Does Obesity Influence the Prognosis of Metastatic Renal Cell Carcinoma in Patients Treated with Vascular Endothelial Growth Factor–Targeted Therapy?

Steffens, Sandra; Grünwald, Viktor; Ringe, Kristina; Seidel, Christoph; Eggers, H.; Schrader, Mark; Wacker, Frank; Kuczyk, Markus A.; Schrader, Andres Jan

doi:10.1634/theoncologist.2011-0213

Cited by 79 publications

(96 citation statements)

References 13 publications

(14 reference statements)

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“…While one study showed that higher than median VFA values were significantly associated with a shorter progression-free survival and OS, the other demonstrated an opposite correlation. 14,15 Finally, greater perirenal fat distance, a proxy of visceral fat, was a significant predictor of ccRCC histopathology in clinical T1a tumours. 29 In the current study, while different obesity measures were significantly associated with hypertension and diabetes, we did not find statistically significant associations between SFA, VFA or VFA% and grade, stage or OS.…”

Section: Discussionmentioning

confidence: 89%

“…4,12 While the reported effects of BMI on RCC have been uniform, reports concerning the effect of visceral adiposity on the pathological and clinical outcomes of RCC are inconsistent. [13][14][15][16][17] Moreover, most previous studies evaluating the predictive value of visceral fat in non-metastatic RCC were conducted among Asian populations, which have relatively lower BMIs than Western populations, and may display a different relationship between BMI and body fat. 18,19 The aim of the current study was to evaluate whether visceral fat area (VFA) and subcutaneous fat area (SFA) were related to tumour characteristics and treatment outcomes in a group of surgically treated, non-metastatic, clear cell RCC (ccRCC) patients from the United States.…”

Section: Introductionmentioning

confidence: 99%

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Association between visceral and subcutaneous adiposity and clinicopathological outcomes in non-metastatic clear cell renal cell carcinoma

Hakimi

Zabor

Bury

et al. 2014

CUAJ

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Introduction: Visceral adiposity has been inconsistently associated with clinicopathologic features and outcomes of clear cell renal cell carcinoma (ccRCC); however, most studies were conducted in non-Western populations. We evaluated the associations between visceral and subcutaneous adiposity and clinicopathological characteristics of non-metastatic ccRCC patients in a Western population. Methods: The medical records of 220 surgically treated ccRCC patients with documented preoperative body mass index (BMI) and computed tomography (CT) scans were retrospectively reviewed. Nineteen patients with stage IV disease were excluded. Visceral (VFA) and subcutaneous fat area (SFA) were computed from preoperative CT scans. Correlations between obesity measures were assessed with Pearson correlation. Associations between obesity measures and pathologic features were evaluated using logistic regression models adjusted for sex. Overall survival (OS) probabilities were estimated using Cox regression analysis. The log-rank test was used for group comparisons. Results: The study cohort comprised 150 men and 51 women. Women had higher SFA (p = 0.01) but lower VFA (p < 0.001) than men. BMI was highly correlated with SFA (r = 0.804) and moderately correlated with VFA (r = 0.542). SFA and VFA were weakly correlated (r = 0.367). An increased BMI was associated with a better OS (p = 0.028). When adjusting for sex, neither SFA nor VFA was significantly associated with tumour grade, stage, or OS. Conclusions: Consistent with prior reports, our study suggests that increased BMI is associated with a better OS for patient with nonmetastatic ccRCC. Despite the high correlation between SFA and BMI, neither SFA nor VFA were significantly associated with tumour stage, grade, or OS in the current study; however, further studies in larger cohorts are required to validate this finding.

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Section: Discussionmentioning

confidence: 89%

Section: Introductionmentioning

confidence: 99%

Association between visceral and subcutaneous adiposity and clinicopathological outcomes in non-metastatic clear cell renal cell carcinoma

Hakimi

Zabor

Bury

et al. 2014

CUAJ

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“…Excess adiposity is associated with increased circulating levels of vascular endothelial growth factor, 46 a key regulator of tumor angiogenesis and the main target for bevacizumab antibody therapy; hence, there is a biologic plausibility that obesity might be a potential predictive biomarker in this setting. This has been tested in the settings of metastatic colorectal cancer 47,48 ; metastatic renal cell carcinoma 49,50 ; and advanced ovarian cancer 51 (listed in Table 3). Several of these studies were retrospective, had small sample sizes, lacked controls of conventional treatment arms, and were underpowered to perform tests for interaction; not unexpectedly, the findings are inconsistent.…”

Section: Obesity As a Treatment Effect Modifiermentioning

confidence: 99%

How to Manage the Obese Patient With Cancer

Renehan

Harvie

Cutress

et al. 2016

JCO

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) is common among patients with cancer. We reviewed management issues in the obese patient with cancer, focusing on how obesity influences treatment selection (including chemotherapy dosing), affects chemotherapy toxicity and surgical complications, and might be a treatment effect modifier. MethodsThe majority of evidence is drawn from observational studies and secondary analyses of trial data, typically analyzed in N 3 3 BMI categories (normal weight, overweight, and obese) matrix structures. We propose a methodological framework for interpretation focusing on sample size and composition, nonlinearity, and unmeasured confounding. ResultsThere is a common perception that obesity is associated with increased treatment-related toxicity. Accordingly, cytotoxic chemotherapy dose reduction is common in patients with elevated BMI. Contrary to this, there is some evidence that full dosing in obese patients does not result in increased toxicity. However, these data are from a limited number of regimens, and fail to fully capture cytotoxic drug pharmacodynamics and pharmacokinetic variability in obese patients. Among patients undergoing surgery, there is evidence that elevated BMI is associated with increased perioperative mortality and increased rates of infectious complications. A novel finding is that these relationships hold after surgery for malignancy, but not for benign indications. There are biologic plausibilities that obesity might be an effect modifier of treatment, but supporting evidence from clinical studies is inconsistent. ConclusionIn line with the ASCO 2012 guidelines, chemotherapy dosing is probably best performed using actual body weight in obese patients. However, specific regimens known to be associated with increased toxicity in this group should be used with caution. There is no guidance on dose for obese patients treated with biologic agents. Currently, there are no specific recommendations for the surgical management of the obese patient with cancer.

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“…However, the lack of effective prognostic prediction markers to stratify the patients remains a major challenge to establish an optimal personalized treatment paradigm of using these antiangiogenic agents to date. In a continuous effort to identify more effective prognostic markers, 'adiposity' has recently attracted research interest as a potential clinical biomarker to evaluate the efficacy of applying VEGF-targeted antiangiogenic therapy to treat a variety of cancers, including colon cancer (7,19), renal cell carcinoma (20,21) and ovarian cancer (9). However, previous studies generated somehow conflicting results (7,19,20,21).…”

Section: Discussionmentioning

confidence: 99%

“…In a continuous effort to identify more effective prognostic markers, 'adiposity' has recently attracted research interest as a potential clinical biomarker to evaluate the efficacy of applying VEGF-targeted antiangiogenic therapy to treat a variety of cancers, including colon cancer (7,19), renal cell carcinoma (20,21) and ovarian cancer (9). However, previous studies generated somehow conflicting results (7,19,20,21). In the present study, a CAD approach was developed for the first time to quantitatively extract adiposity-related image features and to demonstrate the feasibility of applying multivariate data analysis models to stratify EOC patients with and without potential clinical benefit by receiving maintenance bevacizumab-based chemotherapy.…”

Section: Discussionmentioning

confidence: 99%

Quantitative measurement of adiposity using CT images to predict the benefit of bevacizumab-based chemotherapy in epithelial ovarian cancer patients

et al. 2016

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Abstract. The present study aims to quantitatively measure adiposity-related image features and to test the feasibility of applying multivariate statistical data analysis-based prediction models to generate a novel clinical marker and predict the benefit of epithelial ovarian cancer (EOC) patients with and without maintenance bevacizumab-based chemotherapy. A dataset involving computed tomography (CT) images acquired from 59 patients diagnosed with advanced EOC was retrospectively collected. Among them, 32 patients received maintenance bevacizumab following primary chemotherapy, while 27 did not. A computer-aided detection scheme was developed to automatically segment visceral and subcutaneous fat areas depicted on CT images of abdominal sections, and 7 adiposity-related image features were computed. Upon combining these features with the measured body mass index, multivariate data analyses were performed using three statistical models (multiple linear, logistic and Cox proportional hazards regressions) to analyze the association between the model-generated prediction results and the treatment outcome, including progression-free survival (PFS) and overall survival (OS) of the patients. The results demonstrated that applying all three prediction models yielded a significant association between the adiposity-related image features and patients' PFS or OS in the group of the patients who received maintenance bevacizumab (P<0.010), while there was no significant difference when these prediction models were applied to predict both PFS and OS in the group of patients that did not receive maintenance bevacizumab. Therefore, the present study demonstrated that the use of a quantitative adiposity-related image feature-based statistical model may generate a novel clinical marker to predict who will benefit among EOC patients receiving maintenance bevacizumab-based chemotherapy.

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Does Obesity Influence the Prognosis of Metastatic Renal Cell Carcinoma in Patients Treated with Vascular Endothelial Growth Factor–Targeted Therapy?

Cited by 79 publications

References 13 publications

Association between visceral and subcutaneous adiposity and clinicopathological outcomes in non-metastatic clear cell renal cell carcinoma

Association between visceral and subcutaneous adiposity and clinicopathological outcomes in non-metastatic clear cell renal cell carcinoma

How to Manage the Obese Patient With Cancer

Quantitative measurement of adiposity using CT images to predict the benefit of bevacizumab-based chemotherapy in epithelial ovarian cancer patients

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