A sigh of relief: vaccine-associated hypermetabolic lymphadenopathy following the third COVID-19 vaccine dose is short in duration and uncommonly interferes with the interpretation of [18F]FDG PET-CT studies performed in oncologic patients.

PURPOSE: The incidence of COVID-19 vaccine-associated hypermetabolic lymphadenopathy (VAHL) is high following the administration of the first and second BNT162b2 vaccine doses. The impact of this finding on [18F]FDG PET-CT interpretation and its correlation with the induced humoral immunity have been reported. Assuming the amnestic immune response is different following the third vaccine dose, we aimed to explore the incidence of VAHL over time after the third BNT162b2 dose administration, and its relevance to [18F]FDG PET-CT interpretation in oncologic patients. METHODS: A total of 179 consecutive oncologic patients that underwent [18F]FDG PET-CT after a third BNT162b2 vaccine dose were included. The presence of VAHL was assessed. On VAHL-positive scans, the SUVmax, number, location, and size of the "hot" nodes were recorded. The median time interval between vaccination and imaging was 8 (IQR, 5-14) days. RESULTS: The incidences of all-grade VAHL and grade 3-4 VAHL were 47.5% and 8.9%, respectively. VAHL was identified on 82.5% of studies performed within the first 5 days from vaccination. Grade 3-4 VAHL was observed on 28.1% of studies performed within the first 5 days from vaccination, but was not detected on studies performed more than 5 days from vaccination. Separation between VAHL and malignant lymphadenopathy was not possible in only 2 of the 179 study patients. On a multivariable logistic regression, independent predictors of grade 3-4 VAHL were short time interval between vaccination and imaging (Pv < 0.01), younger age (Pv < 0.01), and lower BMI (Pv = 0.03). CONCLUSION: VAHL is commonly identified on [18F]FDG PET-CT performed within the first 5 days from the third BNT162b2 vaccine dose administration. High-grade VAHL is unlikely to be observed on a scan performed 6 days or longer from vaccination, and is even less likely in older and obese patients.

The Day after Mass COVID-19 Vaccination: Higher Hypermetabolic Lymphadenopathy Detection on PET/CT and Impact on Oncologic Patients Management.

The widespread COVID-19 vaccination led to unexpected PET findings. Notably, axillary and interpectoral lymphadenopathies ipsilateral to the vaccine inoculation were observed. We aimed to assess the hypermetabolic lymphadenopathy (HLN) detection rate on PET/CT. Secondly, we investigated factors that might help in HLN differential diagnosis. A retrospective analysis on 1196 consecutive patients referred for a PET/CT was performed. All patients were asked about the date, type and site of vaccine injections. HLNs were recorded and categorized according to risk classes and SUVmax grades. A statistical analysis was performed to assess the correlation between HLN detection and different clinical/vaccine data. HLN detection rate was 15% and 27% in the No Vac- and vac-groups (p < 0.001), respectively. In the Vac-group, age (p < 0.001) and time interval from vaccine-to-PET (p = 0.010) were inversely correlated with HLN detection. Furthermore, SUVmax significantly changed during time intervals, with lower values beyond 20 days (p < 0.001). In the era of mass COVID-19 vaccination, a higher axillary and interpectoral lymphadenopathies detection ipsilateral to vaccine injection was observed. These PET findings can be wrongly interpreted, complicating cancer patients' management. To minimize these pitfalls, a detailed vaccination anamnesis must be recorded and should take into account the appropriate PET schedule.

COVID-19 Vaccination-Related Uptake on FDG PET/CT: An Emerging Dilemma and Suggestions for Management.

As mass COVID-19 vaccination is underway, radiologists are encountering transient FDG uptake in normal or enlarged axillary, supraclavicular, and cervical lymph nodes after ipsilateral deltoid vaccination. This phenomenon may confound interpretation in patients with cancer undergoing FDG PET/CT. In this article, we present our institutional approach for management of COVID-19 vaccine-related lymphadenopathy on FDG PET/CT according to early experience. We suggest performing PET/CT at least 2 weeks after vaccination in patients with a cancer for which interpretation is anticipated to be potentially impacted by the vaccination but optimally 4-6 weeks after vaccination given increased immunogenicity of mRNA vaccines and potentially longer time for resolution than lymphadenopathy after other vaccines. PET/CT should not be delayed when clinically indicated to be performed sooner. Details regarding vaccination should be collected at the time of PET/CT to facilitate interpretation. Follow-up recommendations for postvaccination lymphadenopathy are provided, considering the lymph node's morphology and likely clinical relevance. Consideration should be given to administering the vaccine in the arm contralateral to a unilateral cancer to avoid confounding FDG uptake on the side of cancer. Our preliminary experience and suggested institutional approach should guide radiologists in management of patients with cancer undergoing PET/CT after COVID-19 vaccination.

Coordination and optimization of FDG PET/CT and COVID-19 vaccination; Lessons learned in the early stages of mass vaccination.

As the world embarks on mass vaccination for COVID-19, we are beginning to encounter unintended dilemmas in imaging oncology patients; particularly with regards to FDG PET/CT. In some cases, vaccine-related lymphadenopathy and FDG uptake on PET/CT can mimic cancer and lead to confounding imaging results. These cases where findings overlap with cancer pose a significant dilemma for diagnostic purposes, follow-up, and management leading to possible treatment delays, unnecessary repeat imaging and sampling, and patient anxiety. These cases can largely be avoided by optimal coordination between vaccination and planned imaging as well as preemptive selection of vaccine administration site. This coordination hinges on patient, oncologist, and radiologists' awareness of this issue and collaboration. Through close communication and patient education, we believe this will eliminate significant challenges for our oncology patients as we strive to end this pandemic.

Hypermetabolic lymphadenopathy following administration of BNT162b2 mRNA Covid-19 vaccine: incidence assessed by [18F]FDG PET-CT and relevance to study interpretation.

PURPOSE: Nationwide mass vaccination against Covid-19 started in Israel in late 2020. Soon we identified on [18F]FDG PET-CT studies vaccine-associated hypermetabolic lymphadenopathy (VAHL) in axillary or supraclavicular lymph nodes (ASLN) ipsilateral to the vaccination site. Sometimes, differentiation between the malignant and benign nature of the hypermetabolic lymphadenopathy (HLN) could not be made, and equivocal HLN (EqHL) was reported. The purpose of the study was to determine the overall incidence of VAHL after BNT162b2 vaccination and also its relevance to PET-CT interpretation in oncologic patients. METHODS: A total of 951 consecutive patients that underwent [18F]FDG PET-CT studies in our department were interviewed regarding the sites and dates of the vaccine doses. A total of 728 vaccinated patients (All-Vac group) were included: 346 received the first dose only (Vac-1 group) and 382 received the booster dose as well (Vac-2 group). Studies were categorized as no HLN, malignant-HLN (MHL), VAHL, or EqHL. In studies with VAHL, location, [18F]FDG-intensity uptake and nodes size were recorded. RESULTS: The incidences of HLN were 45.6%, 36.4%, and 53.9% in All-Vac, Vac-1, and Vac-2 groups, respectively. VAHL was reported in 80.1% of vaccinated patients with HLN. Lower incidences of VAHL were found during the first 5 days or in the third week after the first vaccine and beyond 20 days after the booster dose. In 49 of 332 (14.8%) vaccinated patients, we could not determine whether HLN was MHL or VAHL. Breast cancer and lymphoma were the leading diseases with EqHL. CONCLUSION: VAHL is frequently observed after BNT162b2 administration, more commonly and with higher intensity following the booster dose. To minimize false and equivocal reports in oncological patients, timing of [18F]FDG PET-CT should be based on the time intervals found to have a lower incidence of VAHL, and choice of vaccine injection site should be advised, mainly in patients where ASLN are a relevant site of tumor involvement.