Metabolic intratumoral heterogeneity (ITH) is known to be related to cancer treatment outcome. However, information on the temporal changes in metabolic ITH during chemotherapy and the correlations between metabolic changes and treatment outcomes in patients with pancreatic cancer is sparse. We aimed to analyze the temporal changes in metabolic ITH and the predictive role of its changes in advanced pancreatic cancer patients who underwent palliative chemotherapy. Methods: We prospectively enrolled patients with unresectable locally advanced or metastatic pancreatic cancer before first-line palliative chemotherapy. 18F-FDG PET was performed at baseline and at the first response follow-up. SUVs, volumetric parameters, and textural features of the primary pancreatic tumor were analyzed. Relationships between the parameters at baseline and first follow-up were assessed, as well as changes in the parameters with treatment response, progression-free survival (PFS), and overall survival (OS). Results: Among 63 enrolled patients, the best objective response rate was 25.8% (95% confidence interval [CI], 14.6%-37.0%). The median PFS and OS were 7.1 mo (95% CI, 5.1-9.7 mo) and 10.1 mo (95% CI, 8.6-12.7 mo), respectively. Most parameters changed significantly during the first-line chemotherapy, in a way of reducing ITH. Metabolic ITH was more profoundly reduced in responders than in nonresponders. Multiple Cox regression analysis identified high baseline compacity (P = 0.023) and smaller decreases in SUVpeak (P = 0.007) and entropy gray-level cooccurrence matrix (P = 0.033) to be independently associated with poor PFS. Patients with a high carbohydrate antigen 19-9 (P = 0.042), high pretreatment SUVpeak (P = 0.008), and high coefficient of variance at first follow-up (P = 0.04) showed worse OS. Conclusion: Reduction in metabolic ITH during palliative chemotherapy in advanced pancreatic cancer patients is associated with treatment response and might be predictive of PFS and OS.

中文翻译：

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晚期胰腺癌姑息化疗期间时间变化在肿瘤内代谢异质性中的预测作用：一项前瞻性队列研究。

已知代谢物肿瘤内异质性（ITH）与癌症治疗结果相关。然而，关于胰腺癌患者中代谢ITH的时间变化以及代谢变化与治疗结果之间相关性的信息很少。我们旨在分析代谢性ITH的时间变化及其变化对晚期姑息性化疗的胰腺癌患者的预测作用。方法：我们对一线姑息性化疗前未切除的局部晚期或转移性胰腺癌患者进行了前瞻性研究。在基线和首次随访时进行18F-FDG PET。SUV，体积参数和原发性胰腺肿瘤的纹理特征进行了分析。评估了基线和首次随访时参数之间的关系，以及参数随治疗反应，无进展生存期（PFS）和总体生存期（OS）的变化。结果：在63名入组患者中，最佳客观缓解率为25.8％（95％置信区间[CI]，14.6％-37.0％）。PFS和OS的中位数分别为7.1 mo（95％CI，5.1-9.7 mo）和10.1 mo（95％CI，8.6-12.7 mo）。一线化疗期间，大多数参数发生了显着变化，从而降低了ITH的发生率。与无反应者相比，有反应者中代谢型ITH的减少更为显着。多重Cox回归分析确定较高的基线适应症（P = 0.023）和SUVpeak的降低幅度较小（P = 0.007）和熵灰度共生矩阵（P = 0.033）与不良的PFS独立相关。具有高碳水化合物抗原19-9（P = 0.042），具有较高治疗前SUVpeak（P = 0.008）和较高首次随访变异性系数（P = 0.04）的患者表现出较差的OS。结论：晚期胰腺癌患者姑息化疗期间代谢ITH的降低与治疗反应有关，并可能预示PFS和OS。