Introduction: Tumor growth rate (TGR; percent size change per month [%/m]) is postulated to be an early radiological biomarker to overcome limitations of RECIST. This study aimed to assess the impact of TGR in neuroendocrine tumors (NETs) and potential clinical and therapeutic applications.
Materials and methods: Patients (pts) with advanced grade (G) 1/2 NETs from the pancreas or small bowel initiating systemic treatment (ST) or watch and wait (WW) were eligible. Baseline and follow-up scans were retrospectively reviewed to calculate TGR at pretreatment (TGR0), first follow-up (TGRfirst), and 3(±1) months of study entry (TGR3m).
Results: Out of 905 pts screened, 222 were eligible. Best TGRfirst (222 pts) cutoff was 0.8 (area under the curve, 0.74). When applied to TGR3m (103 pts), pts with TGR3m <0.8 (66.9%) versus TGR3m ≥ 0.8 (33.1%) had longer median progression-free survival (PFS; 26.3 m; 95% confidence interval [CI] 19.5-32.4 vs. 9.3 m; 95% CI, 6.1-22.9) and lower progression rate at 12 months (7.3% vs. 56.8%; p = .001). WW (vs. ST) and TGR3m ≥ 0.8 (hazard ratio [HR], 3.75; 95% CI, 2.21-6.34; p < .001) were retained as factors associated with a shorter PFS in multivariable Cox regression. TGR3m (HR, 3.62; 95% CI, 1.97-6.64; p < .001) was also an independent factor related to shorter PFS when analysis was limited to pts with stable disease (81 pts). Out of the 60 pts with TGR0 data available, 60% of pts had TGR0 < 4%/month. TGR0 ≥ 4 %/month (HR, 2.22; 95% CI, 1.15-4.31; p = .018) was also an independent factor related to shorter PFS.
Conclusion: TGR is an early radiological biomarker able to predict PFS and to identify patients with advanced NETs who may require closer radiological follow-up.
Implications for practice: Tumor growth rate at 3 months (TGR3m) is an early radiological biomarker able to predict progression-free survival and to identify patients with advanced neuroendocrine tumors who may require closer radiological follow-up. It is feasible to calculate TGR3m in clinical practice and it could be a useful tool for guiding patient management. This biomarker could also be implemented in future clinical trials to assess response to therapy.
摘要
介绍。肿瘤生长率 [TGR；每月尺寸变化百分比 (%/m)]被认为是克服 RECIST 局限性的早期放射性生物标志物。本研究旨在评估TGR对神经内分泌肿瘤 (NET) 的影响以及潜在的临床和治疗应用。
材料和方法。开始全身治疗 (ST) 或观察等待 (WW) 的晚期1/2 级(G)胰腺或小肠NET患者均符合条件。我们回顾性地查看了基线和随访扫描结果，以计算治疗前 (TGR0)、首次随访 (TGRfirst) 和参与研究 3(±1) 个月 (TGR3m) 时的TGR。
结果。在筛选的 905 名患者中，有 222 名患者符合条件。TGRfirst(222 名患者)的最佳截止值为 0.8(曲线下面积，0.74)。当应用于 TGR3m(103 名患者)时，TGR3m <0.8 (66.9%) 与 TGR3m ≥ 0.8 (33.1%) 的患者具有较长的中位无进展生存期 [PFS；26.3 个月；95% 置信区间 (CI)19.5–32.4 与 9.3 个月；95% CI，6.1–22.9]，并且 12 个月时的进展率较低(7.3% 与 56.8%；p = 0.001)。在多变量 Cox 回归中，WW (vs. ST) 和 TGR3m ≥ 0.8 [风险比 (HR)，3.75；95% CI，2.21–6.34；p < 0.001]仍是PFS较短的相关因素。当仅分析疾病稳定的患者(81 名)时，TGR3m(HR，3.62；95% CI，1.97–6.64；p < 0.001)也是与PFS较短相关的独立因素。在可提供 TGR0 数据的 60 名患者中，60% 患者的 TGR0 < 4%/月。TGR0 ≥ 4 %/月(HR，2.22；95% CI，1.15–4.31；p = 0.018)也是与PFS较短相关的独立因素。
结论。TGR是一种早期放射性生物标志物，能够预测PFS并确定可能需要接受更密切放射学随访的晚期NET患者。
实践意义:3 个月时的肿瘤生长率 (TGR3m) 是一种早期放射性生物标志物，能够预测无进展生存期并确定可能需要更密切接受放射学随访的晚期神经内分泌肿瘤患者。在临床实践中计算 TGR3m 是可行的，它可以成为指导患者管理的有用工具。也可以在未来的临床试验中应用该生物标志物，评估治疗效果。
Keywords: NET; Neuroendocrine tumor; Progression‐free survival; TGR; Tumor growth rate.
© AlphaMed Press 2019.