COVID-19 Vaccination and Imaging Misinterpretation: An Interview With Lacey McIntosh, DO, MPH

The United States is, according to a recent declaration from President Joe Biden, aiming to offer all US adults vaccination against SARS-CoV-2, the virus that causes COVID-19, by May 2021.¹ To date, furthermore, more than 30 people per 100 across the country have received at least 1 dose of a currently approved vaccine.²

The vaccination program is likely to improve overall survival in the population of patients with cancer, given the high risk of COVID-19-related mortality in this group. The clinical considerations related to vaccination in this population are, however, not yet established, and some research suggests that oncologists and patients should be aware of the potential manifestations of vaccination on imaging and the consequences this might have on disease assessment, treatment monitoring, and decision-making.

A recent article published in the American Journal of Roentgenology suggests that vaccination can result in axillary, supraclavicular, and/or cervical lymph node enlargement on the side of the injection. Such enlargement may, according to the authors, lead to confounding results and/or even misinterpretation of fluorodeoxyglucose (FDG) positron emission tomographic/computer tomographic (PET/CT) imaging in some cases.

While lymphadenopathy has previously been reported with other vaccines, notably those against seasonal influenza and human papillomavirus, the widespread use of SARS-CoV-2 vaccination necessitates awareness in the clinical community of the potential for confounding findings on imaging, in particular with FDG PET/CT. Clinician awareness of vaccine site and timing can be useful with coordination of imaging to help avoid these manifestations that can, in some cases, interfere with the accuracy of the examinations. Yet given the number of patients with cancer who have received — or are likely to soon receive — vaccination, some scans may not be interpretable, leading to treatment indecision in the face of potentially aggressive disease.

PET/CT is used for a variety of indications in oncology, including lesion characterization, disease staging, monitoring response to treatment, and surveillance for recurrence. Often, treatment decisions and disease status rely heavily on the results of this imaging. These studies can be difficult for physicians to get for their patients, so we want to make sure that when they are done, they are done well and give us the best chance to get the information we need with clear results.

In some cases, a recent vaccine just prior to imaging can potentially result in confusing findings rendering the study not useful and even lead to misinterpretation if information about vaccination is not available to the reading radiologist.

How serious do you consider the problem to be in practice?

Dr McIntosh: In many cases, the findings we see are easy to attribute to the vaccine and pose no significant interpretive challenges. However, in patients with certain cancers or diseases that manifest primarily in lymph nodes (lymphoma or Castleman disease) and cancers that are prone to involve vaccine-pattern lymph nodes (breast cancer, trunk or upper extremity melanoma or sarcoma, lung cancer [particularly upper lobe], or head and neck cancer), tracer uptake and nodal enlargement from recent vaccine administration can appear identical to what we see in lymph nodes involved by cancer. Unfortunately, although timing can be helpful, there are no specific features or a reliable standardized uptake value threshold that can differentiate between inflammation from vaccination and cancer.

Therefore, in these particular cases, even with adequate information about a recent vaccination, we may not be able to differentiate vaccine-related uptake from cancer. Management of vaccine-related findings is different in patients with cancer than in the general population, who can often be managed conservatively. This can lead to additional imaging and biopsies that might otherwise not have been needed and result in patient anxiety and delays in treatment initiation or treatment change decisions.

While this certainly involves the minority of PET/CT images, the issues caused by these confusing results are very real and have huge implications for these affected patients and their cancer care. So far, early in the process of mass vaccination, we have encountered this most frequently with breast and lung cancers and lymphoma.

What can treating clinicians do to reduce the likelihood of scan misinterpretation?

Dr McIntosh: Working together with our oncology colleagues, we should think about vaccination timing in the context of planned imaging and coordinate accordingly as it can prevent many of these potentially confounding cases. In the current climate of COVID-19 vaccine scarcity, we are not recommending delays in vaccination. We are also not recommending delays in indicated imaging. But, in patients with cancers that might have results confounded by vaccine manifestations, we are recommending optimization of the site and timing of vaccine administration.

We suggest the following:

• If a patient has a cancer that has laterality and might involve the same lymph nodes as the vaccine, we are recommending that clinicians advise these patients to ask for their vaccine on the opposite side.
• If feasible, in patients with cancers prone to confounding imaging findings, we are suggesting to avoid performing PET/CT imaging in the first 2 weeks after vaccination. Ideally, we think 4 to 6 weeks is preferable, but we also realize that this is not always possible in this population. These timelines are based on our studies with prior vaccines and early experience with the COVID-19 vaccine and might need to be revised if we find that these highly immunogenic mRNA vaccines elicit a more potent and prolonged response on imaging.
• When arranging follow-up imaging aimed at clarifying confounding results, clinicians must keep in mind subsequent vaccine doses.

Can data sharing mitigate the risk the dilemma poses?

Dr McIntosh: Data sharing is essential in mitigating the risk of producing confusing results on an imaging study. Adding specific questions about vaccine brand, site, and date of administration to PET/CT intake forms and interviews can provide the reading radiologist with the necessary information to aid in interpretation. However, even with access to adequate information about vaccination, a vaccine performed shortly before imaging may still result in overlapping findings that the radiologist cannot differentiate from cancer.

Similarly, questions about cancer history as part of the pre-vaccination questionnaires could aid in guiding patients to receive vaccines on the side opposite of their lateral cancer. If clinicians are aware of the vaccination schedule and imaging is routine without urgent indication, PET/CT imaging can be reasonably rescheduled to avoid confusing results. 

How might data sharing-related problems be best mitigated in the current phase of widespread vaccination across the country?

Dr McIntosh: With increasing awareness, this dilemma can be more easily mitigated and coordinated in a big, well-connected healthcare system, where we can pick up the phone and talk to each other; but we are definitely encountering more challenges with information about vaccination and care performed outside of the system.  Prevention is the best way of solving the problem.

Disclosures: Some authors have declared affiliations with or received funding from the pharmaceutical industry. Please refer to the original study for a full list of disclosures.

References

1. Fact Sheet: President Biden to announce All Americans to be eligible for vaccinations by May 1, puts the nation on a path to get closer to normal by July 4^th. Press release. Washington, DC: The White House; March 11, 2021.
2. Coronavirus (COVID-19) vaccinations. Oxford, United Kingdom: Our World in Data. Updated March 15, 2021.
3. McIntosh LJ, Bankier AA, Vijayaraghavan GR, Licho R, Rosen MP. COVID-19 vaccination-related uptake on FDG PET/CT: an emerging dilemma and suggestions for management. AJR Am J Roentgenol. Published online March 1, 2021. doi:10.2214/AJR.21.25728

This article originally appeared on Cancer Therapy Advisor