Epidermal Growth Factor Receptor Expression in Pretreatment Biopsies From Head and Neck Squamous Cell Carcinoma As a Predictive Factor for a Benefit From Accelerated Radiation Therapy in a Randomized Controlled Trial

Bentzen, Søren M.; Atasoy, Beste Melek; Daley, Frances; Dische, Stanley; Richman, P. I.; Saunders, Michele I.; Trott, Klaus R.; Wilson, George D.

doi:10.1200/jco.2005.06.411

Cited by 233 publications

(141 citation statements)

References 30 publications

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“…Bentzen and co-workers performed IHC on 304 patients randomised to receive CHART vs conventionally fractionated radiotherapy. They concluded that there was a significant benefit from strongly accelerated CHART in patients with high EGFR expression and no benefit in patients with a low EGFR index (Bentzen et al, 2005). These results suggest that the predictive value of EGFR to radiotherapy may be dependent on the dose fractionation regimen.…”

Section: Discussionmentioning

confidence: 99%

Combined analysis of VEGF and EGFR predicts complete tumour response in rectal cancer treated with preoperative radiotherapy

et al. 2008

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The ability to predict complete pathologic response or sensitivity to radiation before treatment would have a significant impact on the selection of patients for preoperative radiotherapy or chemo-radiation therapy schedules. The aim of this study was to determine the value of epidermal growth factor receptor (EGFR), vascular endothelial growth factor (VEGF), p53, Bcl-2 and apoptosis proteaseactivating factor-1 (APAF-1) as predictors of complete pathologic tumour regression in patients undergoing preoperative radiotherapy for advanced rectal cancer. Pretreatment tumour biopsies from predominantly cT3 patients undergoing a preoperative high-dose-rate brachytherapy protocol were immunostained for EGFR, VEGF, p53, Bcl-2 and APAF-1. Immunoreactivity was evaluated by three pathologists. Cut-off scores for tumour marker positivity were obtained by receiver-operating characteristic (ROC) curve analysis. The association of marker expression with complete pathologic response was analysed in univariate and multivariable analysis. Multi-marker phenotypes of the independent protein markers were evaluated. In multivariable analysis, loss of VEGF (P-value ¼ 0.009; odds ratio (OR) (95% CI) ¼ 0.24 (0.08 -0.69)) and positive EGFR (P-value ¼ 0.01; OR (95% CI) ¼ 3.82 (1.37 -10.6)) both demonstrated independent predictive value for complete pathologic response. The odds of complete response were 12.8 for the multi-marker combination of VEGF-negative and EGFR-positive tumours. Of the 34 EGFR-negative-and VEGFpositive cases, 32 (94.1%) had no complete pathologic response. The combined analysis of VEGF and EGFR is predictive of complete pathologic response in patients undergoing preoperative radiotherapy. In addition, the findings of this study have identified a subgroup of simultaneous EGFR-negative and VEGF-positive patients who are highly resistant to radiotherapy and should perhaps be considered candidates for innovative neoadjuvant combined modalities.

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Section: Discussionmentioning

confidence: 99%

Combined analysis of VEGF and EGFR predicts complete tumour response in rectal cancer treated with preoperative radiotherapy

et al. 2008

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“…In order to progress to individualized treatment and reduce treatment-related toxicity, patient selection is of major clinical relevance. A well-known method for patient selection is the immunohistochemical detection of EGFR expression in biopsy-derived sections of HNSCC (6,7). However, uncertainties such as biopsy accuracy and tumor heterogeneity affect the specificity and reliability of the procedure, and results showed prognostic value but not predictive value (8).…”

Section: Introductionmentioning

confidence: 99%

PET of EGFR with ⁶⁴Cu‐cetuximab‐F(ab′)₂ in mice with head and neck squamous cell carcinoma xenografts

Dijk

Yim

Franssen

et al. 2015

Contrast Media & Molecular

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a Overexpression of the epidermal growth factor receptor (EGFR) is linked to an adverse outcome in various solid tumors. Cetuximab is an EGFR inhibitor, which in combination with radiotherapy improves locoregional control and survival in a subgroup of patients with head and neck squamous cell carcinomas (HNSCCs). The aim of this study was to develop and characterize an EGFR-directed PET tracer, 64 Cu-cetuximab-F(ab′) 2 , to determine the systemic accessibility of EGFR. Mice with HNSCC xenografts, UT-SCC-8 (n = 6) or UT-SCC-45 (n = 6), were imaged 24 h post injection with 64 Cu-NODAGA-cetuximab-F(ab′) 2 using PET/CT. One mouse for each tumor model was co-injected with excess unlabeled cetuximab 3 days before radiotracer injection to determine non-EGFR-mediated uptake. Ex vivo biodistribution of the tracer was determined and tumors were analyzed by autoradiography and immunohistochemistry. The SUV max of UT-SCC-8 tumors was higher than that of UT-SCC-45: 1.5 ± 1.0 and 0.8 ± 0.2 (p < 0.05), respectively. SUV max after in vivo blocking of EGFR with cetuximab was 0.4. Immunohistochemistry showed that UT-SCC-8 had a significantly higher EGFR expression than UT-SCC-45: 0.50 ± 0.19 versus 0.12 ± 0.08 (p < 0.005), respectively. Autoradiography indicated that 64 Cu-cetuximab-F(ab′) 2 uptake correlated with EGFR expression in both tumors: r = 0.86 ± 0.06 (UT-SCC-8) and 0.90 ± 0.06 (UT-SCC-45).64 Cu-cetuxmab-F(ab′) 2 is a promising PET tracer to determine expression of EGFR in vivo. Clinically, this tracer has the potential to be used to determine cetuximab targeting of tumors and possibly to non-invasively monitor the response to EGFR-inhibitor treatment.

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“…ERBB1 by hetero-dimerization with other members of the ERBB receptor family (ERBB2, ERBB3, ERBB4), is rapidly activated at a low level in response to therapeutically relevant ionizing radiation exposure (~2 Gy) in multiple tumor cell types, including GBM cells. [69][70][71][72][73][74][75][76][77][78][79][80][81][82][83][84][85] Receptor activation is in part due to the actions of paracrine factors such as heregulins and TGFα, and some laboratories have shown that overexpression of truncated soluble extracellular portions of ERBB1 and ERBB3 can suppress ERBB receptor signaling; thus these molecules could be a useful future yet-to-be-explored gene therapeutic tools in GBM. 86,87 Hence, although irradiation of GBM cells causes death and is used therapeutically, it theoretically also has potential to enhance proliferation in the surviving fraction of cells and promote long-term resistance to multiple cytotoxic stresses.…”

Section: How Are Gbm Cells So Resistant To Therapeutic Intervention? mentioning

confidence: 99%

Searching for a cure: Gene therapy for glioblastoma

Dent

Yacoub

Park

et al. 2008

Cancer Biology & Therapy

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Glioblastoma multiforme (GBM) is an invariably fatal malignancy. The lethality of GBM has been linked to the highly invasive nature of GBM cells, their escape from immune cell oversight and their high degree of resistance to multiple established therapeutic modalities. The resistance of GBM cells to undergo death processes has, in part, been associated with mutations of specific oncogenes and altered expression of other signaling molecules that lead to reduced capacities to activate multiple apoptosis pathways as well as altered rates of DNA repair and autophagy in response to cytotoxic drugs and cellular stresses. This review will examine how gene therapeutic approaches have been used in the past and are continuing to be used alongside cell signaling modulators and DNA damaging agents as clinical tools to treat GBM. The concerted use of established and novel signal transduction modulatory agents on GBM survival may have potential to lower the apoptotic threshold and facilitate killing in this lethal malignancy.

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Epidermal Growth Factor Receptor Expression in Pretreatment Biopsies From Head and Neck Squamous Cell Carcinoma As a Predictive Factor for a Benefit From Accelerated Radiation Therapy in a Randomized Controlled Trial

Cited by 233 publications

References 30 publications

Combined analysis of VEGF and EGFR predicts complete tumour response in rectal cancer treated with preoperative radiotherapy

Combined analysis of VEGF and EGFR predicts complete tumour response in rectal cancer treated with preoperative radiotherapy

PET of EGFR with ⁶⁴Cu‐cetuximab‐F(ab′)₂ in mice with head and neck squamous cell carcinoma xenografts

Searching for a cure: Gene therapy for glioblastoma

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Epidermal Growth Factor Receptor Expression in Pretreatment Biopsies From Head and Neck Squamous Cell Carcinoma As a Predictive Factor for a Benefit From Accelerated Radiation Therapy in a Randomized Controlled Trial

Cited by 233 publications

References 30 publications

Combined analysis of VEGF and EGFR predicts complete tumour response in rectal cancer treated with preoperative radiotherapy

Combined analysis of VEGF and EGFR predicts complete tumour response in rectal cancer treated with preoperative radiotherapy

PET of EGFR with 64Cu‐cetuximab‐F(ab′)2 in mice with head and neck squamous cell carcinoma xenografts

Searching for a cure: Gene therapy for glioblastoma

Contact Info

Product

Resources

About

PET of EGFR with ⁶⁴Cu‐cetuximab‐F(ab′)₂ in mice with head and neck squamous cell carcinoma xenografts