EGFR Status Assessment for Better Care of Early Stage Non-Small Cell Lung Carcinoma: What Is Changing in the Daily Practice of Pathologists?
TL;DR: In this article, the impact of the management of biological samples in laboratories and perspectives for pathologists within the framework of EGFR TKIs in early stage NSCLC are discussed.
Abstract: The recent emergence of novel neoadjuvant and/or adjuvant therapies for early stage (I-IIIA) non-small cell lung carcinoma (NSCLC), mainly tyrosine kinase inhibitors (TKIs) targeting EGFR mutations and immunotherapy or chemo-immunotherapy, has suddenly required the evaluation of biomarkers predictive of the efficacy of different treatments in these patients. Currently, the choice of one or another of these treatments mainly depends on the results of immunohistochemistry for PD-L1 and of the status of EGFR and ALK. This new development has led to the setup of different analyses for clinical and molecular pathology laboratories, which have had to rapidly integrate a number of new challenges into daily practice and to establish new organization for decision making. This review outlines the impact of the management of biological samples in laboratories and discusses perspectives for pathologists within the framework of EGFR TKIs in early stage NSCLC.
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01 Jan 2023
TL;DR: In this paper , the authors summarize and explain standardized microscopic evaluation and scoring approaches for immunohistochemical stainings, focusing on commonly used and generally feasible approaches for different cellular compartments and comment on their utility in diagnostics and research practice.
Abstract: Immunohistochemistry is widely used in diagnostic and scientific analysis of urothelial carcinoma. Objective interpretation of staining results is mandatory for accuracy and comparability in diagnostic and therapeutic patient care as well as research. Herein we summarize and explain standardized microscopic evaluation and scoringScorings approaches for immunohistochemical stainings. We focus on commonly used and generally feasible approaches for different cellular compartments and comment on their utility in diagnostics and research practice.
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Howard Hughes Medical Institute1, Johns Hopkins University2, Swim Across America3, Boston University4, University of Turin5, Life Technologies6, Indiana University7, Indiana University Health8, Ludwig Institute for Cancer Research9, University of Pennsylvania10, University of Ulsan11, University of São Paulo12, Amgen13, Karolinska Institutet14, University of Colorado Boulder15, Memorial Sloan Kettering Cancer Center16, Indiana University – Purdue University Indianapolis17
TL;DR: The ability of circulating tumor DNA (ctDNA) to detect tumors in 640 patients with various cancer types was evaluated and suggested that ctDNA is a broadly applicable, sensitive, and specific biomarker that can be used for a variety of clinical and research purposes.
Abstract: The development of noninvasive methods to detect and monitor tumors continues to be a major challenge in oncology. We used digital polymerase chain reaction-based technologies to evaluate the ability of circulating tumor DNA (ctDNA) to detect tumors in 640 patients with various cancer types. We found that ctDNA was detectable in >75% of patients with advanced pancreatic, ovarian, colorectal, bladder, gastroesophageal, breast, melanoma, hepatocellular, and head and neck cancers, but in less than 50% of primary brain, renal, prostate, or thyroid cancers. In patients with localized tumors, ctDNA was detected in 73, 57, 48, and 50% of patients with colorectal cancer, gastroesophageal cancer, pancreatic cancer, and breast adenocarcinoma, respectively. ctDNA was often present in patients without detectable circulating tumor cells, suggesting that these two biomarkers are distinct entities. In a separate panel of 206 patients with metastatic colorectal cancers, we showed that the sensitivity of ctDNA for detection of clinically relevant KRAS gene mutations was 87.2% and its specificity was 99.2%. Finally, we assessed whether ctDNA could provide clues into the mechanisms underlying resistance to epidermal growth factor receptor blockade in 24 patients who objectively responded to therapy but subsequently relapsed. Twenty-three (96%) of these patients developed one or more mutations in genes involved in the mitogen-activated protein kinase pathway. Together, these data suggest that ctDNA is a broadly applicable, sensitive, and specific biomarker that can be used for a variety of clinical and research purposes in patients with multiple different types of cancer.
3,533 citations
TL;DR: Continued research into new drugs and combination therapies is required to expand the clinical benefit to a broader patient population and to improve outcomes in NSCLC.
Abstract: Important advancements in the treatment of non-small cell lung cancer (NSCLC) have been achieved over the past two decades, increasing our understanding of the disease biology and mechanisms of tumour progression, and advancing early detection and multimodal care. The use of small molecule tyrosine kinase inhibitors and immunotherapy has led to unprecedented survival benefits in selected patients. However, the overall cure and survival rates for NSCLC remain low, particularly in metastatic disease. Therefore, continued research into new drugs and combination therapies is required to expand the clinical benefit to a broader patient population and to improve outcomes in NSCLC.
2,410 citations
TL;DR: Surgical resection remains the primary and preferred approach to the treatment of stage I and II NSCLC, and mediastinal lymph node sampling at the time of curative intent surgical resection can be performed without increased morbidity.
1,180 citations
TL;DR: In patients with stage IB to IIIA EGFR mutation-positive NSCLC, disease-free survival was significantly longer among those who received osimertinib than among thoseWho received placebo.
Abstract: Background Osimertinib is standard-of-care therapy for previously untreated epidermal growth factor receptor (EGFR) mutation–positive advanced non–small-cell lung cancer (NSCLC). The effic...
843 citations
TL;DR: In this article, the authors made a distinction between non-small-cell lung cancer (NSCLC) and small-cell cancer (SCLC), and showed that although overall mortality from lung cancer has been...
Abstract: Background Lung cancer is made up of distinct subtypes, including non–small-cell lung cancer (NSCLC) and small-cell lung cancer (SCLC). Although overall mortality from lung cancer has been...
699 citations