International multicenter study comparing COVID-19 in patients with cancer to patients without cancer: Impact of risk factors and treatment modalities on survivorship.

Background: In this international multicenter study, we aimed to determine the independent risk factors associated with increased 30 day mortality and the impact of cancer and novel treatment modalities in a large group of patients with and without cancer with COVID-19 from multiple countries. Methods: We retrospectively collected de-identified data on a cohort of patients with and without cancer diagnosed with COVID-19 between January and November 2020 from 16 international centers. Results: We analyzed 3966 COVID-19 confirmed patients, 1115 with cancer and 2851 without cancer patients. Patients with cancer were more likely to be pancytopenic and have a smoking history, pulmonary disorders, hypertension, diabetes mellitus, and corticosteroid use in the preceding 2 wk (p≤0.01). In addition, they were more likely to present with higher inflammatory biomarkers (D-dimer, ferritin, and procalcitonin) but were less likely to present with clinical symptoms (p≤0.01). By country-adjusted multivariable logistic regression analyses, cancer was not found to be an independent risk factor for 30 day mortality (p=0.18), whereas lymphopenia was independently associated with increased mortality in all patients and in patients with cancer. Older age (≥65y) was the strongest predictor of 30 day mortality in all patients (OR = 4.47, p<0.0001). Remdesivir was the only therapeutic agent independently associated with decreased 30 day mortality (OR = 0.64, p=0.036). Among patients on low-flow oxygen at admission, patients who received remdesivir had a lower 30 day mortality rate than those who did not (5.9 vs 17.6%; p=0.03). Conclusions: Increased 30 day all-cause mortality from COVID-19 was not independently associated with cancer but was independently associated with lymphopenia often observed in hematolgic malignancy. Remdesivir, particularly in patients with cancer receiving low-flow oxygen, can reduce 30 day all-cause mortality. Funding: National Cancer Institute and National Institutes of Health.

The molecular heterogeneity of the precancerous breast affects drug efficacy.

In the therapeutic domain, targeted therapies have been shown to be generally more effective when given to patients with tumors that harbor the targeted aberration. This principle has not been tested in cancer prevention despite evidence that molecular heterogeneity accompanies the multi-step progression to invasive disease. We hypothesized that efficacy of agents targeting the precancerous state varies based on timing of the treatment relative to the underlying molecular changes. MCF10A cell line-based model of the multi-step progression to TNBC was used. Global proteomic patterns were obtained and growth-inhibitory effects of selected agents were correlated with the underlying molecular stage of progression. These analyses revealed that most protein alterations were acquired in the normal-to-atypia (preneoplasia) transition, with only handful aberrations acquired hereafter. The efficacy of small molecule inhibitors of the AKT/MEK pathway was associated with the underlying pathway levels. Similarly, fluvastatin was more effective in inhibiting cell proliferation earlier in the progression model. However, the nonspecific inhibitors, aspirin and metformin, were equally ineffective in inhibiting proliferation across the progression model. Our data provides proof-of-principle that in the prevention domain, treatment with agents developed to target specific pathways, will need to consider the molecular heterogeneity of the precancerous breast in order to achieve maximum efficacy.

International Multicenter Study Comparing Cancer to Non-Cancer Patients with COVID-19: Impact of Risk Factors and Treatment Modalities on Survivorship.

Background: In this international multicenter study we aimed to determine the independent risk factors associated with increased 30-day mortality and the impact of novel treatment modalities in a large group of cancer and non-cancer patients with COVID-19 from multiple countries. Methods: We retrospectively collected de-identified data on a cohort of cancer and non-cancer patients diagnosed with COVID-19 between January and November 2020, from 16 international centers. Results: We analyzed 3966 COVID-19 confirmed patients, 1115 cancer and 2851 non-cancer patients. Cancer patients were more likely to be pancytopenic, and have a smoking history, pulmonary disorders, hypertension, diabetes mellitus, and corticosteroid use in the preceding two weeks (p≤0.01). In addition, they were more likely to present with higher inflammatory biomarkers (D-dimer, ferritin and procalcitonin), but were less likely to present with clinical symptoms (p≤0.01). By multivariable logistic regression analysis, cancer was an independent risk factor for 30-day mortality (OR 1.46; 95% CI 1.03 to 2.07; p=0.035). Older age (≥65 years) was the strongest predictor of 30-day mortality in all patients (OR 4.55; 95% CI 3.34 to6.20; p< 0.0001). Remdesivir was the only therapeutic agent independently associated with decreased 30-day mortality (OR 0.58; CI 0.39-0.88; p=0.009). Among patients on low-flow oxygen at admission, patients who received remdesivir had a lower 30-day mortality rate than those who did not (5.9% vs 17.6%; p=0.03). Conclusions: Cancer is an independent risk factor for increased 30-day all-cause mortality from COVID-19. Remdesivir, particularly in patients receiving low-flow oxygen, can reduce 30-day all-cause mortality. Condensed Abstract: In this large multicenter worldwide study of 4015 patients with COVID-19 that included 1115 patients with cancer, we found that cancer is an independent risk factor for increased 30-day all-cause mortality. Remdesivir is a promising treatment modality to reduce 30-day all-cause mortality.

Fully automated preparation of 68Ga-PSMA-11 at curie level quantity using cyclotron-produced 68Ga for clinical applications.

68Ga-PSMA-11 is currently one of the most investigated PET agents for imaging both recurrent prostate cancer and relevant metastases; however, the production and distribution of 68Ga-PSMA-11 is limited to a supply of only a few daily doses when using a commercially available 68Ge/68Ga generator. 68Ge/68Ga generators deliver only a modest amount of activity, up to 1850 MBq (50 mCi), when new, but it decreases with time. Additionally, the production of 68Ga/68Ge generators has not been able to meet the increasing demand of 68Ga radiotracers. In response to the need for a more economically viable alternative, the focus of this study was to provide a simple and efficient method for producing 68Ga-PSMA-11, using cyclotron-produced 68Ga that is ready for routine clinical practice.