Top Line: Personalized medicine is coming to radiation oncology.
The Study: We’re finally making headway in adapting therapy not just to risk-based natural histories of disease but actual individual tumor radiosensitivites. Previous studies have pointed to the feasibility of using fluorine-18-labeled fluoromisonidazole (18F-FMISO) PET to reliably identify tumor hypoxia. Here’s a prospective investigation into whether such bioimaging-apparent hypoxia, or rather lack thereof, can point us towards more radiosensitive HPV+ oropharyngeal cancers. They took 19 patients with T1-2 p16+ oropharyngeal cancer and resected the primary tumors but not the nodal disease. Patients were treated with chemoradiation (CRT) and underwent 18F-FMISO PET before and during CRT to identify hypoxia. 15 of 19 either had no hypoxia (n=6) or hypoxia that resolved 5-10 days after starting treatment (n=9). These patients received just 30 Gy in 15 fractions while those with residual hypoxia continued on to 70 Gy. All 15 patients had planned neck dissection at 4 months which revealed a complete pathologic response in 11 (73%). Locoregional control at 2 years was 94%, granted after pre-planned neck dissections. More germane, grade 3+ toxicity occurred in 0 patients. With tri-modality therapy. A secondary analysis of whole genome sequencing of tumor samples from 17 enrollees revealed the presence of small deletions with microhomology (indicative of a defect in double strand break repair) was significantly higher among responders to 30 Gy, which was externally validated on a cohort similarly-treated at Mayo.
TBL: The use of biologic imaging, particularly in combination with genome sequencing, may identify a majority of HPV-associated oropharyngeal cancers that can be eradicated with a radiation dose so low as to carry almost no long-term toxicity. | Riaz, J Natl Cancer Inst 2021