Myerson R J, Genovesi D, Lockett M A, Birnbaum E, Fleshman J, Fry R, Kodner I, Menteer J, Picus J, Read T, Walz B
Washington University School of Medicine, St. Louis, MO, USA.
Int J Radiat Oncol Biol Phys. 1999 Feb 1;43(3):537-43. doi: 10.1016/s0360-3016(98)00435-0.
Randomized Swedish studies demonstrate the efficacy of a 5-fraction course of preoperative radiotherapy for rectal carcinoma. The present study evaluates the results in a single U.S. institution over a 20-year period with a similar regimen.
During the period of 1975-1995, 83 patients received pelvic radiotherapy of 20 Gy/5 fractions, followed by immediate surgery for rectal cancer. These patients represented 21% of cases receiving preoperative treatment; the remainder received 45-50 Gy preoperatively. The 5-fraction course was used for lesions deemed readily resectable but too bulky for conservative endocavitary treatment. Since 1990, it has been our policy to administer postoperative chemotherapy to medically fit patients who prove to have pathologic Stage II or III disease. Patient characteristics including age (mean 65 years, range 23-90), gender (45% male), and location within the rectum were comparable to our previously reported cases that received 45 Gy/25 fractions preoperatively. However, the group selected for 5 fractions preoperatively had relatively fewer lesions that were tethered (20% vs. 61%), circumferential (11% vs. 20%), or near obstructing (1% vs. 16%).
With a post treatment follow-up of 1-15 years (mean 4.7), there have been 3 local failures and 12 distant failures, with an actuarial local control of 95%, and disease-specific survival of 77% at 5 and 10 years. Grade > or = 3 perioperative or late toxicity occurred in 11 cases (13%), including 3 (3.5%) late bowel obstructions. Stage II or III disease was found in 56% of the cases, 74% of which were free of disease at last follow-up. However, patients with Stage II or III lesions that were significantly tethered or fixed had a 40% greater likelihood of recurring than similar stage lesions that were, at most, slightly tethered. Sphincter-preserving surgery was possible in 60% of the patients. In recent years, postoperative chemotherapy has been administered to 16 patients with Stage II or III disease; this has been well tolerated, with only 1 late toxicity (cystitis managed medically). When compared with a matched group of cases receiving conventionally fractionated preoperative radiation, there were no significant differences in perioperative morbidity and nonradiotherapeutic cost generating factors (length of hospital stay, duration of postoperative antibiotics, blood loss at surgery).
Patients with resectable rectal cancer who received 20 Gy/5 fractions preoperative radiotherapy to the pelvis had excellent local and distant control of disease. These patients were able to undergo sphincter-preserving surgery and postoperative chemotherapy. It would be of interest to conduct a randomized trial comparing short course with longer course (45 or 50 Gy) preoperative radiotherapy for resectable T3 lesions. The results of this study suggest that, in general, differences in toxicity, local control, and disease-free survival would probably be < 10%. However, since the results of this study suggest that patients with significantly tethered lesions may be better served with the higher dose and longer duration course of radiation, clinical degree of fixation should be included as a stratification parameter, and stopping criteria should be included for tethered lesions.
瑞典的随机研究证明了直肠癌术前5次分割放疗疗程的疗效。本研究评估了美国一家机构在20年期间采用类似方案的结果。
1975年至1995年期间，83例患者接受了20 Gy/5次分割的盆腔放疗，随后立即进行直肠癌手术。这些患者占接受术前治疗病例的21%；其余患者术前接受45 - 50 Gy放疗。5次分割疗程用于那些被认为易于切除但体积太大而无法进行保守腔内治疗的病变。自1990年以来，我们的政策是对经医学评估适合且病理分期为II期或III期疾病的患者进行术后化疗。患者特征包括年龄（平均65岁，范围23 - 90岁）、性别（45%为男性）以及在直肠内的位置，与我们之前报道的术前接受45 Gy/25次分割放疗的病例相当。然而，术前选择接受5次分割放疗的组中，病变受牵拉（20%对61%）、呈环形（11%对20%）或接近梗阻（1%对16%）的情况相对较少。
治疗后随访1 - 15年（平均4.7年），出现3例局部复发和12例远处复发，精算局部控制率为95%，5年和10年的疾病特异性生存率为77%。11例患者（13%）发生≥3级围手术期或晚期毒性反应，包括3例（3.5%）晚期肠梗阻。56%的病例为II期或III期疾病，其中74%在最后一次随访时无疾病。然而，与最多仅有轻微受牵拉的类似分期病变相比，II期或III期且受牵拉或固定明显的病变复发可能性高40%。60%的患者可行保留括约肌手术。近年来，16例II期或III期疾病患者接受了术后化疗；耐受性良好，仅1例出现晚期毒性反应（药物治疗的膀胱炎）。与一组匹配的接受常规分割术前放疗的病例相比，围手术期发病率和非放疗费用产生因素（住院时间、术后抗生素使用时间、手术失血）无显著差异。
接受盆腔20 Gy/5次分割术前放疗的可切除直肠癌患者对疾病有良好的局部和远处控制。这些患者能够接受保留括约肌手术和术后化疗。进行一项随机试验比较可切除T3病变的短疗程与长疗程（45或50 Gy）术前放疗将很有意义。本研究结果表明，总体而言，毒性、局部控制和无病生存率的差异可能<10%。然而，由于本研究结果表明受牵拉明显的病变患者可能从更高剂量和更长疗程的放疗中获益更多，临床固定程度应作为分层参数，对于受牵拉病变应纳入停止标准。
