在本届恶性淋巴瘤（2023 ICML）国际会议上，Massimo Federico教授在“聚焦霍奇金淋巴瘤”专题会议中，针对“早期FDG-PET适应性治疗局限期霍奇金淋巴瘤：EORTC/LYSA/FIL H10随机组间试验10年随访分析”进行了精彩报告。《肿瘤瞭望》特别邀请Federico教授就此话题进行了深度访谈。

 

Federico教授：根据目前的指南，I/II期HL患者的标准治疗是联合治疗，即化疗加受累野照射。在过去的20年里，学者们做了一些研究以明确是否可以避免放疗或在前两个疗程结果不理想的情况下升级化疗方案。基于此，我们设计了H10研究，这是一项随机Ⅲ期临床试验，比较正电子发射断层扫描（PET）适应性方案、疗法或放化疗相结合的标准疗法。

 

但该试验中的消息是，计划采用受累淋巴结照射（INRT）进行放射治疗。这意味着只有在治疗开始时的阳性部位才给予放疗照射，以限制照射区域。对于那些在早期PET评估后仍为阳性的患者，则提供两个疗程的升级版BEACOPP。对于那些对初始治疗有良好反应且转为PET阴性的患者，则继续采用单一化疗。对于那些PET阳性的患者则修改治疗策略，在最初两个疗程的ABVD的基础上，增加两个疗程的升级版BEACOPP。

 

Oncology Frontier：Could you please introduce the current treatment status of patients with stage I/II Hodgkin lymphoma?What treatment methods can be used?

 

According to the current guidelines，the standard treatment of patients with the stage one and two Hodgkin lymphoma is a combined treatment that means chemotherapy plus involved-field radiotherapy.Over the last 20 years，several approaches have been done to see if it’s possible to avoid radiotherapy or to escalate the chemotherapy regiments in case of unsatisfactory response to the first two courses.Based on these two approaches，we designed the H10 study that was a randomized phase three clinical trial comparing positron emission tomography(PET)adopted regimen，therapies or a standard treatment that combines the chemo plus radiotherapy.

 

But the news in that trial where that radiotherapy was planned with the involved-node approach.That means very limited area to be irradiated，the only case of positivity at the beginning of the treatment.And for those patients that following early PET were still positive，the program was designed to offer escalated BEACOPP for two courses.So most importantly，for those patients that had a good response to initial therapy and became PET-negative，the approach was continued with chemotherapy alone.For those patients that were PET positive，modify treatment strategy，adding escalated BEACOPP for two courses to the initial two courses of ABVD.

 

Federico教授：这项研究的主要结果是，PET阳性是一个有效的结局预测指标。与PET阴性的患者相比，随着时间的推移，PET阳性的患者治疗失败的风险更高。在PET阳性的情况下，将BEACOPP添加到标准治疗中可以延长无进展生存期（PFS），尽管与5年前的数据相比，10年随访数据显示PFS改善的显著性降低了。在PET阴性并接受单独化疗或化疗联合INRT治疗的患者中，接受联合治疗方案的患者PFS更长。在我们研究的所有亚组中，标准组和试验组的总生存（OS）都很高。

 

总之，化疗-放疗联合INRT是一个安全的方案，并且与第二恶性肿瘤的增高风险无关。同样，对于那些经过两个疗程ABVD治疗后PET仍阳性的患者，给予升级版BEACOPP也是一个好的选择，因为两个疗程的BEACOPP与第二恶性肿瘤风险的增加无关。

 

Oncology Frontier：An oral study reported by your team analeted of the randomized intergroup EORTC/LYSA/FIL H10 trial，is 10 years long term follow-up data，could you talk about this study in detail?

 

The main results of this study are that PET positive is a strong predictor of outcome.Patients with PET positivity have a higher risk of failure over time compared to patients PET negative.The addition of BEACOPP to the standard treatment in case of PET positivity，translate in a better progression free survival，although after 10 years of follow up，this difference is less evident compared to the analysis we performed 5 years ago.In the group of patients with PET negativity and treated with chemotherapy alone or chemotherapy plus involved-node radiotherapy.The combined regimen was associated with a better progression free survival.In all subgroups we studied，the overall survival was excellent in both the standard and experimental arm.

 

In conclusion，combined chemo-radiotherapy with involved-node radiotherapy is a safe approach and is not associated with an excess of risk of second malignancy.The same is for the group of patients that are PET positive after two courses of ABVD escalating to BEACOPP is a good choice because two courses of BEACOPP are not associated with an increase at the risk of second malignancy over time.

 

Federico教授：这项研究的意义在于，两种方法都是利用PET来避免放疗和加强对PET阳性患者的治疗，且都获得了良好的结局。所以，目前我们有两种治疗选择。如果接受INRT，则复发的风险低；如果在PET阳性的情况下接受BEACOPP，则能够延长PFS，且两种方案下的患者生存率没有差异。因此，我们可以告知患者并让患者自行选择，是接受较少的治疗但可能会存在较高的复发风险，或者是接受强度较高的治疗来降低复发的风险。

 

Oncology Frontier：What are the implications of this research?Could you share the significance of this study from your clinical experience?

 

So the implication of this study are that both the approaches use PET for avoiding radiotherapy and intensifying treatment for patients PET positive is associated with an excellent outcome.So There are two opportunities，the same chance of overall survival.If you use also involved-node radiotherapy，you have a lower risk of relapse.If you use BEACOPP in case of PET positivity，you improve the chance to remain disease free for a longer period of time.However，no differences in terms of survival emerged.So the patients can be informed and make the decision if they prefer to be treated less with a higher risk of curable relapse or to be cured in a little bit more intense way，reducing the risk of relapse.

 

Massimo Federico教授

意大利摩德纳雷焦艾米利亚大学诊断医学、临床和公共卫生系。