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The classical Hodgkin lymphoma tumor microenvironment: macrophages and gene expression-based modeling

2014· review· en· W2074047902 on OpenAlex
David W. Scott, Christian Steidl

Why this work is in the frame

A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.

affAt least one author lists a Canadian institution in the pinned OpenAlex snapshot.

Bibliographic record

VenueHematology · 2014
Typereview
Languageen
FieldMedicine
TopicLymphoma Diagnosis and Treatment
Canadian institutionsBC Cancer Agency
Fundersnot available
KeywordsABVDDacarbazineMedicineTumor microenvironmentOncologyBCL6CD163BleomycinImmunohistochemistryLymphomaCancer researchPathologyInternal medicineBiologyChemotherapyImmunologyCancerAntibodyPhenotypeGeneVincristineB cell

Abstract

fetched live from OpenAlex

Despite the high cure rate in classical Hodgkin lymphoma (CHL), more accurate tailoring of upfront treatment is required to maximize cure while avoiding unnecessary short- and long-term treatment side effects. To this end, the unique tumor microenvironment of CHL has been searched extensively for prognostic biomarkers. Beyond targeted immunohistochemistry (IHC) studies, gene expression profiling (GEP) of diagnostic whole tissue biopsies has allowed a de novo approach to biomarker discovery. Among numerous candidate biomarkers, an association between the number of tumor-associated macrophages in the microenvironment and outcomes after ABVD (doxorubicin + bleomycin + vinblastine + dacarbazine) chemotherapy emerged, and multiple subsequent studies have validated this biological relationship using IHC. These studies have also defined key aspects for macrophage interrogation, including the characteristics of the CD68 and CD163 antibodies, appropriate scoring methodologies, and the identification of specific patient populations in which macrophage IHC may not be prognostic. The GEP studies also led to the development of gene expression-based prognostic models for advanced-stage CHL, with new technologies allowing reliable gene expression quantitation using RNA from routinely produced formalin-fixed paraffin-embedded biopsies. The bridge to predictive biomarkers that can be used reliably to inform upfront treatment selection requires further studies to demonstrate that these biomarkers can identify robustly, at diagnosis, patients at high risk of treatment failure with ABVD and that this risk may be overcome using alternative treatments.

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.

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)0.000
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesMeta-epidemiology (narrow)
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Not applicable · Consensus signal: none
GenreCandidate signal: Review · Consensus signal: Review
Teacher disagreement score0.982
Threshold uncertainty score1.000

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0020.000
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 head0.026
GPT teacher head0.297
Teacher spread0.271 · 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