proteins

2026-09-29 | Semaglutide for Treating Paediatric Craniopharyngioma-Related Obesity: A Multicentre Case Series.

Obesity is a complication of childhood craniopharyngioma that remains difficult to treat. We investigated whether semaglutide was associated with a decrease in BMI among adolescents with craniopharyngioma-related obesity. This multicentre retrospective study included 20 patients < 18 years old with craniopharyngioma and obesity (BMI > 2 WHO Z-score) from 2019 to 2024 (source population: 139 children with craniopharyngioma, including 36 children with obesity). They received off-label semaglutide with dose titration (0.25-2 mg/week), tailored to tolerance and clinical response. The primary outcome was the within-patient comparison of BMI change from -12 months to treatment initiation and from initiation to +12 months. At semaglutide initiation, patients were 14.0 ± 3.9 years old, the interval since craniopharyngioma diagnosis was 6.3 ± 4.7 years, and BMI was 33.4 ± 3.9 kg/m2 (3.2 ± 0.7 Z-score). Tumour treatment was surgery alone (8/20), surgery and proton therapy (11/20), or proton therapy alone (1/20). All patients had growth hormone and TSH deficiency; 19/20 had ACTH and AVP deficiency. In the year before treatment, patients gained 3.5 ± 4.4 kg/m2 in BMI and 0.6 ± 1.6 in BMI Z-score; after 1 year of semaglutide therapy, they lost 2.5 ± 3.9 kg/m2 in BMI and 0.5 ± 0.5 in BMI Z-score (paired comparisons, p < 0.001 and p = 0.004, respectively). During treatment, BMI decreased by 10% or more in 40% of patients (95% CI: 19%-64%). Gastrointestinal side effects occurred in 30% of patients but were mild. No cases of treatment discontinuation, pituitary insufficiency decompensation or tumour recurrence were observed. Semaglutide was associated with reversal of weight gain among adolescents with craniopharyngioma-related obesity.

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2026-09-27 | Hypothalamic obesity in pediatric vs. adult craniopharyngioma: mechanisms, management, and cardiometabolic outcomes.

Hypothalamic obesity (HO) is a treatment-related complication in craniopharyngioma (CP) survivors that markedly impairs long-term health and quality of life. Although overall survival exceeds 90% for both pediatric and adult CP, HO prevalence and clinical course differ substantially by age at onset. We aimed to compare HO manifestations, mechanisms, and treatment response between pediatric and adult CP cohorts. We conducted a scoping review of studies published between 2000 and 2025, comparing pediatric (childhood-onset) versus adult-onset CP cohorts, classified by age at diagnosis. Data on obesity prevalence, mechanistic pathways, therapeutic interventions, and cardiometabolic outcomes were extracted and synthesized. In pediatric CP survivors, obesity rates rise from 5.7% pre-treatment to 57% post-treatment; in adults, from 19.2% to 29.2%. HO severity correlates with the extent of hypothalamic damage by Puget and QST grading. Key mechanisms include disrupted melanocortin signaling, central leptin and insulin resistance, and neuroinflammation via resistin-TLR4 and NLRP3 pathways. GLP-1 receptor agonists (exenatide, semaglutide) have produced marked weight loss in small case series (up to 17% over 6 months with semaglutide), but randomized trials did not meet their primary weight outcomes and direct pediatric-versus-adult comparisons are lacking. Bariatric procedures yield moderate success; sleeve gastrectomy achieves 5-year weight loss comparable to that in non-CP controls (21.7% vs. 21.8%), whereas Roux-en-Y gastric bypass is less effective than in controls (22.7% vs. 32.0%). Both cohorts face significant long-term risks: 2.2-fold higher all-cause mortality and 9.3-fold higher diabetes risk in adults, non-alcoholic fatty liver disease in 47% of pediatric survivors, metabolic dysfunction-associated fatty liver disease in 67.4% of adults, and insulin resistance in approximately 30% of pediatric patients. HO following CP shows distinct age-dependent trajectories in prevalence, underlying mechanisms, and clinical course; suggested age-related differences in treatment response remain to be confirmed in direct comparative studies. Tailored management integrating mechanistic insights and age-specific therapies is critical to mitigating the cardiometabolic burden in these patients.

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2026-09-15 | Injection-site pain after switching from somatrogon to somapacitan in children reporting pain or discomfort during once-weekly growth hormone therapy: a prospective single-arm switch study.

Once-weekly growth hormone (GH) formulations, such as somatrogon and somapacitan, may reduce the burden of treatment, but injection-site pain can affect treatment preference. Clinical data on patient-reported injection-site pain and preference after switching between once-weekly GH formulations remain limited, particularly in children who experience injection-site pain. To describe changes in perceived injection-site pain and treatment preference after switching from somatrogon to somapacitan in children who reported injection-site pain or discomfort during somatrogon therapy. This prospective single-arm switch study included 19 children with GH deficiency who had received somatrogon for at least 4 weeks, reported injection-site pain or discomfort during routine clinical care, and agreed to switch to somapacitan. Pain scores for prior somatrogon use and current somapacitan use were assessed once after at least 4 weeks of somapacitan treatment, using the Numerical Rating Scale and/or Faces Rating Scale according to age. A 5-point Likert questionnaire evaluated device usability, pain at needle insertion, pain during injection, pain after injection, and treatment preference. Paired t-tests and binomial tests were used for the main analyses, and Wilcoxon signed-rank tests were performed as sensitivity analyses for paired pain-score comparisons. The mean age was 9.6 ± 2.6 years. Diagnoses included isolated GH deficiency (n = 17) and panhypopituitarism after craniopharyngioma surgery (n = 2). Pain scores decreased after switching (Numerical Rating Scale: 6.5 ± 2.6 vs 1.6 ± 1.7; Faces Rating Scale: 3.8 ± 1.1 vs 1.1 ± 1.1; both p < 0.001). All participants preferred continued use of somapacitan (p < 0.001), and questionnaire responses favored somapacitan for pain at needle insertion and pain during injection. In children who reported injection-site pain or discomfort during somatrogon therapy and agreed to switch, pain scores and treatment preference improved after switching to somapacitan. These findings support considering a switch to another once-weekly GH formulation when injection-site pain affects treatment preference.

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2026-05-12 | Linear growth and metabolic outcomes of growth hormone treatment in childhood-onset craniopharyngioma: the OUTSPREAD study.

Growth hormone (GH) deficiency is common following craniopharyngioma resection. This study aimed to compare growth status and metabolic parameters before and after GH treatment for patients with craniopharyngioma. This retrospective study included 134 patients with multicenter study for Ideal Outcomes of Pediatric Rare Endocrine and Metabolic Diseases in Korea (OUTSPREAD study), who received GH treatment for ≥1 year. Data on growth and metabolic parameters before and after GH treatment (at 1, 2, and 3 years, and at the end of treatment) were collected. The mean age at diagnosis was 7.6 years, with GH treatment initiated at 9.4 years and concluded at 15.7 years. Before GH treatment, height and weight were below average, while body mass index (BMI) was above average. Following GH treatment, height and weight significantly increased while BMI decreased. Analysis using a sex-, age- and steroid dose- adjusted linear mixed model showed significantly decreased aspartate aminotransferase, alanine aminotransferase and total cholesterol levels after treatment. Random glucose levels increased slightly but remained within the normal range, and glycosylated hemoglobin levels remained stable. This is the first longitudinal report showing the positive effects of GH treatment for craniopharyngioma in Korean patients. After surgery for craniopharyngioma, GH treatement is essential for patients with GH deficiency. In this first multicenter Korean cohort evaluating long-term growth and metabolic outcomes, GH treatment significantly improved height, weight, and BMI SDS. Hepatic indices (AST/ALT) and lipid parameters (total cholesterol) decreased during treatment. Random glucose increased slightly but remained within the normal range, and HbA1c showed no significant change. These findings support GH treatment as a key component of long-term management with benefits beyond linear growth.

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2026-03-30 | Children with craniopharyngioma resection had better response to recombinant human growth hormone therapy than those with idiopathic short stature.

To compare growth response and rhGH dosage requirements between children with craniopharyngioma post-resection (CP group, n=18) and those with idiopathic short stature (ISS group, n=18). A retrospective analysis (2010-2020) was conducted on pediatric patients who received rhGH therapy. Key parameters compared between CP and ISS groups included: growth velocity (GV), rhGH dose (IU/kg/d), height, height standard deviation score (HtSDS), IGF-1 standard deviation score (IGF-1 SDS), body mass index (BMI), bone age (BA) and bone age to chronological age ratio (BA/CA). CP patients were older at baseline with lower HtSDS and BA/CA. Both groups had similar annual growth velocities over three years. The CP group achieved comparable height gains with half the rhGH dose of the ISS group. IGF-1 SDS increased in CP but decreased in ISS, normalizing in both. Long-term, CP patients maintained lower BA/CA and achieved higher terminal height. In this observational cohort, children with CP received approximately half the rhGH dose used in children with ISS, yet achieved comparable growth velocity and greater near-adult height.

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cell therapies

2026-03-11 | Are Routine Lumbar Drains Necessary for Endoscopic Reconstruction after Resection of Anterior and Central Skull Base Tumors?

The expanded endonasal approach (EEA) is historically associated with high rates of postoperative cerebrospinal fluid (CSF) leak. Therefore, many surgeons advocate for routine lumbar drain (LD) placement despite mixed evidence of their efficacy. We report outcomes for anterior and central skull base reconstructions after EEA without LDs. A retrospective review was conducted evaluating consecutive patients undergoing EEAs for resection of central and anterior skull base pathology from 2015 to 2024 at two academic institutions. Incidence of postoperative CSF leak. Eighty-five patients underwent a total of 89 EEAs. Patients were predominantly female (62.9%) with an average age of 45.1 years (range 11 months-84 years). Tumors included primarily craniopharyngiomas (49.4%) and meningiomas (46.1%). No LDs were placed perioperatively, and there was an 100% intraoperative high-flow CSF leak rate. Skull base reconstruction was performed using pedicled nasoseptal flaps (NSFs) in all cases, tensor fascia lata grafts in 82 cases, and fat grafts in 78 cases. The postoperative CSF leak rate was 7.9%. Suprasellar tumors were associated with lower rates of postoperative CSF leak compared with tuberculum sella and planum sphenoidale pathology ( p  = 0.030), whereas meningiomas trended toward higher CSF leak rates compared with craniopharyngiomas ( p  = 0.059). We report a low rate of postoperative CSF leak without LD placement after EEA. Our results suggest that successful skull base reconstructions may be performed with multilayered closures using vascularized NSFs without the need for routine CSF diversion.

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2026-02-09 | In-situ bone flap combined with a nasoseptal flap or a free mucosa flap for skull base reconstruction after endoscopic resection of craniopharyngiomas: A series of 115 cases.

Previous reports have indicated that in comparison with the use of a nasal septal flap (NSF) for skull base reconstruction, the use of a free mucosal flap (FMF) is associated with an increased incidence of cerebrospinal fluid (CSF) leakage in patients with intraoperative high-flow CSF leakage but less nasal trauma. The authors previously reported that the use of an in situ bone flap (ISBF) was beneficial for controlling postoperative CSF leakage. The objective of this study was twofold. The first aim was to analyze the risk factors associated with postoperative CSF leakage. Second, the CSF leakage rate was compared between the two reconstruction techniques for different risk factors and total Sino-Nasal Outcome Test-20 (SNOT-20) scores. The results verify the feasibility of the use of an ISBF combined with an FMF for skull base reconstruction to control postoperative CSF leakage. Furthermore, the findings clarify the choice of skull base reconstruction in different situations. A retrospective review of 115 patients with craniopharyngiomas treated between May 2018 and June 2022 was conducted. Reconstruction of the skull base was performed in 67 patients using a combination of ISBF and NSF by October 2020 and in 48 patients using a combination of ISBF and FMF after October 2020. The overall rate of postoperative CSF leakage was 8.7%. According to the univariate analysis, a BMI ≥ 25 (20.7% vs. 4.9%, p = 0.016) and predominantly solid tumors (15.1% vs. 3.2%, p = 0.042) were associated with higher rates of postoperative CSF leakage. In the multivariate analysis, a BMI ≥ 25 and a solid component > 50% were identified as independent risk factors for postoperative CSF leakage. The mean SNOT-20 score was lower in the ISBF + FMF group than in the ISBF + NSF group at six months after surgery (13 ± 12.7 vs. 16 ± 16, p = 0.037). With respect to the repair of skull base defects by using the ISBF, the application of FMF controlled the postoperative CSF leakage rate within an acceptable range. Furthermore, it offered advantages over NSF in terms of SNOT-20 scores at six months post-operatively. A BMI ≥ 25 and a solid component > 50% were independent risk factors for postoperative CSF leakage. NSF remains a more suitable option for patients with a BMI ≥ 25.

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2026-01-12 | Giant Craniopharyngioma Complicated by Cerebrospinal Fluid Ascites in a 7-Year-Old Boy: A Case Report and Review of Literature.

Craniopharyngioma (CPG) is a rare benign brain tumor often affecting the sellar/parasellar region in children. Giant variants can cause severe intracranial pressure and hydrocephalus and require ventriculoperitoneal (VP) shunting. A seven-year-old boy presented with a two-year history of headaches, as well as recent visual deterioration, altered sensorium, and vomiting. MRI brain revealed a cystic mass in the sellar and suprasellar regions causing mild hydrocephalus. After tumor excision and VP shunt placement, he developed abdominal CSF ascites, requiring shunt revisions, including ventriculoatrial shunt, and later suffered from a pseudomonas infection, leading to death from acute respiratory distress syndrome and hospital-acquired pneumonia. This case highlights the rare but critical complication of CSF ascites following VP shunting in a child with giant craniopharyngioma, emphasizing the importance of early recognition and timely intervention. Clinicians should be aware of this potential complication, as it requires careful diagnostic workup and management strategies, including shunt modifications and consideration of alternative shunting options.

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2025-02-28 | The microsurgical advantage of huge cystic craniopharyngioma following long-term cystic aspirations via Ommaya reservoir: A case report.

Craniopharyngiomas are histologically benign tumors with a relatively high recurrence rate. Surgical removal is challenging due to proximity to critical brain structures. This report introduces a staged operation strategy for a huge cystic craniopharyngioma. An 8-year-old girl presented with diplopia and decreased visual acuity. Brain magnetic resonance imaging revealed a large, 10-cm-sized cystic mass encasing both the anterior and middle cerebral arteries and the optic nerve. An Ommaya reservoir was placed for periodic cyst aspirations over a period of 15 months. Subsequent magnetic resonance imaging indicated a reduction in cyst size, with an increasingly distinct tumor-pial interface evident on T2-weighted images. The tumor, initially entwined with neurovascular structures, gradually became delineated from these critical components. She underwent a secondary surgical intervention utilizing a bifrontal interhemispheric approach. Intraoperatively, the tumor was meticulously dissected and totally excised without compromising surrounding critical structures, while the tumor's origin, the pituitary stalk, underwent partial resection. There was no worsening of vision after surgery. She was on minirin medication, and there was no recurrence during the 1-year follow-up. Microsurgery of huge cystic craniopharyngioma following long-term cyst aspirations via Ommaya reservoir could present an efficacious strategy to diminish complication risks in pediatric patients.

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2025-02-02 | Multicenter study on 2-year outcomes of dual application of hydroxyapatite cranioplasty and a nasoseptal flap following endoscopic endonasal surgery for tuberculum sellae meningiomas or craniopharyngiomas.

The authors evaluated the intermediate-term outcomes of a skull base reconstruction technique using hydroxyapatite cranioplasty combined with a nasoseptal flap following endoscopic endonasal surgery (EES) for suprasellar tumors. Specifically, the evaluation focused on the avoidance of lumbar CSF drainage, prevention of CSF leakage, and incidence of postoperative complications, including meningitis and nasoseptal flap necrosis, during a minimum follow-up of 2 years. This multicenter study included patients who met the following criteria: 1) underwent EES for tuberculum sellae meningiomas or craniopharyngiomas, 2) received dual application of hydroxyapatite cranioplasty and reconstruction using a nasoseptal flap, 3) had a follow-up duration of at least 2 years, and 4) did not undergo lumbar drainage of CSF postoperatively. The success rate of reconstruction was determined based on postoperative CSF leakage, associated complications, meningitis, postoperative hospital length of stay (LOS), and would dehiscence. A total of 198 patients from three institutions diagnosed with tuberculum sellae meningioma (86 patients) or craniopharyngioma (112 patients) were included in this study. The median follow-up duration was 39 months. No patient underwent postoperative lumbar drainage of CSF. Postoperatively, only 3 patients (1.5%) experienced CSF leaks requiring reoperation. The median hospital LOS after surgery was 5 days. Other postoperative complications included atypical meningitis in 5 patients and wound dehiscence in 3 patients during the follow-up period. All patients with nonbacterial meningitis were treated with intravenous antibiotics and dexamethasone medication for 2 weeks. The combination of hydroxyapatite cranioplasty and a nasoseptal flap in reconstruction following EES decreased the requirement for postoperative lumbar CSF drainage and shortened hospital LOSs with minimal morbidities. Nevertheless, careful attention to the risks of meningitis and central necrosis of a nasoseptal flap is crucial for optimizing patient outcomes.

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small molecules

2026-09-23 | Modern craniopharyngioma management: three illustrative cases with distinct therapeutic strategies

Craniopharyngioma treatment is increasingly multimodal, with options including surgery, radiation therapy, targeted molecular therapy (for papillary craniopharyngiomas), and a combination of these. As such, management of craniopharyngioma is complex, and strategies depend on patient-specific and tumor-specific factors. Nonetheless, literature regarding treatment selection is lacking. As such, this video details three distinct clinical scenarios of craniopharyngioma management. The authors specifically highlight the role of planned subtotal resection for endocrine preservation in adamantinomatous pediatric craniopharyngioma, gross-total resection for progressive adamantinomatous craniopharyngioma in an adult, and targeted molecular therapy for progressive symptomatic papillary craniopharyngioma. The video can be found here: https://stream.cadmore.media/r10.3171/2026.7.FOCVID26109

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2026-08-21 | Hunger, satiety, and eating behavior after craniopharyngioma - narrative review on current management and future therapeutic perspectives.

Craniopharyngiomas are low-grade, intracranial tumors frequently associated with dysfunction of the hypothalamic-pituitary axes and the development of obesity. This narrative review aimed to evaluate the potential contribution of eating behaviors, while also identifying perspectives for future therapeutic intervention. Searches were performed across five bibliographic databases. All peer-reviewed published studies involving childhood-onset or adult-onset craniopharyngioma populations were considered eligible when they examined eating behavior in relation to pharmacological or surgical interventions, neuroimaging, endocrine responses, energy expenditure, sleep, and/or neuropsychological outcomes. The available evidence regarding eating behavior in individuals with craniopharyngioma was limited, with only 10 of the 82 included studies employing validated measures of eating behavior. Eating behavior was assessed as a primary outcome in seven studies, as a secondary outcome in twelve studies, and discussed without formal measurement in thirty-one studies. Only one randomized controlled trial with the melanocortin-4 receptor (MC4R) agonist setmelanotide was identified that successfully targeted eating behavior (hyperphagia) modification and achieved significant weight loss as an intervention for craniopharyngioma-related obesity. Greater insight into eating behavior in this population, supported by long-term studies using validated assessment tools, is required to clarify the mechanisms underlying craniopharyngioma-associated obesity and confirm effectiveness and tolerability of medical treatment with MC4R-agonists.

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2026-08-16 | [Recent Advances in the Treatment of Craniopharyngioma:A Breakthrough in Molecular Targeted Therapy].

Craniopharyngiomas are benign sellar and parasellar tumors that present significant clinical challenge because of their close proximity to the optic apparatus, hypothalamus, and pituitary gland. Recent molecular studies have identified distinct driver mutations, namely, CTNNB1 in adamantinomatous craniopharyngiomas and BRAF V600E in papillary craniopharyngiomas, leading to a deeper understanding of tumor biology and treatment strategies. Advances in endoscopic endonasal transsphenoidal surgery have improved surgical safety and expanded the indications for minimally invasive resection, whereas radiotherapy remains an effective option for residual or recurrent disease. Molecular targeted therapy with BRAF and MEK inhibitors has resulted in remarkable tumor shrinkage in papillary craniopharyngiomas harboring the BRAF V600E mutation, and recent clinical studies have established this approach as a promising treatment option. These agents have emerged not only as effective treatment options for recurrent or refractory disease but also as promising options for neoadjuvant treatment and function-preserving management. Future treatment strategies are likely to incorporate molecular subtypes, patient age, and functional outcomes to achieve individualized care. In addition, the development of reliable preoperative molecular diagnostic techniques, including liquid biopsy, may further facilitate the integration of targeted therapies into routine clinical practice.

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2026-08-14 | Molecular therapy for papillary craniopharyngioma: a multi-institutional analysis of practice patterns across the RAPID Consortium.

Targeted therapy for BRAF V600E mutant papillary craniopharyngioma (PCP) has been rapidly accepted, though given the rarity of the tumor, there is limited guidance for appropriate use. Here, we retrospectively evaluated current practice patterns for the implementation of targeted therapeutics and their outcomes in the treatment of papillary craniopharyngioma (PCP). Practice patterns at the institutions in the Registry for Adenomas of the Pituitary and Related Disorders (RAPID) for treatment of BRAF V600E mutated PCPs using targeted therapy were evaluated. Baseline clinical and demographic variables were retrospectively recorded. Imaging response was evaluated. Dosing, treatment course, adverse events (AEs) and other therapeutic strategies employing BRAF/MEK inhibitors were studied. Adjuvant and/or salvage therapies, including radiation and surgery were recorded. Most patients demonstrated at least partial response to BRAF and/or BRAF/MEK inhibition (13/19, 72.2%). No patients progressed through therapy. Grade 0-2 AEs occurred in 79% of cases, and nine (47.4%) patients eventually discontinued therapy. Radiation-sparing regimens demonstrated similar radiographic response rates and had smaller residual tumor volume after treatment completion (23.7 vs. 612.4 mm3, p = 0.040) compared to those receiving radiation. BRAF monotherapy demonstrated similar rates of response to therapy, but fewer Grade 3-4 AEs (0% vs. 28.5%) than dual therapy. Long-course therapy (> 4 cycles) resulted in radiographic response (p = 0.024) more often than a short-course (≤ 4 cycles), with similar AEs. Median follow-up duration was 19 months from surgery (range: 8-63). Critical insights into molecular therapeutic practice patterns for treatment of PCP were identified. Radiation-sparing, mono-therapeutic, and prolonged treatment duration are feasible options and warrant further study.

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2026-08-11 | Multidisciplinary Management of Pediatric Craniopharyngioma: From Diagnosis to Long-Term Outcomes

Background: Pediatric craniopharyngiomas are rare, histologically differentiated epithelial tumors arising in the sellar–suprasellar region. Despite their low-grade classification, these tumors are associated with significant long-term morbidity because of their proximity to critical neurovascular and hypothalamic structures. Management remains challenging and requires a careful balance between durable tumor control and the preservation of neurological, endocrine, and neurocognitive functions. Methods: This narrative review summarizes the current evidence concerning the epidemiology, molecular pathogenesis, clinical presentation, diagnostic evaluation, and treatment strategies for pediatric craniopharyngiomas. Emphasis is placed on anatomical and hypothalamic involvement-based classifications, evolving surgical philosophies, and the role of multimodal management. Results: Advances in molecular characterization have resulted in the delineation of two distinct subtypes—adamantinomatous and papillary craniopharyngiomas—with different biological drivers and therapeutic implications. Surgical management has evolved from historically aggressive gross total resection to risk-adapted, anatomy-driven approaches that prioritize hypothalamic preservation. In selected patients, subtotal resection combined with modern radiotherapy provides tumor control comparable to that of radical surgery, with reduced morbidity. Endoscopic endonasal and microsurgical transcranial approaches play complementary roles, with approach selection guided by tumor anatomy, hypothalamic involvement, and surgical expertise. Emerging targeted therapies and intracystic treatments further expand therapeutic options. Conclusions: The contemporary management of pediatric craniopharyngiomas emphasizes individualized, multidisciplinary strategies focused on functional preservation rather than anatomical radicality alone. Integration of molecular insights, advanced imaging, and long-term outcome data is essential to further improve survival and quality of life in this vulnerable population.

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antibodies

2026-08-01 | NE09 Craniopharyngiomas, clinical and surgical outcomes: results of a single-center retrospective study

Abstract Background Craniopharyngioma is a rare tumor associated with endocrine, metabolic, and cognitive morbidity due to its close relationship with critical structures, particularly the hypothalamus. Methods This retrospective single-center study evaluated 68 patients treated between 2003 and 2025 to assess the impact of surgical approach, tumor topography, and intraoperative findings, including hypothalamic and pituitary stalk involvement, on functional, oncological, and survival outcomes. Results The cohort included 22 papillary and 46 adamantinomatous craniopharyngiomas. Preoperatively, hypopituitarism, diabetes insipidus (DI), obesity, and cognitive deficits were present in 31.8%, 12.1%, 24.2%, and 39.4% of patients, respectively. The endoscopic endonasal transsphenoidal approach (EEA) was the most frequently used surgical technique, and gross total resection (GTR) was achieved in 47% of cases. Residual tumor was observed in 53% of patients and was significantly associated with hypothalamic infiltration, pituitary stalk resection, and surgical approach. Papillary histology was the only independent predictor of a lower risk of residual disease. Surgical complications were uncommon and mainly consisted of hydrocephalus. Postoperatively, endocrine and metabolic morbidity increased, with hypopituitarism affecting 79.6% of patients, permanent DI 54.7%, and obesity 42.2%. During a mean follow-up of 62 months, recurrence or progression occurred in 40% of cases. Residual tumor, surgical approach, and tumor location were significant predictors of recurrence/progression. Mortality occurred in 10.8% of patients and was strongly associated with hypothalamic infiltration, postoperative cognitive deficits, and non-EEA approaches. Conclusions: Tumor–hypothalamus relationship emerged as the strongest determinant of surgical radicality, postoperative morbidity, and long-term survival, while EEA provided superior resection rates and lower complication rates.

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2026-07-17 | Functional Outcomes of Pediatric Craniopharyngiomas in Relation to Treatment Approach

Abstract The objective of this study was to establish functional outcomes after treatment of pediatric craniopharyngiomas, stratifying by both treatment approach and extent of resection. We retrospectively reviewed the electronic medical records of pediatric patients who underwent neurosurgical intervention for craniopharyngioma at the Children's National Hospital (CNH) in Washington, DC, from 2002 to 2022. Inclusion criteria were patients younger than 21 years at the time of presentation, Ommaya reservoir placement, or craniopharyngioma resection at CNH, with follow-up data available. Standard statistical analyses were performed. Forty patients underwent a total of 59 procedures. Mean age at initial presentation was 8.6 years, with a mean clinical follow-up length of 65.5 months. A single procedure (resection or Ommaya reservoir) was performed in 72.5% (n = 29) of patients. Eighty-five percent (n = 34) of craniopharyngiomas were located in the intrasuprasellar region. Seventy-seven percent (n = 31) of initial procedures were open craniotomies, 15% (n = 6) Ommaya reservoir placement, and 7.5% (n = 3) endoscopic endonasal resections. Fifteen percent of patients (n = 6) underwent surgery at an outside hospital prior to presentation at CNH. Gross total resection (GTR) was the intent in 23 initial resections, and GTR was achieved in 16 (69.5%). Forty-five percent of patients (n = 18) received postoperative radiation, and 27.5% of patients received postoperative neuropsychological evaluation (n = 11). No complications were reported in 80.5% of procedures (n = 33). When endocrine outcomes were compared by approach, open craniotomy versus endoscopic endonasal approach versus Ommaya, statistically significant differences were found in adrenal insufficiency (p < 0.001), hypothyroidism (p = 0.01), and diabetes insipidus (p < 0.001). When endocrine outcomes were compared by extent of resection, GTR versus subtotal resection versus Ommaya, statistically significant differences were found in adrenal insufficiency (p < 0.001), hypothyroidism (p < 0.001), growth hormone deficiency (p = 0.03), and diabetes insipidus (p < 0.001). No statistically significant differences were seen in visual or neurological outcomes by extent of resection or by resection approach. Patients with craniopharyngioma experience both treatment and disease-related morbidity. No significant differences were seen in the majority of postoperative visual and neurological outcomes when comparing treatment approach or extent of resection. However, the neurological findings are limited by power and formal neuropsychiatric testing. Our results motivate the development of novel therapeutic strategies to better preserve functional status.

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2026-07-15 | When the cure becomes the curse: Radiation-induced glioma of the pons in children surviving craniopharyngioma.

The standard of care for pediatric craniopharyngioma (CP) is either complete surgical resection or limited debulking surgery followed by adjuvant radiotherapy (RT). Recent data favor the latter approach. We present a multi-center case series of three children with CP treated with subtotal surgery and adjuvant RT for CP who eventually developed radiation-induced glioma (RIG) of the pons. The median age at diagnosis of CP was 6 years. Photon RT was administered in two patients and proton RT in one, at a median dose of 54 Gy delivered in 30 fractions. Pontine glioma was first identified on imaging after a median interval of 8 years from initial RT (range 4.5 - 9.75 years), incidentally in two asymptomatic patients during routine surveillance, and associated with symptoms of brainstem involvement in one. A biopsy was performed in two patients. One showed diffuse astrocytoma with MYCN, PDGFRA, and MDM2 amplification and a novel fusion (RBD7-FLI1), while the other case had an inconclusive histopathology. Re-irradiation (re-RT) (54 Gy/30 fractions and 30 Gy/10 fractions) was applied in two patients, and one patient received bevacizumab treatment. All three patients succumbed with a median survival of 7.5 months (range 4.0-58 months). Radiation-induced glioma of the pons is a rare and serious complication occurring in patients previously treated by RT for childhood CP. This secondary tumor is uniformly associated with a dramatic course regardless of the treatment modalities and resources. This highlights the need for clinical vigilance and further research to prevent it.

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2026-07-01 | Recurrence Predictors in Operated Cases of Craniopharyngioma

Background: Craniopharyngiomas are benign tumors that develop in the sellar and suprasellar region of the brain. Their location often leads to significant health complications due to the pressure exerted on nearby critical structures. Surgical removal remains the cornerstone of treatment. One of the major challenges is the high rate of recurrence, which affects approximately 30% to 40% of patients, even after seemingly successful surgery. Gaining these insights of causes of recurrence is crucial for guiding treatment choices and planning effective long-term follow-up care. Objectives: To identify the recurrence predictors of craniopharyngioma and correlate it with other factors. Methods: This observational study was carried out at a tertiary care center over a four-year period, from January 2020 to January 2024 that included 25 patients who underwent surgical removal of craniopharyngiomas. Based on their postoperative follow-up, patients were divided into two groups: those who experienced tumor recurrence and those who did not. Data were collected based on each patient’s demographics, symptoms, imaging findings, tumor subtype, and the presence of β-catenin expression through immunohistochemistry. Results: In this study, the overall recurrence rate of craniopharyngiomas was 40%. Recurrence was notably higher in certain subgroups like in males (68%). Tumors with calcifications on imaging were also more likely to recur (88%). A strong association was also observed between beta-catenin expression and the likelihood of recurrence. In contrast, no significant link was found between recurrence and factors such as gender, preoperative hormonal status. Conclusion: Our findings suggest that younger age at diagnosis, the presence of calcification are all significantly associated with a higher risk of tumor recurrence. Additionally, positive β-catenin immunoreactivity emerged as a potential biomarker for identifying tumors with more aggressive behavior.

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2026-06-03 | The Role of Genetic Mutations in CTNNB1 and APC Genes on the Craniopharyngioma

Craniopharyngioma occurs in about 0.5 to 2 per million people each year and has a bimodal distribution, 5 to 14 years and 50 to 74 years. Many experts consider craniopharyngioma to be a chronic disease because it tends to recur even when completely surgically removed. The tumor itself is usually not dangerous, as it is benign and rarely becomes malignant. However, the location of the tumor is such that it can compress the pituitary gland, leading to hormonal dysfunction. There are two types of craniopharyngiomas: adamantiomatous and papillary. The former occurs more commonly in children, while the latter is more common in adults. Adamantiomatous craniopharyngiomas arise from cells in an embryonic structure called the craniopharyngeal canal. They can be solid or form a hollow (cystic) structure filled with a dark brown to black fluid (similar to motor oil) and are often calcified. Papillary craniopharyngiomas are rarer and arise from cells in the anterior pituitary gland. They are usually wellcircumscribed and can also be solid or cystic, although they are filled with a yellow, viscous fluid. Craniopharyngioma is caused by abnormalities of mbryonic tissue in the sellar and parasellar regions. Adamantiomatous craniopharyngioma, which occurs more frequently in children, and papillary craniopharyngioma, which occurs more frequently in adults, have different embryonic origins.

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2026-07-15 | Dual AI models for gamma knife radiosurgery in craniopharyngioma: prescription dose modeling and outcome risk prediction.

Gamma Knife radiosurgery (GKRS) is an established adjunct for residual or recurrent craniopharyngioma, yet prescription dose selection remains experience-driven and long-term failure risk is difficult to individualize. Machine learning may support more consistent planning and risk-informed follow-up. To develop and internally validate two complementary AI models for craniopharyngioma GKRS: (1) prescription dose prediction and (2) treated-lesion progression risk prediction. In this retrospective single-center cohort, we trained a random forest regressor to predict delivered single-fraction margin dose (Gy) from baseline clinical and tumor features and a random forest classifier to estimate the probability of treated-lesion progression using baseline features and delivered dose. Internal validation used cross-validation with discrimination and calibration metrics. Seventy-two treated tumors were analyzed. Prescription dose prediction showed clinically tight error, with MAE 1.30 Gy and RMSE 1.65 Gy (R² 0.21), indicating the model approximated physician dosing patterns within ~1-2 Gy for most cases. For outcome modeling, risk prediction achieved ROC-AUC 0.75 and PR-AUC 0.582, with reasonable calibration (Brier score 0.112; recalibration slope 0.86, intercept 0.096). Together, the two models enabled simultaneous estimation of an expected prescription dose and an individualized probability of long-term treated-lesion failure, supporting risk stratification beyond dose alone. A dual-model AI framework for craniopharyngioma GKRS is feasible and provides both dose estimates and individualized long-horizon failure risk predictions, with potential to standardize prescriptions and tailor surveillance intensity. Not applicable.

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2026-07-09 | Gamma Knife treatment of papillary craniopharyngioma: a single-center study of tumor control and predictors of progression.

Papillary craniopharyngioma (PCP) is a rare sellar tumor distinct from adamantinomatous type. Although Gamma Knife radiosurgery (GKRS) treats craniopharyngiomas effectively, dedicated PCP-only GKRS outcome series are scarce. We evaluated tumor control and prognostic factors following GKRS for PCP. We retrospectively analyzed 34 patients with histologically confirmed PCP who underwent GKRS at Beijing Tiantan Hospital (2002-2025) for residual/recurrent disease after surgery. Primary endpoint was progression-free survival (PFS). Kaplan-Meier and Cox regression analyses identified prognostic factors. Thirty-four patients (18 males, mean age 41.7 ± 13.6 years) received GKRS with median marginal dose 12 Gy to median tumor volume 1.10 cm³. With a median clinical follow-up of 54.10 months, the 1-, 3-, and 5-year PFS rates were 91.18%, 82.35%, and 73.53%, respectively. Overall survival was 94.12%. Disease control rate was 70.59%. Exploratory analysis with limited statistical power (10 events, EPV = 3.3) suggested potential associations between tumor volume > 1.1 cm³ (HR = 3.86, P = 0.061) and preoperative hypogonadism (HR = 3.94, P = 0.058) with progression, though these findings require validation in larger cohorts. Visual deterioration was significantly higher in progression group (80.0% vs. 16.7%, P = 0.002). Most patients (61.8%) maintained good quality of life. GKRS provides effective long-term tumor control for postoperative PCP patients with acceptable safety profile. Exploratory hypothesis-generating analysis suggested potential associations between tumor volume and preoperative gonadal function status with progression, though these findings require validation in adequately powered studies. These findings support GKRS as a valuable treatment option in the multimodal management of PCP, particularly for patients with residual or recurrent disease after surgery.

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2026-05-12 | Stereotactic radiosurgery for pediatric craniopharyngiomas: a multicenter retrospective study.

The role of stereotactic radiosurgery in the management of pediatric craniopharyngiomas remains incompletely defined, particularly with respect to long-term disease control and late treatment-related morbidity. This multicenter study evaluates long-term tumor control and functional outcomes following Gamma Knife radiosurgery (GKRS) in pediatric patients with craniopharyngiomas. We retrospectively analyzed 33 pediatric patients (< 18 years) treated with GKRS for residual or recurrent craniopharyngiomas at two independent and experienced neurosurgery centers. Radiological tumor control, recurrence-free survival, visual and endocrinological outcomes were assessed longitudinally. Kaplan-Meier and Cox regression were used to identify factors affecting outcomes. The mean age at GKRS was 11.8 years, and the mean tumor volume was 2.3 cm³. The median follow-up was 122.8 months (IQR 79.4-204.3 months). Recurrence-free survival rates at 1, 3, 5, and 10 years were 84.8%, 78.6%, 67.7%, and 48.6%, respectively. Among patients with tumor progression, 66.7% experienced out-of-field recurrence, whereas in-field failures were less common and occurred after a significantly longer interval (63.9 ± 7.7 vs. 19.6 ± 18.3 months; p < 0.01). Visual function remained stable or improved in 97% of patients. One patient experienced visual deterioration (3.0%) related to tumor progression. New-onset endocrinological deficits were uncommon and occurred in patients with pre-existing hypopituitarism (6/27, 22.2% vs. 0/6, 0%, p = 0.003). GKRS provides durable control of treated tumor volumes with minimal long-term visual and endocrinological morbidity in selected pediatric patients with craniopharyngiomas. Late disease progression predominantly occurred outside the treated volume, while in-field recurrences were less frequent and characterized by a longer latency.

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2026-04-14 | Gamma knife radiosurgery in pediatric neuro-oncology: histology-specific outcomes and age-adapted procedural strategies.

Gamma Knife radiosurgery (GKRS) is increasingly applied in pediatric neuro-oncology; however, integrated analyses of outcomes and procedural factors remain limited. This study evaluated histology-specific outcomes and technical considerations of GKRS for pediatric brain tumors. This study retrospectively analyzed 139 GKRS procedures performed in 108 pediatric patients (age 3-18 years) with brain tumors between 2002 and 2024. The clinical, radiological, dosimetric, and anesthetic data were analyzed. Progression-free survival (PFS) was estimated by Kaplan-Meier analysis and stratified by tumor histology. The mean age at GKRS was 12.4 years (M: F ratio 1:1.16). The most common histologies were craniopharyngiomas (31 procedures), vestibular schwannomas (20), and pilocytic astrocytomas (16). The mean target coverage was 96.9% and the mean prescription dose was 18 Gy. Frameless mask fixation was feasible from age 6 and frame-based fixation from age 12. General anesthesia was required in 25.9%, predominantly in younger or uncooperative patients (8.5 vs 14.0 years, p < 0.001). Pediatric-type diffuse high-grade gliomas had the poorest outcomes (PFS 2.6 months, 100% mortality). Craniopharyngiomas showed high recurrence (48%) but a long failure interval (35.8 months) and low mortality (8%). Benign and low-grade tumors showed durable local control with a 5-year PFS exceeding 70%. GKRS provides durable local control in selected benign and low-grade pediatric brain tumors; however, outcomes remain poor in aggressive histologies, with high rates of progression and mortality. These findings highlight the importance of histology-based patient selection and integration of GKRS into multimodal treatment strategies. Age-adapted procedural approaches facilitate safe application in pediatric patients.

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2026-02-27 | Two-Week Interval Hypofractionated Stereotactic Radiosurgery for Benign Intracranial Tumors: Volumetric Kinetics and Radiobiological Rationale.

Hypofractionated stereotactic radiosurgery (hfSRS) is increasingly used for benign intracranial tumors that are large or located near critical neural structures to reduce treatment-related toxicity. However, the optimal interval between fractions remains poorly defined, particularly for slowly proliferating benign tumors. This study evaluated clinical outcomes and longitudinal volumetric response patterns following Gamma Knife hfSRS delivered at fixed two-week intervals, with particular attention to the biological relevance of fraction timing. We retrospectively analyzed 126 patients with benign intracranial tumors, including meningioma, non-functioning pituitary neuroendocrine tumor (PitNET), vestibular schwannoma, and craniopharyngioma, treated between 2016 and 2022. Treatment was delivered in 2-5 fractions at fixed two-week intervals using Gamma Knife radiosurgery. Radiological outcomes included tumor control rate and longitudinal volumetric changes, while clinical outcomes included visual, auditory, and endocrine function. Propensity score matching was performed in PitNET and vestibular schwannoma cohorts to compare hfSRS with single-fraction stereotactic radiosurgery while minimizing baseline imbalances. The overall tumor control rate was 98.4%. Across the entire cohort, tumors demonstrated a median volume reduction of -0.64% per month. In the propensity score-matched PitNET cohort, tumor control was comparable between treatment groups, whereas hfSRS was associated with earlier and greater volumetric reduction over time compared with single-fraction treatment. In the matched vestibular schwannoma cohort, long-term tumor control was similar between groups; however, transient tumor enlargement occurred more frequently after hfSRS without adversely affecting long-term tumor control or functional hearing outcomes. Hypofractionated stereotactic radiosurgery delivered at fixed two-week intervals achieved excellent tumor control with acceptable toxicity in selected benign intracranial tumors. These findings support the clinical feasibility of a fixed two-week inter-fraction interval and suggest that fraction timing may represent a biologically relevant treatment parameter influencing early volumetric response patterns without compromising long-term outcomes.

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