Multiparametric MRI radiomics for predicting disease-free survival and high-risk histopathological features for tumor recurrence in endometrial cancer.

Background: Current preoperative imaging is insufficient to predict survival and tumor recurrence in endometrial cancer (EC), necessitating invasive procedures for risk stratification. Purpose: To establish a multiparametric MRI radiomics model for predicting disease-free survival (DFS) and high-risk histopathologic features in EC. Methods: This retrospective study included 71 patients with histopathology-proven EC and preoperative MRI over a 10-year period. Clinicopathology data were extracted from health records. Manual MRI segmentation was performed on T2-weighted (T2W), apparent diffusion coefficient (ADC) maps and dynamic contrast-enhanced T1-weighted images (DCE T1WI). Radiomic feature (RF) extraction was performed with PyRadiomics. Associations between RF and histopathologic features were assessed using logistic regression. Associations between DFS and RF or clinicopathologic features were assessed using the Cox proportional hazards model. All RF with univariate analysis p-value < 0.2 were included in elastic net analysis to build radiomic signatures. Results: The 3-year DFS rate was 68% (95% CI = 57%-80%). There were no significant clinicopathologic predictors for DFS, whilst the radiomics signature was a strong predictor of DFS (p<0.001, HR 3.62, 95% CI 1.94, 6.75). From 107 RF extracted, significant predictive elastic net radiomic signatures were established for deep myometrial invasion (p=0.0097, OR 4.81, 95% CI 1.46, 15.79), hysterectomy grade (p=0.002, OR 5.12, 95% CI 1.82, 14.45), hysterectomy histology (p=0.0061, OR 18.25, 95% CI 2.29,145.24) and lymphovascular space invasion (p<0.001, OR 5.45, 95% CI 2.07, 14.36). Conclusion: Multiparametric MRI radiomics has the potential to create a non-invasive a priori approach to predicting DFS and high-risk histopathologic features in EC.

Assessment of Interobserver Agreement Among Gynecologic Pathologists Between Three-Tier Versus Binary Pattern-based Classification Systems for HPV-associated Endocervical Adenocarcinoma.

The three-tier (A vs. B vs. C) pattern-based (Silva) classification system is a strong and fairly reproducible predictor of the risk of lymph node involvement and recurrence of human papillomavirus (HPV)-associated endocervical adenocarcinoma (EA). Recently, a binary pattern-based classification system has been proposed which incorporates the Silva pattern and lymphovascular invasion (LVI) to assign tumors as "low risk" or "high risk" and this may have superior prognostic significance compared with the three-tier system as well as current International Federation of Gynecology and Obstetrics (FIGO) staging of cervix-confined disease. The interobserver reproducibility of this binary system, however, is unknown. Representative slides from 59 HPV-associated EAs (1-3 slides/case) were independently reviewed by 5 gynecologic pathologists who participated in an online training module before the study. In the first review, a pattern was assigned using the three-tier system. On the second review, a "low risk" or "high risk" designation was assigned and the presence or absence of LVI was specifically documented. Interobserver agreement was assessed using Fleiss' kappa. The binary system showed improved interobserver agreement (kappa=0.634) compared with the three-tier system (kappa=0.564), with a higher proportion of cases having agreement between at least 4/5 reviewers (86% vs. 73%). Nineteen and 8 cases showed improved and worse interobserver agreement using the binary system, respectively; the remainder showed no change. 3/5 reviewers showed no intraobserver discrepancy while the remaining 2 did in a small subset of cases (n=2 and 4, respectively). In this study, a binary pattern-based classification system showed improved interobserver agreement compared with the traditional three-tier system.

Correlating the KELIM (CA125 elimination rate constant K) score and the chemo-response score as predictors of chemosensitivity in patients with advanced ovarian carcinoma.

BACKGROUND: The objective of this study is to assess the correlation between the pre-operative CA125 Elimination rate constant K(KELIM) score and the intraoperative chemo-response score (CRS) in patients with advanced high grade serous ovarian cancer(HGSC) treated with neoadjuvant chemotherapy(NACT). METHODS: This is a retrospective cohort study of patients with Stage III-IV HGSC treated with NACT from March 2010 to December 2019 at Princess Margaret Cancer Center, Toronto, Canada. KELIM scores were calculated based on the tool devised by You et al. available online. CRS was assessed using an established 3-tier scoring system. An association analysis was performed to determine if the KELIM score assessed during NACT can predict CRS score at the time of interval cytoreductive surgery(ICS). RESULTS: 172 patients were included in this analysis. Patients with CRS 1-2 had a lower median Platinum Free Interval(PFI) (9.24 vs 13.64 months, p = 0.005), lower median progression free survival(PFS) (14.99 vs 20.29 months, p = 0.003) and lower 5-year overall survival(OS) (63.8% vs 69.7%, p = 0.54) compared to patients with CRS3. Among patients with CRS 1-2(n = 115), 68.7% had KELIM <1, while 56.2% of patients with CRS3 had KELIM ≥1(56.2%), p = 0.0017, suggesting a correlation between the KELIM and CRS scores. Furthermore, patients with KELIM ≥1 and CRS3 had significantly higher PFS compared to other groups(median PFS 28.27 months vs 17.66 months for KELIM ≥1/CRS 1/2; 17.13 months for KELIM <1/CRS 3; and 14.53 months for KELIM <1/CRS 1-2, p = 0.003). CONCLUSION: The biochemical KELIM score correlated with the surgical pathologic CRS score and may predict pathological response to chemotherapy. This information can be utilized to tailor and personalize treatment in patients with advanced ovarian malignancy.

HER2-low and Overexpression in Mucinous Ovarian Cancer: Analysis of ASCO/CAP and ToGA Immunohistochemical Scoring.

Mucinous ovarian carcinoma is an uncommon malignancy characterized by resistance to chemotherapy and poor survival in the metastatic setting. HER2 amplification is a frequent late event in carcinogenesis, yet the incidence of HER2-low in mucinous ovarian carcinoma is unknown. Further, the optimal method for determining overexpression in these tumors is not established. We sought to assess the ASCO/CAP and ToGA trial scoring methods for HER2 IHC with correlation to FISH, p53, and mismatch repair protein status and to determine the incidence of HER2-low in mucinous ovarian carcinoma. A total of 29 tumors from 23 patients were included. Immunohistochemistry for HER2, p53, MLH1, PMS2, MSH2, and MSH6 was performed. Scoring was performed according to the ASCO/CAP and ToGA trial criteria. HER2 FISH was performed and scored according to the ASCO/CAP criteria. The proportion of HER2-low, defined as 1+ or 2+ staining with negative FISH, was determined. Using ASCO/CAP, 26% demonstrated 3+ while 35% demonstrated 2+ staining. Using ToGA, 30% demonstrated 3+ while 57% demonstrated 2+ staining. By FISH, 26% were positive for HER2 amplification. Both systems captured all FISH-positive cases; the use of ASCO/CAP resulted in fewer equivocal and false-positive cases. Among HER2-negative cases, 88% were HER2-low. Aberrant p53 expression was detected in 55% of cases; mismatch repair deficiency was not identified in any cases. ASCO/CAP guidelines are accurate and resource-effective in determining HER2 overexpression in mucinous ovarian carcinoma. HER2-low is common in these tumors; further studies to determine the role of HER2-targeted therapy including antibody-drug conjugates are indicated.