Valentina Bruno

Dissecting endometrial cancer complexity in response to standard and targeted therapies

Abstract Endometrial cancer (EC) is one of the most common gynecologic malignancies amongst women worldwide. Its incidence and mortality rates have been increasing in the last decade. In the present work, we built a patient EC-derived organoid (PDOs) platform that faithfully recapitulated tumor phenotype, genomic alterations, and expression profiles of matched-primary cancer tissues. Interestingly, we found that the response of EC-derived PDOs to both standard therapy and a wide range of targeted drugs accordingly to their specific druggable genetic alterations was congruent with that of the originating patients. We also isolated and genomically characterized matched-PDO stromal cells, specifically cancer-associated fibroblasts (CAFs). Unlike PDOs matched CAFs were poorly responsive and underwent to pro-inflammatory senescence upon treatment with standard therapy. Collectively, our findings established a EC-PDOs preclinical platform which allows assessing the therapeutic response of tumor and surrounding tumor microenvironment cellular landscape.

Robotic-assisted single-port and multi-port surgical staging in early-stage endometrial cancer: a propensity matched comparison.

Robotic-assisted surgery has emerged as an effective method for managing endometrial cancer. Recently, the new Da Vinci Single-Port (SP) was developed with the aim of minimizing surgery-related morbidity, using a single-port approach. The present research evaluated outcomes of apparent early-stage endometrial cancer patients undergoing single- and multi-port robotic-assisted surgery. This is a retrospective study. Data of consecutive patients affected by early-stage endometrial cancer who had robotic-assisted staging (including hysterectomy, bilateral salpingo-oophorectomy and nodal staging) with Da Vinci SP were matched 1:1 with a cohort of patients undergoing robotic-assisted surgery with the multi-port Da Vinci Xi. The matching was conducted by a propensity-score comparison. Fifty patient pairs (50 undergoing single-port surgical staging vs. 50 undergoing multiple-port surgical staging) were included. Demographic and baseline characteristics were balanced between groups. Median (skin to skin) operative time (minutes) was similar between groups (120 (range, 70-229) in the single-port vs. 115 (range, 60-205) in the multi-port group; p = 0.367). Estimated blood loss was comparable between groups (p = 0.317). No intra-operative complications or intra-operative blood transfusions were recorded. The median length of hospital stay was similar between groups (p = 0.269). Overall, 10 (10 %) patients developed 90-day surgery-related complications: six (12 %) and four (8 %) in the single- and multi-port group, respectively (p = 0.740). One (2 %) and two (4 %) patients experienced severe (grade 3 or more) 90-day complications after single- and multi-port robotic-assisted staging (p = 1.00). Introducing Da Vinci SP appears to be safe and feasible. The single-port approach does not increase operative time and complication rates in comparison to the multi-port robotic-assisted system.

The impact of Substantial LYMphovascular space invasion on sentinel lymph nodes status and recurrence in Endometrial Cancer patients: SLYM-EC a multicenter retrospective study

To evaluate the prognostic impact of substantial lymph vascular space invasion (LVSI) on the sentinel lymph node involvement and recurrence rate of patients with apparent uterine-confined endometrial cancer. We enrolled consecutive patients with apparent confined endometrial cancer who underwent surgical staging with sentinel node mapping from 14 European reference centers. LVSI was analyzed semi-quantitatively, according to a 3-tiered scoring system classified as absent, focal, and substantial. Among 2352 eligible patients, 1980 were included in the analysis. Upon final pathology 226 patients (11.4 %) had SLNs involvement. LVSI was diagnosed focal in 152 patients (7.7 %), whereas 357 patients (18.0 %) showed substantial LVSI. Focal or substantial LVSI rate were significantly higher in patients with positive SLNs when compared to patients without SLNs involvement (p < 0.0001). On overall patient-based analysis, the sensitivity, specificity, positive predictive value, and negative predictive value of LVSI for sentinel lymph node metastases were 73 %, 80 %, 32 %, and 96 %, respectively. The 3-year multivariate analysis of recurrence-free survival showed that only the presence of substantial LVSI, and grade 3 disease were associated with relapse. Neither positive sentinel lymph node, deep myometrial infiltration, nor age at surgery were statistically significant. In patients having undergone sentinel node biopsy, positive LVSI demonstrated moderate sensitivity and reasonable specificity in detecting SLN involvement. LVSI positivity does not correlate with nodal involvement. The presence of substantial LVSI remains a strong independent risk factor for recurrence, indicating a role for potential hematogenous dissemination in patients with early-stage disease.