Department of Radiation Oncology, Rutgers Cancer Institute of New Jersey, New Brunswick.
Biometrics Division, Rutgers Cancer Institute of New Jersey, New Brunswick.
JAMA Oncol. 2019 May 1;5(5):689-695. doi: 10.1001/jamaoncol.2018.5911.
To date, there is no well-defined standard of care for early-stage pediatric Hodgkin lymphoma (HL), which may include chemotherapy alone or combined modality therapy (CMT) with chemotherapy followed by radiotherapy. Although the use of radiotherapy in pediatric HL is decreasing, this strategy remains controversial.
To examine the use of CMT in pediatric HL and its association with improved overall survival using data from a large cancer registry.
DESIGN, SETTING, AND PARTICIPANTS: This observational cohort study used data from the National Cancer Database to evaluate clinical features and survival outcomes among 5657 pediatric patients (age, 0.1-21 years) who received a diagnosis of stage I or II HL in the United States from January 1, 2004, to December 31, 2015. Statistical analysis was conducted from May 1 to November 1, 2018.
Patients received definitive treatment with chemotherapy or CMT, defined as chemotherapy followed by radiotherapy.
Kaplan-Meier survival curves were used to examine overall survival. The association between CMT use, covariables, and overall survival was assessed in multivariable Cox proportional hazards regression models. Use of radiotherapy was assessed over time.
Among the 11 546 pediatric patients with HL in the National Cancer Database, 5657 patients (3004 females, 2596 males, and 57 missing information on sex; mean [SD] age, 17.1 [3.6] years) with stage I or II classic HL were analyzed. Of these patients, 2845 (50.3%) received CMT; use of CMT vs chemotherapy alone was associated with younger age (<16 years, 1102 of 2845 [38.7%] vs 856 of 2812 [30.4%]; P < .001), male sex (1369 of 2845 [48.1%] vs 1227 of 2812 [43.6%]; P < .001), stage II disease (2467 of 2845 [86.7%] vs 2376 of 2812 [84.5%]; P = .02), and private health insurance (2065 of 2845 [72.6%] vs 1949 of 2812 [69.3%]; P = .002). The 5-year overall survival was 94.5% (confidence limits, 93.8%, 95.8%) for patients who received chemotherapy alone and 97.3% (confidence limits, 96.4%, 97.9%) for those who received CMT, which remained significant in the intention-to-treat analysis and multivariate analysis (adjusted hazard ratio for CMT, 0.57; 95% CI, 0.42-0.78; P < .001). In the sensitivity analysis, the low-risk cohort (stage I-IIA) and adolescent and young adult patients had the greatest benefit from CMT (adjusted hazard ratio, 0.47; 95% CI, 0.40-0.56; P < .001). The use of CMT decreased by 24.8% from 2004 to 2015 (from 59.7% [271 of 454] to 34.9% [153 of 438]).
In this study, pediatric patients with early-stage HL receiving CMT experienced improved overall survival 5 years after treatment. There is a nationwide decrease in the use of CMT, perhaps reflecting the bias of ongoing clinical trials designed to avoid consolidation radiotherapy. This study represents the largest data set to date examining the role of CMT in pediatric HL.
重要性：迄今为止，对于早期儿科霍奇金淋巴瘤（HL），尚无明确的治疗标准，这种疾病可能包括单独化疗或联合化疗（CMT）联合化疗后放疗。尽管儿科 HL 中放疗的应用正在减少，但这种策略仍存在争议。
目的：利用大型癌症数据库的数据，研究儿科 HL 中 CMT 的应用及其与提高总体生存率之间的关系。
设计、地点和参与者：这项观察性队列研究使用了国家癌症数据库的数据，评估了美国 2004 年 1 月 1 日至 2015 年 12 月 31 日期间接受 I 期或 II 期 HL 诊断的 5657 名儿科患者（年龄 0.1-21 岁）的临床特征和生存结果。统计分析于 2018 年 5 月 1 日至 11 月 1 日进行。
暴露：患者接受了明确的化疗或 CMT 治疗，CMT 定义为化疗后放疗。
主要结局和测量：采用 Kaplan-Meier 生存曲线评估总生存率。多变量 Cox 比例风险回归模型评估 CMT 使用、协变量与总生存率的关系。评估了放疗的使用随时间的变化。
结果：在国家癌症数据库中 11546 名患有 HL 的儿科患者中，对 5657 名患有 I 期或 II 期经典 HL 的患者（3004 名女性，2596 名男性，57 名信息缺失）进行了分析。这些患者中，2845 名（50.3%）接受了 CMT；与单独化疗相比，CMT 的使用与更年轻的年龄（<16 岁，2845 名中的 1102 名[38.7%]与 2812 名中的 856 名[30.4%]；P < .001）、男性（2845 名中的 1369 名[48.1%]与 2812 名中的 1227 名[43.6%]；P < .001）、II 期疾病（2845 名中的 2467 名[86.7%]与 2812 名中的 2376 名[84.5%]；P = .02）和私人医疗保险（2845 名中的 2065 名[72.6%]与 2812 名中的 1949 名[69.3%]；P = .002）相关。接受单独化疗的患者 5 年总生存率为 94.5%（置信区间，93.8%，95.8%），接受 CMT 的患者为 97.3%（置信区间，96.4%，97.9%），这在意向治疗分析和多变量分析中仍然具有统计学意义（CMT 的调整后的危险比为 0.57；95%置信区间，0.42-0.78；P < .001）。在敏感性分析中，低危队列（I-IIA 期）和青少年及年轻成人患者从 CMT 中获益最大（调整后的危险比为 0.47；95%置信区间，0.40-0.56；P < .001）。CMT 的使用率从 2004 年的 59.7%（454 名中的 271 名）下降到 2015 年的 34.9%（438 名中的 153 名），下降了 24.8%。
结论和相关性：在这项研究中，接受 CMT 的早期儿科 HL 患者在治疗后 5 年的总体生存率提高。CMT 的应用正在减少，这可能反映了正在进行的旨在避免巩固性放疗的临床试验的偏见。本研究代表了迄今为止检查 CMT 在儿科 HL 中作用的最大数据集。
