Laboratory of Experimental Radiotherapy, Department of Oncology, KU Leuven - University of Leuven , Leuven , Belgium.
Department of Radiation Oncology, UZ Leuven - University Hospitals Leuven , Leuven , Belgium.
Acta Oncol. 2019 Oct;58(10):1358-1365. doi: 10.1080/0284186X.2019.1646432. Epub 2019 Aug 21.
To explore whether a higher neoadjuvant radiation dose increases the probability of a pathological complete response (pCR) or pathological major response (pMR) response in oesophageal cancer patients. Between 2000 and 2017, 1048 patients from four institutions were stratified according to prescribed neoadjuvant radiation doses of 36.0 Gy (13.3%), 40.0 Gy (7.4%), 41.4 Gy (20.1%), 45.0 Gy (25.5%) or 50.4 Gy (33.7%) in 1.8-2.0 Gy fractions. Endpoints were pCR (tumour regression grade (TRG) 1) and pMR (TRG 1 + 2). Multivariable binary (TRG 1 + 2 vs. TRG > 2) and ordinal (TRG 1 vs. TRG 2 vs. TRG > 2) logistic regression analyses were performed, with subgroup analyses according to histology (squamous cell carcinoma (SCC) vs. adenocarcinoma (AC)). Variables entered in the regression model along with neoadjuvant radiation dose were clinical tumour stage (cT), histology, chemotherapy regimen, induction chemotherapy and time from neoadjuvant chemoradiation to surgery. A pCR was observed in 312 patients (29.8%); in 22.7% patients with AC and in 49.6% patients with SCC. No radiation dose-response relation was observed for pCR (OR = 1.01, 95% CI: 0.98-1.05 for AC and OR = 1.03, 95% CI: 0.96-1.10 for SCC). A pMR was observed in 597 patients (57.0%); in 53.4% patients with AC and in 67.2% patients with SCC. A higher radiation dose increased the probability of achieving pMR (OR = 1.04, 95% CI: 1.02-1.05). Factors reducing this probability were advanced cT stage (reference = cT1-2; cT3: OR = 0.54, 95% CI: 0.37-0.80; cT4: OR = 0.45, 95% CI: 0.24-0.84), AC histology (reference = SCC; OR = 0.62, 95% CI: 0.44-0.88), the use of non-platinum based chemotherapy in SCC patients (OR = 0.30, 95% CI: 0.10-0.91) and platinum based chemotherapy without induction chemotherapy in patients with AC (OR = 0.56, 95% CI: 0.42-0.76). The radiation dose-response relation was confirmed in a subgroup analysis of histologic subtypes (OR = 1.02, 95% CI: 1.01-1.04 for AC and OR = 1.05, 95% CI: 1.02-1.08 for SCC). Neoadjuvant radiation dose impacts pathological response in terms of pMR in oesophageal cancer patients. No radiation dose-response effect was observed for pCR. Further prospective trials are needed to investigate the dose-response relation in terms of pCR.
探讨新辅助放疗剂量增加能否提高食管癌患者病理完全缓解（pCR）或病理主要缓解（pMR）的概率。2000 年至 2017 年，来自四个机构的 1048 名患者根据预设的新辅助放疗剂量分为 36.0Gy（13.3%）、40.0Gy（7.4%）、41.4Gy（20.1%）、45.0Gy（25.5%）或 50.4Gy（33.7%），剂量分割为 1.8-2.0Gy。终点为 pCR（肿瘤消退分级（TRG）1）和 pMR（TRG 1+2）。采用多变量二分类（TRG 1+2 与 TRG>2）和有序（TRG 1 与 TRG 2 与 TRG>2）逻辑回归分析，根据组织学（鳞状细胞癌（SCC）与腺癌（AC））进行亚组分析。纳入回归模型的变量与新辅助放化疗剂量一起为临床肿瘤分期（cT）、组织学、化疗方案、诱导化疗以及新辅助放化疗至手术的时间。312 名患者（29.8%）观察到 pCR；在 22.7%的 AC 患者和 49.6%的 SCC 患者中观察到 pCR。pCR 未观察到与放疗剂量的相关性（AC 的 OR=1.01，95%CI：0.98-1.05；SCC 的 OR=1.03，95%CI：0.96-1.10）。597 名患者（57.0%）观察到 pMR；在 53.4%的 AC 患者和 67.2%的 SCC 患者中观察到 pMR。较高的放疗剂量增加了达到 pMR 的概率（OR=1.04，95%CI：1.02-1.05）。降低这种概率的因素包括较晚的 cT 分期（参考 cT1-2；cT3：OR=0.54，95%CI：0.37-0.80；cT4：OR=0.45，95%CI：0.24-0.84）、AC 组织学（参考 SCC；OR=0.62，95%CI：0.44-0.88）、SCC 患者非铂类化疗（OR=0.30，95%CI：0.10-0.91）和 AC 患者无诱导化疗的铂类化疗（OR=0.56，95%CI：0.42-0.76）。在组织学亚型的亚组分析中证实了放疗剂量与反应的关系（AC 的 OR=1.02，95%CI：1.01-1.04；SCC 的 OR=1.05，95%CI：1.02-1.08）。新辅助放疗剂量影响食管癌患者的病理反应，表现在 pMR 方面。pCR 未观察到放疗剂量效应。需要进一步的前瞻性试验来研究 pCR 方面的剂量反应关系。
