Crane Christopher H, Skibber John M, Birnbaum Elisa H, Feig Barry W, Singh Anurag K, Delclos Marc E, Lin Edward H, Fleshman James W, Thames Howard D, Kodner Ira J, Lockett Mary Ann, Picus Joel, Phan Thinh, Chandra Anshu, Janjan Nora A, Read Thomas E, Myerson Robert J
Department of Radiation Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA.
Int J Radiat Oncol Biol Phys. 2003 Sep 1;57(1):84-9. doi: 10.1016/s0360-3016(03)00532-7.
To compare the outcome from preoperative chemoradiation (CXRT) and from radiation therapy (RT) in the treatment of rectal cancer in two large, single-institutional experiences.
Between 1978 and 1995, 403 patients with localized, nonmetastatic, clinically staged T3 or T4 rectal cancer patients were treated with preoperative RT alone at two institutions. Patients at institution 1 (n = 207) were treated with pelvic CXRT exclusively, and patients at institution 2 were treated (except for 8 given CXRT) with pelvic RT alone (n = 196). In addition, a third group (n = 61) was treated with CXRT at institution 2 between 1998 and 2000 after a policy change. Both institutions delivered 45 Gy in five fractions as a standard dose, but institution 2 used 20 Gy in five fractions in selected cases (n = 26). At both institutions, concurrent chemotherapy consisted of a continuous infusion of 5-fluorouracil (5-FU) at a dosage of 1500 mg/m(2)/week. The end points were response, sphincter preservation (SP), relapse-free survival (RFS), pelvic disease control (PC), and overall survival (OS).
Median follow-up was 63 months for all living patients at institution 1 and in the primary group of institution 2. Multivariate analysis of the patients in these groups showed that the use of concurrent chemotherapy improved tumor response (T-stage downstaging, 62% vs. 42%, p = 0.001, and pathologic complete response, 23% vs. 5% p < 0.0001), but did not significantly improve LC, RFS, or OS. Follow-up for the secondary group at institution 2 was insufficient to allow the analysis of these endpoints. In the subset of patients receiving 45 Gy who had rectal tumors < or /=6 cm from the anal verge (institution 1: n = 132; institution 2 primary: n = 79; institution 2 secondary: n = 33), there was a significant improvement in SP with the use of concurrent chemotherapy (39% at institution 1 compared with 13% in the primary group at institution 2, p < 0.0001). A logistic regression analysis of clinical prognostic factors indicated that the use of concurrent chemotherapy independently influenced SP in these low tumors (p = 0.002). This finding was supported by a 36% SP rate in the secondary group at institution 2. Thus SP increased after the addition of chemotherapy at institution 2.
The use of concurrent 5-FU with preoperative radiation therapy for T3 and T4 rectal cancer independently increases tumor response and may contribute to increased SP in patients with low rectal cancer.
在两项大型单机构研究中比较术前放化疗（CXRT）与放射治疗（RT）治疗直肠癌的效果。
1978年至1995年间，两家机构对403例局部、非转移性、临床分期为T3或T4的直肠癌患者仅进行术前放疗。机构1的207例患者仅接受盆腔CXRT，机构2的患者（除8例接受CXRT外）仅接受盆腔RT（196例）。此外，1998年至2000年间，机构2政策改变后，第三组61例患者接受了CXRT。两家机构均以45 Gy分5次作为标准剂量，但机构2在部分病例（26例）中采用20 Gy分5次。在两家机构，同步化疗均为持续输注5-氟尿嘧啶（5-FU），剂量为1500 mg/m²/周。终点指标为反应、括约肌保留（SP）、无复发生存期（RFS）、盆腔疾病控制（PC）和总生存期（OS）。
机构1所有存活患者及机构2主要组患者的中位随访时间为63个月。对这些组患者的多因素分析显示，同步化疗可改善肿瘤反应（T分期降期，62%对42%，p = 0.001；病理完全缓解，23%对5%，p < 0.0001），但对局部控制、RFS或OS无显著改善。机构2次要组的随访时间不足，无法分析这些终点指标。在距肛缘≤6 cm的直肠肿瘤且接受45 Gy放疗的患者亚组中（机构1：132例；机构2主要组：79例；机构2次要组：33例），同步化疗使SP显著提高（机构1为39%，机构2主要组为13%，p < 0.0001）。对临床预后因素的逻辑回归分析表明，同步化疗独立影响这些低位肿瘤患者的SP（p = 0.002）。机构2次要组36%的SP率支持了这一发现。因此，机构2在加用化疗后SP增加。
T3和T4期直肠癌术前放疗联合5-FU同步化疗可独立提高肿瘤反应，并可能有助于提高低位直肠癌患者的括约肌保留率。
