Challenges and opportunities in patient-specific, motion-managed and PET/CT-guided radiation therapy of lung cancer: review and perspective

Abstract

The increasing interest in combined positron emission tomography (PET) and computed tomography (CT) to guide lung cancer radiation therapy planning has been well documented. Motion management strategies during treatment simulation PET/CT imaging and treatment delivery have been proposed to improve the precision and accuracy of radiotherapy. In light of these research advances, why has translation of motion-managed PET/CT to clinical radiotherapy been slow and infrequent? Solutions to this problem are as complex as they are numerous, driven by large inter-patient variability in tumor motion trajectories across a highly heterogeneous population. Such variation dictates a comprehensive and patient-specific incorporation of motion management strategies into PET/CT-guided radiotherapy rather than a one-size-fits-all tactic. This review summarizes challenges and opportunities for clinical translation of advances in PET/CT-guided radiotherapy, as well as in respiratory motion-managed radiotherapy of lung cancer. These two concepts are then integrated into proposed patient-specific workflows that span classification schemes, PET/CT image formation, treatment planning, and adaptive image-guided radiotherapy delivery techniques.

Figure 1

Landscape of potential approaches to patient care in motion-managed and PET/CT-guided radiotherapy of lung cancer. Across the stages of patient care, numerous approaches offer increasingly complex strategies. Details of each approach are given in Table  2.

Figure 2

Comparison of ungated (A) and quiescent period gated (B) [¹⁸ F]FDG PET image reconstructions. The maximum standardized uptake value (SUV) is increased in the gated image of a detached lesion and the SUV profiles (C) show clear sharpening of the gated uptake spatial distribution (black line). This improvement in quantification would potentially alter the definition of biological targets for motion-compensated and PET/CT-guided radiotherapy.

Figure 3

Example workflow of patient-specific motion management and PET/CT guidance for lung cancer radiotherapy. Beginning with patient classification based on diagnostic factors, motion is either suppressed or compensated for during the PET/CT acquisition. Static, respiratory-gated, or respiratory motion-tracked images are then used to define biological targets for treatment plans. Radiotherapy is delivered under image guidance when motion is suppressed, during a particular respiratory gate that is matched to the plan or throughout the respiratory cycle by predictively tracking the motion.

Figure 4

Four-dimensional cone beam computed tomography for image-guided radiotherapy. Images acquired at the time of treatment delivery are sorted into temporal phases according to the time-dependent diaphragm position. Coronal (A), transaxial (B) and sagittal (C) views at 30 percent phase show the gross tumor volume (red contour), planning target volume (orange contour) and esophagus (green contour). The PTV was defined on the maximum intensity projection of a respiratory-gated simulation CT. While the PTV encompasses the motion of the lesion prior to treatment delivery, its definition may be enhanced through individual phase adaption as part of a motion-managed and PET/CT-guided radiotherapy regimen.

Figure 5

Examples of motion management strategies for two patients receiving PET/CT-guided radiotherapy. The top row de s a patient whose baseline diagnostic factors indicate a highly period tumor motion and respiratory pattern, suitable for respiratory motion-tracked PET/CT and motion-tracked radiotherapy. The bottom row illustrates a patient whose chaotic respiratory pattern makes them suitable for PET/CT and radiotherapy under active breathing control (ABC) and prospective respiratory gating during a finite time period. Figure adapted from Liu et al. and Chin et al.[29,65,76].