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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.

SUBMITTER: Cascone T

PROVIDER: S-EPMC8376947 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature

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

Cascone Tina T Weissferdt Annikka A Godoy Myrna C B MCB William William N WN Leung Cheuk H CH Lin Heather Y HY Basu Sreyashi S Yadav Shalini S SS Pataer Apar A Mitchell Kyle G KG Khan Md Abdul Wadud MAW Shi Yushu Y Haymaker Cara C Solis Luisa M LM Parra Edwin R ER Kadara Humam H Wistuba Ignacio I II Sharma Padmanee P Allison James P JP Ajami Nadim J NJ Wargo Jennifer A JA Jenq Robert R RR Gibbons Don L DL Lee J Jack JJ Swisher Stephen G SG Vaporciyan Ara A AA Heymach John V JV Sepesi Boris B

Nature communications 20210819 1

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 t ...[more]

PMID: 34413300

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Project description:BackgroundOur objective was to explore the safety and feasibility of immune checkpoint inhibitors (ICIs) in the neoadjuvant treatment of non-small cell lung cancer (NSCLC).MethodsEmbase, PubMed and Web of Science were systematically searched from 1st January 2018 to 1st August 2021 for studies with data on the treatment-related adverse reactions (TRAE), immune-related adverse events (irAE), perioperative information, major pathological response (MPR), pathologic complete remission (pCR) and objective response rate (ORR). The QUADAS-2 tool was used to assess the quality of the studies, then the data were transformed for meta-analysis. Review Manager 5.3 (Cochrane) was used for statistical analyses with a P value of <0.05 considered significant.ResultsThirteen studies with 358 patients were included in this meta-analysis, of which, 218 patients received ICI and chemotherapy-containing regimens and 140 patients received neoadjuvant ICIs only. The 157 (72.0%) patients who received combined neoadjuvant therapy showed a higher incidence of TRAEs, while only 37 (26.4%) patients who received neoadjuvant ICIs experienced TRAEs. Grade 3 or higher irAEs were observed in 92 (25.7%) patients, of which, 81 patients belonged to the neoadjuvant immunochemotherapy subgroup. The surgical resection rate was between 38.5-100%, with only two patients experiencing a delay in surgery. Complication rates were between 3.6-100% in the 8 studies that reported postoperative complications, with more postoperative complications [35 (18.9%)] identified in the neoadjuvant immunochemotherapy subgroup. Of which 176 patients achieved MPR, 126 received ICI and chemotherapy combined neoadjuvant therapy. Seventy-one of 95 patients who had achieved pCR had undergone ICI and chemotherapy. Compared with the neoadjuvant immunotherapy group, patients undergoing ICI and chemotherapy achieved more radiological response [118 (54.1%)] than patients undergoing ICIs [25 (17.9%)] only. The odds ratio (OR) value of the MPR/pCR/ORR rate in the neoadjuvant immunochemotherapy group was higher [OR =0.55/0.32/0.39, 95% confidence interval (CI): 0.44-0.66/0.22-0.44/0.26-0.53, P=0.0004/0.14/<0.0001] after transformation.DiscussionNeoadjuvant immunotherapy shows lower toxicity and fewer perioperative complications. ICI combined chemotherapy can achieve more pathological relief and clinical benefits in the neoadjuvant treatment of NSCLC but is associated with increased irAE and perioperative complications. However, the small sample size limits the reliability of the research.

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

Publications

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

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