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Translational Lung Cancer Research

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https://www.readbyqxmd.com/read/30505716/tumor-mutational-burden-in-non-small-cell-lung-cancer-the-pathologist-s-point-of-view
#1
REVIEW
Frédérique Penault-Llorca, Nina Radosevic-Robin
In non-small cell lung cancer (NSCLC), the pathologist has contributed to the development of personalized medicine from the determination of the right histological type to EGFR and ALK/ROS1 molecular screening for targeted therapies. With the development of immunotherapies, pathologists intervene forefront with programmed death-ligand 1 (PD-L1) immunohistochemical testing, companion test for pembrolizumab monotherapy, first line and complementary test to the other programmed cell death-1 (PD-1) PD-L1 inhibitors...
December 2018: Translational Lung Cancer Research
https://www.readbyqxmd.com/read/30505715/implementing-tumor-mutational-burden-tmb-analysis-in-routine-diagnostics-a-primer-for-molecular-pathologists-and-clinicians
#2
REVIEW
Michael Allgäuer, Jan Budczies, Petros Christopoulos, Volker Endris, Amelie Lier, Eugen Rempel, Anna-Lena Volckmar, Martina Kirchner, Moritz von Winterfeld, Jonas Leichsenring, Olaf Neumann, Stefan Fröhling, Roland Penzel, Michael Thomas, Peter Schirmacher, Albrecht Stenzinger
Tumor mutational burden (TMB) is a new biomarker for prediction of response to PD-(L)1 treatment. Comprehensive sequencing approaches (i.e., whole exome and whole genome sequencing) are ideally suited to measure TMB directly. However, as their applicability in routine diagnostics is currently limited by high costs, long turnaround times and poor availability of fresh tissue, targeted next-generation sequencing (NGS) of formalin-fixed and paraffin-embedded (FFPE) samples appears to be a more feasible and straight-forward approach for TMB approximation, which can be seamlessly integrated in already existing diagnostic workflows and pipelines...
December 2018: Translational Lung Cancer Research
https://www.readbyqxmd.com/read/30505714/challenges-and-unanswered-questions-for-the-next-decade-of-immune-oncology-research-in-nsclc
#3
REVIEW
Niki Karachaliou, Manuel Fernandez-Bruno, Jillian Wilhelmina Paulina Bracht, Rafael Rosell
Over the last 20 years there have been great advances in the treatment of lung cancer. Immune checkpoint blockade together with targeted therapies have provided oncologists with the means to improve survival of non-small cell lung cancer (NSCLC) and patients with a better quality of life and therapies with manageable toxicity. Maybe in a short period of time the possibility of a cure in metastatic NSCLC will be raised. Therefore, continued research into new drugs, biomarkers and especially combination therapies is necessary in order to expand the clinical benefit of the current treatments to a broader population of NSCLC patients...
December 2018: Translational Lung Cancer Research
https://www.readbyqxmd.com/read/30505713/predictive-markers-for-anti-pd-1-pd-l1-therapy-in-non-small-cell-lung-cancer-where-are-we
#4
REVIEW
Matthew Evans, Brendan O'Sullivan, Matthew Smith, Philippe Taniere
The selection of patients for immunotherapy remains challenging given the lack of highly specific and highly sensitive biomarkers. Nevertheless, it is essential that testing laboratories are able to fulfil licencing criteria by providing the tests which have been validated as providing useful predictive information. Programmed cell death protein 1 (PD-1) expression assessment is now established in routine practice, although the situation regarding the selection of a particular assay remains complex, and testing protocols are likely to change in future...
December 2018: Translational Lung Cancer Research
https://www.readbyqxmd.com/read/30505712/approach-to-evaluating-tumor-mutational-burden-in-routine-clinical-practice
#5
REVIEW
John Truesdell, Vincent A Miller, David Fabrizio
Immune checkpoint inhibition with monoclonal antibodies has emerged as a promising therapeutic approach but in most tumor types responses are unpredictable and observed in a minority of treated patients. Positive and negative predictive biomarkers for efficacy of these costly drugs are desperately needed. Immunohistochemistry (IHC) for programmed death ligand (PD-L1) expression in tumor and inflammatory infiltrate has emerged as one predictive biomarker of some value. However, multiple confounders including those inherent to any IHC and the unique complexities of the biology of the immune response have limited its utility...
December 2018: Translational Lung Cancer Research
https://www.readbyqxmd.com/read/30505711/measuring-tumor-mutation-burden-in-non-small-cell-lung-cancer-tissue-versus-liquid-biopsy
#6
REVIEW
Francesca Fenizia, Raffaella Pasquale, Cristin Roma, Francesca Bergantino, Alessia Iannaccone, Nicola Normanno
The introduction in the clinic of immune checkpoint inhibitors (IOs) has represented an important improvement for the treatment of patients with advanced non-small cell lung cancer (NSCLC). These drugs have shown a higher activity as compared with chemotherapy in both first- and second-line of treatment, with some patients experiencing a long-lasting response. More recently, combinations of IOs have entered clinical trials in different tumor types including NSCLC. Nevertheless, IOs are active only in a subgroup of patients and biomarkers for appropriate patients' selection are urgently needed to offer the patients an effective therapy, and also to manage the costs...
December 2018: Translational Lung Cancer Research
https://www.readbyqxmd.com/read/30505710/methods-of-measurement-for-tumor-mutational-burden-in-tumor-tissue
#7
REVIEW
Bárbara Meléndez, Claude Van Campenhout, Sandrine Rorive, Myriam Remmelink, Isabelle Salmon, Nicky D'Haene
Immunotherapies based on immune checkpoint inhibitors are emerging as an innovative treatment for different types of advanced cancers. While the utility of immune checkpoint inhibitors has been clearly demonstrated, the response rate is highly variable across individuals. Due to the cost and toxicity of these immunotherapies, a critical challenge in this field is the identification of predictive biomarkers to discriminate which patients may respond to immunotherapy. Recently, a high tumor mutational burden (TMB) has been identified as a genetic signature that is associated with a favorable outcome for immune checkpoint inhibitor therapy...
December 2018: Translational Lung Cancer Research
https://www.readbyqxmd.com/read/30505709/clinical-utility-of-tumor-mutational-burden-in-patients-with-non-small-cell-lung-cancer-treated-with-immunotherapy
#8
REVIEW
Lizza E Hendriks, Etienne Rouleau, Benjamin Besse
Anti-programmed death (ligand)-1 [anti-PD-(L)1] therapies such as pembrolizumab, nivolumab or atezolizumab have become standard of care for non-small cell lung cancer (NSCLC) patients either in first line or beyond. PD-L1 expression level allows enriching the treated population with responders, but it is still not an optimal biomarker. Even in patients with PD-L1 tumor proportion score (TPS) levels of ≥50% treated with first line pembrolizumab overall response rate (ORR) is only 44.8% and overall survival at one year is 70%...
December 2018: Translational Lung Cancer Research
https://www.readbyqxmd.com/read/30505708/the-clinical-utility-of-tumor-mutational-burden-in-non-small-cell-lung-cancer
#9
REVIEW
Laurent Greillier, Pascale Tomasini, Fabrice Barlesi
Despite advances made during the last two decades, lung cancer remains the leading cause of cancer-related death worldwide. Recently, immune checkpoint inhibitors (ICIs) became available for the treatment of advanced non-small cell lung cancer (NSCLC) patients. Although ICIs showed a survival advantage in comparison with chemotherapy in the second and first-line setting, overall response rate is only around 20% and a large proportion of patients will undergo disease progression within the first weeks of treatment...
December 2018: Translational Lung Cancer Research
https://www.readbyqxmd.com/read/30505707/tumor-mutational-burden-assessment-as-a-predictive-biomarker-for-immunotherapy-in-lung-cancer-patients-getting-ready-for-prime-time-or-not
#10
REVIEW
Simon Heeke, Paul Hofman
The emergence of immunotherapy as a first- or second-line of treatment has revolutionized the therapeutic management of lung cancer patients. However, not all lung cancer patients receive the same benefit from this treatment, leading to limitations in the number of patients who can receive anti-PD-1/PD-L1 checkpoint inhibitors because some secondary toxicity has been associated with immunotherapy, and because some patients would benefit more from chemotherapy. In this context, the selection of patients is currently based on PD-L1 immunohistochemistry (IHC), specifically on the percentage of PD-L1 positive tumor cells...
December 2018: Translational Lung Cancer Research
https://www.readbyqxmd.com/read/30505706/a-scalable-solution-for-tumor-mutational-burden-from-formalin-fixed-paraffin-embedded-samples-using-the-oncomine-tumor-mutation-load-assay
#11
Ruchi Chaudhary, Luca Quagliata, Jermann Philip Martin, Ilaria Alborelli, Dinesh Cyanam, Vinay Mittal, Warren Tom, Janice Au-Young, Seth Sadis, Fiona Hyland
Background: Tumor mutational burden (TMB) is an increasingly important biomarker for immune checkpoint inhibitors. Recent publications have described strong association between high TMB and objective response to mono- and combination immunotherapies in several cancer types. Existing methods to estimate TMB require large amount of input DNA, which may not always be available. Methods: In this study, we develop a method to estimate TMB using the Oncomine Tumor Mutation Load (TML) Assay with 20 ng of DNA, and we characterize the performance of this method on various formalin-fixed, paraffin-embedded (FFPE) research samples of several cancer types...
December 2018: Translational Lung Cancer Research
https://www.readbyqxmd.com/read/30505705/spotlight-on-tumor-mutational-burden-in-patients-with-non-small-cell-lung-carcinoma
#12
Marius Ilie, Paul Hofman
No abstract text is available yet for this article.
December 2018: Translational Lung Cancer Research
https://www.readbyqxmd.com/read/30450300/-translational-lung-cancer-research-the-7-th-ame-journal-indexed-in-scie
#13
(no author information available yet)
No abstract text is available yet for this article.
October 2018: Translational Lung Cancer Research
https://www.readbyqxmd.com/read/30450299/update-on-the-management-of-malignant-peritoneal-mesothelioma
#14
REVIEW
Paul H Sugarbaker
Malignant peritoneal mesothelioma (MPM) is a rare disease whose natural history is confined to the peritoneal space. Systemic chemotherapy has little impact on survival of patients with MPM. A surgical procedure with a goal of resection of all visible evidence of disease, called cytoreductive surgery (CRS) has been utilized in MPM patients. Also, regional chemotherapy with hyperthermic intraperitoneal chemotherapy (HIPEC) and normothermic intraperitoneal chemotherapy long-term (NIPEC-LT) have been effectively utilized in MPM patients...
October 2018: Translational Lung Cancer Research
https://www.readbyqxmd.com/read/30450298/a-randomized-phase-ii-study-of-pleurectomy-decortication-preceded-or-followed-by-neo-adjuvant-chemotherapy-in-patients-with-early-stage-malignant-pleural-mesothelioma-eortc-1205
#15
REVIEW
Jo Raskin, Veerle Surmont, Robin Cornelissen, Paul Baas, Paul E Y van Schil, Jan P van Meerbeeck
Radical multimodality treatment for malignant pleural mesothelioma (MPM) is controversial, with intense debate (but lack of data) about which surgical procedure to perform [extrapleural pneumonectomy (EPP) or pleurectomy/decortication (PD)], if any. In order to perform a randomized comparison, the most optimal sequence of surgery and chemotherapy should be determined. EORTC 1205 is a clinical trial randomizing between upfront surgery, followed by chemotherapy (cisplatin plus pemetrexed) and deferred surgery, following neoadjuvant chemotherapy in early stage (T1-3 N0-2 M0) MPM (irrespective of histological subtype)...
October 2018: Translational Lung Cancer Research
https://www.readbyqxmd.com/read/30450297/is-there-a-role-for-prophylactic-radiotherapy-to-intervention-tract-sites-in-patients-with-malignant-pleural-mesothelioma
#16
REVIEW
Paul Halford, Amelia O Clive
Malignant pleural mesothelioma has a high morbidity and poor prognosis. Most patients undergo invasive pleural interventions to either facilitate diagnosis and/or alleviate symptoms from malignant pleural effusion. Procedure tract metastasis (PTM) are a well-known complication of pleural procedures in mesothelioma and there has been longstanding debate regarding the role of prophylactic irradiation of tracts in preventing them. This review summarises the existing evidence surrounding this controversial topic...
October 2018: Translational Lung Cancer Research
https://www.readbyqxmd.com/read/30450296/current-chemotherapy-strategies-in-malignant-pleural-mesothelioma
#17
REVIEW
Cornedine Jannette de Gooijer, Paul Baas, Jacobus Adrianus Burgers
Malignant pleural mesothelioma (MPM) is an aggressive malignancy with a 5-year survival rate of ~10%. Since most patients present with irresectable disease, the vast majority is treated with chemotherapy. The only registered therapy for MPM is platinum-pemetrexed doublet therapy, although only up to half of patients have clinical benefit from this palliative treatment. Of the anti-angiogenesis agents, only bevacizumab and nintedanib have shown activity with platinum-pemetrexed doublet therapy. Other anti-angiogenesis agents like thalidomide did not prolong (progression free) survival or response rate...
October 2018: Translational Lung Cancer Research
https://www.readbyqxmd.com/read/30450295/combined-modality-treatment-in-mesothelioma-a-systemic-literature-review-with-treatment-recommendations
#18
REVIEW
Charlotte De Bondt, Ioannis Psallidas, Paul E Y Van Schil, Jan P van Meerbeeck
In spite of recent progress, malignant pleural mesothelioma (MPM) remains synonymous with poor prognosis. A selected minority (<10%) of patients is eligible for a radical treatment with a combination of systemic chemotherapy (CT) and/or surgery and/or radiotherapy (RT), in an effort to maintain locoregional tumor control after achieving a macroscopically complete resection (MCR). However, as of yet there is no standard of care for this so-called multimodality treatment. As its potential gain is still limited (approximately one year added to overall survival), we must balance its efficacy with its cumulative toxicity...
October 2018: Translational Lung Cancer Research
https://www.readbyqxmd.com/read/30450294/extended-pleurectomy-decortication-the-current-role
#19
REVIEW
Rocco Bilancia, Marco Nardini, David A Waller
Extended pleurectomy/decortication (EPD) has been formally defined but there remain technical areas of debate between practitioners. This is partly attributable to the relative rarity of this operation which is largely confined to a small number of specialist centres. Nevertheless, there is a widespread acceptance that extended pleurectomy/decortication (P/D) is a realistic and favourable alternative to extrapleural pneumonectomy. There may, however, remain a small number of clinical cases where this more extensive operation may be indicated...
October 2018: Translational Lung Cancer Research
https://www.readbyqxmd.com/read/30450293/extrapleural-pneumonectomy-still-indicated
#20
REVIEW
Andreas Domen, Lawek Berzenji, Jeroen M H Hendriks, Suresh Krishan Yogeswaran, Patrick Lauwers, Jan P Van Meerbeeck, Paul E Van Schil
The optimal treatment of malignant pleural mesothelioma (MPM) has not yet been established and is still under investigation. Surgery is one of the pillars in the multimodality approach with the purpose of removing as much as visible tumor as possible and to relieve symptoms. To date, two major surgical procedures are available for removal or debulking of MPM that is considered to be resectable: [extended (e)] pleurectomy/decortication (P/D) and extrapleural pneumonectomy (EPP). Historically, EPP was regarded as the only way to achieve a macroscopic complete resection...
October 2018: Translational Lung Cancer Research
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