Advances in Treatment of Lung Cancer With Targeted Therapy

2012 ◽  
Vol 136 (5) ◽  
pp. 504-509 ◽  
Author(s):  
Philip T. Cagle ◽  
Lucian R. Chirieac
Keyword(s):  
Lung Cancer ◽  
Clinical Trials ◽  
Targeted Therapy ◽  
Targeted Therapies ◽  
Diagnostic Techniques ◽  
Molecular Diagnostic ◽  
Molecular Testing ◽  
Molecular Diagnostic Techniques ◽  
Molecular Abnormalities ◽  
Pathologic Features

Context.—Ongoing preclinical investigations and clinical trials involving new targeted therapies promise to improve survival for patients with lung cancer. Targeted therapeutic agents, based on genetic mutations and signaling pathways altered in lung cancer, have added significantly to our armamentarium for lung cancer treatment while minimizing drug toxicity. To date, 4 targeted therapies have been approved for treatment of lung cancer by the US Food and Drug Administration: gefitinib in 2002, erlotinib in 2003, bevacizumab in 2006, and crizotinib in 2011. Objective.—To review targeted therapies in lung cancer, the molecular biomarkers that identify patients likely to benefit from these targeted therapies, the basic molecular biology principles, selected molecular diagnostic techniques, and pathologic features correlated with molecular abnormalities in lung cancer. To review new molecular abnormalities described in lung cancer that are predictive for response to novel promising targeted agents in various phases of clinical trials. Data Sources.—Review of the literature covering the molecular abnormalities of lung cancer with a focus on the molecular diagnostics and targeted therapy. Special emphasis is placed on summarizing evolving technologies useful in the diagnosis and characterization of lung cancer. Conclusions.—Molecular testing of lung cancer expands the expertise of the pathologist, who will identify the tumor markers that are predictive of sensitivity or resistance to various targeted therapies and allow patients with cancer to be selected for highly effective and less toxic therapies.

Matching insurance claims data with EMR molecular status data in non-small cell lung cancer (NSCLC) patients: Understanding real-world molecular testing and prevalence rates at the site and investigator level.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e20568-e20568
Author(s):  
Michael Gregory Cushion ◽  
Bhavani Krishnan ◽  
Jeff Paul Hodge ◽  
Jaya Chandra Balusu ◽  
Joseph Wagner ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Clinical Trials ◽  
Targeted Therapy ◽  
Real World ◽  
Targeted Therapies ◽  
Claims Data ◽  
Molecular Testing ◽  
Insurance Claims ◽  
Insurance Claims Data ◽  
Nsclc Patients

e20568 Background: Many targeted therapy clinical trials require a somatic gene mutation/alteration for eligibility. We assessed the feasibility of leveraging Real-World Data (RWD) to enrol NSCLC patients into clinical trials. Methods: US insurance claims data were extracted to identify lung cancer patients. These data were matched with EMR data also containing NSCLC patients’ details regarding the occurrence and results of molecular testing for EGFR, ALK, ROS1, JAK2, HER2 and RET somatic alterations, achieving a level of granular detail beyond that available in each individual dataset. A one-year extraction period was applied, with no gender or age restrictions. Results: Results for the matched dataset are summarised in the table below - the overall patient record match was 89.6%. Conclusions: The observed prevalence correlated reasonably well with literature reported prevalence for the molecular biomarkers associated commercially available targeted therapies in NSCLC (EGFR, ALK, ROS1). The sample size for the remaining biomarkers was too small to draw conclusions, though the presence of data correlating to these is of interest, considering that there are no currently approved targeted therapies in NSCLC tailored to these predictive biomarkers. This approach could be expanded upon to recruit patients into targeted therapy clinical trials as the dataset is fully linkable to sites and investigators. With the emergence of broad genomic profiling, the availability of molecular data to support clinical trial enrolment is also expected to grow.[Table: see text]

scholarly journals THER-01. Targeted therapy and intracranial metastatic disease: a population-based retrospective cohort study

2021 ◽  
Vol 3 (Supplement_3) ◽  
pp. iii12-iii12
Author(s):  
Anders Erickson ◽  
Steven Habbous ◽  
Frances Wright ◽  
Aisha Lofters ◽  
Katarzyna Jerzak ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Lung Cancer ◽  
Clinical Trials ◽  
Targeted Therapy ◽  
Targeted Therapies ◽  
Retrospective Cohort ◽  
Her2 Positive ◽  
Her2 Positive Breast Cancer ◽  
Intracranial Metastatic Disease ◽  
Positive Breast Cancer

Abstract Background Targeted therapies have been hypothesized to prolong survival in the management of patients with intracranial metastatic disease (IMD), but, paradoxically, to increase IMD incidence by improving systemic disease control and prolonging survival from the primary tumor. The real-world benefits of targeted therapy in management of patients with IMD are unclear, as clinical trials have excluded patients with IMD and lacked endpoints reporting intracranial outcomes. Methods This retrospective cohort study included all patients in Ontario, Canada, diagnosed with IMD from 2005 to 2018 with primary diagnoses of breast cancer, lung or bronchus cancer, or melanoma, and control patients matched by primary disease without IMD. Kaplan-Meier and multivariable Cox regression analyses were performed to compare overall survival (OS) between patient sub-cohorts divided by primary disease and stratified by targeted therapy receipt or IMD status. Results Post-IMD targeted therapy was associated with prolonged OS in patients with HER2-positive breast cancer (HR 0.41; 95% CI, 0.33–0.5), EGFR-positive lung cancer (HR 0.28; 95% CI, 0.23–0.34), and BRAF-positive melanoma (HR 0.2; 95% CI, 0.14–0.29), compared to those who did not receive post-IMD targeted therapy. Presence of IMD was associated with shorter OS in patients with metastatic HER2-positive breast cancer (HR 1.8; 95% CI, 1.56–2.08) and metastatic EGFR-positive lung cancer (HR 1.22; 95% CI, 1.08–1.39) but not metastatic BRAF-positive melanoma (HR 1.11; 95% CI, 0.77–1.61), compared to those without IMD. Conclusions Our findings show that real-world use of targeted therapies was associated with prolonged OS in patients with IMD in the setting of HER2-positive breast cancer, EGFR-positive lung cancer, and BRAF-positive melanoma. Inclusion of patients with IMD in clinical trials and use of endpoints that interrogate IMD will be critical to determine the role of targeted therapies in the management of patients with IMD.

Biomarker utilization in non-small cell lung cancer, are we treating after testing?

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 9609-9609
Author(s):  
Elias Makhoul ◽  
Jong Taek Kim ◽  
Wenjuan Zhang ◽  
Jean Raphael Lopategui ◽  
Ani Sarkis Balmanoukian ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Targeted Therapy ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Targeted Therapies ◽  
Small Cell ◽  
Molecular Testing ◽  
Small Cell Lung ◽  
Nsclc Patients

9609 Background: Targeted therapy in EGFR and ALK mutated non-small cell lung cancer (NSCLC) has been the standard of care for nearly a decade with subsequent FDA approvals for ROS1 and BRAF V600 mutated NSCLC occurring in 2016 and 2017. However, recent studies have shown suboptimal utilization of genomic profiling results in these patients. In 1 recent study of community oncologists, ~70% of EGFR/ALK+ patients received appropriate targeted therapy, while patients with other gene mutations (including BRAF and ROS1) only received targeted therapy ~30% of the time. Left unanswered was what patients were receiving instead and why. Additionally, it is unknown if this finding is generalizable to the academic setting. We aimed to investigate whether in our patient population, NSCLC patients with actionable mutations received associated FDA approved therapies and if not why. Methods: The pathology database was queried for all NSCLC with molecular testing (including qPCR, FISH and NGS) from 2009 to 2019. Patients with sensitizing EGFR, ALK, ROS1 or BRAF mutations that were detected after the first FDA approval for their respective targeted therapies were included for analysis with those lost to follow up subsequently excluded. Basic demographic and clinical variables were collected as well as treatment records. Results: 2160 NSCLC patients were evaluated (2160 EGFR, 1417 ALK, 810 ROS1, 589 BRAF). 468 patients were identified with targetable mutations (411 EGFR, 46 ALK, 5 ROS1, 6 BRAF). No patient had more than 1 targetable mutation. Of those patients, 248 were at an advanced stage and had clinical follow up (202 EGFR, 37 ALK, 4 ROS1, 5 BRAF). Of those patients 197/202 (97.5%), 33/37 (89.2%), 3/4 (75%) and 1/5 (20%) received EGFR, ALK, ROS1 or BRAF targeted therapy respectively. Across biomarkers 14/248 patients (5.6%) did not receive subsequent targeted therapy. 10 patients (5 EGFR, 3 ALK, 1 ROS1 and 1 BRAF) passed away before targeted therapy could be initiated. Physician choice and missed findings accounted for the remaining four cases. Conclusions: The vast majority of advanced NSCLC patients analyzed in this study received appropriate targeted therapy matched to genomic findings. The main reason (~4% of total cases) that patients did not receive therapy was due to rapidly progressive disease and death before it could be initiated. These findings are at odds with those published from the community setting. This may be due to multiple factors, including clinician education, ease of access to targeted therapies across patient populations and incomplete data in the previous study populations.

scholarly journals Moraxella catarrhalis: from Emerging to Established Pathogen

2002 ◽  
Vol 15 (1) ◽  
pp. 125-144 ◽  
Author(s):  
Cees M. Verduin ◽  
Cees Hol ◽  
André Fleer ◽  
Hans van Dijk ◽  
Alex van Belkum
Keyword(s):  
Moraxella Catarrhalis ◽  
Current Knowledge ◽  
Bacterial Species ◽  
Bacterial Pathogen ◽  
Diagnostic Techniques ◽  
Human Infection ◽  
Molecular Diagnostic ◽  
Molecular Diagnostic Techniques ◽  
Pathogenic Potential ◽  
The Past

SUMMARY Moraxella catarrhalis (formerly known as Branhamella catarrhalis) has emerged as a significant bacterial pathogen of humans over the past two decades. During this period, microbiological and molecular diagnostic techniques have been developed and improved for M. catarrhalis, allowing the adequate determination and taxonomic positioning of this pathogen. Over the same period, studies have revealed its involvement in respiratory (e.g., sinusitis, otitis media, bronchitis, and pneumonia) and ocular infections in children and in laryngitis, bronchitis, and pneumonia in adults. The development of (molecular) epidemiological tools has enabled the national and international distribution of M. catarrhalis strains to be established, and has allowed the monitoring of nosocomial infections and the dynamics of carriage. Indeed, such monitoring has revealed an increasing number of Β-lactamase-positive M. catarrhalis isolates (now well above 90%), underscoring the pathogenic potential of this organism. Although a number of putative M. catarrhalis virulence factors have been identified and described in detail, their relationship to actual bacterial adhesion, invasion, complement resistance, etc. (and ultimately their role in infection and immunity), has been established in a only few cases. In the past 10 years, various animal models for the study of M. catarrhalis pathogenicity have been described, although not all of these models are equally suitable for the study of human infection. Techniques involving the molecular manipulation of M. catarrhalis genes and antigens are also advancing our knowledge of the host response to and pathogenesis of this bacterial species in humans, as well as providing insights into possible vaccine candidates. This review aims to outline our current knowledge of M. catarrhalis, an organism that has evolved from an emerging to a well-established human pathogen.

scholarly journals Morphological and Genetic Heterogeneity of Synchronous Multifocal Lung Adenocarcinoma in a Chinese Cohort

2020 ◽  
Author(s):  
Donglin Zhu ◽  
Dan Cao ◽  
Minghong Shen ◽  
Jinghuan Lv
Keyword(s):  
Lung Cancer ◽  
Primary Lung Cancer ◽  
Gene Mutations ◽  
Tumor Location ◽  
Chinese Patients ◽  
Molecular Testing ◽  
Additional Tool ◽  
Molecular Features ◽  
Pathologic Features ◽  
Genotypic Analysis

Abstract Background: Synchronous multifocal lung cancer (SMLC) is seen with increasing frequency in clinical practice globally. Because of innate variation in clinical management and outcome, it is vital to distinguish properly between synchronous multifocal primary lung cancer (SMPLC) and intrapulmonary metastasis (IM). The pathologic features and principal classification criteria of multifocal lung cancer remain unclear. Methods: We have collected a unique cohort of Chinese patients with SMLC, and fully explored the morphologic, immunohistochemical, and molecular features of the disease. Twenty-one SMLC patients with a total of 50 tumors were included in our study. The pathological features presented by these cases were analyzed, including tumor location, tumor size, pathological types, predominant pattern of adenocarcinoma, and immunohistochemical staining. We undertook molecular testing of nine driver oncogenes associated with lung cancer, including EGER, KRAS, BRAF, NRAS, ALK, ROS1, RET, HER2, and PIK3CA. Results: According to Martini-Melamed classification and refined standard, 8 and 17 cases were considered as SMPLC respectively. Gene mutations were identified in 18 tumors (36%). There were 12 patients had different gene mutations. Conclusions: We demonstrate that conventional morphological assessment is not sufficient to establish clearly the clonal relationship of SMPLC. Instead the evaluation of histological subtypes, including non-mucinous adherent components, is required. Multiplex genotypic analysis may also prove a useful additional tool.

Unusual endophytic non-enhancing tumour in the renal pelvis: a diagnostic dilemma

2021 ◽  
Vol 14 (9) ◽  
pp. e245037
Author(s):  
Murali Krishna ◽  
Santosh Kumar ◽  
Kalpesh Mahesh Parmar ◽  
Venkatesh Dhana Sekaran
Keyword(s):  
Renal Cell ◽  
Cell Cancer ◽  
Diagnostic Techniques ◽  
Molecular Diagnostic ◽  
Molecular Diagnostic Techniques ◽  
Imaging Features ◽  
Diagnostic Dilemma ◽  
Upper Tract Urothelial Cancer ◽  
Cell Variant ◽  
Clear Cell Variant

Renal cell cancer (RCC) is incidentally detected on imaging in 50%–60% of cases. Among the RCCs, clear cell variant is most common and classically seen as heterogenous enhancing lesion on CT imaging. Hypoenhancing mass presents a diagnostic dilemma with differential diagnosis being urothelial carcinoma, fat poor angiomyolipoma, oncocytoma or rarer variants of RCC. Such cases require further evaluation in form of urine cytology or newer molecular diagnostic techniques. Here, we present a case of renal mass with minimal enhancement on CT scan and imaging features suggestive of upper tract urothelial cancer. Final histopathology revealed the mass to be chromophobe variant of renal cell carcinoma.

Diagnosis of melioidosis: the role of molecular techniques

2021 ◽  
Vol 16 (4) ◽  
pp. 271-288
Author(s):  
Ian Gassiep ◽  
Delaney Burnard ◽  
Michelle J Bauer ◽  
Robert E Norton ◽  
Patrick N Harris
Keyword(s):  
Laboratory Diagnosis ◽  
Diagnostic Techniques ◽  
Molecular Techniques ◽  
Molecular Diagnostic ◽  
Clinical Samples ◽  
Molecular Diagnostic Techniques ◽  
Detection And Identification ◽  
Life Years ◽  
Culture Independent ◽  
Future Utility

Melioidosis is an emerging infectious disease with an estimated global burden of 4.64 million disability-adjusted life years per year. A major determinant related to poor disease outcomes is delay to diagnosis due to the fact that identification of the causative agent Burkholderia pseudomallei may be challenging. Over the last 25 years, advances in molecular diagnostic techniques have resulted in the potential for rapid and accurate organism detection and identification direct from clinical samples. While these methods are not yet routine in clinical practice, laboratory diagnosis of infectious diseases is transitioning to culture-independent techniques. This review article aims to evaluate molecular methods for melioidosis diagnosis direct from clinical samples and discuss current and future utility and limitations.

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