Janjan N A, Crane C, Feig B W, Cleary K, Dubrow R, Curley S, Vauthey J N, Lynch P, Ellis L M, Wolff R, Lenzi R, Abbruzzese J, Pazdur R, Hoff P M, Allen P, Brown T, Skibber J
Departments of Radiation Oncology, The University of Texas, M.D. Anderson Cancer Center, Houston 77030, USA.
Am J Clin Oncol. 2001 Apr;24(2):107-12. doi: 10.1097/00000421-200104000-00001.
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/m2/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 400 to 425 mg/m2 of 5-FU plus 20 mg/m2 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 non-responders 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.
本研究的目的是确定术前放疗联合持续输注5-氟尿嘧啶（5-FU）化疗的反应是否可预测局部晚期直肠癌患者的生存情况。117例患者接受了术前放化疗（CTX/XRT），即在5周内分25次给予45 Gy放疗，并持续输注5-FU（300 mg/m²/天）。经直肠超声（u）确定的治疗前分期分布为：uT2N0占2%，uT3N0占47%，uT3N1占49%，uT4N0占2%；13%（15例）患者未进行经直肠超声检查。完成CTX/XRT后约6周进行手术。辅助化疗在手术切除后每28天进行一次，共4至6个周期，方案为5-FU 400至425 mg/m²加亚叶酸钙20 mg/m²，持续5天。在接受辅助化疗的74例患者中，疾病的术前分期为T3N0 31例，T3N1 43例。中位随访时间为46个月（范围2至89个月）。病理肿瘤分期为Tis-2N0占26%，T2N1占5%，T3N0占21%，T3N1占15%，T4N0占5%，T4N1占1%；32例（27%）患者经病理证实对术前CTX/XRT完全缓解（CR）。72例（62%）患者出现肿瘤降期。59%的患者可行保留括约肌手术（SP）。反应者的中位无病生存期（DFS）和总生存率分别为46个月和47个月；无反应者的这些指标分别为38个月和41个月。对数秩分析显示，对CTX/XRT有任何反应（p < 0.00001）、对CTX/XRT完全缓解（p < 0.009）和行SP（p < 0.012）的患者，远处无转移生存率提高。同样，这些参数也显著影响DFS率（CTX/XRT p < 0.00001；CR p < 0.006；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）影响。多因素分析中，只有临床大小（p < 0.002）仍然是局部控制的重要因素。多因素分析中导致癌症特异性生存显著改善的因素包括对术前CTX/XRT有任何反应（p < 0.017）和给予辅助化疗（p < 0.034）。对术前CTX/XRT有任何反应可提高远处无转移生存率和无病生存率。多因素分析证实，对术前CTX/XRT的反应可预测局部晚期直肠癌患者总生存的改善情况。术前接受与放疗同时进行的基于5-FU化疗无反应的患者，辅助5-FU治疗时远处转移率较高。
