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Jung NY, Park JB. Von Hippel-Lindau Disease : A Comprehensive Review of Diagnosis, Genetics, Clinical Challenges, and Surveillance. J Korean Neurosurg Soc 2025; 68:338-349. [PMID: 40109021 PMCID: PMC12062539 DOI: 10.3340/jkns.2025.0018] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2025] [Revised: 03/13/2025] [Accepted: 03/15/2025] [Indexed: 03/22/2025] Open
Abstract
von Hippel-Lindau (VHL) disease is a genetic condition predisposing individuals to the development of benign and malignant tumors across various organs. This review explores the intricate genetic underpinnings of VHL disease, its clinical manifestations, and the associated malignancy risks. The latest diagnostic criteria, surveillance guidelines, and advancements in therapeutic strategies, including the Food and Drug Administration-approved hypoxia-inducible factor-2α inhibitor, belzutifan, are focused on. Through a multidisciplinary approach, tailored surveillance programs aim to improve patient outcomes while balancing intervention risks. Emerging technologies such as wholebody magnetic resonance imaging and liquid biopsies hold promises for enhancing non-invasive surveillance. This review underscores the significance of ongoing research and interdisciplinary care in managing this complex syndrome.
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Affiliation(s)
- Na Young Jung
- Department of Neurosurgery, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, Korea
| | - Jun Bum Park
- Department of Neurosurgery, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, Korea
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2
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Zare A, Zare A, Khaboushan AS, Hajikarimloo B, Sheehan JP. Stereotactic radiosurgery in the management of central nervous system hemangioblastomas: a systematic review and meta-analysis. Neurosurg Rev 2025; 48:303. [PMID: 40091097 PMCID: PMC11911270 DOI: 10.1007/s10143-025-03454-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2024] [Revised: 02/16/2025] [Accepted: 03/05/2025] [Indexed: 03/19/2025]
Abstract
Central nervous system (CNS) hemangioblastomas are rare, benign vascular tumors occurring sporadically or with von Hippel-Lindau (VHL) disease. While resection remains the primary treatment for symptomatic lesions, stereotactic radiosurgery (SRS) has emerged as an alternative where surgery is not feasible. This research aims to investigate the efficacy and safety of SRS for CNS hemangioblastomas, focusing on long-term outcomes and identifying key prognostic factors. A systematic search was conducted in PubMed, Scopus, Embase, Web of Science, and Cochrane Library till October 4th, 2024. Studies investigating the efficacy of SRS for CNS hemangioblastomas were included. The risk of bias was assessed using the ROBINS-I tool. Meta-analysis, subgroup analysis, and meta-regression were performed using the R programming language. A total of 28 studies with 627 patients and 1761 lesions were included. Our meta-analysis demonstrated pooled overall, 5- and 10-year local tumor control rates of 89% (95% CI: 85-92%), 87% (95% CI: 82-91%), and 80% (95% CI: 63-91%), respectively. Tumor response assessment revealed that 28% (95% CI: 19-40%) of lesions had regression, while 59% (95% CI: 46-70%) remained stable. VHL-associated lesions had a higher control than sporadic tumors at the 5-year follow-up (VHL: 94% (95% CI: 90-97%) vs. Sporadic: 82% (95% CI: 76-86%), P < 0.01). Pooled adverse events were 11% (95% CI: 8-15%). Meta-regression identified the female sex as a positive predictor for tumor control and lower adverse event rate (P < 0.01 and P = 0.02, respectively), while higher marginal and maximum radiation doses correlated with increased adverse events (P = 0.02 and P = 0.03, respectively). SRS represents a reasonably effective and safe treatment option for CNS hemangioblastomas, particularly in VHL-associated lesions. Patient demographics, VHL status, and tumor characteristics have been analyzed to identify factors potentially impacting treatment outcomes.
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Affiliation(s)
- Amirhossein Zare
- Department of Neurosurgery, Tehran University of Medical Sciences, Tehran, Iran
| | - Amirhessam Zare
- Department of Neurosurgery, Tehran University of Medical Sciences, Tehran, Iran
| | | | - Bardia Hajikarimloo
- Department of Neurological Surgery, University of Virginia, Charlottesville, VA, USA
| | - Jason P Sheehan
- Department of Neurological Surgery, University of Virginia, Charlottesville, VA, USA.
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3
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Tos SM, Hajikarimloo B, Mantziaris G, Shaaban A, Pham D, Dayawansa S, Wei Z, McKendrick LM, Niranjan A, Lunsford LD, Peker S, Samanci Y, Liscak R, May J, Mathieu D, Picozzi P, Franzini A, Warnick RE, Schoenhals JE, Palmer JD, Xu Z, Sheehan JP. Comparative analysis of stereotactic radiosurgery outcomes for supratentorial hemangioblastomas in von hippel-lindau disease and sporadic cases: A multi-center international study. J Clin Neurosci 2024; 129:110879. [PMID: 39426317 DOI: 10.1016/j.jocn.2024.110879] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2024] [Accepted: 10/14/2024] [Indexed: 10/21/2024]
Abstract
BACKGROUND Hemangioblastomas (HBs) are rare, benign central nervous system (CNS) neoplasms that rarely occur in the supratentorial. Resection with the goal of gross total resection (GTR) is often considered the primary treatment. Stereotactic radiosurgery (SRS) has been utilized more commonly in unresectable or partially resected cases. In this study, we aimed to evaluate SRS's effectiveness and clinical outcomes in supratentorial HBs. METHODS A retrospective analysis of multi-centers from 1993 to 2022 was conducted on patients with supratentorial HB treated with SRS. RESULTS The study included 13 patients with 30 supratentorial HBs (24 von Hippel-Lindau (VHL), 6 sporadic). Median age was 26 years. Most tumors were solid (86.2 %). SRS was primary treatment in 86.7 % of cases and adjuvant in 13.3 %. VHL lesions were significantly smaller than sporadic ones (0.2 vs. 3.7 cc, p = 0.009). Median margin dose was higher in VHL cases (17 vs. 13.0 Gy, P = 0.031). For VHL cases, local control (LC) was 100 % at 6 months, 96 % (95 % CI: 88 %, 100 %) from 12 to 60 months post-SRS. For sporadic cases, LC was 100 % at 6 months, 80 % (95 % CI: 52 %, 100 %) from 12 to 60 months post-SRS (p = 0.39). No adverse radiation events or mortality occurred. CONCLUSION SRS demonstrated a promising role in the clinical course of supratentorial HBs. It can be considered an effective alternative to surgical resection and even a first-line therapeutic option in appropriately selected cases.
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Affiliation(s)
- Salem M Tos
- Department of Neurological Surgery, University of Virginia, Charlottesville, VA, USA.
| | - Bardia Hajikarimloo
- Department of Neurological Surgery, University of Virginia, Charlottesville, VA, USA
| | - Georgios Mantziaris
- Department of Neurological Surgery, University of Virginia, Charlottesville, VA, USA
| | - Ahmed Shaaban
- Department of Neurological Surgery, University of Virginia, Charlottesville, VA, USA
| | - Duy Pham
- Department of Neurological Surgery, University of Virginia, Charlottesville, VA, USA
| | - Sam Dayawansa
- Department of Neurological Surgery, University of Virginia, Charlottesville, VA, USA
| | - Zhishuo Wei
- Department of Neurological Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
| | - Lindsay M McKendrick
- Department of Neurological Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
| | - Ajay Niranjan
- Department of Neurological Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
| | - L Dade Lunsford
- Department of Neurological Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
| | - Selcuk Peker
- Department of Neurological Surgery, Koc University School of Medicine, Istanbul, Turkey
| | - Yavuz Samanci
- Department of Neurological Surgery, Koc University School of Medicine, Istanbul, Turkey
| | - Roman Liscak
- Department of Stereotactic and Radiation Neurosurgery, Na Homolce Hospital, Prague, Czech Republic
| | - Jaromir May
- Department of Stereotactic and Radiation Neurosurgery, Na Homolce Hospital, Prague, Czech Republic
| | - David Mathieu
- Department of Neurological Surgery, Université de Sherbrooke, Centre de recherche du CHUS, Canada
| | - Piero Picozzi
- Department of Neurological Surgery, IRCCS Humanitas Research Hospital, Milan, Italy
| | - Andrea Franzini
- Department of Neurological Surgery, IRCCS Humanitas Research Hospital, Milan, Italy
| | - Ronald E Warnick
- Gamma Knife Center, Jewish Hospital, Mayfield Clinic, Cincinnati, OH, USA
| | | | - Joshua D Palmer
- Department of Radiation Oncology, The Ohio State University, OH, USA
| | - Zhiyuan Xu
- Department of Neurological Surgery, University of Virginia, Charlottesville, VA, USA
| | - Jason P Sheehan
- Department of Neurological Surgery, University of Virginia, Charlottesville, VA, USA.
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Fabi F, Chamberland È, D’Astous M, Michaud K, Côté M, Thibault I. Radiosurgically Treated Recurrent Cerebellar Hemangioblastoma: A Case Report and Literature Review. Curr Oncol 2024; 31:3968-3977. [PMID: 39057165 PMCID: PMC11276307 DOI: 10.3390/curroncol31070293] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2024] [Revised: 06/25/2024] [Accepted: 07/03/2024] [Indexed: 07/28/2024] Open
Abstract
BACKGROUND Cystic, sporadic hemangioblastomas (HBLs) represent a unique, therapeutically challenging subset of central nervous system tumors, mainly due to their unpredictable growth patterns and potential for symptomatic progression. This study aims to explore the complexities surrounding the diagnosis, treatment, and long-term management of these lesions. METHODS A comprehensive literature review was performed, and a detailed case study of a 56-year-old patient with a cystic, sporadic cerebellar HBL was produced. RESULTS The case highlights the multiphasic growth pattern typical of cystic, sporadic HBLs, characterized by periods of dormancy and subsequent rapid expansion. An initial surgical intervention offered temporary control. Tumor recurrence, mainly through cystic enlargement, was treated by SRS. A subsequent recurrence, again caused by cystic growth, eventually led to the patient's death. The intricacies of treatment modalities, focusing on the transition from surgical resection to stereotactic radiosurgery (SRS) upon recurrence, are discussed. Parameters indicating impending tumor growth, coupled with symptomatic advances, are also explored. CONCLUSIONS The management of cystic, sporadic cerebellar HBLs requires a strategic approach that can be informed by radiological characteristics and tumoral behavior. This study underscores the importance of a proactive, individualized management plan and suggests guidelines that could inform clinical decision making.
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Affiliation(s)
- François Fabi
- Service de Radio-Oncologie du Département de Médecine Spécialisée, Centre Intégré de Cancérologie (CIC), Hôpital de l’Enfant-Jésus, Centre Hospitalier Universitaire (CHU) de Québec-Université Laval, Quebec City, QC G1J 1Z4, Canada;
| | - Ève Chamberland
- Service de Physique Médicale et de Radioprotection, CHU de Québec-Université Laval, Quebec City, QC G1J 1Z4, Canada
| | - Myreille D’Astous
- Service de Neurochirurgie du Département de Chirurgie, Hôpital de l’Enfant-Jésus, CHU de Québec-Université Laval, Quebec City, QC G1J 1Z4, Canada
| | - Karine Michaud
- Service de Neurochirurgie du Département de Chirurgie, Hôpital de l’Enfant-Jésus, CHU de Québec-Université Laval, Quebec City, QC G1J 1Z4, Canada
| | - Martin Côté
- Service de Neurochirurgie du Département de Chirurgie, Hôpital de l’Enfant-Jésus, CHU de Québec-Université Laval, Quebec City, QC G1J 1Z4, Canada
| | - Isabelle Thibault
- Service de Radio-Oncologie du Département de Médecine Spécialisée, Centre Intégré de Cancérologie (CIC), Hôpital de l’Enfant-Jésus, Centre Hospitalier Universitaire (CHU) de Québec-Université Laval, Quebec City, QC G1J 1Z4, Canada;
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Vergauwen E, Klingler JH, Krüger MT, Steiert C, Kuijpers R, Rosahl S, Vanbinst AM, Andreescu CE, Gläsker S. Optic nerve and chiasm hemangioblastomas in von Hippel-Lindau disease: report of 12 cases and review of the literature. Front Oncol 2024; 14:1334564. [PMID: 39045559 PMCID: PMC11263193 DOI: 10.3389/fonc.2024.1334564] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2023] [Accepted: 06/19/2024] [Indexed: 07/25/2024] Open
Abstract
Introduction Optic nerve and chiasm hemangioblastomas are rare tumors, occurring sporadically or in the context of von Hippel-Lindau (VHL) disease. They have only been portrayed in isolated case reports and small cohorts. Their natural history and therapeutic strategies are only scarcely described. To better characterize these rare tumors, we retrospectively analyzed an optic nerve and chiasm hemangioblastoma series of 12 VHL patients. By combining our own experience to a review of all known cases in literature, we intended to create treatment recommendations for optic nerve and chiasm hemangioblastomas in VHL patients. Methods We reviewed two electronic databases in the hospitals of our senior authors, searching for VHL patients with optic nerve or chiasm hemangioblastomas. Clinical data were summarized. Tumor size and growth rate were measured on contrast enhanced MRI. Comparable data were collected by literature review of all available cases in VHL patients (Pubmed, Trip, Google and Google Scholar). Results Of 269 VHL patients, 12 had optic nerve or chiasm hemangioblastomas. In 10 of 12 patients, tumors were diagnosed upon annual ophthalmoscopic/MRI screening. Of 8 patients who were asymptomatic at diagnosis, 7 showed absent or very slow annual progression, without developing significant vision impairment. One patient developed moderate vision impairment. Two symptomatic patients suffered from rapid tumor growth and progressive vision impairment. Both underwent late-stage surgery, resulting in incomplete resection and progressive vision impairment. One patient presented with acute vision field loss. A watchful-waiting approach was adopted because the hemangioblastoma was ineligible for vision-sparing surgery. One patient developed progressive vision impairment after watchful waiting. In the literature we found 45 patient cases with 48 hemangioblastomas. Discussion When optic nerve and chiasm hemangioblastomas are diagnosed, we suggest annual MRI follow-up as long as patients do not develop vision impairment. If tumors grow fast, threaten the contralateral eye, or if patients develop progressive vision deficiency; surgical resection must be considered because neurological impairment is irreversible, and resection of large tumors carries a higher risk of further visual decline.
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Affiliation(s)
- Evelynn Vergauwen
- Department of Neurosurgery, Vrije Universiteit Brussel, Jette, Belgium
- Department of Neurology, Algemeen Ziekenhuis (AZ) Klina, Brasschaat, Belgium
| | - Jan-Helge Klingler
- Department of Neurosurgery, Freiburg University Medical Center, Freiburg, Germany
| | - Marie T. Krüger
- Department of Neurosurgery, Freiburg University Medical Center, Freiburg, Germany
- University College London (UCL) Functional Neurosurgery Unit, National Hospital for Neurology and Neurosurgery, London, United Kingdom
| | - Christine Steiert
- Department of Neurosurgery, Freiburg University Medical Center, Freiburg, Germany
| | - Robert Kuijpers
- Department of Ophthalmology, Vrije Universiteit Brussel, Jette, Belgium
| | - Steffen Rosahl
- Department of Neurosurgery, Helios Klinikum Erfurt, Erfurt, Germany
| | | | | | - Sven Gläsker
- Department of Neurosurgery, Vrije Universiteit Brussel, Jette, Belgium
- Neurosurgery Section, Gesundheitsverbund Landkreis Konstanz (GLKN), Singen am Hohentwiel, Germany
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Brabo EP, de Almeida SA, Rafful PP, Rosado-de-Castro PH, Vieira Neto L. 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. ARCHIVES OF ENDOCRINOLOGY AND METABOLISM 2024; 68:e230181. [PMID: 38788146 PMCID: PMC11156175 DOI: 10.20945/2359-4292-2023-0181] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/11/2023] [Accepted: 03/20/2024] [Indexed: 05/26/2024]
Abstract
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.
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Affiliation(s)
- Eloá Pereira Brabo
- Serviço de Oncologia, Hospital Universitário Clementino Fraga Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brasil
- Grupo de Oncologia D'Or, Instituto D'Or de Pesquisa e Ensino (IDOR), Rio de Janeiro, RJ, Brasil
| | | | - Patrícia Piazza Rafful
- Departamento de Radiologia, Instituto D'Or de Pesquisa e Ensino (IDOR), Rio de Janeiro, RJ, Brasil
- Departamento de Radiologia, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brasil
| | - Paulo Henrique Rosado-de-Castro
- Departamento de Radiologia, Instituto D'Or de Pesquisa e Ensino (IDOR), Rio de Janeiro, RJ, Brasil
- Departamento de Radiologia, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brasil
- Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brasil
| | - Leonardo Vieira Neto
- Departamento de Clínica Médica e Serviço de Endocrinologia, Faculdade de Medicina, Universidade Federal do Rio de Janeiro, Hospital Universitário Clementino Fraga Filho, Rio de Janeiro, RJ, Brasil,
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Garrido E, Ngoc HL, Guyotat J, Pelissou-Guyotat I, Jacquesson T, Delabar V, Manet R, Gallet C, Fenouil T, Streichenberger N, Vasiljevic A, Meyronet D, Jouanneau E, Ducray F, Dumot C, Picart T. Predictors of Progression in a Series of 81 Adult Patients Surgically Managed for an Intracranial Hemangioblastoma: Implications for the Postoperative Follow-Up. Cancers (Basel) 2024; 16:1261. [PMID: 38610939 PMCID: PMC11010926 DOI: 10.3390/cancers16071261] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2024] [Revised: 03/20/2024] [Accepted: 03/20/2024] [Indexed: 04/14/2024] Open
Abstract
The aim was to identify predictors of progression in a series of patients managed for an intracranial hemangioblastoma, in order to guide the postoperative follow-up modalities. The characteristics of 81 patients managed for an intracranial hemangioblastoma between January 2000 and October 2022 were retrospectively analyzed. The mean age at diagnosis was of 48 ± 16 years. Eleven (14%) patients had von Hippel-Lindau disease. The most frequent tumor location was the cerebellar hemispheres (n = 51, 65%) and 11 (14%) patients had multicentric hemangioblastomas. A gross total resection was achieved in 75 (93%) patients. Eighteen (22%) patients had a local progression, with a median progression-free survival of 56 months 95% CI [1;240]. Eleven (14%) patients had a distant progression (new hemangioblastoma and/or growth of an already known hemangioblastoma). Local progression was more frequent in younger patients (39 ± 14 years vs. 51 ± 16 years; p = 0.005), and those with von Hippel-Lindau disease (n = 8, 44% vs. n = 3, 5%, p < 0.0001), multiple cerebral locations (n = 3, 17% vs. n = 2, 3%, p = 0.02), and partial tumoral resection (n = 4, 18% vs. n = 1, 2%, p = 0.0006). Therefore, it is advisable to propose a postoperative follow-up for at least 10 years, and longer if at least one predictor of progression is present.
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Affiliation(s)
- Elisabeth Garrido
- Department of Neurosurgery, Rouen University Hospital, 1 Rue de Germont, 76000 Rouen, France;
| | - Huy Le Ngoc
- Department of Neurosurgery, Hospital Bach Mai, 78 Giai Phong, Phuong Mai, Dong Da, Ha Noi 116305, Vietnam;
| | - Jacques Guyotat
- Department of Neurosurgery, Hôpital Neurologique Pierre Wertheimer, Groupe Hospitalier Est, Hospices Civils de Lyon, 59 Boulevard Pinel, 69500 Bron, France; (J.G.); (I.P.-G.); (T.J.); (V.D.); (R.M.); (C.G.); (E.J.); (C.D.)
| | - Isabelle Pelissou-Guyotat
- Department of Neurosurgery, Hôpital Neurologique Pierre Wertheimer, Groupe Hospitalier Est, Hospices Civils de Lyon, 59 Boulevard Pinel, 69500 Bron, France; (J.G.); (I.P.-G.); (T.J.); (V.D.); (R.M.); (C.G.); (E.J.); (C.D.)
| | - Timothée Jacquesson
- Department of Neurosurgery, Hôpital Neurologique Pierre Wertheimer, Groupe Hospitalier Est, Hospices Civils de Lyon, 59 Boulevard Pinel, 69500 Bron, France; (J.G.); (I.P.-G.); (T.J.); (V.D.); (R.M.); (C.G.); (E.J.); (C.D.)
- Faculty of Medicine Lyon Est, Université Claude Bernard Lyon 1, 8 Avenue Rockefeller, 69003 Lyon, France; (T.F.); (N.S.); (A.V.); (D.M.); (F.D.)
| | - Violaine Delabar
- Department of Neurosurgery, Hôpital Neurologique Pierre Wertheimer, Groupe Hospitalier Est, Hospices Civils de Lyon, 59 Boulevard Pinel, 69500 Bron, France; (J.G.); (I.P.-G.); (T.J.); (V.D.); (R.M.); (C.G.); (E.J.); (C.D.)
| | - Romain Manet
- Department of Neurosurgery, Hôpital Neurologique Pierre Wertheimer, Groupe Hospitalier Est, Hospices Civils de Lyon, 59 Boulevard Pinel, 69500 Bron, France; (J.G.); (I.P.-G.); (T.J.); (V.D.); (R.M.); (C.G.); (E.J.); (C.D.)
| | - Clémentine Gallet
- Department of Neurosurgery, Hôpital Neurologique Pierre Wertheimer, Groupe Hospitalier Est, Hospices Civils de Lyon, 59 Boulevard Pinel, 69500 Bron, France; (J.G.); (I.P.-G.); (T.J.); (V.D.); (R.M.); (C.G.); (E.J.); (C.D.)
| | - Tanguy Fenouil
- Faculty of Medicine Lyon Est, Université Claude Bernard Lyon 1, 8 Avenue Rockefeller, 69003 Lyon, France; (T.F.); (N.S.); (A.V.); (D.M.); (F.D.)
- Cancer Research Centre of Lyon (CRCL) INSERM 1052, CNRS 5286, 28 Rue Laennec, 69008 Lyon, France
- Department of Neuropathology, Groupe Hospitalier Est, Hospices Civils de Lyon, 59 Boulevard Pinel, 69500 Bron, France
| | - Nathalie Streichenberger
- Faculty of Medicine Lyon Est, Université Claude Bernard Lyon 1, 8 Avenue Rockefeller, 69003 Lyon, France; (T.F.); (N.S.); (A.V.); (D.M.); (F.D.)
- Department of Neuropathology, Groupe Hospitalier Est, Hospices Civils de Lyon, 59 Boulevard Pinel, 69500 Bron, France
- CNRS UMR 5310—INSERM U1217, Institut NeuroMyogène, 8 Avenue Rockefeller, 69008 Lyon, France
| | - Alexandre Vasiljevic
- Faculty of Medicine Lyon Est, Université Claude Bernard Lyon 1, 8 Avenue Rockefeller, 69003 Lyon, France; (T.F.); (N.S.); (A.V.); (D.M.); (F.D.)
- Cancer Research Centre of Lyon (CRCL) INSERM 1052, CNRS 5286, 28 Rue Laennec, 69008 Lyon, France
- Department of Neuropathology, Groupe Hospitalier Est, Hospices Civils de Lyon, 59 Boulevard Pinel, 69500 Bron, France
| | - David Meyronet
- Faculty of Medicine Lyon Est, Université Claude Bernard Lyon 1, 8 Avenue Rockefeller, 69003 Lyon, France; (T.F.); (N.S.); (A.V.); (D.M.); (F.D.)
- Cancer Research Centre of Lyon (CRCL) INSERM 1052, CNRS 5286, 28 Rue Laennec, 69008 Lyon, France
- Department of Neuropathology, Groupe Hospitalier Est, Hospices Civils de Lyon, 59 Boulevard Pinel, 69500 Bron, France
| | - Emmanuel Jouanneau
- Department of Neurosurgery, Hôpital Neurologique Pierre Wertheimer, Groupe Hospitalier Est, Hospices Civils de Lyon, 59 Boulevard Pinel, 69500 Bron, France; (J.G.); (I.P.-G.); (T.J.); (V.D.); (R.M.); (C.G.); (E.J.); (C.D.)
- Faculty of Medicine Lyon Est, Université Claude Bernard Lyon 1, 8 Avenue Rockefeller, 69003 Lyon, France; (T.F.); (N.S.); (A.V.); (D.M.); (F.D.)
- Cancer Research Centre of Lyon (CRCL) INSERM 1052, CNRS 5286, 28 Rue Laennec, 69008 Lyon, France
| | - François Ducray
- Faculty of Medicine Lyon Est, Université Claude Bernard Lyon 1, 8 Avenue Rockefeller, 69003 Lyon, France; (T.F.); (N.S.); (A.V.); (D.M.); (F.D.)
- Cancer Research Centre of Lyon (CRCL) INSERM 1052, CNRS 5286, 28 Rue Laennec, 69008 Lyon, France
- Department of Neuro-Oncology, Hôpital Neurologique Pierre Wertheimer, Groupe Hospitalier Est, Hospices Civils de Lyon, 59 Boulevard Pinel, 69500 Bron, France
| | - Chloe Dumot
- Department of Neurosurgery, Hôpital Neurologique Pierre Wertheimer, Groupe Hospitalier Est, Hospices Civils de Lyon, 59 Boulevard Pinel, 69500 Bron, France; (J.G.); (I.P.-G.); (T.J.); (V.D.); (R.M.); (C.G.); (E.J.); (C.D.)
- Faculty of Medicine Lyon Est, Université Claude Bernard Lyon 1, 8 Avenue Rockefeller, 69003 Lyon, France; (T.F.); (N.S.); (A.V.); (D.M.); (F.D.)
- CarMeN Laboratoire, INSERM, INRAER, Université Claude Bernard Lyon 1, 59 Boulevard Pinel, 69500 Bron, France
| | - Thiebaud Picart
- Department of Neurosurgery, Hôpital Neurologique Pierre Wertheimer, Groupe Hospitalier Est, Hospices Civils de Lyon, 59 Boulevard Pinel, 69500 Bron, France; (J.G.); (I.P.-G.); (T.J.); (V.D.); (R.M.); (C.G.); (E.J.); (C.D.)
- Faculty of Medicine Lyon Est, Université Claude Bernard Lyon 1, 8 Avenue Rockefeller, 69003 Lyon, France; (T.F.); (N.S.); (A.V.); (D.M.); (F.D.)
- Cancer Research Centre of Lyon (CRCL) INSERM 1052, CNRS 5286, 28 Rue Laennec, 69008 Lyon, France
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Yoo KH, Park DJ, Marianayagam NJ, Gu X, Pollom EL, Soltys SG, Chang SD, Meola A. Stereotactic Radiosurgery for Cranial and Spinal Hemangioblastomas: A Single-Institution Retrospective Series. Neurosurgery 2024; 94:630-642. [PMID: 37967154 DOI: 10.1227/neu.0000000000002728] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2023] [Accepted: 08/27/2023] [Indexed: 11/17/2023] Open
Abstract
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.
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Affiliation(s)
- Kelly H Yoo
- Department of Neurosurgery, Stanford University School of Medicine, Stanford , California , USA
| | - David J Park
- Department of Neurosurgery, Stanford University School of Medicine, Stanford , California , USA
| | - Neelan J Marianayagam
- Department of Neurosurgery, Stanford University School of Medicine, Stanford , California , USA
| | - Xuejun Gu
- Department of Radiation Oncology, Stanford University School of Medicine, Stanford , California , USA
| | - Erqi L Pollom
- Department of Radiation Oncology, Stanford University School of Medicine, Stanford , California , USA
| | - Scott G Soltys
- Department of Radiation Oncology, Stanford University School of Medicine, Stanford , California , USA
| | - Steven D Chang
- Department of Neurosurgery, Stanford University School of Medicine, Stanford , California , USA
| | - Antonio Meola
- Department of Neurosurgery, Stanford University School of Medicine, Stanford , California , USA
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Xue J, Mo C. A case report of cerebellar hemangioblastoma simulated brain metastasis shown by magnetic resonance imaging. Medicine (Baltimore) 2024; 103:e37162. [PMID: 38335432 PMCID: PMC10860963 DOI: 10.1097/md.0000000000037162] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/05/2023] [Accepted: 01/15/2024] [Indexed: 02/12/2024] Open
Abstract
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.
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Affiliation(s)
- Jiaxing Xue
- Department of Neurosurgery, People’s Hospital of Dingzhou, Dingzhou, China
| | - Chenlong Mo
- Department of Neurosurgery, People’s Hospital of Dingzhou, Dingzhou, China
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10
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Lestrovaya AI, Golanov AV, Konovalov NA, Pronin IN, Danilina II, Strunina YV. [Stereotactic radiotherapy of spinal hemangioblastoma]. ZHURNAL VOPROSY NEIROKHIRURGII IMENI N. N. BURDENKO 2024; 88:63-70. [PMID: 39670781 DOI: 10.17116/neiro20248806163] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/14/2024]
Abstract
Hemangioblastoma (HAB) is a benign, richly vascularized tumor that accounts for 2-6% of all spinal cord neoplasms and ranks third in the structure of intramedullary space-occupying lesions of the spinal cord. Hemangioblastoma may occur sporadically or, in approximately 30% of cases, as part of the clinical picture of a hereditary disease, von Hippel-Lindau disease. The aim of this study was to evaluate the efficacy and safety of stereotactic irradiation of hemangioblastomas of the spinal localization in patients with sporadic and von Hippel-Lindau-associated hemangioblastomas The results of stereotactic radiotherapy were evaluation of 210 spinal hemangioblastomas in 74 patients. Follow-up observation was available for 67 patients with 166 tumors. The observation period ranged from 6 to 193 months. Tumor growth control with an average follow-up period of 48 months (6-193) was 99%. The use of radiosurgery and hypofractionation for spinal hemangioblastoma, including associated with VHL syndrome, allows achieving high rates of relapse-free survival and tumor growth control with minimal toxicity, including with long-term follow-up. However, in the presence of a pronounced clinical picture, removal of GAB using a microsurgical approach remains the method of choice, since regression of existing symptoms rarely occurs after stereotactic radiotherapy. Increasing the total and single doses does not lead to improved results.
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Affiliation(s)
| | - A V Golanov
- Burdenko Neurosurgical Center, Moscow, Russia
- Federal State Budgetary Educational Institution of the Russian Ministry of Health, Moscow, Russia
| | - N A Konovalov
- Burdenko Neurosurgical Center, Moscow, Russia
- Federal State Budgetary Educational Institution of the Russian Ministry of Health, Moscow, Russia
| | - I N Pronin
- Burdenko Neurosurgical Center, Moscow, Russia
- Federal State Budgetary Educational Institution of the Russian Ministry of Health, Moscow, Russia
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Laviv Y, Saraf D, Oxman L, Zvi IB. Supratentorial hemangioblastoma: correlation between phenotype, gender and vascular territory affected. Neurosurg Rev 2023; 46:281. [PMID: 37875641 DOI: 10.1007/s10143-023-02194-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2023] [Revised: 09/17/2023] [Accepted: 10/19/2023] [Indexed: 10/26/2023]
Abstract
Supratentorial hemangioblastomas are rare, vascular lesions. The presence of peri-tumoral cysts and edema has meaningful clinical, diagnostic and therapeutic implications. Nevertheless, the pathogenesis of both cyst and edema formation is not fully understood. This study sought to determine if the radiologic phenotype of supratentorial hemangioblastoma is affected by the different cerebral arterial circulations. Review of the English-language literature from 1973 to 2023 yielded 53 cases of parenchymal supratentorial hemangioblastomas eligible for analysis. Patients were divided by the vascular territorial distribution of the lesions: anterior circulation (n = 36) or posterior circulation (n = 17), and the groups were compared for demographic, clinical, radiologic and molecular variables. Univariate analyses yielded a significant difference between the groups in five variables. Cystic changes and "classic" radiological phenotype were associated with hemangioblastomas of the posterior circulation (OR = 0.19, p = 0.045 and OR = 0.287, p = 0.048, respectively), while female gender, significant peritumoral edema and purely solid phenotype were associated with hemangioblastomas of the anterior circulation (OR = 3.384, p = 0.045 and OR = 5.25, p = 0.05 and OR = 14.0, p = 0.015; respectively). On multivariate analysis, solid phenotype and female gender remained significantly associated with the anterior circulation (OR = 36.04, p = 0.014 and OR = 4.45, p = 0.045). The incidence of von-Hippel Lindau disease was higher in the anterior-circulation group. Cystic tumors were present in all females in the posterior-circulation group compared to 43.4% in the anterior-circulation group (OR = 20.714, 95% CI 1.061 to 404.122; p = 0.045). Based on historical cases of supratentorial hemangioblastoma, this study shows that different tumor phenotypes are associated with the different cerebral circulations. Gender was also associated with differences in tumor distribution and radiologic phenotype. These novel data may improve our understanding of unique vascular diseases of the central nervous system.
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Affiliation(s)
- Yosef Laviv
- Department of Neurosurgery, Rabin Medical Center - Beilinson Hospital, Petach Tikva, Israel.
- Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
| | - David Saraf
- Department of Neurosurgery, Rabin Medical Center - Beilinson Hospital, Petach Tikva, Israel
- Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Liat Oxman
- Department of Neurosurgery, Rabin Medical Center - Beilinson Hospital, Petach Tikva, Israel
- Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Ido Ben Zvi
- Department of Neurosurgery, Rabin Medical Center - Beilinson Hospital, Petach Tikva, Israel
- Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
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12
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Elbeltagy M, Abbassy M. Neurofibromatosis type1, type 2, tuberous sclerosis and Von Hippel-Lindau disease. Childs Nerv Syst 2023; 39:2791-2806. [PMID: 37819506 DOI: 10.1007/s00381-023-06160-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/12/2023] [Accepted: 09/16/2023] [Indexed: 10/13/2023]
Abstract
Neurocutaneous syndromes (also known as phakomatoses) are heterogenous group of disorders that involve derivatives of the neuroectoderm. Each disease has diagnostic and pathognomonic criteria, once identified, thorough clinical examination to the patient and the family members should be done. Magnetic resonance imaging (MRI) is used to study the pathognomonic findings withing the CNS (Evans et al. in Am J Med Genet A 152A:327-332, 2010). This chapter includes the 4 most common syndromes faced by neurosurgeons and neurologists; neurofibromatosis types 1 and 2, tuberous sclerosis and Von Hippel-Lindau disease. Each syndrome has specific genetic anomaly that involves a tumor suppressor gene and the loss of inhibition of specific pathways. The result is a spectrum of cutaneous manifestations and neoplasms.
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Affiliation(s)
- M Elbeltagy
- Department of Neurosurgery, Cairo University, 1 University Street, Giza Governorate, 12613, Egypt.
- Department of Neurosurgery, Children's Cancer Hospital Egypt, Sekat Hadid Al Mahger, Zeinhom, El Sayeda Zeinab, Cairo Governorate, 4260102, Egypt.
| | - M Abbassy
- Department of Neurosurgery, Children's Cancer Hospital Egypt, Sekat Hadid Al Mahger, Zeinhom, El Sayeda Zeinab, Cairo Governorate, 4260102, Egypt
- Department of Neurosurgery, Alexandria University, 22 El-Gaish Rd, Al Azaritah WA Ash Shatebi, Bab Sharqi, Alexandria Governorate, 5424041, Egypt
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13
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Poiset SJ, Reddy A, Tucker CM, Kenyon LC, Judy KD, Shi W. Hemangioblastoma with late leptomeningeal metastasis: a case report. J Med Case Rep 2023; 17:102. [PMID: 36935497 PMCID: PMC10026473 DOI: 10.1186/s13256-023-03812-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2022] [Accepted: 02/08/2023] [Indexed: 03/21/2023] Open
Abstract
BACKGROUND Hemangioblastoma of the central nervous system is an uncommon benign neoplasm, with about 25% of cases in patients with von Hippel-Lindau disease. The incidence of metastasis is rare, particularly in patients without von Hippel-Lindau disease. We report a case of hemangioblastoma with leptomeningeal dissemination as a late recurrence. CASE PRESENTATION A 65-year-old Caucasian man with a history of World Health Organization grade I hemangioblastoma of the cerebellar vermis underwent gross total resection in 1997. In early 2018, he developed intracranial recurrences with diffuse leptomeningeal disease of the entire spine. The patient underwent resection of intracranial recurrence, followed by palliative craniospinal irradiation. The disease progressed quickly, and he died 8 months after recurrence. CONCLUSIONS Despite a benign pathology, hemangioblastoma has a low risk of metastasis. The outcome for hemangioblastoma patients with metastasis is poor. Multidisciplinary care for patients with metastatic hemangioblastoma warrants further investigation, and an effective systemic option is urgently needed. Regular lifelong follow-up of at-risk patients is recommended.
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Affiliation(s)
- Spencer J Poiset
- Department of Radiation Oncology, Sidney Kimmel Medical College, Thomas Jefferson University, 111 S 11 ST, Suite G301, Philadelphia, PA, 19107, USA
| | | | - Catherine M Tucker
- Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University, Philadelphia, PA, USA
| | - Lawrence C Kenyon
- Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University, Philadelphia, PA, USA
| | - Kevin D Judy
- Department of Neurological Surgery, Thomas Jefferson University, Philadelphia, PA, USA
| | - Wenyin Shi
- Department of Radiation Oncology, Sidney Kimmel Medical College, Thomas Jefferson University, 111 S 11 ST, Suite G301, Philadelphia, PA, 19107, USA.
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Shepherd STC, Drake WM, Turajlic S. The road to systemic therapy in von Hippel-Lindau (VHL) disease: Are we there yet? Eur J Cancer 2023; 182:15-22. [PMID: 36708612 DOI: 10.1016/j.ejca.2022.12.011] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2022] [Accepted: 12/14/2022] [Indexed: 12/24/2022]
Abstract
Pathogenic germline mutations in VHL gene cause von Hippel-Lindau (VHL) disease, an autosomal dominant hereditary cancer syndrome associated with high penetrance of benign and malignant neoplasms, including clear cell renal cell carcinoma (ccRCC), central nervous system haemangioblastomas (CNS-HB), retinal angiomas, phaeochromocytomas and pancreatic neuroendocrine tumours (pNET). Management of VHL disease involves lifelong radiological and biochemical surveillance, often leading to repeat surgical intervention causing significant morbidity and mortality. Systemic therapy that prevents or reduces the need for surgical intervention could improve clinical outcomes and quality of life for affected individuals. Belzutifan is a second-generation small molecule hypoxia-inducible factor 2α (HIF-2α) inhibitor recently approved by US and UK regulators for the treatment of VHL (disease)-associated ccRCC, CNS-HB and pNET. While this is a welcome step forward, it is vital that we consider in what circumstances these drugs are recommended and how they fit into the overall management of VHL disease. In this personal view article, we reflect on the history of the use of systemic therapy in localised VHL disease and consider open questions relating to the use of HIF-2α inhibitors, including the need to involve medical oncologists in the multidisciplinary team moving forward. Indeed, VHL disease is the perfect paradigm for similar settings in the future.
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Affiliation(s)
- Scott T C Shepherd
- Cancer Dynamics Laboratory, The Francis Crick Institute, Midland Road, London, UK; Renal and Skin Units, The Royal Marsden NHS Foundation Trust, London, UK; Melanoma and Kidney Cancer Team, The Institute of Cancer Research, London, UK
| | - William M Drake
- Department of Endocrinology, St. Bartholomew's Hospital, London, UK
| | - Samra Turajlic
- Cancer Dynamics Laboratory, The Francis Crick Institute, Midland Road, London, UK; Renal and Skin Units, The Royal Marsden NHS Foundation Trust, London, UK; Melanoma and Kidney Cancer Team, The Institute of Cancer Research, London, UK.
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15
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Chen L, Xiong Z, Zhou Y, Li Y, Xie Y, Xiong Y, Wanggou S, Li X. Clinical characteristics, surgical management, and prognostic factors for supratentorial hemangioblastoma: A retrospective study. Front Surg 2023; 9:1092140. [PMID: 36760665 PMCID: PMC9902503 DOI: 10.3389/fsurg.2022.1092140] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2022] [Accepted: 12/28/2022] [Indexed: 01/25/2023] Open
Abstract
Background Supratentorial hemangioblastoma is an extremely rare neoplasm. The aim of this study is to delineate the clinical features among cystic and solid supratentorial hemangioblastoma patients and evaluate the risk factors for progression-free survival (PFS). Methods We conducted a literature search in PubMed for histopathologically identified supratentorial hemangioblastoma between 1947 and 2021 and extracted and collected the clinical features of patients treated at our own institute. The rate of PFS was determined using Kaplan-Meier analysis. Differences in categorical factors, such as the location of tumor and diagnosis of von Hippel-Lindau disease, were analyzed using the Pearson χ 2 test. A Cox regression analysis was performed to evaluate the association between various variates and survival outcomes. Results A total of 237 cases of supratentorial hemangioblastoma were identified from 169 studies. A survival analysis found that patients with cystic tumors had a significantly better prognosis than those with solid tumors (log-rank, p = 0.0122). Cox regression analysis suggested that cystic hemangioblastoma (hazard ratio (HR): 0.186, 95% CI: 0.043-0.803, p < 0.05) and gross total resection (GTR) (HR: 0.126, 95% CI: 0.049-0.323, p < 0.001) were significant predictors of longer survival (PFS) for supratentorial hemangioblastoma. Following an analysis of 13 supratentorial hemangioblastoma cases from our institute, we validated that cystic tumor had improved prognosis than solid tumor (log-rank, p = 0.0096) and GTR was superior to subtotal resection (log-rank, p = 0.0029). Conclusions Cystic hemangioblastoma vs. solid hemangioblastoma may be two tumoral statuses with different clinical features, and a specific treatment strategy should be considered.
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Affiliation(s)
- Long Chen
- Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, China,Xiangya School of Medicine, Central South University, Changsha, China,Hunan International Scientific and Technological Cooperation Base of Brain Tumor Research, Xiangya Hospital, Central South University, Changsha, China
| | - Zujian Xiong
- Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, China,Xiangya School of Medicine, Central South University, Changsha, China,Hunan International Scientific and Technological Cooperation Base of Brain Tumor Research, Xiangya Hospital, Central South University, Changsha, China
| | - Yian Zhou
- School of Mathematics and Statistics, Central South University, Changsha, China
| | - Yanwen Li
- Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, China,Xiangya School of Medicine, Central South University, Changsha, China,Hunan International Scientific and Technological Cooperation Base of Brain Tumor Research, Xiangya Hospital, Central South University, Changsha, China
| | - Yuanyang Xie
- Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, China,Hunan International Scientific and Technological Cooperation Base of Brain Tumor Research, Xiangya Hospital, Central South University, Changsha, China
| | - Yi Xiong
- Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, China,Xiangya School of Medicine, Central South University, Changsha, China,Hunan International Scientific and Technological Cooperation Base of Brain Tumor Research, Xiangya Hospital, Central South University, Changsha, China
| | - Siyi Wanggou
- Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, China,Hunan International Scientific and Technological Cooperation Base of Brain Tumor Research, Xiangya Hospital, Central South University, Changsha, China,Correspondence: Siyi Wanggou Xuejun Li
| | - Xuejun Li
- Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, China,Hunan International Scientific and Technological Cooperation Base of Brain Tumor Research, Xiangya Hospital, Central South University, Changsha, China,Correspondence: Siyi Wanggou Xuejun Li
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16
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Li DF, Guo XJ, Song SP, Li HB. Rare massive hepatic hemangioblastoma: A case report. World J Gastrointest Oncol 2022; 14:2415-2421. [PMID: 36568941 PMCID: PMC9782622 DOI: 10.4251/wjgo.v14.i12.2415] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/30/2022] [Revised: 10/02/2022] [Accepted: 11/07/2022] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND Hepatic hemangioblastoma is an extremely rare disease; only three cases have been reported in the literature, and its magnetic resonance imaging (MRI) findings are unreported.
CASE SUMMARY We report a case of incidental hepatic hemangioblastoma. The patient had no history of von Hippel-Lindau disease or associated clinical signs. Computed tomography and MRI showed a large tumor occupying almost half of the right side of the liver with expansive growth, well-defined borders, heterogeneous mildly progressive enhancement, and visibly enlarged blood supply vessels. Flow voids were observed on T2-weighted imaging. Both diffusion-weighted imaging (DWI) and apparent diffusion coefficient (ADC) map findings of the mass were predominantly inhomogeneous. Postoperative pathology indicated a diagnosis of hemangioblastoma.
CONCLUSION Enlarged peripheral blood-supplying vessels and progressive enhancement seem to be typical imaging features of hepatic hemangioblastoma. However, a solid significantly enhanced mass with a low signal on DWI and a high signal on ADC may also be helpful for the diagnosis of hepatic hemangioblastoma.
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Affiliation(s)
- De-Fu Li
- Department of Radiology, Fuyong People’s Hospital of Shenzhen Baoan, Shenzhen 518103, Guangdong Province, China
| | - Xue-Jun Guo
- Department of Radiology, Peking University Shenzhen Hospital, Shenzhen 518036, Guangdong Province, China
| | - Shi-Peng Song
- Department of Hepatobiliary Surgery, Fuyong People’s Hospital of Shenzhen Baoan, Shenzhen 518103, Guangdong Province, China
| | - Hong-Bing Li
- Department of Radiology, Fuyong People’s Hospital of Shenzhen Baoan, Shenzhen 518103, Guangdong Province, China
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17
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Takami H, Graffeo CS, Perry A, Brown DA, Meyer FB, Burns TC, Parney IF. Presentation, imaging, patterns of care, growth, and outcome in sporadic and von Hippel-Lindau-associated central nervous system hemangioblastomas. J Neurooncol 2022; 159:221-231. [PMID: 35902552 DOI: 10.1007/s11060-022-04021-8] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2022] [Accepted: 04/19/2022] [Indexed: 11/25/2022]
Abstract
OBJECT Hemangioblastoma is a relatively rare neoplasm occurring mostly in the cerebellum that may arise sporadically or in the context of von Hippel-Lindau (VHL) syndrome. Presentation, imaging, natural history, surgical patterns of care, and outcomes are incompletely defined for this uncommon lesion. We reviewed our large institutional series to help clarify these issues. METHODS Retrospective analysis of consecutive, neurosurgically managed CNS hemangioblastomas at Mayo Clinic, 1988-2018. RESULTS Two hundred and eighty five hemangioblastomas were treated in 184 unique patients (115 sporadic, 69 VHL). Compared to sporadic patients, VHL patients were younger (36.7 vs 51.7 years; p < 0.0001), were treated while asymptomatic more commonly (47.3 vs 4.2%; p < 0.0001), had smaller lesions (6.6 vs 13.9 mL; p < 0.0001), and harbored lesions with associated cysts less frequently (51.0 vs 75.0%; p = 0.0002). Macrocystic tumor architecture was associated with larger lesion size and greater symptom severity. Solid lesions later formed cysts at a median 130 months. Growth in both total volume and solid component accelerated after cyst formation (10.6 and 6.0 times median rate prior to cyst emergence). VHL patients died at a younger age (47.9 vs 74.5, p = 0.0017) and were more likely to die of direct disease sequelae. Though treatment-free survival time was significantly longer in sporadic cases, a substantial fraction (> 40%) developed tumor recurrence/progression requiring additional treatment. CONCLUSIONS Hemangioblastoma presentation varies with etiology and clinical course is more complicated in VHL cases. Nodular lesions often develop cysts over time which is associated with accelerated tumor growth. Sporadic cases have a previously unappreciated but substantial risk of late recurrence/progression requiring treatment.
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Affiliation(s)
- Hirokazu Takami
- Department of Neurologic Surgery, Mayo Clinic, 200 First St. SW, Rochester, MN, 55905, USA
| | - Christopher S Graffeo
- Department of Neurologic Surgery, Mayo Clinic, 200 First St. SW, Rochester, MN, 55905, USA
| | - Avital Perry
- Department of Neurologic Surgery, Mayo Clinic, 200 First St. SW, Rochester, MN, 55905, USA
| | - Desmond A Brown
- Department of Neurologic Surgery, Mayo Clinic, 200 First St. SW, Rochester, MN, 55905, USA
| | - Fredric B Meyer
- Department of Neurologic Surgery, Mayo Clinic, 200 First St. SW, Rochester, MN, 55905, USA
| | - Terry C Burns
- Department of Neurologic Surgery, Mayo Clinic, 200 First St. SW, Rochester, MN, 55905, USA
| | - Ian F Parney
- Department of Neurologic Surgery, Mayo Clinic, 200 First St. SW, Rochester, MN, 55905, USA.
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18
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Yoda RA, Cimino PJ. Neuropathologic features of central nervous system hemangioblastoma. J Pathol Transl Med 2022; 56:115-125. [PMID: 35501672 PMCID: PMC9119802 DOI: 10.4132/jptm.2022.04.13] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2022] [Accepted: 04/13/2022] [Indexed: 12/04/2022] Open
Abstract
Hemangioblastoma is a benign, highly vascularized neoplasm of the central nervous system (CNS). This tumor is associated with loss of function of the VHL gene and demonstrates frequent occurrence in von Hippel-Lindau (VHL) disease. While this entity is designated CNS World Health Organization grade 1, due to its predilection for the cerebellum, brainstem, and spinal cord, it is still an important cause of morbidity and mortality in affected patients. Recognition and accurate diagnosis of hemangioblastoma is essential for the practice of surgical neuropathology. Other CNS neoplasms, including several tumors associated with VHL disease, may present as histologic mimics, making diagnosis challenging. We outline key clinical and radiologic features, pathophysiology, treatment modalities, and prognostic information for hemangioblastoma, and provide a thorough review of the gross, microscopic, immunophenotypic, and molecular features used to guide diagnosis.
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Affiliation(s)
- Rebecca A. Yoda
- Department of Laboratory Medicine and Pathology, Division of Neuropathology, University of Washington, Seattle, WA, USA
- Department of Laboratory Medicine and Pathology, Division of Cytopathology, University of Washington, Seattle, WA, USA
- Corresponding Author: Rebecca A. Yoda, MD, Department of Laboratory Medicine and Pathology, University of Washington, 325 9th Avenue, Box 359791, Seattle, WA 98104-2499, USA Tel: +1-206-744-3145, Fax: +1-206-744-8240, E-mail:
| | - Patrick J. Cimino
- Department of Laboratory Medicine and Pathology, Division of Neuropathology, University of Washington, Seattle, WA, USA
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19
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Jejurkar MA, Lagad SG, Ranjan R. Recurrence of Sporadic Intracranial Cerebellar Hemangioblastoma: Case Report and Literature Review. Neurol India 2021; 69:508-510. [PMID: 33904491 DOI: 10.4103/0028-3886.314560] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022]
Affiliation(s)
- Madhavi Ashok Jejurkar
- Department of Pharmacy Practice (Pharm-D), Indira College of Pharmacy, Pune, Maharashtra, India
| | - Shrenil Gulab Lagad
- Department of Pharmacy Practice (Pharm-D), Indira College of Pharmacy, Pune, Maharashtra, India
| | - Rakesh Ranjan
- Consultant, Neurosurgery, Aditya Birla Memorial Hospital, Pune, Maharashtra, India
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Yang B, Li Z, Wang Y, Zhang C, Zhang Z, Zhang X. Central Nervous System Hemangioblastoma in a Pediatric Patient Associated With Von Hippel-Lindau Disease: A Case Report and Literature Review. Front Oncol 2021; 11:683021. [PMID: 34109129 PMCID: PMC8180858 DOI: 10.3389/fonc.2021.683021] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2021] [Accepted: 04/28/2021] [Indexed: 11/13/2022] Open
Abstract
Background Hemangioblastoma is a benign tumor of the central nervous system and may appear as a component of von Hippel-Lindau (VHL) disease. At present, approximately 40 cases of optic nerve HGBs have been reported in the literature. VHL disease is a rare autosomal-dominant inherited cancer syndrome with different phenotypes caused by variants in the VHL gene. Herein, the authors describe a case of a pediatric patient with VHL disease and with optic nerve HGB, a rare phenotypic expression. The purpose of this study was to explore the genotype-phenotype, clinical features, treatment and follow-up of VHL-associated hemangioblastomas in pediatric patients. Case Description A 12-year-old boy presented with vision loss, headache and dizziness at our hospital. Magnetic resonance imaging (MRI) revealed a large (19.8 mm*18.5 mm*23.5 mm) irregular mass located in the suprasellar region. The mass was successfully removed after craniotomy and microsurgical treatment. The pathological diagnosis was left optic nerve HGB. Genetic analyses showed p.Pro86Leu (c. 257C>T) heterozygous missense mutations in the VHL gene. Conclusion This is the first reported pediatric case of VHL-associated optic nerve HGB. The genotype-phenotype correlation of VHL disease may provide new evidences for predicting tumor penetrance and survival. Gross tumor resection combined with stereotactic radiosurgery might be the most beneficial treatment.
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Affiliation(s)
- Bo Yang
- Department of Neurosurgery, First Hospital of Jilin University, Changchun, China
| | - Zhenyu Li
- Department of Pediatrics, First Hospital of Jilin University, Changchun, China
| | - Yubo Wang
- Department of Neurosurgery, First Hospital of Jilin University, Changchun, China
| | - Chaoling Zhang
- Department of Neurosurgery, First Hospital of Jilin University, Changchun, China
| | - Zhen Zhang
- Department of Neurosurgery, First Hospital of Jilin University, Changchun, China
| | - Xianfeng Zhang
- Department of Neurosurgery, First Hospital of Jilin University, Changchun, China
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21
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Lee JH, Jeon SH, Park CK, Park SH, Yoon HI, Chang JH, Suh CO, Kang SJ, Lim DH, Kim IA, Kim JH, Im JH, Kim SH, Wee CW, Kim IH. The Role of Postoperative Radiotherapy in Intracranial Solitary Fibrous Tumor/Hemangiopericytoma: A Multi-Institutional Retrospective Study (KROG 18-11). Cancer Res Treat 2021; 54:65-74. [PMID: 33781051 PMCID: PMC8756112 DOI: 10.4143/crt.2021.142] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2021] [Accepted: 03/23/2021] [Indexed: 11/21/2022] Open
Abstract
Purpose To evaluate the role of postoperative radiotherapy (PORT) in intracranial solitary fibrous tumor/hemangiopericytoma (SFT/HPC). Methods and Materials A total of 133 patients with histologically confirmed HPC were included from 8 institutions. Gross total resection (GTR) and subtotal resection (STR) were performed in 86 and 47 patients, respectively. PORT was performed in 85 (64%) patients. The prognostic effects of sex, age, performance, WHO grade, location, size, Ki-67, surgical extent, and PORT on local control (LC), distant metastasis-free survival (DMFS), progression-free survival (PFS), and overall survival (OS) were estimated by univariate and multivariate analyses. Results The 10-year PFS, and OS rates were 45%, and 71%, respectively. The multivariate analysis suggested that PORT significantly improved LC (p<0.001) and PFS (p<0.001). The PFS benefit of PORT was maintained in the subgroup of GTR (p=0.001), WHO grade II (p=0.001) , or STR (p<0.001). In the favorable subgroup of GTR and WHO grade II, PORT was also significantly related to better PFS (p=0.028). WHO grade III was significantly associated with poor DMFS (p=0.029). In the PORT subgroup, the 0-0.5 cm margin of the target volume showed an inferior LC to a large margin with 1.0-2.0 cm (p=0.021). Time-dependent Cox proportion analysis showed that distant failures were significantly associated with poor OS (p=0.003). Conclusion This multicenter study supports the role of PORT in disease control of intracranial SFT/HPC, irrespective of the surgical extent and grade. For LC, PORT should enclose the tumor bed with sufficient margin.
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Affiliation(s)
- Joo Ho Lee
- Department of Radiation Oncology, Seoul National University Hospital, Seoul National University, College of Medicine, Seoul, Korea.,Institute of Radiation Medicine, Medical Research Center, Seoul National University Hospital, Seoul, Korea
| | - Seung Hyuck Jeon
- Department of Radiation Oncology, Seoul National University Hospital, Seoul National University, College of Medicine, Seoul, Korea
| | - Chul-Kee Park
- Department of Neurosurgery, Seoul National University Hospital, Seoul, Korea
| | - Sung-Hye Park
- Department of Pathology, Seoul National University, College of Medicine, Yonsei Cancer Center, Yonsei University Health System, Seoul, Korea
| | - Hong In Yoon
- Department of Radiation Oncology, Yonsei Cancer Center, Yonsei University Health System, Seoul, Korea
| | - Jong Hee Chang
- Department of Neurosurgery, Severance Hospital, Yonsei University Health System, Seoul, Korea
| | - Chang-Ok Suh
- Department of Radiation Oncology, Yonsei Cancer Center, Yonsei University Health System, Seoul, Korea.,Department of Radiation Oncology, CHA Bundang Medical Center, CHA University School of Medicine, Seongnam, Korea
| | - Su Jeong Kang
- Department of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Do Hoon Lim
- Department of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - In Ah Kim
- Department of Radiation Oncology, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Jin Hee Kim
- Department of Radiation Oncology, Keimyung University Dongsan Hospital, School of Medicine, Daegu, Korea
| | - Jung Ho Im
- Department of Radiation Oncology, CHA Bundang Medical Center, CHA University School of Medicine, Seongnam, Korea
| | - Sung-Hwan Kim
- Department of Radiation Oncology, St. Vincent's Hospital, Suwon, Korea
| | - Chan Woo Wee
- Department of Radiation Oncology, SMG-SNU Boramae Medical Center, Seoul, Korea
| | - Il Han Kim
- Department of Radiation Oncology, Seoul National University Hospital, Seoul National University, College of Medicine, Seoul, Korea
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22
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Pruteanu DP, Olteanu DE, Cosnarovici R, Mihut E, Nagy V. Genetic predisposition in pediatric oncology. Med Pharm Rep 2020; 93:323-334. [PMID: 33225257 PMCID: PMC7664724 DOI: 10.15386/mpr-1576] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2020] [Revised: 03/10/2020] [Accepted: 07/25/2020] [Indexed: 11/23/2022] Open
Abstract
Identifying patients with a genetic predisposition for developing malignant tumors has a significant impact on both the patient and family. Recognition of genetic predisposition, before diagnosing a malignant pathology, may lead to early diagnosis of a neoplasia. Recognition of a genetic predisposition syndrome after the diagnosis of neoplasia can result in a change of treatment plan, a specific follow-up of adverse treatment effects and, of course, a long-term follow-up focusing on the early detection of a second neoplasia. Responsible for genetic syndromes that predispose individuals to malignant pathology are germline mutations. These mutations are present in all cells of conception, they can be inherited or can occur de novo. Several mechanisms of inheritance are described: Mendelian autosomal dominant, Mendelian autosomal recessive, X-linked patterns, constitutional chromosomal abnormality and non-Mendelian inheritance. In the following review we will present the most important genetic syndromes in pediatric oncology.
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Affiliation(s)
- Doina Paula Pruteanu
- Department of Pediatric Oncology, "Prof. Dr. Ion Chiricuta" Oncology Institute, Cluj-Napoca, Romania.,Department of Radiation Oncology, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania
| | - Diana Elena Olteanu
- Department of Pediatric Oncology, "Prof. Dr. Ion Chiricuta" Oncology Institute, Cluj-Napoca, Romania
| | - Rodica Cosnarovici
- Department of Pediatric Oncology, "Prof. Dr. Ion Chiricuta" Oncology Institute, Cluj-Napoca, Romania
| | - Emilia Mihut
- Department of Pediatric Oncology, "Prof. Dr. Ion Chiricuta" Oncology Institute, Cluj-Napoca, Romania
| | - Viorica Nagy
- Department of Pediatric Oncology, "Prof. Dr. Ion Chiricuta" Oncology Institute, Cluj-Napoca, Romania.,Department of Radiation Oncology, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania
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23
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Liu Z, Li L, Yi Z, Duan H, Lu R, Li C, Li L, Gong K. Biological and clinical impact of central nervous system hemangioblastomas in Chinese patients with von Hippel-Lindau disease: implications for treatment. Hered Cancer Clin Pract 2020; 18:21. [PMID: 33110457 PMCID: PMC7583299 DOI: 10.1186/s13053-020-00153-y] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2020] [Accepted: 10/19/2020] [Indexed: 12/15/2022] Open
Abstract
Objective Central nervous system (CNS) hemangioblastomas (HGBs) are the most frequent cause of mortality in patients with von Hippel-Lindau (VHL) genetic syndrome. However, there is a lack of large studies on the clinical features and optimal management of HGBs in Chinese patients. Methods VHL-related HGB cases treated surgically at our hospital from 2012 to 2019 were evaluated. Patients and family members meeting the clinical diagnostic criteria underwent genetic testing. Clinical, genetic and relevant imaging data were analyzed. Results Eighty-five VHL patients from 34 pedigrees in 16 Chinese provinces who underwent 121 operations for CNS HGBs were enrolled. Multiple operations were associated with a younger age at first operation (OR = 0.926, 95% CI = 0.871–0.985, P = 0.014, threshold: 27.5, sensitivity: 72.2%, specificity: 71.2%) and a longer postoperative period (OR = 1.096, 95% CI = 1.015–1.184, P = 0.019, threshold: 10.5, sensitivity: 66.7%, specificity: 76.3%). The age at first operation was younger in children than in their parents (23 pairs, P < 0.001). The age at first operation was younger in siblings born later than in those born earlier (10 pairs, P = 0.01). Most untreated tumors (98.2%) remained relatively stable during follow-up (range, 0.5–7; median, 2). However, new tumors continued to emerge (0.14 tumor/year). Conclusion VHL-associated CNS HGB is a long-term chronic disease with repeated attacks, likely with genetic anticipation in Chinese pedigrees. When the age at first operation is under 27.5 years, or the postoperative period is longer than 10.5 years, the risk of multiple operations is increased. While most unresected HGBs remain stable after surgery, new tumors may still slowly emerge; hence, scheduled follow-ups are necessary.
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Affiliation(s)
- Zhen Liu
- Department of Neurosurgery, Peking University First Hospital, No. 8 Xishiku Street, Xicheng District, Beijing, 100034 China
| | - Liang Li
- Department of Neurosurgery, Peking University First Hospital, No. 8 Xishiku Street, Xicheng District, Beijing, 100034 China
| | - Zhiqiang Yi
- Department of Neurosurgery, Peking University First Hospital, No. 8 Xishiku Street, Xicheng District, Beijing, 100034 China
| | - Hongzhou Duan
- Department of Neurosurgery, Peking University First Hospital, No. 8 Xishiku Street, Xicheng District, Beijing, 100034 China
| | - Runchun Lu
- Department of Neurosurgery, Peking University First Hospital, No. 8 Xishiku Street, Xicheng District, Beijing, 100034 China
| | - Chunwei Li
- Department of Neurosurgery, Peking University First Hospital, No. 8 Xishiku Street, Xicheng District, Beijing, 100034 China
| | - Lei Li
- Department of Urology, Peking University First Hospital, Beijing, 100034 China
| | - Kan Gong
- Department of Urology, Peking University First Hospital, Beijing, 100034 China
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24
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Mak G, Algird A, Greenspoon J, Provias J, Hirte H. Cervicomedullary hemangioblastoma treated with bevacizumab. Neurooncol Adv 2020; 2:vdaa076. [PMID: 32908970 PMCID: PMC7470470 DOI: 10.1093/noajnl/vdaa076] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2022] Open
Affiliation(s)
- Gloria Mak
- Department of Medicine, McMaster University, Hamilton, Ontario, Canada
| | - Almunder Algird
- Department of Surgery, McMaster University, Hamilton, Ontario, Canada
| | | | - John Provias
- Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada
| | - Hal Hirte
- Department of Oncology, McMaster University, Hamilton, Ontario, Canada
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25
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Qiu J, Cai D, Yang F, Zhou J, Gong Y, Cai L, Gong K. Stereotactic radiosurgery for central nervous system hemangioblastoma in von Hippel-Lindau disease: A systematic review and meta-analysis. Clin Neurol Neurosurg 2020; 195:105912. [PMID: 32474257 DOI: 10.1016/j.clineuro.2020.105912] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2020] [Accepted: 05/10/2020] [Indexed: 12/23/2022]
Abstract
Von Hippel-Lindau (VHL) disease is a dominantly inherited disorder marked by multiorgan tumors, such as central nervous system benign hemangioblastomas (CHB). Stereotactic radiosurgery (SRS) has also been used to treat CHB for a long time. The purpose of this meta-analysis is to provide a long-term outcome of SRS for VHL-associated CHB by reviewing published studies. We completed a Pubmed/Embase/SCOPUS/Cochrane Library literature search to get eligible studies published from January 1990 to December 2019 about using SRS to treat VHL-associated CHB. 15 studies met eligibility for qualitative systematic review, of which nine studies were ultimately eligible for quantity meta-analysis of 5-year tumor control rates (TCR), representing 170 subjects with a total of 660 lesions. Gamma Knife was the most published SRS method for VHL-associated CHB. The pooled 5-year TCR across the nine studies was 0.919 (95 %CI: 0.881-0.957). The pooled 5-year TCR for only intracranial lesions across eight studies was 0.917 (95 %CI: 0.876-0.957). Individual patient data were extracted from 9 studies, representing 298 lesions of 70 subjects. Sex, tumor volume, radiosurgery methods, marginal doses, maximum doses, the number of tumors for radiosurgery, age at the time of radiosurgery, tumor locations were not proven to be associated with tumor progression. SRS offered a satisfactory 5-year tumor control of CHB for VHL patients. Despite the paucity of randomized control trials, SRS is recommended to patients with limited surgical alternatives. However, the long-term outcomes and underlying factors associated with tumor progression remain to be investigated.
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Affiliation(s)
- Jianhui Qiu
- Department of Urology, Peking University First Hospital, Beijing, China; Institute of Urology, Peking University, Beijing, China; National Urological Cancer Center, Beijing, China
| | - Desheng Cai
- Department of Urology, Peking University First Hospital, Beijing, China; Institute of Urology, Peking University, Beijing, China; National Urological Cancer Center, Beijing, China
| | - Fan Yang
- Department of Urology, Peking University First Hospital, Beijing, China
| | - Jingcheng Zhou
- Department of Urology, Peking University First Hospital, Beijing, China; Institute of Urology, Peking University, Beijing, China; National Urological Cancer Center, Beijing, China
| | - Yanqing Gong
- Department of Urology, Peking University First Hospital, Beijing, China; Institute of Urology, Peking University, Beijing, China; National Urological Cancer Center, Beijing, China
| | - Lin Cai
- Department of Urology, Peking University First Hospital, Beijing, China; Institute of Urology, Peking University, Beijing, China; National Urological Cancer Center, Beijing, China
| | - Kan Gong
- Department of Urology, Peking University First Hospital, Beijing, China; Institute of Urology, Peking University, Beijing, China; National Urological Cancer Center, Beijing, China.
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26
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Klingler JH, Gläsker S, Bausch B, Urbach H, Krauss T, Jilg CA, Steiert C, Puzik A, Neumann-Haefelin E, Kotsis F, Agostini H, Neumann HPH, Beck J. Hemangioblastoma and von Hippel-Lindau disease: genetic background, spectrum of disease, and neurosurgical treatment. Childs Nerv Syst 2020; 36:2537-2552. [PMID: 32507909 PMCID: PMC7575510 DOI: 10.1007/s00381-020-04712-5] [Citation(s) in RCA: 33] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/25/2020] [Accepted: 05/28/2020] [Indexed: 12/13/2022]
Abstract
INTRODUCTION Hemangioblastomas are rare, histologically benign, highly vascularized tumors of the brain, the spinal cord, and the retina, occurring sporadically or associated with the autosomal dominant inherited von Hippel-Lindau (VHL) disease. Children or adults with VHL disease have one of > 300 known germline mutations of the VHL gene located on chromosome 3. They are prone to develop hemangioblastomas, extremely rarely starting at age 6, rarely at age 12-18, and, typically and almost all, as adults. There is a plethora of VHL-associated tumors and cysts, mainly in the kidney, pancreas, adrenals, reproductive organs, and central nervous system. Due to a lack of causal treatment, alleviation of symptoms and prevention of permanent neurological deficits as well as malignant transformation are the main task. Paucity of data and the nonlinear course of tumor progression make management of pediatric VHL patients with hemangioblastomas challenging. METHODS The Freiburg surveillance protocol was developed by combining data from the literature and our experience of examinations of > 300 VHL patients per year at our university VHL center. RESULTS Key recommendations are to start screening of patients at risk by funduscopy with dilated pupils for retinal tumors with admission to school and with MRI of the brain and spinal cord at age 14, then continue biannually until age 18, with emergency MRI in case of neurological symptoms. Indication for surgery remains personalized and should be approved by an experienced VHL board, but we regard neurological symptoms, rapid tumor growth, or critically large tumor/cyst sizes as the key indications to remove hemangioblastomas. Since repeated surgery on hemangioblastomas in VHL patients is not rare, modern neurosurgical techniques should encompass microsurgery, neuronavigation, intraoperative neuromonitoring, fluorescein dye-based intraoperative angiography, intraoperative ultrasound, and minimally invasive approaches, preceded in selected cases by endovascular embolization. Highly specialized neurosurgeons are able to achieve a very low risk of permanent morbidity for the removal of hemangioblastomas from the cerebellum and spinal cord. Small retinal tumors of the peripheral retina can be treated by laser coagulation, larger tumors by cryocoagulation or brachytherapy. CONCLUSION We consider management at experienced VHL centers mandatory and careful surveillance and monitoring of asymptomatic lesions are required to prevent unnecessary operations and minimize morbidity.
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Affiliation(s)
- Jan-Helge Klingler
- Department of Neurosurgery, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Breisacher Str. 64, 79106, Freiburg, Germany.
| | - Sven Gläsker
- Department of Neurosurgery, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Breisacher Str. 64, 79106, Freiburg, Germany
- Department of Neurosurgery, Universitair Ziekenhuis Brussel, VUB University, Brussels, Belgium
| | - Birke Bausch
- Department of Medicine II, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany
| | - Horst Urbach
- Department of Neuroradiology, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany
| | - Tobias Krauss
- Department of Radiology, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany
| | - Cordula A Jilg
- Department of Urology, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany
| | - Christine Steiert
- Department of Neurosurgery, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Breisacher Str. 64, 79106, Freiburg, Germany
| | - Alexander Puzik
- Department of Pediatric Hematology and Oncology, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany
| | - Elke Neumann-Haefelin
- Department of Medicine IV, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany
| | - Fruzsina Kotsis
- Department of Medicine IV, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany
| | - Hansjürgen Agostini
- Eye Center, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany
| | - Hartmut P H Neumann
- Section for Preventive Medicine, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany
| | - Jürgen Beck
- Department of Neurosurgery, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Breisacher Str. 64, 79106, Freiburg, Germany
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27
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Byun J, Yoo HJ, Kim JH, Kim YH, Cho YH, Hong SH, Kim CJ. Growth rate and fate of untreated hemangioblastomas: clinical assessment of the experience of a single institution. J Neurooncol 2019; 144:147-154. [PMID: 31201685 DOI: 10.1007/s11060-019-03213-z] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2019] [Accepted: 06/11/2019] [Indexed: 01/28/2023]
Abstract
BACKGROUND The growth rate and natural history of untreated hemangioblastomas remain unclear. This study investigated the natural history of untreated intracranial hemangioblastomas and predictors of tumor growth using volumetric assessment. METHOD This study retrospectively enrolled 31 patients with untreated hemangioblastomas between 2004 and 2017 who were followed up for at least 12 months. The 31 patients had a total of 52 hemangioblastomas. RESULTS The 31 patients included 11 (35.5%) men and 20 (64.5%) women, of mean age 42.5 years. Seventeen (54.8%) patients were genetically diagnosed with Von Hippel-Lindau (VHL) disease. Of the 52 lesions, 33 (63.5%) grew during the follow-up period, whereas 19 (36.5%) remained stable. Overall mean actual growth rate (AGR) was 1.94 cm3/year, 2.38 cm3/year in the VHL and 1.79 cm3/year in the non-VHL group (p = 0.31). Overall mean relative growth rate (RGR) was 21%/year, 26%/year in the VHL and 19%/year in the non-VHL group. Time to 50% treatment probability was 34 months. The 1, 3, 5, and 7-year treatment probabilities were 11.5%, 50.1%, 52.7%, and 73%, respectively. The presence of only symptomatic lesions was significantly predictive of the growth of intracranial hemangioblastoma (odds ratio: 5.0, p = 0.02). CONCLUSION The overall growth rate of intracranial hemangioblastoma was faster than that of other benign intracranial tumors, with symptomatic lesions being the only meaningful predictor of tumor growth. Because of their rapid growth rate and high probability of treatment, a wait and scan management strategy should be carefully applied to intracranial hemangioblastomas.
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Affiliation(s)
- Joonho Byun
- Department of Neurological Surgery, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Korea
| | - Hee Jun Yoo
- Department of Neurological Surgery, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Korea
| | - Jeong Hoon Kim
- Department of Neurological Surgery, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Korea.
| | - Young Hoon Kim
- Department of Neurological Surgery, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Korea
| | - Young Hyun Cho
- Department of Neurological Surgery, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Korea
| | - Seok Ho Hong
- Department of Neurological Surgery, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Korea
| | - Chang Jin Kim
- Department of Neurological Surgery, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Korea
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28
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Kotecha R, Mehta MP, Chang EL, Brown PD, Suh JH, Lo SS, Das S, Samawi HH, Keith J, Perry J, Sahgal A. Updates in the management of intradural spinal cord tumors: a radiation oncology focus. Neuro Oncol 2019; 21:707-718. [PMID: 30977511 PMCID: PMC6556849 DOI: 10.1093/neuonc/noz014] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2022] Open
Abstract
Primary spinal cord tumors represent a hetereogeneous group of central nervous system malignancies whose management is complex given the relatively uncommon nature of the disease and variety of tumor subtypes, functional neurologic deficits from the tumor, and potential morbidities associated with definitive treatment. Advances in neuroimaging; integration of diagnostic, prognostic, and predictive molecular testing into tumor classification; and developments in neurosurgical techniques have refined the current role of radiotherapy in the multimodal management of patients with primary spinal cord tumors, and corroborated the need for prospective, multidisciplinary discussion and treatment decision making. Radiotherapeutic technological advances have dramatically improved the entire continuum from treatment planning to treatment delivery, and the development of stereotactic radiosurgery and proton radiotherapy provides new radiotherapy options for patients treated in the definitive, adjuvant, or salvage setting. The objective of this comprehensive review is to provide a contemporary overview of the management of primary intradural spinal cord tumors, with a focus on radiotherapy.
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Affiliation(s)
- Rupesh Kotecha
- Department of Radiation Oncology, Miami Cancer Institute, Baptist Health South Florida, Miami, Florida, USA
- Herbert Wertheim College of Medicine, Florida International University, Miami, Florida, USA
| | - Minesh P Mehta
- Department of Radiation Oncology, Miami Cancer Institute, Baptist Health South Florida, Miami, Florida, USA
- Herbert Wertheim College of Medicine, Florida International University, Miami, Florida, USA
| | - Eric L Chang
- Department of Radiation Oncology, University of Southern California, Los Angeles, California, USA
| | - Paul D Brown
- Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota, USA
| | - John H Suh
- Department of Radiation Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, Ohio, USA
- Rose Ella Burkhardt Brain Tumor and Neuro-Oncology Center, Taussig Cancer Institute, Cleveland, Ohio, USA
- Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, Ohio, USA
| | - Simon S Lo
- Department of Radiation Oncology, University of Washington, Seattle, Washington, USA
| | - Sunit Das
- Li Ka Shing Knowledge Institute, St. Michael’s Hospital, Toronto, Ontario, Canada
| | - Haider H Samawi
- Division of Hematology/Oncology, St Michael’s Hospital, Toronto, Ontario, Canada
| | - Julia Keith
- Department of Anatomical Pathology, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario, Canada
| | - James Perry
- Department of Neurology, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario, Canada
| | - Arjun Sahgal
- Department of Radiation Oncology, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario, Canada
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29
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Liebenow B, Tatter A, Dezarn WA, Isom S, Chan MD, Tatter SB. Gamma Knife Stereotactic Radiosurgery favorably changes the clinical course of hemangioblastoma growth in von Hippel-Lindau and sporadic patients. J Neurooncol 2019; 142:471-478. [PMID: 30729402 PMCID: PMC6805133 DOI: 10.1007/s11060-019-03118-x] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2018] [Accepted: 02/01/2019] [Indexed: 02/08/2023]
Abstract
PURPOSE This is the first single-institution study of its size to characterize the treatment impact and to address the question of whether hemangioblastoma treatment with Gamma Knife Stereotactic Radiosurgery (GKRS) in both sporadic and VHL patients changes the characteristic saltatory hemangioblastoma growth pattern. METHODS The authors reviewed a single-institution tumor registry to identify patients who had received GKRS for hemangioblastomas between January 1st, 1999, and December 31st, 2017. RESULTS 15 patients with 101 lesions met search criteria with a median age of first GKRS of 39.2 years (interquartile range [IQR] of 25.7-57.4 years), including 96 VHL and 5 sporadic lesions. The median time from GKRS to last follow-up was 5.4 years (IQR 2.3-11.5 years). 4 lesions (4%) and 3 patients (20%) experienced a local failure. The 1-year, 3-year, and 5-year freedom from new hemangioblastoma formation rates were 97%, 80%, and 46% respectively. Multivariate analysis revealed a reduction in tumor volume after GKRS. Several variables associated with a greater percent reduction in volume from GKRS to last follow-up: non-cystic status (p = .01), no prior craniotomy (p = .04), and follow-up time from GKRS (p < .0001). CONCLUSIONS GKRS is a successful long-term treatment option for hemangioblastomas changing the clinical course from saltatory growth to reduction in tumor volume. Non-cystic tumors and those without prior craniotomy were associated with a greater percent reduction in volume from GKRS at last follow-up.
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Affiliation(s)
- Brittany Liebenow
- Departments of Neurosurgery, Wake Forest School of Medicine, Medical Center Blvd, Winston-Salem, NC, 27157, USA.
| | - Abigail Tatter
- Departments of Neurosurgery, Wake Forest School of Medicine, Medical Center Blvd, Winston-Salem, NC, 27157, USA
| | - William A Dezarn
- Radiation Oncology, Wake Forest School of Medicine, Winston-Salem, NC, USA
| | - Scott Isom
- Biostatistical Sciences, Wake Forest School of Medicine, Winston-Salem, NC, USA
| | - Michael D Chan
- Radiation Oncology, Wake Forest School of Medicine, Winston-Salem, NC, USA
| | - Stephen B Tatter
- Departments of Neurosurgery, Wake Forest School of Medicine, Medical Center Blvd, Winston-Salem, NC, 27157, USA
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Kord Valeshabad A, Xiao L, Amin-Hanjani S, Alsadi A, Valyi-Nagy T, Kim J. Sporadic Hemangioblastoma of the Cavernous Sinus and Meckel's Cave. J Neurol Surg Rep 2018; 79:e98-e102. [PMID: 30574445 PMCID: PMC6291399 DOI: 10.1055/s-0038-1676455] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2018] [Accepted: 08/28/2018] [Indexed: 11/01/2022] Open
Abstract
Objectives To describe an extremely rare case of sporadic hemangioblastoma (HB) within the cavernous sinus and Meckel's cave with extension to the cerebellopontine angle (CPA) cistern. Methods A 73-year-old male presented with hearing loss, unilateral ptosis, and facial numbness. Results The imaging showed a complex cystic-solid mass centered at the left cavernous sinus and Meckel's cave with extension to the CPA cistern. Patient underwent retrosigmoid craniectomy for partial resection of the CPA angle component of the mass. Surgical pathology confirmed the diagnosis of HB and patient was scheduled for subsequent radiotherapy of the residual mass. Conclusions We present an exceptional case of supratentorial HB without associated von Hippel-Lindau (VHL) disease, which was predominantly located in the cavernous sinus and Meckel's cave and led to multiple cranial nerve symptoms. We describe imaging characteristics and radiologic-pathologic correlation of this atypically located HB, which can be difficult to consider in the differential diagnosis presurgically.
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Affiliation(s)
- Ali Kord Valeshabad
- Department of Radiology, University of Illinois at Chicago, Chicago, Illinois, United States
| | - Lekui Xiao
- Department of Radiology, University of Illinois at Chicago, Chicago, Illinois, United States
| | - Sepideh Amin-Hanjani
- Department of Neurosurgery, University of Illinois at Chicago, Chicago, Illinois, United States
| | - Alaa Alsadi
- Department of Pathology, University of Illinois at Chicago, Chicago, Illinois, United States
| | - Tibor Valyi-Nagy
- Department of Pathology, University of Illinois at Chicago, Chicago, Illinois, United States
| | - Jinsuh Kim
- Department of Radiology, University of Alabama at Birmingham, Birmingham, Alabama, United States
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Practice Patterns of Stereotactic Radiotherapy in Pediatrics: Results From an International Pediatric Research Consortium. J Pediatr Hematol Oncol 2018; 40:522-526. [PMID: 30247288 DOI: 10.1097/mph.0000000000001290] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
PURPOSE/OBJECTIVES There is little consensus regarding the application of stereotactic radiotherapy (SRT) in pediatrics. We evaluated patterns of pediatric SRT practice through an international research consortium. MATERIALS AND METHODS Eight international institutions with pediatric expertise completed a 124-item survey evaluating patterns of SRT use for patients 21 years old and younger. Frequencies of SRT use and median margins applied with and without SRT were evaluated. RESULTS Across institutions, 75% reported utilizing SRT in pediatrics. SRT was used in 22% of brain, 18% of spine, 16% of other bone, 16% of head and neck, and <1% of abdomen/pelvis, lung, and liver cases across sites. Of the hypofractionated SRT cases, 42% were delivered with definitive intent. Median gross tumor volume to planning target volume margins for SRT versus non-SRT plans were 0.2 versus 1.4 cm for brain, 0.3 versus 1.5 cm for spine/other bone, 0.3 versus 2.0 cm for abdomen/pelvis, 0.7 versus 1.5 cm for head and neck, 0.5 versus 1.7 cm for lung, and 0.5 versus 2.0 cm for liver sites. CONCLUSIONS SRT is commonly utilized in pediatrics across a range of treatment sites. Margins used for SRT were substantially smaller than for non-SRT planning, highlighting the utility of this approach in reducing treatment volumes.
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Huang Y, Chan L, Bai HX, Li X, Zhang Z, Wang Y, Cao Y, Karakousis G, Huang R, Xiao B, Zhang PJ, Yang L. Assessment of care pattern and outcome in hemangioblastoma. Sci Rep 2018; 8:11144. [PMID: 30042517 PMCID: PMC6057968 DOI: 10.1038/s41598-018-29047-9] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2017] [Accepted: 07/02/2018] [Indexed: 11/09/2022] Open
Abstract
Due to its rarity, current literature assessing prognostic factors and survival outcomes of hemangioblastoma is limited. Patients with histologically confirmed hemangioblastoma were identified from the US National Cancer Data Base. 1488 patients met inclusion criteria. 644 patients underwent gross total resection (GTR), 220 subtotal resection (STR)/biopsy, 60 stereotactic radiosurgery (SRS), 15 external beam radiotherapy (EBRT), 51 surgery followed by radiotherapy (SR + RT) and 498 no treatment. Independent predictors of shorter OS included age ≥ 40 (HR, 3.897; 95% CI, 2.341-6.487; p < 0.001), Charlson-Deyo score ≥ 1(HR, 1.756; 95% CI, 1.213-2.544; p = 0.003), tumor location in the brainstem (HR, 1.955; 95% CI, 1.129-3. 384; p = 0.017) compared to cerebellum, no treatment (HR, 2530; 95% CI, 1.533-4.177; p < 0.001) and receipt of EBRT (HR, 2.860; 95% CI, 1.073-7.618; p = 0.036) compared to STR/biopsy. GTR was associated with longer OS (HR 0.617; 95% CI, 0.391-0.974; p = 0.038), while SRS had comparable OS to STR/biopsy. The overall trend of OS by treatment modality was consistent after matching to age- and sex-matched US population data. In patients younger than 40 years, treatment was not a significant predictor of OS. In conclusion, GTR remained the optimal treatment for hemangioblastoma. SRS may perform similarly to surgery alone. Treatment was not a significant predictor of survival in younger patients.
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Affiliation(s)
- Yuqian Huang
- Department of Neurology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, 410011, China
| | - Lilian Chan
- Perelman School of Medicine, Philadelphia, Pennsylvania, 19104, United States
| | - Harrison X Bai
- Department of Radiology, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania, 19104, United States
| | - Xuejun Li
- Department of Neurosurgery, Xiangya Hospital, Central South University, Hunan, 410011, China
| | - Zishu Zhang
- Department of Radiology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, 410011, China
| | - Yinyan Wang
- Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
| | - Ya Cao
- Cancer Research Institute, School of Basic Medicine, Central South University, Changsha, Hunan, 410078, China
| | - Giorgos Karakousis
- Department of Surgery, Hospital of the University of Pennsylvania, Silverstein, Philadelphia, Pennsylvania, 19104, United States
| | - Raymond Huang
- Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, 02120, United States
| | - Bo Xiao
- Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan, 410011, China.
| | - Paul J Zhang
- Department of Pathology and Laboratory Medicine, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania, 19104, United States
| | - Li Yang
- Department of Neurology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, 410011, China.
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Nguyen HS, Doan NB, Gelsomino M, Shabani S, Awad AJ, Kaushal M, Mortazavi MM. Intracranial hemangioblastoma - A SEER-based analysis 2004-2013. Oncotarget 2018; 9:28009-28015. [PMID: 29963258 PMCID: PMC6021332 DOI: 10.18632/oncotarget.25534] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2018] [Accepted: 05/14/2018] [Indexed: 02/02/2023] Open
Abstract
Introduction Intracranial hemangioblastoma (HB) is a rare pathology. Limited data exist regarding its epidemiology. Methods With the SEER-18 registry database, information from all patients diagnosed with intracranial HB from 2004 to 2013 were extracted, including age, gender, race, marital status, presence of surgery, extent of surgery, receipt of radiation, tumor size, tumor location, and follow-up data. Age-adjusted incidence rates and overall survival (OS). Cox proportional hazards model was employed for both univariate and multivariate analyses. Results A total of 1307 cases were identified. The overall incidence of intracranial hemangioblastoma is 0.153 per 100,000 person-years [95% confidence interval (CI)=0.145–0.162]. Through univariate analysis, age < 40 [hazard ratio (HR)=0.277, p<0.001], no radiation [HR=0.56, p=0.047], and presence of surgery [HR=0.576, p=0.012] are significant positive prognostic factors. Caucasian race [HR=1.42, p=0.071] and female gender [HR=0.744, p=0.087] exhibit noticeable trends towards positive prognosis. Through multivariate analysis, younger age [HR=1.053, p < 0.01], race [HR=1.916, p<0.01], and presence of surgery [HR=0.463, p<0.01 were significant independent prognostic factors. Conclusion Clinical factors such as younger age, Caucasian race, and presence of surgery are significant independent factors for overall survival in patients with HBs. Though analysis regarding extent of surgery did not produce a meaningful relationship, this may be related to surgical bias / expertise. Moreover, no validation for radiation therapy was identified, but this may be related to short follow up intervals and the variable growth patterns of HBs.
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Affiliation(s)
- Ha Son Nguyen
- Department of Neurosurgery, Medical College of Wisconsin, Milwaukee, Wisconsin, USA.,California Institute of Neuroscience, Thousand Oaks, California, USA
| | - Ninh B Doan
- Department of Neurosurgery, Medical College of Wisconsin, Milwaukee, Wisconsin, USA.,Department of Neurosurgery, University of South Alabama, Mobile, Alabama, USA
| | - Michael Gelsomino
- Department of Neurosurgery, Medical College of Wisconsin, Milwaukee, Wisconsin, USA
| | - Saman Shabani
- Department of Neurosurgery, Medical College of Wisconsin, Milwaukee, Wisconsin, USA
| | - Ahmed J Awad
- Department of Neurosurgery, Medical College of Wisconsin, Milwaukee, Wisconsin, USA.,Faculty of Medicine and Health Sciences, An-Najah National University, Nablus, Palestine
| | - Mayank Kaushal
- Department of Neurosurgery, Medical College of Wisconsin, Milwaukee, Wisconsin, USA
| | - Martin M Mortazavi
- National Skull Base Center, Thousand Oaks, California, USA.,California Institute of Neuroscience, Thousand Oaks, California, USA
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VHL-Associated Optic Nerve Hemangioblastoma Treated with Stereotactic Radiosurgery. J Kidney Cancer VHL 2018; 5:1-6. [PMID: 29911000 PMCID: PMC5989481 DOI: 10.15586/jkcvhl.2018.104] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2018] [Accepted: 05/15/2018] [Indexed: 12/12/2022] Open
Abstract
Central nervous system hemangioblastomas are generally restricted to the cerebellum, spinal cord, and brainstem. Supratentorial hemangioblastomas are uncommon, and optic nerve hemangioblastomas are extremely rare, with fewer than 25 reports including this case. In this report, we present the case of a 36-year-old woman with von Hippel–Lindau (VHL) disease who presented with progressive diminution of vision in the left eye due to a retrobulbar optic nerve hemangioblastoma. The patient had a history of cerebellar/spinal hemangioblastomas and pancreatic cysts, and her father and brother were patients with VHL disease. Gadolinium-enhanced magnetic resonance imaging showed intraorbital retrobulbar–enhanced mass on the left optic nerve. The optic nerve hemangioblastoma was treated with fractionated stereotactic radiosurgery using Novalis. Eighteen months after the stereotactic radiosurgery, the tumor volume decreased although the patient lost vision. This report presents an extremely rare case of optic nerve hemangioblastoma, which is the first case treated with stereotactic radiosurgery.
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Staudt MD, Hebb MO. Staged multi-modality treatment approaches for giant cerebellopontine angle hemangioblastomas. J Clin Neurosci 2018; 53:224-228. [PMID: 29685408 DOI: 10.1016/j.jocn.2018.04.027] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2018] [Accepted: 04/09/2018] [Indexed: 11/30/2022]
Abstract
Giant hemangioblastomas (HBs) located in the cerebellopontine angle (CPA) present rare, high risk neurosurgical challenges. En bloc resection has been traditionally recommended for HBs, however this approach may pose unacceptable risk with giant tumors. Alternative treatment strategies have not been well described and the relevant literature is scant. This case review includes an illustrative patient with a giant, symptomatic CPA HB. It was felt that the neurovascular and tumor attributes were favorable for a multi-modality treatment strategy rather than circumferential dissection to remove this formidable tumor. A staged approach consisting of preoperative HB devascularization, debulking and piecemeal resection followed by radiosurgery for a small residuum produced an excellent clinical outcome. Variations of this unconventional multi-modality strategy may reduce the perioperative morbidity of carefully selected patients with giant CPA HBs. A thorough literature review is provided.
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Affiliation(s)
- Michael D Staudt
- Department of Clinical Neurological Sciences, Schulich School of Medicine and Dentistry, Western University, London, Ontario, Canada
| | - Matthew O Hebb
- Department of Clinical Neurological Sciences, Schulich School of Medicine and Dentistry, Western University, London, Ontario, Canada.
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36
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Alshafai N, Maduri R, Shail M, Chirchiglia D, Meyronet D, Signorelli F. Surgical approach for suprasellar hemangioblastomas preserving the pituitary stalk: Review of the literature and report of a further case. Clin Neurol Neurosurg 2018; 168:147-152. [PMID: 29550691 DOI: 10.1016/j.clineuro.2018.03.010] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2017] [Revised: 03/03/2018] [Accepted: 03/08/2018] [Indexed: 11/30/2022]
Abstract
Hemangioblastomas (HBLs) are challenging vascular tumours with rare suprasellar location Surgery is recommended in patients with visual impairment, endocrine disorders or hydrocephalus. Surgical removal of pituitary stalk HBLs is challenging due to their location and high vascularity. Our narrative review was guided by the question: "what is the more suitable surgical approach to excise a suprasellar HBL?". Pertinent English literature was scrutinized from database inception to October 2016. Eighteen articles matched our selection criteria. Among the surgically treated patients, 4 were treated through a trans-sphenoidal (TS) approach, 13 through a transcranial approach (2 of them after TS failure). Five other cases were treated with radiotherapy (adjuvant in 3 cases) and 9 patients were managed with simple observation and/or medical treatment. We add a case of complete suprasellar HBL resection through an orbito-zygomatic (OZ) craniotomy with extradural anterior clinoidectomy (EAC). To achieve satisfactory oncologic results with acceptable morbidity for symptomatic suprasellar HBLs, complete tumour removal with pituitary stalk sparing should be attempted through an OZ craniotomy with EAC that provides adequate exposure of the tumour, its vascular supply and the adjacent neural structures.
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Affiliation(s)
- Nabeel Alshafai
- Alshafai Neurosurgical Academy (A.N.A.), Toronto, Ontario, Canada
| | - Rodolfo Maduri
- Department of Clinical Neurosciences, Service of Neurosurgery, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland
| | - Mrigank Shail
- Xavier University School of Medicine, Aruba, The Netherlands
| | | | - David Meyronet
- Centre de Pathologie et de Neuropathologie Est, Hospices Civils de Lyon, Lyon, France
| | - Francesco Signorelli
- Department of Neurosurgery, Hôpital Pierre Wertheimer, Hospices Civils de Lyon, Lyon, France; Division of Neurosurgery, Department of Basic Medical Sciences, Neurosciences and Sense Organs, University "Aldo Moro" of Bari, Italy.
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Nambu S, Otani R, Higuchi F, Uzuka T, Matsuda H, Kim P, Ueki K. Histology of hemangioblastoma treated with stereotactic radiosurgery confirms its effectiveness. J Clin Neurosci 2018; 51:43-45. [PMID: 29483011 DOI: 10.1016/j.jocn.2018.02.003] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2017] [Accepted: 02/05/2018] [Indexed: 10/18/2022]
Abstract
Hemangioblastoma is usually amenable to total surgical resection, but indication for surgery can be hampered by its location, multiplicity, or repeated recurrences frequently observed in patients with von Hippel Lindau disease (VHLD). Stereotactic radiosurgery (SRS) has been administered for such cases as an alternative therapeutic option with generally favorable clinical response, but the effect of SRS has not been underscored by histological examination of the treated hemangioblastoma. Here we present histology of VHLD-associated hemangioblastoma tissue resected three months after SRS because of cyst enlargement. It confirmed that hemangioblastoma cells totally disappeared after SRS with a marginal dose of 20 Gy. Furthermore, Electron microscope revealed that endothelial cells of the vascular structure disappeared while maintaining the basement membranes, and leakage of intraluminal contents was observed around the structure. We showed the SRS was effective for hemangioblastoma pathologically at least with the marginal dose of 20 Gy. Leakage of intraluminal contents from the damaged vascular structure losing the endothelial cells is one possible mechanism for the cyst enlargement, and it may be a reason of poor control rate of SRS for the cystic hemangioblastoma.
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Affiliation(s)
- Shohei Nambu
- Department of Neurosurgery, Dokkyo Medical University, 880 Kitakobayashi, Mibu-machi, Shimotsuga-gun, Tochigi 321-0293, Japan
| | - Ryohei Otani
- Department of Neurosurgery, Dokkyo Medical University, 880 Kitakobayashi, Mibu-machi, Shimotsuga-gun, Tochigi 321-0293, Japan.
| | - Fumi Higuchi
- Department of Neurosurgery, Dokkyo Medical University, 880 Kitakobayashi, Mibu-machi, Shimotsuga-gun, Tochigi 321-0293, Japan
| | - Takeo Uzuka
- Department of Neurosurgery, Dokkyo Medical University, 880 Kitakobayashi, Mibu-machi, Shimotsuga-gun, Tochigi 321-0293, Japan
| | - Hadzki Matsuda
- Department of Neurosurgery, Dokkyo Medical University, 880 Kitakobayashi, Mibu-machi, Shimotsuga-gun, Tochigi 321-0293, Japan
| | - Phyo Kim
- Department of Neurosurgery, Dokkyo Medical University, 880 Kitakobayashi, Mibu-machi, Shimotsuga-gun, Tochigi 321-0293, Japan
| | - Keisuke Ueki
- Department of Neurosurgery, Dokkyo Medical University, 880 Kitakobayashi, Mibu-machi, Shimotsuga-gun, Tochigi 321-0293, Japan
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Stereotactic radiosurgery for central nervous system hemangioblastoma: systematic review and meta-analysis. J Neurooncol 2017; 137:11-22. [PMID: 29204841 DOI: 10.1007/s11060-017-2697-0] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/24/2017] [Accepted: 11/24/2017] [Indexed: 01/10/2023]
Abstract
Hemangioblastomas are rare, benign, vascular tumors of the central nervous system (CNS), often associated with von-hippel lindau (VHL) disease. Current therapeutic options include microsurgical resection or stereotactic radiosurgery (SRS). With no randomized controlled studies and minimal data beyond single-institution reviews, the optimal management approach for patients with CNS hemangioblastomas is unclear. We completed a Pubmed/SCOPUS literature search from January 1990 to January 2017 for eligible studies on SRS for CNS hemangioblastomas. Relevant articles were identified and reviewed in accordance to the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines. 26 studies met eligibility criteria for qualitative synthesis, representing 596 subjects and 1535 tumors. The Gamma Knife was the most published SRS method for CNS hemangioblastomas. After critical study appraisal for intra-study bias, 14 studies were used for quantitative meta-analysis of 5-year progression free survival (PFS). The pooled 5-year PFS across all eligible studies was 88.4%. No difference was observed between spine versus intracranial studies. Individual patient data (IPD) was extracted from 14 studies, representing 322 tumors. Univariate analysis of IPD revealed that VHL patients were younger, and had smaller tumors compared to those with sporadic disease. Adverse events were associated with increasing marginal dose, independent of tumor volume. VHL status, sex, radiosurgical method, tumor location, and tumor volume were not found to be significantly associated with tumor progression. Multiple studies show excellent tumor control at 5-year follow up, however, the long-term efficacy of SRS for CNS hemangioblastomas still needs to be investigated, and the studies exploring the role of SRS for early treatment of asymptomatic lesions is wanting.
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Management Strategies and Outcomes for VHL-related Craniospinal Hemangioblastomas. J Kidney Cancer VHL 2017; 4:37-44. [PMID: 28868236 PMCID: PMC5573741 DOI: 10.15586/jkcvhl.2017.90] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2017] [Accepted: 08/06/2017] [Indexed: 02/06/2023] Open
Abstract
Hemangioblastomas are rare and benign tumors accounting for less than 2% of all central nervous system (CNS) tumors. The vast majority of hemangioblastomas occur sporadically, whereas a small number of cases, especially in younger patients, are associated with Von Hippel–Lindau (VHL) syndrome. It is thought that loss of tumor suppressor function of the VHL gene results in stabilization of hypoxia-inducible factor alpha with downstream activation of cellular proliferative and angiogenic genes that promote tumorigenesis. VHL-related hemangioblastomas predominantly occur in the cerebellum and spine. Lesions are often diagnosed on contrast-enhanced craniospinal MRIs, and the diagnosis of VHL occurs through assessment for germline VHL mutations. Surgical resection remains the primary treatment modality for symptomatic or worrisome lesions, with excellent local control rates and neurological outcomes. Stereotactic radiotherapy can be employed in patients who are deemed high risk for surgery, have multiple lesions, or have non-resectable lesions. Given the tendency for development of either new or multiple lesions, close radiographic surveillance is often recommended for asymptomatic lesions.
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Cheng J, Liu W, Hui X, Zhang S, Ju Y. Pediatric central nervous system hemangioblastomas: different from adult forms? A retrospective series of 25 cases. Acta Neurochir (Wien) 2017; 159:1603-1611. [PMID: 28752202 DOI: 10.1007/s00701-017-3275-0] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2017] [Accepted: 07/12/2017] [Indexed: 02/05/2023]
Abstract
BACKGROUND Pediatric hemangioblastomas are rare, and the clinical features, timing of surgical intervention, optimal treatment, and clinical outcomes are still unclear. METHODS We performed a retrospective study of all patients with CNS hemangioblastomas who were treated at West China Hospital from January 2003 to March 2015. Patients under the age of 16 years were included in the study. The medical records of these patients were reviewed and statistically analyzed. RESULTS Twenty-five children (15 females and ten males, [mean age 12.6 ± 4.7 years, range 1-16 years]) presented with hemangioblastomas. Tumors were detected in the cerebellum, brainstem, and spinal cord in 40, 28, and 32% of patients, respectively. Sixteen children (64%) had VHL syndrome. The most frequent symptoms were those related to increased intracranial pressure. The mean duration of symptoms was 1.5 ± 2.1 months. Preoperative hydrocephalus was noted in 11 children (44%). Gross total resection was achieved in all children. Clinical symptoms improved in 19 children (76%), unchanged in four children (16%), and aggravated in two children (8%), respectively. The mean follow-up was 44.5 ± 32.3 months. Five patients (20%) experienced disease progression. Using univariate analysis, both tumor-associated cysts (P = 0.027) and VHL disease (P = 0.032) were significantly related to postoperative outcomes. CONCLUSIONS Pediatric hemangioblastomas have many different clinical features compared with adult cases. A high degree of suspicion for VHL disease should be raised in pediatric hemangioblastomas. Despite many challenges involved, surgical outcomes for pediatric hemangioblastomas are favorable. Lifelong follow-up is mandatory to detect the disease progression.
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Affiliation(s)
- Jian Cheng
- Department of Neurosurgery West China Hospital, Sichuan University, 37 Guo Xue Xiang, Wu Hou District, Chengdu, 610041, Sichuan, People's Republic of China
| | - Wenke Liu
- Department of Neurosurgery West China Hospital, Sichuan University, 37 Guo Xue Xiang, Wu Hou District, Chengdu, 610041, Sichuan, People's Republic of China
| | - Xuhui Hui
- Department of Neurosurgery West China Hospital, Sichuan University, 37 Guo Xue Xiang, Wu Hou District, Chengdu, 610041, Sichuan, People's Republic of China
| | - Si Zhang
- Department of Neurosurgery West China Hospital, Sichuan University, 37 Guo Xue Xiang, Wu Hou District, Chengdu, 610041, Sichuan, People's Republic of China
| | - Yan Ju
- Department of Neurosurgery West China Hospital, Sichuan University, 37 Guo Xue Xiang, Wu Hou District, Chengdu, 610041, Sichuan, People's Republic of China.
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Yamauchi M, Okada T, Okada T, Yamamoto A, Fushimi Y, Arakawa Y, Miyamoto S, Togashi K. Differential diagnosis of posterior fossa brain tumors: Multiple discriminant analysis of Tl-SPECT and FDG-PET. Medicine (Baltimore) 2017; 96:e7767. [PMID: 28816956 PMCID: PMC5571693 DOI: 10.1097/md.0000000000007767] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/25/2022] Open
Abstract
This study investigated the combined capability of thallium-201 (Tl)-SPECT and fluorine-18-fluoro-deoxy-glucose (FDG)-PET for differential diagnosis of posterior fossa brain tumors using multiple discriminant analysis.This retrospective study was conducted under approval of the institutional review board. In the hospital information system, 27 patients with posterior fossa intra-axial tumor between January 2009 and June 2015 were enrolled and grouped as the following 7 entities: low grade glioma (LGG) 6, anaplastic astrocytoma (AA) 2, glioblastoma (GBM) 3, medulloblastoma (MB) 3, hemangioblastoma (HB) 6, metastatic tumor (Mets) 3, and malignant lymphoma (ML) 4. Tl and FDG uptakes were measured at the tumors and control areas, and several indexes were derived. Using indexes selected by the stepwise method, discriminant analysis was conducted with leave-one-out cross-validation.The predicted accuracy for tumor classification was 70.4% at initial analysis and 55.6% at cross-validation to differentiate 7 tumor entities. HB, LGG, and ML were well-discriminated, but AA was located next to LGG. GBM, MB, and Mets largely overlapped and could not be well distinguished even applying multiple discriminant analysis. Correct classification in the original and cross-validation analyses was 44.4% and 33.3% for Tl-SPECT and 55.6% and 48.1% for FDG-PET.
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Affiliation(s)
| | | | - Tsutomu Okada
- Department of Diagnostic Imaging and Nuclear Medicine
| | | | | | - Yoshiki Arakawa
- Department of Neurosurgery, Kyoto University Graduate School of Medicine, Kyoto, Japan
| | - Susumu Miyamoto
- Department of Neurosurgery, Kyoto University Graduate School of Medicine, Kyoto, Japan
| | - Kaori Togashi
- Department of Diagnostic Imaging and Nuclear Medicine
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Dreijerink KM, van der Horst-Schrivers AN, Links TP, Giles RH. Von Hippel-Lindau disease: a multidisciplinary neoplasia syndrome. INTERNATIONAL JOURNAL OF ENDOCRINE ONCOLOGY 2017. [DOI: 10.2217/ije-2016-0021] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022] Open
Affiliation(s)
- Koen M Dreijerink
- Department of Endocrine Oncology, University Medical Center Utrecht, Utrecht, The Netherlands
| | | | - Thera P Links
- Department of Endocrinology, University Medical Center Groningen, Groningen, The Netherlands
| | - Rachel H Giles
- Department of Nephrology and Hypertension, Regenerative Medicine Center Utrecht, University Medical Center Utrecht, Utrecht, the Netherlands
- Dutch VHL Patient Organization, Belangenvereniging VHL, Gouda, The Netherlands
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Pan J, Ho AL, D'Astous M, Sussman ES, Thompson PA, Tayag AT, Pangilinan L, Soltys SG, Gibbs IC, Chang SD. Image-guided stereotactic radiosurgery for treatment of spinal hemangioblastoma. Neurosurg Focus 2017; 42:E12. [DOI: 10.3171/2016.10.focus16361] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Abstract
OBJECTIVE
Stereotactic radiosurgery (SRS) has been an attractive treatment option for hemangioblastomas, especially for lesions that are surgically inaccessible and in patients with von Hippel-Lindau (VHL) disease and multiple lesions. Although there has been a multitude of studies examining the utility of SRS in intracranial hemangioblastomas, SRS has only recently been used for spinal hemangioblastomas due to technical limitations. The purpose of this study is to provide a long-term evaluation of the effectiveness of image-guided radiosurgery in halting tumor progression and providing symptomatic relief for spinal hemangioblastomas.
METHODS
Between 2001 and 2011, 46 spinal hemangioblastomas in 28 patients were treated using the CyberKnife image-guided radiosurgery system at the authors' institution. Fourteen of these patients also had VHL disease. The median age at treatment was 43.5 years (range 19–85 years). The mean prescription radiation dose to the tumor periphery was 21.6 Gy (range 15–35 Gy). The median tumor volume was 0.264 cm3 (range 0.025–70.9 cm3). Tumor response was evaluated on serial, contrast-enhanced CT and MR images. Clinical response was evaluated by clinical and imaging evaluation.
RESULTS
The mean follow-up for the cohort was 54.3 months. Radiographic follow-up was available for 19 patients with 34 tumors; 32 (94.1%) tumors were radiographically stable or displayed signs of regression. Actuarial control rates at 1, 3, and 5 years were 96.1%, 92.3%, and 92.3%, respectively. Clinical evaluation on follow-up was available for 13 patients with 16 tumors; 13 (81.2%) tumors in 10 patients had symptomatic improvement. No patient developed any complications related to radiosurgery.
CONCLUSIONS
Image-guided SRS is safe and effective for the primary treatment of spinal hemangioblastomas and is an attractive alternative to resection, especially for those with VHL disease.
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Affiliation(s)
| | | | | | | | | | | | | | - Scott G. Soltys
- 2Radiation Oncology, Stanford University School of Medicine, Stanford, California
| | - Iris C. Gibbs
- 2Radiation Oncology, Stanford University School of Medicine, Stanford, California
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Peyrl A, Frischer J, Hainfellner JA, Preusser M, Dieckmann K, Marosi C. Brain tumors - other treatment modalities. HANDBOOK OF CLINICAL NEUROLOGY 2017; 145:547-560. [PMID: 28987193 DOI: 10.1016/b978-0-12-802395-2.00034-1] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/07/2023]
Abstract
Management of tumors of the central nervous system is challenging for clinicians for various reasons, including complex diagnostic procedures, limited penetration of drugs into brain tissue, and the prerequisite to preserve brain function in any case of therapeutic intervention. Therapeutic success is dependent on the efforts, skills, and cooperation of involved specialists and disciplines. Knowledge and ability to apply adequate therapeutic modalities in an interdisciplinary approach in due time are crucial, necessitating coordination of diagnostic procedures and therapeutic interventions by means of multidisciplinary brain tumor boards. In this chapter we present in brief the essential current standards and future perspectives for therapy modalities that complement surgery of brain tumors.
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Affiliation(s)
- Andreas Peyrl
- Department of Pediatrics, Medical University of Vienna, Vienna, Austria
| | - Josa Frischer
- Department of Neurosurgery, Medical University of Vienna, Vienna, Austria; Comprehensive Cancer Center - Central Nervous System Tumors Unit (CCC-CNS), Medical University of Vienna, Vienna, Austria
| | - Johannes A Hainfellner
- Comprehensive Cancer Center - Central Nervous System Tumors Unit (CCC-CNS), Medical University of Vienna, Vienna, Austria; Institute of Neurology, Medical University of Vienna, Vienna, Austria.
| | - Matthias Preusser
- Comprehensive Cancer Center - Central Nervous System Tumors Unit (CCC-CNS), Medical University of Vienna, Vienna, Austria; Department of Medicine I, Medical University of Vienna, Vienna, Austria
| | - Karin Dieckmann
- Comprehensive Cancer Center - Central Nervous System Tumors Unit (CCC-CNS), Medical University of Vienna, Vienna, Austria; Department of Radiotherapy, Medical University of Vienna, Vienna, Austria
| | - Christine Marosi
- Comprehensive Cancer Center - Central Nervous System Tumors Unit (CCC-CNS), Medical University of Vienna, Vienna, Austria; Department of Medicine I, Medical University of Vienna, Vienna, Austria
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Laviv Y, Thomas A, Kasper EM. Hypervascular Lesions of the Cerebellopontine Angle: The Relevance of Angiography as a Diagnostic and Therapeutic Tool and the Role of Stereotactic Radiosurgery in Management. A Comprehensive Review. World Neurosurg 2016; 100:100-117. [PMID: 28049034 DOI: 10.1016/j.wneu.2016.12.091] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/03/2016] [Revised: 12/18/2016] [Accepted: 12/20/2016] [Indexed: 01/08/2023]
Abstract
BACKGROUND The cerebellopontine angle (CPA) is a narrowed skull base area containing important cranial nerves and vessels and bordering with eloquent areas of the posterior fossa. Tumors of the CPA are a heterogeneous group and can have extradural, intradural/extra-axial, or intra-axial origins. Their vascular supply changes depending on their anatomic origin. Symptomatic, large CPA tumors require surgical resection in order to prevent irreversible, severe neurological damages. However, its tight and strategical location make surgery in the CPA very challenging and require appropriate pre-surgical planning. Pre-surgical diagnosis is of great importance as it allows us to choose the optimal management for the particular patient. This is of further significance when encountering high-risk lesions such as hypervascular tumors. Neurosurgeons should utilize every available pre-surgical diagnostic modalities as well as neo-adjuvant treatments in order to reduce such risks. METHODS We review all reported cases of hypervascular lesions of the CPA and discuss the roles of angiography and stereotactic radiosurgery in their management. RESULTS Three lesions of the CPA can be considered as truly hypervascular: hemangioblastomas, hemangiopericytomas and paragangliomas. All lesions share many radiological features. However, each lesion has a different anatomical origin and hence, has a characteristic vascular supply. Pre-surgical angiography can be utilized as a diagnostic tool to narrow down the differential diagnosis of a vascular CPA lesion, based on the predominant supplying vessel. In addition, pre-surgical embolization at time of angiography will narrow the associated surgical risks. CONCLUSIONS Angiography is a crucial diagnostic and therapeutic tool, helping both in narrowing the presurgical differential diagnosis and in controlling intraoperative bleeding. Because of the high surgical risks associated with resection of vascular tumors in the CPA, noninvasive treatments, such as stereotactic radiosurgery, also may have a crucial role.
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Affiliation(s)
- Yosef Laviv
- Division of Neurosurgery, Department of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA.
| | - Ajith Thomas
- Division of Neurosurgery, Department of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA
| | - Ekkehard M Kasper
- Division of Neurosurgery, Department of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA
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Campero A, Ajler P, Fernandez J, Isolan G, Paiz M, Rivadeneira C. [Hemangioblastomas of the posterior fossa: Report of 16 cases and literature review]. Surg Neurol Int 2016; 7:S855-S860. [PMID: 27999708 PMCID: PMC5154206 DOI: 10.4103/2152-7806.194490] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2016] [Accepted: 08/06/2016] [Indexed: 11/04/2022] Open
Abstract
OBJECTIVE The aim of this study is to describe the results of 16 patients with posterior fossa hemangioblastoma, treated with microsurgical techniques. METHOD Between June 2005 and December 2015, 16 patients with posterior fossa hemangioblastoma were operated on, underwent microsurgical resection. The sex, age, imaging findings, symptoms, and postoperative results were analyzed. RESULTS Eleven patients were men and 5 were women. The average age of the patients was 44 years. The most common form was cystic with nodule (57%); in 31% of the cases the lesion was purely solid. One case (6%) showed a lesion purely cystic, and one case was solid-cystic (6%). The major presenting symptoms were headache and cerebellar syndrome (43%); in 25% of the cases the patients suffered intracranial hypertension syndrome. The total resection was achieved in all the cases; in one patient an embolization was performed before surgery. Regarding postoperative complications: two patients developed ataxia (improved after three months), 1 patient presented a CSF leak (improve with an external spinal drainage). In addition, one patient died because postoperative complications. CONCLUSION The major features in patients with posterior fossa hemangioblastoma are a cystic with nodule form, presenting symptoms of headache and cerebellar syndrome. The total resection is possible, with a low morbi-mortality rate.
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Affiliation(s)
- Alvaro Campero
- Servicio de Neurocirugía, Hospital Padilla, Tucumán, Argentina; Servicio de Neurocirugía, Sanatorio 9 de Julio, Tucumán, Argentina
| | - Pablo Ajler
- Servicio de Neurocirugía, Hospital Italiano de Buenos Aires, Buenos Aires, Argentina; Instituto Universitario del Hospital Italiano de Buenos Aires, Buenos Aires, Argentina
| | - Julio Fernandez
- Servicio de Neurocirugía, Hospital Padilla, Tucumán, Argentina
| | - Gustavo Isolan
- Departamento de Cirugía, División de Post Graduación, Universidad Federal de Río Grande del Sur, Porto Alegre, Brasil
| | - Martin Paiz
- Servicio de Neurocirugía, Hospital Padilla, Tucumán, Argentina
| | - Conrado Rivadeneira
- Servicio de Neurocirugía, Hospital Padilla, Tucumán, Argentina; Servicio de Neurocirugía, Sanatorio 9 de Julio, Tucumán, Argentina
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Silva D, Grabowski MM, Juthani R, Sharma M, Angelov L, Vogelbaum MA, Chao S, Suh J, Mohammadi A, Barnett GH. Gamma Knife radiosurgery for intracranial hemangioblastoma. J Clin Neurosci 2016; 31:147-51. [PMID: 27422585 DOI: 10.1016/j.jocn.2016.03.008] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2016] [Accepted: 03/08/2016] [Indexed: 11/25/2022]
Abstract
Gamma knife radiosurgery (GKRS) has become a treatment option for intracranial hemangioblastomas, especially in patients with poor clinical status and also high-risk surgical candidates. The objective of this study was to analyze clinical outcome and tumor control rates. Retrospective chart review revealed 12 patients with a total of 20 intracranial hemangioblastomas treated with GKRS from May 1998 until December 2014. Kaplan-Meier plots were used to calculate the actuarial local tumor control rates and rate of recurrence following GKRS. Univariate analysis, including log rank test and Wilcoxon test were used on the Kaplan-Meier plots to evaluate the predictors of tumor progression. Two-tailed p value of <0.05 was considered as significant. Median follow-up was 64months (2-184). Median tumor volume pre-GKRS was 946mm(3) (79-15970), while median tumor volume post-GKRS was 356mm(3) (30-5404). Complications were seen in two patients. Tumor control rates were 100% at 1year, 90% at 3years, and 85% at 5years, using the Kaplan-Meier method. There were no statistically significant univariate predictors of progression identified, although there was a trend towards successful tumor control in solid tumors (p=0.07). GKRS is an effective and safe option for treating intracranial hemangioblastoma with favorable tumor control rates.
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Affiliation(s)
- Danilo Silva
- Rose Ella Burkhardt Brain Tumor Center, Department of Neurosurgery and Radiation Oncology, Neurological Institute, Cleveland Clinic, OH 44124, USA.
| | - Mathew M Grabowski
- Rose Ella Burkhardt Brain Tumor Center, Department of Neurosurgery and Radiation Oncology, Neurological Institute, Cleveland Clinic, OH 44124, USA
| | - Rupa Juthani
- Rose Ella Burkhardt Brain Tumor Center, Department of Neurosurgery and Radiation Oncology, Neurological Institute, Cleveland Clinic, OH 44124, USA
| | - Mayur Sharma
- Rose Ella Burkhardt Brain Tumor Center, Department of Neurosurgery and Radiation Oncology, Neurological Institute, Cleveland Clinic, OH 44124, USA
| | - Lilyana Angelov
- Rose Ella Burkhardt Brain Tumor Center, Department of Neurosurgery and Radiation Oncology, Neurological Institute, Cleveland Clinic, OH 44124, USA
| | - Michael A Vogelbaum
- Rose Ella Burkhardt Brain Tumor Center, Department of Neurosurgery and Radiation Oncology, Neurological Institute, Cleveland Clinic, OH 44124, USA
| | - Samuel Chao
- Rose Ella Burkhardt Brain Tumor Center, Department of Neurosurgery and Radiation Oncology, Neurological Institute, Cleveland Clinic, OH 44124, USA
| | - John Suh
- Rose Ella Burkhardt Brain Tumor Center, Department of Neurosurgery and Radiation Oncology, Neurological Institute, Cleveland Clinic, OH 44124, USA
| | - Alireza Mohammadi
- Rose Ella Burkhardt Brain Tumor Center, Department of Neurosurgery and Radiation Oncology, Neurological Institute, Cleveland Clinic, OH 44124, USA
| | - Gene H Barnett
- Rose Ella Burkhardt Brain Tumor Center, Department of Neurosurgery and Radiation Oncology, Neurological Institute, Cleveland Clinic, OH 44124, USA
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Giammattei L, Messerer M, Aghakhani N, David P, Herbrecht A, Richard S, Parker F. Surgical resection of medulla oblongata hemangioblastomas: outcome and complications. Acta Neurochir (Wien) 2016; 158:1333-41. [PMID: 27185165 DOI: 10.1007/s00701-016-2834-0] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2016] [Accepted: 05/04/2016] [Indexed: 10/21/2022]
Abstract
OBJECT The purpose of this study was to analyze the surgical outcome and complications of a single-center series of medulla oblongata (MO) hemangioblastomas. METHODS We retrospectively reviewed the medical charts of all medulla oblongata hemangioblastomas operated on at our institution between 1996 and 2015. All patients had a pre- and postoperative MRI and a minimum follow-up of 6 months. Patients were scored according to the Karnofsky Performance Scale (KPS) and McCormick Scale at the moment of admission, discharge and the last follow-up. RESULTS Thirty-one surgical procedures were performed on 27 patients (16 females and 11 males). The mean age was 33 years, and 93 % of patients had von Hippel Lindau (VHL) disease. Three patients experienced very complicated postoperative courses, with one case ending in the death of the patient. Two patients required tracheostomy. According to McCormick's classification, 7 (23 %) of the 31 operations resulted in aggravation and 23 (74 %) in no change. Considering the seven patients with aggravation at discharge, four patients (60 %) returned to their preoperative status, one (14 %) improved but remained below his preoperative McCormick grade and two (29 %) did not improve. At last follow-up, KPS was ameliorated in 53 %, stable in 40 % and worsened in 7 % of cases. CONCLUSION Surgery of medulla oblongata hemangioblastomas is a challenging procedure characterized by an acceptable morbidity. Transient morbidity is not negligible even if the long-term outcome is in most cases favorable. A compromised neurological condition seems to be the best predictor of unfavorable outcome.
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Sharma M, Balasubramanian S, Silva D, Barnett GH, Mohammadi AM. Laser interstitial thermal therapy in the management of brain metastasis and radiation necrosis after radiosurgery: An overview. Expert Rev Neurother 2016; 16:223-32. [DOI: 10.1586/14737175.2016.1135736] [Citation(s) in RCA: 68] [Impact Index Per Article: 7.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/10/2023]
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Abstract
The etiologies of brain tumors are in the most cases unknown, but improvements in genetics and DNA screening have helped to identify a wide range of brain tumor predisposition disorders. In this review we are discussing some of the most common predisposition disorders, namely: neurofibromatosis type 1 and 2, schwannomatosis, rhabdoid tumor predisposition disorder, nevoid basal cell carcinoma syndrome (Gorlin), tuberous sclerosis complex, von Hippel-Lindau, Li-Fraumeni and Turcot syndromes. Recent findings from the GLIOGENE collaboration and the newly identified glioma causing gene POT1, will also be discussed. Genetics. We will describe these disorders from a genetic and clinical standpoint, focusing on the difference in clinical symptoms depending on the underlying gene or germline mutation. Central nervous system (CNS) tumors. Most of these disorders predispose the carriers to a wide range of symptoms. Herein, we will focus particularly on tumors affecting the CNS and discuss improvements of targeted therapy for the particular disorders.
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Affiliation(s)
- Gunnar Johansson
- Department of Radiation Sciences, Oncology, Umeå University, Umeå, Sweden
| | - Ulrika Andersson
- Department of Radiation Sciences, Oncology, Umeå University, Umeå, Sweden
| | - Beatrice Melin
- Department of Radiation Sciences, Oncology, Umeå University, Umeå, Sweden
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