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Record W4387043588 · doi:10.1016/j.euros.2023.09.003

Feasibility and Impact of Immunohistochemistry-based Molecular Subtyping for Muscle-invasive Bladder Cancer in Patients Treated with Radiation-based Therapy

2023· article· en· W4387043588 on OpenAlexafffund
Charles Hesswani, Chelsea Jackson, Gautier Marcq, Céline Hardy, Ronald Kool, José João Mansure, Fadi Brimo, David M. Berman, Wassim Kassouf

Bibliographic record

VenueEuropean Urology Open Science · 2023
Typearticle
Languageen
FieldMedicine
TopicBladder and Urothelial Cancer Treatments
Canadian institutionsQueen's UniversityMcGill University Health Centre
FundersMcGill University
KeywordsSubtypingImmunohistochemistryBladder cancerMedicineOncologyInternal medicineInterquartile rangeRadiation therapyCystectomyTissue microarrayPathologyCancer

Abstract

fetched live from OpenAlex

Background: Distinct molecular subtypes of muscle-invasive bladder cancer (MIBC) have been identified via gene expression profiling. Objective: We investigated the feasibility of a simple immunohistochemistry (IHC)-based Lund subtyping method and the association of MIBC subtypes with oncological outcomes for patients after bladder-preserving radiation-based therapy. Design setting and participants: Transurethral resected tumor tissues from 104 patients treated with radiation-based therapy were sampled on tissue microarray blocks. Outcome measurements and statistical analysis: The expression of KRT5, GATA3, and p16 proteins was scored via digital image analysis. Hierarchical clustering was used to classify tumors as the basal subtype or one of two luminal subtypes: genomically unstable (GU) or urothelial-like (URO). Subtypes were evaluated for association with complete response (CR), recurrence-free survival (RFS), and overall survival (OS). Results and limitations: < 0.05). IHC-based subtype classification was feasible in most patients (89%). The subtype was basal in 23.6%, GU in 14.0%, URO in 31.2%, and unclassified in 31.2% of patients. No significant differences in CR, RFS, or OS were observed between the molecular subtypes. Limitations include the retrospective design and relatively small sample size. Conclusions: IHC-based molecular MIBC subtyping using a three-antibody algorithm is feasible in most patients treated with radiation-based therapy. MIBC subtype was not associated with response or survival. Further prospective studies are warranted to confirm the lack of association between molecular subtype and survival in patients treated with trimodal therapy. Patient summary: For patients with invasive bladder cancer treated with radiation-based therapy, we classified tumors into different subtypes using just three molecular stains. This method is cheaper and more widely available than the usual approach. However, we did not find an association between different cancer subtypes and survival.

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 score0.035
Threshold uncertainty score0.459

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0010.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.001
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 head0.029
GPT teacher head0.342
Teacher spread0.313 · 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

Citations4
Published2023
Admission routes2
Has abstractyes

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