Willner Jochen, Baier Kurt, Caragiani Ekaterini, Tschammler Axel, Flentje Michael
Department of Radiation Oncology, University of Würzburg, Würzburg, Germany.
Int J Radiat Oncol Biol Phys. 2002 Feb 1;52(2):382-9. doi: 10.1016/s0360-3016(01)01823-5.
To evaluate the influence of total dose and tumor volume on local control and survival in primary radiotherapy of non-small-cell lung cancer (NSCLC).
We retrospectively analyzed the clinical course and CT-derived pre- and post-therapeutic tumor volume data of 135 patients with NSCLC undergoing primary radiotherapy at our department between 1989 and 1996. Among these, a total of 192 spatially separated tumor volumes (135 primary tumors, 1 additional intrapulmonary tumor, and 56 involved lymph nodes) were available for analysis. In all patients, treatment was planned using CT-based three-dimensional treatment planning. The dose to each tumor volume was derived from the individual dose plans. Mean total dose was 59.9 Gy (range: 30-80 Gy). All but 3 patients were followed until death. For local control analysis, each tumor was analyzed separately, and its remission status was determined in serial follow-up CT scans. A total of 784 CT scans were analyzed. Actuarial local control analysis was performed for the 192 separated tumor volumes, and survival analysis was performed for the 135 patients. Tumor control probability was calculated using a Poisson statistical model.
Overall 1- and 2-year local control rate was 50% and 37%, respectively. The 2-year local control rate for tumors <50 ccm, 50-200 ccm, and >200 ccm was 51%, 22%, and 10%, respectively (p = 0.02). The 2-year local control rate for dose levels < or = 60 Gy and >60 Gy was 28% and 43% (p < 0.001). For the subgroup of 147 tumors smaller than 100 ccm, the local control rate increased up to 70% (1 year) and 51% (2 years) with doses of more than 60 Gy. For tumors larger than 100 ccm, no dose effect was seen. Only 2 of 45 tumors >100 ccm were controlled more than 2 years. Multivariate analysis revealed tumor volume, total dose, histopathologic type, and grading as significant and independent prognostic factors for local control. The number of delay days by split course (if used) and application of chemotherapy was not found to influence local control. Overall 1- and 2-year survival rate was 42% and 13%. Total radiation dose, chemotherapy, and T and N stage---but not tumor volume---were found to be independent and significant prognostic factors for survival in multivariate analysis.
Tumor volume is an important predictor of local control in NSCLC. We found a clear dose effect for local control and survival in NSCLC. Long-term local control for a significant proportion of patients seems possible for small tumors only (<100 ccm, i.e., maximum diameter 6 cm) with doses of 70 Gy and more. Tumors of > or = 100 ccm are unlikely to be controlled long term by conventional doses up to 70 Gy. These results support dose escalation in patients with NSCLC.
评估总剂量和肿瘤体积对非小细胞肺癌（NSCLC）原发性放射治疗中局部控制和生存的影响。
我们回顾性分析了1989年至1996年间在我院接受原发性放射治疗的135例NSCLC患者的临床病程以及CT衍生的治疗前和治疗后肿瘤体积数据。其中，共有192个空间上分离的肿瘤体积（135个原发性肿瘤、1个额外的肺内肿瘤和56个受累淋巴结）可供分析。所有患者均采用基于CT的三维治疗计划进行治疗。每个肿瘤体积的剂量来自个体剂量计划。平均总剂量为59.9 Gy（范围：30 - 80 Gy）。除3例患者外，所有患者均随访至死亡。对于局部控制分析，每个肿瘤单独分析，并在系列随访CT扫描中确定其缓解状态。共分析了784次CT扫描。对192个分离的肿瘤体积进行精算局部控制分析，对135例患者进行生存分析。使用泊松统计模型计算肿瘤控制概率。
总体1年和2年局部控制率分别为50%和37%。体积<50 ccm、50 - 200 ccm和>200 ccm的肿瘤2年局部控制率分别为51%、22%和10%（p = 0.02）。剂量水平≤60 Gy和>60 Gy的2年局部控制率分别为28%和43%（p < 0.001）。对于147个小于100 ccm的肿瘤亚组，剂量超过60 Gy时，局部控制率在1年时升至70%，2年时升至51%。对于大于100 ccm的肿瘤，未观察到剂量效应。45个大于100 ccm的肿瘤中只有2个在2年以上得到控制。多因素分析显示肿瘤体积、总剂量、组织病理学类型和分级是局部控制的重要且独立的预后因素。分割疗程（若采用）的延迟天数和化疗的应用未发现影响局部控制。总体1年和2年生存率分别为42%和13%。多因素分析发现总放射剂量、化疗以及T和N分期——而非肿瘤体积——是生存的独立且重要的预后因素。
肿瘤体积是NSCLC局部控制的重要预测因素。我们发现NSCLC在局部控制和生存方面有明显的剂量效应。对于仅小肿瘤（<100 ccm，即最大直径6 cm）给予70 Gy及以上剂量，似乎有可能使相当比例的患者获得长期局部控制。直径≥100 ccm的肿瘤不太可能通过高达70 Gy的常规剂量长期得到控制。这些结果支持NSCLC患者进行剂量递增。
