Department of Radiation Oncology, Tenon University Hospital, Sorbonne University, Paris, France.
Department of Radiation Oncology, Genolier Clinic, Genolier, Switzerland.
Eur J Cancer. 2019 Nov;121:130-143. doi: 10.1016/j.ejca.2019.08.022. Epub 2019 Sep 28.
Concomitant external-beam radiochemotherapy (5-fluorouracil-mitomycin C) has become the standard of care in anal cancer since the '90s. A pooled analysis of individual patient data from 7 major trials was performed quantifying the effect of radiation therapy (RT)-related parameters on the outcome of patients with anal cancer.
Pooling databases from combined modality trials, the impact of RT parameters (total dose, gap duration, OTT: overall treatment time) on outcome including locoregional failure (LRF), 5-year progression free survival (PFS) and toxicities were investigated. Individual patient data were received for 10/13 identified published studies conducted from 1987 to 2008 (n = 3031). A Cox regression model was used (landmark = 3 months after RT for first follow-up).
After data inspection indicating severe heterogeneity between trials, only 1343 patients from 7/10 studies received were analysed (the most recent ones, since 1994; median follow-up = 4.1 years). A higher overall 5-year LRF rate [22.8% (95% confidence interval [CI] 22.3-27.3%)] significantly correlated with longer OTT (p = 0.03), larger tumour size (p < 0.001) and male gender (p = 0.045). Although significant differences were not observed, subset analyses for LRF (dose range: 50.4-59 Gy) seemed to favour lower doses (p = 0.412), and when comparing a 2-week gap versus 3 (dose: 59.4 Gy), results suggested 3 weeks might be detrimental (p = 0.245). For a 2-week gap versus none (dose range: 55-59.4 Gy), no difference was observed (p = 0.89). Five-year PFS was 65.7% (95% CI: 62.8-68.5%). Higher PFS rates were observed in women (p < 0.001), smaller tumour sizes (p < 0.001) and shorter OTT (p = 0.025). Five-year overall survival [76.7% (95% CI: 73.9%-79.3%)] correlated positively with female gender (p < 0.001), small tumour size (p = 0.027) and short OTT (p = 0.026). Descriptive toxicity data are presented.
For patients receiving concurrent external-beam doublet chemoradiation, a longer OTT seems detrimental to outcome. Further trials involving modern techniques may better define optimal OTT and total dose.
自 20 世纪 90 年代以来，外照射放化疗（5-氟尿嘧啶-丝裂霉素 C）已成为肛门癌的标准治疗方法。对来自 7 项主要试验的个体患者数据进行了汇总分析，以量化放射治疗（RT）相关参数对肛门癌患者结局的影响。
通过合并模式试验的数据库，研究 RT 参数（总剂量、间隔时间、OTT：总治疗时间）对包括局部区域失败（LRF）、5 年无进展生存率（PFS）和毒性在内的结局的影响。对 10/13 项已发表的研究进行了个体患者数据的接收，这些研究于 1987 年至 2008 年进行（n=3031）。使用 Cox 回归模型（landmark=RT 后 3 个月进行首次随访）。
数据检查表明试验之间存在严重的异质性后，仅对来自 7/10 项研究的 1343 名患者进行了分析（最最近的研究，自 1994 年开始；中位随访时间为 4.1 年）。较高的 5 年局部区域失败率[22.8%（95%置信区间 [CI] 22.3-27.3%）]与较长的 OTT（p=0.03）、更大的肿瘤大小（p<0.001）和男性性别（p=0.045）显著相关。尽管没有观察到显著差异，但 LRF 的亚组分析（剂量范围：50.4-59 Gy）似乎有利于较低的剂量（p=0.412），当比较 2 周间隔与 3 周间隔（剂量：59.4 Gy）时，结果表明 3 周间隔可能不利（p=0.245）。对于 2 周间隔与无间隔（剂量范围：55-59.4 Gy），无差异（p=0.89）。5 年 PFS 为 65.7%（95%CI：62.8%-68.5%）。女性（p<0.001）、较小的肿瘤大小（p<0.001）和较短的 OTT（p=0.025）观察到较高的 PFS 率。5 年总生存率[76.7%（95%CI：73.9%-79.3%）]与女性性别（p<0.001）、肿瘤小（p=0.027）和 OTT 短（p=0.026）呈正相关。描述性毒性数据。
对于接受同步外照射双药放化疗的患者，较长的 OTT 似乎对结局不利。涉及现代技术的进一步试验可能更好地确定最佳 OTT 和总剂量。
