Sclafani Francesco, Brown Gina, Cunningham David, Rao Sheela, Tekkis Paris, Tait Diana, Morano Federica, Baratelli Chiara, Kalaitzaki Eleftheria, Rasheed Shahnawaz, Watkins David, Starling Naureen, Wotherspoon Andrew, Chau Ian
Department of Medicine, The Royal Marsden NHS Foundation Trust, London and Surrey, United Kingdom.
Department of Radiology, The Royal Marsden NHS Foundation Trust, London and Surrey, United Kingdom.
Oncologist. 2017 Jun;22(6):728-736. doi: 10.1634/theoncologist.2016-0396. Epub 2017 May 5.
The potential of chemotherapy as salvage treatment after failure of neoadjuvant chemoradiotherapy for locally advanced rectal cancer (LARC) has never been explored. We conducted a single-center, retrospective analysis to address this question.
Patients with newly diagnosed LARC who were inoperable or candidates for extensive (i.e., beyond total mesorectal excision [TME]) surgery after long-course chemoradiotherapy and who received salvage chemotherapy were included. The primary objective was to estimate the proportion of patients who became suitable for TME after chemotherapy.
Forty-five patients were eligible (39 candidates for extensive surgery and 6 unresectable). Previous radiotherapy was given concurrently with chemotherapy in 43 cases (median dose: 54.0 Gy). Oxaliplatin- and irinotecan-based salvage chemotherapy was administered in 40 (88.9%) and 5 (11.1%) cases, respectively. Eight patients (17.8%) became suitable for TME after chemotherapy, 10 (22.2%) ultimately underwent TME with clear margins, and 2 (4.4%) were managed with a watch and wait approach. Additionally, 13 patients had extensive surgery with curative intent. Three-year progression-free survival and 5-year overall survival in the entire population were 30.0% (95% confidence interval [CI]: 15.0-46.0) and 44.0% (95% CI: 26.0-61.0), respectively. For the curatively resected and "watch and wait" patients, these figures were 52.0% (95% CI: 27.0-73.0) and 67.0% (95% CI: 40.0-84.0), respectively.
Systemic chemotherapy may be an effective salvage strategy for LARC patients who fail to respond to chemoradiotherapy and are inoperable or candidates for beyond TME surgery. According to our study, one out of five patients may become resectable or be spared from an extensive surgery after systemic chemotherapy.
High-quality evidence to inform the optimal management of rectal cancer patients who are inoperable or candidates for beyond total mesorectal excision surgery following standard chemoradiotherapy is lacking. We show for the first time that systemic chemotherapy may be beneficial and result in one out of five poor prognosis patients becoming resectable or being spared from an extensive surgical approach. Although mores studies are needed to confirm these data, administering salvage systemic chemotherapy in this setting may have the potential to minimize morbidity associated with extensive surgical procedures and improve long-term oncological outcome.
新辅助放化疗失败后，化疗作为局部晚期直肠癌（LARC）挽救性治疗的潜力从未被探究过。我们进行了一项单中心回顾性分析来解决这个问题。
纳入新诊断为LARC且无法手术或在长程放化疗后适合进行广泛手术（即超出全直肠系膜切除术 [TME]）并接受挽救性化疗的患者。主要目的是评估化疗后适合行TME的患者比例。
45例患者符合条件（39例适合广泛手术，6例不可切除）。43例患者（中位剂量：54.0 Gy）先前放疗与化疗同步进行。分别有40例（88.9%）和5例（11.1%）患者接受了基于奥沙利铂和伊立替康的挽救性化疗。8例患者（17.8%）化疗后适合行TME，10例（22.2%）最终行切缘阴性的TME手术，2例（4.4%）采用观察等待策略。此外，13例患者进行了根治性广泛手术。整个人群的3年无进展生存率和5年总生存率分别为30.0%（95%置信区间 [CI]：15.0 - 46.0）和44.0%（95% CI：26.0 - 61.0）。对于根治性切除和“观察等待”的患者，这些数字分别为52.0%（95% CI：27.0 - 73.0）和67.0%（95% CI：40.0 - 84.0）。
对于对放化疗无反应且无法手术或适合进行超出TME手术的LARC患者，全身化疗可能是一种有效的挽救策略。根据我们的研究，五分之一的患者在全身化疗后可能变得可切除或避免进行广泛手术。
缺乏高质量证据来指导标准放化疗后无法手术或适合进行超出全直肠系膜切除手术的直肠癌患者的最佳管理。我们首次表明全身化疗可能有益，使五分之一预后不良的患者变得可切除或避免进行广泛手术。尽管需要更多研究来证实这些数据，但在此情况下给予挽救性全身化疗可能有潜力将与广泛手术相关的发病率降至最低，并改善长期肿瘤学结局。
