Grabenbauer G G, Steininger H, Meyer M, Fietkau R, Brunner T, Heinkelmann P, Hornung J, Iro H, Spitzer W, Kirchner T, Sauer R, Distel L
Department of Radiation Therapy, University Hospitals of Erlangen, Germany.
Radiother Oncol. 1998 May;47(2):175-83. doi: 10.1016/s0167-8140(98)00016-4.
To determine whether the immunohistochemical expression of proliferation-associated antigens (proliferating cell nuclear antigen, MIB1) and the nuclear p53 reactivity in addition to total tumor volume, nodal CT density and T and N category are predictive for overall survival and locoregional tumor control in patients with squamous cell carcinoma of the head and neck region.
Between October 1989 and September 1993, 87 patients with biopsy proven head and neck cancer were randomly allocated to receive radiation alone or simultaneous radiation and chemotherapy as part of a multicenter trial with a total of 298 randomized patients. There were only inoperable lesions in UICC (1992) stage III (8%) and IV (92%). Radiotherapy was delivered with 180 cGy twice daily up to a total dose of 7020 cGy in 51 days. Three cycles of 2340 cGy each were separated by a rest period of 11 days. Chemotherapy consisted of cis-DDP, 5-fluorouracil and leucovorin and was repeated on days 22 and 44. Routinely-processed paraffin-embedded sections were stained using monoclonal antibodies for detection of proliferation-associated antigens (MIB1 and PCNA) and p53 oncoprotein to determine the labeling index (LI). In addition, the total tumor volume and the percentage of necrosis were measured using CT data. The median follow-up was 3.9 years (range 1.9-5.0 years).
The overall survival and locoregional control for all 87 patients were 34 and 39% at 3 years, respectively. The addition of chemotherapy resulted in a better overall survival (27 versus 47%, P = 0.03) but did not influence locoregional control (31 versus 47%, P = 0.08). In univariate analysis, nodal CT density (P < 0.0001), total tumor volume (P < 0.0001), age (P = 0.001) and the MIB1-LI (P = 0.04) had a significant impact on overall survival. However, in the final Cox model only the nodal CT density (P = 0.0003) and age (P = 0.05) were independent prognostic factors for survival and only the nodal CT density (P = 0.0006) was an independent prognostic factor for locoregional control. The expression of the p53 oncoprotein was not found to have a clear predictive value.
Nodal CT density, total tumor volume and age will remain the relevant prognostic factors in stage III/IV head and neck cancer.
除了总肿瘤体积、淋巴结CT密度以及T和N分期外，确定增殖相关抗原（增殖细胞核抗原、MIB1）的免疫组化表达和核p53反应性是否可预测头颈部鳞状细胞癌患者的总生存期和局部区域肿瘤控制情况。
1989年10月至1993年9月期间，87例经活检证实为头颈部癌的患者被随机分配接受单纯放疗或同步放化疗，这是一项共有298例随机患者的多中心试验的一部分。UICC（1992年）III期（8%）和IV期（92%）均为不可手术病变。放疗每天两次，每次180 cGy，在51天内总剂量达7020 cGy。三个周期，每个周期2340 cGy，间隔休息11天。化疗由顺铂、5-氟尿嘧啶和亚叶酸组成，在第22天和第44天重复进行。常规处理的石蜡包埋切片用单克隆抗体染色，以检测增殖相关抗原（MIB1和PCNA）和p53癌蛋白，从而确定标记指数（LI）。此外，利用CT数据测量总肿瘤体积和坏死百分比。中位随访时间为3.9年（范围1.9 - 5.0年）。
所有87例患者3年时的总生存期和局部区域控制率分别为34%和39%。加用化疗可提高总生存期（27%对47%，P = 0.03），但不影响局部区域控制（31%对47%，P = 0.08）。单因素分析中，淋巴结CT密度（P < 0.0001）、总肿瘤体积（P < 0.0001）、年龄（P = 0.001）和MIB1-LI（P = 0.04）对总生存期有显著影响。然而，在最终的Cox模型中，只有淋巴结CT密度（P = 0.0003）和年龄（P = 0.05）是生存的独立预后因素，只有淋巴结CT密度（P = 0.0006）是局部区域控制的独立预后因素。未发现p53癌蛋白的表达有明确的预测价值。
淋巴结CT密度、总肿瘤体积和年龄仍是III/IV期头颈部癌的相关预后因素。
