John M, Pajak T, Flam M, Hoffman J, Markoe A, Wolkov H, Paris K
Central California Cancer Research Group, University of California, San Francisco, and St. Agnes Hospital, Fresno, California, USA.
Cancer J Sci Am. 1996 Jul-Aug;2(4):205-11.
Radiation Therapy Oncology Group experience with chemoradiation for anal cancer has shown a local failure rate of 20% to 30% with radiotherapy doses of 45 to 50 cGy. This study was undertaken to assess the effect of higher radiotherapy doses on toxicity, local control, and survival in this disease.
Forty-seven patients with anal cancers measuring > or = 2 cm were treated with a concurrent combination of two cycles of 5-fluorouracil infusion (1000 mg/m2 over 24 hrs for 4 days) and mitomycin C (10 mg/m2 bolus) plus 59.6 Gy of pelvic and perineal radiotherapy administered over 8.5 weeks, including a 2-week rest period. Patients were followed for toxicity, disease status, and colostomy-free survival. Twenty-three (49%) patients had advanced (T3-4) primary tumors; 42 (92%) patients had NO disease, and 36 (77%) patients had squamous histology. For perspective, a comparative analysis was made with 147 patients treated on the previous RTOG protocol for anal cancers (RTOG 87-04) with identical chemotherapy but radiotherapy doses of 40 to 50.4 Gy.
Transient hematologic and skin toxicity predominated during treatment or in early follow-up. One patient developed septicemia and died of multiple gastrointestinal toxicities. Twelve (26%) patients had greater than grade 3 complications and, of these, 9 (20%) had hematologic side effects alone. A comparative analysis with 147 patients treated on RTOG protocol 87-04 showed no significant differences in pretreatment characteristics of disease extent, performance status, or histology. A mandatory 2-week split in the current chemoradiation protocol contrasted with 12% of patients having a 2-week or greater treatment break in RTOG 87-04. Patients treated on the current protocol (RTOG 92-08) had a markedly lower incidence of > or = grade 3 dermal toxicity (34% vs. 55%) but a higher colostomy rate at 1 year (23% vs. 6%) and at 2 years (30% vs. 7%) compared with RTOG 87-04.
Numerical increases in radiotherapy dose over those used in conventional chemotherapy regimens for anal cancers do not appear to increase local control when given in split-course fashion. For higher radiotherapy doses (> 50 Gy) to increase local control, radiation may have to be given in continuous fashion, which almost certainly means that our threshold of acceptable acute toxicity, particularly dermal toxicity, may have to be raised.
放射治疗肿瘤学组对肛管癌进行放化疗的经验表明，放疗剂量为45至50 cGy时，局部失败率为20%至30%。本研究旨在评估更高放疗剂量对该疾病毒性、局部控制和生存的影响。
47例肛管癌直径≥2 cm的患者接受了两个周期的5-氟尿嘧啶输注（1000 mg/m²，24小时内持续4天）和丝裂霉素C（10 mg/m²推注）联合盆腔及会阴放疗59.6 Gy，放疗时间为8.5周，包括2周休息期。对患者进行毒性、疾病状态和无结肠造口生存情况的随访。23例（49%）患者有进展期（T3-4）原发性肿瘤；42例（92%）患者无淋巴结转移，36例（77%）患者为鳞状组织学类型。为作对比分析，选取了147例按照先前放射治疗肿瘤学组肛管癌治疗方案（RTOG 87-04）进行治疗的患者，这些患者接受了相同的化疗，但放疗剂量为40至50.4 Gy。
治疗期间或早期随访时，主要出现短暂的血液学和皮肤毒性。1例患者发生败血症，死于多种胃肠道毒性反应。12例（26%）患者出现3级以上并发症，其中9例（20%）仅出现血液学副作用。与按照RTOG 87-04方案治疗的147例患者对比分析显示，疾病范围、体能状态或组织学的治疗前特征无显著差异。当前放化疗方案中有强制性的2周休息期，而在RTOG 87-04中12%的患者有2周或更长时间的治疗中断。与RTOG 87-04相比，按照当前方案（RTOG 92-08）治疗的患者≥3级皮肤毒性发生率显著较低（34%对55%），但1年时结肠造口率较高（23%对6%），2年时结肠造口率也较高（30%对7%）。
与肛管癌传统化疗方案中使用的放疗剂量相比，分次给予更高放疗剂量似乎并不会提高局部控制率。要通过更高放疗剂量（>50 Gy）提高局部控制率，可能必须连续给予放疗，这几乎肯定意味着我们可接受的急性毒性阈值，尤其是皮肤毒性阈值，可能必须提高。
