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The number of metabolic features as a significant prognostic factor in patients with metastatic renal cell carcinoma.

ABSTRACT: The effect of metabolic characteristics on the prognosis of patients with metastatic renal cell carcinoma remains controversial. We investigated the associations between metabolic features of each individual and disease prognosis in patients with metastatic renal cell carcinoma. Data of 1,584 patients with metastatic renal cell carcinoma from a multi-institutional database were retrospectively analyzed. The entire cohort was stratified into three subgroups according to how many patients had abnormal metabolic features (hypertension, diabetes mellitus, and low body mass index). The Kaplan-Meier and Cox proportional analyses were performed to investigate the associations between abnormal metabolic features and disease prognosis. mThere were 465 subjects without any metabolic features, 995 with one or two, and 124 with three. When the survival outcomes were compared according to the number of metabolic features, patients with higher numbers of metabolic features had significantly shorter overall and cancer-specific survival than those with fewer metabolic features (all p values <0.05). The multivariate Cox analysis showed that the number of metabolic features was an independent predictor for shorter cancer-specific and overall survival (all p values < 0.05). When performing subgroup analysis according to the cellular type, significant results were only obtained among the clear cell subtype subgroup, with the association not being significant in the non-clear cell subtype cohort. Patients with more metabolic features had significantly worse survival outcomes than those with fewer metabolic features. However, the association was only statistically significant in patients with clear cell-type metastatic renal cell carcinoma.

SUBMITTER: Yuk HD

PROVIDER: S-EPMC7181597 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature

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The number of metabolic features as a significant prognostic factor in patients with metastatic renal cell carcinoma.

Yuk Hyeong Dong HD Hwang Eu Chang EC Park Jae Young JY Jeong Chang Wook CW Song Cheryn C Seo Seong Il SI Byun Seok-Soo SS Kwak Cheol C Hong Sung-Hoo SH Kang Minyong M Chung Jinsoo J Lee Hakmin H

Scientific reports 20200424 1

The effect of metabolic characteristics on the prognosis of patients with metastatic renal cell carcinoma remains controversial. We investigated the associations between metabolic features of each individual and disease prognosis in patients with metastatic renal cell carcinoma. Data of 1,584 patients with metastatic renal cell carcinoma from a multi-institutional database were retrospectively analyzed. The entire cohort was stratified into three subgroups according to how many patients had abno ...[more]

PMID: 32332797

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Project description:The purpose of the study was to identify a comprehensive prognostic system of pretreatment clinical parameters in 425 patients (pts) with metastatic renal-cell carcinoma treated with different subcutaneous (s.c.) recombinant cytokine-based home therapies in consecutive trials. Treatment consisted of (A) s.c. interferon-alpha 2a (INF-alpha), s.c. interleukin-2 (IL-2) (n=102 pts), (B) s.c. IFN-alpha 2a, s.c. IL-2, and i.v. 5-fluorouracil (5-FU) (n=235 pts) or (C) s.c. IFN-alpha 2a, s.c. IL-2, and i.v. 5-FU combined with p.o. 13-cis-retinoic acid (13cRA) (n=88 pts). Kaplan-Meier survival analysis, log-rank statistics, and Cox regression analysis were employed to identify risk factors and to create a multiple risk factor model. The following pretreatment risk factors were identified by univariate analysis: (1) three and more metastatic sites, (2) presence of liver, lymph node or bone metastases, (3) neutrophil count > or = 6500 cells microl(-1), (4) serum lactate dehydrogenase level (LDH) > or = 220 U l(-1), and (5) serum C-reactive protein level (CRP) > or = 11 mg l(-1). Cox regression analysis with forward stepwise variable selection identified neutrophil count as the major prognostic factor (hazard ratio=1.9, P<0.001), while serum levels of LDH and CRP, time between diagnosis of tumour and onset of metastatic disease, number of metastatic sites, and bone metastases were significant but somewhat less important prognostic variables within the multiple risk factor model (hazard ratio < or = 1.5). Patients were assigned to one of the three risk groups according to cumulative risk defined as the sum of simplified risk s.c.ores for six pretreatment variables. Low-, intermediate-, and high-risk patients achieved a median overall survival of 32+ months (95% CI 24, 43; 5-year survival of 27%), 18+ months (95% CI 15, 20; 5-year survival of 11%), and 8+ months (95% CI 6, 10; 5-year survival of 5%), respectively. These prognostic categories are helpful both in individual patient care and in the assessment of patients entering prospective clinical trials.

Project description:BackgroundResponse remains an important endpoint in clinical cancer trials. However, the prognostic utility of best tumor response in metastatic renal cell carcinoma (mRCC) remains vague.ObjectiveTo define the prognostic relevance of the depth of remission in mRCC.Design, setting, and participantsPooled data from the Pfizer database for 2749 patients from phase 2 and 3 clinical trials in mRCC were analyzed. Tumor shrinkage was categorized according to the best percentage change in the sum of the largest diameter of target lesions. Outcome was computed using Kaplan-Meier curves and correlation was assessed via Cox regression, including a 6-mo landmark.InterventionSunitinib, sorafenib, axitinib, temsirolimus, or temsirolimus and interferon-α.Outcome measurements and statistical analysisCategorized tumor shrinkage, overall survival (OS), progression free survival (PFS).Results and limitationsMajor tumor shrinkage of 60% or more occurred in approximately 10% of patients and was associated with median OS of 54.5 mo. OS expectations steadily decreased with depth of remission (26.4, 16.6, 10.4, and 7.3 mo). The association was maintained when stratified by type of therapy, line of therapy, and performance status. Cox proportional regression analyses for the 6-mo landmark confirmed the prognostic relevance of major tumor shrinkage (hazard ratio 0.29, 95% confidence interval 0.22-0.39; p<0.001). The major limitation of our study is the variability of imaging intervals among studies.ConclusionsThis is the first and largest analysis of best tumor response in mRCC. We demonstrate that depth of remission is an independent prognostic factor in mRCC.Patient summaryIt remains unknown whether tumor shrinkage during therapy is needed to achieve clinical activity in metastatic renal cell carcinoma. Our analysis shows that the magnitude of tumor shrinkage correlates with better survival in patients. This observation may be used as a clinical research tool in future trials.Trial registrationNCT00054886, NCT00077974, NCT00267748, NCT00338884, NCT00137423, NCT00083889, NCT00065468, NCT00678392.

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The number of metabolic features as a significant prognostic factor in patients with metastatic renal cell carcinoma.

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The number of metabolic features as a significant prognostic factor in patients with metastatic renal cell carcinoma.

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