The biology and management of non-small cell lung cancer

Nature, Journal Year: 2018, Volume and Issue: 553(7689), P. 446 - 454

Published: Jan. 1, 2018

Language: Английский

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Metastatic non-small cell lung cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up

Annals of Oncology, Journal Year: 2018, Volume and Issue: 29, P. iv192 - iv237

Published: July 26, 2018

Primary lung cancer remains the most common malignancy after non-melanocytic skin cancer, and deaths from exceed those any other worldwide [1.IARC. Cancer Incidence, Mortality Prevalence Worldwide GLOBOCAN 2012. http://gco.iarc.fr/Google Scholar]. In 2012, was frequently diagnosed in males with an estimated 1.2 million incident cases worldwide. Among females, leading cause of death more developed countries second less The highest incidence is found Central/Eastern Europe Asia age-standardised rates 53.5 50.4 per 100 000, respectively. European projections for 2017 indicate a 10.7% drop 5 years 33.3/100 000 rise 5.1% 14.6/100 females [2.Malvezzi M. Carioli G. Bertuccio P. et al.European mortality predictions year 2017, focus on cancer.Ann Oncol. 2017; 28: 1117-1123Abstract Full Text PDF PubMed Scopus (153) Google Contrary to United States, rate increasing [3.Jemal A. Ward E.M. Johnson C.J. al.Annual Report Nation Status Cancer, 1975-2014, Featuring Survival.J Natl Inst. 109 (djx 0130)Crossref (592) number cancer-related represent both genders, accounting 24% 15% respectively Non-small cell (NSCLC) accounts 80%–90% cancers, while small (SCLC) has been decreasing frequency many over past two decades [4.Jemal Bray F. Center M.M. al.Global statistics.CA J Clin. 2011; 61: 69-90Crossref (28678) During last 25 years, distribution histological types NSCLC changed: squamous carcinoma (SCC), formerly predominant histotype, decreased, adenocarcinoma increased genders. Europe, similar trends have occurred men, women, SCC are still [5.Forman D. Brewster Incidence Five Continents. IARC Press, Lyon2013Google World Health Organization (WHO) estimates that 1.59 globally year, 71% them caused by smoking. Tobacco smoking main geographical temporal patterns disease largely reflect tobacco consumption during previous decades. Both prevention cessation can lead reduction large fraction cancers [6.Ordonez-Mena J.M. Schottker B. Mons U. al.Quantification smoking-associated risk advancement periods: meta-analysis individual participant data cohorts CHANCES consortium.BMC Med. 2016; 14: 62Crossref active control measures, begun decline men reaching plateau women Scholar, 7.Malvezzi Levi 2013.Ann 2013; 24: 792-800Abstract (275) 8.Jemal Ma J. Rosenberg P.S. al.Increasing among young southern midwestern States.J Clin 2012; 30: 2739-2744Crossref (55) 9.Hashim Boffetta La Vecchia C. al.The global decrease mortality: disparities.Ann 27: 926-933Abstract (177) Several factors described as factors, including exposure asbestos, arsenic, radon non-tobacco-related polycyclic aromatic hydrocarbons. Hypotheses about indoor air pollution (e.g. coal-fuelled stoves cooking fumes) made relatively high burden non-smoking-related some [10.Malhotra Malvezzi Negri E. al.Risk worldwide.Eur Respir 48: 889-902Crossref There evidence higher cities than rural settings but confounding outdoor may be responsible this pattern. About 500 annually attributed lifetime never-smokers Absence history characterises 19% female compared 9% male States [11.Novello S. Stabile L. Siegfried Gender-related Differences Lung Cancer. IASLC Multidisciplinary Approach Thoracic Oncology. Aurora, CO2014Google 12.McCarthy W. Meza R. Jeon Moolgavkar Chapter 6: never smokers: epidemiology prediction models.Risk Anal. 32: S69.Crossref (0) An increase proportion observed, especially Asian [13.Toh C.K. Gao Lim W.T. al.Never-smokers cancer: epidemiologic distinct entity.J 2006; 2245-2251Crossref (271) These new epidemiological resulted ‘non-smoking-associated cancer’ being considered entity, where specific molecular genetic tumour characteristics identified [14.Couraud Souquet P.J. Paris al.BioCAST/IFCT-1002: features never-smokers.Eur 2015; 45: 1403-1414Crossref (40) Use non-cigarette products such cigars pipes increasing. A pooled analysis highlighted risk, particularly head neck smokers (former current) [15.Malhotra Borron Freedman N.D. al.Association between Cigar or pipe men: five Cohort studies.Cancer Prev Res (Phila). 10: 704-709Crossref Familial reported several registry-based studies careful adjustment [16.Lorenzo Bermejo Hemminki K. aggregation habits: simulation effect shared environmental familial cancer.Cancer Epidemiol Biomarkers Prev. 2005; 1738-1740Crossref recent study heritability at 18% components remain unidentified. Genome-wide association (GWAS) susceptibility loci CHRNA3, CHRNA5, TERT, BRCA2, CHECK2 human leukocyte antigen (HLA) region [17.Mucci L.A. Hjelmborg J.B. Harris J.R. al.Familial twins Nordic Countries.JAMA. 315: 68-76Crossref (301) 18.Timofeeva M.N. Hung R.J. Rafnar T. al.Influence variation risk: 14 900 29 485 controls.Hum Mol Genet. 21: 4980-4995Crossref (147) 19.Wang Y. McKay J.D. al.Rare variants BRCA2 CHEK2 affect cancer.Nat 2014; 46: 736-741Crossref (179) Another trial, 266 56 450 controls descent, 18 genome-wide significance, which 10 were previously unknown. Interestingly, four latter associated overall six only [20.McKay Han al.Large-scale identifies heterogeneity across subtypes.Nat 49: 1126-1132Crossref (160) Changes therapeutic scenario 15 emphasised need multidisciplinary approach cancer. Data show high-volume centres teams efficient managing patients low-volume non-multidisciplinary centres, providing complete staging, better adherence guidelines survival [21.Freeman R.K. Van Woerkom Vyverberg Ascioti A.J. thoracic conference treatment cancer.Eur Cardiothorac Surg. 2010; 38: 1-5Crossref (76) 22.Forrest L.M. McMillan D.C. McArdle C.S. Dunlop D.J. evaluation impact team, single centre, inoperable non-small-cell cancer.Br 93: 977-978Crossref (148) boards influence providers’ initial plans 26%–40% [23.Schmidt H.M. Roberts Bodnar A.M. al.Thoracic tumor board routinely impacts esophageal prospective cohort study.Ann Thorac 99: 1719-1724Abstract absolute reach proper precise morphological biological definition often requires challenging tissue sampling, decisions depending information obtained specimen collected diagnosis. Bronchoscopy technique ideally suited large, central lesions offers advantage minimal morbidity. used bronchial washing, brushing, transbronchial biopsy, diagnostic yield 65%–88% [24.Ost D.E. Ernst Lei X. al.Diagnostic complications bronchoscopy peripheral lesions. Results AQuIRE Registry.Am Crit Care 193: 68-77Crossref 25.Rivera M.P. Mehta A.C. Wahidi Establishing diagnosis management 3rd ed: American College Chest Physicians evidence-based clinical practice guidelines.Chest. 143: e142S-e165SAbstract (530) 26.van der Drift M.A. van Wilt G.J. Thunnissen F.B. Janssen J.P. timing cost-effectiveness washing pulmonary malignant tumors.Chest. 128: 394-400Abstract (65) By combining direct bronchoscopic airway visualisation ultrasound-guided biopsy lesion, endobronchial ultrasound (EBUS) provides 75%–85% centrally located [27.Herth Becker H.D. Conventional vs needle aspiration: randomized trial.Chest. 2004; 125: 322-325Abstract (350) 28.Paone Nicastri Lucantoni al.Endobronchial ultrasound-driven lesions.Chest. 3551-3557Abstract (185) Fibre optic allows regional lymph nodes EBUS and/or endoscopic (EUS). EBUS-guided aspiration (TBNA) invasive least accurate mediastinoscopy [29.Adams Shah P.L. Edmonds Test performance mediastinal staging systematic review meta-analysis.Thorax. 2009; 64: 757-762Crossref (291) shown cytological specimens EBUS-TBNA suitable testing epidermal growth factor receptor (EGFR), Kirsten rat sarcoma viral oncogene homologue (KRAS) anaplastic lymphoma kinase (ALK) status [30.Nakajima Kimura H. Takeuchi al.Treatment ALK inhibitor EML4-ALK fusion gene detection using aspiration.J 5: 2041-2043Abstract (21) 31.Nakajima Yasufuku Nakagawara al.Multigene mutation metastatic non-small aspiration.Chest. 140: 1319-1324Abstract (97) 32.Rekhtman N. Brandt S.M. Sigel al.Suitability cytology paradigms carcinoma: accuracy subtyping feasibility EGFR KRAS testing.J 451-458Abstract (200) 33.Sakairi Nakajima al.EML4-ALK assessment node samples aspiration.Clin Res. 16: 4938-4945Crossref (140) Scholar]; however, collection broader should encouraged. case lesions, transthoracic percutaneous fine core under imaging guidance [typically computed tomography (CT)] proposed [34.Chan E.Y. Gaur Ge al.Management solitary nodule.Arch Pathol Lab 141: 927-931Crossref (8) Needle > 88% yield, sensitivity 90% false-negative 22% [25.Rivera 35.Choi S.H. Chae E.J. Kim J.E. al.Percutaneous CT-guided nodules smaller 1 cm: outcomes 305 procedures tertiary referral center.AJR Am Roentgenol. 201: 964-970Crossref 36.Fontaine-Delaruelle Gamondes al.Negative predictive value core-needle biopsy: multicenter study.Chest. 148: 472-480Abstract (36) 37.Lee Park C.M. Lee K.H. al.C-arm cone-beam nodules: experience 1108 patients.Radiology. 271: 291-300Crossref (118) 38.Takeshita Masago Kato al.CT-guided fine-needle biopsies lesions: single-center 750 Japan.AJR 204: 29-34Crossref (43) significant disadvantage procedural pneumothorax, ranging 17% 50% [37.Lee presence pleural effusion, thoracentesis could tool palliative treatment. If fluid examination negative, image-guided surgical thoracoscopy carried out. More invasive, approaches [mediastinoscopy, mediastinotomy, thoracoscopy, video-assisted thorascopic surgery (VATS), secondary lesion resection etc.] workup when techniques cannot allow Histological crucial exact detailed available technology allow. Diagnosis based upon criteria laid out WHO classification [39.Travis W.D. Brambilla Burke A.P. al.WHO Classification Tumours Lung, Pleura, Thymus Heart.4th edition. Lyon, France2015Google This details surgically resected tumours but, importantly, also assessing reporting not met 40.Travis Noguchi al.Diagnosis cytology: implications 2011 International Association Study Cancer/American Society/European Respiratory Society classification.Arch 137: 668-684Crossref (251) 41.Travis al.International cancer/american society/european respiratory society international adenocarcinoma.J 244-285Abstract (3131) Most present advanced stage unresectable disease, therefore all treatment-determining diagnoses must cytology-type samples. Sampling primary accessible metastases, taken vision usually assistance, greatly increases (hit rate). facilitate well limited material handled accordingly; ensuring processing likely sparingly each step, since tests required [42.Dietel Bubendorf Dingemans (NSCLC): recommendations Expert Group.Thorax. 71: 177-184Crossref (89) Immunohistochemistry (IHC) become key biomarker assessment. possible morphology alone, panel IHC recommended determine subtype Thyroid transcription (TTF1) positivity probable adenocarcinoma, p40 SCC; if neither positive NSCLC-not otherwise specified (NOS). staining reduce NSCLC-NOS < 10% [IV, A]. Pathologists urged conserve every diagnosis, use sections avoid excessive investigation, clinically relevant. After next consideration therapy-predictive testing. will driven availability treatments vary widely different geopolitical health systems [43.Lindeman N.I. Cagle P.T. Beasley M.B. al.Molecular guideline selection tyrosine inhibitors: Pathologists, Molecular Pathology.J 8: 823-859Abstract (588) 44.Kerr K.M. Edelman M.J. al.Second ESMO consensus pathology biomarkers 25: 1681-1690Abstract (191) 45.Lindeman Aisner al.Updated targeted Pathology.Arch 2018; 142: 321-346Crossref (257) Contemporary now evolved into streams, one targetable, addictive, oncogenic alterations immuno-oncology therapy personalised medicine synopsis table Table 1.Table 1A NSCLCBiomarkerMethodUseLoE, GoREGFR mutationAny appropriate, validated method, subject external quality assuranceTo select EGFR-sensitising mutations respond TKI therapyI, AALK rearrangementAny assurance. FISH historical standard becoming therapy-determining test, provided method against orthogonal test approach. NGS emerging technologyTo rearrangements AROS1 rearrangementFISH trial-validated standard. confirmatory currently lacks specificity. technology. External assurance essentialTo ROS1 therapyII, ABRAF BRAF V600-sensitising inhibitor, without MEK APD-L1 expressionIHC identify PD-L1 expression appropriate level population(s) determined intended drug line therapy. Only trial assays validated. Internal enrich benefit anti-PD-1 anti-PD-L1 For pembrolizumab, companion nivolumab atezolizumab, complementaryI, AALK, kinase; EGFR, receptor; FISH, fluorescent situ hybridisation; GoR, grade recommendation; IHC, immunohistochemistry; LoE, evidence; MEK, mitogen-activated protein NGS, next-generation sequencing; NSCLC, cancer; PD-1, programmed 1; PD-L1, death-ligand TKI, inhibitor. Open tab ALK, drivers addiction strong excellent targets. They generally mutually exclusive much never- (never smoked who cigarettes lifetime), long-time ex- (> years) light-smokers (< pack-years) they smoke. vast majority oncogene-addicted adenocarcinomas. Patients, general, tend younger, gender East ethnicity enriches EGFR-mutant tumours. Nonetheless, suggest advanced, possible, definite, tested 46.Kalemkerian G.P. Narula Kennedy E.B. Clinical Oncology Endorsement Pathologists/International Cancer/Association Pathology Practice Guideline Update.J 36: 911-919PubMed SCC, except rare circumstances never-, light-smoker Testing involving genes mandatory countries. V600E rapidly approaching first-line BRAF/MEK inhibitors approved, HER2 (human 2) MET exon RET NTRK1 (neurotropic tropomyosin 1) evolving targets/biomarkers

Language: Английский

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Immune checkpoint inhibitors for patients with advanced lung cancer and oncogenic driver alterations: results from the IMMUNOTARGET registry

Annals of Oncology, Journal Year: 2019, Volume and Issue: 30(8), P. 1321 - 1328

Published: May 15, 2019

Language: Английский

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Non–Small Cell Lung Cancer, Version 3.2022, NCCN Clinical Practice Guidelines in Oncology

Journal of the National Comprehensive Cancer Network, Journal Year: 2022, Volume and Issue: 20(5), P. 497 - 530

Published: May 1, 2022

NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Non-Small Cell Lung Cancer (NSCLC) provide recommended management patients with NSCLC, including diagnosis, primary treatment, surveillance relapse, and subsequent treatment. Patients metastatic lung cancer who are eligible targeted therapies or immunotherapies now surviving longer. This selection from the NSCLC focuses on actionable mutations.

Language: Английский

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Systemic Therapy for Locally Advanced and Metastatic Non–Small Cell Lung Cancer

JAMA, Journal Year: 2019, Volume and Issue: 322(8), P. 764 - 764

Published: Aug. 27, 2019

Importance

Non–small cell lung cancer remains the leading cause of death in United States. Until last decade, 5-year overall survival rate for patients with metastatic non–small was less than 5%. Improved understanding biology has resulted development new biomarker–targeted therapies and led to improvements advanced or disease.

Observations

Systemic therapy is selected according presence specific biomarkers. Therefore, all should undergo molecular testing relevant mutations expression protein PD-L1 (programmed ligand 1). Molecular alterations that predict response treatment (eg,EGFRmutations,ALKrearrangements,ROS1rearrangements, andBRAFV600E mutations) are present approximately 30% cancer. Targeted these improves progression-free compared cytotoxic chemotherapy. For example, somatic activating theEGFRgene 20% Tyrosine kinase inhibitors such as gefitinib, erlotinib, afatinib improve susceptibleEGFRmutations. In overexpression ALK protein, significantly better crizotinib (a tyrosine inhibitor) combination pemetrexed either cisplatin carboplatin (platinum-based chemotherapy) (74% vs 45%, respectively;P < .001) (median, 10.9 months 7.0 months;P .001). Subsequent generations have improved agents. without biomarkers indicating susceptibility targeted treatments, immune checkpoint inhibitor–containing regimens monotherapy chemotherapy superior alone. These advances biomarker-directed survival. currently exceeds 25% among whose tumors high (tumor proportion score ≥50%) 40% withALK-positive tumors.

Conclusions Relevance

subtypes more newer empirical

Language: Английский

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Understanding and targeting resistance mechanisms in NSCLC

Nature reviews. Cancer, Journal Year: 2017, Volume and Issue: 17(11), P. 637 - 658

Published: Oct. 25, 2017

Language: Английский

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Kinase drug discovery 20 years after imatinib: progress and future directions

Nature Reviews Drug Discovery, Journal Year: 2021, Volume and Issue: 20(7), P. 551 - 569

Published: May 17, 2021

Language: Английский

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Updated Molecular Testing Guideline for the Selection of Lung Cancer Patients for Treatment With Targeted Tyrosine Kinase Inhibitors: Guideline From the College of American Pathologists, the International Association for the Study of Lung Cancer, and the Association for Molecular Pathology

Archives of Pathology & Laboratory Medicine, Journal Year: 2018, Volume and Issue: 142(3), P. 321 - 346

Published: Jan. 22, 2018

Context.— In 2013, an evidence-based guideline was published by the College of American Pathologists, International Association for Study Lung Cancer, and Molecular Pathology to set standards molecular analysis lung cancers guide treatment decisions with targeted inhibitors. New evidence has prompted evaluation additional laboratory technologies, targetable genes, patient populations, tumor types testing. Objective.— To systematically review update 2013 affirm its validity; assess new genetic discoveries, therapies; issue update. Design.— The convened expert panel develop help define key questions literature search terms, abstracts full articles, draft recommendations. Results.— Eighteen recommendations were drafted. also updated 3 from guideline. Conclusions.— largely reaffirmed allow testing cytology samples, require improved assay sensitivity, recommend against use immunohistochemistry EGFR Key include ROS1 all adenocarcinoma patients; inclusion genes (ERBB2, MET, BRAF, KRAS, RET) laboratories that perform next-generation sequencing panels; as alternative fluorescence in situ hybridization ALK and/or testing; 5% sensitivity assays T790M mutations patients secondary resistance inhibitors; cell-free DNA “rule in” when tissue is limited or hard obtain.

Language: Английский

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Efficacy of Selpercatinib in RET Fusion–Positive Non–Small-Cell Lung Cancer

New England Journal of Medicine, Journal Year: 2020, Volume and Issue: 383(9), P. 813 - 824

Published: Aug. 26, 2020

RET fusions are oncogenic drivers in 1 to 2% of non-small-cell lung cancers (NSCLCs). In patients with fusion-positive NSCLC, the efficacy and safety selective inhibition unknown.We enrolled advanced NSCLC who had previously received platinum-based chemotherapy those were untreated separately a phase 1-2 trial selpercatinib. The primary end point was an objective response (a complete or partial response) as determined by independent review committee. Secondary points included duration response, progression-free survival, safety.In first 105 consecutively at least chemotherapy, percentage 64% (95% confidence interval [CI], 54 73). median 17.5 months CI, 12.0 could not be evaluated), 63% responses ongoing follow-up 12.1 months. Among 39 patients, 85% 70 94), 90% 6 11 measurable central nervous system metastasis enrollment, intracranial 91% 59 100). most common adverse events grade 3 higher hypertension (in 14% patients), increased alanine aminotransferase level 12%), aspartate 10%), hyponatremia 6%), lymphopenia 6%). A total 12 531 (2%) discontinued selpercatinib because drug-related event.Selpercatinib durable efficacy, including activity, mainly low-grade toxic effects untreated. (Funded Loxo Oncology others; LIBRETTO-001 ClinicalTrials.gov number, NCT03157128.).

Language: Английский

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Proteogenomic Characterization Reveals Therapeutic Vulnerabilities in Lung Adenocarcinoma

Cell, Journal Year: 2020, Volume and Issue: 182(1), P. 200 - 225.e35

Published: July 1, 2020

To explore the biology of lung adenocarcinoma (LUAD) and identify new therapeutic opportunities, we performed comprehensive proteogenomic characterization 110 tumors 101 matched normal adjacent tissues (NATs) incorporating genomics, epigenomics, deep-scale proteomics, phosphoproteomics, acetylproteomics. Multi-omics clustering revealed four subgroups defined by key driver mutations, country, gender. Proteomic phosphoproteomic data illuminated downstream copy number aberrations, somatic fusions identified vulnerabilities associated with events involving KRAS, EGFR, ALK. Immune subtyping a complex landscape, reinforced association STK11 immune-cold behavior, underscored potential immunosuppressive role neutrophil degranulation. Smoking-associated LUADs showed correlation other environmental exposure signatures field effect in NATs. Matched NATs allowed identification differentially expressed proteins diagnostic utility. This proteogenomics dataset represents unique public resource for researchers clinicians seeking to better understand treat adenocarcinomas.

Language: Английский

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