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Pre-treatment Prediction Model in Endometrioid Adenocarcinoma of the Uterus Using Somatic Mutations
Abstracts / Gynecologic Oncology 143 (2016) 194–223
excluded as all patients received 6 cycles of chemotherapy. Our cohort consisted of 163 patients with stage I-IC3 disease. Clinical, pathologic, recurrence and survival data were abstracted from electronic medical records. Kaplan-Meier analysis was performed to compare progression-free (PFS) and overall survival (OS) between groups. Results: Among 163 eligible patients, the median age was 53 years (range 30-88). The majority of patients were Caucasian (83%). One hundred thirty-three (82%) patients received 6 cycles and 30 (18%) received 3 cycles of adjuvant carboplatin and paclitaxel. Recurrence rate was comparable between groups (13% vs. 23% for 3 vs 6 cycles, p = 0.3). There were no statistically significant differences between PFS (hazard ratio [HR] 0.65; 95% confidence interval [CI] 0.27-1.56, p = 0.4) and OS (HR 0.52; 95% CI 0.18-1.45, p = 0.2). Conclusion: Compared to 6 cycles of carboplatin and paclitaxel, 3 cycles may be comparable with respect to recurrence in patients diagnosed with early surgical stage I OCCC.
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Results: 19,553 genes were evaluated for mutations in EEC in TCGA database. 62 patients met the definition of high risk and 128 for low risk. The prediction strategy including number of somatic mutations per gene had an area under the ROC curve (AUC) between 59% and 68%. The strategy including variant allele frequency for each somatic mutation was found to have significantly better classifiers with an AUC = 91%. Lasso and ridge methods have identified 53 mutations that together have the highest predictability for high risk EEC features. Conclusion: We defined a prediction model for risk levels of EEC composed of 53 genes with an AUC of 91%. A prediction model that includes intra-tumor genetic heterogeneity information could be an effective classifier for stratification of risk in EEC and thus guide clinical management. Validation of this prediction model has been planned using next generation sequencing on endometrial tumors in our department tumor repository.
doi:10.1016/j.ygyno.2016.08.292
Patterns of failure and the potential role for localized therapy inpatients with recurrent endometrial adenocarcinoma M Hodeib, M. Zakhour, M. Kamrava, J.G. Cohen. University of California Los Angeles Medical Center, Los Angeles, California
doi:10.1016/j.ygyno.2016.08.291
Pre-treatment Prediction Model in Endometrioid Adenocarcinoma of the Uterus Using Somatic Mutations E. Salinas, D. Dai, A. Newtson, M. McDonald, M. Goodheart, K. Leslie, J. Gonzalez-Bosquet. University of Iowa Hospitals and Clinics, Iowa City, IA Objectives: Surgical staging of endometrioid endometrial cancer (EEC) can be used to individualize adjuvant treatment, but in patients with low-grade, minimally invasive disease the benefits of comprehensive staging are unclear. Risk stratification intraoperatively may be limited by accessibility to reliable frozen section. To date there is no preoperative predictive model that accurately identifies women with high risk EEC. Our aim was to evaluate the performance of a prediction model to identify risk levels of EEC using somatic mutations. Methods: The Cancer Genome Atlas (TCGA) mutation dataset for EEC was used for the analysis. Classification of EEC risk was based on the results of GOG 33 and GOG 99. The prediction model was built based on the number of somatic mutations for each gene, and variant allele frequencies for somatic mutations in each gene that were derived from the re-analysis of the original exome sequencing data. Somatic mutations in EEC were used to formulate algorithms for classification into high and low risk. Prediction model algorithms were performed using R statistical package for statistical computing and graphics (www.r-project.org) as background, and Bioconductor packages as open source software for bioinformatics (bioconductor.org).
Objectives: To determine the patterns of endometrial adenocarcinoma (EAC)recurrence and the potential rolefor localized treatment such as surgical excision or SBRT Methods: An IRB-approved retrospective chart review identified consecutive patients treated between 1/2000 and 12/2014with a diagnosis of EACat a single institution. Only patients with recurrent disease, availablepathology reports,and at least 6 months of followup were included.Demographic, clinical, and histological information was abstracted from medical records. Chi-square, Fisher’s exact, and Mann Whitney U tests were used for statistical analysis. Results: Of the 599 consecutive patients with a diagnosis of EAC, 55 patients had recurrent disease andmet inclusion criteria. Three patients had progressive disease during adjuvant treatment and were excluded from further analysis leaving a total of 52 patients. Median age at diagnosis was 63 years (range 35-89).The distribution of stages at the time of diagnosis were: 31 (59%) stage IA or IB, 5 (10%) stage II, 15 (29%) stage III, and 1 (2%) stageIV.Primary treatment included hysterectomy +/- BSO in 24 (46%) patients, surgery/radiation (RT) in 10 (19%) patients, surgery/chemotherapy in 5(10%) patients,triple modality therapy in 12 (23%) patients, and chemoradiation alone in 1 (2%) patient. Median follow-up from the date of diagnosis was 46 months (range 6-175) with a median disease free interval of 17 months (range 1-96) and overall survival of 52 months (range 6-175). Forty (77%) of 52 patients with recurrence presented with oligometastatic disease (≤ 5 sites). The most common site of recurrence was the pelvis. In the setting of first recurrence, 11 (28%) patients with oligometastatic disease were treated with chemotherapy/hormonal agents alone, 28 (70%) had treatment regimens which included localized therapy (surgery or RT), and one patient died of a pulmonary saddle embolus before receiving treatment. Seven (64%) patients treated with systemic therapy had persistent or progressive disease, versus 8 (29%) of those whose treatment regimens included localized treatment (p = 0.06). Patients who received localized therapy were more likely to have b 3 disease sites (p = 0.02). Median overall survival was 52 months (range 7 to 175) in patients with oligometastatic recurrence, compared to 25 months (range 4 to 172) in those with N5 sites of recurrent disease (p = 0.05). Conclusion: 77% of recurrent EAC presents with a limited number of metastatic sites. Local treatment of metastatic sites in combination
excluded as all patients received 6 cycles of chemotherapy. Our cohort consisted of 163 patients with stage I-IC3 disease. Clinical, pathologic, recurrence and survival data were abstracted from electronic medical records. Kaplan-Meier analysis was performed to compare progression-free (PFS) and overall survival (OS) between groups. Results: Among 163 eligible patients, the median age was 53 years (range 30-88). The majority of patients were Caucasian (83%). One hundred thirty-three (82%) patients received 6 cycles and 30 (18%) received 3 cycles of adjuvant carboplatin and paclitaxel. Recurrence rate was comparable between groups (13% vs. 23% for 3 vs 6 cycles, p = 0.3). There were no statistically significant differences between PFS (hazard ratio [HR] 0.65; 95% confidence interval [CI] 0.27-1.56, p = 0.4) and OS (HR 0.52; 95% CI 0.18-1.45, p = 0.2). Conclusion: Compared to 6 cycles of carboplatin and paclitaxel, 3 cycles may be comparable with respect to recurrence in patients diagnosed with early surgical stage I OCCC.
215
Results: 19,553 genes were evaluated for mutations in EEC in TCGA database. 62 patients met the definition of high risk and 128 for low risk. The prediction strategy including number of somatic mutations per gene had an area under the ROC curve (AUC) between 59% and 68%. The strategy including variant allele frequency for each somatic mutation was found to have significantly better classifiers with an AUC = 91%. Lasso and ridge methods have identified 53 mutations that together have the highest predictability for high risk EEC features. Conclusion: We defined a prediction model for risk levels of EEC composed of 53 genes with an AUC of 91%. A prediction model that includes intra-tumor genetic heterogeneity information could be an effective classifier for stratification of risk in EEC and thus guide clinical management. Validation of this prediction model has been planned using next generation sequencing on endometrial tumors in our department tumor repository.
doi:10.1016/j.ygyno.2016.08.292
Patterns of failure and the potential role for localized therapy inpatients with recurrent endometrial adenocarcinoma M Hodeib, M. Zakhour, M. Kamrava, J.G. Cohen. University of California Los Angeles Medical Center, Los Angeles, California
doi:10.1016/j.ygyno.2016.08.291
Pre-treatment Prediction Model in Endometrioid Adenocarcinoma of the Uterus Using Somatic Mutations E. Salinas, D. Dai, A. Newtson, M. McDonald, M. Goodheart, K. Leslie, J. Gonzalez-Bosquet. University of Iowa Hospitals and Clinics, Iowa City, IA Objectives: Surgical staging of endometrioid endometrial cancer (EEC) can be used to individualize adjuvant treatment, but in patients with low-grade, minimally invasive disease the benefits of comprehensive staging are unclear. Risk stratification intraoperatively may be limited by accessibility to reliable frozen section. To date there is no preoperative predictive model that accurately identifies women with high risk EEC. Our aim was to evaluate the performance of a prediction model to identify risk levels of EEC using somatic mutations. Methods: The Cancer Genome Atlas (TCGA) mutation dataset for EEC was used for the analysis. Classification of EEC risk was based on the results of GOG 33 and GOG 99. The prediction model was built based on the number of somatic mutations for each gene, and variant allele frequencies for somatic mutations in each gene that were derived from the re-analysis of the original exome sequencing data. Somatic mutations in EEC were used to formulate algorithms for classification into high and low risk. Prediction model algorithms were performed using R statistical package for statistical computing and graphics (www.r-project.org) as background, and Bioconductor packages as open source software for bioinformatics (bioconductor.org).
Objectives: To determine the patterns of endometrial adenocarcinoma (EAC)recurrence and the potential rolefor localized treatment such as surgical excision or SBRT Methods: An IRB-approved retrospective chart review identified consecutive patients treated between 1/2000 and 12/2014with a diagnosis of EACat a single institution. Only patients with recurrent disease, availablepathology reports,and at least 6 months of followup were included.Demographic, clinical, and histological information was abstracted from medical records. Chi-square, Fisher’s exact, and Mann Whitney U tests were used for statistical analysis. Results: Of the 599 consecutive patients with a diagnosis of EAC, 55 patients had recurrent disease andmet inclusion criteria. Three patients had progressive disease during adjuvant treatment and were excluded from further analysis leaving a total of 52 patients. Median age at diagnosis was 63 years (range 35-89).The distribution of stages at the time of diagnosis were: 31 (59%) stage IA or IB, 5 (10%) stage II, 15 (29%) stage III, and 1 (2%) stageIV.Primary treatment included hysterectomy +/- BSO in 24 (46%) patients, surgery/radiation (RT) in 10 (19%) patients, surgery/chemotherapy in 5(10%) patients,triple modality therapy in 12 (23%) patients, and chemoradiation alone in 1 (2%) patient. Median follow-up from the date of diagnosis was 46 months (range 6-175) with a median disease free interval of 17 months (range 1-96) and overall survival of 52 months (range 6-175). Forty (77%) of 52 patients with recurrence presented with oligometastatic disease (≤ 5 sites). The most common site of recurrence was the pelvis. In the setting of first recurrence, 11 (28%) patients with oligometastatic disease were treated with chemotherapy/hormonal agents alone, 28 (70%) had treatment regimens which included localized therapy (surgery or RT), and one patient died of a pulmonary saddle embolus before receiving treatment. Seven (64%) patients treated with systemic therapy had persistent or progressive disease, versus 8 (29%) of those whose treatment regimens included localized treatment (p = 0.06). Patients who received localized therapy were more likely to have b 3 disease sites (p = 0.02). Median overall survival was 52 months (range 7 to 175) in patients with oligometastatic recurrence, compared to 25 months (range 4 to 172) in those with N5 sites of recurrent disease (p = 0.05). Conclusion: 77% of recurrent EAC presents with a limited number of metastatic sites. Local treatment of metastatic sites in combination