Radiation therapy for patients with lung cancer may be less toxic using a functional lung avoidance treatment plan guided by xenon-enhanced ventilation CT (XeCT). In a clinical study at the National Taiwan University Hospital, only 17% of patients developed radiation pneumonitis, the most severe radiation-induced adverse effect, a significant improvement compared to historic norms.
Chemoradiotherapy is the recommended treatment for inoperable or locally advanced non-small cell lung cancer (NSCLC), but toxicities from this treatment are a significant concern. Approximately 30% of patients develop grade 2 or higher radiation pneumonitis (lung inflammation), which seriously affects their quality-of-life.
Currently, radiotherapy treatment planning is based on anatomic imaging and the premise that all lung tissues are equally important. But for lung cancer patients with chronic pulmonary disease, dose may be more accurately delivered based on functional, rather than anatomical, lung volume – a hypothesis that is now being investigated worldwide.
Principal investigators Yu-Sen Huang and Yeun-Chung Chang, also at the National Taiwan University College of Medicine, and colleagues tested this approach in a phase 2 clinical trial of 36 patients with NSCLC. They investigated whether radiotherapy planning guided by XeCT, which has been proven feasible and safe for visualizing lung ventilation, could reduce the rate of grade 2 or higher radiation pneumonitis. The idea is to use the XeCT images to minimize radiation dose to regions of functional lung, while favouring radiation deposition in areas of non-functioning lung.
For the study, patients initially underwent pre-treatment XeCT and pulmonary function tests to determine lung ventilation. Each subject had an unenhanced baseline CT scan of the whole thorax, followed by a five-cycle respiration with a xenon gas rebreathing system (during which they inhaled a mixture of 30% nonradioactive xenon and 70% oxygen) and then a XeCT scan during breath-hold at full inspiration. Finally, patients inhaled 100% oxygen for 1 min, and underwent a post-washout XeCT at full inspiration. The total time for the XeCT exam was 20–25 minutes.
The XeCT images displayed the ventilated areas of lung enhanced by xenon in colour, and areas with poor or no enhancement as black. After subtracting baseline CT images from the xenon wash-in images, the researchers generated xenon-enhanced functional lung volumes and imported them into the treatment planning system for registration with the planning CT.
The researchers created a standard plan without reference to XeCT, and a functional-lung-avoidance plan (fAP) optimized to lower dose to functional lung without compromising target volume coverage and organ-at-risk dose constraints. They treated all patients with fAP, using intensity-modulated radiotherapy or volumetric-modulated arc therapy to deliver 60 Gy of thoracic irradiation in 30 fractions. The patients were followed up with chest CT and clinical examinations at 90-day intervals.
Writing in the International Journal of Radiation Oncology Biology Physics, the researchers report that total functional lung sparing was significantly better in the fAP treatments. The total functional lung volume receiving more than 20 Gy decreased from 23.3% to 20.6% and the mean lung dose from 14.3 to 12.4 Gy. Importantly, the predicted risk of grade 2 or greater radiation pneumonitis reduced from 5.7% to 4.0%, while the predicted risk of developing symptomatic radiation pneumonitis within six months of treatment decreased from 6.3% to 4.4%.
Neural network generates lung ventilation images from CT scans
Five of the 36 patients developed grade 2 radiation pneumonitis and one developed grade 3 radiation pneumonitis, significantly lower than expected from historical controls. There were no grade 4 or greater toxic effects. The researchers point out, however, that the advantage of providing better sparing of the functional lung was counterbalanced by a higher maximal dose within the targets and less conformal target dose distributions.
Despite its benefits, XeCT is expensive and limited in availability, and requires strong cooperation between the radiology and radiation oncology departments. The researchers also acknowledge that recent technological advances in modern radiotherapy may outweigh the expected benefits of fAP treatments. But they believe that their study provides robust evidence for the benefit of XeCT-guided functional lung avoidance in radiotherapy, and are continuing their research.
