Citations

Abstract Craniopharyngiomas are rare parasellar tumors, and papillary craniopharyngiomas (PCPs) represent 8 to 20% of cases. Interim analysis of retrospective data collected from the Registry of Adenomas of the Pituitary and Related Disorders (RAPID). Fourteen U.S.-based academic skull base centers between 2011 and 2023. Patients with PCPs. Demographic, imaging, surgical, and outcome variables. Ninety-nine patients with PCPs were included. The mean age was 51.8 ± 14.7, and 57.6% were male. Most tumors showed mixed cystic/solid components (67.5%), were transinfundibular (50.0%), and were treated with an endoscopic endonasal approach (74.5%), with 51.1% demonstrating gross total resection (GTR). Pituitary stalk was preserved in 51.9%. Permanent arginine vasopressin deficiency was seen in 67.1% and was associated with pituitary stalk sacrifice (p = 0.003). Cerebrospinal fluid leak was the most common nonendocrine postsurgical, 30-day complication (9.1%), reason for return to the operating room (3.1%), and reason for 90-day readmission (8.1%). Most patients (63.9%) received no adjuvant therapy; GTR was associated with decreased radiotherapy use (p = 0.0001). BRAFV600E mutation was detected in 64/69 tumors tested, although only one patient was treated with a BRAF inhibitor. A mean follow-up of 12.3 ± 14.6 months was seen for the group. RAPID consortium enabled the largest real-world clinical information dataset for PCPs. Early findings support that GTR and stalk preservation are important to outcomes. Iterative analysis and discussion of data led to the generation of a framework for future studies to fully leverage the capabilities of multicenter registries.

Abstract Purpose: Craniopharyngiomas are rare parasellar tumors, and papillary craniopharyngiomas (PCP) represent 8-20% of cases. We assessed surgical outcomes of these very rare tumors among patients treated in the last decade. Methods: Retrospective data from the Registry of Adenomas of the Pituitary and Related Disorders (RAPID) were used to evaluate patients with PCP treated between 2011 and 2023 at 14 US-based academic skull base centers. Demographic, imaging, surgical, and outcome variables were analyzed. Results: Ninety-nine patients with PCP were included. Mean age was 51.8±14.7 and 57.6% were male. Most tumors showed mixed cystic/solid components (67.5%), were trans-infundibular (50.0%), and were treated endoscopically (74.5%), with 51.1% demonstrating gross total resection (GTR). Pituitary stalk was preserved in 51.9%. Permanent arginine vasopressin deficiency was seen in 68.8% and was associated with pituitary stalk sacrifice (p=0.02). Cerebrospinal fluid leak was the most common nonendocrine postsurgical, 30-day complication (9.1%), reason for return to the operating room (3.1%), and reason for 90-day readmission (8.1%). Return to the operating room was associated with discharge to a skilled nursing or rehabilitation facility (p=0.0001). Most patients (63.9%) received no adjuvant therapy; GTR was associated with decreased radiotherapy use (p=0.0001). BRAFV600E mutation was detected in 64/69 tumors tested, although only 1 patient was treated with a BRAF inhibitor. Conclusion: To our knowledge, the RAPID consortium enabled the largest real-world clinical information dataset for PCP. Our data can be used as a benchmark for short-term surgical outcomes. Longer-term follow-up studies are needed to understand how to optimize outcomes from each treatment modality.

Abstract Patients with brain metastases (BMETS) frequently emphasize the impact on quality of life (QOL) over prolongation of life at the time of making treatment decisions. Thus, it is critical to evaluate patient-reported health utility scores after treatment of BMETS. Stereotactic surgery (SRS) is becoming the most frequent treatment modality. The objective of this study was to determine the changes in the EuroQol- 5 Dimension (EQ-5D) in patients with BMETS treated with SRS. The NPA SRS Registry is a multi-institutional collaboration prospectively collecting information from patients undergoing SRS since 2017. We queried the registry for the results of the baseline and follow-up EQ-5D questionnaire, with a utility index score given based on the patient’s responses for five domains: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. The cohort included 522 cases treated with SRS between 2017 and 2023; 264 (47.8%), 197 (35.7%), and 91 (16.5%) had 1, 2-4, and 5-14 metastases, respectively. The mean EQ-5D score at the time of SRS was 0.551 (SD=0.443). At the last follow-up after SRS, 107 (34.0%) patients indicated improvement from their EQ-5D baseline while 51 (16.2%) were stable. The score decreased in 113 patients (35.9%) while 44 (13.9%) showed mixed changes (i.e., domain sub-scores both increased and decreased). For mobility, usual activities, pain/discomfort, and anxiety/depression domains patients experienced similar rates of improvement (21.0%-22.5%). In the self-care domain, 32 (10.2%) patients reported improvement, 232 (73.7%) reported no change and 89 (28.3%) had worsening scores. Our study provided the first longitudinal prospective real-world data using the EQ-5D, a health utility tool, in patients with BMETS treated with SRS. In more than half of the cases, the patients reported improved or stable EQ-5D scores over time after treatment. Factors independent of treatment that may prompt worsening QOL following SRS are being identified and will be presented.

Abstract IFN regulatory factor 4 (IRF4) is a key transcription factor that promotes effector CD8+ T cell differentiation and expansion. The roles of IRF4 in regulating the CD8+ T cell response to cytokines have not been explored. In this article, we show that IL-2 and IL-15 signaling and STAT5 activation regulate IRF4 expression in CD8+ T cells. Gene-expression profile analysis has also revealed that IRF4 is required for expression of the receptors of IL-2 family cytokines CD122 and CD127. We found that IRF4 binds directly to CD122 and CD127 gene loci, indicating that it may directly promote CD122 and CD127 gene transcription. As a consequence, IRF4-deficient CD8+ T cells show diminished sensitivity to IL-2, IL-15, and IL-7 treatment in vitro. Furthermore, we found that IRF4-deficient CD8+ T cells had lower expression of CD122 and CD127 in vivo during influenza virus infection. These data suggest that IRF4 regulates the sensitivity of CD8+ T cells to IL-2 family cytokines, which correlates with the diminished effector and memory CD8+ T cell responses in IRF4-deficient CD8+ T cells.