A new study published in JAMA Network Open reveals that persistent tumor hypoxia during chemoradiotherapy (CRT) is a significant predictor of distant metastasis in patients with head and neck squamous cell carcinoma (HNSCC). The research, involving 281 patients, highlights the potential of using 18F-fluoromisonidazole (FMISO) positron emission tomography (PET) to identify high-risk individuals who may benefit from more aggressive treatment strategies.
The study, conducted at a single academic referral center from 2004 to 2021, included patients with HNSCC enrolled in two prospective clinical trials. Researchers assessed tumor hypoxia using FMISO PET scans taken before and during CRT. The primary outcome was distant metastasis (DM), defined as biopsy-proven HNSCC outside the primary site and regional lymph nodes.
Key Findings on Hypoxia and Metastasis
The results indicated that persistent intratreatment hypoxia was associated with a 3.5-fold increased risk of distant metastasis (hazard ratio, 3.51; 95% CI, 1.05-11.79; P = .04) and worse overall survival (hazard ratio, 2.66; 95% CI, 1.14-6.19; P = .02). Notably, none of the patients with hypoxia-negative disease before CRT experienced distant metastasis.
According to the study, 26.0% of patients had hypoxia-negative disease before CRT, 49.1% had hypoxia-positive disease before CRT that turned hypoxia-negative during CRT, and 24.9% had persistently hypoxia-positive disease. The median follow-up was 58 months.
Clinical Implications and Future Directions
The study's findings suggest that FMISO PET could serve as a valuable clinical biomarker for distant metastasis risk in HNSCC patients undergoing CRT. Nancy Y. Lee, MD, the corresponding author of the study from Memorial Sloan Kettering Cancer Center, noted that both the presence and absence of tumor hypoxia may be used as biomarkers to guide individualized therapy. For instance, patients without hypoxia may be candidates for de-escalated CRT, while those with persistent hypoxia might benefit from escalated therapeutic strategies, including novel chemotherapy and immunotherapy regimens.
The researchers emphasize that while locoregional control rates are high with current HNSCC treatments, distant metastasis remains a challenge, necessitating better methods to project DM risk. Tumor hypoxia has been linked to resistance to CRT and metastasis in various cancers. The current study supports the use of FMISO PET as a reliable, noninvasive measurement of tumor hypoxia in HNSCC.
Study Limitations
The authors acknowledge that the study was limited by the relatively small number of DM events, which constrained the ability to perform comprehensive multivariable and subgroup analyses. Additionally, the treatment strategies were heterogeneous, with patients receiving both standard and de-escalated CRT, as well as those with and without primary tumor resection. Future studies with larger cohorts and more DM events are needed to validate these findings and explore hypoxia as an independent risk factor for distant metastasis.
