Poster Presentation 37th TROG Cancer Research Annual Scientific Meeting 2025

De-escalation of Radiation Dose in HPV-associated Oropharyngeal Squamous Cell Carcinoma utilising FMISO PET and MRI and Non-Invasive Biomarkers of Hypoxia (DE-RADIATE) (#104)

Anna Lawless 1 , Sarah Bergamin 1 2 , Nancy Lee 3 , Michael Back 1 2 , Dale Bailey 2 4 , Chris Brown 1 , James Drummond 1 5 , Thomas Eade 1 2 , Alexander Guminski 2 6 , Lisa Parker 1 2 , Adrian Lee 2 6 , Tricia Saurine 7 , Geoffrey Schembri 2 8 , Dasantha Jayamanne 1 2
  1. Department of Radiation Oncology, Royal North Shore Hospital, Sydney, NSW, Australia
  2. Faculty of Medicine and Health, The University of Sydney, Sydney, NSW, Australia
  3. Department of Radiation Oncology, Memorial Sloan Kettering Cancer Centre, New York, United States of America
  4. Department of Nuclear Medicine, Royal North Shore Hospital, Sydney, NSW, Australia
  5. Department of Radiology, Royal North Shore Hospital, Sydney, NSW, Australia
  6. Department of Medical Oncology, Royal North Shore Hospital, Sydney, NSW, Australia
  7. Department of Anatomical Pathology, Royal North Shore Hospital, Sydney, NSW, Australia
  8. Department of Nuclear Medicine, Royal North Shore Hospital, Sydney, NSW, Australia

Background

Despite the subgroup of HPV-associated oropharyngeal squamous cell carcinomas (HPVOPC) being both more radiosensitive and carrying significantly improved prognosis compared to non-HPV-associated OPC, radiation therapy (RT) dose is not currently tailored to the biology of the individual patient’s tumour. Phase II data suggests FMISO-PET can be safely used to select patients with non-hypoxic HPVOPC for radical RT dose de-escalation to 30Gy with a phase III trial currently underway in the USA.

 

Aims

The primary outcome is to utilise FMISO-PET to select patients with non-hypoxic HPVOPC for RT dose de-escalation and demonstrate this approach is associated with high rates of pathologic complete response. Secondary outcomes include disease-free and overall survival, acute and late toxicities, patient-reported quality of life, and correlation between FMISO PET and oxygen-enhanced MRI assessments of tumour hypoxia. 

 

Methods

This protocol is based on the ‘30 ROC’ trial from Memorial Sloan Kettering Cancer Centre. Patients with cT1-2N1-2b HPVOPC or cTxN1-2b carcinoma of unknown primary (CUP) (AJCC 7th edition) with dual p16 and HPV positivity will undergo surgical resection of the primary (TORS/clear margins not mandated) or EUA and core biopsies (for CUP). Pre-treatment and intra-treatment (after 2 weeks of RT) FMISO-PET will be performed. Patients with non-hypoxic tumours initially or after 2 weeks of RT will undergo RT dose de-escalation (30Gy) with concurrent chemotherapy (cisplatin or carboplatin/5FU). Remaining patients will receive standard of care RT (70Gy) with concurrent chemotherapy. All patients in the de-escalation arm will undergo mandatory neck dissection 4 months after completion of RT to assess pathologic response.

 

Results

Recruitment will commence in October 2024 at Royal North Shore Hospital in Sydney. Intended sample size is 20. Preliminary results are expected in late 2025.

 

Conclusions

This is the first Australian trial utilising FMISO-PET to select patients with HPVOPC for radical radiation dose de-escalation.