【作者】 任骅；

【导师】 王绿化； 李晔雄； 肖建平；

【作者基本信息】 中国协和医科大学 ， 肿瘤学， 2010， 博士

【摘要】 第一部分：化疗方案对局部晚期非小细胞肺癌同步放化疗的影响分析目的分析不同化疗方案对局部晚期非小细胞肺癌同步放化疗的影响。方法1999-2005年接受同步放化疗的局部晚期非小细胞肺癌患者共106例(Ⅲa期29例,Ⅲb期77例)。采用回顾性队列研究分析不同化疗方案组对生存和毒性反应的影响结果全组中55例患者接受含紫杉醇方案的同步放化疗,21例患者接受拓扑替康方案、26例患者接受PE方案、4例患者接受其他方案的同步放化疗。全组中位生存期18.6月,1、3年总生存率分别为72.2%和27.5%。分析其中接受含紫杉醇方案、拓扑替康方案和PE方案同步放化疗的102例患者的生存率和毒性反应,三组中位生存期分别为16.3月、27.3月和29.1月。紫杉醇方案组的中位生存期(16.3月)低于合并的拓扑替康／PE方案组的中位生存期(27.3月),单因素和多因素分析都显示二者差别的显著性(p<0.05).N分期也是生存率的影响因素。治疗毒性方面,紫杉醇方案组的放射性肺炎发生率更高(27.3%：10.6%),p=0.03；血液毒性更少(16.4%：29.8%),无统计学差异(p=0.108)；食道炎的发生率相近(29.1%vs 34.0%)。结论：局部晚期非小细胞肺癌同步放化疗的不同化疗方案与患者的生存和治疗毒性相关第二部分：简化调强技术应用于局部晚期非小细胞肺癌同步放化疗的剂量学比较研究目的探讨简化调强放疗技术(sIMRT)在局部晚期非小细胞肺癌(NSCLC)的应用特点,为临床治疗的技术选择提供依据。方法对14例接受同步放化疗的初治的Ⅲ期非小细胞肺癌患者分别设计5个野三维适形放疗(3DCRT5f)、5个野sIMRT (sIMRT5f)、5个野调强放疗(IMRT5f)和7个野调强放疗(IMRT7f)计划,利用剂量体积直方图评价不同照射技术的靶区和正常组织照射剂量、适形指数和不均匀指数。处方剂量为60Gy分30次。同时通过总机器跳数间接比较不同照射技术的治疗时间。结果靶区适形指数以IMRT7f最好,靶区剂量不均匀指数以3DCRT5f最不均匀。所有患者sIMRT计划和IMRT计划均可满足对双肺V20的限定要求,而8例患者3DCRT计划的V20>30%；所有患者sIMRT计划和IMRT计划均可满足脊髓的限定要求,而5例患者3DCRT计划的脊髓最大剂量>45Gy；各计划心脏V30和V50均相似,V30均<40%。机器子野跳数IMRT>sIMRT>3DCRT,而IMRT5f与IMRT7f的相当,3DCRT5f、sIMRT5f、IMRT5f和IMRT7f的子野跳数平均值分别为476±23、523±29、764±51和793±44。结论对接受同步放化疗的初治的Ⅲ期非小细胞肺癌患者采用sIMRT计划比3DCRT计划和IMRT计划具最优时效比。第三部分：肺部恶性肿瘤立体定向放射治疗的相关因素分析目的探讨和发现在肺部恶性肿瘤立体定向放射治疗中与局部控制和总生存率的相关的因素。材料与方法全部入组分析病例均为经病理证实恶性肺部肿瘤患者。立体定向放射治疗SBRT中位处方剂量和分割为50GY和5次,其生物有效剂量中位数(α／β：10)为100GY。涉及肺部多处病变患者的生存相关因素时,应用肿瘤区总体积(肿瘤区总体积)和病变平均有效生物剂量(10)分别替代参数肿瘤区体积和有效生物剂量(10)进行分析。结果2004年6月至2008年6月共治疗84病例的103病灶,未发现严重毒性反应(>2级)。原发组和复发／转移组的2年局部控制率分别为93.5%和91.3%。有效生物剂量是唯一在单因素分析(P=0.004)和多变量分析性(P=0.049)均提示差异显著性的因素。原发组和复发／转移组的2年总生存率分别为43.0%和33.6%。单变量分析显示：原发肿瘤,位置为周边型,(平均有效生物剂量病变(10)≥72),病灶平均有效生物剂量(10)≥100和肿瘤区总体积(<28毫升)是有利的因素。多变量分析显示只有病灶平均有效生物剂量(P=0.001)显示与总生存活率的相关性。结论立体定向放射治疗可以为原发和复发／转移性肺肿瘤提供良好的局部控制,原发性肺癌患者有更好的总生存率。本研究显示了有效生物剂量和局部控制以及总生存率的关系。肿瘤区体积与总生存的关系为在单变量分析中表明是有意义的,但多变量分析中没有显著性。本研究引入的改良参数-病变平均有效生物剂量(10)和肿瘤区总体积的应用价值还需要更多的研究来评估。更多还原

【Abstract】 PartⅠ:Effect of different concurrent chemotherapy regimens on locally advanced non-small-cell lung carcinomaPurpose:To retrospectively analyze the effects of different concurrent chemotherapy regimens on locally advanced non-small-cell lung carcinoma (NSCLC).Methods:Data were analyzed from 106 patients diagnosed as locally advanced NSCLC(Ⅲa:29Ⅲb:77) and received concurrent radiotherapy with various chemotherapy regimens. Analysis was performed for overall survival and toxicity (grade≥2).Results:Paclitaxel based chemotherapy regimen was delivered in 55 patients, whereas 21 patients with topotecan regimen and 26 patients with PE (cisplatin and etopside) regimen,4 patients with others. The median survival time was 18.6 months, the overall 1-and 3-year survival rate were 72.2% and 27.5%, respectively. Survival and toxicity analysis were performed in 102 patients which include paclitaxel, topotecan and PE groups, the median survival time was 16.3 months,27.3 months and 29.1 months, respectively. The overall survivals of topotecan and PE groups were superior to paclitaxol based group, but not signifcant (p=0.32). Howerevr, when topotecan and PE group were combined (47 patients) and compared to paclitaxel based regimen group, the median survival was poorer in patients with paclitaxol based regimen (16.3 months vs.27.3 months), and both in univariate and multivariate analysis paclitaxol based chemotherapy regimen was significantly associated with poorer survival (p< 0.05). N stage was significant in the COX multivariate regression model. Paclitaxel based regimen was associated with more acute radiation pneumonitis,27.3%versus 10.6%, (p=0.03), less blood toxicity (16.4%vs 29.8%) (p=0.108) and almost same esophagitis(29.1% vs 34.0%).Conclusions:This retrospective cohort study showed a correlation between concurrent chemotherapy regimens with survival and toxicity in patients with locally advanced NSCLC. PartⅡ:Comparison of dose distribution with Simplified IMRT to different curative radiotherapy plans of non-small cell lung cancer (NSCLC)Purpose To evaluate the dose distribution of target volume and normal tissues with different treatment planning such as three dimensional conformal radiotherapy (3DCRT), simplified intensity modulated radiotherapy (sIMRT), and intensity modulated radiotherapy (IMRT) for patients with locally advanced non-small cell lung carcinoma (NSCLC). Methods 14 patients with stage III NSCLC underwent concurrent chemotherapy were enrolled in this study.5-field 3DCRT, sIMRT and 5-field or 7-field IMRT plans were performed for each patient. The dose distributions of target volume and normal tissues, conformal index (CI) and heterogeneous index (HI) were analyzed using the dose-volume histogram for these techniques. The prescription dose was 60Gy in 30 fractions. The total MU were also analyzed to compare excution time indirectly. Results The CI for PTV was superior with MRT7f, sIMRT5f to 3DCRT5f. Conversely, the HI for PTV was 3DCRT5f>sIMRT5f>IMRT7f. The mean of total MU for 3DCRT5f, sIMRT5f, IMRT5f and IMRT7f was 476±23,523±29,764±51 and 793±44 (MRT>sIMRT>3DCRT), respectively. Conclusions Comparing with the 3DCRT plans and the IMRT plans, sIMRT plan was the optimal plan for clinical practice. sIMRT and IMRT radiotherapy techniques can protect lung and spinal cord well with this prescription dose. PartⅢ:Clinical Outcomes of Patients with Malignant Lung Lesions Treated with SBRTPurpose To investigate factors associated with local control and survival benefit of stereotactic body radiation therapy (SBRT) in patients with lung malignancies Methods and Materials Patients with pathologically proven malignant lung lesions were treated using SBRT with median prescribed dose of 50 Gy in 5 fractions. The median biologically effective dose assumingα/βratios of 10 Gy (BED 10) was 100 Gy. (GTVall and lesion average BED (10), instead of GTV and BED(10), were used in patients with multiple lesions in the overall survival related factors analysis). Results 103 lesions were treated in 84 patients between June 2004 and June 2008. No severe (Grade>2) toxicities were noted.2-year local control rates were 93.5%,91.3% for primary and recurrent/metastatic groups respectively. BED(10) was significant for local control in uni-variate (P=0.004) and multi-variate analyses (P=0.049).2 year overall survival rates were 43.0% and 33.6% for the Primary and recurrent/metastatic groups. Uni-variate analysis showed that primary tumor, peripheral location, (lesion average BED (10)≥72), lesion average BED (10)≥100 and GTVall<28ml were favorable factors. Multi-variate analysis showed that only lesion average BED (10) was significant associated with overall survival (P=0.001. Conclusions SBRT provides excellent local control for both primary and recurrent/metastatic lung malignancies. Overall survival was better in primary lung cancer patients. BED(10)-control and BED(10)-survival relationship were shown in this study. Tumor volume was shown to be important by uni-variate analysis but failed in multi-variate analysis for overall survival. Additional studies are needed to test the values of lesion average BED(10) and GTVall.更多还原