Functional lung avoidance and response-adaptive escalation (FLARE) RT: Multimodality plan dosimetry of a precision radiation oncology strategy

Abstract

Purpose Non-small cell lung cancer (NSCLC) patient radiation therapy (RT) is planned without consideration of spatial heterogeneity in lung function or tumor response. We assessed the dosimetric and clinical feasibility of functional lung avoidance and response-adaptive escalation (FLARE) RT to reduce dose to [99mTc]MAA-SPECT/CT perfused lung while redistributing an escalated boost dose within [18F]FDG-PET/CT-defined biological target volumes (BTV). Methods Eight stage IIB-IIIB NSCLC patients underwent FDG-PET/CT and MAA-SPECT/CT treatment planning scans. Perfused lung objectives were derived from scatter/collimator/attenuation-corrected MAA-SPECT uptake relative to ITV-subtracted lung to maintain < 20 Gy mean lung dose (MLD). Prescriptions included 60 Gy to the planning target volume (PTV) and concomitant boost of 74 Gy mean to biological target volumes (BTV=GTV+PET gradient segmentation) scaled to each BTV voxel by relative FDG-PET SUV. Dose-painting-by-numbers prescriptions were integrated into commercial treatment planning systems via uptake threshold discretization. Dose constraints for lung, heart, cord, and esophagus were defined. FLARE RT plans were optimized with volumetric modulated arc therapy (VMAT), proton pencil beam scanning (PBS) with 3%-3mm robust optimization, and combination of PBS (avoidance) plus VMAT (escalation). The high boost dose region was evaluated within a standardized SUVpeak structure. FLARE RT plans were compared to reference VMAT plans. Linear regression between radiation dose to BTV and normalized FDG PET SUV at every voxel was conducted, from which Pearson linear correlation coefficients and regression slopes were extracted. Spearman rank correlation coefficients were estimated between radiation dose to lung and normalized SPECT uptake. Dosimetric differences between treatment modalities were evaluated by Friedman non-parametric paired test with multiple sampling correction. Results No unacceptable violations of PTV and normal tissue objectives were observed in 24 FLARE RT plans. Compared to reference VMAT plans, FLARE VMAT plans achieved a higher mean dose to BTV (73.7 Gy vs. 61.3 Gy), higher mean dose to SUVpeak (89.7 Gy vs. 60.8 Gy), and lower mean dose to highly perfused lung (7.3 Gy vs. 14.9 Gy). These dosimetric gains came at the expense of higher mean heart dose (9.4 Gy vs. 5.8 Gy) and higher maximum cord dose (50.1 Gy vs. 44.6 Gy) relative to the reference VMAT plans. Between FLARE plans, FLARE VMAT achieved higher dose to the SUVpeak ROI than FLARE PBS (89.7 Gy vs. 79.2 Gy, p = 0.01), while FLARE PBS delivered lower dose to lung than FLARE VMAT (11.9 Gy vs 15.6 Gy, p < 0.001). Voxelwise linear dose redistribution slope between BTV dose and FDG PET uptake was higher in magnitude for FLARE PBS+VMAT (0.36 Gy per %SUVmax) compared to FLARE VMAT (0.27 Gy per %SUVmax) or FLARE PBS alone (0.17 Gy per %SUVmax). Conclusions FLARE RT is clinically feasible with VMAT and PBS. A combination of PBS for functional lung avoidance and VMAT for FDG PET dose escalation balanced t...

Functional perfusion image guided radiation treatment planning for locally advanced lung cancer

“…FA planning yielded a 7.6 Gy reduction in MLD (MLD of 7.3 Gy with FA planning versus 14.9 Gy on SR planning). Meanwhile, dose to the heart dose was 9.4 versus 5.8 Gy, and maximum dose to spinal cord was 50.1 versus 44.6 Gy relative to reference VMAT plans [22]. Shioyama et al performed a study with the purpose to preserve functional lung using perfusion imaging and IMRT for advanced-stage NSCLC [24].…”

Task Group 174 Report: Utilization of [18F]Fluorodeoxyglucose Positron Emission Tomography ([18F]FDG‐PET) in Radiation Therapy

“…The extent of improvement depends on the size of the patient, with larger cross-section patients deriving greater benefit compared to smaller cross-section patients. This can allow for administration of lower activities to patients (and thus lower radiation dose to the patient) or shorter acquisition times, or improved imaging of faster decaying positron emitting radiopharmaceuticals such as 15 O.…”

“…11 [ 18 F] FDG-PET/CT has been shown to change the extent of disease identification and delineation in 15%-20% of cancer patients compared to CT alone in a retrospective analysis. 12 Consequently, [ 18 F]FDG-PET/CT-guided RT planning has seen increasing use in head and neck cancer, 13 lung cancer, [14][15][16] breast cancer, 17,18 esophageal cancer, 19 non-Hodgkin's lymphoma, 20 gynecologic cancer, 21 rectal cancer, 22 and anal cancer. 23 The advantages of combined anatomic and functional imaging have led to widespread adoption of PET/CT in RT clinics.…”

Technical Note: Deriving ventilation imaging from 4DCT by deep convolutional neural network

“…Functional imaging is emerging as a potentially important tool in the planning and evaluation of lung cancer radiotherapy plans. Lung function avoidance has been applied in intensity‐modulated radiation therapy (IMRT) planning to limit dose delivered to well‐functioning lung parts . Conventional methods to obtain lung ventilation images include nuclear medicine ventilation–perfusion (VQ) scans, positron emission tomography (PET), single‐photon emission computer tomography (SPECT), or hyperpolarized He‐3 magnetic resonance imaging (MRI) .…”