Lung Dose Escalation

Part of the Medical Radiology book series (MEDRAD)


RTOG 73-01 established standard doses of radiation for the treatment of patients with stage III non-small-cell lung cancer at 60 Gy in 2 Gy per fraction. However, overall survival was still poor, and local failures were a continuing problem. Over the next 30 years, a number of single institution and multi institution studies have been performed, attempting to improve overall survival by reducing local failures through radiation dose escalation either alone or in combination with chemotherapy with promising results. Additionally, new technology has been developed that can improve tumor imaging, deliver more conformal RT with less dose to normal structures, and decreased the set-up uncertainties, which has increased the therapeutic ratio and now allows for even safer dose escalation. The present chapter reviews these studies and discusses the current status of radiation dose escalation for patients with stage III NSCLC.


Dose Escalation Planning Target Volume Maximum Tolerate Dose Clinical Target Volume Gross Tumor Volume 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



Radiation Therapy Oncology Group


Non-small-cell lung cancer


Radiation therapy




Surveillance, epidemiology and end result


Computed tomography


Fluorodeoxyglucose positron emission tomography


Gross tumor volume


Elective nodal irradiation


Clinical tumor volume


Planning target volume








Proton therapy


Intensity-modulated radiation therapy


Twice daily


Maximum tolerated dose


Memorial Sloan–Kettering Cancer Center


University of Michigan


Netherlands Cancer Institute


University of North Carolina


Three-dimensional conformal radiotherapy


Normal-tissue complication probability


Dose-volume histogram


V effective


Relative mean lung dose


Cancer and Leukemia Group B


North Central Cancer Treatment Group


  1. Belderbos JS, Heemsbergen WD, de Jaeger K, Baas P, Lebesque JV (2006) Final results of a Phase I/II dose escalation trial in non-small-cell lung cancer using three-dimensional conformal radiotherapy. Int J Radiat Oncol Biol Phys 66:126–134PubMedCrossRefGoogle Scholar
  2. Bogart JA et al (2010) Phase I study of accelerated conformal radiotherapy for stage I non-small-cell lung cancer in patients with pulmonary dysfunction: CALGB 39904. J Clin Oncol: Off J Am Soc Clin Oncol 28(2):202–206CrossRefGoogle Scholar
  3. Bradley J, Graham MV, Winter K, Purdy JA, Komaki R, Roa WH, Ryu JK, Bosch W, Emami B (2005) Toxicity and outcome results of RTOG 9311: a phase I–II dose escalation study using three-dimensional conformal radiotherapy in patients with inoperable non-small-cell lung carcinoma. Int J Radiat Oncol Biol Phys 61:318–328PubMedCrossRefGoogle Scholar
  4. Bradley JD, Moughan J, Graham MV, Byhardt R, Govindan R, Fowler J, Purdy JA, Michalski JM, Gore E, Choy H (2010) A phase I/II radiation dose escalation study with concurrent chemotherapy for patients with inoperable stages I to III non-small-cell lung cancer: phase I results of RTOG 0117. Int J Radiat Oncol Biol Phys 77:367–372PubMedCrossRefGoogle Scholar
  5. Bral S, Duchateau M, Versmessen H, Verdries D, Engels B, De Ridder M, Tournel K, Collen C, Everaert H, Schallier D, De Greve J, Storme G (2010) Toxicity report of a phase 1/2 dose escalation study in patients with inoperable, locally advanced nonsmall cell lung cancer with helical tomotherapy and concurrent chemotherapy. Cancer 116:241–250PubMedGoogle Scholar
  6. Chen AB et al (2011) Survival outcomes after radiation therapy for stage iii non-small-cell lung cancer after adoption of computed tomography-based simulation. J Clin Oncol: Off j Am Soc Clin Oncol 40:464Google Scholar
  7. Cox JD, Azarnia N, Byhardt RW, Shin KH, Emami B, Pajak TF (1990) A randomized phase I/II trial of hyperfractionated radiation therapy with total doses of 60.0–79.2 Gy: possible survival benefit with greater than or equal to 69.6 Gy in favorable patients with radiation therapy oncology group stage III non-small-cell lung carcinoma: report of Radiation Therapy Oncology Group 83-11. J Clin Oncol 8:1543–1555PubMedGoogle Scholar
  8. Curran W (2000) Phase III comparison of sequential vs. concurrent chemoradiation for patients with unresected stage III non-small-cell lung cancer (NSCLC): initial report of radiation therapy oncology group (RTOG) 9410. Pro Am Soc Clin Oncol 19S:1891aGoogle Scholar
  9. Dillman RO, Herndon J, Seagren SL, Eaton WL Jr, Green MR (1996) 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 88:1210–1215PubMedCrossRefGoogle Scholar
  10. Fried DB, Morris DE, Poole C, Rosenman JG, Halle JS, Detterbeck FC, Hensing TA, Socinski MA (2004) Systematic review evaluating the timing of thoracic radiation therapy in combined modality therapy for limited-stage small-cell lung cancer. J Clin Oncol 22:4837–4845PubMedCrossRefGoogle Scholar
  11. Graham MV, Purdy JA, Emami B, Harms W, Bosch W, Lockett MA, Perez CA (1999) Clinical dose-volume histogram analysis for pneumonitis after 3D treatment for non-small cell lung cancer (NSCLC). Int J Radiat Oncol Biol Phys 45:323–329PubMedCrossRefGoogle Scholar
  12. Hayman JA, Martel MK, Ten Haken RK, Normolle DP, Todd RF, Littles JF, Sullivan MA, Possert PW, Turrisi AT, Lichter AS (2001) Dose escalation in non-small-cell lung cancer using three-dimensional conformal radiation therapy: update of a phase I trial. J Clin Oncol 19:127–136PubMedGoogle Scholar
  13. Komaki R, Scott CB, Sause WT, Johnson DH, Taylor SG, Lee JS, Emami B, Byhardt RW, Curran WJ Jr, Dar AR, Cox JD (1997) Induction cisplatin/vinblastine, irradiation vs. irradiation in unresectable squamous cell lung cancer: failure patterns by cell type in RTOG 88–08/ECOG 4588. Radiation Therapy Oncology Group: Eastern Cooperative Oncology Group. Int J Radiat Oncol Biol Phys 39:537–544PubMedCrossRefGoogle Scholar
  14. Komaki R, Seiferheld W, Ettinger D, Lee JS, Movsas B, Sause W (2002) Randomized phase II chemotherapy and radiotherapy trial for patients with locally advanced inoperable non-small-cell lung cancer: long-term follow-up of RTOG 92-04. Int J Radiat Oncol Biol Phys 53:548–557PubMedCrossRefGoogle Scholar
  15. Narayan S, Henning GT, Ten Haken RK, Sullivan MA, Martel MK, Hayman JA (2004) Results following treatment to doses of 92.4 or 102.9 Gy on a phase I dose escalation study for non-small cell lung cancer. Lung Cancer 44:79–88PubMedCrossRefGoogle Scholar
  16. Perez CA, Stanley K, Rubin P, Kramer S, Brady L, Perez-Tamayo R, Brown GS, Concannon J, Rotman M, Seydel HG (1980) A prospective randomized study of various irradiation doses and fractionation schedules in the treatment of inoperable non-oat-cell carcinoma of the lung: preliminary report by the Radiation Therapy Oncology Group. Cancer 45:2744–2753PubMedCrossRefGoogle Scholar
  17. Rosenman JG, Halle JS, Socinski MA, Deschesne K, Moore DT, Johnson H, Fraser R, Morris DE (2002) High-dose conformal radiotherapy for treatment of stage IIIA/IIIB non-small-cell lung cancer: technical issues and results of a phase I/II trial. Int J Radiat Oncol Biol Phys 54:348–356PubMedCrossRefGoogle Scholar
  18. Rosenzweig KE, Fox JL, Yorke E, Amols H, Jackson A, Rusch V, Kris MG, Ling CC, Leibel SA (2005) Results of a phase I dose escalation study using three-dimensional conformal radiotherapy in the treatment of inoperable nonsmall cell lung carcinoma. Cancer 103:2118–2127PubMedCrossRefGoogle Scholar
  19. Rosenzweig KE, Sura S, Jackson A, Yorke E (2007) Involved-field radiation therapy for inoperable non small-cell lung cancer. J Clin Oncol 25:5557–5561PubMedCrossRefGoogle Scholar
  20. Sause WT, Scott C, Taylor S, Johnson D, Livingston R, Komaki R, Emami B, Curran WJ, Byhardt RW, Turrisi AT et al (1995) Radiation therapy oncology group (RTOG) 88–08 and eastern cooperative oncology group (ECOG) 4588: preliminary results of a phase III trial in regionally advanced, unresectable non-small-cell lung cancer. J Natl Cancer Inst 87:198–205PubMedCrossRefGoogle Scholar
  21. Sejpal S, Komaki R, Tsao A, Chang JY, Liao Z, Wei X, Allen PK, Lu C, Gillin M, Cox JD (2011) Early findings on toxicity of proton beam therapy with concurrent chemotherapy for nonsmall cell lung cancer. CancerGoogle Scholar
  22. Sura S, Gupta V, Yorke E, Jackson A, Amols H, Rosenzweig KE (2008) Intensity-modulated radiation therapy (IMRT) for inoperable non-small cell lung cancer: the Memorial Sloan-Kettering Cancer Center (MSKCC) experience. Radiother Oncol 87:17–23PubMedCrossRefGoogle Scholar
  23. Yeung AR, Li JG, Shi W, Newlin HE, Chvetsov A, Liu C, Palta JR, Olivier K (2009) Tumor localization using cone-beam CT reduces setup margins in conventionally fractionated radiotherapy for lung tumors. Int J Radiat Oncol Biol Phys 74:1100–1107PubMedCrossRefGoogle Scholar
  24. Yuan S, Sun X, Li M, Yu J, Ren R, Yu Y, Li J, Liu X, Wang R, Li B, Kong L, Yin Y (2007) A randomized study of involved-field irradiation versus elective nodal irradiation in combination with concurrent chemotherapy for inoperable stage III non-small-cell lung cancer. Am J Clin Oncol 30:239–244PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg  2011

Authors and Affiliations

  1. 1.University of Florida Proton Therapy InstituteJacksonvilleUSA
  2. 2.Mount Sinai School of MedicineNew YorkUSA

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