乳腺癌患者接种新冠疫苗应该选哪侧
乳腺癌、黑色素瘤、淋巴瘤等癌症有扩散到同侧腋窝淋巴结的倾向。既往研究发现，肌肉注射流感疫苗或人类乳头瘤病毒（HPV）疫苗后，可见腋窝淋巴结肿大。接种新冠疫苗也可能引起癌症同侧腋窝淋巴结反应，既可能被错误地归咎于恶性病变，造成不必要的干预，也可能被错误地归咎于疫苗接种而非癌症，从而可能延误癌症治疗。
2021年6月10日，《美国医学会杂志》肿瘤学分册在线发表耶鲁大学医学院的研究报告，利用18F-氟代脱氧葡萄糖（FDG）正电子发射扫描（PET）计算机扫描（CT）成像对信使核糖核酸（mRNA）新冠疫苗接种后癌症同侧腋窝淋巴结反应进行了观察。
18F-FDG-PET/CT：将原子量为18的氟同位素取代葡萄糖第二个羟基的氧原子，注入人体后，逐渐衰变并发射出正电子，可用计算机数字化扫描成像，能够精准反映人体不同组织对葡萄糖的摄取分布情况。
该单中心回顾研究对2020年12月11日～2021年3月1日在耶鲁大学纽黑文医院接受18F-FDG-PET/CT的全部1290例患者进行新冠疫苗接种筛查。对接种过新冠疫苗的68例（41例接种1次、27例接种2次，51例接种辉瑞疫苗、17例接种莫德纳疫苗）患者进行分析。其中67例由于肿瘤学指征接受18F-PET/CT，均无接种部位同侧淋巴结病。按多维尔标准对淋巴结反应强度进行分级，高于纵隔血池被认为有反应。
结果，其中9例（13%）发生同侧腋窝淋巴结反应：
女性：7例
男性：2例
第1次接种疫苗后：2例（5%）
第2次接种疫苗后：7例（26%，P=0.02；比值比：0.15；95%置信区间：0.01～0.89）
接种辉瑞疫苗后：4例（8%）
接种莫德纳疫苗后：5例（29%）
第2次接种辉瑞疫苗后：3例患者（15%）
第2次接种莫德纳疫苗后：4例患者（57%）
第2次接种至18F-FDG-PET/CT扫描的时间：
淋巴结有反应者：中位10天
淋巴结无反应者：中位12天
根据X射线CT扫描：
淋巴结无反应者：腋窝淋巴结肿大1例（2%）
淋巴结有反应者：腋窝淋巴结肿大5例（56%，P<0.001；比值比：0.02；95%置信区间：0.01～0.19）
疫苗注射部位可见FDG活性：
辉瑞疫苗：6例（12%）
莫德纳疫苗：2例（12%）
因此，该单中心小样本回顾研究结果表明，肌肉注射mRNA新冠疫苗后，同侧腋窝淋巴结反应常见，其中女性比男性更常见、第二次接种后比第一次接种后更常见、莫德纳疫苗比辉瑞疫苗更常见。18F-PET/CT对于检测淋巴结反应高度敏感，无论淋巴结肿大或未肿大，18F-PET/CT扫描淋巴结有反应者X射线CT扫描可见淋巴结肿大仅占56%。该队列患者接种疫苗后最长达32天可见淋巴结FDG摄取增加，推测可能来自对疫苗的炎症免疫反应，具有酷似或掩盖恶性病变的潜在风险。乳腺癌、黑色素瘤、淋巴瘤等有扩散到同侧腋窝淋巴结倾向的癌症患者应在既往或可能受累部位对侧接种新冠疫苗。核医学技师应记录疫苗接种部位、日期、类型以及第一剂与第二剂。
JAMA Oncol. 2021 Jun 10. Online ahead of print.
Association of COVID-19 mRNA Vaccine With Ipsilateral Axillary Lymph Node Reactivity on Imaging.
Mehmet Emin Adin; Edvin Isufi; Michal Kulon; Darko Pucar.
Yale School of Medicine, New Haven, Connecticut.
This cohort study examines ipsilateral axillary nodal reactivity seen on positron emission tomographic and computed tomographic imaging after intramuscular administration of the coronavirus 2019 mRNA vaccines.
Intramuscular coronavirus 2019 (COVID-19) vaccinations could induce ipsilateral axillary lymph node reactivity that may be falsely attributed to malignant abnormality, prompting unwarranted interventions, or it may be falsely attributed to vaccination rather than cancer, potentially delaying cancer care. We aimed to investigate Moderna and Pfizer COVID-19 vaccine-related nodal reactivity on 18F-flurodeoxyglocose (FDG) positron emission tomographic (PET)/computed tomographic (CT) scans.
METHODS: All patients (n=1290) who underwent FDG-PET/CT scans between December 11, 2020 and March 1, 2021 at the Yale New Haven Hospital were screened for COVID-19 vaccination. Sixty-eight patients who received at least 1 dose of COVID-19 vaccine were analyzed. Sixty-seven of 68 patients had PET/CT for oncologic indications, none of which was adenopathy ipsilateral to the vaccination site. Intensity of lymph node activity was graded by Deauville criteria; activity more intense than mediastinal blood pool was considered reactive.
RESULTS: Reactive ipsilateral axillary lymph nodes developed in 9 of these 68 patients (13%), 7 women and 2 men. After the first vaccine dose, in 2 of 41 patients (5%) and after the second vaccine dose, in 7 of 27 patients (26%) (Fisher exact P=.02; odds ratio [OR], 0.15; CI, 0.01-0.89), 3 (15%) for the Pfizer vaccine and 4 (57%) for the Moderna vaccine. Median time from the second vaccine dose to the FDG-PET/CT scan was 10 days in patients with nodal reactivity and 12 days in those without nodal reactivity. On CT scan, axillary lymph nodes were enlarged (≥10 mm short axis) in 1 of 59 patients (2%) with nonreactive nodes and in 5 of 9 patients (56%) with reactive nodes (Fisher exact P<.001; OR, 0.02; 95% CI, 0.01-0.19). Overall, FDG-activity was seen at the injection site in 6 of 51 patients (12%) for Pfizer and 2 of 17 patients (12%) for Moderna vaccines.
DISCUSSION: Axillary lymphadenopathy following intramuscular vaccine has been observed with influenza and human papilloma virus vaccines, and recently with COVID-19 mRNA vaccines. We found that ipsilateral axillary nodal reactivity occurred after the first vaccine dose in 2 patients (5%) and after the second vaccine dose in 7 (26%); 4 patients (57%) after the second dose of the Moderna vaccine and 3 (15%) after the second dose of the Pfizer vaccine. In the Moderna trial, axillary swelling and tenderness on patient survey was reported in 1322 (11.6%) patients after the first dose (567 [5%] placebo) and in 1654 (16%) after the second dose (444 [4.3%] placebo) of vaccine; in the Pfizer trial, only unsolicited reactions were recorded. 18F-Flurodeoxyglocose-PET/CT is highly sensitive for detection of reactivity in nonenlarged or enlarged lymph nodes, explaining higher frequency of nodal reactivity in this study relative to the Moderna trial after the second dose. In the present study, only 5 patients (56%) with nodal reactivity on PET had nodal enlargement on CT findings. Increased nodal FDG uptake, presumably from an inflammatory immune response to the vaccine, was observed up to 32 days after vaccination in this cohort, harboring the potential risk of mimicking or masking malignant disease. Patients with cancer with a propensity for spread to ipsilateral axillary lymph nodes—breast cancer, melanoma, lymphomas—should have the COVID-19 vaccine in the axilla contralateral to the previously or potentially involved site. Nuclear medicine technologists should document vaccine site, date, type, and first vs second dose. In this cohort, ipsilateral axillary nodal activity was much less common after the first vaccine dose, and women were more likely to develop reactive nodes, an important implication for breast cancer imaging concordant with the statement issued by the Society of Breast Imaging.
LIMITATIONS: This was a single institutional study with limited sample size and follow-up, comparing 2 COVID-19 vaccines available at Yale School of Medicine in early vaccination stage. However, the study was conducted by strict and reproducible PET and CT criteria, and provides a framework for the future studies in this field.
CONCLUSIONS: Ipsilateral axillary nodal reactivity is commonly seen after the intramuscular administration of the COVID-19 mRNA vaccines, more so after the second dose than after the first, and more commonly with the Moderna than the Pfizer vaccine.
DOI: 10.1001/jamaoncol.2021.1794