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.

High pathologic misdiagnosis of cervical adenocarcinoma in situ.

OBJECTIVE: The objectives of this research were to evaluate cases of adenocarcinoma in situ (AIS) and early invasive adenocarcinoma (AC) of the uterine cervix in order to: (1) calculate the pathologic discordance between initial biopsies and final surgical excision specimens and (2) describe the clinical and pathologic factors associated with discordance. MATERIALS AND METHODS: The University of California, Irvine and Long Beach Memorial tumor registries were used to identify 105 women with AIS and early AC treated between 1990 and 2008. The primary endpoint measured was change in diagnosis when comparing pathology from the initial biopsy to specimens from a large loop excision of the transformation zone (LLETZ), cold knife cone (CKC), or hysterectomy. The variables studied were: age, endocervical curettage (ECC), co-existing cervical intraepithelial neoplasia (CIN), race, and insurance type, as surrogates for socioeconomic status. RESULTS: Initial biopsies were diagnosed as AIS and AC in 44% and 56% of patients, respectively. Of the patients with a biopsy diagnosis ofAIS, 29% had a final diagnosis of AC after excisional procedure, and this discordance was not associated with any of the factors studied. CONCLUSIONS: A concerning high rate of discordance between colposcopic-guided punch biopsy and final pathology reinforces the current guidelines to always perform an excisional biopsy following diagnosis of AIS on punch biopsy.

Malignant eccrine spiradenoma of the vulva: a case report and review of the literature.

Malignant eccrine spiradenoma is a rare skin tumor of sweat gland origin. We present the first reported case of this tumor in the female genitalia. Due to the rarity of this tumor, there has yet to be an established standard of care. The present case is that of a 41-year-old woman with malignant eccrine spiradenoma of the periclitoral region. She had an 18-month history of a recurrent, painful mass adjacent to the clitoris. Her diagnosis was made after excision of the cystic tumor. The patient then underwent a partial radical vulvectomy with bilateral sentinel lymph node sampling. As malignant eccrine spiradenoma is a rare tumor, no standard care exists for treatment and postoperative management. Based on our review of the literature, wide local excision appears to be the preferred initial treatment. Furthermore, adjuvant chemotherapy and/or radiation does not seem to improve survival in patients with advanced or recurrent cancer. Although lymph node sampling and/or lymphadenectomy is frequently reported in the treatment of this tumor, hematogenous metastasis can also occur. Therefore, these patients require close postoperative follow-up for recurrent disease.

Development of a nested polymerase chain reaction for amplification of a sequence of the p57 gene of Renibacterium salmoninarum that provides a highly sensitive method for detection of the bacterium in salmonid kidney.

Nucleic acid-based assays have shown promise for diagnosing Renibacterium salmoninarum in tissues and body fluids of salmonids. Development of a nested polymerase chain reaction (PCR) method to detect a 320 bp DNA segment of the gene encoding the p57 protein of R. salmoninarum is described. Whereas a conventional PCR for a 383 bp segment of the p57 gene reliably detected 1000 R. salmoninarum cells per reaction in kidney tissue, the nested PCR detected as few as 10 R. salmoninarum per reaction in kidney tissue. Two DNA extraction methods for the nested PCR were compared and the correlation between replicate samples was generally higher in samples extracted by the QIAamp system compared with those extracted by the phenol/chloroform method. The specificity of the nested PCR was confirmed by testing DNA extracts of common bacterial fish pathogens and a panel of bacterial species reported to cause false-positive reactions in the enzyme-linked immunosorbent assay (ELISA) and the fluorescent antibody test (FAT) for R. salmoninarum. Kidney samples from 74 naturally infected chinook salmon were examined by the nested PCR, the ELISA, and the FAT, and the detected prevalences of R. salmoninarum were 61, 47, and 43%, respectively.

Quality of life with three antihypertensive treatments. Cilazapril, atenolol, nifedipine.

A multicenter, randomized double-blind study of 6 months' duration was performed in 540 patients (average age 54 years, 57% male) with mild-to-moderate essential hypertension to determine the relative effects on quality of life of cilazapril, atenolol, and nifedipine retard. Quality of life was assessed by using both a self-administered and an interviewer-administered questionnaire; the assessment included a complaint score (symptoms checklist), Health Status Index, assessment of work satisfaction, Psychological General Well-being Index, Profile of Mood States subscales, and life satisfaction assessment. Psychomotor function was measured by the Reitan Trail Making test B. At the end of the trial, diastolic blood pressure had fallen by an average of 15 mm Hg in all three groups, but significantly (p = 0.01) more patients taking cilazapril required the addition of a diuretic (36%) compared with those taking atenolol (25%) or nifedipine retard (24%). No significant differences in quality of life were observed between cilazapril and atenolol during the trial. Symptomatic complaints increased on nifedipine retard (p = 0.02) and contributed to a higher discontinuation rate (21% discontinued treatment compared with 13% and 14% taking atenolol and cilazapril, respectively, p = 0.04). However, a possible improvement in the fatigue subscale (p = 0.04) was also observed on nifedipine retard. The 95% confidence intervals showed that none of the drugs in this trial produced an effect equivalent to that previously reported between captopril and methyldopa in the Psychological General Well Being Index or between captopril and methyldopa or propranolol in Trail Making test B.(ABSTRACT TRUNCATED AT 250 WORDS)