Review Article| Volume 34, ISSUE 1, P109-125, February 2020

Radiation Therapy for Thoracic Malignancies

Published:October 30, 2019DOI:


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        • Bray F.
        • Ferlay J.
        • Soerjomataram I.
        • et al.
        Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries.
        CA Cancer J Clin. 2018; 68: 394-424
        • Harris J.P.
        • Murphy J.D.
        • Hanion A.L.
        • et al.
        A population-based comparative effectiveness study of radiation therapy techniques in stage III non-small cell lung cancer.
        Int J Radiat Oncol Biol Phys. 2014; 88: 872-874
        • Sher D.J.
        • Koshy M.
        • Liptay M.J.
        • et al.
        Influence of conformal radiotherapy technique on survial after chemoradiotherapy for patients with stage III non-small cell lung cancer in the National Cancer Data Base.
        Cancer. 2014; 120: 2360-2368
        • Koshy M.
        • Malik R.
        • Spiotto M.
        • et al.
        Association between intensity modulated radiation therapy and survival in patients with stage III non-small cell lung cancer treated with chemoradiotherapy.
        Lung Cancer. 2017; 108: 222-227
        • Maguire P.D.
        • Marks L.B.
        • Sibley G.S.
        • et al.
        73.6Gy and beyond: hyperfrationated, accelerated radiotherapy for non-small-cell lung cancer.
        J Clin Oncol. 2001; 19: 705-711
        • Bogart J.A.
        • Aronowitz J.N.
        Localized non-small cell lung cancer: adjuvant radiotherapy in the era of effective systemic therapy.
        Clin Cancer Res. 2005; 11: 5004s-5010s
        • Bradley J.D.
        • Wahab S.
        • Lockett M.A.
        • et al.
        Elective nodal failures are uncommon in medically inoperable patients with Stage I non-small-cell lung carcinoma treated with limited radiotherapy fields.
        Int J Radiat Oncol Biol Phys. 2003; 56: 342-347
        • 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.
        Int J Radiat Oncol Biol Phys. 2005; 63: 324-333
        • Videtic G.M.
        • Stephans K.L.
        The role of stereotactic body radiotherapy in the management of non-small cell lung cancer: an emerging standard for the medically inoperable patient?.
        Curr Oncol Rep. 2010; 12: 235-241
        • Chua K.L.M.
        • Sin I.
        • Fong K.W.
        • et al.
        Stereotactic body radiotherapy for early stage lung cancer-historical developments and future strategies.
        Chin Clin Oncol. 2017; 6: S20
        • Nagata Y.
        • Kimura T.
        Stereotactic body radiotherapy (SBRT) for Stage I lung cancer.
        Jpn J Clin Oncol. 2018; 48: 405-409
        • Fernando H.C.
        • Timmerman R.
        American College of Surgeons Oncology Group Z4099/Radiation Therapy Oncology Group 1021: a randomized study of sublobar resection compared with stereotactic body radiotherapy for high-risk stage I non-small cell lung cancer.
        J Thorac Cardiovasc Surg. 2012; 144: S35-S38
      1. Trial of Either Surgery or Stereotactic Radiotherapy for Early Stage (IA) Lung Cancer (ROSEL).
        (Available at:) (Accessed June 20, 2018)
      2. Randomized Study to Compare CyperKnife to Surgical Resection in Stage I Non–Small Cell Lung Cancer (STARS).
        (Available at:) (Accessed June 20, 2018)
        • Chang J.Y.
        • Senan S.
        • Paul M.A.
        • et al.
        Stereotactic ablative radiotherapy versus lobectomy for operable stage I non-small-cell lung cancer: a pooled analysis of two randomised trials.
        Lancet Oncol. 2015; 16: 630-637
      3. Ca Sublobar Resection (SR) Versus Stereotactic Ablative Radiotherapy (SAbR) for Lung Cancer (STABLE-MATES).
        (Available at:) (Accessed June 20, 2018)
      4. Veteran Affairs Lung Cancer or Stereotactic Radiotherapy (VALOR). Available at: Accessed June 5, 2018.

      5. Radical Resection vs. Ablative Stereotactic Radiotherapy in Patients with Operable Stage I NSCLC (POSTILV).
        (Available at:) (Accessed June 20, 2018)
      6. A Study to Determine the Feasibility and Acceptability of Conducting a Phase III Randomised Controlled Trial Comparing Stereotactic Ablative Radiotherapy with Surgery in paTients with Peripheral Stage I Non-Small Cell Lung Cancer cOnsidered Higher Risk of Complications from Surgical Resection (SABRTOOTHv1).
        (Available at:) (Accessed July 31, 2019)
        • Liao Z.
        • Lee J.J.
        • Komaki R.
        • et al.
        Bayesian adaptive randomization trial of passive scattering proton therapy and intensity-modulated photon radiotherapy for locally advanced non-small-cell lung cancer.
        J Clin Oncol. 2018; 36: 1813-1822
        • Chang J.Y.
        • Zhang X.
        • Knopf A.
        • et al.
        Consensus guidelines for implementing pencil-beam scanning proton therapy for thoracic malignancies on behalf of the PTCOG Thoracic and Lymphoma Subcommittee.
        Int J Radiat Oncol Biol Phys. 2017; 99: 41-50
        • Natavithya C.
        • Gomez D.R.
        • Wei X.
        • et al.
        Phase 2 study of stereotactic body radiation therapy and stereotactic body proton therapy for high-risk, medically inoperable, early-stage non-small cell lung cancer.
        Int J Radiat Oncol Biol Phys. 2018; 101: 558-563
        • Timmerman R.D.
        • Paulus R.
        • Pass H.I.
        • et al.
        Stereotactic body radiation therapy for operable early-stage lung cancer: findings from the NRG oncology RTOG 0618 trial.
        JAMA Oncol. 2018; 4: 1263-1266
        • Bezjak A.
        • Paulus R.
        • Gaspar L.E.
        • et al.
        Safety and efficacy of a five-fraction stereotactic body radiotherapy schedule for centrally located non-small-cell lung Cancer: NRG Oncology/RTOG 0813 trial.
        J Clin Oncol. 2019; 37: 1316-1325
        • Chaudhuri A.A.
        • Tang C.
        • Binkley M.S.
        • et al.
        Stereotactic ablative radiotherapy (SABR) for treatment of central and ultra-central lung tumors.
        Lung Cancer. 2015; 89: 50-56
        • Tekatli H.
        • Haasbeek N.
        • Dahele M.
        • et al.
        Outcomes of hypofractionated high-dose radiotherapy in poor-risk patients with “ultracentral” non-small cell lung cancer.
        J Thorac Oncol. 2016; 11: 1081-1089
        • Daly M.
        • Novak J.
        • Monjazeb A.
        P2.05-056 safety of stereotactic body radiotherapy for central, ultracentral, and paramediastinal lung tumors.
        J Thorac Oncol. 2017; 12: S1066
        • Raman S.
        • Yau V.
        • Pineda S.
        • et al.
        Ultracentral tumors treated with stereotactic body radiotherapy: Singleinstitution experience.
        Clin Lung Cancer. 2018; 19: e803-e810
        • Chang J.H.
        • Poon I.
        • Erler D.
        • et al.
        The safety and effectiveness of stereotactic body radiotherapy for central versus ultracentral lung tumors.
        Radiother Oncol. 2018; 129: 277-283
        • Nguyen K.N.B.
        • Hause D.J.
        • Novak J.
        • et al.
        Tumor control and toxicity after SBRT for ultracentral, central, and paramediastinal lung tumors.
        Pract Radiat Oncol. 2019; 9: e196-e202
        • Aupérin A.
        • Le Péchoux C.
        • Rolland E.
        • et al.
        Meta-analysis of concomitant versus sequential radiochemotherapy in locally advanced non-small-cell lung cancer.
        J Clin Oncol. 2010; 28: 2181-2190
        • Bezjak A.
        • Temin S.
        • Franklin G.
        • et al.
        Definitive and adjuvant radiotherapy in locally advanced non-small-cell lung cancer: american society of clinical oncology clinical practice guideline endorsement of the american society for radiation oncology evidence-based clinical practice guideline.
        J Clin Oncol. 2015; 33: 2100-2105
        • Dillman R.O.
        • Herndon J.
        • Seagren S.L.
        • et al.
        Improved survival in stage III non-small-cell lung cancer: seven-year follow-up of cancer and leukemia group B (CALGB) 8433 trial.
        J Natl Cancer Inst. 1996; 88: 1210-1215
        • Curran Jr., W.J.
        • Paulus R.
        • Langer C.J.
        • 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: 1452-1460
        • Vokes E.E.
        • Herndon 2nd, J.E.
        • Kelley M.J.
        • et al.
        Induction chemotherapy followed by chemoradiotherapy compared with chemoradiotherapy alone for regionally advanced unresectable stage III Non-small-cell lung cancer: cancer and Leukemia Group B.
        J Clin Oncol. 2007; 25: 1698-1704
        • Kelly K.
        • Chansky K.
        • Gaspar L.E.
        • et al.
        Phase III trial of maintenance gefitinib or placebo after concurrent chemoradiotherapy and docetaxel consolidation in inoperable stage III non-small-cell lung cancer: SWOG S0023.
        J Clin Oncol. 2008; 26: 2450-2456
        • Ahn J.S.
        • Ahn Y.C.
        • Kim J.H.
        • et al.
        Multinational randomized phase III trial with or without consolidation chemotherapy using docetaxel and cisplatin after concurrent chemoradiation in inoperable stage III non-small-cell lung cancer: KCSG-LU05-04.
        J Clin Oncol. 2015; 33: 2660-2666
        • Bradley J.D.
        • Paulus R.
        • Komaki R.
        • et al.
        Standard-dose versus high-dose conformal radiotherapy with concurrent and consolidation carboplatin plus paclitaxel with or without cetuximab for patients with stage IIIA or IIIB non-small-cell lung cancer (RTOG 0617): a randomised, two-by-two factorial phase 3 study.
        Lancet Oncol. 2015; 16: 187-199
        • Senan S.
        • Brade A.
        • Wang L.H.
        • et al.
        PROCLAIM: randomized phase III trial of pemetrexed-cisplatin or etoposide-cisplatin plus thoracic radiation therapy followed by consolidation chemotherapy in locally advanced nonsquamous non-small-cell lung cancer.
        J Clin Oncol. 2016; 34: 953-962
        • Antonia S.J.
        • Villegas A.
        • Daniel D.
        • et al.
        Overall survival with durvalumab after chemoradiotherapy in stage III NSCLC.
        N Engl J Med. 2018; 379: 2342-2350
        • Belani C.P.
        • Choy H.
        • Bonomi P.
        • et al.
        Combined chemoradiotherapy regimens of paclitaxel and carboplatin for locally advanced non-small-cell lung cancer: a randomized phase II locally advanced multi-modality protocol.
        J Clin Oncol. 2005; 23: 5883-5891
        • Lee J.O.
        • Kim T.M.
        • Lee S.H.
        • et al.
        Anaplastic lymphoma kinase translocation: a predictive biomarker of pemetrexed in patients with non-small cell lung cancer.
        J Thorac Oncol. 2011; 6: 1474-1480
        • Yuan S.
        • Sun X.
        • Li M.
        • et al.
        A randomized study of involved-field irradiation versus elective nodal irradiation in combination with concurrent chemotherapy for inoperable stage III nonsmall cell lung cancer.
        Am J Clin Oncol. 2007; 30: 239-244
        • Speirs C.K.
        • DeWees T.A.
        • Rehman S.
        • et al.
        Heart dose is an independent dosimetric predictor of overall survival in locally advanced non-small cell lung cancer.
        J Thorac Oncol. 2017; 12: 293-301
        • Chun S.G.
        • Hu C.
        • Choy H.
        • et al.
        Impact of intensity-modulated radiation therapy technique for locally advanced non-small-cell lung cancer: a secondary analysis of the NRG oncology RTOG 0617 randomized clinical trial.
        J Clin Oncol. 2017; 35: 56-62
        • Johnson-Hart C.N.
        • Price G.J.
        • Faivre-Finn C.
        • et al.
        Residual setup errors towards the heart after image guidance linked with poorer survival in lung cancer patients: do we need stricter IGRT protocols?.
        Int J Radiat Oncol Biol Phys. 2018; 102: 434-442
        • Movsas B.
        • Hu C.
        • Sloan J.
        • et al.
        Quality of life analysis of a radiation dose-escalation study of patients with non-small-cell lung cancer: a secondary analysis of the radiation therapy oncology group 0617 randomized clinical trial.
        JAMA Oncol. 2016; 2: 359-367
        • Chang J.Y.
        • Verma V.
        • Li M.
        • et al.
        Proton beam radiotherapy and concurrent chemotherapy for unresectable stage III non-small cell lung cancer: final results of a phase 2 study.
        JAMA Oncol. 2017; 3: e172032
        • Albain K.S.
        • Swann R.S.
        • Rusch V.W.
        • et al.
        Radiotherapy plus chemotherapy with or without surgical resection for stage III non-small-cell lung cancer: a phase III randomised controlled trial.
        Lancet. 2009; 374: 379-386
        • Kim H.K.
        • Cho J.H.
        • Choi Y.S.
        • et al.
        Outcomes of neoadjuvant concurrent chemoradiotherapy followed by surgery for non-small-cell lung cancer with N2 disease.
        Lung Cancer. 2016; 96: 56-62
        • Lee H.
        • Ahn Y.C.
        • Pyo H.
        • et al.
        Pretreatment clinical mediastinal nodal bulk and extent do not influence survival in N2-positive stage IIIA non-small cell lung cancer patients treated with trimodality therapy.
        Ann Surg Oncol. 2014; 21: 2083-2090
        • Thomas M.
        • Rube C.
        • Hoffknecht P.
        • et al.
        Effect of preoperative chemoradiation in addition to preoperative chemotherapy: a randomised trial in stage III non-small-cell lung cancer.
        Lancet Oncol. 2008; 9: 636-648
        • Pless M.
        • Stupp R.
        • Ris H.B.
        • et al.
        Induction chemoradiation in stage IIIA/N2 non-small-cell lung cancer: a phase 3 randomised trial.
        Lancet. 2015; 386: 1049-1056
        • Katakami N.
        • Tada H.
        • Mitsudomi T.
        • et al.
        A phase 3 study of induction treatment with concurrent chemoradiotherapy versus chemotherapy before surgery in patients with pathologically confirmed N2 stage IIIA nonsmall cell lung cancer (WJTOG9903).
        Cancer. 2012; 118: 6126-6135
        • Girard N.
        • Mornex F.
        • Douillard J.Y.
        • et al.
        Is neoadjuvant chemoradiotherapy a feasible strategy for stage IIIA-N2 non-small cell lung cancer? Mature results of the randomized IFCT-0101 phase II trial.
        Lung Cancer. 2010; 69: 86-93
        • Arriagada R.
        • Auperin A.
        • Burdett S.
        • et al.
        • NSCLC Meta-analyses Collaborative Group
        Adjuvant chemotherapy, with or without postoperative radiotherapy, in operable non-small-cell lung cancer: Two meta-analyses of individual patient data.
        Lancet. 2015; 375: 1267-1277
        • Le Pechoux C.
        Role of postoperative radiotherapy in resected non-small cell lung cancer: a reassessment based on neew data.
        Oncologist. 2011; 16: 672-681
        • PORT Meta-analysis Trialists Group
        Postoperative radiotherapy for non-small cell lung cancer.
        Cochrane Database Syst Rev. 2015; (CD002142)
        • Lally B.E.
        • Zelterman D.
        • Colasanto J.M.
        • et al.
        Postoperative radiotherapy for stage II or III non-small-cell lung caner using the surveillance, epidemiology, and end results database.
        J Clin Oncol. 2006; 24: 2998-3006
        • Lally B.E.
        • Detterbeck F.C.
        • Geiger A.M.
        • et al.
        The risk of death from heart diseae in patients with nonsmall cell lung cancer who receive postoperative radiotherapy: Analysis of the Surveillance , Epidemiology, and End Results database.
        Cancer. 2007; 110: 911-917
        • Douillard J.Y.
        • Rosell R.
        • De Lena M.
        • et al.
        Impact of postoperative radiation therapy on survival in patietns with complete resection and stage I, II or IIIA non-small-cell lung cancer treated witih adjuvant chemotherapy: The Adjuvant Navelbine International Trialist Association (ANITA) randomized trial.
        Int J Radiat Oncol Biol Phys. 2008; 72: 695-701
        • Robinson C.G.
        • Patel A.P.
        • Bradley J.D.
        • et al.
        Postoperative radiotherapy for pathologic N2 non-small-cell lung cancer treated with adjuvant chemotherapy: a review of the National Cancer Data Base.
        J Clin Oncol. 2015; 33: 870-876
        • Zhang H.
        • Zhang D.X.
        • Ju T.
        • et al.
        The effect of postoperative radiotherapy on the survival of patients with resectable stage III-N2 non-small-cell lung cancer: a systematic review and meta-analysis.
        Neoplasma. 2019; 2019 ([pii:18123N965])
        • Formenti S.C.
        • Demaria S.
        Radiation therapy to convert the tumor into an in situ vaccine.
        Int J Radiat Oncol Biol Phys. 2012; 84: 879-880
        • Demaria S.
        • Golden E.B.
        • Formenti S.C.
        Role of local radiation therapy in cancer immunotherapy.
        JAMA Oncol. 2015; 1: 1325-1332
        • Reits E.A.
        • Hodge J.W.
        • Herberts C.A.
        • et al.
        Radiation modulates the peptide repertoire, enhances MHC class I expression, and induces successful antitumor immunotherapy.
        J Exp Med. 2006; 203: 1259-1271
        • Sharabi A.B.
        • Lim M.
        • DeWeese T.L.
        • et al.
        Radiation and checkpoint blockade immunotherapy: radiosensitisation and potential mechanisms of synergy.
        Lancet Oncol. 2015; 16: e498-e509
        • Sharabi A.B.
        • Nirschl C.J.
        • Kochel C.M.
        • et al.
        Stereotactic radiation therapy augments antigen-specific pd-1-mediated antitumor immune responses via cross-presentation of tumor antigen.
        Cancer Immunol Res. 2015; 3: 345-355
        • Gupta A.
        • Probst H.C.
        • Vuong V.
        • et al.
        Radiotherapy promotes tumor-specific effector CD8+ T cells via dendritic cell activation.
        J Immunol. 2012; 189: 558-566
        • Liao Y.P.
        • Wang C.C.
        • Butterfield L.H.
        • et al.
        Ionizing radiation affects human MART-1 melanoma antigen processing and presentation by dendritic cells.
        J Immunol. 2004; 173: 2462-2469
        • Herter-Sprie G.S.
        • Koyama S.
        • Korideck H.
        • et al.
        Synergy of radiotherapy and PD-1 blockade in Kras-mutant lung cancer.
        JCI Insight. 2016; 16: e87415
        • Twyman-Saint Victor C.
        • Rech A.J.
        • Maity A.
        • et al.
        Radiation and dual checkpoint blockade activate non-redundant immune mechanisms in cancer.
        Nature. 2015; 520: 373-377
        • Shaverdian N.
        • Lisberg A.E.
        • Bornazyan K.
        • et al.
        Previous radiotherapy and the clinical activity and toxicity of pembrolizumab in the treatment of non-small-cell lung cancer: a secondary analysis of the KEYNOTE-001 phase 1 trial.
        Lancet Oncol. 2017; 18: 895-903
      7. Tokito T, MS, Kurata T, et al. Overall Survival with Durvalumab vs. Placebo after Chemoradiotherapy in Stage III NSCLC: PACIFIC. 58th annual meeting of Japanese Lung Cancer Society 2017: Yokohama, October 14–15, 2017. p. S1–4.

        • Ning M.S.
        • Gomez D.R.
        • Heymach J.V.
        • et al.
        Stereotactic ablative body radiation for oligometastatic and oligoprogressive disease.
        Transl Lung Cancer Res. 2019; 8: 97-106
        • Gomez D.R.
        • Blumenschein Jr., G.R.
        • Lee J.J.
        • et al.
        Local consolidative therapy versus maintenance therapy or observation for patients with oligometastatic non-smallcell lung cancer without progression after first-line systemic therapy: a multicentre, randomised, controlled, phase 2 study.
        Lancet Oncol. 2016; 17: 1672-1682
        • Iyengar P.
        • Wardak Z.
        • Gerber D.E.
        • et al.
        Consolidative radiotherapy for limited metastatic non-small-cell lung cancer: a phase 2 randomized clinical trial.
        JAMA Oncol. 2018; 4: e173501
        • Palma D.A.
        • Haasbeek C.J.
        • Rodrigues G.B.
        • et al.
        Stereotactic ablative radiotherapy for comprehensive treatment of oligometastatic tumors (SABR-COMET): study protocol for a randomized phase II trial.
        BMC Cancer. 2012; 12: 305
        • Panje C.M.
        • Dedes K.J.
        • Matter-Walstra K.
        • et al.
        A cost-effectiveness analysis of consolidative local therapy in oligometastatic non-squamous non-small cell lung cancer (NSCLC).
        Radiother Oncol. 2018; 129: 257-263
        • Weickhardt A.J.
        • Scheier B.
        • Burke J.M.
        • et al.
        Local ablative therapy of oligoprogressive disease prolongs disease control by tyrosine kinase inhibitors in oncogene-addicted non-small-cell lung cancer.
        J Thorac Oncol. 2012; 7: 1807-1814
        • Chan O.S.H.
        • Lee V.H.F.
        • Mok T.S.K.
        • et al.
        The role of radiotherapy in epidermal growth factor receptor mutation-positive patients with oligoprogression: a matched-cohort analysis.
        Clin Oncol (R Coll Radiol). 2017; 29: 568-575