TY - JOUR
T1 - Growth rates of genetically defined renal tumors
T2 - Implications for active surveillance and intervention
AU - Ball, Mark W.
AU - An, Julie Y.
AU - Gomella, Patrick T.
AU - Gautam, Rabindra
AU - Ricketts, Christopher J.
AU - Vocke, Cathy D.
AU - Schmidt, Laura S.
AU - Merino, Maria J.
AU - Srinivasan, Ramaprasad
AU - Malayeri, Ashkan A.
AU - Metwalli, Adam R.
AU - Linehan, W. Marston
N1 - Funding Information:
Supported by the Intramural Research Program of the National Institutes of Health (NIH), National Cancer Institute, Center for Cancer Research. Funded in part with federal funds from the Frederick National Laboratory for Cancer Research, NIH, under contract HHSN261200800001E. This research was made possible through the NIH Medical Research Scholars Program, a public-private partnership supported jointly by the NIH and contributions to the Foundation for the NIH from the Doris Duke Charitable Foundation (Grant No. 2014194), the American Association for Dental Research, the Colgate-Palmolive Company, Genentech, Elsevier, and other private donors.
Funding Information:
Supported by the Intramural Research Program of the National Institutes of Health (NIH), National Cancer Institute, Center for Cancer Research. Funded in part with federal funds from the Frederick National Laboratory for Cancer Research, NIH, under contract HHSN261200800001E. This research was made possible through the NIH Medical Research Scholars Program, a public-private partnership supported jointly by the NIH and contributions to the Foundation for the NIH from the Doris Duke Charitable Foundation (Grant No. 2014194), the American Association
Publisher Copyright:
Copyright © 2020 American Society of Clinical Oncology. All rights reserved.
PY - 2020/4/10
Y1 - 2020/4/10
N2 - PURPOSE Published series of growth rates of renal tumors on active surveillance largely consist of tumors without pathologic or genetic data. Growth kinetics of genetically defined renal tumors are not well known. Here, we evaluate the growth of genetically defined renal tumors and their association with patient clinical and genetic characteristics. PATIENTS AND METHODS We evaluated patients with an inherited kidney cancer susceptibility syndrome as a result of a pathologic germline alteration of VHL, MET, FLCN, or BAP1 with at least 1 solid renal mass managed with active surveillance at our institution. Tumor growth rates (GR) were calculated and patients were stratified by genetic alteration and other clinical and genetic factors to analyze differences in growth rates using linear regression and comparative statistics. RESULTS A total of 292 patients with 435 genetically defined tumors were identified, including 286 VHL-deficient, 91 FLCN-deficient, 52 MET-activated, and 6 BAP1-deficient tumors. There were significant differences in GRs when stratified by genetic alteration. BAP1-deficient tumors had the fastest median GR (0.6 cm/y; interquartile range [IQR], 0.57-0.68 cm/y), followed by VHL-deficient tumors (GR, 0.37 cm/y; IQR, 0.25-0.57 cm/y), FLCN-deficient tumors (GR, 0.10 cm/y; IQR, 0.04-0.24 cm/y), and tumors with MET activation (GR, 0.15 cm/y; IQR, 0.053-0.32 cm/y; P, .001). Tumors from the same patient had similar GRs. Younger age was independently associated with higher GR (P = .005). CONCLUSION In a cohort of genetically defined tumors, tumor growth rates varied in a clinically and statistically different manner according to genetic subtype. Rapid growth of BAP1-deficient tumors indicates that these patients should be managed with caution. The faster growth of tumors in younger patients may support more frequent imaging, whereas the slower growth of other tumors may support extended surveillance beyond annual imaging in some instances.
AB - PURPOSE Published series of growth rates of renal tumors on active surveillance largely consist of tumors without pathologic or genetic data. Growth kinetics of genetically defined renal tumors are not well known. Here, we evaluate the growth of genetically defined renal tumors and their association with patient clinical and genetic characteristics. PATIENTS AND METHODS We evaluated patients with an inherited kidney cancer susceptibility syndrome as a result of a pathologic germline alteration of VHL, MET, FLCN, or BAP1 with at least 1 solid renal mass managed with active surveillance at our institution. Tumor growth rates (GR) were calculated and patients were stratified by genetic alteration and other clinical and genetic factors to analyze differences in growth rates using linear regression and comparative statistics. RESULTS A total of 292 patients with 435 genetically defined tumors were identified, including 286 VHL-deficient, 91 FLCN-deficient, 52 MET-activated, and 6 BAP1-deficient tumors. There were significant differences in GRs when stratified by genetic alteration. BAP1-deficient tumors had the fastest median GR (0.6 cm/y; interquartile range [IQR], 0.57-0.68 cm/y), followed by VHL-deficient tumors (GR, 0.37 cm/y; IQR, 0.25-0.57 cm/y), FLCN-deficient tumors (GR, 0.10 cm/y; IQR, 0.04-0.24 cm/y), and tumors with MET activation (GR, 0.15 cm/y; IQR, 0.053-0.32 cm/y; P, .001). Tumors from the same patient had similar GRs. Younger age was independently associated with higher GR (P = .005). CONCLUSION In a cohort of genetically defined tumors, tumor growth rates varied in a clinically and statistically different manner according to genetic subtype. Rapid growth of BAP1-deficient tumors indicates that these patients should be managed with caution. The faster growth of tumors in younger patients may support more frequent imaging, whereas the slower growth of other tumors may support extended surveillance beyond annual imaging in some instances.
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U2 - 10.1200/JCO.19.02263
DO - 10.1200/JCO.19.02263
M3 - Article
C2 - 32083993
AN - SCOPUS:85083002980
SN - 0732-183X
VL - 38
SP - 1146
EP - 1153
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
IS - 11
ER -