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Simple Summary: In patients with locally advanced cervical cancer, the availability of imaging techniques for accurately defining the residual tumor would be clinically relevant for selecting patients who could be offered a more tailored surgery. The novelty of this prospective study is the development of multiparametric predictive models of histopathological response using a unique data set with three imaging modalities (transvaginal ultrasound, magnetic resonance (MRI) and 18F-FDG-PET/CT) evaluated at three time points ("baseline", two ("early") and five ("final") weeks after treatment). In a cohort of 88 patients, the predictive models retrieved integrating morphometric, vascular, perfusion and metabolic parameters, demonstrated that two imaging approaches (MRI and PET/CT at "final" evaluation or PET/CT at "baseline" and "final" evaluation) are sufficient to identify possible residual disease after chemotherapy. These findings could be useful in selecting patients with residual disease, helping clinicians to tailor the radicality of the surgical approach. Purpose: This study aimed to develop predictive models for pathological residual disease after neoadjuvant chemoradiation (CRT) in locally advanced cervical cancer (LACC) by integrating parameters derived from transvaginal ultrasound, MRI and PET/CT imaging at different time points and time intervals. Methods: Patients with histologically proven LACC, stage IB2–IVA, were prospectively enrolled. For each patient, the three examinations were performed before, 2 and 5 weeks after treatment ("baseline", "early" and "final", respectively). Multivariable logistic regression models to predict complete vs. partial pathological response (pR) were developed and a cost analysis was performed. Results: Between October 2010 and June 2014, 88 patients were included. Complete or partial pR was found in 45.5% and 54.5% of patients, respectively. The two most clinically useful models in pR prediction were (1) using percentage variation of SUVmax retrieved at PET/CT "baseline" and "final" examination, and (2) including high DWI signal intensity (SI) plus, ADC, and SUVmax collected at "final" evaluation (area under the curve (95% Confidence Interval): 0.80 (0.71–0.90) and 0.81 (0.72–0.90), respectively). Conclusion: The percentage variation in SUVmax in the time interval before and after completing neoadjuvant CRT, as well as DWI SI plus ADC and SUVmax obtained after completing neoadjuvant CRT, could be used to predict residual cervical cancer in LACC patients. From a cost point of view, the use of MRI and PET/CT is preferable. [ABSTRACT FROM AUTHOR]

Simple Summary: This study investigated the immunohistochemical expression of 14 biological markers as potential prognostic/therapeutic factors in vulvar squamous cell carcinoma, comparing 53 node-negative (Group A) and 48 node-positive (Group B) patients. Our results show a significantly higher p16 expression (surrogate of HPV-related tumors) in the vulvar samples of non-metastatic patients. In Group B, PD-L1 positivity and high EGFR expression were found in the vast majority of vulvar and/or nodal specimens. VEGF showed strong/moderate-diffuse expression in almost 14% of all vulvar samples. A mutated p53 and over-expressed PD-L1 showed a significant association with nodal metastasis. Our results support a potential role of immune checkpoint inhibitors and anti-VEGF and anti-EGFR drugs, especially in patients with worse prognosis (metastatic, HPV-independent). A panel including EGFR, VEGF, PDL1, p16, and p53 might be performed routinely in primary tumor and repeated in case of lymph node metastases to identify changes in marker expression. Introduction: The study's aim was to investigate the immunohistochemical (IHC) expression of biological markers as potential prognostic/therapeutic factors in vulvar squamous cell carcinoma (VSCC). Methodology: A series of 101 patients surgically treated at our center from 2016 to 2020 were retrospectively enrolled: 53 node-negative (Group A) and 48 node-positive (Group B). A total of 146 samples, 101 from primary tumor (T) and 45 from nodal metastases (N), were investigated. The IHC panel included: p16, p53, MLH1, MSH2, MSH6, PMS2, PD-L1, CD3, HER2/neu, ER, PR, EGFR, VEGF, and CD31. The reactions were evaluated on qualitative and semi-quantitative scales. Generalized Linear Model (GLM) and cluster analysis were performed in R statistical environment. A distance plot compared the IHC panel of T with the correspondent N. Results: In Group A: p16-positive expression (surrogate of HPV-dependent pathway) was significantly higher (20.8% vs. 6.2%, p = 0.04). In Group B: PD-L1 positivity and high EGFR expression were found, respectively, in 77.1% and 97.9% patients (T and/or N). Overall, p16-negative tumors showed a higher PD-L1 expression (60.9% vs. 50.0%). In both groups: tumoral immune infiltration (CD3 expression) was mainly moderate/intense (80% vs. 95%); VEGF showed strong/moderate-diffuse expression in 13.9% of T samples; CD31, related to tumoral microvessel density (MVD), showed no difference between groups; a mutated p53 and over-expressed PD-L1 showed significant association with nodal metastasis, with Odds Ratios (OR) of 4.26 (CI 95% = 1.14–15.87, p = 0.03) and 2.68 (CI 95% = 1.0–7.19, p < 0.05), respectively; since all mismatch repair proteins (MMR) showed a retained expression and ER, PR, and HER2/neu were negative, they were excluded from further analysis. The cluster analysis identified three and four sub-groups of molecular profiles, respectively, in Group A and B, with no difference in prognosis. The molecular signature of each N and corresponding T diverged significantly in 18/41 (43.9%) cases. Conclusions: Our results support a potential role of immune checkpoint inhibitors and anti-VEGF and anti-EGFR drugs especially in patients with worse prognosis (metastatic, HPV-independent). A panel including EGFR, VEGF, PDL1, p16, and p53 might be performed routinely in primary tumor and repeated in case of lymph node metastases to identify changes in marker expression. [ABSTRACT FROM AUTHOR]

Simple Summary: Endometrial cancer (EC) reportedly have a better prognosis in patients with coexistent adenomyosis. It is possible to hypothesize that this difference may be attributable to different clinical profiles. On this account, we aimed to define the clinical profile of endometrial cancer (EC) patients with and without adenomyosis through a systematic review and meta-analysis. We included 8 studies with 5681 patients and found that EC women with adenomyosis were less likely to be nulliparous than EC women without adenomyosis, while no significant differences were found with regard to age, BMI, and premenopausal status. A better endometrial cancer (EC) prognosis in patients with coexistent adenomyosis has been reported. Unfortunately, it is still unclear if this better prognosis is related to a more favorable clinical profile of adenomyosis patients. We aimed to evaluate differences in the clinical profiles of EC patients with and without adenomyosis. A systematic review and meta-analysis was performed by searching seven electronics databases for all studies that allowed extraction of data about clinical characteristics in EC patients with and without adenomyosis. Clinical characteristics assessed were: age, Body Mass Index (BMI), premenopausal status, and nulliparity. Mean difference in mean ± standard deviation (SD) or odds ratio (OR) for clinical characteristics between EC patients with and without adenomyosis were calculated for each included study and as a pooled estimate, and graphically reported on forest plots with a 95% confidence interval (CI). The Z test was used for assessing the overall effect by considering a p value < 0.05 as significant. Overall, eight studies with 5681 patients were included in the qualitative analysis, and seven studies with 4366 patients in the quantitative analysis. Pooled mean difference in mean ± SD between EC women with and without adenomyosis was −1.19 (95% CI: −3.18 to 0.80; p = 0.24) for age, and 0.23 (95% CI: −0.62 to 1.07; p = 0.60) for BMI. When compared to EC women without adenomyosis, EC women with adenomyosis showed a pooled OR of 1.53 (95% CI: 0.92 to 2.54; p = 0.10) for premenopausal status, and of 0.60 (95% CI: 0.41 to 0.87; p = 0.007) for nulliparity. In conclusion, there are not significant differences in clinical characteristics between EC patients with and without adenomyosis, with the exception for nulliparity. Clinical features seem to not underlie the better EC prognosis of patients with adenomyosis compared to patients without adenomyosis. [ABSTRACT FROM AUTHOR]