Impact of adjuvant treatment on outcome in high-risk early-stage endometrial cancer: a retrospective three-center study.

OBJECTIVE: High grade and non-endometrioid endometrial cancers carry a poor prognosis, and the lack of randomized prospective data has led to a wide range of practice regarding adjuvant therapy. The objective of this study was to evaluate the outcomes of different treatment strategies in patients with high-risk, early-stage endometrial cancer. METHODS: Patients with high-grade endometrioid, serous endometrial cancer and carcinosarcoma diagnosed between 2000 and 2012 were identified from databases in three gynecologic oncology divisions, in Toronto and in Israel. Adjuvant treatment practices differed across the centers, creating a heterogeneous cohort. A comparison of stage I patients stratified by adjuvant treatment was undertaken. Log-rank tests and Cox proportional hazards models were employed to compare recurrence and survival across treatment groups. RESULTS: 490patients with high risk endometrial cancer were identified, among them 213 patients with stage I disease. Israeli patients received more chemotherapy (41% vs 10% in stage I disease; P<0.001) than patients in Toronto. Chemotherapy was not associated with improved disease-free, disease-specific or overall survival, nor was it associated with fewer distant recurrences (50% vs 54%). Radiation was also not associated with improved recurrence or survival, nor did it affect the pattern of recurrence. On Cox multivariable analysis, neither radiation treatment nor chemotherapy were significantly associated with outcome (HR for recurrence, 0.72 for pelvic radiation (P=0.46) and 1.99 for chemotherapy (P=0.09); HR for death, 0.67 for pelvic radiation (P=0.29) and 1.03 for chemotherapy (P=0.94)). CONCLUSIONS: In this retrospective analysis, neither adjuvant radiation nor chemotherapy were associated with improved outcome in stage I, high risk endometrial cancer.

Cutaneous Hemorrhage Types as Supportive Factors for Predicting Chronic Immune Thrombocytopenia in Children.

Our objective was to assess risk factors for developing chronic immune thrombocytopenia (ITP) in children. The charts of all consecutive children diagnosed with ITP between 2000 and 2015 at a single center were retrospectively reviewed, and clinical characteristics at initial presentation were analyzed. Sixty-two children were included in the study (mean age, 6.15 y); 44 (71%) were found to have acute ITP, and 18 (29%) developed chronic ITP (permanent or relapsing thrombocytopenia >12 mo). In a univariate analysis, cutaneous hemorrhages were observed significantly more in acute patients (90.9%) than in chronic patients (61.1%). Patients who had acute ITP were more likely to present with a combination of petechiae, purpura, and/or ecchymosis (75%) than patients with chronic disease (44.4%, P=0.010). In multivariate analysis, older age increased the risk (odds ratio=1.1; P<0.05) for chronic disease, and manifestations of combination skin hemorrhages (petechiae/purpura/ecchymosis) reduced the risk (odds ratio=0.167; P<0.05). In conclusion, the most important risk factor for chronic disease is older age. Skin hemorrhage types were found to be a supportive factor for the prediction process: the combination of petechia/purpura/ecchymosis was associated with a lower risk for developing chronic disease compared with petechiae alone. Future studies should assess the prognostic value of skin hemorrhage types that are a simple way to predict the course of ITP in children.

Abdominopelvic cytoreduction rates and recurrence sites in stage IV ovarian cancer: is there a case for thoracic cytoreduction?

OBJECTIVE: We report the rates of optimal abdominopelvic cytoreduction and the sites of recurrence in stage IV ovarian cancer patients, with particular attention to the potential impact of thoracic cytoreduction on treatment results in patients with intra-thoracic spread. METHODS: A historic cohort study of all stage IV ovarian cancer patients diagnosed between 1994 and 2010 and underwent abdominopelvic cytoreductive surgery. Controls were stage IIIc patients. Statistical analyses included χ(2) test, Cox proportional hazards regression models and Kaplan-Meier curves with log-rank tests. RESULTS: Group 1 included 76 stage IV patients, 55% with thoracic spread. Group 2 included 142 stage IIIc patients. Age, histology, primary peritoneal tumor and ascites rates were similar for the two groups. Respective rates of optimal abdominopelvic cytoreduction were 68% vs. 83.5% (p<0.05), median time to progression 5.3 vs. 12.3 months (p<0.01) and overall survival 27.2 vs. 46.1 months (p<0.01). Optimal cytoreduction and survival rates were similar for all group 1 patients regardless of spread location. Sites of recurrence in stage IV were abdomen (59.3%), thorax (6.8%), both (28.8%) or other (5.1%). The four patients with thoracic recurrence alone were all initially diagnosed with malignant pleural effusion. Three of them developed abdominal recurrence within 15‒6 months. CONCLUSIONS: Optimal abdominopelvic cytoreduction was achievable in stage IV patients, although in significantly fewer patients than in stage IIIc. Sites of recurrence were rarely thorax alone, implying that thoracic debulking is likely to change the course of disease in only few patients and thus should be carefully individualized.

Young Israeli women with epithelial ovarian cancer: prevalence of BRCA mutations and clinical correlates.

OBJECTIVE: The current study investigates disease patterns and outcomes in young Israeli epithelial ovarian cancer (EOC) patients and their association with BRCA mutation status. METHODS: Consecutive EOC patients diagnosed at or below 50 years in a single institution between 1995-2011 were identified. All patients are referred for genetic counseling and testing for the predominant Jewish BRCA mutations: BRCA1-185delAG, BRCA1-5382insC, and BRCA2-6174delT. A comparison between BRCA mutation carriers and non-carriers was undertaken across demographic, pathologic, and clinical features; recurrence and survival were compared using the Kaplan-Meier method and associations with the variables of interest were analyzed using the Cox proportional hazards method. RESULTS: One hundred eighty-six patients diagnosed with EOC at 50 years or younger were included, with a total follow-up of 1,088 person years. Mean age at diagnosis was 44±5 years. Of 113 patients with documented BRCA testing, 49.6% carried a germline BRCA mutation, compared with 29% in the general Israeli EOC population (p=0.001). BRCA mutation carriers had a higher rate of serous tumors (75% vs. 64%, p=0.040) and higher CA125 levels at diagnosis (median, 401 vs. 157, p=0.001) than non-carriers. No significant association between BRCA mutations and recurrence (hazard ratio [HR]=1.03; p=0.940) or survival (HR=1.40; p=0.390) was found. CONCLUSION: BRCA mutations are encountered in almost 50% of young Israeli ovarian cancer patients; they are associated with serous tumors and high CA125 levels at diagnosis, but are not independently associated with recurrence or survival in this patient population.