Pathologic features of response to neoadjuvant anti-PD-1 in resected non-small-cell lung carcinoma: a proposal for quantitative immune-related pathologic response criteria (irPRC)

Neoadjuvant anti-PD-1 may improve outcomes for patients with resectable NSCLC and provides a critical window for examining pathologic features associated with response. Resections showing major pathologic response to neoadjuvant therapy, defined as ≤10% residual viable tumor (RVT), may predict impro...

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Bibliographic Details
Published in:	Annals of oncology 2018-08, Vol.29 (8), p.1853-1860
Main Authors:	Cottrell, T.R., Thompson, E.D., Forde, P.M., Stein, J.E., Duffield, A.S., Anagnostou, V., Rekhtman, N., Anders, R.A., Cuda, J.D., Illei, P.B., Gabrielson, E., Askin, F.B., Niknafs, N., Smith, K.N., Velez, M.J., Sauter, J.L., Isbell, J.M., Jones, D.R., Battafarano, R.J., Yang, S.C., Danilova, L., Wolchok, J.D., Topalian, S.L., Velculescu, V.E., Pardoll, D.M., Brahmer, J.R., Hellmann, M.D., Chaft, J.E., Cimino-Mathews, A., Taube, J.M.
Format:	Article
Language:	eng
Subjects:	Adult Antineoplastic Agents, Immunological - pharmacology Antineoplastic Agents, Immunological - therapeutic use Antineoplastic Combined Chemotherapy Protocols - pharmacology Antineoplastic Combined Chemotherapy Protocols - therapeutic use Carcinoma, Non-Small-Cell Lung - immunology Carcinoma, Non-Small-Cell Lung - pathology Carcinoma, Non-Small-Cell Lung - therapy Editor's Choice Feasibility Studies Humans Ipilimumab - pharmacology Ipilimumab - therapeutic use irPRC Lung - immunology Lung - pathology Lung - surgery lung carcinoma Lung Neoplasms - immunology Lung Neoplasms - pathology Lung Neoplasms - therapy neoadjuvant Neoadjuvant Therapy - methods Neoplasm, Residual Nivolumab - pharmacology Nivolumab - therapeutic use Original pathologic response PD-1 Pneumonectomy Prognosis Programmed Cell Death 1 Receptor - antagonists & inhibitors Programmed Cell Death 1 Receptor - immunology Reproducibility of Results Treatment Outcome
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Summary:	Neoadjuvant anti-PD-1 may improve outcomes for patients with resectable NSCLC and provides a critical window for examining pathologic features associated with response. Resections showing major pathologic response to neoadjuvant therapy, defined as ≤10% residual viable tumor (RVT), may predict improved long-term patient outcome. However, %RVT calculations were developed in the context of chemotherapy (%cRVT). An immune-related %RVT (%irRVT) has yet to be developed. The first trial of neoadjuvant anti-PD-1 (nivolumab, NCT02259621) was just reported. We analyzed hematoxylin and eosin-stained slides from the post-treatment resection specimens of the 20 patients with non-small-cell lung carcinoma who underwent definitive surgery. Pretreatment tumor biopsies and preresection radiographic ‘tumor’ measurements were also assessed. We found that the regression bed (the area of immune-mediated tumor clearance) accounts for the previously noted discrepancy between CT imaging and pathologic assessment of residual tumor. The regression bed is characterized by (i) immune activation—dense tumor infiltrating lymphocytes with macrophages and tertiary lymphoid structures; (ii) massive tumor cell death—cholesterol clefts; and (iii) tissue repair—neovascularization and proliferative fibrosis (each feature enriched in major pathologic responders versus nonresponders, P
ISSN:	0923-7534 1569-8041