Challenges in optimizing chemoradiation in locally advanced non small-cell lung cancers in India

Sushma Agrawal

doi:10.4103/2278-330X.119893

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Review Article

02 (

); 265-271

doi:

10.4103/2278-330X.119893

Challenges in optimizing chemoradiation in locally advanced non small-cell lung cancers in India

Sushma Agrawal^1,

1 Department of Radiotherapy, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, India

*Corresponding author: Dr. Sushma Agrawal. sushmaagrawal@yahoo.co.uk

Published: 2020-12-31

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Abstract

Data supporting use of concurrent chemoradiation in locally advanced lung cancers comes from clinical trials from developed countries. Applicability and outcomes of such schedules in developing countries is not widely reported. There are various challenges in delivering chemoradiation in locally advanced non small cell lung cancer in developing countries which is highlighted by an audit of patients treated with chemoradiation in our center. This article deals with the challenges in the context of a developing country. We conclude that sequential chemoradiotherapy is better tolerated than concurrent chemoradiation in Indian patients with locally advanced non-small cell lung cancers. Patients with stage IIIa, normal weight or overweight, and adequate baseline pulmonary function should be offered concurrent chemoradiation.

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References

Ferlay J, Bray F, Pisani P, Parkin DM. GLOBOCAN 2002: Cancer Incidence, Mortality and Prevalence Worldwide. IARC Cancer Base No. 5. Version 2.0, Lyon: IARC Press; 2004.
Parkin DM, Bray F, Ferlay J, Pisani P. Global cancer statistics, 2002. CA Cancer J Clin 2005;55:74-108.
National Cancer Registry Programme (NCRP). A Consolidated report of the population based cancer registries data, cancer statistics 2002-2006, Indian Council of Medical Research, New Delhi.
Behera D, Balamugesh T. Lung cancer in India. Indian J Chest Dis Allied Sci 2004;46:269-81.
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. BMJ 1995;311:899-909.
Auperin A, Le Pechoux C, Pignon JP, Koning C, Jeremic B, Clamon G, et al. On behalf of the Meta-Analysis of cisplatin/carboplatin based Concomitant Chemotherapy in non-small cell Lung Cancer (MAC3-LC) Group. Concomitant radiochemotherapy based on platin compounds in patients with locally advanced non-small cell lung cancer (NSCLC): A meta-analysis of individual data from 1764 patients. Ann Oncol 2006;17:473-83.
O′Rourke N, Macbeth F. Is concurrent chemoradiation the standard of care for locally advanced non-small cell lung cancer? A review of guidelines and evidence. Clin Oncol 2010;22:347-55.
Kepka L, Casas F, Perin B, Abdel-Wahab S, Saghatelyan T, Vashkevitch L, et al. Radiochemotherapy for lung cancer in developing countries. Clinn Oncol 2009;21:536-42.
Dasgupta A, Dasgupta C, Basu S, Majumdar A. A prospective and randomized study of radiotherapy, sequential chemotherapy radiotherapy and concomitant chemotherapy-radiotherapy in unresectable non small cell carcinoma of the lung. J Cancer Res Ther 2006;2:47-51.
Behzadi A, Ung Y, Lowe V, Deschamps C. The role of positron emission tomography in the management of non-small cell lung cancer. Can J Surg 2009;52:235-42.
Macbeth FR, Abratt RP, Cho KH, Stephens RJ, Jeremic B, International Atomic Energy Agency. Lung cancer management in limited resource settings: Guidelines for appropriate good care. Radiother Oncol 2007;82:123-31.
Chen KY, Chen JH, Shih JY, Yang CH, Yu CJ, Yang PC. Octogenarians with advanced non small cell lung cancer: Treatment modalities, survival and prognostic factors. J Thorac Oncol 2010;5:82-9.
Casas F, Kepka L, Agarwal JP, Dawotola D, Gaye P, Abdel-Wahab S, et al. Radiochemotherapy in the elderly with lung cancer. Expert Rev Anticancer Ther 2009;9:1405-11.
De Ruysscher D, Botterweck A, Dirx M, Pijls-Johannesma M, Wanders R, Hochstenbag 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.
Phernambucq EC, Spoelstra FO, Verbakel WF, Postmus PE, Melissant CF, Maassen van den Brink KI, et al. Outcomes of concurrent chemoradiotherapy in patients with stage III non-small-cell lung cancer and significant comorbidity. Ann Oncol 2011;22:132-8.
Ademuyiwa FO, Johnson CS, White AS, Breen TE, Harvey J, Neubauer M, et al. Prognostic factors in stage III non-small cell lung cancer. Clin Lung Cancer 2007;8:478-82.
Cakir S, Egehan I. A randomised clinical trial of radiotherapy plus cisplatin versus radiotherapy alone in stage III nonsmall cell lung cancer. Lung Cancer 2004;43:309-16.
Clamon G, Herndon J, Cooper R, Chang AY, Rosenman J, Green MR. Radiosensitization with carboplatin for patients with unresectable stage III non-small-cell lung cancer: A phase III trial of the Cancer and Leukemia Group B and the Eastern Cooperative Oncology Group. J Clin Oncol 1999;17:4-11.
Niho S, Ohe Y, Ishikura S, Atagi S, Yokoyama A, Ichinose Y, et al. Induction chemotherapy followed by gefitinib and concurrent thoracic radiotherapy for unresectable locally advanced adenocarcinoma of the lung: A multicenter feasibility study (JCOG 0402). Ann Oncol 2012;23:2253-8.
Ready N, Jänne PA, Bogart J, Dipetrillo T, Garst J, Graziano S, et al. Chemoradiotherapy and gefitinib in stage III non-small cell lung cancer with epidermal growth factor receptor and KRAS mutation analysis: Cancer and leukemia group B (CALGB) 30106, a CALGB-stratified phase II trial. J Thorac Oncol 2010;5:1382-90.
Kathy SA, John JC, Andrew TT III, David RG, William BF, Joseph IC. Concurrent cisplatin, etoposide, and chest radiotherapy in pathologic stage IIIB no-small-cell lung cancer: A Southwest Oncology Group Phase II Study, SWOG 9019. J Clin Oncol 2002;20:3454-60.
Palma DA, Senan S, Tsujino K, Barriger RB, Rengan R, Moreno M, et al. Predicting radiation pneumonitis after chemoradiation therapy for lung cancer: An international individual patient data meta-analysis. Int J Radiat Oncol Biol Phys 2013;85:444-50.
Perez CA, Bauer M, Edelstein S, Gillespie BW, Birch R. Impact of tumor control on survival in carcinoma of the lung treated with irradiation. Int J Radiat Oncol Biol Phys 1986;12:539-47.
Cox JD, Pajak TF, Asbell S, Russell AH, Pederson J, Byhardt RW, et al. Interruptions of high-dose radiation therapy decrease long-term survival of favorable patients with unresectable non-small cell carcinoma of the lung: Analysis of 1244 cases from 3 Radiation Therapy Oncology Group (RTOG) trials. Int J Radiat Oncol Biol Phys 1993;27:493-8.
Saunders M, Dische S, Barrett A, Harvey A, Gibson D, Parmar M. Continuous hyperfractionated accelerated radiotherapy (CHART) versus conventional radiotherapy in non-small-cell lung cancer: A randomized multicentre trial. CHART Steering Committee. Lancet 1997;350:161-5.
Bradley J, Paulus R, Paulus R, Curran WJ, Robert F, Fossella F et al. A randomized phase III comparison of standard-dose (60 Gy) versus high-dose (74 Gy) conformal chemoradiotherapy +/- cetuximab for stage IIIa/IIIb non-small cell lung cancer: Preliminary ﬁndings on radiation dose in RTOG 0617. Int J Radiat Oncol Biol Phys 2011;81(Suppl):176.
Elderbos JS, Heemsbergen WD, De Jaeger K, Baas P, Lebesque JV. 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 2006;66:126-34.
Liao ZX, Komaki RR, Thames HD Jr, Liu HH, Tucker SL, Mohan R, et al. Influence of technologic advances on outcomes in patients with unresectable, locally advanced non small-cell lung cancer receiving concomitant chemoradiotherapy. Int J Radiat Oncol Biol Phys 2010;76:775-81.
Bradley JD, Bae K, Graham MV, Byhardt R, Govindan R, Fowler J, et al. Primary analysis of the phase IIcomponent 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;28:2475-80.
Stinchcombe TE, Morris DE, Lee CB, Moore DT, Hayes DN, Halle JS, et al. Induction chemotherapy with carboplatin, irinotecan, and paclitaxel followed by high dose three-dimension conformal thoracic radiotherapy (74 Gy) with concurrent carboplatin, paclitaxel, and gefitinib in unresectable stage IIIA and stage IIIB nonsmall cell lung cancer. J Thorac Oncol 2008;3:250-7.
Kwa SL, Lebesque JV, Theuws JC, Marks LB, Munley MT, Bentel G, et al. Radiation pneumonitis as a function of mean lung dose: An analysis of pooled data of 540 patients. Int J Radiat Oncol Biol Phys 1998;42:1-9.
van Baardwijk A, Bosmans G, Boersma L, Wanders S, Dekker A, Dingemans AM, et al. Individualized radical radiotherapy of non-small-cell lung cancer based on normal tissue dose constraints: A feasibility study. Int J Radiat Oncol Biol Phys 2008;71:1394-401.
Baas P, Belderbos JS, van den Heuvel M. Chemoradiation therapy in nonsmall cell lung cancer. Curr Opin Oncol 2011;23:140-9.
Abratt RP. Modelling tumour and treated lung volume influences in the irradiation of non-small-cell lung cancer patients. Int J Radiat Oncol Biol Phys 2001;49:481-5.
Lester J, Coles B, Macbeth FR, Toy E. Palliative radiotherapy for non-small cell lung cancer. Cochrane Database Syst Rev 2006;4:CD002143.
Macbeth FR, Bolger JJ, Hopwood P, Bleehen NM, Cartmell J, Girling DJ, et al. Randomized trial of palliative two-fraction versus more intensive 13-fraction radiotherapy for patients with inoperable non-small cell lung cancer and good performance status. Medical Research Council Lung Cancer Working Party. Clin Oncol 1996;8:167-75.
Medical Research Council Lung Cancer Working Party. Randomised trial of palliative two fraction versus more intensive 13 fraction radiotherapy for patients with inoperable non-small cell lung cancer (NSCLC) and good performance status. Clin Oncol 1996;8:167-75
Zatloukal P, Petruzelka L, Zemanova M, Havel L, Janku F, Judas L, 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.
Furuse K, Fukuoka M, Kawahara M, Nishikawa H, Takada Y, Kudoh S, 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;17:2692-9.
Belderbos J, Uitterhoeve L, van Zandwijk N, Belderbos H, Rodrigus P, van de Vaart P, et al. Randomised trial of sequential versus concurrent chemo-radiotherapy in patients with inoperable non-small cell lung cancer (EORTC 08972-22973). Eur J Cancer 2007;43:114-21.
Werner-Wasik M, Paulus R, Curran WJ Jr, Byhardt R. Acute Esophagitis and late lung toxicity in concurrent chemoradiotherapy trials in patients with locally advanced non-small-cell lung cancer: Analysis of the radiation therapy oncology group (RTOG) database. Clin Lung Cancer 2011;12:245-51.
Aupe′rin A, Le Pe′choux C, Rolland E, Curran WJ, Furuse K, Fournel P, et al. Meta-analysis of concomitant versus sequential radiochemotherapy in locally advanced non-small-cell lung cancer. J Clin Oncol 2010:28:2181-90.
Kappers I, Belderbos JS, Burgers JA, van Zandwijk N, Groen HJ, Klomp HM. Non-small cell lung carcinoma of the superior sulcus: favorable outcomes of combined modality treatment in carefully selected patients. Lung Cancer 2008;59:385-90.
Friedel G, Budach W, Dippon J, Spengler W, Eschmann SM, Pfannenberg C, et al. Phase II trial of a trimodality regimen for stage III non-small-cell lung cancer using chemotherapy as induction treatment with concurrent hyperfractionated chemoradiation with carboplatin and paclitaxel followed by subsequent resection: A single-center study. J Clin Oncol 2010;28:942-8.
Kappers I, Belderbos JS, Burgers JA, van Zandwijk N, Groen HJ, Klomp HM, et al. Non-small cell lung carcinoma of the superior sulcus: Favorable outcomes of combined modality treatment in carefully selected patients. Lung Cancer 2008;59:385-90
Rusch VW, Giroux DJ, Kraut MJ, Crowly J, Hazuka M, Winton T, et al. Induction chemoradiation and surgical resection for superior sulcus nonsmall cell lung carcinoma: Long term survival results of Southwest oncology group trial 9416(Intergroup trial 0160). J Clin Oncol 2007;25:313-8.
Havlik RJ, Yancik R, Long S, Ries L, Edwards B. The National Institute on Aging and the National Cancer Institute SEER collaborative study on comorbidity and early diagnosis of cancer in the elderly. Cancer 1994;74 (7 Suppl):2101-6.
Davidoff AJ, Gardner JF, Seal B, Edelman MJ, Wedding U, Lacombe D. Population-based estimates of survival benefit associated with combined modality therapy in elderly patients with locally advanced non-small cell lung cancer. J Thorac Oncol 2011;6:934-41.
Atagi S, Kawahara M, Tamura T, Noda K, Watanabe K, Yokoyama A, et al. Standard thoracic radiotherapy with or without concurrent daily low-dose carboplatin in elderly patients with locally advanced non-small cell lung cancer: A phase III trial of the Japan Clinical Oncology Group (JCOG9812). Jpn J Clin Oncol 2005;35:195-201.
Langer C, Scott C, Byhatdt R,Werner-Wasik M. Effect of advanced age on outcome in Radiation Therapy Oncology Group studies of locally advanced NSCLC (LANSCLC). Lung Cancer 2000;29:104.
Pallis AG, Gridelli C, van Meerbeeck JP, Greillier L, Wedding U, Lacombe D, et al. EORTC Elderly Task Force and Lung Cancer Group and International Society for Geriatric Oncology (SIOG) experts′ opinion for the treatment of non-small-cell lung cancer in an elderly population. Ann Oncol 2010;21:692-706.

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[1] Ferlay J, Bray F, Pisani P, Parkin DM. GLOBOCAN 2002: Cancer Incidence, Mortality and Prevalence Worldwide. IARC Cancer Base No. 5. Version 2.0, Lyon: IARC Press; 2004.

[2] Parkin DM, Bray F, Ferlay J, Pisani P. Global cancer statistics, 2002. CA Cancer J Clin 2005;55:74-108.

[3] National Cancer Registry Programme (NCRP). A Consolidated report of the population based cancer registries data, cancer statistics 2002-2006, Indian Council of Medical Research, New Delhi.

[4] Behera D, Balamugesh T. Lung cancer in India. Indian J Chest Dis Allied Sci 2004;46:269-81.

[5] 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. BMJ 1995;311:899-909.

[6] Auperin A, Le Pechoux C, Pignon JP, Koning C, Jeremic B, Clamon G, et al. On behalf of the Meta-Analysis of cisplatin/carboplatin based Concomitant Chemotherapy in non-small cell Lung Cancer (MAC3-LC) Group. Concomitant radiochemotherapy based on platin compounds in patients with locally advanced non-small cell lung cancer (NSCLC): A meta-analysis of individual data from 1764 patients. Ann Oncol 2006;17:473-83.

[7] O′Rourke N, Macbeth F. Is concurrent chemoradiation the standard of care for locally advanced non-small cell lung cancer? A review of guidelines and evidence. Clin Oncol 2010;22:347-55.

[8] Kepka L, Casas F, Perin B, Abdel-Wahab S, Saghatelyan T, Vashkevitch L, et al. Radiochemotherapy for lung cancer in developing countries. Clinn Oncol 2009;21:536-42.

[9] Dasgupta A, Dasgupta C, Basu S, Majumdar A. A prospective and randomized study of radiotherapy, sequential chemotherapy radiotherapy and concomitant chemotherapy-radiotherapy in unresectable non small cell carcinoma of the lung. J Cancer Res Ther 2006;2:47-51.

[10] Behzadi A, Ung Y, Lowe V, Deschamps C. The role of positron emission tomography in the management of non-small cell lung cancer. Can J Surg 2009;52:235-42.

[11] Macbeth FR, Abratt RP, Cho KH, Stephens RJ, Jeremic B, International Atomic Energy Agency. Lung cancer management in limited resource settings: Guidelines for appropriate good care. Radiother Oncol 2007;82:123-31.

[12] Chen KY, Chen JH, Shih JY, Yang CH, Yu CJ, Yang PC. Octogenarians with advanced non small cell lung cancer: Treatment modalities, survival and prognostic factors. J Thorac Oncol 2010;5:82-9.

[13] Casas F, Kepka L, Agarwal JP, Dawotola D, Gaye P, Abdel-Wahab S, et al. Radiochemotherapy in the elderly with lung cancer. Expert Rev Anticancer Ther 2009;9:1405-11.

[14] De Ruysscher D, Botterweck A, Dirx M, Pijls-Johannesma M, Wanders R, Hochstenbag 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.

[15] Phernambucq EC, Spoelstra FO, Verbakel WF, Postmus PE, Melissant CF, Maassen van den Brink KI, et al. Outcomes of concurrent chemoradiotherapy in patients with stage III non-small-cell lung cancer and significant comorbidity. Ann Oncol 2011;22:132-8.

[16] Ademuyiwa FO, Johnson CS, White AS, Breen TE, Harvey J, Neubauer M, et al. Prognostic factors in stage III non-small cell lung cancer. Clin Lung Cancer 2007;8:478-82.

[17] Cakir S, Egehan I. A randomised clinical trial of radiotherapy plus cisplatin versus radiotherapy alone in stage III nonsmall cell lung cancer. Lung Cancer 2004;43:309-16.

[18] Clamon G, Herndon J, Cooper R, Chang AY, Rosenman J, Green MR. Radiosensitization with carboplatin for patients with unresectable stage III non-small-cell lung cancer: A phase III trial of the Cancer and Leukemia Group B and the Eastern Cooperative Oncology Group. J Clin Oncol 1999;17:4-11.

[19] Niho S, Ohe Y, Ishikura S, Atagi S, Yokoyama A, Ichinose Y, et al. Induction chemotherapy followed by gefitinib and concurrent thoracic radiotherapy for unresectable locally advanced adenocarcinoma of the lung: A multicenter feasibility study (JCOG 0402). Ann Oncol 2012;23:2253-8.

[20] Ready N, Jänne PA, Bogart J, Dipetrillo T, Garst J, Graziano S, et al. Chemoradiotherapy and gefitinib in stage III non-small cell lung cancer with epidermal growth factor receptor and KRAS mutation analysis: Cancer and leukemia group B (CALGB) 30106, a CALGB-stratified phase II trial. J Thorac Oncol 2010;5:1382-90.

[21] Kathy SA, John JC, Andrew TT III, David RG, William BF, Joseph IC. Concurrent cisplatin, etoposide, and chest radiotherapy in pathologic stage IIIB no-small-cell lung cancer: A Southwest Oncology Group Phase II Study, SWOG 9019. J Clin Oncol 2002;20:3454-60.

[22] Palma DA, Senan S, Tsujino K, Barriger RB, Rengan R, Moreno M, et al. Predicting radiation pneumonitis after chemoradiation therapy for lung cancer: An international individual patient data meta-analysis. Int J Radiat Oncol Biol Phys 2013;85:444-50.

[23] Perez CA, Bauer M, Edelstein S, Gillespie BW, Birch R. Impact of tumor control on survival in carcinoma of the lung treated with irradiation. Int J Radiat Oncol Biol Phys 1986;12:539-47.

[24] Cox JD, Pajak TF, Asbell S, Russell AH, Pederson J, Byhardt RW, et al. Interruptions of high-dose radiation therapy decrease long-term survival of favorable patients with unresectable non-small cell carcinoma of the lung: Analysis of 1244 cases from 3 Radiation Therapy Oncology Group (RTOG) trials. Int J Radiat Oncol Biol Phys 1993;27:493-8.

[25] Saunders M, Dische S, Barrett A, Harvey A, Gibson D, Parmar M. Continuous hyperfractionated accelerated radiotherapy (CHART) versus conventional radiotherapy in non-small-cell lung cancer: A randomized multicentre trial. CHART Steering Committee. Lancet 1997;350:161-5.

[26] Bradley J, Paulus R, Paulus R, Curran WJ, Robert F, Fossella F et al. A randomized phase III comparison of standard-dose (60 Gy) versus high-dose (74 Gy) conformal chemoradiotherapy +/- cetuximab for stage IIIa/IIIb non-small cell lung cancer: Preliminary ﬁndings on radiation dose in RTOG 0617. Int J Radiat Oncol Biol Phys 2011;81(Suppl):176.

[27] Elderbos JS, Heemsbergen WD, De Jaeger K, Baas P, Lebesque JV. 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 2006;66:126-34.

[28] Liao ZX, Komaki RR, Thames HD Jr, Liu HH, Tucker SL, Mohan R, et al. Influence of technologic advances on outcomes in patients with unresectable, locally advanced non small-cell lung cancer receiving concomitant chemoradiotherapy. Int J Radiat Oncol Biol Phys 2010;76:775-81.

[29] Bradley JD, Bae K, Graham MV, Byhardt R, Govindan R, Fowler J, et al. Primary analysis of the phase IIcomponent 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;28:2475-80.

[30] Stinchcombe TE, Morris DE, Lee CB, Moore DT, Hayes DN, Halle JS, et al. Induction chemotherapy with carboplatin, irinotecan, and paclitaxel followed by high dose three-dimension conformal thoracic radiotherapy (74 Gy) with concurrent carboplatin, paclitaxel, and gefitinib in unresectable stage IIIA and stage IIIB nonsmall cell lung cancer. J Thorac Oncol 2008;3:250-7.

[31] Kwa SL, Lebesque JV, Theuws JC, Marks LB, Munley MT, Bentel G, et al. Radiation pneumonitis as a function of mean lung dose: An analysis of pooled data of 540 patients. Int J Radiat Oncol Biol Phys 1998;42:1-9.

[32] van Baardwijk A, Bosmans G, Boersma L, Wanders S, Dekker A, Dingemans AM, et al. Individualized radical radiotherapy of non-small-cell lung cancer based on normal tissue dose constraints: A feasibility study. Int J Radiat Oncol Biol Phys 2008;71:1394-401.

[33] Baas P, Belderbos JS, van den Heuvel M. Chemoradiation therapy in nonsmall cell lung cancer. Curr Opin Oncol 2011;23:140-9.

[34] Abratt RP. Modelling tumour and treated lung volume influences in the irradiation of non-small-cell lung cancer patients. Int J Radiat Oncol Biol Phys 2001;49:481-5.

[35] Lester J, Coles B, Macbeth FR, Toy E. Palliative radiotherapy for non-small cell lung cancer. Cochrane Database Syst Rev 2006;4:CD002143.

[36] Macbeth FR, Bolger JJ, Hopwood P, Bleehen NM, Cartmell J, Girling DJ, et al. Randomized trial of palliative two-fraction versus more intensive 13-fraction radiotherapy for patients with inoperable non-small cell lung cancer and good performance status. Medical Research Council Lung Cancer Working Party. Clin Oncol 1996;8:167-75.

[37] Medical Research Council Lung Cancer Working Party. Randomised trial of palliative two fraction versus more intensive 13 fraction radiotherapy for patients with inoperable non-small cell lung cancer (NSCLC) and good performance status. Clin Oncol 1996;8:167-75

[38] Zatloukal P, Petruzelka L, Zemanova M, Havel L, Janku F, Judas L, 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.

[39] Furuse K, Fukuoka M, Kawahara M, Nishikawa H, Takada Y, Kudoh S, 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;17:2692-9.

[40] Belderbos J, Uitterhoeve L, van Zandwijk N, Belderbos H, Rodrigus P, van de Vaart P, et al. Randomised trial of sequential versus concurrent chemo-radiotherapy in patients with inoperable non-small cell lung cancer (EORTC 08972-22973). Eur J Cancer 2007;43:114-21.

[41] Werner-Wasik M, Paulus R, Curran WJ Jr, Byhardt R. Acute Esophagitis and late lung toxicity in concurrent chemoradiotherapy trials in patients with locally advanced non-small-cell lung cancer: Analysis of the radiation therapy oncology group (RTOG) database. Clin Lung Cancer 2011;12:245-51.

[42] Aupe′rin A, Le Pe′choux C, Rolland E, Curran WJ, Furuse K, Fournel P, et al. Meta-analysis of concomitant versus sequential radiochemotherapy in locally advanced non-small-cell lung cancer. J Clin Oncol 2010:28:2181-90.

[43] Kappers I, Belderbos JS, Burgers JA, van Zandwijk N, Groen HJ, Klomp HM. Non-small cell lung carcinoma of the superior sulcus: favorable outcomes of combined modality treatment in carefully selected patients. Lung Cancer 2008;59:385-90.

[44] Friedel G, Budach W, Dippon J, Spengler W, Eschmann SM, Pfannenberg C, et al. Phase II trial of a trimodality regimen for stage III non-small-cell lung cancer using chemotherapy as induction treatment with concurrent hyperfractionated chemoradiation with carboplatin and paclitaxel followed by subsequent resection: A single-center study. J Clin Oncol 2010;28:942-8.

[45] Kappers I, Belderbos JS, Burgers JA, van Zandwijk N, Groen HJ, Klomp HM, et al. Non-small cell lung carcinoma of the superior sulcus: Favorable outcomes of combined modality treatment in carefully selected patients. Lung Cancer 2008;59:385-90

[46] Rusch VW, Giroux DJ, Kraut MJ, Crowly J, Hazuka M, Winton T, et al. Induction chemoradiation and surgical resection for superior sulcus nonsmall cell lung carcinoma: Long term survival results of Southwest oncology group trial 9416(Intergroup trial 0160). J Clin Oncol 2007;25:313-8.

[47] Havlik RJ, Yancik R, Long S, Ries L, Edwards B. The National Institute on Aging and the National Cancer Institute SEER collaborative study on comorbidity and early diagnosis of cancer in the elderly. Cancer 1994;74 (7 Suppl):2101-6.

[48] Davidoff AJ, Gardner JF, Seal B, Edelman MJ, Wedding U, Lacombe D. Population-based estimates of survival benefit associated with combined modality therapy in elderly patients with locally advanced non-small cell lung cancer. J Thorac Oncol 2011;6:934-41.

[49] Atagi S, Kawahara M, Tamura T, Noda K, Watanabe K, Yokoyama A, et al. Standard thoracic radiotherapy with or without concurrent daily low-dose carboplatin in elderly patients with locally advanced non-small cell lung cancer: A phase III trial of the Japan Clinical Oncology Group (JCOG9812). Jpn J Clin Oncol 2005;35:195-201.

[50] Langer C, Scott C, Byhatdt R,Werner-Wasik M. Effect of advanced age on outcome in Radiation Therapy Oncology Group studies of locally advanced NSCLC (LANSCLC). Lung Cancer 2000;29:104.

[51] Pallis AG, Gridelli C, van Meerbeeck JP, Greillier L, Wedding U, Lacombe D, et al. EORTC Elderly Task Force and Lung Cancer Group and International Society for Geriatric Oncology (SIOG) experts′ opinion for the treatment of non-small-cell lung cancer in an elderly population. Ann Oncol 2010;21:692-706.

Challenges in optimizing chemoradiation in locally advanced non small-cell lung cancers in India

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