Carolina Maria Sassu

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.

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.

Focus on Trabectedin in Ovarian Cancer: What Do We Still Need to Know?

In the era of single and combination maintenance therapies as well as platinum and Poly (ADP-ribose) polymerase inhibitors (PARPi) resistance, the choice of subsequent treatments following first-line platinum-based chemotherapy in recurrent ovarian cancer (ROC) patients has become increasingly complex. Within the ovarian cancer treatment algorithm, particularly in the emerging context of PARPi resistance, the role of trabectedin, in combination with pegylated liposomal doxorubicin (PLD) still preserves its significance. This paper offers valuable insights into the multifaceted role and mechanism of action of trabectedin in ROC. The main results of clinical trials and studies involving trabectedin/PLD, along with hints of Breast Cancer genes (BRCA)-mutated and BRCAness phenotype cases, are critically discussed. Moreover, this review provides and contextualizes potential scenarios of administering trabectedin in combination with PLD in ROC, according to established guidelines and beyond.

Fertility-sparing surgery for women with stage I cervical cancer of 4 cm or larger: a systematic review

To investigate current evidence on oncological, fertility and obstetric outcomes of patients with stage I cervical cancer of 4 cm or larger undergoing fertility-sparing surgery (FSS). Systematic review of studies including women affected by stage I cervical cancer ≥4 cm who underwent FSS. Main outcome measures: disease-free survival (DFS), overall survival (OS), pregnancy rate, live birth rate, premature delivery rate. Fifteen studies met all eligibility criteria for this systematic review, involving 48 patients affected by cervical cancer ≥4 cm who completed FSS. Three patients (6.3%) experienced a recurrence and one of them (2.1%) died of disease. The 5-year DFS rate was 92.4%. The 5-year OS rate was 97.6%. A significantly shorter 5-year DFS was reported for high-risk patients (G3, non-squamous histotype, diameter ≥5 cm) compared with low-risk (74.7% vs. 100%; log-rank test, p=0.024). Data about fertility outcomes were available for 12 patients. Five patients out of 12 (41.7%) attempted to conceive with an estimated pregnancy rate of 80%, a live birth rate of 83.3% and a premature delivery rate of 20%. Women with high tumor grade, aggressive histology and tumor size ≥5 cm have a higher risk of recurrence. Oncologic outcomes are encouraging among low-risk patients; however, the lack of high-quality studies makes it difficult to draw any firm conclusions. Prospective multicentric clinical trials with a proper selection of inclusion/exclusion criteria should be conducted in women with low-risk factors, strong desire to preserve their fertility and high likelihood to conceive.

Subjective assessment and IOTA ADNEX model in evaluation of adnexal masses in patients with history of breast cancer

ABSTRACTObjectiveTo evaluate the performance of subjective assessment and the Assessment of Different NEoplasias in the adneXa (ADNEX) model in discriminating between benign and malignant adnexal tumors and between metastatic and primary adnexal tumors in patients with a personal history of breast cancer.MethodsThis was a retrospective single‐center study including patients with a history of breast cancer who underwent surgery for an adnexal mass between 2013 and 2020. All patients had been examined with transvaginal or transrectal ultrasound using a standardized examination technique and all ultrasound reports had been stored and were retrieved for the purposes of this study. The specific diagnosis suggested by the original ultrasound examiner in the retrieved report was analyzed. For each mass, the ADNEX model risks were calculated prospectively and the highest relative risk was used to categorize each into one of five categories (benign, borderline, primary Stage I, primary Stages II–IV or metastatic ovarian cancer) for analysis of the ADNEX model in predicting the specific tumor type. The performance of subjective assessment and the ADNEX model in discriminating between benign and malignant adnexal tumors and between primary and metastatic adnexal tumors was evaluated, using final histology as the reference standard.ResultsIncluded in the study were 202 women with a history of breast cancer who underwent surgery for an adnexal mass. At histology, 93/202 (46.0%) masses were benign, 76/202 (37.6%) were primary malignancies (four borderline and 72 invasive tumors) and 33/202 (16.3%) were metastases. The original ultrasound examiner classified correctly 79/93 (84.9%) benign adnexal masses, 72/76 (94.7%) primary adnexal malignancies and 30/33 (90.9%) metastatic tumors. Subjective ultrasound evaluation had a sensitivity of 93.6%, specificity of 84.9% and accuracy of 89.6%, while the ADNEX model had higher sensitivity (98.2%) but lower specificity (78.5%), with similar accuracy (89.1%), in discriminating between benign and malignant ovarian masses. Subjective evaluation had a sensitivity of 51.5%, specificity of 88.8% and accuracy of 82.7% in distinguishing metastatic and primary tumors (including benign, borderline and invasive tumors), and the ADNEX model had a sensitivity of 63.6%, specificity of 84.6% and similar accuracy (81.2%).ConclusionsThe performance of subjective assessment and the ADNEX model in discriminating between benign and malignant adnexal masses in this series of patients with history of breast cancer was relatively similar. Both subjective assessment and the ADNEX model demonstrated good accuracy and specificity in discriminating between metastatic and primary tumors, but the sensitivity was low. © 2023 International Society of Ultrasound in Obstetrics and Gynecology.

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.