Barbara Costantini

Exploring PIPAC for managing platinum resistant and refractory ovarian cancer with peritoneal spread: A collaborative multi-institutional study

Platinum-resistant or refractory epithelial ovarian cancer (EOC) remains a significant clinical challenge, often leading to rapid progression and poor prognosis. Palliative treatments aimed at improving quality of life are warranted. To assess the feasibility and potential benefits of Pressurized IntraPeritoneal Aerosol Chemotherapy (PIPAC) in patients with platinum-resistant or refractory EOC. Prospective multicenter observational study (2016-2023). feasibility, defined as completion of ≥3 planned PIPAC cycles within 120 days without ≥ grade 3 treatment related adverse events (CTCAE v5.0). Secondary endpoints: safety; disease control (RECIST 1.1); changes in Peritoneal Cancer Index and Fagotti score; ascites control; CA-125 response; conversion to cytoreductive surgery (±HIPEC); and overall survival (OS). Forty patients were enrolled. Ninety-seven percent of procedures were completed. Feasibility was 65.0 % (26/40; 95 % CI 49.51-77.87); no grade ≥3 events occurred. Key secondary outcomes included a clinical benefit rate of 35 % in the intention-to-treat (ITT) population and 53.8 % in the per-protocol (PP) population, median time to ascites resolution of one cycle, and median overall survival of 14 months (17 months in PP). Higher white blood cell count and ascites volume were significantly associated with progression (p = 0.035 and p = 0.025). Three platinum-refractory patients became eligible for surgery, two underwent optimal cytoreduction. Median OS was 14 months (17 months in PP). A non-significant trend toward longer OS was observed in platinum-refractory versus platinum-resistant disease (18 vs 9 months; p = 0.093). PIPAC is a feasible, well-tolerated option in platinum-resistant and refractory EOC with potential to stabilize disease, relieve ascites and enable surgery in selected cases.

Failure of early interval debulking surgery after standard neoadjuvant chemotherapy: May bevacizumab add something? A large retrospective study

Data are limited on the use of bevacizumab in neoadjuvant setting for High-Grade Serous ovarian Cancer (HGSC) patients. This study explores the effect of adding bevacizumab to standard neoadjuvant chemotherapy (NACT) following the failure of early Interval Debulking Surgery (eIDS). This monocentric study retrospectively enrolled FIGO stage IIIC-IV HGSC patients (2017-2021), persisting unresectable after three NACT cycles. Eligible patients had an ECOG performance status ≤2, were aged 40-75 years, and had no contraindications to bevacizumab administration. Patients were stratified whether they added bevacizumab from cycles 4 to 6 (CPB group) or not (CP group). The primary endpoint was the cytoreduction rate after six cycles (delayed IDS, dIDS). Overall, 58(23 %) patients received neoadjuvant bevacizumab(CPB), and 190 (77 %) did not (CP). Delayed IDS was performed in 117(47.6 %) patients (CPB:31-53.4 %; CP:86-45.8 %; p = 0.38), with complete gross resection rates of 83.9 % and 88.5 %, respectively (p = 0.72). Severe postoperative complications were comparable (CP: 8 %, CPB: 9.7 %, p = 0.069). Median overall survival (OS) for dIDS patients showed no significant difference (CPB: not reached, CP:38 months, p = 0.55), nor did progression-free survival (PFS; CPB:14 months, CP:12 months, p = 0.830). Conversely, among 130(52 %) patients persisting unresectable, bevacizumab significantly improved OS in the CPB group (not reached vs.18 months, p = 0.015), although PFS remained similar (CPB: 6 months, CP: 7 months, p = 0.741). While adding bevacizumab to NACT does not seem to increase the dIDS rate, it significantly extends OS in unresectable patients. Its use may be a valuable option in selected cases after eIDS' failure.

Hyperthermic Intraperitoneal Chemotherapy in Platinum-Sensitive Recurrent Ovarian Cancer: A Randomized Trial on Survival Evaluation (HORSE; MITO-18)

PURPOSE To investigate whether the addition of hyperthermic intraperitoneal chemotherapy (HIPEC) to secondary cytoreductive surgery (SCS) without neoadjuvant chemotherapy has a benefit on progression-free survival (PFS), as opposed to SCS alone in patients with platinum-sensitive recurrent epithelial ovarian cancer (platinum-free interval, >6 months). METHODS This was a multicenter randomized phase III study. Random assignment was performed at the time of surgery in cases with residual tumor ≤0.25 cm. HIPEC with cisplatin (CDDP) 75 mg/m 2 for 60 minutes at 41.5°C was administered at the end of surgery in the experimental arm. Both groups received postoperative platinum-based chemotherapy. The primary end point was PFS. The safety profile and postrecurrence survival (PRS) were the secondary end points. RESULTS A total of 167 patients underwent random assignment, 82 patients to SCS plus HIPEC (experimental arm) and 85 to SCS alone (control arm). The median follow-up was 83 months (IQR, 64-102). The median PFS was 23 months (95% CI, 17 to 29) in the group that underwent surgery alone and 25 months (95% CI, 18 to 32) in the group that underwent cytoreductive surgery with HIPEC. The probability of PRS at 5 years was 61.6% (95% CI, 50.8 to 72.4) in the SCS group and 75.9% (95% CI, 66.5 to 85.3) in the SCS plus HIPEC group. The incidence of postoperative adverse events of any grade was similar between the two groups. CONCLUSION The addition of HIPEC to complete or nearly complete primary SCS did not confer a benefit in terms of PFS in patients with platinum-sensitive peritoneal recurrence.

Predictive factors of surgical complications after pelvic exenteration for gynecological malignancies: a large single-institution experience

To evaluate pre-operative predictors of early (<30 days) severe complications (grade Dindo 3+) in patients with gynecological malignancy submitted to pelvic exenteration (PE). We retrospectively analyzed 129 patients submitted to surgery at Fondazione Policlinico Gemelli between 2010 and 2019. We included patients affected by primary or recurrent/persistent cervical, endometrial, or vulvar/vaginal cancers. Post-operative complications were graded according to the Dindo classification. Logistic regression was used to analyze potential predictors of complications. We performed 63 anterior PE, 10 posterior PE, and 56 total PE. The incidence of early severe post-operative complications was 27.9% (n=36), and the early mortality rate was 2.3% (n=3). More frequent complications were related to the urinary diversion and intestinal surgery. In univariable analysis, hemoglobin ≤10 g/dL (odds ratio [OR]=4.2; 95% confidence interval [CI]=1.65-10.7; p=0.003), low albumin levels (OR=3.9; 95% CI=1.27-12.11; p=0.025), diabetes (OR=4.15; 95% CI=1.22-14.1; p=0.022), 2+ comorbidities at presentation (OR=5.18; 95% CI=1.49-17.93; p=0.012) were predictors of early severe complications. In multivariable analysis, only low hemoglobin and comorbidities at presentation were independent predictors of complications. Pelvic exenteration is an aggressive surgery characterized by a high rate of post-operative complications. Pre-operative assessment of comorbidities and patient health status are crucial to better select the right candidate for this type of surgery.

Hyperthermic Intra-peritoneal Chemotherapy (HIPEC) in Ovarian Cancer Recurrence

The purpose of this study is to determine the role of surgery followed by hyperthermic intra-peritoneal chemotherapy (HIPEC) versus surgery alone in patients with platinum-sensitive first recurrence of ovarian cancer. Moreover it is a prospective randomized multicenter trial, aimed to investigate the prognostic role of surgery plus HIPEC versus surgery alone in terms of progression free interval, overall survival, morbidity and mortality, second recurrence pattern, quality of life with EORTC QLQ-C30 and QLQ OV28 questionnaires.