Importance of critical evaluation of genomic findings reported following comprehensive tumor molecular profiling (CTMP) for discussion within molecular tumor boards (MTB).
Authors: Lebedeva Alexandra , Ivanov Maxim , Kuznetsova Olesya , Sharova Margarita , Ignatova Ekaterina , Tryakin Alexey , Mileyko Vladislav , Fedyanin Mikhail , Nosov Dmitry 
Published: June 2022

e18623

Background: As precision oncology evolves, a growing number of physicians refer cancer patients for CTMP. Oftentimes, CTMP cannot be performed at local centers and patients turn to third-party facilities or commercial solutions. CTMP findings summarized in molecular profiling reports are used by physicians as a basis for MTB. Methods: A molecular tumor board was developed at our cancer center for patients who had undergone CTMP via NGS. Before each MTB, experts in cancer biology and bioinformatics performed reported alteration annotation, interpretation and critical evidence evaluation for each patient, not taking into account the recommendations provided in the original CTMP reports. Results: In total, 29 patients with various tumor types (31% CRC, 25% NSCLC, 10% SOC, 8% Breast; 26% other) who had undergone CTMP in a third-party for-profit organization (2 international, 4 Russian based organizations) were evaluated for discussion at MTB. In 4 CTMP reports therapy recommendations were compiled at odds with principles of evidence-based medicine and did not contain information on detected molecular alteration and, thus, these patients were not discussed within MTB. In 48% (12/25) of reports discussed within MTB, ranking of genomic findings based on potential clinical evidence and actionability was not provided. 24% (6/25) of the reports did not comply with the ASCO recommendations on genomic findings reporting in oncology. In 8 (32%) reports, only drug classes and not specific drugs were recommended. A total of 362 alterations were identified in 25 CTMP reports. Of those, 93 (26%) were not annotated according to the well-established HGVS nomenclature of sequence variants. Out of these 93, 32 (34%) could not be further identified using various genomic tools. Following our interpretation of the reported variants, 16 (4.4%) of the reported variants were found to be benign and, in fact, well-established population polymorphisms (gnomAD MAF > 1%). Only in 40% (10/25) of the reports, genomic alterations were classified based on their origin (somatic/likely germline). For 10 patients, 18 additional therapy options were recommended. Finally, 3-4 hours of preparatory work was required in order to reevaluate the reported findings following CTMP. Conclusions: As tumor molecular profiling becomes a more available tool for precision oncology, the number of patients requiring treatment strategy correction increases. Specific treatment plans can be set up following a discussion within a multidisciplinary team at MTB. Due to the lack of standardization of molecular profiling reporting, thorough preparatory work by experts trained in cancer biology is required before each MTB. Such preliminary work ensures time efficient discussion at MTB, requiring no more than 15 minutes of the physician’s time.