Defining local-regional control and its importance in locally advanced non-small cell lung carcinoma

Mitchell Machtay, Rebecca Paulus, Jennifer Moughan, Ritsuko Komaki, J Effrey Bradley, Hak Choy, Kathy Albain, Benjamin Movsas, William T Sause, Walter J Curran, Mitchell Machtay, Rebecca Paulus, Jennifer Moughan, Ritsuko Komaki, J Effrey Bradley, Hak Choy, Kathy Albain, Benjamin Movsas, William T Sause, Walter J Curran

Abstract

Introduction: Local-regional control (LRC) rates for non-small cell lung cancer after chemoradiotherapy were studied (using two different definitions of LRC) for the association between LRC and survival.

Methods: Seven legacy Radiation Therapy Ooncology Group trials of chemoradiotherapy for locally advanced non-small cell lung cancer were analyzed. Two different definitions of LRC were studied: (1) freedom from local progression (FFLP-LRC), the traditional Radiation Therapy Oncology Group methodology, in which a failure is intrathoracic tumor progression by World Health Oorganization criteria; and (2) response-mandatory (strict-LRC), in which any patient not achieving at least partial response was considered to have failure at day 0. Testing for associations between LRC and survival was performed using a Cox multivariate model that included other potential predictive factors.

Results: A total of 1390 patients were analyzed. The LRC rate at 3 years was 38% based on the FFLP-LRC definition and 14% based on the strict-LRC definition. Performance status, concurrent chemotherapy, and radiotherapy dose intensity (biologically equivalent dose) were associated with better LRC (using either definition). With the strict-LRC definition (but not FFLP-LRC), age was also important. There was a powerful association between LRC and overall survival (p, 0.0001) on univariate and multivariate analyses. Age, performance status, chemotherapy sequencing, and biologically equivalent dose were also significantly associated with survival. Histology and gender were also significant if the strict-LRC model was used.

Conclusions: LRC is associated with survival. The definition of LRC affects the results of these analyses. A consensus definition of LRC, incorporating functional imaging and/or central review, is needed, with the possibility of using LRC as a surrogate end point in future trials.

Figures

Figure 1
Figure 1
Freedom from Local Progression (FFLP-LRC) for all patients (n=1,390)
Figure 2
Figure 2
Response-mandatory Local-regional Control (strict-LRC) for all patients (n=1,390)
Figure 3
Figure 3
Overall survival in patients with (solid lines) or without (dashed lines) local control as defined by the FFLP-LRC or strict-LRC definitions.

References

    1. Perez CA, Bauer M, Edelstein S, Gillespie BW, Birch R. Impact o ftumor control on survival in carcinoma of the lung treated with irradiation. Int J Radiat Oncol Biol Phys. 1986 Apr;12(4):539–47. PMID 3009368.
    1. Marino P, Preatoni A, Cantoni A. Randomized trials of radiotherapy alone versus combined chemotherapy and radiotherapy in stages IIIa and IIIb nonsmall cell lung cancer. A meta-analysis. Cancer. 1995 Aug 15;76(4):593–601. PMID 8625152.
    1. Perez CA, Pajak TF, 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 Cancer. 1987 Jun 1;59(11):1874–81. Radiation Therapy Oncology Group. PMID 3032394.
    1. Le Chevalier T, Arriagada R, Quoix E, et al. Radiotherapy alone versus combined chemotherapy and radiotherapy in nonresectable non-small-cell lung cancer: first analysis of a randomized trial in 353 patients. J Natl Cancer Inst. 1991 Mar 20;83(6):417–23. PMID 1847977.
    1. Sause W, Kolesar P, Taylor S, IV, et al. Final results of phase III trial in regionally advanced unresectable non-small cell lung cancer: Radiation Therapy Oncology Group, Eastern Cooperative Oncology Group, and Southwest Oncology Group. Chest. 2000 Feb;117(2):358–64. PMID 10669675.
    1. Byhardt RW, Scott CB, Ettinger DS, et al. Concurrent hyperfractionated irradiation and chemotherapy for unresectable nonsmall cell lung cancer. Results of Radiation Therapy Oncology Group 90-15. Cancer. 1995 May 1;75(9):2337–44. PMID 7712445.
    1. Lee JS, Scott C, Komaki R, et al. Concurrent chemoradiation therapy with oral etoposide and cisplatin for locally advanced inoperable non-small-cell lung cancer: radiation therapy oncology group protocol 91–06. J Clin Oncol. 1996 Apr;14(4):1055–64. PMID 8648357.
    1. Komaki R, Scott C, Ettinger D, et al. Randomized study of chemotherapy/radiation therapy combinations for favorable patients with locally advanced inoperable nonsmall cell lung cancer: Radiation Therapy Oncology Group (RTOG) 92-04. Int J Radiat Oncol Biol Phys. 1997 Apr 1;38(1):149–55. PMID 9212017.
    1. Albain KS, Swann RS, Rusch VW, 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 Aug 1;374(9687):379–86. Epub 2009 Jul 24. PMID 19632716.
    1. Curran WJ, Paulus R, Langer CJ, 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 Oct 5;103(19):1452–60.
    1. Movsas B, Scott C, Langer C, et al. Randomized trial of amifostine in locally advanced non-small-cell lung cancer patients receiving chemotherapy and hyperfractionated radiation: radiation therapy oncology group trial 98–01. J Clin Oncol. 2005 Apr 1;23(10):2145–54. PMID 15800308.
    1. Mac Manus M, Hicks RJ. The use of positron emission tomography (PET) in the staging/evaluation, treatment, and follow-up of patients with lung cancer: a critical review. Int J Radiat Oncol Biol Phys. 2008 Dec 1;72(5):1298–306. PMID 19028270.
    1. Rosenzweig KE, Fox JL, Yorke E. Results of a phase I dose-escalation study using three-dimensional conformal radiotherapy in the treatment of inoperable nonsmall cell lung carcinoma. Cancer. 2005 May 15;103(10):2118–27. PMID 15830346.
    1. Bradley JD, Bae K, Graham MV. Primary analysis of the phase II component of a phase I/II dose intensification study using three-dimensional conformal radiation therapy and concurrent chemotherapy for patients with inoperable non-small-cell lung cancer: RTOG 0117. J Clin Oncol. 2010 May 10;28(14):2475–80. Epub 2010 Apr 5. PMID 20368547.
    1. Wang L, Correa CR, Zhao L. The effect of radiation dose and chemotherapy on overall survival in 237 patients with Stage III non-small-cell lung cancer. Int J Radiat Oncol Biol Phys. 2009 Apr 1;73(5):1383–90. Epub 2008 Oct 17. PMID 18929449.
    1. Mac Manus MP, Hicks RJ, Matthews JP, et al. Positron emission tomography is superior to computed tomography scanning for response-assessment after radical radiotherapy or chemoradiotherapy in patients with non-small-cell lung cancer. J Clin Oncol. 2003 Apr 1;21(7):1285–92. PMID 12663716.
    1. Ryu JS, Choi NC, Fischman AJ, et al. FDG-PET in staging and restaging non-small cell lung cancer after neoadjuvant chemoradiotherapy: correlation with histopathology. Lung Cancer. 2002 Feb;35(2):179–87. PMID 11804691.
    1. Machtay M, Bae K, Movsas B, et al. Higher biologically effective dose of radiotherapy is associated with improved outcomes for locally advanced NSCLC treated with chemoradiation: ana analysis of the Radiation Therapy Oncology Group. Int J RAdiat Oncol Biol Phys. 2010 Oct 25; epub. PMID 20980108.

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