Experimental and Clinical Oncology, Department of Immunology, Genetics and Pathology; Uppsala University, Uppsala, Sweden.
Regional Cancer Center of Southeast Sweden and Department of Biomedical and Clinical Sciences, Medical Faculty, Linköping University, Linköping, Sweden.
J Clin Oncol. 2022 May 1;40(13):1487-1496. doi: 10.1200/JCO.21.02407. Epub 2022 Jan 25.
Balancing disease control and toxicity from chemotherapy and radiotherapy (RT) when treating early-stage classical Hodgkin lymphoma (cHL) is important. Available data on long-term toxicity after RT for cHL mostly refer to RT techniques no longer in use. We aimed to describe long-term toxicity from modern limited-field (LF)-RT after two or four cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD).
This study included all patients with cHL treated with two or four cycles of ABVD and 30 Gy LF-RT during 1999-2005 in Sweden. Patients (n = 215) and comparators (n = 860), matched for age, gender, and region of residence, were cross-checked against national health registries for malignancies, diseases of the circulatory system (DCS), and diseases of the respiratory system (DRS) from the day of diagnosis of cHL.
The risk of a malignancy was higher for patients than comparators, hazard ratio (HR) 1.5 (95% CI, 1.0 to 2.4), as was the risk for DCS 1.5 (95% CI, 1.1 to 2.0) and for DRS 2.6 (95% CI, 1.6 to 4.3). The median follow-up was 16 years (range, 12-19 years). Of individual diagnoses in DCS, only venous thromboembolism was statistically significantly elevated. If the first 6 months (ie, time of active treatment for cHL) were excluded and censoring at relapse of cHL or diagnosis of any malignancy, the increased HR for venous thromboembolism diminished. Most of the excess risk for DRS consisted of asthma, HR 3.5 (95% CI, 1.8 to 6.8). Patients diagnosed with DRS were significantly younger than comparators.
Compared with toxicity from earlier RT techniques, excess morbidity was not eliminated, but lower than previously reported. The elevated risk of DRS was driven by diagnosis of asthma, which could in part be explained by misdiagnosis of persisting pulmonary toxicity.
在治疗早期经典霍奇金淋巴瘤(cHL)时,平衡化疗和放疗(RT)的疾病控制和毒性非常重要。关于 cHL 接受 RT 后长期毒性的现有数据主要是指不再使用的 RT 技术。我们旨在描述在接受两个或四个周期多柔比星、博来霉素、长春碱和达卡巴嗪(ABVD)治疗后,采用现代局限性(LF)RT 治疗的 cHL 患者的长期毒性。
这项研究包括 1999 年至 2005 年间在瑞典接受两个或四个周期 ABVD 治疗和 30 Gy LF-RT 的所有 cHL 患者。患者(n=215)和对照组(n=860),按照年龄、性别和居住地区匹配,与国家健康登记处交叉核对,以确定从 cHL 诊断之日起恶性肿瘤、循环系统疾病(DCS)和呼吸系统疾病(DRS)的发病情况。
与对照组相比,患者发生恶性肿瘤的风险更高,风险比(HR)为 1.5(95%CI,1.0 至 2.4),DCS 风险为 1.5(95%CI,1.1 至 2.0),DRS 风险为 2.6(95%CI,1.6 至 4.3)。中位随访时间为 16 年(范围,12-19 年)。在 DCS 的个别诊断中,只有静脉血栓栓塞症具有统计学显著意义。如果排除前 6 个月(即 cHL 积极治疗时间),并以 cHL 复发或任何恶性肿瘤的诊断为终点进行 censoring,则静脉血栓栓塞症的 HR 升高会减弱。DRS 风险升高主要是由哮喘引起的,HR 为 3.5(95%CI,1.8 至 6.8)。诊断为 DRS 的患者明显比对照组年轻。
与早期 RT 技术的毒性相比,发病率的增加并未消除,但低于先前的报告。DRS 风险升高是由哮喘诊断引起的,部分原因可能是对持续肺部毒性的误诊。