Optical Coherence Tomography Angiography-Navigated Laser Photocoagulation of Retinal Hemangioblastomas in Patients With von Hippel-Lindau Disease.

Purpose: To describe optical coherence tomography angiography (OCTA)-guided navigated laser photocoagulation (LP) using the Navilas Laser System for treating retinal hemangioblastomas (RHs) associated with von Hippel-Lindau disease (VHLD). Methods: Patients with VHLD were screened using ophthalmoscopy and widefield OCTA. Detected RHs were classified with regard to tumor morphology (endophytic, sessile, exophytic, recurrent) and size. Then, 6 × 6- or 3 × 3-mm2 en face OCTA scans of the RHs were uploaded to the Navilas system, generating a merged image combining the scan and Navilas fundus photography. LP was planned by placing laser spots in the OCTA scan and executed with the Navilas system. Treatment efficacy was assessed by conducting OCTA scans immediately after LP and at follow-up visits. Results: Fifteen RHs were detected in 10 patients (median, one RH; range, one to four). Twelve RHs were treatment naive (exophytic [3], sessile [3], and endophytic [6]), and there were three recurrent RHs in pretreated areas. Total applied energy per tumor correlated with tumor size (P < 0.001). After a mean first follow-up of 3.6 ± 1.5 months (range, 0.9-5.3), nine RHs exhibited complete regression (60%), five partial regression (33.3%), and one no regression (6.7%). No correlation between tumor morphology and treatment success was observed (P = 0.32). However, a correlation between treatment success and tumor size trended toward significance (P = 0.08), with a 100% success rate observed for small RHs. Conclusions: OCTA-guided LP via the Navilas Laser System is a promising technique, especially beneficial for targeting small RHs. Combining OCTA and ophthalmoscopy improves tumor detection, underscoring the utility of this approach. Translational Relevance: OCTA-guided LP enables highly precise and safe treatment of early-stage RHs, minimizing possible complications caused by LP or the tumor itself.

Characterization of spinal hemangioblastomas in patients with and without von Hippel-Lindau, and YAP expression.

INTRODUCTION: Hemangioblastoma (HB) is a benign tumor of the central nervous system, associated with von Hippel-Lindau disease (VHL), or sporadic. The aim of this study was to compare and examine the clinical-pathological profile of patients with spinal hemangioblastoma and YAP expression. METHODS: A retrospective, descriptive, comparative study. All patients who underwent surgery for spinal HB between 2016 and 2023 were included. Clinical and radiological data were collected and analyzed. An immunohistochemistry panel including NeuN, neurofilaments (NF), and YAP-1, was performed. RESULTS: Nine patients were studied, six women and three men. Four patients had previously diagnosed VHL. The tumor location included: four cervical (44.44%), two thoracic (22.22%), two pontine with cervical extension (22.22%) and one patient with two lesions, one cervical and one thoracic (11.11%). Non-significant clinical differences were identified between VHL and sporadic patients. Imaging evidenced seven extramedullary and three intramedullary tumors. Histologically, intra-tumoral and perivascular axonal tracts were observed in all cases. One third of the tumors (two with VHL and one sporadic) presented extramedullary hematopoiesis. Seven cases (77.8%) expressed nuclear YAP (three with VHL and four sporadic HBs). The surgical outcome was good and only one patient with VHL undergoing subtotal resection had recurrence. CONCLUSIONS: Spinal HBs can be associated with VHL or be sporadic. To the best of our knowledge, this is the first study to describe YAP expression in HB. It is important to investigate the involvement of the Hippo pathway in HBs as a possible therapeutic target.

Computed tomography-guided percutaneous cryoablation of hereditary adrenal pheochromocytoma in three patients.

OBJECTIVES: Pheochromocytomas (PHEO) are neuroendocrine tumors rarely diagnosed in children. We are reporting on the management challenges of three adolescent patients who present with hereditary PHEO. CASE PRESENTATION: The index patient and his male sibling presented with bilateral PHEO, while a third patient presented with a unilateral PHEO, all associated with von Hippel-Lindau (VHL) syndrome. The patients were treated with computed tomography (CT)-guided percutaneous cryoablation (CRA) of the adrenal lesions, with varying degrees of success. CONCLUSIONS: CT-guided percutaneous CRA of hereditary PHEO has not been reported in the pediatric population and may represent a novel treatment strategy that reduces the risk of intraprocedural complications and adrenal insufficiency (AI).

Expression of somatostatin receptors in hemangioblastomas associated with von Hippel-Lindau disease as a novel diagnostic, therapeutic, and follow-up opportunity: A case report and literature review.

Hemangioblastomas associated with von Hippel-Lindau (VHL) disease are frequently multiple and recur during prolonged follow-up. Currently, no systemic treatment is available for these tumors. Recent studies have shown the expression of somatostatin receptors in these types of hemangioblastomas. Notably, increased somatostatin receptor expression in a tumor, as determined by peptide-receptor radionuclide imaging, is a predictive factor of response to treatment with somatostatin analogs and peptide-receptor radionuclide therapy. The aim of this study was to describe the case of a patient with increased expression of somatostatin receptors in a suprasellar hemangioblastoma associated with VHL disease and conduct a literature review on somatostatin receptor expression in patients with VHL-associated hemangioblastomas. We describe herein the case of a 51-year-old man with VHL disease who had a suprasellar hemangioblastoma detected on magnetic resonance imaging. Peptide-receptor radionuclide imaging using gallium-68-DOTATOC (68Ga-DOTATOC) identified increased expression of somatostatin receptors in the suprasellar hemangioblastoma, along with multiple pancreatic neuroendocrine tumors and bilateral pheochromocytomas. The patient was treated for 1 year with lanreotide, a somatostatin analog. A repeat 68Ga-DOTATOC 1 year after starting lanreotide revealed decreased radiotracer uptake by the hemangioblastoma, consistent with a metabolic response. The presence of somatostatin receptors in hemangioblastomas associated with VHL disease is a novel finding. The decreased expression of these receptors after treatment with a somatostatin analog, as described in the present case, positions the somatostatin receptor as a new target for novel diagnostic, therapeutic, and follow-up opportunities in patients with VHL disease.

Screening and surveillance recommendations for central nervous system hemangioblastomas in pediatric patients with Von Hippel-Lindau disease.

PURPOSE: Von Hippel-Lindau (VHL) disease is an autosomal-dominantly inherited tumor predisposition syndrome. One of the most common tumors are central nervous system (CNS) hemangioblastomas. Recommendations on the initiation and continuation of the screening and surveillance program for CNS tumors in pediatric VHL patients are based on small case series and thus low evidence level. To derive more robust screening recommendations, we report on the largest monocentric pediatric cohort of VHL patients. METHODS: We performed a retrospective analysis on a pediatric cohort of 99 VHL patients consulted at our VHL center from 1992 to 2023. Clinical, surgical, genetic, and imaging data were collected and statistically analyzed. RESULTS: 42 patients (50% male) developed CNS hemangioblastomas, of whom 18 patients (56% male) underwent hemangioblastoma surgery (mean age at first surgery: 14.9 ± 1.9 years; range 10.2-17). The first asymptomatic patient was operated on at the age of 13.2 years due to tumor progress. Truncating VHL mutation carriers had a significantly higher manifestation rate (HR = 3.7, 95% CI: 1.9-7.4, p < 0.0001) and surgery rate (HR = 3.3, 95% CI: 1.2-8.9, p = 0.02) compared with missense mutation carriers. CONCLUSION: We recommend starting MRI imaging at the age of 12 years with examination intervals every (1-) 2 years depending on CNS involvement. Special attention should be paid to patients with truncating variants. Affected families should be educated regularly on potential tumor-associated symptoms to enable timely MRI imaging and eventually intervention, as CNS hemangioblastoma may develop before screening begins. GERMAN CLINICAL TRIALS REGISTER REGISTRATION NUMBER: DRKS00029553, date of registration 08/16/2022, retrospectively registered.

[Preclinical diagnostics of von Hippel-Lindau syndrome in a child].

The description of the child aged 5 months with the von Hippel-Lindau syndrome without any manifestations of this syndrome is presented. The reason for the molecular genetic examination was the presence of cases of this syndrome in the family (mother and sister). The heterozygous variant c.355T>C p.F119L was found in the VHL gene. An objective examination revealed no pathology. A comprehensive laboratory and instrumental examination aimed at searching for components of the von Hippel-Lindau syndrome, including a blood test for metanephrines and normetanephrines, ultrasound of the abdominal organs, examination of the fundus, also did not reveal any abnormalities. Given the results of molecular genetic diagnosis, the child remains under observation and will undergo regular examinations to identify components of the von Hippel-Lindau syndrome, including blood/urine tests for normetanephrines.

A case report of cerebellar hemangioblastoma simulated brain metastasis shown by magnetic resonance imaging.

RATIONALE: Hemangioblastomas occur both sporadically and as an important component of von Hippel-Lindau (VHL) disease. The typical MRI features of hemangioblastoma are cysts with enhanced cystic wall nodules in the cerebellum or lesions with uniform enhancement on the surface or inside the spinal cord. If there is edema around hemangioblastoma, it is easy to be misdiagnosed as brain metastasis on MRI. PATIENT CONCERNS: A 41-year-old male patient was found to have a lump in the pancreas during a health examination 3 months ago. Subsequently, the patient underwent surgical treatment. The postoperative pathology suggests that the pancreatic lesion is a neuroendocrine tumor. The patient subsequently came to our hospital for consultation on further treatment plans. Abnormal signals were found in the right cerebellum during pituitary magnetic resonance imaging (MRI) before the development of a treatment plan for neuroendocrine tumors. Subsequently, the patient underwent cerebellar mass resection surgery. The pathological result after the surgery was hemangioblastoma. DIAGNOSIS: The patient underwent surgery to remove the tumor and was diagnosed with hemangioblastoma by pathological examination. Subsequently, the patient's genetic testing results confirmed the diagnosis of VHL syndrome. INTERVENTIONS: The patient underwent cerebellar mass resection surgery. OUTCOMES: The patient recovered after surgical resection. LESSONS: In this report, we emphasize the atypical MRI manifestations of hemangioblastoma. For patients with VHL syndrome-related hemangioblastoma, genetic testing is necessary for the patient and their family members.

Percutaneous microwave ablation on management of hereditary renal cell carcinoma in Von Hippel-Lindau disease.

BACKGROUND: The effect of microwave ablation (MWA) for the renal cell carcinoma (RCC) in Von Hippel-Lindau (VHL) disease is unclear. OBJECTIVE: To assess the safety, Technique efficacy, renal function and oncological outcome of MWA for RCC in VHL patients. METHODS: Consecutive patients with RCCs in VHL disease treated by MWA were retrospectively collected from November 2009 to October 2020. The technical efficacy rate and complications were assessed. The outcomes of pre- and post-ablative eGFR were compared. The local recurrent-free survival (LRFS), renal-cancer-free survival (RCFS), cancer-specific survival (CSS), overall survival (OS) and complications were presented. RESULTS: A total of 10 patients (mean age, 39.0 years ± 10.7 [SD]; 3 women) with 28 RCCs (mean tumor size, 3.0 cm ± 0.34; mean tumor volume, 20.7 mL ± 43.3) treated with MWA were included. Th median follow-up time was 52 months(IQR:27-80). The overall technical efficacy rate was 100% with no major complications occurred. No significant statistical difference between pre-ablative and postablative creatinine level (102.0 µmol/L ± 30.4 vs 112.3 µmol/L ± 38.7, p = 0.06), but the pre-ablative eGFR level was significantly higher than the post-ablative eGFR (78.0 mL/(min*1.73m2) ± 28.6 vs 72 mL/(min*1.73m2) ± 31.4, p = 0.04), with the mean decrease of 5.86 ml/(min*1.73m2). The local recurrent-free survival(LRFS) and renal-cancer-free survival (RCFS) were 100% and 60%, respectively. The cancer specifical survival (CSS) and overall survival (OS) were 95.5% and 100%, respectively. CONCLUSION: Microwave ablation is a safe and feasible method for the treatment of RCC in VHL disease, preserving renal function and yielding satisfactory oncological outcomes.

Epidemiology and economic burden of Von Hippel-Lindau Disease-associated central nervous system hemangioblastomas and pancreatic neuroendocrine tumors in the United States.

BACKGROUND: To date, real-world evidence around the clinical and economic burden related to von Hippel-Lindau (VHL) disease is limited. Therefore, this study characterized the prevalence, healthcare resource utilization (HRU), and economic burden of von Hippel-Lindau-associated central nervous system hemangioblastoma (VHL-CNS-Hb) and pancreatic neuroendocrine tumors (VHL-pNET) in the United States (US). METHODS: Patients with VHL-CNS-Hb or VHL-pNET were identified from Optum's de-identified Clinformatics® Data Mart Database (2007-2020) and matched 1:5 to control patients without VHL disease or CNS-Hb/pNET. Prevalence rates of VHL-CNS-Hb and VHL-pNET (standardized by age and sex) in 2019 were estimated. HRU and healthcare costs (2020 US dollars) were compared between the VHL-CNS-Hb/VHL-pNET and control cohorts. RESULTS: In 2019, US prevalence rates of VHL-CNS-Hb and VHL-pNET were estimated to be 1.12 cases per 100,000 (3,678 patients) and 0.12 cases per 100,000 (389 patients), respectively. Patients with VHL-CNS-Hb (N = 220) had more inpatient, outpatient, and emergency department visits and $49,645 higher annual healthcare costs than controls (N = 1,100). Patients with VHL-pNET (N = 20) had more inpatient and outpatient visits and $56,580 higher annual healthcare costs than controls (N = 100). Costs associated with surgical removal of CNS-Hb and pNET were particularly high. CONCLUSIONS: In this retrospective, claims-based study, both VHL-CNS-Hb and VHL-pNET were associated with substantial HRU and healthcare costs, particularly tumor reduction surgery-related costs. These findings provide important insight for healthcare payers regarding the expected real-world costs that enrollees with VHL-CNS-Hb and VHL-pNET may incur over the course of their disease.

Belzutifan for von Hippel-Lindau Disease: Pancreatic Lesion Population of the Phase 2 LITESPARK-004 Study.

PURPOSE: Primary analysis of the ongoing, single-arm, phase 2 LITESPARK-004 study (NCT03401788) showed clinically meaningful antitumor activity in von Hippel-Lindau (VHL) disease-associated renal cell carcinoma (RCC) and other neoplasms with belzutifan treatment. We describe results of belzutifan treatment for VHL disease-associated pancreatic lesions [pancreatic neuroendocrine tumors (pNET) and serous cystadenomas]. PATIENTS AND METHODS: Adults with VHL diagnosis based on germline VHL alteration, ≥1 measurable RCC tumor, no renal tumor >3 cm or other VHL neoplasm requiring immediate surgery, Eastern Cooperative Oncology Group performance status of 0 or 1, and no prior systemic anticancer treatment received belzutifan 120 mg once daily. End points included objective response rate (ORR), duration of response (DOR), progression-free survival (PFS), and linear growth rate (LGR) in all pancreatic lesions and pNETs per RECIST version 1.1 by independent review committee, and safety. RESULTS: All 61 enrolled patients (100%) had ≥1 pancreatic lesion and 22 (36%) had ≥1 pNET measurable at baseline. Median follow-up was 37.8 months (range, 36.1-46.1). ORR was 84% [51/61; 17 complete responses (CR)] in pancreatic lesions and 91% (20/22; 7 CRs) in pNETs. Median DOR and median PFS were not reached in pancreatic lesions or pNETs. After starting treatment, median LGR for pNETs was -4.2 mm per year (range, -7.9 to -0.8). Eleven patients (18%) had ≥1 grade 3 treatment-related adverse event (AE). No grade 4 or 5 treatment-related AEs occurred. CONCLUSIONS: Belzutifan continued to show robust activity and manageable safety in VHL disease-associated pNETs.

Al18F-NOTA-Octreotide PET/CT and 18F-FDG PET/CT for Detecting Cerebellar Hemangioblastoma in a Patient With Von Hippel-Lindau Disease.

ABSTRACT: Von Hippel-Lindau disease is a hereditary syndrome associated with various benign and malignant tumors, including hemangioblastomas. A 42-year-old man with a history of Von Hippel-Lindau disease underwent surgery for pancreatic neuroendocrine tumor and renal clear cell carcinoma and was recommended to undergo Al18F-NOTA-octreotide and 18F-FDG PETCT examination to assess potential metastases. 18F-FDG PET/CT showed low uptake in the right cerebellum, which demonstrated increased Al18F-NOTA-octreotide activity. Cerebellar mass resection surgery was performed. Pathological result was consistent with hemangioblastoma. This case report indicates the significant role of Al18F-NOTA-octreotide in the diagnosis of hemangioblastoma.

CT-derived radiomics predict the growth rate of renal tumours in von Hippel-Lindau syndrome.

AIM: To predict renal tumour growth patterns in von Hippel-Lindau syndrome by utilising radiomic features to assist in developing personalised surveillance plans leading to better patient outcomes. MATERIALS AND METHODS: The study evaluated 78 renal tumours in 55 patients with histopathologically-confirmed clear cell renal cell carcinomas (ccRCCs), which were segmented and radiomics were extracted. Volumetric doubling time (VDT) classified the tumours into fast-growing (VDT <365 days) or slow-growing (VDT ≥365 days). Volumetric and diametric growth analyses were compared between the groups. Multiple logistic regression and random forest classifiers were used to select the best features and models based on their correlation and predictability of VDT. RESULTS: Fifty-five patients (mean age 42.2 ± 12.2 years, 27 men) with a mean time difference of 3.8 ± 2 years between the baseline and preoperative scans were studied. Twenty-five tumours were fast-growing (low VDT, i.e., <365 days), and 53 tumours were slow-growing (high VDT, i.e., ≥365 days). The median volumetric and diametric growth rates were 1.71 cm3/year and 0.31 cm/year. The best feature using univariate analysis was wavelet-HLL_glcm_ldmn (area under the receiver operating characteristic [ROC] curve [AUC] of 0.80, p<0.0001), and with the random forest classifier, it was log-sigma-0-5-mm-3D_glszm_ZonePercentage (AUC: 79). The AUC of the ROC curves using multiple logistic regression was 0.74, and with the random forest classifier was 0.73. CONCLUSION: Radiomic features correlated with VDT and were able to predict the growth pattern of renal tumours in patients with VHL syndrome.

Renal Neuroendocrine Tumor: A Case Report with Evaluation of Grading Criteria and Relationship with Carbonic Anhydrase 9 Immunoreactivity.

Neuroendocrine tumors (NETs) are only exceptionally primary to the kidney. At present, scant information is known regarding the behavior and prognosis of renal NETs, especially according to the assessment of grading parameters used for NETs originating from other more commonplace sites such as the pancreas and lungs. There are only rare reports of grade assessment in renal NETs, with most of these reports relying upon now antiquated World Health Organization gastroenteropancreatic and lung/thymus criteria. As an additional prognostic factor, positive CA9 staining in NETs may correlate with elevated grade, stage and risk of metastasis while serving as a potential target of chemotherapy and immunotherapy and indicator of Von Hippel-Lindau Syndrome. Rarer still are descriptions of renal NETs presenting with renal cell carcinoma in the ipsilateral or contralateral kidney. Thus, we present a patient with a primary renal NET of the right kidney with regional lymphovascular invasion and distant metastasis with an emphasis on grading criteria concordant with the World Health Organization 2022 gastroenteropancreatic and lung/thymus systems. In addition, we discuss unusual staining for CA9 in the patient's tumor and a concomitant left kidney clear cell renal cell carcinoma that may act as a clinicopathologic mimic of Von Hippel-Lindau Syndrome.

Stereotactic Radiosurgery for Cranial and Spinal Hemangioblastomas: A Single-Institution Retrospective Series.

BACKGROUND AND OBJECTIVES: Stereotactic radiosurgery (SRS) has been an attractive treatment modality for both cranial and spinal hemangioblastomas, especially for multiple lesions commonly associated with von Hippel-Lindau (VHL) disease. This study aims to provide the largest long-term analysis of treatment efficacy and adverse effects of SRS for cranial and spinal hemangioblastomas at a single institution. METHODS: We evaluated the clinical and radiological outcomes of patients with hemangioblastomas treated with CyberKnife SRS at our institute from 1998 to 2022. The follow-up data were available for 135 hemangioblastomas in 35 patients. Twenty-eight patients had 123 hemangioblastomas associated with VHL, and 7 had 12 sporadic hemangioblastomas. The median age was 36 years, and the median tumor volume accounted for 0.4 cc. The SRS was administered with the median single-fraction equivalent dose of 18 Gy to the 77% median isodose line. RESULTS: At a median follow-up of 57 months (range: 3-260), only 20 (16.2%) of the VHL-associated and 1 (8.3%) sporadic hemangioblastomas progressed. The 5-year local tumor control rate was 91.3% for all hemangioblastomas, 91.7% among the sporadic lesions, and 92.9% in patients with VHL. SRS improved tumor-associated symptoms of 98 (74.8%) of 131 symptomatic hemangioblastomas, including headache, neck pain, dizziness, visual disturbances, dysesthesia, ataxia, motor impairment, seizures, and dysphagia. Two patients developed radiation necrosis (5.7%), and 1 of them required surgical resection. CONCLUSION: SRS is a safe and effective treatment option for patients with hemangioblastomas in critical locations, such as the brainstem, cervicomedullary junction, and spinal cord, and in patients with multiple hemangioblastomas associated with VHL disease.

The kidney imaging surveillance scoring system (KISSS): using qualitative MRI features to predict growth rate of renal tumors in patients with von-Hippel Lindau (VHL) syndrome.

OBJECTIVE: To determine the reliability of an MRI-based qualitative kidney imaging surveillance scoring system (KISSS) and assess which imaging features predict growth rate (GR) of renal tumors in patients with VHL. MATERIALS AND METHODS: We identified 55 patients with VHL with 128 renal tumors who underwent intervention from 2015 to 2020 at the National Cancer Institute. All patients had 2 preoperative MRIs at least 3 months apart. Two fellowship-trained radiologists scored each tumor on location and MR-sequence-specific imaging parameters from the earlier MRI. Weighted kappa was used to determine the degree of agreement between radiologists for each parameter. GR was calculated as the difference in maximum tumor dimension over time (cm/year). Differences in mean growth rate (MGR) within categories of each imaging variable were assessed by ANOVA. RESULTS: Apart from tumor margin and renal sinus, reliability was at least moderate (K > 0.40) for imaging parameters. Median initial tumor size was 2.1 cm, with average follow-up of 1.2 years. Tumor MGR was 0.42 cm/year. T2 hypointense, mixed/predominantly solid, and high restricted diffusion tumors grew faster. When comparing different combinations of these variables, the model with the lowest mean error among both radiologists utilized only solid/cystic and restricted diffusion features. CONCLUSIONS: We demonstrate a novel MR-based scoring system (KISSS) that has good precision with minimal training and can be applied to other qualitative radiology studies. A subset of imaging variables (T2 intensity; restricted diffusion; and solid/cystic) were independently associated with growth rate in VHL renal tumors, with the combination of the latter two most optimal. Additional validation, including in sporadic RCC population, is warranted.

von Hippel-Lindau disease-related neoplasia with an emphasis on renal manifestations.

von Hippel-Lindau (VHL) disease is characterized by biallelic inactivation of the VHL gene leading to abnormal or absent VHL protein function, and constitutive activation of hypoxia-inducible factors (HIF) that leads to pro-tumorigenic signaling. Individuals with VHL disease develop numerous cysts and tumors involving multiple organs including the kidneys, central nervous system, endolymphatic sac, lungs, pancreatobiliary system, adrenal glands, epididymis, and/or broad ligament. On histologic examination, these lesions show morphologic overlap as they are frequently characterized by cells with clear cytoplasm and prominent vascularity. In addition to distinguishing non-renal tumors from metastatic clear cell renal cell carcinoma, understanding site-specific histopathologic and immunophenotypic features of these tumors has several applications. This includes distinguishing VHL-related tumors from those that arise sporadically and lack VHL gene alterations, guiding further genetic workup, and helping distinguish between different genetic predisposition syndromes. In this context, immunohistochemical studies for markers such as paired box 8 (PAX-8), carbonic anhydrase 9 (CA9), and glucose transporter 1 (GLUT-1) have an important role in routine clinical practice and represent cost-effective diagnostic tools. The recent development of targeted therapeutics directed against HIF-mediated signaling represents a significant milestone in the management of VHL disease and highlights the importance of accurately diagnosing and characterizing the wide spectrum of VHL disease-associated lesions.

Management of Renal Malignancies in Von Hippel-Lindau Syndrome: Lessons Learned from a Series of Six Patients from Sri Lanka.

Management of renal malignancies in Von Hippel-Lindau (VHL) is challenging. We present six patients [mean age = 35.1 years (range: 24-54), males = 5] with VHL syndrome with multiple bilateral renal malignancies and the lessons learned during their management. The number of tumors at the time of presentation ranged from 1 to 6, while the number of new lesions varied from 1 to 3. Different combinations of radical nephrectomy (n = 2), partial nephrectomy (n = 7), and focal therapy (n = 6) were used appropriately. Median follow-up was 36 months (range: 12-72). Two patients developed new lesions which were managed with focal therapy. Nephron-sparing approaches are successful even in bilateral, multifocal, large, and recurring renal tumors associated with VHL. Awareness about the availability of efficacious surgical and minimally invasive measures would reduce psychosocial problems faced by patients and their families due to the social stigma associated with malignancies running in a family and burden of renal replacement therapy.

The outcome of central nervous system hemangioblastomas in Von Hippel-Lindau (VHL) disease treated with belzutifan: a single-institution retrospective experience.

PURPOSE: Belzutifan is a Hypoxia Inducible Factor 2-alpha inhibitor approved in 2021 by the FDA for the treatment of renal cell carcinoma (RCC) in patients with Von-Hippel Landau (VHL) disease. These patients can also present with central nervous system (CNS) hemangioblastomas (HBs). We aim to study the effectiveness and adverse effects of belzutifan for CNS HBs, by reporting our preliminary institutional experience. METHODS: We present a series of VHL patients with CNS HBs undergoing treatment with belzutifan for RCC. All the included patients met the RECIST inclusion criteria. The clinical and radiological outcome measures included: Objective response rate (ORR), time-to-response (TTR), adverse events (AE), and patient response. Patient response was classified as partial response (PR), complete response (CR), progressive disease (PD), or stable disease (SD). RESULTS: Seven patients with 25 HBs were included in our study. A belzutifan dose of 120 mg/day PO was administered for a median of 13 months (range 10-17). Median follow up time was 15 months (range 10-24). An ORR of 71% was observed. The median TTR was 5 months (range: 1-10). None of the patients showed CR, while 5 patients (71.4%) showed PR and 2 (28.5%) showed SD. Among patients with SD the maximum tumor response was 20% [increase/decrease] of the lesion diameter. All the patients experienced decreased hemoglobin concentration, fatigue, and dizziness. None of the patients experienced severe anemia (grade 3-4 CTCAE). CONCLUSION: Belzutifan appears to be an effective and safe treatment for CNS hemangioblastoma in VHL patients. Further clinical trials to assess the long-term effectiveness of the medication are required.