Perirenal Fat Thickness Significantly Associated with Prognosis of Metastatic Renal Cell Cancer Patients Receiving Anti-VEGF Therapy

Kang Ning; Zhen Li; Huiming Liu; Xi Tian; Jun Wang; Yi Wu; Longbin Xiong; Xiangpeng Zou; Yulu Peng; Zhaohui Zhou; Fangjian Zhou; Chunping Yu; Junhang Luo; Hailiang Zhang; Pei Dong; Zhiling Zhang

doi:10.3390/nu14163388

Perirenal Fat Thickness Significantly Associated with Prognosis of Metastatic Renal Cell Cancer Patients Receiving Anti-VEGF Therapy

Nutrients. 2022 Aug 18;14(16):3388. doi: 10.3390/nu14163388.

Authors

Kang Ning^{1

2}, Zhen Li^{1

2}, Huiming Liu^{2

3}, Xi Tian⁴, Jun Wang^{1

2}, Yi Wu⁵, Longbin Xiong^{1

2}, Xiangpeng Zou^{1

2}, Yulu Peng^{1

2}, Zhaohui Zhou^{1

2}, Fangjian Zhou^{1

2}, Chunping Yu^{1

2}, Junhang Luo⁶, Hailiang Zhang⁴, Pei Dong^{1

2}, Zhiling Zhang^{1

2}

Affiliations

¹ Department of Urology, Sun Yat-sen University Cancer Center, Guangzhou 510080, China.
² State Key Laboratory of Oncology in Southern China, Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, China.
³ Department of Medical Imaging, Sun Yat-sen University Cancer Center, Guangzhou 510080, China.
⁴ Department of Urology, Fudan University Shanghai Cancer Center, Shanghai 201102, China.
⁵ State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou 510080, China.
⁶ Department of Urology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China.

Abstract

Although high body mass index (BMI) was reported to associate with a better prognosis for metastatic renal cell cancer (mRCC) patients receiving anti-vascular endothelial growth factor (anti-VEGF) therapy, it is an imperfect proxy for the body composition, especially in Asian patients with a lower BMI. The role of visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), and perirenal fat thickness (PRFT) in mRCC patients was still unknown. Therefore, a multicenter retrospective study of 358 Chinese mRCC patients receiving anti-VEGF therapy was conducted and their body composition was measured via computed tomography. We parameterized VAT, SAT and PRFT according to their median value and BMI according to Chinese criteria (overweight: BMI ≥ 24). We found VAT, SAT, and PRFT (all p < 0.05) but not BMI, significantly associated with overall survival (OS) and progression-free survival (PFS). Multivariate Cox analysis identified PRFT was the independent predictor of OS and PFS, and IMDC expanded with PRFT showed the highest C-index in predicting OS (OS:0.71) compared with VAT, SAT, and BMI. PRFT could increase the area under the curve of the traditional International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) model in OS (70.54% increase to 74.71%) and PFS (72.22% increase to 75.03%). PRFT was introduced to improve the IMDC model and PRFT-modified IMDC demonstrated higher AIC in predicting OS and PFS compared with the traditional IMDC model. Gene sequencing analysis (n = 6) revealed that patients with high PRFT had increased angiogenesis gene signatures (NES = 1.46, p = 0.04) which might explain why better drug response to anti-VEGF therapy in mRCC patients with high PRFT. The main limitation is retrospective design. This study suggests body composition, especially PRFT, is significantly associated with prognosis in Chinese mRCC patients receiving anti-VEGF therapy. PRFT-modified IMDC model proposed in this study has better clinical predictive value.

Keywords: adipose tissue; anti-VEGF therapy; body composition; prognosis; renal cell carcinoma.

Publication types

Multicenter Study

MeSH terms

Angiogenesis Inhibitors / therapeutic use
Carcinoma, Renal Cell* / drug therapy
Humans
Intra-Abdominal Fat / diagnostic imaging
Intra-Abdominal Fat / pathology
Kidney Neoplasms* / diagnostic imaging
Kidney Neoplasms* / drug therapy
Prognosis
Retrospective Studies

Substances

Angiogenesis Inhibitors

Grants and funding

This study was supported by the National Natural Science Foundation of China (No. 81972382 and 81872091), the National Key R&D Program of China (No. 2017YFC1309001), Fundamental Research Funds for Central Universities, Sun Yat-sun University (No. 19ykzd46) and the Natural Science Foundation for Distinguished Young Scholars of Guangdong Province (No. 2021B1515020077).