Association Between Androgen Deprivation Therapy and Mortality Among Patients With Prostate Cancer and COVID-19.

Importance: Androgen deprivation therapy (ADT) has been theorized to decrease the severity of SARS-CoV-2 infection in patients with prostate cancer owing to a potential decrease in the tissue-based expression of the SARS-CoV-2 coreceptor transmembrane protease, serine 2 (TMPRSS2). Objective: To examine whether ADT is associated with a decreased rate of 30-day mortality from SARS-CoV-2 infection among patients with prostate cancer. Design, Setting, and Participants: This cohort study analyzed patient data recorded in the COVID-19 and Cancer Consortium registry between March 17, 2020, and February 11, 2021. The consortium maintains a centralized multi-institution registry of patients with a current or past diagnosis of cancer who developed COVID-19. Data were collected and managed using REDCap software hosted at Vanderbilt University Medical Center in Nashville, Tennessee. Initially, 1228 patients aged 18 years or older with prostate cancer listed as their primary malignant neoplasm were included; 122 patients with a second malignant neoplasm, insufficient follow-up, or low-quality data were excluded. Propensity matching was performed using the nearest-neighbor method with a 1:3 ratio of treated units to control units, adjusted for age, body mass index, race and ethnicity, Eastern Cooperative Oncology Group performance status score, smoking status, comorbidities (cardiovascular, pulmonary, kidney disease, and diabetes), cancer status, baseline steroid use, COVID-19 treatment, and presence of metastatic disease. Exposures: Androgen deprivation therapy use was defined as prior bilateral orchiectomy or pharmacologic ADT administered within the prior 3 months of presentation with COVID-19. Main Outcomes and Measures: The primary outcome was the rate of all-cause 30-day mortality after COVID-19 diagnosis for patients receiving ADT compared with patients not receiving ADT after propensity matching. Results: After exclusions, 1106 patients with prostate cancer (before propensity score matching: median age, 73 years [IQR, 65-79 years]; 561 (51%) self-identified as non-Hispanic White) were included for analysis. Of these patients, 477 were included for propensity score matching (169 who received ADT and 308 who did not receive ADT). After propensity matching, there was no significant difference in the primary end point of the rate of all-cause 30-day mortality (OR, 0.77; 95% CI, 0.42-1.42). Conclusions and Relevance: Findings from this cohort study suggest that ADT use was not associated with decreased mortality from SARS-CoV-2 infection. However, large ongoing clinical trials will provide further evidence on the role of ADT or other androgen-targeted therapies in reducing COVID-19 infection severity.

Drug-Microbiota Interaction in Colon Cancer Therapy: Impact of Antibiotics.

Colon adenocarcinoma is one of the most common malignancies, and it is highly lethal. Chemotherapy plays an important role in the treatment of colon cancer at various stages of the disease. The gut microbiome has emerged as a key player in colon cancer development and progression, and it can also alter the therapeutic agent's efficacy and toxicities. Antibiotics can directly and/or indirectly affect the balance of the gut microbiome and, therefore, the clinical outcomes. In this article, we provided an overview of the composition of the gut microbiome under homeostasis and the mechanistic links between gut microbiota and colon cancer. The relationship between the use of oral antibiotics and colon cancer, as well as the impact of the gut microbiome on the efficacy and toxicities of chemotherapy in colon cancer, are discussed. Potential interventions to modulate microbiota and improve chemotherapy outcomes are discussed. Further studies are indicated to address these key gaps in the field and provide a scientific basis for the design of novel microbiota-based approaches for prevention/use as adjuvant therapeutics for patients with colon cancer.

Collagen fragments quantified in serum as measures of desmoplasia associate with survival outcome in patients with advanced pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDAC) patients have poor prognosis and poor response to treatment. This is largely due to PDAC being associated with a dense and active stroma and tumor fibrosis (desmoplasia). Desmoplasia is characterized by excessive degradation and formation of the extracellular matrix (ECM) generating collagen fragments that are released into circulation. We evaluated the association of specific collagen fragments measured in pre-treatment serum with outcome in patients with PDAC. Matrix metalloprotease (MMP)-degraded type I collagen (C1M), type III collagen (C3M), type IV collagen (C4M) and a pro-peptide of type III collagen (PRO-C3) were measured by ELISA in pre-treatment serum from a randomized phase 3 clinical trial of patients with stage III/IV PDAC treated with 5-fluorouracil based therapy (n = 176). The collagen fragments were evaluated for their correlation (r, Spearman) with serum CA19-9 and for their association with overall survival (OS) based on Cox-regression analyses. In this phase 3 PDAC trial, pre-treatment serum collagen fragment levels were above the reference range for 67%-98% of patients, with median values in PDAC approximately two-fold higher than reference levels. Collagen fragment levels did not correlate with CA19-9 (r = 0.049-0.141, p = ns). On a continuous basis, higher levels of all collagen fragments were associated with significantly shorter OS. When evaluating degradation (C3M) and formation (PRO-C3) of type III collagen further, higher PRO-C3 was associated with poor OS (>25th percentile cut-point, HR = 2.01, 95%CI = 1.33-3.05) and higher C3M/PRO-C3 ratio was associated with improved OS (>25th percentile cut-point, HR = 0.53, 95%CI = 0.34-0.80). When adjusting for CA19-9 and clinical covariates, PRO-C3 remained significant (HR = 1.65, 95%CI = 1.09-2.48). In conclusion, collagen remodeling quantified in pre-treatment serum as a surrogate measure of desmoplasia was significantly associated with OS in a phase 3 clinical PDAC trial, supporting the link between desmoplasia, tumorigenesis, and response to treatment. If validated, these biomarkers may have prognostic and/or predictive potential in future PDAC trials.

Cost reduction associated with heparin-induced thrombocytopenia panel ordering for enoxaparin versus heparin for prophylactic and therapeutic use: A retrospective analysis in a community hospital setting.

BACKGROUND: Most hospitals still use unfractionated heparin (UFH) as the primary agent for venous thromboembolism (VTE) prophylaxis in the hospital setting due to ease of use and insignificant cost. However, the risk of heparin-induced thrombocytopenia (HIT) has led some groups to favor other options for therapeutic and prophylactic anticoagulation. This is particularly relevant in light of recent data demonstrating a lower rate of HIT in patients receiving enoxaparin compared with UFH. This study examines the cost-effectiveness of enoxaparin, compared to UFH for prophylactic and therapeutic usage in hospitals. METHODS: We conducted a retrospective chart review of patients who underwent HIT panel testing at the Inspira Health Network, Vineland campus (an approximately 262-bedded community hospital located in southern New Jersey that services a population of approximately 61,050) from the period of April 1, 2015 through December 31, 2016. The starting date represents the time from which enoxaparin became the primary alternative anticoagulant available at this hospital. Records of the total usage and cost of UFH and enoxaparin for the specified time period were collected from the hospital pharmacy database for evaluation, as were records of HIT panels. The information was analyzed to determine the frequency of HIT panel testing orders for patients receiving UFH versus those receiving enoxaparin. Annual cost-savings for the hospital were extrapolated using the comparative incidence of HIT panels and associated costs, including increased length of stay, hematology/oncology consultation, use of an alternative anticoagulant, critical bleeding requiring transfusion, and complications of HIT-associated thrombosis. These variables were multiplied by the incidence rate for each specified drug and usage to determine the daily cost for each drug. RESULTS: The use of enoxaparin did not result in a significant decrease in the ordering of HIT panels in the hospital, with a relative rate ratio of 0.948 (95% confidence interval: 0.336, 2.21). When the data were stratified to examine prophylactic and therapeutic anticoagulation, there was a marked difference in the frequency of HIT testing. The rate ratio of HIT panel orders for patients receiving therapeutic enoxaparin rather than intravenous (IV) UFH was 0.118 (0.006, 0.625). These numbers were used to extrapolate the total daily cost of enoxaparin compared with IV UFH; therapeutic enoxaparin cost $30.66, while IV UFH cost $162.30. IV UFH use was associated with a higher incidence rate of HIT panel orders, and consequently a higher daily cost due to the likelihood of increased length of stay, use of alternative anticoagulation, bleeding requiring transfusion, and request for expert consultation. CONCLUSION: In this study, the use of enoxaparin was associated with a significant cost-saving over IV UFH when used for therapeutic anticoagulation, but this cost saving was not observed for prophylactic anticoagulation.