Bujko Krzysztof, Michalski Wojciech, Kepka Lucyna, Nowacki Marek P, Nasierowska-Guttmejer Anna, Tokar Piotr, Dymecki Dariusz, Pawlak Mariusz, Lesniak Tadeusz, Richter Piotr, Wojnar Andrzej, Chmielik Ewa
Department of Radiotherapy, Maria Sklodowska-Curie Memorial Cancer Center, Warsaw, Poland.
Int J Radiat Oncol Biol Phys. 2007 Feb 1;67(2):369-77. doi: 10.1016/j.ijrobp.2006.08.065. Epub 2006 Nov 21.
To compare 5 x 5 Gy preoperative radiotherapy with immediate surgery vs. preoperative chemoradiotherapy (50.4 Gy, 5-fluorouracil, leucovorin) with delayed surgery in a randomized trial for cT3-T4 low-lying rectal cancer. Despite the downstaging effect of chemoradiotherapy, similar long-term outcomes were observed in both groups.
The Cox model was used to evaluate the prognostic value of ypTN ("yp" denotes that pathologic classification was performed after initial multimodality therapy) categories and the surgical margin status in 291 patients.
Disease-free survival (DFS) (hazard ratio [HR] 1.05, 95% confidence interval [CI], 0.73-1.51), distant metastases (HR, 1.17; 95% CI, 0.77-1.78), and local control (HR, 1.45; 95% CI, 0.74-2.84) were similar in both arms. The ypN status was the only independent prognostic factor for DFS (p < 0.001). An interaction (p = 0.016) between N stage and the assigned treatment was demonstrated. For ypN-negative patients, DFS was similar in both arms (HR, 0.83, 95% CI, 0.47-1.48); however, for ypN-positive patients, DFS was worse in the chemoradiotherapy arm (HR, 1.73; 95% CI, 1.07-2.77). The 4-year (median follow-up) DFS rate in N-positive patients was 51% in the 5 x 5-Gy arm vs. 25% in the chemoradiotherapy arm. The corresponding 4-year rates for the incidence of local recurrence and distant metastases were 14% vs. 27% (HR, 1.95; 95% CI, 0.78-4.86) and 38% vs. 68% (HR, 2.05; 95% CI, 1.21-3.48).
N-positive disease after chemoradiotherapy indicates radiochemoresistance. N-positive disease after 5 x 5 Gy RT includes both radiosensitive and radioresistant tumors, because the interval between radiotherapy and surgery was too short for radiosensitive cancer to undergo necrosis. Thus, the greater risk of distant metastases recorded in the chemoradiotherapy arm suggests that radiochemoresistance of nodal metastases from rectal cancer is associated with a high potential for developing distant metastases.
在一项针对cT3 - T4低位直肠癌的随机试验中，比较5×5 Gy术前放疗后立即手术与术前放化疗（50.4 Gy，5 - 氟尿嘧啶，亚叶酸钙）后延迟手术的效果。尽管放化疗有降期作用，但两组的长期结局相似。
采用Cox模型评估291例患者的ypTN（“yp”表示在初始多模式治疗后进行病理分类）类别和手术切缘状态的预后价值。
两组的无病生存期（DFS）（风险比[HR] 1.05，95%置信区间[CI]，0.73 - 1.51）、远处转移（HR，1.17；95% CI，0.77 - 1.78）和局部控制（HR，1.45；95% CI，0.74 - 2.84）相似。ypN状态是DFS的唯一独立预后因素（p < 0.001）。N分期与分配的治疗之间存在交互作用（p = 0.016）。对于ypN阴性患者，两组的DFS相似（HR，0.83，95% CI，0.47 - 1.48）；然而，对于ypN阳性患者，放化疗组的DFS更差（HR，1.73；95% CI，1.07 - 2.77）。N阳性患者中，5×5 Gy组4年（中位随访）DFS率为51%，放化疗组为25%。局部复发和远处转移发生率的相应4年率分别为14%对27%（HR，1.95；95% CI，0.78 - 4.86）和38%对68%（HR，2.05；95% CI，1.21 - 3.48）。
放化疗后N阳性疾病表明对放化疗耐药。5×5 Gy放疗后N阳性疾病包括放射敏感和放射抵抗性肿瘤，因为放疗与手术之间的间隔时间过短，放射敏感癌无法发生坏死。因此，放化疗组记录的远处转移风险更高表明直肠癌淋巴结转移的放化疗耐药与发生远处转移的高可能性相关。
