局部晚期非小细胞肺癌同步放化疗肺部恶性肿瘤立体定向放射治疗的相关因素分析
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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。
PartⅠ:Effect of different concurrent chemotherapy regimens on locally advanced non-small-cell lung carcinoma
Purpose: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 SBRT
Purpose 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.
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。
PartⅠ:Effect of different concurrent chemotherapy regimens on locally advanced non-small-cell lung carcinoma
Purpose: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 SBRT
Purpose 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.
引文
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梁军等(2006).肺癌三维适形放疗与常规放疗剂量学优势的比较.临床肿瘤学杂志.11：814-817.
吴开良等(2002).肺癌不同放射治疗技术剂量学比较研究.中华放射肿瘤学杂志.11：231-234.
Baumann P等(2006) Factors important for efficacy of stereotactic body radiotherapy of medically inoperable stage I lung cancer. A retrospective analysis of.patients treated in the Nordic countries. Acta Oncol.45:787-795.
Baumann P等(2009). Outcome in a prospective phase Ⅱ trial of medical inoperable stage Ⅰ non-small cell lung cancer patients treated with stereotactic body radiotherapy. J Clin Oncol. 27:3290-3296.
Chang JY等(2008) Stereotactic body radiation therapy in centrally and superiorly located stage Ⅰ or isolated recurrent non-small-cell lung cancer. Int J Radiat Oncol Biol Phys.72:967-971.
Hoyer M等(2006) Prospective study on sterotactic radiotherapy of limited-stage non-small-cell lung cancer. Int J Radiat Oncol Biol Phys.66:s128-135.
Koto M等(2007) A phase Ⅱ study on stereotactic body radiotherapy for stage Ⅰ non-small cell lung cancer. Radiother Oncol.85:429-434.
Nagata Y等(2005). Clinical outcomes of a phase Ⅰ/Ⅱ study of 48 Gy of stereotactic body radiotherapy in 4 fractions for primary lung cancer using a stereotactic body frame. Int J Radiat Oncol Biol Phys.63:1427-1431.
Onimaru R等(2008) Steep dose-response relationship for stage Ⅰ non-small-cell lung cancer using hypofractionated high-dose irradiation by real-time tumor-tracking radiotherapy. Int J Radiat Oncol Biol Phys.70:374-381.
Onishi H等(2004). Stereotactic hypofractionated high-dose irradiation for stage Ⅰ nonsmall cell lung carcinoma:Clinical outcomes in 245 subjects in a Japanese multiinstitutional study. Cancer. 101:1623-1631.
Rusthoven KE等(2009). Multi-Institutional phase Ⅰ/Ⅱ trial of stereotactic body radiation therapy for lung metastases. J Clin Oncol.27:1579-1584.
Schefter TE等(2006). A phase Ⅰ/Ⅱ trial of stereotactic body radiation therapy (SBRT) for lung metastases:Initial report of dose escalation and early toxicity. Int J Radiat Oncol Biol Phys.66:S120-S127.
Takeda A等(2009) Stereotactic body radiation therapy for primary lung cancer at a dose of 50 Gy total in five fractions to the periphery of the planning target volume calculated using a superposition algorithm. Int J Radiat Oncol Biol Phys.73:112-118.
Timmerman R等(2003).Extracranial stereotactic radioablation:Results of a phase Ⅰ study in medically inoperable stage Ⅰ non-small cell lung cancer. Chest.124:1946-1953.
Timmerman R等(2006). Excessive toxicity when treating central tumors in a phase Ⅱ study of stereotactic body radiation therapy for medically inoperable early-stage lung cancer. J Clin Oncol 24:4833-4839.
Uematsu M等(2001) Computed tomographyguided frameless stereotactic radiotherapy for stage Ⅰ non-small cell lung cancer:a 5-year experience. Int J Radiat Oncol Biol Phys.51:666-670.
Wang S等(2006) Analysis of clinical and dosimetric factors associated with treatment-related pneumontis(TRP) in patients with non-small-cell lung cancer (NSCLC) treated with concurrent chemotherapy and three-dimensional conformal radiotherapy (3D-CRT). Int J Radiat Oncol Biol Phys.66:1399-1407.
Wu Y等(2002). A randomized trial of systematic nodal dissection in resectable non-small cell lung cancer. Lung Cancer.36:1-6.
Albain KS等(2002) Concurrent cisplatin,etoposide, and chest radiotherapy in pathologic stage ⅢB non-smallcell lung cancer:A Southwest Oncology Group Phase Ⅱ Study, SWOG 9019. J Clin Oncol. 20:3454-3460.
Angela M等(2006) Phase Ⅱ Study of Consolidation Paclitaxel After Concurrent Chemoradiation in Poor-Risk Stage Ⅲ Non-Small-Cell Lung Cancer:SWOG S9712. J clin Oncol.24(33):5242-46
Ansari R等(1991) A phase Ⅲ study of thoracic irradiation with or without concomitant cisplatin inlocoregional unresectable non-small cell lung cancer. Proc Am Soc Clin Oncol.10:241.
Belani CP等(2005) Combined chemoradiotherapy regimens of paclitaxel and carboplatin for locally advanced non-small cell lung cancer:a randomized phase Ⅱ local advanced multi-modality protocol.J
Broadcast Huber RM等(2004) Induction chemotherapy and following simultaneous radiochemotherapy versus induction chemotherapy and radiotherapy alone in inoperable NSCLC(stage ⅢA/ⅢB); Update of CT/RT 99/97. (ASCO annual meeting proceeding 2004 Abstract#7075)Clin Oncol.23(25) 5883-5891.
Carter DL等(2004) A randomized phase Ⅲ trial of combined paclitaxel, carboplatin, and radiation therapy followed by either weekly paclitaxel observation in patients with stage Ⅲ non-small cell lung cancer. (ASCO annual meeting proceeding 2004 Abstract#7076).
Choi NC等(1981) Improved survival of patients with unresectable non-small cell bronchogenic carcinoma by an innovated high-dose en-bloc radiotherapeutic approach. Cancer.48:101-109.
Curran WJ等(2003) Long-term benefit is observed in a phase Ⅲ comparison of sequential vs concurrent chemoradiation for patients with unresected stage Ⅲ NSCLC:RTOG 9410. Proc Am Soc Clin Oncol.22:621
David SE等(2008) NCCN practice guidline in oncology 2008:Non-small cell lung cancer.30-31 Edelstein MP等(1996). Potentiation of radiation therapy by vinorelbine in non-small cell lung cancer. Semin Oncol.23(suppl 5):41
Dillman R等(1990) Arandomized trial of induction chemotherapy plus high-dose radiation versus radiation alone in stage Ⅲ non-small cell lung cancer. N Engl J Med.323:940-945.
Forouzannia A等(2004) A phase I study of Topotecan, as a radiosensitizer, for thoracic malignanies. Lung cancer.44:111-119
Fournel P等(2005) Randomized phase Ⅲ trial of sequential chemoradiotherapy compared with concurrent chemoradiotherapy in locally advanced non-small-cell lung cancer:Groupe
Lyon-Saint-Etienne d'Oncologie Thoracique-Groupe FranA§ais de Pneumo-CancA(?)rologie NPC 95-01 Study. J Clin Oncol.23(25):5910-7
Fu KK等(1985) Biological basis for the interaction of chemotherapeutic agents and radiation therapy.cancer.55:21-23.
Furuse K等(1999) Phase Ⅲ study of concurrent versus sequential thoracic radiotherapy in combination with mitomycine,vinblastin and cisplatine in unresectable stage Ⅲ non-small cell lung cancer.J clin Oncol.17:2692
Gandara DR等(2006) Long-term survival with concurrent chemoradiation therapy followed by consolidation docetaxel in stage ⅢB non-small-cell lung cancer:a phase Ⅱ Southwest Oncology Group Study (S9504). Clin Lung Cancer.8(2):116-121.
Hanna等(2007) Phase Ⅲ trial of cisplatin plus etopside plus concurrent chest radiation with or without consolidation docetaxel in patients with inoperable stage Ⅲnon small cell lung cancer:HOG LUN 01-24/USO-023.Proc Am Soc Clin Oncol, abstract 7512
Hall BE等(1962) Treatment of far advanced cancer with S-fiuorouracil, used alone and in combination with irradiation. Cancer Chemother Rep.16:369-386.
Kelly K等(2007) Updated analysis for SWOG 0023:a radomized phase 3 trial of geftinib versus placebo maintenance after definitive chemoradiation followed by docetaxel and in patients with locally advanced s tage Ⅲ non-small cell lung cancer.Proc Am Soc Clin Oncol.abstract 7513
Kim JH等(1992) Poteniation of radiation reponse in human carcinoma cells in vitro and murine fibrosarcoma in vivo by topotecan, an inhibitor nof DNA topoisomerseI. Int J Radiat Oncol Biol Phys, 22(3):515-8
Lallev A等(1993) Effect of radiation and topoisomerase Ⅱ inhibitors on DNA synthesis in mammalian cells.Eur J Biochem.216:177.
Lau DH等(1998) Southwest Oncology Group phase Ⅱ trial of concurrent carboplatin, etoposide, and radiation for poor-risk stage Ⅲ non-smallcell lung cancer. J Clin Oncol.16:3078-3081
Lechevalier T等(1991) Radiotherapy alone versus combined chemotherapy and radiotherapy in non-resectable non-small cell lung cancer:first analyses of a randomized trial in 353 patients. J Natl Cancer Inst.83:417-422.
LeChevalier T等(1992) Significant effect of adjuvant chemotherapy on survival in locally advanced non-small-cell lung cacinoma [letter]. J Natl Cancer Inst.84:58
Mark A等(2005) Randomized Phase Ⅱ Trial of Induction Chemotherapy Followed by Concurrent Chemotherapy and Dose-Escalated Thoracic Conformal Radiotherapy (74 Gy) in Stage Ⅲ non-small-cell lung cancer:CALGB 30105. J Clin Oncol 26(15):2457-2463
Perez CA等(1986) Impact of tumor control on survival in carcinoma of the lung treated with irradiation. Int J Radiat Oncol Biol Phys.12:539-547.
Perez CA等(1987) Long term observations of the patterns of failure in patients with unresectable non-oat cell carcinoma of the lung treated with definitive radiotherapy. Cancer.59:1874-1881.
Ready N等(2004) Initial cohort toxicity evaluation for chemoradiotherapy (CRT) and ZD1839 in stage Ⅲ non-small cell lung cancer:A CALGB stratified phase Ⅱ trial. J Clin Oncol 22:7078
Saka H等(1997) Irinotecan (CPT 11)and concurrent radiotherapy in locally advanced non-small cell lung cancer (NSCLC):A phase Ⅱ study of Japan clinical oncology group(JCOG9504) (abstract 1607) [J]. Proc Am Soc Clin Oncol.16 (2):447a.
Sause WT等(1995) RTOG 8808 and ECOG 4588. Preliminary results of a phase Ⅲ trial in regionally advanced unresectable non-small cell lung cancer. J Natl Cancer Inst.87:198-205.
Schaake-Koning C等(1992) Effects of concomitant cisplatin and radiotherapy on inoperable.N Engl J Med.326:524-530.
Soresi E等(1988),Clerici M,Grilli R et al.A randomized clinical trial comparing radiation therapy vs. radiation therapy plus cis-dichlorodiammine platinum in the treatment of locally advanced non-small cell lung cancer. Semin Oncol.15:20-25
Trodella L等(2006) Induction cisplatin-gemcitabine-paclitaxel plus concurrent radiotherapy and gemcitabine in the multimodality treatment of unresectable stage ⅢB non-small cell lung cancer. Lung Cancer.54(3):331-8
Trovo M等(1992) Radiotherapy versus radiotherapy enhanced by cisplatin in stage Ⅲ non-small cell lung cancer. Int. J. Radiation Oncology Biol. Phys.24:11-15
Vokes EE等(2002) Randomized phase Ⅱ study of cisplatin with gemcitabine or paclitaxel or vinorelbine as induction chemotherapy followed by concomitant chemoradiotherapy for stage ⅢB non-small-cell lung cancer:cancer and leukemia group B study 9431. J Clin Oncol. 20(20):4191-4198.
Vokes EE等(2007) Induction chemotherapy followed by chemoradiotherapy compared with chemoradiotherapy alone for regionally advanced unresectable stage Ⅲ non-small-cell lung cancer:cancer and leukemia Group. J clin oncol.25:1698-1704
Wheeler RH等(1995) Cisplatin lus radiation therapy.J Infusional Chermother.5;61
Zaneli GD等(1997) Paclitaxel as a radiosensitiser:a proposed schedule of administration based on in vitro data and pharmacokinetic calculations.Eur J Cancer.33:486.
Zatloukal P等(2004) Chemoradiotherapy versus sequential chemoradiotherapy. Concurrent with cisplatin and vinorelbinein locally advanced non-small cell lung cancer:a randomized study. Lung Cancer.46:87-98.
周宗玫等(2005).放射治疗合并盐酸拓普替康治疗局部晚期非小细胞肺癌的Ⅰ期临床研究.肿瘤防治研究.32(2)：116-118
Curran W.T等(2003). Long-term benefit is observed in a phase Ⅲ comparison of sequential vs concurrent chemoradiation for patients with unresected stage Ⅲ NSCLC:RTOG 9410. Proc Am Soc Clin Oncol.22:621
Fournel P等(2005). Randomized phase Ⅲ trial of sequential chemoradiotherapy compared with concurrent chemoradiotherapy in locally advanced non-small-cell lung cancer:Groupe Lyon-Saint-Etienne d'Oncologie Thoracique-Groupe FranA§ais de Pneumo-CancA(?)rologie NPC 95-01 Study. J Clin Oncol.23(25):5910-7
Furuse K等(1999). Phase Ⅲ study of concurrent versus sequential thoracic radiotherapy in combination with mitomycin, Vindesine, and cisplatin in unresctable stage Ⅲ non-small cell lung cancer. J Clin Oncol 17:2692-2699.
Gandara DR等(2006). Long-term survival with concurrent chemoradiation therapy followed by consolidation docetaxel in stage ⅢB non-small-cell lung cancer:a phase Ⅱ Southwest Oncology Group Study (S9504). Clin Lung Cancer.8(2):116-121.
Lechevalier T等 (1991). Radiotherapy alone versus combined chemotherapy and radiotherapy in non-resectable non-small cell lung cancer:first analyses of a randomized trial in 353 patients. J Natl Cancer Inst 83:417-422.
Vokes EE等(2002). Randomized phase Ⅱ study of cisplatin with gemcitabine or paclitaxel or vinorelbine as induction chemotherapy followed by concomitant chemoradiotherapy for stage ⅢB non-small-cell lung cancer:cancer and leukemia group B study 9431. J Clin Oncol. 20(20):4191-4198
Zatloukal P等 (2004). chemorad iotherapy versus sequential chemoradiotherapy. Concurrent with cisplatin and vinorelbinein locally advanced non-small cell lung cancer:a randomized study. Lung Cancer.46:87-98.
王绿化等(2008).肿瘤放射治疗学(第四版).北京：中国协和医大出版社,578-611
王小震等(2006)等.Ⅲ期非小细胞肺癌放疗加紫杉醇卡铂同步化疗的临床实验结果.中华放射 肿瘤学杂志.15：270-274
朱向帜等(2007).三维适形治疗局部晚期非小细胞肺癌预后因素分析.中华肿瘤杂志.29(10)：748-753
Chang JY等(2006). Significant reduction of nomal tissue dose by proton radiotherapy compared with three dimensional conformal or intensity-modulated radiation therapy in stage Ⅰ or stage Ⅲ non-small-cell lung cancer. Int J Radiat Oncol Biol Phys.65:1087-1096.
chavaudra J等(2001). Definition of volumes in external radiotherapy:ICRU reports 50 and 62. Cancer Radiother.5:472-478.
Feuvret L等(2006). Conformity index:a review. Int J Radiat Oncol Biol Phys.64:333-342.
Graham M等(1999). Clinical dose-volume histogram analysis for pneumonitis after 3D treatment for non-small cell lung cancer(NSCLC).Int J Radiat Oncol Biol Phys.45:323-329.
Liu HH等(2004), Feasibility of sparing lung and other thoracic structures with intensity-modulated radiotherapy for non-small-cell lung cancer. Int J Radiat Oncol Biol Phys.58:1268-1279.
Murshed H等(2004). Dose and volume reduction for normal lung using intensity-modulated radiotherapy for advanced-stage non-small-cell lung cancer. Int J Radiat Oncol Biol Phys.58:1258-1267.
Schallenkamp JM等(2006). Incidence of radiation pneumonitis after thoracic irradition: dose-volume correlates. Int J Radiat Oncol Biol Phys.64:333-342.
Tsujino K等(2003). Predictive value of dose-volume histogram parameters for predicting radiation pneumonitis after concurrent chemoradiation for lung cancer. Int J Radiat Oncol Biol Phys,2003, 55:110-115.
Wang S等(2006). Investigation of clinical and dosimetric facors associated with postoperative pulmonary complications in esophageal cancer treated with concurrent chemoradiotherapy followed by surgery. Int J Radiat Oncol Biol Phys.64:692-699.
耿辉等(2006).一种简单调强放疗技术应用的初步研究.中华放射肿瘤学杂志.15：411-415.
梁军等(2006).肺癌三维适形放疗与常规放疗剂量学优势的比较.临床肿瘤学杂志.11：814-817.
吴开良等(2002).肺癌不同放射治疗技术剂量学比较研究.中华放射肿瘤学杂志.11：231-234.
Baumann P等(2006) Factors important for efficacy of stereotactic body radiotherapy of medically inoperable stage I lung cancer. A retrospective analysis of.patients treated in the Nordic countries. Acta Oncol.45:787-795.
Baumann P等(2009). Outcome in a prospective phase Ⅱ trial of medical inoperable stage Ⅰ non-small cell lung cancer patients treated with stereotactic body radiotherapy. J Clin Oncol. 27:3290-3296.
Chang JY等(2008) Stereotactic body radiation therapy in centrally and superiorly located stage Ⅰ or isolated recurrent non-small-cell lung cancer. Int J Radiat Oncol Biol Phys.72:967-971.
Hoyer M等(2006) Prospective study on sterotactic radiotherapy of limited-stage non-small-cell lung cancer. Int J Radiat Oncol Biol Phys.66:s128-135.
Koto M等(2007) A phase Ⅱ study on stereotactic body radiotherapy for stage Ⅰ non-small cell lung cancer. Radiother Oncol.85:429-434.
Nagata Y等(2005). Clinical outcomes of a phase Ⅰ/Ⅱ study of 48 Gy of stereotactic body radiotherapy in 4 fractions for primary lung cancer using a stereotactic body frame. Int J Radiat Oncol Biol Phys.63:1427-1431.
Onimaru R等(2008) Steep dose-response relationship for stage Ⅰ non-small-cell lung cancer using hypofractionated high-dose irradiation by real-time tumor-tracking radiotherapy. Int J Radiat Oncol Biol Phys.70:374-381.
Onishi H等(2004). Stereotactic hypofractionated high-dose irradiation for stage Ⅰ nonsmall cell lung carcinoma:Clinical outcomes in 245 subjects in a Japanese multiinstitutional study. Cancer. 101:1623-1631.
Rusthoven KE等(2009). Multi-Institutional phase Ⅰ/Ⅱ trial of stereotactic body radiation therapy for lung metastases. J Clin Oncol.27:1579-1584.
Schefter TE等(2006). A phase Ⅰ/Ⅱ trial of stereotactic body radiation therapy (SBRT) for lung metastases:Initial report of dose escalation and early toxicity. Int J Radiat Oncol Biol Phys.66:S120-S127.
Takeda A等(2009) Stereotactic body radiation therapy for primary lung cancer at a dose of 50 Gy total in five fractions to the periphery of the planning target volume calculated using a superposition algorithm. Int J Radiat Oncol Biol Phys.73:112-118.
Timmerman R等(2003).Extracranial stereotactic radioablation:Results of a phase Ⅰ study in medically inoperable stage Ⅰ non-small cell lung cancer. Chest.124:1946-1953.
Timmerman R等(2006). Excessive toxicity when treating central tumors in a phase Ⅱ study of stereotactic body radiation therapy for medically inoperable early-stage lung cancer. J Clin Oncol 24:4833-4839.
Uematsu M等(2001) Computed tomographyguided frameless stereotactic radiotherapy for stage Ⅰ non-small cell lung cancer:a 5-year experience. Int J Radiat Oncol Biol Phys.51:666-670.
Wang S等(2006) Analysis of clinical and dosimetric factors associated with treatment-related pneumontis(TRP) in patients with non-small-cell lung cancer (NSCLC) treated with concurrent chemotherapy and three-dimensional conformal radiotherapy (3D-CRT). Int J Radiat Oncol Biol Phys.66:1399-1407.
Wu Y等(2002). A randomized trial of systematic nodal dissection in resectable non-small cell lung cancer. Lung Cancer.36:1-6.
Albain KS等(2002) Concurrent cisplatin,etoposide, and chest radiotherapy in pathologic stage ⅢB non-smallcell lung cancer:A Southwest Oncology Group Phase Ⅱ Study, SWOG 9019. J Clin Oncol. 20:3454-3460.
Angela M等(2006) Phase Ⅱ Study of Consolidation Paclitaxel After Concurrent Chemoradiation in Poor-Risk Stage Ⅲ Non-Small-Cell Lung Cancer:SWOG S9712. J clin Oncol.24(33):5242-46
Ansari R等(1991) A phase Ⅲ study of thoracic irradiation with or without concomitant cisplatin inlocoregional unresectable non-small cell lung cancer. Proc Am Soc Clin Oncol.10:241.
Belani CP等(2005) Combined chemoradiotherapy regimens of paclitaxel and carboplatin for locally advanced non-small cell lung cancer:a randomized phase Ⅱ local advanced multi-modality protocol.J
Broadcast Huber RM等(2004) Induction chemotherapy and following simultaneous radiochemotherapy versus induction chemotherapy and radiotherapy alone in inoperable NSCLC(stage ⅢA/ⅢB); Update of CT/RT 99/97. (ASCO annual meeting proceeding 2004 Abstract#7075)Clin Oncol.23(25) 5883-5891.
Carter DL等(2004) A randomized phase Ⅲ trial of combined paclitaxel, carboplatin, and radiation therapy followed by either weekly paclitaxel observation in patients with stage Ⅲ non-small cell lung cancer. (ASCO annual meeting proceeding 2004 Abstract#7076).
Choi NC等(1981) Improved survival of patients with unresectable non-small cell bronchogenic carcinoma by an innovated high-dose en-bloc radiotherapeutic approach. Cancer.48:101-109.
Curran WJ等(2003) Long-term benefit is observed in a phase Ⅲ comparison of sequential vs concurrent chemoradiation for patients with unresected stage Ⅲ NSCLC:RTOG 9410. Proc Am Soc Clin Oncol.22:621
David SE等(2008) NCCN practice guidline in oncology 2008:Non-small cell lung cancer.30-31 Edelstein MP等(1996). Potentiation of radiation therapy by vinorelbine in non-small cell lung cancer. Semin Oncol.23(suppl 5):41
Dillman R等(1990) Arandomized trial of induction chemotherapy plus high-dose radiation versus radiation alone in stage Ⅲ non-small cell lung cancer. N Engl J Med.323:940-945.
Forouzannia A等(2004) A phase I study of Topotecan, as a radiosensitizer, for thoracic malignanies. Lung cancer.44:111-119
Fournel P等(2005) Randomized phase Ⅲ trial of sequential chemoradiotherapy compared with concurrent chemoradiotherapy in locally advanced non-small-cell lung cancer:Groupe
Lyon-Saint-Etienne d'Oncologie Thoracique-Groupe FranA§ais de Pneumo-CancA(?)rologie NPC 95-01 Study. J Clin Oncol.23(25):5910-7
Fu KK等(1985) Biological basis for the interaction of chemotherapeutic agents and radiation therapy.cancer.55:21-23.
Furuse K等(1999) Phase Ⅲ study of concurrent versus sequential thoracic radiotherapy in combination with mitomycine,vinblastin and cisplatine in unresectable stage Ⅲ non-small cell lung cancer.J clin Oncol.17:2692
Gandara DR等(2006) Long-term survival with concurrent chemoradiation therapy followed by consolidation docetaxel in stage ⅢB non-small-cell lung cancer:a phase Ⅱ Southwest Oncology Group Study (S9504). Clin Lung Cancer.8(2):116-121.
Hanna等(2007) Phase Ⅲ trial of cisplatin plus etopside plus concurrent chest radiation with or without consolidation docetaxel in patients with inoperable stage Ⅲnon small cell lung cancer:HOG LUN 01-24/USO-023.Proc Am Soc Clin Oncol, abstract 7512
Hall BE等(1962) Treatment of far advanced cancer with S-fiuorouracil, used alone and in combination with irradiation. Cancer Chemother Rep.16:369-386.
Kelly K等(2007) Updated analysis for SWOG 0023:a radomized phase 3 trial of geftinib versus placebo maintenance after definitive chemoradiation followed by docetaxel and in patients with locally advanced s tage Ⅲ non-small cell lung cancer.Proc Am Soc Clin Oncol.abstract 7513
Kim JH等(1992) Poteniation of radiation reponse in human carcinoma cells in vitro and murine fibrosarcoma in vivo by topotecan, an inhibitor nof DNA topoisomerseI. Int J Radiat Oncol Biol Phys, 22(3):515-8
Lallev A等(1993) Effect of radiation and topoisomerase Ⅱ inhibitors on DNA synthesis in mammalian cells.Eur J Biochem.216:177.
Lau DH等(1998) Southwest Oncology Group phase Ⅱ trial of concurrent carboplatin, etoposide, and radiation for poor-risk stage Ⅲ non-smallcell lung cancer. J Clin Oncol.16:3078-3081
Lechevalier T等(1991) Radiotherapy alone versus combined chemotherapy and radiotherapy in non-resectable non-small cell lung cancer:first analyses of a randomized trial in 353 patients. J Natl Cancer Inst.83:417-422.
LeChevalier T等(1992) Significant effect of adjuvant chemotherapy on survival in locally advanced non-small-cell lung cacinoma [letter]. J Natl Cancer Inst.84:58
Mark A等(2005) Randomized Phase Ⅱ Trial of Induction Chemotherapy Followed by Concurrent Chemotherapy and Dose-Escalated Thoracic Conformal Radiotherapy (74 Gy) in Stage Ⅲ non-small-cell lung cancer:CALGB 30105. J Clin Oncol 26(15):2457-2463
Perez CA等(1986) Impact of tumor control on survival in carcinoma of the lung treated with irradiation. Int J Radiat Oncol Biol Phys.12:539-547.
Perez CA等(1987) Long term observations of the patterns of failure in patients with unresectable non-oat cell carcinoma of the lung treated with definitive radiotherapy. Cancer.59:1874-1881.
Ready N等(2004) Initial cohort toxicity evaluation for chemoradiotherapy (CRT) and ZD1839 in stage Ⅲ non-small cell lung cancer:A CALGB stratified phase Ⅱ trial. J Clin Oncol 22:7078
Saka H等(1997) Irinotecan (CPT 11)and concurrent radiotherapy in locally advanced non-small cell lung cancer (NSCLC):A phase Ⅱ study of Japan clinical oncology group(JCOG9504) (abstract 1607) [J]. Proc Am Soc Clin Oncol.16 (2):447a.
Sause WT等(1995) RTOG 8808 and ECOG 4588. Preliminary results of a phase Ⅲ trial in regionally advanced unresectable non-small cell lung cancer. J Natl Cancer Inst.87:198-205.
Schaake-Koning C等(1992) Effects of concomitant cisplatin and radiotherapy on inoperable.N Engl J Med.326:524-530.
Soresi E等(1988),Clerici M,Grilli R et al.A randomized clinical trial comparing radiation therapy vs. radiation therapy plus cis-dichlorodiammine platinum in the treatment of locally advanced non-small cell lung cancer. Semin Oncol.15:20-25
Trodella L等(2006) Induction cisplatin-gemcitabine-paclitaxel plus concurrent radiotherapy and gemcitabine in the multimodality treatment of unresectable stage ⅢB non-small cell lung cancer. Lung Cancer.54(3):331-8
Trovo M等(1992) Radiotherapy versus radiotherapy enhanced by cisplatin in stage Ⅲ non-small cell lung cancer. Int. J. Radiation Oncology Biol. Phys.24:11-15
Vokes EE等(2002) Randomized phase Ⅱ study of cisplatin with gemcitabine or paclitaxel or vinorelbine as induction chemotherapy followed by concomitant chemoradiotherapy for stage ⅢB non-small-cell lung cancer:cancer and leukemia group B study 9431. J Clin Oncol. 20(20):4191-4198.
Vokes EE等(2007) Induction chemotherapy followed by chemoradiotherapy compared with chemoradiotherapy alone for regionally advanced unresectable stage Ⅲ non-small-cell lung cancer:cancer and leukemia Group. J clin oncol.25:1698-1704
Wheeler RH等(1995) Cisplatin lus radiation therapy.J Infusional Chermother.5;61
Zaneli GD等(1997) Paclitaxel as a radiosensitiser:a proposed schedule of administration based on in vitro data and pharmacokinetic calculations.Eur J Cancer.33:486.
Zatloukal P等(2004) Chemoradiotherapy versus sequential chemoradiotherapy. Concurrent with cisplatin and vinorelbinein locally advanced non-small cell lung cancer:a randomized study. Lung Cancer.46:87-98.
周宗玫等(2005).放射治疗合并盐酸拓普替康治疗局部晚期非小细胞肺癌的Ⅰ期临床研究.肿瘤防治研究.32(2)：116-118