Immune checkpoint blockade such as ipilimumab and anti-PD1 monoclonal antibodies have significantly improved survival in advanced melanoma. Biomarkers are urgently needed as a majority of patients do not respond, despite treatment-related toxicities. We analysed pre-treatment 18F-fluorodeoxyglucose positron emission tomography/computerised tomography (FDG PET/CT) parameters to assess its correlation with patient outcome. This retrospective study evaluated pre-treatment FDG PET/CT scans in a discovery cohort of patients with advanced melanoma treated with ipilimumab or anti-PD1. Pre-treatment scans were assessed for maximum tumoral standardised uptake value (SUVmax), metabolic tumour volume (MTV) and spleen to liver ratio (SLR). Progression-free survival (PFS) and overall survival (OS) were characterised and modelled using univariable and multivariable analyses. Correlation of SLR and OS was validated in an independent cohort. Blood parameters and stored sera of patients from the discovery cohort was analysed to investigate biological correlates with SLR. Of the 90 evaluable patients in the discovery cohort: 50 received ipilimumab monotherapy, 20 received anti-PD1 monotherapy, and 20 patients received ipilimumab followed by anti-PD1 upon disease progression. High SLR > 1.1 was associated with poor PFS (median 1 vs 3 months; HR 3.14, p = 0.008) for patients treated with ipilimumab. High SLR was associated with poor OS after ipilimumab (median 1 vs 21 months; HR 5.83, p = 0.0001); as well as poor OS after first line immunotherapy of either ipilimumab or anti-PD1 (median 1 vs 14 months; HR 3.92, p = 0.003). The association of high SLR and poor OS after ipilimumab was validated in an independent cohort of 110 patients (median 2.3 months versus 11.9 months, HR 3.74). SLR was associated with poor OS in a multi-variable model independent of stage, LDH, absolute lymphocyte count and MTV. Pre-treatment Spleen to liver ratio (SLR) > 1.1 was associated with poor outcome after ipilimumab in advanced melanoma. This parameter warrants prospective evaluation.

中文翻译：

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基于 18F-FDG PET/CT 的脾肝比与转移性黑色素瘤患者使用易普利姆玛的临床结果相关

免疫检查点阻断剂如易普利姆玛和抗 PD1 单克隆抗体显着提高了晚期黑色素瘤的生存率。尽管存在治疗相关毒性，但大多数患者仍无反应，因此迫切需要生物标志物。我们分析了治疗前的 18F-氟脱氧葡萄糖正电子发射断层扫描/计算机断层扫描 (FDG PET/CT) 参数，以评估其与患者预后的相关性。这项回顾性研究评估了一组接受易普利姆玛或抗 PD1 治疗的晚期黑色素瘤患者的治疗前 FDG PET/CT 扫描。评估治疗前扫描的最大肿瘤标准化摄取值 (SUVmax)、代谢肿瘤体积 (MTV) 和脾肝比 (SLR)。使用单变量和多变量分析表征和建模无进展生存期 (PFS) 和总生存期 (OS)。SLR 和 OS 的相关性在独立队列中得到验证。分析来自发现队列的患者的血液参数和储存的血清，以研究与 SLR 的生物学相关性。在发现队列中的 90 名可评估患者中：50 名接受易普利姆玛单药治疗，20 名接受抗 PD1 单药治疗，20 名患者在疾病进展时接受易普利姆玛和抗 PD1 治疗。对于接受易普利姆玛治疗的患者，高 SLR > 1.1 与较差的 PFS（中位 1 个月 vs 3 个月；HR 3.14，p = 0.008）相关。高 SLR 与 ipilimumab 后较差的 OS 相关（中位 1 个月 vs 21 个月；HR 5.83，p = 0.0001）；以及伊匹单抗或抗 PD1 的一线免疫治疗后较差的 OS（中位 1 个月 vs 14 个月；HR 3.92，p = 0.003）。在 110 名患者的独立队列中验证了 ipilimumab 后高 SLR 和较差 OS 之间的关联（中位 2.3 个月对 11.9 个月，HR 3.74）。在独立于分期、LDH、绝对淋巴细胞计数和 MTV 的多变量模型中，SLR 与较差的 OS 相关。治疗前脾肝比 (SLR) > 1.1 与晚期黑色素瘤患者接受易普利姆玛治疗后的不良结局相关。该参数值得进行前瞻性评估。LDH、绝对淋巴细胞计数和MTV。治疗前脾肝比 (SLR) > 1.1 与晚期黑色素瘤患者接受易普利姆玛治疗后的不良结局相关。该参数值得进行前瞻性评估。LDH、绝对淋巴细胞计数和MTV。治疗前脾肝比 (SLR) > 1.1 与晚期黑色素瘤患者接受易普利姆玛治疗后的不良结局相关。该参数值得进行前瞻性评估。