MétaCan
Menu
Back to cohort

Role of the total mutation burden (TMB) and tumor-infiltrating lymphocytes (TILs) on the development of second primary cancer after complete resection of non-small cell lung cancer (NSCLC).

2020· article· en· W3030975652 on OpenAlexaff
Marie-Pier Gauthier, Maryam Karimi, Stefan Michiels, Lesley Seymour, Élisabeth Brambilla, Thierry Le Chevalier, Jean‐Charles Soria, Robert A. Kratzke, Stephen L. Graziano, Ramaswamy Govindan, Ming‐Sound Tsao, Frances A. Shepherd

Bibliographic record

VenueJournal of Clinical Oncology · 2020
Typearticle
Languageen
FieldMedicine
TopicMultiple and Secondary Primary Cancers
Canadian institutionsUniversity of TorontoUniversity Health NetworkQueen's UniversityPrincess Margaret Cancer Centre
Fundersnot available
KeywordsMedicineHazard ratioLung cancerOncologyInternal medicineTumor-infiltrating lymphocytesStage (stratigraphy)non-small cell lung cancer (NSCLC)Proportional hazards modelCancerConfidence intervalImmunotherapy

Abstract

fetched live from OpenAlex

e21092 Background: Risk of developing SPC after complete surgical resection of NSCLC has been reported to be 3-6% per person-year. We hypothesized that genomic instability, as assessed by high TMB, and the absence of TILs in the primary tumor might be associated with SPC. Methods: The LACE [Lung Adjuvant Cisplatin Evaluation])-BIO database was used, which includes 3 randomized trials. TMB and TILs were analyzed on FFPE specimens. TMB was categorized into tertiles (high > 7.8 mutations/MB, moderate i.e. > 4 and < = 7.8, low < 4) and TILs as marked vs. other. Associations on competing time-to-event endpoints (SPC, and death without developing SPC) were evaluated using the Fine and Gray model stratified by trail and adjusted on treatment, age, gender, tumor stage, nodal stage, histology, performance status and surgery type. Results: TMB and TILs assessments were available for 879 patients without missing clinical covariates; 85 patients had marked TILs. During follow-up, 47 SPCs had been observed and 392 deaths without developing SPC. Regarding TMB, a significant association was found between low TMB and death without SPC (sub-distribution hazard ratio SHR = 1.36(1.06-1.74), see Table), suggesting a higher risk of death without SPC among patient with low TMB compared to those with moderate TMB; no strong effect was observed for SPC. Regarding TILs, a trend was observed between marked TILS and a lower risk of death (SHR = 0.70 [0.47-1.04]) but to a lesser extent for SPC (SHR = 0.80 [0.28-2.28]). Conclusions: This is the first study of the effect of genomic instability (measured by TMB) and host immune response (measured by TILs) in completely resected NSCLC on competing events of SPC and death, suggesting associations between TMB, TILs and death-without-SPC . There was no statistically significant association with SPC. However, the number of SPCs was small; these findings requires validation in other early stage lung cancer cohorts. [Table: see text]

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: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.709
Threshold uncertainty score0.673

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0010.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0010.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.001
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 head0.057
GPT teacher head0.364
Teacher spread0.307 · 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

Citations0
Published2020
Admission routes1
Has abstractyes

Explore more

Same venueJournal of Clinical OncologySame topicMultiple and Secondary Primary CancersFrench-language works237,207