LONDON – Expression of the epidermal growth factor receptor predicts whether patients with laryngeal cancer will benefit from hypoxia modification in addition to accelerated radiotherapy.
Study findings reported May 9 at the European Society for Therapeutic Radiation Oncology (ESTRO) Anniversary Conference showed that low expression was associated with higher disease-specific survival and locoregional control than was high expression in patients who received ARCON (accelerated radiotherapy with carbogen and nicotinamide).
Dr. Nick Slevin
EGFR expression is prognostic for patients who are treated with conventional fractionated radiotherapy, but did not predict response in patients undergoing just AR (accelerated radiotherapy) without hypoxia modification.
"EGFR can activate different downstream signaling pathways [in the tumor cell] that – once activated – can influence tumor cell survival, proliferation, [and] migration," all of which can contribute to tumor progression, said Monique Nijkamp, a Ph.D. student in the radiation oncology department of St. Radboud University Medical Centre in Nijmegen, the Netherlands.
High expression has already been linked to worse outcome in patients who were treated with radiotherapy for head and neck cancer (Cancer Res. 2002;62:7350-6). Ms. Nijkamp said that EGFR could be activated by ionizing radiation, and could account for resistance to radiotherapy in some treated individuals.
Hypothesizing that ARCON may help to overcome this resistance, Ms. Nikamp and coworkers examined 272 biopsy samples taken from 345 patients who had been treated with accelerated radiotherapy, with or without hypoxia modification, in a phase III study.
Preliminary results of the study were reported last September at the ESTRO 29 meeting in Barcelona. They showed that ARCON significantly improved regional – but not locoregional – tumor control, compared with AR alone. All of the patients in the trial had advanced-stage laryngeal cancer.
The latest findings suggest that patients with high expression may not gain any extra benefit from the addition of hypoxia modification. Indeed, although not statistically significant, better 5-year locoregional control (88% vs. 71%) and disease-specific survival (91% vs. 78%) were seen in patients with low EGFR expression than in those with high EGFR expression who were treated with ARCON.
Ms. Nijkamp suggested that perhaps high EGFR–expressing tumors were rapidly activating downstream signaling pathways that negated the effects of hypoxia modification. No difference in outcomes was found according to EGFR expression in the AR alone arm.
"There is concern over the methodologies used to measure EGFR, and this could have a large bearing on what conclusions can be drawn from studies," said Dr. Nick Slevin, who was invited to comment on the findings.
"From the literature and from this study, it appears that high EGFR laryngeal cancers benefit from accelerated radiotherapy, but that low EGFR tumors do not," added Dr. Slevin, a consultant clinical oncologist at the Christie NHS Foundation Trust and the University of Manchester (England).
"I think it’s a fair summary to also say that high-EGFR tumors benefit from AR but not from CON [carbogen and nicotinamide] and that low-EGFR tumors benefit from the CON but not the AR. ... So I’m not sure ARCON is the right approach for all tumors."
Other approaches to hypoxia modification for low EGFR–expressing tumors (such as oral nimorazole) may overcome the logistic difficulties of delivering carbogen and nicotinamide, he added.
The study was supported by the Dutch Cancer Society. Ms. Nijkamp and Dr. Slevin declared they had no financial conflicts of interest.