[F]FDG-PET 能够在头颈部鳞状细胞癌新辅助免疫检查点阻断早期准确识别病理反应。
[F]FDG-PET accurately identifies pathological response early upon neoadjuvant immune checkpoint blockade in head and neck squamous cell carcinoma.
机构信息
Department of Head and Neck Oncology and Surgery, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
Department of Maxillofacial Surgery, Amsterdam University Medical Center, Amsterdam, The Netherlands.
出版信息
Eur J Nucl Med Mol Imaging. 2022 May;49(6):2010-2022. doi: 10.1007/s00259-021-05610-x. Epub 2021 Dec 27.
PURPOSE
To investigate the utility of [F]FDG-PET as an imaging biomarker for pathological response early upon neoadjuvant immune checkpoint blockade (ICB) in patients with head and neck squamous cell carcinoma (HNSCC) before surgery.
METHODS
In the IMCISION trial (NCT03003637), 32 patients with stage II‒IVb HNSCC were treated with neoadjuvant nivolumab with (n = 26) or without (n = 6) ipilimumab (weeks 1 and 3) before surgery (week 5). [F]FDG-PET/CT scans were acquired at baseline and shortly before surgery in 21 patients. Images were analysed for SUV, SUV, metabolic tumour volume (MTV), and total lesion glycolysis (TLG). Major and partial pathological responses (MPR and PPR, respectively) to immunotherapy were identified based on the residual viable tumour in the resected primary tumour specimen (≤ 10% and 11-50%, respectively). Pathological response in lymph node metastases was assessed separately. Response for the 2 [F]FDG-PET-analysable patients who did not undergo surgery was determined clinically and per MR-RECIST v.1.1. A patient with a primary tumour MPR, PPR, or primary tumour MR-RECIST-based response upon immunotherapy was called a responder.
RESULTS
Median ΔSUV, ΔSUV, ΔMTV, and ΔTLG decreased in the 8 responders and were significantly lower compared to the 13 non-responders (P = 0.05, P = 0.002, P < 0.001, and P < 0.001). A ΔMTV or ΔTLG of at least - 12.5% detected a primary tumour response with 95% accuracy, compared to 86% for the EORTC criteria. None of the patients with a ΔTLG of - 12.5% or more at the primary tumour site developed a relapse (median FU 23.0 months since surgery). Lymph node metastases with a PPR or MPR (5 metastases in 3 patients) showed a significant decrease in SUV (median - 3.1, P = 0.04). However, a SUV increase (median + 2.1) was observed in 27 lymph nodes (in 11 patients), while only 13 lymph nodes (48%) contained metastases in the corresponding neck dissection specimen.
CONCLUSIONS
Primary tumour response assessment using [F]FDG-PET-based ΔMTV and ΔTLG accurately identifies pathological responses early upon neoadjuvant ICB in HNSCC, outperforming the EORTC criteria, although pseudoprogression is seen in neck lymph nodes. [F]FDG-PET could, upon validation, select HNSCC patients for response-driven treatment adaptation in future trials.
TRIAL REGISTRATION
CLINICALTRIALS
gov/ , NCT03003637, December 28, 2016.
目的
研究 [F]FDG-PET 作为一种成像生物标志物，用于评估头颈部鳞状细胞癌（HNSCC）患者在手术前新辅助免疫检查点阻断（ICB）早期的病理反应。
方法
在 IMCISION 试验（NCT03003637）中，32 例 II-IVb 期 HNSCC 患者在手术前（第 5 周）接受新辅助纳武单抗治疗（n=26）或不接受纳武单抗（n=6）加伊匹单抗（第 1 周和第 3 周）。21 例患者在基线和手术前不久进行 [F]FDG-PET/CT 扫描。通过 SUV、SUV、代谢肿瘤体积（MTV）和总病变糖酵解（TLG）分析图像。根据切除原发肿瘤标本中残留的存活肿瘤（分别为≤10%和 11-50%），确定主要和部分病理反应（MPR 和 PPR）对免疫治疗的反应。分别评估淋巴结转移的病理反应。对未接受手术的 2 例 [F]FDG-PET 可分析患者的反应，根据临床和基于 MR-RECIST v.1.1 的磁共振成像进行评估。在免疫治疗中有原发肿瘤 MPR、PPR 或基于 MR-RECIST 的反应的患者被称为应答者。
结果
8 例应答者的 SUV、SUV、MTV 和 TLG 的 ΔSUV、ΔSUV、ΔMTV 和 ΔTLG 中位数降低，与 13 例无应答者相比，这些值显著降低（P=0.05，P=0.002，P<0.001，P<0.001）。ΔMTV 或 ΔTLG 至少减少-12.5%可检测到原发肿瘤反应，准确率为 95%，而 EORTC 标准为 86%。在原发肿瘤部位 ΔTLG 减少-12.5%或更多的患者中，没有发生复发（自手术以来的中位随访时间为 23.0 个月）。有 PPR 或 MPR（3 例患者 5 个转移灶）的淋巴结转移灶的 SUV 显著降低（中位数-3.1，P=0.04）。然而，在 27 个淋巴结（11 例患者）中观察到 SUV 增加（中位数+2.1），而在相应的颈部淋巴结清扫标本中仅发现 13 个淋巴结（48%）含有转移灶。
结论
使用基于 [F]FDG-PET 的 ΔMTV 和 ΔTLG 的原发肿瘤反应评估，可在新辅助 ICB 早期准确识别 HNSCC 的病理反应，优于 EORTC 标准，尽管颈部淋巴结可见假性进展。[F]FDG-PET 可在未来的试验中验证，以选择对反应驱动的治疗适应的 HNSCC 患者。
临床试验
https://www.clinicaltrials.gov/，NCT03003637，2016 年 12 月 28 日。
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