Prognostic significance of plasma osteopontin in patients with locally advanced head and neck squamous cell carcinoma (HNSCC) treated with chemoradiation on TROG 02.02 phase III trial.

Abstract

5506 Background: High plasma osteopontin (OPN) levels have been reported to be an adverse prognostic factor in HNSCC, to correlate with tumor hypoxia and to be predictive of benefit from hypoxia targeted therapy. We sought to confirm the prognostic and predictive significance of OPN in patients treated on a large international trial. Methods: Patients with previously untreated Stage III or IV HNSCC were randomized to receive definitive radiotherapy concurrently with cisplatin or cisplatin plus the hypoxic cell cytotoxin, tirapazamine (TPZ). As previously reported there were no significant differences in any outcome parameter by randomization arm. Eligibility criteria for this prospective substudy included availability of plasma samples and absence of major radiation therapy deviations. Plasma OPN was measured by ELISA. OPN concentrations according to tertiles and median were analysed for overall survival (OS), and time to locoregional failure (TTLRF), adjusting for prognostic factors (site, T category, N category, hemoglobin, performance status). An additional analysis was performed in patients with available p16 immunohistochemistry results. Results: 578/853 patients were eligible and had a median OPN level of 544 µg/L (range: 7 - 2640). High OPN levels were not associated with worse overall survival (HR 1.03 for highest tertile and 0.98 for middle tertile, p=0.95) or time to locoregional failure (HR 0.91 for highest and 0.93 for middle, p=0.91). There was no interaction between OPN and treatment arm for OS or TTLRF (p=0.51 for both). For the highest tertile the 2-year OS was 70% on control arm and 71% on TPZ arm (HR=1.11, p=0.67). Similarly for p16 negative patients in the highest tertile, the 2 year OS was 69% on control arm and 73% on TPZ arm (HR=1.13, p=0.82). Conclusions: In contrast to previous reports we found no evidence that high plasma OPN levels were associated with an adverse prognosis in HNSCC, or were predictive of benefit with hypoxia targeting therapy. Supported by 1 R01 CA118582 and NHMRC project grant.