DataSheet_2_Nomogram for predicting prognosis of patients with metastatic melanoma after immunotherapy: A Chinese population–based analysis.pdf

BackgroundPrevious studies indicated the evidence that baseline levels of thyroid antibodies, thyroid status, and serum lactate dehydrogenase (LDH) and M stage may influence the prognosis of patients with advanced or metastatic melanoma treated with immune checkpoint inhibitors that targets programmed cell death-1 (PD-1) or programmed death ligand 1, which reported that dramatic improvements in survival rates were observed; however, the presence of controversy has prevented consensus from being reached. Study objectives were to develop a nomogram to identify several prognostic factors in Chinese patients with metastatic melanoma receiving immunotherapy.
MethodsThis retrospective study included 231 patients from Sun Yat-sen University Cancer Center, and patients were split into internal cohort (n = 165) and external validation cohort (n = 66). We developed a nomogram for the prediction of response and prognosis on the basis of the levels of serum thyroid peroxidase antibody (A-TPO), free T3 (FT3), and LDH and M stage that were measured at the baseline of anti–PD-1 infusion. In addition, the follow-up lasted at least until 5 years after the treatment or mortality. RECIST v1.1 was used to classify treatment responses.
ResultsChi-square test showed that PD-1 antibody was more effective in patients with melanoma with high level baseline FT4 or earlier M stage. A multivariate Cox analysis showed that baseline FT3 (P = 0.009), baseline A-TPO (P = 0.016), and LDH (P = 0.013) levels and M stage (P < 0.001) independently predicted overall survival (OS) in patients with melanoma. The above factors are integrated, and a prediction model is established, i.e., nomogram. Survival probability area-under-the-curve values of 1, 2, and 3 years in the training, internal validation, and external validation cohorts showed the prognostic accuracy and clinical applicability of nomogram (training: 0.714, 0.757, and 0.764; internal validation: 0.7171963, 0.756549, and 0.7651486; external validation: 0.748, 0.710, and 0.856). In addition, the OS of low-risk (total score ≤ 142.65) versus high-risk (total score > 142.65) patients varied significantly in both training group (P < 0.0001) and external validation cohort (P = 0.0012).
ConclusionsAccording to this study, baseline biomarkers are associated with response to immunotherapy and prognosis among patients with metastatic melanoma. Treatment regimens can be tailor-made on the basis of these biomarkers.

背景
既往研究表明，基线甲状腺抗体水平、甲状腺功能状态、血清乳酸脱氢酶（LDH）水平以及M分期，可影响接受程序性死亡受体1（PD-1）或程序性死亡配体1（programmed death ligand 1）靶向免疫检查点抑制剂治疗的晚期或转移性黑色素瘤患者的预后；已有研究报道此类患者的生存率得到显著改善，但目前仍存在争议，尚未达成共识。本研究旨在开发一款列线图，以明确接受免疫治疗的中国转移性黑色素瘤患者的多项预后因素。
方法
本项回顾性研究纳入了来自中山大学肿瘤防治中心的231例患者，将其分为内部队列（n=165）与外部验证队列（n=66）。我们基于抗PD-1输注基线时检测的血清甲状腺过氧化物酶抗体（A-TPO）、游离三碘甲状腺原氨酸（FT3）、LDH水平以及M分期，开发了一款用于预测治疗应答与预后的列线图。此外，随访持续至治疗后至少5年或至患者死亡。采用实体瘤疗效评价标准v1.1（RECIST v1.1）对治疗应答进行分类。
结果
卡方检验显示，基线游离甲状腺素（FT4）水平较高或M分期较早的黑色素瘤患者，PD-1单抗治疗效果更优。多因素Cox分析结果表明，基线FT3（P=0.009）、基线A-TPO（P=0.016）、LDH（P=0.013）水平以及M分期（P<0.001）是黑色素瘤患者总生存期（OS）的独立预测因素。我们将上述因素整合，建立了预测模型即列线图。训练队列、内部验证队列与外部验证队列的1、2、3年总生存期曲线下面积分别为：训练队列0.714、0.757、0.764；内部验证队列0.7171963、0.756549、0.7651486；外部验证队列0.748、0.710、0.856，上述结果证实了列线图的预后预测准确性与临床适用性。此外，低风险组（总评分≤142.65）与高风险组（总评分>142.65）患者的总生存期在训练组（P<0.0001）与外部验证队列（P=0.0012）中均存在显著差异。
结论
本研究表明，基线生物标志物与转移性黑色素瘤患者的免疫治疗应答及预后相关。可基于这些生物标志物为患者制定个体化治疗方案。