Abstract
The purpose of this study was to evaluate the effect of obesity and obesity-associated factors on the outcomes of patients with cervical cancer. Outcomes were evaluated in 591 patients with FIGO Ib to IV cervical cancer treated uniformly with definitive radiation. Patients were stratified into 3 groups based upon pretreatment Body Mass Index (BMI): A ≤ 18.5; B 18.6 – 34.9; and C ≥ 35. The 5-year freedom from failure rates were 58, 59, and 73% for BMI groups A, B, and C (p = 0.01). Overall survival rates were 50, 59, and 68%, respectively (p = 0.02). High expression of phosphorylated AKT (pAKT) was associated with poor outcomes only in non-obese patients. Obese patients with PI3K pathway mutant tumors had a trend toward favorable outcomes, while a similar effect was not observed in non-obese patients. Compared to similar tumors from non-obese hosts, PIK3CA and PTEN mutant tumors from obese patients failed to express high levels of phosphorylated AKT and its downstream targets. These results show that patients with obesity at the time of diagnosis of cervical cancer exhibit improved outcomes after radiation. PI3K/AKT pathway mutations are common in obese patients, but are not associated with activation of AKT signaling.
Highlights
Increasing body mass index (BMI) has been associated with increased cancer-related mortality
There were no significant differences in the traditional patient- and tumor-related prognostic factors of age, tumor stage, pretreatment 18F-fluoro-deoxy-glucose (FDG) positron emission tomography (PET) lymph node (LN) status and histology relative to the patient’s Body Mass Index (BMI)
We have previously reported that cervical tumor FDG uptake quantified by Standardized Uptake Value (SUV) on pretreatment FDGpositron emission tomography (PET) scans is associated with poor prognosis [4]
Summary
Increasing body mass index (BMI) has been associated with increased cancer-related mortality. Xu and colleagues reported results from the Cancer Genome Atlas (TCGA) showing lower mortality in cervical cancer patients with higher BMI values [3]. The analysis by Xu using TCGA data demonstrated lower mortality in cervical cancer patients with higher BMI values, these patients were treated with a variety of techniques and outcome data was not prospectively collected. The aim of the current study was to use a well-annotated clinical database to evaluate the association of obesity and cervix cancer patient outcomes after uniform treatment with curative intent radiation. A prospectively collected institutional tumor bank was used to determine whether obesity associated factors (metformin, insulin, and PI3K/AKT signaling) were associated with outcomes in the context of definitive radiation treatment
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