Before or After: Evolving Neoadjuvant Approaches to Locally Advanced Non-Small Cell Lung Cancer

Jennifer Lewis, Erin A Gillaspie, Evan C Osmundson, Leora Horn, Jennifer Lewis, Erin A Gillaspie, Evan C Osmundson, Leora Horn

Abstract

The treatment of patients with stage IIIA (N2) non-small cell lung cancer (NSCLC) is one of the most challenging and controversial areas of thoracic oncology. This heterogeneous group is characterized by varying tumor size and location, the potential for involvement of surrounding structures, and ipsilateral mediastinal lymph node spread. Neoadjuvant chemotherapy, administered prior to definitive local therapy, has been found to improve survival in patients with stage IIIA (N2) NSCLC. Concurrent chemoradiation has also been evaluated in phase III studies in efforts to improve control of locoregional disease. In certain instances, a tri-modality approach involving concurrent chemoradiation followed by surgery, may offer patients the best chance for cure. In this article, we provide an overview of the trials evaluating neoadjuvant therapy in patients with stage IIIA (N2) NSCLC that have resulted in current practice strategies, and we highlight the areas of uncertainty in the management of this challenging disease. We also review the current ongoing research and future directions in the management of stage IIIA (N2) NSCLC.

Keywords: induction chemotherapy; mediastinal disease; neoadjuvant chemoradiation; neoadjuvant chemotherapy; stage IIIA non-small cell lung cancer; tri-modality.

References

    1. American Cancer Soceity. Cancer Facts & Figures 2017. Atlanta: American Cancer Society; (2017).
    1. van Meerbeeck JP, Kramer GW, Van Schil PE, Legrand C, Smit EF, Schramel F, 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(6):442–50.10.1093/jnci/djk093
    1. Andre F, Grunenwald D, Pignon JP, Dujon A, Pujol JL, Brichon PY, et al. Survival of patients with resected N2 non-small-cell lung cancer: evidence for a subclassification and implications. J Clin Oncol (2000) 18(16):2981–9.10.1200/JCO.2000.18.16.2981
    1. Katsuki H, Shimada K, Koyama A, Okita M, Yamaguchi Y. Long-term intermittent adjuvant chemotherapy for primary, resected lung cancer. J Thorac Cardiovasc Surg (1975) 70(4):590–605.
    1. Martini N, Flehinger BJ. The role of surgery in N2 lung cancer. Surg Clin North Am (1987) 67(5):1037–49.10.1016/S0039-6109(16)44341-0
    1. Martini N, Flehinger BJ, Zaman MB, Beattie EJ., Jr Prospective study of 445 lung carcinomas with mediastinal lymph node metastases. J Thorac Cardiovasc Surg (1980) 80(3):390–9.
    1. Bains MS. Surgical treatment of lung cancer. Chest (1991) 100(3):826–37.10.1378/chest.100.3.826
    1. Johnson DH, Piantadosi S. Chemotherapy for resectable stage III non-small-cell lung cancer – can that dog hunt? J Natl Cancer Inst (1994) 86(9):650–1.10.1093/jnci/86.9.650
    1. Farray D, Mirkovic N, Albain KS. Multimodality therapy for stage III non-small-cell lung cancer. J Clin Oncol (2005) 23(14):3257–69.10.1200/JCO.2005.03.008
    1. Martini N, Kris MG, Gralla RJ, Bains MS, McCormack PM, Kaiser LR, et al. The effects of preoperative chemotherapy on the resectability of non-small cell lung carcinoma with mediastinal lymph node metastases (N2 M0). Ann Thorac Surg (1988) 45(4):370–9.10.1016/S0003-4975(98)90007-8
    1. Vokes EE, Bitran JD, Hoffman PC, Ferguson MK, Weichselbaum RR, Golomb HM. Neoadjuvant vindesine, etoposide, and cisplatin for locally advanced non-small cell lung cancer. Final report of a phase 2 study. Chest (1989) 96(1):110–3.
    1. Pujol JL, Rossi JF, Le Chevalier T, Daures JP, Rouanet P, Douillard JY, et al. Pilot study of neoadjuvant ifosfamide, cisplatin, and etoposide in locally advanced non-small cell lung cancer. Eur J Cancer (1990) 26(7):798–801.10.1016/0277-5379(90)90155-M
    1. Burkes RL, Ginsberg RJ, Shepherd FA, Blackstein ME, Goldberg ME, Waters PF, et al. Induction chemotherapy with mitomycin, vindesine, and cisplatin for stage III unresectable non-small-cell lung cancer: results of the Toronto Phase II Trial. J Clin Oncol (1992) 10(4):580–6.10.1200/JCO.1992.10.4.580
    1. Martini N, Kris MG, Flehinger BJ, Gralla RJ, Bains MS, Burt ME, et al. Preoperative chemotherapy for stage IIIa (N2) lung cancer: the Sloan-Kettering experience with 136 patients. Ann Thorac Surg (1993) 55(6):1365–73; discussion 73–4.10.1016/0003-4975(93)91072-U
    1. Darwish S, Minotti V, Crino L, Rossetti R, Maranzano E, Checcaglini F, et al. Neoadjuvant cisplatin and etoposide for stage IIIA (clinical N2) non-small cell lung cancer. Am J Clin Oncol (1994) 17(1):64–7.10.1097/00000421-199402000-00014
    1. Sugarbaker DJ, Herndon J, Kohman LJ, Krasna MJ, Green MR. Results of cancer and leukemia group B protocol 8935. A multiinstitutional phase II trimodality trial for stage IIIA (N2) non-small-cell lung cancer. Cancer and Leukemia Group B Thoracic Surgery Group. J Thorac Cardiovasc Surg (1995) 109(3):473–83; discussion 83–5.10.1016/S0022-5223(95)70278-4
    1. Elias AD, Skarin AT, Leong T, Mentzer S, Strauss G, Lynch T, et al. Neoadjuvant therapy for surgically staged IIIA N2 non-small cell lung cancer (NSCLC). Lung Cancer (1997) 17(1):147–61.10.1016/S0169-5002(97)00658-2
    1. Van Zandwijk N, Smit EF, Kramer GW, Schramel F, Gans S, Festen J, et al. Gemcitabine and cisplatin as induction regimen for patients with biopsy-proven stage IIIA N2 non-small-cell lung cancer: a phase II study of the European Organization for Research and Treatment of Cancer Lung Cancer Cooperative Group (EORTC 08955). J Clin Oncol (2000) 18(14):2658–64.10.1200/JCO.2000.18.14.2658
    1. Betticher DC, Hsu Schmitz SF, Totsch M, Hansen E, Joss C, von Briel C, et al. Mediastinal lymph node clearance after docetaxel-cisplatin neoadjuvant chemotherapy is prognostic of survival in patients with stage IIIA pN2 non-small-cell lung cancer: a multicenter phase II trial. J Clin Oncol (2003) 21(9):1752–9.10.1200/JCO.2003.11.040
    1. O’Brien ME, Splinter T, Smit EF, Biesma B, Krzakowski M, Tjan-Heijnen VC, et al. Carboplatin and paclitaxol (Taxol) as an induction regimen for patients with biopsy-proven stage IIIA N2 non-small cell lung cancer. an EORTC phase II study (EORTC 08958). Eur J Cancer (2003) 39(10):1416–22.10.1016/S0959-8049(03)00319-8
    1. De Marinis F, Nelli F, Migliorino MR, Martelli O, Cortesi E, Treggiari S, et al. Gemcitabine, paclitaxel, and cisplatin as induction chemotherapy for patients with biopsy-proven stage IIIA(N2) nonsmall cell lung carcinoma: a phase II multicenter study. Cancer (2003) 98(8):1707–15.10.1002/cncr.11662
    1. Cappuzzo F, Selvaggi G, Gregorc V, Mazzoni F, Betti M, Rita Migliorino M, et al. Gemcitabine and cisplatin as induction chemotherapy for patients with unresectable stage IIIA-bulky N2 and stage IIIB nonsmall cell lung carcinoma: an Italian Lung Cancer Project Observational Study. Cancer (2003) 98(1):128–34.10.1002/cncr.11460
    1. Burkes RL, Shepherd FA, Blackstein ME, Goldberg ME, Waters PF, Patterson GA, et al. Induction chemotherapy with mitomycin, vindesine, and cisplatin for stage IIIA (T1-3, N2) unresectable non-small-cell lung cancer: final results of the Toronto phase II trial. Lung Cancer (2005) 47(1):103–9.10.1016/j.lungcan.2004.06.004
    1. Biesma B, Manegold C, Smit HJ, Willems L, Legrand C, Passioukov A, et al. Docetaxel and cisplatin as induction chemotherapy in patients with pathologically-proven stage IIIA N2 non-small cell lung cancer: a phase II study of the European organization for research and treatment of cancer (EORTC 08984). Eur J Cancer (2006) 42(10):1399–406.10.1016/j.ejca.2006.01.049
    1. Garrido P, Gonzalez-Larriba JL, Insa A, Provencio M, Torres A, Isla D, 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(30):4736–42.10.1200/JCO.2007.12.0014
    1. Chaft JE, Rusch V, Ginsberg MS, Paik PK, Finley DJ, Kris MG, et al. Phase II trial of neoadjuvant bevacizumab plus chemotherapy and adjuvant bevacizumab in patients with resectable nonsquamous non-small-cell lung cancers. J Thorac Oncol (2013) 8(8):1084–90.10.1097/JTO.0b013e31829923ec
    1. Ou W, Li N, Wang SY, Li J, Liu QW, Huang QA, et al. Phase 2 trial of neoadjuvant bevacizumab plus pemetrexed and carboplatin in patients with unresectable stage III lung adenocarcinoma (GASTO 1001). Cancer (2016) 122(5):740–7.10.1002/cncr.29800
    1. Pass HI, Pogrebniak HW, Steinberg SM, Mulshine J, Minna J. Randomized trial of neoadjuvant therapy for lung cancer: interim analysis. Ann Thorac Surg (1992) 53(6):992–8.10.1016/0003-4975(92)90373-C
    1. Rosell R, Gomez-Codina J, Camps C, Maestre J, Padille J, Canto A, et al. A randomized trial comparing preoperative chemotherapy plus surgery with surgery alone in patients with non-small-cell lung cancer. N Engl J Med (1994) 330(3):153–8.10.1056/NEJM199401203300301
    1. Roth JA, Fossella F, Komaki R, Ryan MB, Putnam JB, Jr, Lee JS, et al. A randomized trial comparing perioperative chemotherapy and surgery with surgery alone in resectable stage IIIA non-small-cell lung cancer. J Natl Cancer Inst (1994) 86(9):673–80.10.1093/jnci/86.9.673
    1. Depierre A, Milleron B, Moro-Sibilot D, Chevret S, Quoix E, Lebeau B, et al. Preoperative chemotherapy followed by surgery compared with primary surgery in resectable stage I (except T1N0), II, and IIIa non-small-cell lung cancer. J Clin Oncol (2002) 20(1):247–53.10.1200/JCO.20.1.247
    1. Burdett S, Stewart LA, Rydzewska L. A systematic review and meta-analysis of the literature: chemotherapy and surgery versus surgery alone in non-small cell lung cancer. J Thorac Oncol (2006) 1(7):611–21.10.1016/S1556-0864(15)30371-3
    1. Thomas M, Rube C, Hoffknecht P, Macha HN, Freitag L, Linder A, et al. Effect of preoperative chemoradiation in addition to preoperative chemotherapy: a randomised trial in stage III non-small-cell lung cancer. Lancet Oncol (2008) 9(7):636–48.10.1016/S1470-2045(08)70156-6
    1. Albain KS, Swann RS, Rusch VW, Turrisi AT, III, Shepherd FA, Smith C, 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) 374(9687):379–86.10.1016/S0140-6736(09)60737-6
    1. Palazzi M, Cataldo I, Gramaglia A, De Toma D, Milani F, Ravasi G. Preoperative concomitant cisplatin/VP16 and radiotherapy in stage III non-small cell lung cancer. Int J Radiat Oncol Biol Phys (1993) 27(3):621–5.10.1016/0360-3016(93)90388-C
    1. Favaretto A, Paccagnella A, Tomio L, Sartori F, Cipriani A, Zuin R, et al. Pre-operative chemoradiotherapy in non-small cell lung cancer stage III patients. Feasibility, toxicity and long-term results of a phase II study. Eur J Cancer (1996) 32A(12):2064–9.10.1016/S0959-8049(96)00248-1
    1. Albain KS, Rusch VW, Crowley JJ, Rice TW, Turrisi AT, III, Weick JK, 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(8):1880–92.10.1200/JCO.1995.13.8.1880
    1. Eberhardt W, Wilke H, Stamatis G, Stuschke M, Harstrick A, Menker H, et al. Preoperative chemotherapy followed by concurrent chemoradiation therapy based on hyperfractionated accelerated radiotherapy and definitive surgery in locally advanced non-small-cell lung cancer: mature results of a phase II trial. J Clin Oncol (1998) 16(2):622–34.10.1200/JCO.1998.16.2.622
    1. Winton T, Livingston R, Johnson D, Rigas J, Johnston M, Butts C, et al. Vinorelbine plus cisplatin vs. observation in resected non-small-cell lung cancer. N Engl J Med (2005) 352(25):2589–97.10.1056/NEJMoa043623
    1. Kreuter M, Vansteenkiste J, Fischer JR, Eberhardt W, Zabeck H, Kollmeier J, et al. Randomized phase 2 trial on refinement of early-stage NSCLC adjuvant chemotherapy with cisplatin and pemetrexed versus cisplatin and vinorelbine: the TREAT study. Ann Oncol (2013) 24(4):986–92.10.1093/annonc/mds578
    1. Gilligan D, Nicolson M, Smith I, Groen H, Dalesio O, Goldstraw P, et al. Preoperative chemotherapy in patients with resectable non-small cell lung cancer: results of the MRC LU22/NVALT 2/EORTC 08012 multicentre randomised trial and update of systematic review. Lancet (2007) 369(9577):1929–37.10.1016/S0140-6736(07)60714-4
    1. Pisters KM, Vallieres E, Crowley JJ, Franklin WA, Bunn PA, Jr, Ginsberg RJ, et al. Surgery with or without preoperative paclitaxel and carboplatin in early-stage non-small-cell lung cancer: Southwest Oncology Group Trial S9900, an intergroup, randomized, phase III trial. J Clin Oncol (2010) 28(11):1843–9.10.1200/JCO.2009.26.1685
    1. Felip E, Rosell R, Maestre JA, Rodriguez-Paniagua JM, Moran T, Astudillo J, et al. Preoperative chemotherapy plus surgery versus surgery plus adjuvant chemotherapy versus surgery alone in early-stage non-small-cell lung cancer. J Clin Oncol (2010) 28(19):3138–45.10.1200/JCO.2009.27.6204
    1. Evans NR, III, Li S, Wright CD, Allen MS, Gaissert HA. The impact of induction therapy on morbidity and operative mortality after resection of primary lung cancer. J Thorac Cardiovasc Surg (2010) 139(4):991–6.e1–2.10.1016/j.jtcvs.2009.11.070
    1. Mansour Z, Kochetkova EA, Ducrocq X, Vasilescu MD, Maxant G, Buggenhout A, et al. Induction chemotherapy does not increase the operative risk of pneumonectomy! Eur J Cardiothorac Surg (2007) 31(2):181–5.10.1016/j.ejcts.2006.11.008
    1. Stefani A, Alifano M, Bobbio A, Grigoroiu M, Jouni R, Magdeleinat P, et al. Which patients should be operated on after induction chemotherapy for N2 non-small cell lung cancer? Analysis of a 7-year experience in 175 patients. J Thorac Cardiovasc Surg (2010) 140(2):356–63.10.1016/j.jtcvs.2010.02.018
    1. Taylor SG, Trybula M, Bonomi PD, Faber LP, Lee MS, Reddy S, et al. Simultaneous cisplatin fluorouracil infusion and radiation followed by surgical resection in regionally localized stage III, non-small cell lung cancer. Ann Thorac Surg (1987) 43(1):87–91.10.1016/S0003-4975(10)60173-7
    1. Pincus M, Reddy S, Lee MS, Bonomi P, Taylor S, Rowland K, et al. Preoperative combined modality therapy for stage III M0 non-small cell lung carcinoma. Int J Radiat Oncol Biol Phys (1988) 15(1):189–95.10.1016/0360-3016(88)90365-3
    1. Faber LP, Kittle CF, Warren WH, Bonomi PD, Taylor SG, Reddy S, et al. Preoperative chemotherapy and irradiation for stage III non-small cell lung cancer. Ann Thorac Surg (1989) 47(5):669–75; discussion 76–7.10.1016/0003-4975(89)90115-X
    1. Recine D, Rowland K, Reddy S, Lee MS, Bonomi P, Taylor S, et al. Combined modality therapy for locally advanced non-small cell lung carcinoma. Cancer (1990) 66(11):2270–8.10.1002/1097-0142(19901201)66:11<2270::AID-CNCR2820661104>;2-H
    1. Strauss GM, Herndon JE, Sherman DD, Mathisen DJ, Carey RW, Choi NC, et al. Neoadjuvant chemotherapy and radiotherapy followed by surgery in stage IIIA non-small-cell carcinoma of the lung: report of a Cancer and Leukemia Group B phase II study. J Clin Oncol (1992) 10(8):1237–44.10.1200/JCO.1992.10.8.1237
    1. Weiden PL, Piantadosi S. Preoperative chemotherapy (cisplatin and fluorouracil) and radiation therapy in stage III non-small cell lung cancer. A phase 2 study of the LCSG. Chest (1994) 106(6 Suppl):344S–7S.10.1378/chest.106.6.344S
    1. Choi NC, Carey RW, Daly W, Mathisen D, Wain J, Wright C, et al. Potential impact on survival of improved tumor downstaging and resection rate by preoperative twice-daily radiation and concurrent chemotherapy in stage IIIA non-small-cell lung cancer. J Clin Oncol (1997) 15(2):712–22.10.1200/JCO.1997.15.2.712
    1. Thomas M, Rube C, Semik M, von Eiff M, Freitag L, Macha HN, et al. Impact of preoperative bimodality induction including twice-daily radiation on tumor regression and survival in stage III non-small-cell lung cancer. J Clin Oncol (1999) 17(4):1185.10.1200/JCO.1999.17.4.1185
    1. D’Angelillo RM, Trodella L, Ciresa M, Cellini F, Fiore M, Greco C, et al. Multimodality treatment of stage III non-small cell lung cancer: analysis of a phase II trial using preoperative cisplatin and gemcitabine with concurrent radiotherapy. J Thorac Oncol (2009) 4(12):1517–23.10.1097/JTO.0b013e3181b9e860
    1. Shah AA, Berry MF, Tzao C, Gandhi M, Worni M, Pietrobon R, et al. Induction chemoradiation is not superior to induction chemotherapy alone in stage IIIA lung cancer. Ann Thorac Surg (2012) 93(6):1807–12.10.1016/j.athoracsur.2012.03.018
    1. Sher DJ, Fidler MJ, Liptay MJ, Koshy M. Comparative effectiveness of neoadjuvant chemoradiotherapy versus chemotherapy alone followed by surgery for patients with stage IIIA non-small cell lung cancer. Lung Cancer (2015) 88(3):267–74.10.1016/j.lungcan.2015.03.015
    1. Higgins K, Chino JP, Marks LB, Ready N, D’Amico TA, Clough RW, et al. Preoperative chemotherapy versus preoperative chemoradiotherapy for stage III (N2) non-small-cell lung cancer. Int J Radiat Oncol Biol Phys (2009) 75(5):1462–7.10.1016/j.ijrobp.2009.01.069
    1. Decaluwe H, De Leyn P, Vansteenkiste J, Dooms C, Van Raemdonck D, Nafteux P, et al. Surgical multimodality treatment for baseline resectable stage IIIA-N2 non-small cell lung cancer. Degree of mediastinal lymph node involvement and impact on survival. Eur J Cardiothorac Surg (2009) 36(3):433–9.10.1016/j.ejcts.2009.04.013
    1. Cerfolio RJ, Maniscalco L, Bryant AS. The treatment of patients with stage IIIA non-small cell lung cancer from N2 disease: who returns to the surgical arena and who survives. Ann Thorac Surg (2008) 86(3):912–20; discussion 20.10.1016/j.athoracsur.2008.04.073
    1. Auperin A, Le Pechoux 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(13):2181–90.10.1200/JCO.2009.26.2543
    1. Chen M, Jiang GL, Fu XL, Wang LJ, Qian H, Chen GY, et al. The impact of overall treatment time on outcomes in radiation therapy for non-small cell lung cancer. Lung Cancer (2000) 28(1):11–9.10.1016/S0169-5002(99)00113-0
    1. Bese NS, Hendry J, Jeremic B. Effects of prolongation of overall treatment time due to unplanned interruptions during radiotherapy of different tumor sites and practical methods for compensation. Int J Radiat Oncol Biol Phys (2007) 68(3):654–61.10.1016/j.ijrobp.2007.03.010
    1. Martins RG, D’Amico TA, Loo BW, Jr, Pinder-Schenck M, Borghaei H, Chaft JE, et al. The management of patients with stage IIIA non-small cell lung cancer with N2 mediastinal node involvement. J Natl Compr Canc Netw (2012) 10(5):599–613.10.6004/jnccn.2012.0062
    1. Douillard JY, Rosell R, De Lena M, Riggi M, Hurteloup P, Mahe MA, et al. Impact of postoperative radiation therapy on survival in patients with complete resection and stage I, II, or IIIA non-small-cell lung cancer treated with adjuvant chemotherapy: the adjuvant Navelbine International Trialist Association (ANITA) Randomized Trial. Int J Radiat Oncol Biol Phys (2008) 72(3):695–701.10.1016/j.ijrobp.2008.01.044
    1. Burdett S, Rydzewska L, Tierney J, Fisher D, Parmar MK, Arriagada R, et al. Postoperative radiotherapy for non-small cell lung cancer. Cochrane Database Syst Rev (2016) 10:CD002142.10.1002/14651858.CD002142.pub4
    1. Belani CP, Choy H, Bonomi P, Scott C, Travis P, Haluschak J, et al. Combined chemoradiotherapy regimens of paclitaxel and carboplatin for locally advanced non-small-cell lung cancer: a randomized phase II locally advanced multi-modality protocol. J Clin Oncol (2005) 23(25):5883–91.10.1200/JCO.2005.55.405
    1. Ohe Y, Ohashi Y, Kubota K, Tamura T, Nakagawa K, Negoro S, et al. Randomized phase III study of cisplatin plus irinotecan versus carboplatin plus paclitaxel, cisplatin plus gemcitabine, and cisplatin plus vinorelbine for advanced non-small-cell lung cancer: Four-Arm Cooperative Study in Japan. Ann Oncol (2007) 18(2):317–23.10.1093/annonc/mdl377
    1. Senan S, Brade A, Wang LH, Vansteenkiste J, Dakhil S, Biesma B, et al. PROCLAIM: randomized phase III trial of pemetrexed-cisplatin or etoposide-cisplatin plus thoracic radiation therapy followed by consolidation chemotherapy in locally advanced nonsquamous non-small-cell lung cancer. J Clin Oncol (2016) 34(9):953–62.10.1200/JCO.2015.64.8824
    1. . (2017). Available from:
    1. Liang J, Bi N, Wu S, Chen M, Lv C, Zhao L, et al. Etoposide and cisplatin versus paclitaxel and carboplatin with concurrent thoracic radiotherapy in unresectable stage III non-small cell lung cancer: a multicenter randomized phase III trial. Ann Oncol (2017) 28(4):777–83.10.1093/annonc/mdx009
    1. Kramer GW, Legrand CL, van Schil P, Uitterhoeve L, Smit EF, Schramel F, et al. Quality assurance of thoracic radiotherapy in EORTC 08941: a randomised trial of surgery versus thoracic radiotherapy in patients with stage IIIA non-small-cell lung cancer (NSCLC) after response to induction chemotherapy. Eur J Cancer (2006) 42(10):1391–8.10.1016/j.ejca.2006.01.052
    1. Bradley JD, Paulus R, Komaki R, Masters G, Blumenschein G, Schild S, et al. Standard-dose versus high-dose conformal radiotherapy with concurrent and consolidation carboplatin plus paclitaxel with or without cetuximab for patients with stage IIIA or IIIB non-small-cell lung cancer (RTOG 0617): a randomised, two-by-two factorial phase 3 study. Lancet Oncol (2015) 16(2):187–99.10.1016/S1470-2045(14)71207-0
    1. Suntharalingam M, Paulus R, Edelman MJ, Krasna M, Burrows W, Gore E, et al. Radiation therapy oncology group protocol 02-29: a phase II trial of neoadjuvant therapy with concurrent chemotherapy and full-dose radiation therapy followed by surgical resection and consolidative therapy for locally advanced non-small cell carcinoma of the lung. Int J Radiat Oncol Biol Phys (2012) 84(2):456–63.10.1016/j.ijrobp.2011.11.069
    1. Samson P, Crabtree TD, Robinson CG, Morgensztern D, Broderick S, Krupnick AS, et al. Defining the ideal time interval between planned induction therapy and surgery for stage IIIA non-small cell lung cancer. Ann Thorac Surg (2017) 103(4):1070–5.10.1016/j.athoracsur.2016.09.053
    1. Gao SJ, Corso CD, Wang EH, Blasberg JD, Detterbeck FC, Boffa DJ, et al. Timing of surgery after neoadjuvant chemoradiation in locally advanced non-small cell lung cancer. J Thorac Oncol (2017) 12(2):314–22.10.1016/j.jtho.2016.09.122
    1. Zhong W, Yang X, Yan H, Zhang X, Su J, Chen Z, et al. Phase II study of biomarker-guided neoadjuvant treatment strategy for IIIA-N2 non-small cell lung cancer based on epidermal growth factor receptor mutation status. J Hematol Oncol (2015) 8:54.10.1186/s13045-015-0151-3
    1. Schaake EE, Kappers I, Codrington HE, Valdes Olmos RA, Teertstra HJ, van Pel R, et al. Tumor response and toxicity of neoadjuvant erlotinib in patients with early-stage non-small-cell lung cancer. J Clin Oncol (2012) 30(22):2731–8.10.1200/JCO.2011.39.4882
    1. . (2017). Available from:
    1. Juweid ME, Cheson BD. Positron-emission tomography and assessment of cancer therapy. N Engl J Med (2006) 354(5):496–507.10.1056/NEJMra050276
    1. Berghmans T, Dusart M, Paesmans M, Hossein-Foucher C, Buvat I, Castaigne C, et al. Primary tumor standardized uptake value (SUVmax) measured on fluorodeoxyglucose positron emission tomography (FDG-PET) is of prognostic value for survival in non-small cell lung cancer (NSCLC): a systematic review and meta-analysis (MA) by the European Lung Cancer Working Party for the IASLC Lung Cancer Staging Project. J Thorac Oncol (2008) 3(1):6–12.10.1097/JTO.0b013e31815e6d6b
    1. Bharat AGB, Rusch VW, Bains MS, Rizk NP. Role of PET scan in predicting response to neoadjuvant chemotherapy and long-term outcomes for stage II lung cancer. ASCO Meet Abstr (2014) 32(15_suppl):7574.10.1200/jco.2014.32.15_suppl.7574
    1. Hoekstra CJ, Stroobants SG, Smit EF, Vansteenkiste J, van Tinteren H, Postmus PE, et al. Prognostic relevance of response evaluation using [18F]-2-fluoro-2-deoxy-D-glucose positron emission tomography in patients with locally advanced non-small-cell lung cancer. J Clin Oncol (2005) 23(33):8362–70.10.1200/JCO.2005.01.1189
    1. Chaft JE, Dunphy M, Naidoo J, Travis WD, Hellmann M, Woo K, et al. Adaptive neoadjuvant chemotherapy guided by (18)F-FDG PET in resectable non-small cell lung cancers: the NEOSCAN trial. J Thorac Oncol (2016) 11(4):537–44.10.1016/j.jtho.2015.12.104

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