Department of Clinical Oncology, North Wales Cancer Treatment Centre, Rhyl, LL18 5UJ United Kingdom.
J Clin Oncol. 2011 Mar 10;29(8):1042-9. doi: 10.1200/JCO.2010.29.7697. Epub 2011 Jan 24.
To assess long-term clinical outcomes of preoperative chemoradiotherapy of magnetic resonance imaging (MRI)-defined locally advanced rectal adenocarcinoma using concurrent irinotecan and capecitabine.
One hundred ten patients without distant metastases entered this phase II trial North West/North Wales Clinical Oncology Group (NWCOG) -2 after MRI demonstration of tumor threatening (≤ 2 mm) or involving mesorectal fascia. Pelvic radiotherapy was given to 45 Gy in 25 fractions over 5 weeks with concurrent oral capecitabine at 650 mg/m(2) twice per day continuously days 1 through 35 and intravenous irinotecan at 60 mg/m(2) once weekly weeks 1 to 4. One hundred seven patients subsequently underwent surgical resection.
Comparing prechemoradiotherapy MRI scans with histology of the resected specimen, 72 patients (67%) had their initial MRI T stage downstaged and 64 patients (80%) had their N stage downstaged. Twenty-four patients (22%) demonstrated a pathologic complete response (ypCR) and 98 patients (92%) demonstrated a negative circumferential resection margin (> 1 mm). Three-year local recurrence-free survival was 96.9%, metastasis-free survival (MFS) was 71.1%, disease-free survival was (DFS) 63.5%, and overall survival (OS) was 88.2%. By univariate analysis, lower histologic stage was significantly associated with superior MFS, DFS, and OS, whether expressed as ypT0-2 versus ypT3-4, ypN0 versus ypN1-2, or ypCR/microfoci (near-ypCR) versus other patients. By multivariate analysis both ypN stage (P = .048) and ypCR/microfoci/others (P = .013) remained significant predictors of DFS but only ypCR/microfoci/others for OS (P = .005) with no difference in outcome between ypCR compared to microfoci.
This regimen demonstrates high response rates and promising long-term survival. Downstaging to ypCR/microfoci may be a useful short-term surrogate for long-term survival but needs validation in large phase III trials powered for survival outcomes.
评估磁共振成像（MRI）定义的局部晚期直肠腺癌术前放化疗的长期临床结果，使用伊立替康和顺铂。
110 名无远处转移的患者进入这项西北/北威尔士临床肿瘤学组（NWCOG）-2 期临床试验，这些患者在 MRI 显示肿瘤有威胁（≤2mm）或累及中直肠筋膜后。盆腔放疗给予 45 Gy，分 25 次，每周 1 次给予静脉伊立替康 60mg/m2，持续 4 周，同时每天口服卡培他滨 650mg/m2，持续 35 天。107 例患者随后接受了手术切除。
比较术前放化疗的 MRI 扫描和切除标本的组织学，72 例（67%）患者的初始 MRI T 分期降级，64 例（80%）患者的 N 分期降级。24 例（22%）患者显示病理完全缓解（ypCR），98 例（92%）患者显示阴性环周切缘（>1mm）。3 年局部无复发生存率为 96.9%，无转移生存（MFS）为 71.1%，无病生存（DFS）为 63.5%，总生存（OS）为 88.2%。单因素分析表明，较低的组织学分期与 MFS、DFS 和 OS 显著相关，无论是 ypT0-2 与 ypT3-4、ypN0 与 ypN1-2 还是 ypCR/微灶（接近 ypCR）与其他患者相比。多因素分析显示，ypN 分期（P=.048）和 ypCR/微灶/其他（P=.013）仍是 DFS 的显著预测因素，但只有 ypCR/微灶/其他是 OS 的显著预测因素（P=.005），ypCR 与微灶之间的生存结果无差异。
该方案显示出较高的反应率和有前途的长期生存。ypCR/微灶的降期可能是长期生存的一个有用的短期替代指标，但需要在大型 III 期试验中验证其对生存结果的影响。
