Abstract: PD59-03
Sources of Funding: none

Introduction

Renal cell carcinoma develops in 25-60% of patients von Hippel-Lindau (VHL), which is characterized by germline mutations in the VHL gene. The paradigm for treating renal tumors in VHL includes active surveillance for lesions less than 3 cm, and surgical resection for lesions greater than 3 cm. Knowledge of growth rates for renal lesions in VHL guide surveillance schedules. While the risk of developing RCC is related to VHL genotype, it is unknown if VHL genotype can influence tumor growth rate. We sought to characterize growth rate for VHL-associated renal tumors and to determine if the type of germline mutation in VHL influences tumor growth kinetics._x000D_

Methods

Patients with solid, enhancing renal tumors with at least 3 cross sectional imaging studies and known germline mutation status were retrospectively reviewed. In patients with multiple index lesions, all lesions were analyzed. Renal tumor size was measured as the largest single-dimension diameter. Growth rates were calculated using linear regression. Germline mutations were categorized into missense, partial deletion, frameshift, deletion, splice donor, amino acid insertion, and splice acceptor. The effect of germline mutation type on renal tumor kinetics was assessed with the Wilcoxon-ranksum or Kruskall Wallis tests. _x000D_

Results

A total of 246 tumors in 161 patients and 1341 time-point measurements were included for analysis. Median growth rate for the entire cohort was 3.5 mm (interquartile range 2.4-5.1 mm). Median growth rates were similar for all mutation categories: 3.4 mm for missense (n=111), 3.5 mm for partial deletion (n=71), 3.2 mm for nonsense (n=28), 4.5 mm for frameshift (n=16), 2.5 mm for deletion (n=8), 3.4 mm for splice donor (n=4), 3.9 mm for amino acid insertion (n=3), and 4.9 mm for splice acceptor (n=3) (Figure 1). There was no difference in growth rates between missense and non-missense tumors (p=0.1) _x000D_

Conclusions

The majority of VHL-associated renal tumors have a growth rate of less than 5 mm per year. Where no association was identified between germline mutation type and single-dimension VHL renal tumor growth kinetics, further study is needed to determine the impact of somatic mutations on tumor development and growth kinetics. _x000D_

Funding

none