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Penault-Llorca F, Socinski MA. Emerging molecular testing paradigms in non-small cell lung cancer management-current perspectives and recommendations. Oncologist 2025; 30:oyae357. [PMID: 40126879 PMCID: PMC11966107 DOI: 10.1093/oncolo/oyae357] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2024] [Accepted: 11/20/2024] [Indexed: 03/26/2025] Open
Abstract
Advances in molecular testing and precision oncology have transformed the clinical management of lung cancer, especially non-small cell lung cancer, enhancing diagnosis, treatment, and outcomes. Practical guidelines offer insights into selecting appropriate biomarkers and assays, emphasizing the importance of comprehensive testing. However, real-world data reveal the underutilization of biomarker testing and consequently targeted therapies. Molecular testing often occurs late in diagnosis or not at all in clinical practice, leading to delayed or inadequate treatment. Enhancing precision requires adherence to best practices by all health care professionals involved, which can ultimately improve lung cancer patient outcomes. The future of precision oncology for lung cancer will likely involve a more personalized approach, starting increasingly from earlier disease settings, with novel and more complex targeted therapies, immunotherapies, and combination regimens, and relying on liquid biopsies, muti-detection advanced genomic technologies and data integration, with artificial intelligence as a central orchestrator. This review presents the currently known actionable mutations in lung cancer and new upcoming ones that are likely to enter clinical practice soon and provides an overview of established and emerging concepts in testing methodologies. Challenges are discussed and best practice recommendations are made that are relevant today, will continue to be relevant in the future, and are likely to be relevant for other cancer types too.
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Affiliation(s)
- Frédérique Penault-Llorca
- Department of Pathology, Centre Jean Perrin, Université Clermont Auvergne, INSERM, U1240 Imagerie Moléculaire et Stratégies Théranostiques, Clermont Ferrand F-63000, France
| | - Mark A Socinski
- Oncology and Hematology, AdventHealth Cancer Institute, Orlando, FL 32804, United States
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Narita D, Hishinuma E, Ebina-Shibuya R, Miyauchi E, Matsukawa N, Motoike IN, Kinoshita K, Koshiba S, Tsukita Y, Notsuda H, Kimura N, Saito R, Murakami K, Fujino N, Ichikawa T, Yamada M, Tamada T, Sugiura H. Histological and genetic features and therapeutic responses of lung cancers explored via the global analysis of their metabolome profile. Lung Cancer 2025; 200:108082. [PMID: 39884221 DOI: 10.1016/j.lungcan.2025.108082] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2024] [Revised: 01/01/2025] [Accepted: 01/06/2025] [Indexed: 02/01/2025]
Abstract
BACKGROUND Lung cancer is the deadliest disease globally, with more than 120,000 diagnosed cases and more than 75,000 deaths annually in Japan. Several treatment options for advanced lung cancer are available, and the discovery of biomarkers will be useful for personalized medicine. Using metabolome analysis, we aimed to identify biomarkers for diagnosis and treatment response by examining the changes in metabolites associated with lung cancer progression. METHODS Plasma samples from patients with recurrent or metastatic non-small cell lung carcinomas diagnosed at Tohoku University Hospital between 2019 and 2024 were used in this study. Metabolomic analysis was performed using the Biocrates Life Sciences MxP Quant 500 kit. Multivariate, principal component, and orthogonal partial least squares discriminant analyses were performed. RESULTS The triglyceride and phosphatidylcholine concentrations were higher in the patients with early than in those with advanced lung adenocarcinomas. However, the cholesterol ester concentrations were higher for the patients with advanced lung cancer. The concentrations of hexosylceramide were higher in patients with early lung adenocarcinoma than in those with squamous cell carcinoma. Relative to epidermal growth factor receptor (EGFR)-mutation negative cases, the EGFR-mutation positive cases showed marked differences between the ceramide and triglyceride concentrations. For the best therapeutic effect of EGFR-TKI treatment, the hexosylceramide (HexCer) (d18:1/24:0), ceramide (Cer) (d18:2/22:0), and ceramide (Cer) (d18:2/24:0) concentrations were higher for the stable and progressive disease groups. The concentrations of phosphatidylcholine (PC) ae C42:2, sphingomyelin (SM) C24:1, and lysophosphatidylcholine (lysoPC) a C18:2 were higher in the partial response group treated with immune checkpoint inhibitors and chemotherapy. CONCLUSION Metabolomic analysis may be useful for the diagnosis and treatment of lung cancer and may provide clues for new therapeutic strategies. PC ae C42:2, SM C24:1, and lysoPC a C18:2 can serve as predictive biomarkers for monitoring the therapeutic effects of the combination of immune checkpoint inhibitors and chemotherapy.
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Affiliation(s)
- Daisuke Narita
- Department of Respiratory Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan
| | - Eiji Hishinuma
- Advanced Research Center for Innovations in Next Generation Medicine, Tohoku University, Sendai, Japan; Tohoku Medical Megabank Organization, Tohoku University, Sendai, Japan
| | - Risa Ebina-Shibuya
- Department of Respiratory Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan.
| | - Eisaku Miyauchi
- Department of Respiratory Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan
| | - Naomi Matsukawa
- Tohoku Medical Megabank Organization, Tohoku University, Sendai, Japan
| | - Ikuko N Motoike
- Tohoku Medical Megabank Organization, Tohoku University, Sendai, Japan; Systems Bioinformatics, Graduate School of Information Sciences, Tohoku University, Sendai, Japan
| | - Kengo Kinoshita
- Advanced Research Center for Innovations in Next Generation Medicine, Tohoku University, Sendai, Japan; Tohoku Medical Megabank Organization, Tohoku University, Sendai, Japan; Systems Bioinformatics, Graduate School of Information Sciences, Tohoku University, Sendai, Japan
| | - Seizo Koshiba
- Advanced Research Center for Innovations in Next Generation Medicine, Tohoku University, Sendai, Japan; Tohoku Medical Megabank Organization, Tohoku University, Sendai, Japan
| | - Yoko Tsukita
- Department of Respiratory Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan
| | - Hirotsugu Notsuda
- Department of Thoracic Surgery, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Japan
| | - Nozomu Kimura
- Department of Respiratory Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan
| | - Ryota Saito
- Department of Respiratory Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan
| | - Koji Murakami
- Department of Respiratory Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan
| | - Naoya Fujino
- Department of Respiratory Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan
| | - Tomohiro Ichikawa
- Department of Respiratory Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan
| | - Mitsuhiro Yamada
- Department of Respiratory Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan
| | - Tsutomu Tamada
- Department of Respiratory Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan
| | - Hisatoshi Sugiura
- Department of Respiratory Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan
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Batra U, Nathany S. Biomarker testing in lung cancer: from bench to bedside. Oncol Rev 2025; 18:1445826. [PMID: 39834530 PMCID: PMC11743711 DOI: 10.3389/or.2024.1445826] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2024] [Accepted: 12/12/2024] [Indexed: 01/22/2025] Open
Abstract
Non-small-cell lung cancer (NSCLC) is the poster child of personalized medicine. With increased knowledge about biomarkers and the consequent improvement in survival rates, NSCLC has changed from being a therapeutic nihilistic disease to that characterized by therapeutic enthusiasm. The routine biomarkers tested in NSCLC are EGFR, ALK, and ROS1. However, several additional biomarkers have been added to the diagnostic landscape. Current guidelines recommend testing at least seven biomarkers upfront at the time of NSCLC diagnosis-emphasizing the wide range of targets and corresponding therapies that can be leveraged for disease management. Sequential single-gene testing is not only time-consuming but also leads to tissue exhaustion. Multigene panel testing using next-generation sequencing (NGS) offers an attractive diagnostic substitute that aligns with the evolving dynamics of precision medicine. NGS enables the identification of point mutations, insertions, deletions, copy number alterations, fusion genes, and microsatellite instability information needed to guide the potential use of targeted therapy. This article reviews the existing guidelines, proposed recommendations for NGS in non-squamous NSCLC, real-world data on its use, and the advantages of adopting broader panel-based NGS testing over single-gene testing.
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Affiliation(s)
- Ullas Batra
- Medical Oncology, Rajiv Gandhi Cancer Institute and Research Centre, New Delhi, India
| | - Shrinidhi Nathany
- Hematology and Bone Marrow Transplant, Fortis Memorial Research Institute, Gurgaon, Haryana, India
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Mendivelso-González DF, Castañeda-Motta C, Romero-Rojas AE, Carvajal-Fierro CA, Parra-Medina R. ALK-rearranged primary mixed mucinous and non-mucinous lung adenocarcinoma: A case report. REVISTA ESPANOLA DE PATOLOGIA : PUBLICACION OFICIAL DE LA SOCIEDAD ESPANOLA DE ANATOMIA PATOLOGICA Y DE LA SOCIEDAD ESPANOLA DE CITOLOGIA 2025; 58:100796. [PMID: 39827507 DOI: 10.1016/j.patol.2024.100796] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/13/2024] [Revised: 07/13/2024] [Accepted: 08/14/2024] [Indexed: 01/22/2025]
Abstract
Lung cancer exhibits a diverse array of morphological manifestations and molecular changes, significantly influencing patient diagnosis, prognosis, and treatment strategies. We present the case of a 47-year-old man with a history of smoking, who presented to the emergency room with a 12-month history of haemoptysis. A chest computed tomography (CT) scan revealed a mass in the right upper lobe of the lung and bilateral lung nodules. He underwent a diagnostic wedge resection, which confirmed mixed mucinous and non-mucinous lung adenocarcinoma exhibiting acinar, papillary and micropapillary growth patterns. Molecular studies identified rearrangements in the ALK gene, and staging images revealed central nervous system and bone metastases. This case presents an unusual morphology of mixed mucinous and non-mucinous lung adenocarcinoma and highlights the importance of using immunohistochemical and molecular markers to determine tumour biology.
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Affiliation(s)
| | | | | | - Carlos Andrés Carvajal-Fierro
- Department of Thoracic Surgery, Instituto Nacional de Cancerología, Bogotá, Colombia; Unidd Funcional Clínica de Oncología Torácica, Centro de Tratamiento e Investigación sobre Cáncer (CTIC) Luis Carlos Sarmiento Angulo, Bogotá, Colombia
| | - Rafael Parra-Medina
- Department of Pathology, Instituto Nacional de Cancerología, Bogotá, Colombia; Research Institute, Fundación Universitaria de Ciencias de la Salud (FUCS), Bogotá, Colombia.
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Carretero-Barrio I, Pijuan L, Illarramendi A, Curto D, López-Ríos F, Estébanez-Gallo Á, Castellvi J, Granados-Aparici S, Compañ-Quilis D, Noguera R, Esteban-Rodríguez I, Sánchez-Güerri I, Ramos-Guerra AD, Ortuño JE, Garrido P, Ledesma-Carbayo MJ, Benito A, Palacios J. Concordance in the estimation of tumor percentage in non-small cell lung cancer using digital pathology. Sci Rep 2024; 14:24163. [PMID: 39406837 PMCID: PMC11480438 DOI: 10.1038/s41598-024-75175-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2024] [Accepted: 10/03/2024] [Indexed: 10/19/2024] Open
Abstract
The incorporation of digital pathology in clinical practice will require the training of pathologists in digital skills. Our study aimed to assess the reliability among pathologists in determining tumor percentage in whole slide images (WSI) of non-small cell lung cancer (NSCLC) using digital image analysis, and study how the results correlate with the molecular findings. Pathologists from nine centers were trained to quantify epithelial tumor cells, tumor-associated stromal cells, and non-neoplastic cells from NSCLC WSI using QuPath. Then, we conducted two consecutive ring trials. In the first trial, analyzing four WSI, reliability between pathologists in the assessment of tumor cell percentage was poor (intraclass correlation coefficient (ICC) 0.09). After performing the first ring trial pathologists received feedback. The second trial, comprising 10 WSI with paired next-generation sequencing results, also showed poor reliability (ICC 0.24). Cases near the recommended 20% visual threshold for molecular techniques exhibited higher values with digital analysis. In the second ring trial reliability slightly improved and human errors were reduced from 5.6% to 1.25%. Most discrepancies arose from subjective tasks, such as the annotation process, suggesting potential improvement with future artificial intelligence solutions.
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Affiliation(s)
- Irene Carretero-Barrio
- Department of Pathology, Hospital Universitario Ramón y Cajal, Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), 28034, Madrid, Spain
- Faculty of Medicine, Universidad de Alcalá, 28801, Alcalá de Henares, Spain
- CIBERONC, 28029, Madrid, Spain
| | - Lara Pijuan
- Department of Pathology, Hospital Universitari Bellvitge, L'Hospitalet de Llobregat, 08097, Barcelona, Spain
| | - Adrián Illarramendi
- Department of Pathology, Hospital Universitario 12 de Octubre, 28041, Madrid, Spain
| | - Daniel Curto
- Department of Pathology, Hospital Universitario 12 de Octubre, 28041, Madrid, Spain
| | - Fernando López-Ríos
- CIBERONC, 28029, Madrid, Spain
- Department of Pathology, Hospital Universitario 12 de Octubre, 28041, Madrid, Spain
| | - Ángel Estébanez-Gallo
- Department of Pathology, Hospital Universitario Marqués de Valdecilla, 39011, Santander, Spain
| | - Josep Castellvi
- CIBERONC, 28029, Madrid, Spain
- Department of Pathology, Hospital Universitario Vall D'Hebron, 08035, Barcelona, Spain
| | - Sofía Granados-Aparici
- CIBERONC, 28029, Madrid, Spain
- Department of Pathology, Medical School, University of Valencia-INCLIVA, 46010, Valencia, Spain
| | | | - Rosa Noguera
- CIBERONC, 28029, Madrid, Spain
- Department of Pathology, Medical School, University of Valencia-INCLIVA, 46010, Valencia, Spain
| | | | | | - Ana Delia Ramos-Guerra
- CIBER-BBN, ISCIII, 28029, Madrid, Spain
- Biomedical Image Technologies, ETSI Telecomunicación, Universidad Politécnica de Madrid, 28040, Madrid, Spain
| | - Juan Enrique Ortuño
- CIBER-BBN, ISCIII, 28029, Madrid, Spain
- Biomedical Image Technologies, ETSI Telecomunicación, Universidad Politécnica de Madrid, 28040, Madrid, Spain
| | - Pilar Garrido
- Faculty of Medicine, Universidad de Alcalá, 28801, Alcalá de Henares, Spain
- CIBERONC, 28029, Madrid, Spain
- Medical Oncology Department, Hospital Universitario Ramón y Cajal, Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), 28034, Madrid, Spain
| | - María Jesús Ledesma-Carbayo
- CIBER-BBN, ISCIII, 28029, Madrid, Spain
- Biomedical Image Technologies, ETSI Telecomunicación, Universidad Politécnica de Madrid, 28040, Madrid, Spain
| | - Amparo Benito
- Department of Pathology, Hospital Universitario Ramón y Cajal, Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), 28034, Madrid, Spain
- Faculty of Medicine, Universidad de Alcalá, 28801, Alcalá de Henares, Spain
| | - José Palacios
- Department of Pathology, Hospital Universitario Ramón y Cajal, Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), 28034, Madrid, Spain.
- Faculty of Medicine, Universidad de Alcalá, 28801, Alcalá de Henares, Spain.
- CIBERONC, 28029, Madrid, Spain.
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Tang H, Li YX, Lian JJ, Ng HY, Wang SSY. Personalized treatment using predictive biomarkers in solid organ malignancies: A review. TUMORI JOURNAL 2024; 110:386-404. [PMID: 39091157 DOI: 10.1177/03008916241261484] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/04/2024]
Abstract
In recent years, the influence of specific biomarkers in the diagnosis and prognosis of solid organ malignancies has been increasingly prominent. The relevance of the use of predictive biomarkers, which predict cancer response to specific forms of treatment provided, is playing a more significant role than ever before, as it affects diagnosis and initiation of treatment, monitoring for efficacy and side effects of treatment, and adjustment in treatment regimen in the long term. In the current review, we explored the use of predictive biomarkers in the treatment of solid organ malignancies, including common cancers such as colorectal cancer, breast cancer, lung cancer, prostate cancer, and cancers associated with high mortalities, such as pancreatic cancer, liver cancer, kidney cancer and cancers of the central nervous system. We additionally analyzed the goals and types of personalized treatment using predictive biomarkers, and the management of various types of solid organ malignancies using predictive biomarkers and their relative efficacies so far in the clinical settings.
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Ramalingam SS, Carlisle JW. Encorafenib plus binimetinib for BRAF V600E-mutant metastatic NSCLC: clinical implications of the phase 2 PHAROS study. Future Oncol 2024; 20:2503-2508. [PMID: 39225598 PMCID: PMC11537293 DOI: 10.1080/14796694.2024.2391270] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2024] [Accepted: 08/08/2024] [Indexed: 09/04/2024] Open
Abstract
Drs. Ramalingam and Carlisle discuss the incidence and pathophysiology of BRAF V600E-mutant metastatic non-small cell lung cancer and current treatment options. The podcast provides an overview of the data from the recent Pfizer-sponsored phase 2 PHAROS (NCT03915951) study, which were the basis for the recent US Food and Drug Administration approval of encorafenib plus binimetinib for BRAF V600E-mutant metastatic non-small cell lung cancer.
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Affiliation(s)
- Suresh S Ramalingam
- Department of Hematology and Medical Oncology, Winship Cancer Institute of Emory University School of Medicine, Atlanta, GA 30322, USA
| | - Jennifer W Carlisle
- Department of Hematology and Medical Oncology, Winship Cancer Institute of Emory University School of Medicine, Atlanta, GA 30322, USA
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Lim CH, Um SW, Kim HK, Choi YS, Pyo HR, Ahn MJ, Choi JY. 18F-Fluorodeoxyglucose Positron Emission Tomography-Based Risk Score Model for Prediction of Five-Year Survival Outcome after Curative Resection of Non-Small-Cell Lung Cancer. Cancers (Basel) 2024; 16:2525. [PMID: 39061165 PMCID: PMC11274931 DOI: 10.3390/cancers16142525] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2024] [Revised: 07/09/2024] [Accepted: 07/10/2024] [Indexed: 07/28/2024] Open
Abstract
The aim of our retrospective study is to develop and assess an imaging-based model utilizing 18F-FDG PET parameters for predicting the five-year survival in non-small-cell lung cancer (NSCLC) patients after curative surgery. A total of 361 NSCLC patients who underwent curative surgery were assigned to the training set (n = 253) and the test set (n = 108). The LASSO regression model was used to construct a PET-based risk score for predicting five-year survival. A hybrid model that combined the PET-based risk score and clinical variables was developed using multivariate logistic regression analysis. The predictive performance was determined by the area under the curve (AUC). The individual features with the best predictive performances were co-occurrence_contrast (AUC = 0.675) and SUL peak (AUC = 0.671). The PET-based risk score was identified as an independent predictor after adjusting for clinical variables (OR 5.231, 95% CI 1.987-6.932; p = 0.009). The hybrid model, which integrated clinical variables, significantly outperformed the PET-based risk score alone in predictive accuracy (AUC = 0.771 vs. 0.696, p = 0.022), a finding that was consistent in the test set. The PET-based risk score, especially when integrated with clinical variables, demonstrates good predictive ability for five-year survival in NSCLC patients following curative surgery.
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Affiliation(s)
- Chae Hong Lim
- Department of Nuclear Medicine, Soonchunhyang University College of Medicine, Seoul 04401, Republic of Korea
| | - Sang-Won Um
- Division of Pulmonary and Critical Care Medicine, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 03181, Republic of Korea
| | - Hong Kwan Kim
- Department of Thoracic and Cardiovascular Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 03181, Republic of Korea
| | - Yong Soo Choi
- Department of Thoracic and Cardiovascular Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 03181, Republic of Korea
| | - Hong Ryul Pyo
- Department of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 03181, Republic of Korea
| | - Myung-Ju Ahn
- Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 03181, Republic of Korea
| | - Joon Young Choi
- Department of Nuclear Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 03181, Republic of Korea
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Ramos R, Moura CS, Costa M, Lamas NJ, Correia R, Garcez D, Pereira JM, Sousa C, Vale N. Enhancing Lung Cancer Care in Portugal: Bridging Gaps for Improved Patient Outcomes. J Pers Med 2024; 14:446. [PMID: 38793028 PMCID: PMC11121920 DOI: 10.3390/jpm14050446] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2024] [Revised: 04/18/2024] [Accepted: 04/22/2024] [Indexed: 05/26/2024] Open
Abstract
Lung cancer has the highest incidence and cancer-related mortality worldwide. In Portugal, it ranks as the fourth most common cancer, with nearly 6000 new cases being diagnosed every year. Lung cancer is the main cause of cancer-related death among males and the third cause of cancer-related death in females. Despite the globally accepted guidelines and recommendations for what would be the ideal path for a lung cancer patient, several challenges occur in real clinical management across the world. The recommendations emphasize the importance of adequate screening of high-risk individuals, a precise tumour biopsy, and an accurate final diagnosis to confirm the neoplastic nature of the nodule. A detailed histological classification of the lung tumour type and a comprehensive molecular characterization are of utmost importance for the selection of an efficacious and patient-directed therapeutic approach. However, in the context of the Portuguese clinical organization and the national healthcare system, there are still several gaps in the ideal pathway for a lung cancer patient, involving aspects ranging from the absence of a national lung cancer screening programme through difficulties in histological diagnosis and molecular characterization to challenges in therapeutic approaches. In this manuscript, we address the most relevant weaknesses, presenting several proposals for potential solutions to improve the management of lung cancer patients, helping to decisively improve their overall survival and quality of life.
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Affiliation(s)
- Raquel Ramos
- PerMed Research Group, Center for Health Technology and Services Research (CINTESIS), Rua Doutor Plácido da Costa, 4200-450 Porto, Portugal; (R.R.); (C.S.)
- CINTESIS@RISE, Faculty of Medicine, University of Porto, Alameda Professor Hernâni Monteiro, 4200-319 Porto, Portugal
- Molecular Diagnostics Laboratory, Unilabs Portugal, Centro Empresarial Lionesa Porto, Rua Lionesa, 4465-671 Leça do Balio, Portugal; (M.C.); (N.J.L.)
| | - Conceição Souto Moura
- Pathology Laboratory, Unilabs Portugal, Rua Manuel Pinto de Azevedo 173, 4100-321 Porto, Portugal;
| | - Mariana Costa
- Molecular Diagnostics Laboratory, Unilabs Portugal, Centro Empresarial Lionesa Porto, Rua Lionesa, 4465-671 Leça do Balio, Portugal; (M.C.); (N.J.L.)
| | - Nuno Jorge Lamas
- Molecular Diagnostics Laboratory, Unilabs Portugal, Centro Empresarial Lionesa Porto, Rua Lionesa, 4465-671 Leça do Balio, Portugal; (M.C.); (N.J.L.)
- Anatomic Pathology Service, Pathology Department, Centro Hospitalar Universitário de Santo António (CHUdSA), Largo Professor Abel Salazar, 4099-001 Porto, Portugal
- Life and Health Sciences Research Institute (ICVS), School of Medicine, Campus de Gualtar, University of Minho, Rua da Universidade, 4710-057 Braga, Portugal
| | - Renato Correia
- Technology & Innovation Department, Unilabs Portugal, Rua Manuel Pinto de Azevedo 173, 4100-321 Porto, Portugal; (R.C.); (D.G.)
| | - Diogo Garcez
- Technology & Innovation Department, Unilabs Portugal, Rua Manuel Pinto de Azevedo 173, 4100-321 Porto, Portugal; (R.C.); (D.G.)
| | - José Miguel Pereira
- Radiology Department, Unilabs Portugal, Rua de Diogo Botelho 485, 4150-255 Porto, Portugal;
| | - Carlos Sousa
- PerMed Research Group, Center for Health Technology and Services Research (CINTESIS), Rua Doutor Plácido da Costa, 4200-450 Porto, Portugal; (R.R.); (C.S.)
- Molecular Diagnostics Laboratory, Unilabs Portugal, Centro Empresarial Lionesa Porto, Rua Lionesa, 4465-671 Leça do Balio, Portugal; (M.C.); (N.J.L.)
| | - Nuno Vale
- PerMed Research Group, Center for Health Technology and Services Research (CINTESIS), Rua Doutor Plácido da Costa, 4200-450 Porto, Portugal; (R.R.); (C.S.)
- CINTESIS@RISE, Faculty of Medicine, University of Porto, Alameda Professor Hernâni Monteiro, 4200-319 Porto, Portugal
- Department of Community Medicine, Health Information and Decision (MEDCIDS), Faculty of Medicine, University of Porto, Rua Doutor Plácido da Costa, 4200-450 Porto, Portugal
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Fernandes G, Rodrigues A, Matos C, Barata F, Cirnes L, Ferreira L, Lopes JA, Felizardo M, Fidalgo P, Brito U, Parente B. Liquid biopsy in the management of advanced lung cancer: Implementation and practical aspects. Cancer Treat Res Commun 2023; 36:100725. [PMID: 37321073 DOI: 10.1016/j.ctarc.2023.100725] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2023] [Revised: 05/10/2023] [Accepted: 06/04/2023] [Indexed: 06/17/2023]
Abstract
Non-small-cell lung cancer (NSCLC) is a major cause of cancer-related death worldwide. In recent years, the discovery of actionable molecular alterations has changed the treatment paradigm of the disease. Tissue biopsies have been the gold standard for the identification of targetable alterations but present several limitations, calling for alternatives to detect driver and acquired resistance alterations. Liquid biopsies reveal great potential in this setting and also in the evaluation and monitoring of treatment response. However, several challenges currently hamper its widespread adoption in clinical practice. This perspective article evaluates the potential and challenges associated with liquid biopsy testing, considering a Portuguese expert panel dedicated to thoracic oncology point of view, and providing practical insights for its implementation based on the experience and applicability in the Portuguese context.
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Affiliation(s)
- Gabriela Fernandes
- Pulmonology Department, Centro Hospitalar e Universitário de São João, EPE, Porto, Portugal, Faculdade de Medicina da Universidade do Porto, Porto, Portugal, IBMC/i3S - Instituto de Biologia Molecular e Celular/Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal.
| | | | - Cláudia Matos
- Lung Unit, Champalimaud Foundation, Lisboa, Portugal
| | - Fernando Barata
- Pulmonology Department, Centro Hospitalar e Universitário de Coimbra, EPE - Hospitais da Universidade de Coimbra, Coimbra, Portugal
| | | | | | - José Albino Lopes
- Pulmonology Department, ULSAM, Viana do Castelo, Portugal; Unidade CUF de Oncologia, Hospital CUF Porto, Porto Portugal
| | | | - Paula Fidalgo
- Medical Oncology Department, Centro Hospitalar Universitário do Porto, Porto, Portugal
| | - Ulisses Brito
- Pulmonology Department, Centro Hospitalar e Universitário do Algarve, Faro, Portugal
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Mitsudomi T, Tan D, Yang JCH, Ahn MJ, Batra U, Cho BC, Cornelio G, Lim T, Mok T, Prabhash K, Reungwetwattana T, Ren SX, Singh N, Toyooka S, Wu YL, Yang PC, Yatabe Y. Expert Consensus Recommendations on Biomarker Testing in Metastatic and Nonmetastatic NSCLC in Asia. J Thorac Oncol 2023; 18:436-446. [PMID: 36379356 DOI: 10.1016/j.jtho.2022.10.021] [Citation(s) in RCA: 27] [Impact Index Per Article: 13.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2022] [Revised: 10/07/2022] [Accepted: 10/19/2022] [Indexed: 11/15/2022]
Abstract
INTRODUCTION Most published guidelines for genomic biomarker testing in NSCLC reflect the disease epidemiology and treatments readily available in Europe and North America. Nevertheless, 60% of annual global NSCLC cases occur in Asia, where patient characteristics, tumor molecular profiles, and treatments vary greatly from the Western world. For example, mutations in the EGFR occur at a higher prevalence in Asia than in other world regions. Although medical associations such as the International Association for the Study of Lung Cancer, European Society for Medical Oncology, and American Society of Clinical Oncology have described principles for tumor genomic biomarker testing in NSCLC, there is a need for recommendations specific for Asia. METHODS This report provides consensus recommendations for NSCLC biomarker testing from Asian lung cancer experts for clinicians working in Asia to improve patient care. Biomarker testing approaches for actionable genetic alterations in EGFR, ALK, ROS1, and others are discussed. RESULTS These recommendations are divided into nonmetastatic and metastatic forms of adenocarcinoma and squamous cell carcinoma. Owing to the higher prevalence of EGFR mutations in Asia, the experts emphasized the need for EGFR testing to include not just common mutations (exon 19 deletions and L858R substitutions) but also other uncommon EGFR mutations. In addition to the assessment of biomarkers in the tumor tissue, the role of assessing tumor biomarkers by liquid biopsy is discussed. CONCLUSION This consensus provides practical recommendations for biomarker testing in nonmetastatic and metastatic Asian NSCLC patients.
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Affiliation(s)
- Tetsuya Mitsudomi
- Division of Thoracic Surgery, Faculty of Medicine, Kindai University-Osaka-Sayama, Osaka, Japan.
| | - Daniel Tan
- Division of Medical Oncology, National Cancer Center Singapore, Singapore, Singapore
| | | | - Myung-Ju Ahn
- Section of Hematology-Oncology, Samsung Medical Center, School of Medicine, Sungkyunkwan University, Seoul, Republic of Korea
| | - Ullas Batra
- Rajiv Gandhi Cancer Institute & Research Centre, Rohini, New Delhi, India
| | - Byoung-Chul Cho
- Division of Medical Oncology, Yonsei Cancer Center, Seoul, Republic of Korea
| | - Gerardo Cornelio
- Cancer Institute, St. Luke's Medical Center-Global City, University of the Philippines-Philippine General Hospital, Metro Manila, Philippines
| | - Tony Lim
- Department of Anatomical Pathology, Singapore General Hospital, Singapore, Singapore
| | - Tony Mok
- State Key Laboratory in Translational Oncology, Department of Clinical Oncology, The Chinese University of Hong Kong, Shatin, NT, Hong Kong, People's Republic of China
| | - Kumar Prabhash
- Department of Medical Oncology, Tata Memorial Hospital and Advanced Centre for Treatment Research and Education in Cancer (ACTREC), Homi Bhabha National Institute (HBNI), Mumbai, India
| | - Thanyanan Reungwetwattana
- Division of Medical Oncology, Department of Medicine, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand
| | - Sheng-Xiang Ren
- Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, People's Republic of China
| | - Navneet Singh
- Department of Pulmonary Medicine, Postgraduate Institute of Medical Education & Research, Chandigarh, India
| | - Shinichi Toyooka
- Department of Thoracic Surgery, Okayama University Hospital, Okayama, Japan
| | - Yi-Long Wu
- Department of Pulmonary Oncology, Guangdong Lung Cancer Institute, Guangdong Provincial People's Hospital and Guangdong Academy of Medical Sciences, Guangzhou, People's Republic of China
| | - Pan-Chyr Yang
- Department of Internal Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan
| | - Yasushi Yatabe
- Department of Diagnostic Pathology, National Cancer Center Hospital, Tokyo, Japan
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12
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Isla D, Lozano MD, Paz-Ares L, Salas C, de Castro J, Conde E, Felip E, Gómez-Román J, Garrido P, Belén Enguita A. [New update to the guidelines on testing predictive biomarkers in non-small-cell lung cancer: a National Consensus of the Spanish Society of Pathology and the Spanish Society of Medical Oncology]. REVISTA ESPANOLA DE PATOLOGIA : PUBLICACION OFICIAL DE LA SOCIEDAD ESPANOLA DE ANATOMIA PATOLOGICA Y DE LA SOCIEDAD ESPANOLA DE CITOLOGIA 2023; 56:97-112. [PMID: 37061248 DOI: 10.1016/j.patol.2023.02.002] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/02/2023] [Accepted: 02/08/2023] [Indexed: 04/17/2023]
Abstract
Non-small cell lung cancer (NSCLC) presents the greatest number of identified therapeutic targets, some of which have therapeutic utility. Currently, detecting EGFR, BRAF, KRAS and MET mutations, ALK, ROS1, NTRK and RET translocations, and PD-L1 expression in these patients is considered essential. The use of next-generation sequencing (NGS) facilitates precise molecular diagnosis and allows the detection of other emerging mutations, such as the HER2 mutation and predictive biomarkers for immunotherapy responses. In this consensus, a group of experts in the diagnosis and treatment of NSCLC selected by the Spanish Society of Pathology (SEAP) and the Spanish Society of Medical Oncology (SEOM) have evaluated currently available information and propose a series of recommendations to optimize the detection and use of biomarkers in daily clinical practice.
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Affiliation(s)
- Dolores Isla
- Hospital Clínico Universitario Lozano Blesa, IIS Aragón, Sociedad Española de Oncología Médica (SEOM), Zaragoza, España
| | - María D Lozano
- Clínica Universidad de Navarra, Sociedad Española de Citología (SEC), Sociedad Española de Anatomía Patológica (SEAP), Pamplona, España
| | - Luis Paz-Ares
- Hospital Universitario 12 de Octubre, Sociedad Española de Oncología Médica (SEOM), Madrid, España
| | - Clara Salas
- Hospital Universitario Puerta de Hierro, Sociedad Española de Anatomía Patológica (SEAP), Madrid, España
| | - Javier de Castro
- Hospital Universitario La Paz, Instituto de Investigación Hospital Universitario La Paz (IdiPAZ), Sociedad Española de Oncología Médica (SEOM), Madrid, España
| | - Esther Conde
- Hospital Universitario 12 de Octubre, Instituto de Investigación Hospital Universitario 12 de Octubre (i+12), Sociedad Española de Anatomía Patológica (SEAP), Madrid, España
| | - Enriqueta Felip
- Hospital Universitario Vall d'Hebron, Sociedad Española de Oncología Médica (SEOM), Barcelona, España
| | - Javier Gómez-Román
- Universidad de Cantabria, Hospital Universitario Marqués de Valdecilla, Instituto de Investigación Sanitaria Valdecilla (IDIVAL), Sociedad Española de Anatomía Patológica (SEAP), Santander, España
| | - Pilar Garrido
- Hospital Universitario Ramón y Cajal, Sociedad Española de Oncología Médica (SEOM), Madrid, España
| | - Ana Belén Enguita
- Hospital Universitario 12 de Octubre, Sociedad Española de Anatomía Patológica (SEAP), Madrid, España.
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13
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Simarro J, Pérez-Simó G, Mancheño N, Ansotegui E, Muñoz-Núñez CF, Gómez-Codina J, Juan Ó, Palanca S. Impact of Molecular Testing Using Next-Generation Sequencing in the Clinical Management of Patients with Non-Small Cell Lung Cancer in a Public Healthcare Hospital. Cancers (Basel) 2023; 15:cancers15061705. [PMID: 36980591 PMCID: PMC10046107 DOI: 10.3390/cancers15061705] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2022] [Revised: 02/10/2023] [Accepted: 03/06/2023] [Indexed: 03/14/2023] Open
Abstract
Next-generation sequencing (NGS) is a molecular approach able to provide a comprehensive molecular profile of non-small cell lung cancer (NSCLC). The broad spectrum of biomarker-guided therapies has positioned molecular diagnostic laboratories as a central component of patient clinical management. Here, we show the results of an UNE-EN ISO 15189:2022 NGS-accredited assay in a cohort of 350 patients. TP53 (51.0%), KRAS (26.6%) and EGFR (12.9%) were the most frequently mutated genes. Furthermore, we detected co-occurring and mutually exclusive alterations, as well as distinct molecular profiles according to sex and smoking habits. Actionable genetic alterations were significantly more frequent in female patients (80.5%, p < 0.001) and in never-smoker patients (87.7%, p < 0.001). When NGS was established as the main molecular testing strategy, 36.4% of patients received at least one line of targeted treatment. Among 200 patients with stage IV NSCLC, first-line treatment with targeted therapies was associated with a longer progression-free survival (PFS) (13.4 months (95% CI, 10.2–16.6) (p = 0.001)). Similarly, the overall survival (OS) of patients receiving at least one targeted drug was significantly longer (26.2 months (95% CI, 11.8–40.5) (p < 0.001)). Our results show that the implementation of NGS in the public healthcare system has provided a broader application of precision medicine.
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Affiliation(s)
- Javier Simarro
- Molecular Biology Unit, Service of Clinical Analysis, Hospital Universitario y Politécnico La Fe, 46026 Valencia, Spain
- Clinical and Translational Cancer Research Group, Instituto de Investigación Sanitaria La Fe (IIS La Fe), 46026 Valencia, Spain
| | - Gema Pérez-Simó
- Molecular Biology Unit, Service of Clinical Analysis, Hospital Universitario y Politécnico La Fe, 46026 Valencia, Spain
- Clinical and Translational Cancer Research Group, Instituto de Investigación Sanitaria La Fe (IIS La Fe), 46026 Valencia, Spain
| | - Nuria Mancheño
- Pathology Department, Hospital Universitario y Politécnico La Fe, 46026 Valencia, Spain
| | - Emilio Ansotegui
- Pulmonology Department, Hospital Universitario y Politécnico La Fe, 46026 Valencia, Spain
| | | | - José Gómez-Codina
- Clinical and Translational Cancer Research Group, Instituto de Investigación Sanitaria La Fe (IIS La Fe), 46026 Valencia, Spain
- Medical Oncology Department, Hospital Universitario y Politécnico La Fe, 46026 Valencia, Spain
| | - Óscar Juan
- Medical Oncology Department, Hospital Universitario y Politécnico La Fe, 46026 Valencia, Spain
| | - Sarai Palanca
- Molecular Biology Unit, Service of Clinical Analysis, Hospital Universitario y Politécnico La Fe, 46026 Valencia, Spain
- Clinical and Translational Cancer Research Group, Instituto de Investigación Sanitaria La Fe (IIS La Fe), 46026 Valencia, Spain
- Biochemistry and Molecular Biology Department, Universidad de Valencia, 46010 Valencia, Spain
- Correspondence: ; Tel.: +34-961-244586
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14
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Arriola E, Bernabé R, Campelo RG, Biscuola M, Enguita AB, López-Ríos F, Martínez R, Mezquita L, Palanca S, Pareja MJ, Zugazagoitia J, Arrabal N, García JF, Carcedo D, de Álava E. Cost-Effectiveness of Next-Generation Sequencing Versus Single-Gene Testing for the Molecular Diagnosis of Patients With Metastatic Non-Small-Cell Lung Cancer From the Perspective of Spanish Reference Centers. JCO Precis Oncol 2023; 7:e2200546. [PMID: 36862967 DOI: 10.1200/po.22.00546] [Citation(s) in RCA: 23] [Impact Index Per Article: 11.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/04/2023] Open
Abstract
PURPOSE The aim of this study was to assess the cost-effectiveness of using next-generation sequencing (NGS) versus single-gene testing (SgT) for the detection of genetic molecular subtypes and oncogenic markers in patients with advanced non-small-cell lung cancer (NSCLC) in the setting of Spanish reference centers. METHODS A joint model combining decision tree with partitioned survival models was developed. A two-round consensus panel was performed to describe clinical practice of Spanish reference centers, providing data on testing rate, prevalence of alterations, turnaround times, and treatment pathways. Treatment efficacy data and utility values were obtained from the literature. Only direct costs (euros, 2022), obtained from Spanish databases, were included. A lifetime horizon was considered, so a 3% discount rate for future costs and outcomes was considered. Both deterministic and probabilistic sensitivity analyses were performed to assess uncertainty. RESULTS A target population of 9,734 patients with advanced NSCLC was estimated. If NGS was used instead of SgT, 1,873 more alterations would be detected and 82 more patients could potentially be enrolled in clinical trials. In the long term, using NGS would provide 1,188 additional quality-adjusted life-years (QALYs) in the target population compared with SgT. On the other hand, the incremental cost of NGS versus SgT in the target population was €21,048,580 euros for a lifetime horizon (€1,333,288 for diagnosis phase only). The obtained incremental cost-utility ratios were €25,895 per QALY gained, below the standard cost-effectiveness thresholds. CONCLUSION Using NGS in Spanish reference centers for the molecular diagnosis of patients with metastatic NSCLC would be a cost-effective strategy over SgT.
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Affiliation(s)
| | - Reyes Bernabé
- Institute of Biomedicine of Sevilla (IBiS), Virgen del Rocio University Hospital/CSIC/University of Sevilla/CIBERONC, Seville, Spain
| | - Rosario García Campelo
- Hospital Universitario de A Coruña, A Coruña Institute of Biomedicine of A Coruña (INIBIC), A Coruña, Spain
| | - Michele Biscuola
- Institute of Biomedicine of Sevilla (IBiS), Virgen del Rocio University Hospital/CSIC/University of Sevilla/CIBERONC, Seville, Spain
| | | | | | | | | | - Sarai Palanca
- Hospital Universitario y Politécnico de La Fe, Valencia, Spain.,University of Valencia, Spain
| | - María Jesús Pareja
- Institute of Biomedicine of Sevilla (IBiS), Virgen del Rocio University Hospital/CSIC/University of Sevilla/CIBERONC, Seville, Spain
| | - Jon Zugazagoitia
- Hospital Universitario 12 de octubre, Madrid, Spain.,Hospital Universitario 12 de Octubre (i+12), Madrid, Spain.,Hospital Universitario 12 de Octubre (i+12) / Spanish National Cancer Research Center (CNIO), Madrid, Spain.,CIBERONC, Madrid, Spain
| | | | | | | | - Enrique de Álava
- Institute of Biomedicine of Sevilla (IBiS), Virgen del Rocio University Hospital/CSIC/University of Sevilla/CIBERONC, Seville, Spain.,University of Seville, Seville, Spain
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15
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De Castro J, Insa A, Collado-Borrell R, Escudero-Vilaplana V, Martínez A, Fernandez E, Sullivan I, Arrabal N, Carcedo D, Manzaneque A. Economic burden of locoregional and metastatic relapses in resectable early-stage non-small cell lung cancer in Spain. BMC Pulm Med 2023; 23:69. [PMID: 36809990 PMCID: PMC9942326 DOI: 10.1186/s12890-023-02356-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2022] [Accepted: 02/07/2023] [Indexed: 02/24/2023] Open
Abstract
BACKGROUND There are scarce data of the costs of non-small cell lung cancer (NSCLC) recurrence in Spain. The objective of this study is to assess the economic burden of disease recurrence, for both locoregional and/or metastatic relapses, after appropriate early-stage NSCLC treatment in Spain. MATERIALS AND METHODS A two-round consensus panel of Spanish oncologists and hospital pharmacists was conducted to collect information on patient's flow, treatments, use of healthcare resources and sick leaves in patients with relapsed NSCLC. A decision-tree model was developed to calculate the economic burden of disease recurrence after appropriate early-stage NSCLC. Both direct and indirect costs were considered. Direct costs included drug acquisition and healthcare resources costs. Indirect costs were estimated using the human-capital approach. Unit costs were obtained from national databases (euros of 2022). A multi-way sensitivity analysis was performed to provide a range to the mean values. RESULTS Among a cohort of 100 patients with relapsed NSCLC, 45 patients would have locoregional relapse (36.3 would eventually progress to metastasis and 8.7 would be considered in remission) and 55 patients would have metastatic relapse. Over time, 91.3 patients would experience a metastatic relapse (55 as first relapse and 36.6 after previous locoregional relapse). The overall cost incurred by the 100-patients cohort is €10,095,846 (€9,336,782 direct costs, €795,064 indirect costs). The average cost of a locoregional relapse is €25,194 (€19,658 direct costs, €5536 indirect costs), while the average cost a patient with metastasis who receives up to 4 lines of treatment is €127,167 (€117,328 direct, €9839 indirect). CONCLUSIONS To our knowledge, this is the first study that specifically quantifies the cost of relapse in NSCLC in Spain. Our findings shown that the overall cost of a relapse after appropriate treatment of early-stage NSCLC patients is substantial, and it increases considerably in the metastatic relapse setting, mainly due to the high cost and long duration of first-line treatments.
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Affiliation(s)
- Javier De Castro
- grid.81821.320000 0000 8970 9163Hospital Universitario La Paz, Madrid, Spain
| | - Amelia Insa
- grid.411308.fHospital Clínico Universitario de Valencia, Valencia, Spain
| | - Roberto Collado-Borrell
- grid.410526.40000 0001 0277 7938Hospital General Universitario Gregorio Marañon, Madrid, Spain
| | | | - Alex Martínez
- grid.411083.f0000 0001 0675 8654Hospital Universitari Vall d’Hebron, Barcelona, Spain
| | | | - Ivana Sullivan
- grid.413396.a0000 0004 1768 8905Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
| | - Natalia Arrabal
- grid.476717.40000 0004 1768 8390Roche Farma S.A., Madrid, Spain
| | | | - Alba Manzaneque
- grid.414875.b0000 0004 1794 4956Hospital Universitari Mútua Terrassa, Barcelona, Spain
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16
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ALREHAILI AMANIA, GHARIB AMALF, ALGHAMDI SALEHALI, ALHAZMI AYMAN, AL-SHEHRI SAADS, HAGAG HOWAIDAM, ALSAEEDI FOUZEYYAHALI, ALHUTHALI HAYAAM, RAAFAT NERMIN, ETEWA RASHAL, ELSAWY WAELH. Evaluation of TET Family Gene Expression and 5-Hydroxymethylcytosine as Potential Epigenetic Markers in Non-small Cell Lung Cancer. In Vivo 2023; 37:445-453. [PMID: 36593050 PMCID: PMC9843776 DOI: 10.21873/invivo.13098] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2022] [Revised: 11/07/2022] [Accepted: 11/30/2022] [Indexed: 01/04/2023]
Abstract
BACKGROUND/AIM DNA methylation is the most studied epigenetic modification in cancer. Ten-eleven translocation enzymes (TET) catalyze the oxidation of 5-methylcytosine (5-mC) to 5-hydroxymethylcytosine (5-hmC) in the DNA. In the current research, we aimed to evaluate the role of 5-hmC and TET enzymes in non-small cell lung cancer (NSCLC) patients and their possible association with outcomes. PATIENTS AND METHODS ELISA was used to measure the 5-hmC levels in genomic DNA and qRT-PCR was used to evaluate TET1, TET2, and TET3 mRNAs expression levels in NSCLC tissues and their paired normal controls. RESULTS The levels of 5-hmC were significantly lower in NSCLC tissues than in normal tissues, with a mean ±SD of 0.28±0.37 vs. 1.84±0.58, respectively (t=22.77, p<0.0001), and this reduction was correlated with adverse clinical features. In addition, all TET genes were significantly down-regulated in NSCLC tissues in comparison to their matched normal tissues. The mean±SD level of TET1-mRNA was 38.48±16.38 in NSCLC vs. 80.65±11.25 in normal tissues (t=21.33, p<0.0001), TET2-mRNA level in NSCLC was 5.25±2.78 vs. 9.52±1.01 in normal tissues (t=14.48, p<0.0001), and TET3-mRNA level in NSCLC was 5.21±2.8 vs. 9.51±0.86 in normal tissues (t=14.75, p<0.0001). Downregulation of TET genes was correlated with poor clinical features. CONCLUSION 5-HmC levels as well as TET1, TET2, and TET3 mRNA levels were reduced in NSCLC tissues. The reduced levels of 5-hmC and TET mRNAs were associated with adverse clinical features, suggesting that the level of 5-hmC may serve as a valuable prognostic biomarker for NSCLC.
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Affiliation(s)
- AMANI A. ALREHAILI
- Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Taif University, Taif, Kingdom of Saudi Arabia
| | - AMAL F. GHARIB
- Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Taif University, Taif, Kingdom of Saudi Arabia
| | - SALEH ALI ALGHAMDI
- Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Taif University, Taif, Kingdom of Saudi Arabia
| | - AYMAN ALHAZMI
- Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Taif University, Taif, Kingdom of Saudi Arabia
| | - SAAD S. AL-SHEHRI
- Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Taif University, Taif, Kingdom of Saudi Arabia
| | - HOWAIDA M. HAGAG
- Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Taif University, Taif, Kingdom of Saudi Arabia,Department of Pathology, Faculty of Medicine, Al-Azhar University, Cairo, Egypt
| | - FOUZEYYAH ALI ALSAEEDI
- Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Taif University, Taif, Kingdom of Saudi Arabia
| | - HAYAA M. ALHUTHALI
- Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Taif University, Taif, Kingdom of Saudi Arabia
| | - NERMIN RAAFAT
- Medical Biochemistry Department, Faculty of Medicine, Zagazig University, Zagazig, Egypt
| | - RASHA L. ETEWA
- Pathology Department, College of Medicine, Jouf University, Sakaka, Kingdom of Saudi Arabia
| | - WAEL H. ELSAWY
- Department of Clinical Oncology, Faculty of Medicine, Zagazig University, Zagazig, Egypt
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17
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Lozano MD, Benito A, Labiano T, Pijuan L, Tejerina E, Torres H, Gómez-Román J. Recommendations for optimizing the use of cytology in the diagnosis and management of patients with lung cancer. REVISTA ESPANOLA DE PATOLOGIA : PUBLICACION OFICIAL DE LA SOCIEDAD ESPANOLA DE ANATOMIA PATOLOGICA Y DE LA SOCIEDAD ESPANOLA DE CITOLOGIA 2023; 56:58-68. [PMID: 36599601 DOI: 10.1016/j.patol.2022.04.001] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/22/2022] [Accepted: 04/01/2022] [Indexed: 01/31/2023]
Abstract
Non-small cell lung cancer (NSCLC) is one of the oncological entities with the greatest evolution in molecular diagnosis due to the large number of diagnostic biomarkers and new treatments approved by international regulatory agencies. An accurate, early diagnosis using the least amount of tissue is the goal for the establishing and developing precision medicine for these patients. Rapid on-site evaluation (ROSE) provides cytological samples of optimal quantity and quality for a complete diagnosis of NSCLC. The usefulness of cytological samples has been demonstrated, not only for massive parallel sequencing but also for the quantification of the expression of programmed death-ligand 1 (PD-L1) and tumour mutational burden (TMB). Pre-analytical, analytical, and post-analytical recommendations are made for the management and appropriate use of cytological samples in order to obtain all the information necessary for the diagnosis and treatment of patients with NSCLC according to current quality parameters.
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Affiliation(s)
| | | | | | - Lara Pijuan
- Hospital Universitari Bellvitge, L'Hospitalet de Llobregat, Spain
| | - Eva Tejerina
- Hospital Universitario Puerta de Hierro, Madrid, Spain
| | - Héctor Torres
- Hospital Universitario Central de Asturias, Oviedo, Spain
| | - Javier Gómez-Román
- Hospital Universitario Marqués de Valdecilla, Universidad de Cantabria, IDIVAL, Santander, Spain
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18
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Gholami L, Ivari JR, Nasab NK, Oskuee RK, Sathyapalan T, Sahebkar A. Recent Advances in Lung Cancer Therapy Based on Nanomaterials: A Review. Curr Med Chem 2023; 30:335-355. [PMID: 34375182 DOI: 10.2174/0929867328666210810160901] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2021] [Revised: 06/22/2021] [Accepted: 06/26/2021] [Indexed: 11/22/2022]
Abstract
Lung cancer is one of the commonest cancers with a significant mortality rate for both genders, particularly in men. Lung cancer is recognized as one of the leading causes of death worldwide, which threatens the lives of over 1.6 million people every day. Although cancer is the leading cause of death in industrialized countries, conventional anticancer medications are unlikely to increase patients' life expectancy and quality of life significantly. In recent years, there are significant advances in the development and applications of nanotechnology in cancer treatment. The superiority of nanostructured approaches is that they act more selectively than traditional agents. This progress led to the development of a novel field of cancer treatment known as nanomedicine. Various formulations based on nanocarriers, including lipids, polymers, liposomes, nanoparticles and dendrimers have opened new horizons in lung cancer therapy. The application and expansion of nano-agents lead to an exciting and challenging research era in pharmaceutical science, especially for the delivery of emerging anti-cancer agents. The objective of this review is to discuss the recent advances in three types of nanoparticle formulations for lung cancer treatments modalities, including liposomes, polymeric micelles, and dendrimers for efficient drug delivery. Afterward, we have summarized the promising clinical data on nanomaterials based therapeutic approaches in ongoing clinical studies.
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Affiliation(s)
- Leila Gholami
- Nanotechnology Research Center, Institute of Pharmaceutical Technology, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Jalil Rouhani Ivari
- Department of Medical Biotechnology and Nanotechnology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Niloofar Khandan Nasab
- Department of Medical Biotechnology and Nanotechnology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Reza Kazemi Oskuee
- Applied Biomedical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Thozhukat Sathyapalan
- Academic Diabetes, Endocrinology and Metabolism, Hull York Medical School, University of Hull, United Kingdom of Great Britain and Northern Ireland
| | - Amirhossein Sahebkar
- Applied Biomedical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.,Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad 9177948564, Iran.,School of Medicine, The University of Western Australia, Perth, Australia.,School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
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19
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Rossi S, Marinello A, Pagliaro A, Franceschini D, Navarria P, Finocchiaro G, Toschi L, Scorsetti M, Santoro A. Current treatment approaches for brain metastases in ALK/ ROS1/ NTRK-positive non-small-cell lung cancer. Expert Rev Anticancer Ther 2023; 23:29-41. [PMID: 36548111 DOI: 10.1080/14737140.2023.2162044] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
INTRODUCTION Oncogene-addicted non-small cell lung cancer (NSCLC) patients present a high incidence of CNS metastases either at diagnosis or during the course of the disease. In this case, patients present with worse prognosis and are often excluded from clinical trials unless brain metastases are pre-treated or clinically stable. AREAS COVERED As a result of the discovery of several oncogenic drivers in ALK/ROS1/NTRK-positive NSCLC, targeted agents have been tested in several trials. We evaluate and compare the intracranial efficacy of available targeted agents in ALK/ROS1/NTRK-positive NSCLC based on subgroup analysis from pivotal trials. EXPERT OPINION Last-generation ALK inhibitors have shown slightly superior intracranial activity but pivotal trials do not consider the same endpoints for intracranial efficacy, therefore data are not comparable. Local treatments for BM including surgical resection, stereotactic radiosurgery (SRS) and WBRT, should be integrated with systemic therapies basing on specific criteria like presence of oligoprogression or symptomatic progression.
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Affiliation(s)
- Sabrina Rossi
- Medical Oncology and Hematology Unit, IRCCS Humanitas Research Hospital, Milan, Italy
| | - Arianna Marinello
- Department of Biomedical Sciences, Humanitas University, Milan, Italy
| | - Arianna Pagliaro
- Department of Biomedical Sciences, Humanitas University, Milan, Italy
| | - Davide Franceschini
- Department of Radiotherapy and Radiosurgery, IRCCS Humanitas Research Hospital, Milan, Italy
| | - Pierina Navarria
- Department of Radiotherapy and Radiosurgery, IRCCS Humanitas Research Hospital, Milan, Italy
| | - Giovanna Finocchiaro
- Medical Oncology and Hematology Unit, IRCCS Humanitas Research Hospital, Milan, Italy
| | - Luca Toschi
- Medical Oncology and Hematology Unit, IRCCS Humanitas Research Hospital, Milan, Italy
| | - Marta Scorsetti
- Department of Biomedical Sciences, Humanitas University, Milan, Italy.,Department of Radiotherapy and Radiosurgery, IRCCS Humanitas Research Hospital, Milan, Italy
| | - Armando Santoro
- Medical Oncology and Hematology Unit, IRCCS Humanitas Research Hospital, Milan, Italy.,Department of Biomedical Sciences, Humanitas University, Milan, Italy
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20
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Hofman V, Heeke S, Bontoux C, Chalabreysse L, Barritault M, Bringuier PP, Fenouil T, Benzerdjeb N, Begueret H, Merlio JP, Caumont C, Piton N, Sabourin JC, Evrard S, Syrykh C, Vigier A, Brousset P, Mazieres J, Long-Mira E, Benzaquen J, Boutros J, Allegra M, Tanga V, Lespinet-Fabre V, Salah M, Bonnetaud C, Bordone O, Lassalle S, Marquette CH, Ilié M, Hofman P. Ultrafast Gene Fusion Assessment for Nonsquamous NSCLC. JTO Clin Res Rep 2022; 4:100457. [PMID: 36718140 PMCID: PMC9883235 DOI: 10.1016/j.jtocrr.2022.100457] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2022] [Revised: 12/23/2022] [Accepted: 12/27/2022] [Indexed: 12/31/2022] Open
Abstract
Introduction Gene fusion testing of ALK, ROS1, RET, NTRK, and MET exon 14 skipping mutations is guideline recommended in nonsquamous NSCLC (NS-NSCLC). Nevertheless, assessment is often hindered by the limited availability of tissue and prolonged next-generation sequencing (NGS) testing, which can protract the initiation of a targeted therapy. Therefore, the development of faster gene fusion assessment is critical for optimal clinical decision-making. Here, we compared two ultrafast gene fusion assays (UFGFAs) using NGS (Genexus, Oncomine Precision Assay, Thermo Fisher Scientific) and a multiplex reverse-transcriptase polymerase chain reaction (Idylla, GeneFusion Assay, Biocartis) approach at diagnosis in a retrospective series of 195 NS-NSCLC cases and five extrapulmonary tumors with a known NTRK fusion. Methods A total of 195 NS-NSCLC cases (113 known gene fusions and 82 wild-type tumors) were included retrospectively. To validate the detection of a NTRK fusion, we added five NTRK-positive extrathoracic tumors. The diagnostic performance of the two UFGFAs and standard procedures was compared. Results The accuracy was 92.3% and 93.1% for Idylla and Genexus, respectively. Both systems improved the sensitivity for detection by including a 5'-3' imbalance analysis. Although detection of ROS1, MET exon 14 skipping, and RET was excellent with both systems, ALK fusion detection was reduced with sensitivities of 87% and 88%, respectively. Idylla had a limited sensitivity of 67% for NTRK fusions, in which only an imbalance assessment was used. Conclusions UFGFA using NGS and reverse-transcriptase polymerase chain reaction approaches had an equal level of detection of gene fusion but with some technique-specific limitations. Nevertheless, UFGFA detection in routine clinical care is feasible with both systems allowing faster initiation of therapy and a broad degree of screening.
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Affiliation(s)
- Véronique Hofman
- Laboratory of Clinical and Experimental Pathology, Centre Hospitalier Universitaire de Nice, Université Côte d’Azur, Nice, France,Hospital-Integrated Biobank (BB-0033-00025), Hôpital Pasteur, Nice, France,FHU OncoAge, Hôpital Pasteur, Université Côte d’Azur, Nice, France,Inserm U1081, CNRS UMR 7413, IRCAN, Nice, France
| | - Simon Heeke
- Department of Thoracic/Head & Neck Medical Oncology, the University of Texas, MD Anderson Cancer Center, Houston, Texas
| | - Christophe Bontoux
- Laboratory of Clinical and Experimental Pathology, Centre Hospitalier Universitaire de Nice, Université Côte d’Azur, Nice, France,Hospital-Integrated Biobank (BB-0033-00025), Hôpital Pasteur, Nice, France,FHU OncoAge, Hôpital Pasteur, Université Côte d’Azur, Nice, France,Inserm U1081, CNRS UMR 7413, IRCAN, Nice, France
| | - Lara Chalabreysse
- Department of Pathology, Hospices Civils de Lyon, Groupement Hospitalier Est - HCL, Bron, France, University Claude Bernard, Lyon, France
| | - Marc Barritault
- Department of Pathology, Molecular Biology of Tumors, Hospices Civils de Lyon, Groupement Hospitalier Est - HCL, Bron, France
| | - Pierre Paul Bringuier
- Department of Pathology, Molecular Biology of Tumors, Hospices Civils de Lyon, Groupement Hospitalier Est - HCL, Bron, France
| | - Tanguy Fenouil
- Department of Pathology, Hospices Civils de Lyon, Groupement Hospitalier Est - HCL, Bron, France, University Claude Bernard, Lyon, France
| | - Nazim Benzerdjeb
- Department of Pathology, Hospices Civils de Lyon, Hôpital Lyon Sud, Pierre-Bénite, France, University Claude Bernard, Lyon, France,Department of Cancer Cell Plasticity, Cancer Research Center of Lyon, INSERM U1052, CNRS UMR5286, Lyon, France
| | - Hugues Begueret
- Department of Pathology, Centre Hospitalier Universitaire Bordeaux, Hôpital Haut-Lévêque, Pessac, France
| | - Jean Philippe Merlio
- Department of Histology and Molecular Pathology of Tumors, Centre Hospitalier Universitaire Bordeaux, Pessac, France
| | - Charline Caumont
- Department of Histology and Molecular Pathology of Tumors, Centre Hospitalier Universitaire Bordeaux, Pessac, France
| | - Nicolas Piton
- Department of Pathology and INSERM U1245, CHU de Rouen, Normandie Université, Rouen, France
| | | | - Solène Evrard
- Department of Pathology, IUCT-Oncopole, Toulouse, France
| | | | - Anna Vigier
- Department of Pathology, IUCT-Oncopole, Toulouse, France
| | | | - Julien Mazieres
- Department of Pneumology, CHU Toulouse-Hôpital Larrey, Université Paul Sabatier, Toulouse, France
| | - Elodie Long-Mira
- Laboratory of Clinical and Experimental Pathology, Centre Hospitalier Universitaire de Nice, Université Côte d’Azur, Nice, France,Hospital-Integrated Biobank (BB-0033-00025), Hôpital Pasteur, Nice, France,FHU OncoAge, Hôpital Pasteur, Université Côte d’Azur, Nice, France,Inserm U1081, CNRS UMR 7413, IRCAN, Nice, France
| | - Jonathan Benzaquen
- FHU OncoAge, Hôpital Pasteur, Université Côte d’Azur, Nice, France,Inserm U1081, CNRS UMR 7413, IRCAN, Nice, France,Department of Pulmonary Medicine and Thoracic Oncology, Centre Hospitalier Universitaire de Nice, Université Côte d’Azur, Nice, France
| | - Jacques Boutros
- FHU OncoAge, Hôpital Pasteur, Université Côte d’Azur, Nice, France,Inserm U1081, CNRS UMR 7413, IRCAN, Nice, France,Department of Pulmonary Medicine and Thoracic Oncology, Centre Hospitalier Universitaire de Nice, Université Côte d’Azur, Nice, France
| | - Maryline Allegra
- Hospital-Integrated Biobank (BB-0033-00025), Hôpital Pasteur, Nice, France
| | - Virginie Tanga
- Hospital-Integrated Biobank (BB-0033-00025), Hôpital Pasteur, Nice, France
| | - Virginie Lespinet-Fabre
- Laboratory of Clinical and Experimental Pathology, Centre Hospitalier Universitaire de Nice, Université Côte d’Azur, Nice, France
| | - Myriam Salah
- Hospital-Integrated Biobank (BB-0033-00025), Hôpital Pasteur, Nice, France
| | | | - Olivier Bordone
- Laboratory of Clinical and Experimental Pathology, Centre Hospitalier Universitaire de Nice, Université Côte d’Azur, Nice, France
| | - Sandra Lassalle
- Laboratory of Clinical and Experimental Pathology, Centre Hospitalier Universitaire de Nice, Université Côte d’Azur, Nice, France,Hospital-Integrated Biobank (BB-0033-00025), Hôpital Pasteur, Nice, France,FHU OncoAge, Hôpital Pasteur, Université Côte d’Azur, Nice, France,Inserm U1081, CNRS UMR 7413, IRCAN, Nice, France
| | - Charles-Hugo Marquette
- FHU OncoAge, Hôpital Pasteur, Université Côte d’Azur, Nice, France,Inserm U1081, CNRS UMR 7413, IRCAN, Nice, France,Department of Pulmonary Medicine and Thoracic Oncology, Centre Hospitalier Universitaire de Nice, Université Côte d’Azur, Nice, France
| | - Marius Ilié
- Laboratory of Clinical and Experimental Pathology, Centre Hospitalier Universitaire de Nice, Université Côte d’Azur, Nice, France,Hospital-Integrated Biobank (BB-0033-00025), Hôpital Pasteur, Nice, France,FHU OncoAge, Hôpital Pasteur, Université Côte d’Azur, Nice, France,Inserm U1081, CNRS UMR 7413, IRCAN, Nice, France
| | - Paul Hofman
- Laboratory of Clinical and Experimental Pathology, Centre Hospitalier Universitaire de Nice, Université Côte d’Azur, Nice, France,Hospital-Integrated Biobank (BB-0033-00025), Hôpital Pasteur, Nice, France,FHU OncoAge, Hôpital Pasteur, Université Côte d’Azur, Nice, France,Inserm U1081, CNRS UMR 7413, IRCAN, Nice, France,Corresponding author. Address for correspondence: Paul Hofman, MD, PhD, Laboratoire de Pathologie Clinique et Expérimentale, Centre Hospitalier Universitaire de Nice, Hôpital Pasteur, 30 Voie Romaine, 06000 Nice, France.
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21
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New update to the guidelines on testing predictive biomarkers in non-small-cell lung cancer: a National Consensus of the Spanish Society of Pathology and the Spanish Society of Medical Oncology. Clin Transl Oncol 2022; 25:1252-1267. [PMID: 36571695 PMCID: PMC10119050 DOI: 10.1007/s12094-022-03046-9] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2022] [Accepted: 12/07/2022] [Indexed: 12/27/2022]
Abstract
Non-small cell lung cancer (NSCLC) presents the greatest number of identified therapeutic targets, some of which have therapeutic utility. Currently, detecting EGFR, BRAF, KRAS and MET mutations, ALK, ROS1, NTRK and RET translocations, and PD-L1 expression in these patients is considered essential. The use of next-generation sequencing facilitates precise molecular diagnosis and allows the detection of other emerging mutations, such as the HER2 mutation and predictive biomarkers for immunotherapy responses. In this consensus, a group of experts in the diagnosis and treatment of NSCLC selected by the Spanish Society of Pathology and the Spanish Society of Medical Oncology have evaluated currently available information and propose a series of recommendations to optimize the detection and use of biomarkers in daily clinical practice.
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22
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Guarga L, Paco N, Vela E, Clèries M, Corral J, Delgadillo J, Pontes C, Borràs JM. Changes in Treatment Patterns and Costs for Lung Cancer Have Not Resulted in Relevant Improvements in Survival: A Population-Based Observational Study in Catalonia. Cancers (Basel) 2022; 14:cancers14235791. [PMID: 36497274 PMCID: PMC9735431 DOI: 10.3390/cancers14235791] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2022] [Revised: 11/11/2022] [Accepted: 11/22/2022] [Indexed: 11/27/2022] Open
Abstract
OBJECTIVE Few published studies have described multidisciplinary therapeutic strategies for lung cancer. This study aims to describe the different approaches used for treating lung cancer in Catalonia in 2014 and 2018 and to assess the associated cost and impact on patient survival. METHODS A retrospective observational cohort study using data of patients with lung cancer from health care registries in Catalonia was carried out. We analyzed change in treatment patterns, costs and survival according to the year of treatment initiation (2014 vs. 2018). The Kaplan-Meier method was used to estimate survival, with the follow-up until 2021. RESULTS From 2014 to 2018, the proportion of patients undergoing surgery increased and treatments for unresectable tumors decreased, mainly in younger patients. Immunotherapy increased by up to 9% by 2018. No differences in patient survival were observed within treatment patterns. The mean cost per patient in the first year of treatment increased from EUR 14,123 (standard deviation [SD] 4327) to EUR 14,550 (SD 3880) in surgical patients, from EUR 4655 (SD 3540) to EUR 5873 (SD 6455) in patients receiving curative radiotherapy and from EUR 4723 (SD 7003) to EUR 6458 (SD 10,116) in those treated for unresectable disease. CONCLUSIONS From 2014 to 2018, surgical approaches increased in younger patients. The mean cost of treating patients increased, especially in pharmaceutical expenditure, mainly related to the use of several biomarker-targeted treatments. While no differences in overall patient survival were observed, it seems reasonable to expect improvements in this outcome in upcoming years as more patients receive innovative treatments.
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Affiliation(s)
- Laura Guarga
- Servei Català de la Salut (CatSalut), 08007 Barcelona, Spain
- Departament de Farmacologia, de Terapèutica i de Toxicologia, Universitat Autònoma de Barcelona, 08193 Barcelona, Spain
| | - Noelia Paco
- Servei Català de la Salut (CatSalut), 08007 Barcelona, Spain
| | - Emili Vela
- Servei Català de la Salut (CatSalut), 08007 Barcelona, Spain
- Digitalization for the Sustainability of the Healthcare System (DS3), Bellvitge Biomedical Research Institute (IDIBELL), 08006 Barcelona, Spain
| | - Montse Clèries
- Servei Català de la Salut (CatSalut), 08007 Barcelona, Spain
- Digitalization for the Sustainability of the Healthcare System (DS3), Bellvitge Biomedical Research Institute (IDIBELL), 08006 Barcelona, Spain
| | - Julieta Corral
- Pla Director d’Oncologia, Departament de Salut, Hospitalet del Llobregat, 08908 Barcelona, Spain
- Bellvitge Biomedical Research Institute (IDIBELL), 08006 Barcelona, Spain
| | | | - Caridad Pontes
- Servei Català de la Salut (CatSalut), 08007 Barcelona, Spain
- Departament de Farmacologia, de Terapèutica i de Toxicologia, Universitat Autònoma de Barcelona, 08193 Barcelona, Spain
- Digitalization for the Sustainability of the Healthcare System (DS3), Bellvitge Biomedical Research Institute (IDIBELL), 08006 Barcelona, Spain
| | - Josep Maria Borràs
- Pla Director d’Oncologia, Departament de Salut, Hospitalet del Llobregat, 08908 Barcelona, Spain
- Bellvitge Biomedical Research Institute (IDIBELL), 08006 Barcelona, Spain
- Departament de Ciències Clíniques, Universitat de Barcelona, Campus de Bellvitge, 08907 Barcelona, Spain
- Correspondence:
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23
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Aide N, Weyts K, Lasnon C. Prediction of the Presence of Targetable Molecular Alteration(s) with Clinico-Metabolic 18 F-FDG PET Radiomics in Non-Asian Lung Adenocarcinoma Patients. Diagnostics (Basel) 2022; 12:diagnostics12102448. [PMID: 36292136 PMCID: PMC9601118 DOI: 10.3390/diagnostics12102448] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2022] [Revised: 09/30/2022] [Accepted: 10/07/2022] [Indexed: 11/16/2022] Open
Abstract
This study aimed to investigate if combining clinical characteristics with pre-therapeutic 18 F-fluorodeoxyglucose (18 F-FDG) positron emission tomography (PET) radiomics could predict the presence of molecular alteration(s) in key molecular targets in lung adenocarcinoma. This non-interventional monocentric study included patients with newly diagnosed lung adenocarcinoma referred for baseline PET who had tumour molecular analyses. The data were randomly split into training and test datasets. LASSO regression with 100-fold cross-validation was performed, including sex, age, smoking history, AJCC cancer stage and 31 PET variables. In total, 109 patients were analysed, and it was found that 63 (57.8%) patients had at least one molecular alteration. Using the training dataset (n = 87), the model included 10 variables, namely age, sex, smoking history, AJCC stage, excessKustosis_HISTO, sphericity_SHAPE, variance_GLCM, correlation_GLCM, LZE_GLZLM, and GLNU_GLZLM. The ROC analysis for molecular alteration prediction using this model found an AUC equal to 0.866 (p < 0.0001). A cut-off value set to 0.48 led to a sensitivity of 90.6% and a positive likelihood ratio (LR+) value equal to 2.4. After application of this cut-off value in the unseen test dataset of patients (n = 22), the test presented a sensitivity equal to 90.0% and an LR+ value of 1.35. A clinico-metabolic 18 F-FDG PET phenotype allows the detection of key molecular target alterations with high sensitivity and negative predictive value. Hence, it opens the way to the selection of patients for molecular analysis.
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Affiliation(s)
- Nicolas Aide
- UNICAEN, INSERM 1086 ANTICIPE, Normandy University, 14000 Caen, France
| | - Kathleen Weyts
- Nuclear Medicine Department, Comprehensive Cancer Centre F. Baclesse, UNICANCER, 14000 Caen, France
| | - Charline Lasnon
- UNICAEN, INSERM 1086 ANTICIPE, Normandy University, 14000 Caen, France
- Nuclear Medicine Department, Comprehensive Cancer Centre F. Baclesse, UNICANCER, 14000 Caen, France
- Correspondence: ; Tel.: +33-261-455-268; Fax: +33-231-455-101
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24
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Pujol N, Heeke S, Bontoux C, Boutros J, Ilié M, Hofman V, Marquette CH, Hofman P, Benzaquen J. Molecular Profiling in Non-Squamous Non-Small Cell Lung Carcinoma: Towards a Switch to Next-Generation Sequencing Reflex Testing. J Pers Med 2022; 12:1684. [PMID: 36294823 PMCID: PMC9605324 DOI: 10.3390/jpm12101684] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2022] [Revised: 10/07/2022] [Accepted: 10/08/2022] [Indexed: 11/05/2022] Open
Abstract
Molecular diagnosis of lung cancer is a constantly evolving field thanks to major advances in precision oncology. The wide range of actionable molecular alterations in non-squamous non-small cell lung carcinoma (NS-NSCLC) and the multiplicity of mechanisms of resistance to treatment resulted in the need for repeated testing to establish an accurate molecular diagnosis, as well as to track disease evolution over time. While assessing the increasing complexity of the molecular composition of tumors at baseline, as well as over time, has become increasingly challenging, the emergence and implementation of next-generation sequencing (NGS) testing has extensively facilitated molecular profiling in NS-NSCLC. In this review, we discuss recent developments in the molecular profiling of NS-NSCLC and how NGS addresses current needs, as well as how it can be implemented to address future challenges in the management of NS-NSCLC.
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Affiliation(s)
- Nina Pujol
- Centre Antoine-Lacassagne, Department of Radiation Oncology, Côte d’Azur University, 06000 Nice, France
| | - Simon Heeke
- Department of Thoracic/Head and Neck Medical Oncology, MD Anderson Cancer Center, Houston, TX 77030, USA
| | - Christophe Bontoux
- Laboratory of Clinical and Experimental Pathology, Côte d’Azur University, Pasteur 1 Hospital, Centre Hospitalier Universitaire de Nice, FHU OncoAge, Biobank BB-0033-00025, 06000 Nice, France
- CNRS UMR 7284, INSERM U1081, Institute of Research on Cancer and Aging, Côte d’Azur University, 06000 Nice, France
| | - Jacques Boutros
- CNRS UMR 7284, INSERM U1081, Institute of Research on Cancer and Aging, Côte d’Azur University, 06000 Nice, France
- Department of Pulmonary Medicine and Thoracic Oncology, Côte d’Azur University, Pasteur 1 Hospital, Centre Hospitalier Universitaire de Nice, FHU OncoAge, 06000 Nice, France
| | - Marius Ilié
- Laboratory of Clinical and Experimental Pathology, Côte d’Azur University, Pasteur 1 Hospital, Centre Hospitalier Universitaire de Nice, FHU OncoAge, Biobank BB-0033-00025, 06000 Nice, France
- CNRS UMR 7284, INSERM U1081, Institute of Research on Cancer and Aging, Côte d’Azur University, 06000 Nice, France
| | - Véronique Hofman
- Laboratory of Clinical and Experimental Pathology, Côte d’Azur University, Pasteur 1 Hospital, Centre Hospitalier Universitaire de Nice, FHU OncoAge, Biobank BB-0033-00025, 06000 Nice, France
- CNRS UMR 7284, INSERM U1081, Institute of Research on Cancer and Aging, Côte d’Azur University, 06000 Nice, France
| | - Charles-Hugo Marquette
- CNRS UMR 7284, INSERM U1081, Institute of Research on Cancer and Aging, Côte d’Azur University, 06000 Nice, France
- Department of Pulmonary Medicine and Thoracic Oncology, Côte d’Azur University, Pasteur 1 Hospital, Centre Hospitalier Universitaire de Nice, FHU OncoAge, 06000 Nice, France
| | - Paul Hofman
- Laboratory of Clinical and Experimental Pathology, Côte d’Azur University, Pasteur 1 Hospital, Centre Hospitalier Universitaire de Nice, FHU OncoAge, Biobank BB-0033-00025, 06000 Nice, France
- CNRS UMR 7284, INSERM U1081, Institute of Research on Cancer and Aging, Côte d’Azur University, 06000 Nice, France
| | - Jonathan Benzaquen
- CNRS UMR 7284, INSERM U1081, Institute of Research on Cancer and Aging, Côte d’Azur University, 06000 Nice, France
- Department of Pulmonary Medicine and Thoracic Oncology, Côte d’Azur University, Pasteur 1 Hospital, Centre Hospitalier Universitaire de Nice, FHU OncoAge, 06000 Nice, France
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25
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de Alava E, Pareja MJ, Carcedo D, Arrabal N, García JF, Bernabé-Caro R. Cost-effectiveness analysis of molecular diagnosis by next-generation sequencing versus sequential single testing in metastatic non-small cell lung cancer patients from a south Spanish hospital perspective. Expert Rev Pharmacoecon Outcomes Res 2022; 22:1033-1042. [PMID: 35593180 DOI: 10.1080/14737167.2022.2078310] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
Abstract
BACKGROUND To assess the cost-effectiveness of using next-generation sequencing (NGS) compared to sequential single-testing (SST) for molecular diagnostic and treatment of patients with advanced non-small cell lung cancer (NSCLC) from a Spanish single-center perspective, the Hospital Universitario Virgen del Rocio (HUVR). RESEARCH DESIGN AND METHODS A decision-tree model was developed to assess the alterations detection alterations and diagnostic cost in patients with advanced NSCLC, comparing NGS versus SST. Model inputs such as testing, positivity rates, or treatment allocation were obtained from the literature and the clinical practice of HUVR experts through consultation. Several sensitivity analyses were performed to test the robustness of the model. RESULTS Using NGS for molecular diagnosis of a 100-patients hypothetical cohort, 30 more alterations could be detected and 3 more patients could be enrolled in clinical-trials than using SST. On the other hand, diagnostic costs were increased up to €20,072 using NGS instead of SST. Using NGS time-to-results would be reduced from 16.7 to 9 days. CONCLUSIONS The implementation of NGS at HUVR for the diagnostic of patients with advanced NSCLC provides significant clinical benefits compared to SST in terms of alterations detected, treatment with targeted-therapies and clinical-trial enrollment, and could be considered a cost-effective strategy.
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Affiliation(s)
- Enrique de Alava
- Pathology Unit, Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocio/CSIC/Universidad de Sevilla, Seville, Spain.,Department of Normal and Pathological Cytology and Histology, School of Medicine, University of Seville, Seville, Spain
| | - María Jesús Pareja
- Managing Director of the Health Management Area of South Sevilla, Spain.,Coordinator of the Clinical Laboratory Network of Andalucia
| | | | | | | | - Reyes Bernabé-Caro
- Institute for Biomedical Research in Seville (IBIS/ SNRC/Seville University), Sevilla, Spain
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26
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Ilié M, Hofman V, Bontoux C, Heeke S, Lespinet-Fabre V, Bordone O, Lassalle S, Lalvée S, Tanga V, Allegra M, Salah M, Bohly D, Benzaquen J, Marquette CH, Long-Mira E, Hofman P. Setting Up an Ultra-Fast Next-Generation Sequencing Approach as Reflex Testing at Diagnosis of Non-Squamous Non-Small Cell Lung Cancer; Experience of a Single Center (LPCE, Nice, France). Cancers (Basel) 2022; 14:2258. [PMID: 35565387 PMCID: PMC9104603 DOI: 10.3390/cancers14092258] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/18/2022] [Accepted: 04/28/2022] [Indexed: 12/12/2022] Open
Abstract
The number of genomic alterations required for targeted therapy of non-squamous non-small cell lung cancer (NS-NSCLC) patients has increased and become more complex these last few years. These molecular abnormalities lead to treatment that provides improvement in overall survival for certain patients. However, these treated tumors inexorably develop mechanisms of resistance, some of which can be targeted with new therapies. The characterization of the genomic alterations needs to be performed in a short turnaround time (TAT), as indicated by the international guidelines. The origin of the tissue biopsies used for the analyses is diverse, but their size is progressively decreasing due to the development of less invasive methods. In this respect, the pathologists are facing a number of different challenges requiring them to set up efficient molecular technologies while maintaining a strategy that allows rapid diagnosis. We report here our experience concerning the development of an optimal workflow for genomic alteration assessment as reflex testing in routine clinical practice at diagnosis for NS-NSCLC patients by using an ultra-fast-next generation sequencing approach (Ion Torrent Genexus Sequencer, Thermo Fisher Scientific). We show that the molecular targets currently available to personalized medicine in thoracic oncology can be identified using this system in an appropriate TAT, notably when only a small amount of nucleic acids is available. We discuss the new challenges and the perspectives of using such an ultra-fast NGS in daily practice.
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Affiliation(s)
- Marius Ilié
- Laboratory of Clinical and Experimental Pathology, Pasteur Hospital, Université Côte d’Azur, 06000 Nice, France; (M.I.); (V.H.); (C.B.); (V.L.-F.); (O.B.); (S.L.); (S.L.); (E.L.-M.)
- Biobank-related Hospital (BB-0033-00025), Pasteur Hospital, 06000 Nice, France; (V.T.); (M.A.); (M.S.); (D.B.)
- FHU OncoAge, Pasteur Hospital, Université Côte d’Azur, 06000 Nice, France; (J.B.); (C.-H.M.)
- Inserm U1081, CNRS UMR 7413, IRCAN, 06100 Nice, France
| | - Véronique Hofman
- Laboratory of Clinical and Experimental Pathology, Pasteur Hospital, Université Côte d’Azur, 06000 Nice, France; (M.I.); (V.H.); (C.B.); (V.L.-F.); (O.B.); (S.L.); (S.L.); (E.L.-M.)
- Biobank-related Hospital (BB-0033-00025), Pasteur Hospital, 06000 Nice, France; (V.T.); (M.A.); (M.S.); (D.B.)
- FHU OncoAge, Pasteur Hospital, Université Côte d’Azur, 06000 Nice, France; (J.B.); (C.-H.M.)
- Inserm U1081, CNRS UMR 7413, IRCAN, 06100 Nice, France
| | - Christophe Bontoux
- Laboratory of Clinical and Experimental Pathology, Pasteur Hospital, Université Côte d’Azur, 06000 Nice, France; (M.I.); (V.H.); (C.B.); (V.L.-F.); (O.B.); (S.L.); (S.L.); (E.L.-M.)
- Biobank-related Hospital (BB-0033-00025), Pasteur Hospital, 06000 Nice, France; (V.T.); (M.A.); (M.S.); (D.B.)
- FHU OncoAge, Pasteur Hospital, Université Côte d’Azur, 06000 Nice, France; (J.B.); (C.-H.M.)
- Inserm U1081, CNRS UMR 7413, IRCAN, 06100 Nice, France
| | - Simon Heeke
- Department of Thoracic/Head and Neck Medical Oncology, MD Anderson Cancer Center, Houston, TX 77030, USA;
| | - Virginie Lespinet-Fabre
- Laboratory of Clinical and Experimental Pathology, Pasteur Hospital, Université Côte d’Azur, 06000 Nice, France; (M.I.); (V.H.); (C.B.); (V.L.-F.); (O.B.); (S.L.); (S.L.); (E.L.-M.)
| | - Olivier Bordone
- Laboratory of Clinical and Experimental Pathology, Pasteur Hospital, Université Côte d’Azur, 06000 Nice, France; (M.I.); (V.H.); (C.B.); (V.L.-F.); (O.B.); (S.L.); (S.L.); (E.L.-M.)
- Biobank-related Hospital (BB-0033-00025), Pasteur Hospital, 06000 Nice, France; (V.T.); (M.A.); (M.S.); (D.B.)
| | - Sandra Lassalle
- Laboratory of Clinical and Experimental Pathology, Pasteur Hospital, Université Côte d’Azur, 06000 Nice, France; (M.I.); (V.H.); (C.B.); (V.L.-F.); (O.B.); (S.L.); (S.L.); (E.L.-M.)
- Biobank-related Hospital (BB-0033-00025), Pasteur Hospital, 06000 Nice, France; (V.T.); (M.A.); (M.S.); (D.B.)
- FHU OncoAge, Pasteur Hospital, Université Côte d’Azur, 06000 Nice, France; (J.B.); (C.-H.M.)
- Inserm U1081, CNRS UMR 7413, IRCAN, 06100 Nice, France
| | - Salomé Lalvée
- Laboratory of Clinical and Experimental Pathology, Pasteur Hospital, Université Côte d’Azur, 06000 Nice, France; (M.I.); (V.H.); (C.B.); (V.L.-F.); (O.B.); (S.L.); (S.L.); (E.L.-M.)
| | - Virginie Tanga
- Biobank-related Hospital (BB-0033-00025), Pasteur Hospital, 06000 Nice, France; (V.T.); (M.A.); (M.S.); (D.B.)
| | - Maryline Allegra
- Biobank-related Hospital (BB-0033-00025), Pasteur Hospital, 06000 Nice, France; (V.T.); (M.A.); (M.S.); (D.B.)
| | - Myriam Salah
- Biobank-related Hospital (BB-0033-00025), Pasteur Hospital, 06000 Nice, France; (V.T.); (M.A.); (M.S.); (D.B.)
| | - Doriane Bohly
- Biobank-related Hospital (BB-0033-00025), Pasteur Hospital, 06000 Nice, France; (V.T.); (M.A.); (M.S.); (D.B.)
| | - Jonathan Benzaquen
- FHU OncoAge, Pasteur Hospital, Université Côte d’Azur, 06000 Nice, France; (J.B.); (C.-H.M.)
- Inserm U1081, CNRS UMR 7413, IRCAN, 06100 Nice, France
- Department of Pulmonary Medicine and Thoracic Oncology, Pasteur Hospital, 06000 Nice, France
| | - Charles-Hugo Marquette
- FHU OncoAge, Pasteur Hospital, Université Côte d’Azur, 06000 Nice, France; (J.B.); (C.-H.M.)
- Inserm U1081, CNRS UMR 7413, IRCAN, 06100 Nice, France
- Department of Pulmonary Medicine and Thoracic Oncology, Pasteur Hospital, 06000 Nice, France
| | - Elodie Long-Mira
- Laboratory of Clinical and Experimental Pathology, Pasteur Hospital, Université Côte d’Azur, 06000 Nice, France; (M.I.); (V.H.); (C.B.); (V.L.-F.); (O.B.); (S.L.); (S.L.); (E.L.-M.)
- Biobank-related Hospital (BB-0033-00025), Pasteur Hospital, 06000 Nice, France; (V.T.); (M.A.); (M.S.); (D.B.)
- FHU OncoAge, Pasteur Hospital, Université Côte d’Azur, 06000 Nice, France; (J.B.); (C.-H.M.)
- Inserm U1081, CNRS UMR 7413, IRCAN, 06100 Nice, France
| | - Paul Hofman
- Laboratory of Clinical and Experimental Pathology, Pasteur Hospital, Université Côte d’Azur, 06000 Nice, France; (M.I.); (V.H.); (C.B.); (V.L.-F.); (O.B.); (S.L.); (S.L.); (E.L.-M.)
- Biobank-related Hospital (BB-0033-00025), Pasteur Hospital, 06000 Nice, France; (V.T.); (M.A.); (M.S.); (D.B.)
- FHU OncoAge, Pasteur Hospital, Université Côte d’Azur, 06000 Nice, France; (J.B.); (C.-H.M.)
- Inserm U1081, CNRS UMR 7413, IRCAN, 06100 Nice, France
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de la Haba-Rodriguez J, Lloret FF, Salgado MAV, Arce MO, Gutiérrez AC, Jiménez JGD, Zambrano CB, Alonso RMR, López RL, Salas NR. SEOM-GETTHI clinical guideline for the practical management of molecular platforms (2021). Clin Transl Oncol 2022; 24:693-702. [PMID: 35362851 PMCID: PMC8986692 DOI: 10.1007/s12094-022-02817-8] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/22/2022] [Indexed: 12/13/2022]
Abstract
The improvement of molecular alterations in cancer as well as the development of technology has allowed us to bring closer to clinical practice the determination of molecular alterations in the diagnosis and treatment of cancer. The use of multidetermination platforms is spreading in most Spanish hospitals. The objective of these clinical practice guides is to review their usefulness, and establish usage guidelines that guide their incorporation into clinical practice.
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Affiliation(s)
- Juan de la Haba-Rodriguez
- Department of Medical Oncology, Hospital Universitario Reina Sofia, Instituto Maimonides de Investigacion Biomedica, Universidad de Córdoba, Córdoba, Spain
| | | | | | - Martín Oré Arce
- Department of Medical Oncology, Hospital Marina Baixa de Villajoyosa, Alicante, Spain
| | - Ana Cardeña Gutiérrez
- Department of Medical Oncology, Hospital Universitario Nuestra Señora de la Candelaria, Tenerife, Spain
| | | | - Carmen Beato Zambrano
- Department of Medical Oncology, Hospital Universitario de Jerez de la Frontera, Cádiz, Spain
| | | | - Rafael López López
- Department of Medical Oncology, Complejo Hospitalario Universitario de Santiago, La Coruña, Spain
| | - Nuria Rodriguez Salas
- Department of Medical Oncology, Hospital La Paz, P de la Castellana, 261 - 28046, Madrid, Spain.
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Liu S, Liu X, Wang T, Zeng C, Ren B, Yu X, Xu M, Li W, Qiao Z, You C, Yang Q, Chen M. Effective Systemic Treatment of Choroidal Metastases NSCLC With Surgery After Crizotinib: A Case Report. Front Oncol 2022; 12:789941. [PMID: 35433411 PMCID: PMC9009287 DOI: 10.3389/fonc.2022.789941] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2021] [Accepted: 03/02/2022] [Indexed: 11/16/2022] Open
Abstract
Choroidal metastasis as an initial presenting feature of lung cancer with EML4-ALK translocation is exceedingly rare and greatly impacts patient quality of life (QOL). There are no recommended treatments for such patients, and palliative care remains limited. It is unclear whether surgical resection of primary pulmonary lesions, systemic antitumor therapy, targeted therapy, or localized ocular therapy are effective in treating choroidal metastases in EML4-ALK rearranged oligometastatic non-small cell lung cancer (NSCLC). Here, we present the case of choroidal metastases secondary to lung cancer and EML4-ALK translocation in a 57-year-old woman who firstly underwent resection of lung lesions followed by oral administration of crizotinib without local treatment or systemic chemotherapy. Since then she had a rapid and complete response to crizotinib with 27 months of progression-free survival.
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Affiliation(s)
- Shilan Liu
- Department of Respiratory and Critical Care Medicine, Chengdu Fifth People’s Hospital, Chengdu, China
- Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Xiao Liu
- Department of Respiratory and Critical Care Medicine, Chengdu Fifth People’s Hospital, Chengdu, China
| | - Ting Wang
- Lung Cancer Center, West China Hospital of Sichuan University, Chengdu, China
| | - Chunhua Zeng
- Department of Respiratory and Critical Care Medicine, Chengdu Fifth People’s Hospital, Chengdu, China
| | - Baichen Ren
- Department of Respiratory and Critical Care Medicine, Chengdu Fifth People’s Hospital, Chengdu, China
| | - Xiaodan Yu
- Department of Respiratory and Critical Care Medicine, Chengdu Fifth People’s Hospital, Chengdu, China
| | - Min Xu
- Department of Respiratory and Critical Care Medicine, Chengdu Fifth People’s Hospital, Chengdu, China
| | - Wenjuan Li
- Department of Respiratory and Critical Care Medicine, Chengdu Fifth People’s Hospital, Chengdu, China
| | - Zhihui Qiao
- Department of Respiratory and Critical Care Medicine, Chengdu Fifth People’s Hospital, Chengdu, China
| | - Chuanyun You
- Department of Respiratory and Critical Care Medicine, Chengdu Fifth People’s Hospital, Chengdu, China
| | - Qinghui Yang
- Department of Respiratory and Critical Care Medicine, Chengdu Fifth People’s Hospital, Chengdu, China
| | - Mei Chen
- Department of Respiratory and Critical Care Medicine, Chengdu Fifth People’s Hospital, Chengdu, China
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Rojo F, Conde E, Torres H, Cabezón-Gutiérrez L, Bautista D, Ramos I, Carcedo D, Arrabal N, García JF, Galán R, Nadal E. Clinical and economic impact of 'ROS1-testing' strategy compared to a 'no-ROS1-testing' strategy in advanced NSCLC in Spain. BMC Cancer 2022; 22:292. [PMID: 35303812 PMCID: PMC8933896 DOI: 10.1186/s12885-022-09397-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2021] [Accepted: 03/08/2022] [Indexed: 11/13/2022] Open
Abstract
Background Detection of the ROS1 rearrangement is mandatory in patients with advanced or metastatic non-small cell lung cancer (NSCLC) to allow targeted therapy with specific inhibitors. However, in Spanish clinical practice ROS1 determination is not yet fully widespread. The aim of this study is to determine the clinical and economic impact of sequentially testing ROS1 in addition to EGFR and ALK in Spain. Methods A joint model (decision-tree and Markov model) was developed to determine the cost-effectiveness of testing ROS1 strategy versus a no-ROS1 testing strategy in Spain. Distribution of ROS1 techniques, rates of testing, positivity, and invalidity of biomarkers included in the analysis (EGFR, ALK, ROS1 and PD-L1) were based on expert opinion and Lungpath real-world database. Treatment allocation depending on the molecular testing results was defined by expert opinion. For each treatment, a 3-states Markov model was developed, where progression-free survival (PFS) and overall survival (OS) curves were parameterized using exponential extrapolations to model transition of patients among health states. Only medical direct costs were included (€ 2021). A lifetime horizon was considered and a discount rate of 3% was applied for both costs and effects. Both deterministic and probabilistic sensitivity analyses were performed to address uncertainty. Results A target population of 8755 patients with advanced NSCLC (non-squamous or never smokers squamous) entered the model. Over a lifetime horizon, the ROS1 testing scenario produced additional 157.5 life years and 121.3 quality-adjusted life years (QALYs) compared with no-ROS1 testing scenario. Total direct costs were increased up to € 2,244,737 for ROS1 testing scenario. The incremental cost-utility ratio (ICUR) was 18,514 €/QALY. Robustness of the base-case results were confirmed by the sensitivity analysis. Conclusions Our study shows that ROS1 testing in addition to EGFR and ALK is a cost-effective strategy compared to no-ROS1 testing, and it generates more than 120 QALYs in Spain over a lifetime horizon. Despite the low prevalence of ROS1 rearrangements in NSCLC patients, the clinical and economic consequences of ROS1 testing should encourage centers to test all advanced or metastatic NSCLC (non-squamous and never-smoker squamous) patients. Supplementary Information The online version contains supplementary material available at 10.1186/s12885-022-09397-4.
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Affiliation(s)
- Federico Rojo
- Hospital Universitario Fundación Jiménez Diaz - CIBERONC, Madrid, Spain
| | - Esther Conde
- Hospital Universiario 12 de Octubre-CIBERONC, Madrid, Spain
| | - Héctor Torres
- Hospital Universitario Central de Asturias, Oviedo, Spain
| | | | | | | | - David Carcedo
- Hygeia Consulting, S.A, Madrid, Spain. .,Hygeia Consulting, Barcelona, Spain.
| | | | | | | | - Ernest Nadal
- Catalan Institute of Oncology, Hospital Duran i Reynals, IDIBELL, L'Hospitalet de Llobregat, Spain
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Salas C, Martín-López J, Martínez-Pozo A, Hernández-Iglesias T, Carcedo D, Ruiz de Alda L, García JF, Rojo F. Real-world biomarker testing rate and positivity rate in NSCLC in Spain: Prospective Central Lung Cancer Biomarker Testing Registry (LungPath) from the Spanish Society of Pathology (SEAP). J Clin Pathol 2022; 75:193-200. [PMID: 33722840 PMCID: PMC8862081 DOI: 10.1136/jclinpath-2020-207280] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2020] [Revised: 12/28/2020] [Accepted: 12/30/2020] [Indexed: 01/09/2023]
Abstract
AIM The aim of this study was to describe the testing rate and frequency of molecular alterations observed in the Lung Cancer Biomarker Testing Registry (LungPath). METHODS A descriptive study of NSCLC biomarker determinations collected from March 2018 to January 2019, from 38 Spanish hospitals, was carried out. Only adenocarcinoma and not otherwise specified histologies were included for epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK), c-ros oncogene 1 (ROS1) and programmed death ligand-1 (PD-L1) expression. The testing rate and the positivity rate were calculated. Multivariate logistic regression was used to explore the joint relationship between independent explanatory factors and both testing and positivity rates. Two models were adjusted: one with sample type and histology as independent factors, and the other adding the testing rate or the positivity rate of the other biomarkers. RESULTS 3226 patient samples were analysed, where EGFR, ALK, ROS1 and PD-L1 information was collected (a total of 12 904 determinations). Overall, 9118 (71.4%) determinations were finally assessed. EGFR (91.4%) and ALK (80.1%) were the mainly tested biomarkers. Positivity rates for EGFR, ALK, ROS1 and PD-L1 were 13.6%, 3.4%, 2.0% and 49.2%, respectively. Multivariate models showed a lower testing rate for ALK in surgical pieces, fine-needle aspiration or other types of samples versus biopsies. CONCLUSIONS Despite the high testing rate in EGFR and ALK in NSCLC, the real-world evidence obtained from the LungPath demonstrates that ROS1 and PD-L1 were not determined in a significant portion of patients. LungPath provides crucial information to improve the coverage in molecular testing in lung cancer, to monitor the positivity rate and the introduction of new biomarker testing in clinical practice.
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Affiliation(s)
- Clara Salas
- Hospital Universitario Puerta de Hierro, Majadahonda, Madrid, Spain
- External Quality Asessment (GCP) of the Spanish Society of Pathology (SEAP), Madrid, Spain
| | | | - Antonio Martínez-Pozo
- External Quality Asessment (GCP) of the Spanish Society of Pathology (SEAP), Madrid, Spain
- Pathology Department, Hospital Clinic, IDIBAPS, University of Barcelona, Barcelona, Spain
| | | | | | | | | | - Federico Rojo
- External Quality Asessment (GCP) of the Spanish Society of Pathology (SEAP), Madrid, Spain
- IIS-Fundacion Jimenez Diaz University Hospital CIBERONC, Madrid, Spain
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Gürün Kaya A, Çiledağ A, Erol S, Öz M, Doğan Mülazımoğlu D, Işık Ö, Özakıncı H, Çiftçi F, Şen E, Ceyhan K, Kaya A, Karnak D, Çelik G, İsmail S. Evaluation of lung cancer biomarkers profile for the decision of targeted therapy in EBUS-TBNA cytological samples. Scott Med J 2022; 67:18-27. [PMID: 35147461 DOI: 10.1177/00369330221078995] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Abstract
BACKGROUND Guidelines recommend performing biomarker tests for epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK), BRAF and ROS proto-oncogene-1(ROS1) genes and protein expression of programmed death ligand-1(PD-L1) in patients with non-small lung cell carcinoma (NSCLC). Studies reported that endobronchial ultrasound-transbronchial needle aspiration (EBUS-TBNA) can provide sufficient material for cancer biomarker analyses, but there are still concerns about the subject. AIM The purpose of the study was to assess the adequacy of EBUS-TBNA for testing lung cancer biomarkers. METHODS We retrospectively reviewed patients with NSCLC whose EBUS-TBNA was analysed for EGFR, ALK, ROS-1, BRAF and PD-L1 expression between December 2011 and December 2020. RESULTS A total of 394 patients were enrolled in the study. EGFR mutation and ALK fusion were the most common studied biomarkers. EBUS-TBNA adequacy rate for biomarker tests was found 99.0% for EGFR, 99.1 for ALK, 97.2% for ROS1, 100% for BRAF and 99.3% for PD-L1 testing. Multivariate analysis revealed the histological type, history of treatment for NSCL, size, or 18-fluorodeoxyglucose uptake of sampled lesion did not show any association with TBNA adequacy for biomarker testing. CONCLUSION EBUS-TBNA can provide adequate material for biomarker testing for EGFR, ALK, ROS-1, BRAF and PD-L1 expression.
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Affiliation(s)
- Aslıhan Gürün Kaya
- Department of Chest Diseases, 63990Ankara University Faculty of Medicine, Ankara, Turkey
| | - Aydın Çiledağ
- Department of Chest Diseases, 63990Ankara University Faculty of Medicine, Ankara, Turkey
| | - Serhat Erol
- Department of Chest Diseases, 63990Ankara University Faculty of Medicine, Ankara, Turkey
| | - Miraç Öz
- Department of Chest Diseases, 63990Ankara University Faculty of Medicine, Ankara, Turkey
| | | | - Özlem Işık
- Department of Chest Diseases, 63990Ankara University Faculty of Medicine, Ankara, Turkey
| | - Hilal Özakıncı
- Department of Pathology, 63990Ankara University Faculty of Medicine, Ankara, Turkey
| | - Fatma Çiftçi
- Department of Chest Diseases, 63990Ankara University Faculty of Medicine, Ankara, Turkey
| | - Elif Şen
- Department of Chest Diseases, 63990Ankara University Faculty of Medicine, Ankara, Turkey
| | - Koray Ceyhan
- Department of Pathology, 63990Ankara University Faculty of Medicine, Ankara, Turkey
| | - Akın Kaya
- Department of Chest Diseases, 63990Ankara University Faculty of Medicine, Ankara, Turkey
| | - Demet Karnak
- Department of Chest Diseases, 63990Ankara University Faculty of Medicine, Ankara, Turkey
| | - Gökhan Çelik
- Department of Chest Diseases, 63990Ankara University Faculty of Medicine, Ankara, Turkey
| | - Savaş İsmail
- Department of Chest Diseases, 63990Ankara University Faculty of Medicine, Ankara, Turkey
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Finall A, Davies G, Jones T, Emlyn G, Huey P, Mullard A. Integration of rapid PCR testing as an adjunct to NGS in diagnostic pathology services within the UK: evidence from a case series of non-squamous, non-small cell lung cancer (NSCLC) patients with follow-up. J Clin Pathol 2022; 76:391-399. [PMID: 35042754 DOI: 10.1136/jclinpath-2021-207987] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/06/2021] [Accepted: 12/02/2021] [Indexed: 11/04/2022]
Abstract
AIMS Somatic genetic testing in non-squamous, non-small cell lung carcinoma (NSCLC) patients is required to highlight subgroups eligible for a number of novel oncological therapies. This study aims to determine whether turnaround times for reporting epidermal growth factor receptors (EGFR) by next-generation sequencing (NGS) alone is sufficient to meet the needs of lung cancer patients. METHODS We performed a retrospective case series with follow-up. Outcomes of EGFR testing (102 tests) in 96 patients by NGS were compared with a rapid, fully automated PCR-based platform (Idylla) in local histopathology laboratories. RESULTS Turnaround time for reporting NGS was 17 calendar days. Reporting using the Idylla EGFR Mutation Test, by contrast, gave a potential turnaround time of 3.8 days from request to authorisation. Three-quarters of patients presenting with stage IV disease had a performance status of 0, 1, or 2 but 18% experienced rapid clinical deterioration (p<0.05). A third of these patients were deceased by the time NGS reports were available. CONCLUSIONS We discuss issues around integrating rapid PCR testing alongside NGS in multidisciplinary care pathways and strategies for mitigating against foreseeable difficulties. Dual testing for stage IV non-squamous, NSCLC patients has the potential to improve care and survival outcomes by providing access to the right test at the right time.
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Affiliation(s)
- Alison Finall
- Cellular Pathology, Swansea Bay University Health Board, Port Talbot, UK .,Medical School, Swansea University, Swansea, UK
| | - Gareth Davies
- Cellular Pathology, Swansea Bay University Health Board, Port Talbot, UK
| | - Trevor Jones
- Cellular Pathology, Swansea Bay University Health Board, Port Talbot, UK
| | - Gwion Emlyn
- Cellular Pathology, Betsi Cadwaladr University Health Board, Bangor, UK
| | - Pearl Huey
- Cellular Pathology, Betsi Cadwaladr University Health Board, Bangor, UK
| | - Anna Mullard
- Oncology, Betsi Cadwaladr University Health Board, Bangor, UK
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Horgan D, Curigliano G, Rieß O, Hofman P, Büttner R, Conte P, Cufer T, Gallagher WM, Georges N, Kerr K, Penault-Llorca F, Mastris K, Pinto C, Van Meerbeeck J, Munzone E, Thomas M, Ujupan S, Vainer GW, Velthaus JL, André F. Identifying the Steps Required to Effectively Implement Next-Generation Sequencing in Oncology at a National Level in Europe. J Pers Med 2022; 12:72. [PMID: 35055387 PMCID: PMC8780351 DOI: 10.3390/jpm12010072] [Citation(s) in RCA: 24] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2021] [Revised: 12/16/2021] [Accepted: 12/29/2021] [Indexed: 02/07/2023] Open
Abstract
Next-generation sequencing (NGS) may enable more focused and highly personalized cancer treatment, with the National Comprehensive Cancer Network and European Society for Medical Oncology guidelines now recommending NGS for daily clinical practice for several tumor types. However, NGS implementation, and therefore patient access, varies across Europe; a multi-stakeholder collaboration is needed to establish the conditions required to improve this discrepancy. In that regard, we set up European Alliance for Personalised Medicine (EAPM)-led expert panels during the first half of 2021, including key stakeholders from across 10 European countries covering medical, economic, patient, industry, and governmental expertise. We describe the outcomes of these panels in order to define and explore the necessary conditions for NGS implementation into routine clinical care to enable patient access, identify specific challenges in achieving them, and make short- and long-term recommendations. The main challenges identified relate to the demand for NGS tests (governance, clinical standardization, and awareness and education) and supply of tests (equitable reimbursement, infrastructure for conducting and validating tests, and testing access driven by evidence generation). Recommendations made to resolve each of these challenges should aid multi-stakeholder collaboration between national and European initiatives, to complement, support, and mutually reinforce efforts to improve patient care.
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Affiliation(s)
- Denis Horgan
- European Alliance for Personalised Medicine, Avenue de l’Armee/Legerlaan 10, 1040 Brussels, Belgium
| | - Giuseppe Curigliano
- European Institute of Oncology, IRCCS, Via Giuseppe Ripamonti, 435, 20141 Milan, Italy; (G.C.); (E.M.)
- Department of Oncology and Hemato-Oncology, University of Milan, Via Festa del Perdono, 7, 20122 Milan, Italy
| | - Olaf Rieß
- Institute of Medical Genetics and Applied Genomics, University of Tuebingen, Calwerstrasse 7, 72070 Tuebingen, Germany;
| | - Paul Hofman
- Laboratory of Clinical and Experimental Pathology, University of Côte d’Azur, FHU OncoAge, Biobank BB-0033-00025, Pasteur Hospital, 30 Avenue de la voie Romaine, CEDEX 01, 06001 Nice, France;
| | - Reinhard Büttner
- Institute for Pathology, University Hospital Cologne, Kerpener Str. 62, 50937 Cologne, Germany;
| | - Pierfranco Conte
- The Veneto Institute of Oncology, IRCCS, Via Gattamelata, 64, 35128 Padua, Italy;
- Department of Surgical, Oncological and Gastroenterological Sciences, University of Padua, Via Giustiniani, 2, 35124 Padua, Italy
| | - Tanja Cufer
- Medical Faculty, University of Ljubljana, Vrazov trg 2, 1000 Ljubljana, Slovenia;
| | - William M. Gallagher
- School of Biomolecular and Biomedical Science, University College Dublin, Belfield, D04 V1W8 Dublin, Ireland;
| | - Nadia Georges
- Exact Sciences, Quai du Seujet 10, 1201 Geneva, Switzerland;
| | - Keith Kerr
- School of Medicine and Dentistry, University of Aberdeen, Foresterhill, Aberdeen AB25 2ZD, UK;
| | - Frédérique Penault-Llorca
- Centre Jean Perrin, 58, Rue Montalembert, CEDEX 01, 63011 Clermont-Ferrand, France;
- Department of Pathology, University of Clermont Auvergne, INSERM U1240, 49 bd François Mitterrand, CS 60032, 63001 Clermont-Ferrand, France
| | - Ken Mastris
- Europa Uomo, Leopoldstraat 34, 2000 Antwerp, Belgium;
| | - Carla Pinto
- AstraZeneca, Rua Humberto Madeira 7, 1800 Oeiras, Portugal;
| | - Jan Van Meerbeeck
- Antwerp University Hospital, University of Antwerp, Wijlrijkstraat 10, 2650 Edegem, Belgium;
| | - Elisabetta Munzone
- European Institute of Oncology, IRCCS, Via Giuseppe Ripamonti, 435, 20141 Milan, Italy; (G.C.); (E.M.)
| | - Marlene Thomas
- F. Hoffmann-La Roche Ltd., Grenzacherstrasse 124, 4070 Basel, Switzerland;
| | - Sonia Ujupan
- Eli Lilly and Company, Rue du Marquis 1, Markiesstraat, 1000 Brussels, Belgium;
| | - Gilad W. Vainer
- Department of Pathology, Hadassah Hebrew-University Medical Center, Hebrew University of Jerusalem, Kalman Ya’akov Man St, Jerusalem 91905, Israel;
| | - Janna-Lisa Velthaus
- University Medical Center Hamburg-Eppendorf, Martinistraße 52, 20251 Hamburg, Germany;
| | - Fabrice André
- Institut Gustave Roussy, 114 Rue Edouard Vaillant, 94805 Villejuif, France;
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Martín-López J, Rojo F, Martínez-Pozo A, Hernández-Iglesias T, Carcedo D, de Alda LR, García JF, Salas C. Biomarker testing strategies in non-small cell lung cancer in the real-world setting: analysis of methods in the Prospective Central Lung Cancer Biomarker Registry (LungPath) from the Spanish Society of Pathology (SEAP). J Clin Pathol 2021; 76:327-332. [PMID: 34903610 PMCID: PMC10176377 DOI: 10.1136/jclinpath-2021-208034] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2021] [Accepted: 11/09/2021] [Indexed: 11/04/2022]
Abstract
AIMS The aim of this study is to extend the analysis of the Lung Cancer Biomarker Testing Registry (LungPath), by analysing the techniques used in the determination of epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK), c-ros oncogene 1 (ROS1) and programmed death ligand-1 (PD-L1) for the diagnostic of patients with advanced non-small-cell lung cancer (NSCLC). METHODS Information of the technique used for the determination of EGFR, ALK, ROS1 and PD-L1 was recorded from March 2018 to January 2019 from 44 centres, but only 34 centres matched with the 38 centres previously analysed, allowing to analyse the techniques used in 8970 matched determinations of EGFR, ALK, ROS1 and PD-L1. Therefore, a by-centre analysis studied the level of implementation of the techniques in the 44 centres, while a by-determination analysis made it possible to assess the overall frequency of the techniques used on the 9134 matched samples. RESULTS By-centre analysis showed that only 46.5% and 25.6% of the centres used reflex strategies for ALK and ROS1 determination, respectively. By-determination analysis showed that 94.4% of EGFR determinations were performed by PCR, 80.7% of ALK determinations were performed by IHC with clone D5F3, while 55.7% of ROS1 determinations were performed by IHC with clone D4D6. 22C3 were the PD-L1 clone more used (43.5%) followed by SP263 clone (31.1%). CONCLUSIONS The real-world evidence obtained from LungPath shows the effort of Spanish hospitals in performing biomarker determination in NSCLC with different methodologies despite that next-generation sequencing (NGS) utilisation in the year of the analysis was low. Biomarker determination results could be optimised with the incorporation of sequencing methods such as NGS in pathology departments.
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Affiliation(s)
- Javier Martín-López
- Pathology Department, Hospital Universitario Puerta del Hierro Majadahonda, Madrid, Spain
| | - Federico Rojo
- Pathology Department, Hospital Universitario Fundacion Jimenez Diaz-CIBERONC, Madrid, Spain.,External Quality Asessment (GCP), Spanish Society of Anatomical Pathology, Madrid, Spain
| | - Antonio Martínez-Pozo
- External Quality Asessment (GCP), Spanish Society of Anatomical Pathology, Madrid, Spain.,Pathology Department, Hospital Clinic de Barcelona, Barcelona, Spain
| | | | | | | | | | - Clara Salas
- Pathology Department, Hospital Universitario Puerta del Hierro Majadahonda, Madrid, Spain.,External Quality Asessment (GCP), Spanish Society of Anatomical Pathology, Madrid, Spain
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Pathak N, Chitikela S, Malik PS. Recent advances in lung cancer genomics: Application in targeted therapy. ADVANCES IN GENETICS 2021; 108:201-275. [PMID: 34844713 DOI: 10.1016/bs.adgen.2021.08.004] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
Abstract
Genomic characterization of lung cancer has not only improved our understanding of disease biology and carcinogenesis but also revealed several therapeutic opportunities. Targeting tumor dependencies on specific genomic alterations (oncogene addiction) has accelerated the therapeutic developments and significantly improved the outcomes even in advanced stage of disease. Identification of genomic alterations predicting response to specific targeted treatment is the key to success for this "personalized treatment" approach. Availability of multiple choices of therapeutic options for specific genomic alterations highlight the importance of optimum sequencing of drugs. Multiplex gene testing has become mandatory in view of constantly increasing number of therapeutic targets and effective treatment options. Influence of genomic characteristics on response to immunotherapy further makes comprehensive genomic profiling necessary before therapeutic decision making. A comprehensive elucidation of resistance mechanisms and directed treatments have made the continuum of care possible and transformed this deadly disease into a chronic condition. Liquid biopsy-based approach has made the dynamic monitoring of disease possible and enabled treatment optimizations accordingly. Current lung cancer management is the perfect example of "precision-medicine" in clinical oncology.
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Affiliation(s)
- Neha Pathak
- Department of Medical Oncology, Dr. B.R.A.I.R.C.H., All India Institute of Medical Sciences, New Delhi, India
| | - Sindhura Chitikela
- Department of Medical Oncology, Dr. B.R.A.I.R.C.H., All India Institute of Medical Sciences, New Delhi, India
| | - Prabhat Singh Malik
- Department of Medical Oncology, Dr. B.R.A.I.R.C.H., All India Institute of Medical Sciences, New Delhi, India.
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Cheng Y, Zhang T, Xu Q. Therapeutic advances in non-small cell lung cancer: Focus on clinical development of targeted therapy and immunotherapy. MedComm (Beijing) 2021; 2:692-729. [PMID: 34977873 PMCID: PMC8706764 DOI: 10.1002/mco2.105] [Citation(s) in RCA: 44] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2021] [Revised: 11/20/2021] [Accepted: 11/22/2021] [Indexed: 02/05/2023] Open
Abstract
Lung cancer still contributes to nearly one-quarter cancer-related deaths in the past decades, despite the rapid development of targeted therapy and immunotherapy in non-small cell lung cancer (NSCLC). The development and availability of comprehensive genomic profiling make the classification of NSCLC more precise and personalized. Most treatment decisions of advanced-stage NSCLC have been made based on the genetic features and PD-L1 expression of patients. For the past 2 years, more than 10 therapeutic strategies have been approved as first-line treatment for certain subgroups of NSCLC. However, some major challenges remain, including drug resistance and low rate of overall survival. Therefore, we discuss and review the therapeutic strategies of NSCLC, and focus on the development of targeted therapy and immunotherapy in advanced-stage NSCLC. Based on the latest guidelines, we provide an updated summary on the standard treatment for NSCLC. At last, we discussed several potential therapies for NSCLC. The development of new drugs and combination therapies both provide promising therapeutic effects on NSCLC.
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Affiliation(s)
- Yuan Cheng
- Laboratory of Aging Research and Cancer Drug TargetState Key Laboratory of Biotherapy and Cancer CenterNational Clinical Research Center for GeriatricsWest China HospitalSichuan UniversityChengduChina
| | - Tao Zhang
- Laboratory of Aging Research and Cancer Drug TargetState Key Laboratory of Biotherapy and Cancer CenterNational Clinical Research Center for GeriatricsWest China HospitalSichuan UniversityChengduChina
| | - Qing Xu
- Department of OncologyShanghai Tenth People's HospitalTongji University School of MedicineShanghaiChina
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Šutić M, Vukić A, Baranašić J, Försti A, Džubur F, Samaržija M, Jakopović M, Brčić L, Knežević J. Diagnostic, Predictive, and Prognostic Biomarkers in Non-Small Cell Lung Cancer (NSCLC) Management. J Pers Med 2021; 11:1102. [PMID: 34834454 PMCID: PMC8624402 DOI: 10.3390/jpm11111102] [Citation(s) in RCA: 53] [Impact Index Per Article: 13.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2021] [Revised: 10/21/2021] [Accepted: 10/25/2021] [Indexed: 12/25/2022] Open
Abstract
Lung cancer is the leading cause of cancer-related deaths worldwide. Despite growing efforts for its early detection by screening populations at risk, the majority of lung cancer patients are still diagnosed in an advanced stage. The management of lung cancer has dramatically improved in the last decade and is no longer based on the "one-fits-all" paradigm or the general histological classification of non-small cell versus small cell lung cancer. Emerging options of targeted therapies and immunotherapies have shifted the management of lung cancer to a more personalized treatment approach, significantly influencing the clinical course and outcome of the disease. Molecular biomarkers have emerged as valuable tools in the prognosis and prediction of therapy response. In this review, we discuss the relevant biomarkers used in the clinical management of lung tumors, from diagnosis to prognosis. We also discuss promising new biomarkers, focusing on non-small cell lung cancer as the most abundant type of lung cancer.
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Affiliation(s)
- Maja Šutić
- Division of Molecular Medicine, Ruđer Bošković Institute, 10000 Zagreb, Croatia; (M.Š.); (A.V.); (J.B.)
| | - Ana Vukić
- Division of Molecular Medicine, Ruđer Bošković Institute, 10000 Zagreb, Croatia; (M.Š.); (A.V.); (J.B.)
| | - Jurica Baranašić
- Division of Molecular Medicine, Ruđer Bošković Institute, 10000 Zagreb, Croatia; (M.Š.); (A.V.); (J.B.)
| | - Asta Försti
- Hopp Children’s Cancer Center (KiTZ), 69120 Heidelberg, Germany;
- Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany
| | - Feđa Džubur
- German Cancer Consortium (DKTK), 69120 Heidelberg, Germany; (F.D.); (M.S.); (M.J.)
- Clinical Department for Respiratory Diseases Jordanovac, University Hospital Centre Zagreb, School of Medicine, University of Zagreb, 10000 Zagreb, Croatia
| | - Miroslav Samaržija
- German Cancer Consortium (DKTK), 69120 Heidelberg, Germany; (F.D.); (M.S.); (M.J.)
- Clinical Department for Respiratory Diseases Jordanovac, University Hospital Centre Zagreb, School of Medicine, University of Zagreb, 10000 Zagreb, Croatia
| | - Marko Jakopović
- German Cancer Consortium (DKTK), 69120 Heidelberg, Germany; (F.D.); (M.S.); (M.J.)
- Clinical Department for Respiratory Diseases Jordanovac, University Hospital Centre Zagreb, School of Medicine, University of Zagreb, 10000 Zagreb, Croatia
| | - Luka Brčić
- Diagnostic and Research Institute of Pathology, Medical University of Graz, 8010 Graz, Austria;
| | - Jelena Knežević
- Division of Molecular Medicine, Ruđer Bošković Institute, 10000 Zagreb, Croatia; (M.Š.); (A.V.); (J.B.)
- Faculties for Dental Medicine and Health, University of Osijek, 31000 Osijek, Croatia
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Guirado M, Sanchez-Hernandez A, Pijuan L, Teixido C, Gómez-Caamaño A, Cilleruelo-Ramos Á. Quality indicators and excellence requirements for a multidisciplinary lung cancer tumor board by the Spanish Lung Cancer Group. Clin Transl Oncol 2021; 24:446-459. [PMID: 34665437 PMCID: PMC8525055 DOI: 10.1007/s12094-021-02712-8] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2021] [Accepted: 09/18/2021] [Indexed: 12/24/2022]
Abstract
Multidisciplinary care is needed to decide the best therapeutic approach and to provide optimal care to patients with lung cancer (LC). Multidisciplinary teams (MDTs) are optimal strategies for the management of patients with LC and have been associated with better outcomes, such as an increase in quality of life and survival. The Spanish Lung Cancer Group has promoted this review about the current situation of the existing national LC-MDTs, which also offers a set of excellence requirements and quality indicators to achieve the best care in any patient with LC. Time and sufficient resources; leadership; administrative and institutional support; and recording of activity are key factors for the success of LC-MDTs. A set of excellence requirements in terms of staff, resources and organization of the LC-MDT have been proposed. At last, a list of quality indicators has been agreed to achieve and measure the performance of current LC-MDTs.
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Affiliation(s)
- M Guirado
- Medical Oncology Department, Hospital General Universitario de Elche, 03203, Elche, Spain
| | - A Sanchez-Hernandez
- Medical Oncology Department, Consorcio Hospitalario Provincial de Castellón, 12002, Castellón de la Plana, Spain
| | - L Pijuan
- Pathology Department, Bellvitge University Hospital, 08907, L'Hospitalet de Llobregat, Spain
| | - C Teixido
- Thoracic Oncology Unit, Department of Pathology, IDIBAPS, Hospital Clinic of Barcelona, C. de Villarroel, 170, 08036, Barcelona, Spain.
| | - A Gómez-Caamaño
- Department of Radiation Oncology, Hospital Clínico Universitario Santiago de Compostela, 15706, Santiago de Compostela, Spain
| | - Á Cilleruelo-Ramos
- Thoracic Surgery Department, Hospital Clínico Universitario Valladolid, 47005, Valladolid, Spain
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[Multidisciplinary consensus on optimizing the detection of NTRK gene alterations in tumours]. REVISTA ESPAÑOLA DE PATOLOGÍA : PUBLICACIÓN OFICIAL DE LA SOCIEDAD ESPAÑOLA DE ANATOMÍA PATOLÓGICA Y DE LA SOCIEDAD ESPAÑOLA DE CITOLOGÍA 2021; 54:250-262. [PMID: 34544555 DOI: 10.1016/j.patol.2021.05.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/02/2021] [Revised: 04/16/2021] [Accepted: 05/13/2021] [Indexed: 11/21/2022]
Abstract
The recent identification of rearrangements of neurotrophic tyrosine receptor kinase (NTRK) genes and the development of specific fusion protein inhibitors, such as larotrectinib and entrectinib, have revolutionized the diagnostic and clinical management of patients presenting with tumours with these alterations. Tumours that harbour NTRK fusions are found in both adults and children and are either rare tumours with common NTRK fusions that may be diagnostic, or more common tumours with rare NTRK fusions. To assess the currently available evidence, 3key Spanish medical societies (the Spanish Society of Medical Oncology (SEOM), the Spanish Society of Pathology (SEAP) and the Spanish Society of Paediatric Haematology and Oncology (SEHOP) have brought together a group of experts to develop a consensus document that includes guidelines on the diagnostic, clinical and therapeutic aspects of NTRK-fusion tumours. It also discusses the challenges related to the routine detection of these genetic alterations in a mostly public health care system.
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40
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Exosomes in Lung Cancer: Actors and Heralds of Tumor Development. Cancers (Basel) 2021; 13:cancers13174330. [PMID: 34503141 PMCID: PMC8431734 DOI: 10.3390/cancers13174330] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2021] [Revised: 08/24/2021] [Accepted: 08/25/2021] [Indexed: 12/16/2022] Open
Abstract
Lung cancer is a leading cause of cancer-related death worldwide and in most cases, diagnosis is reached when the tumor has already spread and prognosis is quite poor. For that reason, the research for new biomarkers that could improve early diagnosis and its management is essential. Exosomes are microvesicles actively secreted by cells, especially by tumor cells, hauling molecules that mimic molecules of the producing cells. There are multiple methods for exosome isolation and analysis, although not standardized, and cancer exosomes from biological fluids are especially difficult to study. Exosomes' cargo proteins, RNA, and DNA participate in the communication between cells, favoring lung cancer development by delivering signals for growth, metastasis, epithelial mesenchymal transition, angiogenesis, immunosuppression and even drug resistance. Exosome analysis can be useful as a type of liquid biopsy in the diagnosis, prognosis and follow-up of lung cancer. In this review, we will discuss recent advances in the role of exosomes in lung cancer and their utility as liquid biopsy, with special attention to isolating methods.
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41
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Garrido P, Hladun R, de Álava E, Álvarez R, Bautista F, López-Ríos F, Colomer R, Rojo F. Multidisciplinary consensus on optimising the detection of NTRK gene alterations in tumours. Clin Transl Oncol 2021; 23:1529-1541. [PMID: 33620682 PMCID: PMC8238709 DOI: 10.1007/s12094-021-02558-0] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2020] [Accepted: 01/24/2021] [Indexed: 12/21/2022]
Abstract
The recent identification of rearrangements of neurotrophic tyrosine receptor kinase (NTRK) genes and the development of specific fusion protein inhibitors, such as larotrectinib and entrectinib, have revolutionised the diagnostic and clinical management of patients presenting with tumours with these alterations. Tumours that harbour NTRK fusions are found in both adults and children; and they are either rare tumours with common NTRK fusions that may be diagnostic, or more prevalent tumours with rare NTRK fusions. To assess currently available evidence on this matter, three key Spanish medical societies (the Spanish Society of Medical Oncology (SEOM), the Spanish Society of Pathological Anatomy (SEAP), and the Spanish Society of Paediatric Haematology and Oncology (SEHOP) have brought together a group of experts to develop a consensus document that includes guidelines on the diagnostic, clinical, and therapeutic aspects of NTRK-fusion tumours. This document also discusses the challenges related to the routine detection of these genetic alterations in a mostly public Health Care System.
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Affiliation(s)
- P. Garrido
- Sociedad Española de Oncología Médica (SEOM), Departamento de Oncología Médica, Hospital Universitario Ramón y Cajal, Universidad de Alcalá, IRYCIS, CIBERONC, Madrid, Spain
| | - R. Hladun
- Sociedad Española de Hematología y Oncologías Pediátricas (SEHOP), Departamento de Oncología, Hematología y Trasplante de Progenitores Hematopoyéticos Pediátricos, Hospital Universitario Vall d’Hebron, Barcelona, Spain
| | - E. de Álava
- Sociedad Española de Anatomía Patológica (SEAP), Departamento de Citología e Histología Normal y Patológica, Hospital Universitario Virgen del Rocío, Instituto de Biomedicina de Sevilla (IBiS), CSIC, Facultad de Medicina, Universidad de Sevilla, CIBERONC, Sevilla, Spain
| | - R. Álvarez
- Sociedad Española de Oncología Médica (SEOM), Departamento de Oncología Médica, Hospital Universitario Gregorio Marañón. Instituto Investigación Sanitaria Gregorio Marañon (IISGM), Madrid, Spain
| | - F. Bautista
- Sociedad Española de Hematología y Oncologías Pediátricas (SEHOP), Oncología Pediátrica, Departamento de Hematología y Trasplante de Células Madre Hematopoyéticas, Hospital Universitario Infantil Niño Jesús, Madrid, Spain
| | - F. López-Ríos
- Sociedad Española de Anatomía Patológica (SEAP), Departamento de Patología, Laboratorio de Dianas Terapéuticas, Hospital Universitario HM Sanchinarro, CIBERONC, Madrid, Spain
| | - R. Colomer
- Sociedad Española de Oncología Médica (SEOM), Departamento de Oncología Médica, Hospital Universitario La Princesa, Universidad Autónoma de Madrid, Cátedra UAM-Fundación Instituto Roche de Medicina Personalizada de Precisión, Madrid, Spain
| | - F. Rojo
- Sociedad Española de Anatomía Patológica (SEAP), Departamento de Patología, IIS-Fundación Universitaria Jiménez Díaz, CIBERONC, Madrid, Spain
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Nadal E, Bautista D, Cabezón-Gutiérrez L, Ortega AL, Torres H, Carcedo D, Ruiz de Alda L, Garcia JF, Vieitez P, Rojo F. Clinical and economic impact of current ALK rearrangement testing in Spain compared with a hypothetical no-testing scenario. BMC Cancer 2021; 21:689. [PMID: 34112097 PMCID: PMC8194132 DOI: 10.1186/s12885-021-08407-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2021] [Accepted: 05/25/2021] [Indexed: 11/15/2022] Open
Abstract
BACKGROUND Currently biomarkers play an essential role in diagnosis, treatment, and management of cancer. In non-small cell lung cancer (NSCLC) determination of biomarkers such as ALK, EGFR, ROS1 or PD-L1 is mandatory for an adequate treatment decision. The aim of this study is to determine the clinical and economic impact of current anaplastic lymphoma kinase testing scenario in Spain. METHODS A joint model, composed by decision-tree and Markov models, was developed to estimate the long-term health outcomes and costs of NSCLC patients, by comparing the current testing scenario for ALK in Spain vs a hypothetical no-testing. The current distribution of testing strategies for ALK determination and their sensitivity and specificity data were obtained from the literature. Treatment allocation based on the molecular testing result were defined by a panel of Spanish experts. To assess long-term effects of each treatment, 3-states Markov models were developed, where progression-free survival and overall survival curves were extrapolated using exponential models. Medical direct costs (expressed in €, 2019) were included. A lifetime horizon was used and a discount rate of 3% was applied for both costs and health effects. Several sensitivity analyses, both deterministic and probabilistic, were performed in order test the robustness of the analysis. RESULTS We estimated a target population of 7628 NSCLC patients, including those with non-squamous histology and those with squamous carcinomas who were never smokers. Over the lifetime horizon, the current ALK testing scenario produced additional 5060 and 3906 life-years and quality-adjusted life-years (QALY), respectively, compared with the no-testing scenario. Total direct costs were increased up to € 51,319,053 for testing scenario. The incremental cost-effectiveness ratio was 10,142 €/QALY. The sensitivity analyses carried out confirmed the robustness of the base-case results, being the treatment allocation and the test accuracy (sensitivity and specificity data) the key drivers of the model. CONCLUSIONS ALK testing in advanced NSCLC patients, non-squamous and never-smoker squamous, provides more than 3000 QALYs in Spain over a lifetime horizon. Comparing this gain in health outcomes with the incremental costs, the resulting incremental cost-effectiveness ratio reinforces that testing non-squamous and never-smoker squamous NSCLC is a cost-effective strategy in Spain.
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Affiliation(s)
- Ernest Nadal
- Catalan Institute of Oncology, Hospital Duran i Reynals, IDIBELL, L'Hospitalet de Llobregat, Spain
| | | | | | | | - Héctor Torres
- Hospital Universitario Central de Asturias, Oviedo, Spain
| | | | | | | | | | - Federico Rojo
- Hospital Universitario Fundacion Jimenez Diaz - CIBERONC, Madrid, Spain
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Yang Y, Lu J, Ma Y, Xi C, Kang J, Zhang Q, Jia X, Liu K, Du S, Kocher F, Seeber A, Gridelli C, Provencio M, Seki N, Tomita Y, Zhang X. Evaluation of the reporting quality of clinical practice guidelines on lung cancer using the RIGHT checklist. Transl Lung Cancer Res 2021; 10:2588-2602. [PMID: 34295664 PMCID: PMC8264321 DOI: 10.21037/tlcr-21-405] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2021] [Accepted: 06/11/2021] [Indexed: 01/09/2023]
Abstract
BACKGROUND In recent years, the number of clinical practice guidelines (CPGs) for lung cancer has increased, but the quality of these guidelines has not been systematically assessed so far. Our aim was to assess the reporting quality of CPGs on lung cancer published since 2018 using the International Reporting Items for Practice Guidelines in Health Care (RIGHT) instrument. METHODS We systematically searched the major electronic literature databases, guideline databases and medical society websites from January 2018 to November 2020 to identify all CPGs for small cell and non-small cell lung cancer (NSCLC). The search and extraction were completed using standardized forms. The quality of included guidelines was evaluated using the RIGHT statement. We present the results descriptively, including a stratification by selected determinants. RESULTS A total of 49 CPGs were included. The mean proportion across the guidelines of the 22 items of the RIGHT checklist that were appropriately reported was 57.9%. The items most common to be poorly reported were quality assurance (item 17) and description of the role of funders (item 18b), both of which were reported in only one guideline. The proportions of items within each of the seven domains of the RIGHT checklist that were correctly reported were Basic information 75.9%; background 83.2%; evidence 44.5%; recommendations 55.4%; review and quality assurance 12.2%; funding and declaration and management of interests 42.9%; and other information 38.1%. The reporting quality of guidelines did not differ between publication years. CPGs published in journals with impact factor >30 tended to be best reported. CONCLUSIONS Our results revealed that reporting in CPGs for lung cancer is suboptimal. Particularly the declaration of funding and quality assurance are poorly reported in recent CPGs on lung cancer.
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Affiliation(s)
- Yongjie Yang
- Department of Pharmacy, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China;,Henan Key Laboratory of Precision Clinical Pharmacy, Zhengzhou University, Zhengzhou, China
| | - Jingli Lu
- Department of Pharmacy, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China;,Henan Key Laboratory of Precision Clinical Pharmacy, Zhengzhou University, Zhengzhou, China
| | - Yanfang Ma
- School of Chinese Medicine of Hong Kong Baptist University, Hong Kong, China
| | - Chen Xi
- Department of Pharmacy, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China;,Henan Key Laboratory of Precision Clinical Pharmacy, Zhengzhou University, Zhengzhou, China
| | - Jian Kang
- Department of Pharmacy, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China;,Henan Key Laboratory of Precision Clinical Pharmacy, Zhengzhou University, Zhengzhou, China
| | - Qiwen Zhang
- Department of Pharmacy, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China;,Henan Key Laboratory of Precision Clinical Pharmacy, Zhengzhou University, Zhengzhou, China
| | - Xuedong Jia
- Department of Pharmacy, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China;,Henan Key Laboratory of Precision Clinical Pharmacy, Zhengzhou University, Zhengzhou, China
| | - Kefeng Liu
- Department of Pharmacy, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China;,Henan Key Laboratory of Precision Clinical Pharmacy, Zhengzhou University, Zhengzhou, China
| | - Shuzhang Du
- Department of Pharmacy, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China;,Henan Key Laboratory of Precision Clinical Pharmacy, Zhengzhou University, Zhengzhou, China
| | - Florian Kocher
- Department of Hematology and Oncology, Comprehensive Cancer Center Innsbruck, Medical University Innsbruck, Innsbruck, Austria
| | - Andreas Seeber
- Department of Hematology and Oncology, Comprehensive Cancer Center Innsbruck, Medical University Innsbruck, Innsbruck, Austria
| | - Cesare Gridelli
- A.O.R.N. San Giuseppe Moscati, Contrada Amoretta, Avellino, AV, Italy
| | - Mariano Provencio
- Medical Oncology Department, Hospital Universitario Puerta de Hierro Majadahonda, Madrid, Spain
| | - Nobuhiko Seki
- Division of Medical Oncology, Department of Internal Medicine, Teikyo University School of Medicine, Tokyo, Japan
| | - Yusuke Tomita
- Department of Respiratory Medicine, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
| | - Xiaojian Zhang
- Department of Pharmacy, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China;,Henan Key Laboratory of Precision Clinical Pharmacy, Zhengzhou University, Zhengzhou, China
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Conde E, Hernandez S, Benito A, Caminoa A, Garrido P, Lopez-Rios F. Screening for ROS1 fusions in patients with advanced non-small cell lung carcinomas using the VENTANA ROS1 (SP384) Rabbit Monoclonal Primary Antibody. Expert Rev Mol Diagn 2021; 21:437-444. [PMID: 33899645 DOI: 10.1080/14737159.2021.1919512] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
Introduction: The development of several ROS1 inhibitors means that the importance of accurately identifying ROS1-positive lung cancer patients has never been greater. Therefore, it is crucial that ROS1 testing assays become more standardized.Areas covered: Based on primary literature, combined with personal diagnostic and research experience, this review provide a pragmatic update on the use of the recently released VENTANA ROS1 (SP384) Rabbit Monoclonal Primary Antibody.Expert opinion: This assay provides high sensitivity, so it is an excellent analytical option when screening for ROS1 fusions in patients with advanced non-small cell lung carcinomas.
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Affiliation(s)
- Esther Conde
- Pathology and Laboratory of Therapeutic Targets, Hospital Universitario HM Sanchinarro, HM Hospitales, CIBERONC, Madrid, Spain
| | - Susana Hernandez
- Pathology and Laboratory of Therapeutic Targets, Hospital Universitario HM Sanchinarro, HM Hospitales, Madrid, Spain
| | - Amparo Benito
- Pathology, Ramon Y Cajal University Hospital, Madrid, Spain
| | | | - Pilar Garrido
- Medical Oncology, Ramon Y Cajal University Hospital, CIBERONC, Madrid, Spain
| | - Fernando Lopez-Rios
- Pathology and Laboratory of Therapeutic Targets, Hospital Universitario HM Sanchinarro, HM Hospitales, CIBERONC, Madrid, Spain
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Martin-Deleon R, Teixido C, Lucena CM, Martinez D, Fontana A, Reyes R, García M, Viñolas N, Vollmer I, Sanchez M, Jares P, Pérez FM, Vega N, Marin E, Marrades RM, Agustí C, Reguart N. EBUS-TBNA Cytological Samples for Comprehensive Molecular Testing in Non-Small Cell Lung Cancer. Cancers (Basel) 2021; 13:2084. [PMID: 33923116 PMCID: PMC8123471 DOI: 10.3390/cancers13092084] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2021] [Revised: 04/12/2021] [Accepted: 04/19/2021] [Indexed: 02/07/2023] Open
Abstract
Clinical guidelines promote the identification of several targetable biomarkers to drive treatment decisions in advanced non-small cell lung cancer (NSCLC), but half of all patients do not have a viable biopsy. Specimens from endobronchial-ultrasound transbronchial needle aspiration (EBUS-TBNA) are an alternative source of material for the initial diagnosis of NSCLC, however their usefulness for a complete molecular characterization remains controversial. EBUS-TBNA samples were prospectively tested for several biomarkers by next-generation sequencing (NGS), nCounter, and immunohistochemistry (PD-L1). The primary objectives were to assess the sensitivity of EBUS-TBNA samples for a comprehensive molecular characterization and to compare its performance to the reference standard of biopsy samples. Seventy-two EBUS-TBNA procedures were performed, and 42 NSCLC patients were diagnosed. Among all cytological samples, 92.9% were successfully genotyped by NGS, 95.2% by nCounter, and 100% by immunohistochemistry. There were 29 paired biopsy samples; 79.3% samples had enough tumor material for genomic genotyping, and 96.6% for PD-L1 immunohistochemistry. A good concordance was found between both sources of material: 88.9% for PD-L1, 100% for NGS and nCounter. EBUS-TBNA is a feasible alternative source of material for NSCLC genotyping and allows the identification of patient candidates for personalized therapies with high concordance when compared with biopsy.
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Affiliation(s)
- Roberto Martin-Deleon
- Department of Respiratory Medicine, Thoracic Oncology Unit, Hospital Clínic of Barcelona, 08036 Barcelona, Spain; (R.M.-D.); (C.M.L.); (A.F.); (R.M.M.); (C.A.)
| | - Cristina Teixido
- Translational Genomic and Targeted Therapeutics in Solid Tumors, August Pi i Sunyer Biomedical Research Institute (IDIBAPS), 08036 Barcelona, Spain; (C.T.); (R.R.); (N.V.); (E.M.)
- Department of Pathology, Thoracic Oncology Unit, Hospital Clínic of Barcelona, 08036 Barcelona, Spain; (D.M.); (M.G.); (P.J.); (F.M.P.); (N.V.)
| | - Carmen Mª Lucena
- Department of Respiratory Medicine, Thoracic Oncology Unit, Hospital Clínic of Barcelona, 08036 Barcelona, Spain; (R.M.-D.); (C.M.L.); (A.F.); (R.M.M.); (C.A.)
| | - Daniel Martinez
- Department of Pathology, Thoracic Oncology Unit, Hospital Clínic of Barcelona, 08036 Barcelona, Spain; (D.M.); (M.G.); (P.J.); (F.M.P.); (N.V.)
| | - Ainhoa Fontana
- Department of Respiratory Medicine, Thoracic Oncology Unit, Hospital Clínic of Barcelona, 08036 Barcelona, Spain; (R.M.-D.); (C.M.L.); (A.F.); (R.M.M.); (C.A.)
| | - Roxana Reyes
- Translational Genomic and Targeted Therapeutics in Solid Tumors, August Pi i Sunyer Biomedical Research Institute (IDIBAPS), 08036 Barcelona, Spain; (C.T.); (R.R.); (N.V.); (E.M.)
- Department of Medical Oncology, Thoracic Oncology Unit, Hospital Clínic of Barcelona, 08036 Barcelona, Spain
| | - Mireia García
- Department of Pathology, Thoracic Oncology Unit, Hospital Clínic of Barcelona, 08036 Barcelona, Spain; (D.M.); (M.G.); (P.J.); (F.M.P.); (N.V.)
| | - Nuria Viñolas
- Translational Genomic and Targeted Therapeutics in Solid Tumors, August Pi i Sunyer Biomedical Research Institute (IDIBAPS), 08036 Barcelona, Spain; (C.T.); (R.R.); (N.V.); (E.M.)
- Department of Medical Oncology, Thoracic Oncology Unit, Hospital Clínic of Barcelona, 08036 Barcelona, Spain
| | - Ivan Vollmer
- Department of Radiology, Thoracic Oncology Unit, Hospital Clínic of Barcelona, 08036 Barcelona, Spain; (I.V.); (M.S.)
| | - Marcelo Sanchez
- Department of Radiology, Thoracic Oncology Unit, Hospital Clínic of Barcelona, 08036 Barcelona, Spain; (I.V.); (M.S.)
| | - Pedro Jares
- Department of Pathology, Thoracic Oncology Unit, Hospital Clínic of Barcelona, 08036 Barcelona, Spain; (D.M.); (M.G.); (P.J.); (F.M.P.); (N.V.)
| | - Francisco Manuel Pérez
- Department of Pathology, Thoracic Oncology Unit, Hospital Clínic of Barcelona, 08036 Barcelona, Spain; (D.M.); (M.G.); (P.J.); (F.M.P.); (N.V.)
| | - Naiara Vega
- Department of Pathology, Thoracic Oncology Unit, Hospital Clínic of Barcelona, 08036 Barcelona, Spain; (D.M.); (M.G.); (P.J.); (F.M.P.); (N.V.)
| | - Elba Marin
- Translational Genomic and Targeted Therapeutics in Solid Tumors, August Pi i Sunyer Biomedical Research Institute (IDIBAPS), 08036 Barcelona, Spain; (C.T.); (R.R.); (N.V.); (E.M.)
| | - Ramón Mª Marrades
- Department of Respiratory Medicine, Thoracic Oncology Unit, Hospital Clínic of Barcelona, 08036 Barcelona, Spain; (R.M.-D.); (C.M.L.); (A.F.); (R.M.M.); (C.A.)
| | - Carlos Agustí
- Department of Respiratory Medicine, Thoracic Oncology Unit, Hospital Clínic of Barcelona, 08036 Barcelona, Spain; (R.M.-D.); (C.M.L.); (A.F.); (R.M.M.); (C.A.)
| | - Noemi Reguart
- Translational Genomic and Targeted Therapeutics in Solid Tumors, August Pi i Sunyer Biomedical Research Institute (IDIBAPS), 08036 Barcelona, Spain; (C.T.); (R.R.); (N.V.); (E.M.)
- Department of Medical Oncology, Thoracic Oncology Unit, Hospital Clínic of Barcelona, 08036 Barcelona, Spain
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Peg V, López-García MÁ, Comerma L, Peiró G, García-Caballero T, López ÁC, Suárez-Gauthier A, Ruiz I, Rojo F. PD-L1 testing based on the SP142 antibody in metastatic triple-negative breast cancer: summary of an expert round-table discussion. Future Oncol 2021; 17:1209-1218. [DOI: 10.2217/fon-2020-1100] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022] Open
Abstract
Triple-negative breast cancer (TNBC) is more aggressive than other breast cancer subtypes. TNBC is characterized by increased expression of Programmed Death-ligand 1 (PD-L1), a signal used by many tumors to escape the immune response. Expression of PD-L1 is a positive predictor of response to immunotherapy; therefore, it should be investigated in TNBC in order to select patients who may benefit from anti-PD-L1 therapies. While many PD-L1 assays are available, only the VENTANA platform with the anti-PD-L1 (SP142) antibody is licensed as a companion diagnostic device for selecting patients with metastatic/advanced TNBC who are candidates for treatment with atezolizumab. In this article, we provide a summary of an expert round-table discussion about PD-L1 testing, using the SP142 antibody in metastatic TNBC.
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Affiliation(s)
- Vicente Peg
- Departamento de Anatomia Patològica, Vall d’Hebron Hospital Universitari, Barcelona Hospital Campus, Barcelona, Spain; Grupo de Patología Molecular, Vall d'Hebron Institut de Recerca (VHIR), Barcelona, Spain; Centro de Investigación Biomédica en Red en Cáncer (CIBERONC), Instituto de Salud Carlos III, Madrid, Spain; Universitat Autònoma de Barcelona, Bellaterra, Spain
| | - María Ángeles López-García
- Servicio de Anatomía Patológica, Hospital Universitario Virgen del Rocío, Sevilla (Spain); Centro de Investigacion Biomédica en Red en Cáncer (CIBERONC), Instituto de Salud Carlos III, Madrid, Spain
| | - Laura Comerma
- Departamento de Anatomía Patológica, Hospital del Mar, Barcelona, Spain
| | - Gloria Peiró
- Departamento de Patología, Hospital General Universitario de Alicante, Instituto de Investigación Sanitaria y Biomédica de Alicante (ISABIAL), Alicante, Spain
| | - Tomás García-Caballero
- Departamento de Ciencias Morfológicas, Facultad de Medicina y Odontología, Universidad de Santiago, Santiago de Compostela, Spain
| | - Ángel Concha López
- Servicio de Anatomía Patológica, Complejo Hospitalario Universitario A Coruña, Biobanco INIBIC, A Coruña, Spain
| | - Ana Suárez-Gauthier
- Departamento de Anatomía Patológica, Laboratorio de Dianas Terapéuticas, Hospital Universitario HM Sanchinarro, Madrid, Spain
| | - Irune Ruiz
- Servicio de Patología, Hospital Universitario Donostia, Donostia, Spain
| | - Federico Rojo
- Servicio de Anatomía Patológica, IIS-Fundación Jiménez Díaz-CIBERONC, Madrid, Spain
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Challenges of ICC and FISH in the Field of Targeted Therapies from Cell Block to Smears. JOURNAL OF MOLECULAR PATHOLOGY 2021. [DOI: 10.3390/jmp2020006] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
Abstract
In the era of personalized medicine, there is an increasing demand for comprehensive and complex diagnosis using minimally invasive techniques. Nowadays, it is mandatory to integrate biomarkers in the diagnostic process, as well as in the treatment and clinical management of many cancer patients. Patients with non-small cell lung cancer (NSCLC), for instance, are frequently diagnosed in advanced stages, at a point when only cytological material or small biopsies can be obtained. This pathology constitutes an interesting challenge for the testing of biomarkers in cytology. Furthermore, there is a growing development of imaging techniques that guide non-invasive approaches to obtain small biopsies or cytological samples. This has allowed fine needle aspiration cytology and fine needle aspiration biopsy (FNAC, FNAB) to become front-line procedures in the management of patients with NSCLC. It is well known that the list of biomarkers to be tested in these patients continues to increase. Nevertheless, there are several of essential biomarkers that should always be analyzed in all patients with NSCLC, not only in non-squamous but also in some squamous carcinomas (SqCC). Some of them, such as PDL1, are tested by immunocytochemistry (ICC), while others, mainly ALK and ROS1, can be tested by ICC and confirmed using other techniques such a Fluorescence In Situ Hybridization (FISH). Other biomarkers, namely EGFR and BRAF mutations, are currently evaluated by polymerase chain reaction (PCR)-based techniques including Next-Generation Sequencing (NGS). In this review, we will address the particularities and challenges that ICC and FISH pose in different types of cytological samples from an eminently practical point of view.
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The evolving landscape of biomarker testing for non-small cell lung cancer in Europe. Lung Cancer 2021; 154:161-175. [PMID: 33690091 DOI: 10.1016/j.lungcan.2021.02.026] [Citation(s) in RCA: 131] [Impact Index Per Article: 32.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2020] [Revised: 02/18/2021] [Accepted: 02/21/2021] [Indexed: 12/31/2022]
Abstract
The discovery of oncogenic driver mutations rendering non-small cell lung cancer (NSCLC) targetable by small-molecule inhibitors, and the development of immunotherapies, have revolutionised NSCLC treatment. Today, instead of non-selective chemotherapies, all patients with advanced NSCLC eligible for treatment (and increasing numbers with earlier, less extensive disease) require fast and comprehensive screening of biomarkers for first-line patient selection for targeted therapy, chemotherapy, or immunotherapy (with or without chemotherapy). To avoid unnecessary re-biopsies, biomarker screening before first-line treatment should also include markers that are actionable from second-line onwards; PD-L1 expression testing is also mandatory before initiating treatment. Population differences exist in the frequency of oncogenic driver mutations: EGFR mutations are more frequent in Asia than Europe, whereas the converse is true for KRAS mutations. In addition to approved first-line therapies, a number of emerging therapies are being investigated in clinical trials. Guidelines for biomarker testing vary by country, with the number of actionable targets and the requirement for extensive molecular screening strategies expected to increase. To meet diagnostic demands, rapid screening technologies for single-driver mutations have been implemented. Improvements in DNA- and RNA-based next-generation sequencing technologies enable analysis of a group of genes in one assay; however, turnaround times remain relatively long. Consequently, rapid screening technologies are being implemented alongside next-generation sequencing. Further challenges in the evolving landscape of biomarker testing in NSCLC are actionable primary and secondary resistance mechanisms to targeted therapies. Therefore, comprehensive testing on re-biopsies, collected at the time of disease progression, in combination with testing of circulating tumour DNA may provide important information to guide second- or third-line therapies. Furthermore, longitudinal biomarker testing can provide insights into tumour evolution and heterogeneity during the course of the disease. We summarise best practice strategies for Europe in the changing landscape of biomarker testing at diagnosis and during treatment.
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Concurrent EGFR mutation and ALK rearrangement in stage IV lung adenocarcinoma-a case report and a literature review. Porto Biomed J 2021; 6:e124. [PMID: 33884320 PMCID: PMC8055486 DOI: 10.1097/j.pbj.0000000000000124] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2020] [Accepted: 11/26/2020] [Indexed: 12/24/2022] Open
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Imyanitov EN, Iyevleva AG, Levchenko EV. Molecular testing and targeted therapy for non-small cell lung cancer: Current status and perspectives. Crit Rev Oncol Hematol 2020; 157:103194. [PMID: 33316418 DOI: 10.1016/j.critrevonc.2020.103194] [Citation(s) in RCA: 292] [Impact Index Per Article: 58.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2020] [Revised: 11/14/2020] [Accepted: 11/17/2020] [Indexed: 02/07/2023] Open
Abstract
Molecular testing has become a mandatory component of the non-small cell lung cancer (NSCLC) management. The detection of EGFR, BRAF and MET mutations as well as the analysis of ALK, ROS1, RET and NTRK translocations have already been incorporated in the NSCLC diagnostic standards, and the inhibitors of these kinases are in routine clinical use. There are emerging biomarkers, e.g., KRAS G12C substitutions and HER2 activating alterations, which are likely to enter NSCLC guidelines upon the approval of the corresponding drugs. In addition to genetic examination, NSCLCs are usually subjected to the analysis of PD-L1 protein expression in order to direct the use of immune checkpoint inhibitors. Comprehensive NSCLC testing for multiple predictive markers requires the analysis of distinct biological molecules (DNA, RNA, proteins) and, therefore, the involvement of different analytical platforms (PCR, DNA sequencing, immunohistochemistry, FISH). There are ongoing efforts aimed at the integration of multiple NSCLC molecular assays into a single diagnostic pipeline.
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Affiliation(s)
- Evgeny N Imyanitov
- Department of Tumor Growth Biology, N.N. Petrov Institute of Oncology, St.-Petersburg, 197758, Russia; Department of Medical Genetics, St.-Petersburg Pediatric Medical University, St.-Petersburg, 194100, Russia; Department of Oncology, I.I. Mechnikov North-Western Medical University, St.-Petersburg, 195067, Russia.
| | - Aglaya G Iyevleva
- Department of Tumor Growth Biology, N.N. Petrov Institute of Oncology, St.-Petersburg, 197758, Russia; Department of Medical Genetics, St.-Petersburg Pediatric Medical University, St.-Petersburg, 194100, Russia
| | - Evgeny V Levchenko
- Department of Oncology, I.I. Mechnikov North-Western Medical University, St.-Petersburg, 195067, Russia; Department of Thoracic Oncology, N.N. Petrov Institute of Oncology, St.-Petersburg, 197758, Russia
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