Tumor-dose-rate variations during robotic radiosurgery of oligo and multiple brain metastases.

PURPOSE: For step-and-shoot robotic stereotactic radiosurgery (SRS) the dose delivered over time, called local tumor-dose-rate (TDR), may strongly vary during treatment of multiple lesions. The authors sought to evaluate technical parameters influencing TDR and correlate TDR to clinical outcome. MATERIAL AND METHODS: A total of 23 patients with 162 oligo (1-3) and multiple (>3) brain metastases (OBM/MBM) treated in 33 SRS sessions were retrospectively analyzed. Median PTV were 0.11 cc (0.01-6.36 cc) and 0.50 cc (0.12-3.68 cc) for OBM and MBM, respectively. Prescription dose ranged from 16 to 20 Gy prescribed to the median 70% isodose line. The maximum dose-rate for planning target volume (PTV) percentage p in time span s during treatment (TDRs,p) was calculated for various p and s based on treatment log files and in-house software. RESULTS: TDR60min,98% was 0.30 Gy/min (0.23-0.87 Gy/min) for OBM and 0.22 Gy/min (0.12-0.63 Gy/min) for MBM, respectively, and increased by 0.03 Gy/min per prescribed Gy. TDR60min,98% strongly correlated with treatment time (ρ = -0.717, p < 0.001), monitor units (MU) (ρ = -0.767, p < 0.001), number of beams (ρ = -0.755, p < 0.001) and beam directions (ρ = -0.685, p < 0.001) as well as lesions treated per collimator (ρ = -0.708, P < 0.001). Median overall survival (OS) was 20 months and 1­ and 2­year local control (LC) was 98.8% and 90.3%, respectively. LC did not correlate with any TDR, but tumor response (partial response [PR] or complete response [CR]) correlated with all TDR in univariate analysis (e.g., TDR60min,98%: hazard ration [HR] = 0.974, confidence interval [CI] = 0.952-0.996, p = 0.019). In multivariate analysis only concomitant targeted therapy or immunotherapy and breast cancer tumor histology remained a significant factor for tumor response. Local grade ≥2 radiation-induced tissue reactions were noted in 26.3% (OBM) and 5.2% (MBM), respectively, mainly influenced by tumor volume (p < 0.001). CONCLUSIONS: Large TDR variations are noted during MBM-SRS which mainly arise from prolonged treatment times. Clinically, low TDR corresponded with decreased local tumor responses, although the main influencing factor was concomitant medication.

Combined stereotactic body radiotherapy and trans-arterial chemoembolization as initial treatment in BCLC stage B-C hepatocellular carcinoma.

PURPOSE: We retrospectively evaluated the efficacy and safety of stereotactic body radiotherapy (SBRT) combined with trans-arterial chemoembolization (TACE) as initial therapy in Barcelona Clinic Liver Cancer (BCLC) system stage B-C hepatocellular carcinoma (HCC). PATIENTS AND METHODS: Seventy-two patients received a single dose of TACE followed by SBRT 4 weeks later. All patients had tumor sizes ≥5 cm, at least 700 ml of disease-free liver, Child-Pugh (CP) score ≤ B7 and tumor nodules ≤5. SBRT dose, ranging from 6â€¯× 5-8 Gy or 5-10â€¯× 4 Gy, was individualized according to normal tissue constraints. No subsequent scheduled treatment was delivered unless disease progression was observed. Local control (LC), overall survival (OS), progression-free survival (PFS), response rate (RR), and toxicity were evaluated. RESULTS: The patients' characteristics were: median age 60 years (range 28-87 years); CP score A/B (n = 68/4); BCLC stage B/C (n = 51/21); solitary/multifocal (n = 37/35); portal vein invasion (n = 18). The median tumor size and GTV were 11.2 cm (range 5.0-23.6 cm) and 751 cm3 (range 41-4009 cm3), respectively. The median equivalent dose in 2 Gy per fraction (EQD2, α/ß = 10) was 37.3 Gy2 (range, 28-72 Gy2). The median follow-up time was 16.8 months (range, 3-96 months). The objective RR was 68% and the 1­year LC rate was 93.6% (95% CI, 87.6-100%). The median OS was 19.8 months (95% CI, 11.6-30.6 months). SBRT-related grade 3 or higher adverse gastrointestinal events and treatment-related death occurred in three (2.8%) and one patient (1.4%) respectively. No patient developed classical radiation-induced liver injury. CONCLUSION: Our experience suggests that combined TACE and SBRT can be a safe and effective initial therapy for BCLC stage B-C HCC with appropriate patient selection. Further prospective trials are warranted.

Breathing-motion-compensated robotic guided stereotactic body radiation therapy : Patterns of failure analysis.

PURPOSE: We retrospectively evaluated the patterns of failure for robotic guided real-time breathing-motion-compensated (BMC) stereotactic body radiation therapy (SBRT) in the treatment of tumors in moving organs. PATIENTS AND METHODS: Between 2011 and 2016, a total of 198 patients with 280 lung, liver, and abdominal tumors were treated with BMC-SBRT. The median gross tumor volume (GTV) was 12.3 cc (0.1-372.0 cc). Medians of mean GTV BEDα/ß =10 Gy (BED = biological effective dose) was 148.5 Gy10 (31.5-233.3 Gy10) and prescribed planning target volume (PTV) BEDα/ß =10 Gy was 89.7 Gy10 (28.8-151.2 Gy10), respectively. We analyzed overall survival (OS) and local control (LC) based on various factors, including BEDs with α/ß ratios of 15 Gy (lung metastases), 21 Gy (primary lung tumors), and 27 Gy (liver metastases). RESULTS: Median follow-up was 10.4 months (2.0-59.0 months). The 2­year actuarial LC was 100 and 86.4% for primary early and advanced stage lung tumors, respectively, 100% for lung metastases, 82.2% for liver metastases, and 90% for extrapulmonary extrahepatic metastases. The 2­year OS rate was 47.9% for all patients. In uni- and multivariate analysis, comparatively lower PTV prescription dose (equivalence of 3 × 12-13 Gy) and higher average GTV dose (equivalence of 3 × 18 Gy) to current practice were significantly associated with LC. For OS, Karnofsky performance score (100%), gender (female), and SBRT without simultaneous chemotherapy were significant prognostic factors. Grade 3 side effects were rare (0.5%). CONCLUSIONS: Robotic guided BMC-SBRT can be considered a safe and effective treatment for solid tumors in moving organs. To reach sufficient local control rates, high average GTV doses are necessary. Further prospective studies are warranted to evaluate these points.

Direct dose correlation of MRI morphologic alterations of healthy liver tissue after robotic liver SBRT.

PURPOSE: For assessing healthy liver reactions after robotic SBRT (stereotactic body radiotherapy), we investigated early morphologic alterations on MRI (magnetic resonance imaging) with respect to patient and treatment plan parameters. PATIENTS AND METHODS: MRI data at 6-17 weeks post-treatment from 22 patients with 42 liver metastases were analyzed retrospectively. Median prescription dose was 40 Gy delivered in 3-5 fractions. T2- and T1-weighted MRI were registered to the treatment plan. Absolute doses were converted to EQD2 (Equivalent dose in 2Gy fractions) with α/ß-ratios of 2 and 3 Gy for healthy, and 8 Gy for modelling pre-damaged liver tissue. RESULTS: Sharply defined, centroid-shaped morphologic alterations were observed outside the high-dose volume surrounding the GTV. On T2-w MRI, hyperintensity at EQD2 isodoses of 113.3 ± 66.1 Gy2, 97.5 ± 54.7 Gy3, and 66.5 ± 32.0 Gy8 significantly depended on PTV dimension (p = 0.02) and healthy liver EQD2 (p = 0.05). On T1-w non-contrast MRI, hypointensity at EQD2 isodoses of 113.3 ± 49.3 Gy2, 97.4 ± 41.0 Gy3, and 65.7 ± 24.2 Gy8 significantly depended on prior chemotherapy (p = 0.01) and total liver volume (p = 0.05). On T1-w gadolinium-contrast delayed MRI, hypointensity at EQD2 isodoses of 90.6 ± 42.5 Gy2, 79.3 ± 35.3 Gy3, and 56.6 ± 20.9 Gy8 significantly depended on total (p = 0.04) and healthy (p = 0.01) liver EQD2. CONCLUSIONS: Early post-treatment changes in healthy liver tissue after robotic SBRT could spatially be correlated to respective isodoses. Median nominal doses of 10.1-11.3 Gy per fraction (EQD2 79-97 Gy3) induce characteristic morphologic alterations surrounding the lesions, potentially allowing for dosimetric in-vivo accuracy assessments. Comparison to other techniques and investigations of the short- and long-term clinical impact require further research.

Treatment planning for spinal radiosurgery : A competitive multiplatform benchmark challenge.

PURPOSE: To investigate the quality of treatment plans of spinal radiosurgery derived from different planning and delivery systems. The comparisons include robotic delivery and intensity modulated arc therapy (IMAT) approaches. Multiple centers with equal systems were used to reduce a bias based on individual's planning abilities. The study used a series of three complex spine lesions to maximize the difference in plan quality among the various approaches. METHODS: Internationally recognized experts in the field of treatment planning and spinal radiosurgery from 12 centers with various treatment planning systems participated. For a complex spinal lesion, the results were compared against a previously published benchmark plan derived for CyberKnife radiosurgery (CKRS) using circular cones only. For two additional cases, one with multiple small lesions infiltrating three vertebrae and a single vertebra lesion treated with integrated boost, the results were compared against a benchmark plan generated using a best practice guideline for CKRS. All plans were rated based on a previously established ranking system. RESULTS: All 12 centers could reach equality (n = 4) or outperform (n = 8) the benchmark plan. For the multiple lesions and the single vertebra lesion plan only 5 and 3 of the 12 centers, respectively, reached equality or outperformed the best practice benchmark plan. However, the absolute differences in target and critical structure dosimetry were small and strongly planner-dependent rather than system-dependent. Overall, gantry-based IMAT with simple planning techniques (two coplanar arcs) produced faster treatments and significantly outperformed static gantry intensity modulated radiation therapy (IMRT) and multileaf collimator (MLC) or non-MLC CKRS treatment plan quality regardless of the system (mean rank out of 4 was 1.2 vs. 3.1, p = 0.002). CONCLUSIONS: High plan quality for complex spinal radiosurgery was achieved among all systems and all participating centers in this planning challenge. This study concludes that simple IMAT techniques can generate significantly better plan quality compared to previous established CKRS benchmarks.

Lipiodol versus diaphragm in 4D-CBCT-guided stereotactic radiotherapy of hepatocellular carcinomas.

PURPOSE: The purpose of this work was to investigate the potential of lipiodol as a direct tumor surrogate alternative to the diaphragm surrogate on four-dimensional cone-beam computed tomography (4D-CBCT) image guidance for stereotactic radiotherapy of hepatocellular carcinomas. METHODS: A total of 29 hepatocellular carcinomas (HCC) patients treated by stereotactic radiotherapy following transarterial chemoembolization (TACE) with homogeneous or partial defective lipiodol retention were included. In all, 4-7 pretreatment 4D-CBCT scans were selected for each patient. For each scan, either lipiodol or the diaphragm was used for 4D registration. Resulting lipiodol/diaphragm motion ranges and position errors relative to the reconstructed midventilation images were analyzed to obtain the motion variations, and group mean (ΔM), systematic (Σ), and random (σ) errors of the treatment setup. RESULTS: Of the lipiodolized tumors, 55 % qualified for direct localization on the 4D-CBCT. Significant correlations of lipiodol and diaphragm positions were found in the left-right (LR), craniocaudal (CC), and anteroposterior (AP) directions. ΔM and σ obtained with lipiodol and diaphragm were similar, agreed to within 0.5 mm in the LR and AP, and 0.3 mm in the CC directions, and Σ differed by 1.4 (LR), 1.1 (CC), and 0.6 (AP) mm. Variations of diaphragm motion range > 5 mm were not observed with lipiodol and in one patient with diaphragm. The margin required for the tumor prediction error using the diaphragm surrogate was 6.7 (LR), 11.7 (CC), and 4.1 (AP) mm. CONCLUSION: Image-guidance combining lipiodol with 4D-CBCT enabled accurate localization of HCC and thus margin reduction. A major limitation was the degraded lipiodol contrast on 4D-CBCT.

Inverse treatment planning for spinal robotic radiosurgery: an international multi-institutional benchmark trial.

Stereotactic radiosurgery (SRS) is the accurate, conformal delivery of high-dose radiation to well-defined targets while minimizing normal structure doses via steep dose gradients. While inverse treatment planning (ITP) with computerized optimization algorithms are routine, many aspects of the planning process remain user-dependent. We performed an international, multi-institutional benchmark trial to study planning variability and to analyze preferable ITP practice for spinal robotic radiosurgery. 10 SRS treatment plans were generated for a complex-shaped spinal metastasis with 21 Gy in 3 fractions and tight constraints for spinal cord (V14Gy < 2 cc, V18Gy < 0.1 cc) and target (coverage > 95%). The resulting plans were rated on a scale from 1 to 4 (excellent-poor) in five categories (constraint compliance, optimization goals, low-dose regions, ITP complexity, and clinical acceptability) by a blinded review panel. Additionally, the plans were mathemati-cally rated based on plan indices (critical structure and target doses, conformity, monitor units, normal tissue complication probability, and treatment time) and compared to the human rankings. The treatment plans and the reviewers' rankings varied substantially among the participating centers. The average mean overall rank was 2.4 (1.2-4.0) and 8/10 plans were rated excellent in at least one category by at least one reviewer. The mathematical rankings agreed with the mean overall human rankings in 9/10 cases pointing toward the possibility for sole mathematical plan quality comparison. The final rankings revealed that a plan with a well-balanced trade-off among all planning objectives was preferred for treatment by most par-ticipants, reviewers, and the mathematical ranking system. Furthermore, this plan was generated with simple planning techniques. Our multi-institutional planning study found wide variability in ITP approaches for spinal robotic radiosurgery. The participants', reviewers', and mathematical match on preferable treatment plans and ITP techniques indicate that agreement on treatment planning and plan quality can be reached for spinal robotic radiosurgery.

Comparison of 3D and 4D Monte Carlo optimization in robotic tracking stereotactic body radiotherapy of lung cancer.

PURPOSE: To investigate the adequacy of three-dimensional (3D) Monte Carlo (MC) optimization (3DMCO) and the potential of four-dimensional (4D) dose renormalization (4DMCrenorm) and optimization (4DMCO) for CyberKnife (Accuray Inc., Sunnyvale, CA) radiotherapy planning in lung cancer. MATERIALS AND METHODS: For 20 lung tumors, 3DMCO and 4DMCO plans were generated with planning target volume (PTV5 mm) = gross tumor volume (GTV) plus 5 mm, assuming 3 mm for tracking errors (PTV3 mm) and 2 mm for residual organ deformations. Three fractions of 60 Gy were prescribed to ≥ 95 % of the PTV5 mm. Each 3DMCO plan was recalculated by 4D MC dose calculation (4DMCrecal) to assess the dosimetric impact of organ deformations. The 4DMCrecal plans were renormalized (4DMCrenorm) to 95 % dose coverage of the PTV5 mm for comparisons with the 4DMCO plans. A 3DMCO plan was considered adequate if the 4DMCrecal plan showed ≥ 95 % of the PTV3 mm receiving 60 Gy and doses to other organs at risk (OARs) were below the limits. RESULTS: In seven lesions, 3DMCO was inadequate, providing < 95 % dose coverage to the PTV3 mm. Comparison of 4DMCrecal and 3DMCO plans showed that organ deformations resulted in lower OAR doses. Renormalizing the 4DMCrecal plans could produce OAR doses higher than the tolerances in some 4DMCrenorm plans. Dose conformity of the 4DMCrenorm plans was inferior to that of the 3DMCO and 4DMCO plans. The 4DMCO plans did not always achieve OAR dose reductions compared to 3DMCO and 4DMCrenorm plans. CONCLUSION: This study indicates that 3DMCO with 2 mm margins for organ deformations may be inadequate for Cyberknife-based lung stereotactic body radiotherapy (SBRT). Renormalizing the 4DMCrecal plans could produce degraded dose conformity and increased OAR doses; 4DMCO can resolve this problem.

Quantifying variability of intrafractional target motion in stereotactic body radiotherapy for lung cancers.

In lung stereotactic body radiotherapy (SBRT), variability of intrafractional target motion can negate the potential benefits of four-dimensional (4D) treatment planning that aims to account for the dosimetric impacts of organ motion. This study used tumor motion data obtained from CyberKnife SBRT treatments to quantify the reproducibility of probability motion function (pmf) of 37 lung tumors. The reproducibility of pmf was analyzed with and without subtracting the intrafractional baseline drift from the original motion data. Statistics of intrafractional tumor motion including baseline drift, target motion amplitude and period, were also calculated. The target motion amplitude significantly correlates with variations (1SD) of motion amplitude and baseline drift. Significant correlation between treatment time and variations (1 SD) of motion amplitude was observed in anterior-posterior (AP) motion, but not in craniocaudal (CC) and left-right (LR) motion. The magnitude of AP and LR baseline drifts significantly depend on the treatment time, while the CC baseline drift does not. The reproducibility of pmf as a function of time can be well described by a two-exponential function with a fast and slow component. The reproducibility of pmf is over 60% for the CC motion and over 50% for the AP and LR motions when baseline variations were subtracted from the original motion data. It decreases to just over 30% for the CC motion and about 20% for the AP and LR motion, otherwise. 4D planning has obvious limitations due to variability of intrafractional target motion. To account for potential risks of overdosing critical organs, it is important to simulate the dosimetric impacts of intra- and interfractional baseline drift using population statistics obtained from SBRT treatments.

Evaluation of dose prediction error and optimization convergence error in four-dimensional inverse planning of robotic stereotactic lung radiotherapy.

Inverse optimization of robotic stereotactic lung radiotherapy is typically performed using relatively simple dose calculation algorithm on a single instance of breathing geometry. Variations of patient geometry and tissue density during respiration could reduce the dose accuracy of these 3D optimized plans. To quantify the potential benefits of direct four-dimensional (4D) optimization in robotic lung radiosurgery, 4D optimizations using 1) ray-tracing algorithm with equivalent path-length heterogeneity correction (4EPL(opt)), and 2) Monte Carlo (MC) algorithm (4MC(opt)), were performed in 25 patients. The 4EPL(opt) plans were recalculated using MC algorithm (4MC(recal)) to quantify the dose prediction errors (DPEs). Optimization convergence errors (OCEs) were evaluated by comparing the 4MC(recal) and 4MC(opt) dose results. The results were analyzed by dose-volume histogram indices for selected organs. Statistical equivalence tests were performed to determine the clinical significance of the DPEs and OCEs, compared with a 3% tolerance. Statistical equivalence tests indicated that the DPE and the OCE are significant predominately in GTV D98%. The DPEs in V20 of lung, and D2% of cord, trachea, and esophagus are within 1.2%, while the OCEs are within 10.4% in lung V20 and within 3.5% in trachea D2%. The marked DPE and OCE suggest that 4D MC optimization is important to improve the dosimetric accuracy in robotic-based stereotactic body radiotherapy, despite the longer computation time.

Dosimetric evaluation of four-dimensional dose distributions of CyberKnife and volumetric-modulated arc radiotherapy in stereotactic body lung radiotherapy.

Advanced image-guided stereotatic body lung radiotherapy techniques using volumetric-modulated arc radiotherapy (VMAT) with four-dimensional cone-beam computed tomography (4D CBCT) and CyberKnife with real-time target tracking have been clinically implemented by different authors. However, dosimetric comparisons between these techniques are lacking. In this study, 4D CT scans of 14 patients were used to create VMAT and CyberKnife treatment plans using 4D dose calculations. The GTV and the organs at risk (OARs) were defined on the end-exhale images for CyberKnife planning and were then deformed to the midventilation images (MidV) for VMAT optimization. Direct 4D Monte Carlo dose optimizations were performed for CyberKnife (4D(CK)). Four-dimensional dose calculations were also applied to VMAT plans to generate the 4D dose distributions (4D(VMAT)) on the exhale images for direct comparisons with the 4D(CK) plans. 4D(CK) and 4D(VMAT) showed comparable target conformity (1.31 ± 0.13 vs. 1.39 ± 0.24, p = 0.05). GTV mean doses were significantly higher with 4D(CK). Statistical differences of dose volume metrics were not observed in the majority of OARs studied, except for esophagus, with 4D(VMAT) yielding marginally higher D1% than 4D(CK). The normal tissue volumes receiving 80%, 50%, and 30% of the prescription dose (V80%, V50%, and V30%) were higher with 4D(VMAT), whereas 4D(CK) yielded slightly higher V10% in posterior lesions than 4D(VMAT). VMAT resulted in much less monitor units and therefore greater delivery efficiency than CyberKnife. In general, it was possible to produce dosimetrically acceptable plans with both techniques. The selection of treatment modality should consider the dosimetric results as well as the patient's tolerance of the treatment process specific to the SBRT technique.

A sub-analysis of multi-center planning radiosurgery for intracranial metastases through automation (MC-PRIMA) comparing UK and international centers.

OBJECTIVES: A sub-analysis of the MC-PRIMA study was performed to compare the plan quality of stereotactic radiosurgery (SRS) to multiple brain metastases (MBM) between UK and other international centres. METHODS AND MATERIALS: Six centres from the UK and nineteen from other international centres autoplanned using Multiple Brain Mets™ (AutoMBM; Brainlab, Munich, Germany) software for a five MBM study case from a prior planning competition that was originally organized by the Trans-Tasmania Radiation Oncology Group (TROG). Twenty-three dosimetric metrics and the resulting composite plan score per the TROG planning competition were compared between the UK and other international centres. Planning experience and planning time from each planner were recorded and statistically compared. RESULTS: Planning experiences between two groups are equal. Except for mean dose to the hippocampus, all other 22 dosimetric metrics were comparable between two groups. The inter-planner variations in these 23 dosimetric metrics and the composite plan score were also statistically equivalent. Planning time is slightly longer in the UK group (mean = 86.8 min) with a mean difference of 50.3 min. CONCLUSIONS: AutoMBM effectively achieves standardization of the plan quality of SRS to MBM within UK and further against the other international centres. Significant planning efficiency gain by AutoMBM both among the UK and other international centres may help to increase the capacity of SRS service by alleviating the clinical and technical loadings.

Investigation of four-dimensional (4D) Monte Carlo dose calculation in real-time tumor tracking stereotatic body radiotherapy for lung cancers.

PURPOSE: 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. METHODS: 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 path-length (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. RESULTS: 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%. CONCLUSIONS: 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.

Accuracy and sensitivity of four-dimensional dose calculation to systematic motion variability in stereotatic body radiotherapy (SBRT) for lung cancer.

The dynamic movement of radiation beam in real-time tumor tracking may cause overdosing to critical organs surrounding the target. The primary objective of this study was to verify the accuracy of the 4D planning module incorporated in CyberKnife treatment planning system. The secondary objective was to evaluate the error that may occur in the case of a systematic change of motion pattern. Measurements were made using a rigid thorax phantom. Target motion was simulated with two waveforms (sin and cos4) of different amplitude and frequency. Inversely optimized dose distributions were calculated in the CyberKnife treatment planning system using the 4D Monte Carlo dose calculation algorithm. Each plan was delivered to the phantom assuming (1) reproducible target motion,and (2) systematic change of target motion pattern. The accuracy of 4D dose calculation algorithm was assessed using GAFCHROMIC EBT2 films based on 5%/3 mm γ criteria. Treatment plans were considered acceptable if the percentage of pixels passing the 5%/3 mm γ criteria was greater than 90%. The mean percentages of pixels passing were 95% for the target and 91% for the static off-target structure, respectively, with reproducible target motion. When systematic changes of the motion pattern were introduced during treatment delivery, the mean percentages of pixels passing decreased significantly in the off-target films (48%; p < 0.05), but did not change significantly in the target films (92%; p = 0.324) compared to results of reproducible target motion. These results suggest that the accuracy of 4D dose calculation, particularly in off-target stationary structure, is strongly tied to the reproducibility of target motion and that the solutions of 4D planning do not reflect the clinical nature of nonreproducible target motion generally.

Investigation of four-dimensional (4D) Monte Carlo dose calculation in real-time tumor tracking stereotatic body radiotherapy for lung cancers.

PURPOSE: 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. METHODS AND MATERIALS: Dose distributions were optimized on reference 3D images at end of exhale phase of a 4DCT dataset for twenty-five lung cancer patients treated with 60 Gy / 3Fx or 48 Gy / 4Fx. Deformable image registrations (DIR) 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 path-length (EPL) algorithm (3DEPL dose and 4DEPL dose) were recalculated with the Monte Carlo algorithm (3DMC dose and 4DMC dose). Dosimetric variations of V60Gy / 48Gy and D99 of GTV, mean doses to the lung and the heart and maximum dose (D1 ) 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 4DMC to 3DMC doses, from 4DMC to 4DEPL doses, and from 4DMC to 3DEPL doses, respectively. RESULTS: Comparing 4DMC to 3DEPL plans, V60Gy / 48Gy and D99 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 4DMC to 4DEPL plans found decreased V60Gy / 48Gy and D99 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 4DMC to 3DMC doses, V60Gy / 48Gy and D99 of GTV was reduced by 5.2 ± 8.8 %and 2.6 ± 3.3 Gy, and normal tissues hardly changed from 4DMC to 3DMC doses. The corresponding decreases of gEUD and TCP were 2.8 ± 4.0 Gy and 1.6 ± 2.4%. CONCLUSION: The large discrepancy between original 3DEPL plan and benchmarking 4DMC 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 V60Gy / 48Gy and D99 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. This article is protected by copyright. All rights reserved.

Palliative Liver Radiotherapy (RT) for Symptomatic Hepatocellular Carcinoma (HCC).

This study aims at evaluating the symptom response, response duration, and toxicity of single dose palliative liver radiotherapy (RT) for symptomatic HCC patients. We reviewed unresectable HCC patients treated with palliative RT in our institution. Eligible patients were unsuitable or refractory to trans-arterial chemoembolization (TACE) and stereotactic body radiotherapy (SBRT), with an index symptom of pain or abdominal discomfort. The primary outcome was the percentage of patients with clinical improvement of index symptom at 1 month. Secondary outcomes were response duration, toxicities, alpha-feto protein (AFP) response, and radiological response. Fifty-two patients were included in the study. The index symptom was pain in 34 patients (65.4%), and abdominal discomfort (34.6%) in 18 patients. At 1 month, 51.9% of patients had improvement of symptoms. Median time to symptom progression was 89 days (range: 12-392 days). Treatment was well tolerated with only 2 patients (3.8%) developing grade 3 GI toxicities. AFP response, radiological response rate, and disease control rate at 3 months were 48.6%, 15.1%, and 54.5% respectively. Half of the patients had improvement of index symptoms after receiving palliative liver RT with median response duration of 3 months. The treatment was well tolerated with minimal toxicities.

Linking dose delivery accuracy and planning target margin in radiosurgery based on dose-volume histograms derived from measurement-guided dose reconstruction.

In radiosurgery (SRS), the geometric uncertainties of machine-related delivery including image-guidance and hence the planning target volume (PTV) are often evaluated by the end-to-end gamma (γ) comparison that carries no information about the clinical relevance of deviations of individual SRS plans during delivery quality assurance (DQA). A proof-of-concept method was proposed to derive the PTV against both the plan- and the machine-specific delivery errors directly from the clinically relevant dose-volume histograms (DVHs) using measured-guided dose reconstruction (MGDR) during DQA. A liquid-filled detector array and a rotating phantom were used to measure sixteen arc-based radiosurgery treatments with 1 and 2 mm gross tumor volume (GTV)-to-PTV margins, producing MGDR-3D dose distribution on both the phantom and the patient CT for γ index and clinical DVH evaluations, respectively. The PTV was considered optimal when the MGDR showed the desired prescription dose coverage (V pres ) of the GTV (100% in this study). Associations of the binary V pres outcomes (

In-vivo treatment accuracy analysis of active motion-compensated liver SBRT through registration of plan dose to post-therapeutic MRI-morphologic alterations.

BACKGROUND/PURPOSE: In-vivo-accuracy analysis (IVA) of dose-delivery with active motion-management (gating/tracking) was performed based on registration of post-radiotherapeutic MRI-morphologic-alterations (MMA) to the corresponding dose-distributions of gantry-based/robotic SBRT-plans. METHODS: Forty targets in two patient cohorts were evaluated: (1) gantry-based SBRT (deep-inspiratory breath-hold-gating; GS) and (2) robotic SBRT (online fiducial-tracking; RS). The planning-CT was deformably registered to the first post-treatment contrast-enhanced T1-weighted MRI. An isodose-structure cropped to the liver (ISL) and corresponding to the contoured MMA was created. Structure and statistical analysis regarding volumes, surface-distance, conformity metrics and center-of-mass-differences (CoMD) was performed. RESULTS: Liver volume-reduction was -43.1 ±â€¯148.2 cc post-RS and -55.8 ±â€¯174.3 cc post-GS. The mean surface-distance between MMA and ISL was 2.3 ±â€¯0.8 mm (RS) and 2.8 ±â€¯1.1 mm (GS). ISL and MMA volumes diverged by 5.1 ±â€¯23.3 cc (RS) and 16.5 ±â€¯34.1 cc (GS); the median conformity index of both structures was 0.83 (RS) and 0.80 (GS). The average relative directional errors were ≤0.7 mm (RS) and ≤0.3 mm (GS); the median absolute 3D-CoMD was 3.8 mm (RS) and 4.2 mm (GS) without statistically significant differences between the two techniques. Factors influencing the IVA included GTV and PTV (p = 0.041 and p = 0.020). Four local relapses occurred without correlation to IVA. CONCLUSIONS: For the first time a method for IVA was presented, which can serve as a benchmarking-tool for other treatment techniques. Both techniques have shown median deviations <5 mm of planned dose and MMA. However, IVA also revealed treatments with errors ≥5 mm, suggesting a necessity for patient-specific safety-margins. Nevertheless, the treatment accuracy of well-performed active motion-compensated liver SBRT seems not to be a driving factor for local treatment failure.

Comparison of platelet-albumin-bilirubin (PALBI), albumin-bilirubin (ALBI), and child-pugh (CP) score for predicting of survival in advanced hcc patients receiving radiotherapy (RT).

PURPOSE: This work evaluated the prognostic performance of Child-Pugh (CP), albumin-bilirubin (ALBI) and platelet-albumin-bilirubin (PALBI) scores in hepatocellular carcinoma (HCC) patients undergoing radiotherapy (RT). RESULTS: The study included 174 consecutive patients with 63% at CP A5 (n = 110) and 34% at CP A6 (n = 64). The median ALBI score was -2.39 (range: -3.61 to -1.41) with 34.5% at grade A1 (n = 60) and 65.5% at grade A2 (n = 114). The median PALBI score was -2.39 (range -3.39 to -1.24) with 33.3% at grade 1 (n = 58), 41.4% at grade 2 (n = 72) and 25.3% at grade 3 (n = 44). With a median follow-up of 21.7 months, the median OS of the entire cohort was 22.2 months. OS was significantly associated with the PALBI grade (p = 0.002) and for the ALBI grade (p = 0.00495), but not for the CP score (p = 0.46). The PALBI grade has a significantly higher AUC compared than the ALBI grade or CP scores in predicting OS. The PALBI grade was predictive of CP score decline ≥2 (20% grade 3 vs. 5.3% grade 1/2 p = 0.05) but the ALBI and CP scores were not. CONCLUSION: Among CP A HCC patients receiving radiotherapy, the PALBI and ALBI grade maybe a better prognostic tool than the CP score. The role of PALBI in predicting liver toxicity warranted further exploration. METHODS: We retrospectively reviewed HCC patients treated with individualized hypo-fractionated radiotherapy (IHRT) using stereotactic technique from 2006 to 2015. We collected CP, ALBI and PALBI scores prior to treatment and analyzed their correlation with overall survival (OS) and liver toxicity.