Direct Oral Anticoagulants vs Low-Molecular-Weight Heparin and Recurrent VTE in Patients With Cancer: A Randomized Clinical Trial.

Importance: In patients with cancer who have venous thromboembolism (VTE) events, long-term anticoagulation with low-molecular-weight heparin (LMWH) is recommended to prevent recurrent VTE. The effectiveness of a direct oral anticoagulant (DOAC) compared with LMWH for preventing recurrent VTE in patients with cancer is uncertain. Objective: To evaluate DOACs, compared with LMWH, for preventing recurrent VTE and for rates of bleeding in patients with cancer following an initial VTE event. Design, Setting, and Participants: Unblinded, comparative effectiveness, noninferiority randomized clinical trial conducted at 67 oncology practices in the US that enrolled 671 patients with cancer (any invasive solid tumor, lymphoma, multiple myeloma, or chronic lymphocytic leukemia) who had a new clinical or radiological diagnosis of VTE. Enrollment occurred from December 2016 to April 2020. Final follow-up was in November 2020. Intervention: Participants were randomized in a 1:1 ratio to either a DOAC (n = 335) or LMWH (n = 336) and were followed up for 6 months or until death. Physicians and patients selected any DOAC or any LMWH (or fondaparinux) and physicians selected drug doses. Main Outcomes and Measures: The primary outcome was the recurrent VTE rate at 6 months. Noninferiority of anticoagulation with a DOAC vs LMWH was defined by the upper limit of the 1-sided 95% CI for the difference of a DOAC relative to LMWH of less than 3% in the randomized cohort that received at least 1 dose of assigned treatment. The 6 prespecified secondary outcomes included major bleeding, which was assessed using a 2.5% noninferiority margin. Results: Between December 2016 and April 2020, 671 participants were randomized and 638 (95%) completed the trial (median age, 64 years; 353 women [55%]). Among those randomized to a DOAC, 330 received at least 1 dose. Among those randomized to LMWH, 308 received at least 1 dose. Rates of recurrent VTE were 6.1% in the DOAC group and 8.8% in the LMWH group (difference, -2.7%; 1-sided 95% CI, -100% to 0.7%) consistent with the prespecified noninferiority criterion. Of 6 prespecified secondary outcomes, none were statistically significant. Major bleeding occurred in 5.2% of participants in the DOAC group and 5.6% in the LMWH group (difference, -0.4%; 1-sided 95% CI, -100% to 2.5%) and did not meet the noninferiority criterion. Severe adverse events occurred in 33.8% of participants in the DOAC group and 35.1% in the LMWH group. The most common serious adverse events were anemia and death. Conclusions and Relevance: Among adults with cancer and VTE, DOACs were noninferior to LMWH for preventing recurrent VTE over 6-month follow-up. These findings support use of a DOAC to prevent recurrent VTE in patients with cancer. Trial Registration: ClinicalTrials.gov Identifier: NCT02744092.

Trends in oncological imaging during the COVID-19 pandemic through the vaccination era.

BACKGROUND: This study examines the impact that the COVID-19 pandemic has had on computed tomography (CT)-based oncologic imaging utilization. METHODS: We retrospectively analyzed cancer-related CT scans during four time periods: pre-COVID (1/5/20-3/14/20), COVID peak (3/15/20-5/2/20), post-COVID peak (5/3/20-12/19/20), and vaccination period (12/20/20-10/30/21). We analyzed CTs by imaging indication, setting, and hospital type. Using percentage decrease computation and Student's t-test, we calculated the change in mean number of weekly cancer-related CTs for all periods compared to the baseline pre-COVID period. This study was performed at a single academic medical center and three affiliated hospitals. RESULTS: During the COVID peak, mean CTs decreased (-43.0%, p < 0.001), with CTs for (1) cancer screening, (2) initial workup, (3) cancer follow-up, and (4) scheduled surveillance of previously treated cancer dropping by 81.8%, 56.3%, 31.7%, and 45.8%, respectively (p < 0.001). During the post-COVID peak period, cancer screenings and initial workup CTs did not return to prepandemic imaging volumes (-11.4%, p = 0.028; -20.9%, p = 0.024). The ED saw increases in weekly CTs compared to prepandemic levels (+31.9%, p = 0.008), driven by increases in cancer follow-up CTs (+56.3%, p < 0.001). In the vaccination period, cancer screening CTs did not recover to baseline (-13.5%, p = 0.002) and initial cancer workup CTs doubled (+100.0%, p < 0.001). The ED experienced increased cancer-related CTs (+75.9%, p < 0.001), driven by cancer follow-up CTs (+143.2%, p < 0.001) and initial workups (+46.9%, p = 0.007). CONCLUSIONS AND RELEVANCE: The pandemic continues to impact cancer care. We observed significant declines in cancer screening CTs through the end of 2021. Concurrently, we observed a 2× increase in initial cancer workup CTs and a 2.4× increase in cancer follow-up CTs in the ED during the vaccination period, suggesting a boom of new cancers and more cancer examinations associated with emergency level acute care.

Trends in Academic Productivity Among Radiologists During the COVID-19 Pandemic.

PURPOSE: There is a scarcity of literature examining changes in radiologist research productivity during the COVID-19 pandemic. The current study aimed to investigate changes in academic productivity as measured by publication volume before and during the COVID-19 pandemic. METHODS: This single-center, retrospective cohort study included the publication data of 216 researchers consisting of associate professors, assistant professors, and professors of radiology. Wilcoxon's signed-rank test was used to identify changes in publication volume between the 1-year-long defined prepandemic period (publications between May 1, 2019, and April 30, 2020) and COVID-19 pandemic period (May 1, 2020, to April 30, 2021). RESULTS: There was a significantly increased mean annual volume of publications in the pandemic period (5.98, SD = 7.28) compared with the prepandemic period (4.98, SD = 5.53) (z = -2.819, P = .005). Subset analysis demonstrated a similar (17.4%) increase in publication volume for male researchers when comparing the mean annual prepandemic publications (5.10, SD = 5.79) compared with the pandemic period (5.99, SD = 7.60) (z = -2.369, P = .018). No statistically significant changes were found in similar analyses with the female subset. DISCUSSION: Significant increases in radiologist publication volume were found during the COVID-19 pandemic compared with the year before. Changes may reflect an overall increase in academic productivity in response to clinical and imaging volume ramp down.

Trends in cancer imaging by indication, care setting, and hospital type during the COVID-19 pandemic and recovery at four hospitals in Massachusetts.

BACKGROUND: We aimed to investigate the effects of COVID-19 on computed tomography (CT) imaging of cancer. METHODS: Cancer-related CTs performed at one academic hospital and three affiliated community hospitals in Massachusetts were retrospectively analyzed. Three periods of 2020 were considered as follows: pre-COVID-19 (1/5/20-3/14/20), COVID-19 peak (3/15/20-5/2/20), and post-COVID-19 peak (5/3/20-11/14/20). 15 March 2020 was the day a state of emergency was declared in MA; 3 May 2020 was the day our hospitals resumed to non-urgent imaging. The volumes were assessed by (1) Imaging indication: cancer screening, initial workup, active cancer, and surveillance; (2) Care setting: outpatient and inpatient, ED; (3) Hospital type: quaternary academic center (QAC), university-affiliated community hospital (UACH), and sole community hospitals (SCHs). RESULTS: During the COVID-19 peak, a significant drop in CT volumes was observed (-42.2%, p < 0.0001), with cancer screening, initial workup, active cancer, and cancer surveillance declining by 81.7%, 54.8%, 30.7%, and 44.7%, respectively (p < 0.0001). In the post-COVID-19 peak period, cancer screening and initial workup CTs did not recover (-11.7%, p = 0.037; -20.0%, p = 0.031), especially in the outpatient setting. CT volumes for active cancer recovered, but inconsistently across hospital types: the QAC experienced a 9.4% decline (p = 0.022) and the UACH a 41.5% increase (p < 0.001). Outpatient CTs recovered after the COVID-19 peak, but with a shift in utilization away from the QAC (-8.7%, p = 0.020) toward the UACH (+13.3%, p = 0.013). Inpatient and ED-based oncologic CTs increased post-peak (+20.0%, p = 0.004 and +33.2%, p = 0.009, respectively). CONCLUSIONS: Cancer imaging was severely impacted during the COVID-19 pandemic. CTs for cancer screening and initial workup did not recover to pre-COVID-19 levels well into 2020, a finding that suggests more patients with advanced cancers may present in the future. A redistribution of imaging utilization away from the QAC and outpatient settings, toward the community hospitals and inpatient setting/ED was observed.

cMET inhibitor crizotinib impairs angiogenesis and reduces tumor burden in the C3(1)-Tag model of basal-like breast cancer.

UNLABELLED: Epidemiologic studies have associated obesity with increased risk of the aggressive basal-like breast cancer (BBC) subtype. Hepatocyte growth factor (HGF) signaling through its receptor, cMET, is elevated in obesity and is a pro-tumorigenic pathway strongly associated with BBC. We previously reported that high fat diet (HFD) elevated HGF, cMET, and phospho-cMET in normal mammary gland, with accelerated tumor development, compared to low fat diet (LFD)-fed lean controls in a murine model of BBC. We also showed that weight loss resulted in a significant reversal of HFD-induced effects on latency and elevation of HGF/cMET signaling in normal mammary and cMET in normal mammary and tumors. Here, we sought to inhibit BBC tumor progression in LFD- and HFD-fed C3(1)-Tag BBC mice using a small molecule cMET inhibitor, and began crizotinib treatment (50 mg/kg body weight by oral gavage) upon identification of the first palpable tumor. We next investigated if administering crizotinib in a window prior to tumor development would inhibit or delay BBC tumorigenesis. TREATMENT: Crizotinib significantly reduced mean tumor burden by 27.96 and 37.29 %, and mean tumor vascularity by 35.04 and 33.52 %, in our LFD- and HFD-fed C3(1)-Tag BBC mice, respectively. PREVENTION: Crizotinib significantly accelerated primary tumor progression in both diet groups but had no effect on total tumor progression or total tumor burden. In sum, cMET inhibition by crizotinib limited tumor development and microvascular density in basal-like tumor-bearing mice but did not appear to be an effective preventive agent for BBC.