Niraparib first-line maintenance therapy in patients with newly diagnosed advanced ovarian cancer: final overall survival results from the PRIMA/ENGOT-OV26/GOG-3012 trial.

BACKGROUND: The phase III PRIMA/ENGOT-OV26/GOG-3012 trial met its primary endpoint. Niraparib first-line maintenance significantly prolonged progression-free survival (PFS) among patients with newly diagnosed advanced ovarian cancer that responded to first-line platinum-based chemotherapy, regardless of homologous recombination deficiency (HRD) status. Final overall survival (OS) results are reported. PATIENTS AND METHODS: Patients were randomized 2:1 to niraparib or placebo, stratified by response to first-line treatment, receipt of neoadjuvant chemotherapy, and tumor HRD status. After reaching 60% target maturity, OS was evaluated via a stratified log-rank test using randomization stratification factors and summarized using Kaplan-Meier methodology. OS testing was hierarchical [overall population first, then the homologous recombination-deficient (HRd) population]. Other secondary outcomes and long-term safety were assessed; an updated, ad hoc analysis of investigator-assessed PFS was also conducted (cut-off date, 8 April 2024). RESULTS: The median follow-up was 73.9 months. In the overall population, the OS hazard ratio was 1.01 [95% confidence interval (CI) 0.84-1.23; P = 0.8834] for niraparib (n = 487) versus placebo (n = 246). In the HRd (n = 373) and homologous recombination-proficient (n = 249) populations, the OS hazard ratios were 0.95 (95% CI 0.70-1.29) and 0.93 (95% CI 0.69-1.26), respectively. Subsequent poly(ADP-ribose) polymerase inhibitor therapy was received by 11.7% and 15.8% of niraparib patients and 37.8% and 48.4% of placebo patients in the overall and HRd populations, respectively. The 5-year PFS rate numerically favored niraparib in the overall (niraparib, 22%; placebo, 12%) and HRd populations (niraparib, 35%; placebo, 16%). Myelodysplastic syndromes/acute myeloid leukemia incidence was <2.5% (niraparib, 2.3%; placebo, 1.6%). No new safety signals were observed. CONCLUSIONS: In patients with newly diagnosed advanced ovarian cancer at high risk of recurrence, there was no difference in OS between treatment arms. In the HRd population, patients alive at 5 years were two times as likely to be progression free with niraparib treatment than placebo. Long-term safety remained consistent with the established niraparib safety profile.

Successful response to docetaxel treatment in recurrent ovarian granulosa cell tumor: a case report.

BACKGROUND: Ovarian granulosa cell tumor (GCT) is primarily treated surgically. Treatment for advanced or recurrent disease includes primary or adjuvant chemotherapy. Data about the efficacy of treatment with paclitaxel are limited, without data about the role of docetaxel in treating recurrent GCT. CASE: A 68-year-old patient with Stage IA ovarian GCT diagnosed ten years earlier, presented with a third episode of recurrent disease. Following the first event of recurrent disease, she underwent a second laparotomy followed by BEP chemotherapy. Because of new liver masses, she was treated with paclitaxel, with complete response. Following diagnosis of new liver lesions, third-line chemotherapy with docetaxel was initiated, resulting in stable disease and a PFI of 24 months. CONCLUSION: Docetaxel might be a good alternative for treating recurrent GCT.

Doxorubicin levels in the serum and ascites of patients with ovarian cancer.

AIMS: To investigate the diffusion and accumulation of doxorubicin metabolites in the ascites of patients with ovarian cancer following intravenous injection, as a model for intraperitoneal accumulation of drugs. METHODS: The concentrations of doxorubicin and its metabolites [Doxorubicinol (Dox-ol), 7-deoxydoxorubicinolone (7d-Dox-ol-on) and 7-deoxydoxorubicinone (7d-Dox-on)] were measured using high-performance liquid chromatography in the serum and in the ascites of seven patients with recurrent ovarian carcinoma suffering from symptomatic ascites and treated with intravenous doxorubicin. RESULTS: Doxorubicin metabolites accumulated in the peritoneal cavity. The concentrations of the doxorubicin metabolites were initially higher in the serum compared to the ascitic fluid, but following several hours the doxorubicin metabolites became higher in the ascites, and remained detectable in the ascites for up to 168h, long after disappearance from the serum. CONCLUSIONS: Doxorubicin metabolites accumulate in the ascites and are cleared more slowly from the peritoneal compartment than from the serum. Accumulation in the peritoneal cavity with prolonged half-life should be considered when administering medication in patients with ascites.

HPV-related vulvar intraepithelial neoplasia: outcome of different management modalities.

OBJECTIVE: To evaluate the outcome of various management schemes for HPV-related vulvar intraepithelial neoplasia (VIN, usual type). METHODS: Retrospective chart review of patients with histologically diagnosed grade 2/3-VIN who had at least one year of follow-up. The variables that were collected included patient characteristics, management modalities, and clinical outcome. RESULTS: Fifty patients with a median age of 45 years old were evaluated. The median duration of follow-up was 43.5 months (12-186). Complete response (CR) and partial response occurred in 28 (56%) and 4 (8%), respectively. Nineteen of 28 patients with CR recurred with VIN. Surgical excision yielded higher CR (77%) than did either ablational techniques (21-33%) or topical immunotherapy (33%). CONCLUSION: In this experience, surgical excision for VIN, usual type, resulted in better therapeutic success rates than other treatment modalities. Management schemes should be individualized based on extent of disease and patient compliance.

Adjuvant therapy for patients with stage I papillary serous endometrial cancer.

Uterine papillary serous carcinoma (UPSC) is an aggressive variant of endometrial cancer characterized by a high recurrence rate and poor prognosis. Several studies have demonstrated that UPSC has a tendency to manifest with extra-uterine disease, even for tumors which appear to be limited to the endometrium. The data on adjuvant chemotherapy for stage I UPSC are limited, and the available studies are generally under-powered to assess if chemotherapy improves survival. However, we believe that, patients with UPSC should receive complete surgical staging, including omentectomy and peritoneal biopsies, and then until the results of larger series or randomized controlled trials will be available, we feel that combined radiotherapy and chemotherapy is justified for all stage I UPSC.

Cervical cancer in pregnant women: laparoscopic evaluation before delaying treatment.

BACKGROUND: Cervical carcinoma diagnosed during pregnancy generates conflicting concerns between control of malignancy and continuation of pregnancy. CASE: An invasive cervical carcinoma FIGO Stage IB2 was diagnosed in a 33-year-old primigravida during the first trimester of pregnancy. Because the patient strongly desired to preserve her pregnancy, laparoscopic lymphadenectomy was performed at 16 weeks of gestation to determine the extension of disease. Negative lymph node status was found and the patient was counseled about the possibility of proceeding until adequate fetal maturity had been achieved. An elective cesarean section and radical hysterectomy were performed at 36 weeks, followed by postoperative chemoradiation therapy. The clinical and Pap smear follow-up remain normal after four years. CONCLUSION: Pregnant women diagnosed with early stage cervical carcinoma should receive a complete evaluation including lymphadenectomy before considering delayed therapy. This strategy seems to be an acceptable option in well-defined conditions, and offers these patients the possibility of maternity.

Can parametrectomy be avoided in early cervical cancer? An algorithm for the identification of patients at low risk for parametrial involvement.

AIMS: To assess the rate of parametrial involvement in a large cohort of patients who underwent radical hysterectomy for cervical cancer and to suggest an algorithm for the triage of patients to simple hysterectomy or simple trachelectomy. METHODS: Multicenter retrospective study of patients with cervical cancer stage I through IIA who underwent radical hysterectomy and pelvic lymphadenectomy. The patients were divided into 2 groups according to whether or not the parametrium was involved. The two groups were compared with regard to the clinical and histopathological variables. Logistic regression of the variables potentially assessable prior to definitive hysterectomy such as age, tumor size, lymph-vascular space invasion (LVSI) and nodal involvement was performed. RESULTS: Five hundred and thirty patients had specific histological data on parametrial involvement and in 58 (10.9%) patients, parametria was involved. Parametrial involvement was significantly associated with older age, tumors larger than 2 cm, deeper invasion, LVSI, involved surgical margins, and the presence of nodal metastasis. By triaging patients with a tumor ≤ 2 cm and no LVSI, the parametrial involvement rate was 1.8% (2/112 patients). With further triage of patients with negative nodes, the rate of parametrial involvement was 0% (0/107 patients). CONCLUSION: Using a pre-operative triage algorithm, patients with early small lesions, no LVSI and no nodal involvement may be spared radical surgical procedures and parametrectomy. Further prospective data are urgently needed.

Expression of matrix metalloproteinase-2 and mutant p53 is increased in hydatidiform mole as compared with normal placenta.

Matrix metalloproteinases (MMPs) are group of enzymes thought to play an important role in trophoblastic and tumor invasion. The aim of our study was to investigate the trophoblastic expression of MMPs and p53 in normal trophoblast and hydatidiform moles (HM). Paraffin sections of 45 specimens, including 14 complete hydatidiform moles (CM), 15 partial hydatidiform moles (PM), 8 atypical partial hydatidiform moles (aPM), and 8 controls were selected. Classification of HM was established on histologic criteria and supported by the DNA ploidy results. Tissue sections from each case were immunostained with monoclonal antibodies, cytokeratin-7, MMP-2, MMP-9, tissue inhibitors of metalloproteinases (TIMP)-1, and p53 wild type (p53wt) and mutant types (mutp53). Staining for cytokeratin-7 revealed a positive reaction in 93% of the samples. MMP-2 was mainly expressed in the syncytiotrophoblast of HM and found in 62% of aPM, 60% PM, and 93% CM. The mutp53 was mainly and focally expressed in syncytiotrophoblastic cells and was found in 63% of aPM, 80% PM, and 93% CM. Expression of MMP-2 and mutp53 was both significantly greater in HM vs control group (P < 0.05) and greater in CM vs PM and aPM (P < 0.05). No significant difference was observed for cytokeratin-7, MMP-9, TIMP-1, and p53wt between the HM subgroups and between HM and control group. MMP-2 and mutp53 are overexpressed in HM as compared with normal trophoblast and might participate in the invasive behavior of the HM.