Eertwegh, Alfons J. M.
AU - Poortmans, Philip M.
AU - Klumpen, Heinz-Josef
AU - van den Berg, Hetty A.
AU - Smilde, Tineke J.
AU - Vanneste, Ben G. L.
AU - Aarts, Maureen J.
AU - Incrocci, Luca
AU - van den Bergh, Alfons C. M.
AU - Jozwiak, Katarzyna
AU - van den Belt-Dusebout, Alexandra W.
AU - Horenblas, Simon
AU - Gietema, Jourik A.
AU - van Leeuwen, Flora E.
AU - Schaapveld, Michael
PY - 2018/8/20
Y1 - 2018/8/20
N2 - PurposeTesticular cancer (TC) treatment increases risk of subsequent malignant neoplasms (SMNs). It is unknown whether changes in TC treatment over time have affected SMN risk.MethodsSolid 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.ResultsAfter 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(2) 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(2) 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).ConclusionRadiotherapy and platinum-containing chemotherapy are associated with increased solid SMN risk, specifically with GI SMNs.
AB - PurposeTesticular cancer (TC) treatment increases risk of subsequent malignant neoplasms (SMNs). It is unknown whether changes in TC treatment over time have affected SMN risk.MethodsSolid 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.ResultsAfter 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(2) 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(2) 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).ConclusionRadiotherapy and platinum-containing chemotherapy are associated with increased solid SMN risk, specifically with GI SMNs.
KW - LONG-TERM SURVIVORS
KW - CHILDHOOD-CANCER
KW - 2ND CANCERS
KW - MOLECULAR-MECHANISMS
KW - CHEMOTHERAPY
KW - RADIOTHERAPY
KW - CISPLATIN
KW - MANAGEMENT
KW - MORTALITY
KW - NEOPLASMS
KW - SURVIVORS
U2 - 10.1200/JCO.2017.77.4174
DO - 10.1200/JCO.2017.77.4174
M3 - Article
C2 - 29989856
SN - 0732-183X
VL - 36
SP - 2504
EP - 2513
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
IS - 24
ER -