Researchers Pioneer Individualized Radiotherapy Using Dual-Tracer PET

Radiation therapy traditionally uses a uniform dose for specific tumor types, often leading to inadequate treatment due to the unique characteristics of individual tumors. Researchers from Sweden and Germany have initiated a study investigating whether biologically individualized radiotherapy, guided by dual-tracer PET imaging, can enhance treatment effectiveness for patients with advanced head-and-neck squamous cell carcinoma (HNSCC).

The research team, led by Marta Lazzeroni from Stockholm University, assessed 28 patients who underwent two pre-treatment PET/CT scans. These scans utilized two different tracers: 18 F-fluoromisonidazole (FMISO) to measure radioresistance and 18 F-FDG to evaluate tumor cellularity. This dual approach addresses the inherent radiosensitivity and heterogeneity of tumors, factors that significantly impact treatment outcomes.

Lazzeroni explained that “FMISO provides information on hypoxia-related radioresistance, but tumor control also strongly depends on the number of clonogenic cells, which is not captured by hypoxia imaging alone.” The study marks a pioneering effort to integrate both FMISO and FDG PET data within a unified framework to enhance dose escalation tailored to individual tumor profiles.

Innovative Treatment Planning and Results

Using the data from the PET scans, the researchers created voxel-level maps to assess oxygen partial pressure (pO2) in the tumors, subsequently defining a hypoxic target volume (HTV). The FDG scans provided insight into the distribution of clonogenic tumor cell density, which directly influences the necessary dose to achieve a specific tumor control probability (TCP).

The automated planning system generated volumetric-modulated arc therapy plans that included 35 treatment fractions with an integrated boost for radioresistant subvolumes, while ensuring safe sparing of critical organs. Each treatment plan achieved an average biologically equivalent dose of 81±3.2 Gy to the HTV, successfully adhering to clinical safety standards for protecting the brainstem, spinal cord, and mandible. Notably, parotid glands were spared in 75% of cases.

The results indicate a significant advancement in the field, suggesting that the personalized dose-escalation strategy is clinically feasible and could be integrated into current treatment protocols. The research team also conducted a radiobiological evaluation, calculating TCP based on the planned dose distribution and PET-derived data. The findings revealed TCP values exceeding 90% for all patients, a substantial improvement compared to the typical 60% tumor control rates documented in existing clinical literature for HNSCC.

Future Directions and Clinical Implications

While these promising results stem from pre-treatment PET images, the researchers acknowledge that biological changes during the course of treatment, particularly fluctuations in tumor hypoxia, may influence the effectiveness of their approach. They propose that future studies could benefit from longitudinal imaging, including PET/CT scans at intervals during treatment, to monitor the evolving tumor biology. This would enable adaptive replanning to ensure optimal tumor control while minimizing damage to healthy tissue.

Lazzeroni emphasizes the need for further validation, stating, “This study was designed as a feasibility and modeling investigation, and the next step is prospective clinical validation.” The group led by Anca-L Grosu in Germany is currently planning prospective clinical trials. These trials aim to integrate ongoing PET imaging into treatment protocols to facilitate biologically adaptive radiotherapy, optimizing outcomes for patients with HNSCC.

The findings of this study have been published in the Journal of Nuclear Medicine, marking a significant step forward in the quest for more personalized and effective cancer treatments.