Zhou Li, Barros E Silva Milton Jose, Hsiao Edward, Eroglu Zeynep, Sandhu Shahneen, Samoylenko Igor, Lo Serigne N, Carlino Matteo S, Au-Yeung George, Gonzalez Maria, Spillane Andrew J, Pennington Thomas E, Shannon Kerwin F, Kapoor Rony, Burton Elizabeth M, Tawbi Hussein A, Amaria Rodabe N, Blank Christian U, Duprat João Pedreira, Brito de Paula Rafaela, Gyorki David E, Saw Robyn P M, Ch'Ng Sydney, Rawson Robert V, Scolyer Richard A, Pires da Silva Ines, Akkooi Alexander C J van, Long Georgina V, Menzies Alexander M
Melanoma Institute Australia, The University of Sydney, Sydney, New South Wales, Australia.
Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education, Beijing), Department of Renal Cancer and Melanoma, Peking University Cancer Hospital and Institute, Beijing, China.
J Immunother Cancer. 2025 Mar 25;13(3):e011483. doi: 10.1136/jitc-2025-011483.
Neoadjuvant immunotherapy has become the new standard of care for stage III melanoma. This study sought to describe the metabolic changes seen with fludeoxyglucose-18-positron emission tomography (FDG-PET) following neoadjuvant immunotherapy in patients with melanoma and explore associations with pathological response and recurrence-free survival (RFS).
Data from patients with macroscopic stage III nodal melanoma treated with neoadjuvant checkpoint inhibitor therapy were pooled from five melanoma centers. All patients underwent baseline and preoperative FDG-PET and CT assessments, and all had surgery. Pathological response was determined using the International Neoadjuvant Melanoma Consortium criteria, radiological response using Response Evaluation Criteria in Solid Tumors (RECIST) criteria, and FDG-PET response using European Organization for Research and Treatment of Cancer (EORTC) criteria. The primary endpoint was to explore the associations of metabolic and radiological responses with pathological response; secondary endpoints were RFS outcomes stratified by each response category.
115 patients were included, 69% male, median age 59 years (27-92), 43% BRAF mutant, and median follow-up was 22.2 months (95% CI 13.7 to 26.4). 40 patients received anti-PD-1 monotherapy, 20 patients received pembrolizumab combined with lenvatinib, and 55 patients received ipilimumab and nivolumab. The major pathological response (MPR) rate was 62%, and the pathological complete response rate was 51%. RECIST response underestimated pathological response; patients achieving RECIST stable disease (38%) had a 50% chance of achieving MPR. The FDG-PET metabolic response rate was 73%, with most achieving an MPR (80%), especially in patients with a complete metabolic response (CMR, 96% MPR). A small proportion of patients (10%) had stable metabolic disease on FDG-PET, and all these patients were non-MPR. Patients with progressive metabolic disease were also in the majority non-MPR (79%). Patients with MPR, complete response/partial response on CT, and CMR/partial metabolic response on FDG-PET had a favorable 24-month RFS (95.6%, 97.3%, and 93.7%, respectively), with FDG-PET able to identify a greater proportion of patients with favorable progression-free survival (PFS) than pathology or CT (73%, 62%, and 43%, respectively).
Neoadjuvant immunotherapy has high FDG-PET response rates in melanoma. FDG-PET response associates with pathological response and confers impressive RFS, suggesting this could be an important clinical tool.
新辅助免疫疗法已成为III期黑色素瘤的新治疗标准。本研究旨在描述黑色素瘤患者新辅助免疫治疗后18F-氟脱氧葡萄糖正电子发射断层扫描（FDG-PET）所见的代谢变化，并探讨其与病理反应和无复发生存期（RFS）的关联。
从五个黑色素瘤中心汇总接受新辅助检查点抑制剂治疗的宏观III期淋巴结黑色素瘤患者的数据。所有患者均接受了基线和术前FDG-PET及CT评估，且均接受了手术。使用国际新辅助黑色素瘤联盟标准确定病理反应，使用实体瘤疗效评价标准（RECIST）确定放射学反应，使用欧洲癌症研究与治疗组织（EORTC）标准确定FDG-PET反应。主要终点是探讨代谢和放射学反应与病理反应的关联；次要终点是按每种反应类别分层的RFS结果。
纳入115例患者，男性占69%，中位年龄59岁（27-92岁），43%为BRAF突变型，中位随访时间为22.2个月（95%CI 13.7至26.4）。40例患者接受抗PD-1单药治疗，20例患者接受帕博利珠单抗联合乐伐替尼治疗，55例患者接受伊匹木单抗和纳武单抗治疗。主要病理反应（MPR）率为62%，病理完全缓解率为51%。RECIST反应低估了病理反应；达到RECIST稳定疾病（38%）的患者有50%的机会达到MPR。FDG-PET代谢反应率为73%，大多数患者达到MPR（80%），尤其是在完全代谢反应（CMR）患者中（96%达到MPR）。一小部分患者（10%）在FDG-PET上表现为代谢稳定疾病，所有这些患者均未达到MPR。代谢性疾病进展的患者大多数也未达到MPR（79%）。达到MPR、CT上完全缓解/部分缓解以及FDG-PET上CMR/部分代谢反应的患者24个月RFS良好（分别为95.6%、97.3%和93.7%），与病理或CT相比，FDG-PET能够识别出更大比例的无进展生存期（PFS）良好的患者（分别为73%、62%和43%）。
新辅助免疫疗法在黑色素瘤中具有较高的FDG-PET反应率。FDG-PET反应与病理反应相关，并赋予令人印象深刻的RFS，表明这可能是一种重要的临床工具。
