Volumetric modulated arc therapy versus intensity-modulated proton therapy in the irradiation of infra diaphragmatic Hodgkin Lymphoma in female patients.

PURPOSE: To investigate the role of infra diaphragmatic intensity-modulated proton therapy (IMPT) compared to volumetric modulated arc therapy (VMAT) for female Hodgkin Lymphoma (HL) patients and to estimate the risk of secondary cancer and ovarian failure. METHODS: A comparative treatment planning study was performed on 14 patients, and the results were compared according to conventional dose-volume metrics. In addition, estimates of the excess absolute risk (EAR) of secondary cancer induction were determined for the bowel, the bladder and the rectum. For the ovaries, the risk of ovarian failure was estimated. RESULTS: The dosimetric findings demonstrate the equivalence between VMAT and IMPT in terms of target coverage. A statistically significant reduction of the mean and near-to-maximum doses was proven for the organs at risk. The EAR ratio estimated for IMPT to VMAT was 0.51 ± 0.32, 0.32 ± 0.35 and 0.05 ± 0.11 for the bowel, bladder and rectum, respectively. Concerning the risk of ovarian failure for the chronologic age ranging from 18 to 46 years, the expected net loss in fertility years ranged from 4.8 to 3.0 years for protons and 12.0 to 5.7 years for photons. CONCLUSION: This in-silico study confirmed the beneficial role of IMPT from a dosimetric point of view. Mathematical models suggested that the use of protons might be further advantageous due to the expected reduction of the risk of secondary cancer induction and its milder impact on the reduction of fertility.

Volumetric modulated arc therapy versus intensity-modulated proton therapy in the postoperative irradiation of thymoma.

BACKGROUND: To investigate the role of intensity-modulated proton therapy (IMPT) compared to volumetric modulated arc therapy (VMAT) for the radiation treatment of thymoma cancer. METHODS: Twenty patients were retrospectively planned for IMPT [with (IMPT_R1 or IMPT_R2 according to the approach adopted) and without robust optimization] and VMAT. The results were compared according to dose-volume metrics on the clinical and planning target volumes (CTV and PTV) and the main organs at risk (heart, breasts, lungs, spinal cord and oesophagus). Estimates of the excess absolute risk (EAR) of secondary cancer induction were determined for the oesophagus, the breasts and the composite lungs. For the heart, the relative risk (RR) of chronic heart failure (CHF) was assessed. RESULTS: IMPT and VMAT plans resulted equivalent in terms of target coverage for both the CTV and the PTV. The CTV homogeneity index resulted in 0.03 ± 0.01 and 0.04 ± 0.01 for VMAT and all IMPT plans, respectively. The conformality index resulted in 1.1 ± 0.1 and 1.2 ± 0.1 for VMAT and all IMPT plans. The mean dose to the breasts resulted in 10.5 ± 5.0, 4.5 ± 3.4, 4.7 ± 3.5 and 4.6 ± 3.4 Gy for VMAT, IMPT, IMPT_R1 and IMPT_R2. For the lungs, the mean dose was 9.6 ± 2.3, 3.5 ± 1.5, 3.6 ± 1.6 and 3.8 ± 1.4 Gy; for the heart: 8.7 ± 4.4, 4.3 ± 1.9, 4.5 ± 2.0 and 4.4 ± 2.4 Gy and for the oesophagus 8.2 ± 3.5, 2.2 ± 3.4, 2.4 ± 3.6 and 2.5 ± 3.5 Gy. The RR for CHF was 1.6 ± 0.3 for VMAT and 1.3 ± 0.2 for IMPT (R1 or R2). The EAR was 3.6 ± 0.v vs 1.0 ± 0.6 or 1.2 ± 0.6 (excess cases/10,000 patients year) for the oesophagus; 17.4 ± 6.5 vs 5.7 ± 3.2 or 6.1 ± 3.8 for the breasts and 24.8 ± 4.3 vs 8.1 ± 2.7 or 8.7 ± 2.3 for the composite lungs for VMAT and IMPT_R, respectively. CONCLUSION: The data from this in-silico study suggest that intensity-modulated proton therapy could be significantly advantageous in the treatment of thymoma patients with particular emphasis to a substantial reduction of the risk of cardiac failure and secondary cancer induction. Robust planning is a technical pre-requisite for the safety of the delivery.

Volumetric modulated arc therapy versus intensity-modulated proton therapy in neoadjuvant irradiation of locally advanced oesophageal cancer.

BACKGROUND: To investigate the role of intensity-modulated proton therapy (IMPT) compared to volumetric modulated arc therapy (VMAT), realised with RapidArc and RapidPlan methods (RA_RP) for neoadjuvant radiotherapy in locally advanced oesophagal cancer. METHODS: Twenty patients were retrospectively planned for IMPT (with two fields, (IMPT_2F) or with three fields (IMPT_3F)) and RA_RP and the results were compared according to dose-volume metrics. Estimates of the excess absolute risk (EAR) of secondary cancer induction were determined for the lungs. For the cardiac structures, the relative risk (RR) of coronary artery disease (CAD) and chronic heart failure (CHF) were estimated. RESULTS: Both the RA_RP and IMPT approached allowed to achieve the required coverage for the gross tumour volume, (GTV) and the clinical and the planning target volumes, CTV and PTV (V98% > 98 for CTV and GTV and V95% > 95 for the PTV)). The conformity index resulted in 0.88 ± 0.01, 0.89 ± 0.02 and 0.89 ± 0.02 for RA_RP, IMPT_2F and IMPT_3F respectively. With the same order, the homogeneity index for the PTV resulted in 5.6 ± 0.6%, 4.4 ± 0.9% and 4.5 ± 0.8%. Concerning the organs at risk, the IMPT plans showed a systematic and statistically significant incremental sparing when compared to RA_RP, especially for the heart. The mean dose to the combined lungs was 8.6 ± 2.9 Gy for RA_RP, 3.2 ± 1.5 Gy and 2.9 ± 1.2 Gy for IMPT_2F and IMPT_3F. The mean dose to the whole heart resulted to 9.9 ± 1.9 Gy for RA_RP compared to 3.7 ± 1.3 Gy or 4.0 ± 1.4 Gy for IMPT_2F or IMPT_3F; the mean dose to the left ventricle resulted to 6.5 ± 1.6 Gy, 1.9 ± 1.5 Gy, 1.9 ± 1.6 Gy respectively. Similar sparing effects were observed for the liver, the kidneys, the stomach, the spleen and the bowels. The EAR per 10,000 patients-years of secondary cancer induction resulted in 19.2 ± 5.7 for RA_RP and 6.1 ± 2.7 for IMPT_2F or 5.7 ± 2.4 for IMPT_3F. The RR for the left ventricle resulted in 1.5 ± 0.1 for RA_RP and 1.1 ± 0.1 for both IMPT sets. For the coronaries, the RR resulted in 1.6 ± 0.4 for RA_RP and 1.2 ± 0.3 for protons. CONCLUSION: With regard to cancer of the oesophagogastric junction type I and II, the use of intensity-modulated proton therapy seems to have a clear advantage over VMAT. In particular, the reduction of the heart and abdominal structures dose could result in an optimised side effect profile. Furthermore, reduced risk of secondary neoplasia in the lung can be expected in long-term survivors and would be a great gain for cured patients.

Performance of a Knowledge-Based Model for Optimization of Volumetric Modulated Arc Therapy Plans for Single and Bilateral Breast Irradiation.

PURPOSE: To evaluate the performance of a model-based optimisation process for volumetric modulated arc therapy, VMAT, applied to whole breast irradiation. METHODS AND MATERIALS: A set of 150 VMAT dose plans with simultaneous integrated boost were selected to train a model for the prediction of dose-volume constraints. The dosimetric validation was done on different groups of patients from three institutes for single (50 cases) and bilateral breast (20 cases). RESULTS: Quantitative improvements were observed between the model-based and the reference plans, particularly for heart dose. Of 460 analysed dose-volume objectives, 13% of the clinical plans failed to meet the constraints while the respective model-based plans succeeded. Only in 5 cases did the reference plans pass while the respective model-based failed the criteria. For the bilateral breast analysis, the model-based plans resulted in superior or equivalent dose distributions to the reference plans in 96% of the cases. CONCLUSIONS: Plans optimised using a knowledge-based model to determine the dose-volume constraints showed dosimetric improvements when compared to earlier approved clinical plans. The model was applicable to patients from different centres for both single and bilateral breast irradiation. The data suggests that the dose-volume constraint optimisation can be effectively automated with the new engine and could encourage its application to clinical practice.

A broad scope knowledge based model for optimization of VMAT in esophageal cancer: validation and assessment of plan quality among different treatment centers.

BACKGROUND: To evaluate the performance of a broad scope model-based optimisation process for volumetric modulated arc therapy applied to esophageal cancer. METHODS AND MATERIALS: A set of 70 previously treated patients in two different institutions, were selected to train a model for the prediction of dose-volume constraints. The model was built with a broad-scope purpose, aiming to be effective for different dose prescriptions and tumour localisations. It was validated on three groups of patients from the same institution and from another clinic not providing patients for the training phase. Comparison of the automated plans was done against reference cases given by the clinically accepted plans. RESULTS: Quantitative improvements (statistically significant for the majority of the analysed dose-volume parameters) were observed between the benchmark and the test plans. Of 624 dose-volume objectives assessed for plan evaluation, in 21 cases (3.3 %) the reference plans failed to respect the constraints while the model-based plans succeeded. Only in 3 cases (<0.5 %) the reference plans passed the criteria while the model-based failed. In 5.3 % of the cases both groups of plans failed and in the remaining cases both passed the tests. CONCLUSIONS: Plans were optimised using a broad scope knowledge-based model to determine the dose-volume constraints. The results showed dosimetric improvements when compared to the benchmark data. Particularly the plans optimised for patients from the third centre, not participating to the training, resulted in superior quality. The data suggests that the new engine is reliable and could encourage its application to clinical practice.

Evaluation of the Machine Performance Check application for TrueBeam Linac.

BACKGROUND: Machine Performance Check (MPC) is an application to verify geometry and beam performances of TrueBeam Linacs, through automated checks based on their kV-MV imaging systems. In this study, preliminary tests with MPC were analyzed using all photon beam energies of our TrueBeam, comparing whenever possible with external independent checks. METHODS: Data acquisition comprises a series of 39 images (12 with kV and 27 with MV detector) acquired at predefined positions without and with the IsoCal phantom in the beam, and with particular MLC pattern settings. MPC performs geometric and dosimetric checks. The geometric checks intend to test the treatment isocenter size and its coincidence with imaging devices, the positioning accuracy of the imaging systems, the collimator, the gantry, the jaws, the MLC leaves and the couch position. The dosimetric checks: refer to a reference MV image and give the beam output, uniformity and center change relative to the reference. MPC data were acquired during 10 repetitions on different consecutive days. Alternative independent checks were performed. Geometric: routine mechanical tests, Winston-Lutz test for treatment isocenter radius. Dosimetric: the 2D array StarCheck (PTW) was used just after the MPC data acquisition. RESULTS: Results were analyzed for 6, 10, 15 MV flattened, and 6, 10 MV FFF beams. Geometric checks: treatment isocenter was between 0.31 ± 0.01 mm and 0.42 ± 0.02 mm with MPC, compared to 0.27 ± 0.01 mm averaged on all energies with the Winston-Lutz test. Coincidence of kV and MV imaging isocenters was within 0.36 ± 0.0 and 0.43 ± 0.06 mm, respectively (0.4 ± 0.1 mm with external tests). Positioning accuracy of MLC was within 0.5 mm; accuracy of jaws was 0.04 ± 0.02, 0.10 ± 0.05, -1.01 ± 0.03, 0.92 ± 0.04 mm for X1, X2, Y1, Y2 jaws, respectively, with MPC. Dosimetric tests: the output stability relative to the baseline was in average 0.15 ± 0.07% for MPC to compare with 0.3 ± 0.2% with the independent measurement. CONCLUSIONS: MPC proved to be a reliable, fast and easy to use method for checking the machine performances on both geometric and dosimetric aspects.

On the pre-clinical validation of a commercial model-based optimisation engine: application to volumetric modulated arc therapy for patients with lung or prostate cancer.

PURPOSE: To evaluate the performance of a model-based optimisation process for volumetric modulated arc therapy applied to advanced lung cancer and to low risk prostate carcinoma patients. METHODS AND MATERIALS: Two sets each of 27 previously treated patients, were selected to train models for the prediction of dose-volume constraints. The models were validated on the same sets of plans (closed-loop) and on further two sets each of 25 patients not used for the training (open-loop). RESULTS: Quantitative improvements (statistically significant for the majority of the analysed dose-volume parameters) were observed between the benchmark and the test plans. In the pass-fail analysis, the rate of criteria not fulfilled was reduced in the lung patient group from 11% to 7% in the closed-loop and from 13% to 10% in the open-loop studies; in the prostate patient group it was reduced from 4% to 3% in the open-loop study. CONCLUSIONS: Plans were optimised using a knowledge-based model to determine the dose-volume constraints. The results showed dosimetric improvements when compared to the benchmark data, particularly in the sparing of organs at risk. The data suggest that the new engine is reliable and could encourage its application to clinical practice.

Assessment of a model based optimization engine for volumetric modulated arc therapy for patients with advanced hepatocellular cancer.

BACKGROUND: To evaluate in-silico the performance of a model-based optimization process for volumetric modulated arc therapy (RapidArc) applied to hepatocellular cancer treatments. PATIENTS AND METHODS: 45 clinically accepted RA plans were selected to train a knowledge-based engine for the prediction of individualized dose-volume constraints. The model was validated on the same plans used for training (closed-loop) and on a set of other 25 plans not used for the training (open-loop). Dose prescription, target size, localization in the liver and arc configuration were highly variable in both sets to appraise the power of generalization of the engine. Quantitative dose volume histogram analysis was performed as well as a pass-fail analysis against a set of 8 clinical dose-volume objectives to appraise the quality of the new plans. RESULTS: Qualitative and quantitative equivalence was observed between the clinical and the test plans. The use of model-based optimization lead to a net improvement in the pass-rate of the clinical objectives compared to the plans originally optimized with standard methods (this pass-rate is the frequency of cases where the objectives are respected vs. the cases where constraints are not fulfilled). The increase in the pass-rate resulted of 2.0%, 0.9% and 0.5% in a closed-loop and two different open-loop validation experiments. CONCLUSIONS: A knowledge-based engine for the optimization of RapidArc plans was tested and lead to clinically acceptable plans in the case of hepatocellular cancer radiotherapy. More studies are needed before a broad clinical use.

On the robustness of VMAT-SABR treatment plans against isocentre positioning uncertainties.

BACKGROUND: To appraise the robustness of VMAT dose distributions against uncertainties in the positioning of the patients when single fraction SABRT treatments are planned. METHODS: A set of 18 patients (8 lung, 5 brain, 5 spinal or para-spinal) treated with VMAT in a single fraction of 24Gy were retrospectively analyzed. All approved plans were re-calculated by applying shifts to the isocentre of ±0.5, ±1, ±1.5, ±2 and ±3 mm along the primary X, Y and Z axes. Dose calculations were performed with the AAA and the Acuros engines. Quantitative analysis of DVH was performed on a total of 36 references (18 patients with AAA, 18 with Acuros) and 1080 re-calculated plans to measure the potential degree of deterioration of the plans according to the simulated errors. RESULTS: The dose to the CTV was essentially not affected by the isocenter shifts in all cases. Concerning PTV, The main impact was observed on the near-to-minimum dose D99%. No relevant impact was observed on organs at risk in the case of lung patients. In the case of patients treated in the spinal or para-spinal region, the near-to-maximum dose to the spine showed, in the worst scenario, referring to Acuros calculation, a potential average increase of 0.3Gy with a maximum of 1.9Gy (from 10.3 to 12.2 Gy) or 18%. This was partially mitigated to 12% with 1 mm and to 5% with 0.5 mm shifts. CONCLUSIONS: The study showed that shifts in the position of the isocenter as large as 3 mm tend to have modest impacts on the quality of the VMAT plans, scored by means of conventional DVH parameters. From the data shown, the VMAT approach should be considered adequately robust for single fraction SABR.

Monte Carlo simulation of TrueBeam flattening-filter-free beams using varian phase-space files: comparison with experimental data.

PURPOSE: Phase-space files for Monte Carlo simulation of the Varian TrueBeam beams have been made available by Varian. The aim of this study is to evaluate the accuracy of the distributed phase-space files for flattening filter free (FFF) beams, against experimental measurements from ten TrueBeam Linacs. METHODS: The phase-space files have been used as input in PRIMO, a recently released Monte Carlo program based on the PENELOPE code. Simulations of 6 and 10 MV FFF were computed in a virtual water phantom for field sizes 3 × 3, 6 × 6, and 10 × 10 cm(2) using 1 × 1 × 1 mm(3) voxels and for 20 × 20 and 40 × 40 cm(2) with 2 × 2 × 2 mm(3) voxels. The particles contained in the initial phase-space files were transported downstream to a plane just above the phantom surface, where a subsequent phase-space file was tallied. Particles were transported downstream this second phase-space file to the water phantom. Experimental data consisted of depth doses and profiles at five different depths acquired at SSD = 100 cm (seven datasets) and SSD = 90 cm (three datasets). Simulations and experimental data were compared in terms of dose difference. Gamma analysis was also performed using 1%, 1 mm and 2%, 2 mm criteria of dose-difference and distance-to-agreement, respectively. Additionally, the parameters characterizing the dose profiles of unflattened beams were evaluated for both measurements and simulations. RESULTS: Analysis of depth dose curves showed that dose differences increased with increasing field size and depth; this effect might be partly motivated due to an underestimation of the primary beam energy used to compute the phase-space files. Average dose differences reached 1% for the largest field size. Lateral profiles presented dose differences well within 1% for fields up to 20 × 20 cm(2), while the discrepancy increased toward 2% in the 40 × 40 cm(2) cases. Gamma analysis resulted in an agreement of 100% when a 2%, 2 mm criterion was used, with the only exception of the 40 × 40 cm(2) field (∼95% agreement). With the more stringent criteria of 1%, 1 mm, the agreement reduced to almost 95% for field sizes up to 10 × 10 cm(2), worse for larger fields. Unflatness and slope FFF-specific parameters are in line with the possible energy underestimation of the simulated results relative to experimental data. CONCLUSIONS: The agreement between Monte Carlo simulations and experimental data proved that the evaluated Varian phase-space files for FFF beams from TrueBeam can be used as radiation sources for accurate Monte Carlo dose estimation, especially for field sizes up to 10 × 10 cm(2), that is the range of field sizes mostly used in combination to the FFF, high dose rate beams.

On the determination of reference levels for quality assurance of flattening filter free photon beams in radiation therapy.

PURPOSE: New definitions for some dosimetric parameters for use in quality assurance of flattening filter free (FFF) beams generated by medical linear accelerators have been suggested. The present study aims to validate these suggestions and to propose possible reference levels. METHODS: The main characteristics of FFF photon beams were described in terms of: field size, penumbra, unflatness, slope, and peak-position parameters. Data were collected for 6 and 10 MV-FFF beams from three different Varian TrueBeam Linacs. Measurements were performed with a 2D-array (Starcheck system from PTW-Freiburg) and with the portal dosimetry method GLAaS utilizing the build-in portal imager of TrueBeam. Data were also compared to ion chamber measurements. A cross check validation has been performed on a FFF beam of 6 MV generated by a Varian Clinac-iX upgraded to FFF capability. RESULTS: All the parameters suggested to characterize the FFF beams resulted easily measurable and little variation was observed among different Linacs. Referring to two reference field sizes of 10 × 10 and 20 × 20 cm(2), at SDD = 100 cm and d = dmax, from the portal dosimetry data, the following results (averaging X and Y profiles) were obtained. Field size: 9.95 ± 0.02 and 19.98 ± 0.03 cm for 6 MV-FFF (9.94 ± 0.02 and 19.98 ± 0.03 cm for 10 MV-FFF). Penumbra: 2.7 ± 0.3 and 2.9 ± 0.3 mm for 6 MV-FFF (3.1 ± 0.2 and 3.3 ± 0.3 for 10 MV-FFF). Unflatness: 1.11 ± 0.01 and 1.25 ± 0.01 for 6 MV-FFF (1.21 ± 0.01 and 1.50 ± 0.01 for 10 MV-FFF). Slope: 0.320 ± 0.020%/mm and 0.43 ± 0.015%/mm for 6 MV-FFF (0.657 ± 0.023%/mm and 0.795 ± 0.017%/mm for 10 MV-FFF). Peak Position -0.2 ± 0.2 and -0.4 ± 0.2 mm for 6 MV-FFF (-0.3 ± 0.2 and 0.7 ± 0.3 mm for 10 MV-FFF). Results would depend upon measurement depth. With thresholds set to at least 95% confidence level from the measured data and to account for possible variations between detectors and methods and experimental settings, a tolerance set of: 1 mm for field size and penumbra, 0.04 for unflatness, 0.1%/mm for slope, and 1 mm for peak position could be proposed from our data. CONCLUSIONS: The parameters proposed for the characterization and routine control of stability of profiles of FFF beams appear to be a viable solution with a strong similarity to the conventional parameters used for flattened beams. The results from three different TrueBeams and the cross-validation against a Clinac-iX suggested the possible generalization of the methods and the possibility to use common tolerances for the parameters. The data showed also the reproducibility of beam characteristics among different systems (of the same vendor) and the resulting parameter values could therefore be possibly generalized.

Hypofractionation with VMAT versus 3DCRT in post-operative patients with prostate cancer.

AIMS: To retrospectively evaluate and compare the incidence of acute genitourinary (aGU), upper gastrointestinal (uGI) and rectal (lGI) injuries after radiotherapy with hypo-fractionation by volumetric modulation arc therapy (VMAT, the Hypo-RapidArc group) and conventional fractionation by three-dimensional conformal radiotherapy (3DCRT) in patients with localized prostate cancer treated, after radical prostatectomy, with prostatic bed irradiation. PATIENTS AND METHODS: Between 2007 and 2012, 84 consecutive patients with clinically localized prostate cancer submitted to radical prostatectomy were also treated with irradiation to the prostate bed. Forty-five received 3DCRT and 39 Hypo-RapidArc. The median age was 67 and 69 years for 3DCRT and Hypo-RapidArc groups respectively. The median dose to the prostatic bed was 70 Gy in both groups: 2 Gy/fraction in the 3DCRT group and 2.5 Gy/fraction in the Hypo-RapidArc group. After radical prostatectomy, the median time-to-RT was 15 and 16 months respectively. Acute and late toxicities were scored according to the Radiation Therapy and Oncology Group/European Organization for Research and Treatment of Cancer system. RESULTS: Grade 2aGU was recorded in 16% of cases in the 3DRCT group and in 10% in the Hypo-RapidArc group. No acute grade 2 upper gastrointestinal (uGI) toxicities were found in the 3DCRT versus 5% in the Hypo-RapidArc group. The incidence of grade 2 lower gastrointestinal (lGI) toxicities was 22% in the 3DCRT group versus 15% in the Hypo-RapidArc group. No grade 3 or greater toxicities were found in either group. In both groups, good planning target volume coverage was achieved: V95% was recorded as 96.3 ± 3.6% (mean ± standard deviation) and 95.7 ± 8.9 for the 3DRCT and the Hypo-RapidArc groups, respectively. The mean rectal volume dose receiving at least 70 Gy was 9.1 ± 10.8% and 0.1 ± 0.6% respectively. The mean dose to the bladder was 49.5 ± 12.3 Gy and 37.2 ± 5.2 Gy respectively. Significant correlation between late rectal toxicity and the maximum dose to the rectum, V70Gy, was found in the 3DCRT group, while no significant correlations were found for acute toxicity. CONCLUSION: The results presented in this study demonstrate the feasibility of a moderate hypo-fractionation regimen with RapidArc in the postoperative setting. Longer-term data are needed to confirm late toxicity profiles.

Intensity modulated proton beam radiation for brachytherapy in patients with cervical carcinoma.

PURPOSE: To evaluate intensity modulated proton therapy (IMPT) in patients with cervical cancer in terms of coverage, conformity, and dose-volume histogram (DVH) parameters correlated with recommendations from magnetic resonance imaging (MRI)-guided brachytherapy. METHODS AND MATERIALS: Eleven patients with histologically proven cervical cancer underwent primary chemoradiation for the pelvic lymph nodes, the uterus, the cervix, and the parametric region, with a symmetric margin of 1 cm. The prescription was for 50.4 Gy, with 1.8 Gy per fraction. The prescribed dose to the parametria was 2.12 Gy up to 59.36 Gy in 28 fractions as a simultaneous boost. For several reasons, the patients were unable to undergo brachytherapy. As an alternative, IMPT was planned with 5 fractions of 6 Gy to the cervix, including the macroscopic tumor with an MRI-guided target definition, with an isotropic margin of 5 mm for planning target volume (PTV) definition. Groupe-Europeen de Curietherapie and European society for Radiotherapy and Oncology (GEC-ESTRO) criteria were used for DVH evaluation. Reference comparison plans were optimized for volumetric modulated rapid arc (VMAT) therapy with the RapidArc (RA). RESULTS: The dose to the high-risk volume was calculated with α/ß = 10 with 89.6 Gy. For IMPT, the clinical target volume showed a mean dose of 38.2 ± 5.0 Gy (35.0 ±1.8 Gy for RA). The D98% was 31.9 ± 2.6 Gy (RA: 30.8 ± 1.0 Gy). With regard to the organs at risk, the 2Gy Equivalent Dose (EQD2) (α/ß = 3) to 2 cm(3) of the rectal wall, sigmoid wall, and bladder wall was 62.2 ± 6.4 Gy, 57.8 ± 6.1 Gy, and 80.6 ± 8.7 Gy (for RA: 75.3 ± 6.1 Gy, 66.9 ± 6.9 Gy, and 89.0 ± 7.2 Gy, respectively). For the IMPT boost plans in combination with external beam radiation therapy, all DVH parameters correlated with <5% risk for grades 2 to 4 late gastrointestinal and genitourinary toxicity. CONCLUSION: In patients who are not eligible for brachytherapy, IMPT as a boost technique additionally to external beam radiation therapy provides good target coverage and conformity and superior DVH parameters, compared with recommendations to MRI-guided brachytherapy. For selected patients, IMPT might be a valid alternative to brachytherapy and also superior to reference VMAT plans.

Critical appraisal of the accuracy of Acuros-XB and Anisotropic Analytical Algorithm compared to measurement and calculations with the compass system in the delivery of RapidArc clinical plans.

BACKGROUND: The accuracy of the two dose calculation engines available for RapidArc planning (both released for clinical use) is investigated in comparison to the COMPASS data. METHODS: Two dose calculation algorithms (Acuros-XB and Anisotropic Analytic Algorithm (AAA)) were used to calculate RA plans and compared to calculations with the Collapsed Cone Convolution algorithm (CC) from the COMPASS system (IBA Dosimetry). CC calculations, performed on patient data, are based on experimental fluence measurements with a 2D array of ion chambers mounted on the linac head. The study was conducted on clinical cases treated with RA. Five cases for each of the following groups were included: Brain, Head and Neck, Thorax, Pelvis and stereotactic body radiation therapy for hypo-fractionated treatments with small fields. COMPASS measurements were performed with the iMatrixx-2D array. RapidArc plans were optimized for delivery using 6MV photons from a Clinac-iX (Varian, Palo Alto, USA). RESULTS: For almost all parameters, the better agreement was between Acuros-XB and COMPASS independently from the anatomical site and fractionation. The same result was obtained from the mean dose difference per organ with Acuros-CC average differences below 0.5% while for AAA-CC data, average deviations exceeded 0.5% and in the case of the pelvis 1%. Relevance of observed differences determined with the 3D gamma analysis resulted in a pass rate exceeding 99.5% for Acuros-CC and exceeding 97.5% for AAA-CC. CONCLUSIONS: This study demonstrated that i) a good agreement exists between COMPASS-CC calculations based on measured fluences with respect to dose distributions obtained with both Acuros-XB and AAA algorithms; ii) 3D dose distributions reconstructed from actual delivery coincide very precisely with the planned data; iii) a slight preference in favor of Acuros-XB was observed suggesting the preference for this algorithm in clinical applications.

Dosimetric comparison between VMAT with different dose calculation algorithms and protons for soft-tissue sarcoma radiotherapy.

BACKGROUND: To appraise the potential of volumetric modulated arc therapy (VMAT, RapidArc) and proton beams to simultaneously achieve target coverage and enhanced sparing of bone tissue in the treatment of soft-tissue sarcoma with adequate target coverage. MATERIAL AND METHODS: Ten patients presenting with soft-tissue sarcoma of the leg were collected for the study. Dose was prescribed to 66.5 Gy in 25 fractions to the planning target volume (PTV) while significant maximum dose to the bone was constrained to 50 Gy. Plans were optimised according to the RapidArc technique with 6 MV photon beams or for intensity modulated protons. RapidArc photon plans were computed with: 1) AAA; 2) Acuros XB as dose to medium; and 3) Acuros XB as dose to water. RESULTS: All plans acceptably met the criteria of target coverage (V95% >90-95%) and bone sparing (D(1 cm3) <50 Gy). Significantly higher PTV dose homogeneity was found for proton plans. Near-to-maximum dose to bone was similar for RapidArc and protons, while volume receiving medium/low dose levels was minimised with protons. Similar results were obtained for the remaining normal tissue. Dose distributions calculated with the dose to water option resulted ~5% higher than corresponding ones computed as dose to medium. CONCLUSION: High plan quality was demonstrated for both VMAT and proton techniques when applied to soft-tissue sarcoma.

Volumetric modulated arc therapy with flattening filter free beams for isolated abdominal/pelvic lymph nodes: report of dosimetric and early clinical results in oligometastatic patients.

BACKGROUND: SBRT is a safe and efficient strategy to locally control multiple metastatic sites. While research in the physics domain for Flattening Filter Free Beams (FFF) beams is increasing, there are few clinical data of FFF beams in clinical practice. Here we reported dosimentric and early clinical data of SBRT and FFF delivery in isolated lymph node oligometastatic patients. METHODS: Between October 2010 and March 2012, 34 patients were treated with SBRT for oligometastatic lymph node metastasis on a Varian TrueBeam(TM) treatment machine using Volumetric Modulated Arc Therapy (RapidArc). We retrospectively evaluated a total of 25 patients for isolated lymph node metastases in abdomen and/or pelvis treated with SBRT and FFF (28 treatments). Acute toxicity was recorded. Local control evaluation was scored by means of CT scan and/or PET scan. RESULTS: All dosimetric results are in line with what published for the same type of stereotactic abdominal lymph node metastases treatments and fractionation, using RapidArc. All 25 FFF SBRT patients completed the treatment. Acute gastrointestinal toxicity was minimal: one patient showed Grade 1 gastrointestinal toxicity. Three other patients presented Grade 2 toxicity. No Grade 3 or higher was recorded. All toxicities were recovered within one week. The preliminary clinical results at the median follow up of 195 days are: complete response in 12 cases, partial response in 11, stable disease in 5, with an overall response rate of 82%; no local progression was recorded. CONCLUSIONS: Data of dosimetrical findings and acute toxicity are excellent for patients treated with SBRT with VMAT using FFF beams. Preliminary clinical results showed a high rate of local control in irradiated lesion. Further data and longer follow up are needed to assess late toxicity and definitive clinical outcomes.

Phase I-II study of hypofractionated simultaneous integrated boost using volumetric modulated arc therapy for adjuvant radiation therapy in breast cancer patients: a report of feasibility and early toxicity results in the first 50 treatments.

BACKGROUND: To report results in terms of feasibility and early toxicity of hypofractionated simultaneous integrated boost (SIB) approach with Volumetric Modulated Arc Therapy (VMAT) as adjuvant treatment after breast-conserving surgery. METHODS: Between September 2010 and May 2011, 50 consecutive patients presenting early-stage breast cancer were submitted to adjuvant radiotherapy with SIB-VMAT approach using RapidArc in our Institution (Istituto Clinico Humanitas ICH). Three out of 50 patients were irradiated bilaterally (53 tumours in 50 patients). All patients were enrolled in a phase I-II trial approved by the ICH ethical committee. All 50 patients enrolled in the study underwent VMAT-SIB technique to irradiate the whole breast with concomitant boost irradiation of the tumor bed. Doses to whole breast and surgical bed were 40.5 Gy and 48 Gy respectively, delivered in 15 fractions over 3 weeks. Skin toxicities were recorded during and after treatment according to RTOG acute radiation morbidity scoring criteria with a median follow-up of 12 months (range 8-16). Cosmetic outcomes were assessed as excellent/good or fair/poor. RESULTS: The median age of the population was 68 years (range 36-88). According to AJCC staging system, 38 breast lesions were classified as pT1, and 15 as pT2; 49 cases were assessed as N0 and 4 as N1. The maximum acute skin toxicity by the end of treatment was Grade 0 in 20/50 patients, Grade 1 in 32/50, Grade 2 in 0 and Grade 3 in 1/50 (one of the 3 cases of bilateral breast irradiation). No Grade 4 toxicities were observed. All Grade 1 toxicities had resolved within 3 weeks. No significant differences in cosmetic scores on baseline assessment vs. 3 months and 6 months after the treatment were observed: all patients were scored as excellent/good (50/50) compared with baseline; no fair/poor judgment was recorded. No other toxicities or local failures were recorded during follow-up. CONCLUSIONS: The 3-week course of postoperative radiation using VMAT with SIB showed to be feasible and was associated with acceptable acute skin toxicity profile. Long-term follow-up data are needed to assess late toxicity and clinical outcomes.

Volumetric modulation arc radiotherapy with flattening filter-free beams compared with static gantry IMRT and 3D conformal radiotherapy for advanced esophageal cancer: a feasibility study.

PURPOSE: A feasibility study was performed to evaluate RapidArc (RA), and the potential benefit of flattening filter-free beams, on advanced esophageal cancer against intensity-modulated radiotherapy (IMRT) and three-dimensional conformal radiotherapy (3D-CRT). METHODS AND MATERIALS: The plans for 3D-CRT and IMRT with three to seven and five to seven fixed beams were compared against double-modulated arcs with avoidance sectors to spare the lungs for 10 patients. All plans were optimized for 6-MV photon beams. The RA plans were studied for conventional and flattening filter-free (FFF) beams. The objectives for the planning target volume were the volume receiving ≥ 95% or at most 107% of the prescribed dose of <1% with a dose prescription of 59.4 Gy. For the organs at risk, the lung volume (minus the planning target volume) receiving ≥ 5 Gy was <60%, that receiving 20 Gy was <20%-30%, and the mean lung dose was <15.0 Gy. The heart volume receiving 45 Gy was <20%, volume receiving 30 Gy was <50%. The spinal dose received by 1% was <45 Gy. The technical delivery parameters for RA were assessed to compare the normal and FFF beam characteristics. RESULTS: RA and IMRT provided equivalent coverage and homogeneity, slightly superior to 3D-CRT. The conformity index was 1.2 ± 0.1 for RA and IMRT and 1.5 ± 0.2 for 3D-CRT. The mean lung dose was 12.2 ± 4.5 for IMRT, 11.3 ± 4.6 for RA, and 10.8 ± 4.4 for RA with FFF beams, 18.2 ± 8.5 for 3D-CRT. The percentage of volume receiving ≥ 20 Gy ranged from 23.6% ± 9.1% to 21.1% ± 9.7% for IMRT and RA (FFF beams) and 39.2% ± 17.0% for 3D-CRT. The heart and spine objectives were met by all techniques. The monitor units for IMRT and RA were 457 ± 139, 322 ± 20, and 387 ± 40, respectively. RA with FFF beams showed, compared with RA with normal beams, a ∼20% increase in monitor units per Gray, a 90% increase in the average dose rate, and 20% reduction in beam on time (owing to different gantry speeds). CONCLUSION: RA demonstrated, compared with conventional IMRT, a similar target coverage and some better dose sparing to the organs at risk; the advantage against conventional 3D-CRT was more evident. RA with FFF beams resulted in minor improvements in plan quality but with the potential for additional useful reduction in the treatment time.

Critical appraisal of Acuros XB and Anisotropic Analytic Algorithm dose calculation in advanced non-small-cell lung cancer treatments.

PURPOSE: To assess the clinical impact of the Acuros XB algorithm (implemented in the Varian Eclipse treatment-planning system) in non-small-cell lung cancer (NSCLC) cases. METHODS AND MATERIALS: A CT dataset of 10 patients presenting with advanced NSCLC was selected and contoured for planning target volume, lungs, heart, and spinal cord. Plans were created for 6-MV and 15-MV beams using three-dimensional conformal therapy, intensity-modulated therapy, and volumetric modulated arc therapy with RapidArc. Calculations were performed with Acuros XB and the Anisotropic Analytical Algorithm. To distinguish between differences coming from the different heterogeneity management and those coming from the algorithm and its implementation, all the plans were recalculated assigning Hounsfield Unit (HU) = 0 (Water) to the CT dataset. RESULTS: Differences in dose distributions between the two algorithms calculated in Water were <0.5%. This suggests that the differences in the real CT dataset can be ascribed mainly to the different heterogeneity management, which is proven to be more accurate in the Acuros XB calculations. The planning target dose difference was stratified between the target in soft tissue, where the mean dose was found to be lower for Acuros XB, with a range of 0.4% ± 0.6% (intensity-modulated therapy, 6 MV) to 1.7% ± 0.2% (three-dimensional conformal therapy, 6 MV), and the target in lung tissue, where the mean dose was higher for 6 MV (from 0.2% ± 0.2% to 1.2% ± 0.5%) and lower for 15 MV (from 0.5% ± 0.5% to 2.0% ± 0.9%). Mean doses to organs at risk presented differences up to 3% of the mean structure dose in the worst case. No particular or systematic differences were found related to the various modalities. Calculation time ratios between calculation time for Acuros XB and the Anisotropic Analytical Algorithm were 7 for three-dimensional conformal therapy, 5 for intensity-modulated therapy, and 0.2 for volumetric modulated arc therapy with RapidArc. CONCLUSION: The availability of Acuros XB could improve patient dose estimation, increasing the data consistency of clinical trials.

Volumetric modulated arc-based hypofractionated stereotactic radiotherapy for the treatment of selected intracranial arteriovenous malformations: dosimetric report and early clinical experience.

PURPOSE: To evaluate, with a dosimetric and clinical feasibility study, RapidArc (a volumetric modulated arc technique) for hypofractionated stereotactic radiotherapy treatment of large arteriovenous malformations (AVMs). METHODS AND MATERIALS: Nine patients were subject to multimodality imaging (magnetic resonance, computed tomography, and digital subtraction angiography) to determine nidus and target volumes, as well as involved organs at risk (optical structures, inner ear, brain stem). Plans for multiple intensity-modulated arcs with a single isocenter were optimized for a fractionation of 25 Gy in 5 fractions. All plans were optimized for 6-MV photon beams. Dose-volume histograms were analyzed to assess plan quality. Delivery parameters were reported to appraise technical features of RapidArc, and pretreatment quality assurance measurements were carried out to report on quality of delivery. RESULTS: Average size of AVM nidus was 26.2 cm(3), and RapidArc plans provided complete target coverage with minimal overdosage (V(100%) = 100% and V(110%) < 1%) and excellent homogeneity (<6%). Organs at risk were highly spared. The D(1%) to chiasm, eyes, lenses, optic nerves, and brainstem (mean ± SD) was 6.4 ± 8.3, 1.9 ± 3.8, 2.3 ± 2.2, 0.7 ± 0.9, 4.4 ± 7.2, 12.2 ± 9.6 Gy, respectively. Conformity index (CI(95%)) was 2.2 ± 0.1. The number of monitor units per gray was 277 ± 45, total beam-on time was 2.5 ± 0.3 min. Planning vs. delivery γ pass rate was 98.3% ± 0.9%. None of the patients developed acute toxicity. With a median follow-up of 9 months, 3 patients presented with deterioration of symptoms and were found to have postradiation changes but responded symptomatically to steroids. These patients continue to do well on follow-up. One patient developed headache and seizures, which was attributed to intracranial bleed, confirmed on imaging. CONCLUSION: Hypofractionated stereotactic radiotherapy can be successfully delivered using the RapidArc form of volumetric arc technology for intracranial AVMs. The quality of delivery and calculated parameters are in agreement with each other and are in line with published reports for other sites.