Pretreatment tumor-related leukocytosis misleads positron emission tomography-computed tomography during lymph node staging in gynecological malignancies

概要

〔目的(Purpose)〕
Accurate lymph node staging is highly important for determining the optimal treatment strategy and for predicting the treatment outcomes in cancer patients. False-positive detection of distant nodes can result in unnecessary surgical resection or radiotherapy to the suspected nodes, which can cause increased toxicities. The aim of this study was to investigate the impact of pretreatment tumor-related leukocytosis (TRL) on the diagnostic performance of 18F-FDG-PET/CT in detecting pelvic and paraaortic lymph node metastasis.

〔方法ならびに成績(Methods/Results)〕
Using clinical data obtained from 551 gynecological cancer patients, we first evaluated the impact of pretreatment tumor TRL on the diagnostic performance of 18F-FDG-PET/CT in detecting pelvic and paraaortic lymph node metastasis. Then, using tumor samples obtained from gynecological cancer patients as well as animal models of gynecological cancers, we performed mechanistic investigations focusing on the myeloid-derived suppressor cells (MDSC)-mediated premetastatic niche and 18F- FDG-uptake.
We demonstrated that pretreatment TRL misleads I8F-FDG-PET/CT during lymph node stating in gynecological malignancies. In the mechanistic investigations, we found that the false-positive 18F-FDG-PET/CT result for detecting nodal metastasis was reproduced in the animal models of TRL-positive cancer bearing G-CSF expressing cervical cancer cells. We also showed that increased 18F-FDG uptake in non-metastatic nodes could be explained by the MDSC-mediated premetastatic niche formation in which proinflammatory factors, such as S100A8 or S100A9, are abundantly expressed.

〔総括(Conclusion)〕
Pretreatment TRL was associated with increased false-positive 18F-FDG-PET/CT results during lymph node staging in gynecological cancer patients. The MDSC-mediated premetastatic niche created in the lymph node of TRL-positive patients misleads 18F-FDG-PET/CT for detecting nodal metastasis.