Implementation and Clinical Utility of an Integrated Academic-Community Regional Molecular Tumor Board

Abstract

Purpose Precision oncology develops and implements evidence-based personalized therapies that are based on specific genetic targets within each tumor. However, a major challenge that remains is the provision of a standardized, up-to-date, and evidenced-based precision medicine initiative across a geographic region. Materials and Methods We developed a statewide molecular tumor board that integrates academic and community oncology practices. The Precision Medicine Molecular Tumor Board (PMMTB) has three components: a biweekly Web-based teleconference tumor board meeting provided as a free clinical service, an observational research registry, and a monthly journal club to establish and revise evidence-based guidelines for off-label therapies. The PMMTB allows for flexible and rapid implementation of treatment, uniformity in practice, and the ability to track outcomes. Results We describe the implementation of the PMMTB and its first year of activity. Seventy-seven patient cases were presented, 48 were enrolled in a registry, and 38 had recommendations and clinical follow-up. The 38 subjects had diverse solid tumors (lung, 45%; GI, 21%; breast, 13%; other, 21%). Of these subjects, targeted therapy was recommended for 32 (84%). Clinical trials were identified for 24 subjects (63%), and nontrial targeted medicines for 16 (42%). Nine subjects (28%) received recommended therapy with a response rate of 17% (one of six) and a clinical benefit rate (partial response + stable disease) of 38% (three of eight). Although clinical trials often were identified, patients rarely enrolled. Conclusion The PMMTB provides a model for a regional molecular tumor board with clinical utility. This work highlights the need for outcome registries and improved access to clinical trials to pragmatically implement precision oncology.

The rise of rapid implementation: a worked example of solving an existing problem with a new method by combining concept analysis with a systematic integrative review

“…However, the assessment of literature reviews meant that not all of the criteria were applicable thus lowering assessment scores for these specific studies on the QAT 49]. The antecedents for rapid implementation are clinical practice antecedents e.g., precision medicine [43][44][45][46][47]55], and are being viewed across the biomedical enterprise, such as molecular immunohaematology (molecular oncology) [46], molecular profiling (oncology) [45], molecular tumour boards (precision oncology) [55], and genotyping (biostatistics) [44]. These are rapidly evolving areas that require rapid deployment of actionable data.…”

“…The fundamental basis of rapid implementation is clinical practicewith its need for fast information on which to base good clinical decisions. It is exemplified here by precision medicine, which is amongst those areas leading the field in the application of rapid implementation approaches and ideas [43][44][45][46]55]. Attributes of rapid implementation (adapting methods, procedures, and frameworks) are challenging traditional implementation and the consequence is that rapid implementation can help bridge time-gaps between research and practice (working on, for example, research practice and clinical policy simultaneously, or re-thinking and shortening the length of trials).…”

MTORC1/2 Inhibition as a Therapeutic Strategy forPIK3CAMutant Cancers

“…Following IRB approval (UW IRB #2015-1370), retrospective analysis was performed to identify those patients with activating alterations of the PI3K/AKT/MTOR pathway for which the offlabel use of everolimus was considered through the University of Wisconsin Carbone Cancer Center (UWCCC) Precision Medicine Molecular Tumor Board (8). Treatment response was evaluated per standard RECIST v1.1 response criteria (21).…”

“…Significant interest exists in whether cancers with PIK3CA mutations can be treated with targeted therapies, although an effective means of targeting these cancers has yet to be developed. As more patients undergo sequencing, these data are being interpreted through institutional molecular tumor boards and sequencing companies are promoting the off-label use of the MTORC1 inhibitors, everolimus and temsirolimus (8).…”

Variant classification in precision oncology

“…During the last few years, the use of diagnostic genetic analyses of tumor samples has markedly expanded, facilitating the growth of precision oncology through the identification of a continuously increasing number of therapeutic targets and molecularly defined stratification of patients . Panel‐based next‐generation sequencing (NGS) for the detection of tumor‐specific somatic mutations is already widely available in routine clinical use and a number of bioinformatics tools have been developed for their assessment, including data quality, which is paramount for all subsequent steps (for summaries of these tools see Refs.…”