Session Item

Intratumoral hypoxia is known to increase radioresistance of head-and-neck squamous cell carcinoma (HNSCC). [¹⁸F]FMISO PET imaging is able to non-invasively display and monitor tumor hypoxia; however, it requires considerable logistic efforts, especially if performed in radiotherapy treatment position. We therefore aimed to explore the role of dynamic interleukin-6 (IL-6) plasma levels as a potential endogenous blood-based biomarker to monitor tumor hypoxia in HNSCC patients.

Twenty-seven HNSCC patients undergoing definitive cisplatin-based chemoradiation within a prospective trial (DRKS00003830) had stored blood samples available that were analyzed regarding their plasma IL-6 levels at several time points during chemoradiation. The intratumoral hypoxic subvolume (HSV) was quantified in treatment weeks 0, 2 and 5 of chemoradiation using [¹⁸F]FMISO PET/CT imaging. Pearson’s correlation analyses were performed in order to assess the association between IL-6 plasma levels and PET-based hypoxia. A multiple regression analysis including several patient- and tumor-related factors was used to reveal potential confounder variables for the association between both parameters. Furthermore, the diagnostic power of IL-6 in terms of early tumor hypoxia response prediction was investigated with receiver-operating characteristic (ROC) analyses. Cox analyses were performed to study the impact of IL-6 levels on the progression-free (PFS) and overall survival (OS).

Mean IL-6 plasma concentrations ranged at 15.1, 19.6 and 31.0 pg/mL in weeks 0, 2 and 5 of chemoradiation, respectively. IL-6 plasma levels strongly correlated with the intratumoral HSV at all analyzed time points (week 0: r=0.775, p<0.001, week 2: r=0.553, p=0.007, week 5: r=0.734, p<0.001). Additionally, IL-6 levels in week 2 were found significantly higher in patients with missing early tumor hypoxia response within the first two treatment weeks (p=0.016) and could predict early hypoxia response with an AUC of 0.822 (p=0.031). Persistence of elevated IL-6 levels in week 5 corresponded to a decrease in PFS (HR=1.013, p=0.078) and OS (HR=1.018, p=0.013).

IL-6 plasma levels correlated with [¹⁸F]FMISO PET-detected intratumoral hypoxia in HNSCC patients. Furthermore, IL-6 was able to predict early hypoxia response during chemoradiation. Following external validation, IL-6 may serve as an endogenous blood hypoxia marker that could be used for hypoxia-based personalized radiotherapy concepts.