Inter-institutional variability of knowledge-based plan prediction of left whole breast irradiation.

PURPOSE: Within a multi-institutional project, we aimed to assess the transferability of knowledge-based (KB) plan prediction models in the case of whole breast irradiation (WBI) for left-side breast irradiation with tangential fields (TF). METHODS: Eight institutions set KB models, following previously shared common criteria. Plan prediction performance was tested on 16 new patients (2 pts per centre) extracting dose-volume-histogram (DVH) prediction bands of heart, ipsilateral lung, contralateral lung and breast. The inter-institutional variability was quantified by the standard deviations (SDint) of predicted DVHs and mean-dose (Dmean). The transferability of models, for the heart and the ipsilateral lung, was evaluated by the range of geometric Principal Component (PC1) applicability of a model to test patients of the other 7 institutions. RESULTS: SDint of the DVH was 1.8 % and 1.6 % for the ipsilateral lung and the heart, respectively (20 %-80 % dose range); concerning Dmean, SDint was 0.9 Gy and 0.6 Gy for the ipsilateral lung and the heart, respectively (<0.2 Gy for contralateral organs). Mean predicted doses ranged between 4.3 and 5.9 Gy for the ipsilateral lung and 1.1-2.3 Gy for the heart. PC1 analysis suggested no relevant differences among models, except for one centre showing a systematic larger sparing of the heart, concomitant to a worse PTV coverage, due to high priority in sparing the left anterior descending coronary artery. CONCLUSIONS: Results showed high transferability among models and low inter-institutional variability of 2% for plan prediction. These findings encourage the building of benchmark models in the case of TF-WBI.

Knowledge-based multi-institution plan prediction of whole breast irradiation with tangential fields.

PURPOSE: To quantify inter-institute variability of Knowledge-Based (KB) models for right breast cancer patients treated with tangential fields whole breast irradiation (WBI). MATERIALS AND METHODS: Ten institutions set KB models by using RapidPlan (Varian Inc.), following previously shared methodologies. Models were tested on 20 new patients from the same institutes, exporting DVH predictions of heart, ipsilateral lung, contralateral lung, and contralateral breast. Inter-institute variability was quantified by the inter-institute SDint of predicted DVHs/Dmean. Association between lung sparing vs PTV coverage strategy was also investigated. The transferability of models was evaluated by the overlap of each model's geometric Principal Component (PC1) when applied to the test patients of the other 9 institutes. RESULTS: The overall inter-institute variability of DVH/Dmean ipsilateral lung dose prediction, was less than 2% (20%-80% dose range) and 0.55 Gy respectively (1SD) for a 40 Gy in 15 fraction schedule; it was < 0.2 Gy for other OARs. Institute 6 showed the lowest mean dose prediction value and no overlap between PTV and ipsilateral lung. Once excluded, the predicted ipsilateral lung Dmean was correlated with median PTV D99% (R2 = 0.78). PC1 values were always within the range of applicability (90th percentile) for 7 models: for 2 models they were outside in 1/18 cases. For the model of institute 6, it failed in 7/18 cases. The impact of inter-institute variability of dose calculation was tested and found to be almost negligible. CONCLUSIONS: Results show limited inter-institute variability of plan prediction models translating in high inter-institute interchangeability, except for one of ten institutes. These results encourage future investigations in generating benchmarks for plan prediction incorporating inter-institute variability.

Long-term proactive management of psoriasis with calcipotriol and betamethasone dipropionate foam: an Italian consensus through a combined nominal group technique and Delphi approach.

BACKGROUND: Although long-term management of psoriasis is paramount, this approach is challenging in clinical practice. In the recent PSO-LONG trial, a fixed-dose combination of betamethasone dipropionate (BD) and calcipotriol (Cal) foam applied twice a week on non-consecutive days for 52 weeks (proactive treatment) reduced the risk of relapse. However, the role of Cal/BD foam in the long-term management of psoriasis needs further clarifications. The ProActive Management (PAM) program, a nationwide Italian project, aims at reaching a consensus on the role of proactive management of psoriasis. METHODS: A steering committee generated some statements through the nominal group technique (NGT). The statements were voted by an expert panel in an adapted Delphi voting process. RESULTS: Eighteen statements were proposed, and the majority of them (14/18) reached a consensus during the Delphi voting. The need to provide long-term proactive topical treatment to reduce the risk of relapse for the treatment of challenging diseases sites or in patients where phototherapy or systemic therapies are contraindicated/ineffective was widely recognized. A consensus was reached about the possibility to associate the proactive treatment with systemic and biological therapies, without the need for dose intensification, thus favoring a prolonged remission. Moreover, the proactive treatment was recognized as more effective than weekend therapy in increasing time free from relapses. Approaches to improve adherence, on the other hand, need further investigation. CONCLUSIONS: The inclusion in guidelines of a proactive strategy among the effective treatment options will be a fundamental step in the evolution of a mild-moderate psoriasis therapeutic approach.

Variations in Head and Neck Treatment Plan Quality Assessment Among Radiation Oncologists and Medical Physicists in a Single Radiotherapy Department.

BACKGROUND: Agreement between planners and treating radiation oncologists (ROs) on plan quality criteria is essential for consistent planning. Differences between ROs and planning medical physicists (MPs) in perceived quality of head and neck cancer plans were assessed. MATERIALS AND METHODS: Five ROs and four MPs scored 65 plans for in total 15 patients. For each patient, the clinical (CLIN) plan and two or four alternative plans, generated with automated multi-criteria optimization (MCO), were included. There was always one MCO plan aiming at maximally adhering to clinical plan requirements, while the other MCO plans had a lower aimed quality. Scores were given as follows: 1-7 and 1-2, not acceptable; 3-5, acceptable if further planning would not resolve perceived weaknesses; and 6-7, straightway acceptable. One MP and one RO repeated plan scoring for intra-observer variation assessment. RESULTS: For the 36 unique observer pairs, the median percentage of plans for which the two observers agreed on a plan score (100% = 65 plans) was 27.7% [6.2, 40.0]. In the repeat scoring, agreements between first and second scoring were 52.3% and 40.0%, respectively. With a binary division between unacceptable (scores 1 and 2) and acceptable (3-7) plans, the median inter-observer agreement percentage was 78.5% [63.1, 86.2], while intra-observer agreements were 96.9% and 86.2%. There were no differences in observed agreements between RO-RO, MP-MP, and RO-MP pairs. Agreements for the highest-quality, automatically generated MCO plans were higher than for the CLIN plans. CONCLUSIONS: Inter-observer differences in plan quality scores were substantial and could result in inconsistencies in generated treatment plans. Agreements among ROs were not better than between ROs and MPs, despite large differences in training and clinical role. High-quality automatically generated plans showed the best score agreements.

Use of knowledge based DVH predictions to enhance automated re-planning strategies in head and neck adaptive radiotherapy.

This study aimed to investigate if a commercial, knowledge-based tool for radiotherapy planning could be used to estimate the amount of sparing in organs at risk (OARs) in the re-planning strategy for adaptive radiotherapy (ART). Eighty head and neck (HN) VMAT Pareto plans from our institute's database were used to train a knowledge-based planning (KBP) model. An evaluation set of another 20 HN patients was randomly selected. For each patient in the evaluation set, the planning computed tomography (CT) and 2 sets of on-board cone-beam CT, corresponding to the middle and second half of the radiotherapy treatment course, were extracted. The original plan was re-calculated on a daily deformed CT (delivered dose-volume histogram (DVH)) and compared with the KBP DVH predictions and with the final KBP DVH after optimisation of the plan, which was performed on the same image sets. To evaluate the feasibility of this method, the range of KBP DVH uncertainties was compared with the gains obtained from re-planning. DVH differences and receiver operating characteristic (ROC) curve analysis were used for this purpose. On average, final KBP uncertainties were smaller than the gain in re-planning. Statistical tests confirmed significant differences between the two groups. ROC analysis showed KBP performance in terms of area under the curve values higher than 0.7, which confirmed a good accuracy in predicted values. Overall, for 48% of cases, KBP predicted a desirable outcome from re-planning, and the final dose confirmed an effective gain in 47% of cases. We have established a systematic workflow to identify effective OAR sparing in re-planning based on KBP predictions that can be implemented in an on-line, ART process.

EPID-based 3D dosimetry for pre-treatment FFF VMAT stereotactic body radiotherapy plan verification using dosimetry CheckTM.

PURPOSE: The software Dosimetry Check (DC) reconstructs the 3D dose distribution on CT images data set by using EPID measured signal. This study aimed to evaluate DC for stereotactic body radiotherapy (SBRT) with unflattened photon beams (FFF) for dosimetric independent plan verification in pre-treatment modality. METHODS: DC v.4.1 was configured for Varian TrueBeam STx FFF beams equipped with EPID aS-1200. The DC FFF models were tested using arc open fields (from 1×1 cm2 to 15×15 cm2) and VMAT (Volumetric Modulated Arc Therapy) SBRT plans on phantom and patient CTs. DC dose distributions (DDC) were compared with that calculated by Eclipse with Acuros XB algorithm (DAXB) and one measured by Octavius 1000 SRS detector (DOCT). All differences were quantified in terms of the local 3D gamma passing rate (%GP), DVH and point dose differences. RESULTS: DC was configured for FFF VMAT using an appropriate correction procedure. %GP2%2mm (mean±standard deviation) of DOCT-DDC was 96.3±2.7% for open fields whereas it was 90.1±5.9% for plans on homogeneous phantom CT. However, average %GP3%3mm of DAXB-DDC was 95.0±4.1 for treatments on patient CT. The fraction of plans passing the %GP3%3mm DQA tolerance level [10% (50%) of maximum dose threshold] were 20/20 (14/20) and 18/20 (16/20) for OCT on phantom CT and DC on patient CT, respectively. CONCLUSIONS: DC characterization for FFF beams was performed. For stereotactic VMAT plan verifications DC showed good agreement with TPS whereas underlined discrepancies with Octavius in the high dose regions. A customized tolerance level is required for EPID-based VMAT FFF pre-treatment verification when DC system is applied.

The influence of small field output factors simulated uncertainties on the calculated dose in VMAT plans for brain metastases: a multicentre study.

OBJECTIVES: This multicentric study was carried out to investigate the impact of small field output factors (OFs) inaccuracies on the calculated dose in volumetric arctherapy (VMAT) radiosurgery brain plans. METHODS: Nine centres, realised the same five VMAT plans with common planning rules and their specific clinical equipment Linac/treatment planning system commissioned with their OFs measured values (OFbaseline). In order to simulate OFs errors, two new OFs sets were generated for each centre by changing only the OFs values of the smallest field sizes (from 3.2 × 3.2 cm2 to 1 × 1 cm2) with well-defined amounts (positive and negative). Consequently, two virtual machines for each centre were recommissioned using the new OFs and the percentage dose differences ΔD (%) between the baseline plans and the same plans recalculated using the incremented (OFup) and decremented (OFdown) values were evaluated. The ΔD (%) were analysed in terms of planning target volume (PTV) coverage and organs at risk (OARs) sparing at selected dose/volume points. RESULTS: The plans recalculated with OFdown sets resulted in higher variation of doses than baseline within 1.6 and 3.4% to PTVs and OARs respectively; while the plans with OFup sets resulted in lower variation within 1.3% to both PTVs and OARs. Our analysis highlights that OFs variations affect calculated dose depending on the algorithm and on the delivery mode (field jaw/MLC-defined). The Monte Carlo (MC) algorithm resulted significantly more sensitive to OFs variations than all of the other algorithms. CONCLUSION: The aim of our study was to evaluate how small fields OFs inaccuracies can affect the dose calculation in VMAT brain radiosurgery treatments plans. It was observed that simulated OFs errors, return dosimetric calculation accuracies within the 3% between concurrent plans analysed in terms of percentage dose differences at selected dose/volume points of the PTV coverage and OARs sparing. ADVANCES IN KNOWLEDGE: First multicentre study involving different Planning/Linacs about undetectable errors in commissioning output factor for small fields.

Computed Tomography to Cone Beam Computed Tomography Deformable Image Registration for Contour Propagation Using Head and Neck, Patient-Based Computational Phantoms: A Multicenter Study.

PURPOSE: To investigate the performance of various algorithms for deformable image registration (DIR) for propagating regions of interest (ROIs) using multiple commercial platforms, from computed tomography to cone beam computed tomography (CBCT) and megavoltage computed tomography. METHODS AND MATERIALS: Fourteen institutions participated in the study using 5 commercial platforms: RayStation (RaySearch Laboratories, Stockholm, Sweden), MIM (Cleveland, OH), VelocityAI and SmartAdapt (Varian Medical Systems, Palo Alto, CA), and ABAS (Elekta AB, Stockholm, Sweden). Algorithms were tested on synthetic images generated with the ImSimQA (Oncology Systems Limited, Shrewsbury, UK) package by applying 2 specific deformation vector fields (DVF) to real head and neck patient datasets. On-board images from 3 systems were used: megavoltage computed tomography from Tomotherapy and 2 kinds of CBCT from a clinical linear accelerator. Image quality of the system was evaluated. The algorithms' accuracy was assessed by comparing the DIR-mapped ROIs returned by each center with those of the reference, using the Dice similarity coefficient and mean distance to conformity metrics. Statistical inference on the validation results was carried out to identify the prognostic factors of DIR performance. RESULTS: Analyzing 840 DIR-mapped ROIs returned by the centers, it was demonstrated that DVF intensity and image quality were significant prognostic factors of DIR performance. The accuracy of the propagated contours was generally high, and acceptable DIR performance can be obtained with lower-dose CBCT image protocols. CONCLUSIONS: The performance of the systems proved to be image quality specific, depending on the DVF type and only partially on the platforms. All systems proved to be robust against image artifacts and noise, except the demon-based software.

Community approach for reducing small field measurement errors: Experience over 24 centres.

PURPOSE: The complexity of the modern Stereotactic Body Radiation Therapy (SBRT) techniques requires comprehensive quality assurance programs, to ensure the right treatment to the patient. Dosimetry of small radiation fields is a challenge especially for radiotherapy centres starting to work on this issue. The matter to be discussed here concerns the need of detailed measurement procedures and cross checks to be paired to the usual recommendations on detectors and correction factors. MATERIALS AND METHODS: The presented work involved 24 Italian radiotherapy centres, with the specific purpose to minimize systematic errors in output factor measurements over different radiotherapy centres. Using the unshielded silicon diode IBA Razor, reference curves for the relative signal ratio (RSR) as a function of beam size were created for each Linac family. RESULTS: With this study we have demonstrated consistency of small field dosimetry on all the centres involved, moreover all radiotherapy centres using Razor are allowed to compare measurements amongst each other and centres with values deviating more than 5% from the reference curve are advised to repeat their measurements. With this procedure, some critical issues were detected from two centres in RSR measurements, that, if implemented into the own treatment planning system, would induce an unwanted overdosage larger than 5%. CONCLUSIONS: The proposed approach could allow one to envision high-skilled therapy centres providing support to those featuring minor experience and could represent an important strategy for the clinical implementation of emerging technologies at high quality levels. The methodology adopted exploits crowd knowledge methods which could be applied in others areas of radiation dosimetry.

Pareto-optimal plans as ground truth for validation of a commercial system for knowledge-based DVH-prediction.

PURPOSE: Treatment plans manually generated in clinical routine may suffer from variations and inconsistencies in quality. Using such plans for validating a DVH prediction algorithm might obscure its intrinsic prediction accuracy. In this study we used a recently published large database of Pareto-optimal prostate cancer plans to assess the prediction accuracy of a commercial knowledge-based DVH prediction algorithm, RapidPlan. The database plans were consistently generated with automated planning using an independent optimizer, and can be considered as aground truth of plan quality. METHODS: Prediction models were generated using training sets with 20, 30, 45, 55 and 114 Pareto-optimal plans. Model-20 and Model-30 were built using 5 groups of randomly selected training patients. For 60 independent Pareto-optimal validation plans, predicted and database DVHs were compared. RESULTS: For model-114, differences between predicted and database mean doses of more than ±â€¯10% in rectum, anus and bladder, occurred for 23.3%, 55.0%, and 6.7% of the validation plans, respectively. For rectum V65Gy and V75Gy, differences outside the ±10% range were observed in 21.7% and 70.0% of validation plans, respectively. For 61.7% of validation plans, inaccuracies in predicted rectum DVHs resulted in a deviation in predicted NTCP for rectal bleeding outside ±10%. With smaller training sets the DVH prediction performance deteriorated, showing dependence on the selected training patients. CONCLUSION: Even when analysed with Pareto-optimal plans with highly consistent quality, clinically relevant deviations in DVH predictions were observed. Such deviations could potentially result in suboptimal plans for new patients. Further research on DVH prediction models is warranted.

Intensity-modulated radiation therapy and volumetric modulated arc therapy versus conventional conformal techniques at high energy: Dose assessment and impact on second primary cancer in the out-of-field region.

The aim of this work was to estimate peripheral neutron and photon doses associated with the conventional 3D conformal radiotherapy techniques in comparison to modern ones such as Intensity modulated radiation therapy and volumetric modulated arc therapy. Assessment in terms of second cancer incidence ought to peripheral doses was also considered. For that, a dosimetric methodology proposed by the authors has been applied beyond the region where there is no CT information and, thus, treatment planning systems do not calculate and where, nonetheless, about one third of second primary cancers occurs.

A multi-center output factor intercomparison to uncover systematic inaccuracies in small field dosimetry.

Large uncertainties in output factor (OF) small fields dosimetry motivated multicentric studies. The focus of the study was the determination of the OFs, for different linacs and radiosurgery units, using new-generation detectors. Intercomparison studies between radiotherapy centers improved quality dosimetry practices. Results confirmed the effectiveness of the studies to uncover large systematic inaccuracies in small field dosimetry.

Performance of commercially available deformable image registration platforms for contour propagation using patient-based computational phantoms: A multi-institutional study.

PURPOSE: To investigate the performance of various algorithms for deformable image registration (DIR) to propagate regions of interest (ROIs) using multiple commercial platforms. METHODS AND MATERIALS: Thirteen institutions participated in the study with six commercial platforms: RayStation (RaySearch Laboratories, Stockholm, Sweden), MIM (Cleveland, OH, USA), VelocityAI and Smart Adapt (Varian Medical Systems, Palo Alto, CA, USA), Mirada XD (Mirada Medical Ltd, Oxford, UK), and ABAS (Elekta AB, Stockholm, Sweden). The DIR algorithms were tested on synthetic images generated with the ImSimQA package (Oncology Systems Limited, Shrewsbury, UK) by applying two specific Deformation Vector Fields (DVF) to real patient data-sets. Head-and-neck (HN), thorax, and pelvis sites were included. The accuracy of the algorithms was assessed by comparing the DIR-mapped ROIs from each center with those of reference, using the Dice Similarity Coefficient (DSC) and Mean Distance to Conformity (MDC) metrics. Statistical inference on validation results was carried out in order to identify the prognostic factors of DIR performances. RESULTS: DVF intensity, anatomic site and participating center were significant prognostic factors of DIR performances. Sub-voxel accuracy was obtained in the HN by all algorithms. Large errors, with MDC ranging up to 6 mm, were observed in low-contrast regions that underwent significant deformation, such as in the pelvis, or large DVF with strong contrast, such as the clinical tumor volume (CTV) in the lung. Under these conditions, the hybrid DIR algorithms performed significantly better than the free-form intensity based algorithms and resulted robust against intercenter variability. CONCLUSIONS: The performances of the systems proved to be site specific, depending on the DVF type and the platforms and the procedures used at the various centers. The pelvis was the most challenging site for most of the algorithms, which failed to achieve sub-voxel accuracy. Improved reproducibility was observed among the centers using the same hybrid registration algorithm.

Knowledge-based treatment planning: An inter-technique and inter-system feasibility study for prostate cancer.

PURPOSE: Helical Tomotherapy (HT) plans were used to create two RapidPlan knowledge-based (KB) models to generate plans with different techniques and to guide the optimization in a different treatment planning system for prostate plans. Feasibility and performance of these models were evaluated. MATERIAL AND METHODS: two sets of 35 low risk (LR) and 30 intermediate risk (IR) prostate cancer cases who underwent HT treatments were selected to train RapidPlan models. The KB predicted constraints were used to perform new 20KB plans using RapidArc technique (KB-RA) (inter-technique validation), and to optimise 20 new HT (KB-HT) plans in the Tomoplan (inter-system validation). For each validation modality, KB plans were benchmarked with the manual plans created by an expert planner (EP). RESULTS: RapidPlan was successfully configured using HT plans. The KB-RA plans fulfilled the clinical dose-volume requirements in 100% and 92% of cases for planning target volumes (PTVs) and organs at risk (OARs), respectively. For KB-HT plans these percentages were found to be a bit lower: 90% for PTVs and 86% for OARs. In comparison to EP plans, the KB-RA plans produced higher bladder doses for both LR and IR, and higher rectum doses for LR. KB-HT and EP plans produced similar results. CONCLUSION: RapidPlan can be trained to create models by using plans of a different treatment modality. These models were suitable for generating clinically acceptable plans for inter-technique and inter-system applications. The use of KB models based on plans of consolidated technique could be useful with a new treatment modality.

Small field output factors evaluation with a microDiamond detector over 30 Italian centers.

PURPOSE: The aim of the study was a multicenter evaluation of MLC&jaws-defined small field output factors (OF) for different linear accelerator manufacturers and for different beam energies using the latest synthetic single crystal diamond detector commercially available. The feasibility of providing an experimental OF data set, useful for on-site measurements validation, was also evaluated. METHODS: This work was performed in the framework of the Italian Association of Medical Physics (AIFM) SBRT working group. The project was subdivided in two phases: in the first phase each center measured OFs using their own routine detector for nominal field sizes ranging from 10×10cm2 to 0.6×0.6cm2. In the second phase, the measurements were repeated in all centers using the PTW 60019 microDiamond detector. RESULTS: The project enrolled 30 Italian centers. Micro-ion chambers and silicon diodes were used for OF measurements in 24 and 6 centers respectively. Gafchromic films and TLDs were used for very small field OFs in 3 and 1 centers. Regarding the measurements performed with the user's detectors, OF standard deviations (SD) for field sizes down to 2×2cm2 were in all cases <2.7%. In the second phase, a reduction of around 50% of the SD was obtained using the microDiamond detector. CONCLUSIONS: The measured values presented in this multicenter study provide a consistent dataset for OFs that could be a useful tool for improving dosimetric procedures in centers. The microDiamond data present a small variation among the centers confirming that this detector can contribute to improve overall accuracy in radiotherapy.

Technical Note: Multicenter study of TrueBeam FFF beams with a new stereotactic diode: Can a common small field signal ratio curve be defined?

PURPOSE: Small radiation fields (<30 mm) are typically involved in stereotactic body radiation therapy procedures. Output factor measurements are subjected to large uncertainties. The signal ratio (SR) readings, defined as the ratio of central axis reading, respectively, in the actual field size and in the reference field size, were evaluated in several centers and a common mathematical description of the SR curve was investigated. METHODS: A couple of new unshielded stereotactic diodes (Razor, IBA) was tested under eight different TrueBeams using 10 MV flattering filter free beams with high dose rate (2400 MU/min). Small fields, ranging from 6 to 50 mm, were analyzed in terms of profiles and central axis point measurements. SRs were normalized to 30 mm field and were calculated as a function of nominal field size (NFS) and effective field size (EFS). From SRs acquired using Razor1 (four centers), a theoretical equation was extrapolated. Three centers with Razor2 were used to test the mathematical relationship. Finally, the two diodes were directly compared in the last center. RESULTS: The EFS was systematically smaller than NFS (p < 0.01) for all field size ranges, with mean difference of 0.9 ± 0.5 mm. The SR fits using the NFS and EFS had, respectively, R2 = 0.989 and R2 ≫ 0.999. The Razor2 centers' mean deviation from the predicted SRs, using the NFS and EFS fits, was, respectively, 3.4% and 0.5%. The maximum deviations were 5.0% (6 mm field size) for NFS and 1.9% for EFS. Maximum deviation of 0.5% between the two Razors was observed. CONCLUSIONS: EFS measurements were confirmed to be mandatory when comparing SRs over different centers. An equation establishing a functional relation between SRs and the EFS was obtained and tested for the new Razor diode.

Lung stereotactic ablative body radiotherapy: A large scale multi-institutional planning comparison for interpreting results of multi-institutional studies.

PURPOSE: A large-scale multi-institutional planning comparison on lung cancer SABR is presented with the aim of investigating possible criticism in carrying out retrospective multicentre data analysis from a dosimetric perspective. METHODS: Five CT series were sent to the participants. The dose prescription to PTV was 54Gy in 3 fractions of 18Gy. The plans were compared in terms of PTV-gEUD2 (generalized Equivalent Uniform Dose equivalent to 2Gy), mean dose to PTV, Homogeneity Index (PTV-HI), Conformity Index (PTV-CI) and Gradient Index (PTV-GI). We calculated the maximum dose for each OAR (organ at risk) considered as well as the MLD2 (mean lung dose equivalent to 2Gy). The data were stratified according to expertise and technology. RESULTS: Twenty-six centers equipped with Linacs, 3DCRT (4% - 1 center), static IMRT (8% - 2 centers), VMAT (76% - 20 centers), CyberKnife (4% - 1 center), and Tomotherapy (8% - 2 centers) collaborated. Significant PTV-gEUD2 differences were observed (range: 105-161Gy); mean-PTV dose, PTV-HI, PTV-CI, and PTV-GI were, respectively, 56.8±3.4Gy, 14.2±10.1%, 0.70±0.15, and 4.9±1.9. Significant correlations for PTV-gEUD2 versus PTV-HI, and MLD2 versus PTV-GI, were observed. CONCLUSIONS: The differences in terms of PTV-gEUD2 may suggest the inclusion of PTV-gEUD2 calculation for retrospective data inter-comparison.

Multicentre treatment planning inter-comparison in a national context: The liver stereotactic ablative radiotherapy case.

PURPOSE: To compare five liver metastasis stereotactic ablative radiotherapy (SABR) plans optimised in fourteen centres with 3D-Conformal-RT, IMRT, VMAT, CyberKnife and Tomotherapy and identify possible dosimetric differences. METHODS: Dose prescription was 75 Gy in 3 fractions, normalised at 67%-95% isodose. RESULTS: Excluding few cases, all institutions achieved the planning objectives. Differences up to 40% and 25% in mean dose to liver and PTV were found. No significant correlations between technological factors and DVH for target and OARs were observed; the optimisation strategies selected by the planners played a key role in the planning procedure. CONCLUSIONS: The human factor and the constraints imposed to the target volume have a greater dosimetric impact than treatment planning and radiation delivery technology in stereotactic treatment of liver metastases. Significant differences found both in terms of dosimetric target coverage and OAR sparing should be taken into consideration before starting a multi-institutional SARB clinical trial.

Toxicity and cosmetic outcome of hypofractionated whole-breast radiotherapy: predictive clinical and dosimetric factors.

PURPOSE: The objective of this study is to evaluate toxicity and cosmetic outcome in breast cancer patients treated with adjuvant hypo fractionated radiotherapy to the whole breast, and to identify the risk factors for toxicity. METHODS AND MATERIALS: Two hundred twelve women with early breast cancer underwent conserving surgery were enrolled in the study. The patients received 40.05 Gy in 15 daily fractions, 2.67 Gy per fraction. The boost to the tumor bed was administered with a total dose of 9 Gy in 3 consecutive fractions in 55 women. Physician-rated acute and late toxicity and cosmetic outcome (both subjective and objective) were prospectively assessed during and after radiotherapy. RESULTS: In our population study the mean age was 63 with the 17% (36 pts) of the women younger than 50 years.The median follow-up was 34 months. By the end of RT, 35 patients out of 212 (16%) no acute toxicity, according to the RTOG criteria, while 145 (68%) and 31 patients (15%) developed grade 1 and grade 2 acute skin toxicity, respectively.Late skin toxicity evaluation was available for all 212 patients with a minimum follow up of 8 months. The distribution of toxicity was: 39 pts (18%) with grade 1 and 2 pts (1%) with grade 2. No worse late skin toxicity was observed.Late subcutaneous grade 0-1 toxicity was recorded in 208 patients (98%) and grade 2 toxicity in 3 patients (2%), while grade 3 was observed in 1 patient only. At last follow up, a subjective and objective good or excellent cosmetic outcome was reported in 93% and 92% of the women, respectively. At univariate and multivariate analysis, the late skin toxicity was correlated with the additional boost delivery (p=0.007 and p=0.023). Regarding the late subcutaneous tissue, a correlation with diabetes was found (p=0.0283). CONCLUSION: These results confirm the feasibility and safety of the hypofractionated radiotherapy in patients with early breast cancer. In our population the boost administration was resulted to be a significant adverse prognostic factor for acute and late toxicity. Long-term follow up is need to confirm this finding.

Hypofractionated stereotactic radiation therapy for recurrent glioblastoma: single institutional experience.

BACKGROUND: Glioblastoma (GBM) is the most common malignant primary brain tumor in adults. Tumor control and survival have improved with the use of radiotherapy (RT) plus concomitant and adjuvant chemotherapy, but the prognosis remain poor. In most cases the recurrence occurs within 7-9 months after primary treatment. Currently, many approaches are available for the salvage treatment of patients with recurrent GBM, including resection, re-irradiation or systemic agents, but no standard of care exists. METHODS: We analysed a cohort of patients with recurrent GBM treated with frame-less hypofractionated stereotactic radiation therapy with a total dose of 25 Gy in 5 fractions. RESULTS: Of 91 consecutive patients with newly diagnosed GBM treated between 2007 and 2012 with conventional adjuvant chemo-radiation therapy, 15 underwent salvage RT at recurrence. The median time interval between primary RT and salvage RT was 10.8 months (range, 6-54 months). Overall, patients undergoing salvage RT showed a longer survival, with a median survival of 33 vs. 9.9 months (p= 0.00149). Median overall survival (OS) from salvage RT was 9.5 months. No patients demonstrated clinically significant acute morbidity, and all patients were able to complete the prescribed radiation therapy without interruption. CONCLUSION: Our results suggest that hypofractionated stereotactic radiation therapy is effective and safe in recurrent GBM. However, until prospective randomized trials will confirm these results, the decision for salvage treatment should remain individual and based on a multidisciplinary evaluation of each patient.