The past,present,and future of radiotherapy for stage IV non-small cell lung cancer
Lu Bing, Su Shengfa, He Zhixu
Department of Thoracic Oncology,Affiliated Hospital of Guizhou Medical University,Guizhou Cancer Hospital,Guiyang 550004,China (Lu B,Su SF); Guizhou Medical University,Guizhou Cancer Hospital,Guiyang 550025,China (He ZX);
Abstract：The efficacy of palliative care was definitive with two-dimensional radiotherapy for stage IV non-small cell lung cancer (NSCLC).However,theimpact of radiotherapy on survival was not well indicated,and some study resultsindicating prolonged survival were not accepted. Along with the advancesin three-dimensional radiotherapy (3DRT),wide application of comprehensive treatment,and the understanding of the association between different metastatic status and survival,prospective and retrospective studies have demonstrated that chemotherapy combined with 3DRT for primary tumor is more effective than chemoradiotherapy alone in improving symptoms and prolonging survival,especially for oligometastases of stage IV NSCLC.The dose to primary tumor is closely related to survival,and high-dose radiotherapy may be more likely to prolong survival. Further studies,however,areneeded to take into accountproblems such as thedose,timing,and technical selection of radiotherapy.
Lu Bing,Su Shengfa,He Zhixu. The past,present,and future of radiotherapy for stage IV non-small cell lung cancer[J]. Chinese Journal of Radiation Oncology, 2018, 27(1): 29-34.
[1] Postmus PE,Brambilla E,Chansky K,et al. The IASLC lung Cancer Staging Project:proposals for revision of the M descriptors in the forthcoming (seventh) edition of the TNM classification of lung cancer[J].J Thorac Oncol,2007,2(8):686-693.DOI:10.1097/JTO.0b013e31811f4703 [2] Eberhardt WEE,Mitchell A,Crowley J,et al. The IASLC lungcancer staging project:proposals for the revision of theM descriptors in the forthcoming eighth edition of theTNM classification of lung cancer[J].J ThoracOncol,2015,10(11):1515-1522.DOI:10.1097/JTO.0000000000000673 [3] SchillerJH. 晚期非小细胞肺癌的化疗[A]//Pass HI,Mitchell JB,Johnson DH,等.肺癌[M].冯玉麟,刘春涛,译.北京:人民卫生出版社,2002:819-832 [4] Morgensztern D,Waqar S,Subramanian J,et al. Improving survival for stageⅣnon-small cell lung cancer:a surveillance,epidemiology,and end results survey from1990 to 2005[J].J ThoracOncol,2009,4(12):1524-1529.DOI:10.1097/JTO.0b013e3181ba3634 [5] Gerber DE,Gandhi L,Costa DB.Management and future directions in non-small cell lungcancer with known activating mutations[J].AmSocClinOncolEduc Book,2014,e353-e365.DOI:10.14694/EdBook_AM.2014.34.e353 [6] Higginson DS,Chen RC,Tracton G,et al. The impact of local and regional disease extent onoverall survival in patients with advanced stage ⅢB/IVnon-small cell lung carcinoma[J].Int J RadiatOncolBiolPhys,2012,84(3):e385-e392.DOI:10.1016/j.ijrobp.2012.04.045 [7] Rusthoven KE,Hammerman SF,Kavanagh BD,et al. Is there a role for consolidative stereotactic bodyradiation therapy following first-line systemictherapy for metastatic lung cancer? A patterns-of-failure analysis[J].ActaOncol,2009,48(4):578-583.DOI:10.1080/02841860802662722 [8] Wagner H Jr. Just enough palliation:radiation dose and outcome in patients with non-small-cell lung cancer[J].J ClinOncol,2008,26(24):3920-3922.DOI:10.1200/JCO.2008.17.3674 [9] Schiller JH,Harrington D,Belani CP,et al. Comparison of four chemotherapy regimens for advancednon-small-cell lung cancer[J].N Engl J Med,2002,346(2):92-98.DOI:10.1056/NEJMoa011954 [10] Nagata Y,Negoro Y,Aoki T,et al. Clinical outcomes of 3D conformal hypofractionated single high-dose radiotherapyfor one or two lung tumors using a stereotactic body frame[J].Int J RadiatOncolBiolPhys,2002,52(4):1041-1046.DOI:10.1016/S0360-3016(01)02731-6 [11] SplinterTAW,Van SchilPE,KramerGWPM,et al. Randomized trial of surgery versus radiotherapy inpatients with stage ⅢA(N2) non–small-cell lungcancer after a response to induction chemotherapy:EORTC 08941[J].Clin Lung Cancer,2000,2(1):69-72.DOI:10.3816/CLC.2000.n.020 [12] LangendijkJA,TenVeldeGPM,AaronsonNK,et al. Qualityoflifeafterpalliativeradiotherapyinnon-small cell lung cancer:a prospective study[J].Int J RadiatOncolBiolPhys,2000,47(1):149-155.DOI:10.1016/S0360-3016(99)00540-4 [13] Nestle U,Nieder C,Walter M,et al. A palliative accelerated irradiation regimen for advanced non-small-cell lung cancerVS.conventionally fractionated 60GY:results of a randomized equivalence study[J].Int J RadiatOncolBiolPhys,2000,48(1):95-103.DOI:10.1016/S0360-3016(00)00607-6 [14] Bezjak A,Dixon P,Brundage M,et al. Randomizedphase Ⅲ trialofsingleversusfractionated thoracic radiation in the palliation of patients with lung cancer (NCIC CTG SC.15)[J].Int J RadiatOncolBiolPhys,2002,54(3):719-728.DOI:10.1016/S0360-3016(02)02989-9 [15] Sundstrøm S,Bremnes R,Aasebø U,et al. Hypofractionated palliative radiotherapy (17 Gy per twofractions) in advanced non–small-cell lung carcinomais comparable to standard fractionation for symptomcontrol and survival:a national phase Ⅲ trial[J].J ClinOncol,2004,22(5):801-810.DOI:10.1200/JCO.2004.06.123 [16] Kramer GWPM,Wanders SL,Noordijk EM,et al. Results of the Dutch national study of the palliativeeffect of irradiation using two different treatment schemes for non–small-cell lung cancer[J].J ClinOncol,2005,23(13):2962-2970.DOI:10.1200/JCO.2005.01.685 [17] Rodrigues G,Videtic GMM,Sur R,et al. Palliative thoracic radiotherapy in lung cancer:an American society for radiation oncologyevidence-based clinical practice guideline[J].PractRadiatOncol,2011,1(2):60-71.DOI:10.1016/j.prro.2011.01.005 [18] Fairchild A,Harris K,Barnes E,et al. Palliative thoracic radiotherapy for lung cancer:a systematic review[J].J ClinOncol,2008,26(24):4001-4011.DOI:10.1200/JCO.2007.15.3312 [19] 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 YH,Lu B,Zhou HN,et al. Clinical results of Ⅳ non-small cell lung cancer with concurrent radiotherapy[J].Chin J Radiat Oncol,2009,18(1):52-56.DOI:10.3760/cma.j.issn.1004-4221.2009.01.052 [20] Fang LC,Komaki R,Allen P,et al. Comparison of outcomes for patients with medically inoperable stage Ⅰ non-small-cell lung cancer treated with two-dimensional vs.three-dimensional radiotherapy[J].Int J RadiatOncolBiolPhys,2006,66(1):108-116.DOI:10.1016/j.ijrobp.2006.04.015 [21] Rusch V,Albain K,Turrisi A,et al. O-035Phase Ⅲ trial of concurrent chemotherapy and radiotherapy (CT/RT) vsCT/RT followed by surgical resection for stage Ⅲ a (pN2) non-small-cell lung cancer (NSCLC):outcomes and implications for surgical management in North American Intergroup 0139(RTOG 9309)[J].Lung Cancer,2005,49(S2):S15.DOI:10.1016/S0169-5002(05)80167-9 [22] Modi A,Vohra HA,WeedenDF.Does surgery for primary non-small cell lung cancer and cerebral metastasis have any impact on survival?[J].InteractCardiovascThoracSurg,2009,8(4):467-473.DOI:10.1510/icvts.2008.195776 [23] Ashworth AB,Senan S,Palma DA,et al. An individual patient data meta-analysis of outcomes and prognostic factors after treatment of oligometastatic non-smallcell lung cancer[J].Clin Lung Cancer,2014,15(5):346-355.DOI:10.1016/j.cllc.2014.04.003[24] 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):463-472.DOI:10.3760/cma.j.issn.1004-4221.2011.06.006.Su SF,Lu B,Zhang B,et al. A prospective study on concurrent chemotherapy and thoracic three-dimensional radiotherapy for stage Ⅳ non-small cell lung cancer (1)—survival and toxicity[J].Chin J Radiat Oncol,2011,20(6):463-472.DOI:10.3760/cma.j.issn.1004-4221.2011.06.006 [25] 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 [26] 张波,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(四)—近期疗效对生存的影响[J].中华放射肿瘤学杂志,2012,21(1):29-34.DOI:10.3760/cma.j.issn.1004-4221.2012.01.010.Zhang B,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 (4)——The impact of response on survival[J].Chin J Radiat Oncol,2012,21(1):29-34.DOI:10.3760/cma.j.issn.1004-4221.2012.01.010 [27] 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 [28] Ouyang WW,Su SF,Hu YX,et al. Radiation dose and survival of patients withstage Ⅳ non-small cell lung cancer undergoingconcurrent chemotherapy and thoracicthree-dimensional radiotherapy:reanalysisof the findings of a single-center prospectivestudy[J].BMC Cancer,2014,14:491-498.DOI:10.1186/1471-2407-14-491 [29] Su SF,Li T,Lu B,et al. Three-dimensional radiation therapy to the primary tumor with concurrent chemotherapy in patients with stage Ⅳnon-small cell lung cancer:results of a multicenter phase 2 study from PPRA-RTOG,China[J].Int J RadiatOncolBiolPhys,2015,93(4):769-777.DOI:10.1016/j.ijrobp.2015.08.012 [30] Koshy M,Malik R,Mahmood U,et al. Comparative effectiveness of aggressive locoregional therapy inmetastatic lung cancer:associations between high-dose thoracicradiation therapy and/or chemoradiation therapy and survival in alarge population-based cohort[J].Int J RadiatOncolBiolPhys,2015,93(3S):S68.DOI:10.1016/j.ijrobp.2015.07.163 [31] Machtay M,Bae K,Movsas B,et al. Higherbiologicallyeffectivedose ofradiotherapyisassociated withimprovedoutcomes forlocally advancednon-small cell lung carcinoma treated with chemoradiation:an analysis of the Radiation Therapy Oncology Group[J].Int J RadiatOncolBiolPhys,2012,82(1):425-434.DOI:10.1016/j.ijrobp.2010.09.004 [32] Jeremic B,Ghosh S,Fidarova E,et al. The international atomic energy agencyrandomized trial on chemotherapy with orwithout radiation therapy in advancednon-small cell lung cancer (NCT00864331)[J].Int J RadiatOncolBiolPhys,2017,99(2S):S103-S104.DOI:10.1016/j.ijrobp.2017.06.247 [33] Hellman S,Weichselbaum RR.Oligometastases[J].J ClinOncol,1995,13(1):8-10.DOI:10.1200/JCO.1995.13.1.8 [34] Sheu T,Heymach JV,Swisher SG,et al. Propensity score-matched analysisof comprehensive local therapy foroligometastatic non-small cell lungcancer that did not progress afterfront-line chemotherapy[J].Int J RadiatOncolBiolPhys,2014,90(4):850-857.DOI:10.1016/j.ijrobp.2014.07.012 [35] Parikh RB,Cronin AM,Kozono DE,et al. Definitive primary therapy in patients presentingwith oligometastatic non-small cell lung cancer[J].Int J RadiatOncolBiolPhys,2014,89(4):880-887.DOI:10.1016/j.ijrobp.2014.04.007 [36] Flannery TW,Suntharalingam M,Regine WF,et al. Long-term survival in patients with synchronous,solitary brain metastasis from non-small-cell lung cancer treated with radiosurgery[J].Int J RadiatOncolBiolPhys,2008,72(1):19-23.DOI:10.1016/j.ijrobp.2007.12.031 [37] Lopez Guerra JL,Gomez D,Zhuang Y,et al. Prognostic impact ofradiation therapy to the primary tumor in patients with non-small celllung cancer and oligometastasis at diagnosis[J].Int J RadiatOncolBiolPhys,2012,84(1):e61-e67.DOI:10.1016/j.ijrobp.2012.02.054 [38] Ouyang WW,Su SF,Ma Z,et al. Prognosis of non-small cell lung cancer patientswith bone oligometastases treated concurrentlywith thoracic three-dimensional radiotherapy andchemotherapy[J].RadiatOncol,2014,9:147.DOI:10.1186/1748-717X-9-147 [39] Su SF,Hu YX,Ouyang WW,et al. Might radiation therapy in addition tochemotherapy improve overall survival ofpatients with non-oligometastaticstage ⅠV non-small cell lung cancer?:secondaryanalysis of two prospective studies[J].BMC Cancer,2016,16:908.DOI:10.1186/s12885-016-2952-3 [40] 王春兰,苏胜发,欧阳伟炜,等.器官和病灶联合定义寡转移Ⅳ期NSCLC原发灶三维根治剂量放疗的意义—PPRA-RTOG 003再分析[J].中华放射肿瘤学杂志,2016,25(6):576-581.DOI:10.3760/cma.j.issn.1004-4221.2016.06.007.Wang CL,Su SF,Ouyang WW,et al. Significance of three-dimensional radical radiotherapy dose determined by organ-lesion combination for primary tumor of oligometastatic stage ⅠV NSCLC:a reanalysis of PPRA-RTOG 003[J].Chin J Radiat Oncol,2016,25(6):576-581.DOI:10.3760/cma.j.issn.1004-4221.2016.06.007 [41] Gomez DR,Blumenschein GR Jr,Lee JJ,et al. Local consolidative therapy versus maintenance therapy orobservation for patients with oligometastatic non-small-celllung cancer without progression after first-line systemictherapy:a multicentre,randomised,controlled,phase 2 study[J].Lancet Oncol,2016,17(12):1672-1682.DOI:10.1016/S1470-2045(16)30532-0 [42] Tamjeed Ahmed. Phase 2 trial of chemotherapy followed by consolidative radiation therapy forinitial treatment of oligomer tastaticNSCLC[J].J ClinOncol,2016,35(15S):460S [43] Su SF,Hu YX,Ouyang WW,et al. Overall survival and toxicities regarding thoracicthree-dimensional radiotherapy with concurrentchemotherapy for stage Ⅳ non-small cell lungcancer:results of a prospective single-center study[J].BMC Cancer,2013,13:474.DOI:10.1186/1471-2407-13-474 [44] Shaverdian N,Lisberg AE,Bornazyan K,et al. Impact of prior radiation therapy on the efficacyand toxicity of pembrolizumab in the treatmentof non-small cell lung cancer[J].Int J Radiat Oncol Biol Phys,2017,99(2S):S151.DOI:10.1016/j.ijrobp.2017.06.350 [45] Lovly CM,Iyengar P,Gainor JF,et al. Managing resistance to EFGR-and ALK-targeted therapies[J].Am Soc Clin Oncol Educ Book,2017,37:607-618.DOI:10.14694/EDBK_176251
2018, Vol. 27 
