Growth of Hemangioblastomas in von Hippel-Lindau Disease Demonstrates Power-law Scaling of Complex Systems. (16th November 2020)

• Record Type: Journal Article
• Authors: Tong, Ai P; Pomeraniec, Isaac J; Mastorakos, Panagiotis; Chittiboina, Prashant; Lonser, Russell R; Zaghloul, Kareem A
• Is Part Of: Neurosurgery. Volume 67(2010)Supplement 1
• Publication Date: 2020-11-16
• Subjects: Nervous system -- Surgery -- Periodicals; 617.48005
• DOI: 10.1093/neuros/nyaa447_868
• Languages: English
• ISSNs: 0148-396X

Abstract

Abstract: INTRODUCTION: Patients with von Hippel-Lindau (VHL) disease suffer from a germline mutation that portends the shortest life expectancy of all tumor predisposition syndromes. These patients typically develop multiple symptomatic hemangioblastomas throughout the central nervous system that lead to numerous surgeries and require rigorous long-term interdisciplinary surveillance. Prior modeling suggests tumor growth depends on cell proliferation in the periphery that is fractal. Whether growth of VHL hemangioblastomas occur in a similar manner is unknown and could help reveal growth mechanisms to target for clinical therapy. METHODS: Patients with VHL and hemangioblastomas enrolled in a natural history protocol at the National Institutes of Health were included for analysis. 208 patients with 514 total tumors were followed over a median of 40 months. Relative growth rates of solid hemangioblastomas (170 of cerebellum, 197 of spine) were analyzed for follow-up intervals of five to seven months since presentation for a total of 1628 and 1592 measurements, respectively. Power-law was assessed with maximum-likelihood estimation method with permutation. Modified Kolmogorov-Smirnov testing assessed for significance. This analysis was repeated for cystic hemangioblastomas (55 of cerebellum, 36 of spine) with 553 and 440 measurements, respectively. RESULTS: Mean tumor volumes of the cerebellum and spine were 156 (range 10 - 14, 453) mm 3 and 277 (range 10 - 15, 309) mm 3, respectively. Growth patterns of solid tumors of the spine but not of the cerebellum exhibited power-law scaling. Cystic hemangioblastomas of both the cerebellum and spine demonstrated power-law scaling as the tumors grew more than 29.6% and 6.5% over six months, respectively. CONCLUSION: Preliminary findings suggest that growth patterns of cystic hemangioblastomas in both the cerebellum and spine follow a power-law scale seen in complex systems. This scaling may help clarify treatment targets for VHL hemangioblastomas. Further comparison of cystic and solid tumors throughout the brain and spinal cord with symptom profile is ongoing and will further elucidate the appropriate role and timing of surgical intervention and serial follow up.