A field strength independent MR radiomics model to predict pathological complete response in locally advanced rectal cancer.

PURPOSE: Aim of this study was to develop a generalised radiomics model for predicting pathological complete response after neoadjuvant chemo-radiotherapy in locally advanced rectal cancer patients using pre-CRT T2-weighted images acquired at a 1.5 T and a 3 T scanner. METHODS: In two institutions, 195 patients were scanned: 136 patients were scanned on a 1.5 T MR scanner, 59 patients on a 3 T MR scanner. Gross tumour volumes were delineated on the MR images and 496 radiomic features were extracted, applying the intensity-based (IB) filter. Features were standardised with Z-score normalisation and an initial feature selection was carried out using Wilcoxon-Mann-Whitney test: The most significant features at 1.5 T and 3 T were selected as main features. Several logistic regression models combining the main features with a third one selected by those resulting significant were elaborated and evaluated in terms of area under curve (AUC). A tenfold cross-validation was repeated 300 times to evaluate the model robustness. RESULTS: Three features were selected: maximum fractal dimension with IB = 0-50, energy and grey-level non-uniformity calculated on the run-length matrix with IB = 0-50. The AUC of the model applied to the whole dataset after cross-validation was 0.72, while values of 0.70 and 0.83 were obtained when 1.5 T and 3 T patients were considered, respectively. CONCLUSIONS: The model elaborated showed good performance, even when data from patients scanned on 1.5 T and 3 T were merged. This shows that magnetic field intensity variability can be overcome by means of selecting appropriate image features.

Characterization of an inorganic scintillator for small-field dosimetry in MR-guided radiotherapy.

INTRODUCTION: Aim of this study is to dosimetrically characterize a new inorganic scintillator designed for magnetic resonance-guided radiotherapy (MRgRT) in the presence of 0.35 tesla magnetic field (B). METHODS: The detector was characterized in terms of signal to noise ratio (SNR), reproducibility, dose linearity, angular response, and dependence by energy, field size, and B orientation using a 6 MV magnetic resonance (MR)-Linac and a water tank. Field size dependence was investigated by measuring the output factor (OF) at 1.5 cm. The results were compared with those measured using other detectors (ion chamber and synthetic diamond) and those calculated using a Monte Carlo (MC) algorithm. Energy dependence was investigated by acquiring a percentage depth dose (PDD) curve at two field sizes (3.32 × 3.32 and 9.96 × 9.96 cm2 ) and repeating the OF measurements at 5 and 10 cm depths. RESULTS: The mean SNR was 116.3 ± 0.6. Detector repeatability was within 1%, angular dependence was <2% and its response variation based on the orientation with respect to the B lines was <1%. The detector has a temporal resolution of 10 Hz and it showed a linear response (R2  = 1) in the dose range investigated. All the OF values measured at 1.5 cm depth using the scintillator are in accordance within 1% with those measured with other detectors and are calculated using the MC algorithm. PDD values are in accordance with MC algorithm only for 3.32 × 3.32 cm2 field. Numerical models can be applied to compensate for energy dependence in case of larger fields. CONCLUSION: The inorganic scintillator in the present form can represent a valuable detector for small-field dosimetry and periodic quality controls at MR-Linacs such as dose stability, OFs, and dose linearity. In particular, the detector can be effectively used for small-field dosimetry at 1.5 cm depth and for PDD measurements if the field dimension of 3.32 × 3.32 cm2 is not exceeded.

On the accuracy of bulk synthetic CT for MR-guided online adaptive radiotherapy.

PURPOSE: MR-guided radiotherapy (MRgRT) relies on the daily assignment of a relative electron density (RED) map to allow the fraction specific dose calculation. One approach to assign the RED map consists of segmenting the daily magnetic resonance image into five different density levels and assigning a RED bulk value to each level to generate a synthetic CT (sCT). The aim of this study is to evaluate the dose calculation accuracy of this approach for applications in MRgRT. METHODS: A planning CT (pCT) was acquired for 26 patients with abdominal and pelvic lesions and segmented in five levels similar to an online approach: air, lung, fat, soft tissue and bone. For each patient, the median RED value was calculated for fat, soft tissue and bone. Two sCTs were generated assigning different bulk values to the segmented levels on pCT: The sCTICRU uses the RED values recommended by ICRU46, and the sCTtailor uses the median patient-specific RED values. The same treatment plan was calculated on two the sCTs and the pCT. The dose calculation accuracy was investigated in terms of gamma analysis and dose volume histogram parameters. RESULTS: Good agreement was found between dose calculated on sCTs and pCT (gamma passing rate 1%/1 mm equal to 91.2% ± 6.9% for sCTICRU and 93.7% ± 5.3% b or sCTtailor). The mean difference in estimating V95 (PTV) was equal to 0.2% using sCTtailor and 1.2% using sCTICRU, respect to pCT values CONCLUSIONS: The bulk sCT guarantees a high level of dose calculation accuracy also in presence of magnetic field, making this approach suitable to MRgRT. This accuracy can be improved by using patient-specific RED values.

Evaluation of a simplified optimizer for MR-guided adaptive RT in case of pancreatic cancer.

PURPOSE: Magnetic resonance-guided adaptive radiotherapy (MRgART) is considered a promising resource for pancreatic cancer, as it allows to online modify the dose distribution according to daily anatomy. This study aims to compare the dosimetric performance of a simplified optimizer implemented on a MR-Linac treatment planning system (TPS) with those obtained using an advanced optimizer implemented on a conventional Linac. METHODS: Twenty patients affected by locally advanced pancreatic cancer (LAPC) were considered. Gross tumor volume (GTV) and surrounding organ at risks (OARs) were contoured on the average 4DCT scan. Planning target volume was generated from GTV by adding an isotropic 3 mm margin and excluding overlap areas with OARs. Treatment plans were generated by using the simple optimizer for the MR-Linac in intensity-modulated radiation therapy (IMRT) and the advanced optimizer for conventional Linac in IMRT and volumetric modulated arc therapy (VMAT) technique. Prescription dose was 40 Gy in five fractions. The dosimetric comparison was performed on target coverage, dosimetric indicators, and low dose diffusion. RESULTS: The simplified optimizer of MR-Linac generated clinically acceptable plans in 80% and optimal plans in 55% of cases. The number of clinically acceptable plans obtained using the advanced optimizer of the conventional Linac with IMRT was the same of MR-Linac, but the percentage of optimal plans was higher (65%). Using the VMAT technique, it is possible to obtain clinically acceptable plan in 95% and optimal plans in 90% of cases. The advanced optimizer combined with VMAT technique ensures higher target dose homogeneity and minor diffusion of low doses, but its actual optimization time is not suitable for MRgART. CONCLUSION: Simplified optimization solutions implemented in the MR-Linac TPS allows to elaborate in most of cases treatment plans dosimetrically comparable with those obtained by using an advanced optimizer. A superior treatment plan quality is possible using the VMAT technique that could represent a breakthrough for the MRgART if the modern advancements will lead to shorter optimization times.

A new frontier of image guidance: Organs at risk avoidance with MRI-guided respiratory-gated intensity modulated radiotherapy: Technical note and report of a case.

The case of a 50-year-old man affected by a rhabdomiosarcoma metastatic lesion in the left flank Is reported. The patient was addressed to 50.4 Gy radiotherapy with concomitant chemotherapy in order to locally control the lesion. A Tri-60-Co magnetic resonance hybrid radiotherapy unit was used for treatment delivery and a respiratory gating protocol was applied for the different breathing phases (Free Breathing, Deep Inspiration Breath Hold and Final Expiration Breath Hold). Three intensity modulated radiation therapy (IMRT) plans were calculated and Final Expiration Breath Hold plan was finally selected due to the absence of PTV coverage differences and better organs at risk sparing (i.e. kidneys). This case report suggests that organs at risk avoidance with MRI-guided respiratory-gated Radiotherapy is feasible and particularly advantageous whenever sparing the organs at risk is of utmost dosimetric or clinical importance.

Delta radiomics for rectal cancer response prediction with hybrid 0.35 T magnetic resonance-guided radiotherapy (MRgRT): a hypothesis-generating study for an innovative personalized medicine approach.

The aim of this study was to evaluate the variation of radiomics features, defined as "delta radiomics", in patients undergoing neoadjuvant radiochemotherapy (RCT) for rectal cancer treated with hybrid magnetic resonance (MR)-guided radiotherapy (MRgRT). The delta radiomics features were then correlated with clinical complete response (cCR) outcome, to investigate their predictive power. A total of 16 patients were enrolled, and 5 patients (31%) showed cCR at restaging examinations. T2*/T1 MR images acquired with a hybrid 0.35 T MRgRT unit were considered for this analysis. An imaging acquisition protocol of 6 MR scans per patient was performed: the first MR was acquired at first simulation (t0) and the remaining ones at fractions 5, 10, 15, 20 and 25. Radiomics features were extracted from the gross tumour volume (GTV), and each feature was correlated with the corresponding delivered dose. The variations of each feature during treatment were quantified, and the ratio between the values calculated at different dose levels and the one extracted at t0 was calculated too. The Wilcoxon-Mann-Whitney test was performed to identify the features whose variation can be predictive of cCR, assessed with a MR acquired 6 weeks after RCT and digital examination. The most predictive feature ratios in cCR prediction were the L_least and glnu ones, calculated at the second week of treatment (22 Gy) with a p value = 0.001. Delta radiomics approach showed promising results and the quantitative analysis of images throughout MRgRT treatment can successfully predict cCR offering an innovative personalized medicine approach to rectal cancer treatment.

Fractal-based radiomic approach to predict complete pathological response after chemo-radiotherapy in rectal cancer.

The aim of this study was to propose a methodology to investigate the tumour heterogeneity and evaluate its ability to predict pathologically complete response (pCR) after chemo-radiotherapy (CRT) in locally advanced rectal cancer (LARC). This approach consisted in normalising the pixel intensities of the tumour and identifying the different sub-regions using an intensity-based thresholding. The spatial organisation of these subpopulations was quantified using the fractal dimension (FD). This approach was implemented in a radiomic workflow and applied to 198 T2-weighted pre-treatment magnetic resonance (MR) images of LARC patients. Three types of features were extracted from the gross tumour volume (GTV): morphological, statistical and fractal features. Feature selection was performed using the Wilcoxon test and a logistic regression model was calculated to predict the pCR probability after CRT. The model was elaborated considering the patients treated in two institutions: Fondazione Policlinico Universitario "Agostino Gemelli" of Rome (173 cases, training set) and University Medical Centre of Maastricht (25 cases, validation set). The results obtained showed that the fractal parameters of the subpopulations have the highest performance in predicting pCR. The predictive model elaborated had an area under the curve (AUC) equal to 0.77 ± 0.07. The model reliability was confirmed by the validation set (AUC = 0.79 ± 0.09). This study suggests that the fractal analysis can play an important role in radiomics, providing valuable information not only about the GTV structure, but also about its inner subpopulations.

Can automation in radiotherapy reduce costs?

BACKGROUND: Computerized automation is likely to play an increasingly important role in radiotherapy. The objective of this study was to report the results of the first part of a program to implement a model for economical evaluation based on micro-costing method. To test the efficacy of the model, the financial impact of the introduction of an automation tool was estimated. A single- and multi-center validation of the model by a prospective collection of data is planned as the second step of the program. MATERIAL AND METHODS: The model was implemented by using an interactive spreadsheet (Microsoft Excel, 2010). The variables to be included were identified across three components: productivity, staff, and equipment. To calculate staff requirements, the workflow of Gemelli ART center was mapped out and relevant workload measures were defined. Profit and loss, productivity and staffing were identified as significant outcomes. Results were presented in terms of earnings before interest and taxes (EBIT). Three different scenarios were hypothesized: baseline situation at Gemelli ART (scenario 1); reduction by 2 minutes of the average duration of treatment fractions (scenario 2); and increased incidence of advanced treatment modalities (scenario 3). By using the model, predicted EBIT values for each scenario were calculated across a period of eight years (from 2015 to 2022). RESULTS: For both scenarios 2 and 3 costs are expected to slightly increase as compared to baseline situation that is particularly due to a little increase in clinical personnel costs. However, in both cases EBIT values are more favorable than baseline situation (EBIT values: scenario 1, 27%, scenario 2, 30%, scenario 3, 28% of revenues). CONCLUSION: A model based on a micro-costing method was able to estimate the financial consequences of the introduction of an automation tool in our radiotherapy department. A prospective collection of data at Gemelli ART and in a consortium of centers is currently under way to prospectively validate the model.

Adaptive optimization by 6 DOF robotic couch in prostate volumetric IMRT treatment: rototranslational shift and dosimetric consequences.

The purpose of this study was to investigate the magnitude and dosimetric relevance of translational and rotational shifts on IGRT prostate volumetric-modulated arc therapy (VMAT) using Protura six degrees of freedom (DOF) Robotic Patient Positioning System. Patients with cT3aN0M0 prostate cancer, treated with VMAT simultaneous integrated boost (VMAT-SIB), were enrolled. PTV2 was obtained adding 0.7 cm margin to seminal vesicles base (CTV2), while PTV1 adding to prostate (CTV1) 0.7 cm margin in all directions, except 1.2 cm, as caudal margin. A daily CBCT was acquired before dose delivery. The translational and rotational displacements were corrected through Protura Robotic Couch, collected and applied to the simulation CT to obtain a translated CT (tCT) and a rototranslated CT (rtCT) on which we recalculated the initial treatment plan (TP). We analyzed the correlation between dosimetric coverage, organs at risk (OAR) sparing, and translational or rotational displacements. The dosimetric impact of a rototranslational correction was calculated. From October 2012 to September 2013, a total of 263 CBCT scans from 12 patients were collected. Translational shifts were < 5 mm in 81% of patients and the rotational shifts were < 2° in 93% of patient scans. The dosimetric analysis was performed on 172 CBCT scans and calculating 344 VMAT-TP. Two significant linear correlations were observed between yaw and the V20 femoral heads and between pitch rotation and V50 rectum (p < 0.001); rototranslational correction seems to impact more on PTV2 than on PTV1, especially when margins are reduced. Rotational errors are of dosimetric significance in sparing OAR and in target coverage. This is relevant for femoral heads and rectum because of major distance from isocenter, and for seminal vesicles because of irregular shape. No correlation was observed between translational and rotational errors. A study considering the intrafractional error and the deformable registration is ongoing.

Automatic delineation for replanning in nasopharynx radiotherapy: what is the agreement among experts to be considered as benchmark?

BACKGROUND AND PURPOSE: Anatomic changes during head and neck radiotherapy require replanning. The primary aim of this study is the definition of the agreement among experts in the head and neck automatic delineation frame to use as benchmark. The secondary goal is to assess the reliability of automatic delineation for nasopharynx radiotherapy and time saving. MATERIAL AND METHODS: A computed tomography (CT) scan was acquired in 10 nasopharynx patients along intensity-modulated radiotherapy (IMRT) treatment for replanning. Deformable registration with replanning autocontouring of the structures was performed using VelocityAI 2.3© software defining Structure Set A. The optimization of these contours was obtained through revision by a skilled operator, drawing Structure Set B. An ex novo Structure Set C was segmented on the replanning CT-scan by an expert delineation team. The mean Dice's Similarity Index (mDSI) was calculated between Structure Set A and B, A and C, and between B and C for each volume. All segmentation times for organs at risk (OARs) and clinical target volume (CTV) were recorded and compared. RESULTS: We validated the replanning autocontoured Structure Sets for 10 patients. For volumetric analysis we observed mDSI values of 0.87 for the OARs, 0.70 for nodes, 0.90 for CTV in the Structure Set A-B comparison and respectively of 0.74, 0.63 and 0.78 for the Structure Set A-C one, and 0.78, 0.78 and 0.85 for Structure Set B-C, which represents the existing expert based benchmark. We calculated a mean saved time in Structure Set B of 30 minutes. CONCLUSIONS: Autocontouring procedures offer considerable segmentation time saving with acceptable reliability of the contours, even if an independent check procedure for their optimization is still required to increase their adherence to referential benchmark gold standard among experts, which stands at a 0.80 DSI value.

Whole-brain radiotherapy combined with surgery or stereotactic radiotherapy in patients with brain oligometastases: long-term analysis.

OBJECTIVE: To verify whether the treatment of brain oligometastases with whole-brain radiotherapy (WBRT) plus stereotactic radiotherapy (SRT) or surgical resection results in different outcomes. METHODS: Files of patients affected by brain metastases submitted to surgical resection followed by WBRT (group A) or WBRT + SRT (group B) were retrospectively selected for this study. The two treatment groups were matched for the following potential prognostic factors: WBRT schedule, age, gender, performance status, tumor type, number of brain metastases, extra-cerebral metastases, and recursive partitioning analysis class (RPA). The outcomes of patients in both groups were evaluated in terms of toxicity, local control, and overall survival. RESULTS: Total of 97 patients were selected (56 male; 42 female) who were respectively submitted to surgical resection followed by WBRT (group A, n = 50 patients) or WBRT + SRT (Group B, n = 47 patients). Median follow-up was 95 months (range, 8-171 months). The 1-year local control rates were 46.0% and 69.0% respectively. No significant difference in local tumor control was observed between group A and B (p = 0.10). Median overall survival was 15 and 19 months in group A and B, respectively. One-year survival was 56.0% and 62%, respectively. No difference was observed in the two groups (p = 0.40). CONCLUSION: Surgery remains the main therapeutic approach in symptomatic patients; nevertheless, our data support the use of WBRT plus SRT in one or two brain metastases smaller than 3 cm.

Evaluation of a generalized knowledge-based planning performance for VMAT irradiation of breast and locoregional lymph nodes-Internal mammary and/or supraclavicular regions.

PURPOSE: To evaluate the performance of eleven Knowledge-Based (KB) models for planning optimization (RapidPlantm (RP), Varian) of Volumetric Modulated Arc Therapy (VMAT) applied to whole breast comprehensive of nodal stations, internal mammary and/or supraclavicular regions. METHODS AND MATERIALS: Six RP models have been generated and trained based on 120 VMAT plans data set with different criteria. Two extra-structures were delineated: a PTV for the optimization and a ring structure. Five more models, twins of the previous models, have been created without the need of these structures. RESULTS: All models were successfully validated on an independent cohort of 40 patients, 30 from the same institute that provided the training patients and 10 from an additional institute, with the resulting plans being of equal or better quality compared with the clinical plans. The internal validation shows that the models reduce the heart maximum dose of about 2 Gy, the mean dose of about 1 Gy and the V20Gy of 1.5 Gy on average. Model R and L together with model B without optimization structures ensured the best outcomes in the 20% of the values compared to other models. The external validation observed an average improvement of at least 16% for the V5Gy of lungs in RP plans. The mean heart dose and for the V20Gy for lung IPSI were almost halved. The models reduce the maximum dose for the spinal canal of more than 2 Gy on average. CONCLUSIONS: All KB models allow a homogeneous plan quality and some dosimetric gains, as we saw in both internal and external validation. Sub-KB models, developed by splitting right and left breast cases or including only whole breast with locoregional lymph nodes, have shown good performances, comparable but slightly worse than the general model. Finally, models generated without the optimization structures, performed better than the original ones.

Single-arm phase II study of conformal radiation therapy and temozolomide plus fractionated stereotactic conformal boost in high-grade gliomas: final report.

PURPOSE: To assess survival, local control and toxicity using fractionated stereotactic conformal radiotherapy (FSCRT) boost and temozolomide in high-grade gliomas (HGGs). PATIENTS AND METHODS: Patients affected by HGG, with a CTV(1)(clinical target volume, representing tumor bed ± residual tumor + a margin of 5 mm) ≤ 8 cm were enrolled into this phase II study. Radiotherapy (RT, total dose 6,940 cGy) was administered using a combination of two different techniques: three-dimensional conformal radiotherapy (3D-CRT, to achieve a dose of 5,040 or 5,940 cGy) and FSCRT boost (19 or 10 Gy) tailored by CTV(1)diameter (≤ 6 cm and > 6 cm, respectively). Temozolomide (75 mg/m(2)) was administered during the first 2 or 4 weeks of RT. After the end of RT, temozolomide (150-200 mg/m(2)) was administered for at least six cycles. The sample size of 41 patients was assessed by the single proportion-powered analysis. RESULTS: 41 patients (36 with glioblastoma multiforme [GBM] and five with anaplastic astrocytoma [AA]) were enrolled; RTOG neurological toxicities G1-2 and G3 were 12% and 3%, respectively. Two cases of radionecrosis were observed. At a median follow-up of 44 months (range 6-56 months), global and GBM median overall survival (OS) were 30 and 28 months. The 2-year survival rate was significantly better compared to the standard treatment (63% vs. 26.5%; p < 0.00001). Median progression-free survival (PFS) was 11 months, in GBM patients 10 months. CONCLUSION: FSCRT boost plus temozolomide is well tolerated and seems to increase survival compared to the standard treatment in patients with HGG.

Correlation functions for Elekta aSi EPIDs used as transit dosimeter for open fields.

In-vivo dosimetry techniques are currently being applied only by a few Centers because they require time-consuming implementation measurements, and workload for detector positioning and data analysis. The transit in-vivo dosimetry performed by the electronic portal imaging device (EPID) avoids the problem of solid-state detector positioning on the patient. Moreover, the dosimetric characterization of the recent Elekta aSi EPIDs in terms of signal stability and linearity make these detectors useful for the transit in-vivo dosimetry with 6, 10 and 15 MV photon beams. However, the implementation of the EPID transit dosimetry requires several measurements. Recently, the present authors have developed an in-vivo dosimetry method for 3D CRT based on correlation functions defined by the ratios between the transit signal, st (w,L), by the EPID and the phantom midplane dose, Dm(w,L), at the source to axis distance (SAD) as a function of the phantom thickness, w, and the square field dimensions, L. When the phantom midplane was positioned at distance, d, from the SAD, the ratios st(w,L)/s't(d,w,L) were used to take into account the variation of the scattered photon contributions on the EPID as a function of d and L.The aim of this paper is the implementation of a procedure that uses generalized correlation functions obtained by nine Elekta Precise linac beams. The procedure can be used by other Elekta Precise linacs equipped with the same aSi EPIDs, assuming the stabilities of the beam output factors and the EPID signals. The procedure here reported avoids measurements in solid water equivalent phantoms needed to implement the in-vivo dosimetry method in the radiotherapy department. A tolerance level ranging between ± 5% and ± 6% (depending on the type of tumor) was estimated for the comparison between the reconstructed isocenter dose, Diso, and the computed dose, Diso,TPS, by the treatment planning system (TPS).

Breast in vivo dosimetry by EPID.

An electronic portal imaging device (EPID) is an effective detector for in vivo transit dosimetry. In fact, it supplies two-dimensional information, does not require special efforts to be used during patient treatment, and can supply data in real time. In the present paper, a new procedure has been proposed to improve the EPID in vivo dosimetry accuracy by taking into account the patient setup variations. The procedure was applied to the breast tangential irradiation for the reconstruction of the dose at the breast midpoint, Dm. In particular, the patient setup variations were accounted for by comparing EPID images versus digitally reconstructed radiographies. In this manner, EPID transit signals were obtained corresponding to the geometrical projections of the breast midpoint on the EPID for each therapy session. At the end, the ratios R between D(m) and the doses computed by the treatment planning system (TPS) at breast midpoints, D(m,TPS), were determined for 800 therapy sessions of 20 patients. Taking into account the method uncertainty, tolerance levels equal to ± 5% have been determined for the ratio R.The improvement of in vivo dosimetry results obtained (taking into account patient misalignment) has been pointed out comparing the R values obtained with and with-out considering patient setup variations. In particular, when patient misalignments were taken into account, the R values were within ± 5% for 93% of the checks; when patient setup variations were not taken into account, the R values were within ± 5% in 72% of the checks. This last result points out that the transit dosimetry method overestimates the dose discrepancies if patient setup variations are not taken into account for dose reconstruction. In this case, larger tolerance levels have to be adopted as a trade-off between workload and ability to detect errors, with the drawback being that some errors (such as the ones in TPS implementation or in beam calibration) cannot be detected, limiting the in vivo dosimetry efficacy.The paper also reports preliminary results about the possibility of reconstructing a dose profile perpendicular to the beam central axis reaching from the apex to the lung and passing through the middle point of the breast by an algorithm, similar to the one used for dose reconstruction at breast midpoint. In particular, the results have shown an accuracy within ± 3% for the dose profile reconstructed in the breast (excluding the interface regions) and an underestimation of the lung dose.

Optimized stereotactic volumetric modulated arc therapy as an alternative to brachytherapy for vaginal cuff boost. A dosimetric study.

We evaluate the role of stereotactic body radiotherapy using volumetric modulated arc therapy (VMAT) technique as an alternative to high-dose rate brachytherapy (HDR-BT) in the treatment of vaginal cuff in postoperative endometrial cancer. CT scans of 8 patients were used in this study. The clinical target volume (CTV) was defined as the 0.5 cm tissue around the applicator (then subtracting the applicator). Total dose was 30Gy delivered in 5 fractions. In HDR-BT, dose was prescribed at a distance of 0.5 cm from the surface applicator. For VMAT irradiation, a planning target volume (PTV) was obtained from CTV by an expansion of 3 mm. Two VMAT plans were generated using a full arc rotation. The first plan was optimized with an anatomy-based optimization module (PO-VMAT) using a 1mm multileaf collimator beam margin to enhance dose heterogeneity and dose fallout outside the target. The second plan was generated with a full-inverse planning module (FI-VMAT). Conformity (CI100, CI50, CI25), gradient (GI) indexes, and integral doses were calculated. To account for various dose heterogeneity distributions we calculated the equivalent uniform dose (EUD) using the Niemerko model. A Kruskal-Wallis analysis of variance followed by Dunn's-type multiple comparisons was performed. Dose distributions were more heterogeneous with HDR-BT: Dmean was 144.2% of prescription dose for CTV in HDR-BT and 118.5 and 108.6% for PTV in PO-VMAT and FI-VMAT, respectively. The mean values of EUD for CTV were 136.9%, 130.0 %, and 111.0% of prescription dose in HDR-BT, PO-VMAT, and FI-VMAT plans, respectively. GI indexes were 2.81, 3.41, and 4.14 for HDR-BT, PO-VMAT, and FI-VMAT, respectively. Near-maximal doses (D0.1cc) for rectum and bladder were significantly higher in HDR-BT plans compared to PO-VMAT and FI-VMAT plans (rectum: 131.2% vs112.8% vs 112.0%, respectively; bladder: 129.2% vs 108.7%, and 109.8%, respectively). PO-VMAT plans were able to mimic the HDR-BT dose distribution, showing a successful capability of highly conformal dose distribution, EUD values similar to HDR-BT, and steep dose-gradient outside PTV, then providing a reasonable alternative to brachytherapy.

Reliability of ITV approach to varying treatment fraction time: a retrospective analysis based on 2D cine MR images.

BACKGROUND: Internal Target Volume (ITV) is one of the most common strategies to passively manage tumour motion in Radiotherapy (RT). The reliability of this approach is based on the assumption that the tumour motion estimated during pre-treatment 4D Computed Tomography (CT) acquisition is representative of the motion during the whole RT treatment. With the introduction of Magnetic Resonance-guided RT (MRgRT), it has become possible to monitor tumour motion during the treatment and verify this assumption. Aim of this study was to investigate the reliability of the ITV approach with respect to the treatment fraction time (TFT) in abdominal and thoracic lesions. METHODS: A total of 12 thoracic and 15 abdominal lesions was analysed. Before treatment, a 10-phase 4DCT was acquired and ITV margins were estimated considering the envelope of the lesion contoured on the different 4DCT phases. All patients underwent MRgRT treatment in free-breathing, monitoring the tumour position on a sagittal plane with 4 frames per second (sec). ITV margins were projected on the tumour trajectory and the percentage of treatment time in which the tumour was inside the ITV (%TT) was measured to varying of TFT. The ITV approach was considered moderately reliable when %TT ≥ 90% and strongly reliable when %TT ≥ 95%. Additional ITV margins required to achieve %TT ≥ 95% were also calculated. RESULTS: In the analysed cohort of patients, ITV strategy can be considered strongly reliable only for lung lesions with TFT ≤ 7 min (min). The ITV strategy can be considered only moderately reliable for abdominal lesions, and additional margins are required to obtain %TT ≥ 95%. Considering a TFT ≤ 4 min, additional margins of 2 mm in cranio-caudal (CC) and 1 mm in antero-posterior (AP) are suggested for pancreatic lesions, 3 mm in CC and 2 mm in AP for renal and liver ones. CONCLUSIONS: On the basis of the analysed cases, the ITV approach appears to be reliable in the thorax, while it results more challenging in the abdomen, due to the higher uncertainty in ITV definition and to the observed larger intra and inter-fraction motion variability. The addition of extra margins based on the TFT may represent a valid tool to compensate such limitations.

AVATAR: Analysis for Visual Acuity Prediction After Eye Interventional Radiotherapy.

AIM: The aim of this study was to detect clinical factors predictive of loss of visual acuity after treatment in order to develop a predictive model to help identify patients at risk of visual loss. PATIENTS AND METHODS: This was a retrospective review of patients who underwent interventional radiotherapy (brachytherapy) with 106Ru plaque for primary uveal melanoma. A predictive nomogram for visual acuity loss at 3 years from treatment was developed. RESULTS: A total of 152 patients were selected for the study. The actuarial probability of conservation of 20/40 vision or better was 0.74 at 1 year, 0.59 at 3 years, and 0.54 at 5 years after treatment. Factors positively correlated with loss of visual acuity included: age at start of treatment (p=0.004) and longitudinal basal diameter (p=0.057), while distance of the posterior margin of the tumor from the foveola was inversely correlated (p=0.0007). CONCLUSION: We identified risk factors affecting visual function and developed a predictive model and decision support tool (AVATAR nomogram).

External Validation of Early Regression Index (ERITCP) as Predictor of Pathologic Complete Response in Rectal Cancer Using Magnetic Resonance-Guided Radiation Therapy.

PURPOSE: Tumor control probability (TCP)-based early regression index (ERITCP) is a radiobiological parameter that showed promising results in predicting pathologic complete response (pCR) on T2-weighted 1.5 T magnetic resonance (MR) images of patients with locally advanced rectal cancer. This study aims to validate the ERITCP in the context of low-tesla MR-guided radiation therapy, using images acquired with different magnetic field strength (0.35 T) and image contrast (T2/T1). Furthermore, the optimal timing for pCR prediction was estimated, calculating the ERI index at different biologically effective dose (BED) levels. METHODS AND MATERIALS: Fifty-two patients with locally advanced rectal cancer treated with neoadjuvant chemoradiation therapy were enrolled in this multi-institutional retrospective study. For each patient, a 0.35 T T2/T1-weighted MR image was acquired during simulation and on each treatment day. Gross tumor volume was contoured according to International Commission on Radiation Units Report 83 guidelines. According to the original definition, ERITCP was calculated considering the residual tumor volume at BED = 25 Gy. ERI was also calculated in correspondence with several BED levels: 13, 21, 32, 40, 46, 54, 59, and 67. The predictive performance of the different ERI indices were evaluated in terms of receiver operating characteristic curve. The robustness of ERITCP with respect to the interobserver variability was also evaluated considering 2 operators and calculating the intraclass correlation index. RESULTS: Fourteen patients showed pCR. ERITCP correctly 47 of 52 cases (accuracy = 90%), showing good results in terms of sensitivity (86%), specificity (92%), negative predictive value (95%), and positive predictive value (80%). The analysis at different BED levels shows that the best predictive performance is obtained when this parameter is calculated at BED = 25 Gy (area under the curve = 0.93). ERITCP results are robust with respect to interobserver variability (intraclass correlation index = 0.99). CONCLUSIONS: This study confirmed the validity and the robustness of ERITCP as a pCR predictor in the context of low-tesla MR-guided radiation therapy and indicate 25 Gy as the best BED level to perform predictions.

Online adaptive magnetic resonance guided radiotherapy for pancreatic cancer: state of the art, pearls and pitfalls.

BACKGROUND: Different studies have proved in recent years that hypofractionated radiotherapy (RT) improves overall survival of patients affected by locally advanced, unresectable, pancreatic cancer. The clinical management of these patients generally leads to poor results and is considered very challenging, due to different factors, heavily influencing treatment delivery and its outcomes. Firstly, the dose prescribed to the target is limited by the toxicity that the highly radio-sensitive organs at risk (OARs) surrounding the disease can develop. Treatment delivery is also complicated by the significant inter-fractional and intra-fractional variability of therapy volumes, mainly related to the presence of hollow organs and to the breathing cycle. The recent introduction of magnetic resonance guided radiotherapy (MRgRT) systems leads to the opportunity to control most of the aforementioned sources of uncertainty influencing RT treatment workflow in pancreatic cancer. MRgRT offers the possibility to accurately identify radiotherapy volumes, thanks to the high soft-tissue contrast provided by the Magnetic Resonance imaging (MRI), and to monitor the tumour and OARs positions during the treatment fraction using a high-temporal cine MRI. However, the main advantage offered by the MRgRT is the possibility to online adapt the RT treatment plan, changing the dose distribution while the patient is still on couch and successfully addressing most of the sources of variability. SHORT CONCLUSION: Aim of this study is to present and discuss the state of the art, the main pitfalls and the innovative opportunities offered by online adaptive MRgRT in pancreatic cancer treatment.