Improved overall survival among responders to preoperative chemoradiation for locally advanced rectal cancer
Improved overall survival among responders to preoperative chemoradiation for locally advanced rectal cancer
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DOI：
10.1097/00000421-200104000-00001
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发表时间：
2001-04-01
影响因子：
2.6
通讯作者：
Skibber, J
中科院分区：
文献类型：
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作者：
Janjan, NA;Crane, C;Skibber, J
本研究的目的是确定持续输注5-氟尿嘧啶(5-FU)对手术前放疗和化疗的反应是否可以预测局部晚期直肠癌患者的生存。117例患者行术前放化疗(CTX/XRT)，5周内连续滴注5-FU 300 mg/m(2)/d，45Gy25次/次。治疗前uT2N0占2%，uT3N0占47%，uT3N1占49%，uT4N0占2%，13%的患者(15例)未行直肠内超声检查。在CTX/XRT完成约6周后，进行手术。术后辅助化疗：5-FU 300~425 mg/m(2)+亚叶酸钙20 mg/m(2)，每28天1次，共4~6个周期。74例接受辅助化疗的患者中，术前T3N0期31例，T3N1期43例。中位随访时间为46个月(2~89个月)。病理分期Tis-2N0为26%，T2N1为5%，T3N0为21%，T3N1为15%，T4N0为5%，T4N1为1%，32例(27%)术前CTX/XRT完全缓解(CR)。72例(62%)肿瘤分期下降。59%的患者可以采用括约肌保留术(SP)。有反应者的中位DFS和总存活率分别为46个月和47个月；无反应者的中位DFS和总存活率分别为38个月和41个月。LOG-RANK分析显示，CTX/XRT(p<；0.00001)、CR对CTX/XRT(p<；0.009)和SP(p<；0.012)的任何反应均可提高无远处转移生存率。同样，这些参数也显著影响DFS率(CTX/XRT p<；0.00001；CR p<；0.006；和SP p<；0.008)。单因素分析显示，盆腔疾病的控制受临床大小(P<；0.002)和SP(P<；0.016)的影响。在多变量分析中，只有临床规模(P<；0.002)仍然是局部控制的重要因素。在多变量分析中，导致癌症特异性存活率显著改善的因素包括术前对环磷酰胺/X射线放射治疗的反应(p<；0.017)和辅助性化疗的管理(p<；0.034)。术前对CTX/XRT的任何反应均可提高无远处转移和无瘤存活率。多变量分析证实，术前对CTX/XRT的反应可预测局部进展期直肠癌患者总体生存率的改善。术前以5-FU为基础的化疗配合放疗无效的患者，辅以5-FU治疗的远处转移率较高。关键词：直肠癌-术前CTX/XRT-生存。
The aim of this study was to determine if the response to preoperative radiation and chemotherapy with continuous infusion 5-fluorouracil (5-FU) was predictive for survival among patients with locally advanced rectal cancer. Preoperative chemoradiation (CTX/XRT) that delivered 45 Gy in 25 fractions over 5 weeks with continuous infusion 5-FU (300 mg/m(2)/day) was given to 117 patients. The pretreatment stage distribution, as determined by endorectal ultrasound (u), included uT2N0 in 2%, uT3N0 in 47%, uT3N1 in 49%, and uT4N0 in 2% of cases; endorectal ultrasound was not performed in 13% of cases (15 patients). Approximately 6 weeks after completion of CTX/ XRT, surgery was performed. Adjuvant chemotherapy, consisting of 300 to 425 mg/m(2) of 5-FU plus 20 mg/m(2) leucovorin for 5 days, was administered every 28 days for 4 to 6 cycles after surgical resection. Among the 74 patients treated with adjuvant chemotherapy, the preoperative stage of disease was 31 with T3N0 and 43 T3N1. Median follow-up was 46 months (range 2 to 89 months). The pathologic tumor stages were Tis-2N0 in 26%, T2N1 in 5%, T3N0 in 21%, T3N1 in 15%, T4N0 in 5%, and T4N1 in 1%; a complete response (CR) to preoperative CTX/XRT was pathologically confirmed in 32 (27%) of patients. Tumor down-staging occurred in 72 (62%) cases. A sphincter-saving procedure (SP) was possible in 59% of patients. The median DFS and overall survival rates for responders were 46 months and 47 months, respectively; for nonresponders these outcome measures were 38 months and 41 months, respectively. Log-rank analysis showed that the distant metastatic-free survival rates improved with any response to CTX/XRT (p < 0.00001), CR to CTX/XRT (p < 0.009) and SP (p < 0.012). Likewise, these parameters also significantly influenced DFS rates (CTX/XRT p < 0.00001; CR p < 0.006; and SP p < 0.008). Control of pelvic disease was influenced by clinical size (p < 0.002) and SP (p < 0.016) on univariate analysis. On multivariate analysis only clinical size (p < 0.002) continued to be a significant factor for local control. Factors on multivariate analysis that resulted in significant improvements in cancer-specific survival included any response to preoperative CTX/XRT (p < 0.017) and administration of adjuvant chemotherapy (p < 0.034). Any response to preoperative CTX/XRT improved distant metastatic-free and disease-free survival rates. Multivariate analysis confirmed that a response to preoperative CTX/XRT predicted for improvements in overall survival among patients with locally advanced rectal cancer. Patients who fail to respond to preoperative 5-FU based chemotherapy given concomitantly with radiation have higher rates of distant metastases with adjuvant 5-FU therapy. Key Words: Rectal cancer-Preop CTX/XRT-Survival.