三维适形放疗治疗局部晚期肺癌的预后和毒性分析
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摘要
目的 评估三维适形放疗治疗局部晚期非小细胞肺癌的疗效、毒性及预后因素。
材料和方法 2001年11月至2005年3月期间我院采用三维适形放疗治疗组织学证实的局部晚期(ⅢA／B)非小细胞肺癌患者113例，分析全组患者的1，2，3年生存率和中位生存期及预后因素。
结果 全组1，2，3年生存率分别为61.4％，32.1％，22.7％。中位生存期为17月，其中单独放疗组16月，序贯放化疗组18月，同步放化疗组16月。单因素分析显示疗前胸背痛、疗前卡氏评分、血红蛋白、白蛋白水平、大体肿瘤体积(GTV)体积及近期疗效是影响预后的因素，P值分别为0.033、0.000、0.042、0.028、0.024、0.021；多因素分析显示仅疗前卡氏评分是肺癌独立预后因素。
结论 三维适形放疗治疗局部晚期非小细胞肺癌显示了较好的疗效；放疗前卡氏评分是影响局部晚期非小细胞肺癌预后的主要因素。
Objective: To evaluate our institution's experience and identify prognostic factors for LA-NSCLC using 3D conformal radiotherapy. Methods one hundred and eighteen patients with stage Ⅲ A/B non-small-cell lung cancer (LA-NSCLC) were treated with 3D-CRT at CAMS from Nov. 2001 to Feb. 2005. 113 patients were eligible to analyse. 45 cases received radiotherapy alone; 39 cases received concurrent chemoradiation (paclitaxol plus carboplatin in 32 patients, Topotecan in 7 patients); 29 cases received sequential chemoradiation, mostly with platinum-based regiment. Thoracic radiation dose ranged from 26Gy to 75Gy (median 60Gy). GTV and PTV were collected from the 3D treatment plans in 79 and 101 patients, respectively. Results The overall 1、2 and 3-year overall survival rate was 61.4%, 32.1% and 22.7%, respectively, with a median survival time of 17 months. In univariate analysis, the following characteristics were significantly associated with survival: absence of chest pain, good karnofsky performance status (KPS), albumin>4.2g/L, hemoglobin≥140g/L and 130g/L for male and female, respectively, response to radiotherapy and GTV<100cm3. Multivariate analysis revealed that good KPS was the only independent risk factor for survival. Conclusion Three-dimensional conformal radiotherapy is effective in the
材料和方法 2001年11月至2005年3月期间我院采用三维适形放疗治疗组织学证实的局部晚期(ⅢA／B)非小细胞肺癌患者113例，分析全组患者的1，2，3年生存率和中位生存期及预后因素。
结果 全组1，2，3年生存率分别为61.4％，32.1％，22.7％。中位生存期为17月，其中单独放疗组16月，序贯放化疗组18月，同步放化疗组16月。单因素分析显示疗前胸背痛、疗前卡氏评分、血红蛋白、白蛋白水平、大体肿瘤体积(GTV)体积及近期疗效是影响预后的因素，P值分别为0.033、0.000、0.042、0.028、0.024、0.021；多因素分析显示仅疗前卡氏评分是肺癌独立预后因素。
结论 三维适形放疗治疗局部晚期非小细胞肺癌显示了较好的疗效；放疗前卡氏评分是影响局部晚期非小细胞肺癌预后的主要因素。
Objective: To evaluate our institution's experience and identify prognostic factors for LA-NSCLC using 3D conformal radiotherapy. Methods one hundred and eighteen patients with stage Ⅲ A/B non-small-cell lung cancer (LA-NSCLC) were treated with 3D-CRT at CAMS from Nov. 2001 to Feb. 2005. 113 patients were eligible to analyse. 45 cases received radiotherapy alone; 39 cases received concurrent chemoradiation (paclitaxol plus carboplatin in 32 patients, Topotecan in 7 patients); 29 cases received sequential chemoradiation, mostly with platinum-based regiment. Thoracic radiation dose ranged from 26Gy to 75Gy (median 60Gy). GTV and PTV were collected from the 3D treatment plans in 79 and 101 patients, respectively. Results The overall 1、2 and 3-year overall survival rate was 61.4%, 32.1% and 22.7%, respectively, with a median survival time of 17 months. In univariate analysis, the following characteristics were significantly associated with survival: absence of chest pain, good karnofsky performance status (KPS), albumin>4.2g/L, hemoglobin≥140g/L and 130g/L for male and female, respectively, response to radiotherapy and GTV<100cm3. Multivariate analysis revealed that good KPS was the only independent risk factor for survival. Conclusion Three-dimensional conformal radiotherapy is effective in the
引文
1 Graham MV, Purdy JA, Emami B, et al. 3-D conformal radiotherapy for lung cancer: the Washington University experience. Front Radiat Ther Oncol 1996;29:188-198.
2 Dillman RO, Seagren SL, Propert KJ, et al. A randomized trial of induction chemotherapy plus high-dose radiation versus radiation alone in stage III non-small cell lung cancer. N Engl J Med 1990; 323:940-945.
3 Sause W, Scott C, Taylor S, et al. Radiation Therapy Oncology Group (RTOG) 8808 and Eastern Cooperative Oncology Group (ECOG) 4588: preliminary results of phase III trial in regionally advanced , unresectable non-small cell lung cancer. J Natl Cancer Inst 1995; 87: 198-205.
4 LeChevalier T, Arriagada R, Quoix E, et al. Radiotherapy alone versus combined chemotherapy and radiotherapy in nonresectable non-small-cell lung cancer: First analysis of a randomized trial in 353 patients. J Natl Cancer Inst 1991; 83: 417-423.
5 Sibley GS, Mundt AJ, Shapiro C, et al. The treatment of stage III non-small cell lung cancer using high dose conformal radiotherapy. Int J Radiat Oncol Biol Phys, 1995,33: 1001-1007.
6 Armstrong J , Raben A , Zelefsky M ,et al. Promising survival with??3-dimensional conformal radiation therapy for NSCLC. Radiother Oncol, 1997,44:17-22.
7 Sim S, Rosenzweig KE, Schindelheim R, et al: Induction chemotherapy plus three-dimensional conformal radiation therapy on the definitive treatment of advanced non-small cell lung cancer. Int J Radiat Oncol Biol Phys 2001, 51: 660-665.
8 Hansen O, Paarup H, Sorensen P, et al: Curative radiotherapy of local advanced non-small-cell lung cancer. Eight years of experience from Odense. Ugeskr Laeger. 2005,167(37):3497-502.
9 王颖杰，王绿化，王鑫，等．91例非小细胞肺癌三维适形放疗的临床分析．中华放射肿瘤杂志2005，14：241-244．
10 Furuse K, Fukuoka M, Kawahara M, et al: Phase Ⅲ Study of Concurrent Versus Sequential Thoracic Radiotherapy in Combination With Mitomycin, Vindesine, and Cisplatin in Unresectable Stage Ⅲ Non-Small-Cell Lung Cancer. J Clin Oncol 1999, 17: 2692-2699.
11 Curran WJ, Scott CB, Langer C J, et al: Long-term benefit is observed in a phase Ⅲ comparison of sequential vs concurrent chemo-radiation for patients with unresected stage Ⅲ NSCLC: RTOG 9410. Proc Am Soc Clin Oncol 22:621,2003 (abstr 2499).
12 Founel P, Robinet G, Thomas P, et al: 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 Fran9ais de Pneumo-Cancerologie NPC 95-01 Study. J Clin Oncol 2005, 23: 5910-5917.
13 Ramalingam S, Pawlish K, Gadgeel S, et al. Lung cancer in young patients: Analysis of a Surveillance, Epidemiology, and End Results Database. Am J Clin Oncol 1998; 16: 651-657.
14 Stanley KE, Prognostic factors for survival in patients with inoperable lung cancer. J Natl Cancer Inst 1980; 65: 25-32.
15 Werner-Wasik M, Scott C, Cox JD, et al. Recursive partitioning analysis of 1999 Radiation Therapy Oncology Group (RTOG) patients with locally-advanced non-small-cell lung cancer (LA-NSCLC): identification of five groups with different survival. Int J Radiat Oncol Biol Phys 2000; 48 (5): 1475-1482.
16 Basaki K, Abe Y, Aoki M, et al. Prognostic factors for survival in stage III non-small-cell lung cancer treated with definitive radiation therapy: impact of tumor volume. Int J Radiat Oncol Biol Phys 2006; 64 (2): 449-454.
17 Stinchcombe TE, Morris DE, Moore DT, et al; Post-chemotherapy gross tumor volume is predictive of survival in patients with stage III non-small cell lung cancer treated with combined modality therapy. Lung Cancer 2006; 52: 67-74.
18 Bradley JD, Ieumwananonthachai N, Purdy J, et al. Gross tumor??volume, critical prognostic factor in patients treated with three-dimensional conformal radiation therapy for non-small-cell lung carcinoma. Int J Radiat Oncol Biol Phys 2002; 52(1): 49-57.1 Tyldesley s, Boyd C, Shulze K, et al: Estimating the need for radiotherapy for lung cancer: An evidence-based, epidemiologic approach. Int J Radiat Oncol Biol Phys 49:973-985, 2001.
2 LeChevalier T, Arriagada R, Quoix E, et al. Radiotherapy alone versus combined chemotherapy and radiotherapy in nonresectable non-small-cell lung cancer: First analysis of a randomized triall in 353 patients. J Natl Cancer Inst 1991:83:417-423.
3 王颖杰，王绿化，冯勤付，等．肺癌三维适形放射治疗中肺和食管损伤的相关因素分析．中国肺癌杂志，2005，8(5)：454-458．
4 Graham MV, Purdy JA, Emami B, et al. Clinical dose-volume histogram analysis for pneumonitis after 3D treatment for non-small cell lung cancer (NSCLC). Int J Radiat Oncol Biol Phys 1999;45:323-329.
5 Tsujino K, Hirota S, Endo M, et al. 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.
6 Chang DT, Olivier KR, Morris CG, et al. The impact of heterogeneity correction on dosimetric parameters that predict for radiation pneumonitis. Int J Radiat Oncol Biol Phys 2006 ; 65(1): 125-131.7 Hayman JA, Martek MK, Ten Haken RK, et al: Dose escalation in non-small-cell lung cancer using three-dimentional conformal radiation therapy : Update of a phase I trial. J Clin Oncol 19 :127-136,2001.
8 Anscher MS, Kong FM, Marks LB, et al: Changes in plasma transforming growth factor beta during radiotherapy and the risk of symptomatic radiation-induced pneumonitis. Int J Radiat Oncol Biol Phys 37 :253-258, 1997.
9 http://ctep. cancer.gov/reporting/ctc.html
10 Kocak Z, Evans ES, Zhou SM, et al. Challenges in defining radiation pneumonitis in patients with lung cancer. Int J Radiat Oncol Biol Phys 2005;62(3): 635-638.
11 Onishi H, Kuriyama K, Yamaguchi M, et al. Concurrent two-dimensional radiotherapy and weekly docetaxel in the treatment of stage III non-small cell lung cancer: A good local response but no good survival due to radiation pneumonitis. Lung Cancer 2003; 40:79-84.
12 Robnett TJ, Machtay M, Vines EF, et al. Factors predicting severe radiation pneumonitis in patients receiving definitive chemoradiation for lung cancer. Int J Radiat Oncol Biol Phys 2000;48:89-94.
13 Yorke ED, Jackson A, Rosenzweig KE, et al: Dose-volume factors contributing to the incidence of radiation pneumonitis in??Non-Small-Cell lung cancer patients treated with three-dimensional conformal radiation therapy. Int J Radiat Oncol Biol Phys 54 (2) :329-339,2002.
14 Yorke ED, Jackson A, Rosenzweig KE, et al: Correlation of dosimetric factors and radiation pneumonitis for Non-Small-Cell lung cancer patients in a recently completed dose escalation study. Int J Radiat Oncol Biol Phys 63 (3):672-682, 2005.
15 Hope AJ, Naqa EI, Bradley JD, et al: Radiation pneumonitis/fibrosis risk based on dosimetric, clinical, and location-related factors. Int J Radiat Oncol Biol Phys 65(1): 112-124,2006.
16 Willner J, Jost A, Baier K, et al: A little to a lot or a lot to a little? An analysis of pneumonitis risk from dose-volume histogram parameters of the lung in patients with lung cancer theated with 3-D conformal radiotherapy. Strahlentrer Onkol 179:548-556, 2003
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26 王淑莲 中国协和医科大学博士毕业论文 2006待发表．
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20 Graham MV, Purdy JA, Emami B, et al. Clinical dose-volume histogram analysis for pneumonitis after 3D treatment for non-small-cell lung cancer (NSCLC). Int J Radiat Oncol Biol Phys, 1999,45:323-329.
21 Hernando ML, Marks LB, Bentel GC, et al. Radiation-induced pulmonary toxicity: A dose-volume histogram analysis in 201 patients with lung cancer. Int J Radiat Oncol Biol Phys , 2001, 51:650-659.
22 Kwa SL, Lebesque JV, Theuws JC, et al. Radiation pneumonitis as a function of mean lung dose: An analysis of pooled data of 540 patients. Int J Radiat Oncol Biol Phys, 1998, 42:1-9.
23 Tsujino K, Hirota S, Endo M, et al. 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.
24 Singh AK, Lockett MA, Bradley JD: Predictors of radiation-induced esophageal toxicity in patients with non-small cell lung cancer treated with three-dimensional conformal radiation therapy. Int J Radiat Oncol??Biol Phys,2003, 55:337-341.
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27 Van de Steene J, Van den Heuvel F, Bel A, et al. Electronic portal imaging with on-line correction of setup error in thoracic irradiation: clinical evaluation. Int JRadiat Oncol Biol Phys, 1998,40:967-976.
28 Samson MJ, van Sornsen de Koste JR, de Boer HC, et al. An analysis of anatomic landmark mobility and setup deviations in radiotherapy for lung cancer. Int J Radiat Oncol Biol Phys, 1999,43:827-832.
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30 http://ctep.cancer.gov/reporting/ctc.html.
2 Dillman RO, Seagren SL, Propert KJ, et al. A randomized trial of induction chemotherapy plus high-dose radiation versus radiation alone in stage III non-small cell lung cancer. N Engl J Med 1990; 323:940-945.
3 Sause W, Scott C, Taylor S, et al. Radiation Therapy Oncology Group (RTOG) 8808 and Eastern Cooperative Oncology Group (ECOG) 4588: preliminary results of phase III trial in regionally advanced , unresectable non-small cell lung cancer. J Natl Cancer Inst 1995; 87: 198-205.
4 LeChevalier T, Arriagada R, Quoix E, et al. Radiotherapy alone versus combined chemotherapy and radiotherapy in nonresectable non-small-cell lung cancer: First analysis of a randomized trial in 353 patients. J Natl Cancer Inst 1991; 83: 417-423.
5 Sibley GS, Mundt AJ, Shapiro C, et al. The treatment of stage III non-small cell lung cancer using high dose conformal radiotherapy. Int J Radiat Oncol Biol Phys, 1995,33: 1001-1007.
6 Armstrong J , Raben A , Zelefsky M ,et al. Promising survival with??3-dimensional conformal radiation therapy for NSCLC. Radiother Oncol, 1997,44:17-22.
7 Sim S, Rosenzweig KE, Schindelheim R, et al: Induction chemotherapy plus three-dimensional conformal radiation therapy on the definitive treatment of advanced non-small cell lung cancer. Int J Radiat Oncol Biol Phys 2001, 51: 660-665.
8 Hansen O, Paarup H, Sorensen P, et al: Curative radiotherapy of local advanced non-small-cell lung cancer. Eight years of experience from Odense. Ugeskr Laeger. 2005,167(37):3497-502.
9 王颖杰，王绿化，王鑫，等．91例非小细胞肺癌三维适形放疗的临床分析．中华放射肿瘤杂志2005，14：241-244．
10 Furuse K, Fukuoka M, Kawahara M, et al: Phase Ⅲ Study of Concurrent Versus Sequential Thoracic Radiotherapy in Combination With Mitomycin, Vindesine, and Cisplatin in Unresectable Stage Ⅲ Non-Small-Cell Lung Cancer. J Clin Oncol 1999, 17: 2692-2699.
11 Curran WJ, Scott CB, Langer C J, et al: Long-term benefit is observed in a phase Ⅲ comparison of sequential vs concurrent chemo-radiation for patients with unresected stage Ⅲ NSCLC: RTOG 9410. Proc Am Soc Clin Oncol 22:621,2003 (abstr 2499).
12 Founel P, Robinet G, Thomas P, et al: 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 Fran9ais de Pneumo-Cancerologie NPC 95-01 Study. J Clin Oncol 2005, 23: 5910-5917.
13 Ramalingam S, Pawlish K, Gadgeel S, et al. Lung cancer in young patients: Analysis of a Surveillance, Epidemiology, and End Results Database. Am J Clin Oncol 1998; 16: 651-657.
14 Stanley KE, Prognostic factors for survival in patients with inoperable lung cancer. J Natl Cancer Inst 1980; 65: 25-32.
15 Werner-Wasik M, Scott C, Cox JD, et al. Recursive partitioning analysis of 1999 Radiation Therapy Oncology Group (RTOG) patients with locally-advanced non-small-cell lung cancer (LA-NSCLC): identification of five groups with different survival. Int J Radiat Oncol Biol Phys 2000; 48 (5): 1475-1482.
16 Basaki K, Abe Y, Aoki M, et al. Prognostic factors for survival in stage III non-small-cell lung cancer treated with definitive radiation therapy: impact of tumor volume. Int J Radiat Oncol Biol Phys 2006; 64 (2): 449-454.
17 Stinchcombe TE, Morris DE, Moore DT, et al; Post-chemotherapy gross tumor volume is predictive of survival in patients with stage III non-small cell lung cancer treated with combined modality therapy. Lung Cancer 2006; 52: 67-74.
18 Bradley JD, Ieumwananonthachai N, Purdy J, et al. Gross tumor??volume, critical prognostic factor in patients treated with three-dimensional conformal radiation therapy for non-small-cell lung carcinoma. Int J Radiat Oncol Biol Phys 2002; 52(1): 49-57.1 Tyldesley s, Boyd C, Shulze K, et al: Estimating the need for radiotherapy for lung cancer: An evidence-based, epidemiologic approach. Int J Radiat Oncol Biol Phys 49:973-985, 2001.
2 LeChevalier T, Arriagada R, Quoix E, et al. Radiotherapy alone versus combined chemotherapy and radiotherapy in nonresectable non-small-cell lung cancer: First analysis of a randomized triall in 353 patients. J Natl Cancer Inst 1991:83:417-423.
3 王颖杰，王绿化，冯勤付，等．肺癌三维适形放射治疗中肺和食管损伤的相关因素分析．中国肺癌杂志，2005，8(5)：454-458．
4 Graham MV, Purdy JA, Emami B, et al. Clinical dose-volume histogram analysis for pneumonitis after 3D treatment for non-small cell lung cancer (NSCLC). Int J Radiat Oncol Biol Phys 1999;45:323-329.
5 Tsujino K, Hirota S, Endo M, et al. 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.
6 Chang DT, Olivier KR, Morris CG, et al. The impact of heterogeneity correction on dosimetric parameters that predict for radiation pneumonitis. Int J Radiat Oncol Biol Phys 2006 ; 65(1): 125-131.7 Hayman JA, Martek MK, Ten Haken RK, et al: Dose escalation in non-small-cell lung cancer using three-dimentional conformal radiation therapy : Update of a phase I trial. J Clin Oncol 19 :127-136,2001.
8 Anscher MS, Kong FM, Marks LB, et al: Changes in plasma transforming growth factor beta during radiotherapy and the risk of symptomatic radiation-induced pneumonitis. Int J Radiat Oncol Biol Phys 37 :253-258, 1997.
9 http://ctep. cancer.gov/reporting/ctc.html
10 Kocak Z, Evans ES, Zhou SM, et al. Challenges in defining radiation pneumonitis in patients with lung cancer. Int J Radiat Oncol Biol Phys 2005;62(3): 635-638.
11 Onishi H, Kuriyama K, Yamaguchi M, et al. Concurrent two-dimensional radiotherapy and weekly docetaxel in the treatment of stage III non-small cell lung cancer: A good local response but no good survival due to radiation pneumonitis. Lung Cancer 2003; 40:79-84.
12 Robnett TJ, Machtay M, Vines EF, et al. Factors predicting severe radiation pneumonitis in patients receiving definitive chemoradiation for lung cancer. Int J Radiat Oncol Biol Phys 2000;48:89-94.
13 Yorke ED, Jackson A, Rosenzweig KE, et al: Dose-volume factors contributing to the incidence of radiation pneumonitis in??Non-Small-Cell lung cancer patients treated with three-dimensional conformal radiation therapy. Int J Radiat Oncol Biol Phys 54 (2) :329-339,2002.
14 Yorke ED, Jackson A, Rosenzweig KE, et al: Correlation of dosimetric factors and radiation pneumonitis for Non-Small-Cell lung cancer patients in a recently completed dose escalation study. Int J Radiat Oncol Biol Phys 63 (3):672-682, 2005.
15 Hope AJ, Naqa EI, Bradley JD, et al: Radiation pneumonitis/fibrosis risk based on dosimetric, clinical, and location-related factors. Int J Radiat Oncol Biol Phys 65(1): 112-124,2006.
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