Adjuvant Hypofractionated Whole Breast Irradiation (WBI) vs. Accelerated Partial Breast Irradiation (APBI) in Postmenopausal Women with Early Stage Breast Cancer: 5Years Update of the HYPAB Trial.

Therapeutical strategies in breast cancer are continuously updating. Recent researches assessed the possibility of irradiating only the surgical bed in selected patients (Partial Breast Irradiation, PBI). In 2014 we designed a study to evaluate toxicity and cosmesis of APBI using Volumetric Modulated Arc Therapy-Rapid Arc compared with hypofractionated whole breast irradiation (WBI). We present here the 5-years updated data. HYPAB was a single-institution randomized trial that recruited 172 patients from 2015 to 2018. Patients underwent conserving surgery and were randomized to either adjuvant WBI (40.5Gy/15 fractions with simultaneous boost to 48 Gy to tumoral bed) or APBI (30Gy/5 fractions), both delivered with VMAT-RA technique. Clinical evaluation was performed during the first visit, once a week during radiotherapy and during follow up. Cosmesis was assessed using the Harvard Scale for Breast Cosmesis. At the time of the analysis 161 patients were eligible, 53% in the WBI and 47% in the APBI group, with a median follow-up of 67 months. Most common late skin toxicities were G1 fibrosis (32%) and oedema (28%) and were higher in the WBI group; no G3 toxicities were observed. Cosmesis was rated poor in only 6 cases. 147 patients had no evidence of disease at the last follow-up, and no patients died of the disease. Mature results confirm the safety and efficacy of APBI in selected early stage breast cancer patients. Late toxicity is improved in the APBI arm at the cost of a slight increase in local relapse. Further studies are ongoing to better elucidate the use of APBI as a de-escalation approach.

Long term results of a phase II trial of hypofractionated adjuvant radiotherapy for early-stage breast cancer with volumetric modulated arc therapy and simultaneous integrated boost.

PURPOSE: to report toxicity and cosmetic outcome with a median follow-up of 6 years of a phase II trial of hypofractionated radiotherapy with volumetric modulated arc therapy (VMAT) and simultaneous integrated boost (SIB) for early-stage breast cancer after conservative surgery. MATERIALS AND METHODS: From August 2010 to September 2014, patients requiring adjuvant radiotherapy for early-stage breast cancer were treated according to a phase I-II protocol with SIB to 40.5 and 48 Gy to the breast and the boost region, respectively, with VMAT technique. The primary endpoint evaluated the treatment feasibility regarding adherence to required dose constraints for target, heart and lungs. Acute and late toxicity, local and distant control were secondary endpoints. RESULTS: 450 patients were included in the trial and analysed after a median follow-up of 6 years. Acute toxicity was already presented in a previous paper. Regarding late toxicity, 93% of patients had no skin alteration at five years, while 5.3% and 1.3% did record G1 and G2 residual toxicity, respectively. Cosmetic outcome was scored good or excellent in almost all cases (97.2%), fair only in 2.3% of patients. Residual tenderness in the irradiated breast was reported by 10% of patients. Cosmesis and breast pain improved during follow-up. Two cases of G2 pneumonitis and two cases of ischemic cardiopathy were registered during follow-up. Five cases presented local recurrence in the homolateral breast, four patients had a new primary cancer in the contralateral breast, while distant metastasis developed in 7 patients. CONCLUSION: After more than six years, hypofractionated VMAT with SIB for adjuvant radiotherapy in early-stage breast cancer patients remains a safe and effective approach. Mature data on skin toxicity and cosmetic outcome are encouraging. However, longer follow-up is required to evaluate local control, cardiac toxicity and secondary carcinogenesis.

The impact of scanning data measurements on the Acuros dose calculation algorithm configuration.

BACKGROUND: Many dose calculation algorithms for radiotherapy planning need to be configured for each clinical beam using pre-defined measurements. An optimization process adjusts the physical parameters able to estimate the energy released in the medium in any geometrical condition. This work investigates the impact of measured input data quality on the configuration of the type "c" Acuros-XB dose calculation algorithm in the Eclipse (Varian Medical Systems) treatment planning system. METHODS: Different datasets were acquired with the BeamScan water phantom (PTW) to configure 6 MV beams, for both flattened (6X) and flattening filter free mode (6FFF) for a Varian TrueBeam: (i) a correct dataset measured using a Semiflex-3D ion chamber, (ii) a set in missing lateral scatter conditions (MLS), (iii) a set with incorrect effective point of measurement (EPoM), (iv) sets acquired with PinPoint-3D chamber, DiodeP, microDiamond detectors. The Acuros-XB dose calculation algorithm (version 15.6) was configured using the reference dataset, the sets measured with the different detectors, with intentional errors, and using the representative beam data (RBD) made available by the vendor. The physical parameters obtained from each optimization process (spectrum, mean radial energy, electron contamination), were analyzed and compared. Calculated data were finally compared against the input and reference measurements. RESULTS: Concerning the physical parameters, the configurations presenting the largest differences were the MLS conditions (mean radial energy) and the incorrect EPoM (electron contamination). The calculation doses relative to the input data present low accuracy, with mean differences > 2% in some conditions. The PinPoint-3D ion chamber presented lower accuracy for the 6FFF beam. Regarding the RBD, calculations compared well with the input data used for the configuration, but not with the reference data. CONCLUSION: The MLS conditions and the incorrect setting of the EPoM lead to erroneous configurations and should be avoided. The choice of an appropriate detector is important. Whenever the representative beam data is used, a careful check under more clinical geometrical conditions is advised.

Technical Note: Flattening filter free beam from Halcyon linac: Evaluation of the profile parameters for quality assurance.

INTRODUCTION: The use of flattening filter free (FFF) beams generated by standard linear accelerators is increasing in the clinical practice. The radiation intensity peaked toward the beam central axis is properly managed in the optimization process of treatment planning through intensity modulation. Specific FFF parameters for profile analysis, as unflatness and slope for FFF beams, based on the renormalization factor concept has been introduced for quality assurance purposes. Recently, Halcyon, an O-ring based linear accelerator equipped with a 6 MV FFF beam only has been introduced by Varian. METHODS: Renormalization factors and related fit parameters according to Fogliata et al. ["Definition of parameters for quality assurance of FFF photon beams in radiation therapy," Med. Phys. 39, 6455-6464 (2012)] have been evaluated for the 6 MV FFF beam generated by Halcyon units. The Halcyon representative beam data provided by Varian were used. Dose fall-off at the field edges was matched with an unflattened beam generated by a 6 MV from a TrueBeam linac. Consistency of the results was evaluated against measurements on a clinical Halcyon unit, as well as a TrueBeam 6 MV FFF for comparison. RESULTS: The five parameters in the analytical equation for estimating the renormalization factor were determined with an R2 of 0.997. The comparison of the unflatness parameters between the Halcyon representative and hospital beam data was consistent within a range of 0.6%. Consistently with the computed parameters, the Halcyon profiles resulted in a less pronounced peak than TrueBeam. CONCLUSION: Renormalization factors and related fit parameters from the 6 MV FFF beam generated by the Varian Halcyon unit are provided.

Treatment planning comparison of volumetric modulated arc therapy employing a dual-layer stacked multi-leaf collimator and helical tomotherapy for cervix uteri.

PURPOSE: To ascertain the dosimetric performance of a new delivery system (the Halcyon system, H) equipped with dual-layer stacked multi-leaf collimator (MLC) for risk-adapted targets in cervix uteri cancer patients compared to another ring-based system in clinical operation (Helical Tomotherapy, HT). METHODS: Twenty patients were retrospectively included in a treatment planning study (10 with positive lymph nodes and 10 without). The dose prescription (45Gy to the primary tumour volume and a simultaneously integrated boost up to 55Gy for the positive patients) and the clinical planning objectives were defined consistently as recommended by an ongoing multicentric clinical trial. Halcyon plans were optimised for the volumetric modulated arc therapy. The plan comparison was performed employing the quantitative analysis of the dose-volume histograms. RESULTS: The coverage of the primary and nodal target volumes was comparable for both techniques and both subsets of patients. The primary planning target volume (PTV) receiving at least 95% of the prescription isodose ranged from 97.2 ± 1.1% (node-negative) to 99.1 ± 1.2% (node-positive) for H and from 96.5 ± 1.9% (node-negative) to 98.3 ± 0.9% (node-positive) for HT. The uncertainty is expressed at one standard deviation from the cohort of patient per each group. For the nodal clinical target volumes, the dose received by 98% of the planning target volume ranged 55.5 ± 0.1 to 56.0 ± 0.8Gy for H and HT, respectively. The only significant and potentially relevant differences were observed for the bowels. In this case, V40Gy resulted 226.3 ± 35.9 and 186.9 ± 115.9 cm3 for the node-positive and node-negative patients respectively for Halcyon. The corresponding findings for HT were: 258.9 ± 60.5 and 224.9 ± 102.2 cm3. On the contrary, V15Gy resulted 1279.7 ± 296.5 and 1557.2 ± 359.9 cm3 for HT and H respectively for node-positive and 1010.8 ± 320.9 versus 1203.8 ± 332.8 cm3 for node-negative. CONCLUSION: This retrospective treatment planning study, based on the dose constraints derived from the Embrace II study protocol, suggested the essential equivalence between Halcyon based and Helical Tomotherapy based plans for the intensity-modulated rotational treatment of cervix uteri cancer. Different levels of sparing were observed for the bowels with H better protecting in the high-dose region and HT in the mid-low dose regions. The clinical impact of these differences should be further addressed.

The Potential Role of Intensity-modulated Proton Therapy in the Regional Nodal Irradiation of Breast Cancer: A Treatment Planning Study.

AIMS: To investigate the role of intensity-modulated proton therapy (IMPT) for regional nodal irradiation in patients with breast carcinoma in comparison with volumetric-modulated arc therapy (VMAT). MATERIALS AND METHODS: A cohort of 20 patients (10 in the breast-conserving surgery group and 10 post-mastectomy patients with tissue expander implants) was investigated. Proton plans were also computed using robust optimisation methods. Plan quality was assessed by means of dose-volume histograms and scored with conventional metrics. Estimates of the risk of secondary cancer induction (excess absolute risk, EAR) were carried out, taking into account fractionation, repopulation and repair. RESULTS: Concerning target coverage, the data proved a substantial equivalence of VMAT and IMPT: for example, coverage for the 50 Gy target, expressed in terms of V98%, was 47.8 ± 0.4, 47.6 ± 0.4, 47.3 ± 0.8, consistent with the objective of 47.5 Gy, for post-mastectomy patients for the three groups of patients. Also, the conformality of the dose distributions was similar for the two techniques, about 1.1, without statistically significant differences. Organ at risk planning aims were achieved for all structures for both techniques. The mean dose to the ipsilateral lung was 10.8 ± 1.1, 6.2 ± 0.8, 7.2 ± 1.0; for the contralateral lung was 3.2 ± 0.7, 0.3 ± 0.2, 0.4 ± 0.2; for the contralateral breast was: 3.1 ± 0.7, 0.3 ± 0.3 and 0.3 ± 0.3, whereas it was 3.9 ± 0.9, 0.4 ± 0.3 and 0.5 ± 0.5, respectively, for the heart for VMAT, IMPT and robust IMPT plans over the whole group of patients. Robust optimisation affected the near-to-maximum dose values for contralateral lung and breast, the mean dose for the heart and ipsilateral lung, with a deterioration ranging from 20 to 40% of the nominal value of IMPT plans (e.g. from 8.1 ± 6.4 to 11.4 ± 8.8 for the heart compared with 16.2 ± 5.2 for the VMAT plans). The numerical values of EAR per 10 000 patient-years were about one order of magnitude higher for VMAT than for IMPT for contralateral structures: 11.66 ± 2.01, 0.89 ± 0.80, 0.98 ± 0.77 for the contralateral breast and the three groups of plans, respectively; 14.31 ± 2.75, 1.42 ± 0.80, 1.78 ± 0.87 for the contralateral lung; and 34.86 ± 2.64, 18.85 ± 2.15, 20.98 ± 2.35 for the ipsilateral lung. CONCLUSION: IMPT with or without robust optimisation seems to be a potentially promising approach for the radiation treatment of breast cancer when nodal volumes should be irradiated. This was measured in terms of dosimetric advantage and predicted clinical benefit. In fact, the significant reduction in estimated EAR could add further clinical value to the dosimetric sparing of the organs at risk achievable with IMPT.

RapidPlan knowledge based planning: iterative learning process and model ability to steer planning strategies.

PURPOSE: To determine if the performance of a knowledge based RapidPlan (RP) planning model could be improved with an iterative learning process, i.e. if plans generated by an RP model could be used as new input to re-train the model and achieve better performance. METHODS: Clinical VMAT plans from 83 patients presenting with head and neck cancer were selected to train an RP model, CL-1. With this model, new plans on the same patients were generated, and subsequently used as input to train a novel model, CL-2. Both models were validated on a cohort of 20 patients and dosimetric results compared. Another set of 83 plans was realised on the same patients with different planning criteria, by using a simple template with no attempt to manually improve the plan quality. Those plans were employed to train another model, TP-1. The differences between the plans generated by CL-1 and TP-1 for the validation cohort of patients were compared with respect to the differences between the original plans used to build the two models. RESULTS: The CL-2 model presented an improvement relative to CL-1, with higher R2 values and better regression plots. The mean doses to parallel organs decreased with CL-2, while D1% to serial organs increased (but not significantly). The different models CL-1 and TP-1 were able to yield plans according to each original strategy. CONCLUSION: A refined RP model allowed the generation of plans with improved quality, mostly for parallel organs at risk and, possibly, also the intrinsic model quality.

Collimator scatter factor: Monte Carlo and in-air measurements approaches.

BACKGROUND: Linac output as a function of field sizes has a phantom and a head scatter component. This last term can be measured in-air with appropriate build-up ensuring a complete electron equilibrium and the absence of the contaminant electrons. Equilibrium conditions could be achieved using a build-up cap or a mini-phantom. Monte Carlo simulations in a virtual phantom mimicking a mini-phantom were analysed with the aim of better understanding the setup conditions for measuring the collimator scatter factor that is the head scatter component of the linac output factors. METHODS: Beams of 6 and 15 MV from a TrueBeam, with size from 4 × 4 to 40 × 40 cm2 were simulated in cylindrical acrylic phantoms 20 cm long, of different diameters, from 0.5 to 4 cm, with the cylinder axis coincident with the beam central axis. The PRIMO package, based on PENELOPE Monte Carlo code, was used. The phase-space files for a Varian TrueBeam linac, provided by the linac vendor, were used for the linac head simulation. Depth dose curves were analysed, and collimator scatter factors estimated at different depth in the different phantom conditions. Additionally, in-air measurements using acyrilic and brass build-up caps, as well as acrylic mini-phantom were acquired for 6 and 18 MV beams from a Varian Clinac DHX. RESULTS: The depth dose curves along the cylinders were compared, showing, in each phantom, very similar curves for all analysed field sizes, proving the correctness in estimating the collimator scatter factor in the mini-phantom, provided to position the detector to a sufficient depth to exclude electron contamination. The results were confirmed by the measurements, where the acrylic build-up cap showed to be inadequate to properly estimate the collimator scatter factors, while the mini-phantom and the brass caps gave reasonable measurements. CONCLUSION: A better understanding of the beam characteristics inside a virtual mini-phantom through the analysis of depth dose curves, showed the critical points of using the acrylic build-up cap, and suggested the use of the mini-phantom for the collimator scatter factor measurements in the medium-large field size range.

Evaluation of target dose inhomogeneity in breast cancer treatment due to tissue elemental differences.

BACKGROUND: Monte Carlo simulations were run to estimate the dose variations generated by thedifference arising from the chemical composition of the tissues. METHODS: CT datasets of five breast cancer patients were selected. Mammary gland was delineated as clinical target volume CTV, as well as CTV_lob and CTV_fat, being the lobular and fat fractions of the entire mammary gland. Patients were planned for volumetric modulated arc therapy technique, optimized in the Varian Eclipse treatment planning system. CT, structures and plans were imported in PRIMO, based on Monte Carlo code Penelope, to run three simulations: AdiMus, where the adipose and muscle tissues were automatically assigned to fat and lobular fractions of the breast; Adi and Mus, where adipose and muscle, respectively were assigned to the whole mammary gland. The specific tissue density was kept identical from the CT dataset. Differences in mean doses in the CTV_lob and CTV_fat structures were evaluated for the different tissue assignments. Differences generated by the tissue composition and estimated by Acuros dose calculations in Eclipse were also analysed. RESULTS: From Monte Carlo simulations, the dose in the lobular fraction of the breast, when adipose tissue is assigned in place of muscle, is overestimated by 1.25 ± 0.45%; the dose in the fat fraction of the breast with muscle tissue assignment is underestimated by 1.14 ± 0.51%. Acuros showed an overestimation of 0.98 ± 0.06% and an underestimation of 0.21 ± 0.14% in the lobular and fat portions, respectively. Reason of this dissimilarity resides in the fact that the two calculations, Monte Carlo and Acuros, differently manage the range of CT numbers and the material assignments, having Acuros an overlapping range, where two tissues are both present in defined proportions. CONCLUSION: Although not clinically significant, the dose deposition difference in the lobular and connective fat fraction of the breast tissue lead to an improved knowledge of the possible dose distribution and homogeneity in the breast radiation treatment.

RapidPlan head and neck model: the objectives and possible clinical benefit.

BACKGROUND: To evaluate a knowledge based planning model for RapidPlan (RP) generated for advanced head and neck cancer (HNC) patient treatments, as well its ability to possibly improve the clinical plan quality. The stability of the model was assessed also for a different beam geometry, different dose fractionation and different management of bilateral structures (parotids). METHODS: Dosimetric and geometric data from plans of 83 patients presenting HNC were selected for the model training. All the plans used volumetric modulated arc therapy (VMAT, RapidArc) to treat two targets at dose levels of 69.96 and 54.45 Gy in 33 fractions with simultaneous integrated boost. Two models were generated, the first separating the ipsi- and contra-lateral parotids, while the second associating the two parotids to a single structure for training. The optimization objectives were adjusted to the final model to better translate the institutional planning and dosimetric strategies and trade-offs. The models were validated on 20 HNC patients, comparing the RP generated plans and the clinical plans. RP generated plans were also compared between the clinical beam arrangement and a simpler geometry, as well as for a different fractionation scheme. RESULTS: RP improved significantly the clinical plan quality, with a reduction of 2 Gy, 5 Gy, and 10 Gy of the mean parotid, oral cavity and laryngeal doses, respectively. A simpler beam geometry was deteriorating the plan quality, but in a small amount, keeping a significant improvement relative to the clinical plan. The two models, with one or two parotid structures, showed very similar results. NTCP evaluations indicated the possibility of improving (NTCP decreasing of about 7%) the toxicity profile when using the RP solution. CONCLUSIONS: The HNC RP model showed improved plan quality and planning stability for beam geometry and fractionation. An adequate choice of the objectives in the model is necessary for the trade-offs strategies.

Moderate hypofractionated radiotherapy with volumetric modulated arc therapy and simultaneous integrated boost for pelvic irradiation in prostate cancer.

PURPOSE: The optimal treatment for unfavourable intermediate/high-risk prostate cancer is still debated. In the present study, the pattern of toxicity and early clinical outcome of patients with localized prostate cancer was analyzed. METHODS: A cohort of 90 patients treated on pelvic lymph nodes from 2010 to 2015 was selected. All patients were treated with Volumetric Modulated Arc Therapy (VMAT), and Simultaneous integrated boost (SIB) in 28 fractions; the prostate, the seminal vesicle and the pelvic lymph node received total doses of 74.2, 65.5, and 51.8 Gy, respectively. End points were the detection of acute and late toxicities graded according to the Common Toxicity Criteria CTCAE version 3, evaluating the rectal, genito-urinary and gastro-intestinal toxicity. Correlation of OARs dose parameters and related toxicities was explored. Preliminary overall survival and Progression-free survival (PFS) were evaluated. RESULTS: With a median follow-up of 25 months, no interruptions for treatment-related toxicity were recorded. Univariate analysis among dosimetric data and acute toxicities showed no correlations. Regarding late toxicity: the dose received by a rectal volume of 90 cm3 was found to be significant for toxicity prediction (p = 0.024). PFS was 90.6% and 60.2% at 2 and 4 years, respectively. PFS correlates with age (p = 0.011) and Gleason score (p = 0.011). Stratifying the PSA nadir in quartiles, its value was significant (p = 0.016) in predicting PFS, showing a reduction of PFS of 2 months for each PSA-nadir increase of 0.1 ng/ml. CONCLUSION: HRT with VMAT and SIB on the whole pelvis in unfavourable prostate cancer patients is effective with a mild pattern of toxicity.

Clinical results of stereotactic body radiotherapy (SBRT) in the treatment of isolated local recurrence of pancreatic cancer after R0 surgery: A retrospective study.

OBJECTIVE: To evaluate the efficacy and the feasibility of SBRT for selected patients with isolated local recurrence of pancreatic cancer after radical surgery. METHODS: A retrospective analysis was performed on patients treated with SBRT for isolated local recurrence from resected pancreatic adenocarcinoma, after multidisciplinary board evaluation. Prescription dose was 45 Gy in 6 fractions for all patients. Primary end-point was freedom from local progression (FFLP). Secondary end-points were overall survival (OS), progression free survival (PFS) and toxicity. Local control was defined according to RECIST criteria. Acute and late toxicity was scored according to the NCI Common Terminology Criteria for Adverse Events (CTCAE) v4.0. RESULTS: Between January 2011 and February 2015, 31 patients with isolated local recurrence of resected pancreatic cancer were treated with SBRT. Pancreato-duodenectomy (PD) was performed on 24 patients and distal pancreatectomy (DP) in 7 cases, all with radical resection (R0). Median local recurrence disease free interval (DFI) was 14 months. Median follow-up was 12 months. FFLP was 91% and 82% at 1 and 2-years, respectively. Median PFS was 9 months. Median OS was 18 months. At univariate analysis, OS was correlated with a DFI>18 months. No cases of acute G3 toxicity or greater occurred. CONCLUSIONS: SBRT seems to be an effective and safe therapeutic option for isolated local recurrence of pancreatic cancer after surgery. Encouraging local control rate, very low toxicity profile and effective pain control suggest the crucial role of SBRT in the treatment of these long-survivors selected patients.

Can Stereotactic Body Radiation Therapy Be a Viable and Efficient Therapeutic Option for Unresectable Locally Advanced Pancreatic Adenocarcinoma? Results of a Phase 2 Study.

PURPOSE: To assess the efficacy of stereotactic body radiotherapy in patients with unresectable locally advanced pancreatic cancer. MATERIALS AND METHODS: All patients received a prescription dose of 45 Gy in 6 fractions. Primary end point was freedom from local progression. Secondary end points were overall survival, progression-free survival, and toxicity. Actuarial survival analysis and univariate or multivariate analysis were investigated. RESULTS: Forty-five patients were enrolled in a phase 2 trial. Median follow-up was 13.5 months. Freedom from local progression was 90% at 2 years. On univariate ( P < .03) and multivariate analyses ( P < .001), lesion size was statistically significant for freedom from local progression. Median progression-free survival and overall survival were 8 and 13 months, respectively. On multivariate analysis, tumor size ( P < .001) and freedom from local progression ( P < .002) were significantly correlated with overall survival. Thirty-two (71%) patients with locally advanced pancreatic cancer received chemotherapy before stereotactic body radiotherapy. Median overall survival from diagnosis was 19 months. Multivariate analysis showed that freedom from local progression ( P < .035), tumor diameter ( P < .002), and computed tomography before stereotactic body radiotherapy ( P < .001) were significantly correlated with overall survival from diagnosis. CONCLUSION: Stereotactic body radiotherapy is a safe and effective treatment for patients with locally advanced pancreatic cancer with no G3 toxicity or greater and could be a promising therapeutic option in multimodality treatment regimen.

A geometrical model for the Monte Carlo simulation of the TrueBeam linac.

Monte Carlo simulation of linear accelerators (linacs) depends on the accurate geometrical description of the linac head. The geometry of the Varian TrueBeam linac is not available to researchers. Instead, the company distributes phase-space files of the flattening-filter-free (FFF) beams tallied at a plane located just upstream of the jaws. Yet, Monte Carlo simulations based on third-party tallied phase spaces are subject to limitations. In this work, an experimentally based geometry developed for the simulation of the FFF beams of the Varian TrueBeam linac is presented. The Monte Carlo geometrical model of the TrueBeam linac uses information provided by Varian that reveals large similarities between the TrueBeam machine and the Clinac 2100 downstream of the jaws. Thus, the upper part of the TrueBeam linac was modeled by introducing modifications to the Varian Clinac 2100 linac geometry. The most important of these modifications is the replacement of the standard flattening filters by ad hoc thin filters. These filters were modeled by comparing dose measurements and simulations. The experimental dose profiles for the 6 MV and 10 MV FFF beams were obtained from the Varian Golden Data Set and from in-house measurements performed with a diode detector for radiation fields ranging from 3 × 3 to 40 × 40 cm(2) at depths of maximum dose of 5 and 10 cm. Indicators of agreement between the experimental data and the simulation results obtained with the proposed geometrical model were the dose differences, the root-mean-square error and the gamma index. The same comparisons were performed for dose profiles obtained from Monte Carlo simulations using the phase-space files distributed by Varian for the TrueBeam linac as the sources of particles. Results of comparisons show a good agreement of the dose for the ansatz geometry similar to that obtained for the simulations with the TrueBeam phase-space files for all fields and depths considered, except for the 40 × 40 cm(2) field where the ansatz geometry was able to reproduce the measured dose more accurately. Our approach overcomes some of the limitations of using the Varian phase-space files. It makes it possible to: (i) adapt the initial beam parameters to match measured dose profiles; (ii) reduce the statistical uncertainty to arbitrarily low values; and (iii) assess systematic uncertainties (type B) by using different Monte Carlo codes. One limitation of using phase-space files that is retained in our model is the impossibility of performing accurate absolute dosimetry simulations because the geometrical description of the TrueBeam ionization chamber remains unknown.

Total monitor units influence on plan quality parameters in volumetric modulated arc therapy for breast case.

PURPOSE: To investigate the correlation between total monitor units (MU), dosimetric findings, and pre-treatment quality assurance for volumetric modulated arc therapy (VMAT) by RapidArc (RA). METHODS AND MATERIALS: Ten patients with breast cancer were considered. Dose prescriptions were: 48 Gy and 40.5 Gy in 15 fractions to, respectively, PTV(Boost) and PTVWholeBreast. A reference plan was optimized and four more plans using the "MU Objective", a tool for total MU controlling, were prepared imposing ± 20 and ± 50% total MU for inducing different complexities. Plan objectives were: D95% > 95% for both PTVs, and D2% < 107% for PTV(Boost); mean dose < 9.5 Gy and V20 Gy < 10% for ipsilateral lung; V18 Gy < 5% for heart; mean dose <3 Gy for controlateral breast; furthermore V5 Gy, V10 Gy, V20 Gy, and V30 Gy to body were minimized. Plans were evaluated in terms of technical parameters, dosimetric plan objectives findings and pre-treatment quality assurance (QA). RESULTS: Concerning PTVs, there were no significant differences for target coverage (D95%); mean doses for ipsilateral lung and controlateral breast, and V18 Gy for heart decreased with MUs increasing, reaching a plateau with reference plan. Body volume receiving low dose (V5-10 Gy) was minimized for reference plans. All plans had GAI (3 mm, 3%) > 95%. CONCLUSIONS: The data suggest that the best plan is the reference one, where the "MU Objective" tool was not used during optimisation. Nevertheless, it is advisable to use the "MU Objective" tool for re-planning when low GAI is found to increase its value. In this case, attention should be paid to OARs dose limits, since their values may be increased.

Evaluation of an aSi-EPID with flattening filter free beams: applicability to the GLAaS algorithm for portal dosimetry and first experience for pretreatment QA of RapidArc.

PURPOSE: To demonstrate the feasibility of portal dosimetry with an amorphous silicon mega voltage imager for flattening filter free (FFF) photon beams by means of the GLAaS methodology and to validate it for pretreatment quality assurance of volumetric modulated arc therapy (RapidArc). METHODS: The GLAaS algorithm, developed for flattened beams, was applied to FFF beams of nominal energy of 6 and 10 MV generated by a Varian TrueBeam (TB). The amorphous silicon electronic portal imager [named mega voltage imager (MVI) on TB] was used to generate integrated images that were converted into matrices of absorbed dose to water. To enable GLAaS use under the increased dose-per-pulse and dose-rate conditions of the FFF beams, new operational source-detector-distance (SDD) was identified to solve detector saturation issues. Empirical corrections were defined to account for the shape of the profiles of the FFF beams to expand the original methodology of beam profile and arm backscattering correction. GLAaS for FFF beams was validated on pretreatment verification of RapidArc plans for three different TB linacs. In addition, the first pretreatment results from clinical experience on 74 arcs were reported in terms of γ analysis. RESULTS: MVI saturates at 100 cm SDD for FFF beams but this can be avoided if images are acquired at 150 cm for all nominal dose rates of FFF beams. Rotational stability of the gantry-imager system was tested and resulted in a minimal apparent imager displacement during rotation of 0.2 ± 0.2 mm at SDD = 150 cm. The accuracy of this approach was tested with three different Varian TrueBeam linacs from different institutes. Data were stratified per energy and machine and showed no dependence with beam quality and MLC model. The results from clinical pretreatment quality assurance, provided a gamma agreement index (GAI) in the field area for six and ten FFF beams of (99.8 ± 0.3)% and (99.5 ± 0.6)% with distance to agreement and dose difference criteria set to 3 mm/3% with 2 mm/2% thresholds, GAI resulted (95.7.0 ± 2.3)% and (97.2 ± 2.1)%. CONCLUSIONS: The GLAaS methodology, introduced in clinical practice for conventional flattened photon beams for machine, IMRT, and RapidArc quality assurance, was successfully adapted for FFF beams of Varian TrueBeam Linac. The detector saturation effects could be eliminated if the portal images acquired at 150 cm for all nominal dose rates of FFF beams.

Dosimetric evaluation of photon dose calculation under jaw and MLC shielding.

PURPOSE: The accuracy of photon dose calculation algorithms in out-of-field regions is often neglected, despite its importance for organs at risk and peripheral dose evaluation. The present work has assessed this for the anisotropic analytical algorithm (AAA) and the Acuros-XB algorithms implemented in the Eclipse treatment planning system. Specifically, the regions shielded by the jaw, or the MLC, or both MLC and jaw for flattened and unflattened beams have been studied. METHODS: The accuracy in out-of-field dose under different conditions was studied for two different algorithms. Measured depth doses out of the field, for different field sizes and various distances from the beam edge were compared with the corresponding AAA and Acuros-XB calculations in water. Four volumetric modulated arc therapy plans (in the RapidArc form) were optimized in a water equivalent phantom, PTW Octavius, to obtain a region always shielded by the MLC (or MLC and jaw) during the delivery. Doses to different points located in the shielded region and in a target-like structure were measured with an ion chamber, and results were compared with the AAA and Acuros-XB calculations. Photon beams of 6 and 10 MV, flattened and unflattened were used for the tests. RESULTS: Good agreement between calculated and measured depth doses was found using both algorithms for all points measured at depth greater than 3 cm. The mean dose differences (± 1SD) were -8% ± 16%, -3% ± 15%, -16% ± 18%, and -9% ± 16% for measurements vs AAA calculations and -10% ± 14%, -5% ± 12%, -19% ± 17%, and -13% ± 14% for Acuros-XB, for 6X, 6 flattening-filter free (FFF), 10X, and 10FFF beams, respectively. The same figures for dose differences relative to the open beam central axis dose were: -0.1% ± 0.3%, 0.0% ± 0.4%, -0.3% ± 0.3%, and -0.1% ± 0.3% for AAA and -0.2% ± 0.4%, -0.1% ± 0.4%, -0.5% ± 0.5%, and -0.3% ± 0.4% for Acuros-XB. Buildup dose was overestimated with AAA, while Acuros-XB gave results more consistent with measurements. From RapidArc plan analysis the average difference between calculation and measurement in the shielded region was -0.3% ± 0.4% and -2.5% ± 1.2% for AAA and Acuros-XB, respectively, relative to the mean target dose value (1.6% ± 2.3%, -12.7% ± 4.0% if relative to each local value). These values were compared with the corresponding differences in the target structure: -0.7% ± 2.3% for AAA, and -0.5% ± 2.3% for Acuros-XB. CONCLUSIONS: The two algorithms analyzed showed encouraging results in predicting out-of-field region dose for clinical use.

Critical appraisal of volumetric-modulated arc therapy compared with electrons for the radiotherapy of cutaneous Kaposi's sarcoma of lower extremities with bone sparing.

OBJECTIVE: To evaluate the use of volumetric-modulated arc therapy [VMAT, RapidArc® (RA); Varian Medical Systems, Palo Alto, CA] for the treatment of cutaneous Kaposi's sarcoma (KS) of lower extremities with adequate target coverage and high bone sparing, and to compare VMAT with electron beam therapy. METHODS: 10 patients were planned with either RA or electron beams. The dose was prescribed to 30 Gy, 10 fractions, to mean the planning target volume (PTV), and significant maximum dose to bone was limited to 30 Gy. Plans were designed for 6-MV photon beams for RA and 6 MeV for electrons. Dose distributions were computed with AcurosXB® (Varian Medical Systems) for photons and with a Monte Carlo algorithm for electrons. RESULTS: V(90%) was 97.3±1.2 for RA plans and 78.2±2.6 for electrons; similarly, V(107%) was 2.5±2.2 and 37.7±3.4, respectively. RA met coverage criteria. Concerning bone sparing, D(2%) was 29.6±1.1 for RA and 31.0±2.4 for electrons. Although acceptable for bone involvement, pronounced target coverage violations were obtained for electron plans. Monitor units were similar for electrons and RA, although for the latter they increased when superior bone sparing was imposed. Delivery times were 12.1±4.0 min for electrons and 4.8±1.3 min for the most modulated RA plans. CONCLUSION: High plan quality was shown for KS in the lower extremities using VMAT, and this might simplify their management in comparison with the more conventional usage of electrons, particularly in institutes with limited staff resources and heavy workloads. ADVANCES IN KNOWLEDGE: VMAT is also dosimetrically extremely advantageous in a typology of treatments where electron beam therapy is mainly considered to be effective owing to the limited penetration of the beams.

Radiotherapy with volumetric modulated arc therapy for hepatocellular carcinoma patients ineligible for surgery or ablative treatments.

PURPOSE: The aim of this article is to report the dosimetric and clinical findings in the treatment of primary hepatocellular carcinoma (HCC) with volumetric modulated arc therapy (VMAT, RapidArc). METHODS AND MATERIALS: A total of 138 patients were investigated. Dose prescription ranged from 45-66 Gy. Most patients (88.4 %) presented AJCC stage III or IV and 83 % were N0-M0. All were classified as Barcelona Clinic Liver Cancer (BCLC) stage A-C. All patients were treated using 10 MV photons with single or multiple, coplanar or non-coplanar arcs, and cone-down technique in case of early response of tumors. RESULTS: The patients' median age was 66 years (range 27-87 years), 83 % were treated with 60 Gy (12 % at 45 Gy, 6 % at 66 Gy), 62 % with cone-down, 98 % with multiple arcs. The mean initial planning target volume (PTV) was 777 ± 632 cm(3); the mean final PTV (after the cone-down) was 583 ± 548 cm(3). High target coverage was achieved. The final PTV was V98% > 98 %. Kidneys received on average 5 and 8 Gy (left and right), while the maximum dose to the spinal cord was 22 Gy; mean doses to esophagus and stomach were 23 Gy and 15 Gy, respectively. The average volume of healthy liver receiving more than 30 Gy was 294 ± 145 cm(3). Overall survival at 12 months was 45 %; median survival was 10.3 months (95 % confidence interval 7.2-13.3 months). Actuarial local control at 6 months was 95 % and 93.7 % at 12 months. The median follow-up was 9 months and a maximum of 28 months. CONCLUSION: This study showed from the dosimetric point of view the feasibility and technical appropriateness of RapidArc for the treatment of HCC. Clinical results were positive and might suggest, with appropriate care, to consider RapidArc as an additional therapeutic opportunity for these patients.

Small field segments surrounded by large areas only shielded by a multileaf collimator: comparison of experiments and dose calculation.

PURPOSE: Complex radiotherapy fields delivered using a tertiary multileaf collimator (MLC) often feature small open segments surrounded by large areas of the beam only shielded by the MLC. The aim of this study was to test the ability of two modern dose calculation algorithms to accurately calculate the dose in these fields which would be common, for example, in volumetric modulated arc treatment (VMAT) and study the impact of variations in dosimetric leaf gap (DLG), focal spot size, and MLC transmission in the beam models. METHODS: Nine test fields with small fields (0.6-3 cm side length) surrounded by large MLC shielded areas (secondary collimator 12 × 12 cm(2)) were created using a 6 MV beam from a Varian Clinac iX linear accelerator with 120 leaf MLC. Measurements of output factors and profiles were performed using a diamond detector (PTW) and compared to two dose calculations algorithms anisotropic analytical algorithm [(AAA) and Acuros XB] implemented on a commercial radiotherapy treatment planning system (Varian Eclipse 10). RESULTS: Both calculation algorithms predicted output factors within 1% for field sizes larger than 1 × 1 cm(2). For smaller fields AAA tended to underestimate the dose. Profiles were predicted well for all fields except for problems of Acuros XB to model the secondary penumbra between MLC shielded fields and the secondary collimator. A focal spot size of 1 mm or less, DLG 1.4 mm and MLC transmission of 1.4% provided a generally good model for our experimental setup. CONCLUSIONS: AAA and Acuros XB were found to predict the dose under small MLC defined field segments well. While DLG and focal spot affect mostly the penumbra, the choice of correct MLC transmission will be essential to model treatments such as VMAT accurately.