Roy Kessous

High-grade uterine cancer with ambiguous features – a clinicopathological study

Endometrial endometrioid carcinoma FIGO grade 3 (EC3) and endometrial serous carcinoma (SEC), sometimes present diagnostic challenges due to overlapping and ambiguous features. The prognostic significance of assigning histological subtype remains debatable due to conflicting clinical outcome data. This study examined definite and ambiguous EC3 and SEC cases to compare clinicopathologic characteristics and prognosis. This is a retrospective study of 129 patients diagnosed with EC3 and SEC at a single tertiary center between 2006-2022. Pathological slides were revised and classified as definite or ambiguous for EC3 and SEC. Survival, progression-free survival, and associations between tumor histologic type and clinicopathologic characteristics were analyzed. Definite SEC displayed higher mortality compared to definite EC3 (68.2 % vs. 41.4 %, p = 0.023) as well as a non-significant trend towards lower 5-year survival (p = 0.096). Ambiguous SEC also showed higher mortality compared to ambiguous EC3 (68.8 % vs. 37.5 %, p = 0.020) and a non-significant trend towards lower 5-year survival (p = 0.098). Several parameters suggest that ambiguous cases are intermediate between the definite EC3 (lower) and definite SEC (higher) groups. Rates of lymph node metastases (EC3 6.9 %; ambiguous 16.4 % and SEC 29.5 %; p = 0.013), broad ligament involvement (EC3 0 %; ambiguous 1.8 % and SEC 11.4 %; p = 0.016), and omental involvement (EC3 3.4 %; ambiguous 10.9 % and SEC 29.5 %; p = 0.002). A similar trend was observed for ovarian involvement, but it did not reach statistical significance (EC3 6.9 %; ambiguous 12.7 % and SEC 22.7 %; p = 0.055). Ambiguous cases may represent an intermediate group that displays clinicopathologic features which are more aggressive than in EC3, yet more favorable than in SEC. These results hold implications for managing patients with high-grade endometrial carcinomas, as identifying an intermediate group may inform treatment strategies and prognostic evaluations.

Multiple lines of chemotherapy for patients with high‐grade ovarian cancer: Predictors for response and effect on survival

AbstractGuidelines for the treatment of tubo‐ovarian cancer patients beyond third line are lacking. We aimed to evaluate the effect of response in each line on patient's outcome as well as identify variables that predict response for additional line of chemotherapy. A cohort study was performed including all patients with advanced high‐grade ovarian cancer. Survival analysis was performed using Kaplan‐Meier curves and log‐rank tests. Odds ratios and hazard ratios were calculated using multilevel, mixed‐effects logistic regression and Cox regression, adjusting for repeated measures within individual patients. Two‐hundred thirty‐eight patients were included and underwent up to 10 lines of chemotherapy. The median progression‐free survival was 15.6 and overall survival (OS) was 55.6 months. Response rates dropped with each additional line and by line 5, most patients (61%) became refractory and only 16% had any type of response (complete 4% or partial 12%). By line 2, whether a patient had partial disease (PR), stable disease (SD) or progressive disease (PD) did not have an effect on the OS. From line 2, whether a patient had PR, SD or PD did not have an effect on chemotherapy‐free interval. Number of previous lines and time from previous line were the only variables that significantly correlated with both outcome of patients and response to the next line. In conclusion, time interval from the previous line of chemotherapy is the major clinical factor that predicts beneficial effect of another line of treatment in patients with ovarian cancer.

Carboplatin plus paclitaxel weekly dose‐dense chemotherapy for high‐grade ovarian cancer: A re‐evaluation

AbstractIntroductionWe compared oncologic and clinical outcomes in patients with advanced ovarian cancer who received dose‐dense weekly paclitaxel with 3‐weekly carboplatin with those who received standard 3‐weekly chemotherapy.Material and methodsComparison of all consecutive patients with advanced (International Federation of Gynecology and Obstetrics stages III‐IV) ovarian cancer who received a dose‐dense protocol between 2010 and 2016 with an immediate historical cohort of consecutive patients who received standard chemotherapy. Patients who received less than three cycles of treatment were excluded.ResultsIn all, 246 patients were included in the study, of whom 128 received the dose‐dense protocol and 118 were treated with the standard Q3‐week protocol. Patients in the dose‐dense group had significantly better progression‐free survival than those receiving the standard protocol (median progression‐free survival 22 vs 15 months; log rank = 0.026). The overall survival of patients in the dose‐dense group was also better than that of the patients in the standard protocol group; however, this difference was not statistically significant (median overall survival 66 vs 54 months; log rank = 0.185). The dose‐dense protocol remained significantly associated with favorable survival outcome in multivariable analysis adjusted for stage, histologic type, cytoreductive results and neoadjuvant chemotherapy. The use of the dose‐dense protocol was associated with higher rates of gastrointestinal, dermatologic, neurologic and hematologic side effects.ConclusionDespite the limitations associated with the comparison to a historical cohort, a dose‐dense chemotherapy protocol resulted in a significantly improved progression‐free survival and the overall survival tended to be better, but this difference did not reach statistical significance compared with the standard chemotherapy protocol, and may be considered as a treatment alternative, albeit with some increased side effects.

CA‐125 reduction during neoadjuvant chemotherapy is associated with success of cytoreductive surgery and outcome of patients with advanced high‐grade ovarian cancer

AbstractIntroductionThe objective was to assess whether an early response to neoadjuvant chemotherapy in women with advanced ovarian cancer may predict short‐ and long‐term clinical outcome.Material and methodsThis is a retrospective study of all women with stage III‐IV tubo‐ovarian cancer treated with neoadjuvant chemotherapy at a single center in Montreal between 2003 and 2014. Logistic regression models were used to evaluate the association between cancer antigen 125 (CA‐125) levels during neoadjuvant chemotherapy and debulking success. Cox proportional hazard models were used to estimate hazard ratios and their respective 95% CI for death and recurrence. Harrell's concordance indices were calculated to evaluate which variables best predicted the chemotherapy‐free interval and overall survival in our population.ResultsIn all, 105 women were included. Following the first, second, and third cycles of neoadjuvant chemotherapy, CA‐125 levels had a median reduction of 43.2%, 85.4%, and 92.9%, respectively, compared with CA‐125 levels at diagnosis. As early as the second cycle, CA‐125 was associated with overall survival (hazard ratio 1.03, 95% CI 1.01‐1.05, per 50 U/mL increment). By the third cycle, CA‐125 did not only predict overall survival (hazard ratio 1.04, 95% CI 1.01‐1.08), but it predicted overall survival better than the success of debulking surgery (Harrell's concordance index 0.646 vs 0.616). Both absolute CA‐125 levels and relative reduction in CA‐125 levels after 2 and 3 cycles predicted the chance to achieve complete debulking (P < .05).ConclusionsReduction of CA‐125 levels during neoadjuvant chemotherapy provides an early predictive tool that strongly correlates with successful cytoreductive surgery and long‐term clinical outcome in women with advanced high‐grade serous and endometrioid ovarian cancer.