Is There a Future for 74 Gy Radiation Treatment of NSCLC after RTOG 0617? A Comparison of the RTOG Study Results with Our Own Department’s 74 Gy NSCLC Cohort
Author(s)
Christina Schröder1,2*,
Eyck Blank1,
Dietrich Sidow1,
Rita Engenhart-Cabillic2,
André Buchali1
Affiliation(s)
1 Departement of Radiooncology, Ruppiner Kliniken GmbH, Neuruppin, Germany. 2 Departement of Radiooncology, University Hospital, Justus Liebig University, Giessen and Marburg, Germany.
1 Departement of Radiooncology, Ruppiner Kliniken GmbH, Neuruppin, Germany. 2 Departement of Radiooncology, University Hospital, Justus Liebig University, Giessen and Marburg, Germany.
ABSTRACT
Background and Purpose: There have been a number of different efforts trying to improve the outcome of NSCLC patients treated with radiotherapy (RT). Contrary to most expectations, the long awaiting results of the RTOG 0617 trial didn’t show any benefit of dose escalation to 74 Gy. In this unicentric retrospective analysis we compare the RTOG 0617 result with the outcome of our own 74-Gy-NSCLC cohort. Methods and Material: Since October 2009, 80 patients with NSCLC were treated with 74 Gy in 37 fractions, of which 69 patients were eligible for a retrospective analysis of local and distant failure, survival time and treatment related toxicity. A subgroup analysis was done for patients with a possible follow-up of at least 18 month. Results: Complete local remission could be achieved in 18 patients (26.1%); 26 patients (37.7%) had a partial remission and 3 patients (4.4%) a stable local disease. Local failure occurred in 12 patients (17.3%). Distant failure occurred in 27 patients (39.1%). The median survival time was 43.7 weeks (95% CI: 25.2 - 62.3 weeks). 5 patients (6.3%) developed RT induced side effects. As for the analyzed subgroup, a complete or partial local remission could be achieved in 29 patients (61.7%). Local failure occurred in 11 patients (23.4%) and 20 patients (42.6%) developed distant metastases. The 18-month overall survival was 38.3% and the median survival time was 51.7 weeks (95% CI: 27.2 - 76.3 weeks). Conclusion: The results of this retrospective analysis indicate that 74 Gy total radiation dose might not lead to results as bad as indicated by the RTOG 0617 trial. It might therefore be a suitable treatment concept for people with NSCLC.
Background and Purpose: There have been a number of different efforts trying to improve the outcome of NSCLC patients treated with radiotherapy (RT). Contrary to most expectations, the long awaiting results of the RTOG 0617 trial didn’t show any benefit of dose escalation to 74 Gy. In this unicentric retrospective analysis we compare the RTOG 0617 result with the outcome of our own 74-Gy-NSCLC cohort. Methods and Material: Since October 2009, 80 patients with NSCLC were treated with 74 Gy in 37 fractions, of which 69 patients were eligible for a retrospective analysis of local and distant failure, survival time and treatment related toxicity. A subgroup analysis was done for patients with a possible follow-up of at least 18 month. Results: Complete local remission could be achieved in 18 patients (26.1%); 26 patients (37.7%) had a partial remission and 3 patients (4.4%) a stable local disease. Local failure occurred in 12 patients (17.3%). Distant failure occurred in 27 patients (39.1%). The median survival time was 43.7 weeks (95% CI: 25.2 - 62.3 weeks). 5 patients (6.3%) developed RT induced side effects. As for the analyzed subgroup, a complete or partial local remission could be achieved in 29 patients (61.7%). Local failure occurred in 11 patients (23.4%) and 20 patients (42.6%) developed distant metastases. The 18-month overall survival was 38.3% and the median survival time was 51.7 weeks (95% CI: 27.2 - 76.3 weeks). Conclusion: The results of this retrospective analysis indicate that 74 Gy total radiation dose might not lead to results as bad as indicated by the RTOG 0617 trial. It might therefore be a suitable treatment concept for people with NSCLC.
Cite this paper
Schröder, C. , Blank, E. , Sidow, D. , Engenhart-Cabillic, R. and Buchali, A. (2015) Is There a Future for 74 Gy Radiation Treatment of NSCLC after RTOG 0617? A Comparison of the RTOG Study Results with Our Own Department’s 74 Gy NSCLC Cohort. Journal of Cancer Therapy, 6, 642-647. doi: 10.4236/jct.2015.68071.
Schröder, C. , Blank, E. , Sidow, D. , Engenhart-Cabillic, R. and Buchali, A. (2015) Is There a Future for 74 Gy Radiation Treatment of NSCLC after RTOG 0617? A Comparison of the RTOG Study Results with Our Own Department’s 74 Gy NSCLC Cohort. Journal of Cancer Therapy, 6, 642-647. doi: 10.4236/jct.2015.68071.
References
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http://dx.doi.org/10.1016/j.ijrobp.2009.04.029 [2] Bradley, J. (2005) A Review of Radiation Dose Escalation Trials for Non-Small Cell Lung Cancer within the Radiation Therapy Oncology Group. Seminars in Oncology, 32, 111-113.
http://dx.doi.org/10.1053/j.seminoncol.2005.03.020 [3] Bradley, J.D., Paulus, R., Komaki, R., et al. (2013) A Randomized Phase III Comparison of Standard-Dose (60 Gy) versus High-Dose (74 Gy) Conformal Chemoradiotherapy with or without Cetuximab for Stage III Non-Small Cell Lung Cancer: Results on Radiation Dose in RTOG 0617. ASCO Meeting Abstracts, 31, 7501. [4] Chi, A., Nguyen, N.P., Welsh, J.S., et al. (2014) Strategies of Dose Escalation in the Treatment of Locally Advanced Non-Small Cell Lung Cancer: Image Guidance and beyond. Frontiers in Oncology, 4, 156.
http://dx.doi.org/10.3389/fonc.2014.00156 [5] Cox, J.D. (2012) Are the Results of RTOG 0617 Mysterious? International Journal of Radiation Oncology, Biology, Physics, 82, 1042-1044.
http://dx.doi.org/10.1016/j.ijrobp.2011.12.032 [6] Guckenberger, P.D.M., Kavanagh, A. and Partridge, M. (2012) Combining Advanced Radiotherapy Technologies to Maximize Safety and Tumor Control Probability in Stage III Non-Small Cell Lung Cancer. Strahlentherapie und Onkologie, 188, 894-900.
http://dx.doi.org/10.1007/s00066-012-0161-9 [7] Harada, H., Nishio, M., Murakami, H., et al. (2013) Dose-Escalation Study of Three-Dimensional Conformal Thoracic Radiotherapy with Concurrent S-1 and Cisplatin for Inoperable Stage III Non-Small-Cell Lung Cancer. Clinical Lung Cancer, 14, 440-445.
http://dx.doi.org/10.1016/j.cllc.2013.01.003 [8] Howlader, N., Noone, A.M., Krapcho, M., et al. (2014) SEER Cancer Statistics Review, 1975-2011. National Cancer Institute, Bethesda.
http://seer.cancer.gov/csr/1975_2011/ [9] Kong, F.M., Hayman, J.A. and Griffith, K.A. (2006) Final Toxicity Results of a Radiation-Dose Escalation Study in Patients with Non-Small-Cell Lung Cancer (NSCLC): Predictors for Radiation Pneumonitis and Fibrosis. International Journal of Radiation Oncology, Biology, Physics, 65, 1075-1086.
http://dx.doi.org/10.1016/j.ijrobp.2006.01.051 [10] Liao, Z.X., Komaki, R.R., Thames Jr., H.D., et al. (2010) Influence of Technologic Advances on Outcomes in Patients with Unresectable, Locally Advanced Non-Small-Cell Lung Cancer Receiving Concomitant Chemoradiotherapy. International Journal of Radiation Oncology, Biology, Physics, 76, 775-781.
http://dx.doi.org/10.1016/j.ijrobp.2009.02.032 [11] Partridge, M., Ramos, M., Sardaro, A. and Brada, M. (2011) Dose Escalation for Non-Small Cell Lung Cancer: Analysis and Modelling of Published Literature. Radiotherapy and Oncology, 99, 6-11.
http://dx.doi.org/10.1016/j.radonc.2011.02.014 [12] Philipp, J. and Baumann, M. (2014) Caution with Hypofractionated Dose-Escalating Radiotherapy in Non-Small Cell Lung Cancer. Strahlentherapie und Onkologie, 190, 597-599.
http://dx.doi.org/10.1007/s00066-014-0667-4 [13] Rosenman, J.G., Halle, J.S., Socinski, M.A., et al. (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. International Journal of Radiation Oncology, Biology, Physics, 54, 348-356.
http://dx.doi.org/10.1016/S0360-3016(02)02958-9 [14] Saunders, M., Royas, A., Lyn, E., et al. (1998) Experience with Dose Escalation Using CHARTWEL (Continuous Hyperfractionated Accelerated Radiotherapy Weekend Less) in Non-Small-Cell Lung Cancer. British Journal of Cancer, 78, 1323-1328.
http://dx.doi.org/10.1038/bjc.1998.678 [15] Saunders, M., Dische, S., Barrett, A., et al. (1997) Continuous Hyperfractionated Accelerated Radiotherapy (CHART) versus Conventional Radiotherapy in Non-Small-Cell Lung Cancer: A Randomised Multicentre Trial. The Lancet, 350, 161-165.
http://dx.doi.org/10.1016/S0140-6736(97)06305-8 [16] Schroder, C., Ivo, M. and Buchali, A. (2013) Does High-Dose Radiotherapy Benefit Palliative Lung Cancer Patients? Strahlentherapie und Onkologie, 189, 771-776.
http://dx.doi.org/10.1007/s00066-013-0360-z [17] Socinski, M.A., Morris, D.E. and Halle, J.S. (2004) Induction and Concurrent Chemotherapy with High-Dose Thoracic Conformal Radiation Therapy in Unresectable Stage IIIA and IIIB Non-Small-Cell Lung Cancer: A Dose-Escalation Phase I Trial. Journal of Clinical Oncology, 22, 4341-4350.
http://dx.doi.org/10.1200/JCO.2004.03.022 [18] Terakedis, B. and Sause, W. (2011) Radiation Dose Escalation in Stage III Non-Small-Cell Lung Cancer. Frontiers in Oncology, 1, 47.
http://dx.doi.org/10.3389/fonc.2011.00047 [19] Wang, L., Correa, C.R., Zhao, L., et al. (2009) The Effect of Radiation Dose and Chemotherapy on Overall Survival in 237 Patients With Stage III Non-Small-Cell Lung Cancer. International Journal of Radiation Oncology, Biology, Physics, 73, 1383-1390.
http://dx.doi.org/10.1016/j.ijrobp.2008.06.1935 [20] Wurstbauer, K., Deutschmann, H., Dagn, K., et al. (2013) DART-Bid (Dose-Differentiated Accelerated Radiation Therapy, 1.8 Gy Twice Daily)—A Novel Approach for Non-Resected NSCLC: Final Results of a Prospective Study, Correlating Radiation Dose to Tumor Volume. Radiation Oncology, 8, 49.
http://dx.doi.org/10.1186/1748-717X-8-49
[1] Bradley, J.D., Moughan, J., Graham, M.V., et al. (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. International Journal of Radiation Oncology, Biology, Physics, 77, 367-372.
http://dx.doi.org/10.1016/j.ijrobp.2009.04.029 [2] Bradley, J. (2005) A Review of Radiation Dose Escalation Trials for Non-Small Cell Lung Cancer within the Radiation Therapy Oncology Group. Seminars in Oncology, 32, 111-113.
http://dx.doi.org/10.1053/j.seminoncol.2005.03.020 [3] Bradley, J.D., Paulus, R., Komaki, R., et al. (2013) A Randomized Phase III Comparison of Standard-Dose (60 Gy) versus High-Dose (74 Gy) Conformal Chemoradiotherapy with or without Cetuximab for Stage III Non-Small Cell Lung Cancer: Results on Radiation Dose in RTOG 0617. ASCO Meeting Abstracts, 31, 7501. [4] Chi, A., Nguyen, N.P., Welsh, J.S., et al. (2014) Strategies of Dose Escalation in the Treatment of Locally Advanced Non-Small Cell Lung Cancer: Image Guidance and beyond. Frontiers in Oncology, 4, 156.
http://dx.doi.org/10.3389/fonc.2014.00156 [5] Cox, J.D. (2012) Are the Results of RTOG 0617 Mysterious? International Journal of Radiation Oncology, Biology, Physics, 82, 1042-1044.
http://dx.doi.org/10.1016/j.ijrobp.2011.12.032 [6] Guckenberger, P.D.M., Kavanagh, A. and Partridge, M. (2012) Combining Advanced Radiotherapy Technologies to Maximize Safety and Tumor Control Probability in Stage III Non-Small Cell Lung Cancer. Strahlentherapie und Onkologie, 188, 894-900.
http://dx.doi.org/10.1007/s00066-012-0161-9 [7] Harada, H., Nishio, M., Murakami, H., et al. (2013) Dose-Escalation Study of Three-Dimensional Conformal Thoracic Radiotherapy with Concurrent S-1 and Cisplatin for Inoperable Stage III Non-Small-Cell Lung Cancer. Clinical Lung Cancer, 14, 440-445.
http://dx.doi.org/10.1016/j.cllc.2013.01.003 [8] Howlader, N., Noone, A.M., Krapcho, M., et al. (2014) SEER Cancer Statistics Review, 1975-2011. National Cancer Institute, Bethesda.
http://seer.cancer.gov/csr/1975_2011/ [9] Kong, F.M., Hayman, J.A. and Griffith, K.A. (2006) Final Toxicity Results of a Radiation-Dose Escalation Study in Patients with Non-Small-Cell Lung Cancer (NSCLC): Predictors for Radiation Pneumonitis and Fibrosis. International Journal of Radiation Oncology, Biology, Physics, 65, 1075-1086.
http://dx.doi.org/10.1016/j.ijrobp.2006.01.051 [10] Liao, Z.X., Komaki, R.R., Thames Jr., H.D., et al. (2010) Influence of Technologic Advances on Outcomes in Patients with Unresectable, Locally Advanced Non-Small-Cell Lung Cancer Receiving Concomitant Chemoradiotherapy. International Journal of Radiation Oncology, Biology, Physics, 76, 775-781.
http://dx.doi.org/10.1016/j.ijrobp.2009.02.032 [11] Partridge, M., Ramos, M., Sardaro, A. and Brada, M. (2011) Dose Escalation for Non-Small Cell Lung Cancer: Analysis and Modelling of Published Literature. Radiotherapy and Oncology, 99, 6-11.
http://dx.doi.org/10.1016/j.radonc.2011.02.014 [12] Philipp, J. and Baumann, M. (2014) Caution with Hypofractionated Dose-Escalating Radiotherapy in Non-Small Cell Lung Cancer. Strahlentherapie und Onkologie, 190, 597-599.
http://dx.doi.org/10.1007/s00066-014-0667-4 [13] Rosenman, J.G., Halle, J.S., Socinski, M.A., et al. (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. International Journal of Radiation Oncology, Biology, Physics, 54, 348-356.
http://dx.doi.org/10.1016/S0360-3016(02)02958-9 [14] Saunders, M., Royas, A., Lyn, E., et al. (1998) Experience with Dose Escalation Using CHARTWEL (Continuous Hyperfractionated Accelerated Radiotherapy Weekend Less) in Non-Small-Cell Lung Cancer. British Journal of Cancer, 78, 1323-1328.
http://dx.doi.org/10.1038/bjc.1998.678 [15] Saunders, M., Dische, S., Barrett, A., et al. (1997) Continuous Hyperfractionated Accelerated Radiotherapy (CHART) versus Conventional Radiotherapy in Non-Small-Cell Lung Cancer: A Randomised Multicentre Trial. The Lancet, 350, 161-165.
http://dx.doi.org/10.1016/S0140-6736(97)06305-8 [16] Schroder, C., Ivo, M. and Buchali, A. (2013) Does High-Dose Radiotherapy Benefit Palliative Lung Cancer Patients? Strahlentherapie und Onkologie, 189, 771-776.
http://dx.doi.org/10.1007/s00066-013-0360-z [17] Socinski, M.A., Morris, D.E. and Halle, J.S. (2004) Induction and Concurrent Chemotherapy with High-Dose Thoracic Conformal Radiation Therapy in Unresectable Stage IIIA and IIIB Non-Small-Cell Lung Cancer: A Dose-Escalation Phase I Trial. Journal of Clinical Oncology, 22, 4341-4350.
http://dx.doi.org/10.1200/JCO.2004.03.022 [18] Terakedis, B. and Sause, W. (2011) Radiation Dose Escalation in Stage III Non-Small-Cell Lung Cancer. Frontiers in Oncology, 1, 47.
http://dx.doi.org/10.3389/fonc.2011.00047 [19] Wang, L., Correa, C.R., Zhao, L., et al. (2009) The Effect of Radiation Dose and Chemotherapy on Overall Survival in 237 Patients With Stage III Non-Small-Cell Lung Cancer. International Journal of Radiation Oncology, Biology, Physics, 73, 1383-1390.
http://dx.doi.org/10.1016/j.ijrobp.2008.06.1935 [20] Wurstbauer, K., Deutschmann, H., Dagn, K., et al. (2013) DART-Bid (Dose-Differentiated Accelerated Radiation Therapy, 1.8 Gy Twice Daily)—A Novel Approach for Non-Resected NSCLC: Final Results of a Prospective Study, Correlating Radiation Dose to Tumor Volume. Radiation Oncology, 8, 49.
http://dx.doi.org/10.1186/1748-717X-8-49