scholarly journals Personalized Medicine in the Oncology Clinic: Implementation and Outcomes of the Johns Hopkins Molecular Tumor Board

2017 ◽  
pp. 1-19 ◽  
Author(s):  
W. Brian Dalton ◽  
Patrick M. Forde ◽  
Hyunseok Kang ◽  
Roisin M. Connolly ◽  
Vered Stearns ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Targeted Therapy ◽  
Targeted Therapies ◽  
Progression Free Survival ◽  
Molecular Profiling ◽  
Tumor Board ◽  
Free Survival ◽  
Off Label ◽  
Tumor Boards ◽  
Molecular Tumor Board

Purpose Tumor genomic profiling for personalized oncology therapy is being widely applied in clinical practice even as it is being evaluated more formally in clinical trials. Given the complexities of genomic data and its application to clinical use, molecular tumor boards with diverse expertise can provide guidance to oncologists and patients seeking to implement personalized genetically targeted therapy in practice. Methods A multidisciplinary molecular tumor board reviewed tumor molecular profiling reports from consecutive referrals at the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins over a 3-year period. The tumor board weighed evidence for actionability of genomic alterations identified by molecular profiling and provided recommendations including US Food and Drug Administration–approved drug therapy, clinical trials of matched targeted therapy, off-label use of such therapy, and additional tumor or germline genetic testing. Results One hundred fifty-five patients were reviewed. Actionable genomic alterations were identified in 132 patients (85%). Off-label therapies were recommended in 37 patients (24%). Eleven patients were treated off-label, and 13 patients were enrolled onto clinical trials of matched targeted therapies. Median progression-free survival of patients treated with matched therapies was 5 months ( 95% CI, 2.9 months to not reached), and the progression-free survival probability at 6 months was 43% (95% CI, 26% to 71%). Lack of locally available clinical trials was the major limitation on clinical actionability of tumor profiling reports. Conclusion The molecular tumor board recommended off-label targeted therapies for a quarter of all patients reviewed. Outcomes were heterogeneous, although 43% of patients receiving genomically matched therapy derived clinical benefit lasting at least 6 months. Until more data become available from precision oncology trials, molecular tumor boards can help guide appropriate use of tumor molecular testing to direct therapy.

scholarly journals Individualized Molecular Profiling for Allocation to Clinical Trials Singapore Study—An Asian Tertiary Cancer Center Experience

2021 ◽  
pp. 859-875
Author(s):  
Amanda O. L. Seet ◽  
Aaron C. Tan ◽  
Tira J. Tan ◽  
Matthew C. H. Ng ◽  
David W. M. Tai ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Clinical Trials ◽  
Tumor Tissue ◽  
Molecular Profiling ◽  
Tumor Board ◽  
Cancer Center ◽  
Precision Oncology ◽  
Molecular Tumor Board ◽  
Tumor Types ◽  
Tertiary Cancer Center

PURPOSE Precision oncology has transformed the management of advanced cancers through implementation of advanced molecular profiling technologies to identify increasingly defined subsets of patients and match them to appropriate therapy. We report outcomes of a prospective molecular profiling study in a high-volume Asian tertiary cancer center. PATIENTS AND METHODS Patients with advanced cancer were enrolled onto a prospective protocol for genomic profiling, the Individualized Molecular Profiling for Allocation to Clinical Trials Singapore study, at the National Cancer Center Singapore. Primary objective was to identify molecular biomarkers in patient's tumors for allocation to clinical trials. The study commenced in February 2012 and is ongoing, with the results of all patients who underwent multiplex next-generation sequencing (NGS) testing until December 2018 presented here. The results were discussed at a molecular tumor board where recommendations for allocation to biomarker-directed trials or targeted therapies were made. RESULTS One thousand fifteen patients were enrolled with a median age of 58 years (range 20-83 years). Most common tumor types were lung adenocarcinoma (26%), colorectal cancer (15%), and breast cancer (12%). A total of 1,064 NGS assays were performed, on fresh tumor tissue for 369 (35%) and archival tumor tissue for 687 (65%) assays. TP53 (39%) alterations were most common, followed by EGFR (21%), KRAS (14%), and PIK3CA (10%). Of 405 NGS assays with potentially actionable alterations, 111 (27%) were allocated to a clinical trial after molecular tumor board and 20 (4.9%) were enrolled on a molecularly matched clinical trial. Gene fusions were detected in 23 of 311 (7%) patients tested, including rare fusions in new tumor types and known fusions in rare tumors. CONCLUSION Individualized Molecular Profiling for Allocation to Clinical Trials Singapore demonstrates the feasibility of a prospective broad molecular profiling program in an Asian tertiary cancer center, with the ability to develop and adapt to a dynamic landscape of precision oncology.

A quality outcomes analysis following treatment with personalized genomic cancer medicine.

2014 ◽  
Vol 32 (30_suppl) ◽  
pp. 12-12 ◽  
Author(s):  
Lincoln Nadauld ◽  
Bryce Perkins ◽  
Gary Stone ◽  
Heather Gilbert ◽  
Brian P. Tudor ◽  
...  
Keyword(s):  
Advanced Cancer ◽  
Targeted Therapies ◽  
Cohort Analysis ◽  
Progression Free Survival ◽  
Tumor Board ◽  
Molecular Profile ◽  
Advanced Cancer Patients ◽  
Quality Outcomes ◽  
Free Survival ◽  
Cancer Medicine

12 Background: Personalized genomic cancer medicine is an approach that has long shown efficacy in molecularly-defined subsets of breast and lung cancers, amongst others, but has not been employed more broadly, in part, due to limitations in testing technologies. Recent advances in genomic technologies have increasingly alleviated these constraints, thereby enabling precision cancer medicine. Data regarding the quality outcomes of patients treated with precision cancer medicine is an important next step along the path to widespread employment of this approach. Methods: We performed an IRB-approved retrospective analysis evaluating the use of targeted therapies matched to patients’ molecular aberrations as determined by genomic testing and recommended by a Molecular Tumor Board (MTB). This study assessed whether a detailed molecular profile of advanced solid malignancies including, but not limited to, the lung, gastrointestinal tract, bladder, prostate, ovary, uterus and skin, that were subsequently treated with matched targeted therapies resulted in improvements in three quality outcome measures: 1) Progression Free Survival (PFS), 2) treatment related morbidity, and 3) cost of treatment. Results: Preliminary results of the cohort analysis suggest that the costs associated with genomic targeted therapy are comparable to standard therapies; however, the costs of treatment related morbidities is significantly lower for patients receiving genomic cancer medicine compared to standard chemotherapy approaches. In line with these findings, overall treatment related morbidities are significantly reduced in the genomic cancer medicine cohort compared to a control cohort. Data regarding the Progression Free Survival are pending at the time of this report. Conclusions: These retrospective data suggest that personalized genomic cancer medicine approaches result in decreased morbidities and cost savings compared to standard chemotherapeutic approaches. In patients with advanced cancer, genomic-based treatments appear to be cost-effective, safe and viable option for treating advanced cancer patients. Additional data regarding survival outcomes are required to determine efficacy of treatment.

Implementation and impact of the first two years of a systemwide molecular tumor board at Henry Ford Health System (HFHS).

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e19266-e19266
Author(s):  
Igor I. Rybkin ◽  
Nadia Z Haque ◽  
Kristen Collins ◽  
Louisa Laidlaw ◽  
Tom Mikkelsen
Keyword(s):  
Clinical Trial ◽  
Clinical Trials ◽  
Performance Status ◽  
Tumor Board ◽  
Molecular Testing ◽  
Precision Oncology ◽  
Ecog Performance Status ◽  
Off Label ◽  
Molecular Tumor Board ◽  
The Impact

e19266 Background: HFHS implemented clinically-oriented Precision Medicine Program (PMP) in 2016. As part of the program, multidisciplinary molecular tumor board (MTB) was created to review complex molecular cases, providing guidance to treating medical oncologist in selecting targeted therapies and clinical trials. In some cases MTB recommended genetic counseling or recommended against/for additional molecular testing. MTB consists of oncologists, molecular pathologists, clinical trial staff, and genetic counselors. MTB was designed as teaching platform engaging hematology-oncology fellows into cases analysis and presentation. Here we present preliminary analysis of the impact of the MTB on the HFHS oncology practice. Methods: From 09/08/2017 to 12/31/2019 MTB reviewed 120 cases, 116 cases were used for this analysis. Data was abstracted using Syapse precision oncology platform, MTB recommendation note, electronic medical record (EMR), and molecular test results. Results: Out of 116 pts 83 (72%) were Caucasian, 25 (22%) African American, 4 (3%) Asian, 1 (1%) American Indian. Fifty-two % (n = 21) had an ECOG performance status of 1. Most common primary disease sites were lung (39%, n = 45) brain (12%, n = 15), and hematologic cancers (9%; n = 10), followed by breast (5%, n = 6), prostate (4%, n = 5), colon (3%, n = 4), and others (28%, n = 31). The most common genetic abnormalities discussed were atypical EGFR (n = 15), non-V600 BRAF (n = 10), KRAS (n = 8), BRCA2 (n = 5), NF2 (n = 4), PTEN (n = 4), CSF3R (n = 3), IDH1 (n = 3), TP53 (n = 3), and 29 less common mutations. Thirty five (30%) pts out of 116 total were recommended clinical trials, although only 3 patients (10% of recommended) were enrolled into trials. 31 pts (27%) were recommended off-label therapy, although trials were preferred. 18% of pts (n = 21) were recommended genetics referral, although only 3 have seen Geneticist, with two undergoing germline testing. One pt was discovered to have a germline RET V804M mutation which was originally detected in the cancer. Conclusions: The first two years of data demonstrate the utility of the MTB and provide a basis for ongoing analysis. Through multidisciplinary approach, MTB encourages care coordination and collaboration. MTB resulted in genetics referrals, clinical trial recommendations, and identification of targeted therapy options, including off label. In many cases, MTB recommendations prevented futile therapies and/or additional molecular testing.

Utilization of consultative molecular tumor board in community setting.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 6508-6508 ◽  
Author(s):  
Carol J. Farhangfar ◽  
Oshuna Morgan ◽  
Charlene Concepcion ◽  
Jimmy J. Hwang ◽  
Kathryn Finch Mileham ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Community Setting ◽  
Treatment Decisions ◽  
Tumor Board ◽  
Baseline Survey ◽  
Community Based ◽  
Tumor Boards ◽  
Molecular Tumor Board ◽  
Tumor Types ◽  
Genomics Education

6508 Background: Physicians in the community have a broad range of experience using genomics data to inform treatment decisions. They typically have a heavier patient load than found in academic centers and treat a variety of tumor types. Genomic data has been reportedly used less than anticipated, even when results were actionable. Monthly didactic molecular tumor boards have been implemented in a number of cancer centers to try to fill gaps in knowledge. Methods: A weekly virtual consultative molecular tumor board (MTB) was implemented (Mar 2016) at an academic hybrid, multi-site community-based cancer institute to provide rapid molecularly-driven treatment guidance to physicians, augment genomics education, provide supporting documents for off-label use and clinical trials. A baseline survey was performed prior to first MTB. MTB assessments were summarized and provided to treating physician. Data was abstracted from the electronic medical records and clinical trials management system. Descriptive statistics were utilized to summarize utilization of MTB and treatment recommendations. Results: Genomics testing with a large panel (~600 genes) was requested for 809 patients (Jun 2015-Feb 2017). The MTB received 81 requests for review from 32 physicians from 14 locations. Most commonly reviewed disease sites were lung, ovary, pancreatic, colon, breast and head and neck cancers; 37% of reviews requested were for rare tumors. Median time to review request was 15 days from receipt of results. MTB recommendations were followed in 70% of cases, 16% continued current/other therapy, 11% declined rapidly (hospice/died), and 3% of patients decided against recommendations. Forty-four (44) percent were screened for recommended clinical trials; 26% went on study. Conclusions: Implementation of a weekly virtual consultative MTB facilitates molecularly-driven treatment decisions in community setting, especially in rare tumor types and enhances clinical trial accruals.

The impact of clinical decision making in a molecular tumor board at a tertiary care center.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 3128-3128
Author(s):  
Meena Sadaps ◽  
Kathryn Demski ◽  
Ying Ni ◽  
Vicky Konig ◽  
Brandie Leach ◽  
...  
Keyword(s):  
Decision Making ◽  
Clinical Decision Making ◽  
Clinical Decision ◽  
Genetic Counselors ◽  
Tumor Board ◽  
Treatment Recommendation ◽  
Precision Oncology ◽  
Off Label ◽  
Tumor Boards ◽  
Molecular Tumor Board

3128 Background: Multidisciplinary molecular tumor boards were first established with the onset of precision oncology (PO), as many clinicians were unfamiliar with the interpretation and incorporation of the information into clinical practice. PO has since rapidly evolved and integrated itself into standard of care practices for most cancer patients, yet molecular tumor boards have not grown accordingly and in fact some have been discontinued. There remains a paucity of data in regards to the value and impact of molecular tumor board discussions themselves. We previously reported on our longitudinal experiences in PO ( Sadaps et al, 2018), focusing on the therapeutic impact of matched therapy. Here, we report on the utility of our molecular tumor board in clinical decision making. Methods: We conducted a retrospective review of patients seen at Cleveland Clinic with a solid tumor malignancy who had large panel, next-generation-sequencing (NGS) performed via any commercial platform from November 2019-January 2021. Cases were filtered through a local therapeutic algorithm and then reviewed individually. Initial review was performed by a core genomics committee comprised of 2 oncologists and 2 genetic counselors. Interesting and/or complex cases were flagged for discussion at our bimonthly molecular tumor board, which is regularly attended by medical oncologists, pathologists, genetic counselors, bioinformaticians, and patient care coordinators. Data analyzed included categorization of treatment recommendations and the percentage of cases for which initial recommendations were changed based on tumor board discussion. Results: Of 782 total cases, 575 (73.5%) had a clinically relevant genomics tumor board (GTB) recommendation as compared to 51.7% from our previously reported study. 16.7% of patients had on label recommendation(s) and 86.4% had off label/ clinical trial recommendation(s). 179 (22.9%) patients were recommended for genetic counseling (GC). During our bimonthly GTB, we discussed 173 (22.1%) of these cases. Of the discussed cases, the most common tumor types were hepatobiliary (18.5%), lower gastrointestinal (17.3%), and breast (16.2%). Topics of discussion at GTB included such things as pathologic/histologic/molecular testing, prioritization of available trials, appropriateness of an off label therapy, and need for a genetics consult. Discussion at GTB resulted in a change in treatment recommendation in 63 (36.4%) cases. Conclusions: Discussions from multidisciplinary molecular tumor board impacted treatment decisions for our patients. Referral to GC was also common and should be considered an integral part of somatic sequencing review. Molecular tumor boards remain a crucial platform for treatment guidance and clinical management, especially given the increase in “actionability” over the years due to newly discovered targets and targeted therapies in this rapidly evolving field.

scholarly journals Indicadores (Outcomes) Primários e Secundários em Ensaios Clínicos Oncológicos: Definição e Usos

2014 ◽  
Vol 27 (4) ◽  
pp. 498
Author(s):  
António Vaz-Carneiro ◽  
Ricardo Da Luz ◽  
Margarida Borges ◽  
João Costa
Keyword(s):  
Clinical Trials ◽  
Methodological Issue ◽  
Objective Response ◽  
Disease Free Survival ◽  
Progression Free Survival ◽  
Free Survival ◽  
Patient Reported ◽  
Oncology Clinical Trials ◽  
Alternative Drug ◽  
Selection Of

<strong>Introduction:</strong> The proof of efficacy from a therapeutic intervention in oncology must be defined through well conducted clinical trials. One of the most important methodological issue is the outcome selection needed to calculate measures of association allowing definition of clinical efficacy.<br /><strong>Material and Methods:</strong> We designed a narrative revision based on some of the international regulatory instructions from drug agencies, as well as consensus papers from scientific oncology societies, listing and critically assessing each outcome used in oncology clinical trials.<br /><strong>Results:</strong> We identified as being the most important outcomes in oncology trials the overall survival, the progression free survival/ disease-free survival, the toxicity, the quality of life/patient- reported outcomes and the objective response rate.<br /><strong>Discussion:</strong> The selection of the primary outcome must be based on therapeutic efficacy as well as toxicity, expected survival, alternative drug regimens and even disease prevalence.<br /><strong>Conclusion:</strong> The selection of efficacy outcomes for clinical trials in oncology is very important and its selection must be well justified, and depends on the type of disease, the patients and the drug being studied.<br /><strong>Keywords:</strong> Clinical Trials as Topic; Neoplasms; Medical Oncology; Treatment Outcome.

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