Medical Physics, San Raffaele Scientific Institute, Milano, Italy.
Radiotherapy, San Raffaele Scientific Institute, Milano, Italy.
Radiother Oncol. 2020 Aug;149:174-180. doi: 10.1016/j.radonc.2020.05.019. Epub 2020 May 15.
A previously introduced index based on early tumor (GTV) regression (ERI) during neo-adjuvant radio-chemotherapy of rectal cancer was used to investigate the impact of changes of oxaliplatin (OXA) delivery on the prediction of pathological complete response (pCR) and residual vital cell (RVC) fraction.
Ninety-five patients were treated following an adaptive protocol (41.4 Gy/18fr; 2.3 Gy/fr) delivering a simultaneous integrated boost to the residual GTV in the last 6 fractions (3 Gy/fr). OXA was delivered on days -14, 0 (start of RT) and +14. Based on the oncologist's preference, the last OXA cycle was not administered for 36 patients. MRIs taken at planning and at mid-RT were used to calculate ERI, before the timing of the third OXA cycle. The impact of OXA cycles and the discriminative power of ERI in predicting the pathological response (pCR, RVC >10%) were quantified. Multivariate logistic regression was performed to assess predictive models.
Two patients with complete clinical remission refused surgery (cCR_ww). Complete post-surgical data of 54/59 and 35/36 patients were available for the two groups (3 vs 2 OXA cycles). pCR/pCR + cCR_ww/RVC >10% rates were 31.5/33.9/27.8% and 14.3/14.3/54.3% respectively (p = 0.01-0.07). ERI showed high negative predictive value (85-91%) for all end-points. The logistic predictive model for pCR included ERI (OR: 0.93) and OXA cycles (OR: 3.5), with AUC = 0.78. Internal validation through bootstrap confirmed the robustness of the results.
Late omission of OXA dramatically reduced the pathological response. OXA delivery after the assessment of ERI significantly influenced the relationship between ERI and pCR.
本研究采用一种新的基于直肠癌新辅助放化疗过程中早期肿瘤退缩（ERI）的指数，旨在探讨奥沙利铂（OXA）给药变化对预测病理完全缓解（pCR）和残留活细胞（RVC）分数的影响。
95 例患者接受了适应性方案治疗（41.4Gy/18 次；2.3Gy/次），在最后 6 次（3Gy/次）中对残留 GTV 进行同步整合增敏。OXA 在-14、0（开始放疗）和+14 天给予。根据肿瘤学家的偏好，36 例患者未进行最后一个 OXA 周期。在第三个 OXA 周期开始前，使用计划时和中期放疗时的 MRI 计算 ERI。量化 OXA 周期和 ERI 在预测病理反应（pCR、RVC>10%）中的作用。进行多变量逻辑回归以评估预测模型。
两名完全临床缓解的患者拒绝手术（cCR_ww）。两组中分别有 54/59 和 35/36 例患者有完整的术后数据（3 个和 2 个 OXA 周期）。pCR/pCR+cCR_ww/RVC>10%的发生率分别为 31.5%/33.9%/27.8%和 14.3%/14.3%/54.3%（p=0.01-0.07）。ERI 对所有终点均具有较高的阴性预测值（85-91%）。pCR 的逻辑预测模型包括 ERI（OR：0.93）和 OXA 周期（OR：3.5），AUC=0.78。通过自举法进行内部验证证实了结果的稳健性。
OXA 后期的遗漏显著降低了病理反应。在评估 ERI 后给予 OXA 给药显著影响了 ERI 与 pCR 之间的关系。
