Evidence map›Paper›PMID 37085598›Full record

ArticleBritish journal of cancer2023

Technical development and validation of a clinically applicable microenvironment classifier as a biomarker of tumour hypoxia for soft tissue sarcoma.

Laura J Forker, Becky Bibby, Lingjian Yang, Brian Lane, Joely Irlam, Hitesh Mistry, Mairah Khan, Helen Valentine, James Wylie, Patrick Shenjere and 8 more

Registry-linked trialOpen access · hybridAbstract read
In one paragraph

Article in British journal of cancer, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT06787053 (Selecting Hypoxic Tumours for Treatment Modification), which is not on this map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
1.6field-weighted citation impact, top 16% 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.

NCT06787053 recruitingnot on this mapstarted 2024, after this paper: background citation

Selecting Hypoxic Tumours for Treatment Modification

TypeobservationalSponsorUniversity of ManchesterRan2024 to 2028Enrolled30ConditionsBladder (Urothelial, Transitional Cell) Cancer, Prostate Cancer
3 · Its place in the literature

Who cites it

3 citing papers in PubMed, 6 citations in OpenAlex.

  1. Review
  2. Review
  3. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

18 authors at 6 institutions in 1 country.

Laura J ForkerTranslational Radiobiology Group, Division of Cancer Sciences, The Oglesby Cancer Research Building, The University of Manchester, Manchester Academic Health Science Centre, 555 Wilmslow Road, Manchester, M20 4GJ, UK. laura.forker@manchester.ac.uk.ORCID http://orcid.org/0000-0002-6506-0894
Becky BibbyTranslational Radiobiology Group, Division of Cancer Sciences, The Oglesby Cancer Research Building, The University of Manchester, Manchester Academic Health Science Centre, 555 Wilmslow Road, Manchester, M20 4GJ, UK.
Lingjian YangTranslational Radiobiology Group, Division of Cancer Sciences, The Oglesby Cancer Research Building, The University of Manchester, Manchester Academic Health Science Centre, 555 Wilmslow Road, Manchester, M20 4GJ, UK.
Brian LaneTranslational Radiobiology Group, Division of Cancer Sciences, The Oglesby Cancer Research Building, The University of Manchester, Manchester Academic Health Science Centre, 555 Wilmslow Road, Manchester, M20 4GJ, UK.
Joely IrlamTranslational Radiobiology Group, Division of Cancer Sciences, The Oglesby Cancer Research Building, The University of Manchester, Manchester Academic Health Science Centre, 555 Wilmslow Road, Manchester, M20 4GJ, UK.
Hitesh MistryTranslational Radiobiology Group, Division of Cancer Sciences, The Oglesby Cancer Research Building, The University of Manchester, Manchester Academic Health Science Centre, 555 Wilmslow Road, Manchester, M20 4GJ, UK.ORCID http://orcid.org/0000-0002-9683-1903
Mairah KhanTranslational Radiobiology Group, Division of Cancer Sciences, The Oglesby Cancer Research Building, The University of Manchester, Manchester Academic Health Science Centre, 555 Wilmslow Road, Manchester, M20 4GJ, UK.
Helen ValentineTranslational Radiobiology Group, Division of Cancer Sciences, The Oglesby Cancer Research Building, The University of Manchester, Manchester Academic Health Science Centre, 555 Wilmslow Road, Manchester, M20 4GJ, UK.
James WylieDepartment of Clinical Oncology, The Christie NHS Foundation Trust, Wilmslow Road, Manchester, M20 4BX, UK.
Patrick ShenjereDepartment of Histopathology, The Christie NHS Foundation Trust, Wilmslow Road, Manchester, M20 4BX, UK.
Michael LeahyDepartment of Medical Oncology, The Christie NHS Foundation Trust, Wilmslow Road, Manchester, M20 4BX, UK.
Piers GauntCancer Research UK Clinical Trials Unit, Institute of Cancer and Genomic Sciences, University of Birmingham, Edgbaston, Birmingham, B15 2TT, UK.
Lucinda BillinghamCancer Research UK Clinical Trials Unit, Institute of Cancer and Genomic Sciences, University of Birmingham, Edgbaston, Birmingham, B15 2TT, UK.
Beatrice M SeddonDepartment of Oncology, University College London Hospitals NHS Foundation Trust, 1st Floor Central, 250 Euston Road, London, NW1 2PG, UK.
Rob GrimerDepartment of Orthopaedic Oncology, Royal Orthopaedic Hospital NHS Foundation Trust, Bristol Road South, Northfield, Birmingham, B31 2AP, UK.
Martin RobinsonDepartment of Oncology, Academic Unit of Clinical Oncology (Cancer Clinical Trials Centre), Weston Park Hospital, Whitham Road, Sheffield, S10 2SJ, UK.
Ananya ChoudhuryTranslational Radiobiology Group, Division of Cancer Sciences, The Oglesby Cancer Research Building, The University of Manchester, Manchester Academic Health Science Centre, 555 Wilmslow Road, Manchester, M20 4GJ, UK.
Catharine WestTranslational Radiobiology Group, Division of Cancer Sciences, The Oglesby Cancer Research Building, The University of Manchester, Manchester Academic Health Science Centre, 555 Wilmslow Road, Manchester, M20 4GJ, UK.ORCID http://orcid.org/0000-0002-0839-3449
Manchester Academic Health Science Centre · GBThe Christie NHS Foundation Trust · GBCancer Research UK Clinical Trials Unit · GBRoyal Orthopaedic Hospital · GBUniversity College London Hospitals NHS Foundation Trust · GBWeston Park Cancer Centre · GB

Funding

Cancer Research UK 25354Cancer Research UK 6786
6 · The paper itself

Abstract

backgroundSoft tissue sarcomas (STS) are rare, heterogeneous tumours and biomarkers are needed to inform management. We previously derived a prognostic tumour microenvironment classifier (24-gene hypoxia signature). Here, we developed/validated an assay for clinical application.

methodsTechnical performance of targeted assays (Taqman low-density array, nanoString) was compared in 28 prospectively collected formalin-fixed, paraffin-embedded (FFPE) biopsies. The nanoString assay was biologically validated by comparing to HIF-1α/CAIX immunohistochemistry (IHC) in clinical samples. The Manchester (n = 165) and VORTEX Phase III trial (n = 203) cohorts were used for clinical validation. The primary outcome was overall survival (OS).

resultsBoth assays demonstrated excellent reproducibility. The nanoString assay detected upregulation of the 24-gene signature under hypoxia in vitro, and 16/24 hypoxia genes were upregulated in tumours with high CAIX expression in vivo. Patients with hypoxia-high tumours had worse OS in the Manchester (HR 3.05, 95% CI 1.54-5.19, P = 0.0005) and VORTEX (HR 2.13, 95% CI 1.19-3.77, P = 0.009) cohorts. In the combined cohort, it was independently prognostic for OS (HR 2.24, 95% CI 1.42-3.53, P = 0.00096) and associated with worse local recurrence-free survival (HR 2.17, 95% CI 1.01-4.68, P = 0.04).

conclusionsThis study comprehensively validates a microenvironment classifier befitting FFPE STS biopsies. Future uses include: (1) selecting high-risk patients for perioperative chemotherapy; and (2) biomarker-driven trials of hypoxia-targeted therapies.

Indexed as

SarcomaTumor HypoxiaBiomarkers, TumorHumansHypoxiaPrognosisReproducibility of ResultsTumor MicroenvironmentBiomarkers, Tumor

Identifiers

PMID37085598
PMCPMC10241814
OpenAlexW4366725383

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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.