Radiotherapy & Oncology
Volume 93, Issue 3 , Pages 389-395 , December 2009

Can we optimize chemo-radiation and surgery in locally advanced stage III non-small cell lung cancer based on evidence from randomized clinical trials? A hypothesis-generating study

  • Dirk De Ruysscher

      Affiliations

    • Maastricht University Medical Center, Department of Radiation Oncology (Maastro Clinic), The Netherlands
    • Corresponding Author InformationCorresponding author. Address: Maastricht University Medical Center+, Department of Radiation Oncology (Maastro Clinic), GROW Research Institute, Dr. Tanslaan 12, 6229 ET Maastricht, The Netherlands.
    • ,
  • Cary Dehing

      Affiliations

    • Maastro Clinic, Maastricht, The Netherlands
    • ,
  • Søren M. Bentzen

      Affiliations

    • University of Wisconsin School of Medicine and Public Health, Department of Human Oncology, Madison, WI, USA
    • ,
  • Ruud Houben

      Affiliations

    • Maastro Clinic, Maastricht, The Netherlands
    • ,
  • André Dekker

      Affiliations

    • Maastro Clinic, Maastricht, The Netherlands
    • ,
  • Rinus Wanders

      Affiliations

    • Maastro Clinic, Maastricht, The Netherlands
    • ,
  • Jacques Borger

      Affiliations

    • Maastro Clinic, Maastricht, The Netherlands
    • ,
  • Monique Hochstenbag

      Affiliations

    • Maastricht University Medical Center, Department of Pulmonology, The Netherlands
    • ,
  • Liesbeth Boersma

      Affiliations

    • Maastro Clinic, Maastricht, The Netherlands
    • ,
  • Gijs Geskes

      Affiliations

    • Maastricht University Medical Center, Department of Surgery, The Netherlands
    • ,
  • Anne-Marie C. Dingemans

      Affiliations

    • Maastricht University Medical Center, Department of Pulmonology, The Netherlands
    • ,
  • Gerben Bootsma

      Affiliations

    • Atrium Medical Center, Department of Pulmonology, Heerlen, The Netherlands
    • ,
  • Guido Lammering

      Affiliations

    • Maastro Clinic, Maastricht, The Netherlands
    • ,
  • Philippe Lambin

      Affiliations

    • Maastricht University Medical Center, Department of Radiation Oncology (Maastro Clinic), The Netherlands

Received 6 February 2009 ,Revised 27 May 2009 ,Accepted 1 June 2009.

References 

  1. Non-small Cell Lung Cancer Collaborative Group. Chemotherapy in non-small cell lung cancer: a meta-analysis using updated data on individual patients from 52 randomised clinical trials. Br Med J. 1995;311:899–909
  2. 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 Français de Pneumo-Cancérologie NPC 95-01 Study. J Clin Oncol. 2005;23:5910–5917
  3. Furuse K, Fukuoka M, Kawahara M, et al. Phase III study of concurrent versus sequential thoracic radiotherapy in combination with mitomycin, vindesine, and cisplatin in unresectable stage III non-small-cell lung cancer. J Clin Oncol. 1999;17:2692–2699
  4. Curran WJ, Scott CB, Langer CJ, et al. Long-term benefit is observed in a phase III comparison of sequential vs concurrent chemoradiation for patients with unresectable stage III nsclc: RTOG 94-10. Proc Am Soc Clin Oncol. 2003;22:621a;(Abstr 2499)
  5. Zatloukal P, Petruzelka L, Zemanova M, et al. Concurrent versus sequential chemoradiotherapy with cisplatin and vinorelbine in locally advanced non-small cell lung cancer: a randomized study. Lung Cancer. 2004;46:87–98
  6. Rowell NP, O’rourke NP. Concurrent chemoradiotherapy in non-small cell lung cancer. Cochrane Database Syst Rev. 2004;CD002140
  7. Auperin A, Rolland E, Curran W, et al. Concomitant radio-chemotherapy (RT-CT) versus sequential RT-CT in locally advanced non-small cell lung cancer (NSCLC): a meta-analysis using individual patient data (IPD) from randomised clinical trials (RCTs). J Thorac Oncol. 2007;2:S310;(Abstr A1-05)
  8. Albain KS, Swann RS, Rusch VR, et al. Phase III study of concurrent chemotherapy and full course radiotherapy (CT/RT) versus CT/RT followed by surgical resection for stage IIIA(pN2) non-small cell lung cancer (NSCLC): outcomes update of North American Intergroup 0139 (RTOG 9309). J Clin Oncol. 2005;23:624S;(Abstr 7014)
  9. Van Meerbeeck J, Kramer GW, Van Schil PE, et al. Randomized controlled trial of resection versus radiotherapy after induction chemotherapy in stage IIIA-N2 non-small-cell lung cancer. J Natl Cancer Inst. 2007;99:442–450
  10. Vansteenkiste J, Betticher D, Eberhardt W, et al. Randomized controlled trial of resection versus radiotherapy after induction chemotherapy in stage IIIA-N2 non-small cell lung cancer. J Thorac Oncol. 2007;2:684–685
  11. Albain KS, Rusch VW, Crowley JJ, et al. Concurrent cisplatin/etoposide plus chest radiotherapy followed by surgery for stages IIIA (N2) and IIIB non-small-cell lung cancer: mature results of Southwest Oncology Group phase II study 8805. J Clin Oncol. 1995;13:1880–1892
  12. Pöttgen C, Eberhardt W, Bildat S, et al. Induction chemotherapy followed by concurrent chemotherapy and definitive high-dose radiotherapy for patients with locally advanced non-small-cell lung cancer (stages IIIa/IIIb): a pilot phase I/II trial. Ann Oncol. 2002;13:403–411
  13. Lorent N, De Leyn P, Lievens Y, et al. Long-term survival of surgically staged IIIA-N2 non-small-cell lung cancer treated with surgical combined modality approach: analysis of a 7-year prospective experience. Ann Oncol. 2004;15:1645–1653
  14. Betticher DC, Hsu Schmitz SF, Tötsch M, et al. Prognostic factors affecting long-term outcomes in patients with resected stage IIIA pN2 non-small-cell lung cancer: 5-year follow-up of a phase II study. Br J Cancer. 2006;94:1099–1106
  15. Garrido P, González-Larriba JL, Insa A, et al. Long-term survival associated with complete resection after induction chemotherapy in stage IIIA (N2) and IIIB (T4N0–1) non small-cell lung cancer patients: the Spanish Lung Cancer Group Trial 9901. J Clin Oncol. 2007;25:4736–4742
  16. Martini N, Kris MG, Flehinger BJ, et al. Preoperative chemotherapy for stage IIIa (N2) lung cancer: the Sloan–Kettering experience with 136 patients. Ann Thorac Surg. 1993;55:1365–1373
  17. Machtay M, Hsu C, Komaki R, et al. Effect of overall treatment time on outcomes after concurrent chemoradiation for locally advanced non-small-cell lung carcinoma: analysis of the Radiation Therapy Oncology Group (RTOG) experience. Int J Radiat Oncol Biol Phys. 2005;63:667–671
  18. De Ruysscher D, Pijls-Johannesma M, Bentzen SM, et al. Time between the first day of chemotherapy and the last day of chest radiation is the most important predictor of survival in limited-disease small-cell lung cancer. J Clin Oncol. 2006;24:1057–1063
  19. Kim JJ, Tannock IF. Repopulation of cancer cells during therapy: an important cause of treatment failure. Nat Rev Cancer. 2005;5:516–525
  20. Wilson GD, Bentzen SM, Harari PM. Biologic basis for combining drugs with radiation. Semin Radiat Oncol. 2006;16:2–9
  21. Bentzen SM, Tucker SL. Quantifying the position and steepness of radiation dose–response curves. Int J Radiat Biol. 1997;71:531–542
  22. Martel MK, Ten Haken RK, Hazuka MB, et al. Estimation of tumor control probability model parameters from 3-D dose distributions of non-small cell lung cancer patients. Lung Cancer. 1999;24:31–37
  23. Le Chevalier T, Arriagada R, Quoix E, et al. Radiotherapy alone versus combined chemotherapy and radiotherapy in unresectable non-small cell lung cancer: first analysis of a randomised trial in 353 patients. J Natl Cancer Inst. 1991;83:417–423
  24. Le Chevalier T, Arriagada R, Tarayre M, et al. Significant effect of adjuvant chemotherapy on survival in locally advanced non-small-cell lung carcinoma [letter]. J Natl Cancer Inst. 1992;8:58
  25. Sause W, Scott C, Taylor S, et al. RTOG 88-08, ECOG 4588, preliminary results of a phase III trial in regionally advanced, unresectable non-small cell lung cancer. J Natl Cancer Inst. 1995;87:198–205
  26. Sause W, Kolesar P, Taylor S, et al. Final results of phase III trial in regionally advanced unresectable non-small cell lung cancer. Chest. 2000;117:358–364
  27. Komaki R, Scott CB, Sause 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. Int J Rad Oncol Biol Phys. 1997;39:537–544
  28. Vokes EE, Herndon JE, Kelley MJ, 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
  29. Dehing-Oberije C, De Ruysscher D, van der Weide H, et al. Tumor volume combined with number of positive lymph node stations is a more important prognostic factor than TNM stage for survival of non-small-cell lung cancer patients treated with (chemo)radiotherapy. Int J Radiat Oncol Biol Phys. 2008;70:1039–1044
  30. Fowler WC, Langer CJ, Curran WJ, et al. Postoperative complications after combined neoadjuvant treatment of lung cancer. Ann Thorac Surg. 1993;55:986–989
  31. Deutsch M, Crawford J, Leopold K, et al. Phase II study of neoadjuvant chemotherapy and radiation therapy with thoracotomy in the treatment of clinically staged IIIA non-small cell lung cancer. Cancer. 1994;74:1243–1252
  32. Vora SA, Daly BD, Blaszkowsky L, et al. High dose radiation therapy and chemotherapy as induction treatment for stage III non-small cell lung carcinoma. Cancer. 2000;89:1946–1952
  33. Sonett JR, Krasna MJ, Suntharalingam M, et al. Safe pulmonary resection after chemotherapy and high-dose thoracic radiation. Ann Thorac Surg. 1999;68:316–320
  34. Sonett JR, Suntharalingam M, Edelman MJ, et al. Pulmonary resection after curative intent radiotherapy (>59Gy) and concurrent chemotherapy in non-small-cell lung cancer. Ann Thorac Surg. 2004;78:1200–1205
  35. Weitberg AB, Liu L, Yashar J, et al. Twelve-year follow-up of trimodality therapy for stage IIIA non-small cell lung cancer. J Exp Clin Cancer Res. 2001;20:335–340
  36. Cerfolio RJ, Bryant AS, Spencer SA, et al. Pulmonary resection after high-dose and low-dose chest irradiation. Ann Thorac Surg. 2005;80:1224–1230
  37. Daly BD, Fernando HC, Ketchedjian A, et al. Pneumonectomy after high-dose radiation and concurrent chemotherapy for non-small cell lung cancer. Ann Thorac Surg. 2006;82:227–231
  38. Schild SE, McGinnis WL, Graham D, et al. Results of a Phase I trial of concurrent chemotherapy and escalating doses of radiation for unresectable non-small-cell lung cancer. Int J Radiat Oncol Biol Phys. 2006;65:1106–1111
  39. Bentzen SM. High-tech in radiation oncology: should there be a ceiling?. Int J Radiat Oncol Biol Phys. 2004;58:320–330
  40. Dehing-Oberije C, De Ruysscher D, van Baardwijk A, et al. The importance of patient characteristics for the prediction of radiation-induced lung toxicity. Radiother Oncol. 2009;91:421–426
  41. De Ruysscher D, Wanders S, van Haren E, et al. Selective mediastinal node irradiation on basis of the FDG-PET scan in patients with non-small cell lung cancer: a prospective clinical study. Int J Radiat Oncol Biol Phys. 2005;62:988–994
  42. De Ruysscher D, Botterweck A, Dirx M, et al. Eligibility for concurrent chemotherapy and radiotherapy of locally advanced lung cancer patients: a prospective, population-based study. Ann Oncol. 2009;20:98–102

PII: S0167-8140(09)00299-0

doi: 10.1016/j.radonc.2009.06.004

Radiotherapy & Oncology
Volume 93, Issue 3 , Pages 389-395 , December 2009

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