Trial reportClinical cancer research : an official journal of the American Association for Cancer Research2012
Prognostic and predictive significance of plasma HGF and IL-8 in a phase III trial of chemoradiation with or without tirapazamine in locoregionally advanced head and neck cancer.
Trial report in Clinical cancer research : an official journal of the American Association for Cancer Research, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
24 citing papers in PubMed, 1 synthesis or guideline pooled it, 78 citations in OpenAlex.
- Causal association of serum biomarkers with oral cavity and oropharyngeal cancer: a mendelian randomization study.BMC oral health · 2023Pooled it
- A phase II study evaluating axitinib in patients with unresectable, recurrent or metastatic head and neck cancer.Investigational new drugs · 2015Trial
- Hypoxia, metastatic origin and HPV16 E6/E7 expression differentially shape the radiation response in head and neck squamous cell carcinoma cell lines.Scientific reports · 2026Article
- Promising Targets and Drugs for Improving Head and Neck Cancer Response to Radiotherapy.Current pharmaceutical design · 2026Review
- High IL-8 plasma levels at baseline are predictive of poor overall survival in breast cancer patients receiving chemotherapy.BMC research notes · 2025Article
- CCL4 and MIF: Prognostic Biomarkers for Evaluating the Chemoradiotherapy Response and Prognosis in Patients with ESCC.Journal of Cancer · 2025Article
- AZU1 (HBP/CAP37) and PRKCG (PKC-gamma) may be candidate genes affecting the severity of acute mountain sickness.BMC medical genomics · 2023Article
- Cancer-associated fibroblasts promote the survival of irradiated nasopharyngeal carcinoma cells via the NF-κB pathway.Journal of experimental & clinical cancer research : CR · 2021Article
- Enhancing the efficacy of immunotherapy using radiotherapy.Clinical & translational immunology · 2020Review
- Assessing the interactions between radiotherapy and antitumour immunity.Nature reviews. Clinical oncology · 2019Review
- Cytokines, Chemokines, and Other Biomarkers of Response for Checkpoint Inhibitor Therapy in Skin Cancer.Frontiers in medicine · 2018Review
- Plasma proteins as prognostic biomarkers in radiotherapy treated head and neck cancer patients.Clinical and translational radiation oncology · 2017Article
- Biomarker driven treatment of head and neck squamous cell cancer.Cancers of the head & neck · 2017Review
- Targeting the hypoxic fraction of tumours using hypoxia-activated prodrugs.Cancer chemotherapy and pharmacology · 2016Review
- Phase I study of vandetanib with radiation therapy with or without cisplatin in locally advanced head and neck squamous cell carcinoma.Head & neck · 2016Article
- Plasma macrophage-stimulating protein and hepatocyte growth factor levels are associated with prostate cancer progression.Human cell · 2016Article
- Circulating Cytokine Levels as Markers of Inflammation in Philadelphia Negative Myeloproliferative Neoplasms: Diagnostic and Prognostic Interest.Mediators of inflammation · 2015Review
- Molecular imaging of tumor hypoxia with positron emission tomography.Radiation research · 2014Review
- Defining normoxia, physoxia and hypoxia in tumours-implications for treatment response.The British journal of radiology · 2014Review
- De-escalation treatment protocols for human papillomavirus-associated oropharyngeal squamous cell carcinoma.The Cochrane database of systematic reviews · 2014Article
Corrections and comments
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Authors and funding
13 authors at 3 institutions in 3 countries.
Funding
Abstract
purposeHepatocyte growth factor (HGF) is a hypoxia-induced secreted protein that binds to cMet and regulates interleukin (IL)-8 expression. We evaluated the role of circulating HGF and IL-8 as prognostic and predictive factors for efficacy of tirapazamine (TPZ), a hypoxic cell cytotoxin. EXPERIMENTAL
designPatients with stages III to IV head and neck cancer were randomized to receive radiotherapy with cisplatin (CIS) or CIS plus TPZ (TPZ/CIS). Eligibility for the substudy included plasma sample availability for HGF and IL-8 assay by ELISA and no major radiation deviations (N = 498). Analyses included adjustment for major prognostic factors. p16(INK4A) staining (human papillomavirus surrogate) was carried out on available tumors. Thirty-nine patients had hypoxia imaging with (18)F-fluoroazomycin arabinoside ((18)FAZA)-positron emission tomography.
resultsElevated IL-8 level was associated with worse overall survival (OS) irrespective of treatment. There was an interaction between HGF and treatment arm (P = 0.053); elevated HGF was associated with worse OS in the control but not in the TPZ/CIS arm. Similar trends were observed in analyses restricted to p16(INK4A)-negative patients. Four subgroups defined by high and low HGF/IL-8 levels were examined for TPZ effect; the test for interaction with arm was P = 0.099. TPZ/CIS seemed to be beneficial for patients with high HGF and IL-8 but adverse for low HGF and high IL-8. Only HGF correlated with (18)FAZA tumor standard uptake value.
conclusionsIL-8 is an independent prognostic factor irrespective of treatment. There is an interaction between HGF and treatment arm. Certain subgroups based on IL-8/HGF levels seemed to do better with TPZ/CIS while others did worse, highlighting the complexity of hypoxia targeting in unselected patients.
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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.