背景:在III期非小细胞肺癌(NSCLC)患者中,胸腔放疗强化存在争议。我们旨在根据治疗中的[18F]氟代脱氧葡萄糖([18F]FDG)-PET结果,评估功能子体积中高达74Gy的增强放疗剂量的活性和安全性。
方法:在这个多中心中,随机化,对照非比较2期试验,我们招募了年龄18岁或以上的不可手术的III期NSCLC患者,无EGFR突变或ALK重排,东部肿瘤协作组表现状态为0-1,并且隶属于或受益于社会福利系统,有可评估的肿瘤或淋巴结病变,保留肺功能,以及适合接受根治性放化疗的人。使用中央交互式网络响应系统以非掩蔽方法(1:1;使用最小化方法[随机因素0·8];通过放射治疗技术[调强放射治疗与三维适形放射治疗]以及治疗患者的中心进行分层)随机分配给实验性自适应放射治疗组A,其中只有在42Gy的[18F]FDG-PET上残留代谢阳性的患者接受了增强放疗(33个部分中最高可达74Gy),所有其他患者接受标准放疗剂量(6·5周内33分66Gy),或在6·5周内接受标准放疗组B(33个部位66Gy)。所有患者均接受两个周期的以铂类为基础的诱导化疗周期(紫杉醇175mg/m2,每3周一次,卡铂每3周一次,曲线下面积[AUC]=6,或顺铂80mg/m2静脉内每3周一次,长春瑞滨30mg/m2静脉内第1天和60mg/m2口服[或30mg/m2静脉内]第8天每3周一次)。然后他们同时接受放化疗和铂类化疗(三个周期,共8周,每周一次静脉注射紫杉醇40mg/m2和卡铂AUC=2,或者在第1天静脉注射顺铂80mg/m2和长春瑞滨20mg/m2,在第8天口服40mg/m2(或静脉注射20mg/m2),为期21天的周期)。主要终点是接受至少一剂伴随放化疗的合格患者的15个月局部控制率。该RTEP7-IFCT-1402试验已在ClinicalTrials.gov(NCT02473133)注册,并且正在进行中。
结果:从2015年11月12日至2021年7月7日,我们将158例患者(47例[30%]女性和111例[70%]男性)随机分配到加强放疗组A(81例[51%])或标准放疗组B(77例[49%]]。在A组中,80例(99%)患者接受诱导化疗,68例(84%)接受放化疗,其中42Gy后在[18F]FDG-PET上残留摄取的48人(71%)接受了放疗增强。B组,所有77例患者接受诱导化疗,73例(95%)接受放化疗.归根结底,接受放化疗的合格患者(n=140)的中位随访时间为45·1个月(95%CI39·3~48·3).A组的15个月局部控制率为77·6%(95%CI67·6-87·6%),B组为71·2%(95%CI60·8-81·6%)。在A组68例患者中的20例(29%)和B组73例患者中的33例(45%)中观察到急性(在放化疗开始后的90天内)3-4级不良事件,包括A组5例(7%)患者和B组10例(14%)患者的严重不良事件。最常见的3-4级不良事件是发热性中性粒细胞减少症(A组68例中的7[10%]对B组73例中的16[22%]),和贫血(五[7%]对九[12%])。在急性期,B组中有2例死亡(3%)(1例由于与化疗相关的感染性休克,另一种是由于与研究治疗无关的血型),A组无死亡病例,90天后,A组发生1例与治疗无关的死亡,B组发生2例死亡事件(1例放射性肺炎和1例与治疗无关的肺炎).
结论:胸部放疗增强,基于临时[18F]FDG-PET,导致有意义的局部控制率,两组在危险器官中的不良事件没有差异,与以前的胸部放射强化尝试相反,保证对III期NSCLC患者进行[18F]FDG-PET引导放疗剂量适应的随机3期评估。
背景:2014年全国医院治疗计划。
BACKGROUND: Thoracic radiation intensification is debated in patients with stage III non-small-cell lung cancer (NSCLC). We aimed to assess the activity and safety of a boost radiotherapy dose up to 74 Gy in a functional sub-volume given according to on-treatment [18F]fluorodeoxyglucose ([18F]FDG)-PET results.
METHODS: In this multicentre, randomised, controlled non-comparative phase 2
trial, we recruited patients aged 18 years or older with inoperable stage III NSCLC without EGFR mutation or ALK rearrangement with an Eastern Cooperative Oncology Group performance status of 0-1, and who were affiliated with or a beneficiary of a social benefit system, with evaluable tumour or node lesions, preserved lung function, and who were amenable to curative-intent radiochemotherapy. Patients were randomly allocated using a central interactive web-response system in a non-masked method (1:1; minimisation method used [random factor of 0·8]; stratified by radiotherapy technique [intensity-modulated radiotherapy vs three-dimensional conformal radiotherapy] and by centre at which patients were treated) either to the experimental adaptive radiotherapy group A, in which only patients with positive residual metabolism on [18F]FDG-PET at 42 Gy received a boost radiotherapy (up to 74 Gy in 33 fractions), with all other patients receiving standard radiotherapy dosing (66 Gy in 33 fractions over 6·5 weeks), or to the standard radiotherapy group B (66 Gy in 33 fractions) over 6·5 weeks. All patients received two cycles of induction platinum-based chemotherapy cycles (paclitaxel 175 mg/m2 intravenously once every 3 weeks and carboplatin area under the curve [AUC]=6 once every 3 weeks, or cisplatin 80 mg/m2 intravenously once every 3 weeks and vinorelbine 30 mg/m2 intravenously on day 1 and 60 mg/m2 orally [or 30 mg/m2 intravenously] on day 8 once every 3 weeks). Then they concomitantly received radiochemotherapy with platinum-based chemotherapy (three cycles for 8 weeks, with once per week paclitaxel 40 mg/m2 intravenously and carboplatin AUC=2 or cisplatin 80 mg/m2 intravenously and vinorelbine 20 mg/m2 intravenously on day 1 and 40 mg/m2 orally (or 20 mg/m2 intravenously) on day 8 in 21-day cycles). The primary endpoint was the 15-month local control rate in the eligible patients who received at least one dose of concomitant radiochemotherapy. This RTEP7-IFCT-1402
trial is registered with ClinicalTrials.gov (NCT02473133), and is ongoing.
RESULTS: From Nov 12, 2015, to July 7, 2021, we randomly assigned 158 patients (47 [30%] women and 111 [70%] men) to either the boosted radiotherapy group A (81 [51%]) or to the standard radiotherapy group B (77 [49%)]. In group A, 80 (99%) patients received induction chemotherapy and 68 (84%) received radiochemotherapy, of whom 48 (71%) with residual uptake on [18F]FDG-PET after 42 Gy received a radiotherapy boost. In group B, all 77 patients received induction chemotherapy and 73 (95%) received radiochemotherapy. At the final analysis, the median follow-up for eligible patients who received radiochemotherapy (n=140) was 45·1 months (95% CI 39·3-48·3). The 15-month local control rate was 77·6% (95% CI 67·6-87·6%) in group A and 71·2% (95% CI 60·8-81·6%) in group B. Acute (within 90 days from radiochemotherapy initiation) grade 3-4 adverse events were observed in 20 (29%) of 68 patients in group A and 33 (45%) of 73 patients in group B, including serious adverse events in five (7%) patients in group A and ten (14%) patients in group B. The most common grade 3-4 adverse events were febrile neutropenia (seven [10%] of 68 in group A vs 16 [22%] of 73 in group B), and anaemia (five [7%] vs nine [12%]). In the acute phase, two deaths (3%) occurred in group B (one due to a septic shock related to chemotherapy, and the other due to haemotypsia not related to
study treatment), and no deaths occurred in group A. After 90 days, one additional treatment-unrelated death occurred in group A and two deaths events occurred in group B (one radiation pneumonitis and one pneumonia unrelated to treatment).
CONCLUSIONS: A thoracic radiotherapy boost, based on interim [18F]FDG-PET, led to a meaningful local control rate with no difference in adverse events between the two groups in organs at risk, in contrast with previous attempts at thoracic radiation intensification, warranting a randomised phase 3 evaluation of such [18F]FDG-PET-guided radiotherapy dose adaptation in patients with stage III NSCLC.
BACKGROUND: Programme Hospitalier de Recherche Clinique National 2014.