Camille C Gunderson1, Michelle R Rowland2, Deborah L Wright3, Kelsi L Andrade4, Robert S Mannel5, D Scott McMeekin6, Kathleen N Moore7. 1. Stephenson Cancer Center, University of Oklahoma Health Sciences Center, 800 NE 10th Street, Oklahoma City, OK 73104, USA. Electronic address: camille-gunderson@ouhsc.edu. 2. Stephenson Cancer Center, University of Oklahoma Health Sciences Center, 800 NE 10th Street, Oklahoma City, OK 73104, USA. Electronic address: michelle-rowland@ouhsc.edu. 3. Stephenson Cancer Center, University of Oklahoma Health Sciences Center, 800 NE 10th Street, Oklahoma City, OK 73104, USA. Electronic address: deborah-wright@ouhsc.edu. 4. Stephenson Cancer Center, University of Oklahoma Health Sciences Center, 800 NE 10th Street, Oklahoma City, OK 73104, USA. Electronic address: kelsi-andrade@ouhsc.edu. 5. Stephenson Cancer Center, University of Oklahoma Health Sciences Center, 800 NE 10th Street, Oklahoma City, OK 73104, USA. Electronic address: robert-mannel@ouhsc.edu. 6. Stephenson Cancer Center, University of Oklahoma Health Sciences Center, 800 NE 10th Street, Oklahoma City, OK 73104, USA. Electronic address: scott-mcmeekin@ouhsc.edu. 7. Stephenson Cancer Center, University of Oklahoma Health Sciences Center, 800 NE 10th Street, Oklahoma City, OK 73104, USA. Electronic address: kathleen-moore@ouhsc.edu.
Abstract
OBJECTIVE: In an effort to better incorporate precision medicine into clinical practice, we initiated a pilot project to screen, discuss, and genetically characterize patients with metastatic or recurrent gynecologic malignancies for whom no curative standard of care exists. METHODS: In 7/2014, we initiated a multi-disciplinary Precision Medicine Board (PMB) whose purpose was to apply molecular profiling to select and prioritize early phase clinical trial enrollment for high-risk gynecologic malignancies. Additional objectives were to record outcomes and enable scientific discussions of mutations which may foster local translational research. FoundationOne was the preferred genomic platform; results were reviewed by a team comprised of disease site specialists, phase I trialists, and basic and translational scientists affiliated with the Gynecologic Cancer Program. A detailed database for each patient was created and is followed prospectively for treatment use and resultant outcomes. RESULTS: To date, we have presented 62 cases with interpretable FoundationOne testing on 60 tumor samples (31 ovarian, 18 uterine, 9 cervical, and 4 other female genital tract). Significant genomic alterations were commonly found in all tumor types (median: 3); TP53 (45%) and PIK3CA (27%) were the most frequently noted mutations; however, molecular profiling resulted in identification of few actionable mutations (6%). To date, we have matched 4 patients on therapies based on actionable mutations. CONCLUSIONS: The predominant function of our PMB is establishment of a forum to enhance research while providing clinical care for refractory malignancies. We have matched patients with specific mutations to ongoing trials and are developing investigator-initiated studies based on trends within genomic profiling results. Longer-term follow up will be required to determine the success of this strategy.
OBJECTIVE: In an effort to better incorporate precision medicine into clinical practice, we initiated a pilot project to screen, discuss, and genetically characterize patients with metastatic or recurrent gynecologic malignancies for whom no curative standard of care exists. METHODS: In 7/2014, we initiated a multi-disciplinary Precision Medicine Board (PMB) whose purpose was to apply molecular profiling to select and prioritize early phase clinical trial enrollment for high-risk gynecologic malignancies. Additional objectives were to record outcomes and enable scientific discussions of mutations which may foster local translational research. FoundationOne was the preferred genomic platform; results were reviewed by a team comprised of disease site specialists, phase I trialists, and basic and translational scientists affiliated with the Gynecologic Cancer Program. A detailed database for each patient was created and is followed prospectively for treatment use and resultant outcomes. RESULTS: To date, we have presented 62 cases with interpretable FoundationOne testing on 60 tumor samples (31 ovarian, 18 uterine, 9 cervical, and 4 other female genital tract). Significant genomic alterations were commonly found in all tumor types (median: 3); TP53 (45%) and PIK3CA (27%) were the most frequently noted mutations; however, molecular profiling resulted in identification of few actionable mutations (6%). To date, we have matched 4 patients on therapies based on actionable mutations. CONCLUSIONS: The predominant function of our PMB is establishment of a forum to enhance research while providing clinical care for refractory malignancies. We have matched patients with specific mutations to ongoing trials and are developing investigator-initiated studies based on trends within genomic profiling results. Longer-term follow up will be required to determine the success of this strategy.
Authors: Katherine C Kurnit; Ecaterina E Ileana Dumbrava; Beate Litzenburger; Yekaterina B Khotskaya; Amber M Johnson; Timothy A Yap; Jordi Rodon; Jia Zeng; Md Abu Shufean; Ann M Bailey; Nora S Sánchez; Vijaykumar Holla; John Mendelsohn; Kenna Mills Shaw; Elmer V Bernstam; Gordon B Mills; Funda Meric-Bernstam Journal: Clin Cancer Res Date: 2018-02-02 Impact factor: 12.531
Authors: Caroline M Weipert; Kerry A Ryan; Jessica N Everett; Beverly M Yashar; Arul M Chinnaiyan; J Scott Roberts; Raymond De Vries; Brian J Zikmund-Fisher; Victoria M Raymond Journal: J Genet Couns Date: 2017-08-24 Impact factor: 2.537
Authors: Hossein Taghizadeh; Robert M Mader; Leonhard Müllauer; Stefanie Aust; Stephan Polterauer; Heinz Kölbl; Veronika Seebacher; Christoph Grimm; Alexander Reinthaller; Gerald W Prager Journal: Oncologist Date: 2020-05-08