Characterization of Biology-Guided Radiotherapy Accuracy as a Function of PET Tracer Uptake

Abstract

To characterize the tracking capability and dosimetric accuracy of biology-guided radiotherapy (BgRT) under clinically relevant PET tracer uptake scenarios relative to the background. A custom-made anthropomorphic phantom filled with a liquid 18F-FDG solution including two embedded fillable 22 mm diameter spherical structures mimicking GTV (= CTV) and OAR was coupled to motion stages to create an independent 3D respiratory motion with 22 mm maximum range for target and a 5 mm 1D sinusoidal motion in the OAR. The biology-tracking zone (BTZ) was generated by adding 5 mm margin to the motion extent. The three BgRT scenarios studied were representative of tumors with good (8:1), borderline (4:1) and undesired (2:1) PET biodistributions compared to background. The clinical safety limit of BgRT uses Activity Concentration within the BTZ (AC ≥ 5 kBq/ml) and Normalized Target Signal as a contrast metric (NTS ≧ 2.7 for planning and ≧ 2 for delivery). The BgRT deliveries were repeated 3 times with radiochromic film and integrated ion chamber capturing the target and OAR doses. Tracked dosimetry was assessed using a margin-loss calculation defined as the maximum linear difference in distance between the planned and delivered 97% prescription iso-dose lines. The imaging-only PET images used to create BgRT plans had an AC of 7.0, 5.3, and 1.6 kBq/ml with an NTS of 6.8, 5.3, and 1.8 for 8:1, 4:1, and 2:1 concentrations, respectively. Qualitatively, the target was not visible on the planning PET images 2:1 loading scenario. At delivery, the mean pre-scan activity concentrations were 6.8, 4.7, and 3.7 kBq/ml with corresponding mean NTS of 3.7, 2.6, 1.5 for 8:1, 4:1 and 2:1 deliveries. The pre-scan values of AC or NTS did not satisfy the clinical system safety limits for 4:1 and 2:1 ratio experiments, but the engineering software allowed for the delivery to capture the resulting doses. The deliveries showed a prescription dose coverage to the CTV of 100% for the 8:1 and 4:1 cases, but 88% for the 2:1 case. When compared to the planned dose values, the delivered minimum doses were -7.6%, -8.6% and -10.9%, whereas the maximum dose differences in CTV were 1.2%, 0% and -4.8% of the planned dose distributions of the 8:1, 4:1 and 2:1 cases, respectively. Calculated margin losses were -2.3, -3.8, and -5.5 mm, for the 8:1, 4:1, and 2:1 cases, respectively. The maximum OAR doses were less than the maximum doses predicted on the bounded DVH curves for all scenarios. With sufficient tracer uptake in the target, BgRT can deliver tracked dosimetry for targets with a large respiratory motion profile. Both the good BgRT candidate and borderline cases produced clinically acceptable delivered doses, even though the borderline case was flagged by the clinical system safety checks. As expected, the delivered BgRT dose distributions were suboptimal with reduced tumor over background PET contrast.