The prognostic value of FMISO-PET-based synchronous tumor and lymph node hypoxia outperforms that of tumor hypoxia only in patients with advanced stage HNSSC – secondary analysis of Dresden FMISO trail

Purpose: Primary tumor (Tu) hypoxia based on hypoxia-PET is a known prognostic parameter for locally-advanced head-and-neck squamous cell carcinoma (HNSCC) patients. This secondary analysis of the prospective clinical trial [1] on repeat [18F]fluoromisonidazole (FMISO) PET/CT before and during radiochemotherapy (RCT) compared the prognostic value of synchronous Tu and lymph node metastases (LN) hypoxia with that of hypoxia only determined in Tu.

Methods: Forty-five LN-positive patients with 103 LNs were included in this analysis. FMISO-PETs were performed at baseline, week 1, 2 and 5 of RCT. Based on a qualitative scale, Tu and LN were independently categorized as hypoxic or normoxic, being FMISO uptake higher than or equal to background, respectively. Two prognostic parameters were defined: Tu-hypoxia (patients with a hypoxic Tu, independent of the LN oxygenation status) and synchronous Tu-and-LN-hypoxia. In fifteen patients with a large LN (n = 21) a quantitative analysis of FMISO PET was performed to validate hypoxia scale and to correlate with regional control (RC). Log-rank, uni- and multivariate Cox test were used to assess the parameters’ prognostic impact on locoregional control (LRC), RC and time to progression (TTP).

Results: Synchronous Tu-and-LN-hypoxia was a strong adverse prognostic factor for LRC and TTP at all time-points (p ≤ 0.005) whereas Tu-hypoxia only was significantly associated with poor LRC in week 2 and 5 (p ≤ 0.004) and with short TTP in week 1, 2 and 5 (p ≤ 0.043). The quantitative FMISO parameters correlated with RC. There was a significant correlation between the qualitative and quantitative FMISO parameters (R > 0.6–0.8).

Conclusions: FMISO-based synchronous hypoxia in the primary tumor and lymph node metastases holds strong prognostic information in HNSCC patients outperforming that based on primary tumor hypoxia only. Confirmation in ongoing prospective trials is intended before introducing in personalized radiation oncology.