Transitioning the Molecular Tumor Board from Proof of Concept to Clinical Routine: A German Single-Center Analysis

Abstract

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.

Combined Focused Next-Generation Sequencing Assays to Guide Precision Oncology in Solid Tumors: A Retrospective Analysis from an Institutional Molecular Tumor Board

“…Despite the use of a focused approach to gene diagnostics that did not require high-throughput sequencing equipment, our MTB was able to suggest further rational treatments in about 75% of patients. The rates of implementation of the suggested therapies (approximately 32%) and patient benefits (approximately 10%) lay within the same ranges of previously published reports of other precision-oncology programs [ 13 , 17 , 18 , 19 , 20 , 21 ].…”

“…Even though the superiority of MTTs over conventional therapies is well documented within most approved indications, the concept of tissue-agnostic precision oncology and its utility across tumor types remains to be fully elucidated [ 13 , 14 ]. In particular, even with extensive NGS covering > 200 genes or the complete exome, less than 10% of patients experienced some kind of clinical benefit with MTTs according to recent reports [ 13 , 15 , 16 , 17 , 18 , 19 , 20 , 21 ]. The limited efficacy of precision oncology [ 22 , 23 ] is obviously contradictory to the expenditures for broad molecular profiling, as reported prices for NGS diagnostics range from EUR 500 to more than EUR 20,000 depending on the panel used [ 24 , 25 , 26 , 27 ].…”

“…NGS was supplemented by immunohistochemistry (IHC) staining for programmed death-ligand 1 (PD-L1) and mismatch repair deficiency (MMRD)/microsatellite instability (MSI). Thus, our diagnostic core package focused on well-characterized and actionable molecular alterations, mostly targetable with drugs approved by EMA, while previously published precision oncology programs established diagnostic workflows based on larger gene panels, including up to 1700 genes or whole-exome sequencing (WES) [ 16 , 17 , 19 , 35 , 36 , 37 ]. The results and potential therapeutic options were discussed in the Molecular Tumor Board (MTB) by a panel of experts, including medical oncologists, pathologists, molecular biologists and other physicians from various specialties.…”

Molecular diagnostics and therapies for gastrointestinal tumors: a real-world experience

“…Now, the molecular pathologist is becoming more visible in daily clinical practice, as informed clinical decision making warrants the careful evaluation and interpretation of sequencing results. The importance of this interaction is reflected by the growing number of molecular tumor boards (Hoefflin et al 2021 ).…”

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

“…These data are fundamentally important in the context of Molecular Tumor Boards (MTBs), where experts from different fields, like oncology, bioinformatics, and systems medicine, jointly discuss therapy options for cancer patients based on molecular data. While these advancements have demonstrated their potential to improve patient outcomes already [2,3], the management, analysis, and interpretation of these data poses a challenge to traditional healthcare systems. In research, however, several software tools supporting data processing and interpretation exist, one of which is the cBioPortal for Cancer Genomics [4,5] developed by the Memorial Sloan Kettering Cancer Center (MSKCC).…”