Implementation of a Molecular Tumor Board in Clinical Decision Making at the Medical Center University of Freiburg

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 3579-3579
Author(s):  
Rainer Claus ◽  
Lisa Lutz ◽  
Hauke Busch ◽  
Leman Mehmed ◽  
Agnes Csanadi ◽  
...  

Abstract Introduction: In-depth knowledge about molecular pathogenesis of malignant diseases and rapidly increasing availability of targeted treatment options enables molecularly guided decision-making. We have established a Molecular Tumor Board (MTB) that focuses on patient management based on specific molecular data at the individual patient level. Methods: The MTB has its main focus on hematologic and solid neoplasias progressing during standard treatment, on rare entities and on patients with treatment resistance. The biweekly MTB supports the work of organ-specific boards and external cooperation partners. The MTB multidisciplinary team consists of expert physicians from Hematology, Medical Oncology, Gynecology, Dermatology, Pediatrics and Radiation Oncology as well as Pathology, Molecular biology, Computational Biology and Genetics. Diagnostic and therapeutic recommendations are based on customized diagnostics and a case-by-case literature review. Recommendations are communicated back to the treating physician. Results: In the first year after implementation of the MTB, a total of 92 pts have been discussed in 155 case discussions during 25 MTB meetings. Referred patient cases covered the entire range of malignancies seen by the organ-specific boards including hematologic malignancies. 132 diagnostic recommendations were made in 80/92 (87%) pts, including IHC, ISH or panel sequencing with diagnostic reporting (n=96/72 pts) and exome, genome, transcriptome and/or methylome analysis (n=24/22 pts.). 43 treatment recommendations were made in 39/92 (42%) pts with an implementation rate of 47% (20/43 recommendations in 19/39 pts). Treatment recommendations mainly comprised off-label antibody and tyrosine kinase inhibitor (TKI) therapy (40%) and trial inclusions (28%). Major reasons for non-adherence to recommendations included patient will, death of pts and medical reasons. Objective responses were observed in 5/19 (26%) pts to TKI in- and off-label and antibody off-label treatments. Disease stabilization was achieved in 3/19 (16%) pts. Specifically, the use of PD-(L)1 inhibiting antibodies was suggested in 13 cases (11 off-label) and implemented in 6 cases. Here, 2/6 pts responded or exhibited stable disease upon PD-(L1) blockage. Conclusion: Implementation of a Molecular Tumor Board serves as an interdisciplinary platform for integrating comprehensive molecular data sets as predictive biomarkers in molecular guided, individualized patient care. Our experience demonstrates that individualized treatment recommendation is feasible and effective for a substantial proportion of patients in challenging clinical situations. Disclosures Claus: Roche: Consultancy, Honoraria; Gilead: Consultancy, Honoraria; Janssen-Cilag: Consultancy, Honoraria, Other: Travel Funding.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 3128-3128
Author(s):  
Meena Sadaps ◽  
Kathryn Demski ◽  
Ying Ni ◽  
Vicky Konig ◽  
Brandie Leach ◽  
...  

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.


Circulation ◽  
2015 ◽  
Vol 131 (suppl_1) ◽  
Author(s):  
Michel Krempf ◽  
Ross J Simpson ◽  
Dena R Ramey ◽  
Philippe Brudi ◽  
Hilde Giezek ◽  
...  

Objectives: Little is known about how patient factors influence physicians’ treatment decision-making in hypercholesterolemia. We surveyed physicians’ treatment recommendations in high-risk patients with LDL-C not controlled on statin monotherapy. Methods: Physicians completed a questionnaire pre-randomization for each patient in a double-blind trial (NCT01154036) assessing LDL-C goal attainment rates with different treatment strategies. Patients had LDL-C ≥100 mg/dL after 5 weeks’ atorvastatin 10 mg/day and before randomization. Physicians were asked about treatment recommendations for three scenarios: (1) LDL-C near goal (100-105 mg/dL), (2) LDL-C far from goal (120 mg/dL), then (3) known baseline LDL-C of enrolled patients on atorvastatin 10 mg/day. Factors considered in their choice were specified. Physicians had been informed of projected LDL-C reductions for each treatment strategy in the trial. Regression analysis identified prognostic factors associated with each scenario, and projected LDL-C values for physicians’ treatment choices were compared to actual LDL-C values achieved in the trial. Results: Physicians at 296 sites completed questionnaires for 1535 patients. The most common treatment strategies for all three scenarios were: 1) not to change therapy, 2) double atorvastatin dose, 3) add ezetimibe, 4) double atorvastatin dose and add ezetimibe. Doubling atorvastatin dose was the most common treatment recommendation in all scenarios (43-52% of patients). ‘No change in therapy’ was recommended in 6.5% of patients when LDL-C was assumed far from goal. Treatment recommendations were more aggressive if actual LDL-C was known or considered far from goal. When compared with the ‘no change in therapy’ recommendation, CV risk factors and desire to achieve a more aggressive LDL-C goal were generally considered in decision-making for each treatment choice, regardless of LDL-C scenario. Patients randomized to a more aggressive regimen than recommended by physicians had larger reductions in LDL-C: the actual reduction in LDL-C in patients randomized to ‘add ezetimibe’ was -20.8% versus a projected reduction of -10.0% when physicians recommended ‘doubling atorvastatin dose’. Conclusions: This study provides insight into physicians’ perspectives on clinical management of hypercholesterolemia and highlights a gap in knowledge translation from guidelines to clinical practice. Targeting lower LDL-C and CV risk were key drivers in clinical decision-making but, generally, physicians were more conservative in their treatment choice than guidelines recommend, which may result in poorer LDL-C reduction. When compared with actual outcomes, projected LDL-C control was better if physicians used more comprehensive strategies rather than simply doubling the statin dose.


2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 11035-11035
Author(s):  
Kristen Marrone ◽  
Jessica Tao ◽  
Jenna VanLiere Canzoniero ◽  
Paola Ghanem ◽  
Emily Nizialek ◽  
...  

11035 Background: The accelerated impact of next generation sequencing (NGS) in clinical decision making requires the integration of cancer genomics and precision oncology focused training into medical oncology education. The Johns Hopkins Molecular Tumor Board (JH MTB) is a multi-disciplinary effort focused on integration of NGS findings with critical evidence interpretation to generate personalized recommendations tailored to the genetic footprint of individual patients. Methods: The JH MTB and the Medical Oncology Fellowship Program have developed a 3-month precision oncology elective for fellows in their research years. Commencing fall of 2020, the goals of this elective are to enhance the understanding of NGS platforms and findings, advance the interpretation and characterization of molecular assay outputs by use of mutation annotators and knowledgebases and ultimately master the art of matching NGS findings with available therapies. Fellow integration into the MTB focuses on mentored case-based learning in mutation characterization and ranking by levels of evidence for actionability, with culmination in form of verbal presentations and written summary reports of final MTB recommendations. A mixed methods questionnaire was administered to evaluate progress since elective initiation. Results: Three learners who have participated as of February 2021 were included. Of the two who had completed the MTB elective, each have presented at least 10 cases, with at least 1 scholarly publication planned. All indicated strong agreement that MTB elective had increased their comfort with interpreting clinical NGS reports as well as the use of knowledgebases and variant annotators. Exposure to experts in the field of molecular precision oncology, identification of resources necessary to interpret clinical NGS reports, development of ability to critically assess various NGS platforms, and gained familiarity with computational analyses relevant to clinical decision making were noted as strengths of the MTB elective. Areas of improvement included ongoing initiatives that involve streamlining variant annotation and transcription of information for written reports. Conclusions: A longitudinal elective in the JHU MTB has been found to be preliminarily effective in promoting knowledge mastery and creating academic opportunities related to the clinical application of precision medicine. Future directions will include leveraging of the MTB infrastructure for research projects, learner integration into computational laboratory meetings, and expansion of the MTB curriculum to include different levels of learners from multiple medical education programs. Continued elective participation will be key to understanding how best to facilitate adaptive expertise in assigning clinical relevance to genomic findings, ultimately improving precision medicine delivery in patient care and trial development.


2020 ◽  
Vol 26 (7) ◽  
pp. 992-994 ◽  
Author(s):  
David Tamborero ◽  
◽  
Rodrigo Dienstmann ◽  
Maan Haj Rachid ◽  
Jorrit Boekel ◽  
...  

2018 ◽  
pp. 1-16 ◽  
Author(s):  
Rouven Hoefflin ◽  
Anna-Lena Geißler ◽  
Ralph Fritsch ◽  
Rainer Claus ◽  
Julius Wehrle ◽  
...  

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.


2017 ◽  
pp. 1-19 ◽  
Author(s):  
W. Brian Dalton ◽  
Patrick M. Forde ◽  
Hyunseok Kang ◽  
Roisin M. Connolly ◽  
Vered Stearns ◽  
...  

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.


Diagnosis ◽  
2014 ◽  
Vol 1 (2) ◽  
pp. 189-193 ◽  
Author(s):  
David Allan Watters ◽  
Spencer Wynyard Beasley ◽  
Wendy Crebbin

AbstractProceduralists who fail to review their decision making are unlikely to learn from their experiences, irrespective of whether the operative outcome is successful or not. Teaching junior surgeons to develop ‘insight’ into their own decision making has long been a challenge. Surgeons and staff of the Royal Australasian College of Surgeons worked together to develop a model to help explain the processes around clinical decision making and incorporated this model into a Clinical Decision Making (CDM) training course. In this course, faculty apply the model to specific surgical cases, within the model’s framework of how clinical decisions are made; thus providing an opportunity to identify specific decision making processes as they occur and to highlight some of the learning opportunities they provide. The conversation in this paper illustrates the kinds of case-based interactions which typically occur in the development and teaching of the CDM course.The focus in this, the second of two papers, is on reviewing post-operative clinical decisions made in relation to one case, to improve the quality of subsequent decision making.


2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e18001-e18001
Author(s):  
Timothy Lewis Cannon ◽  
Donald L. Trump ◽  
Laura Knopp ◽  
Hongkun Wang ◽  
Tiffani DeMarco ◽  
...  

e18001 Background: Patient engagement in medical decision-making improves patient related outcomes through compliance and patient satisfaction. The Inova Schar Cancer Institute (ISCI) has a weekly molecular tumor board (MTB) to match comprehensive genomic sequencing results with targeted therapies for patients. The ISCI MTB invites patients to attend and engage in the MTB discussion. We performed a pilot study to investigate the feasibility and satisfaction in patients who attended MTB. Methods: During the time of this study, August 2017 through October 2018, 139 patients were presented and all 20 who were able to attend MTB completed pre-and post- MTB surveys. Patients who did not attend were either not invited by their primary oncologist, unable to attend, or chose not to attend. The survey included six questions related to comprehension, engagement, and satisfaction with the treatment team. Results: There was a statistically significant change for the question “I am satisfied with how well informed I am about targeted therapy” with p = 0.016. All 20 patients answered positively that it was beneficial for them to attend. Many patients expressed concerns about their difficulty understanding the technical aspects of the meeting. Conclusions: Patients who attended MTB reported a higher level of satisfaction after MTB attendance as compared to before MTB. This may reflect a sense of engagement in shared decision making rather than comprehension of genomic information. A more holistic method of studying this practice would include sampling a larger patient population and a formal evaluation of the physicians’ experience with patients attending. Supported by philanthropic funds from the Inova Schar Cancer Institute.


Cancers ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 1151
Author(s):  
Rouven Hoefflin ◽  
Adriana Lazarou ◽  
Maria Elena Hess ◽  
Meike Reiser ◽  
Julius Wehrle ◽  
...  

Molecular precision oncology faces two major challenges: first, to identify relevant and actionable molecular variants in a rapidly changing field and second, to provide access to a broad patient population. Here, we report a four-year experience of the Molecular Tumor Board (MTB) of the Comprehensive Cancer Center Freiburg (Germany) including workflows and process optimizations. This retrospective single-center study includes data on 488 patients enrolled in the MTB from February 2015 through December 2018. Recommendations include individual molecular diagnostics, molecular stratified therapies, assessment of treatment adherence and patient outcomes including overall survival. The majority of MTB patients presented with stage IV oncologic malignancies (90.6%) and underwent an average of 2.1 previous lines of therapy. Individual diagnostic recommendations were given to 487 patients (99.8%). A treatment recommendation was given in 264 of all cases (54.1%) which included a molecularly matched treatment in 212 patients (43.4%). The 264 treatment recommendations were implemented in 76 patients (28.8%). Stable disease was observed in 19 patients (25.0%), 17 had partial response (22.4%) and five showed a complete remission (6.6%). An objective response was achieved in 28.9% of cases with implemented recommendations and for 4.5% of the total population (22 of 488 patients). By optimizing the MTB workflow, case-discussions per session increased significantly while treatment adherence and outcome remained stable over time. Our data demonstrate the feasibility and effectiveness of molecular-guided personalized therapy for cancer patients in a clinical routine setting showing a low but robust and durable disease control rate over time.


2020 ◽  
Author(s):  
Frank P.Y. Lin

AbstractBACKGROUNDThe advances in genome sequencing technologies have provided new opportunities for delivering targeted therapy to patients with advanced cancer. However, these high-throughput assays have also created a multitude of challenges for oncologists in treatment selection, demanding a new approach to support decision-making in clinics.METHODSTo address this unmet need, this paper describes the design of a symbolic reasoning framework using the method of hierarchical task analysis. Based on this framework, an evidence-based treatment recommendation system was implemented for supporting decision-making based on a patient’s clinicopathologic and biomarker profiles.RESULTSThis intelligent framework captures a six-step sequential decision process: (1) concept expansion by ontology matching, (2) evidence matching, (3) evidence grading and value-based prioritisation, (4) clinical hypothesis generation, (5) recommendation ranking, and (6) recommendation filtering. The importance of balancing evidence-based and hypothesis-driven treatment recommendations is also highlighted. Of note, tracking history of inference has emerged to be a critical step to allow rational prioritisation of recommendations. The concept of inference tracking also enables the derivation of a novel measure — level of matching — that helps to convey whether a treatment recommendation is drawn from incomplete knowledge during the reasoning process.CONCLUSIONSThis framework systematically encapsulates oncologist’s treatment decisionmaking process. Further evaluations in prospective clinical studies are warranted to demonstrate how this computational pipeline can be integrated into oncology practice to improve outcomes.


Sign in / Sign up

Export Citation Format

Share Document