Comparison of Treatment Recommendations by Molecular Tumor Boards Worldwide

Purpose Precision oncology holds the promise of improving patient outcome. It is based on the idea that the testing of genomic biomarkers can lead to the recommendation of a treatment option tailored to the specific patient. To derive treatment recommendations from molecular profiles, interdisciplinary molecular tumor boards (MTBs) have been established recently in many academic institutions. The recommendation process in MTBs, however, has not been well defined, which limits applicability to larger clinical trials and patient populations. Methods We created four fictional patients on the basis of recent real cases with genomic information on mutations, fusions, copy numbers, and gene expression. We identified 29 tumor boards from nine countries worldwide and asked them to provide treatment recommendations for the sample patients. In addition, a questionnaire regarding the setup and methods used by MTBs was circulated. Results Five MTBs from four countries provided treatment recommendations and answered the questionnaire. For one patient, three tumor board treatment recommendations were identical, and two tumor boards had identical treatment strategies for the other three patients. There was heterogeneity in the interpretation of tumor and germline aberrations as well as in standards of prioritization. Conclusion Differences in the interpretation and recommendation process contribute to heterogeneity in MTB recommendations. Additional comparative analyses of recommendations could help improve rational decision making and lead to standardization.

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INNV-08. LOW AND INTERMEDIATE GRADE GLIOMA UMBRELLA STUDY OF MOLECULAR GUIDED THERAPIES (LUMOS) STUDY

Neuro-Oncology ◽

10.1093/neuonc/noab196.420 ◽

2021 ◽

Vol 23 (Supplement_6) ◽

pp. vi106-vi107

Author(s):

Benjamin Kong ◽

Hao-Wen Sim ◽

Benhur Amanuel ◽

Bryan Day ◽

Michael Buckland ◽

...

Keyword(s):

Targeted Therapies ◽

Lag Time ◽

Turnaround Time ◽

Molecular Data ◽

Tumor Board ◽

Advisory Panel ◽

Precision Oncology ◽

Genomic Information ◽

Tissue Samples ◽

Met Amplification

Abstract BACKGROUND Grade 2 and 3 (G2/3) gliomas are the second largest group of brain tumors in adults. Although the prognosis for G2/3 gliomas at the time of relapse mirror those of glioblastoma, there are few trials in this space. METHODS LUMOS was a national multi-center pilot study for patients with relapsed G2/3 gliomas designed to match contemporaneous tissue obtained at the time of disease progression with subsequent targeted therapies. The objective was to establish the feasibility of a precision oncology, umbrella approach to obtain and type tissue within a useful timeframe. As a key feature of LUMOS, a multidisciplinary Molecular Tumor Advisory Panel (MTAP) with subspecialty neuro-oncology expertise was formed to interpret the complex genomic information and provide a simplified recommendation to the treating physician. RESULTS Ten patients (median age 42: range 32-62; four G2 astrocytoma, one G3 astrocytoma, three G2 oligoendroglioma, one G3 oligodendroglioma, one mixed tumor) were enrolled in the study. Eight patients had biopsies within 6 months of study entry whilst two underwent a biopsy during the study. All patients had potentially targetable alterations (10 IDH, 3 FGFR, 2 PIK3K, CCND3, NRAS, CDK4, PRPRZ1-MET fusion and MET amplification). Matched therapies were delivered for two patients via compassionate access outside the study. The median turnaround time (TAT) of MTAP reports was 6.2 weeks (range 4.2-9.7 weeks) but 4.6 weeks when lag time for shipping was removed. CONCLUSION LUMOS confirmed that this design was feasible with good turnaround times. The MTAP facilitated education and support for treating physicians. Thes findings support moving to a larger study using contemporaneous and longitudinal tissue samples matched with targeted therapies as part of a comprehensive umbrella study design. Delivery and interpretation of molecular data is a challenge shared across oncology which may be mitigated with a neuro-oncology specific molecular tumor board.

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Präzisionsonkologie und molekulare Tumorboards – Konzepte, Chancen und Herausforderungen

DMW - Deutsche Medizinische Wochenschrift ◽

10.1055/s-0042-120717 ◽

2017 ◽

Vol 142 (22) ◽

pp. 1676-1684 ◽

Cited By ~ 2

Author(s):

Julian Holch ◽

Christoph Westphalen ◽

Wolfgang Hiddemann ◽

Volker Heinemann ◽

Andreas Jung ◽

...

Keyword(s):

Clinical Trials ◽

Genetic Analysis ◽

Treatment Strategies ◽

Standard Of Care ◽

Tumor Board ◽

Precision Oncology ◽

Current Standard ◽

Recent Developments ◽

Tumor Types ◽

New Strategies

AbstractRecent developments in genomics allow a more and more comprehensive genetic analysis of human malignancies, and have sparked hopes that this will contribute to the development of novel targeted, effective and well-tolerated therapies.While targeted therapies have improved the prognosis of many cancer patients with certain tumor types, “precision oncology” also brings along new challenges. Highly personalized treatment strategies require new strategies for clinical trials and translation into routine clinical practice. We review the current technical approaches for “universal genetic testing” in cancer, and potential pitfalls in the interpretation of such data. We then provide an overview of the available evidence supporting treatment strategies based on extended genetic analysis. Based on the available data, we conclude that “precision oncology” approaches that go beyond the current standard of care should be pursued within the framework of an interdisciplinary “molecular tumor board”, and preferably within clinical trials.

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Implementation of Precision Oncology for Patients with Metastatic Breast Cancer in an Interdisciplinary MTB Setting

Diagnostics ◽

10.3390/diagnostics11040733 ◽

2021 ◽

Vol 11 (4) ◽

pp. 733

Author(s):

Elena Sultova ◽

C. Benedikt Westphalen ◽

Andreas Jung ◽

Joerg Kumbrink ◽

Thomas Kirchner ◽

...

Keyword(s):

Breast Cancer ◽

Metastatic Breast Cancer ◽

Molecular Diagnostics ◽

Metastatic Breast ◽

Treatment Recommendations ◽

Tumor Board ◽

Precision Oncology ◽

Survival Ratio ◽

Molecular Alteration ◽

Gene Panel Testing

The advent of molecular diagnostics and the rising number of targeted therapies have facilitated development of precision oncology for cancer patients. In order to demonstrate its impact for patients with metastatic breast cancer (mBC), we initiated a Molecular Tumor Board (MTB) to provide treatment recommendations for mBC patients who had disease progression under standard treatment. NGS (next generation sequencing) was carried out using the Oncomine multi-gene panel testing system (Ion Torrent). The MTB reviewed molecular diagnostics’ results, relevant tumor characteristics, patient’s course of disease and made personalized treatment and/or diagnostic recommendations for each patient. From May 2017 to December 2019, 100 mBC patients were discussed by the local MTB. A total 72% of the mBC tumors had at least one molecular alteration (median 2 per case, range: 1 to 6). The most frequent genetic changes were found in the following genes: PIK3CA (19%) and TP53 (17%). The MTB rated 53% of these alterations as actionable and treatment recommendations were made accordingly for 49 (49%) patients. Sixteen patients (16%) underwent the suggested therapy. Nine out of sixteen patients (56%; 9% of all) experienced a clinical benefit with a progression-free survival ratio ≥ 1.3. Personalized targeted therapy recommendations resulting from MTB case discussions could provide substantial benefits for patients with mBC and should be implemented for all suitable patients.

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

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.3128 ◽

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.

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Virtual Clinical and Precision Medicine Tumor Boards: A Cloud-based Platform-mediated Implementation of Multidisciplinary Reviews among Oncology Centers in the Covid-19 Era. (Preprint)

10.2196/preprints.26220 ◽

2020 ◽

Author(s):

Livio Blasi ◽

Roberto Bordonaro ◽

Vincenzo Serretta ◽

Dario Piazza ◽

Alberto Firenze ◽

...

Keyword(s):

Decision Making ◽

Health Professionals ◽

Clinical Pathways ◽

Prospective Trial ◽

Banking System ◽

Outcome Data ◽

Tumor Board ◽

Time Saving ◽

Tumor Boards ◽

Multidisciplinary Tumor Board

BACKGROUND Multidisciplinary tumor boards play a pivotal role in the patients -centered clinical management and in the decision-making process to provide best evidence -based, diagnostic and therapeutic care to cancer patients. Among the barriers to achieve an efficient multidisciplinary tumor board, lack of time and geographical distance play a major role. Therefore the elaboration of an efficient virtual multidisciplinary tumor board (VMTB) is a key-point to reach a successful oncology team and implement a network among health professionals and institutions. This need is stronger than ever in a Covid-19 pandemic scenario. OBJECTIVE This paper presents a research protocol for an observational study focused on exploring the structuring process and the implementation of a multi-institutional VMTB in Sicily. Other endpoints include analysis of cooperation between participants, adherence to guidelines, patients’ outcomes, and patients satisfaction METHODS This protocol encompasses a pragmatic, observational, multicenter, non-interventional, prospective trial. The study's programmed duration is five years, with a half-yearly analysis of the primary and secondary objectives' measurements. Oncology care health-professionals from various oncology subspecialties at oncology departments in multiple hospitals (academic and general hospitals as well as tertiary centers and community hospitals) are involved in a non-hierarchic fashion. VMTB employ an innovative, virtual, cloud-based platform to share anonymized medical data which are discussed via a videoconferencing system both satisfying security criteria and HIPAA compliance. RESULTS The protocol is part of a larger research project on communication and multidisciplinary collaboration in oncology units and departments spread in the Sicily region in Italy. Results of this study will particularly focus on the organization of VMTB involving oncology units present in different hospitals spread in the area and create a network to allow best patients care pathways and a hub and spoke relationship. Results will also include data concerning organization skills and pitfalls, barriers, efficiency, number and type con clinical cases, and customers’ satisfaction. CONCLUSIONS VMTB represents a unique opportunity to optimize patient’s management in a patient centered approach. An efficient virtualization and data banking system is potentially time-saving, a source for outcome data, and a detector of possible holes in the hull of clinical pathways. The observations and results from this VMTB study may hopefully useful to design nonclinical and organizational interventions that enhance multidisciplinary decision-making in oncology.

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Molecular Subtypes and Precision Oncology in Intrahepatic Cholangiocarcinoma

Journal of Clinical Medicine ◽

10.3390/jcm10132803 ◽

2021 ◽

Vol 10 (13) ◽

pp. 2803

Author(s):

Carolin Czauderna ◽

Martha M. Kirstein ◽

Hauke C. Tews ◽

Arndt Vogel ◽

Jens U. Marquardt

Keyword(s):

Clinical Care ◽

Treatment Options ◽

Treatment Strategies ◽

Specific Treatment ◽

Growth Factor Receptor ◽

Treatment Modalities ◽

Precision Oncology ◽

Recurrence Rates ◽

Isocitrate Dehydrogenase 1 ◽

Liver Cancers

Cholangiocarcinomas (CCAs) are the second-most common primary liver cancers. CCAs represent a group of highly heterogeneous tumors classified based on anatomical localization into intra- (iCCA) and extrahepatic CCA (eCCA). In contrast to eCCA, the incidence of iCCA is increasing worldwide. Curative treatment strategies for all CCAs involve oncological resection followed by adjuvant chemotherapy in early stages, whereas chemotherapy is administered at advanced stages of disease. Due to late diagnosis, high recurrence rates, and limited treatment options, the prognosis of patients remains poor. Comprehensive molecular characterization has further revealed considerable heterogeneity and distinct prognostic and therapeutic traits for iCCA and eCCA, indicating that specific treatment modalities are required for different subclasses. Several druggable alterations and oncogenic drivers such as fibroblast growth factor receptor 2 gene fusions and hotspot mutations in isocitrate dehydrogenase 1 and 2 mutations have been identified. Specific inhibitors have demonstrated striking antitumor activity in affected subgroups of patients in phase II and III clinical trials. Thus, improved understanding of the molecular complexity has paved the way for precision oncological approaches. Here, we outline current advances in targeted treatments and immunotherapeutic approaches. In addition, we delineate future perspectives for different molecular subclasses that will improve the clinical care of iCCA patients.

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Impact of Molecular Tumor Board (MTB) on precision oncology in a community setting

Gynecologic Oncology ◽

10.1016/s0090-8258(21)00987-2 ◽

2021 ◽

Vol 162 ◽

pp. S180

Author(s):

Adam ElNaggar ◽

Gregory Vidal ◽

Ari VanderWalde ◽

Lee Schwartzberg ◽

Axel Grothey ◽

...

Keyword(s):

Community Setting ◽

Tumor Board ◽

Precision Oncology ◽

Molecular Tumor Board

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CATCH: A Prospective Precision Oncology Trial in Metastatic Breast Cancer

JCO Precision Oncology ◽

10.1200/po.20.00248 ◽

2021 ◽

pp. 676-686

Author(s):

Mario Hlevnjak ◽

Markus Schulze ◽

Shaymaa Elgaafary ◽

Carlo Fremd ◽

Laura Michel ◽

...

Keyword(s):

Breast Cancer ◽

Metastatic Breast Cancer ◽

Clinical Management ◽

Metastatic Breast ◽

Previous Treatment ◽

Progression Free Survival ◽

Tumor Board ◽

Precision Oncology ◽

Whole Genome ◽

Free Survival

PURPOSE CATCH (Comprehensive Assessment of clinical feaTures and biomarkers to identify patients with advanced or metastatic breast Cancer for marker driven trials in Humans) is a prospective precision oncology program that uses genomics and transcriptomics to guide therapeutic decisions in the clinical management of metastatic breast cancer. Herein, we report our single-center experience and results on the basis of the first 200 enrolled patients of an ongoing trial. METHODS From June 2017 to March 2019, 200 patients who had either primary metastatic or progressive disease, with any number of previous treatment lines and at least one metastatic site accessible to biopsy, were enrolled. DNA and RNA from tumor tissue and corresponding blood-derived nontumor DNA were profiled using whole-genome and transcriptome sequencing. Identified actionable alterations were brought into clinical context in a multidisciplinary molecular tumor board (MTB) with the aim of prioritizing personalized treatment recommendations. RESULTS Among the first 200 enrolled patients, 128 (64%) were discussed in the MTB, of which 64 (50%) were subsequently treated according to MTB recommendation. Of 53 evaluable patients, 21 (40%) achieved either stable disease (n = 13, 25%) or partial response (n = 8, 15%). Furthermore, 16 (30%) of those patients showed improvement in progression-free survival of at least 30% while on MTB-recommended treatment compared with the progression-free survival of the previous treatment line. CONCLUSION The initial phase of this study demonstrates that precision oncology on the basis of whole-genome and RNA sequencing is feasible when applied in the clinical management of patients with metastatic breast cancer and provides clinical benefit to a substantial proportion of patients.

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Integrating molecular profiles into clinical frameworks through the Molecular Oncology Almanac to prospectively guide precision oncology

Nature Cancer ◽

10.1038/s43018-021-00243-3 ◽

2021 ◽

Author(s):

Brendan Reardon ◽

Nathanael D. Moore ◽

Nicholas S. Moore ◽

Eric Kofman ◽

Saud H. AlDubayan ◽

...

Keyword(s):

Point Of Care ◽

Single Gene ◽

Knowledge Bases ◽

Computational Method ◽

Precision Oncology ◽

Clinical Interpretation ◽

First Order ◽

Molecular Features ◽

Molecular Oncology ◽

Molecular Profiles

AbstractTumor molecular profiling of single gene-variant (‘first-order’) genomic alterations informs potential therapeutic approaches. Interactions between such first-order events and global molecular features (for example, mutational signatures) are increasingly associated with clinical outcomes, but these ‘second-order’ alterations are not yet accounted for in clinical interpretation algorithms and knowledge bases. We introduce the Molecular Oncology Almanac (MOAlmanac), a paired clinical interpretation algorithm and knowledge base to enable integrative interpretation of multimodal genomic data for point-of-care decision making and translational-hypothesis generation. We benchmarked MOAlmanac to a first-order interpretation method across multiple retrospective cohorts and observed an increased number of clinical hypotheses from evaluation of molecular features and profile-to-cell line matchmaking. When applied to a prospective precision oncology trial cohort, MOAlmanac nominated a median of two therapies per patient and identified therapeutic strategies administered in 47% of patients. Overall, we present an open-source computational method for integrative clinical interpretation of individualized molecular profiles.

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Real-world experience of treatment decision-making in carotid stenosis in a neurovascular board

Neurology ◽

10.1212/wnl.0000000000004151 ◽

2017 ◽

Vol 89 (4) ◽

pp. 399-407 ◽

Cited By ~ 3

Author(s):

David Leander Rimmele ◽

Axel Larena-Avellaneda ◽

Anna C. Alegiani ◽

Michael Rosenkranz ◽

Nils Ole Schmidt ◽

...

Keyword(s):

Decision Making ◽

Carotid Artery ◽

Medical Management ◽

Treatment Strategies ◽

Treatment Decision ◽

Treatment Recommendations ◽

Adherence To Treatment ◽

Treatment Decision Making ◽

Time Period ◽

Ica Stenosis

Objective:To describe our experience with consensus-based decision-making for treatment of internal carotid artery (ICA) stenosis by neurologists, interventional neuroradiologists, vascular surgeons, and neurosurgeons in a multidisciplinary neurovascular board and to study adherence to treatment recommendations in the context of uncertainty with respect to the best treatment option.Methods:We established a multidisciplinary neurovascular board meeting twice a week with structured documentation of consensus decisions. Over a time period of 53 months, 614 cases with ICA stenosis were discussed, with 285 (46%) symptomatic and 279 (45%) asymptomatic cases.Results:Recommendation for symptomatic ICA stenosis was revascularization in 76%, medical management alone in 8%, and further diagnostics in 16%. For asymptomatic ICA stenosis, recommendation was randomization in a clinical trial in 29%, revascularization in 27%, medical management alone in 23%, and further diagnostics in 22%. Treatment recommendations were followed in 94% of symptomatic ICA stenosis and 69% of asymptomatic ICA stenosis. Patients in whom carotid artery stenting was recommended for revascularization were younger and showed a higher rate of severe (≥70%) ICA stenosis.Conclusions:Interdisciplinary board decisions are a helpful and transparent tool to assure adherence to guideline recommendations, and to provide consensus-based individualized treatment strategies in clinical practice in the absence of unequivocal evidence.

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