Normal tissue complication probability estimation by the LymanKutcherBurman method does not accurately predict spinal cord tolerance to stereotactic radiosurgery.
ABSTRACT To determine whether normal tissue complication probability (NTCP) analyses of the human spinal cord by use of the LymanKutcherBurman (LKB) model, supplemented by linearquadratic modeling to account for the effect of fractionation, predict the risk of myelopathy from stereotactic radiosurgery (SRS).
From November 2001 to July 2008, 24 spinal hemangioblastomas in 17 patients were treated with SRS. Of the tumors, 17 received 1 fraction with a median dose of 20 Gy (range, 1830 Gy) and 7 received 20 to 25 Gy in 2 or 3 sessions, with cord maximum doses of 22.7 Gy (range, 17.830.9 Gy) and 22.0 Gy (range, 20.226.6 Gy), respectively. By use of conventional values for α/β, volume parameter n, 50% complication probability dose TD(50), and inverse slope parameter m, a computationally simplified implementation of the LKB model was used to calculate the biologically equivalent uniform dose and NTCP for each treatment. Exploratory calculations were performed with alternate values of α/β and n.
In this study 1 case (4%) of myelopathy occurred. The LKB model using radiobiological parameters from Emami and the logistic model with parameters from Schultheiss overestimated complication rates, predicting 13 complications (54%) and 18 complications (75%), respectively. An increase in the volume parameter (n), to assume greater parallel organization, improved the predictive value of the models. Maximumlikelihood LKB fitting of α/β and n yielded better predictions (0.7 complications), with n = 0.023 and α/β = 17.8 Gy.
The spinal cord tolerance to the dosimetry of SRS is higher than predicted by the LKB model using any set of accepted parameters. Only a high α/β value in the LKB model and only a large volume effect in the logistic model with Schultheiss data could explain the low number of complications observed. This finding emphasizes that radiobiological models traditionally used to estimate spinal cord NTCP may not apply to the dosimetry of SRS. Further research with additional NTCP models is needed.

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ABSTRACT: To investigate the dosimetric variations and radiobiological impacts as a consequence of delivering treatment plans of 3D nature in 4D manner based on the 4D Monte Carlo treatment planning framework implemented on Cyberknife. Dose distributions were optimized on reference 3D images at end of exhale phase of a 4DCT dataset for 25 lung cancer patients treated with 60 Gy∕3Fx or 48 Gy∕4Fx. Deformable image registrations between individual 3DCT images to the reference 3DCT image in the 4DCT study were performed to interpolate doses calculated on multiple anatomical geometries back on to the reference geometry to compose a 4D dose distribution that included the tracking beam motion and organ deformation. The 3D and 4D dose distributions that were initially calculated with the equivalent pathlength (EPL) algorithm (3D(EPL) dose and 4D(EPL) dose) were recalculated with the Monte Carlo algorithm (3D(MC) dose and 4D(MC) dose). Dosimetric variations of V(60Gy∕48Gy) and D(99) of GTV, mean doses to the lung and the heart and maximum dose (D(1)) of the spinal cord as a consequence of tracking beam motion in deforming anatomy, dose calculation algorithm, and both were quantified by the relative change from 4D(MC) to 3D(MC) doses, from 4D(MC) to 4D(EPL) doses, and from 4D(MC) to 3D(EPL) doses, respectively. Comparing 4D(MC) to 3D(EPL) plans, V(60Gy ∕ 48Gy) and D(99) of GTV decreased considerably by 13 ± 22% (mean ± 1SD) and 9.2 ± 5.5 Gy but changes of normal tissue doses were not more than 0.5 Gy on average. The generalized equivalent uniform dose (gEUD) and tumor control probability (TCP) were reduced by 14.3 ± 8.8 Gy and 7.5 ± 5.2%, and normal tissue complication probability (NTCP) for myelopathy and pericarditis were close to zero and NTCP for radiation pneumonitis was reduced by 2.5% ± 4.1%. Comparing 4D(MC) to 4D(EPL) plans found decreased V(60Gy∕48Gy) and D(99) by 12.3% ± 21.6% and 7.3 ± 5.3 Gy, the normal tissues doses by 0.5 Gy on average, gEUD and TCP by 13.0 ± 8.6 Gy and 7.1% ± 5.1%. Comparing 4D(MC) to 3D(MC) doses, V(60Gy∕48Gy) and D(99) of GTV was reduced by 5.2% ± 8.8% and 2.6 ± 3.3 Gy, and normal tissues hardly changed from 4D(MC) to 3D(MC) doses. The corresponding decreases of gEUD and TCP were 2.8 ± 4.0 Gy and 1.6 ± 2.4%. The large discrepancy between original 3D(EPL) plan and benchmarking 4D(MC) plan is predominately due to dose calculation algorithms as the tracking beam motion and organ deformation hardly influenced doses of normal tissues and moderately decreased V(60Gy∕48Gy) and D(99) of GTV. It is worth to make a thoughtful weight of the benefits of full 4D(MC) dose calculation and consider 3D(MC) dose calculation as a compromise of 4D(MC) dose calculation considering the multifold computation time.Medical Physics 09/2012; 39(9):547987. DOI:10.1118/1.4739249 · 3.01 Impact Factor 
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ABSTRACT: This study was performed to determine swine spinal cord tolerance to singlefraction, partialvolume irradiation 1 year after receiving uniform irradiation to 30 Gy in 10 fractions. A 10cm length of spinal cord (C3T1) was uniformly irradiated to 30 Gy in 10 consecutive fractions and reirradiated 1 year later with a single radiosurgery dose centered within the previously irradiated segment. Radiosurgery was delivered to a cylindrical volume approximately 5 cm in length and 2 cm in diameter, which was positioned laterally to the cervical spinal cord, resulting in a dose distribution with the 90%, 50%, and 10% isodose lines traversing the ipsilateral, central, and contralateral spinal cord, respectively. Twentythree pigs were stratified into six dose groups with mean maximum spinal cord doses of 14.9 ± 0.1 Gy (n = 2), 17.1 ± 0.3 Gy (n = 3), 19.0 ± 0.1 Gy (n = 5), 21.2 ± 0.1 Gy (n = 5), 23.4 ± 0.2 Gy (n = 5), and 25.4 ± 0.4 Gy (n = 3). The mean percentage of spinal cord volumes receiving ≥10 Gy for the same groups were 34% ± 1%, 40% ± 1%, 46% ± 3%, 52% ± 1%, 56 ± 3%, and 57% ± 1%. The study endpoint was motor neurologic deficit as determined by a change in gait during a 1 year followup period. A steep doseresponse curve was observed with a 50% incidence of paralysis (ED(50)) for the maximum point dose of 19.7 Gy (95% confidence interval, 17.421.4). With two exceptions, histology was unremarkable in animals with normal neurologic status, while all animals with motor deficits showed some degree of demyelination and focal white matter necrosis on the irradiated side, with relative sparing of gray matter. Histologic comparison with a companion study of de novo irradiated animals revealed that retreatment responders had more extensive tissue damage, including infarction of gray matter, only at prescription doses >20 Gy. Pigs receiving spinal radiosurgery 1 year after receiving 30 Gy in 10 fractions were not at significantly higher risk of developing motor deficits than pigs that received radiosurgery alone.International journal of radiation oncology, biology, physics 12/2011; 83(3):10317. DOI:10.1016/j.ijrobp.2011.08.030 · 4.18 Impact Factor 
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ABSTRACT: To identify dosimetric parameters that correlate with acute hematologic toxicity (HT) in patients with squamous cell carcinoma of the anal canal treated with definitive chemoradiotherapy (CRT). We analyzed 33 patients receiving CRT. Pelvic bone (PBM) was contoured for each patient and divided into subsites: ilium, lower pelvis (LP), and lumbosacral spine (LSS). The volume of each region receiving at least 5, 10, 15, 20, 30, and 40 Gy was calculated. Endpoints included grade ≥3 HT (HT3+) and hematologic event (HE), defined as any grade ≥2 HT with a modification in chemotherapy dose. Normal tissue complication probability (NTCP) was evaluated with the LymanKutcherBurman (LKB) model. Logistic regression was used to test associations between HT and dosimetric/clinical parameters. Nine patients experienced HT3+ and 15 patients experienced HE. Constrained optimization of the LKB model for HT3+ yielded the parameters m = 0.175, n = 1, and TD(50) = 32 Gy. With this model, mean PBM doses of 25 Gy, 27.5 Gy, and 31 Gy result in a 10%, 20%, and 40% risk of HT3+, respectively. Compared with patients with mean PBM dose of <30 Gy, patients with mean PBM dose ≥30 Gy had a 14fold increase in the odds of developing HT3+ (p = 0.005). Several lowdose radiation parameters (i.e., PBMV10) were associated with the development of HT3+ and HE. No association was found with the ilium, LP, or clinical factors. LKB modeling confirms the expectation that PBM acts like a parallel organ, implying that the mean dose to the organ is a useful predictor for toxicity. Lowdose radiation to the PBM was also associated with clinically significant HT. Keeping the mean PBM dose <22.5 Gy and <25 Gy is associated with a 5% and 10% risk of HT, respectively.International journal of radiation oncology, biology, physics 03/2012; 84(3):7006. DOI:10.1016/j.ijrobp.2011.12.072 · 4.18 Impact Factor