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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).
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.
Afiliación
  • Cottrell TR; Department of Pathology, Johns Hopkins University SOM, Baltimore, USA.
  • Thompson ED; Department of Pathology, Johns Hopkins University SOM, Baltimore, USA; Department of Oncology, The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University SOM, Baltimore, USA; The Johns Hopkins Bloomberg-Kimmel Institute for Cancer Immunotherapy, Baltimore, USA.
  • Forde PM; Department of Oncology, The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University SOM, Baltimore, USA; The Johns Hopkins Bloomberg-Kimmel Institute for Cancer Immunotherapy, Baltimore, USA.
  • Stein JE; Department of Dermatology, Johns Hopkins University SOM, Baltimore, USA.
  • Duffield AS; Department of Pathology, Johns Hopkins University SOM, Baltimore, USA.
  • Anagnostou V; Department of Oncology, The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University SOM, Baltimore, USA.
  • Rekhtman N; Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, USA.
  • Anders RA; Department of Pathology, Johns Hopkins University SOM, Baltimore, USA; The Johns Hopkins Bloomberg-Kimmel Institute for Cancer Immunotherapy, Baltimore, USA.
  • Cuda JD; Department of Pathology, Johns Hopkins University SOM, Baltimore, USA; Department of Dermatology, Johns Hopkins University SOM, Baltimore, USA.
  • Illei PB; Department of Pathology, Johns Hopkins University SOM, Baltimore, USA; Department of Oncology, The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University SOM, Baltimore, USA.
  • Gabrielson E; Department of Pathology, Johns Hopkins University SOM, Baltimore, USA; Department of Oncology, The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University SOM, Baltimore, USA.
  • Askin FB; Department of Pathology, Johns Hopkins University SOM, Baltimore, USA.
  • Niknafs N; Department of Oncology, The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University SOM, Baltimore, USA.
  • Smith KN; Department of Oncology, The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University SOM, Baltimore, USA; The Johns Hopkins Bloomberg-Kimmel Institute for Cancer Immunotherapy, Baltimore, USA.
  • Velez MJ; Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, USA.
  • Sauter JL; Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, USA.
  • Isbell JM; Thoracic Surgery Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, USA.
  • Jones DR; Thoracic Surgery Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, USA.
  • Battafarano RJ; Department of Surgery, Johns Hopkins University SOM, Baltimore, USA.
  • Yang SC; Department of Surgery, Johns Hopkins University SOM, Baltimore, USA.
  • Danilova L; The Johns Hopkins Bloomberg-Kimmel Institute for Cancer Immunotherapy, Baltimore, USA; Division of Biostatistics and Bioinformatics, The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University SOM, Baltimore, USA.
  • Wolchok JD; Melanoma and Immunotherapeutics Service, Division of Solid Tumor Oncology, Department of Medicine, Ludwig Center for Cancer Immunotherapy, Memorial Sloan Kettering Cancer Center, New York, USA; Weill Cornell Medical College, New York, USA; Parker Institute for Cancer Immunotherapy, Memorial Sloan Ke
  • Topalian SL; The Johns Hopkins Bloomberg-Kimmel Institute for Cancer Immunotherapy, Baltimore, USA; Department of Surgery, Johns Hopkins University SOM, Baltimore, USA.
  • Velculescu VE; Department of Oncology, The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University SOM, Baltimore, USA; The Johns Hopkins Bloomberg-Kimmel Institute for Cancer Immunotherapy, Baltimore, USA.
  • Pardoll DM; Department of Oncology, The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University SOM, Baltimore, USA; The Johns Hopkins Bloomberg-Kimmel Institute for Cancer Immunotherapy, Baltimore, USA.
  • Brahmer JR; Department of Oncology, The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University SOM, Baltimore, USA; The Johns Hopkins Bloomberg-Kimmel Institute for Cancer Immunotherapy, Baltimore, USA.
  • Hellmann MD; Weill Cornell Medical College, New York, USA; Parker Institute for Cancer Immunotherapy, Memorial Sloan Kettering Cancer Center, New York, USA; Thoracic Oncology Service, Division of Solid Tumor Oncology, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, USA.
  • Chaft JE; Weill Cornell Medical College, New York, USA; Thoracic Oncology Service, Division of Solid Tumor Oncology, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, USA.
  • Cimino-Mathews A; Department of Pathology, Johns Hopkins University SOM, Baltimore, USA; Department of Oncology, The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University SOM, Baltimore, USA.
  • Taube JM; Department of Pathology, Johns Hopkins University SOM, Baltimore, USA; Department of Oncology, The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University SOM, Baltimore, USA; The Johns Hopkins Bloomberg-Kimmel Institute for Cancer Immunotherapy, Baltimore, USA; Department of Dermatology
Ann Oncol ; 29(8): 1853-1860, 2018 08 01.
Article en En | MEDLINE | ID: mdl-29982279
ABSTRACT

Background:

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. Patients and

methods:

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.

Results:

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 < 0.05). This distinct constellation of histologic findings was not identified in any pretreatment specimens. Histopathologic features of the regression bed were used to develop 'Immune-Related Pathologic Response Criteria' (irPRC), and these criteria were shown to be reproducible amongst pathologists. Specifically, %irRVT had improved interobserver consistency compared with %cRVT [median per-case %RVT variability 5% (0%-29%) versus 10% (0%-58%), P = 0.007] and a twofold decrease in median standard deviation across pathologists within a sample (4.6 versus 2.2, P = 0.002).

Conclusions:

irPRC may be used to standardize pathologic assessment of immunotherapeutic efficacy. Long-term follow-up is needed to determine irPRC reliability as a surrogate for recurrence-free and overall survival.
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Protocolos de Quimioterapia Combinada Antineoplásica / Carcinoma de Pulmón de Células no Pequeñas / Antineoplásicos Inmunológicos / Pulmón / Neoplasias Pulmonares Tipo de estudio: Prognostic_studies Límite: Adult / Humans Idioma: En Revista: Ann Oncol Asunto de la revista: NEOPLASIAS Año: 2018 Tipo del documento: Article País de afiliación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Protocolos de Quimioterapia Combinada Antineoplásica / Carcinoma de Pulmón de Células no Pequeñas / Antineoplásicos Inmunológicos / Pulmón / Neoplasias Pulmonares Tipo de estudio: Prognostic_studies Límite: Adult / Humans Idioma: En Revista: Ann Oncol Asunto de la revista: NEOPLASIAS Año: 2018 Tipo del documento: Article País de afiliación: Estados Unidos