ABSTRACT
BACKGROUND: Successfully combining targeted agents with chemotherapy is an important future goal for cancer therapy. However, an improvement in patient outcomes requires an enhanced understanding of the tumor biomarkers that predict for drug sensitivity. NRG Oncology/Gynecologic Oncology Group (GOG) Study GOG-86P was one of the first attempts to combine targeted agents (bevacizumab or temsirolimus) with chemotherapy in patients with advanced endometrial cancer. Herein we performed exploratory analyses to examine the relationship between mutations in TP53, the most commonly mutated gene in cancer, with outcomes on GOG-86P. METHODS: TP53 mutational status was determined and correlated with progression-free survival (PFS) and overall survival (OS) on GOG-86P. RESULTS: Mutations in TP53 were associated with improved PFS and OS for patients that received bevacizumab as compared to temsirolimus (PFS: HR 0.48, 95% CI 0.31, 0.75; OS: HR: 0.61, 95% CI 0.38, 0.98). By contrast, there was no statistically significant difference in PFS or OS between arms for cases with WT TP53. CONCLUSIONS: This exploratory study suggests that combining chemotherapy with bevacizumab, but not temsirolimus, may enhance PFS and OS for patients whose tumors harbor mutant p53. These data set the stage for larger clinical studies evaluating the potential of TP53 mutational status as a biomarker to guide choice of treatment for endometrial cancer patients. Clintrials.gov: NCT00977574.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Endometrial Neoplasms/drug therapy , Endometrial Neoplasms/genetics , Mutation , Neoplasm Recurrence, Local/drug therapy , Neoplasm Recurrence, Local/genetics , Tumor Suppressor Protein p53/genetics , Angiogenesis Inhibitors/administration & dosage , Bevacizumab/administration & dosage , Carboplatin/administration & dosage , Clinical Trials, Phase II as Topic , Endometrial Neoplasms/pathology , Epothilones/administration & dosage , Female , Genes, p53 , Humans , Neoplasm Recurrence, Local/pathology , Neoplasm Staging , Paclitaxel/administration & dosage , Progression-Free Survival , Randomized Controlled Trials as Topic , Sirolimus/administration & dosage , Sirolimus/analogs & derivatives , Survival Rate , Treatment OutcomeABSTRACT
Purpose To assess the diagnostic accuracy of fluorine 18 fluorodeoxyglucose (FDG) positron emission tomography (PET) combined with diagnostic contrast material-enhanced computed tomography (CT) in detecting lymph node (LN) metastasis in high-risk endometrial cancer. Materials and Methods This prospective multicenter HIPAA-compliant study had institutional review board approval, and all participants gave written informed consent. Data were accrued between January 2010 and June 2013. Patients underwent PET/CT and pelvic and abdominal lymphadenectomy. Two hundred seven of 215 enrolled patients had PET/CT and pathologic examination results for the abdomen and pelvis. Mean patient age was 62.7 years ± 9.6 (standard deviation). Data in all 23 patients with a positive abdominal examination and in 26 randomly selected patients with a negative abdominal examination were used for this central reader study. Seven independent blinded readers reviewed diagnostic CT and PET/CT results in different sessions 1 month apart. Accuracy was calculated at the participant level, correlating abdominal (right and left para-aortic and common iliac) and pelvic (right and left external iliac and obturator) LN regions with pathologic results, respecting laterality. Reader-average sensitivities, specificities, and areas under the receiver operating characteristic curve (AUCs) of PET/CT and diagnostic CT were compared. Power calculation was for sensitivity and specificity in the abdomen. Results Sensitivities of PET/CT versus diagnostic CT for the detection of LN metastasis were 0.65 (95% confidence interval [CI]: 0.57, 0.72) versus 0.50 (95% CI: 0.43, 0.58) (P = .01) in the abdomen and 0.65 (95% CI: 0.57, 0.72) versus 0.48 (95% CI: 0.41, 0.56) (P = .004) in the pelvis. Corresponding specificities were 0.88 (95% CI: 0.83, 0.92) versus 0.93 (95% CI: 0.89, 0.96) (P = .11) and 0.93 (95% CI: 0.86, 0.96) versus 0.89 (95% CI: 0.82, 0.94) (P = .27), and AUCs were 0.78 (95% CI: 0.66, 0.89) versus 0.74 (95% CI: 0.63, 0.86) (P = .39) and 0.82 (95% CI: 0.71, 0.92) versus 0.73 (95% CI: 0.63, 0.84) (P = .02). Conclusion FDG PET/CT has satisfactory diagnostic accuracy in the detection of abdominal LN metastasis in high-risk endometrial cancer. Compared with diagnostic CT alone, addition of PET to diagnostic CT significantly increased sensitivity in both the abdomen and pelvis while maintaining high specificity. © RSNA, 2017 Online supplemental material is available for this article.
