Clinical actionability of comprehensive genomic profiling for management of rare or refractory cancers

Background. The frequency with which targeted tumor sequencing results will lead to implemented change in care is unclear. Prospective assessment of the feasibility and limitations of using genomic sequencing is critically important. Methods. A prospective clinical study was conducted on 100 patients with diverse-histology, rare, or poor-prognosis cancers to evaluate the clinical actionability of a Clinical Laboratory Improvement Amendments (CLIA)-certified, comprehensive genomic profiling assay (FoundationOne), using formalin-fixed, paraffin-embedded tumors. The primary objectives were to assess utility, feasibility, and limitations of genomic sequencing for genomically guided therapy or other clinical purpose in the setting of a multidisciplinary molecular tumor board. Results. Of the tumors from the 92 patients with sufficient tissue, 88 (96%) had at least one genomic alteration (average 3.6, range 0–10). Commonly altered pathways included p53 (46%), RAS/RAF/MAPK (rat sarcoma; rapidly accelerated fibrosarcoma; mitogen-activated protein kinase) (45%), receptor tyrosine kinases/ligand (44%), PI3K/AKT/mTOR (phosphatidylinositol-4,5-bisphosphate 3-kinase; protein kinase B; mammalian target of rapamycin) (35%), transcription factors/regulators (31%), and cell cycle regulators (30%). Many low frequency but potentially actionable alterations were identified in diverse histologies. Use of comprehensive profiling led to implementable clinical action in 35% of tumors with genomic alterations, including genomically guided therapy, diagnostic modification, and trigger for germline genetic testing. Conclusion. Use of targeted next-generation sequencing in the setting of an institutional molecular tumor board led to implementable clinical action in more than one third of patients with rare and poor-prognosis cancers. Major barriers to implementation of genomically guided therapy were clinical status of the patient and drug access. Early and serial sequencing in the clinical course and expanded access to genomically guided early-phase clinical trials and targeted agents may increase actionability. Implications for Practice: Identification of key factors that facilitate use of genomic tumor testing results and implementation of genomically guided therapy may lead to enhanced benefit for patients with rare or difficult to treat cancers. Clinical use of a targeted next-generation sequencing assay in the setting of an institutional molecular tumor board led to implementable clinical action in over one third of patients with rare and poor prognosis cancers. The major barriers to implementation of genomically guided therapy were clinical status of the patient and drug access both on trial and off label. Approaches to increase actionability include early and serial sequencing in the clinical course and expanded access to genomically guided early phase clinical trials and targeted agents

Clerkship Roles and Responsibilities in a Rapidly Changing Landscape: a National Survey of Internal Medicine Clerkship Directors

BackgroundIn the rapidly changing landscape of undergraduate medical education (UME), the roles and responsibilities of clerkship directors (CDs) are not clear.ObjectiveTo describe the current roles and responsibilities of Internal Medicine CDs.DesignNational annual Clerkship Directors in Internal Medicine (CDIM) cross-sectional survey.ParticipantsOne hundred twenty-nine clerkship directors at all Liaison Committee on Medical Education accredited US medical schools with CDIM membership as of September 1, 2017.Main measuresResponsibilities of core CDs, including oversight of other faculty, and resources available to CDs including financial support and dedicated time.Key resultThe survey response rate was 83% (107/129). Ninety-four percent of the respondents oversaw the core clerkship inpatient experience, while 47.7% (n = 51) and 5.6% (n = 6) oversaw the outpatient and longitudinal integrated clerkships respectively. In addition to oversight, CDs were responsible for curriculum development, evaluation and grades, remediation, scheduling, student mentoring, and faculty development. Less than one-third of CDs (n = 33) received the recommended 0.5 full-time equivalent (FTE) support for their roles, and 15% (n = 16) had less than 20% FTE support. An average 0.41 FTE (SD .2) was spent in clinical work and 0.20 FTE (SD .21) in administrative duties. Eighty-three percent worked with other faculty who assisted in the oversight of departmental UME experiences, with FTE support varying by role and institution. Thirty-five percent of CDs (n = 38) had a dedicated budget for managing their clerkship.ConclusionsThe responsibilities of CDs have increased in both number and complexity since the dissemination of previous guidelines for expectations of and for CDs in 2003. However, resources available to them have not substantially changed