Research Abstract
My focus is GI Oncology, particularly neuroendocrine diseases, hereditary cancer syndromes, and clinical trial development. I was recruited to DFCI and HMS in October 2015 to provide patient care, conduct clinical research of novel therapies, and participate in teaching/training activities. I am an Assistant Professor at HMS, an Associate Physician at BWH and a Senior Physician at DFCI.
Since joining faculty at HMS, DFCI, and BWH in 2015, I have developed my clinical expertise in the care of patients with neuroendocrine tumors and cancer genetics, as one of the key physicians in our neuroendocrine tumor clinic and Gastrointestinal Cancer Genetics and Prevention clinic. In this capacity, my clinical obligations include 5 sessions/week at the outpatient GI Oncology clinic at DFCI and during a sixth clinic session, I see patients in the GI Cancer Genetics and Prevention Clinic at DFCI, evaluating individuals with medical and family histories suggestive of or concerning for GI-related hereditary syndromes. At BWH, I cover the inpatient service 2 weeks/year, which will include supervising and instructing housestaff in care of Medical Oncology patients. I also spend 4 weeks/year as a GI Oncology consultant to the BWH inpatient service. This role involves seeing patients with new or suspected GI oncologic diseases, and also facilitating transfer of care for new GI Oncology patients to the outpatient care setting. As part of my clinical responsibilities, I have integrated supervision and instruction of housestaff which exceeds 50 hours per academic year.
As the pursuits of the Precision Medicine Initiative move forward, the clinical impact of the somatic and germline profile has become much more apparent. Recent analyses demonstrate that clinical response to anti-tumor agents can be influenced by the presence of somatic and germline variants in varied malignancies. The treatment of neuroendocrine tumors (NETs) is not currently driven by molecular profiles or somatic variants, and therefore, identification of genetic variants linked to neuroendocrine cancer holds the potential to redirect patient care. With the support of the Friends of Dana-Farber, I have assessed the clinical implications of pathogenic somatic and germline variants in small intestine neuroendocrine tumors. Utilizing the DFCI neuroendocrine tumor database, which includes prospectively collected annotated clinical information, correlation with the clinical outcomes of participants with the identified molecular profile. I have a manuscript under review describing similar efforts in malignant pheochromocytoma/paraganglioma. I am currently pursuing similar efforts in pancreatic neuroendocrine tumors associated with MEN1 syndrome.
Pheochromocytomas (PHEOs) and paragangliomas (PGLs) are rare NETs, for which few antitumor therapies have been developed. Although most PHEOs/PGLs represent sporadic tumors, up to 35% harbor a germline mutation in hereditary susceptibility genes. I have identified patients with advanced PHEOs/PGLs treated at Dana-Farber Cancer Institute, utilizing one of the largest clinically annotated biobanks of NETs. The results of this analysis suggests that the presence of a pathogenic germline mutation in the SDH gene does not convey susceptibility to certain therapeutic agents which is counter to what has been previously published. Based on these findings and the rare nature of this disease, I am currently the co-Chair with a colleague at the National Institute of Health of the first prospective trial for this rare tumor type in which we plan to analyze the role of the germline and somatic profiles with clinical outcomes in patients with advanced PHEOs/PGLs treated with temozolomide and olaparib. The trial activated November 2020 and continues to enroll nationally.
During my time at DFCI, I have also continued my work in clinical protocol development. In 2016, I completed the mandated DFCI course for clinical protocol development and since then I have written three investigator initiated clinical protocols for patients with metastatic pancreatic adenocarcinoma and one investigator initiated clinical protocol for patients with metastatic carcinoid tumors.
In order to enhance future endeavors in clinical protocol development in pancreatic cancer I have been designated one of two Hale Family Research Center Clinical Investigators and have been invited to a second two-year term. The goals set forth by this position is to further institutional efforts to develop innovative investigator initiated clinical trials for patients with pancreatic cancer in collaboration with the other Hale Center Investigators.
My goal, going forward, is to continue developing such programs—which encourage collaboration across disciplines that will improve patient care—within the Harvard community and beyond.