Department of Oncology (Hu C),Tissue Engineering and Stem Cell Research Center (He ZX),Affiliated Hospital of Guizhou Medical University;Department of Thoracic Oncology (Hu YX,Ma Z,Ouyang WW,Su SF,Li QS,Wang Y,Li HQ,Lu B),Guizhou Cancer Hospital,Guiyang 550004,China
Abstract：Objective To retrospectively analyze the effect of three-dimensional radiotherapy on the survival of patients with stage Ⅳ squamous cell lung cancer. Methods Of the 101 patients collected from two prospective phase Ⅱ studies, 88 were part of the per-protocol set. All patients received platinum-doublet chemotherapy with concurrent radiation to the primary tumor. Primary endpoints were overall survival (OS) and progression-free survival (PFS). Survival was calculated using the Kaplan-Meier estimator, and univariate and multivariate analyses were performed using the log-rank test and Cox model, respectively. Results The 1-, 2-, 3-, and 5-year OS rates of the 88 patients were 42.2%, 13.6%, 8.7%, and 3.1%, respectively, and the median survival time (MST) was 10 months. The 1-, 2-, 3-, and 5-year OS and MST at PTV dose ≥63 Gy were 45.7%, 25.7%, 17.1%, 7.1%, and 11 months, respectively, whereas the 1-, 2-, 3-, and 5-year OS and MST at PTV dose<63 Gy were 39.6%, 4.5%, 2.8%, 0%, and 10 months, respectively (P=0.007). The median PFS at ≥63 Gy and<63 Gy were 9 months and 7 months, respectively (P=0.032). The 1-, 2-, 3-, and 5-year OS and PFS of patients who received 4 cycles of chemotherapy at a PTV dose of ≥63 Gy were 51.9%, 29.6%, 18.5%, 9.9%, and 9 months, respectively (P=0.001 and P=0.012), which were significantly prolonged compared with other treatment modalities. Multivariate analysis showed that PTV ≥63 Gy may be influence the OS of patients (P=0.080). Conclusions Three-dimensional radiotherapy can prolong the survival of patients with stage ⅠV squamous cell lung cancer, as demonstrated by the gradual improvement in OS and PFS following the increase in the intensity of concurrent chemotherapy and radiation therapy. A PTV dose of ≥63 Gy may be influence the OS.
Hu Cheng,Hu Yinxiang,Ma Zhu et al. Effect of three-dimensional radiotherapy on the survival of patients with stage Ⅳ squamous cell lung cancer[J]. Chinese Journal of Radiation Oncology, 2017, 26(9): 1019-1023.
[1] Youlden DR,Cramb SM,Baade PD.The international epidemiology of lung cancer:geographical distribution and secular trends[J].J Thora Oncol,2008,3(8):819-831.DOI:10.1097/JTO.0b013e31818020eb. [2] Miller KD,Siegel RL,Lin CC,et al. Cancer treatment and survivorship statistics,2016[J].Ca A Cancer J Clin,2016,66(4):271-289.DOI:10.3322/caac.21332. [3] Pazares LG,Marinis FD,Dediu M,et al. PARAMOUNT:final overall survival results of the phase Ⅲ study of maintenance pemetrexed versus placebo immediately after induction treatment with pemetrexed plus Cisplatin for advanced nonsquamous non-small-cell lung cancer[J].J Clin Oncol,2013,31(23):2895-2902.DOI:10.1200/JCO.2012.47.1102. [4] Zhou C,Wu Y L,Chen G,et al. BEYOND:a randomized,double-blind,placebo-controlled,multicenter,phase Ⅲ study of first-line carboplatin/paclitaxel plus bevacizumab or placebo in chinese patients with advanced or recurrent nonsquamous non–small-cell lung cancer[J].J Clin Oncol,2015,33(19):2197-2204.DOI:10.1200/JCO.2014.59.4424. [5] Shi Y,Au JS,Thongprasert S,et al. A prospective,molecular epidemiology study of EGFR mutations in Asian patients with advanced non-small-cell lung cancer of adenocarcinoma histology (PIONEER)[J].J Thorac Oncol,2014,9(2):154-162.DOI:10.1097/JTO.0000000000000033. [6] Zhang NN,Liu YT,Ma L,et al. The molecular detection and clinical significance of alk rearrangement in selected advanced non-small cell lung cancer:ALK expression provides insights into ALK targeted therapy[J/OL].Plos One,2014,9(1):e84501.DOI:10.1371/journal.pone.0084501. [7] Wang J,Dong Y,Cai Y,et al. Clinicopathologic characteristics of ALK rearrangements in primary lung adenocarcinoma with identified EGFR and KRAS status[J].J Cancer Res Clin Oncol,2014,140(3):453-460.DOI:10.1007/s00432-014-1584-8. [8] Reck M,Rodríguez-Abreu D,Robinson AG,et al. Pembrolizumab versus chemotherapy for PD-L1-positive non-small-cell lung cancer[J].New Engl J Med,2016,375(19):1823-1833.DOI:10.1056/NEJMoa1606774. [9] Network TCGA.Comprehensive genomic characterization of squamous cell lung cancers[J].Nature,2012,489(7417):519-525.DOI:10.1038/nature11404. [10] Drilon A,Rekhtman N,Ladanyi M,et al. Squamous-cell carcinomas of the lung:emerging biology,controversies,and the promise of targeted therapy[J].Lancet Oncol,2012,13(10):e418-426.DOI:10.1016/S1470-2045(12)70291-7. [11] Masters GA,Temin S,Azzoli CG,et al. Systemic therapy for stage iv non–small-cell lung cancer:american society of clinical oncology clinical practice guideline update[J].J Clin Oncol,2010,27(36):3488-3515.DOI:10.1200/JCO.2015.62.1342. [12] 付和谊,卢冰,周华宁,等.Ⅳ期非小细胞肺癌同期化放疗的临床结果分析[J].中华放射肿瘤学杂志,2009,18(1):52-56.DOI:10.3760/cma.j.issn.1004-4221.2009.01.052. Fu HY,Lu B,Zhou HN,et al. Clinical outcome of concurrent chemo-radiotherapy for patients with stage Ⅳ non-small cell lung cancer[J].Chin J Radiat Oncol,2009,18(1):52-56.DOI:10.3760/cma.j.issn.1004-4221.2009.01.052. [13] 王刚,卢冰,苏胜发,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(二)——不同器官转移状态对生存的影响[J].中华放射肿瘤学杂志,2011,20(6):473-477.DOI:10.3760/cma.j.issn.1004-4221.2011.06.007. Wang G,Lu B,Su SF,et al. A prospective study on concurrent chemotherapy and thoracic three-dimensional radiotherapy for stage Ⅳ non-small cell lung cancer (2) — The impact of different metastasis organs on survival[J].Chin J Radiat Oncol,2011,20(6):473-477.DOI:10.3760/cma.j.issn.1004-4221.2011.06.007. [14] Su SF,Hu YX,Ouyang WW,et al. Overall survival and toxicities regarding thoracic three-dimensional radiotherapy with concurrent chemotherapy for stage ⅠV non-small cell lung cancer:results of a prospective single-center study[J].BMC Cancer,2013,13(1):474.DOI:10.1186/1471-2407-13-474. [15] Su S,Li T,Lu B,et al. Three-dimensional radiation therapy to the primary tumor with concurrent chemotherapy in patients with stage ⅠV non-small cell lung cancer:results of a multicenter phase 2 study from PPRA-RTOG,China[J].Int J Radiat Oncol Biol Phys,2015,93(4):769-777.DOI:10.1016/j.ijrobp.2015.08.012. [16] Padhani AR,Ollivier L.The RECIST criteria:implications for diagnostic radiologists[J].Br J Radiol,2001,74(887):983-986. [17] 刘艳.原发性肺鳞癌的CT表现[J].中国医学影像技术,2002,18(5):436-437. Liu Y.The CT features of primary pulmonary squamous carcinoma[J].Chin Med Imag Technol,2002,18(5):436-437. [18] 李玉,李厚文.肺癌淋巴结转移规律的临床研究[J].中华胸心血管外科杂志,2000,16(1):10-12. Li Y,Li HW.Clinical study of lymph node metastasis in lung cancer[J].Chin J Thora Cardiovascul Surg,2000,16(1):10-12. [19] 李凤虎,卢冰,付和谊,等.546例Ⅳ期非小细胞肺癌远处转移特点的放疗意义分析[J].中华放射肿瘤学杂志,2012,21(2):122-125.DOI:10.3760/cma.j.issn.1004-4221.2012.02.008. Li FH,Lu B,Fu HY,et al. Metastasis features of 546 patients with stage Ⅳ non-small cell lung cancer at first visit and the significance in radiotherapy[J].Chin J Radiat Oncol,2012,21(2):122-125.DOI:10.3760/cma.j.issn.1004-4221.2012.02.008. [20] Mujoomdar A,Austin J H M,Malhotra R,et al. Clinical Predictors of Metastatic Disease to the Brain from Non–Small Cell Lung Carcinoma:PrimaryTumor Size,Cell Type,and Lymph Node Metastases1[J].Radiology,2007,242(3):882-888.DOI:10.1148/radiol.2423051707 [21] Perez C A,Pajak T F,Rubin P,et al. Long-term observations of the patterns of failure in patients with unresectable non-oat cell carcinoma of the lung treated with definitive radiotherapy. Report by the Radiation Therapy Oncology Group.[J].Cancer,1987,59(11):1874-1881. [22] 邓蓉,李涛,李建成,等.Ⅳ期NSCLC化疗同期3DRT前瞻性、多中心Ⅱ期临床研究—不同病理类型生存再分析(PPRA-RTOG003)[J].中华放射肿瘤学杂志,2016,25(10):1051-1056.DOI:10.3760/cma.j.issn.1004-4221.2016.10.006. Deng R,Li T,Li JC,et al. A prospective,multicenter,phase Ⅱ clinical study of three-dimensionalradiotherapy with concurrent chemotherapy for stage ⅠV non-small-cell lung cancer-The impact of different pathological types on survival (PPRA-RTOG003)[J].Chin J Radiat Oncol,2016,25(10):1051-1056.DOI:10.3760/cma.j.issn.1004-4221.2016.10.006 [23] Schiller JH., David Harrigton. Comparison of four chemotherapy regimems for advanced NSCLC[J].N Engl J Med,2002;346:92-8. [24] 龙金华,卢冰,欧阳伟炜,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(三)——不同放疗剂量对生存的影响[J].中华放射肿瘤学杂志,2012,21(1):23-27.DOI:10.3760/cma.j.issn.1004-4221.2012.01.008. Long JH,Lu B,Ouyang WW,et al. A prospective study on concurrent chemotherapy and thoracic three-dimensional radiotherapy for stage Ⅳ non-small cell lung cancer (3)-The impact of radiation dose to thoracic primary tumor on survival[J].Chin J Radiat Oncol,2012,21(1):23-27.DOI:10.3760/cma.j.issn.1004-4221.2012.01.008. [25] Lopez Guerra J L,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].2012,84(1):e61-e67.DOI:10.1016/j.ijrobp.2012.02.054. [26] Smith S L,Palma D,Parhar T.Inoperable early stage non-small cell lung cancer:comorbidity,patterns of care and survival.[J].Lung Cancer,2011,72(1):39-44.DOI:10.1016/j.lungcan.2010.07.015. [27] Kong F M,Ten Haken R K,Schipper M J,et al. High-dose radiation improved local tumor control and overall survival in patients with inoperable/unresectable non-small-cell lung cancer:long-term results of a radiation dose escalation study.[J].International Journal of Radiation Oncology Biology Physics,2005,63(2):324-333.DOI:10.1016/S0169-5002(05)81117-1. [28] Komaki R,Scott C B,Sause W T,et al. Induction cisplatin/vinblastine and irradiation vs.irradiation in unresectable squamous cell lung cancer:Failure patterns by cell type in rtog 88-08/ECOG 4588[J].Int J Radiat Oncol Biol Phys,1997,39(3):537-544. [29] Koshy M,Malik R,Mahmood U,et al. The comparative effectiveness of aggressive thoracic radiotherapy and concurrent chemoradiotherapy in metastatic lung cancer[J].Practical Radiation Oncology,2015,5(6):374-382.DOI:10.1016/j.prro.2015.07.009. [30] Machtay M,Bae K,Movsas B,et al. Higher biologically effective dose of radiotherapy is associated with improved outcomes for locally advanced non–small cell lung carcinoma treated with chemoradiation:an analysis of the radiation therapy oncology group[J].Int J Radiat Oncol Biol Phys,2012,82(1):425-434.DOI:10.1016/j.ijrobp.2010.09.004.
2017, Vol. 26 
