Nodal immune flare mimics nodal disease progression following neoadjuvant immune checkpoint inhibitors in non-small cell lung cancer.

Abstract

Radiographic imaging is the standard approach for evaluating the disease involvement of lymph nodes in patients with operable NSCLC although the impact of neoadjuvant immune checkpoint inhibitors (ICIs) on lymph nodes has not yet been characterized. Herein, we present an ad hoc analysis of the NEOSTAR trial (NCT03158129) where we observed a phenomenon we refer to as "nodal immune flare" (NIF) in which patients treated with neoadjuvant ICIs demonstrate radiologically abnormal nodes post-therapy that upon pathological evaluation are devoid of cancer and demonstrate de novo non-caseating granulomas. Abnormal lymph nodes are analyzed by computed tomography and 18F-fluorodeoxyglucose positron emission tomography/computer tomography to evaluate the size and the maximum standard uptake value post- and pre-therapy in NEOSTAR and an independent neoadjuvant chemotherapy cohort. NIF occurs in 16% (7/44) of patients treated with ICIs but in 0% (0/28) of patients after neoadjuvant chemotherapy. NIF is associated with an inflamed nodal immune microenvironment and with fecal abundance of genera belonging to the family Coriobacteriaceae of phylum Actinobacteria, but not with tumor responses or treatment-related toxicity. Our findings suggest that this apparent radiological cancer progression in lymph nodes may occur due to an inflammatory response after neoadjuvant immunotherapy, and such cases should be evaluated by pathological examination to distinguish NIF from true nodal progression and to ensure appropriate clinical treatment planning.

• Authors: Tina Cascone, Annikka Weissferdt, Myrna C B Godoy, William N William Jr, Cheuk H Leung, Heather Y Lin, Sreyashi Basu, Shalini S Yadav, Apar Pataer, Kyle G Mitchell, Md Abdul Wadud Khan, Yushu Shi, Cara Haymaker, Luisa M Solis, Edwin R Parra, Humam Kadara, Ignacio I Wistuba, Padmanee Sharma, James P Allison, Nadim J Ajami, Jennifer A Wargo, Robert R Jenq, Don L Gibbons, J Jack Lee, Stephen G Swisher, Ara A Vaporciyan, John V Heymach, Boris Sepesi
• Journal: Nature communications (Nat Commun) Vol. 12 Issue 1 Pg. 5045 (08 19 2021) ISSN: 2041-1723 [Electronic] England
• PMID: 34413300 (Publication Type: Clinical Trial, Phase II, Journal Article, Randomized Controlled Trial, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: © 2021. The Author(s).

Chemical References

• Immune Checkpoint Inhibitors

Topics

• Aged
• Carcinoma, Non-Small-Cell Lung (diagnostic imaging, drug therapy, immunology, pathology)
• Disease Progression
• Female
• Humans
• Immune Checkpoint Inhibitors (administration & dosage, adverse effects)
• Lung Neoplasms (diagnostic imaging, drug therapy, immunology, pathology)
• Lymph Nodes (drug effects, immunology, pathology)
• Lymphatic Metastasis
• Male
• Middle Aged
• Multimodal Imaging (methods)
• Neoadjuvant Therapy