Defining the hypoxic target volume based on positron emission tomography for image guided radiotherapy – the influence of the choice of the reference region and conversion function

<p><b>Background:</b> Hypoxia imaged by positron emission tomography (PET) is a potential target for optimization in radiotherapy. However, the implementation of this approach with respect to the conversion of intensities in the images into oxygenation and radiosensitivity maps is not straightforward. This study investigated the feasibility of applying two conversion approaches previously derived for ¹⁸F-labeled fluoromisonidazole (¹⁸F-FMISO)-PET images for the hypoxia tracer ¹⁸F-flortanidazole (¹⁸F-HX4).</p> <p><b>Material and methods:</b> Ten non-small-cell lung cancer patients imaged with ¹⁸F-HX4 before the start of radiotherapy were considered in this study. PET image uptake was normalized to a well-oxygenated reference region and subsequently linear and non-linear conversions were used to determine tissue oxygenations maps. These were subsequently used to delineate hypoxic volumes based partial oxygen pressure (pO₂) thresholds. The results were compared to hypoxic volumes segmented using a tissue-to-background ratio of 1.4 for ¹⁸F-HX4 uptake.</p> <p><b>Results:</b> While the linear conversion function was not found to result in realistic oxygenation maps, the non-linear function resulted in reasonably sized sub-volumes in good agreement with uptake-based segmented volumes for a limited range of pO₂ thresholds. However, the pO₂ values corresponding to this range were significantly higher than what is normally considered as hypoxia. The similarity in size, shape, and relative location between uptake-based sub-volumes and volumes based on the conversion to pO₂ suggests that the relationship between uptake and pO₂ is similar for ¹⁸F-FMISO and ¹⁸F-HX4, but that the model parameters need to be adjusted for the latter.</p> <p><b>Conclusions:</b> A non-linear conversion function between uptake and oxygen partial pressure for ¹⁸F-FMISO-PET could be applied to ¹⁸F-HX4 images to delineate hypoxic sub-volumes of similar size, shape, and relative location as based directly on the uptake. In order to apply the model for e.g., dose-painting, new parameters need to be derived for the accurate calculation of dose-modifying factors for this tracer.</p

Long-term results of a prospective phase II trial of medically inoperable stage I NSCLC treated with SBRT – the Nordic experience

<div><p></p><p><b>Background.</b> Presentation of long term results of a phase II multicenter Nordic trial of medically inoperable stage I non-small cell lung cancer (NSCLC) treated with stereotactic body radiotherapy (SBRT).</p><p><b>Material and methods.</b> We report the extended outcome, focusing on long-term effects, of a prospective cohort of 57 evaluable patients with peripherally located T1N0M0 (72%) and T2N0M0 (28%) NSCLC, treated with SBRT 15 Gy × 3, prescribed to the 67% isodose line encompassing the PTV. The patients were inoperable due to chronic obstructive pulmonary disease (65%), cardiovascular disease (25%) or other illnesses (3%) or refused surgery (7%). Median Karnofsky score pre-treatment was 80% (70–100%). Late effects were defined as occurring > 36 months.</p><p><b>Results.</b> Thirty-eight patients (67%) were relapse free during their entire follow-up. Local control rate at four and five years were 79% (CI 95% 64–95%) and local relapses occurred at 10–76 months post-treatment. Seven local failures were noted, four occurring ≤ 36 months (all T2a-tumors; two isolated and two in combination with out-of-field relapses) and three occurring > 36 months (T1b-tumors n = 3). Thirteen patients had out-of-field failure only as first presentation of recurrence. Overall survival rate and lung cancer-specific survival rate at five years were 30% and 74%, respectively. Toxicity throughout the entire observation period was acceptable without any grade 5 toxicities. Seventeen grade 3–4 toxicities were noted, three presenting > 36 months (rib fracture, dyspnea and ventricle tachycardia). Median follow-up was 41.5 months (3.4–113.0) for the entire cohort and 59.3 months (36.4–113.0) for the 34 patients (60%) with a follow-up of > 36 months.</p><p><b>Conclusion.</b> Throughout the observation period local control was excellent and toxicity limited with no increase in late presenting local relapses or late treatment-related morbidity. This further supports SBRT as an efficient local treatment modality even in a medically impaired patient cohort.</p></div