International Association for the Study of Lung Cancer Study of Reproducibility in Assessment of Pathologic Response in Resected Lung Cancers After Neoadjuvant Therapy

Sanja Dacic; William Travis; Mary Redman; Anjali Saqi; Wendy A Cooper; Alain Borczuk; Jin-Haeng Chung; Carolyn Glass; Javier Martin Lopez; Anja C Roden; Lynette Sholl; Annikka Weissferdt; Juan Posadas; Angela Walker; Hu Zhu; Manuja T Wijeratne; Casey Connolly; Murry Wynes; Neus Bota-Rabassedas; Beatriz Sanchez-Espiridion; J Jack Lee; Sabina Berezowska; Teh-Ying Chou; Keith Kerr; Andrew Nicholson; Claudia Poleri; Kurt A Schalper; Ming-Sound Tsao; David P Carbone; Neal Ready; Tina Cascone; John Heymach; Boris Sepesi; Catherine Shu; Naiyer Rizvi; Josuha Sonett; Nasser Altorki; Mariano Provencio; Paul A Bunn Jr; Mark G Kris; Chandra P Belani; Karen Kelly; Ignacio Wistuba; IASLC Pathology Committee

doi:10.1016/j.jtho.2023.07.017

International Association for the Study of Lung Cancer Study of Reproducibility in Assessment of Pathologic Response in Resected Lung Cancers After Neoadjuvant Therapy

J Thorac Oncol. 2023 Oct;18(10):1290-1302. doi: 10.1016/j.jtho.2023.07.017. Epub 2023 Sep 12.

Authors

Sanja Dacic¹, William Travis², Mary Redman³, Anjali Saqi⁴, Wendy A Cooper⁵, Alain Borczuk⁶, Jin-Haeng Chung⁷, Carolyn Glass⁸, Javier Martin Lopez⁹, Anja C Roden¹⁰, Lynette Sholl¹¹, Annikka Weissferdt¹², Juan Posadas¹³, Angela Walker¹³, Hu Zhu¹³, Manuja T Wijeratne¹³, Casey Connolly¹⁴, Murry Wynes¹⁴, Neus Bota-Rabassedas¹³, Beatriz Sanchez-Espiridion¹³, J Jack Lee¹⁵, Sabina Berezowska¹⁶, Teh-Ying Chou¹⁷, Keith Kerr¹⁸, Andrew Nicholson¹⁹, Claudia Poleri²⁰, Kurt A Schalper²¹, Ming-Sound Tsao²², David P Carbone²³, Neal Ready²⁴, Tina Cascone²⁵, John Heymach²⁵, Boris Sepesi²⁶, Catherine Shu²⁷, Naiyer Rizvi²⁷, Josuha Sonett²⁸, Nasser Altorki²⁹, Mariano Provencio³⁰, Paul A Bunn Jr³¹, Mark G Kris³², Chandra P Belani³³, Karen Kelly¹⁴, Ignacio Wistuba¹³; IASLC Pathology Committee

Affiliations

¹ Department of Pathology, University of Pittsburgh, Pittsburgh, Pennsylvania. Electronic address: sanja.dacic@yale.edu.
² Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, New York.
³ Fred Hutchinson Cancer Center, Seattle, Washington.
⁴ Department of Pathology and Cell Biology, Columbia University Medical Center, New York, New York.
⁵ Tissue Pathology and Diagnostic Oncology, NSW Health Pathology, Royal Prince Alfred Hospital, Sydney, Australia; Faculty of Health and Medicine, University of Sydney, Sydney, Australia; Faculty of Medicine, University of Western Sydney, Sydney, Australia.
⁶ Department of Anatomic/Clinical Pathology, Northwell Health, Greenvale, New York.
⁷ Department of Pathology and Translational Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea.
⁸ Department of Pathology, Duke University School of Medicine, Durham, North Carolina.
⁹ Department of Pathology, Hospital Universitario Puerta de Hierro-Majadahonda, Madrid, Spain.
¹⁰ Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota.
¹¹ Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.
¹² Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
¹³ Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
¹⁴ International Association for the Study of Lung Cancer, Denver, Colorado.
¹⁵ Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, Texas.
¹⁶ Institute of Pathology, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.
¹⁷ Taipei Veterans General Hospital, Taipei, Taiwan.
¹⁸ Department of Pathology, Aberdeen Royal Infirmary, Aberdeen University Medical School, Aberdeen, United Kingdom.
¹⁹ Department of Histopathology, Royal Brompton and Harefield National Health Service Foundation Trust and National Heart and Lung Institute, Imperial College, London, United Kingdom.
²⁰ Independent Consultant in Thoracic Pathology, Buenos Aires, Argentina.
²¹ Department of Pathology and Medicine, Yale School of Medicine, New Haven, Connecticut.
²² Department of Pathology, University Health Network, and Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada.
²³ Comprehensive Cancer Center, Division of Medical Oncology, The Ohio State University, Columbus, USA.
²⁴ Department of Medicine, Duke Medical Center, Durham, North Carolina.
²⁵ Department of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
²⁶ Department of Thoracic and Cardiovascular Surgery, The University of Texas MD Anderson Cancer Center, Houston, Texas.
²⁷ Division of Hematology and Oncology, Columbia University Medical Center, New York, New York.
²⁸ Thoracic Surgery Department, Columbia University New York-Presbyterian Hospital, New York, New York.
²⁹ Department of Cardiothoracic Surgery, Weill Medical College of Cornell University, New York, New York.
³⁰ Department of Medical Oncology, Hospital Universitario Puerta de Hierro-Majadahonda, Madrid, Spain.
³¹ Medical Oncology, Colorado University School of Medicine, Aurora, Colorado.
³² Thoracic Oncology Service, Division of Solid Tumor Oncology, Department of Medicine, Memorial Sloan Kettering Cancer Center and Weill Cornell Medicine, New York, New York.
³³ Penn State Hershey Medical Center, Penn State Cancer Institute, Hershey, Pennsylvania.

PMID: 37702631
DOI: 10.1016/j.jtho.2023.07.017

Abstract

Introduction: Pathologic response has been proposed as an early clinical trial end point of survival after neoadjuvant treatment in clinical trials of NSCLC. The International Association for the Study of Lung Cancer (IASLC) published recommendations for pathologic evaluation of resected lung cancers after neoadjuvant therapy. The aim of this study was to assess pathologic response interobserver reproducibility using IASLC criteria.

Methods: An international panel of 11 pulmonary pathologists reviewed hematoxylin and eosin-stained slides from the lung tumors of resected NSCLC from 84 patients who received neoadjuvant immune checkpoint inhibitors in six clinical trials. Pathologic response was assessed for percent viable tumor, necrosis, and stroma. For each slide, tumor bed area was measured microscopically, and pre-embedded formulas calculated unweighted and weighted major pathologic response (MPR) averages to reflect variable tumor bed proportion.

Results: Unanimous agreement among pathologists for MPR was observed in 68 patients (81%), and inter-rater agreement (IRA) was 0.84 (95% confidence interval [CI]: 0.76-0.92) and 0.86 (95% CI: 0.79-0.93) for unweighted and weighted averages, respectively. Overall, unweighted and weighted methods did not reveal significant differences in the classification of MPR. The highest concordance by both methods was observed for cases with more than 95% viable tumor (IRA = 0.98, 95% CI: 0.96-1) and 0% viable tumor (IRA = 0.94, 95% CI: 0.89-0.98). The most common reasons for discrepancies included interpretations of tumor bed, presence of prominent stromal inflammation, distinction between reactive and neoplastic pneumocytes, and assessment of invasive mucinous adenocarcinoma.

Conclusions: Our study revealed excellent reliability in cases with no residual viable tumor and good reliability for MPR with the IASLC recommended less than or equal to 10% cutoff for viable tumor after neoadjuvant therapy.

Keywords: Lung cancer; MPR; Neoadjuvant therapy; Reproducibility.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Carcinoma, Non-Small-Cell Lung* / pathology
Humans
Lung / pathology
Lung Neoplasms* / pathology
Neoadjuvant Therapy / methods
Reproducibility of Results

Grants and funding

P50 CA228944/CA/NCI NIH HHS/United States