Tumor hypoxia is known to be associated with poor clinical outcome; therefore, patients with hypoxic tumors might benefit from more intensive treatment approaches. This is particularly true for patients with head and neck cancer. Pretreatment assessment of hypoxia in tumors would be desirable, not only to predict prognosis but also to select patients for more aggressive treatment.As an alternative to the invasive polarographic needle electrode method, there is the possibility of using PET with radiopharmaceuticals visualizing hypoxia. Most hypoxia imaging studies on head and cancer have been performed using F-labeled fluoromisonidazole (F-FMISO). A chemically related molecule, F-fluoroazomycin-arabinoside (F-FAZA), seems to have superior kinetic properties and may therefore be the radiopharmaceutical of choice.This minireview summarizes the published literature on animal and human F-FAZA PET studies. Furthermore, future perspectives on how individualized treatment could be applied in patients with hypoxic head and neck tumors are discussed, for instance, the use of hypoxia sensitizers or special intensity-modulated radiation therapy techniques achieving tumor subvolume dose escalation.
Objectives
Most early stage laryngeal squamous cell carcinomas (LSCC) are treated with radiotherapy. Discovery of new biomarkers are needed to improve prediction of outcome after radiotherapy and to identify potential targets for systemic targeted therapy. The ataxia telangiectasia mutated (ATM) gene plays a critical role in DNA damage response induced by ionizing radiation.
Methods
The prognostic value of immunohistochemical expression of pATM, pChk2, and p53 were investigated in 141 patients with T1‐T2 LSCC curatively treated with external beam radiotherapy. Uni‐ and multivariable Cox regression analyses were performed to examine the relation between expression levels of markers and local control.
Results
Local control was significantly worse in cases with high levels of pATM (HR 2.14; 95% CI, 1.08–4.24; P = .03). No significant associations with local control were found for pChk2 and p53 expression. The association of high pATM expression with poor local control was only found for supraglottic LSCC (HR 10.9; 95% CI, 1.40–84.4; P = .02).
Conclusion
Our findings suggest a potential role for ATM in response to radiotherapy in early stage supraglottic LSCC and imply ATM inhibition as a possibility to improve response to radiotherapy.
Level of Evidence
NA Laryngoscope, 130: 1954–1960, 2020
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