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.

Bartl T, et al. J Gynecol Oncol. 2025 Apr;36:e99. https://doi.org/10.3802/jgo.2025.36.e99

BACKGROUND AND PURPOSE: The radiologic evaluation of ongoing myelination is currently limited prenatally. Novel quantitative MR imaging modalities provide relaxometric properties that are linked to myelinogenesis. In this retrospective postmortem imaging study, the capability of Synthetic MR imaging and MR fingerprinting–derived relaxometry for tracking fetal myelin development was investigated. Moreover, the consistency of results for both MR approaches was analyzed. MATERIALS AND METHODS: In 26 cases, quantitative postmortem fetal brain MR data were available (gestational age range, 15 + 1 to 32 + 1; female/male ratio, 14/12). Relaxometric measurements (T1-/T2-relexation times) were determined in the medulla oblongata and the midbrain using Synthetic MR imaging/MR fingerprinting–specific postprocessing procedures (Synthetic MR imaging and MR Robust Quantitative Tool for MR fingerprinting). The Pearson correlations were applied to detect relationships between T1-relaxation times/T2-relaxation times metrics and gestational age at MR imaging. Intraclass correlation coefficients were calculated to assess the consistency of the results provided by both modalities. RESULTS: Both modalities provided quantitative data that revealed negative correlations with gestational age at MR imaging: Synthetic MR imaging–derived relaxation times (medulla oblongata [r = −0.459; P = .021]; midbrain [r = −0.413; P = .040]), T2-relaxation times (medulla oblongata [r = −0.625; P < .001]; midbrain [r = −0.571; P = .003]), and MR fingerprinting–derived T1-relaxation times (medulla oblongata [r = −0.433; P = .035]; midbrain [r = −0.386; P = .062]), and T2-relaxation times (medulla oblongata [r =−0.883; P < .001]; midbrain [r = −0.890; P < .001]).The intraclass correlation coefficient analysis for result consistency between both MR approaches ranged between 0.661 (95% CI, 0.351–0.841) (T2-relaxation times: medulla oblongata) and 0.920 (95% CI, 0.82–0.965) (T1-relaxation times: midbrain). CONCLUSIONS: There is a good-to-excellent consistency between postmortem Synthetic MR imaging and MR fingerprinting myelin quantifications in fetal brains older than 15 + 1 gestational age. The strong correlations between quantitative myelin metrics and gestational age indicate the potential of quantitative MR imaging to identify delayed or abnormal states of myelination at prenatal stages of cerebral development.

This study analyzed subgroups of women with overactive bladder syndrome or mixed urinary incontinence to assess treatment success, time to success, therapy adherence, and demographic and clinical characteristics. This retrospective cohort study was conducted with 1688 female patients diagnosed with overactive bladder or mixed incontinence. Data on patient demographics, clinical characteristics, treatment modalities, and outcomes were analyzed using descriptive statistics and Kaplan-Meier survival analysis. Treatment success levels were categorized into no success, partial success, and complete success. Time to success was assessed using Kaplan-Meier curves. Demographic and clinical characteristics influencing outcomes were evaluated. Patients with mixed incontinence were younger, had a higher body mass index (BMI), had more comorbidities, and had more severe symptoms than those with isolated overactive bladder. Patients with overactive bladder were more often postmenopausal and had better early treatment success. Most patients improved early, though some required long-term follow-up. Significant differences in treatment utilization and outcomes were observed between subgroups. Polypharmacy, obesity, nocturia, and a diagnosis of mixed incontinence were associated with lower rates of success. Local estrogen, subtype of overactive bladder, and fewer medications predicted better outcomes and earlier response. Personalized treatment strategies tailored to patient demographics and treatment history are crucial in managing overactive bladder and mixed incontinence effectively. The findings underscore the importance of long-term adherence to therapy and highlight areas for refining therapeutic interventions to optimize patient outcomes.

The aim of this study was to evaluate the endocervical margin status according to transformation zone (TZ) and high-risk HPV (hr-HPV) subtype in specimens with cone length ≤ 10 mm versus > 10 mm to provide data for informed decision making and patients counseling especially for women wishing to conceive. In this retrospective cohort study, 854 patients who underwent large loop excision of the transformation zone during a nine-year period (2013–2021) for cervical disease were analyzed. The main outcome parameters were excision length, histological result, TZ type, HPV subtype and endocervical margin status. A subgroup analysis was performed according to excision length, with a cut-off value of 10 mm. A two-step surgical procedure was performed in case of an excision length of > 10 mm. The overall rate of positive endocervical margins irrespective of excision length was 17.2%, with 19.3% in specimens with ≤ 10 mm and 15.0% with > 10 mm excision length. Overall, 41.2% of women with a visible TZ and HPV 16/hr infection and 27.0% of women with HPV 18 received an excisional treatment of > 10 mm length without further oncological benefit, respectively. In contrast, assuming that only an excision of ≤ 10 mm length had been performed in women with visible TZ, the rate of clear endocervical margins would have been 63.7% for HPV 16/hr infections and 49.3% for HPV 18 infections. In conclusion, the decision about excision length should be discussed with the patient in terms of oncological safety and the risk of adverse pregnancy events. An excision length > 10 mm increases the number of cases with cervical tissue removed without further oncological benefit, which needs to be taken into account in order to provide an individual therapeutic approach. Furthermore, HPV 18 positivity is related to a higher rate of positive endocervical margins irrespective of TZ.

Einleitung Die Systemtherapie fortgeschrittener oder rezidivierter Vaginal- und Vulvakarzinome wird aufgrund der limitierten Evidenz zumeist in Analogie des Zervixkarzinoms durchgeführt. Platinbasierte Chemotherapien zeigen bei Patientinnen mit Vaginal- und Vulvakarzinomen jedoch nur eingeschränkte Ansprechraten. Checkpointinhibitoren weisen eine vielversprechende klinische Wirksamkeit in der Monotherapie des Vulvakarzinoms auf; analog zu den positiven Ergebnissen der KEYNOTE-826 Studie des Zervixkarzinoms könnte eine kombinierte Chemo- und Immuntherapie auch für Vaginal- und Vulvakarzinome eine Therapieoption darstellen. Material und Methoden Die vorliegende Fallserie beschreibt den klinischen Verlauf jeweils zweier Patientinnen mit PD-L1 positivem, rezidiviertem Vulva- bzw. Vaginalkarzinom, die analog zur KEYNOTE-826 eine kombinierte Chemo- und Immuntherapie (Carboplatin AUC 5 + Paclitaxel 175mg KOF +/– Bevacizumab 15mg/kg KG + Pembrolizumab 200mg 3qw fixed-dose) erhielten [1]. Das Therapieansprechen wurde nach iRECIST mittels CT-Thorax/Abdomen dokumentiert. Alle Tumore wurden mittels TruSight Oncology 500 Assay sequenziert und eine Tumor Mutational Burden (TMB)-Analyse und eine HPV-Typisierung durchgeführt. Ergebnisse Die Vierfach-Kombinationstherapie mit Pembrolizumab zeigte sich für alle Patientinnen ohne Hinweise auf immunassoziierte Nebenwirkungen gut verträglich. Alle Tumore waren Mikrosatelliten-stabil und zeigten eine niedrige TMB (<10 Mutationen/ Megabase). Drei Patientinnen waren HPV-positiv, ein Vulvakarzinom mit Lichen Sclerosus assoziiert. Drei Patientinnen (75.0%) erhielten alle geplanten sechs Zyklen Carboplatin/Paclitaxel, eine Patientin (25.0%) verstarb in Folge eines ausgedehnten Progresses (PD, N. vaginae, PEC) nach 3 Zyklen. Im Restaging zeigte sich nach 4 Zyklen ein partielles Ansprechen (PR, N. vulvae, PEC, HPV negativ), eine stabile Erkrankung (SD, N. vaginae, PEC) und eine unbestätigte Progression („immune unconfirmed“ PD, N. vulvae, adenosquamös). Eine Patientin (25.0%, initial PR) ist weiterhin in Remission und erhält Pembrolizumab/ Bevacizumab als Erhaltungstherapie (PFS 4 Monate), zwei Patientinnen (50.0%) rezidivierten nach 7 (initial uPD) bzw. 8 Monaten (initial SD). Zusammenfassung Die Zugabe von Pembrolizumab zur platinbasierten Kombinationschemotherapie mit Bevacizumab zeigt sich für Patientinnen mit Vaginal- und Vulvakarzinomen klinisch gut verträglich. Eine weiterführende klinische Evaluierung der Therapiekombination erscheint vielversprechend. Article published online: 05 April 2023 © 2023. Thieme. All rights reserved. Georg Thieme Verlag Rüdigerstraße 14, 70469 Stuttgart, Germany