Lesion oxygenation associates with clinical outcomes in premalignant and early stage head and neck tumors treated on a phase 1 trial of photodynamic therapy

在光动力疗法的一期临床试验中,病灶氧合与癌前病变和早期头颈部肿瘤的临床疗效相关。

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Abstract

BACKGROUND: We report on a Phase 1 trial of photodynamic therapy (PDT) for superficial head and neck (H&N) lesions. Due to known oxygen dependencies of PDT, translational measurements of lesion hemoglobin oxygen saturation (S(t)O(2)) and blood volume (tHb) were studied for associations with patient outcomes. METHODS: PDT with aminolevulinc acid (ALA) and escalating light doses was evaluated for high-grade dysplasia, carcinoma-in-situ, and microinvasive carcinomas of the H&N. Among 29 evaluable patients, most (18) had lesions of the tongue or floor of mouth (FOM). Disease was intact in 18 patients and present at surgical margins in 11 patients. In 26 patients, lesion S(t)O(2) and tHb was measured. RESULTS: Local control (LC) at 24 months was 57.5% among all patients. In patients with tongue/FOM lesions LC was 42.7%, and it was 50.1% for those with intact lesions. Lesion tHb was not associated with 3-month complete response (CR), but S(t)O(2) was higher in patients with CR. In tongue/FOM lesions, baseline S(t)O(2) [mean(SE)] was 54(4)% in patients (n=12) with CR versus 23(8)% in patients (n=6) with local recurrence/persistence (p=0.01). Similarly, for intact disease, baseline S(t)O(2) was 54(3)% in patients (n=10) with CR versus 28(8)% in patients (n=5) without CR (p=0.03). In patients with intact disease, higher baseline S(t)O(2) associated with 24-month local control (p=0.02). CONCLUSIONS: Measurement of the physiologic properties of target lesions may allow for identification of patients with the highest probability of benefiting from PDT. This provides opportunity for optimizing light delivery based on lesion characteristics and/or informing ongoing clinical decision-making in patients who would most benefit from PDT.

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