Metabolic parameters on baseline and early [18F]FDG PET/CT as a predictive biomarker for resistance to BRAF/MEK inhibition in advanced cutaneous BRAFV600-mutated melanoma.

IF 3.1 3区 医学 Q1 RADIOLOGY, NUCLEAR MEDICINE & MEDICAL IMAGING
Bernies van der Hiel, Berlinda J de Wit-van der Veen, Alfons J M van den Eertwegh, Wouter V Vogel, Marcel P M Stokkel, Marta Lopez-Yurda, Ronald Boellaard, Ellen W Kapiteijn, Geke A P Hospers, Maureen J B Aarts, Filip Y F L de Vos, Marye J Boers-Sonderen, Astrid A M van der Veldt, Jan Willem B de Groot, John B A G Haanen
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引用次数: 0

Abstract

Background: [18F]FDG PET/CT plays a crucial role in evaluating cancer patients and assessing treatment response, including in BRAF-mutated melanoma. Metabolic tumor volume (MTV) and total lesion glycolysis (TLG) have emerged as promising alternatives to standardized uptake value (SUV)-based measures for tumor assessment. This study evaluates the predictive value of SUVpeak, MTV, and TLG in predicting progression-free survival (PFS) in advanced BRAF-mutated melanoma treated with BRAF/MEK inhibitors.

Results: Seventy-five patients with metastatic melanoma were enrolled in a multi-center trial and treated with vemurafenib/cobimetinib. [18F]FDG-PET/CT scans were performed at baseline, week-2, and week-7. Imaging analysis included SUVpeak, MTV, and TLG of summed metastases, as well as percentage changes over time (∆). Baseline median PET-parameters were SUVpeak 12.59 (range 3.13-50.59), MTV 159mL (range 0-1897 mL), and TLG 1013 (range 1-13162). Baseline MTV was the strongest predictor (AUCT=6 months=0.714), while early changes in MTV, TLG, and especially week-7 ΔSUVpeak% showed similar or improved performance (P = 0.017 vs. baseline SUVpeak). Patients with TLG below the median had significantly prolonged PFS (15.4 vs. 8.5 months, P = 0.024). MTV above optimal cutoff (45.3 mL) was associated with an increased risk of progression/death, even after adjusting for LDH, ECOG status, and metastatic sites (HR = 2.97, 95% CI 1.17-7.52, P = 0.022). At week-2, ∆SUVpeak% was not predictive in a multivariable analysis, but became predictive at week-7 (median ∆SUVpeak%: 64), with a more than three-fold hazard of progression for patients with ∆SUVpeak% below 64% (P = 0.0014); PFS was 5.0 months (95% CI: 4.3-NA) for patients below the median versus 14.7 months (95% CI: 9.2-20.2) for those above or with non-quantifiable scans (P = 0.0002). Median ∆MTV was 95.5% at week-2 and 97.6% at week-7, with significant PFS differences at both time points (week-2: P = 0.020, week-7: P < 0.001). As expected, TLG mirrored MTV. Patients with MTV increases at week-7 after an initial response at week-2 had a median PFS of 5.3 vs. 12.6 months for those with stable or declining MTV (P = 0.0023). Intra-patient metabolic heterogeneity was also associated with outcome, with early reductions in SUVpeak variation between lesions correlating with better PFS.

Conclusion: This study supports the use of MTV and TLG as robust predictive markers for PFS in advanced melanoma treated with BRAF/MEK-inhibitors. Monitoring early PET parameters changes can provide valuable insights into therapeutic response and disease progression.

Trial registration: Clinicaltrials.gov identifier: NCT02414750. Registered 10 April 2015, retrospectively registered.

基线和早期代谢参数[18F]FDG PET/CT作为晚期皮肤brafv600突变黑色素瘤对BRAF/MEK抑制耐药性的预测性生物标志物。
背景:[18F]FDG PET/CT在评估癌症患者和评估治疗反应中起着至关重要的作用,包括braf突变的黑色素瘤。代谢肿瘤体积(MTV)和病变总糖酵解(TLG)已成为替代标准化摄取值(SUV)的肿瘤评估指标。本研究评估了SUVpeak、MTV和TLG在预测BRAF/MEK抑制剂治疗的晚期BRAF突变黑色素瘤的无进展生存期(PFS)中的预测价值。结果:75名转移性黑色素瘤患者参加了一项多中心试验,并接受了vemurafenib/cobimetinib治疗。[18F]在基线、第2周和第7周进行FDG-PET/CT扫描。影像学分析包括总转移灶的SUVpeak、MTV和TLG,以及随时间变化的百分比(∆)。基线pet参数中位数为SUVpeak 12.59(范围3.13-50.59),MTV 159mL(范围0-1897 mL), TLG 1013(范围1-13162)。基线MTV是最强的预测因子(AUCT=6个月=0.714),而MTV, TLG,特别是第7周ΔSUVpeak%的早期变化显示出类似或改善的表现(P = 0.017与基线SUVpeak相比)。TLG低于中位数的患者PFS明显延长(15.4个月vs 8.5个月,P = 0.024)。MTV高于最佳临界值(45.3 mL)与进展/死亡风险增加相关,即使在LDH、ECOG状态和转移部位调整后也是如此(HR = 2.97, 95% CI 1.17-7.52, P = 0.022)。在第2周,在多变量分析中,∆SUVpeak%不能预测,但在第7周具有预测性(中位∆SUVpeak%: 64),∆SUVpeak%低于64%的患者的进展风险超过3倍(P = 0.0014);低于中位数的患者PFS为5.0个月(95% CI: 4.3-NA),高于中位数或无法量化扫描的患者PFS为14.7个月(95% CI: 9.2-20.2) (P = 0.0002)。中位∆MTV在第2周为95.5%,第7周为97.6%,两个时间点的PFS差异均显著(第2周:P = 0.020,第7周:P)。结论:本研究支持使用MTV和TLG作为BRAF/ mek抑制剂治疗的晚期黑色素瘤PFS的可靠预测指标。监测早期PET参数的变化可以为治疗反应和疾病进展提供有价值的见解。试验注册:Clinicaltrials.gov标识符:NCT02414750。注册于2015年4月10日,回顾性注册。
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来源期刊
EJNMMI Research
EJNMMI Research RADIOLOGY, NUCLEAR MEDICINE & MEDICAL IMAGING&nb-
CiteScore
5.90
自引率
3.10%
发文量
72
审稿时长
13 weeks
期刊介绍: EJNMMI Research publishes new basic, translational and clinical research in the field of nuclear medicine and molecular imaging. Regular features include original research articles, rapid communication of preliminary data on innovative research, interesting case reports, editorials, and letters to the editor. Educational articles on basic sciences, fundamental aspects and controversy related to pre-clinical and clinical research or ethical aspects of research are also welcome. Timely reviews provide updates on current applications, issues in imaging research and translational aspects of nuclear medicine and molecular imaging technologies. The main emphasis is placed on the development of targeted imaging with radiopharmaceuticals within the broader context of molecular probes to enhance understanding and characterisation of the complex biological processes underlying disease and to develop, test and guide new treatment modalities, including radionuclide therapy.
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