Tuta Mojca, Boc Nina, Brecelj Erik, Peternel Monika, Velenik Vaneja
Division of Radiology, Institute of Oncology, Ljubljana 1000, Slovenia.
Division of Surgery, Institute of Oncology, Ljubljana 1000, Slovenia.
World J Gastrointest Oncol. 2021 Feb 15;13(2):119-130. doi: 10.4251/wjgo.v13.i2.119.
For locally advanced rectal cancer (LARC), standard therapy [consisting of neoadjuvant chemoradiotherapy (CRT), surgery, and adjuvant chemotherapy (ChT)] achieves excellent local control. Unfortunately, survival is still poor due to distant metastases, which remains the leading cause of death among these patients. In recent years, the concept of total neoadjuvant treatment (TNT) has been developed, whereby all systemic ChT-mainly affecting micrometastases-is applied prior to surgery.
To compare standard therapy and total neoadjuvant therapy for LARC patients with high-risk factors for failure.
In a retrospective study, we compared LARC patients with high-risk factors for failure who were treated with standard therapy or with TNT. High-risk for failure was defined according to the presence of at least one of the following factors: T4 stage; N2 stage; positive mesorectal fascia; extramural vascular invasion; positive lateral lymph node. TNT consisted of 12 wk of induction ChT with capecitabine and oxaliplatin or folinic acid, fluorouracil and oxaliplatin, CRT with capecitabine, and 6-8 wk of consolidation ChT with capecitabine and oxaliplatin or folinic acid, fluorouracil and oxaliplatin prior to surgery. The primary endpoint was pathological complete response (pCR). In total, 72 patients treated with standard therapy and 89 patients treated with TNT were included in the analysis.
Compared to standard therapy, TNT showed a higher proportion of pCR (23% 7%; = 0.01), a lower neoadjuvant rectal score (median: 8.43 14.98; < 0.05), higher T-and N-downstaging (70% and 94% 51% and 86%), equivalent R0 resection (95% 93%), shorter time to stoma closure (mean: 20 33 wk; < 0.05), higher compliance during systemic ChT (completed all cycles 87% 76%; < 0.05), lower proportion of acute toxicity grade ≥ 3 during ChT (3% 14%, < 0.05), and equivalent acute toxicity and compliance during CRT and in the postoperative period. The pCR rate in patients treated with TNT was significantly higher in patients irradiated with intensity-modulated radiotherapy/volumetric-modulated arc radiotherapy than with 3D conformal radiotherapy (32% 9%; < 0.05).
Compared to standard therapy, TNT provides better outcome for LARC patients with high-risk factors for failure, in terms of pCR and neoadjuvant rectal score.
对于局部晚期直肠癌（LARC），标准治疗方案[包括新辅助放化疗（CRT）、手术和辅助化疗（ChT）]可实现出色的局部控制。不幸的是，由于远处转移，患者生存率仍然较低，远处转移仍是这些患者的主要死因。近年来，全新辅助治疗（TNT）的概念应运而生，即在手术前应用所有全身性ChT（主要影响微转移灶）。
比较标准治疗和全新辅助治疗对具有高失败风险因素的LARC患者的疗效。
在一项回顾性研究中，我们比较了接受标准治疗或TNT的具有高失败风险因素的LARC患者。根据以下至少一项因素的存在定义为高失败风险：T4期；N2期；直肠系膜筋膜阳性；壁外血管侵犯；侧方淋巴结阳性。TNT包括在手术前使用卡培他滨和奥沙利铂或亚叶酸、氟尿嘧啶和奥沙利铂进行12周的诱导ChT，使用卡培他滨进行CRT，以及使用卡培他滨和奥沙利铂或亚叶酸、氟尿嘧啶和奥沙利铂进行6 - 8周的巩固ChT。主要终点是病理完全缓解（pCR）。分析共纳入72例接受标准治疗的患者和89例接受TNT的患者。
与标准治疗相比，TNT的pCR比例更高（23%对7%；P = 0.01），新辅助直肠评分更低（中位数：8.43对14.98；P < 0.05），T分期和N分期降期更高（70%和94%对51%和86%），R0切除率相当（95%对93%），造口关闭时间更短（平均：20周对33周；P < 0.05），全身ChT期间的依从性更高（完成所有周期87%对76%；P < 0.05），ChT期间≥3级急性毒性比例更低（3%对14%，P < 0.05），CRT期间以及术后的急性毒性和依从性相当。接受强度调制放疗/容积调制弧形放疗的患者中，接受TNT治疗的患者的pCR率显著高于接受三维适形放疗的患者（32%对9%；P < 0.05）。
与标准治疗相比，对于具有高失败风险因素的LARC患者，TNT在pCR和新辅助直肠评分方面提供了更好的疗效。
