Evidence map›Paper›PMID 29982279›Full record

Trial reportAnnals of oncology : official journal of the European Society for Medical Oncology2018

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).

T R Cottrell, E D Thompson, P M Forde, J E Stein, A S Duffield, V Anagnostou, N Rekhtman, R A Anders, J D Cuda, P B Illei and 20 more

2 registry-linked trialsOpen access · hybridAbstract readClinical Trial, Phase II
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Annals of oncology : official journal of the European Society for Medical Oncology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 346 papers, 7 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
346citing papers in PubMed, 7 pooled it
13.7field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT02259621 phase2active not recruitingnot on this map

Neoadjuvant Nivolumab, or Nivolumab in Combination With Ipilimumab, in Resectable Non-Small-Cell Lung Cancer.

TypeinterventionalSponsorSidney Kimmel Comprehensive Cancer Center at Johns HopkinsRan2014 to 2027Enrolled39ConditionsNon-Small Cell Lung CancerArmsNivolumab, Carboplatin, Paclitaxel, Ipilimumab
NCT05317000 phase2recruitingnot on this mapstarted 2023, after this paper: background citation

A Window Trial of 5-Azacytidine or Nivolumab or Combination Nivolumab Plus 5-Azacytidine in Resectable HPV-Associated Head and Neck Squamous Cell Cancer

TypeinterventionalSponsorBarbara BurtnessRan2023 to 2028Enrolled50ConditionsSquamous Cell Carcinoma of Head and NeckArmsCombination 5-azacytidine and nivolumab, Nivolumab
3 · Its place in the literature

Who cites it

346 citing papers in PubMed, 7 syntheses or guidelines pooled it, 566 citations in OpenAlex.

  1. Updated pan-tumor guidelines for neoadjuvant scoring of pathologic response: a joint SITC and INMC effort.Annals of oncology : official journal of the European Society for Medical Oncology · 2026
    Guideline
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  4. Clinicopathological and prognostic value of tertiary lymphoid structures in lung cancer: a meta-analysis.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2025
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  13. Distinct CD8Cancer cell · 2025
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286 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

30 authors at 6 institutions in 1 country.

T R CottrellDepartment of Pathology, Johns Hopkins University SOM, Baltimore, USA.
E D ThompsonDepartment 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.
P M FordeDepartment 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.
J E SteinDepartment of Dermatology, Johns Hopkins University SOM, Baltimore, USA.
A S DuffieldDepartment of Pathology, Johns Hopkins University SOM, Baltimore, USA.
V AnagnostouDepartment of Oncology, The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University SOM, Baltimore, USA.
N RekhtmanDepartment of Pathology, Memorial Sloan Kettering Cancer Center, New York, USA.
R A AndersDepartment of Pathology, Johns Hopkins University SOM, Baltimore, USA; The Johns Hopkins Bloomberg-Kimmel Institute for Cancer Immunotherapy, Baltimore, USA.
J D CudaDepartment of Pathology, Johns Hopkins University SOM, Baltimore, USA; Department of Dermatology, Johns Hopkins University SOM, Baltimore, USA.
P B IlleiDepartment of Pathology, Johns Hopkins University SOM, Baltimore, USA; Department of Oncology, The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University SOM, Baltimore, USA.
E GabrielsonDepartment of Pathology, Johns Hopkins University SOM, Baltimore, USA; Department of Oncology, The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University SOM, Baltimore, USA.
F B AskinDepartment of Pathology, Johns Hopkins University SOM, Baltimore, USA.
N NiknafsDepartment of Oncology, The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University SOM, Baltimore, USA.
K N SmithDepartment 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.
M J VelezDepartment of Pathology, Memorial Sloan Kettering Cancer Center, New York, USA.
J L SauterDepartment of Pathology, Memorial Sloan Kettering Cancer Center, New York, USA.
J M IsbellThoracic Surgery Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, USA.
D R JonesThoracic Surgery Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, USA.
R J BattafaranoDepartment of Surgery, Johns Hopkins University SOM, Baltimore, USA.
S C YangDepartment of Surgery, Johns Hopkins University SOM, Baltimore, USA.
L DanilovaThe 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.
J D WolchokMelanoma 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 Kettering Cancer Center, New York, USA.
S L TopalianThe Johns Hopkins Bloomberg-Kimmel Institute for Cancer Immunotherapy, Baltimore, USA; Department of Surgery, Johns Hopkins University SOM, Baltimore, USA.
V E VelculescuDepartment 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.
D M PardollDepartment 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.
J R BrahmerDepartment 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.
M D HellmannWeill 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.
J E ChaftWeill 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.
A Cimino-MathewsDepartment of Pathology, Johns Hopkins University SOM, Baltimore, USA; Department of Oncology, The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University SOM, Baltimore, USA.
J M TaubeDepartment 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, Johns Hopkins University SOM, Baltimore, USA. Electronic address: jtaube1@jhmi.edu.
Johns Hopkins University · USMemorial Sloan Kettering Cancer Center · USSidney Kimmel Comprehensive Cancer Center · USBloomberg (United States) · USCornell University · USParker Institute for Cancer Immunotherapy · US

Funding

X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI Hongbiao Carl Lekaye · 1985 to 2026
$347.4M
Translational Research Central ServicesP30CA006973 · NCI · JOHNS HOPKINS UNIVERSITY · PI WILLIAM George NELSON · 1985 to 2026
$208.6M
PD-1/PD-L1 modulation in cancer therapyR01CA142779 · NCI · JOHNS HOPKINS UNIVERSITY · PI PARDOLL, DREW M., TAUBE, JANIS M · 2010 to 2025
$8.2M
Large-Scale Genetic Analyses of Human CancerR01CA121113 · NCI · JOHNS HOPKINS UNIVERSITY · PI ANAGNOSTOU, VALSAMO, VELCULESCU, VICTOR E. · 2006 to 2022
$4.3M
ECOG-ACRIN Thoracic Malignancies Integrated Translational Science CenterU10CA180950 · NCI · EMORY UNIVERSITY · PI RAMALINGAM, SURESH S · 2014 to 2018
$2.9M
Opportunities for Pathology Trainees in Cancer ResearchT32CA193145 · NCI · JOHNS HOPKINS UNIVERSITY · PI ANDERS, ROBERT A., EBERHART, CHARLES G · 2015 to 2025
$2.6M
NCI NIH HHS P30 CA006973NCI NIH HHS P30 CA008748NCI NIH HHS R01 CA121113NCI NIH HHS R01 CA142779NCI NIH HHS T32 CA193145NCI NIH HHS U10 CA180950
6 · The paper itself

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.

Indexed as

AdultAntineoplastic Agents, ImmunologicalAntineoplastic Combined Chemotherapy ProtocolsCarcinoma, Non-Small-Cell LungFeasibility StudiesHumansIpilimumabLungLung NeoplasmsNeoadjuvant TherapyNeoplasm, ResidualNivolumabPneumonectomyPrognosisProgrammed Cell Death 1 ReceptorReproducibility of ResultsAntineoplastic Agents, ImmunologicalIpilimumabNivolumabPDCD1 protein, humanProgrammed Cell Death 1 Receptor

Identifiers

PMID29982279
PMCPMC6096736
OpenAlexW2867613812

What OpenQuestion holds

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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.