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Molecular matching and treatment strategies for advanced stage lung cancer at Dartmouth-Hitchcock Medical Center: A three-year review of a Molecular Tumor Board.

ABSTRACT: Matching of actionable tumor mutations with targeted therapy increases response rates and prolongs survival in lung cancer patients. Drug development and trials targeting genetic alterations are expanding rapidly. We describe the role of a Molecular Tumor Board (MTB) in the design of molecularly informed treatment strategies in our lung cancer patient population. Tumor DNA was sequenced using a 50-gene targeted next-generation sequencing panel. Cases were evaluated by a multidisciplinary MTB who suggested a course of treatment based on each patient's molecular findings. During a three-year period, 21 lung cancer patients were presented at the MTB. All patients lacked common activating EGFR mutations and ALK rearrangements. One patient had Stage IIIb disease; all others were Stage IV; 18 patients had received ?1 prior line of therapy (range 0-5). Suggestions for treatment with a targeted therapy were made for 19/21 (90.5%) patients, and four patients (21%) underwent treatment with a targeted agent, two as part of a clinical trial. Identified barriers to treatment with targeted therapy included: ineligibility for clinical trials (n ?= ?2), lack of interest in study/distance to travel (n ?= ?2), lack of disease progression (n ?= ?2), poor performance status (n ?= ?5), decision to treat next with immunotherapy (n ?= ?3), and unknown (n ?= ?1). For the majority of lung cancer patients, the MTB provided recommendations based on tumor genetic profiles. Identified barriers to treatment suggest that presentation to the MTB at earlier stages of disease may increase the number of patients eligible for treatment with a genetically informed targeted agent.

SUBMITTER: Bernhardt EB

PROVIDER: S-EPMC7322356 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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Molecular matching and treatment strategies for advanced stage lung cancer at Dartmouth-Hitchcock Medical Center: A three-year review of a Molecular Tumor Board.

Bernhardt Erica B EB Chamberlin Mary D MD Gorlov Ivan P IP de Abreu Francine B FB Bloch Katarzyna J KJ Peterson Jason D JD Tsongalis Gregory J GJ Shirai Keisuke K Dragnev Konstantin H KH Miller Todd W TW Tafe Laura J LJ

Practical laboratory medicine 20200612

Matching of actionable tumor mutations with targeted therapy increases response rates and prolongs survival in lung cancer patients. Drug development and trials targeting genetic alterations are expanding rapidly. We describe the role of a Molecular Tumor Board (MTB) in the design of molecularly informed treatment strategies in our lung cancer patient population. Tumor DNA was sequenced using a 50-gene targeted next-generation sequencing panel. Cases were evaluated by a multidisciplinary MTB who ...[more]

PMID: 32613070

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Project description:BackgroundAlthough genetic profiling of tumors is a potentially powerful tool to predict drug sensitivity and resistance, its routine use has been limited because clinicians are often unfamiliar with interpretation and incorporation of the information into practice. We established a Molecular Tumor Board (MTB) to interpret individual patients' tumor genetic profiles and provide treatment recommendations.Patients and methodsDNA from tumor specimens was sequenced in a Clinical Laboratory Improvement Amendments-certified laboratory to identify coding mutations in a 50-gene panel (n = 34) or a 255-gene panel (n = 1). Cases were evaluated by a multidisciplinary MTB that included pathologists, oncologists, hematologists, basic scientists, and genetic counselors.ResultsDuring the first year, 35 cases were evaluated by the MTB, with 32 presented for recommendations on targeted therapies, and 3 referred for potential germline mutations. In 56.3% of cases, MTB recommended treatment with a targeted agent based on evaluation of tumor genetic profile and treatment history. Four patients (12.5%) were subsequently treated with a MTB-recommended targeted therapy; 3 of the 4 patients remain on therapy, 2 of whom experienced clinical benefit lasting >10 months.ConclusionFor the majority of cases evaluated, the MTB was able to provide treatment recommendations based on targetable genetic alterations. The most common reasons that MTB-recommended therapy was not administered stemmed from patient preferences and genetic profiling at either very early or very late stages of disease; lack of drug access was rarely encountered. Increasing awareness of molecular profiling and targeted therapies by both clinicians and patients will improve acceptance and adherence to treatments that could significantly improve outcomes.Implications for practiceCase evaluation by a multidisciplinary Molecular Tumor Board (MTB) is critical to benefit from individualized genetic data and maximize clinical impact. MTB recommendations shaped treatment options for the majority of cases evaluated. In the few patients treated with MTB-recommended therapy, disease outcomes were positive and support genetically informed treatment.

Project description:ContextCertification by an American Board of Medical Specialties (ABMS) member board is emerging as a measure of physician quality.ObjectiveTo identify demographic and educational factors associated with ABMS member board certification of US medical school graduates.Design, setting, and participantsRetrospective study of a national cohort of 1997-2000 US medical school graduates, grouped by specialty choice at graduation and followed up through March 2, 2009. In separate multivariable logistic regression models for each specialty category, factors associated with ABMS member board certification were identified.Main outcome measureABMS member board certification.ResultsOf 42,440 graduates in the study sample, 37,054 (87.3%) were board certified. Graduates in all specialty categories with first-attempt passing scores in the highest tertile (vs first-attempt failing scores) on US Medical Licensing Examination Step 2 Clinical Knowledge were more likely to be board certified; adjusted odds ratios (AORs) varied by specialty category, with the lowest odds for emergency medicine (87.4% vs 73.6%; AOR, 1.82; 95% CI, 1.03-3.20) and highest odds for radiology (98.1% vs 74.9%; AOR, 13.19; 95% CI, 5.55-31.32). In each specialty category except family medicine, graduates self-identified as underrepresented racial/ethnic minorities (vs white) were less likely to be board certified, ranging from 83.5% vs 95.6% in the pediatrics category (AOR, 0.44; 95% CI, 0.33-0.58) to 71.5% vs 83.7% in the other nongeneralist specialties category (AOR, 0.79; 95% CI, 0.64-0.96). With each $50,000 unit increase in debt (vs no debt), graduates choosing obstetrics/gynecology were less likely to be board certified (AOR, 0.89; 95% CI, 0.83-0.96), and graduates choosing family medicine were more likely to be board certified (AOR, 1.13; 95% CI, 1.01-1.26).ConclusionDemographic and educational factors were associated with board certification among US medical school graduates in every specialty category examined; findings varied among specialty categories.

Project description:Purpose:Dramatic advances in our understanding of the molecular pathophysiology of cancer, along with a rapidly expanding portfolio of molecular targeted drugs, have led to a paradigm shift toward personalized, biomarker-driven cancer treatment. Here, we report the 2-year experience of the Comprehensive Cancer Center Freiburg Molecular Tumor Board (MTB), one of the first interdisciplinary molecular tumor conferences established in Europe. The role of the MTB is to recommend personalized therapy for patients with cancer beyond standard-of-care treatment. Methods:This retrospective case series includes 198 patients discussed from March 2015 through February 2017. The MTB guided individual molecular diagnostics, assessed evidence of actionability of molecular alterations, and provided therapy recommendations, including approved and off-label treatments as well as available matched clinical trials. Results:The majority of patients had metastatic solid tumors (73.7%), mostly progressive (77.3%) after a mean of 2.0 lines of standard treatment. Diagnostic recommendations resulted in 867 molecular diagnostic tests for 172 patients (five per case), including exome analysis in 36 cases (18.2%). With a median turnaround time of 28 days, treatment recommendations were given to 104 patients (52.5%). These included single-agent targeted therapies (42.3%), checkpoint inhibitors (37.5%), and combination therapies (18.3%). Treatment recommendations were implemented in 33 of 104 patients (31.7%), of whom 19 (57.6%) showed stable disease or partial response, including 14 patients (7.1% of the entire population) receiving off-label treatments. Conclusion:Personalized extended molecular-guided patient care is effective for a small but clinically meaningful proportion of patients in challenging clinical situations. Limited access to targeted drugs, lack of trials, and submission at late disease stage prevents broader applicability, whereas genome-wide analyses are not a strict requirement for predictive molecular testing.

Dataset Information

Molecular matching and treatment strategies for advanced stage lung cancer at Dartmouth-Hitchcock Medical Center: A three-year review of a Molecular Tumor Board.

Publications

Molecular matching and treatment strategies for advanced stage lung cancer at Dartmouth-Hitchcock Medical Center: A three-year review of a Molecular Tumor Board.

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