Short-term Surgical Outcomes of Papillary Craniopharyngiomas: A Multicenter Study

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Catalino, Duy Pham, Robert C. Rennert, William T Couldwell, and 22 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5245655/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version 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). BRAF V600E 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. Papillary craniopharyngioma multicenter study surgery outcomes INTRODUCTION Craniopharyngiomas are rare parasellar tumors that comprise roughly 5% of all intracranial tumors, with an incidence of 1–2 per one million persons [ 1 – 3 ]. These tumors were first described in the early 20th century and early descriptions of macroscopic features are consistent with distinctions between papillary and adamantinomatous subtypes [ 4 – 6 ]. Papillary craniopharyngiomas (PCP) are more common in patients 45–60 years old, often involve the third ventricle, and have a solid consistency [ 7 , 8 ]. They are less common, accounting for approximately 8–20% of craniopharyngiomas or 600 new cases annually in the United States, and rarely occur in children [ 3 , 9 ]. Craniopharyngiomas remain some of the most challenging parasellar tumors to treat and often require multimodal therapy [ 4 , 10 – 12 ]. Surgical resection remains the initial treatment of choice, and operative mortality rates are low [ 4 , 13 – 16 ]. However, there is increasing sensitivity to the risks of endocrinopathy, hypothalamic injury, and visual pathway injury with aggressive surgical resection [ 17 ]. Adjuvant radiotherapy is widely used for residual or recurrent tumors [ 18 , 19 ]. The recent demonstration of BRAF V600E mutations in PCP may enable use of BRAF-inhibitor targeted therapy as a new treatment paradigm for this disease subtype [ 11 , 20 ]. Given the rarity of PCP, defining an optimal approach to its management can be difficult. The Registry of Adenomas of the Pituitary and Related Disorders (RAPID) is a multicenter collaboration designed to facilitate the study of relatively rare pituitary and related tumors. Our goal is to use disease-oriented data and surgical outcomes to provide insights into patient-oriented outcomes not possible through smaller single-institution series or national administrative datasets [ 21 , 22 ]. We used retrospective data from the RAPID consortium to assess surgical outcomes in patients with PCP and consider the implications for future therapy approaches and areas of research. METHODS Data Source and Study Participants RAPID comprises 14 US academic skull base centers and has both retrospective and prospective study arms [ 21 , 22 ]. Institutional Board Review approval was obtained at each center, and centralized coordination through the Barrow Clinical Outcomes Center was performed. Informed consent was obtained for all prospective registry patients. The registry was queried on September 20, 2024, for diagnosis of craniopharyngioma and all available registry data for 2011 to 2023 were included. For patients with multiple resections, data on the most recent surgical operation were used, and prior treatments were noted. Study Variables Demographic, imaging, surgical, and outcome variables were analyzed. Variables included age at surgery, sex, race, ethnicity, past medical history, medications, and presenting symptoms. Frailty was calculated using the 11-factor modified frailty index (mFI-11). Prior treatments were noted, including surgery and approach, radiotherapy, chemotherapy, and endocrine medications. Tumors were classified relative to their proximity to the infundibulum and optic chiasm, and tumor volume was measured by the ellipsoid method (1/2 × a × b × c). Pituitary stalk preservation was assessed at time of surgery. Results of genetic testing to confirm BRAF mutation status were assessed. Surgical Outcomes Extent of resection (EOR) was assessed by the treating surgical team using intraoperative impression and postoperative imaging. Specifically, gross total resection (GTR) involved full resection of enhancing tumor whereas subtotal resection (STR) involved any partial degree of resection. Outcomes evaluated included surgical complications and a need to return to the operating room (OR), patient postoperative disposition, hospital length of stay (LOS), 90-day readmission rates and reason for readmission, and 90-day postoperative symptoms. Tumor recurrence was evaluated based on clinical or radiographic progression of disease. Use of adjuvant radiotherapy, targeted therapy with BRAF inhibitor, repeat surgery, or other treatments were also assessed. Statistical Analysis Data analysis was performed using SPSS Statistics for Windows (version 27.0; IBM Corp., Armonk, NY). Continuous variables were described by mean and standard deviation while discrete variables were described by percentage. Continuous variables were compared by t-test and one-way analysis of variance while discrete variables were evaluated by chi-square test. Missing data were not inputted and variables with > 25% missing data were excluded. The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) Statement guidelines were used to draft this manuscript. RESULTS Patient Characteristics and Presenting Features A total of 99 PCPs were identified from 14 centers, managed primarily by 29 neurosurgeons and 20 otolaryngologists. Surgeon experience ranged from 1 to 8 PCP cases over 12±5 years of practice. The mean age of the patient cohort at the time of surgery was 51.8±14.7 years; 57.6% were male, and 76.3% were White (Table 1 ). Hypertension (42.9%), hyperlipidemia (23.8%), diabetes mellitus (10.7%), and cardiac disorders (10.7%) were the most common existing illnesses, and the mean mFI-11 score was 1±1. Table 1 Patient characteristics and presenting features Demographics (N = 99) Age, mean years ± SD 51.8±14.7 Males, n (%) 57 (57.6) Race, n (%) (N = 76) White 58 (76.3) Asian 8 (10.5) African American 5 (6.5) Body mass index, mean kg/m 2 ± SD 28.4±6.0 mFI-11 score ± SD 1±1 Past medical history, n (%) (N = 84) Hypertension 36 (42.9) Hyperlipidemia 20 (23.8) Diabetes mellitus 9 (10.7) Cardiac disorders 9 (10.7) Pulmonary disorders 6 (7.1) Cancer 3 (3.6) Hematological disorders 3 (3.6) Presenting features , n (%) Symptoms (N = 85) Vision deficits 69 (81.2) Headaches 53 (62.4) Fatigue 30 (35.3) Cognitive dysfunction 17 (20.0) Weight changes 15 (17.6) Gonadal failure 8 (9.4) Gait imbalance 4 (4.7) Other symptoms 22 (25.9) Prior treatment (N = 84) None 70 (83.3) Radiation 1 (1.2) Surgery 7 (8.3) Other 1 (1.2) Surgery + radiation ± other 5 (6.0) Prior surgery (N = 84) Craniotomy 7 (8.3) Transsphenoidal 5 (6.0) Prior radiation (N = 84) Stereotactic radiosurgery 4 (4.8) Fractionated radiotherapy 2 (2.4) Prior medication (N = 84) 5 (6.0) Abbreviations: mFI-11, 11-item modified frailty index Presenting symptoms included visual deficits (81.2%), headaches (62.4%), and fatigue (35.3%) followed by cognitive dysfunction (20.0%), weight changes (17.6%), gonadal failure (9.4%), and gait imbalance (4.7%) (Table 1 ). 83.3% of patients had no prior treatment whereas 8.3% had prior surgical resection, 1.2% had prior radiation, and 7.1% had a mix of surgery, radiation, and other treatments. Tumor Characteristics and Surgical Approaches Radiographic characteristics included a mean tumor volume of 6.2±4.5 cm 3 (Table 2 ). Cavernous sinus invasion (5.1%), and vascular encasement (27.0%) were uncommon. Tumors generally showed mixed cystic and solid components (67.5%). They were more often trans-infundibular (50.0%) than retro- or pre-infundibular, and most were retro-chiasmatic (75.3%). Endoscopic endonasal surgical approaches (74.5%) were most common, followed by craniotomy (20.4%). The pituitary stalk was preserved in 51.9% of cases. As expected, nearly all resected tumors tested for BRAF mutation were positive (92.8%). Table 2 Tumor characteristics and surgical approaches Tumor volume, cm 3 6.2±4.5 Cavernous sinus invasion, n (%) (N = 78) 4 (5.1) Vascular encasement, n (%) (N = 74) 20 (27.0) Tumor consistency, n (%) (N = 83) Cystic 17 (20.5) Solid 10 (12.0) Mixed cystic and solid 56 (67.5) Tumor classification, n (%) (N = 72) Trans-infundibular 36 (50.0) Pre-infundibular 20 (27.8) Retro-infundibular 16 (22.2) Tumor-chiasm relationship, n (%) (N = 73) Retro-chiasmatic 55 (75.3) Pre-chiasmatic 18 (24.7) Surgical approach, n (%) (N = 98) Endoscopic endonasal 73 (74.5) Craniotomy 20 (20.4) Endoscopic craniotomy 1 (1.0) Microscopic 4 (4.1) Pituitary stalk preserved, n (%) (N = 81) Yes 42 (51.9) No 27 (33.3) Unknown 12 (14.8) BRAF mutation detected, n (%) (N = 69) 64/69 (92.8) Surgical Outcomes GTR was achieved in 55.1%; STR with 75–99% resection (33.3%) and < 75% resection (6.1%) were less frequent (Table 3 ). Cerebrospinal fluid (CSF) leak was the most common nonendocrine complication, seen in 9.1% of patients. A total of 14.3% developed temporary arginine vasopressin deficiency (AVP-D) while 39% showed persistent AVP-D within 30 days of surgery. Hyponatremia was seen in 13.0% of patients. Other complications occurred in ≤ 4% of patients, including worsened vision, reintubation, venous thromboembolism, hematoma, hydrocephalus, cardiac complications, and death. A total of 8.6% of patients returned to the OR, most commonly because of CSF leak. Table 3 Surgical outcomes Extent of resection, n (%) (N = 78) Gross total resection 43 (55.1) 75–99% resection 26 (33.3) < 75% resection 5 (6.4) Other 4 (5.1) Complications within 30 days, n (%) (N = 77) AVP-D Permanent 30 (39.0) Temporary 11 (14.3) Hyponatremia 10 (13.0) CSF leak 7 (9.1) Vision worsening 3 (3.9) Postoperative hematoma 2 (2.6) Pneumonia 2 (2.6) Meningitis 1 (1.3) Reintubation 2 (2.6) Venous thromboembolism 2 (2.6) Cardiac complications 2 (2.6) Hydrocephalus 1 (1.3) Mortality 1 (1.3) Return to OR, n (%) (N = 81) 7 (8.6) CSF leak 3 (3.7) Shunt 2 (2.5) Tumor removal 1 (1.2) First surgery aborted 1 (1.2) 90-day postoperative symptoms, n (%) (N = 79) Hypothyroidism 54 (68.4) AVP-D 53 (67.1) Adrenal insufficiency 52 (65.8) Cognitive dysfunction 11 (13.9) Temperature dysfunction 4 (5.1) Sleep dysfunction 4 (5.1) Hyperphagia 4 (5.1) Abbreviations: AVP-D, arginine vasopressin deficiency; CSF, cerebrospinal fluid; OR, operating room. At 90 days, 68.4% of patients showed postoperative hypothyroidism, 65.8% had adrenal insufficiency, and 67.1% had AVP-D. Between 5.1% and 13.9% reported hyperphagia, sleep dysfunction, temperature dysregulation, and cognitive dysfunction. Postoperatively, nearly all patients were discharged home (92.3%) after an average LOS of 9±12 days (Table 4 ). A total of 21.6% of patients were readmitted within 90 days, most commonly for CSF leak (8.1%), followed by hyponatremia and altered mental status (2.7% each). Fewer than 2% were readmitted for stroke, AVP-D, dizziness, fever, hydrocephalus, or subdural hematoma. Table 4 Postoperative outcomes Disposition, n (%) (N = 78) Home 72 (92.3) SNF/rehabilitation 5 (6.4) Death 1 (1.3) LOS, days 9±12 90-day readmission, n (%) (N = 74) 16 (21.6) CSF leak 6 (8.1) Hyponatremia 2 (2.7) Altered mental status 2 (2.7) Stroke 1 (1.0) AVP-D 1 (1.4) Dizziness 1 (1.4) Fever, lethargy 1 (1.4) Hydrocephalus 1 (1.4) Subdural hematoma 1 (1.4) Postoperative treatment, n (%) (N = 83) None 53 (63.9) Radiotherapy 12 (14.5) Repeat surgery 6 (7.2) Radiation and targeted therapy 1 (1.2) Other 11 (13.3) Time to repeat surgery, mean month ± SD 1.3±14.5 Time to radiotherapy, mean months ± SD 15.8±24.3 Recurrence, n (%) 3 (12.0) Progression-free survival, mean months ± SD 9.0±4.2 Overall survival/follow-up, mean months ± SD 12.3±14.6 Abbreviations: AVP-D, arginine vasopressin deficiency; CSF, cerebrospinal fluid; LOS, length of [hospital] stay; SNF, skilled nursing facility Within the follow-up period of 12.3±14.6 months, most patients did not undergo postoperative treatment (63.9%). Adjuvant radiotherapy was most common (14.5%), followed by repeat surgery (7.2%). One patient was treated with radiotherapy plus BRAF targeted therapy after two prior subtotal resections. The average time to re-resection was 11.3±14.5 months (range 0–43 months) and average time to radiotherapy was 15.8±24.3 months (range 1–79 months). Three patients recurred at an average of 9.0±4.2 months. Given the small number of recurrences and the short follow up period, time-to-recurrence analyses were not performed. Subgroup Analyses We measured the effect of surgical outcomes on complications and need for additional treatment. Compared with STR, GTR was associated with higher likelihood of permanent AVP-D (57.1% [16/28] vs. 80.5% [33/41]; p = 0.04) (Table 5 ). By contrast, GTR was associated with lower rate of adjuvant radiotherapy (4.7% [2/43] vs. 25.8% [8/31], p = 0.01) and additional surgery (4.7% [2/43] vs. 12.9% [4/31], p = 0.01). CSF leak was not associated with EOR, or with prior treatment, mFI-11, surgeon experience, surgical repair strategy, or tumor imaging characteristics (data not shown). However, patients who returned to the OR were more likely to discharge to a skilled nursing facility or rehabilitation unit rather than to home (28.6% vs. 4.1%, p = 0.0001). Patients with pituitary stalk preservation showed lower rates of permanent 90-day panhypopituitarism including in AVP-D (53.8% [21/39] vs. 92.6% [25/27), p = 0.003), adrenal insufficiency (52.6% [20/38] vs. 96.3% [26/27], p = 0.0001), and hypothyroidism (71.1% [27/38] vs. 85.2% [23/27], p = 0.01). Table 5 Subgroup analyses Effect of EOR on complications and outcomes Subtotal resection Gross total resection P value AVP-D 16/28 (57.1%) 33/41 (80.5%) 0.04 Adrenal insufficiency 15/28 (53.6%) 35/41 (85.4%) 0.004 SNF/rehabilitation 4/29 (13.8%) 3/42 (7.1%) 0.7 Recurrence 2/3 (66.7%) 1/16 (6.3%) 0.007 Radiotherapy 8/31 (25.8%) 2/43 (4.7%) 0.01 Additional surgery 4/31 (12.9%) 2/43 (4.7%) 0.01 Follow-up, months 15±14 13±16 0.6 LOS, days 10±16 9±9 0.7 Effect of pituitary stalk preservation on endocrine outcomes Pituitary stalk preserved Pituitary stalk not preserved P value AVP-D 21/39 (53.8%) 25/27 (92.6%) 0.003 Adrenal insufficiency 20/38 (52.6%) 26/27 (96.3%) 0.0001 Hypothyroidism 27/38 (71.1%) 23/27 (85.2%) 0.01 Abbreviations: AVP-D, arginine vasopressin deficiency; LOS, length of [hospital] stay; SNF: skilled nursing facility. DISCUSSION We evaluated a large group of 99 PCPs treated at 14 skull base centers by 29 neurosurgeons. Our analysis represents one of the largest descriptive multicenter, multi-surgeon cohort studies of surgical outcomes for PCP to date. We found that most patients presented with visual changes, headaches, and fatigue. Tumors mostly showed mixed cystic/solid components, and were trans-infundibular and retro-chiasmatic. Endoscopic endonasal surgical approaches were most commonly used. Pituitary stalk preservation was achieved in 52% of cases, which correlated with reduced rates of AVP-D and endocrinopathy. GTR was achieved in 55% of cases and correlated with reduced use of both adjuvant radiotherapy and additional surgery. Targeted BRAF V600E inhibition, in conjunction with radiotherapy, was only used in 1 patient after several STRs. Approximately 68% of patients showed permanent AVP-D at 90 days follow-up. Nearly all patients were discharged home, and reoperation increased the risk of SNF/rehab placement. Patient and Tumor Characteristics Our results are similar to those of others evaluating the presentation and treatment of PCP. Prieto et al. reviewed 350 published cases of PCP and similarly showed headaches, visual deficits, and endocrinopathy were common presenting symptoms [ 23 ]. Mixed solid and cystic components were common, and were often seen with sellar, suprasellar, and ventricular involvement. Prieto et al. showed 57.5% of cases involved the third ventricle; these tumors tended to be more solid and spherical tumors, with greater hypothalamic involvement. Multiple classifications for craniopharyngiomas have been suggested based on their relationship to the infundibulum [ 6 , 24 , 25 ]. Our results add to this classification by including the relationship of the tumor to the optic chiasm. Most tumors were both trans-infundibular (50.0%) and retro-chiasmatic (75.3%), which can create challenges for surgical treatment of the tumor and for postoperative management of AVP-D. Treatment Approaches and Surgical Outcomes Prieto et al. showed that patients underwent a variety of surgical approaches, including endoscopic and microsurgical methods, and only 15% of patients achieved a GTR [ 23 ]. Approximately 75% patients in our series underwent an endoscopic surgical approach and 55% achieved GTR, suggesting tumors in a variety of locations could be treated successfully endoscopically. Nevertheless, our results, similar to others, show that while GTR reduces the risk of tumor recurrence, these outcomes are dependent on tumor adherence and position [ 23 , 24 , 26 – 29 ]. Furthermore, data from Prieto et al. indicate that a normal pituitary stalk is not often identified in sellar-suprasellar lesions with or without extension to the third ventricle. In line with these findings, our results show that pituitary stalk preservation was associated with a decreased frequency of endocrinopathies. Postoperative Treatment We found that most patients (63.9%) did not undergo any further treatment after surgical resection. Others have indicated that greater EOR can improve outcomes and reduce the need for adjuvant therapy [ 30 – 32 ]. Patients returned to the OR most often for repair of CSF leak and return to the OR predicted a higher likelihood of SNF/rehab placement. Despite supportive evidence for the role of BRAF inhibitors [ 20 ], few patients used targeted therapy. It may be challenging for patients to obtain approval for use of such treatments from payors until greater supportive evidence and follow-up is available. Integration of BRAF/MEK inhibitors into treatment algorithms could offer another alternative to surgery but require weighing the benefits of non-operative treatment with its side effects and durability. Our data can serve as a benchmark for short-term surgical outcomes in future comparative studies, but long-term data are needed to fully understand how to select ideal patient populations for each treatment modality and how to optimize treatment outcomes. Strengths and Limitations To our knowledge, the RAPID consortium enabled the largest real-world clinical information dataset for PCP, which is an otherwise rare and poorly understood pathology. Most important, the registry will allow us to update our preliminary analyses with the addition of future prospective patients to augment the current dataset. Future work could focus on outcomes of radiotherapy and targeted therapies based on EOR as well as changes in practice patterns over time and comparison of outcomes in PCP vs. adamantinomatous craniopharyngioma. Limitations of our study are common to all registries. Data are collected retrospectively, which may make it prone to coding inconsistencies or omission. Missing data may limit our ability to draw conclusions, and contributing centers may not be representative of all sites treating patients with PCP, which could bias the data. The nature of the registry might also affect how our data can be compared with those of other investigators. For example, the current prevalence of endoscopic approaches in our series may limit its comparison to prior cranial focused studies, and clinical data of some patients might have been used for analyses of prior works not known to the authors. An additional limitation is the relatively limited median follow-up of 12 months in our dataset. Recurrence and progression of PCP may be delayed [ 23 , 33 , 34 ], which may account for the relatively low rates of additional interventions such as radiotherapy. Longer-term follow-up studies are needed to evaluate the effect of tumor characteristics on outcomes and complications as well as to evaluate practice changes and institutional variations in treatment approaches. CONCLUSION This study from the multicenter RAPID consortium describes patient characteristics, treatment trends, and short-term outcomes of PCP management. Our findings can serve as a foundation for future, longer-term studies and help with development of treatment algorithms for this rare disease. Declarations Competing Interests ASL was previously a consultant for SPIWAY and BK Medical Systems and was an investor in Kogent Surgical; those relationships have ended. JMS’ institution receives funding from Fractyl Health Inc, Amryt, Ascendis, Camurus, Bayer, Sparrow, Recordati, and Abbvie and JMS is a consultant for Xeris and Camurus. VRK is a consultant for Stryker and Integra LifeSciences. JF-M is a consultant for Medtronic, Stryker, and Hotry. MK is a consultant for Altus. All other authors have no relevant financial or non-financial interests to disclose. Funding: This work was supported by Lodestar Foundation and Barrow Neurological Foundation. Author Contribution All authors contributed to the study conception, design, material preparation, and data collection. MPC, DP, and MK analyzed the data and wrote the first draft of the manuscript. All authors commented on the previous versions of the manuscript. All authors read and approved the final manuscript. Acknowledgement We thank the staff of Neuroscience Publications at Barrow Neurological Institute for assistance with manuscript preparation. We acknowledge Dr. Kevin Yuen as a collaborator from Barrow Neurological Institute. Data Availability The data that support the findings of this study are not openly available due to reasons of sensitivity and are available from the corresponding author upon reasonable request. 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Brain Spine 2:100910. 10.1016/j.bas.2022.100910 Agresta G, Campione A, Veiceschi P, Gallo D, Agosti E, Massimi L et al (2023) Clinical and oncological outcomes in single-stage versus staged surgery for pediatric craniopharyngiomas: a multicenter retrospective study. J Endocrinol Invest 46(6):1219–1232. 10.1007/s40618-022-01993-2 Koutourousiou M, Fernandez-Miranda JC, Wang EW, Snyderman CH, Gardner PA (2018) The limits of transsellar/transtuberculum surgery for craniopharyngioma. J Neurosurg Sci 62(3):301–309. 10.23736/S0390-5616.18.04376-X Almeida JP, Kalyvas A, Mohan N, Oswari S, Takami H, Velasquez C et al (2020) Current Results of Surgical Treatment of Craniopharyngiomas: The Impact of Endoscopic Endonasal Approaches. World Neurosurg 142:582–592. 10.1016/j.wneu.2020.05.174 Elliott RE, Jane JA Jr., Wisoff JH (2011) Surgical management of craniopharyngiomas in children: meta-analysis and comparison of transcranial and transsphenoidal approaches. Neurosurgery 69(3):630–643 discussion 43. 10.1227/NEU.0b013e31821a872d Sadashivam S, Menon G, Abraham M, Nair SN (2020) Adult craniopharyngioma: The role of extent of resection in tumor recurrence and long-term functional outcome. Clin Neurol Neurosurg 192:105711. 10.1016/j.clineuro.2020.105711 Duff J, Meyer FB, Ilstrup DM, Laws ER Jr., Schleck CD, Scheithauer BW (2000) Long-term outcomes for surgically resected craniopharyngiomas. Neurosurgery 46(2):291–302 discussion – 5. 10.1097/00006123-200002000-00007 Jannelli G, Calvanese F, Paun L, Raverot G, Jouanneau E (2023) Current Advances in Papillary Craniopharyngioma: State-Of-The-Art Therapies and Overview of the Literature. Brain Sci 13(3). 10.3390/brainsci13030515 Additional Declarations Competing interest reported. ASL was previously a consultant for SPIWAY and BK Medical Systems and was an investor in Kogent Surgical; those relationships have ended. JMS’ institution receives funding from Fractyl Health Inc, Amryt, Ascendis, Camurus, Bayer, Sparrow, Recordati, and Abbvie and JMS is a consultant for Xeris and Camurus. VRK is a consultant for Stryker and Integra LifeSciences. JF-M is a consultant for Medtronic, Stryker, and Hotry. MK is a consultant for Altus. All other authors have no relevant financial or non-financial interests to disclose. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-5245655","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Case Report","associatedPublications":[],"authors":[{"id":370850703,"identity":"cd70a7f3-1536-4ce7-b43b-8ce33de85bab","order_by":0,"name":"Michael P. 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Wu","email":"","orcid":"","institution":"The Ohio State University","correspondingAuthor":false,"prefix":"","firstName":"Kyle","middleName":"C.","lastName":"Wu","suffix":""},{"id":370850735,"identity":"1b1c93e1-12a4-4da4-a5f9-4d6414398ea1","order_by":22,"name":"Adam Mamelak","email":"","orcid":"","institution":"Cedars-Sinai Medical Center","correspondingAuthor":false,"prefix":"","firstName":"Adam","middleName":"","lastName":"Mamelak","suffix":""},{"id":370850736,"identity":"c212caf5-be19-4b67-8d0f-7967d47e98d1","order_by":23,"name":"Mark Pacult","email":"","orcid":"","institution":"Barrow Neurological Institute","correspondingAuthor":false,"prefix":"","firstName":"Mark","middleName":"","lastName":"Pacult","suffix":""},{"id":370850737,"identity":"7c686693-4e96-4078-b166-1c6c35831403","order_by":24,"name":"Andrew S. Little","email":"","orcid":"","institution":"Barrow Neurological Institute","correspondingAuthor":false,"prefix":"","firstName":"Andrew","middleName":"S.","lastName":"Little","suffix":""},{"id":370850738,"identity":"66bc6b7d-20e7-4c1a-9a0a-52cbd8b5c347","order_by":25,"name":"Michael Karsy","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA1klEQVRIiWNgGAWjYDACHjBpA8QJQGwAJYnQkka6lsNQLQxEaNHtOfzs48+289H87AlsUjcK7PIY2Ju3SeDTYna2zXg2b9vt3Jk9D9ikcwySixl4jpXh13KewZiZEahlw40EkJYDiQ0SOWYEtLB/ZvzZdi53P1yL/BsCWs72GDPwth3I3SABt4WHgJYzZ4qZec4l584487DZGuiXxDaetGIL/FrSNzP+KLPL7W9PPng7549dYj/74Y038GkBA0Y2MNkA5rARVA4Gf4hTNgpGwSgYBSMUAADx50l4jUVMmAAAAABJRU5ErkJggg==","orcid":"","institution":"University of Michigan","correspondingAuthor":true,"prefix":"","firstName":"Michael","middleName":"","lastName":"Karsy","suffix":""}],"badges":[],"createdAt":"2024-10-11 11:23:07","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-5245655/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-5245655/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":70112574,"identity":"aad39822-961e-4e7f-abf8-864b3e605088","added_by":"auto","created_at":"2024-11-28 12:47:20","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":736564,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5245655/v1/692f9467-dd00-4f9f-9605-0b0e73a89094.pdf"}],"financialInterests":"Competing interest reported. ASL was previously a consultant for SPIWAY and BK Medical Systems and was an investor in Kogent Surgical; those relationships have ended. JMS’ institution receives funding from Fractyl Health Inc, Amryt, Ascendis, Camurus, Bayer, Sparrow, Recordati, and Abbvie and JMS is a consultant for Xeris and Camurus. VRK is a consultant for Stryker and Integra LifeSciences. JF-M is a consultant for Medtronic, Stryker, and Hotry. MK is a consultant for Altus. All other authors have no relevant financial or non-financial interests to disclose.","formattedTitle":"Short-term Surgical Outcomes of Papillary Craniopharyngiomas: A Multicenter Study","fulltext":[{"header":"INTRODUCTION","content":"\u003cp\u003eCraniopharyngiomas are rare parasellar tumors that comprise roughly 5% of all intracranial tumors, with an incidence of 1\u0026ndash;2 per one million persons [\u003cspan additionalcitationids=\"CR2\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. These tumors were first described in the early 20th century and early descriptions of macroscopic features are consistent with distinctions between papillary and adamantinomatous subtypes [\u003cspan additionalcitationids=\"CR5\" citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. Papillary craniopharyngiomas (PCP) are more common in patients 45\u0026ndash;60 years old, often involve the third ventricle, and have a solid consistency [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. They are less common, accounting for approximately 8\u0026ndash;20% of craniopharyngiomas or 600 new cases annually in the United States, and rarely occur in children [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. Craniopharyngiomas remain some of the most challenging parasellar tumors to treat and often require multimodal therapy [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan additionalcitationids=\"CR11\" citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. Surgical resection remains the initial treatment of choice, and operative mortality rates are low [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan additionalcitationids=\"CR14 CR15\" citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. However, there is increasing sensitivity to the risks of endocrinopathy, hypothalamic injury, and visual pathway injury with aggressive surgical resection [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. Adjuvant radiotherapy is widely used for residual or recurrent tumors [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. The recent demonstration of \u003cem\u003eBRAF\u003c/em\u003e\u003csup\u003e\u003cem\u003eV600E\u003c/em\u003e\u003c/sup\u003e mutations in PCP may enable use of BRAF-inhibitor targeted therapy as a new treatment paradigm for this disease subtype [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eGiven the rarity of PCP, defining an optimal approach to its management can be difficult. The Registry of Adenomas of the Pituitary and Related Disorders (RAPID) is a multicenter collaboration designed to facilitate the study of relatively rare pituitary and related tumors. Our goal is to use disease-oriented data and surgical outcomes to provide insights into patient-oriented outcomes not possible through smaller single-institution series or national administrative datasets [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e, \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. We used retrospective data from the RAPID consortium to assess surgical outcomes in patients with PCP and consider the implications for future therapy approaches and areas of research.\u003c/p\u003e"},{"header":"METHODS","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eData Source and Study Participants\u003c/h2\u003e \u003cp\u003eRAPID comprises 14 US academic skull base centers and has both retrospective and prospective study arms [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e, \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. Institutional Board Review approval was obtained at each center, and centralized coordination through the Barrow Clinical Outcomes Center was performed. Informed consent was obtained for all prospective registry patients. The registry was queried on September 20, 2024, for diagnosis of craniopharyngioma and all available registry data for 2011 to 2023 were included. For patients with multiple resections, data on the most recent surgical operation were used, and prior treatments were noted.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eStudy Variables\u003c/h3\u003e\n\u003cp\u003eDemographic, imaging, surgical, and outcome variables were analyzed. Variables included age at surgery, sex, race, ethnicity, past medical history, medications, and presenting symptoms. Frailty was calculated using the 11-factor modified frailty index (mFI-11). Prior treatments were noted, including surgery and approach, radiotherapy, chemotherapy, and endocrine medications. Tumors were classified relative to their proximity to the infundibulum and optic chiasm, and tumor volume was measured by the ellipsoid method (1/2 \u0026times; a \u0026times; b \u0026times; c). Pituitary stalk preservation was assessed at time of surgery. Results of genetic testing to confirm \u003cem\u003eBRAF\u003c/em\u003e mutation status were assessed.\u003c/p\u003e\n\u003ch3\u003eSurgical Outcomes\u003c/h3\u003e\n\u003cp\u003eExtent of resection (EOR) was assessed by the treating surgical team using intraoperative impression and postoperative imaging. Specifically, gross total resection (GTR) involved full resection of enhancing tumor whereas subtotal resection (STR) involved any partial degree of resection. Outcomes evaluated included surgical complications and a need to return to the operating room (OR), patient postoperative disposition, hospital length of stay (LOS), 90-day readmission rates and reason for readmission, and 90-day postoperative symptoms. Tumor recurrence was evaluated based on clinical or radiographic progression of disease. Use of adjuvant radiotherapy, targeted therapy with BRAF inhibitor, repeat surgery, or other treatments were also assessed.\u003c/p\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003eStatistical Analysis\u003c/h2\u003e \u003cp\u003eData analysis was performed using SPSS Statistics for Windows (version 27.0; IBM Corp., Armonk, NY). Continuous variables were described by mean and standard deviation while discrete variables were described by percentage. Continuous variables were compared by t-test and one-way analysis of variance while discrete variables were evaluated by chi-square test. Missing data were not inputted and variables with \u0026gt;\u0026thinsp;25% missing data were excluded. The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) Statement guidelines were used to draft this manuscript.\u003c/p\u003e \u003c/div\u003e"},{"header":"RESULTS","content":"\u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003ePatient Characteristics and Presenting Features\u003c/h2\u003e \u003cp\u003eA total of 99 PCPs were identified from 14 centers, managed primarily by 29 neurosurgeons and 20 otolaryngologists. Surgeon experience ranged from 1 to 8 PCP cases over 12\u0026plusmn;5 years of practice.\u003c/p\u003e \u003cp\u003eThe mean age of the patient cohort at the time of surgery was 51.8\u0026plusmn;14.7 years; 57.6% were male, and 76.3% were White (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). Hypertension (42.9%), hyperlipidemia (23.8%), diabetes mellitus (10.7%), and cardiac disorders (10.7%) were the most common existing illnesses, and the mean mFI-11 score was 1\u0026plusmn;1.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003ePatient characteristics and presenting features\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"2\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eDemographics (N\u0026thinsp;=\u0026thinsp;99)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge, mean years\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e51.8\u0026plusmn;14.7\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMales, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e57 (57.6)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRace, n (%) (N\u0026thinsp;=\u0026thinsp;76)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eWhite\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e58 (76.3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAsian\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8 (10.5)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAfrican American\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5 (6.5)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBody mass index, mean kg/m\u003csup\u003e2\u003c/sup\u003e\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e28.4\u0026plusmn;6.0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003emFI-11 score\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1\u0026plusmn;1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePast medical history, n (%) (N\u0026thinsp;=\u0026thinsp;84)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHypertension\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e36 (42.9)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHyperlipidemia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e20 (23.8)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDiabetes mellitus\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9 (10.7)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCardiac disorders\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9 (10.7)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePulmonary disorders\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6 (7.1)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCancer\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3 (3.6)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHematological disorders\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3 (3.6)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003ePresenting features\u003c/b\u003e, n (%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSymptoms (N\u0026thinsp;=\u0026thinsp;85)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVision deficits\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e69 (81.2)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHeadaches\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e53 (62.4)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFatigue\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e30 (35.3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCognitive dysfunction\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e17 (20.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eWeight changes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e15 (17.6)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGonadal failure\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8 (9.4)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGait imbalance\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4 (4.7)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOther symptoms\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e22 (25.9)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePrior treatment (N\u0026thinsp;=\u0026thinsp;84)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNone\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e70 (83.3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRadiation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (1.2)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSurgery\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7 (8.3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOther\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (1.2)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSurgery\u0026thinsp;+\u0026thinsp;radiation \u0026plusmn; other\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5 (6.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePrior surgery (N\u0026thinsp;=\u0026thinsp;84)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCraniotomy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7 (8.3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTranssphenoidal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5 (6.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePrior radiation (N\u0026thinsp;=\u0026thinsp;84)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eStereotactic radiosurgery\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4 (4.8)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFractionated radiotherapy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2 (2.4)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePrior medication (N\u0026thinsp;=\u0026thinsp;84)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5 (6.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"2\"\u003eAbbreviations: mFI-11, 11-item modified frailty index\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003ePresenting symptoms included visual deficits (81.2%), headaches (62.4%), and fatigue (35.3%) followed by cognitive dysfunction (20.0%), weight changes (17.6%), gonadal failure (9.4%), and gait imbalance (4.7%) (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). 83.3% of patients had no prior treatment whereas 8.3% had prior surgical resection, 1.2% had prior radiation, and 7.1% had a mix of surgery, radiation, and other treatments.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eTumor Characteristics and Surgical Approaches\u003c/h3\u003e\n\u003cp\u003eRadiographic characteristics included a mean tumor volume of 6.2\u0026plusmn;4.5 cm\u003csup\u003e3\u003c/sup\u003e (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). Cavernous sinus invasion (5.1%), and vascular encasement (27.0%) were uncommon. Tumors generally showed mixed cystic and solid components (67.5%). They were more often trans-infundibular (50.0%) than retro- or pre-infundibular, and most were retro-chiasmatic (75.3%). Endoscopic endonasal surgical approaches (74.5%) were most common, followed by craniotomy (20.4%). The pituitary stalk was preserved in 51.9% of cases. As expected, nearly all resected tumors tested for \u003cem\u003eBRAF\u003c/em\u003e mutation were positive (92.8%).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eTumor characteristics and surgical approaches\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"2\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTumor volume, cm\u003csup\u003e3\u003c/sup\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6.2\u0026plusmn;4.5\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCavernous sinus invasion, n (%) (N\u0026thinsp;=\u0026thinsp;78)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e4 (5.1)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVascular encasement, n (%) (N\u0026thinsp;=\u0026thinsp;74)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e20 (27.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTumor consistency, n (%) (N\u0026thinsp;=\u0026thinsp;83)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCystic\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e17 (20.5)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSolid\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e10 (12.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMixed cystic and solid\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e56 (67.5)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTumor classification, n (%) (N\u0026thinsp;=\u0026thinsp;72)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTrans-infundibular\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e36 (50.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePre-infundibular\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e20 (27.8)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRetro-infundibular\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e16 (22.2)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTumor-chiasm relationship, n (%) (N\u0026thinsp;=\u0026thinsp;73)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRetro-chiasmatic\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e55 (75.3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePre-chiasmatic\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e18 (24.7)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSurgical approach, n (%) (N\u0026thinsp;=\u0026thinsp;98)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEndoscopic endonasal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e73 (74.5)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCraniotomy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e20 (20.4)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEndoscopic craniotomy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1 (1.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMicroscopic\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e4 (4.1)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePituitary stalk preserved, n (%) (N\u0026thinsp;=\u0026thinsp;81)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e42 (51.9)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e27 (33.3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUnknown\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e12 (14.8)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eBRAF\u003c/em\u003e mutation detected, n (%) (N\u0026thinsp;=\u0026thinsp;69)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e64/69 (92.8)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e\n\u003ch3\u003eSurgical Outcomes\u003c/h3\u003e\n\u003cp\u003eGTR was achieved in 55.1%; STR with 75\u0026ndash;99% resection (33.3%) and \u0026lt;\u0026thinsp;75% resection (6.1%) were less frequent (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). Cerebrospinal fluid (CSF) leak was the most common nonendocrine complication, seen in 9.1% of patients. A total of 14.3% developed temporary arginine vasopressin deficiency (AVP-D) while 39% showed persistent AVP-D within 30 days of surgery. Hyponatremia was seen in 13.0% of patients. Other complications occurred in \u0026le;\u0026thinsp;4% of patients, including worsened vision, reintubation, venous thromboembolism, hematoma, hydrocephalus, cardiac complications, and death. A total of 8.6% of patients returned to the OR, most commonly because of CSF leak.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eSurgical outcomes\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"2\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eExtent of resection, n (%) (N\u0026thinsp;=\u0026thinsp;78)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGross total resection\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e43 (55.1)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e75\u0026ndash;99% resection\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e26 (33.3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;75% resection\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e5 (6.4)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOther\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e4 (5.1)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eComplications within 30 days, n (%) (N\u0026thinsp;=\u0026thinsp;77)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAVP-D\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePermanent\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e30 (39.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTemporary\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e11 (14.3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHyponatremia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e10 (13.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCSF leak\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e7 (9.1)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVision worsening\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e3 (3.9)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePostoperative hematoma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2 (2.6)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePneumonia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2 (2.6)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMeningitis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1 (1.3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eReintubation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2 (2.6)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVenous thromboembolism\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2 (2.6)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCardiac complications\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2 (2.6)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHydrocephalus\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1 (1.3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMortality\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1 (1.3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eReturn to OR, n (%) (N\u0026thinsp;=\u0026thinsp;81)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e7 (8.6)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCSF leak\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e3 (3.7)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eShunt\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2 (2.5)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTumor removal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1 (1.2)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFirst surgery aborted\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1 (1.2)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e90-day postoperative symptoms, n (%) (N\u0026thinsp;=\u0026thinsp;79)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHypothyroidism\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e54 (68.4)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAVP-D\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e53 (67.1)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAdrenal insufficiency\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e52 (65.8)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCognitive dysfunction\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e11 (13.9)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTemperature dysfunction\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e4 (5.1)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSleep dysfunction\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e4 (5.1)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHyperphagia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e4 (5.1)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"2\"\u003eAbbreviations: AVP-D, arginine vasopressin deficiency; CSF, cerebrospinal fluid; OR, operating room.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eAt 90 days, 68.4% of patients showed postoperative hypothyroidism, 65.8% had adrenal insufficiency, and 67.1% had AVP-D. Between 5.1% and 13.9% reported hyperphagia, sleep dysfunction, temperature dysregulation, and cognitive dysfunction.\u003c/p\u003e \u003cp\u003ePostoperatively, nearly all patients were discharged home (92.3%) after an average LOS of 9\u0026plusmn;12 days (Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e). A total of 21.6% of patients were readmitted within 90 days, most commonly for CSF leak (8.1%), followed by hyponatremia and altered mental status (2.7% each). Fewer than 2% were readmitted for stroke, AVP-D, dizziness, fever, hydrocephalus, or subdural hematoma.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003ePostoperative outcomes\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"2\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDisposition, n (%) (N\u0026thinsp;=\u0026thinsp;78)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHome\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e72 (92.3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSNF/rehabilitation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5 (6.4)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDeath\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (1.3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLOS, days\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9\u0026plusmn;12\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e90-day readmission, n (%) (N\u0026thinsp;=\u0026thinsp;74)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e16 (21.6)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCSF leak\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6 (8.1)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHyponatremia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2 (2.7)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAltered mental status\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2 (2.7)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eStroke\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (1.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAVP-D\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (1.4)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDizziness\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (1.4)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFever, lethargy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (1.4)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHydrocephalus\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (1.4)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSubdural hematoma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (1.4)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePostoperative treatment, n (%) (N\u0026thinsp;=\u0026thinsp;83)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNone\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e53 (63.9)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRadiotherapy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e12 (14.5)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRepeat surgery\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6 (7.2)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRadiation and targeted therapy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (1.2)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOther\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e11 (13.3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTime to repeat surgery, mean month\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.3\u0026plusmn;14.5\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTime to radiotherapy, mean months\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e15.8\u0026plusmn;24.3\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRecurrence, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3 (12.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eProgression-free survival, mean months\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9.0\u0026plusmn;4.2\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOverall survival/follow-up, mean months\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e12.3\u0026plusmn;14.6\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"2\"\u003eAbbreviations: AVP-D, arginine vasopressin deficiency; CSF, cerebrospinal fluid; LOS, length of [hospital] stay; SNF, skilled nursing facility\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eWithin the follow-up period of 12.3\u0026plusmn;14.6 months, most patients did not undergo postoperative treatment (63.9%). Adjuvant radiotherapy was most common (14.5%), followed by repeat surgery (7.2%). One patient was treated with radiotherapy plus BRAF targeted therapy after two prior subtotal resections. The average time to re-resection was 11.3\u0026plusmn;14.5 months (range 0\u0026ndash;43 months) and average time to radiotherapy was 15.8\u0026plusmn;24.3 months (range 1\u0026ndash;79 months). Three patients recurred at an average of 9.0\u0026plusmn;4.2 months. Given the small number of recurrences and the short follow up period, time-to-recurrence analyses were not performed.\u003c/p\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003eSubgroup Analyses\u003c/h2\u003e \u003cp\u003eWe measured the effect of surgical outcomes on complications and need for additional treatment. Compared with STR, GTR was associated with higher likelihood of permanent AVP-D (57.1% [16/28] vs. 80.5% [33/41]; p\u0026thinsp;=\u0026thinsp;0.04) (Table\u0026nbsp;\u003cspan refid=\"Tab5\" class=\"InternalRef\"\u003e5\u003c/span\u003e). By contrast, GTR was associated with lower rate of adjuvant radiotherapy (4.7% [2/43] vs. 25.8% [8/31], p\u0026thinsp;=\u0026thinsp;0.01) and additional surgery (4.7% [2/43] vs. 12.9% [4/31], p\u0026thinsp;=\u0026thinsp;0.01). CSF leak was not associated with EOR, or with prior treatment, mFI-11, surgeon experience, surgical repair strategy, or tumor imaging characteristics (data not shown). However, patients who returned to the OR were more likely to discharge to a skilled nursing facility or rehabilitation unit rather than to home (28.6% vs. 4.1%, p\u0026thinsp;=\u0026thinsp;0.0001). Patients with pituitary stalk preservation showed lower rates of permanent 90-day panhypopituitarism including in AVP-D (53.8% [21/39] vs. 92.6% [25/27), p\u0026thinsp;=\u0026thinsp;0.003), adrenal insufficiency (52.6% [20/38] vs. 96.3% [26/27], p\u0026thinsp;=\u0026thinsp;0.0001), and hypothyroidism (71.1% [27/38] vs. 85.2% [23/27], p\u0026thinsp;=\u0026thinsp;0.01).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab5\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 5\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eSubgroup analyses\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colspan=\"4\" nameend=\"c4\" namest=\"c1\"\u003e \u003cp\u003e\u003cem\u003eEffect of EOR on complications and outcomes\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cem\u003eSubtotal resection\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cem\u003eGross total resection\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003eP value\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAVP-D\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e16/28 (57.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e33/41 (80.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.04\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAdrenal insufficiency\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e15/28 (53.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e35/41 (85.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.004\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSNF/rehabilitation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4/29 (13.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3/42 (7.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.7\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRecurrence\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2/3 (66.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1/16 (6.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.007\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRadiotherapy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8/31 (25.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2/43 (4.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.01\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAdditional surgery\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4/31 (12.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2/43 (4.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.01\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFollow-up, months\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e15\u0026plusmn;14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e13\u0026plusmn;16\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.6\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLOS, days\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e10\u0026plusmn;16\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9\u0026plusmn;9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.7\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"4\" nameend=\"c4\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eEffect of pituitary stalk preservation on endocrine outcomes\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cem\u003ePituitary stalk preserved\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cem\u003ePituitary stalk not preserved\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003eP value\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAVP-D\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e21/39 (53.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e25/27 (92.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.003\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAdrenal insufficiency\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e20/38 (52.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e26/27 (96.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.0001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHypothyroidism\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e27/38 (71.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e23/27 (85.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.01\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003eAbbreviations: AVP-D, arginine vasopressin deficiency; LOS, length of [hospital] stay; SNF: skilled nursing facility.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e"},{"header":"DISCUSSION","content":"\u003cp\u003eWe evaluated a large group of 99 PCPs treated at 14 skull base centers by 29 neurosurgeons. Our analysis represents one of the largest descriptive multicenter, multi-surgeon cohort studies of surgical outcomes for PCP to date. We found that most patients presented with visual changes, headaches, and fatigue. Tumors mostly showed mixed cystic/solid components, and were trans-infundibular and retro-chiasmatic. Endoscopic endonasal surgical approaches were most commonly used. Pituitary stalk preservation was achieved in 52% of cases, which correlated with reduced rates of AVP-D and endocrinopathy. GTR was achieved in 55% of cases and correlated with reduced use of both adjuvant radiotherapy and additional surgery. Targeted \u003cem\u003eBRAF\u003c/em\u003e\u003csup\u003e\u003cem\u003eV600E\u003c/em\u003e\u003c/sup\u003e inhibition, in conjunction with radiotherapy, was only used in 1 patient after several STRs. Approximately 68% of patients showed permanent AVP-D at 90 days follow-up. Nearly all patients were discharged home, and reoperation increased the risk of SNF/rehab placement.\u003c/p\u003e \u003cdiv id=\"Sec13\" class=\"Section2\"\u003e \u003ch2\u003ePatient and Tumor Characteristics\u003c/h2\u003e \u003cp\u003eOur results are similar to those of others evaluating the presentation and treatment of PCP. Prieto et al. reviewed 350 published cases of PCP and similarly showed headaches, visual deficits, and endocrinopathy were common presenting symptoms [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]. Mixed solid and cystic components were common, and were often seen with sellar, suprasellar, and ventricular involvement. Prieto et al. showed 57.5% of cases involved the third ventricle; these tumors tended to be more solid and spherical tumors, with greater hypothalamic involvement. Multiple classifications for craniopharyngiomas have been suggested based on their relationship to the infundibulum [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e, \u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]. Our results add to this classification by including the relationship of the tumor to the optic chiasm. Most tumors were both trans-infundibular (50.0%) and retro-chiasmatic (75.3%), which can create challenges for surgical treatment of the tumor and for postoperative management of AVP-D.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec14\" class=\"Section2\"\u003e \u003ch2\u003eTreatment Approaches and Surgical Outcomes\u003c/h2\u003e \u003cp\u003ePrieto et al. showed that patients underwent a variety of surgical approaches, including endoscopic and microsurgical methods, and only 15% of patients achieved a GTR [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]. Approximately 75% patients in our series underwent an endoscopic surgical approach and 55% achieved GTR, suggesting tumors in a variety of locations could be treated successfully endoscopically. Nevertheless, our results, similar to others, show that while GTR reduces the risk of tumor recurrence, these outcomes are dependent on tumor adherence and position [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e, \u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e, \u003cspan additionalcitationids=\"CR27 CR28\" citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e]. Furthermore, data from Prieto et al. indicate that a normal pituitary stalk is not often identified in sellar-suprasellar lesions with or without extension to the third ventricle. In line with these findings, our results show that pituitary stalk preservation was associated with a decreased frequency of endocrinopathies.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec15\" class=\"Section2\"\u003e \u003ch2\u003ePostoperative Treatment\u003c/h2\u003e \u003cp\u003eWe found that most patients (63.9%) did not undergo any further treatment after surgical resection. Others have indicated that greater EOR can improve outcomes and reduce the need for adjuvant therapy [\u003cspan additionalcitationids=\"CR31\" citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e]. Patients returned to the OR most often for repair of CSF leak and return to the OR predicted a higher likelihood of SNF/rehab placement. Despite supportive evidence for the role of BRAF inhibitors [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e], few patients used targeted therapy. It may be challenging for patients to obtain approval for use of such treatments from payors until greater supportive evidence and follow-up is available. Integration of BRAF/MEK inhibitors into treatment algorithms could offer another alternative to surgery but require weighing the benefits of non-operative treatment with its side effects and durability. Our data can serve as a benchmark for short-term surgical outcomes in future comparative studies, but long-term data are needed to fully understand how to select ideal patient populations for each treatment modality and how to optimize treatment outcomes.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec16\" class=\"Section2\"\u003e \u003ch2\u003eStrengths and Limitations\u003c/h2\u003e \u003cp\u003eTo our knowledge, the RAPID consortium enabled the largest real-world clinical information dataset for PCP, which is an otherwise rare and poorly understood pathology. Most important, the registry will allow us to update our preliminary analyses with the addition of future prospective patients to augment the current dataset. Future work could focus on outcomes of radiotherapy and targeted therapies based on EOR as well as changes in practice patterns over time and comparison of outcomes in PCP vs. adamantinomatous craniopharyngioma.\u003c/p\u003e \u003cp\u003eLimitations of our study are common to all registries. Data are collected retrospectively, which may make it prone to coding inconsistencies or omission. Missing data may limit our ability to draw conclusions, and contributing centers may not be representative of all sites treating patients with PCP, which could bias the data. The nature of the registry might also affect how our data can be compared with those of other investigators. For example, the current prevalence of endoscopic approaches in our series may limit its comparison to prior cranial focused studies, and clinical data of some patients might have been used for analyses of prior works not known to the authors. An additional limitation is the relatively limited median follow-up of 12 months in our dataset. Recurrence and progression of PCP may be delayed [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e, \u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e, \u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e], which may account for the relatively low rates of additional interventions such as radiotherapy. Longer-term follow-up studies are needed to evaluate the effect of tumor characteristics on outcomes and complications as well as to evaluate practice changes and institutional variations in treatment approaches.\u003c/p\u003e \u003c/div\u003e"},{"header":"CONCLUSION","content":"\u003cp\u003eThis study from the multicenter RAPID consortium describes patient characteristics, treatment trends, and short-term outcomes of PCP management. Our findings can serve as a foundation for future, longer-term studies and help with development of treatment algorithms for this rare disease.\u003c/p\u003e"},{"header":"Declarations","content":"\u003ch2\u003eCompeting Interests\u003c/h2\u003e\u003cp\u003eASL was previously a consultant for SPIWAY and BK Medical Systems and was an investor in Kogent Surgical; those relationships have ended. JMS\u0026rsquo; institution receives funding from Fractyl Health Inc, Amryt, Ascendis, Camurus, Bayer, Sparrow, Recordati, and Abbvie and JMS is a consultant for Xeris and Camurus. VRK is a consultant for Stryker and Integra LifeSciences. JF-M is a consultant for Medtronic, Stryker, and Hotry. MK is a consultant for Altus. All other authors have no relevant financial or non-financial interests to disclose.\u003c/p\u003e\u003ch2\u003eFunding:\u003c/h2\u003e \u003cp\u003eThis work was supported by Lodestar Foundation and Barrow Neurological Foundation.\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eAll authors contributed to the study conception, design, material preparation, and data collection. MPC, DP, and MK analyzed the data and wrote the first draft of the manuscript. All authors commented on the previous versions of the manuscript. All authors read and approved the final manuscript.\u003c/p\u003e\u003ch2\u003eAcknowledgement\u003c/h2\u003e\u003cp\u003eWe thank the staff of Neuroscience Publications at Barrow Neurological Institute for assistance with manuscript preparation. We acknowledge Dr. Kevin Yuen as a collaborator from Barrow Neurological Institute.\u003c/p\u003e\u003ch2\u003eData Availability\u003c/h2\u003e \u003cp\u003eThe data that support the findings of this study are not openly available due to reasons of sensitivity and are available from the corresponding author upon reasonable request.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eMomin AA, Recinos MA, Cioffi G, Patil N, Soni P, Almeida JP et al (2021) Descriptive epidemiology of craniopharyngiomas in the United States. 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Neurosurgery 46(2):291\u0026ndash;302 discussion \u0026ndash;\u0026thinsp;5. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1097/00006123-200002000-00007\u003c/span\u003e\u003cspan address=\"10.1097/00006123-200002000-00007\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eJannelli G, Calvanese F, Paun L, Raverot G, Jouanneau E (2023) Current Advances in Papillary Craniopharyngioma: State-Of-The-Art Therapies and Overview of the Literature. Brain Sci 13(3). \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.3390/brainsci13030515\u003c/span\u003e\u003cspan address=\"10.3390/brainsci13030515\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Papillary craniopharyngioma, multicenter study, surgery, outcomes","lastPublishedDoi":"10.21203/rs.3.rs-5245655/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-5245655/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003ePurpose:\u003c/strong\u003e 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.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods: \u003c/strong\u003eRetrospective 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.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults\u003c/strong\u003e: 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). \u003cem\u003eBRAF\u003c/em\u003e\u003csup\u003e\u003cem\u003eV600E\u003c/em\u003e\u003c/sup\u003e mutation was detected in 64/69 tumors tested, although only 1 patient was treated with a BRAF inhibitor.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion: \u003c/strong\u003eTo 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.\u003c/p\u003e","manuscriptTitle":"Short-term Surgical Outcomes of Papillary Craniopharyngiomas: A Multicenter Study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-11-13 14:42:30","doi":"10.21203/rs.3.rs-5245655/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"92a2d4f8-49c3-4051-9c1f-5f85abd53954","owner":[],"postedDate":"November 13th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2024-11-28T12:39:12+00:00","versionOfRecord":[],"versionCreatedAt":"2024-11-13 14:42:30","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-5245655","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-5245655","identity":"rs-5245655","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}