Influence of FAZA PET hypoxia and HPV-status for the outcome of head and neck squamous cell carcinoma (HNSCC) treated with radiotherapy: Long-term results from the DAHANCA 24 trial (NCT01017224)

• Published in: Radiotherapy and oncology Vol. 151; pp. 126 - 133
• Main Authors: Saksø, Mette, Mortensen, Lise Saksø, Primdahl, Hanne, Johansen, Jørgen, Kallehauge, Jesper, Hansen, Christian Rønn, Overgaard, Jens
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier B.V 01-10-2020
• Subjects: Carcinoma, Squamous Cell - diagnostic imaging; Carcinoma, Squamous Cell - radiotherapy; Cell Hypoxia; FAZA-PET; Head and Neck Neoplasms - diagnostic imaging; Head and Neck Neoplasms - radiotherapy; HNSCC; Humans; Hypoxia; Neoplasm Recurrence, Local; Nitroimidazoles; Outcome; Papillomavirus Infections - complications; Positron Emission Tomography Computed Tomography; Positron-Emission Tomography; Prognostic biomarker; Prospective Studies; Radiopharmaceuticals; Site-of-failure; Squamous Cell Carcinoma of Head and Neck - diagnostic imaging; Squamous Cell Carcinoma of Head and Neck - radiotherapy; FAZA-PET; Hypoxia; Site-of-failure; HNSCC; Outcome; Prognostic biomarker
• ISSN: 0167-8140; 1879-0887
• DOI: 10.1016/j.radonc.2020.08.006

•18F-FAZA imaging was used in a prospective trial of 38 HNSCC patients completing radiotherapy.•Within 5 years of follow-up, nine locoregional treatment failures were observed.•A high tumor-muscle ratio of tracer uptake (TMR ≥1.6) was associated with a higher risk of locoregional failure.•This association remained significant, when accounting for HPV/p16-positivity.•FAZA PET likely identifies cases, where treatment intensification is indicated.
Hypoxic tumor volumes can be visualized with 18F-FAZA PET/CT. In head and neck squamous cell carcinoma (HNSCC), hypoxia is important for the clinical outcome after primary radiotherapy (RT). The outcome is furthermore heavily influenced by the HPV/p16-positivity of oropharyngeal tumors (OPCp16+ tumors). The study purposes were (1) to report on locoregional failures within five years after primary RT in a prospective cohort stratified by both HPV/p16-status and PET hypoxia and (2) to characterize the failure site and the spatial association to PET hypoxia.
From 2009 to 2011, 38 patients with non-metastatic SCC of the larynx, oro-, hypo- and nasopharynx completing primary RT were included in the prospective DAHANCA 24 trial (NCT01017224). Fifteen patients had OPCp16+ tumors. All were imaged with a static FAZA PET/CT prior to treatment. The hypoxia threshold was determined by a tumor-to-muscle ratio (TMR) of 1.6. Recurrences were documented histologically. Imaging of the recurrence was deformable fused with the pre-treatment FAZA PET/CT. The spatial information of recurrence- and hypoxic volumes were compared visually.
Sixteen patients had more hypoxic tumors (high tracer uptake, TMR ≥1.6) before treatment (42%). With a median follow-up of 7.8 years, nine locoregional recurrences were observed, of which seven were in patients with high-uptake tumors (44% and 9%, respectively, HR 5.8 [1.2–28.2]). The risk of locoregional recurrence was highest among patients with more hypoxic, non-OPCp16+ tumors (57% [21–94%]), with a risk difference of 45% [4–86%], when comparing to less hypoxic, non-OPCp16+ tumors. Eight patients had sufficient imaging of the recurrence for co-registration with the FAZA PET/CT. Six had hypoxic primary tumors, and in two, the recurrence was overlapping the baseline hypoxic subvolume.
HNSCC demonstrating a TMR ≥1.6 at baseline is significantly associated with treatment failure after primary RT. In addition to HPV/p16-status, FAZA PET/CT has potential for the selection of tumors requiring treatment intensification.