Prognostic role of transcription factor ARID1A in patients with endometrial cancer of no specific molecular profile (NSMP) subtype.

OBJECTIVE: As more than 50% of newly diagnosed endometrial cancers remain classified as 'no specific molecular subtype' (NSMP) due to a lack of established biomarkers to further improve molecular subtyping, this study aims to evaluate the prognostic value of ARID1A in endometrial cancers of NSMP subtype. METHODS: Prospectively collected molecular profiling data of all consecutive patients with endometrial cancer who underwent primary surgery at our department between August 2017 and June 2022 and for whom both molecular profiling and clinical follow-up data were available were retrospectively evaluated. Tumor specimens were evaluated by combined mismatch repair protein immunohistochemistry and targeted next-generation hotspot sequencing. ARID1A mutational status, as defined by full-length gene sequencing, was matched with risk of recurrence, progression-free and disease-specific survival within the NSMP cohort. RESULTS: A total of 127 patients with endometrial cancer were included. Among 72 patients with tumors of NSMP subtype (56.7%), ARID1A mutations were identified in 24 cases (33.3%). ARID1A mutations were significantly associated with a higher risk of recurrence (37.5% vs 12.5%, OR 4.20, 95% CI 1.28 to 13.80, p=0.018) and impaired progression-free survival (HR 3.96, 95% CI 1.41 to 11.15, p=0.009), but not with disease-specific survival. The results for both risk of recurrence (OR 3.70, 95% CI 1.04 to 13.13, p=0.043) and progression-free survival (HR 3.19, 95% CI 1.10 to 9.25, p=0.033) were confirmed in multivariable analysis compared with advanced tumor stage International Federation of Gynecology and Obstetrics (2009) (FIGO ≥III) and impaired Eastern Clinical Oncology Group performance status (ECOG ≥1). CONCLUSION: ARID1A appears to identify patients with endometrial cancer of NSMP subtypes with a higher risk of recurrence and could be used as a future prognostic biomarker. After clinical validation, ARID1A assessment could help to further sub-classify selected endometrial cancers and improve personalized treatment strategies.

The Prognostic Value of the Fibrinogen-Albumin-Ratio Index (FARI) in Patients with Advanced Vulvar Cancer.

The present study aims to evaluate the pretherapeutic Fibrinogen-Albumin-Ratio Index (FARI), as currently reliable biomarkers to predict therapy response and prognosis of patients with advanced vulvar cancer are missing. Data of 124 consecutive patients, who underwent primary resection for vulvar cancer ≥ pT1b, were retrospectively analyzed. Associations between the FARI and disease recurrence were assessed fitting receiver operating characteristics (ROC) and binary logistic regression models; univariate and multivariable Cox regression models for disease-specific survival (DSS) and progression-free survival (PFS) were performed. A pretherapeutic low FARI cut at its median (<9.67) is significantly associated with younger age (65.5 vs. 74.0 years) and higher risk of recurrence (52.4% vs. 26.2%). The ROC analysis calculates the area under the curve (AUC) of the FARI for a PFS < 6 months of 0.700 and for a DSS < 12 months of 0.706, outperforming fibrinogen and albumin alone. The FARI remained independently predictive for PFS (HR 0.84, 95% CI [0.99−1.03], p = 0.009) and DSS (HR 0.82, 95% CI [0.70−0.99], p = 0.019), also in multivariable survival analysis. Despite the FARI's promising predictive and prognostic value, however, further elucidation of its precise mode of action is warranted before clinical application as it appears to rely only on subtle changes of fibrinogen levels.

Overweight as a Favorable Clinical Biomarker for Checkpoint Inhibitor Therapy Response in Recurrent Gynecologic Cancer Patients.

Despite increasing clinical interest in adapting checkpoint inhibitor (CPI) therapies for patients with gynecologic malignancies, no accurate clinical biomarkers to predict therapy response and prognosis are currently available. Therefore, we aimed to assess the predictive and prognostic value of pretherapeutic body mass index (BMI) for recurrent gynecologic cancer patients as previously validated for other solid tumors. We evaluated patients with programmed cell death ligand 1 (PD-L1) positive and, in endometrial cancer, also mismatch repair deficient (MMR) gynecologic malignancies, who received the PD-1 inhibitor pembrolizumab as monotherapy (200 mg fixed-dose q3 w) from 2017 to 2020 (n = 48). Thirty-six patients receiving at least four courses were included in the final analysis. Associations between a BMI increase per 5 kg/m2 and overall response rate (ORR; complete + partial response), disease control rate (DCR; ORR + stable disease), progression-free (PFS), and overall survival (OS) were assessed. An elevated BMI was univariately associated with ORR (OR 10.93 [CI 2.39-49.82], p = 0.002), DCR (OR 2.19 [CI 0.99-4.83], p = 0.048), prolonged PFS (HR 1.54 [CI 1.03-2.34], p = 0.038), and OS (HR 1.87 [CI 1.07-3.29], p = 0.028). All results could be confirmed in the multivariate analyses. Pretherapeutic BMI therefore appears to be a promising readily available biomarker to identify patients with PD-L1-positive and/or MMR-deficient gynecologic malignancies who could particularly benefit from CPI treatment.

Impact of surgeons' experience and the single-shot perioperative antibiotic prophylaxis on outcome in stapedotomy.

BACKGROUND: The aim of this study was to evaluate whether surgeons´ experience and perioperative single-shot antibiotic prophylaxis affect outcome of patients undergoing stapes surgery. PATIENTS AND METHODS: We retrospectively evaluated audiological outcomes and postoperative complications of 538 consecutive patients who underwent stapes surgery at a single tertiary referral center between 1990 and 2017. Effects of different clinical variables, including single-shot antibiotic prophylaxis and surgeons' experience on outcome were assessed. RESULTS: 538 patients underwent 667 stapedotomies and postoperative complication rate was 7.5% (n = 50). Air conduction and air-bone gap closure improved significantly after surgery (14.2 ± 14.8 dB, p = 0.001; 14.5 ± 12.8 dB, p = 0.001). Multivariate analysis revealed that 6 years or less of surgical experience was independently associated with a higher incidence of persisting or recurrent conductive hearing loss (p = 0.033, OR 5.13) but perioperative application of antibiotics had no significant effect on outcome. CONCLUSION: First, clinical outcome regarding persisting or recurrent conductive hearing loss caused by incus necrosis and prosthesis luxation is linked to surgical performance. This underlines the need for a meticulous training and supervision of less experienced surgeons performing stapes surgery. Second, our results do not support the need for perioperative antibiotic prophylaxis in stapes surgery. Potential standard limitations of retrospective cohort studies (selection bias, confusion bias etc.) could play a role in interpreting our results. However, the probability for these limitations is minimized due to the large patient sample.