br The findings from our study are in
The findings from our study are in sharp Cyclophosphamide to those reported by the two cooperative group trials that reported decrease in survival
associated with increased BMI [12,15]. The cause for this difference is unclear. In the analysis by Modesitt et al. of 5 Gynecologic Oncology Group trial participants who received doxorubicin and cisplatin, the authors suggest that dose capping may have been responsible for decreased survival (approximately 46% of patients with body surface area greater than 2 m2 had capping of doxorubicin, cisplatin or both). However, in that analysis dose capping was not associated with worse prognosis (HR 1.46, p = 0.13) . In comparison to the study by Billingsley et al. that was restricted to Type II cancers and found no asso-ciation with BMI and mortality for Type II endometrial cancer survivors, we found a protective effect in obese patients with non-endometrioid histology and Stage 3 and 4 disease, which may be explained by an increased ability to tolerate adjuvant therapy or better pretreatment performance index. Our study population differed greatly from the patients enrolled in the Gynecologic Oncology Group studies in that only 30% of patients in our population self-identified as white and non-Hispanic. Only 30% of patients in the Gynecologic Oncology Group study identified as non-white, Hispanic, or other. Despite the finding that obesity was associated with improved survival in the sub-group of women with non-endometrioid cancers, and that more black women in our study were in higher body mass index categories then women of other races there was not an association between improved or worsened survival for black women in multivariable modeling in our study. Additionally, in our study we accounted for metformin and statin, which were significantly associated with decreased hazard of death and were not included in the previous studies.
Our data are similar to those of Jeong et al. in that obesity appeared protective until multivariable accounting for confounding factors, most notably age at diagnosis . Mustedt et al. reported that obesity did not adversely affect survival as accounted for by younger age and less advanced disease at time of diagnosis . Similarly, Anderson et al. con-cluded that obesity positively affects survival from endometrial cancer by the diagnosis of less aggressive disease in obese patients . Obesity has a role in carcinogenesis at an earlier age which must be accounted for in studies of the relationship of obesity to cancer survival.
Shortcomings of our study include the data abstraction from retro-spective chart review.
Additionally, patients' weight loss or weight gain could not be accounted for as BMI was recorded at time of diagnosis and not followed longitudinally through survivorship. Medication utilization was subject to bias as presented in the medical record and adherence through phar-macy records was not assessed, and chemotherapy dosing was at the discretion of the attending physicians and not subject to universal capping.
In conclusion, the main effect of high BMI in both endometrioid and non-endometrioid was diagnosis of endometrial cancer at a younger age. These data also suggest that important factors associated with en-dometrial cancer survival in both endometrioid and non-endometrioid subgroups may be medications associated with metabolic diseases including metformin and statins. Future research is needed to under-stand if obese women with endometrial cancer may benefit from antihyperlipidemic or antihyperglycemic therapy. It is unclear as to why our data differ from patients enrolled in Gynecologic Oncology Group cooperative group trials. While the most striking difference between our population and the women who participated in the Gyne-cologic Oncology Group cooperative group trial was race, race was not an independent factor associated with survival in our cohort, and it was not independently associated with high risk features. Further inves-tigation of genetic composition of tumors and the role of metabolic pathways may help us to better understand the relationship of obesity and race in endometrial cancers. Additionally, and the role of chemo-therapy dose capping is also undetermined in this population and in obese cancer patients.
Supplementary data to this article can be found online at https://doi.
Authors have no conflicts of interest to report
All authors contributed equally to the research and writing of the manuscript. Dr. Van Arsdale provided statistics and contributed signifi-cantly to the methods, results and discussion sections. Dr. Miller pro-vided significant contribution to the abstract, introduction, discussion
and results section. Dr. Kuo provided significant contribution to the dis-cussion and provided significant editing. Dr. Isani provided significant contribution to the introduction and extensive edits. Ms. Sanchez pro-vided the data gathering and aided with long-term follow up results. Dr. Nevadunsky served as senior author and contributed significantly to the entire manuscript.