In their recent article in Journal of Clinical Oncology, André et al¹ reported the final analysis of the European Organisation for Research and Treatment of Cancer H10 trial, which examined the role of using positron emission tomography (PET) response to guide de-escalation of therapy via the omission of radiotherapy in early-stage Hodgkin lymphoma. At 5 years, the progression-free survival rate for favorable-risk patients was 99% in PET-negative patients receiving radiotherapy versus 87% in PET-negative patients receiving chemotherapy alone (hazard ratio, 15.8; 95% CI, 3.8 to 66.1), far exceeding the predetermined noninferiority margin of 3.2. Despite this result, the authors concluded that “treatment with chemotherapy only is defensible in individual patients.”^1(p1793) Why define a threshold for a noninferiority clinical trial design, only to disregard the clearly inferior results of the study in the discussion when this threshold is exceeded? Although, certainly, individual patients can achieve excellent outcomes with additional cycles of chemotherapy, this potentially misleading interpretation of the results can have strongly negative implications for patients in clinical practice. The increasing over-application of chemotherapy-alone treatment strategies in early-stage Hodgkin lymphoma in the past decade have led to a decline in overall survival for thousands of patients with Hodgkin lymphoma on a national level.² Results from both the European Organisation for Research and Treatment of Cancer H10 and UK-RAPID trials highlight that even in favorable-risk, PET-negative Hodgkin lymphoma, the addition of radiotherapy adds a significant increase in progression-free survival.³ However, what is not highlighted from these trials is that both trials included additional cycles of chemotherapy, over an established standard of care for favorable-risk Hodgkin lymphoma, of two cycles of chemotherapy plus low-dose (20 Gy) involved-site radiotherapy.⁴ Increasing the number of cycles of chemotherapy and radiotherapy both carry risks of acute and chronic toxicities; ignoring the implication of additional cycles of chemotherapy on the risks of cardiopulmonary disease or second malignancy is not justified by the data.⁵ In the last decade, radiotherapy dose and volumes have significantly decreased (with involved-node radiotherapy used in H10; Fig 1), thereby decreasing toxicity risks.⁶ In a disease where overall survival approaches 100%, all of these factors count. We need to be cautious in trading radiotherapy for additional chemotherapy, while discounting the morbidity of increasing chemotherapy cycles and increased relapses requiring salvage bone marrow transplant.

中文翻译：

---

早期霍奇金淋巴瘤的治疗：我们只是在改变发病率吗？

André等[ ^1]在其最近发表的《临床肿瘤学杂志》上的文章中报告了对欧洲癌症研究和治疗组织H10试验的最终分析，该试验研究了使用正电子发射断层扫描（PET）应答指导降级的作用。通过在早期霍奇金淋巴瘤中省略放射疗法进行治疗。在5年时，接受放疗的PET阴性患者的有利风险患者的无进展生存率为99％，而仅接受化疗的PET阴性患者的无进展生存率为87％（危险比，15.8； 95％CI，3.8至66.1）。 ，远远超过了预定的非劣质性余度3.2。尽管得出了这一结果，但作者得出的结论是“仅对个别患者进行化学疗法治疗是可以辩护的。” ^1（p1793）为什么要为非劣效性临床试验设计定义一个阈值，而仅在超过该阈值时忽略讨论中研究的明显劣等结果？尽管可以肯定的是，个别患者可以通过额外的化疗周期获得出色的治疗效果，但是这种对结果的潜在误导性解释可能会对临床实践中的患者产生严重的负面影响。在过去的十年中，在早期霍奇金淋巴瘤中过度采用单纯化学治疗策略的现象日益增多，导致全国范围内成千上万的霍奇金淋巴瘤患者的总生存率下降。^2个欧洲癌症研究和治疗组织H10和UK-RAPID试验的结果都表明，即使在具有良好风险，PET阴性的霍奇金淋巴瘤中，放疗的加入也显着增加了无进展生存期。³然而，这些试验未强调的是，这两个试验均包括额外的化疗周期，超过已确立的有利风险霍奇金淋巴瘤的护理标准，包括两个周期的化疗加小剂量（20 Gy）累及部位放疗。⁴增加化学疗法和放射疗法的周期数都具有急性和慢性毒性的风险；数据不能忽略忽略额外化疗周期对心肺疾病或继发恶性肿瘤风险的影响。⁵在过去的十年中，放疗的剂量和体积已大大减少（H10中使用了受累结点放疗；图1），从而降低了毒性风险。⁶在总生存率接近100％的疾病中，所有这些因素都很重要。我们需要谨慎对待放疗以换用其他化学疗法，同时要减少增加化学疗法周期和增加复发率（需要抢救骨髓移植）的发病率。