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Non-Small Cell Lung Cancer: Epidemiology, Risk Factors, Treatment, and Survivorship

      Lung cancer is the leading cause of cancer-related mortality not only in the United States but also around the world. In North America, lung cancer has become more predominant among former than current smokers. Yet in some countries, such as China, which has experienced a dramatic increase in the cigarette smoking rate during the past 2 decades, a peak in lung cancer incidence is still expected. Approximately two-thirds of adult Chinese men are smokers, representing one-third of all smokers worldwide. Non-small cell lung cancer accounts for 85% of all lung cancer cases in the United States. After the initial diagnosis, accurate staging of non-small cell lung cancer using computed tomography or positron emission tomography is crucial for determining appropriate therapy. When feasible, surgical resection remains the single most consistent and successful option for cure. However, close to 70% of patients with lung cancer present with locally advanced or metastatic disease at the time of diagnosis. Chemotherapy is beneficial for patients with metastatic disease, and the administration of concurrent chemotherapy and radiation is indicated for stage III lung cancer. The introduction of angiogenesis, epidermal growth factor receptor inhibitors, and other new anticancer agents is changing the present and future of this disease and will certainly increase the number of lung cancer survivors. We identified studies for this review by searching the MEDLINE and PubMed databases for English-language articles published from January 1, 1980, through January 31, 2008. Key terms used for this search included non-small cell lung cancer, adenocarcinoma, squamous cell carcinoma, bronchioalveolar cell carcinoma, large cell carcinoma, lung cancer epidemiology, genetics, survivorship, surgery, radiation therapy, chemotherapy, targeted therapy, bevacizumab, erlotinib, and epidermal growth factor receptor.
      CBDCA ( carboplatin), CT ( computed tomography), EGFR ( epidermal growth factor receptor), FDA ( Food and Drug Administration), GyE ( Gy equivalent), LTLC ( long-term lung cancer), NHEJ ( nonhomologous endjoining), NSCLC ( non-small cell lung cancer), PET ( positron emission tomography), PTX ( paclitaxel), RT ( radiation therapy), SCLC ( small cell lung cancer), SPLC ( subsequent primary lung cancer), TEMLA ( transcervical extended mediastinal lymphadenectomy), TK ( tyrosine kinase), UFT ( uracil-tegafur), VEGF ( vascular endothelial growth factor), VEGFR ( VEGF receptor)
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        • Jemal A
        • Siegel R
        • Ward E
        • et al.
        Cancer statistics, 2008.
        CA Cancer J Clin. 2008 Mar-Apr; 58 (Epub 2008 Feb 20.): 71-96
        • Navada S
        • Lai P
        • Schwartz AG
        • Kalemkerian GP
        Temporal trends in small cell lung cancer: analysis of the national Surveillance Epidemiology and End-Results (SEER) database [abstract 7082].
        J Clin Oncol. 2006; 24: 384S
        • Sher T
        • Dy GK
        • Adjei AA
        Small cell lung cancer.
        Mayo Clin Proc. 2008; 83: 355-367
        • Yang P
        • Allen MS
        • Aubry MC
        • et al.
        Clinical features of 5,628 primary lung cancer patients: experience at Mayo Clinic from 1997 to 2003.
        Chest. 2005; 128: 452-462
        • Zhang H
        • Cai B
        The impact of tobacco on lung health in China.
        Respirology. 2003; 8: 17-21
        • Shaper AG
        • Wannamethee SG
        • Walker M
        Pipe and cigar smoking and major cardiovascular events, cancer incidence and all-cause mortality in middle-aged British men.
        Int J Epidemiol. 2003; 32: 802-808
        • Henley SJ
        • Thun MJ
        • Chao A
        • Calle EE
        Association between exclusive pipe smoking and mortality from cancer and other diseases.
        J Natl Cancer Inst. 2004; 96: 853-861
        • Alberg AJ
        • Brock MV
        • Samet JM
        Epidemiology of lung cancer: looking to the future.
        J Clin Oncol. 2005; 23: 3175-3185
        • Boffetta P
        Human cancer from environmental pollutants: the epidemiological evidence.
        Mutat Res. 2006 Sep 28; 608 (Epub 2006 Jul 13.): 157-162
        • Hackshaw AK
        • Law MR
        • Wald NJ
        The accumulated evidence on lung cancer and environmental tobacco smoke.
        BMJ. 1997; 315: 980-988
        • Whitrow MJ
        • Smith BJ
        • Pilotto LS
        • Pisaniello D
        • Nitschke M
        Environmental exposure to carcinogens causing lung cancer: epidemiological evidence from the medical literature.
        Respirology. 2003; 8: 513-521
        • Vineis P
        • Airoldi L
        • Veglia P
        • et al.
        Environmental tobacco smoke and risk of respiratory cancer and chronic obstructive pulmonary disease in former smokers and never smokers in the EPIC prospective study.
        BMJ. 2005 Feb 5; 330 (Epub 2005 Jan 28.): 277
        • Krinsky NI
        • Johnson EJ
        Carotenoid actions and their relation to health and disease.
        Mol Aspects Med. 2005 Dec; 26 (Epub 2005 Nov 23.): 459-516
        • Ruano-Ravina A
        • Figueiras A
        • Freire-Garabal M
        • Barros-Dios JM
        Antioxidant vitamins and risk of lung cancer.
        Curr Pharm Des. 2006; 12: 599-613
        • Lam WK
        Lung cancer in Asian women—the environment and genes.
        Respirology. 2005; 10: 408-417
        • Siems W
        • Wiswedel I
        • Salerno C
        • et al.
        β-Carotene breakdown products may impair mitochondrial functions—potential side effects of high-dose β-carotene supplementation.
        J Nutr Biochem. 2005; 16: 385-397
        • Freudenheim JL
        • Ritz J
        • Smith-Warner SA
        • et al.
        Alcohol consumption and risk of lung cancer: a pooled analysis of cohort studies.
        Am J Clin Nutr. 2005; 82: 657-667
        • Lee IM
        Physical activity and cancer prevention—data from epidemiologic studies.
        Med Sci Sports Exerc. 2003; 35: 1823-1827
        • Tardon A
        • Lee WJ
        • Delgado-Rodriguez M
        • et al.
        Leisure-time physical activity and lung cancer: a meta-analysis.
        Cancer Causes Control. 2005; 16: 389-397
        • Friedenreich CM
        • Orenstein MR
        Physical activity and cancer prevention: etiologic evidence and biological mechanisms.
        J Nutr. 2002; 132: 3456S-3464S
        • Alfano CM
        • Klesges RC
        • Murray DM
        • et al.
        Physical activity in relation to all-site and lung cancer incidence and mortality in current and former smokers.
        Cancer Epidemiol Biomarkers Prev. 2004; 13: 2233-2241
        • Kunzli N
        • Tager IB
        Air pollution: from lung to heart.
        Swiss Med Wkly. 2005; 135: 697-702
        • Vineis P
        • Husgafvel-Pursiainen K
        Air pollution and cancer: biomarker studies in human populations.
        Carcinogenesis. 2005 Nov; 26 (Epub 2005 Aug 25.): 1846-1855
        • Boffetta P
        Epidemiology of environmental and occupational cancer.
        Oncogene. 2004; 23: 6392-6403
        • Sellers TA
        • Yang P
        Familial and genetic influences on risk of lung cancer.
        in: King RA Rotter JI Motulsky AG The Genetic Basis of Common Diseases. 2nd ed. Oxford University Press, New York, NY2002: 700-712
        • Hwang SJ
        • Cheng LS
        • Lozano G
        • Amos CI
        • Gu X
        • Strong LC
        Lung cancer risk in germline p53 mutation carriers: association between an inherited cancer predisposition, cigarette smoking, and cancer risk.
        Hum Genet. 2003 Aug; 113 (Epub 2003 Jun 11.): 238-243
        • Li X
        • Hemminki K
        Inherited predisposition to early onset lung cancer according to histological type.
        Int J Cancer. 2004; 112: 451-457
        • Bailey-Wilson JE
        • Amos CI
        • Pinney SM
        • et al.
        A major lung cancer susceptibility locus maps to chromosome 6p23-25.
        Am J Human Genet. 2004 Sep; 75 (Epub 2004 Jul 21.): 460-474
        • Thorgeirsson TE
        • Geller F
        • Sulem P
        • et al.
        A variant associated with nicotine dependence, lung cancer and peripheral arterial disease.
        Nature. 2008; 452: 638-642
        • Hung RJ
        • McKay JD
        • Gaborieau V
        • et al.
        A susceptibility locus for lung cancer maps to nicotinic acetylcholine receptor subunit genes on 15q25.
        Nature. 2008; 452: 633-637
      1. Amos CI, Wu X, Broderick P, et al. Genome-wide association scan of tag SNPs identifies a susceptibility locus for lung cancer at 15q25.1 [published online ahead of print April 2, 2008]. Nat Genet, doi:10.1038/ng.109.

        • Arita T
        • Kuramitsu T
        • Kawamura M
        • et al.
        Bronchogenic carcinoma: incidence of metastases to normal sized lymph nodes.
        Thorax. 1995; 50: 1267-1269
        • Marom EM
        • McAdams HP
        • Erasmus JJ
        • et al.
        Staging non-small cell lung cancer with whole-body PET.
        Radiology. 1999; 212: 803-809
        • Weder W
        • Schmid RA
        • Bruchhaus H
        • Hillinger S
        • von Schulthess GK
        • Steinert HC
        Detection of extrathoracic metastases by positron emission tomography in lung cancer.
        Ann Thorac Surg. 1998; 66: 886-892
        • Valk PE
        • Pounds TR
        • Hopkins DM
        • et al.
        Staging non-small cell lung cancer by whole-body positron emission tomographic imaging.
        Ann Thorac Surg. 1995; 60: 1573-1581
        • Pieterman RM
        • van Putten JW
        • Meuzelaar JJ
        • et al.
        Preoperative staging of non-small-cell lung cancer with positron-emission tomography.
        N Engl J Med. 2000; 343: 254-261
        • Eloubeidi MA
        • Cerfolio RJ
        • Chen VK
        • Desmond R
        • Syed S
        • Ojha B
        Endoscopic ultrasound-guided fine needle aspiration of mediastinal lymph node in patients with suspected lung cancer after positron emission tomography and computed tomography scans.
        Ann Thorac Surg. 2005; 79: 263-268
        • Vilmann P
        • Krasnik M
        • Larsen SS
        • Jacobsen GK
        • Clementsen P
        Transesophageal endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) and endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) biopsy: a combined approach in the evaluation of mediastinal lesions.
        Endoscopy. 2005; 37: 833-839
        • Kim K
        • Rice TW
        • Murthy SC
        • et al.
        Combined bronchoscopy, mediastinoscopy, and thoracotomy for lung cancer: who benefits?.
        J Thorac Cardiovasc Surg. 2004; 127: 850-856
        • Kuzdal J
        • Zielinski M
        • Papla B
        • et al.
        Transcervical extended mediastinal lymphadenectomy—the new operative technique and early results in lung cancer staging.
        Eur J Cardiothorac Surg. 2005 Mar; 27 (Epub 2005 Jan 13.): 384-390
        • Kuzdal J
        • Zielinski M
        • Papla B
        • et al.
        The transcervical extended mediastinal lymphadenectomy versus cervical mediastinoscopy in non-small cell lung cancer staging.
        Eur J Cardiothorac Surg. 2007 Jan; 31 (Epub 2006 Nov 20.): 88-94
        • Henschke CI
        • McCauley DI
        • Yankelevitz DF
        • et al.
        Early Lung Cancer Action Project: overall design and findings from baseline screening.
        Lancet. 1999; 354: 99-105
        • International Early Lung Cancer Action Program Investigators
        Survival of patients with stage I lung cancer detected on CT screening.
        N Engl J Med. 2006; 355: 1763-1771
        • US Preventive Services Task Force
        Lung cancer screening: recommendation statement.
        Ann Intern Med. 2004; 140: 738-739
        • Smith R
        • von Eschenbach A
        • Wender R
        • ACS Prostate Cancer Advisory Committee, ACS Colorectal Cancer Advisory Committee, ACS Endometrial Cancer Advisory Committee
        • et al.
        American Cancer Society guidelines for the early detection of cancer: update of early detection guidelines for prostate, colorectal, and endometrial cancers: also: update 2001—testing for early lung cancer detection.
        CA Cancer J Clin. 2001; 51: 38-75
        • Little AG
        No nodes is good nodes [editorial].
        Ann Thorac Surg. 2006; 82: 4-5
        • Ginsberg RJ
        • Rubinstein LV
        • Lung Cancer Study Group
        Randomized trial of lobectomy versus limited resection for T1 N0 non-small cell lung cancer.
        Ann Thorac Surg. 1995; 60: 615-622
        • Miller DL
        • Rowland CM
        • Deschamps C
        • Allen MS
        • Trastek VF
        • Pairolero PC
        Surgical treatment of non-small cell lung cancer 1 cm or less in diameter.
        Ann Thorac Surg. 2002; 73: 1545-1550
        • Okada M
        • Nishio W
        • Sakamoto T
        • et al.
        Effect of tumor size on prognosis in patients with non-small cell lung cancer: the role of segmentectomy as a type of lesser resection.
        J Thorac Cardiovasc Surg. 2005; 129: 87-93
        • Yamato T
        • Tsuchida M
        • Watanabe T
        • et al.
        Early results of a prospective study of limited resection for bronchioloalveolar adenocarcinoma of the lung.
        Ann Thorac Surg. 2001; 71: 971-974
        • Allen MS
        • Darling GE
        • Pechet TT
        • ACOSOG Z0030 Study Group
        • et al.
        Morbidity and mortality of major pulmonary resections in patients with early-stage lung cancer: initial results of the randomized, prospective ACOSOG Z0030 trial.
        Ann Thorac Surg. 2006; 81: 1013-1019
        • Onaitis MW
        • Petersen RP
        • Balderson SS
        • et al.
        Thoracoscopic lobectomy is a safe and versatile procedure: experience with 500 consecutive patients.
        Ann Surg. 2006; 244: 420-425
        • McKenna Jr, RJ
        • Houck W
        • Fuller CB
        Video-assisted thoracic surgery lobectomy: experience with 1,100 cases.
        Ann Thorac Surg. 2006; 81: 421-425
      2. US interim projections by age, sex, race, and Hispanic origin. Washington DC: US Census Bureau.
        (Accessed April 7, 2008.)
        • Dominguez-Ventura A
        • Allen MS
        • Cassivi SD
        • Nichols III, FC
        • Deschamps C
        • Pairolero PC
        Lung cancer in octogenarians: factors affecting morbidity and mortality after pulmonary resection.
        Ann Thorac Surg. 2006; 82: 1175-1179
        • Pfister DG
        • Johnson DH
        • Azzoli CG
        • et al.
        American Society of Clinical Oncology treatment of unresectable non-small-cell lung cancer guideline: updated 2003.
        J Clin Oncol. 2004 Jan 15; 22 (Epub 2003 Dec 22.): 330-353
        • 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
        • International Adjuvant Lung Cancer Trial Collaborative Group
        Cisplatin-based adjuvant chemotherapy in patients with completely resected non-small-cell lung cancer.
        N Engl J Med. 2004; 350: 351-360
        • Winton T
        • Livingston R
        • Johnson D
        • National Cancer Institute of Canada Clinical Trials Group, National Cancer Institute of the United States Intergroup JBR.10 Trial Investigators
        • et al.
        Vinorelbine and cisplatin vs. observation in resected non-small-cell lung cancer.
        N Engl J Med. 2005; 352: 2589-2597
        • Douillard J-Y
        • Rosell R
        • Delena M
        • Adjuvant Navelbine International Trialist Association
        • et al.
        ANITA: phase III adjuvant vinorelbine (N) and cisplatin (P) versus observation (OBS) in completely resected (stage I-III) non-small-cell lung cancer (NSCLC) patients (pts): final results after 70-month median follow-up [abstract 7013].
        J Clin Oncol. 2005; 23 (June 1 suppl): 624s
        • Strauss GM
        • Hernden JE
        • Maddaus MA
        • et al.
        Adjuvant chemotherapy in stage IB non-small cell lung cancer (NSCLC): update of Cancer and Leukemia Group B (CALGB) protocol 9633 [abstract 7007].
        J Clin Oncol. 2006; 24: 365s
        • Xu G
        • Rong T
        • Lin P
        Adjuvant chemotherapy following radical surgery for non-small cell lung cancer: a randomized study on 70 patients.
        Chin Med J (Engl). 2000; 113: 617-620
        • Mineo TC
        • Ambrogi V
        • Corsaro V
        • Roselli M
        Postoperative adjuvant therapy for stage IB non-small cell lung cancer.
        Eur J Cardiothorac Surg. 2001; 20: 378-384
        • Tada H
        • Yasumitu T
        • Iuchi K
        • Taki T
        • Kodama K
        • Mori T
        • Osaka Lung Cancer Study Group
        Randomized study of adjuvant chemotherapy for completely resected non-small cell lung cancer: lack of prognostic significance in DNA ploidy pattern at adjuvant setting [abstract 1250].
        Proc Am Soc Clin Oncol. 2002; 21: 313
        • Imaizumi M
        • Study Group of Adjuvant Chemotherapy for Lung Cancer (Chubu, Japan)
        Postoperative adjuvant cisplatin, vindesine, plus uracil-tegafur chemotherapy increased survival of patients with completely resected p-stage I non-small cell lung cancer.
        Lung Cancer. 2005; 49: 85-94
        • Tada H
        • Tsuchiya R
        • Ichinose Y
        • et al.
        A randomized trial comparing adjuvant chemotherapy versus surgery alone for completely resected pN2 nonsmall cell lung cancer (JCOG9304).
        Lung Cancer. 2004; 43: 167-173
        • Nakagawa M
        • Tanaka F
        • Tsubota N
        • West Japan Study Group for Lung Cancer Surgery (WJSG)
        • et al.
        A randomized phase III trial of adjuvant chemotherapy with UFT for completely resected pathological stage I nonsmall-cell lung cancer: the West Japan Study Group for Lung Cancer Surgery (WJSG); the 4th study.
        Ann Oncol. 2005; 16: 75-80
        • Endo C
        • Saito Y
        • Iwanami H
        • North-east Japan Study Group for Lung Cancer Surgery
        • et al.
        A randomized trial of postoperative UFT therapy in p stage I, II non-small cell lung cancer: north-east Japan Study Group for Lung Cancer Surgery.
        Lung Cancer. 2003; 40: 181-186
        • Kato H
        • Ichinose Y
        • Ohta M
        • Japan Lung Cancer Research Group on Postsurgical Adjuvant Chemotherapy
        • et al.
        A randomized trial of adjuvant chemotherapy with Uracil-Tegafur for adenocarcinoma of the lung.
        N Engl J Med. 2004; 350: 1713-1721
        • Barlesi F
        • Pujol J-L
        • Daures J-P
        Should chemotherapy (Cx) for advanced non-small cell lung cancer (NSCLC) be platinum-based? a literature-based meta-analysis of randomized trials [abstract 7213].
        J Clin Oncol. 2005; 23: 673s
        • D'Addario G
        • Pintilie M
        • Leighl NB
        • Feld R
        • Cerny R
        • Shepherd FA
        Platinum-based versus non-platinum-based chemotherapy in advanced nonsmall-cell lung cancer: a meta-analysis of the published literature.
        J Clin Oncol. 2005 May 1; 23 (Epub 2005 Feb 22.): 2926-2936
        • Mendelsohn J
        • Baselga J
        Status of epidermal growth factor receptor antagonists in the biology and treatment of cancer.
        J Clin Oncol. 2003; 21: 2787-2799
        • Kris MG
        • Natale RB
        • Herbst RS
        • et al.
        Efficacy of gefitinib, an inhibitor of the epidermal growth factor receptor tyrosine kinase, in symptomatic patients with non-small cell lung cancer: a randomized trial.
        JAMA. 2003; 290: 2149-2158
        • Thatcher N
        • Chang A
        • Parikh P
        • et al.
        Gefitinib plus best supportive care in previously treated patients with refractory advanced non-small-cell lung cancer: results from a randomised, placebo controlled, multicentre study (Iressa Survival Evaluation in Lung Cancer).
        Lancet. 2005; 366: 1527-1537
        • Kelly K
        • Gaspar LE
        • Chansky K
        • et al.
        Low incidence of pneumonitis on SWOG 0023: a preliminary analysis of an ongoing phase III trial of concurrent chemoradiotherapy followed by consolidation docetaxel and Iressa/placebo maintenance in patients with inoperable stage III non-small cell lung cancer [abstract 7058].
        J Clin Oncol. 2005; 23 (June 1 suppl): 634s
        • Perez-Soler R
        • Chachoua A
        • Hammond LA
        • et al.
        Determinants of tumor response and survival with erlotinib in patients with non-small-cell lung cancer.
        J Clin Oncol. 2004; 22: 3238-3247
        • Shepherd FA
        • Pereira J
        • Ciuleanu TE
        • et al.
        A randomized placebo-controlled trial of erlotinib in patients with advanced non-small cell lung cancer (NSCLC) following failure on 1st line or 2nd line chemotherapy: a National Cancer Institute of Canada Clinical Trials Group (NCIC CTG) trial [abstract 7022].
        J Clin Oncol. 2004; 22: 622s
        • Paez JG
        • Janne PA
        • Lee JC
        • et al.
        EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy.
        Science. 2004 Jun 4; 304 (Epub 2004 Apr 29.): 1497-1500
        • Lynch TJ
        • Bell DW
        • Sordella R
        • et al.
        Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib.
        N Engl J Med. 2004 May 20; 350 (Epub Apr 29.): 2129-2139
        • Pao W
        • Miller V
        • Zakowski M
        • et al.
        EGF receptor gene mutations are common in lung cancers from “never smokers” and are associated with sensitivity of tumors to gefitinib and erlotinib.
        Proc Natl Acad Sci U S A. 2004 Sep 7; 101 (Epub 2004 Aug 25.): 13306-13311
        • Sordella R
        • Bell DW
        • Haber DA
        • Settleman J
        Gefitinib-sensitizing EGFR mutations in lung cancer activate anti-apoptotic pathways.
        Science. 2004 Aug 20; 305 (Epub 2004 Jul 29.): 1163-1167
        • Sandler AB
        • Gray R
        • Brahmer J
        • et al.
        Randomized phase II/III trial of paclitaxel (P) plus carboplatin (C) with or without bevacizumab (NSC# 704865) in patients with advanced non-squamous, non-small-cell lung cancer (NSCLC): an Eastern Cooperative Oncology Group (ECOG) Trial E4599 [abstract 4].
        J Clin Oncol. 2005; 23: 2s
        • Roswit B
        • Liberson S
        • Ohanian M
        • Kusik H
        • Petrovich Z
        Survival with inoperable lung cancer: controlled national Veterans Administration study of radiation and chemotherapy.
        N Y State J Med. 1976; 76: 560-564
        • Wolf J
        • Patno ME
        • Roswit B
        • D'Esopo N
        Controlled study of survival of patients with clinically inoperable lung cancer treated with radiation therapy.
        Am J Med. 1966; 40: 360-367
        • Perez CA
        Non-small cell carcinoma of the lung: dose-time parameters.
        Cancer Treat Symp. 1985; 2: 131-142
        • Sause WT
        • Scott C
        • Taylor S
        • et al.
        Radiation Therapy Oncology Group (RTOG) 88-08 and Eastern Cooperative Oncology Group (ECOG) 4588: preliminary results of a phase III trial in regionally advanced, unresectable nonsmall-cell lung cancer.
        J Natl Cancer Inst. 1995; 87: 198-205
        • Schaake-Koning C
        • van den Bogaert W
        • Dalesio O
        • et al.
        Effects of concomitant cisplatin and radiotherapy on inoperable non-small-cell lung cancer.
        N Engl J Med. 1992; 326: 524-530
        • 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; 84: 58
        • 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
        • Onishi H
        • Araki T
        • Shirato H
        • et al.
        Stereotactic hypofractionated high-dose irradiation for stage I nonsmall cell lung carcinoma: clinical outcomes in 245 subjects in a Japanese multiinstitutional study.
        Cancer. 2004; 101: 1623-1631
        • Bush DA
        • Slater JD
        • Shin BB
        • Cheek G
        • Miller DW
        • Slater JM
        Hypofractionated proton beam radiotherapy for stage I lung cancer.
        Chest. 2004; 126: 1198-1203
        • Miyamoto T
        • Yamamoto N
        • Nishimura H
        • et al.
        Carbon ion radiotherapy for stage I non-small cell lung cancer.
        Radiother Oncol. 2003; 66: 127-140
        • Sun Z
        • Aubry MC
        • Deschamps C
        • et al.
        Histologic grade is an independent prognostic factor for survival in non-small cell lung cancer: an analysis of 5018 hospital- and 712 population-based cases.
        J Thorac Cardiovasc Surg. 2006; 131: 1014-1020
        • Ebbert JO
        • Yang P
        • Vachon CM
        • et al.
        Lung cancer risk reduction after smoking cessation: observations from a prospective cohort of women.
        J Clin Oncol. 2003; 21: 921-926
        • Schild SE
        • Stella PJ
        • Brooks BJ
        • et al.
        Results of combined-modality therapy for limited-stage small cell lung carcinoma in the elderly.
        Cancer. 2005; 103: 2349-2354
        • Hanna NH
        • Einhorn L
        • Sandler A
        • et al.
        Randomized, phase III trial comparing irinotecan/cisplatin (IP) with etoposide/cisplatin (EP) in patients (pts) with previously untreated, extensive-stage (ES) small cell lung cancer (SCLC) [abstract 7004].
        J Clin Oncol. 2005; 23 (June 1 suppl): 622s
        • Shigematsu H
        • Gazdar AF
        Somatic mutations of epidermal growth factor receptor signaling pathway in lung cancers.
        Int J Cancer. 2006; 118: 257-262
        • Janne PA
        • Engelman JA
        • Johnson BE
        Epidermal growth factor receptor mutations in non-small-cell lung cancer: implications for treatment and tumor biology.
        J Clin Oncol. 2005; 23: 3227-3234
        • Calvo E
        • Baselga J
        Ethnic differences in response to epidermal growth factor receptor tyrosine kinase inhibitors.
        J Clin Oncol. 2006; 24: 2158-2163
        • Fuertesa MA
        • Castillab J
        • Alonsoa C
        • Perez JM
        Cisplatin biochemical mechanism of action: from cytotoxicity to induction of cell death through interconnections between apoptotic and necrotic pathways.
        Curr Med Chem. 2003; 10: 257-266
        • Rosell R
        • Taron M
        • Camps C
        • Lopez-Vivanco G
        Influence of genetic markers on survival in non-small cell lung cancer.
        Drugs Today (Barc). 2003; 39: 775-786
        • Qiao TK
        • Zhou DA
        • Xin L
        • Shu L
        • Wu W
        Concurrent radiotherapy combined with carboplatin and etoposide in limited stage small cell lung cancer [in Chinese].
        Zhonghua Jie He He Hu Xi Za Zhi. 2004; 27: 237-239
        • Gurubhagavatula S
        • Liu G
        • Park S
        • et al.
        XPD and XRCC1 genetic polymorphisms are prognostic factors in advanced non-small-cell lung cancer patients treated with platinum chemotherapy.
        J Clin Oncol. 2004 Jul 1; 22 (Epub 2004 Jun 1.): 2594-2601
        • Bradley J
        • Graham MV
        • Winter K
        • et al.
        Toxicity and outcome results of RTOG 9311: a phase I-II dose-escalation study using three-dimensional conformal radiotherapy in patients with inoperable non-small-cell lung carcinoma.
        Int J Radiat Oncol Biol Phys. 2005; 61: 318-328
        • Connell PP
        • Kron SJ
        • Weichselbaum RR
        Relevance and irrelevance of DNA damage response to radiotherapy.
        DNA Repair (Amst). 2004; 3: 1245-1251
        • Willers H
        • Dahm-Daphi J
        • Powell SN
        Repair of radiation damage to DNA.
        Br J Cancer. 2004; 90: 1297-1301
        • Schild SE
        • Stella PJ
        • Geyer SM
        • et al.
        Phase III trial comparing chemotherapy plus once-daily or twice-daily radiotherapy in stage III non-small-cell lung cancer.
        Int J Radiat Oncol Biol Phys. 2002; 54: 370-378
        • Sugimura H
        • Yang P
        Long-term survivorship in lung cancer.
        Chest. 2006; 129: 1088-1097
        • Visbal AL
        • Williams BA
        • Nichols FC
        • et al.
        Gender differences in nonsmall cell lung cancer survival: an analysis of 4,618 patients diagnosed between 1997-2002.
        Ann Thorac Surg. 2004; 78: 209-215
        • National Cancer Institute
        SEER Cancer Statistics Review, 1973-1999. Bethesda, MD: National Cancer Institute.
        (Accessed April 8, 2008.)
        • Ko CY
        • Maggard M
        • Livingston EH
        Evaluating health utility in patients with melanoma, breast cancer, colon cancer, and lung cancer: a nation-wide, population-based assessment.
        J Surg Res. 2003; 114: 1-5
        • Thomas Jr, PA
        • Rubenstein L
        • The Lung Cancer Study Group
        Malignant disease appearing late after operation for T1 N0 non-small-cell lung cancer.
        J Thorac Cardiovasc Surg. 1993; 106: 1053-1058
        • Komaki R
        • Scott CB
        • Sause WT
        • 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 Radiat Oncol Biol Phys. 1997; 39: 537-544
        • Bonner JA
        • McGinnis WL
        • Stella PJ
        • et al.
        The possible advantage of hyperfractionated thoracic radiotherapy in the treatment of locally advanced nonsmall cell lung carcinoma: results of a North Central Cancer Treatment Group Phase III Study.
        Cancer. 1998; 82: 1037-1048
        • Tucker MA
        • Murray N
        • Shaw EG
        • Lung Cancer Working Cadre
        • et al.
        Second primary cancers related to smoking and treatment of small-cell lung cancer.
        J Natl Cancer Inst. 1997; 89: 1782-1788