Implementation of a Molecular Tumor Board in Clinical Decision Making at the Medical Center University of Freiburg
Authors: Claus Rainer , Lutz Lisa , Busch Hauke , Mehmed Leman , Csanadi Agnes , Weddeling Britta , Fritsch Ralph , Brummer Tilman , Wehrle Julius , Miething Cornelius , Erbes Thalia , Hettmer Simone , Brass Volker , Oehlke Oliver , Demmer Philipp , Meiss Frank , Peters Christoph , Werner Martin , Börries Melanie , Lassmann Silke , Duyster Justus , von Bubnoff Nikolas 
Published: November 2019

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.