Abstract
Approximately 50,000 new cases of head and neck squamous cell carcinoma (HNSCC) are diagnosed worldwide each year and subsequently treated with surgery, chemotherapy, radiotherapy, and/or targeted therapy. The heterogeneity of the patient population in terms of treatment response drives the search for tumor-specific biomarkers. Imaging of biomarkers can reveal patient-specific responses to therapies and, if assessed early after the start of treatment, may allow adaptation of treatment regimens. In this review, tracers that have been tested to monitor treatment efficacy in HNSCC by PET scanning prior to and early after the onset of treatment are discussed. An important imaging target for this application in HNSCC patients is the EGFR. It steers the pathways related to proliferation, hypoxia, DNA damage repair, and apoptosis, all treatment-resistance mechanisms. The anti-EGFR antibody cetuximab has been labeled with various radionuclides and has been tested as an imaging biomarker in several HNSCC models. These studies suggest that EGFR-targeting tracers can be used to monitor EGFR receptor expression in HNSCC and have the potential to noninvasively monitor cetuximab treatment and steer individualized treatment regimens. Multiple factors can influence the uptake of EGFR-targeting tracers. Here, we discuss the relevance of gene and protein overexpression, mutations, and amplifications related to EGFR signaling. In addition, monoclonal antibody properties and the effect on the host immune system are reviewed in light of the future role of EGFR-targeted imaging in HNSCC.
Highlights
For most head and neck squamous cell carcinomas (HNSCC), treatment is with curative intent and consists of surgery and/or radiotherapy, with or without concurrent chemotherapy or targeted therapy
The EGFR is overexpressed in most epithelial malignancies, including HNSCC, is involved in pathways related to the tumor microenvironment and tumor cell metabolism, and controls cell survival mechanisms such as proliferation, hypoxia resistance, DNA damage repair, and apoptosis [2]
A study in 48 HNSCC patients analyzed the change in proliferation rate with 18F-labeled 30-fluoro-30-deoxy-thymidine (18F-FLT) uptake and found that an maximum standard uptake value (SUVmax) decrease of !45% between pretreatment and the first 2 weeks of treatment was associated with significantly better disease-free survival (DFS) (88% vs. 63%; P 1⁄4 0.035; refs. 23, 24)
Summary
For most head and neck squamous cell carcinomas (HNSCC), treatment is with curative intent and consists of surgery and/or radiotherapy, with or without concurrent chemotherapy or targeted therapy. Approximately 50% of patients with locally advanced disease will develop recurrences or metastases within 2 years. Chemotherapeutics, such as cisplatin and 5-fluorouracil (5-FU), are routinely applied in combination with radiotherapy for treating locally advanced HNSCC, which has been shown to have a benefit over radiotherapy alone [1]. Targeted therapies are being investigated, of which the majority focuses on targeting the EGFR. A chimeric monoclonal antibody against the EGFR, is the only agent approved for use in HNSCC patients. Combining radiotherapy with cetuximab resulted in improved disease-free survival (DFS). We discuss PET tracers for HNSCC and their potential as imaging biomarkers, focusing on repetitive assessments. The strengths and pitfalls of EGFR monitoring, such as receptor expression, mutations, and amplifications, are addressed
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