Hypoxia imaging with [F-18] FMISO-PET in head and neck cancer: Potential for guiding intensity modulated radiation therapy in overcoming hypoxia-induced treatment resistance

Abstract

Background and Purpose Positron emission tomography (PET) imaging with [F-18] fluoromisonidazole (FMISO) has been validated as a hypoxic tracer [1, 2]. Head and neck cancer exhibits hypoxia, inducing aggressive biologic traits that impart resistance to treatment. Delivery of modestly higher radiation doses to tumors with stable areas of chronic hypoxia can improve tumor control [3]. Advanced radiation treatment planning (RTP) and delivery techniques such as Intensity Modulated Radiation Therapy (IMRT) can deliver higher doses to a small volume without increasing morbidity. We investigated the utility of co-registered FMISO-PET and CT images to develop clinically feasible RTPs with higher tumor control probabilities (TCP). Methods FMISO-PET images were used to determine hypoxic sub-volumes for boost planning. Example plans were generated for ten of the patients in the study who exhibited significant hypoxia. We created an IMRT plan for each patient with a simultaneous integrated boost (SIB) to the hypoxic sub-volumes. We also varied the boost for two patients. Results A significant (mean 17%, median 15%) improvement in TCP is predicted when the modest additional boost dose to the hypoxic sub-volume is included. Conclusions Combined FMISO-PET imaging and IMRT planning permits delivery of higher doses to hypoxic regions, increasing the predicted TCP (mean 17%) without increasing expected complications.

High Reproducibility of Tumor Hypoxia Evaluated by 18F-Fluoromisonidazole PET for Head and Neck Cancer

“…Dose escalation for a hypoxic tumor is an important consideration for improving the effect of radiotherapy (23)(24)(25). The definition of hypoxic volume is essential for choosing the target for dose escalation.…”

The Clinical Importance of Assessing Tumor Hypoxia: Relationship of Tumor Hypoxia to Prognosis and Therapeutic Opportunities

“…The hypoxic regions delineated by 18 F-FMISO-PET received a 20% dose escalation (84 Gy), while nontarget tissue doses were maintained below normal tissue tolerances, making this a feasible strategy for IMRT therapy planning. In a separate study in 10 H&NC patients, IMRT planning and dose escalations using 18 F-FMISO PET imaging data was shown to increase tumor control probability by an average of 17% as a result of the modeled dose increases (119). Dose painting by numbers (DPBN), which escalates radiation doses based on the intensity of the 18 F-FMISO PET imaging data, enabled additional precision in therapy planning over uniform dose estimates (uniDE) derived from 18 F-FDG (265,266).…”

Imaging Tumor Hypoxia to Advance Radiation Oncology

“…Hypoxic regions cannot be defined by standard pre-treatment computed tomography scans. Hendrickson et al identified hypoxic sub-volumes of head and neck tumors in patients using FMISO-PET imaging and created example plans to simulate boosts of an additional 10 Gy on the prescribed 70 Gy to the primary tumor via intensity-modulated radiation therapy (IMRT) to explore the feasibility and efficacy of this approach (93). They estimated a significant increase of 17% in tumor control probability without unacceptable increases in normal tissue complication probability with this treatment technique (Fig.…”