Valentina Iacobelli

Molecular and biological profile may discriminate between synchronous or metachronous endometrial and ovarian cancer

Nomogram to predict feasibility of minimally invasive interval debulking surgery in advanced ovarian cancer

Currently, there is no clear guidance defining the ideal candidate for minimally invasive interval debulking surgery. This study aimed to identify predictive factors for a minimally invasive approach in patients with advanced ovarian cancer who are candidates for interval debulking surgery after neoadjuvant chemotherapy. This was a single institution retrospective study conducted between January 2014 and June 2020 Perioperative variables were used to predict the likelihood of minimally invasive interval debulking surgery using multivariable models. A nomogram was developed, and internal validation was performed using the bootstrapping correction technique. This nomogram was built to visualize the effect of perioperative variables on the estimated probability of minimally invasive interval debulking surgery in patients with a clinical response after neoadjuvant chemotherapy. We used the four significant perioperative variables according to logistic regression. A total of 108 (28.4%) and 272 (71.6%) patients underwent interval debulking surgery by a minimally invasive or open approach, respectively. Absence of omental cake (odds ratio (OR) 9.15, 95% confidence interval (CI) 4.26 to 19.64, p<0.001), high volume surgeon (OR 5.43, 95% CI 2.75 to 10.71, p<0.001), less than two peritoneal sites involved (OR 2.94, 95% CI 1.34 to 6.43, p=0.007), and CA125 normalization (OR 1.79, 95% CI 1.05 to 3.36, p=0.049) correlated with the feasibility of minimally invasive interval debulking surgery at multivariate analysis. The calibration plot demonstrated good agreement between the predicted and actual probability of minimally invasive interval debulking surgery (p=0.93, Hosmer-Lemeshow test). Our nomogram may serve as a useful tool to choose the surgical approach in patients with advanced ovarian cancer undergoing interval debulking surgery.

Gene actionability according to the ESMO Scale for Clinical Actionability of molecular Targets (ESCAT) in No Specific Molecular Profile (NSMP) endometrial cancer

The No Specific Molecular Profile (NSMP) subtype accounts for ∼30%-40% of endometrial cancer (EC), comprising a heterogeneous group of EC. The primary outcome of this study was the prevalence of actionable genomic alterations in NSMP EC, classified according to the European Society for Medical Oncology (ESMO) Scale for Clinical Actionability of molecular Targets (ESCAT). Oncogenic and likely oncogenic alterations, pathways, and co-mutation patterns were reported. The analysis was stratified by risk group according to the European Society of Gynaecological Oncology (ESGO)-ESMO-European SocieTy for Radiotherapy and Oncology (ESTRO) guidelines. Patients with NSMP EC enrolled in the FPG500 comprehensive cancer genome profiling program (NCT06020625) were included. Two hundred and fifty-three patients with NSMP EC of any International Federation of Gynecology and Obstetrics (FIGO) stage were enrolled between 1 January 2022 and 31 December 2023. Median age was 62 years, and the most frequent histotype was endometrioid (97%). Ninety-five percent of patients were estrogen receptor positive. Two hundred and thirty-three patients (92%) had at least one ESCAT tier I-III alteration. The most frequent variants were in PTEN [88%, 95% confidence interval (CI) 84% to 92%], PIK3CA (42%, 95% CI 36% to 49%), FGFR2 (15%, 95% CI 11% to 20%), and AKT1 (6%, 95% CI 3% to 10%); 4% (95% CI 2% to 8%) of patients had an ESR1 variant, while KRAS G12C was found in 3% (95% CI 1% to 6%) of patients. The majority of PTEN variants were on the R130 hotspot. More frequent PIK3CA hotspot variants were H1047R (9%), E545D/K/Q/A (6%), and E542K (4%). In the overall population, PIK3CA with PIK3R1 (odds ratio [OR] = 0.07, P value = 4.25 × 10 Our findings highlight potentially actionable alterations in NSMP EC patients, supporting the exploration of tailored molecular-matched therapies according to risk groups.