After a brief summary of the current status of poly-ADP ribose polymerase (PARP) inhibitors for ovarian cancer, we summarize the current status of PARP inhibitors for BRCA wild type ovarian cancer, especially regarding gene alterations other than BRCA, homologous recombination deficiency (HRD), and combinations. Discussion of gene alterations other than BRCA include the results of multiple gene panels studying homologous recombination repair deficiency genes and cancer susceptibility genes, and influences of these alterations on efficacy of PARP inhibitors and cancer susceptibility. Discussions of HRD include the results of phase three trials using HRD assay, the definition of HRD assays, and the latest assays. Discussions of combinations include early phase trial results and ongoing trials combining PARP inhibitors with immune checkpoint inhibitors, anti-angiogenic agents, and triplets.
We investigated the efficacy of BNT162b2 mRNA COVID-19 vaccine in patients with B-cell malignancies treated with anti-CD20 antibody. Although T-cell-mediated immune responses were detected even in patients receiving R-CHOP treatment, the S1 antibody titer following BNT162b2 vaccination remained only marginally increased for more than 3 years after the final dose of anti-CD20 antibody. We found no relationship between the percent of B-cells and S1 antibody titer. The duration of this suppression was much longer than we anticipated. Further protection and treatment strategies against COVID-19 for these patients are warranted.
Neuroendocrine carcinomas (NEC) of the female genital tract are aggressive and uncommon tumors, which usually involve the uterine cervix and ovary, and are seen very rarely in the endometrium. Only less than 10 cases of large cell NEC (LCNEC) of the endometrium have been reported in the literature and their radiological findings are not well described. We report here two cases of pathologically proven LCNEC of the uterine endometrium. In both cases, the uterine body was enlarged and the tumor occupied part of the uterine cavity. Endometrial mass exhibited heterogeneous high intensity on T2-weighted magnetic resonance (MR) images, and diffusion-weighted MR images revealed high intensity throughout the tumor, consistent with malignancy. LCNEC is a highly malignant neoplasm without particular findings in terms of diagnostic imaging and pathology, so its preoperative definitive diagnosis is very difficult. However, when laboratory test, pathologic diagnosis and MR imaging suggest a poorly differentiated uterine malignancy, positron emission tomography-computed tomography scan should be performed as a general assessment to help with diagnosis.
Background Although COVID-19 severity in cancer patients is high, the safety and immunogenicity of the BNT162b2 mRNA COVID-19 vaccine in patients undergoing chemotherapy for solid cancers in Japan have not been reported. Methods We investigated the safety and immunogenicity of BNT162b2 in 41 patients undergoing chemotherapy for solid cancers and in healthy volunteers who received 2 doses of BNT162b2. We evaluated serum IgG antibody titers for S1 protein by ELISA at pre-vaccination, prior to the second dose and 14 days after the second vaccination in 24 cancer patients undergoing cytotoxic chemotherapy (CC group), 17 cancer patients undergoing immune checkpoint inhibitor therapy (ICI group) and 12 age-matched healthy volunteers (HV group). Additionally, inflammatory cytokine levels were compared between the HV and ICI groups at pre and the next day of each vaccination. Results Anti-S1 antibody levels were significantly lower in the ICI and CC groups than in the HV group after the second dose (median optimal density: 0.241 [0.063–1.205] and 0.161 [0.07–0.857] vs 0.644 [0.259–1.498], p = 0.0024 and p < 0.0001, respectively). Adverse effect profile did not differ among the three groups, and no serious adverse event occurred. There were no differences in vaccine-induced inflammatory cytokines between the HV and ICI groups. Conclusion Although there were no significant differences in adverse events in three groups, antibody titers were significantly lower in the ICI and CC groups than in the HV group. Further protection strategies should be considered in cancer patients undergoing CC or ICI.
Background Carboplatin is a key drug for ovarian cancer. However, it sometimes induces hypersensitivity reactions (HSRs) that result in the discontinuation of the treatment. Although various desensitization protocols have been reported in previous retrospective studies, a limited number of prospective studies have analyzed these protocols. Methods Patients with platinum-sensitive relapsed ovarian cancer who experienced carboplatin-induced HSRs were treated with diluted solutions of 1/1000, 1/100, 1/10 and an undiluted solution of carboplatin over a 1-h period. If no HSRs occurred within the first two cycles, a short protocol regimen over a 30-min period per solution was followed. The primary endpoint was treatment completion rate. Results Between May 2015 and September 2018, 21 patients were enrolled from two institutions. One patient experienced platinum-sensitive recurrence after the desensitization protocol; thus, 22 sessions were analyzed. Epinephrine use, treatment-related death, and intensive care unit (ICU) admissions did not occur. The median number of desensitization cycles was 6 (range 1–6). Two sessions were discontinued early because of grade 2 dysgeusia and grade 2 malaise. Treatment in two (9.1%) patients was discontinued because of HSR development. The treatment completion rate was 90.9%. Six (27.3%) sessions met the criteria for transition to the short protocol regimen. In 14 (63.6%) sessions, HSRs were observed during infusion of the undiluted solution. The median progression-free survival and overall survival were 14.8 and 23.8 months, respectively. Conclusion This 4-step, 2-h carboplatin desensitization protocol is safe and feasible. Patients require careful monitoring with a rapid response to HSRs, especially during the administration of undiluted solutions.
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