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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. 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. 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. 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. [ABSTRACT FROM AUTHOR]

Abstract 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 TrueBeamTM 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.

Abstract 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.

Abstract 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 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.

Abstract 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.

Abstract 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.

Abstract 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.

Abstract 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_WAR) and 45 Gy to the pelvis and pelvic nodes (PTV_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_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_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_Pelvis. Dose homogeneity resulted slightly improved by RA (Uniformity was defined as U5-95% = D5%-D95%/Dmean). U5-95% for PTV_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_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.

Abstract 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 2Gy/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%~0.0% (D2%~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 ± 1.2Gy against an objective of 80.0Gy). Maximum dose to femurs was D2% = 36.7 ± 5.4Gy against an objective of 47Gy. 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.

Abstract 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.

Abstract 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 V90%>95%, Dmax20 Gy Results For PTVII minus PTVI, V90% was 97.8 ± 3.4% for RA and 94.0 ± 3.5% for IMRT (findings are reported as mean ± 1 standard deviation); D5%-D95% (homogeneity) was 7.3 ± 1.4 Gy (RA) and 11.0 ± 1.1 Gy (IMRT). Conformity index (V95%/VPTVII) was 1.10 ± 0.06 (RA) and 1.14 ± 0.09 (IMRT). MLD was 20 Gy 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 γ Conclusion RapidArc showed dosimetric improvements with respect to IMRT, delivery parameters confirmed its logistical advantages, pre-treatment dosimetry proved its reliability.

Abstract 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; metastastis 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.

Abstract 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 ~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 (ΔD) 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 ΔD was reduced to 2% (93.4 ± 3.2% and 90.1 ± 3.1%, respectively) and improved with ΔD = 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 ΔD = 3%): GAI = 96.7 ± 0.9% for 6° rotations and 98.0 ± 1.1% for 12° 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.

Abstract 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 (Pinnacle3 with physical optimisation). For target volumes, the score ranged from 0.05 ± 0.05 (Pinnacle3 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.