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Record W4388033556 · doi:10.1038/s41591-023-02660-6

Association between pathologic response and survival after neoadjuvant therapy in lung cancer

2023· article· en· W4388033556 on OpenAlexafffund
Julie S. Deutsch, Ashley Cimino‐Mathews, Elizabeth D. Thompson, Mariano Provencio, Patrick M. Forde, Jonathan Spicer, Nicolas Girard, Daphne Wang, Robert A. Anders, Edward Gabrielson, Peter B. Illei, Jaroslaw Jedrych, Ludmila Danilova, Joel Sunshine, Keith M. Kerr, Mia Tran, Judith Bushong, Junliang Cai, Vipul Devas, Jaclyn Neely, David Balli, Tricia R. Cottrell, Alex S. Baras, Janis M. Taube

Bibliographic record

VenueNature Medicine · 2023
Typearticle
Languageen
FieldMedicine
TopicLung Cancer Diagnosis and Treatment
Canadian institutionsQueen's UniversityMcGill University Health Centre
FundersCongressionally Directed Medical Research ProgramsNational Cancer InstituteNational Institutes of HealthOno PharmaceuticalCanadian Association of Thoracic SurgeonsG1 TherapeuticsGenentechF-star TherapeuticsRegeneron PharmaceuticalsU.S. Department of DefenseSanofiLUNGevity FoundationSociety for Immunotherapy of CancerAstraZenecaEli Lilly and CompanyBristol-Myers SquibbMark Foundation For Cancer ResearchMesothelioma Applied Research FoundationPfizerAmgen
KeywordsMedicineLung cancerNeoadjuvant therapyNivolumabOncologyInternal medicineChemotherapyHazard ratioCancerResponse Evaluation Criteria in Solid TumorsPathologyProgressive diseaseImmunotherapyConfidence intervalBreast cancer

Abstract

fetched live from OpenAlex

Neoadjuvant immunotherapy plus chemotherapy improves event-free survival (EFS) and pathologic complete response (0% residual viable tumor (RVT) in primary tumor (PT) and lymph nodes (LNs)), and is approved for treatment of resectable lung cancer. Pathologic response assessment after neoadjuvant therapy is the potential analog to radiographic response for advanced disease. However, %RVT thresholds beyond pathologic complete response and major pathologic response (≤10% RVT) have not been explored. Pathologic response was prospectively assessed in the randomized, phase 3 CheckMate 816 trial (NCT02998528), which evaluated neoadjuvant nivolumab (anti-programmed death protein 1) plus chemotherapy in patients with resectable lung cancer. RVT, regression and necrosis were quantified (0-100%) in PT and LNs using a pan-tumor scoring system and tested for association with EFS in a prespecified exploratory analysis. Regardless of LN involvement, EFS improved with 0% versus >0% RVT-PT (hazard ratio = 0.18). RVT-PT predicted EFS for nivolumab plus chemotherapy (area under the curve = 0.74); 2-year EFS rates were 90%, 60%, 57% and 39% for patients with 0-5%, >5-30%, >30-80% and >80% RVT, respectively. Each 1% RVT associated with a 0.017 hazard ratio increase for EFS. Combining pathologic response from PT and LNs helped differentiate outcomes. When compared with radiographic response and circulating tumor DNA clearance, %RVT best approximated EFS. These findings support pathologic response as an emerging survival surrogate. Further assessment of the full spectrum of %RVT in lung cancer and other tumor types is warranted. ClinicalTrials.gov registration: NCT02998528 .

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.001
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.068
Threshold uncertainty score0.391

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0010.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0000.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.014
GPT teacher head0.349
Teacher spread0.334 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one teacher head, not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designObservational
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations162
Published2023
Admission routes2
Has abstractyes

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