Initiation of a formalized precision medicine program in gynecologic oncology.

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.

Spinal deformity following selective dorsal rhizotomy.

The authors performed a review of 79 patients treated by selective dorsal rhizotomy with laminoplasty, 78 of whom were ambulatory, to determine the prevalence of spinal deformities. The mean radiographic follow-up was 4.2 years, the mean clinical follow-up 5.8 years. Scoliosis (11 degrees -24 degrees ) was identified in 13 children, none of whom had a preexisting deformity. There were no significant differences between preoperative and follow-up thoracic kyphosis or lumbar lordosis, although there was a significant difference in lumbar lordosis between sitting and standing radiographs. No progressive or rigid hyperlordotic deformities were observed in the lumbar spine. Spondylolisthesis was identified in nine children (12%) (8/9 grade I), and one patient required an arthrodesis for pain. Spondylolisthesis was correlated with greater lumbar lordosis, stronger hip abductors, and increased popliteal femoral angles preoperatively, and with stronger hip flexors postoperatively. Back pain was identified in 4 of the 79 patients at last follow-up, 2 of whom had spondylolisthesis. As some cases of spondylolisthesis will remain asymptomatic, periodic radiographic follow-up is recommended.