Valentini V, Coco C, Cellini N, Picciocchi A, Genovesi D, Mantini G, Barbaro B, Cogliandolo S, Mattana C, Ambesi-Impiombato F, Tedesco M, Cosimelli M
Cattedra di Radioterapia, Università Cattolica del Sacro Cuore, Rome, Italy.
Int J Radiat Oncol Biol Phys. 1998 Mar 15;40(5):1067-75. doi: 10.1016/s0360-3016(97)00918-8.
To evaluate whether or not an intermediate dose of preoperative external radiation therapy intensified by systemic chemotherapy could improve the tumor response, sphincter preservation, and tumor control.
Between March 1990 and December 1995, 83 consecutive patients with resectable extraperitoneal adenocarcinoma of the rectum were treated with preoperative chemoradiation: bolus i.v. mitomycin C (MMC), 10 mg/m2, Day 1 plus 24-h continuous infusion i.v. 5-fluorouracil (5FU) 1000 mg/m2, Days 1-4, and concurrent external beam radiotherapy (37.8 Gy). All but 2 patients had T3 disease. Surgery was performed 4-6 weeks after the end of chemoradiation.
Total Grade 3-4 acute toxicity during chemoradiation was observed in 11 (13%) patients: hematological Grade 3 toxicity was recorded in 8 (10%) patients, and Grade 4 toxicity was recorded in 2 (2%) patients. Grade 3 diarrhea was seen in 2 (2%) patients. No patient had major skin or urological acute toxicity. Two patients had no surgery: 1 died before surgery from septic complications after Grade 4 hematological toxicity; 1 refused surgery and is still alive after 6 years. There was no postoperative mortality and the overall perioperative morbidity rate was 25%. The analysis of tumor response involved 81 patients. Overall, 9% (7) of 81 patients had a complete pathologic response. Comparing the stage at the diagnostic workup with the pathologic stage, tumor downstaging was observed in 46 (57%) patients. We had 7 (9%) pT0, 5 (6%) pT1, 33 (41%) pT2, and 36 (44%) pT3. Nodal status downstaging was detected in 46 patients (57%). No evidence of nodal involvement was observed in 59 patients (73%). The incidence of tumor response was affected significantly by the number of quarters of rectal circumference involved (p = 0.03) and, marginally, by the length of the tumor (p = 0.09). The distance between the lower pole of the tumor and the anorectal ring had no influence. Of the patients, 63 (78%) had a sphincter-saving surgical procedure. In 12 (44%) of 27 patients candidate for an APR, the sphincter was preserved, as it was in 19 (95%) of 20 probable candidates. Lengthening of the distance between the anorectal ring and the lower pole of the tumor > 20 mm was observed in 21 patients (26%). Of 63 patients, 4 (6%) had moderate soilage after the sphincter-saving procedure.
Preoperative combined modality therapy seems to afford some potential advantages in nonrandomized trials: patients are able to tolerate higher chemotherapy doses and they experience a lower acute toxicity. Tumor downstaging and resectability rates are high; sphincter preservation is feasible. Larger T3 tumors remained less influenced by this treatment; thus, taking into account the low toxicity rate recorded, a more aggressive schedule should be applied in these resectable tumors.
评估术前全身化疗强化的中等剂量外照射放疗是否能改善肿瘤反应、保留括约肌及控制肿瘤。
1990年3月至1995年12月，83例连续的可切除直肠腹膜外腺癌患者接受术前放化疗：静脉推注丝裂霉素C（MMC），10mg/m²，第1天，加静脉持续输注5-氟尿嘧啶（5FU）1000mg/m²，第1 - 4天，同时进行体外照射放疗（37.8Gy）。除2例患者外，其余均为T3期疾病。放化疗结束后4 - 6周进行手术。
放化疗期间共11例（13%）患者出现3 - 4级急性毒性反应：8例（10%）患者出现3级血液学毒性，2例（2%）患者出现4级毒性反应。2例（2%）患者出现3级腹泻。无患者出现严重皮肤或泌尿系统急性毒性反应。2例患者未进行手术：1例在4级血液学毒性后因感染并发症于手术前死亡；1例拒绝手术，6年后仍存活。无术后死亡病例，围手术期总体发病率为25%。对81例患者进行肿瘤反应分析。总体而言，81例患者中有9%（7例）达到完全病理缓解。将诊断检查时的分期与病理分期进行比较，46例（57%）患者出现肿瘤降期。我们有7例（9%）pT0、5例（6%）pT1、33例（41%）pT2和36例（44%）pT3。46例（57%）患者出现淋巴结分期降期。59例（73%）患者未观察到淋巴结受累证据。肿瘤反应发生率受直肠周径受累象限数影响显著（p = 0.03），受肿瘤长度影响较小（p = 0.09）。肿瘤下极与肛门直肠环之间的距离无影响。63例（78%）患者接受了保留括约肌的手术。在27例适合腹会阴联合切除术（APR）的患者中，12例（44%）保留了括约肌，在20例可能适合的患者中有19例（95%）保留了括约肌。21例（26%）患者观察到肛门直肠环与肿瘤下极之间的距离延长>20mm。63例患者中，4例（6%）在保留括约肌手术后出现中度便污。
术前综合治疗模式在非随机试验中似乎具有一些潜在优势：患者能够耐受更高的化疗剂量，且急性毒性较低。肿瘤降期和可切除率较高；保留括约肌可行。较大的T3肿瘤受该治疗影响较小；因此，考虑到记录的低毒性率，对于这些可切除肿瘤应采用更积极的治疗方案。
