摘要
肽受体放射性核素治疗 (PRRT) 向表达神经内分泌肿瘤 (NEN) 的生长抑素受体 (SSR) 提供靶向放射。我们试图评估肿瘤剂量测定对68 Ga DOTATATE (GaTate) PET/CT 分子成像肿瘤体积 SSR (MITV SSR ) 变化和 RECIST 1.1 反应以及总生存期 (OS) 的预测和预后影响。
方法
对接受 LuTate 治疗并在第二天(2010 年 7 月至 2019 年 1 月)进行定量 SPECT/CT (Q-SPECT/CT) 的胃肠胰 (GEP) NEN 患者进行回顾性评价。使用基于群体的药代动力学模型对每个周期进行单时间点(STP)病变剂量测定。MITV SSR和 RECIST 1.1 在 PRRT 后 3 个月进行测量。
结果
90 名患者接受了 4 个 PRRT 周期的中位数(范围 2-5 个周期;平均 27.4 GBq 累积活动;平均每个周期 7.6 GBq)。68% 接受了至少一个周期的放射增敏化疗 (RSC)。RECIST 1.1 部分缓解率为 24%,其中 70% 稳定,7% 疾病进展。 当根据肿瘤分级和 RSC 进行调整时,可测量病灶中的第 1 周期辐射剂量与局部反应相关(优势比为 1.5 每 50 Gy [95% CI:1.1–2.0],p = 0.002 ) 。MITV SSR的中位变化为 -63%(四分位数范围 -84 至 -29),在单变量或多变量分析中与最严重病变的辐射剂量没有相关性(5.6 每 10 Gy [95% CI: -1.6, 12.8] ,p = 0.133)。5 年 OS 为 68%(95% CI:56-78%)。基线 MITV SSR(风险比 1.1 [95% CI:1.0, 1.2],p = 0.128)和基线 MITV SSR的变化(风险比 1.0 [95% CI:1.0, 1.1],p = 0.223)均与 OS 无关当按肿瘤分级和 RSC 调整时,但 RSC 为 (95% CI: 0.2, 0.8, p = 0.012)。
结论
PRRT 期间肿瘤的放射剂量可以预测放射学反应,但不能预测生存率。生存结果可能与其他生物因素有关。没有证据表明 MITV SSR变化与 OS 相关,但需要进行更大规模的研究。
"点击查看英文标题和摘要"
The relationship between tumour dosimetry, response, and overall survival in patients with unresectable Neuroendocrine Neoplasms (NEN) treated with 177Lu DOTATATE (LuTate)
Abstract
Peptide Receptor Radionuclide Therapy (PRRT) delivers targeted radiation to Somatostatin Receptor (SSR) expressing Neuroendocrine Neoplasms (NEN). We sought to assess the predictive and prognostic implications of tumour dosimetry with respect to response by 68 Ga DOTATATE (GaTate) PET/CT molecular imaging tumour volume of SSR (MITVSSR) change and RECIST 1.1, and overall survival (OS).
Methods
Patients with gastro-entero-pancreatic (GEP) NEN who received LuTate followed by quantitative SPECT/CT (Q-SPECT/CT) the next day (Jul 2010 to Jan 2019) were retrospectively reviewed. Single time-point (STP) lesional dosimetry was performed for each cycle using population-based pharmacokinetic modelling. MITVSSR and RECIST 1.1 were measured at 3-months post PRRT.
Results
Median of 4 PRRT cycles were administered to 90 patients (range 2–5 cycles; mean 27.4 GBq cumulative activity; mean 7.6 GBq per cycle). 68% received at least one cycle with radiosensitising chemotherapy (RSC). RECIST 1.1 partial response was 24%, with 70% stable and 7% progressive disease. Cycle 1 radiation dose in measurable lesions was associated with local response (odds ratio 1.5 per 50 Gy [95% CI: 1.1–2.0], p = 0.002) when adjusted by tumour grade and RSC. Median change in MITVSSR was -63% (interquartile range -84 to -29), with no correlation with radiation dose to the most avid lesion on univariable or multivariant analyses (5.6 per 10 Gy [95% CI: -1.6, 12.8], p = 0.133). OS at 5-years was 68% (95% CI: 56–78%). Neither baseline MITVSSR (hazard ratio 1.1 [95% CI: 1.0, 1.2], p = 0.128) nor change in baseline MITVSSR (hazard ratio 1.0 [95% CI: 1.0, 1.1], p = 0.223) were associated with OS when adjusted by tumour grade and RSC but RSC was (95% CI: 0.2, 0.8, p = 0.012).
Conclusion
Radiation dose to tumour during PRRT was predictive of radiologic response but not survival. Survival outcomes may relate to other biological factors. There was no evidence that MITVSSR change was associated with OS, but a larger study is needed.