Real-World Data From a Molecular Tumor Board: Improved Outcomes in Breast and Gynecologic Cancers Patients With Precision Medicine

PURPOSE Next-generation sequencing is increasingly used in gynecologic and breast cancers. Multidisciplinary Molecular Tumor Board (MTB) may guide matched therapy; however, outcome data are limited. We evaluate the effect of the degree of matching of tumors to treatment as well as compliance to MTB recommendations on outcomes. METHODS Overall, 164 patients with consecutive gynecologic and breast cancers presented at MTB were assessed for clinicopathologic data, next-generation sequencing results, MTB recommendations, therapy received, and outcomes. Matching score (MS), defined as percentage of alterations targeted by treatment over total pathogenic alterations, and compliance to MTB recommendations were analyzed in context of oncologic outcomes. RESULTS Altogether, 113 women were evaluable for treatment after MTB; 54% received matched therapy. Patients with MS ≥ 40% had higher overall response rate (30.8% v 7.1%; P = .001), progression-free survival (PFS; hazard ratio [HR] 0.51; 95% CI, 0.31 to 0.85; P = .002), and a trend toward improved overall survival (HR 0.64; 95% CI, 0.34 to 1.25; P = .082) in univariate analysis. The PFS advantage remained significant in multivariate analysis (HR 0.5; 95% CI, 0.3 to 0.8; P = .006). Higher MTB recommendation compliance was significantly associated with improved median PFS (9.0 months for complete; 6.0 months for partial; 4.0 months for no compliance; P = .004) and overall survival (17.1 months complete; 17.8 months partial; 10.8 months none; P = .046). Completely MTB-compliant patients had higher MS ( P < .001). In multivariate analysis comparing all versus none MTB compliance, overall response (HR 9.5; 95% CI, 2.6 to 35.0; P = .001) and clinical benefit (HR 8.8; 95% CI, 2.4 to 33.2; P = .001) rates were significantly improved with higher compliance. CONCLUSION Compliance to MTB recommendations resulted in higher degrees of matched therapy and correlates with improved outcomes in patients with gynecologic and breast cancers.

The molecular tumor board: a tool for the governance of precision oncology in the real world

Clinical oncology is going through a period of profound change. Targeted therapy, and more recently immunotherapy, have revolutionized the natural history and outcomes of many solid tumors. Clinical oncology is now indissoluble from molecular oncology, a rapidly evolving field. This profound transformation is the rationale for molecular tumor board (MTB) implementation. MTBs represent a resource for the development of precision oncology and clinical practice implementation is a complex and important challenge for the future of clinical and molecular oncology. Economic sustainability of genomic tests, access to drugs or clinical trials according to the MTB recommendation, and expanded use of existing anticancer drugs are required for MTBs to become a useful tool for the governance of precision oncology in the real world. This is an ongoing process, with establishment of MTBs the first step. Continuing to work in collaboration with scientific societies, MTBs are poised to become a homogeneous and well-structured reality that can make the care pathway of the patient with cancer more efficient, with the ultimate goal to offer personalized therapy based on the most advanced scientific knowledge.

Enhancing Cancer care of rural dwellers through telehealth and engagement (ENCORE): protocol to evaluate effectiveness of a multi-level telehealth-based intervention to improve rural cancer care delivery

Background Despite lower cancer incidence rates, cancer mortality is higher among rural compared to urban dwellers. Patient, provider, and institutional level factors contribute to these disparities. The overarching objective of this study is to leverage the multidisciplinary, multispecialty oncology team from an academic cancer center in order to provide comprehensive cancer care at both the patient and provider levels in rural healthcare centers. Our specific aims are to: 1) evaluate the clinical effectiveness of a multi-level telehealth-based intervention consisting of provider access to molecular tumor board expertise along with patient access to a supportive care intervention to improve cancer care delivery; and 2) identify the facilitators and barriers to future larger scale dissemination and implementation of the multi-level intervention. Methods Coordinated by a National Cancer Institute-designated comprehensive cancer center, this study will include providers and patients across several clinics in two large healthcare systems serving rural communities. Using a telehealth-based molecular tumor board, sequencing results are reviewed, predictive and prognostic markers are discussed, and treatment plans are formulated between expert oncologists and rural providers. Simultaneously, the rural patients will be randomized to receive an evidence-based 6-week self-management supportive care program, Cancer Thriving and Surviving, versus an education attention control. Primary outcomes will be provider uptake of the molecular tumor board recommendation and patient treatment adherence. A mixed methods approach guided by the Consolidated Framework for Implementation Research that combines qualitative key informant interviews and quantitative surveys will be collected from both the patient and provider in order to identify facilitators and barriers to implementing the multi-level intervention. Discussion The proposed study will leverage information technology-enabled, team-based care delivery models in order to deliver comprehensive, coordinated, and high-quality cancer care to rural and/or underserved populations. Simultaneous attention to institutional, provider, and patient level barriers to quality care will afford the opportunity for us to broadly share oncology expertise and develop dissemination and implementation strategies that will enhance the cancer care delivered to patients residing within underserved rural communities. Trial registration Clinicaltrials.gov, NCT04758338. Registered 17 February 2021 – Retrospectively registered, http://www.clinicaltrials.gov/

Challenges and Experiences Extending the cBioPortal for Cancer Genomics to a Molecular Tumor Board Platform

In Molecular Tumor Boards (MTBs), therapy recommendations for cancer patients are discussed. To aid decision-making based on the patient’s molecular profile, the research platform cBioPortal was extended based on users’ requirements. Additionally, a comprehensive dockerized workflow was developed to support the deployment of cBioPortal and connected services. In this work, we present the challenges and experiences of nearly two years of implementing and deploying an MTB platform based on cBioPortal and compare those to findings of a previous study.

Molecular Tumor Board

A tumor board is a meeting made up of specialized doctors and other health care providers who regularly gather to discuss cancer cases that are unusual and/or challenging. The goal is to decide on the best possible treatment plan for a patient as a group. This has become a very systematic method in cancer care and is useful in picking up all the available information about the patients, inputs of all concerned doctors and other health care personnels. Molecular Tumour boards are where the molecular informaion about the patients are discussed.

Molecular profiling of advanced solid tumours. The impact of experimental molecular-matched therapies on cancer patient outcomes in early-phase trials: the MAST study

Introduction Molecular-matched therapies have revolutionized cancer treatment. We evaluated the improvement in clinical outcomes of applying an in-house customized Next Generation Sequencing panel in a single institution. Methods Patients with advanced solid tumors were molecularly selected to receive a molecular-matched treatment into early phase clinical trials versus best investigators choice, according to the evaluation of a multidisciplinary molecular tumor board. The primary endpoint was progression-free survival (PFS) assessed by the ratio of patients presenting 1.3-fold longer PFS on matched therapy (PFS2) than with prior therapy (PFS1). Results Of a total of 231 molecularly screened patients, 87 were eligible for analysis. Patients who received matched therapy had a higher median PFS2 (6.47 months; 95% CI, 2.24–14.43) compared to those who received standard therapy (2.76 months; 95% CI, 2.14–3.91, Log-rank p = 0.022). The proportion of patients with a PFS2/PFS1 ratio over 1.3 was significantly higher in the experimental arm (0.33 vs 0.08; p = 0.008). Discussion We demonstrate the pivotal role of the institutional molecular tumor board in evaluating the results of a customized NGS panel. This process optimizes the selection of available therapies, improving disease control. Prospective randomized trials are needed to confirm this approach and open the door to expanded drug access.