COVID-19 vaccination can cause lymphadenopathy and FDG uptake on PET/CT scans, which mimic cancer and confound results for patients undergoing scans to monitor cancer progression.1,2,3

“When imaging findings from vaccination overlap with sites of known potential cancer involvement, the results may be inconclusive,” said Lacey McIntosh, DO, a cancer and molecular imaging radiologist at the University of Massachusetts Medical School/Memorial Health Care in Worcester, who wrote a recent paper on this topic.4

The authors of a recent case study noted, for example, that new findings of uptake in a patient’s right deltoid muscle and axillary lymph nodes were “likely” related to recent COVID-19 vaccination rather than to the patient’s previously diagnosed breast cancer.1


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Situations like this case — when vaccine-related findings overlap with those related to cancer and health care professionals are not able to discern one from the other — are the most common, according to Dr McIntosh. A less common scenario would involve misinterpreting the imaging results of a patient whose vaccine status is unknown, and those findings are wrongly attributed to cancer.

“Most radiologists are aware of this phenomenon, and when this pattern of findings is seen, it can be easily recognized,” Dr McIntosh said. “Having vaccination information can certainly reduce the small likelihood of attributing vaccine-related findings to cancer. Misinterpretation could potentially lead to inaccurate staging, which may actually guide treatment the wrong way. This doesn’t happen often, though.”

The concern is relevant to the type of cancer, according to both Dr McIntosh and Sooha Kim, MBBChir, a clinical oncologist at The Royal Marsden Hospital in London, England.

“With breast cancer, it really can’t be worked out whether we’re looking at disease progression or vaccine uptake,” Dr Kim said. “Even if probability is on your side, you can’t exclude the possibility that we’re looking at disease.”

Downstream Effects

If vaccination confounds the results of FDG PET/CT, it may appear that patients need further follow-up imaging or biopsies that could have otherwise been avoided, Dr McIntosh and colleagues noted in their paper.4 This may result in treatment delays, extra costs associated with imaging and procedures, and increased anxiety.

“Follow-up imaging and procedures may be difficult to obtain because of barriers with cost and insurance coverage,” Dr McIntosh said.

For patients diagnosed with more aggressive cancers, imaging may be particularly problematic, given the time needed for COVID-19 vaccine-related findings to resolve and coordination with subsequent doses in cases of 2-shot series.4

While some research suggests that visible lymphadenopathy may resolve within 2 weeks after vaccination against influenza, a recent paper indicated that 29% of patients who receive COVID-19 vaccination may show uptake for up to 10 weeks.5,6

Recommended Solutions

The risks of confounding results, from treatment delays to negative effects on patients’ quality of life, suggest a need for strategies to avoid performing FDG PET/CT scans around the time of COVID-19 vaccination, according to Dr McIntosh and colleagues.

Patients’ awareness of the timing of vaccination appointments can help, as can health care provider data sharing and clinician communication, particularly in health care systems where vaccine information may not be readily available to the immediate provider, the authors noted.

“Vaccines are generally not being given in the hospital systems, so communication around this is really important,” Dr McIntosh said. “In the US, nearly all vaccines are being given outside of the hospital system; for example, at mass vaccination sites, pharmacies, and grocery stores, which are not connected to the medical systems and electronic medical records, which can make coordination difficult. Some patients have difficulty recalling dates and sides of vaccine administration, and many are not aware of the potential issues between vaccination and imaging.”

This combination of issues necessitates focus on both provider communication and patient education, according to Dr McIntosh and colleagues.

Other strategies, such as ensuring that vaccines are administered on the side opposite a lateral cancer or optimizing timing for COVID-19 vaccinations to be given after indicated imaging may also help, according to Dr McIntosh.

“Further investigation is needed to explore if alternate vaccination sites such as gluteal muscles might be helpful when vaccination is expected to interfere with results,” she said.

Global Impact

Many of the aforementioned issues are relative to the health care system in question. The United States does not have a dedicated health data system — although the COVID-19 pandemic has led to the development of a rudimentary one — and other systems will face challenges specific to their own mechanisms of data sharing and provider communication.7

England’s National Health Service, for example, relies on data transfer among general practitioners (GPs), local hospital systems, and national datasets, each of which may rely on several different, and sometimes incompatible, data storage and sharing systems.

Dr Kim said questions of vaccine uptake are now discussed regularly at multidisciplinary team meetings.

“We often don’t know of the patients’ vaccine status, which becomes problematic when there is an unexpected uptake in the axilla or neck lymph nodes,” Dr Kim said. “There aren’t, however, easily accessible GP data to determine this. You need to ask the patient about when their vaccine was, and the patient’s ability to recall this information may depend on geography. The level of engagement and knowledge varies widely across the country.”

Different approaches to COVID-19 vaccination around the world may result in country-specific issues. Countries with a historically low vaccine uptake, such as Japan, may face their own set of problems as local views about vaccination change, according to Dr McIntosh. This makes awareness of views, both within and among countries, relevant to scan readings.

Looking Ahead

As SARS-CoV-2 continues to evolve, it seems likely that the risk of misinterpreting scans will continue. Given the strong association between cancer diagnosis and the risk of mortality from COVID-19, vaccination in this group is considered essential.8

If booster shots become widely recommended across the United States and the world, the timing of vaccination and other strategies for mitigating the risk of wasted or misinterpreted scans will become of greater importance, according to Dr McIntosh.

“As a greater majority of the US population has become vaccinated, we are seeing less vaccine-related findings on imaging,” Dr McIntosh said. “However, if regular boosters will be required, this will continue to be an issue, and coordination will be key. It is critical for oncology health care practitioners to be aware of this issue and to discuss this with patients to best avoid confounding results.”

References

  1. Eifer M, Eshet Y. Imaging of COVID-19 vaccination at FDG PET/CT. Radiology. 2021;299(2):E248. doi:10.1148/radiol.2020210030

2. Xu G, Lu Y. COVID-19 mRNA vaccination-induced lymphadenopathy mimics lymphoma progression on FDG PET/CT. Clin Nucl Med. 2021;46(4):353-354. doi:10.1097/RLU.0000000000003597

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. Published online March 1, 2021. AJR Am J Roentgenol. doi:10.2214/AJR.21.25728

4. McIntosh LJ, Rosen MP, Mittal K, et al. Coordination and optimization of FDG PET/CT and COVID-19 vaccination; lessons learned in the early stages of mass vaccination. Cancer Treat Rev. 2021;98:102220. doi:10.1016/j.ctrv.2021.102220

5. Shirone N, Shinkai T, Yamane T, et al. Axillary lymph node accumulation on FDG-PET/CT after influenza vaccination. Ann Nucl Med. 2012;26(3):248-252. doi:10.1007/s12149-011-0568-x

6. Eshet Y, Tau N, Alhoubani Y, Kanana N, Domachevsky L, Eifer M. Prevalence of increased FDG PET/CT axillary lymph node uptake beyond 6 weeks after mRNA COVID-19 vaccination. Published online April 27, 2021. Radiology. doi:10.1148/radiol.2021210886

7. Ferguson C. It took a pandemic, but the US finally has (some) centralized medical data. MIT Technology Review. Published June 21, 2021. Accessed July 12, 2021. https://www.technologyreview.com/2021/06/21/1026590/us-covid-database-n3c-nih-privacy/

8. Zhang H, Han H, He T, et al. Clinical characteristics and outcomes of COVID-19-infected cancer patients: a systematic review and meta-analysis. J Natl Cancer Inst. 2021;113(4):371-380. doi:10.1093/jnci/djaa168