A prospective, multicenter, phase II clinical study of three-dimensional radiotherapy with concurrent chemotherapy for stage IV non-small-cell lung cancer—PPRA-RTOG003
Ma Zhu*, Lu Bing, Li Tao, Li Jiancheng, Wang Xiaohu, Lu You, Chen Ming, Bai Yuju, Su Shengfa, Hu Yinxiang, Ouyang Weiwei, Li Qingsong, Li Huiqin, Wang Yu,Zhang Bo
*Department of Oncology, Guizhou Province Cancer Hospital,Affiliated Hospital of Guiyang Medical College,Guiyang 550004,China
Objective To investigate the efficacy and safety of three-dimensional radiotherapy (3DRT) with concurrent chemotherapy for stage IV non-small-cell lung cancer (NSCLC). Methods A total of 198 eligible patients from 2008 to 2012 were enrolled as subjects. With an age ranging between 18 and 80 years and a Karnofsky Performance Status (KPS) score of 70 or more, those patients had no contraindication for radiotherapy and chemotherapy, and were newly diagnosed with stage IV NSCLC confirmed by histology or cytology, as well as limited metastatic disease (≤3 organs). Survival rates and acute toxicities in those patients were evaluated. Results The 3-year follow-up rate was 98.5% and the 3-year sample size was 165. The median overall survival (OS) and progression-free survival (PFS) were 13.0 months (95%CI,11.7-14.3 months) and 9.0 months (95%CI,7.7-10.3 months), respectively, while the 1-, 2-, and 3-year OS rates were 53.5%, 15.8%, and 9.2%, respectively. Multivariate analysis showed that a primary tumor volume smaller than 134 cm3, a stable or increased KPS score after treatment, and a radiation dose of 63 Gy or more were independent prognostic factors for longer survival time (P=0.008;P=0.010;P=0.014). The incidence rates of grade 3-4 neutropenia, thrombocytopenia, anemia, grade 3 radiation esophagitis, and grade 3 radiation pneumonitis were 37.9%, 10.1%, 6.9%, 2.5%, and 6.6%, respectively. The maincause of death was distant metastasis, and only 10% of the patients died of recurrence alone. Conclusions 3DRT with concurrent chemotherapy achieves satisfactory treatment outcomes with tolerable toxicities for stage IV NSCLC. Primary tumor volume, change in the KPS score after treatment, and radiation dose are independent prognostic factors for OS.Clinical Trial Registry Chinese Clinical Reistry,registration number:ChiCTRC10001026.
Ma Zhu,Lu Bing,Li Tao et al. A prospective, multicenter, phase II clinical study of three-dimensional radiotherapy with concurrent chemotherapy for stage IV non-small-cell lung cancer—PPRA-RTOG003[J]. Chinese Journal of Radiation Oncology, 2015, 24(4): 359-363.
[1] Tanaka T, Matsuoka M, Sutani A, et al. Frequency of and variables associated with the EGFR mutation and its subtypes[J]. Int J Cancer,2010,126(3):651-655.DOI:10.1002/ijc.24746. [2] Qian H,Gao F,Wang H,et al. The efficacy and safety of crizotinib in the treatment of anaplastic lymphoma kinase-positive non-small cell lung cancer:a meta-analysis of clinical trials[J]. BMC Cancer,2014,14(1):683.DOI:10.1186/1471-2407-14-683. [3] Schiller JH,Harrington D,Belani CP,et al. Comparison of four chemotherapy regimens for advanced non-small-cell lung cancer[J]. N Engl J Med,2002,346(2):92-98.DOI:10.1056/NEJMoa011954. [4] Morgensztern D,Waqar S,Subramanian J,et al. Improving survival for stage Ⅳ non-small cell lung cancer:a surveillance,epidemiology,and end results survey from 1990 to 2005[J]. J Thorac Oncol,2009,4(12):1524-1529.DOI:10.1097/JTO.0b013e3181ba3634. [5] 苏胜发,卢冰,张波,等.Ⅳ期非小细胞肺癌化疗同期胸部三维放疗的前瞻性临床研究(一)——疗效与不良反应[J].中华放射肿瘤学杂志,2011,20(6):467-472.DOI:10.3760/cma.j.issn.1004-4221.2011.06.006. [6] Lopez-Guerra JL,Gomez D,Zhuang Y,et al. Prognostic impact of radiation therapy to the primary tumor in patients with non-small cell lung cancer and oligometastasis at diagnosis[J]. Int J Radiat Oncol Biol Phys,2012,84(1):61-67.DOI:10.1016/j.ijrobp.2012.02.054. [7] Parikh RB,Cronin AM,Kozono DE,et al. Definitive primary therapy in patients presenting with oligometastatic non-small cell lung cancer[J]. Int J Radiat Oncol Biol Phys,2014,89(4):880-887.DOI:10.1016/j.ijrobp.2014.04.007. [8] De Ruysscher D,Wanders R,van Baardwijk A,et al. Radical treatment of non-small-cell lung cancer patients with synchronous oligometastases:long-term results of a prospective phase Ⅱ trial (Nct01282450)[J]. J Thorac Oncol,2012,7(10):1547-1555.DOI:10.1097/JTO.0b013e318262caf6. [9] Scagliotti GV,Parikh P,von Pawel J,et al. Phase Ⅲ study comparing cisplatin plus gemcitabine with cisplatin plus pemetrexed in chemotherapy-naive patients with advanced-stage non-small-cell lung cancer[J]. J Clin Oncol,2008,26(21):3543-3551.DOI:10.1200/JCO.2007.15.0375. [10] Detterbeck FC,Boffa DJ,Tanoue LT. The new lung cancer staging system[J].Chest,2009,136(1):260-271.DOI:10.1378/chest.08-0978. [11] Werner-Wasik M,Swann RS,Bradley J,et al. Increasing tumor volume is predictive of poor overall and progression-free survival:secondary analysis of the Radiation Therapy Oncology Group 93-11 phase Ⅰ-Ⅱ radiation dose-escalation study in patients with inoperable non-small-cell lung cancer[J]. Int J Radiat Oncol Biol Phys,2008,70(2):385-390.DOI:10.1016/j.ijrobp.2007.06.034. [12] Ouyang WW,Su SF,Hu YX,et al. Radiation dose and survival of patients with stage Ⅳ non-small cell lung cancer undergoing concurrent chemotherapy and thoracic three-dimensional radiotherapy:reanalysis of the findings of a single-center prospective study[J]. BMC Cancer,2014,14(1):491.DOI:10.1186/1471-2407-14-491. [13] Higginson DS,Chen RC,Tracton G,et al. The impact of local and regional disease extent on overall survival in patients with advanced stage ⅢB/Ⅳ non-small cell lung carcinoma[J]. Int J Radiat Oncol Biol Phys,2012,84(3):385-392.DOI:10.1016/j.ijrobp.2012.04.045. [14] Curran WJ Jr, Paulus R,Langer CJ,et al. Sequential vs. concurrent chemoradiation for stage Ⅲ non-small cell lung cancer:randomized phase Ⅲ trial RTOG 9410. J Natl Cancer Inst,2011,103(19):1452-1460.DOI:10.1093/jnci/djr325. [15] Ball D,Smith J,Bishop J,et al. A phase Ⅲ study of radiotherapy with and without continuous-infusion fluorouracil as palliation for non-small-cell lung cancer[J]. Br J Cancer,1997,75(5):690-697. [16] Scagliotti GV,De Marinis F,Rinaldi M,et al. Phase Ⅲ randomized trial comparing three platinum-based doublets in advanced non-small-cell lung cancer[J]. J Clin Oncol,2002,20(21):4285-4291. [17] Fournel 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 Francais de Pneumo-Cancerologie NPC 95-01 Study[J]. J Clin Oncol,2005,23(25):5910-5917.DOI:10.1200/JCO.2005.03.070.