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Background: To analyze RapidPlan knowledge-based models for DVH estimation of organs at risk from breast cancer VMAT plans presenting arc sectors en-face to the breast with zero dose rate, feature imposed during the optimization phase (avoidance sectors AS)., Methods: CT datasets of twenty left breast patients in deep-inspiration breath-hold were selected. Two VMAT plans, PartArc and AvoidArc, were manually generated with double arcs from ~ 300 to ~ 160°, with the second having an AS en-face to the breast to avoid contralateral breast and lung direct irradiation. Two RapidPlan models were generated from the two plan sets. The two models were evaluated in a closed loop to assess the model performance on plans where the AS were selected or not in the optimization., Results: The PartArc plans model estimated DVHs comparable with the original plans. The AvoidArc plans model estimated a DVH pattern with two steps for the contralateral structures when the plan does not contain the AS selected in the optimization phase. This feature produced mean doses of the contralateral breast, averaged over all patients, of 0.4 ± 0.1 Gy, 0.6 ± 0.2 Gy, and 1.1 ± 0.2 Gy for the AvoidArc plan, AvoidArc model estimation, RapidPlan generated plan, respectively. The same figures for the contralateral lung were 0.3 ± 0.1 Gy, 1.6 ± 0.6 Gy, and 1.2 ± 0.5 Gy. The reason was found in the possible incorrect information extracted from the model training plans due to the lack of knowledge about the AS. Conversely, in the case of plans with AS set in the optimization generated with the same AvoidArc model, the estimated and resulting DVHs were comparable. Whenever the AvoidArc model was used to generate DVH estimation for a plan with AS, while the optimization was made on the plan without the AS, the optimizer evidentiated the limitation of a minimum dose rate of 0.2 MU/°, resulting in an increased dose to the contralateral structures respect to the estimation., Conclusions: The RapidPlan models for breast planning with VMAT can properly estimate organ at risk DVH. Attention has to be paid to the plan selection and usage for model training in the presence of avoidance sectors., (© 2022. The Author(s).)

Background: To investigate the performance of a narrow-scope knowledge-based RapidPlan (RP) model for optimisation of intensity-modulated proton therapy (IMPT) and volumetric modulated arc therapy (VMAT) plans applied to patients with pleural mesothelioma. Second, estimate the potential benefit of IMPT versus VMAT for this class of patients., Methods: A cohort of 82 patients was retrospectively selected; 60 were used to "train" a dose-volume histogram predictive model; the remaining 22 provided independent validation. The performance of the RP models was benchmarked, comparing predicted versus achieved mean and near-to-maximum dose for all organs at risk (OARs) in the training set and by quantitative assessment of some dose-volume metrics in the comparison of the validation RP-based data versus the manually optimised training datasets. Treatment plans were designed for a prescription dose of 44 Gy in 22 fractions (proton doses account for a fixed relative biological effectiveness RBE = 1.1)., Results: Training and validation RP-based plans resulted dosimetrically similar for both VMAT and IMPT groups, and the clinical planning aims were met for all structures. The IMPT plans outperformed the VMAT ones for all OARs for the contra-lateral and the mean and low dose regions for the ipsilateral OARs. Concerning the prediction performance of the RP models, the linear regression for the near-to-maximum dose resulted in D achieved  = 1.03D predicted  + 0.58 and D achieved  = 1.02D predicted  + 1.46 for VMAT and IMPT, respectively. For the mean dose it resulted: D achieved  = 0.99D predicted  + 0.34 and D achieved  = 1.05D predicted  + 0.27 respectively. In both cases, the linear correlation between prediction and achievement is granted with an angular coefficient deviating from unity for less than 5%. Concerning the dosimetric comparison between manual plans in the training cohort and RP-based plans in the validation cohort, no clinical differences were observed for the target volumes in both the VMAT and IMPT groups. Similar consistency was observed for the dose-volume metrics analysed for the OAR. This proves the possibility of achieving the same quality of plans with manual procedures (the training set) or with automated RP-based methods (the validation set)., Conclusion: Two models were trained and validated for VMAT and IMPT plans for pleural mesothelioma. The RP model performance resulted satisfactory as measured by the agreement between predicted and achieved (after full optimisation) dose-volume metrics. The IMPT plans outperformed the VMAT plans for all the OARs (with different intensities for contra- or ipsilateral structures). RP-based planning enabled the automation of part of the optimisation and the harmonisation of the dose-volume results between training and validation. The IMPT data showed a systematic significant dosimetric advantage over VMAT. In general, using an RP-based approach can simplify the optimisation workflow in these complex treatment indications without impacting the quality of plans., (© 2022. The Author(s).)

Aim: To investigate the potential role of a novel spatially fractionated radiation therapy (SFRT) method where heterogeneous dose patterns are created in target areas with virtual rods, straight or curving, of variable position, diameter, separation and alignment personalised to a patient's anatomy. The images chosen for this study were CT scans acquired for the external beam part of radiotherapy., Methods: Ten patients with locally advanced cervical cancer were retrospectively investigated with SFRT. The dose prescription was 30 Gy in 5 fractions to 90% target volume coverage. Peak-and-valley (SFRT_1) and peak-only (SFRT_2) strategies were applied to generate the heterogeneous dose distributions. The planning objectives for the target (CTV) were D 90%  ≥ 30 Gy, V 45Gy  ≥ 50-55% and V 60Gy  ≥ 30%. The planning objectives for the organs at risk (OAR) were: D 2cm3  ≤ 23.75 Gy, 17.0 Gy, 19.5 Gy, 17.0 Gy for the bladder, rectum, sigmoid and bowel, respectively. The plan comparison was performed employing the quantitative analysis of the dose-volume histograms., Results: The D 2cm3 was 22.4 ± 2.0 (22.6 ± 2.1) and 13.9 ± 2.9 (13.2 ± 3.0) for the bladder and the rectum for SFRT_1 (SFRT_2). The results for the sigmoid and the bowel were 2.6 ± 3.1 (2.8 ± 3.0) and 9.1 ± 5.9 (9.7 ± 7.3), respectively. The hotspots in the target volume were V 45Gy  = 43.1 ± 7.5% (56.6 ± 5.6%) and V 60Gy  = 15.4 ± 5.6% (26.8 ± 6.6%) for SFRT_1 (SFRT_2). To account for potential uncertainties in the positioning, the dose prescription could be escalated to D 90%  = 33-35 Gy to the CTV without compromising any constraints to the OARs CONCLUSION: In this dosimetric study, the proposed novel planning technique for boosting the cervix uteri was associated with high-quality plans, respecting constraints for the organs at risk and approaching the level of dose heterogeneity achieved with routine brachytherapy. Based on a sample of 10 patients, the results are promising and might lead to a phase I clinical trial.

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 (V 98%  > 98 for CTV and GTV and V 95%  > 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.

Background: To investigate the role of intensity modulated proton therapy (IMPT) compared to volumetric modulated arc therapy (VMAT) for advanced supradiaphragmatic Hodgkin's lymphoma (HL) in young female patients by assessing dosimetric features and modelling the risk of treatment related complications and radiation-induced secondary malignancies., Methods: A group of 20 cases (planned according to the involved-site approach) were retrospectively investigated in a comparative planning study. Intensity modulated proton plans (IMPT) were compared to VMAT RapidArc plans (RA). Estimates of toxicity were derived from normal tissue complication probability (NTCP) calculations with either the Lyman or the Poisson models for a number of endpoints. Estimates of the risk of secondary cancer induction were determined for lungs, breasts, esophagus and thyroid. A simple model-based selection strategy was considered as a feasibility proof for the individualized selection of patients suitable for proton therapy., Results: IMPT and VMAT plans resulted equivalent in terms of target dose distributions, both were capable to ensure high coverage and homogeneity. In terms of conformality, IMPT resulted ~ 10% better than RA plans. Concerning organs at risk, IMPT data presented a systematic improvement (highly significant) over RA for all organs, particularly in the dose range up to 20Gy. This lead to a composite average reduction of NTCP of 2.90 ± 2.24 and a reduction of 0.26 ± 0.22 in the relative risk of cardiac failures. The excess absolute risk per 10,000 patients-years of secondary cancer induction was reduced, with IMPT, of 9.1 ± 3.2, 7.2 ± 3.7 for breast and lung compared to RA. The gain in EAR for thyroid and esophagus was lower than 1. Depending on the arbitrary thresholds applied, the selection rate for proton treatment would have ranged from 5 to 75%., Conclusion: In relation to young female patients with advanced supradiaphragmatic HL, IMPT can in general offer improved dose-volume sparing of organs at risk leading to an anticipated lower risk of early or late treatment related toxicities. This would reflect also in significantly lower risk of secondary malignancies induction compared to advanced photon based techniques. Depending on the selection thresholds and with all the limits of a non-validated and very basic model, it can be anticipated that a significant fraction of patients might be suitable for proton treatments if all the risk factors would be accounted for.

Background: PRIMO is a graphical environment based on PENELOPE Monte Carlo (MC) simulation of radiotherapy beams able to compute dose distribution in patients, from plans with different techniques. The dosimetric characteristics of an HD-120 MLC (Varian), simulated using PRIMO, were here compared with measurements, and also with Acuros calculations (in the Eclipse treatment planning system, Varian)., Materials and Methods: A 10 MV FFF beam from a Varian EDGE linac equipped with the HD-120 MLC was used for this work. Initially, the linac head was simulated inside PRIMO, and validated against measurements in a water phantom. Then, a series of different MLC patterns were established to assess the MLC dosimetric characteristics. Those tests included: i) static fields: output factors from MLC shaped fields (2 × 2 to 10 × 10 cm 2 ), alternate open and closed leaf pattern, MLC transmitted dose; ii) dynamic fields: dosimetric leaf gap (DLG) evaluated with sweeping gaps, tongue and groove (TG) effect assessed with profiles across alternate open and closed leaves moving across the field. The doses in the different tests were simulated in PRIMO and then compared with EBT3 film measurements in solid water phantom, as well as with Acuros calculations. Finally, MC in PRIMO and Acuros were compared in some clinical cases, summarizing the clinical complexity in view of a possible use of PRIMO as an independent dose calculation check., Results: Static output factor MLC tests showed an agreement between MC calculated and measured OF of 0.5%. The dynamic tests presented DLG values of 0.033 ± 0.003 cm and 0.032 ± 0.006 cm for MC and measurements, respectively. Regarding the TG tests, a general agreement between the dose distributions of 1-2% was achieved, except for the extreme patterns (very small gaps/field sizes and high TG effect) were the agreement was about 4-5%. The analysis of the clinical cases, the Gamma agreement between MC in PRIMO and Acuros dose calculation in Eclipse was of 99.5 ± 0.2% for 3%/2 mm criteria of dose difference/distance to agreement., Conclusions: MC simulations in the PRIMO environment were in agreement with measurements for the HD-120 MLC in a 10 MV FFF beam from a Varian EDGE linac. This result allowed to consistently compare clinical cases, showing the possible use of PRIMO as an independent dose calculation check tool.

Background: The aim of this study was to evaluate long-term efficacy and survival prognostic factors of stereotactic body radiation therapy (SBRT) for un-resectable liver metastases in patients enrolled in a prospective phase II trial., Methods and Materials: 5-year local control (LC), overall survival (OS), progression free survival (PFS) and toxicity rates were analyzed in patients with un-resectable liver metastases enrolled in a Phase II Trial on liver SBRT, with a prescription dose of 75Gy in 3 consecutive fractions., Results: A total of 61 patients with 76 lesions were enrolled, with a median follow-up time of 6.1 years. One, three and 5 year LC rates were 94 ± 3.1%, 78.0 ± 5.9% and 78.0 ± 5.9%, without reaching the median LC time. Median OS was 27.6 months and the survival rates were 85.2 ± 4.5%, 31.1 ± 5.9% and 18.0 ± 4.9% at 1, 3 and 5-year after SBRT, respectively. Univariate analysis showed that favorable primary site (colorectal, breast and gynecological) of metastases (p = 0.001) improved survival. Toxicity was moderate. One patient experienced G3 late chest wall pain, which resolved within 1 year from SBRT. No cases of Radiation Induced Liver Disease (RILD) were detected., Conclusions: Long-term results of this Phase II study suggest the efficacy and safety of SBRT for un-resectable liver metastases after 5-year of follow up. Selection of cases with positive prognostic factors may improve long-term survival of these oligo-metastastic patients and may confirm the role of SBRT as an effective alternative local therapy for liver metastases.

Background: The benefits of proton therapy in the treatment of patients with Hodgkin lymphoma (HL) are controversially discussed. Therefore we compared intensitiy modulated proton therapy (IMPT) with intensity modulated radiotherapy (IMRT), in the form of volumetric modulated arc therapy (VMAT) in patients with Hodgkin lymphoma (HL), through a comparative treatment planning study., Methods: Radiation plans for 21 patients with Hodgkin Lymphoma (HL) were computed for IMPT and deep inspiration breath hold (DIBH) VMAT. Plans were optimized and computed assuming deep inspiration breath holding conditions. Dosimetric comparison on standard metrics from dose volume histograms was performed to appraise the relative merits of the two techniques, while proton plan robustness was assessed by re-computing the dose distribution of each plan by varying the Hounsfield Units to stopping power calibration by applying a ± 3 and 4% error., Results: DIBH-VMAT and IMPT both provided excellent coverage, conformity and heterogeneity of the clinical target volume (CTV) and planning target volume (PTV). IMPT reduced mean doses to the breasts, lungs, heart and normal tissue by 38-83%. IMPT significantly reduced mean doses to the heart to < 5 Gy despite bulky mediastinal disease and decreased breast doses in female patients to < 1 Gy. Despite the simulated 3 and 4% miscalibration errors, no remarkable or measurable impact was observed on the organs at risk (OARs)., Conclusions: This is the first comparison between DIBH-VMAT and IMPT in HL treatment. We could demonstrate statistically significant decreases in all dose/volume metrics of the OARs. Regardless of the planning paradigm used, range uncertainties can substantially under dose the PTV, while perhaps not leading to clinically significant deterioration of CTV coverage. With the geometry applied no impact was observed for OARs, suggesting IMPT as a superior technique for potentially reducing future health risks for HL patients.

Background: To appraise the dosimetric features and the quality of the treatment plan for radiosurgery of multiple brain metastases optimized with a novel automated engine and to compare with plans optimized for robotic-based delivery., Methods: A set of 15 patients with multiple brain metastases was selected for this in silico study. The technique under investigation is the recently introduced HyperArc. For all patients, three treatment plans were computed and compared: i: a HyperArc; ii: a standard VMAT; iii) a CyberKnife. Dosimetric features were computed for the clinical target volumes as well as for the healthy brain tissue and the organs at risk., Results: The data showed that the best dose homogeneity was achieved with the VMAT technique. HyperArc allowed to minimize the volume of brain receiving 4Gy (as well as for the mean dose and the volume receiving 12Gy, although not statistically significant). The smallest dose on 1 cm 3 volume for all organs at risk is for CK techniques, and the biggest for VMAT (p < 0.05). The Radiation Planning Index coefficient indicates that, there are no significant differences among the techniques investigated, suggesting an equivalence among these., Conclusion: At treatment planning level, the study demonstrates that the use of HyperArc technique can significantly improve the sparing of the healthy brain while maintaining a full coverage of the target volumes.

Background: The aim of this review is the critical appraisal of the current use of volumetric modulated arc therapy for the radiation therapy management of breast cancer. Both clinical and treatment planning studies were investigated., Material and Methods: A Pubmed/MEDLINE search of the National Library of Medicine was performed to identify VMAT and breast related articles. After a first order rejection of the irrelevant findings, the remaining articles were grouped according to two main categories: clinical vs. planning studies and to some sub-categories (pointing to significant technical features). Main areas of application, dosimetric and clinical findings as well as areas of innovations were defined., Results: A total of 131 articles were identified and of these, 67 passed a first order selection. Six studies reported clinical results while 61 treatment dealed with treatment planning investigations. Among the innovation lines, the use of high intensity photon beams (flattening filter free), altered fractionation schemes (simultaneous integrated boost, accelerated partial breast irradiation, single fraction), prone positioning and modification of standard VMAT (use of dynamic trajectories or hybrid VMAT methods) resulted among the main relevant fields of interest. Approximately 10% of the publications reported upon respiratory gating in conjunction with VMAT., Conclusions: The role of VMAT in the radiation treatment of breast cancer seems to be consolidated in the in-silico arena while still limited evidence and only one phase II trial appeared in literature from the clinical viewpoint. More clinical reports are needed to fully proove the expected dosimetric benefits demonstrated in the planning investigations.

Background: To report toxicity and early clinical outcomes of hypofractionated simultaneous integrated boost (SIB) approach with Volumetric Modulated Arc Therapy (VMAT) as adjuvant treatment after breast-conserving surgery., Methods: Patients presenting early-stage breast cancer were enrolled in a phase II trial., Eligibility Criteria: age > 18 years old, invasive cancer or ductal carcinoma in situ (DCIS), Stage I-II (T < 3 cm and N ≤ 3), breast-conserving surgery without oncoplastic reconstruction. Any systemic therapy was allowed in neoadjuvant or adjuvant setting. All patients underwent VMAT-SIB technique to irradiate the whole breast and 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. Acute and late skin toxicities were recorded. Cosmetic outcome was assessed as excellent/good or fair/poor., Results: The present study focused on results of a cohort of 144 patients with a minimum follow-up of 24 months (median 37, range 24-55 months). Median age was 62 years old (range 30-88). All patients had an invasive carcinoma (no patients with DCIS were present in this subset). At one year, the highest reported skin toxicity was G1, in 14 % of the patients; this data dropped to 4 % at the last follow-up, after more than 2 years. Breast pain was recorded in 21.6 % of the patients 6 months after treatment, while it was present in 3.5 % of the patients at the last follow-up, showing a significant improvement with time. Correlation between liponecrosis and boost target volume was found not significant. Breast pain was correlated with breast volume. No pulmonary or cardiological toxicities were recorded. After an early evaluation of clinical outcomes, only one case presented disease relapse, as liver metastases., Conclusions: The 3-week VMAT-SIB course as adjuvant treatment after breast-conserving surgery showed to be well tolerated and was associated with optimal local control. Long-term follow-up data are needed to assess late toxicity and clinical outcomes.

Background: Hypo-fractionated stereotactic radiotherapy (HSRT) is emerging as a valid treatment option for patients with single, large brain metastases (BMs). We analyzed a set of our patients treated with HSRT. The aim of this study was to evaluate local control (LC), brain distant progression (BDP), toxicity and overall survival (OS)., Methods: From July 2011 to May 2015, 102 patients underwent HSRT consisting of 27Gy/3fractions for lesions 2.1-3 cm and 32Gy/4 fractions for lesions 3.1-5 cm. Local progression was defined as increase of the enhancing abnormality on MRI, and distant progression as new brain metastases outside the irradiated volume. Toxicity in terms of radio-necrosis was assessed using contrast enhanced T1MRI, T2 weighted-MRI and perfusion- MRI., Result: The median maximum diameter of BM was 2.9 cm (range 2.1-5 cm), the median gross target volume (GTV) was 16.3 cm(3) and the median planning target volume (PTV) was 33.7 cm(3) The median,1,2-year local control rate was 30 months, 96, 96 %; the median, 1-2-year rate of BDP was 24 months, 12, 24 %; the median,1,2-year OS was 14 months, 69, 33 %. KPS and controlled extracranial disease were associated with significant survival benefit (p <0.01). Brain radio-necrosis occurred in six patients (5.8 %)., Conclusion: In patients with single, large BMs unsuitable for surgical resection, HSRT is a safe and feasible treatment, with good brain local control and limited toxicity.

Background: Shortening the overall treatment time without increasing acute reactions is one of the major aims in radiotherapy for head and neck cancer (HNC). Volumetric modulated arc therapy (VMAT) with Simultaneous Integrated Boost (SIB) showed improvements in outcome and pattern of toxicity. Patients with stage III-IV HNC treated with VMAT-SIB have been analysed, and doses were correlated to limiting structures and toxicity., Methods: One hundred two patients treated from December 2008 to August 2014 were analysed. Patients were treated with VMAT (RapidArc) and SIB in 33 fractions for a total dose of 69.96 and 54.45Gy, respectively. For organs at risk, D1/3 V, D1/2 V, D2/3 V, the mean dose, VD with D = 10,20,30,40,50,70 Gy were analysed. For targets, D98%, D2%, and V95%, V107%, conformity and homogeneity indexes were calculated. Toxicity was graded according to CTCAE3., Results: Oral cavity V30Gy, V40Gy, and V70Gy, were found correlated with mucosal toxicity grading. Concerning salivary glands, significant was only D2/3V for one of the two parotids. Almost all analysed parameters of the inferior constrictor muscle were significant while no correlations were found for middle and superior constrictors. With median follow-up of 19 months, Overall Survival (OS) at 3 and 5 years was 83 % ± 4 % and 73 % ± 10 %. Mean OS was 51 ± 3 months. Disease Free Survival (DFS) at 3 and 5 years was 71 % ± 7 %, and 34 % ± 16 %. Mean DFS was 43 ± 3 months., Conclusions: RapidArc technology and SIB with 1.65 and 2.12Gy/fraction for 33 fractions showed a good toxicity profile and encouraging trend for OS and DFS for patients with stage III-IV HNC.

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.

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.

Background: Total marrow (lymph-nodes) irradiation (TMI-TMLI) by volumetric modulated arc therapy (VMAT) was shown to be feasible by dosimetric feasibility studies. It was demonstrated that several partially overlapping arcs with different isocenters are required to achieve the desired coverage of the hematopoietic or lymphoid tissues targets and to spare the neighbouring healthy tissues. The effect of isocenter shifts was investigated with the treatment planning system but an in- vivo verification of the procedure was not carried out. The objective of this study was the in-vivo verification of the consistency between the delivered and planned doses using bi-dimensional GafChromic EBT3 films., Methods: In a first phase a phantom study was carried out to quantify the uncertainties under controlled conditions. In a second phase three patients treated with TMLI were enrolled for in-vivo dosimetry. The dose prescription was 2Gy in single fraction. Ten arcs paired on 4-6 isocenters were used to cover the target. Cone Beam Computed Tomography (CBCT) was used to verify the patient positioning at each isocenter. GafChromic EBT3 films were placed below the patient on the top of a dedicated immobilization system specifically designed. The dose maps measured with the EBT3 films were compared with the corresponding calculations along the patient support couch. Gamma Agreement Index (GAI) with dose difference of 5% and distance to agreement of 5 mm was computed., Results: In the phantom study, optimal target coverage and healthy tissue sparing was observed. GAI(5%,5 mm) was 99.4%. For the patient-specific measurements, GAI(5%,5 mm) was greater than 95% and GAI (5%,3 mm) > 90% for all patients., Conclusions: In vivo measurements demonstrated the delivered dose to be in good agreement with the planned one for the TMI-TMLI protocol where partially overlapping arcs with different isocenters are required.

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.

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.

Background: Data in the literature suggest the existence of oligometastatic disease, a state in which metastases are limited in number and site. Different kinds of local therapies have been used for the treatment of limited metastases and in the recent years reports on the use of Stereotactic Ablative radiotherapy (SABR) are emerging and the early results on local control are promising., Patients and Methods: From October 2010 to February 2012, 76 consecutive patients for 118 lung lesions were treated. SABR was performed in case of controlled primary tumor, long-term of progression disease, exclusion of surgery, and number of metastatic sites ≤ 5. Different kinds of primary tumors were treated, the most common were lung and colon-rectal cancer. The total dose prescribed varied according to tumor site and maximum diameter. Dose prescription was 48 Gy in 4 fractions for peripheral lesions, 60 Gy in 8 fractions for central lesions and 60 Gy in 3 fractions for peripheral lesions with diameter ≤ 2 cm., Results: Dosimetric planning objectives were met for the cohort of patients with in particular V98% = 98.1 ± 3.4% for the CTV and mean lung dose of 3.7 ± 3.8 Gy. Radiological response was obtained in the vast majority of patients. The local control at 1, 2 and 3 years was 95%, 89% and 89% respectively. No major pulmonary toxicity, chest pain or rib fracture occurred. The median follow up was 20 months (range 6-45 months). Overall Survival (OS) at 1, 2 and 3 years was 84.1%, 73% and 73% respectively., Conclusions: SABR is feasible with limited morbidity and promising results in terms of local control, survival and toxicity.

Background: To report technical features, early outcome and toxicity of stereotactic body radiation therapy (SBRT) treatments with volumetric modulated arc therapy (RapidArc) for patients with hepatocellular carcinoma (HCC)., Methods: Twenty patients (22 lesions) were prospectively enrolled in a feasibility study. Dose prescription was 50 Gy in 10 fractions. Seven patients (35%) were classified as AJCC stage I-II while 13 (65%) were stages III-IV. Eighteen patients (90%) were Child-Pugh stage A, the remaining were stage B. All patients were treated with RapidArc technique with flattening filter free (FFF) photon beams of 10 MV from a TrueBeam linear accelerator. Technical, dosimetric and early clinical assessment was performed to characterize treatment and its potential outcome., Results: Median age was 68 years, median initial tumor volume was 124 cm3 (range: 6-848). Median follow-up time was 7.4 months (range: 3-13). All patients completed treatment without interruption. Mean actuarial overall survival was of 9.6 ± 0.9 months (95%C.L. 7.8-11.4), median survival was not reached; complete response was observed in 8/22 (36.4%) lesions; partial response in 7/22 (31.8%), stable disease in 6/22 (27.3%), 1/22 (4.4%) showed progression. Toxicity was mild with only 1 case of grade 3 RILD and all other types were not greater than grade 2. Concerning dosimetric data, Paddick conformity index was 0.98 ± 0.02; gradient index was 3.82 ± 0.93; V95% to the clinical target volume was 93.6 ± 7.7%. Mean dose to kidneys resulted lower than 3.0 Gy; mean dose to stomach 4.5 ± 3.0 Gy; D(3) 1(cm) to spinal cord was 8.2 ± 4.5 Gy; D1% to the esophagus was 10.2 ± 9.7 Gy. Average beam on time resulted 0.7 ± 0.2 minutes (range: 0.4-1.4) with the delivery of an average of 4.4 partial arcs (range: 3-6) of those 86% non-coplanar., Conclusions: Clinical results could suggest to introduce VMAT-RapidArc as an appropriate SBRT technique for patients with HCC in view of a prospective dose escalation trial.

Background: To assess the dosimetric effect induced by inter-observer variability in target definition for 3D-conformal RT (3DCRT) and volumetric modulated arc therapy by RapidArc (RA) techniques for rectal cancer treatment., Methods: Ten patients with rectal cancer subjected to neo-adjuvant RT were randomly selected from the internal database. Four radiation oncologists independently contoured the clinical target volume (CTV) in blind mode. Planning target volume (PTV) was defined as CTV + 7 mm in the three directions. Afterwards, shared guidelines between radiation oncologists were introduced to give general criteria for the contouring of rectal target and the four radiation oncologists defined new CTV following the guidelines. For each patient, six intersections (I) and unions (U) volumes were calculated coupling the contours of the various oncologists. This was repeated for the contours drawn after the guidelines. Agreement Index (AI = I/U) was calculated pre and post guidelines. Two RT plans (one with 3DCRT technique using 3-4 fields and one with RA using a single modulated arc) were optimized on each radiation oncologist's PTV. For each plan the PTV volume receiving at least 95% of the prescribed dose (PTV V95%) was calculated for both target and non-target PTVs., Results: The inter-operator AI pre-guidelines was 0.57 and was increased up to 0.69 post-guidelines. The maximum volume difference between the various CTV couples, drawn for each patient, passed from 380 ± 147 cm³ to 137 ± 83 cm³ after the introduction of guidelines. The mean percentage for the non-target PTV V95% was 93.7 ± 9.2% before and 96.6 ± 4.9%after the introduction of guidelines for the 3DCRT, for RA the increase was more relevant, passing from 86.5 ± 13.8% (pre) to 94.5 ± 7.5% (post). The OARs were maximally spared with VMAT technique while the variability between pre and post guidelines was not relevant in both techniques., Conclusions: The contouring inter-observer variability has dosimetric effects in the PTV coverage. The introduction of guidelines increases the dosimetric consistency for both techniques, with greater improvements for RA technique.

Background: To evaluate the feasibility and early side effects of a short course hypo-fractionated SBRT programme with Volumetric Modulated Arc Therapy (VMAT) and Flattening Filter Free (FFF) beams., Methods: A prospective phase I-II study, started on February 2012. Inclusion criteria were: age ≤ 80 years, WHO-PS ≤ 2, PSA ≤ 20 ng/ml, histologically proven prostate adenocarcinoma, T1-T2 stage, no distant metastases, no previous surgery other than TURP, no malignant tumours in the previous 5 years, IPSS 0-7. The schedule was 35 Gy in 5 alternative days. SBRT was delivered with RapidArc VMAT, with 10MV FFF photons. Toxicity assessment was performed according to CTCAE v4.0 scale. EPIC questionnaires assessed Quality-of-Life. Neo-adjuvant/concomitant hormonal-therapy was prescribed according to risk classification. SpaceOAR™ gel was optionally implanted to increase the separation space between the prostate and the rectal wall., Results: Median follow-up was 11 months (range: 5-16); 40 patients were recruited in the protocol and treated. According to NCCN criteria, 26/40 patients were low-risk and 14/40 were intermediate risk. Median age was 70 years (56-80), median initial PSA was 6.25 ng/ml (0.50-13.43 ng/ml). Median Gleason score was 6 (6-7). All patients completed the treatment as programmed (median 11.8 days (9-22). Acute Toxicities were as follow: Rectum G0: 30/40 cases (75%); G1: 6/40 (15%); G2: 4/40 (10%). Genito-urinary: G0: 16/40 (40%); G1: 8/40 (20%); G2: 16/34 (40%). In two G2 urinary retention cases, intermittent catheter was needed. No acute G3 or greater toxicity was found. Median treatment time was 126 sec (120-136). SpaceOAR™ was implanted in 8 patients. PSA reduction from the pre-treatment value of the marker was documented in all patients., Conclusions: Early findings suggest that SBRT with RapidArc and FFF beams for prostate cancer in 5 fractions is feasible and tolerated in acute setting. Longer follow-up is needed for assessment of late toxicity and outcome.

Background: To assess the efficacy and safety of stereotactic body radiotherapy (SBRT) in patients with either unresectable locally advanced pancreatic adenocarcinoma or by locally recurrent disease after surgery., Methods: Between January 2010 and October 2011, 30 patients with unresectable or recurrent pancreatic adenocarcinoma underwent exclusive SBRT. Twenty-one patients (70%) presented with unresectable locally advanced disease and 9 patients (30%) showed local recurrence after surgery. No patients had metastatic disease. Gemcitabine-based chemotherapy was administered to all patients before SBRT. Prescription dose was 45Gy in 6 daily fractions of 7.5Gy. SBRT was delivered using the volumetric modulated arc therapy (VMAT) by RapidArc. Primary end-point of this study was freedom from local progression (FFLP), secondary end-points were overall survival (OS), progression free survival (PFS) and toxicity., Results: Median Clinical Target Volume (CTV) was 25.6 cm3 (3.2-78.8 cm3) and median Planning Target Volume (PTV) was 70.9 cm3 (20.4- 205.2 cm3). The prescription dose was delivered in 25 patients (83%), in 5 patients (17%) it was reduced to 36Gy in 6 fractions not to exceed the dose constraints of organs at risk (OARs). Median follow-up was 11 months (2-28 months). FFLP was 91% at 6 months, 85% at median follow-up and 77% at 1 and 2 years. For the group with prescription dose of 45Gy, FFLP was 96% at 1 and 2 years. The median PFS was 8 months. The OS was 47% at 1 year and median OS was 11 months. At the end of the follow-up, 9 patients (32%) were alive and 4 (14%) were free from progression. No patients experienced G ≥ 3 acute toxicity., Conclusions: Our preliminary results show that SBRT can obtain a satisfactory local control rate for unresectable locally advanced and recurrent pancreatic adenocarcinoma. This fractionation schedule is feasible, and no G ≥ 3 toxicity was observed. SBRT is an effective emerging technique in the multi-modality treatment of locally advanced pancreatic tumors.

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.

Background: To report early outcome and toxicity for inoperable patients with hepatocellular carcinoma (HCC) treated with volumetric modulated arc therapy (VMAT)., Methods: One hundred and thirty eight patients were retrospectively analysed. Dose prescription ranged from 45 to 66 Gy with conventional fractionation regime. Based on AJCC staging, 88.4% presented stage III or IV. Two-thirds (69.6%) were Child-Pugh stage A, the remaining were stage B. According to Barcelona Clinic Liver Cancer staging, 72.5% of patients were classified as stage C., Results: Median age was 66 years, median tumor volume was 516 cm(3) (28 to 3620 cm(3)). The most patients (83%) were treated with 60 Gy. Median follow-up time was 9 months. One-year overall survival rate was 45% (100% for AJCC stage I, 83% for stage II, 45% for stage III and 28% for stage IV), median survival was 10.3 months (95% C.I. 7.2-13.3). Local control was achieved in 94% (of 109 assessable patients), stable disease in 29%, partial response in 53%, complete response in 11%, and progression in 6%. Radiation-induced liver disease was observed in 34 patients (25%). Gastrointestinal grade 3 toxicity was modest with a total of 17 (12.3%) cases for all endpoints., Conclusions: Clinical results could suggest to introduce VMAT as an appropriate technique for the patients with HCC.

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.

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.

Purpose: To report the initial institute experience in terms of dosimetric and technical aspects in stereotactic body radiation therapy (SBRT) delivered using flattening filter free (FFF) beam in patients with liver lesions., Methods and Materials: From October 2010 to September 2011, 55 consecutive patients with 73 primary or metastatic hepatic lesions were treated with SBRT on TrueBeam using FFF beam and RapidArc technique. Clinical target volume (CTV) was defined on multi-phase CT scans, PET/CT, MRI, and 4D-CT. Dose prescription was 75 Gy in 3 fractions to planning target volume (PTV). Constraints for organs at risk were: 700 cc of liver free from the 15 Gy isodose, Dmax < 21 Gy for stomach and duodenum, Dmax < 30 Gy for heart, D0.1 cc < 18 Gy for spinal cord, V15 Gy < 35% for kidneys. The dose was downscaled in cases of not full achievement of dose constraints. Daily cone beam CT (CBCT) was performed., Results: Forty-three patients with a single lesion, nine with two lesions and three with three lesions were treated with this protocol. Target and organs at risk objectives were met for all patients. Mean delivery time was 2.8 ± 1.0 min. Pre-treatment plan verification resulted in a Gamma Agreement Index of 98.6 ± 0.8%. Mean on-line co-registration shift of the daily CBCT to the simulation CT were: -0.08, 0.05 and -0.02 cm with standard deviations of 0.33, 0.39 and 0.55 cm in, vertical, longitudinal and lateral directions respectively., Conclusions: SBRT for liver targets delivered by means of FFF resulted to be feasible with short beam on time.

Background: A new-generation low-energy linear accelerator (UNIQUE) was introduced in the clinical arena during 2009 by Varian Medical Systems. The world's first UNIQUE was installed at Oncology Institute of Southern Switzerland and put into clinical operation in June 2010. The aim of the present contribution was to report experience about its commissioning and first year results from clinical operation., Methods: Commissioning data, beam characteristics and the modeling into the treatment planning system were summarized. Imaging system of UNIQUE included a 2D-2D matching capability and tests were performed to identify system repositioning capability. Finally, since the system is capable of delivering volumetric modulated arc therapy with RapidArc, a summary of the tests performed for such modality to assess its performance in preclinical settings and during clinical usage was included., Results: Isocenter virtual diameter was measured as less than 0.2 mm. Observed accuracy of isocenter determination and repositioning for 2D-2D matching procedures in image guidance was <1.2 mm. Concerning reproducibility and stability over a period of 1 year, deviations from reference were found <0.3 ± 0.2% for linac output, <0.1% for homogeneity, similarly to symmetry. Rotational accuracy of the entire gantry-portal imager system showed a maximum deviation from nominal 0.0 of <1.2 mm. Pre treatment quality assurance of RapidArc plans resulted with a Gamma Agreement Index (fraction of points passing the gamma criteria) of 97.0 ± 1.6% on the first 182 arcs verified., Conclusions: The results of the commissioning tests and of the first period of clinical operation, resulted meeting specifications and having good margins respect to tolerances. UNIQUE was put into operation for all delivery techniques; in particular, as shown by the pre-treatment quality assurance results, it enabled accurate and safe delivery of RapidArc plans.

Purpose: To test feasibility and safety of clinical usage of Flattening Filter Free (FFF) beams for delivering ablative stereotactic body radiation therapy (SBRT) doses to various tumor sites, by means of Varian TrueBeam™ (Varian Medical Systems)., Methods and Materials: Seventy patients were treated with SBRT and FFF: 51 lesions were in the thorax (48 patients),10 in the liver, 9 in isolated abdominal lymph node, adrenal gland or pancreas. Doses ranged from 32 to 75 Gy, depending on the anatomical site and the volume of the lesion to irradiate. Lung lesions were treated with cumulative doses of 32 or 48 Gy, delivered in 4 consecutive fractions. The liver patients were treated in 3 fractions with total dose of 75 Gy. The isolated lymph nodes were irradiated in 6 fractions with doses of 45 Gy. The inclusion criteria were the presence of isolated node, or few lymph nodes in the same lymph node region, in absence of other active sites of cancer disease before the SBRT treatment., Results: All 70 patients completed the treatment. The minimum follow-up was 3 months. Six cases of acute toxicities were recorded (2 Grade2 and 2 Grade3 in lung and 2 Grade2 in abdomen). No patient experienced acute toxicity greater than Grade3. No other types or grades of toxicities were observed at clinical evaluation visits., Conclusions: This study showed that, with respect to acute toxicity, SBRT with FFF beams showed to be a feasible technique in 70 consecutive patients with various primary and metastatic lesions in the body.

Background: A new algorithm for photon dose calculation, Acuros XB, has been recently introduced in the Eclipse, Varian treatment planning system, allowing, similarly to the classic Monte Carlo methods, for accurate modelling of dose deposition in media. Aim of the present study was the assessment of its behaviour in clinical cases., Methods: Datasets from ten breast patients scanned under different breathing conditions (free breathing and deep inspiration) were used to calculate dose plans using the simple two tangential field setting, with Acuros XB (in its versions 10 and 11) and the Anisotropic Analytical Algorithm (AAA) for a 6MV beam. Acuros XB calculations were performed as dose-to-medium distributions. This feature was investigated to appraise the capability of the algorithm to distinguish between different elemental compositions in the human body: lobular vs. adipose tissue in the breast, lower (deep inspiration condition) vs. higher (free breathing condition) densities in the lung., Results: The analysis of the two breast structures presenting densities compatible with muscle and with adipose tissue showed an average difference in dose calculation between Acuros XB and AAA of 1.6%, with AAA predicting higher dose than Acuros XB, for the muscle tissue (the lobular breast); while the difference for adipose tissue was negligible. From histograms of the dose difference plans between AAA and Acuros XB (version 10), the dose of the lung portion inside the tangential fields presented an average difference of 0.5% in the free breathing conditions, increasing to 1.5% for the deep inspiration cases, with AAA predicting higher doses than Acuros XB. In lung tissue significant differences are found also between Acuros XB version 10 and 11 for lower density lung., Conclusions: Acuros XB, differently from AAA, is capable to distinguish between the different elemental compositions of the body, and suggests the possibility to further improve the accuracy of the dose plans computed for actual treatment of patients.

Background: A study was realised to evaluate and determine relative figures of merit of a new algorithm for photon dose calculation when applied to inhomogeneous media., Methods: The new Acuros XB algorithm implemented in the Varian Eclipse treatment planning system was compared against a Monte Carlo method (VMC++), and the Analytical Anisotropic Algorithm (AAA). The study was carried out in virtual phantoms characterized by simple geometrical structures. An insert of different material and density was included in a phantom built of skeletal-muscle and HU = 0 (setting "A"): Normal Lung (lung, 0.198 g/cm3); Light Lung (lung, 0.035 g/cm3); Bone (bone, 1.798 g/cm3); another phantom (setting "B") was built of adipose material and including thin layers of bone (1.85 g/cm3), adipose (0.92 g/cm3), cartilage (1.4745 g/cm3), air (0.0012 g/cm3). Investigations were performed for 6 and 15 MV photon beams, and for a large (13 × 13 cm2) and a small (2.8 × 13 cm2) field., Results: Results are provided in terms of depth dose curves, transverse profiles and Gamma analysis (3 mm/3% and 2 mm/2% distance to agreement/dose difference criteria) in planes parallel to the beam central axis; Monte Carlo simulations were assumed as reference. Acuros XB gave an average gamma agreement, with a 3 mm/3% criteria, of 100%, 86% and 100% for Normal Lung, Light Lung and Bone settings, respectively, and dose to medium calculations. The same figures were 86%, 11% and 100% for AAA, where only dose rescaled to water calculations are possible., Conclusions: In conclusion, Acuros XB algorithm provides a valid and accurate alternative to Monte Carlo calculations for heterogeneity management.

Purpose: A study was performed to assess dosimetric characteristics of volumetric modulated arcs (RapidArc, RA) and fixed field intensity modulated therapy (IMRT) for Whole Abdomen Radiotherapy (WAR) after ovarian cancer., Methods and Materials: Plans for IMRT and RA were optimised for 5 patients prescribing 25 Gy to the whole abdomen (PTV&#95;WAR) and 45 Gy to the pelvis and pelvic nodes (PTV&#95;Pelvis) with Simultaneous Integrated Boost (SIB) technique. Plans were investigated for 6 MV (RA6, IMRT6) and 15 MV (RA15, IMRT15) photons. Objectives were: for both PTVs V90% > 95%, for PTV&#95;Pelvis: Dmax < 105%; for organs at risk, maximal sparing was required. The MU and delivery time measured treatment efficiency. Pre-treatment Quality assurance was scored with Gamma Agreement Index (GAI) with 3% and 3 mm thresholds., Results: IMRT and RapidArc resulted comparable for target coverage. For PTV&#95;WAR, V90% was 99.8 ± 0.2% and 93.4 ± 7.3% for IMRT6 and IMRT15, and 98.4 ± 1.7 and 98.6 ± 0.9% for RA6 and RA15. Target coverage resulted improved for PTV&#95;Pelvis. Dose homogeneity resulted slightly improved by RA (Uniformity was defined as U5-95% = D5%-D95%/Dmean). U5-95% for PTV&#95;WAR was 0.34 ± 0.05 and 0.32 ± 0.06 (IMRT6 and IMRT15), 0.30 ± 0.03 and 0.26 ± 0.04 (RA6 and RA15); for PTV&#95;Pelvis, it resulted equal to 0.1 for all techniques. For organs at risk, small differences were observed between the techniques. MU resulted 3130 ± 221 (IMRT6), 2841 ± 318 (IMRT15), 538 ± 29 (RA6), 635 ± 139 (RA15); the average measured treatment time was 18.0 ± 0.8 and 17.4 ± 2.2 minutes (IMRT6 and IMRT15) and 4.8 ± 0.2 (RA6 and RA15). GAIIMRT6 = 97.3 ± 2.6%, GAIIMRT15 = 94.4 ± 2.1%, GAIRA6 = 98.7 ± 1.0% and GAIRA15 = 95.7 ± 3.7%., Conclusion: RapidArc showed to be a solution to WAR treatments offering good dosimetric features with significant logistic improvements compared to IMRT.

Background: To report about early clinical experience in radiation treatment of head and neck cancer of different sites and histology by volumetric modulated arcs with the RapidArc technology., Methods: During 2009, 45 patients were treated at Istituto Clinico Humanitas with RapidArc (28 males and 17 females, median age 65 years). Of these, 78% received concomitant chemotherapy. Thirty-six patients were treated as exclusive curative intent (group A), three as postoperative curative intent (group B) and six with sinonasal tumours (group C). Dose prescription was at Planning Target Volumes (PTV) with simultaneous integrated boost: 54.45 Gy and 69.96 Gy in 33 fractions (group A); 54.45 Gy and 66 Gy in 33 fractions (group B) and 55 Gy in 25 fractions (group C)., Results: Concerning planning optimization strategies and constraints, as per PTV coverage, for all groups, D98% > 95% and V95% > 99%. As regards organs at risk, all planning objectives were respected, and this was correlated with observed acute toxicity rates. Only 28% of patients experienced G3 mucositis, 14% G3 dermitis 44% had G2 dysphagia. Nobody required feeding tubes to be placed during treatment. Acute toxicity is also related to chemotherapy. Two patients interrupted the course of radiotherapy because of a quick worsening of general clinical condition., Conclusions: These preliminary results stated that volumetric modulated arc therapy in locally advanced head and neck cancers is feasible and effective, with acceptable toxicities.

Background: To report acute toxicity, initial outcome results and planning therapeutic parameters in radiation treatment of advanced lung cancer (stage III) with volumetric modulated arcs using RapidArc (RA)., Methods: Twenty-four consecutive patients were treated with RA. All showed locally advanced non-small cell lung cancer with stage IIIA-IIIB and with large volumes (GTV:299 ± 175 cm3, PTV:818 ± 206 cm3). Dose prescription was 66Gy in 33 fractions to mean PTV. Delivery was performed with two partial arcs with a 6 MV photon beam., Results: From a dosimetric point of view, RA allowed us to respect most planning objectives on target volumes and organs at risk. In particular: for GTV D1% = 105.6 ± 1.7%, D99% = 96.7 ± 1.8%, D5%-D95% = 6.3 ± 1.4%; contra-lateral lung mean dose resulted in 13.7 ± 3.9Gy, for spinal cord D1% = 39.5 ± 4.0Gy, for heart V45Gy = 9.0 ± 7.0Gy, for esophagus D1% = 67.4 ± 2.2Gy. Delivery time was 133 ± 7s. At three months partial remission > 50% was observed in 56% of patients. Acute toxicities at 3 months showed 91% with grade 1 and 9% with grade 2 esophageal toxicity; 18% presented grade 1 and 9% with grade 2 pneumonia; no grade 3 acute toxicity was observed. The short follow-up does not allow assessment of local control and progression free survival., Conclusions: RA proved to be a safe and advantageous treatment modality for NSCLC with large volumes. Long term observation of patients is needed to assess outcome and late toxicity.

Background: To report about initial clinical experience in radiation treatment of carcinoma of prostate with volumetric modulated arcs with the RapidArc (RA) technology., Methods: Forty-five patients with a median age of 72 +/- 3, affected by prostate carcinoma (T1c: 22 patients, T2a-b: 17 patients, T3a-b: 6 patients. N0: 43 patients, N1-Nx: 2 patients, all M0), with initial PSA of 10.0 +/- 3.0 ng/mL, were treated with RapidArc in a feasibility study. All patients were treated with single arc using 6MV photons. Dose prescription ranged between 76 (7 patients) and 78 Gy (38 patients) in 2 Gy/fraction. Plan quality was assessed by means of Dose Volume Histogram (DVH) analysis. Technical parameters of arcs and pre-treatment quality assurance results (Gamma Agreement Index, GAI) are reported to describe delivery features. Early toxicity was scored (according to the Common Terminology Criteria of Adverse Effects scale, CTCAE, scale) at the end of treatment together with biochemical outcome (PSA)., Results: From DVH data, target coverage was fulfilling planning objectives: V95% was in average higher than 98% and V107% approximately 0.0% (D2% approximately 104.0% in average). Homogeneity D5%-D95% ranged between 6.2 +/- 1.0% to 6.7 +/- 1.3%. For rectum, all planning objectives were largely met (e.g. V70Gy = 10.7 +/- 5.5% against an objective of < 25%) similarly for bladder (e.g. D2% = 79.4 +/- 1.2 Gy against an objective of 80.0 Gy). Maximum dose to femurs was D2% = 36.7 +/- 5.4 Gy against an objective of 47 Gy. Monitor Units resulted: MU/Gy = 239 +/- 37. Average beam on time was 1.24 +/- 0.0 minutes. Pre-treatment GAI resulted in 98.1 +/- 1.1%. Clinical data were recorded as PSA at 6 weeks after RT, with median values of 0.4 +/- 0.4 ng/mL. Concerning acute toxicity, no patient showed grade 2-3 rectal toxicity; 5/42 (12%) patients experienced grade 2 dysuria; 18/41 (44%) patients preserved complete or partial erectile function., Conclusion: RapidArc proved to be a safe, qualitative and advantageous treatment modality for prostate cancer.

Background: To report about initial technical and clinical experience in preoperative radiation treatment of rectal cancer with volumetric modulated arcs with the RapidArc (RA) technology., Methods: Twenty-five consecutive patients (pts) were treated with RA. All showed locally advanced rectal adenocarcinoma with stage T2-T4, N0-1. Dose prescription was 44 Gy in 22 fractions (or 45 Gy in 25 fractions). Delivery was performed with single arc with a 6 MV photon beam. Twenty patients were treated preoperatively, five did not receive surgery. Twenty-three patients received concomitant chemotherapy with oral capecitabine. A comparison with a cohort of twenty patients with similar characteristics treated with conformal therapy (3DC) is presented as well., Results: From a dosimetric point of view, RA improved conformality of doses (CI95% = 1.1 vs. 1.4 for RA and 3DC), presented similar target coverage with lower maximum doses, significant sparing of femurs and significant reduction of integral and mean dose to healthy tissue. From the clinical point of view, surgical reports resulted in a down-staging in 41% of cases. Acute toxicity was limited to Grade 1-2 diarrhoea in 40% and Grade 3 in 8% of RA pts, 45% and 5% of 3DC pts, compatible with known effects of concomitant chemotherapy. RA treatments were performed with an average of 2.0 vs. 3.4 min of 3DC., Conclusion: RA proved to be a safe, qualitatively advantageous treatment modality for rectal cancer, showing some improved results in dosimetric aspects.

Purpose: A study was performed comparing dosimetric characteristics of volumetric modulated arcs (RapidArc, RA) and fixed field intensity modulated therapy (IMRT) on patients with bilateral breast carcinoma., Materials and Methods: Plans for IMRT and RA, were optimised for 10 patients prescribing 50 Gy to the breast (PTVII, 2.0 Gy/fraction) and 60 Gy to the tumour bed (PTVI, 2.4 Gy/fraction). Objectives were: for PTVs V(90%)>95%, D(max)<107%; Mean lung dose MLD<15 Gy, V(20Gy)<22%; heart involvement was to be minimised. The MU and delivery time measured treatment efficiency. Pre-treatment dosimetry was performed using EPID and a 2D-array based methods., Results: For PTVII minus PTVI, V(90%) was 97.8 +/- 3.4% for RA and 94.0 +/- 3.5% for IMRT (findings are reported as mean +/- 1 standard deviation); D(5%)-D(95%) (homogeneity) was 7.3 +/- 1.4 Gy (RA) and 11.0 +/- 1.1 Gy (IMRT). Conformity index (V(95%)/V(PTVII)) was 1.10 +/- 0.06 (RA) and 1.14 +/- 0.09 (IMRT). MLD was <9.5 Gy for all cases on each lung, V(20Gy) was 9.7 +/- 1.3% (RA) and 12.8 +/- 2.5% (IMRT) on left lung, similar for right lung. Mean dose to heart was 6.0 +/- 2.7 Gy (RA) and 7.4 +/- 2.5 Gy (IMRT). MU resulted in 796 +/- 121 (RA) and 1398 +/- 301 (IMRT); the average measured treatment time was 3.0 +/- 0.1 minutes (RA) and 11.5 +/- 2.0 (IMRT). From pre-treatment dosimetry, % of field area with gamma <1 resulted 98.8 +/- 1.3% and 99.1 +/- 1.5% for RA and IMRT respectively with EPID and 99.1 +/- 1.8% and 99.5 +/- 1.3% with 2D-array (DeltaD = 3% and DTA = 3 mm)., Conclusion: RapidArc showed dosimetric improvements with respect to IMRT, delivery parameters confirmed its logistical advantages, pre-treatment dosimetry proved its reliability.

Background: To evaluate the performance of three different advanced treatment techniques on a group of complex paediatric cancer cases., Methods: CT images and volumes of interest of five patients were used to design plans for Helical Tomotherapy (HT), RapidArc (RA) and Intensity Modulated Proton therapy (IMP). The tumour types were: extraosseous, intrathoracic Ewing Sarcoma; mediastinal Rhabdomyosarcoma; metastasis of base of skull with bone, para-nasal and left eye infiltration from Nephroblastoma of right kidney; metastatic Rhabdomyosarcoma of the anus; Wilm's tumour of the left kidney with multiple liver metastases. Cases were selected for their complexity regardless the treatment intent and stage. Prescribed doses ranged from 18 to 53.2 Gy, with four cases planned using a Simultaneous Integrated Boost strategy. Results were analysed in terms of dose distributions and dose volume histograms., Results: For all patients, IMP plans lead to superior sparing of organs at risk and normal healthy tissue, where in particular the integral dose is halved with respect to photon techniques. In terms of conformity and of spillage of high doses outside targets (external index (EI)), all three techniques were comparable; CI90% ranged from 1.0 to 2.3 and EI from 0 to 5%. Concerning target homogeneity, IMP showed a variance (D5%-D95%) measured on the inner target volume (highest dose prescription) ranging from 5.9 to 13.3%, RA from 5.3 to 11.8%, and HT from 4.0 to 12.2%. The range of minimum significant dose to the same target was: (72.2%, 89.9%) for IMP, (86.7%, 94.1%) for RA, and (79.4%, 94.8%) for HT. Similarly, for maximum significant doses: (103.8%, 109.4%) for IMP, (103.2%, 107.4%) for RA, and (102.4%, 117.2%) for HT. Treatment times (beam-on time) ranged from 123 to 129 s for RA and from 146 to 387 s for HT., Conclusion: Five complex pediatric cases were selected as representative examples to compare three advanced radiation delivery techniques. While differences were noted in the metrics examined, all three techniques provided satisfactory conformal avoidance and conformation.

Background: To expand and test the dosimetric procedure, known as GLAaS, for amorphous silicon detectors to the RapidArc intensity modulated arc delivery with Varian infrastructures and to test the RapidArc dosimetric reliability between calculation and delivery., Methods: The GLAaS algorithm was applied and tested on a set of RapidArc fields at both low (6 MV) and high (18 MV) beam energies with a PV-aS1000 detector. Pilot tests for short arcs were performed on a 6 MV beam associated to a PV-aS500. RapidArc is a novel planning and delivery method in the category of intensity modulated arc therapies aiming to deliver highly modulated plans with variable MLC shapes, dose rate and gantry speed during rotation. Tests were repeated for entire (360 degrees) gantry rotations on composite dose plans and for short partial arcs (of approximately 6 or 12 degrees) to assess GLAaS and RapidArc mutual relationships on global and fine delivery scales. The gamma index concept of Low and the Modulation Index concept of Webb were applied to compare quantitatively TPS dose matrices and dose converted PV images., Results: The Gamma Agreement Index computed for a Distance to Agreement of 3 mm and a Dose Difference (DeltaD) of 3% was, as mean +/- 1 SD, 96.7 +/- 1.2% at 6 MV and 94.9 +/- 1.3% at 18 MV, over the field area. These findings deteriorated slightly is DeltaD was reduced to 2% (93.4 +/- 3.2% and 90.1 +/- 3.1%, respectively) and improved with DeltaD = 4% (98.3 +/- 0.8% and 97.3 +/- 0.9%, respectively). For all tests a grid of 1 mm and the AAA photon dose calculation algorithm were applied. The spatial resolution of the PV-aS1000 is 0.392 mm/pxl. The Modulation Index for calculations resulted 17.0 +/- 3.2 at 6 MV and 15.3 +/- 2.7 at 18 MV while the corresponding data for measurements were: 18.5 +/- 3.7 and 17.5 +/- 3.7. Partial arcs findings were (for DeltaD = 3%): GAI = 96.7 +/- 0.9% for 6 degrees rotations and 98.0 +/- 1.1% for 12 degrees rotations., Conclusion: The GLAaS method can be considered as a valid Quality Assurance tool for the verification of RapidArc fields. The two implementations (composite rotation or short arcs) allow the verification of either the entire delivery or of short partial segments to possibly identify local discrepancies between delivery and calculations. RapidArc, according to the findings, appears to be a safe delivery method in terms of dosimetric accuracy allowing its clinical application.

Background: To evaluate the performance of seven different TPS (Treatment Planning Systems: Corvus, Eclipse, Hyperion, KonRad, Oncentra Masterplan, Pinnacle and PrecisePLAN) when intensity modulated (IMRT) plans are designed for paediatric tumours., Methods: Datasets (CT images and volumes of interest) of four patients were used to design IMRT plans. The tumour types were: one extraosseous, intrathoracic Ewing Sarcoma; one mediastinal Rhabdomyosarcoma; one metastatic Rhabdomyosarcoma of the anus; one Wilm's tumour of the left kidney with multiple liver metastases. Prescribed doses ranged from 18 to 54.4 Gy. To minimise variability, the same beam geometry and clinical goals were imposed on all systems for every patient. Results were analysed in terms of dose distributions and dose volume histograms., Results: For all patients, IMRT plans lead to acceptable treatments in terms of conformal avoidance since most of the dose objectives for Organs At Risk (OARs) were met, and the Conformity Index (averaged over all TPS and patients) ranged from 1.14 to 1.58 on primary target volumes and from 1.07 to 1.37 on boost volumes. The healthy tissue involvement was measured in terms of several parameters, and the average mean dose ranged from 4.6 to 13.7 Gy. A global scoring method was developed to evaluate plans according to their degree of success in meeting dose objectives (lower scores are better than higher ones). For OARs the range of scores was between 0.75 +/- 0.15 (Eclipse) to 0.92 +/- 0.18 (Pinnacle(3) with physical optimisation). For target volumes, the score ranged from 0.05 +/- 0.05 (Pinnacle(3) with physical optimisation) to 0.16 +/- 0.07 (Corvus)., Conclusion: A set of complex paediatric cases presented a variety of individual treatment planning challenges. Despite the large spread of results, inverse planning systems offer promising results for IMRT delivery, hence widening the treatment strategies for this very sensitive class of patients.