霍奇金淋巴瘤治疗后 40 年内的二次癌症风险。

Second Cancer Risk Up to 40 Years after Treatment for Hodgkin's Lymphoma.

机构信息

From the Departments of Epidemiology (M.S., A.M.E., I.M., I.M.K., F.E.L.), Radiation Oncology (B.M.P.A.), and Hematology (J.P.B.), Netherlands Cancer Institute, and the Department of Hematology, VU University Medical Center Amsterdam (J.M.Z.), Amsterdam, the Netherlands Comprehensive Cancer Organization (M.S., I.M., O.V., M.W.J.L.) and the Departments of Radiation Oncology (J.R.) and Hematology (E.J.P.), University Medical Center Utrecht, Utrecht, the Departments of Radiation Oncology (C.P.M.J.) and Hematology (P.J.L.), Erasmus Medical Center Cancer Institute, Rotterdam, the Department of Radiation Oncology, Leiden University Medical Center, Leiden (A.D.G.K.), the Department of Radiation Oncology, Radboud University Medical Center (R.W.M.M., P.M.P.P.), and the Department of Education and Science, Canisius-Wilhelmina Hospital (I.M.), Nijmegen, the Department of Hematology, Radboud University Medical Center, Nijmegen-Rijnstate, Arnhem (J.M.M.R.), the Departments of Hematology (G.W.I.) and Radiation Oncology (M.B.), University Medical Center Groningen, Groningen, the Department of Radiation Oncology, Dr. Bernard Verbeeten Institute, Tilburg (P.M.P.P.), and the Department of Radiotherapy, Catharina Hospital, Eindhoven (M.L.L.) - all in the Netherlands.

出版信息

N Engl J Med. 2015 Dec 24;373(26):2499-511. doi: 10.1056/NEJMoa1505949.

DOI:10.1056/NEJMoa1505949

PMID:26699166

Abstract

BACKGROUND

Survivors of Hodgkin's lymphoma are at increased risk for treatment-related subsequent malignant neoplasms. The effect of less toxic treatments, introduced in the late 1980s, on the long-term risk of a second cancer remains unknown.

METHODS

We enrolled 3905 persons in the Netherlands who had survived for at least 5 years after the initiation of treatment for Hodgkin's lymphoma. Patients had received treatment between 1965 and 2000, when they were 15 to 50 years of age. We compared the risk of a second cancer among these patients with the risk that was expected on the basis of cancer incidence in the general population. Treatment-specific risks were compared within the cohort.

RESULTS

With a median follow-up of 19.1 years, 1055 second cancers were diagnosed in 908 patients, resulting in a standardized incidence ratio (SIR) of 4.6 (95% confidence interval [CI], 4.3 to 4.9) in the study cohort as compared with the general population. The risk was still elevated 35 years or more after treatment (SIR, 3.9; 95% CI, 2.8 to 5.4), and the cumulative incidence of a second cancer in the study cohort at 40 years was 48.5% (95% CI, 45.4 to 51.5). The cumulative incidence of second solid cancers did not differ according to study period (1965-1976, 1977-1988, or 1989-2000) (P=0.71 for heterogeneity). Although the risk of breast cancer was lower among patients who were treated with supradiaphragmatic-field radiotherapy not including the axilla than among those who were exposed to mantle-field irradiation (hazard ratio, 0.37; 95% CI, 0.19 to 0.72), the risk of breast cancer was not lower among patients treated in the 1989-2000 study period than among those treated in the two earlier periods. A cumulative procarbazine dose of 4.3 g or more per square meter of body-surface area (which has been associated with premature menopause) was associated with a significantly lower risk of breast cancer (hazard ratio for the comparison with no chemotherapy, 0.57; 95% CI, 0.39 to 0.84) but a higher risk of gastrointestinal cancer (hazard ratio, 2.70; 95% CI, 1.69 to 4.30).

CONCLUSIONS

The risk of second solid cancers did not appear to be lower among patients treated in the most recent calendar period studied (1989-2000) than among those treated in earlier periods. The awareness of an increased risk of second cancer remains crucial for survivors of Hodgkin's lymphoma. (Funded by the Dutch Cancer Society.).

摘要

背景

霍奇金淋巴瘤幸存者罹患治疗相关继发恶性肿瘤的风险增加。自 20 世纪 80 年代末引入毒性较低的治疗方法以来，其对第二个癌症的长期风险的影响仍不清楚。

方法

我们在荷兰招募了 3905 名至少在霍奇金淋巴瘤治疗开始后 5 年仍存活的患者。患者在 1965 年至 2000 年期间接受治疗，当时他们的年龄在 15 至 50 岁之间。我们比较了这些患者的第二个癌症风险与一般人群中癌症发病率所预期的风险。在队列内比较了特定治疗的风险。

结果

中位随访 19.1 年后，在 908 例患者中诊断出 1055 例第二癌症，导致研究队列中的标准化发病比（SIR）为 4.6（95%置信区间[CI]，4.3 至 4.9）与一般人群相比。治疗后 35 年或更长时间风险仍然升高（SIR，3.9；95%CI，2.8 至 5.4），研究队列中 40 年时的第二癌症累积发生率为 48.5%（95%CI，45.4 至 51.5）。第二实体癌的累积发生率不因研究期间（1965-1976 年、1977-1988 年或 1989-2000 年）而异（异质性 P=0.71）。尽管与接受不包括腋窝的膈上野放疗的患者相比，接受斗篷野照射的患者乳腺癌风险较低（风险比，0.37；95%CI，0.19 至 0.72），但在 1989-2000 年治疗期间接受治疗的患者与在两个较早时期接受治疗的患者相比，乳腺癌风险并未降低。每平方米体表面积 4.3 克或以上的累积丙卡巴肼剂量（与过早绝经有关）与乳腺癌风险显著降低相关（与无化疗相比的风险比，0.57；95%CI，0.39 至 0.84），但胃肠道癌风险更高（风险比，2.70；95%CI，1.69 至 4.30）。