Bengt Glimelius, Tanweera Khan, Karin Adolfsson, Eva Angenete, Åke Berglund, Kristina Bonde, Nils Elander, Tone Fokstuen, Johan Haux, Israa Imam, Cecilia Lagerbäck, Ingrid Ljuslinder, Andrzej Piwowar, Marie Zajicova, Per J Nilsson
{"title":"采用短程放疗和四个 CAPOX 周期对具有高复发风险标准的局部晚期直肠癌进行全面新辅助治疗：瑞典全国队列研究 (LARCT-US)。","authors":"Bengt Glimelius, Tanweera Khan, Karin Adolfsson, Eva Angenete, Åke Berglund, Kristina Bonde, Nils Elander, Tone Fokstuen, Johan Haux, Israa Imam, Cecilia Lagerbäck, Ingrid Ljuslinder, Andrzej Piwowar, Marie Zajicova, Per J Nilsson","doi":"10.1016/j.eclinm.2024.102771","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Total neoadjuvant treatment (TNT) for locally advanced rectal cancer (LARC) increases pathologic complete response (pCR) rate and reduces the risk of systemic recurrences over chemoradiotherapy (CRT) in randomised trials, e.g., the RAPIDO trial. A modified RAPIDO schedule was prospectively explored in Sweden to evaluate TNT in routine health care before the RAPIDO results were published.</p><p><strong>Methods: </strong>Between July 2016 and June 2020, 273 patients with high-risk LARC (clinical tumour stage cT4, clinical nodal stage cN2, extramural vascular invasion, involved mesorectal fascia or enlarged lateral lymph nodes) were treated in a prospective observational cohort study at 16 hospitals (LARCT-US). Another 189 patients at 18 (including the 16) hospitals were similarly treated (<i>ad modum</i> LARCT-US, AdmL) during the same period. Inclusion and exclusion criteria were identical to the RAPIDO trial. Patients received short-course radiotherapy (5 × 5 Gy for 5 days) followed by four cycles of CAPOX or six FOLFOX-6, followed by total mesorectal excision or, if clinical complete response (cCR), inclusion into a watch-and-wait (W&W) study. The primary endpoint was complete response (CR), i.e., the sum of pCR in specimens and cCR exceeding one year in W&W patients. Safety was assessed in all patients.</p><p><strong>Findings: </strong>Compared to the RAPIDO trial, patients were older, and tumours more advanced. Median follow-up was 4.8 years (IQR 4.2-5.2). In LARCT-US all patients received radiotherapy and 268 (98%) started chemotherapy whereas in AdmL all patients received radiotherapy and chemotherapy. In LARCT-US 34 patients had pCR and 31 sustained cCR resulting in a CR-rate of 24% (95% CI 20-28). In AdmL, results were similar (23%, 95% CI 17-30). Locoregional recurrences were 6% (95% CI 4-10) and 5% (95% CI 2-9), respectively, both at 3 years and at last follow-up. Neurotoxicity, recorded in LARCT-US, was lower than in RAPIDO (EORTC-QLQ-CIPN20 tingling toes or feet mean score 24 (SD 31) vs 43 (SD 37)). One treatment-associated death occurred.</p><p><strong>Interpretation: </strong>Despite older patients and more advanced tumours, results similar to the RAPIDO trial were obtained. Hence, two chemotherapy cycles less do not compromise the results maintaining a high CR-rate. This TNT schedule resulted in favourable outcomes in a nation-wide real-life situation.</p><p><strong>Funding: </strong>Swedish Cancer Society.</p>","PeriodicalId":11393,"journal":{"name":"EClinicalMedicine","volume":"75 ","pages":"102771"},"PeriodicalIF":9.6000,"publicationDate":"2024-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11577565/pdf/","citationCount":"0","resultStr":"{\"title\":\"Total neoadjuvant treatment using short-course radiotherapy and four CAPOX cycles in locally advanced rectal cancer with high-risk criteria for recurrence: a Swedish nationwide cohort study (LARCT-US).\",\"authors\":\"Bengt Glimelius, Tanweera Khan, Karin Adolfsson, Eva Angenete, Åke Berglund, Kristina Bonde, Nils Elander, Tone Fokstuen, Johan Haux, Israa Imam, Cecilia Lagerbäck, Ingrid Ljuslinder, Andrzej Piwowar, Marie Zajicova, Per J Nilsson\",\"doi\":\"10.1016/j.eclinm.2024.102771\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Total neoadjuvant treatment (TNT) for locally advanced rectal cancer (LARC) increases pathologic complete response (pCR) rate and reduces the risk of systemic recurrences over chemoradiotherapy (CRT) in randomised trials, e.g., the RAPIDO trial. A modified RAPIDO schedule was prospectively explored in Sweden to evaluate TNT in routine health care before the RAPIDO results were published.</p><p><strong>Methods: </strong>Between July 2016 and June 2020, 273 patients with high-risk LARC (clinical tumour stage cT4, clinical nodal stage cN2, extramural vascular invasion, involved mesorectal fascia or enlarged lateral lymph nodes) were treated in a prospective observational cohort study at 16 hospitals (LARCT-US). Another 189 patients at 18 (including the 16) hospitals were similarly treated (<i>ad modum</i> LARCT-US, AdmL) during the same period. Inclusion and exclusion criteria were identical to the RAPIDO trial. Patients received short-course radiotherapy (5 × 5 Gy for 5 days) followed by four cycles of CAPOX or six FOLFOX-6, followed by total mesorectal excision or, if clinical complete response (cCR), inclusion into a watch-and-wait (W&W) study. The primary endpoint was complete response (CR), i.e., the sum of pCR in specimens and cCR exceeding one year in W&W patients. Safety was assessed in all patients.</p><p><strong>Findings: </strong>Compared to the RAPIDO trial, patients were older, and tumours more advanced. Median follow-up was 4.8 years (IQR 4.2-5.2). In LARCT-US all patients received radiotherapy and 268 (98%) started chemotherapy whereas in AdmL all patients received radiotherapy and chemotherapy. In LARCT-US 34 patients had pCR and 31 sustained cCR resulting in a CR-rate of 24% (95% CI 20-28). In AdmL, results were similar (23%, 95% CI 17-30). Locoregional recurrences were 6% (95% CI 4-10) and 5% (95% CI 2-9), respectively, both at 3 years and at last follow-up. Neurotoxicity, recorded in LARCT-US, was lower than in RAPIDO (EORTC-QLQ-CIPN20 tingling toes or feet mean score 24 (SD 31) vs 43 (SD 37)). One treatment-associated death occurred.</p><p><strong>Interpretation: </strong>Despite older patients and more advanced tumours, results similar to the RAPIDO trial were obtained. Hence, two chemotherapy cycles less do not compromise the results maintaining a high CR-rate. This TNT schedule resulted in favourable outcomes in a nation-wide real-life situation.</p><p><strong>Funding: </strong>Swedish Cancer Society.</p>\",\"PeriodicalId\":11393,\"journal\":{\"name\":\"EClinicalMedicine\",\"volume\":\"75 \",\"pages\":\"102771\"},\"PeriodicalIF\":9.6000,\"publicationDate\":\"2024-08-05\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11577565/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"EClinicalMedicine\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1016/j.eclinm.2024.102771\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/9/1 0:00:00\",\"PubModel\":\"eCollection\",\"JCR\":\"Q1\",\"JCRName\":\"MEDICINE, GENERAL & INTERNAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"EClinicalMedicine","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1016/j.eclinm.2024.102771","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/9/1 0:00:00","PubModel":"eCollection","JCR":"Q1","JCRName":"MEDICINE, GENERAL & INTERNAL","Score":null,"Total":0}
引用次数: 0
摘要
背景：在RAPIDO试验等随机试验中，局部晚期直肠癌（LARC）的全新辅助治疗（TNT）与化放疗（CRT）相比，可提高病理完全反应率（pCR）并降低全身复发风险。在RAPIDO结果公布之前，瑞典对修改后的RAPIDO计划进行了前瞻性探索，以评估TNT在常规医疗保健中的应用：方法：2016 年 7 月至 2020 年 6 月期间，一项前瞻性观察性队列研究（LARCT-US）在 16 家医院对 273 例高风险 LARC 患者（临床肿瘤分期 cT4、临床结节分期 cN2、壁外血管侵犯、累及直肠间筋膜或外侧淋巴结肿大）进行了治疗。同期，18 家医院（包括这 16 家医院）的另外 189 名患者也接受了类似治疗（ad modum LARCT-US，AdmL）。纳入和排除标准与 RAPIDO 试验相同。患者先接受短程放疗（5 × 5 Gy，5 天），然后接受四个周期的 CAPOX 或六个周期的 FOLFOX-6，最后进行全直肠系膜切除术，如果出现临床完全反应（cCR），则纳入观察和等待（W&W）研究。主要终点是完全反应（CR），即标本中的 pCR 和 W&W 患者超过一年的 cCR 之和。对所有患者进行了安全性评估：与RAPIDO试验相比，患者年龄更大，肿瘤更晚期。中位随访时间为4.8年（IQR为4.2-5.2）。在LARCT-US试验中，所有患者都接受了放疗，268名患者（98%）开始接受化疗，而在AdmL试验中，所有患者都接受了放疗和化疗。在LARCT-US中，34名患者获得pCR，31名患者持续获得cCR，CR率为24%（95% CI 20-28）。AdmL的结果类似（23%，95% CI 17-30）。3年后和最后一次随访时，局部复发率分别为6%（95% CI 4-10）和5%（95% CI 2-9）。LARCT-US记录的神经毒性低于RAPIDO（EORTC-QLQ-CIPN20脚趾或脚趾刺痛平均得分为24（标度31） vs 43（标度37））。发生了一起与治疗相关的死亡事件：尽管患者年龄更大、肿瘤更晚期，但仍获得了与RAPIDO试验相似的结果。因此，减少两个化疗周期并不会影响维持高CR率的结果。这种TNT方案在全国范围内的实际情况中取得了良好的效果：瑞典癌症协会。
Total neoadjuvant treatment using short-course radiotherapy and four CAPOX cycles in locally advanced rectal cancer with high-risk criteria for recurrence: a Swedish nationwide cohort study (LARCT-US).
Background: Total neoadjuvant treatment (TNT) for locally advanced rectal cancer (LARC) increases pathologic complete response (pCR) rate and reduces the risk of systemic recurrences over chemoradiotherapy (CRT) in randomised trials, e.g., the RAPIDO trial. A modified RAPIDO schedule was prospectively explored in Sweden to evaluate TNT in routine health care before the RAPIDO results were published.
Methods: Between July 2016 and June 2020, 273 patients with high-risk LARC (clinical tumour stage cT4, clinical nodal stage cN2, extramural vascular invasion, involved mesorectal fascia or enlarged lateral lymph nodes) were treated in a prospective observational cohort study at 16 hospitals (LARCT-US). Another 189 patients at 18 (including the 16) hospitals were similarly treated (ad modum LARCT-US, AdmL) during the same period. Inclusion and exclusion criteria were identical to the RAPIDO trial. Patients received short-course radiotherapy (5 × 5 Gy for 5 days) followed by four cycles of CAPOX or six FOLFOX-6, followed by total mesorectal excision or, if clinical complete response (cCR), inclusion into a watch-and-wait (W&W) study. The primary endpoint was complete response (CR), i.e., the sum of pCR in specimens and cCR exceeding one year in W&W patients. Safety was assessed in all patients.
Findings: Compared to the RAPIDO trial, patients were older, and tumours more advanced. Median follow-up was 4.8 years (IQR 4.2-5.2). In LARCT-US all patients received radiotherapy and 268 (98%) started chemotherapy whereas in AdmL all patients received radiotherapy and chemotherapy. In LARCT-US 34 patients had pCR and 31 sustained cCR resulting in a CR-rate of 24% (95% CI 20-28). In AdmL, results were similar (23%, 95% CI 17-30). Locoregional recurrences were 6% (95% CI 4-10) and 5% (95% CI 2-9), respectively, both at 3 years and at last follow-up. Neurotoxicity, recorded in LARCT-US, was lower than in RAPIDO (EORTC-QLQ-CIPN20 tingling toes or feet mean score 24 (SD 31) vs 43 (SD 37)). One treatment-associated death occurred.
Interpretation: Despite older patients and more advanced tumours, results similar to the RAPIDO trial were obtained. Hence, two chemotherapy cycles less do not compromise the results maintaining a high CR-rate. This TNT schedule resulted in favourable outcomes in a nation-wide real-life situation.
期刊介绍：
eClinicalMedicine is a gold open-access clinical journal designed to support frontline health professionals in addressing the complex and rapid health transitions affecting societies globally. The journal aims to assist practitioners in overcoming healthcare challenges across diverse communities, spanning diagnosis, treatment, prevention, and health promotion. Integrating disciplines from various specialties and life stages, it seeks to enhance health systems as fundamental institutions within societies. With a forward-thinking approach, eClinicalMedicine aims to redefine the future of healthcare.
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号
