Background: Upper urinary tract urothelial carcinoma (UTUC) accounts for only about 5–10% of all urothelial cancers and is characterized by an aggressive and frequently rapidly fatal behavior. However, detailed knowledge of its molecular profile is still lacking. Materials and methods: We identified, by chart analysis, patients who underwent radical nephroureterectomy or diagnostic biopsy for UTUC between January 2015 and August 2020 at the Santa Maria Hospital of Terni, in Italy. Eligible patients were required to have also adequate clinical informations and follow-up details. The primary objective of the study was to evaluate DNA mismatch repair (MMR) proteins and Nectin-4 immunohistochemical expression in UTUC, looking also for an eventual correlation between these molecular features. The secondary objective was to investigate genomic instability in the case of a MMR protein loss. Expression of proteins was assessed by using immunohistochemistry and microsatellite instability (MSI) performed by next generation sequencing. Nectin-4 expression was reported using an intensity scoring system (score, 0–3+), instead the expression of DNA MMR proteins was indicated as present (no loss) or not present (loss). Results: Thirty four cases have been evaluated and 27 considered eligible for the study with their tumor samples analyzed. Nectin-4 was found to be expressed in 44% of cases and 18.5% of patients showed defective-MMR phenotype. We found a significant correlation between Nectin-4 expression and MSH2/MSH6 protein loss. Out of 7 patients with DNA MMR proteins loss or equivocal phenotype, 3 showed MSI. Conclusions: Our pilot study suggest a possible relationship between Nectin-4 and DNA MMR protein expression in UTUC and a clinically significant correlation between defective MMR phenotype and genomic instability. Because of the possible implications of these data for innovative treatment approaches, the need for further studies in this area is warranted.

PURPOSE Although representing the majority of newly diagnosed cancers, patients with breast cancer appear less vulnerable to COVID-19 mortality compared with other malignancies. In the absence of patients on active cancer therapy included in vaccination trials, a contemporary real-world evaluation of outcomes during the various pandemic phases, as well as of the impact of vaccination, is needed to better inform clinical practice. METHODS We compared COVID-19 morbidity and mortality among patients with breast cancer across prevaccination (February 27, 2020-November 30, 2020), Alpha-Delta (December 1, 2020-December 14, 2021), and Omicron (December 15, 2021-January 31, 2022) phases using OnCovid registry participants (ClinicalTrials.gov identifier: NCT04393974). Twenty-eight-day case fatality rate (CFR28) and COVID-19 severity were compared in unvaccinated versus double-dosed/boosted patients (vaccinated) with inverse probability of treatment weighting models adjusted for country of origin, age, number of comorbidities, tumor stage, and receipt of systemic anticancer therapy within 1 month of COVID-19 diagnosis. RESULTS By the data lock of February 4, 2022, the registry counted 613 eligible patients with breast cancer: 60.1% (n = 312) hormone receptor-positive, 25.2% (n = 131) human epidermal growth factor receptor 2-positive, and 14.6% (n = 76) triple-negative. The majority (61%; n = 374) had localized/locally advanced disease. Median age was 62 years (interquartile range, 51-74 years). A total of 193 patients (31.5%) presented >= 2 comorbidities and 69% (n = 330) were never smokers. In total, 392 (63.9%), 164 (26.8%), and 57 (9.3%) were diagnosed during the prevaccination, Alpha-Delta, and Omicron phases, respectively. Analysis of CFR28 demonstrates comparable estimates of mortality across the three pandemic phases (13.9%, 12.2%, 5.3%, respectively; P = .182). Nevertheless, a significant improvement in outcome measures of COVID-19 severity across the three pandemic time periods was observed. Importantly, when reported separately, unvaccinated patients from the Alpha-Delta and Omicron phases achieved comparable outcomes to those from the prevaccination phase. Of 566 patients eligible for the vaccination analysis, 72 (12.7%) were fully vaccinated and 494 (87.3%) were unvaccinated. We confirmed with inverse probability of treatment weighting multivariable analysis and following a clustered robust correction for participating center that vaccinated patients achieved improved CFR28 (odds ratio [OR], 0.19; 95% CI, 0.09 to 0.40), hospitalization (OR, 0.28; 95% CI, 0.11 to 0.69), COVID-19 complications (OR, 0.16; 95% CI, 0.06 to 0.45), and reduced requirement of COVID-19-specific therapy (OR, 0.24; 95% CI, 0.09 to 0.63) and oxygen therapy (OR, 0.24; 95% CI, 0.09 to 0.67) compared with unvaccinated controls. CONCLUSION Our findings highlight a consistent reduction of COVID-19 severity in patients with breast cancer during the Omicron outbreak in Europe. We also demonstrate that even in this population, a complete severe acute respiratory syndrome coronavirus 2 vaccination course is a strong determinant of improved morbidity and mortality from COVID-19.

Background: Cabozantinib, a standard of care metastatic renal cell carcinoma (mRCC), may be associated with weight and muscle loss. These effects of new generation VEGFR tyrosine kinase inhibitor on muscle mass loss are poorly described.Methods: All cabozantinib‐treated mRCC patients from January 2014 to February 2019 in our institution were included. Clinical data including weight were collected during therapy. Computed tomography images were centrally reviewed for response assessment, and axial sections at the third lumbar vertebrae were used to measure the total muscle area. Toxicities and cabozantinib outcomes were evaluated. Co‐primary endpoints included skeletal muscle loss and weight loss (WL), longitudinally evaluated during treatment. WL has been classified according to CTCAEv5.0: Grade 1 (loss of 5 to <10% of baseline body weight), Grade 2 (loss of 10% to 20% of baseline body weight).Results: Patients were mostly men (70.3%), median age was 59.2 (range: 22.0–78.0) years, and median baseline body mass index was 25.0 (range: 16.4–49.3) kg/cm². Prognosis according to International Metastatic RCC Database Consortium score was good, intermediate, and poor for 13 (13.0%), 63 (63.0%), and 24 (24.0%) patients, respectively. Out of a total of 120 patients, 101 patients with a median follow‐up of 22.3 months (range: 4.5–62.2) were eligible for analysis; 85 experienced muscle loss and muscle loss >10% increased during cabozantinib exposition, especially after 6 months of treatment. At cabozantinib baseline, 71 patients (70.3%) had sarcopenia, and 16/30 (53.3%) non‐sarcopenic patients developed sarcopenia during treatment. Baseline sarcopenia was associated with lower response rates (P = 0.031) and higher grades 3–4 toxicities (P = 0.001). Out of 92 patients included in the WL analysis, 44 (47.8%) and 12 (13.0%) experienced grades 2 and 3 WL, respectively.Conclusions: We report a high incidence of grades 3–4 WL, fourth times higher than reported in prior pivotal trials, and half of the patients developed sarcopenia while on cabozantinib treatment. Weight and muscle mass loss with cabozantinib are underreported and may require further investigations and early management.