Peninsula Oesophago-gastric Surgery Unit, Derriford Hospital, Plymouth, Devon, PL3 5AN, UK.
Peninsula Oesophago-gastric Surgery Unit, Derriford Hospital, Plymouth, Devon, PL3 5AN, UK.
Int J Surg. 2018 Apr;52:126-130. doi: 10.1016/j.ijsu.2018.02.023. Epub 2018 Feb 15.
Early studies investigating the benefits of neoadjuvant therapy in oesophageal cancer showed conflicting results, taking many years before a survival advantage was demonstrated in randomised trials. Gains are modest, limited by progressive disease and toxicity. This study aimed to investigate the relationship between neoadjuvant therapy-associated toxicity and clinical outcomes including survival in patients with potentially curable oesophageal adenocarcinoma.
A cohort of 286 patients undergoing neoadjuvant therapy followed by surgical resection at a single institution was identified from a prospective database. Adverse events from neoadjuvant therapy were recorded and graded. Patients were divided into two groups according to whether they suffered toxicity or not. Clinical outcomes including whether patients completed the neoadjuvant course, whether they proceeded to resection and overall survival, were compared between the groups.
Neoadjuvant therapy-related toxicity was identified in 67/286 patients. 46 patients suffered severe, life-threatening or fatal adverse events. In patients with toxicity, 47% did not complete the chemotherapy course compared to 17% without toxicity, RR 2.7 (95%CI 1.7-4.4), (P < 0.001). In patients suffering toxicity, 17.9% failed to proceed to resection compared with 7.8% in those without toxicity, RR 2.3 (95%CI 1.2-4.6) P = 0.02. Median overall survival was shorter in patients suffering toxicity (20.7 months) compared to those without toxicity (37.8 months), P = 0.008. When patients failing to proceed to resection were excluded, median overall survival was shorter in patients suffering toxicity (26.2 months) compared with those without toxicity (47.8), P = 0.039.
Neoadjuvant therapy-related toxicity is common and can have serious consequences including failure to complete chemotherapy cycles, a higher risk of not proceeding to surgical resection and poorer overall survival. Efforts should be made to reduce toxicity and research should aim to identify responders and factors predictive of toxicity.
早期研究表明新辅助治疗在食管癌中的获益结果存在争议，直到随机试验证明生存优势，这期间经历了多年。获益有限，受到疾病进展和毒性的限制。本研究旨在探讨新辅助治疗相关毒性与临床结局（包括可治愈的食管腺癌患者的生存）之间的关系。
从一个前瞻性数据库中确定了在一家医疗机构接受新辅助治疗后接受手术切除的 286 例患者的队列。记录新辅助治疗的不良事件并进行分级。根据是否发生毒性，将患者分为两组。比较两组患者的新辅助治疗完成情况、是否进行切除以及总生存情况等临床结局。
286 例患者中有 67 例发生了新辅助治疗相关毒性。46 例患者发生严重、威胁生命或致命的不良事件。在发生毒性的患者中，有 47%的患者未完成化疗疗程，而无毒性的患者为 17%，RR 2.7（95%CI 1.7-4.4），（P < 0.001）。在发生毒性的患者中，有 17.9%的患者未能进行切除，而无毒性的患者为 7.8%，RR 2.3（95%CI 1.2-4.6），P = 0.02。发生毒性的患者的中位总生存期（20.7 个月）较无毒性的患者（37.8 个月）更短，P = 0.008。排除未进行切除的患者后，发生毒性的患者的中位总生存期（26.2 个月）仍较无毒性的患者（47.8 个月）更短，P = 0.039。
新辅助治疗相关毒性常见且后果严重，包括无法完成化疗周期、更有可能无法进行手术切除和较差的总生存期。应努力降低毒性，并进行研究以确定反应者和预测毒性的因素。
