Impact of Hyperglycemia in Patients With Cervical Cancer Treated With Definitive Chemoradiation on Overall Survival and Locoregional Control

Impact of Hyperglycemia in Patients With Cervical Cancer Treated With Definitive Chemoradiation on Overall Survival and Locoregional Control

Volume 93  Number 3S  Supplement 2015 were identified. Surgical, pathological, adjuvant therapy, and recurrence and mortality data were collected. U...

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Volume 93  Number 3S  Supplement 2015 were identified. Surgical, pathological, adjuvant therapy, and recurrence and mortality data were collected. Univariate log-rank analyses and Cox regression multivariate analyses (MVA) were performed to identify factors associated with RFS and OS. Results: In the PL EC cohort, median RFS and OS were 112 and 129.8 months, respectively. Endometrioid histology was present in 66% of patients. Adjuvant treatment was CT only in 21%, RT only in 25%, and CRT in 48%; RT included external beam to the pelvis in 96% of patients. There was no significant difference in adjuvant treatment according to substage (ANOVA P Z .13). Age, grade, histology, substage, and adjuvant treatment were significantly associated with RFS and OS. In terms of RFS, PL patients receiving RT only had equivalent RFS (median 122 months, 5y RFS 59%) compared to CRT (median 122 months, 5y RFS 65%), P Z .48. Patients receiving CT only fared worse (median 30 months, 5y RFS 42%, P Z .06 relative to RT and < .01 relative to CRT). Adjusting for age, tumor grade, nonendometrioid histology, and substage on MVA, there was no significant difference in RFS for RT and CT alone (P Z .052), but CRT retained significantly improved RFS relative to CT alone (HR for recurrence 0.34, P < .01). In terms of OS, PL patients receiving RT only or CRT had improved OS (median 134 months, 5y OS 71%, and median 104 months, 5y OS 75%, respectively) compared to CT only (median 80 months, 5y OS 54%), P Z .01 and .03, respectively. Adjusting for age, tumor grade, nonendometrioid histology, and substage on MVA, both RT only and CRT retained association with improved OS relative to CT alone (HR for death, 0.43, P Z .01, and 0.39, P < .01, respectively). No significant difference was noted on MVA between RT alone and CRT Conclusion: For comprehensively surgically staged PL stage III EC in this series, treatment regimens incorporating RT are associated with improved outcome. RT alone appears to be at least equivalent to CT alone for RFS, and both RT alone and CRT are associated with improved OS relative to CT alone. As such, RT is an essential component in the management of stage III PL EC, and should not be omitted if optimal outcome is desired. Author Disclosure: K.V. Albuquerque: None. M.R. Folkert: None. J.S. Mayadev: None. M. Liotta: None. C. Nagel: None. P.R. Sevak: None. M.M. Harkenrider: None. J. Lea: None. R. Hanna: None. W. Small: None. D.S. Miller: None. R.K. Potkul: None. M.A. Elshaikh: None.

24 Impact of Hyperglycemia in Patients With Cervical Cancer Treated With Definitive Chemoradiation on Overall Survival and Locoregional Control J. Gross,1 E.D. Donnelly,2 J.B. Strauss,2 I. Helenowksi,3 J. Lurain,3 E. Berry,3 and N. Neubauer3; 1Northwestern University, Chicago, IL, 2 Northwestern University Robert H. Lurie Comprehensive Cancer Center, Chicago, IL, 3Feinberg School of Medicine, Northwestern University, Chicago, IL Purpose/Objective(s): The Warburg Effect describes the unique characteristic of cancer cells to utilize glucose for metabolism by glycolysis conferring a proliferative advantage over normal cells. Conditions of hyperglycemia may lead to cancer cell proliferation, avoidance of apoptosis, induction of cell invasiveness, and migration leading to metastasis. This study reports the influence of hyperglycemia on overall survival (OS), progression-free survival (PFS), and locoregional control (LRC) in patients receiving chemoradiation therapy (CRT) for cervical cancer. Materials/Methods: We reviewed the records of patients with stage IB1 to IVB cervical cancer who were treated at our institution between January 1, 2000, and December 31, 2009. Eligible patients underwent CRT including low-dose-rate brachytherapy. Hyperglycemia was defined as random blood glucose 110 g/dL and was averaged from each blood draw from each time period: diagnosis to the start of definitive

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treatment, during treatment, and after treatment. Patient and treatment characteristics as well as treatment outcomes (OS, PFS, and LRC) were reviewed and reported based on glycemic status. Patient tumor samples were analyzed for the expression of GLUT1, HIF-1 alpha, and MET genes, and an H-score was assigned. Results: A total of 84 patients with cervical cancer that met all inclusion criteria were identified. The median age was 48 years (range, 29 to 81 years), consisting of International Federation of Gynecology and Obstetrics stages I, II, III, and IV (27.4%, 48.8%, 14.3%, and 9.5%, respectively). The proportion of patients with hyperglycemia before, during, and after definitive treatment was 27.4%, 40.5%, and 31%, respectively. The median follow-up was 38.5 months (mean 52.2, range 3 to 160 months). The 2- and 5-year OS for all patients were 81.9% and 69.8%, respectively. Patients with hyperglycemia after treatment had significantly worse 2-year LRC compared to patients with normal glycemic status (67.1% versus 90.6%, P Z .02), and had a nonsignificant trend toward worse 5-year OS (76.8% versus 55.7%, P Z .08). Posttreatment hyperglycemia was associated with higher median MET H-score (26.5 versus 67.5, P Z .007). On multivariate analysis, there were no significant differences in glycemic status based on race, BMI, stage, nodal positivity, or pack-years smoking. Conclusion: Our findings demonstrate posttreatment hyperglycemia was associated with poorer LRC and a trend toward worse OS. No correlation was seen between hyperglycemia and standard prognostic factors such as stage or nodal positivity. The suggestion that hyperglycemia after CRT for cervical cancer confers a poor prognosis is a novel finding. Further investigation is needed to characterize the relationship between hyperglycemia, tumor genomics, and treatment outcomes. Author Disclosure: J. Gross: None. E.D. Donnelly: None. J.B. Strauss: None. I. Helenowksi: None. J. Lurain: None. E. Berry: None. N. Neubauer: None.

25 Tissue-Based Quantitative Proteomics to Screen and Identify the Potential Biomarker Associated With Early Recurrence/Metastasis of Esophageal Squamous Cell Carcinoma Post Radical Resection M.N. Liu,1 X.L. Fu,1 X.W. Cai,1 and W. Yu2; 1Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China, 2Shanghai Chest Hospital, Shanghai Jiaotong University, Shanghai, China Purpose/Objective(s): Esophageal squamous cell carcinoma (ESCC) is the predominant pathological type in China, where it accounts for more than 90% of all esophageal cancer. In this study, we performed a tissuebased quantitative proteomic study to identify potential biomarkers associated with early recurrence/metastasis(R/M) of ESCC patients after radical resection. Materials/Methods: Esophageal squamous cell carcinoma patients undergoing surgery from January 2001 to December 2009 were evaluated, and 229 patients with 3-field lymphadenectomy were enrolled in this study. Tissue material was procured from patients who had given written informed consent. We examined tumor tissues and their normal counterparts (group D). The tumor tissues were divided into 3 groups according to the status of R/M within 2 years after operation: no R/M (group A), recurrence (group B), and metastasis (group C). Comparative proteomics analysis was performed to screen differential proteins among groups AeD. Then we identified the differential proteins by PCR and Western Blot. Finally, we verified the potential biomarkers by tissue microarray in another large population. Results: With stringent criteria, we identified 456 proteins using proteomics analysis. Using a cutoff value of 0.67 fold for under-expression and 1.5 fold for overexpression in group A compared to group D, and another 0.67 fold for under-expression and 1.5 fold for overexpression in group B/C compared to group A, 13 proteins met our definition of differential expression in a comparison in ESCC with different status of