由国际肺癌研究协会（IASLC）主办的2024世界肺癌大会（WCLC）于2024年9月7日晚在美国圣地亚哥开幕，目前正在如火如荼地进行中。肿瘤瞭望记者奔赴WCLC会议现场，特邀加州大学戴维斯分校综合癌症中心Megan Daly教授对立体定向放射治疗（SBRT）与免疫治疗联合治疗非小细胞肺癌（NSCLC）进行讨论。

 

Megan Daly教授：SBRT有时也称为立体定向消融放射治疗（SABR），是医学上不能手术的早期NSCLC患者或因各种原因拒绝手术的患者的标准治疗方法。SBRT也可以定期用于肺部或身体其他部位的转移的治疗。这是一种很好的治疗方法，因为即使是患有严重合并症的患者也可以进行SBRT。这种治疗方法对肺功能的限制很少，患有严重合并症而不能手术切除的患者仍然可以把SBRT作为备选。而且它是一种非侵入性治疗，因此患者不需要麻醉。患者首先接受CT扫描和固定装置的测量，然后通常在两周后复诊并开始放射治疗，一般接受1～5次治疗。在治疗期间，患者不会有任何感觉。SBRT本质上就像接受X光或CT扫描一样，虽然有一些潜在的副作用，但患者的耐受性通常很好。

 

Dr.Daly:Stereotactic quantitative radiotherapy(SBRT)，sometimes also referred to as stereotactic ablative radiotherapy(SABR)，has become a standard-of-care treatment for patients with medically inoperable early-stage non-small cell lung cancer，or for patients who decline to have surgery，for any number of reasons.It is also periodically used for metastases to the lung or other parts of the body as well.It is a great treatment，because even patients with significant medical comorbidities can undergo stereotactic radiation.There is no real lower limit on pulmonary function，and patients who have significant comorbidities that prevent them from having surgery are still candidates for stereotactic radiation.It is a non-invasive treatment，so patients do not require anesthesia.They come in first for a session where they undergo CT scanning and measurement for a specialized immobilization device.They typically come back to start radiation two weeks later，and undergo between one and five sessions of treatment.During that treatment，they don’t feel anything.Again，it is a non-invasive treatment，essentially like undergoing an X-ray or CT scan.Although there are some potential side effects，they are typically tolerated very well.

 

Megan Daly教授：我认为这项研究的结果为早期NSCLC患者应用SBRT的真实世界临床结果提供了非常好的参照标准。在进行研究设计时，这项研究提供了实现EFS和OS关联分析预期结果的良好数据。这项研究的结果也让我们相信尽管患有严重合并症的患者存在许多竞争性死亡风险，但EFS仍是一个重要的结果，并且与OS密切相关。这项研究的结果还告诉我们，预防复发对这些患者非常重要。

 

Dr.Daly:I think these provide a really nice baseline for real world outcomes with SBRT.When designing studies，they provide nice data for expected outcomes for event-free survival and overall survival，and they also reassure us that although there are many competing risks of death in patients with significant comorbidities，nonetheless，event-free survival is an important outcome and is well correlated with overall survival.It tells us that preventing recurrence is very important for these patients.

 

Megan Daly教授：对于所有的转移性患者，放疗要么在起始治疗时使用，要么在发生有限疾病进展时使用。通常，放疗会与免疫治疗同时进行。例如，在我刚刚参加的一次会议上，我听了几篇探讨了SBRT在免疫治疗发生寡进展患者中应用的摘要，这些研究证明这些患者从中受益。今年《柳叶刀》杂志发表的一项随机对照Ⅱ期CURB临床研究的最新数据也表明，寡进展转移性NSCLC患者从联合SBRT治疗中获益。我们还需要有更大规模的随机III期试验来验证这一结果，但我认为这是有希望的。

 

Dr.Daly:For all of the metastatic patients，radiation is sometimes used either upfront or at the time of limited progression.Often times，these patients are on immunotherapy.For example，in a session I was just in，we heard several abstracts looking at the use of stereotactic radiation in patients who had limited sites of progression on immunotherapy.These studies do suggest benefits for these patients.There are also recent data from the CURB study published in The Lancet this year that suggested benefits for patients who received stereotactic radiation with limited sites of progressing disease，and there will likely be a larger randomized phase III trial testing that hypothesis，but I think it is a promising space.

 

Megan Daly教授：我认为这是一个悬而未决且非常重要的问题。我们确实不清楚放疗和免疫治疗联用的最佳时机，但当我们在局部晚期疾病治疗阶段联用放疗和免疫治疗，并根据其研究结果进行推断时，我们发现研究结果的一致性似乎并不理想。例如，我们看到PACIFIC-2试验是一项阴性结果试验，该试验在局部晚期NSCLC患者中同时进行免疫治疗与放化疗（CRT），与单独CRT相比没有观察到任何获益。与之相比，PACIFIC试验对于同步放化疗后无疾病进展的不可切除Ⅲ期NSCLC患者，加用免疫巩固治疗具有相当大的（约10%）OS获益（免疫巩固组和对照组的5年OS率：42.9%vs 33.1%）。我们不太确定放疗联合免疫方案在早期肺癌治疗中如何应用，因为从免疫学角度来看，与对单个病灶进行消融性放射相比，与化疗联用进行更大范围的放疗，免疫学效应有所不同。我认为目前的研究数据略微倾向于先进行放射治疗，然后再进行免疫治疗，但我们还需要观察一些正在进行的和最近完成的试验的结果。

 

Dr.Daly:I think that is an open question，and it is a very important one.We really don’t know the optimal timing，although when we look at the locally advanced setting and perhaps extrapolate a little bit，we see that concurrence does not seem to be ideal.We saw the PACIFIC-2 trial，for example，was a negative trial looking at concurrent immunotherapy given with chemoradiation in locally advanced disease，and they didn’t see any benefit.In contrast，the PACIFIC-1 trial showed considerable(about 10%)overall survival benefit with adjuvant immunotherapy.We are not quite sure how this applies to the early stage setting，because it is immunologically different to giving larger field radiation with chemotherapy，as compared to giving ablative radiation to a single site of disease.Right now，I would say the data is slightly leaning towards giving radiation first followed by immunotherapy，but we really do need to see the maturation of a few ongoing and recently completed trials.

 

 

该研究对SEER-Medicare数据库中（2007-2020）接受初次SBRT的新诊断Ⅰ-Ⅱ期NSCLC患者的特征进行总结，使用Kaplan-Meier分析描述总体人群和各疾病分期患者的真实世界无进展生存期（rwEFS）和OS，并评估rwEFS和OS之间的相关性。共纳入3014例Ⅰ-ⅡNSCLC患者，中位随访时间为2.4年。诊断时的中位年龄为77.0岁，37.7%为男性，86.9%为白人。总体人群的中位rwEFS为26.2个月，5年rwEFS率为23.8%；总人群中位OS为48.9个月，5年OS率为42.3%。相关性分析表明rwEFS和OS之间存在具有统计学意义的中等相关性（0.74;95%CI:0.72-0.77;P＜0.001）。

 

图1总体人群的rwEFS和各分期患者的rwEFS

 

图2总体人群的真实世界OS和各分期患者的真实世界OS