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

Planchard, David; Popat, Sanjay; Kerr, Keith M.; Novello, Silvia; Smit, Egbert F.; Faivre-Finn, Corinne; Mok, Tony; Reck, Martin; Schil, Paul E. Van; Hellmann, Matthew D.; Peters, Solange

doi:10.1093/annonc/mdy275

Cited by 1,807 publications

(1,988 citation statements)

References 322 publications

(360 reference statements)

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“…tyrosine kinase inhibitors (TKI) for EGFR and BRAF mutated or ALK-and ROS1-translocated tumors, which have facilitated survival rates twice as high as chemotherapy, 3 as well as the development of immune checkpoint inhibitors, which can induce long-term remissions in about 15-20% of metastatic cases. According to international guidelines for molecular testing of lung cancer as updated in 2018, [5][6][7][8] any lung cancer sample (tissue biopsy or cytology) with adenocarcinoma or not-otherwise specified (NOS) histology and adequate tumor cellularity should be tested for routinely treatable mutations with a turnaround time of no more than 10 working days. According to international guidelines for molecular testing of lung cancer as updated in 2018, [5][6][7][8] any lung cancer sample (tissue biopsy or cytology) with adenocarcinoma or not-otherwise specified (NOS) histology and adequate tumor cellularity should be tested for routinely treatable mutations with a turnaround time of no more than 10 working days.…”

Section: Introductionmentioning

confidence: 99%

Combined targeted DNA and RNA sequencing of advanced NSCLC in routine molecular diagnostics: Analysis of the first 3,000 Heidelberg cases

Volckmar

Leichsenring

Kirchner

et al. 2019

Intl Journal of Cancer

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Tyrosine kinase inhibitors currently confer the greatest survival gain for nonsmall cell lung cancer (NSCLC) patients with actionable genetic alterations. Simultaneously, the increasing number of targets and compounds poses the challenge of reliable, broad and timely molecular assays for the identification of patients likely to benefit from novel treatments. Here, we demonstrate the feasibility and clinical utility of comprehensive, NGS‐based genetic profiling for routine workup of advanced NSCLC based on the first 3,000 patients analyzed in our department. Following automated extraction of DNA and RNA from formalin‐fixed, paraffin‐embedded tissue samples, parallel sequencing of DNA and RNA for detection of mutations and gene fusions, respectively, was performed using PCR‐based enrichment with an ion semiconductor sequencing platform. Overall, 807 patients (27%) were eligible for currently approved, EGFR‐/BRAF‐/ALK‐ and ROS1‐directed therapies, while 218 additional cases (7%) with MET, ERBB2 (HER2) and RET alterations could potentially benefit from experimental targeted compounds. In addition, routine capturing of comutations, e.g. TP53 (55%), KEAP1 (11%) and STK11 (11%), as well as the precise typing of fusion partners and involved exons in case of actionable translocations including ALK and ROS1, are prognostic and predictive tools currently gaining importance for further refinement of therapeutic and surveillance strategies. The reliability, low dropout rates (<5%), minimal tissue requirements, fast turnaround times (6 days on average) and lower costs of the diagnostic approach presented here compared to sequential single‐gene testing, highlight its practicability in order to support individualized decisions in routine patient care, enrollment in molecularly stratified clinical trials, as well as translational research.

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Section: Introductionmentioning

confidence: 99%

Combined targeted DNA and RNA sequencing of advanced NSCLC in routine molecular diagnostics: Analysis of the first 3,000 Heidelberg cases

Volckmar

Leichsenring

Kirchner

et al. 2019

Intl Journal of Cancer

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“…Endosonography (endobronchial ultrasound‐guided transbronchial needle aspiration, EBUS‐TBNA; endoscopic ultrasound fine‐needle aspiration, EUS‐b‐FNA) has over time progressively replaced the surgical, diagnostic procedures in patients undergoing investigation for intrathoracic lymphadenopathy owing to its high success rate and safety . Concomitantly, key changes in the treatment of lung cancer (ie, targeted therapy and immunotherapy) have rendered crucial the systematic search for specific driver molecular alterations (ie, EGFR mutation and ALK / ROS1 rearrangements) and other predictive biomarkers (PD‐L1) in patients with advanced disease . As a consequence, the suitability of EBUS‐TBNA samples from lymphadenopathy for the molecular analysis of cancer samples has been investigated in several individual studies .…”

Section: Introductionmentioning

confidence: 99%

Adequacy of endosonography‐derived samples from peribronchial or periesophageal intrapulmonary lesions for the molecular profiling of lung cancer

Livi

Ardizzoni

Cancellieri

et al. 2019

Clinical Respiratory J

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Introduction and Objectives Endosonography is increasingly used for the diagnosis of centrally located, bronchoscopically invisible intrapulmonary lesions, but data regarding its utility for molecular profiling are lacking. We aimed to assess the suitability of endosonography samples obtained from intrapulmonary lesions for cancer genotyping and programmed‐death ligand 1 (PD‐L1) testing. Methods A prospectively collected database regarding 99 consecutive patients undergoing endosonography for the diagnosis of an intrapulmonary lesion was retrospectively reviewed. Genotyping ± PD‐L1 testing was carried out in the 53 patients with advanced lung cancer and was classified as complete if all clinically indicated tests could be performed, incomplete if at least one test could not be carried out, and unsuccessful if the sample was unsuitable for molecular analysis. Results All clinically indicated biomarkers could be tested in 44 (83%) patients, whereas the molecular profiling was classified as incomplete in 6 (11.3%), and unsuccessful in 3 (5.7%). Thirty‐seven genetic alterations (KRAS mutation, 17; EGFR mutation, 17; ALK rearrangement, 3) and 2 cases of PD‐L1 expression >50% were found in 31 (58%) patients. EGFR was successfully analysed in 94.1% of cases, KRAS in 93.9%, ALK in 89%, ROS1 in 90% and PD‐L1 in 63.1%. Conclusion Endosonography‐derived samples from intrapulmonary lesions were suitable for a thorough molecular profiling in most patients. The few cases of incomplete accomplishment of the testing algorithm were related to the failure of PD‐L1 analysis due to the exhaustion of the sample or the lack of sufficient tumour cells in the paraffin‐embedded material.

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“…Lung cancer is the leading cause of cancer‐related death globally, and the overall survival of NSCLC remains dismal. Current treatments include surgery, chemotherapy, radiotherapy, radiofrequency ablation, immunotherapy and molecular targeted therapy . Patients in advanced stages with driving mutations benefit most from targeted therapy.…”

Section: Discussionmentioning

confidence: 99%

Non‐canonical Raf‐1/p70S6K signalling in non–small‐cell lung cancer

Qiu

et al. 2019

J Cellular Molecular Medi

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Lung cancer is the leading cause of cancer‐related death globally, with non–small‐cell lung cancer (NSCLC) being the predominant subtype. Overall survival remains low for NSCLC patients, and novel targets are needed to improve outcome. Raf‐1 is a key component of the Ras/Raf/MEK signalling pathway, but its role and downstream targets in NSCLC are not completely understood. Our previous study indicated a possible correlation between Raf‐1 levels and ribosomal protein S6 kinase (p70S6K) function. In this study, we aimed to investigate whether p70S6K is a downstream target of Raf‐1 in NSCLC. Raf‐1 was silenced in NSCLC cell lines by using small hairpin RNA, and Raf‐1 and p70S6K protein levels were measured via Western blot. p70S6K was then overexpressed following Raf‐1 knock‐down; then, cell proliferation, apoptosis and the cell cycle in NSCLC cell lines were examined. Tumour xenografts with NSCLC cells were then transplanted for in vivo study. Tumours were measured and weighed, and Raf‐1 and p70S6K expression, cell proliferation and apoptosis were examined in tumour tissues by Western blot, Ki‐67 staining and TUNEL staining, respectively. When Raf‐1 was silenced, p70S6K protein levels were markedly decreased in the A549 and H1299 NSCLC cell lines. A significant decrease in NSCLC cell proliferation, a profound increase in apoptosis and cell cycle arrest were observed in vitro following Raf‐1 knock‐down. Overexpression of p70S6K after Raf‐1 depletion effectively reversed these effects. Xenograft studies confirmed these results in vivo. In conclusion, Raf‐1 targets p70S6K as its downstream effector to regulate NSCLC tumorigenicity, making Raf‐1/p70S6K signalling a promising target for NSCLC treatment.

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

Abstract: early initiation of second-line therapy but should also depend on individual retreatment options [III, B].

Cited by 1,807 publications

References 322 publications

Combined targeted DNA and RNA sequencing of advanced NSCLC in routine molecular diagnostics: Analysis of the first 3,000 Heidelberg cases

Combined targeted DNA and RNA sequencing of advanced NSCLC in routine molecular diagnostics: Analysis of the first 3,000 Heidelberg cases

Adequacy of endosonography‐derived samples from peribronchial or periesophageal intrapulmonary lesions for the molecular profiling of lung cancer

Non‐canonical Raf‐1/p70S6K signalling in non–small‐cell lung cancer

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