Assessment of tumor hypoxia by ⁶²Cu-ATSM PET/CT as a predictor of response in head and neck cancer: a pilot study

In radiotherapy and chemotherapy tumor hypoxia is recognized as a major obstacle to effective treatment. We undertook a pilot study in patients with locally advanced head and neck cancer to determine whether there is a relationship between tumor uptake of ⁶²Cu-ATSM and response to chemoradiotherapy.

Seventeen patients were studied using PET/CT with ⁶²Cu-ATSM and ¹⁸F-FDG prior to the initiation of radiotherapy and chemotherapy. All patients had locally advanced head and neck cancer (stage III or IV). Tumor uptake in all patients was measured by region of interest analysis using the maximal standardized uptake value (SUVmax). A total dose of 50.4–70.2 Gy (median 70.2 Gy) was delivered in 29–39 fractions (median 39 fractions) to tumor. In patients with (non CR) and without (CR) residual/recurrent tumors at 2-year post irradiation, the statistical significance of the differences in tumor ⁶²Cu-ATSM SUVmax, T/M ratio, ¹⁸F-FDG SUVmax and tumor volume were analyzed using Student’s t test and Welch test. The relationship between clinical outcome and ⁶²Cu-ATSM/¹⁸F-FDG uptake patterns was analyzed using Kruskal–Wallis test. The correlation between SUVmax of ⁶²Cu-ATSM and ¹⁸F-FDG was compared by Spearman’s rank correlation test.

Two of the 17 patients that were enrolled in our study were excluded from the final analysis. Of the 15 remaining patients, 9 patients were free of disease and 6 patients had residual/recurrent tumors. The SUVmax differed significantly (p < 0.05) between patients with or without residual/recurrent tumor on ⁶²Cu-ATSM PET/CT. Six of the 10 patients with tumors SUVmax >5.00 had residual/recurrent tumor, whereas all of the 5 patients with tumors SUVmax <5.00 were free of disease. There was no significant difference in FDG uptake between patients with and without residual/recurrent tumor.

The results of this pilot study suggested that ⁶²Cu-ATSM uptake may be a predictive indicator of tumor response to chemoradiotherapy in patients with locally advanced head and neck cancer.