Abstract
The seventh edition of the non-small cell lung cancer (NSCLC) TNM staging system was developed by the International Association for the Staging of Lung Cancer (IASLC) Lung Cancer Staging Project by a coordinated international effort to develop data-derived TNM classifications with significant survival differences. Based on these TNM groupings, current 5-year survival estimates in NSLCC range from 73 % in stage IA disease to 13 % in stage IV disease. TNM stage remains the most important prognostic factor in predicting recurrence rates and survival times, followed by tumor histologic grade, and patient sex, age, and performance status. Molecular prognostication in lung cancer is an exploding area of research where interest has moved beyond TNM stage and into individualized genetic tumor analysis with immunohistochemistry, microarray, and mutation profiles. However, despite intense research efforts and countless publications, no molecular prognostic marker has been adopted into clinical use since most fail in subsequent cross-validation with few exceptions. The recent interest in immunotherapy for NSCLC has identified new biomarkers with early evidence that suggests that PD-L1 is a predictive marker of a good response to new immunotherapy drugs but a poor prognostic indicator of overall survival. Future prognostication of outcomes in NSCLC will likely be based on a combination of TNM stage and molecular tumor profiling and yield more precise, individualized survival estimates and treatment algorithms.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Howlader N, Noone AM, Krapcho M, Garshell J, Neyman N, Altekruse SF, Kosary CL, Yu M, Ruhl J, Tatalovich Z, Cho H, Mariotto A, Lewis DR, Chen HS, Feuer EJ, Cronin KA (eds) (2013) SEER cancer statistics review, 1975–2010. National Cancer Institute. Bethesda, MD. http://seer.cancer.gov/csr/1975_2010/, based on November 2012 SEER data submission, posted to the SEER web site, April 2013
Goldstraw P, Crowley J, Chansky K et al (2007) The IASLC lung cancer staging project: proposals for the revision of the TNM stage groupings in the forthcoming (seventh) edition of the TNM classification of malignant tumours. J Thoracic Oncol Official Publ Int Assoc Study Lung Cancer 2(8):706–714
UICC (1968) TNM classification of malignant tumours. UICC, Geneva
Mountain CF, Carr DT, Anderson WA (1974) A system for the clinical staging of lung cancer. Am J Roentgenol Radium Ther Nucl Med 120(1):130–138
Goldstraw P (2009) Staging manual in thoracic oncology. FL Editorial Rx Press, Orange Park
Travis WD (2011) Pathology of lung cancer. Clin Chest Med 32(4):669–692
Meza R, Meernik C, Jeon J, Cote ML (2015) Lung cancer incidence trends by gender, race and histology in the United States, 1973–2010. PLoS ONE 10(3):e0121323
Detterbeck FC, Boffa DJ, Tanoue LT (2009) The new lung cancer staging system. Chest 136(1):260–271
Detterbeck FC, Boffa DJ, Tanoue LT, Wilson LD (2010) Details and difficulties regarding the new lung cancer staging system. Chest 137(5):1172–1180
Hsu PK, Huang HC, Hsieh CC et al (2007) Effect of formalin fixation on tumor size determination in stage I non-small cell lung cancer. Ann Thorac Surg 84(6):1825–1829
Shimizu K, Yoshida J, Nagai K et al (2004) Visceral pleural invasion classification in non-small cell lung cancer: a proposal on the basis of outcome assessment. J Thorac Cardiovasc Surg 127(6):1574–1578
Osaki T, Nagashima A, Yoshimatsu T, Yamada S, Yasumoto K (2004) Visceral pleural involvement in nonsmall cell lung cancer: prognostic significance. Ann Thorac Surg 77(5) (1769–1773, discussion 1773)
Dail D, Hammar S (1994) Pulmonary pathology, 2nd edn. Springer, New York
Rami-Porta R, Ball D, Crowley J et al (2007) The IASLC lung cancer staging project: proposals for the revision of the T descriptors in the forthcoming (seventh) edition of the TNM classification for lung cancer. J Thorac Oncol Official Publ Int Assoc Study Lung Cancer 2(7):593–602
Woodard GA, Jablons DM (2015) The latest in surgical management of stage IIIA non-small cell lung cancer. ASCO Educational Book (in press)
American Joint Committee on Cancer (2009) AJCC cancer staging manual, 7th edn. Springer, New York
Chen VW, Ruiz BA, Hsieh MC, Wu XC, Ries LA, Lewis DR (2014) Analysis of stage and clinical/prognostic factors for lung cancer from SEER registries: AJCC staging and collaborative stage data collection system. Cancer 120(Suppl 23):3781–3792
Shen KR, Meyers BF, Larner JM, Jones DR (2007) Special treatment issues in lung cancer: ACCP evidence-based clinical practice guidelines (2nd edition). Chest 132(3 Suppl):290s–305s
Martini N, Melamed MR (1975) Multiple primary lung cancers. J Thorac Cardiovasc Surg 70(4):606–612
Girard N, Deshpande C, Lau C et al (2009) Comprehensive histologic assessment helps to differentiate multiple lung primary nonsmall cell carcinomas from metastases. Am J Surg Pathol 33(12):1752–1764
Travis WD, Giroux DJ, Chansky K et al (2008) The IASLC lung cancer staging project: proposals for the inclusion of broncho-pulmonary carcinoid tumors in the forthcoming (seventh) edition of the TNM classification for lung cancer. J Thorac Oncol Official Publ Int Assoc Study Lung Cancer 3(11):1213–1223
Stolz A, Harustiak T, Simonek J et al (2015) Long-term outcomes and prognostic factors of patients with pulmonary carcinoid tumors. Neoplasma 13
Elias AD (1997) Small cell lung cancer: state-of-the-art therapy in 1996. Chest 112(4 Suppl):251s–258s
Stupp R, Monnerat C, Turrisi AT 3rd, Perry MC, Leyvraz S (2004) Small cell lung cancer: state of the art and future perspectives. Lung Cancer (Amsterdam, Neth) 45(1):105–117
Govindan R, Page N, Morgensztern D et al (2006) Changing epidemiology of small-cell lung cancer in the United States over the last 30 years: analysis of the surveillance, epidemiologic, and end results database. J Clin Oncol Official J Am Soc Clin Oncol 24(28):4539–4544
Shepherd FA, Crowley J, Van Houtte P et al (2007) The international association for the study of lung cancer lung cancer staging project: proposals regarding the clinical staging of small cell lung cancer in the forthcoming (seventh) edition of the tumor, node, metastasis classification for lung cancer. J Thorac Oncol Official Publ Int Assoc Study Lung Cancer 2(12):1067–1077
Kuo SW, Chen JS, Huang PM, Hsu HH, Lai HS, Lee JM (2014) Prognostic significance of histologic differentiation, carcinoembryonic antigen value, and lymphovascular invasion in stage I non-small cell lung cancer. J Thorac Cardiovasc Surg148(4):1200–1207, e1203
Sun Z, Aubry MC, Deschamps C et al (2006) 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 131(5):1014–1020
Shao W, Xiong X, Chen H et al (2014) Long-term survival outcomes of video-assisted thoracic surgery for patients with non-small cell lung cancer. Chin J Cancer (Res = Chung-Kuo Yen Cheng Yen Chiu) 26(4):391–398
Lee PC, Nasar A, Port JL et al (2013) Long-term survival after lobectomy for non-small cell lung cancer by video-assisted thoracic surgery versus thoracotomy. Ann Thorac Surg 96(3):951–960 (discussion 960–951)
Grossi F, Loprevite M, Chiaramondia M et al (2003) Prognostic significance of K-ras, p53, bcl-2, PCNA, CD34 in radically resected non-small cell lung cancers. Eur J Cancer (Oxford, Engl 1990) 39(9):1242–1250
Luchtenborg M, Jakobsen E, Krasnik M, Linklater KM, Mellemgaard A, Moller H (2012) The effect of comorbidity on stage-specific survival in resected non-small cell lung cancer patients. Eur J Cancer (Oxford, Engl 1990) 48(18):3386–3395
Iachina M, Jakobsen E, Moller H et al (2015) The effect of different comorbidities on survival of non-small cells lung cancer patients. Lung 193(2):291–297
Zhai R, Yu X, Shafer A, Wain JC, Christiani DC (2014) The impact of coexisting COPD on survival of patients with early-stage non-small cell lung cancer undergoing surgical resection. Chest 145(2):346–353
Simmons CP, Koinis F, Fallon MT et al (2015) Prognosis in advanced lung cancer—a prospective study examining key clinicopathological factors. Lung Cancer (Amsterdam, Neth)
Parsons A, Daley A, Begh R, Aveyard P (2010) Influence of smoking cessation after diagnosis of early stage lung cancer on prognosis: systematic review of observational studies with meta-analysis. BMJ (Clin Res ed.) 340:b5569
Ou SH, Zell JA, Ziogas A, Anton-Culver H (2007) Prognostic factors for survival of stage I nonsmall cell lung cancer patients: a population-based analysis of 19,702 stage I patients in the California Cancer Registry from 1989 to 2003. Cancer 110(7):1532–1541
Ou SH, Zell JA, Ziogas A, Anton-Culver H (2008) Low socioeconomic status is a poor prognostic factor for survival in stage I nonsmall cell lung cancer and is independent of surgical treatment, race, and marital status. Cancer 112(9):2011–2020
Hubbard MO, Fu P, Margevicius S, Dowlati A, Linden PA (2012) Five-year survival does not equal cure in non-small cell lung cancer: a surveillance, epidemiology, and end results-based analysis of variables affecting 10- to 18-year survival. J Thorac Cardiovasc Surg 143(6):1307–1313
Rosen JE, Hancock JG, Kim AW, Detterbeck FC, Boffa DJ (2014) Predictors of mortality after surgical management of lung cancer in the National Cancer Database. Ann Thorac Surg 98(6):1953–1960
Bach PB, Cramer LD, Schrag D, Downey RJ, Gelfand SE, Begg CB (2001) The influence of hospital volume on survival after resection for lung cancer. New Engl J Med 345(3):181–188
Groome PA, Bolejack V, Crowley JJ et al (2007) The IASLC lung cancer staging project: validation of the proposals for revision of the T, N, and M descriptors and consequent stage groupings in the forthcoming (seventh) edition of the TNM classification of malignant tumours. J Thorac Oncol Official Publ Int Assoc Study Lung Cancer 2(8):694–705
Olaussen KA, Dunant A, Fouret P et al (2006) DNA repair by ERCC1 in non-small-cell lung cancer and cisplatin-based adjuvant chemotherapy. New Eng J Med 355(10):983–991
Friboulet L, Olaussen KA, Pignon JP et al (2013) ERCC1 isoform expression and DNA repair in non-small-cell lung cancer. New Engl J Med 368(12):1101–1110
Zhu CQ, Tsao MS (2014) Prognostic markers in lung cancer: is it ready for prime time? Transl Lung Cancer Res 3(3):149–158
Shepherd FA, Domerg C, Hainaut P et al (2013) Pooled analysis of the prognostic and predictive effects of KRAS mutation status and KRAS mutation subtype in early-stage resected non-small-cell lung cancer in four trials of adjuvant chemotherapy. J Clin Oncol Official J Am Soc Clin Oncol 31(17):2173–2181
Agullo-Ortuno MT, Diaz-Garcia CV, Agudo-Lopez A et al (2015) Relevance of insulin-like growth factor 1 receptor gene expression as a prognostic factor in non-small-cell lung cancer. J Cancer Res Clin Oncol 141(1):43–53
Tran TN, Selinger CI, Yu B et al (2014) Alterations of insulin-like growth factor-1 receptor gene copy number and protein expression are common in non-small cell lung cancer. J Clin Pathol 67(11):985–991
Dziadziuszko R, Merrick DT, Witta SE et al (2010) Insulin-like growth factor receptor 1 (IGF1R) gene copy number is associated with survival in operable non-small-cell lung cancer: a comparison between IGF1R fluorescent in situ hybridization, protein expression, and mRNA expression. J Clin Oncol Official J Am Soc Clin Oncol 28(13):2174–2180
Go H, Jeon YK, Park HJ, Sung SW, Seo JW, Chung DH (2010) High MET gene copy number leads to shorter survival in patients with non-small cell lung cancer. J Thorac Oncol Official Publ Int Assoc Study Lung Cancer 5(3):305–313
Eberhard DA, Johnson BE, Amler LC et al (2005) Mutations in the epidermal growth factor receptor and in KRAS are predictive and prognostic indicators in patients with non-small-cell lung cancer treated with chemotherapy alone and in combination with erlotinib. J Clin Oncol Official J Am Soc Clin Oncol 23(25):5900–5909
Kosaka T, Yatabe Y, Onozato R, Kuwano H, Mitsudomi T (2009) Prognostic implication of EGFR, KRAS, and TP53 gene mutations in a large cohort of Japanese patients with surgically treated lung adenocarcinoma. J Thorac Oncol Official Publ Int Assoc Study Lung Cancer 4(1):22–29
Anagnostou VK, Lowery FJ, Zolota V et al (2010) High expression of BCL-2 predicts favorable outcome in non-small cell lung cancer patients with non squamous histology. BMC Cancer 10:186
Zhao XD, He YY, Gao J et al (2014) High expression of Bcl-2 protein predicts favorable outcome in non-small cell lung cancer: evidence from a systematic review and meta-analysis. Asian Pac J Cancer Prev APJCP 15(20):8861–8869
Xia Q, Zhu Z, Wang J, Situ D, Zhou N, Jang W (2012) Expression and association of HER2 with prognosis in early-stage (T1-T2N0M0) non-small cell lung cancer. Tumour Biol J Int Soc Oncodev Biol Med 33(5):1719–1725
Liao M, Wang H, Lin Z, Feng J, Zhu D (2001) Vascular endothelial growth factor and other biological predictors related to the postoperative survival rate on non-small cell lung cancer. Lung Cancer (Amsterdam, Neth) 33(2–3):125–132
Zheng CL, Qiu C, Shen MX et al (2015) Prognostic impact of elevation of vascular endothelial growth factor family expression in patients with non-small cell lung cancer: an updated meta-analysis. Asian Pac J Cancer Prev APJCP 16(5):1881–1895
Warth A, Cortis J, Soltermann A et al (2014) Tumour cell proliferation (Ki-67) in non-small cell lung cancer: a critical reappraisal of its prognostic role. Br J Cancer 111(6):1222–1229
Ha SY, Choi SJ, Cho JH et al (2015) Lung cancer in never-smoker Asian females is driven by oncogenic mutations, most often involving EGFR. Oncotarget 6(7):5465–5474
VandenBussche CJ, Illei PB, Lin MT, Ettinger DS, Maleki Z (2014) Molecular alterations in non-small cell lung carcinomas of the young. Hum Pathol 45(12):2379–2387
Maheswaran S, Sequist LV, Nagrath S et al (2008) Detection of mutations in EGFR in circulating lung-cancer cells. New Eng J Med 359(4):366–377
Wang J, Wang K, Xu J, Huang J, Zhang T (2013) Prognostic significance of circulating tumor cells in non-small-cell lung cancer patients: a meta-analysis. PLoS ONE 8(11):e78070
Punnoose EA, Atwal S, Liu W et al (2012) Evaluation of circulating tumor cells and circulating tumor DNA in non-small cell lung cancer: association with clinical endpoints in a phase II clinical trial of pertuzumab and erlotinib. Clin Cancer Res Official J Am Assoc Cancer Res 18(8):2391–2401
Dowler Nygaard A, Spindler KL, Pallisgaard N, Andersen RF, Jakobsen A (2014) Levels of cell-free DNA and plasma KRAS during treatment of advanced NSCLC. Oncol Rep 31(2):969–974
Zhu CQ, Pintilie M, John T et al (2009) Understanding prognostic gene expression signatures in lung cancer. Clin Lung Cancer 10(5):331–340
Carnio S, Novello S, Papotti M, Loiacono M, Scagliotti GV (2013) Prognostic and predictive biomarkers in early stage non-small cell lung cancer: tumor based approaches including gene signatures. Transl Lung Cancer Res 2(5):372–381
Moran A, Fernandez-Marcelo T, Carro J et al (2012) Methylation profiling in non-small cell lung cancer: clinical implications. Int J Oncol 40(3):739–746
Sandoval J, Mendez-Gonzalez J, Nadal E et al (2013) A prognostic DNA methylation signature for stage I non-small-cell lung cancer. J Clin Oncol Off J Am Soc Clin Oncol 31(32):4140–4147
Lokk K, Vooder T, Kolde R et al (2012) Methylation markers of early-stage non-small cell lung cancer. PLoS ONE 7(6):e39813
Kratz JR, He J, Van Den Eeden SK et al (2012) A practical molecular assay to predict survival in resected non-squamous, non-small-cell lung cancer: development and international validation studies. Lancet 379(9818):823–832
Kratz JR, Tham PT, Mulvihill MS et al (2013) Analytical validation of a practical molecular assay prognostic of survival in nonsquamous non-small cell lung cancer. Diagn Mol Pathol Am J Surg Pathol Part B 22(2):65–69
Woodard GA, Gubens MA, Jahan TM et al (2014) Prognostic molecular assay might improve identification of patients at risk for recurrence in early-stage non-small-cell lung cancer. Clin Lung Cancer 15(6):426–432
Van Laar RK (2012) Genomic signatures for predicting survival and adjuvant chemotherapy benefit in patients with non-small-cell lung cancer. BMC Med Genomics 5:30
Tang H, Xiao G, Behrens C et al (2013) A 12-gene set predicts survival benefits from adjuvant chemotherapy in non-small cell lung cancer patients. Clin Cancer Res Official J Am Assoc Cancer Res 19(6):1577–1586
Zhu CQ, Ding K, Strumpf D et al (2010) Prognostic and predictive gene signature for adjuvant chemotherapy in resected non-small-cell lung cancer. J Clin Oncol Official J Am Soc Clin Oncol 28(29):4417–4424
Der SD, Sykes J, Pintilie M et al (2014) Validation of a histology-independent prognostic gene signature for early-stage, non-small-cell lung cancer including stage IA patients. J Thorac Oncol Official Publ Int Assoc Study Lung Cancer 9(1):59–64
Wistuba II, Behrens C, Lombardi F et al (2013) Validation of a proliferation-based expression signature as prognostic marker in early stage lung adenocarcinoma. Clin Cancer Res Official J Am Assoc Cancer Res 19(22):6261–6271
Winton T, Livingston R, Johnson D et al (2005) Vinorelbine plus cisplatin vs. observation in resected non-small-cell lung cancer. New Eng J Med 352(25):2589–2597
Douillard JY, Rosell R, De Lena M et al (2006) Adjuvant vinorelbine plus cisplatin versus observation in patients with completely resected stage IB-IIIA non-small-cell lung cancer (Adjuvant Navelbine International Trialist Association [ANITA]): a randomised controlled trial. Lancet Oncol 7(9):719–727
Network NCC (2014) NCCN non-small cell lung cancer clinical practice guidelines. Version 2. http://www.nccn.org/professionals/physician_gls/pdf/nscl.pdf. Accessed 29 Dec 2013
Stinchcombe TE, Roder J, Peterman AH et al (2013) A retrospective analysis of VeriStrat status on outcome of a randomized phase II trial of first-line therapy with gemcitabine, erlotinib, or the combination in elderly patients (age 70 years or older) with stage IIIB/IV non-small-cell lung cancer. J Thorac Oncol Official Publ Int Assoc Study Lung Cancer 8(4):443–451
Carbone DP, Ding K, Roder H et al (2012) Prognostic and predictive role of the VeriStrat plasma test in patients with advanced non-small-cell lung cancer treated with erlotinib or placebo in the NCIC Clinical Trials Group BR.21 trial. J Thorac Oncol Official Publ Int Assoc Study Lung Cancer 7(11):1653–1660
Yang Y, Xie Y, Xian L (2013) Breast cancer susceptibility gene 1 (BRCA1) predict clinical outcome in platinum- and toxal-based chemotherapy in non-small-cell lung cancer (NSCLC) patients: a system review and meta-analysis. J Exp Clin Cancer Res CR 32:15
Gong W, Zhang X, Wu J et al (2012) RRM1 expression and clinical outcome of gemcitabine-containing chemotherapy for advanced non-small-cell lung cancer: a meta-analysis. Lung Cancer (Amsterdam, Neth) 75(3):374–380
Pardoll DM (2012) The blockade of immune checkpoints in cancer immunotherapy. Nat Rev Cancer 12(4):252–264
Wang A, Wang HY, Liu Y et al (2015) The prognostic value of PD-L1 expression for non-small cell lung cancer patients: A meta-analysis. Eur J Surg Oncol J Eur Soc Surg Oncol Br Assoc Surg Oncol 41(4):450–456
Azuma K, Ota K, Kawahara A et al (2014) Association of PD-L1 overexpression with activating EGFR mutations in surgically resected nonsmall-cell lung cancer. Ann Oncol Official J Eur Soc Med Oncol/ESMO 25(10):1935–1940
Akbay EA, Koyama S, Carretero J et al (2013) Activation of the PD-1 pathway contributes to immune escape in EGFR-driven lung tumors. Cancer Dis 3(12):1355–1363
Tang Y, Fang W, Zhang Y et al (2015) The association between PD-L1 and EGFR status and the prognostic value of PD-L1 in advanced non-small cell lung cancer patients treated with EGFR-TKIs. Oncotarget 6:14209
Patel SP, Kurzrock R (2015) PD-L1 expression as a predictive biomarker in cancer immunotherapy. Mol Cancer Ther 14(4):847–856
Gettinger SN, Horn L, Gandhi L et al (2015) Overall survival and long-term safety of Nivolumab (anti-programmed death 1 antibody, BMS-936558, ONO-4538) in patients with previously treated advanced non-small-cell lung cancer. J Clin Oncol Official J Am Soc Clin Oncol 33(18):2004–2012
Garon EB, Rizvi NA, Hui R et al (2015) Pembrolizumab for the treatment of non-small-cell lung cancer. New Eng J Med 372(21):2018–2028
Topalian SL, Hodi FS, Brahmer JR et al (2012) Safety, activity, and immune correlates of anti-PD-1 antibody in cancer. New Eng J Med 366(26):2443–2454
Brahmer J, Horn L, Gandhi L et al (2014) Nivolumab (anti-PD-1, BMS-936558, ONO-4538) in patients (Pts) with advanced non-small-cell lung cancer (NSCLC): survival and clinical activity by subgroup analysis. ASCO Meet Abs 32(8112)
Brahmer J, Reckamp KL, Baas P et al (2015) Nivolumab versus Docetaxel in advanced squamous-cell non-small-cell lung cancer. New Eng J Med 373(2):123–135
Lynch TJ, Bondarenko I, Luft A et al (2012) Ipilimumab in combination with paclitaxel and carboplatin as first-line treatment in stage IIIB/IV non-small-cell lung cancer: results from a randomized, double-blind, multicenter phase II study. J Clin Oncol Official J Am Soc Clin Oncol 30(17):2046–2054
Sundar R, Soong R, Cho BC, Brahmer JR, Soo RA (2014) Immunotherapy in the treatment of non-small cell lung cancer. Lung Cancer (Amsterdam, Neth) 85(2):101–109
Salvi S, Fontana V, Boccardo S et al (2012) Evaluation of CTLA-4 expression and relevance as a novel prognostic factor in patients with non-small cell lung cancer. Cancer Immunol Immunother CII 61(9):1463–1472
Zheng H, Li Y, Wang X, Zhang X, Wang X (2010) Expression and significance of gp96 and immune-related gene CTLA-4, CD8 in lung cancer tissues. Zhongguo fei ai za zhi = Chin J Lung Cancer 13(8):790–794
Rami-Porta R, Bolejack V, Giroux DJ et al (2014) The IASLC lung cancer staging project: the new database to inform the eighth edition of the TNM classification of lung cancer. J Thorac Oncol Official Publ Int Assoc Study Lung Cancer 9(11):1618–1624
Rusch VW, Asamura H, Watanabe H, Giroux DJ, Rami-Porta R, Goldstraw P (2009) The IASLC lung cancer staging project: a proposal for a new international lymph node map in the forthcoming seventh edition of the TNM classification for lung cancer. J Thorac Oncol Official Publ Int Assoc Study Lung Cancer 4(5):568–577
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2016 Springer International Publishing Switzerland
About this chapter
Cite this chapter
Woodard, G.A., Jones, K.D., Jablons, D.M. (2016). Lung Cancer Staging and Prognosis. In: Reckamp, K. (eds) Lung Cancer. Cancer Treatment and Research, vol 170. Springer, Cham. https://doi.org/10.1007/978-3-319-40389-2_3
Download citation
DOI: https://doi.org/10.1007/978-3-319-40389-2_3
Published:
Publisher Name: Springer, Cham
Print ISBN: 978-3-319-40387-8
Online ISBN: 978-3-319-40389-2
eBook Packages: MedicineMedicine (R0)