局部晚期胰腺癌患者接受15次分割联合化疗时胃和十二指肠的剂量-体积限制
Stomach and duodenum dose-volume constraints for locally advanced pancreatic cancer patients treated in 15 fractions in combination with chemotherapy.
作者信息
Broggi Sara, Passoni Paolo, Tiberio Paolo, Cicchetti Alessandro, Cattaneo Giovanni Mauro, Longobardi Barbara, Mori Martina, Reni Michele, Slim Najla, Del Vecchio Antonella, Di Muzio Nadia G, Fiorino Claudio
机构信息
Medical Physics, San Raffaele Scientific Institute, Milano, Italy.
Radiotherapy, San Raffaele Scientific Institute, Milano, Italy.
出版信息
Front Oncol. 2023 Jan 24;12:983984. doi: 10.3389/fonc.2022.983984. eCollection 2022.
PURPOSE
To assess dosimetry predictors of gastric and duodenal toxicities for locally advanced pancreatic cancer (LAPC) patients treated with chemo-radiotherapy in 15 fractions.
METHODS
Data from 204 LAPC patients treated with induction+concurrent chemotherapy and radiotherapy (44.25 Gy in 15 fractions) were available. Forty-three patients received a simultaneous integrated boost of 48-58 Gy. Gastric/duodenal Common Terminology Criteria for Adverse Events v. 5 (CTCAEv5) Grade ≥2 toxicities were analyzed. Absolute/% duodenal and stomach dose-volume histograms (DVHs) of patients with/without toxicities were compared: the most predictive DVH points were identified, and their association with toxicity was tested in univariate and multivariate logistic regressions together with near-maximum dose (D) and selected clinical variables.
RESULTS
Toxicity occurred in 18 patients: 3 duodenal (ulcer and duodenitis) and 10 gastric (ulcer and stomatitis); 5/18 experienced both. At univariate analysis, V44cc (duodenum: p = 0.02, OR = 1.07; stomach: p = 0.01, OR = 1.12) and D (p = 0.07, OR = 1.19; p = 0.008, OR = 1.12) were found to be the most predictive parameters. Stomach/duodenum V44Gy and stomach D were confirmed at multivariate analysis and found to be sufficiently robust at internal, bootstrap-based validation; the results regarding duodenum D were less robust. No clinical variables or %DVH was significantly associated with toxicity. The best duodenum cutoff values were V44Gy < 9.1 cc (and D < 47.6 Gy); concerning the stomach, they were V44Gy < 2 cc and D < 45 Gy. The identified predictors showed a high negative predictive value (>94%).
CONCLUSION
In a large cohort treated with hypofractionated radiotherapy for LAPC, the risk of duodenal/gastric toxicities was associated with duodenum/stomach DVH. Constraining duodenum V44Gy < 9.1 cc, stomach V44Gy < 2 cc, and stomach D < 45 Gy should keep the toxicity rate at approximately or below 5%. The association with duodenum D was not sufficiently robust due to the limited number of events, although results suggest that a limit of 45-46 Gy should be safe.
目的
评估接受15次分割化疗放疗的局部晚期胰腺癌（LAPC）患者胃和十二指肠毒性的剂量学预测因素。
方法
可获取204例接受诱导+同步化疗及放疗（15次分割，44.25 Gy）的LAPC患者的数据。43例患者接受了48 - 58 Gy的同步整合加量照射。分析胃/十二指肠不良事件通用术语标准第5版（CTCAEv5）≥2级毒性反应。比较发生毒性反应和未发生毒性反应患者的十二指肠和胃的绝对/百分比剂量体积直方图（DVH）：确定最具预测性的DVH点，并在单因素和多因素逻辑回归中测试其与毒性反应的关联，同时纳入接近最大剂量（D）和选定的临床变量。
结果
18例患者出现毒性反应：3例十二指肠毒性（溃疡和十二指肠炎），10例胃毒性（溃疡和口腔炎）；18例中有5例同时出现两种毒性。单因素分析发现，V44cc（十二指肠：p = 0.02，OR = 1.07；胃：p = 0.01，OR = 1.12）和D（十二指肠：p = 0.07，OR = 1.19；胃：p = 0.008，OR = 1.12）是最具预测性的参数。多因素分析证实了胃/十二指肠V44Gy和胃D，并发现其在基于自抽样的内部验证中具有足够的稳健性；十二指肠D的结果稳健性较差。没有临床变量或百分比DVH与毒性反应显著相关。十二指肠的最佳截断值为V44Gy < 9.1 cc（且D < 47.6 Gy）；对于胃，截断值为V44Gy < 2 cc和D < 45 Gy。所确定的预测因素显示出较高的阴性预测值（>94%）。
结论
在接受大分割放疗的LAPC患者大样本队列中，十二指肠/胃毒性风险与十二指肠/胃DVH相关。将十二指肠V44Gy限制在< 9.1 cc、胃V44Gy限制在< 2 cc以及胃D限制在< 45 Gy应可使毒性发生率保持在约5%或以下。由于事件数量有限，与十二指肠D的关联稳健性不足，尽管结果表明45 - 46 Gy的限制应该是安全的。
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