Prospective study of Lipiodol distribution as an imaging marker for doxorubicin pharmacokinetics during conventional transarterial chemoembolization of liver malignancies.

OBJECTIVES: To evaluate the prognostic potential of Lipiodol distribution for the pharmacokinetic (PK) profiles of doxorubicin (DOX) and doxorubicinol (DOXOL) after conventional transarterial chemoembolization (cTACE). METHODS: This prospective clinical trial ( ClinicalTrials.gov : NCT02753881) included 30 consecutive participants with liver malignancies treated with cTACE (5/2016-10/2018) using 50 mg DOX/10 mg mitomycin C emulsified 1:2 with ethiodized oil (Lipiodol). Peripheral blood was sampled at 10 timepoints for standard non-compartmental analysis of peak concentrations (Cmax) and area under the curve (AUC) with dose normalization (DN). Imaging markers included Lipiodol distribution on post-cTACE CT for patient stratification into 1 segment (n = 10), ≥ 2 segments (n = 10), and lobar cTACE (n = 10), and baseline enhancing tumor volume (ETV). Adverse events (AEs) and tumor response on MRI were recorded 3-4 weeks post-cTACE. Statistics included repeated measurement ANOVA (RM-ANOVA), Mann-Whitney, Kruskal-Wallis, Fisher's exact test, and Pearson correlation. RESULTS: Hepatocellular (n = 26), cholangiocarcinoma (n = 1), and neuroendocrine metastases (n = 3) were included. Stratified according to Lipiodol distribution, DOX-Cmax increased from 1 segment (DOX-Cmax, 83.94 ± 75.09 ng/mL; DN-DOX-Cmax, 2.67 ± 2.02 ng/mL/mg) to ≥ 2 segments (DOX-Cmax, 139.66 ± 117.73 ng/mL; DN-DOX-Cmax, 3.68 ± 4.20 ng/mL/mg) to lobar distribution (DOX-Cmax, 334.35 ± 215.18 ng/mL; DN-DOX-Cmax, 7.11 ± 4.24 ng/mL/mg; p = 0.036). While differences in DN-DOX-AUC remained insignificant, RM-ANOVA revealed significant separation of time concentration curves for DOX (p = 0.023) and DOXOL (p = 0.041) comparing 1, ≥ 2 segments, and lobar cTACE. Additional indicators of higher DN-DOX-Cmax were high ETV (p = 0.047) and Child-Pugh B (p = 0.009). High ETV and tumoral Lipiodol coverage also correlated with tumor response. AE occurred less frequently after segmental cTACE. CONCLUSIONS: This prospective clinical trial provides updated PK data revealing Lipiodol distribution as an imaging marker predictive of DOX-Cmax and tumor response after cTACE in liver cancer. KEY POINTS: • Prospective pharmacokinetic analysis after conventional TACE revealed Lipiodol distribution (1 vs. ≥ 2 segments vs. lobar) as an imaging marker predictive of doxorubicin peak concentrations (Cmax). • Child-Pugh B class and tumor hypervascularization, measurable as enhancing tumor volume (ETV) at baseline, were identified as additional predictors for higher dose-normalized doxorubicin Cmax after conventional TACE. • ETV at baseline and tumoral Lipiodol coverage can serve as predictors of volumetric tumor response after conventional TACE according to quantitative European Association for the Study of the Liver (qEASL) criteria.

Reactive axillary lymph nodes after COVID-19 mRNA vaccination: comparison of mRNA vs. attenuated whole-virus vaccines.

OBJECTIVE: To compare the incidence and natural course of reactive axillary lymph nodes (RAL) between mRNA and attenuated whole-virus vaccines using Deauville criteria. METHODS: In this multi-institutional PET-CT study comprising multiple vaccine types (Pfizer-BioNTech/Comirnaty, Moderna/Spikevax, Sinovac/CoronaVac and Janssen vaccines), we evaluated the incidence and natural course of RAL in a large cohort of oncological patients utilizing a standardized Deauville scaling system (n=522; 293 Female, Deauville 3-5 positive for RAL). Univariate and multivariate analyses were conducted to evaluate the predictive value of clinical parameters (absolute neutrophil count [ANC], platelets, age, sex, tumor type, and vaccine-to-PET interval) for PET positivity. RESULTS: Pfizer-BioNTech/Comirnaty and Moderna vaccines revealed similar RAL incidences for the first 20 days after the second dose of vaccine administration (44% for the first 10 days for both groups, 26% vs. 20% for 10-20 days, respectively for Moderna and Pfizer). However, Moderna recipients revealed significantly higher incidences of RAL after 20 days compared to Pfizer-BioNTech/Comirnaty, with nodal reactivity spanning up to the 9th week post-vaccination (15% vs. 4%, respectively P  < 0.001). No RAL was observed in patients who received either a single dose of J&J vaccine or two doses of CroronaVac. Younger patients showed increased likelihood of RAL, otherwise, clinical/demographic parameters were not predictive of RAL ( P  = 0.014 for age, P  > 0.05 for additional clinical/demographic parameters). CONCLUSION: RAL based on strict PET criteria was observed with mRNA but not with attenuated whole-virus vaccines, in line with higher immunogenicity and stronger protection offered by mRNA vaccines.

Ipsilateral Malignant Axillary Lymphadenopathy and Contralateral Reactive Lymph Nodes in a COVID-19 Vaccine Recipient With Breast Cancer.

Vaccine-related axillary nodal enlargement is a common benign condition that many mRNA vaccine receivers experience. However, a false attribution of axillary swelling to vaccination may result in delay in cancer care and potential disease progression, particularly in breast cancer patients presenting with ipsilateral axillary lymphadenopathy. We report the case of a 41-year-old pre-menopausal female who presented with suspicious axillary nodal enlargement and a right breast lump (triple-negative invasive ductal carcinoma) after recent administration of the second dose of Moderna mRNA coronavirus disease 2019 (COVID-19) vaccine. On imaging, bilateral axillary lymph nodes were detected. The ipsilateral right-sided node was proven to be metastatic, whereas contralateral nodes were related to a recent mRNA COVID-19 vaccination. Right-sided lymph node had intense uptake (maximum standardized uptake value [SUVmax] = 5), while the contralateral reactive nodes were mildly avid (SUVmax = 2.6). On magnetic resonance imaging, the right-sided node revealed asymmetric cortical thickening and marked cortical enhancement as opposed to normal-appearing left-sided nodes.

Clinical PET/CT utilization during the COVID-19 pandemic: initial experience at Yale University.

OBJECTIVE: To determine temporal changes in PET/CT utilization during the COVID-19 pandemic and examine the impact of epidemiologic, demographic and oncologic factors on PET/CT utilization. METHODS: Clinical PET-CT utilization between 1 January 2020 and 15 June 2020 at a tertiary academic center was assessed using change-point-detection (CPD) analysis. COVID-19 epidemiologic trend was obtained from Connecticut Department of Public Health records. Demographic and oncologic data were gathered from electronic medical records and PET-CT scans by four reviewers in consensus. RESULTS: A total of 1685 cases were reviewed. CPD analysis identified five distinct phases of PET-CT utilization during COVID-19, with a sharp decline and a gradual recovery. There was a 62.5% decline in case volumes at the nadir. These changes correlated with COVID-19 epidemiologic changes in the state of Connecticut, with a negative correlation between COVID-19 cases and PET-CT utilization (τ = -0.54; P value < 0.001). Statistically significant differences in age, race, cancer type and current and prior scan positivity were observed in these five phases. A greater percentage of young patients and minorities were scanned during the pandemic relative to baseline. PET/CT scanning was less impacted for hematologic malignancies than for solid cancers, with less profound decline and better recovery. DISCUSSION: PET-CT cancer imaging was vulnerable to the COVID-19 pandemic at our institution. Epidemiologic, demographic and oncologic factors affected PET-CT utilization.