Kong Yue, Su Miaoyi, Fang Jun, Chen Mengyuan, Zheng Chao, Jiang Youhua, Tao Kaiyi, Wang Changchun, Qiu Guoqin, Ji Yongling, Wang Yuezhen, Yang Yang
Department of Thoracic Radiation Oncology, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Science, Hangzhou, 310022, China.
Department of Radiotherapy, Quanzhou Guangqian Hospital, Quanzhou, 362321, Fujian, China.
Sci Rep. 2024 Jul 17;14(1):16495. doi: 10.1038/s41598-024-67419-6.
With the success of immunotherapy in advanced esophageal cancer, neoadjuvant chemo-immunotherapy (CIT) is being increasingly used for local staged esophageal cancer, especially in the context of clinical trials, which brings similar pCR with neoadjuvant chemoradiotherapy and shows promising results. However, there is still a part of potentially operable patients can't undergo surgery after neoadjuvant chemo-immunotherapy. The follow-up treatment and prognosis of this population remain unclear. Patients pathologically diagnosed with ESCC, clinical stage T1-3N+M0 or T3-4aNanyM0 (AJCC 8th), PS 0-1 were retrospectively enrolled from 1/2020 to 6/2021 in Zhejiang Cancer Hospital. All patients firstly received PD-1 inhibitors plus chemotherapy (albumin paclitaxel, 260 mg/m on day 1 plus carboplatin AUC = 5 on day 1) every 3 weeks for 2-4 cycles. For those patients who did not receive surgery, definitive radiotherapy with 50.4 Gy/28F or 50 Gy/25F was adopted using VMAT, concurrent with chemotherapy or alone. The concurrent chemotherapy regimens included weekly TC (paclitaxel 50 mg/m, d1, carboplatin AUC = 2, d1) or S1 (60 mg bid d1-14, 29-42). The survival outcomes and treatment toxicity were recorded and analyzed. A total of 56 eligible patients were finally identified from 558 patients who were treated in department of thoracic surgery, among all the patients, 25 (44.6%) received radiotherapy alone, and 31 (55.4%) received chemoradiotherapy after neoadjuvant CIT. The median follow-up was 20.4 months (interquartile range [IQR] 8.7-27 months). The median PFS and OS were 17.9 months (95% confidence interval [CI] 11.0-21.9 months) and 20.5 months (95% CI 11.8-27.9 months), respectively. In the subgroup analysis, the median OS was 26.3 months (95% CI 15.33-NA) for patients exhibiting partial response (PR) to CIT, compared to 17 months (95% CI 8.77-26.4) for those with stable disease (SD) or progressive disease (PD), yielding a hazard ratio (HR) of 0.54 (95% CI 0.27-1.06, P = 0.07). No significant difference was observed for patients received radiotherapy alone or chemoradiotherapy with HR = 0.73 (95% CI 0.72-2.6, P = 0.33). The most common Adverse events (AEs) observed during this study were anemia (98.2%), leukopenia (83.9%), thrombocytopenia (53.6%). AEs of grade ≥ 3 radiation-induced pneumonitis and esophagitis were 12.5% and 32.1%, especially, 6 patients (10.7%) died from esophageal fistula and 2 patients (3.6%) died from grade 5 pneumonitis. For local advanced ESCC patients after neoadjuvant CIT who did not receive surgery, definitive radiotherapy was an optional treatment strategy. However, those patients with no response to CIT also showed poor response to radiotherapy, and particular attention should be paid to treatment related toxicity, especially esophageal fistula.
随着免疫疗法在晚期食管癌治疗中取得成功，新辅助化疗联合免疫疗法（CIT）越来越多地用于局部晚期食管癌，尤其是在临床试验背景下，其带来的病理完全缓解（pCR）与新辅助放化疗相似，并显示出有前景的结果。然而，仍有一部分潜在可手术的患者在新辅助化疗联合免疫疗法后无法接受手术。这部分患者的后续治疗及预后仍不明确。对2020年1月至2021年6月期间在浙江省肿瘤医院回顾性纳入的病理诊断为食管鳞状细胞癌（ESCC）、临床分期为T1 - 3N + M0或T3 - 4aNanyM0（美国癌症联合委员会第8版）、体能状态（PS）为0 - 1的患者进行研究。所有患者首先接受每3周1次的PD - 1抑制剂联合化疗（白蛋白紫杉醇，第1天260mg/m²加卡铂AUC = 5，第1天），共2 - 4个周期。对于未接受手术的患者，采用容积调强弧形放疗（VMAT）给予50.4Gy/28次分割或50Gy/25次分割的根治性放疗，可联合化疗或单独进行。同步化疗方案包括每周紫杉醇联合卡铂（TC，紫杉醇50mg/m²，第1天，卡铂AUC = 2，第1天）或替吉奥（S1，60mg，每日2次，第1 - 14天，第29 - 42天）。记录并分析生存结局和治疗毒性。最终从胸外科治疗的558例患者中确定了56例符合条件的患者，所有患者中，25例（44.6%）仅接受放疗，31例（55.4%）在新辅助CIT后接受放化疗。中位随访时间为20.4个月（四分位间距[IQR] 8.7 - 27个月）。中位无进展生存期（PFS）和总生存期（OS）分别为17.9个月（95%置信区间[CI] 11.0 - 21.9个月）和20.5个月（95% CI 11.8 - 27.9个月）。在亚组分析中，对CIT表现出部分缓解（PR）的患者中位OS为26.3个月（95% CI 15.33 - 无上限[NA]），而疾病稳定（SD）或疾病进展（PD）的患者为17个月（95% CI 8.77 - 26.4），风险比（HR）为0.54（95% CI 0.27 - 1.06，P = 0.07）。单独接受放疗或放化疗的患者未观察到显著差异，HR = 0.73（95% CI 0.72 - 2.6，P = 0.33）。本研究期间观察到的最常见不良事件（AE）为贫血（98.2%）、白细胞减少（83.9%）、血小板减少（53.6%）。≥3级放射性肺炎和食管炎的AE分别为12.5%和32.1%，尤其有6例患者（10.7%）死于食管瘘，2例患者（3.6%）死于5级肺炎。对于新辅助CIT后未接受手术的局部晚期ESCC患者，根治性放疗是一种可选的治疗策略。然而，那些对CIT无反应的患者对放疗反应也较差，应特别关注治疗相关毒性，尤其是食管瘘。
