Primary Results of NRG-RTOG1106/ECOG-ACRIN 6697: A Randomized Phase II Trial of Individualized Adaptive (chemo)Radiotherapy Using Midtreatment ¹⁸F-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography in Stage III Non-Small Cell Lung Cancer.

IF 42.1 1区医学 Q1 ONCOLOGY Journal of Clinical Oncology Pub Date : 2024-11-20 Epub Date: 2024-10-04 DOI:10.1200/JCO.24.00022

Feng-Ming Spring Kong, Chen Hu, Daniel A Pryma, Fenghai Duan, Martha Matuszak, Ying Xiao, Randall Ten Haken, Marilyn J Siegel, Lucy Hanna, Walter J Curran, Mark Dunphy, Daphna Gelblum, Morand Piert, Shruti Jolly, Clifford G Robinson, Andrew Quon, Billy W Loo, Shyam Srinivas, Gregory M Videtic, Sergio L Faria, Catherine Ferguson, Neal E Dunlap, Vijayananda Kundapur, Rebecca Paulus, Barry A Siegel, Jeffrey D Bradley, Mitchell Machtay

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Abstract

Purpose: NRG-RTOG0617 demonstrated a detrimental effect of uniform high-dose radiation in stage III non-small cell lung cancer. NRG-RTOG1106/ECOG-ACRIN6697 (ClinicalTrials.gov identifier: NCT01507428), a randomized phase II trial, studied whether midtreatment ¹⁸F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) can guide individualized/adaptive dose-intensified radiotherapy (RT) to improve and predict outcomes in patients with this disease.

Materials and methods: Patients fit for concurrent chemoradiation were randomly assigned (1:2) to standard (60 Gy/30 fractions) or FDG-PET-guided adaptive treatment, stratified by substage, primary tumor size, and histology. All patients had midtreatment FDG-PET/CT; adaptive arm patients had an individualized, intensified boost RT dose to residual metabolically active areas. The primary therapeutic end point was 2-year centrally reviewed freedom from local-regional progression (FFLP), defined as no progression in or near the planning target volume and/or regional nodes. FFLP was analyzed on a modified intent-to-treat population at a one-sided Z-test significance level of 0.15. The primary imaging end point was centrally reviewed change in SUV_peak from baseline to midtreatment; its association with FFLP was assessed using the two-sided Wald test on the basis of Cox regression.

Results: Of 138 patients enrolled, 127 were eligible. Adaptive-arm patients received a mean 71 Gy in 30 fractions, with mean lung dose 17.9 Gy. There was no significant difference in centrally reviewed 2-year FFLP (59.5% and 54.6% in standard and adaptive arms; P = .66). There were no significant differences in protocol-specified grade 3 toxicities, survival, or progression-free survival (P > .4). Median SUV_peak and metabolic tumor volume (MTV) in the adaptive arm decreased 49% and 54%, from pre-RT to mid-RT PET. However, ΔSUV_peak and ΔMTV were not associated with FFLP (hazard ratios, 0.997; P = .395 and .461).

Conclusion: Midtreatment PET-adapted RT dose escalation as given in this study was safe and feasible but did not improve efficacy outcomes.

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NRG-RTOG1106/ECOG-ACRIN 6697 的初步结果：在 III 期非小细胞肺癌中使用治疗中期 18F 氟脱氧葡萄糖定位发射断层扫描/计算机断层扫描进行个体化适应性（化疗）放疗的随机 II 期试验。

目的：NRG-RTOG0617证明了均匀大剂量放射治疗对III期非小细胞肺癌的不利影响。NRG-RTOG1106/ECOG-ACRIN6697（ClinicalTrials.gov标识符：NCT01507428）是一项随机II期试验，研究治疗中期18F-氟脱氧葡萄糖定位发射断层扫描/计算机断层扫描（FDG-PET/CT）能否指导个体化/自适应剂量强化放疗（RT），以改善和预测该病患者的预后：将适合同期化疗的患者随机分配（1:2）至标准（60 Gy/30次）或FDG-PET指导下的适应性治疗，并根据亚分期、原发肿瘤大小和组织学进行分层。所有患者都接受了治疗中期的 FDG-PET/CT；适应性治疗组患者接受了个体化、强化的增强 RT 剂量，以治疗残留的代谢活跃区。主要治疗终点是2年集中复查的无局部区域进展（FFLP），定义为计划目标体积和/或区域结节内或附近无进展。FFLP是根据修改后的意向治疗人群进行分析的，单侧Z检验显著性水平为0.15。主要影像学终点是集中审查从基线到治疗中期的SUVpeak变化；其与FFLP的关系在Cox回归的基础上使用双侧Wald检验进行评估：在138名入选患者中，127名符合条件。自适应臂患者平均接受了71 Gy的治疗，分30次进行，平均肺部剂量为17.9 Gy。集中复查的2年FFLP无明显差异（标准臂和适应臂分别为59.5%和54.6%；P = .66）。方案规定的 3 级毒性、生存期或无进展生存期无明显差异（P > .4）。适应组的中位 SUVpeak 和代谢肿瘤体积 (MTV) 从 RT 前期到 RT 中期 PET 分别下降了 49% 和 54%。然而，ΔSUVpeak和ΔMTV与FFLP无关（危险比，0.997；P = .395和.461）：结论：本研究中采用的治疗中期 PET 适应性 RT 剂量升级是安全可行的，但并不能改善疗效。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of Clinical Oncology 医学-肿瘤学

CiteScore

41.20

自引率

2.20%

发文量

8215

审稿时长

2 months

期刊介绍： The Journal of Clinical Oncology serves its readers as the single most credible, authoritative resource for disseminating significant clinical oncology research. In print and in electronic format, JCO strives to publish the highest quality articles dedicated to clinical research. Original Reports remain the focus of JCO, but this scientific communication is enhanced by appropriately selected Editorials, Commentaries, Reviews, and other work that relate to the care of patients with cancer.