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BackgroundTriple-negative breast cancer (TNBC) is an aggressive cancer subtype, owing to its high metastatic potential: Patients who develop brain metastases (BMs) have a poor prognosis due to the lack of effective systemic treatments. Surgery and radiation therapy are valid options, while pharmacotherapy still relies on systemic chemotherapy, which has limited efficacy. Among the new treatment strategies available, the antibody-drug conjugate (ADC) sacituzumab govitecan has shown an encouraging activity in metastatic TNBC, even in the presence of BMs.Case presentationA 59-year-old woman was diagnosed with early TNBC and underwent surgery and subsequent adjuvant chemotherapy. A germline pathogenic variant in BReast CAncer gene 2 (BRCA2) was revealed after genetic testing. After 11 months from the completion of adjuvant treatment, she had pulmonary and hilar nodal relapse and began first-line chemotherapy with carboplatin and paclitaxel. However, after only 3 months from starting the treatment, she experienced relevant disease progression, due to the appearance of numerous and symptomatic BMs. Sacituzumab govitecan (10 mg/kg) was started as second-line treatment as part of the Expanded Access Program (EAP). She reported symptomatic relief after the first cycle and received whole-brain radiotherapy (WBRT) concomitantly to sacituzumab govitecan treatment. The subsequent CT scan showed an extracranial partial response and a near-to-complete intracranial response; no grade 3 adverse events were reported, even if sacituzumab govitecan was reduced to 7.5 mg/kg due to persistent G2 asthenia. After 10 months from starting sacituzumab govitecan, a systemic disease progression was documented, while intracranial response was maintained.ConclusionsThis case report supports the potential efficacy and safety of sacituzumab govitecan in the treatment of early recurrent and BRCA-mutant TNBC. Despite the presence of active BMs, our patient had a progression-free survival (PFS) of 10 months in the second-line setting and sacituzumab govitecan was safe when administered together with radiation therapy. Further real-world data are warranted to confirm sacituzumab govitecan efficacy in this patient population.

Hintergrund: Eine verminderte Energiestoffwechselaktivität ist wesentlich für degenerative Zellveränderungen. Bei kultivierten retinalen Pigmentepithelzellen (RPE) können nachweislich phänotypische Veränderungen, die der altersbedingten Makuladegeneration (AMD) ähneln, [zum vollständigen Text gelangen Sie über die oben angegebene URL]

Hintergrund: Das primäre vitreoretinale Lymphom (PVRL) ist eine seltene und aggressive Krebserkrankung des Auges. Das PVRL weist enge Verwandtschaft mit den primären ZNS-Lymphomen (PZNSL) auf. Die Pathogenese des PVRL ist weitgehend ungeklärt. Am wahrscheinlichsten scheint, dass die Lymphomzellen [zum vollständigen Text gelangen Sie über die oben angegebene URL]

Purpose: It remains unknown which factors can divert the choroidal melanocytes or uveal melanoma (UM) cells towards the malignant versus benign genotypes with monosomy-3 or Chromosome(Chr)-6 gain, respectively. Here, we analyzed the outcomes of hyperglycemia on the segregation of Chr3 and -6. Methods: [for full text, please go to the a.m. URL]

Background The omicron (B.1.1.529) variant of SARS-CoV-2 is highly transmissible and escapes vaccine-induced immunity. We aimed to describe outcomes due to COVID-19 during the omicron outbreak compared with the prevaccination period and alpha (B.1.1.7) and delta (B.1.617.2) waves in patients with cancer in Europe. Methods In this retrospective analysis of the multicentre OnCovid Registry study, we recruited patients aged 18 years or older with laboratory-confirmed diagnosis of SARS-CoV-2, who had a history of solid or haematological malignancy that was either active or in remission. Patient were recruited from 37 oncology centres from UK, Italy, Spain, France, Belgium, and Germany. Participants were followed up from COVID-19 diagnosis until death or loss to follow-up, while being treated as per standard of care. For this analysis, we excluded data from centres that did not actively enter new data after March 1, 2021 (in France, Germany, and Belgium). We compared measures of COVID-19 morbidity, which were complications from COVID-19, hospitalisation due to COVID-19, and requirement of supplemental oxygen and COVID-19-specific therapies, and COVID-19 mortality across three time periods designated as the prevaccination (Feb 27 to Nov 30, 2020), alpha-delta (Dec 1, 2020, to Dec 14, 2021), and omicron (Dec 15, 2021, to Jan 31, 2022) phases. We assessed all-cause case-fatality rates at 14 days and 28 days after diagnosis of COVID-19 overall and in unvaccinated and fully vaccinated patients and in those who received a booster dose, after adjusting for country of origin, sex, age, comorbidities, tumour type, stage, and status, and receipt of systemic anti-cancer therapy. This study is registered with ClinicalTrials.gov, NCT04393974, and is ongoing. Findings As of Feb 4, 2022 (database lock), the registry included 3820 patients who had been diagnosed with COVID-19 between Feb 27, 2020, and Jan 31, 2022. 3473 patients were eligible for inclusion (1640 [47.4%] were women and 1822 [52.6%] were men, with a median age of 68 years [IQR 57-77]). 2033 (58.5%) of 3473 were diagnosed during the prevaccination phase, 1075 (31.0%) during the alpha-delta phase, and 365 (10.5%) during the omicron phase. Among patients diagnosed during the omicron phase, 113 (33.3%) of 339 were fully vaccinated and 165 (48.7%) were boosted, whereas among those diagnosed during the alpha-delta phase, 152 (16.6%) of 915 were fully vaccinated and 21 (2.3%) were boosted. Compared with patients diagnosed during the prevaccination period, those who were diagnosed during the omicron phase had lower case-fatality rates at 14 days (adjusted odds ratio [OR] 0.32 [95% CI 0.19-0.61) and 28 days (0.34 [0.16-0.79]), complications due to COVID-19 (0.26 [0.17-0.46]), and hospitalisation due to COVID-19 (0.17 [0.09-0.32]), and had less requirements for COVID-19-specific therapy (0.22 [0.15-0.34]) and oxygen therapy (0.24 [0.14-0.43]) than did those diagnosed during the alpha-delta phase. Unvaccinated patients diagnosed during the omicron phase had similar crude case-fatality rates at 14 days (ten [25%] of 40 patients vs 114 [17%] of 656) and at 28 days (11 [27%] of 40 vs 184 [28%] of 656) and similar rates of hospitalisation due to COVID-19 (18 [43%] of 42 vs 266 [41%] of 652) and complications from COVID-19 (13 [31%] of 42 vs 237 [36%] of 659) as those diagnosed during the alpha-delta phase. Interpretation Despite time-dependent improvements in outcomes reported in the omicron phase compared with the earlier phases of the pandemic, patients with cancer remain highly susceptible to SARS-CoV-2 if they are not vaccinated against SARS-CoV-2. Our findings support universal vaccination of patients with cancer as a protective measure against morbidity and mortality from COVID-19. Copyright (C) 2022. Published by Elsevier Ltd. All rights reserved.