Matteo Bruno

Gliomatosis peritonei with ovarian teratoma: an international multicenter case series

Gliomatosis peritonei (GP) is a rare condition characterized by peritoneal implants of mature glial tissue, macroscopically resembling peritoneal carcinomatosis. It is usually associated with ovarian mature or immature teratoma. To describe the clinical characteristics, treatment, and prognosis of cases with GP. Multi-center retrospective study of patients diagnosed with ovarian teratoma and GP between 2000 and 2023. Non-gynecological GP cases were excluded. Overall, 23 patients were included. Median age was 25 years (range; 10-38). Median ovarian tumor size was 19 cm (range; 6-35). The main symptom was abdominal pain (n = 13). Histology was mature teratoma in 13% (n = 3), and immature teratoma in 87% (n = 20) of cases, of which 90% (n = 18) was pure teratomas and 10% (n = 2) was mixed with yolk sac tumor. Overall, 60% were grade 3. Fertility-sparing surgery was performed in 87% (n = 20, of them 18 underwent unilateral salpingo-oophorectomy and 2 cystectomy ± further biopsies) without macroscopic residual disease in 91% (n = 21), and 78% (n = 18) were diagnosed at stage I. Adjuvant chemotherapy was given in 7 cases, only with grade 2 or more. Twelve women relapsed after a median of 43 months. However, only 2 relapses had immature teratoma components. Three patients had a second relapse after a median of 9 months. Over a median follow-up of 81 months (range; 7-270), the entire cohort remained alive and 3 live births were reported. GP is mostly associated with high-grade early-stage immature teratoma in young patients. Resection of peritoneal implants is crucial for the accurate diagnosis and optimal treatment planning. Relapses are mostly mature, therefore, offering fertility-sparing treatment in pre-menopausal cases could be considered.

Real-life observational study on niraparib in older patients with primary tubo-ovarian cancer: a focus on safety and efficacy

Abstract Background Niraparib is approved for maintenance treatment of tubo-ovarian cancer patients, but data on older patients are limited. This retrospective study evaluated its safety and efficacy in primary advanced tubo-ovarian cancer, focusing on patients ≥ 75 years. Methods Women aged ≥ 50 years diagnosed with primary high-grade serous tubo-ovarian cancer, treated with niraparib between 2019–2023, were enrolled. Patients were stratified into three groups: A (50–64 years), B (65–74 years), and C (≥ 75 years). The primary outcome was progression-free survival. The secondary outcomes were toxicity and dose reduction. Results 127 patients were identified: 62 (48.8%) group A, 26 (20.5%) group B, and 39 (30.7%) group C. Baseline characteristics were comparable across groups, excluding a higher proportion of interval cytoreductive surgeries ( p  = 0.001), residual tumor ( p  = 0.01) and Eastern Cooperative Oncology Group (ECOG) > 1 ( p  = 0.01) in group C. Most patients started niraparib at 200 mg/day with dose reductions primarily occurred within fourth cycle. Dose reductions were observed in 77.4%, 69.2% and 56.4% of patients in groups A, B, and C, respectively ( p  = 0.08). In patients ≥ 75 years, 26 (66.7%) discontinued treatment due to disease progression (48.7%) or toxicity (17.9%). There were no significant differences in common or grade ≥ 3 adverse events between groups. Progression-free survival was 12 months (95%CI: 2.0–25.0) for group A, 29 months (95%CI: 11.0–52.0) for group B, and 16 months (95%CI: 1.0–31.0) for group C ( p  = 0.78). Conclusions Our findings suggest that niraparib is safe and well-tolerated in aged ≥ 75 years. Concerns about toxicity should not preclude the enrollment of elderly patients in treatment regiments.

Comprehensive genomic profiling and clinico-pathologic characterization of primary ovarian leiomyosarcoma

Primary ovarian leiomyosarcomas are exceptionally rare, accounting for less than 0.1% of ovarian malignancies. Their treatment strategies remain poorly defined, and data on comprehensive genomic profiling are lacking. This study aims to characterize the pathological features and genomic landscape of primary ovarian leiomyosarcoma, highlighting similarities with uterine leiomyosarcomas based on available literature. We retrospectively analyzed 7 histologically confirmed cases of primary ovarian leiomyosarcoma diagnosed between 2013 and 2023 at a tertiary referral center. Clinical data, histopathological findings, and immunohistochemical profiles were reviewed. Genomic profiling was performed using the TruSight Oncology 500 assay, targeting 523 cancer-related genes. Only oncogenic or likely oncogenic alterations (Tier classification system I-II) were considered. All patients had International Federation of Gynecology and Obstetrics stage IA disease and underwent radical surgery. Two patients experienced pelvic recurrence; both showed increased Ki-67 and complete loss of estrogen and progesterone receptors in the relapsed tumors. Histologically, tumors exhibited spindle or epithelioid morphology with variable atypia and mitotic indices. Genomic profiling revealed a high prevalence of TP53 (71%) and PTEN (57%) alterations. Additional copy number alterations were identified in homologous recombination repair genes (BRCA2, CHEK1/2, and ATM), fibroblast growth factor (FGF) family members (FGF7/9/14), and platelet-derived growth factor receptor beta. Tumor mutational burden was low to medium in all cases, and microsatellite status was stable. Primary ovarian leiomyosarcomas exhibit a complex genomic landscape marked by genomic instability, sharing key alterations with uterine leiomyosarcomas. TP53 and PTEN mutations may play a central role in their pathogenesis. This first genomic profiling analysis of ovarian leiomyosarcomas provides a basis for further research and potential targeted therapeutic approaches in this rare malignancy.

Reply to: 'Enhancing cervical cancer surveillance: Utilizing inflammatory markers for improved recurrence detection in low-resource settings and a call for prospective multi-centric studies'

The potential role of systemic inflammatory markers in predicting recurrence in early-stage cervical cancer

The influence of systemic inflammatory markers on early-stage cervical cancer (ECC) patients is contradictory. No previous study analyzed whether these markers may be suggestive of recurrence. The aim of this study was to assess whether the inflammatory markers level of patients with recurrence during surveillance was different from those of patients without recurrence representing a risk factor for recurrence. Retrospective, single-center, observational study. Patients with 2009 FIGO EEC surgically treated between 2012 and 2019 were included. Baseline inflammatory markers were evaluated on the results of the complete blood count (CBC) and coagulation tests. Inflammatory markers of relapsed patients were evaluated on the last CBC performed before the relapse diagnosis. Inflammatory markers of patients with no recurrence were evaluated on the available CBC taken at the same median follow-up time as the one from relapsed patients. 174 patients were included. Baseline Systemic immune inflammation index (SII) > 663 and Systemic inflammation response index (SIRI) > 0.98 were associated with significant risk of recurrence. SII>663 and Neutrophil to lymphocyte ratio (NLR) > 2.41 were associated with increased risk of death. Significant changes between relapsed (n = 23) and non-relapsed (n = 151) patients in median values of SII (615 versus 490, p-value = 0.001), SIRI (0.74 versus 1.05, p-value = 0.005), NRL (2.95 versus 2.15, p-value = 0.0035), and MLR (0.26 versus 0.22 p-value = 0.020), showed that different levels of inflammatory markers could help identifying recurrent disease during surveillance. Baseline SII>663 and SIRI>0.98 were associated with increased risk of recurrence. Higher median values of SII, SIRI, NLR and MLR in relapsed patients highlight their potential association with recurrence.

Robotic approach for the treatment of gynecological cancers recurrences: A ten-year single-institution experience.

Although the management of gynecological cancers recurrences may be challenging, due to the heterogeneity of recurrent disease, the aim of this work is to present a descriptive analysis of gynecological malignancies recurrences in our institution treated by robotic approach. We performed a retrospective review and analysis of data of patients who underwent robotic surgery for recurrent gynecological malignancies at Catholic University of the Sacred Hearth, Rome, from January 2013 to January 2024. A total of 54 patients underwent successful robotic cytoreductive surgery. The median age was 63 years; the median BMI was 33 kg/m Robotic approach in the treatment of recurrent gynecological cancers should be considered in selected patients with oligometastatic disease, in high-volume centers with expert surgeons, particularly in obese patients.

Olaparib dose reduction in BRCA-mutated platinum-sensitive ovarian cancer recurrence: real-world data.

The poly (adenosine diphosphate-ribose) polymerase inhibitor olaparib has demonstrated significant efficacy in treating patients with BRCA-mutated patients with ovarian cancer. However, adverse events, particularly hematologic toxicities, often necessitate dose reduction or treatment interruption. Our study investigates the survival outcomes associated with olaparib dose reduction in patients with recurrent ovarian cancer in a real-world setting. We conducted a retrospective analysis on patients with BRCA-mutated ovarian cancer treated with olaparib in a recurrent setting from 2019 to 2022. Patients were categorized based on dose-reduction status: no reduction (olaparib 600 mg; group 1), dose reduction level 1 (olaparib 500 mg; group 2), and dose reduction level 2 (olaparib 400 mg; group 3). These dose levels were selected by current guideline-based protocols for olaparib dose modification. Primary endpoints were progression-free survival and overall survival, while secondary endpoints included comparing the reduction rates and safety between the 3 groups. Eighty-seven patients were included, with 45 (52%) receiving dose reduction. The median progression-free survival for patients on standard dose was 27 months, compared to 28 and 32 months for groups 2 and 3, respectively (HR 1.587, 95% CI 0.673 to 2.744, p = .323). The median overall survival was 44 months for group 1, 52 for group 2, and 43 for group 3 (HR 0.737, 95% CI 0.413 to 1.317, p = .296). Grade ≥3 adverse events occurred in 2 patients (4.7%) of group 1, leading to a dose interruption without a reduction. Fatigue (n = 15; 35.7%) and nausea (n = 14; 33.3%) have often been reported in patients on the standard dose group. In our cohort, olaparib dose reduction did not adversely affect oncological outcomes in patients with recurrent ovarian cancer. These results suggest that a reduced dosing strategy is a viable option in patients experiencing treatment-related adverse events. However, these findings should be confirmed in larger clinical data.