Abstract 1107: Prospective observational study to evaluate the efficacy of oxygen saturation endoscopic imaging for radiotherapeutic response in head and neck squamous cell carcinoma
Authors: Tomizawa Kento , Motegi Atsushi , Hirata Hidenari , Yamashita Hiroki , Sunakawa Hironori , Okano Wataru , Enokida Tomohiro , Fujisawa Takeshi , Zenda Sadamoto , Nakamura Masaki , Hojo Hidehiro , Abe Seiichiro , Sakuramachi Madoka , Igaki Hiroshi , Saito Yutaka , Matsuura Kazuto , Tahara Makoto , Yano Tomonori , Akimoto Tetsuo 
Published: March 2024

Abstract
Background: Radiotherapy (RT) has a pivotal role in the management of head and neck squamous cell carcinoma (HNSCC), providing effective tumor control and functional preservation. Hypoxia is a cause of radioresistance in HNSCC. We have developed an oxygen saturation endoscopic imaging (OXEI) method to assess real-time tissue oxygenation levels. However, the clinical significance of OXEI in patients with HNSCC receiving RT remains unclear. We evaluated the association between pretreatment tumor oxygen saturation (StO2) quantified by OXEI and clinical outcomes of patients with HNSCC receiving RT.
Methods: We prospectively recruited patients with HNSCC scheduled to receive RT at 2 institutions. The primary endpoint was the association between pretreatment tumor StO2 and complete response (CR) rate 8 weeks after completion of RT. Secondary endpoints evaluated the impact of StO2 on 1-year overall survival (OS) and progression-free survival (PFS) rates after RT initiation. We also evaluated the cumulative incidence of local failure (LF). To explore the relationship between tumor hypoxia assessed by OXEI and gene expression profile, we performed RNA sequencing of 4 tumor samples collected from 2 patients (2 samples/patient) before RT. The hypoxia score for each sample was calculated by gene set variation analysis based on HNSCC mRNA-based hypoxia signatures. We performed gene set enrichment analysis (GSEA) to evaluate whether the biological pathways (Hallmark, Reactome, and KEGG gene sets) showed significant associations with tumor hypoxia.
Results: Of the 50 patients enrolled from March 2019 to February 2022, we analyzed 37 who underwent RT and OXEI. Thirty-six (97%) patients received current platinum-based chemotherapy. The median (range) pretreatment tumor StO2 of 60 (45-84)% was lower than that of normal mucosa, 66 (56-84)% (P &lt; 0.01). Patients with tumor StO2 &lt; 60% were classified as the hypoxia group (n =19), and those with tumor StO2 ≥ 60% as the non-hypoxia group (n =18). The CR rate 8 weeks after RT was not significantly different between the hypoxia and non-hypoxia groups (84% vs. 100%, respectively; P = 0.23). After a median (range) follow-up of 33 (9-45) months, the hypoxia group had worse 1-year PFS (74% vs. 94%, P = 0.017) and OS (89% vs. 100%, P = 0.015) and higher LF rates (21% vs. 6%, P = 0.036) compared with the non-hypoxia group. RNA sequencing confirmed that tumor StO2 reflected expression-based hypoxia scores. GSEA showed upregulation of reactive oxygen species (ROS) and KEAP1-NFE2L2 pathways in hypoxic samples (StO2 of 59%) compared with non-hypoxic samples (StO2 of 70%; adjusted P &lt; 0.01), consistent with the fact that hypoxic stress increases ROS production.
Conclusion: Our findings suggest that pretreatment tumor StO2 quantified by OXEI correlates with 1-year PFS, OS, and LF rates of patients with HNSCC receiving RT.
Citation Format: Kento Tomizawa, Atsushi Motegi, Hidenari Hirata, Hiroki Yamashita, Hironori Sunakawa, Wataru Okano, Tomohiro Enokida, Takeshi Fujisawa, Sadamoto Zenda, Masaki Nakamura, Hidehiro Hojo, Seiichiro Abe, Madoka Sakuramachi, Hiroshi Igaki, Yutaka Saito, Kazuto Matsuura, Makoto Tahara, Tomonori Yano, Tetsuo Akimoto. Prospective observational study to evaluate the efficacy of oxygen saturation endoscopic imaging for radiotherapeutic response in head and neck squamous cell carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1107.