Machine learning and lean six sigma for targeted patient-specific quality assurance of volumetric modulated arc therapy plans.

Background and purpose: Radiotherapy plans with excessive complexity exhibit higher uncertainties and worse patient-specific quality assurance (PSQA) results, while the workload of measurement-based PSQA can impact the efficiency of the radiotherapy workflow. Machine Learning (ML) and Lean Six Sigma, a process optimization method, were implemented to adopt a targeted PSQA approach, aiming to reduce workload, risk of failures, and monitor complexity. Materials and methods: Lean Six Sigma was applied using DMAIC (define, measure, analyze, improve, and control) steps. Ten complexity metrics were computed for 69,811 volumetric modulated arc therapy (VMAT) arcs from 28,612 plans delivered in our Institute (2013-2021). Outlier complexities were defined as >95th-percentile of the historical distributions, stratified by treatment. An ML model was trained to predict the gamma passing rate (GPR-3 %/1mm) of an arc given its complexity. A decision support system was developed to monitor the complexity and expected GPR. Plans at risk of PSQA failure, either extremely complex or with average GPR <90 %, were identified. The tool's impact was assessed after nine months of clinical use. Results: Among 1722 VMAT plans monitored prospectively, 29 (1.7 %) were found at risk of failure. Planners reacted by performing PSQA measurement and re-optimizing the plan. Occurrences of outlier complexities remained stable within 5 %. The expected GPR increased from a median of 97.4 % to 98.2 % (Mann-Whitney p < 0.05) due to plan re-optimization. Conclusions: ML and Lean Six Sigma have been implemented in clinical practice enabling a targeted measurement-based PSQA approach for plans at risk of failure to improve overall quality and patient safety.

Deep learning-based optimization of field geometry for total marrow irradiation delivered with volumetric modulated arc therapy.

BACKGROUND: Total marrow (lymphoid) irradiation (TMI/TMLI) is a radiotherapy treatment used to selectively target the bone marrow and lymph nodes in conditioning regimens for allogeneic hematopoietic stem cell transplantation. A complex field geometry is needed to cover the large planning target volume (PTV) of TMI/TMLI with volumetric modulated arc therapy (VMAT). Five isocenters and ten overlapping fields are needed for the upper body, while, for patients with large anatomical conformation, two specific isocenters are placed on the arms. The creation of a field geometry is clinically challenging and is performed by a medical physicist (MP) specialized in TMI/TMLI. PURPOSE: To develop convolutional neural networks (CNNs) for automatically generating the field geometry of TMI/TMLI. METHODS: The dataset comprised 117 patients treated with TMI/TMLI between 2011 and 2023 at our Institute. The CNN input image consisted of three channels, obtained by projecting along the sagittal plane: (1) average CT pixel intensity within the PTV; (2) PTV mask; (3) brain, lungs, liver, bowel, and bladder masks. This "averaged" frontal view combined the information analyzed by the MP when setting the field geometry in the treatment planning system (TPS). Two CNNs were trained to predict the isocenters coordinates and jaws apertures for patients with (CNN-1) and without (CNN-2) isocenters on the arms. Local optimization methods were used to refine the models output based on the anatomy of the patient. Model evaluation was performed on a test set of 15 patients in two ways: (1) by computing the root mean squared error (RMSE) between the CNN output and ground truth; (2) with a qualitative assessment of manual and generated field geometries-scale: 1 = not adequate, 4 = adequate-carried out in blind mode by three MPs with different expertise in TMI/TMLI. The Wilcoxon signed-rank test was used to evaluate the independence of the given scores between manual and generated configurations (p < 0.05 significant). RESULTS: The average and standard deviation values of RMSE for CNN-1 and CNN-2 before/after local optimization were 15 ± 2/13 ± 3 mm and 16 ± 2/18 ± 4 mm, respectively. The CNNs were integrated into a planning automation software for TMI/TMLI such that the MPs could analyze in detail the proposed field geometries directly in the TPS. The selection of the CNN model to create the field geometry was based on the PTV width to approximate the decision process of an experienced MP and provide a single option of field configuration. We found no significant differences between the manual and generated field geometries for any MP, with median values of 4 versus 4 (p = 0.92), 3 versus 3 (p = 0.78), 4 versus 3 (p = 0.48), respectively. Starting from October 2023, the generated field geometry has been introduced in our clinical practice for prospective patients. CONCLUSIONS: The generated field geometries were clinically acceptable and adequate, even for an MP with high level of expertise in TMI/TMLI. Incorporating the knowledge of the MPs into the development cycle was crucial for optimizing the models, especially in this scenario with limited data.

Impact of inter-observer variability on first axillary level dosimetry in breast cancer radiotherapy: An AIRO multi-institutional study.

This study quantified the incidental dose to the first axillary level (L1) in locoregional treatment plan for breast cancer. Eighteen radiotherapy centres contoured L1-L4 on three different patients (P1,2,3), created the L2-L4 planning target volume (single centre planning target volume, SC-PTV) and elaborated a locoregional treatment plan. The L2-L4 gold standard clinical target volume (CTV) along with the gold standard L1 contour (GS-L1) were created by an expert consensus. The SC-PTV was then replaced by the GS-PTV and the incidental dose to GS-L1 was measured. Dosimetric data were analysed with Kruskal-Wallis test. Plans were intensity modulated radiotherapy (IMRT)-based. P3 with 90° arm setup had statistically significant higher L1 dose across the board than P1 and P2, with the mean dose (Dmean) reaching clinical significance. Dmean of P1 and P2 was consistent with the literature (77.4% and 74.7%, respectively). The incidental dose depended mostly on L1 proportion included in the breast fields, underlining the importance of the setup, even in case of IMRT.

Twenty Years of Advancements in a Radiotherapy Facility: Clinical Protocols, Technology, and Management.

BACKGROUND: Hypo-fractionation can be an effective strategy to lower costs and save time, increasing patient access to advanced radiation therapy. To demonstrate this potential in practice within the context of temporal evolution, a twenty-year analysis of a representative radiation therapy facility from 2003 to 2022 was conducted. This analysis utilized comprehensive data to quantitatively evaluate the connections between advanced clinical protocols and technological improvements. The findings provide valuable insights to the management team, helping them ensure the delivery of high-quality treatments in a sustainable manner. METHODS: Several parameters related to treatment technique, patient positioning, dose prescription, fractionation, equipment technology content, machine workload and throughput, therapy times and patients access counts were extracted from departmental database and analyzed on a yearly basis by means of linear regression. RESULTS: Patients increased by 121 ± 6 new per year (NPY). Since 2010, the incidence of hypo-fractionation protocols grew thanks to increasing Linac technology. In seven years, both the average number of fractions and daily machine workload decreased by -0.84 ± 0.12 fractions/year and -1.61 ± 0.35 patients/year, respectively. The implementation of advanced dose delivery techniques, image guidance and high dose rate beams for high fraction doses, currently systematically used, has increased the complexity and reduced daily treatment throughput since 2010 from 40 to 32 patients per 8 h work shift (WS8). Thanks to hypo-fractionation, such an efficiency drop did not affect NPY, estimating 693 ± 28 NPY/WS8, regardless of the evaluation time. Each newly installed machine was shown to add 540 NPY, while absorbing 0.78 ± 0.04 WS8. The COVID-19 pandemic brought an overall reduction of 3.7% of patients and a reduction of 0.8 fractions/patient, to mitigate patient crowding in the department. CONCLUSIONS: The evolution of therapy protocols towards hypo-fractionation was supported by the use of proper technology. The characteristics of this process were quantified considering time progression and organizational aspects. This strategy optimized resources while enabling broader access to advanced radiation therapy. To truly value the benefit of hypo-fractionation, a reimbursement policy should focus on the patient rather than individual treatment fractionation.

Multimodal Treatments for Brain Metastases from Renal Cell Carcinoma: Results of a Multicentric Retrospective Study.

The aim of this study was to evaluate the clinical outcomes of a large series of brain metastatic renal cell carcinoma (BMRCC) patients treated in three Italian centers. METHODS: A total of 120 BMRCC patients with a total of 176 lesions treated were evaluated. Patients received surgery plus postoperative HSRS, single-fraction SRS, or hypofractionated SRS (HSRS). Local control (LC), brain distant failure (BDF), overall survival (OS), toxicities, and prognostic factors were assessed. RESULTS: The median follow-up time was 77 months (range 16-235 months). Surgery plus HSRS was performed in 23 (19.2%) cases, along with SRS in 82 (68.3%) and HSRS in 15 (12.5%). Seventy-seven (64.2%) patients received systemic therapy. The main total dose and fractionation used were 20-24 Gy in single fraction or 32-30 Gy in 4-5 daily fractions. Median LC time and 6 month and 1, 2 and 3 year LC rates were nr, 100%, 95.7% ± 1.8%, 93.4% ± 2.4%, and 93.4% ± 2.4%. Median BDF time and 6 month and 1, 2 and 3 year BDF rates were n.r., 11.9% ± 3.1%, 25.1% ± 4.5%, 38.7% ± 5.5%, and 44.4% ± 6.3%, respectively. Median OS time and 6 month and 1, 2 and 3 year OS rates were 16 months (95% CI: 12-22), 80% ± 3.6%, 58.3% ± 4.5%, 30.9% ± 4.3%, and 16.9% ± 3.6, respectively. No severe neurological toxicities occurred. Patients with a favorable/intermediate IMDC score, a higher RCC-GPA score, an early occurrence of BMs from primary diagnosis, absence of EC metastases, and a combined local treatment (surgery plus adjuvant HSRS) had a better outcome. CONCLUSIONS: SRS/HSRS is proven to be an effective local treatment for BMRCC. A careful evaluation of prognostic factors is a valid step to manage the optimal therapeutic strategy for BMRCC patients.

Radiosurgery of limited brain metastases from primary solid tumor: results of the randomized phase III trial (NCT02355613) comparing treatments executed with a specialized or a C-arm linac-based platform.

BACKGROUND: Comparative prospective data regarding different radiosurgery (SRS) modalities for treating brain metastases (BMs) from solid tumors are not available. To investigate with a single institute phase III randomized trial whether SRS executed with linac (Arm-B) is superior to a dedicated multi-source gamma-ray stereotactic platform (Arm-A). METHODS: Adults patients with 1-4 BMs from solid tumors up to 30 mm in maximum diameter were randomly assigned to arms A and B. The primary endpoint was cumulative incidence of symptomatic (grade 2-3) radionecrosis (CIRN). Secondary endpoints were local progression cumulative incidence (CILP), distant brain failure, disease-free survival (DFS), and overall survival (OS). RESULTS: A total of 251 patients were randomly assigned to Arm-A (121) or Arm-B (130). The 1-year RN cumulative incidence was 6.7% in whole cohort, 3.8% (95% CI 1.9-7.4%) in Arm-B, and 9.3% (95% CI 6.2-13.8%) in the Arm-A (p = 0.43). CIRN was influenced by target volume irradiated only for the Arm-A (p << 0.001; HR 1.36 [95% CI 1.25-1.48]). Symptomatic RN occurred in 56 cases at a median time of 10.3 months (range 1.15-54.8 months), 27 in the Arm-B at a median time of 15.9 months (range 4.9-54.8 months), and 29 in the Arm-A at a median time of 6.9 months (1.2-32.3 months), without statistically significant differences between the two arms. No statistically significant differences were recorded between the two arms in CILP, BDF, DFS or OS. The mean beam-on time to deliver SRS was 49.0 ± 36.2 min in Arm-A, and 3.1 ± 1.6 min in Arm-B. CONCLUSIONS: Given the technical differences between the treatment platforms investigated in this single-institution study, linac-based SRS (Arm-B) did not lead to significantly lower grade 2-3 RN rates versus the multi-source gamma-ray system (Arm-A) in a population of patients with limited brain metastases of small volume. No significant difference in local control was observed between both arms. For Arm-B, the treatment delivery time was significantly lower than for Arm-A. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT02355613.

Knowledge-based DVH estimation and optimization for breast VMAT plans with and without avoidance sectors.

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

Geometric contour variation in clinical target volume of axillary lymph nodes in breast cancer radiotherapy: an AIRO multi-institutional study.

OBJECTIVES: To determine interobserver variability in axillary nodal contouring in breast cancer (BC) radiotherapy (RT) by comparing the clinical target volume of participating single centres (SC-CTV) with a gold-standard CTV (GS-CTV). METHODS: The GS-CTV of three patients (P1, P2, P3) with increasing complexity was created in DICOM format from the median contour of axillary CTVs drawn by BC experts, validated using the simultaneous truth and performance-level estimation and peer-reviewed. GS-CTVs were compared with the correspondent SC-CTVs drawn by radiation oncologists, using validated metrics and a total score (TS) integrating all of them. RESULTS: Eighteen RT centres participated in the study. Comparative analyses revealed that, on average, the SC-CTVs were smaller than GS-CTV for P1 and P2 (by -29.25% and -27.83%, respectively) and larger for P3 (by +12.53%). The mean Jaccard index was greater for P1 and P2 compared to P3, but the overlap extent value was around 0.50 or less. Regarding nodal levels, L4 showed the highest concordance with the GS. In the intra-patient comparison, L2 and L3 achieved lower TS than L4. Nodal levels showed discrepancy with GS, which was not statistically significant for P1, and negligible for P2, while P3 had the worst agreement. DICE similarity coefficient did not exceed the minimum threshold for agreement of 0.70 in all the measurements. CONCLUSIONS: Substantial differences were observed between SC- and GS-CTV, especially for P3 with altered arm setup. L2 and L3 were the most critical levels. The study highlighted these key points to address. ADVANCES IN KNOWLEDGE: The present study compares, by means of validated geometric indexes, manual segmentations of axillary lymph nodes in breast cancer from different observers and different institutions made on radiotherapy planning CT images. Assessing such variability is of paramount importance, as geometric uncertainties might lead to incorrect dosimetry and compromise oncological outcome.

Charlson comorbidity index and G8 in older old adult(≥80 years) hepatocellular carcinoma patients treated with stereotactic body radiotherapy.

INTRODUCTION: Hepatocellular Carcinoma (HCC) is characterized, in Western countries, by higher incidence and mortality rates in the older adult population. In frail patients, limited therapeutic resources are available due to limited expected benefit concerning the risk of treatment-related toxicity. The aim of our study is to evaluate the role of Stereotactic Body Radiotherapy (SBRT) in the clinical management of older old adults (age ≥ 80 years) HCC patients and to identify predictors of efficacy and toxicity. MATERIAL AND METHODS: Clinical and treatment-related data of older old adults HCC patients treated with SBRT at our institution were retrospectively reviewed. Statistical analysis was carried out to identify variables correlated with impaired outcome and toxicity. RESULTS: Forty-two patients were included, accounting for 63 treated tumors. Median age was 85 (range 80-91) years. Median Charlson Comorbidity Index (CCI) and G8 scores were 10 (range 7-16) and 11 (range 8-14), respectively. SBRT was administered to a median BED10 of 103 Gy10. Median follow-up interval was 11 (range 3-40) months. Two years Local Control (LC), Progression-Free Survival (PFS), and Overall Survival (OS) were 93%, 31%, and 43%, respectively. Acute toxicity occurred in 28% (n = 13) of treatments. A G8 score > 10 was associated with improved survival (p = 0.045), while a CCI ≥10 was correlated with increased acute toxicity (p = 0.021). CONCLUSIONS: SBRT is a safe and effective option in older old adults HCC patients. A comprehensive geriatric assessment (CGA) is advised before treatment decisions to select optimal candidates for SBRT.

Critical Re-Evaluation of a Failure Mode Effect Analysis in a Radiation Therapy Department After 10 Years.

PURPOSE: Failure mode effect analysis (FMEA) is a proactive methodology that allows one to analyze a process, regardless of whether an adverse event occurs. In our radiation therapy (RT) department, a first FMEA was performed in 2009. In this paper we critically re-evaluate the RT process after 10 years and present it in terms of a lesson learned. METHODS AND MATERIALS: A working group (WG), led by a qualified clinical risk engineer, which included radiation oncologists, physicists, a radiation therapist, and a nurse, evaluated the possible failure modes (FMs) of the RT process. For each FM, the estimated frequency of occurrence (O, range 1-4), the expected severity of the damage (S, range 1-5), and the detectability lack (D, range 1-4) were scored. A risk priority number (RPN) was obtained as RPN = OxSxD. The data were compared with the 2009 edition. RESULTS: In the 2020 analysis, 67 FMs were identified (27 in the 2009 series). The absolute risk values of the previous 3 highest FMs were generally reduced. The patient identification risk (highest value in the 2009 analysis) was reduced from 48.0 to 6.9, becoming the 51st RPN score, thanks to a patient barcode recognition within the bunker. The 2020 highest risk values regarded: (i-2020) the patient's inadequate recollection and reporting of his/her medical history (ie, anamnesis) during the first medical examination and (ii-2020) the incorrect interpretation of tumor and normal tissue in computed tomography images. The WG proposed corrective actions. CONCLUSIONS: In this single institution experience, the 10-year FMEA analysis showed a reduction in the previous higher RPN values thanks to the corrective actions taken. The new FMs and subsequent RPNs reveal the need for a continuous iterative improvement process.

Hypofractionated Whole Breast Irradiation and Simultaneous Integrated Boost in Large-breasted Patients: Long-term Toxicity and Cosmesis.

INTRODUCTION: The purpose of this study was to evaluate the impact of breast size on long-term toxicity and cosmesis in patients with breast cancer treated with hypofractionated simultaneous integrated boost (SIB) using volumetric modulated arc therapy (VMAT). PATIENTS AND METHODS: Patients with early stage breast cancer were treated with 3-week hypofractionated SIB-VMAT to the whole breast (40.5 Gy) and tumor bed (48 Gy). Two cohorts were identified: small/medium- (< 1000 cm3) and large- (> 1000 cm3) breasted patients. Acute and late (at 2 and 5 years) skin toxicity and cosmetic data were analyzed. Univariate and multivariate analysis evaluated associations between toxicity and dosimetric/anatomical variables. RESULTS: From August 2010 to March 2017, a total of 1160 patients were treated; 831 had at least 2 years of follow-up and were analyzed. Treated skin area (TSA) receiving at least 20 Gy > 400 cm2 and V105% of Boost > 5 cm3 were significant predictors for acute skin toxicity. Multivariate analysis at 2 years was significant for boost volume > 70 cm3, TSA > 400 cm2, and breast size > 1500 cm3. At 5 year analysis (352 patients), none of the analyzed variables was significant. For cosmetic outcome, only the breast size (> 1000 cm3) and the boost size > 70 cm3 at 2 and 5 years, respectively, confirmed significance. CONCLUSIONS: The TSA > 400 cm2 resulted as a significant predictor of both acute and late skin toxicity at 2 years; however, at 5 years, no breast size or dosimetric parameter suggested indications for increased toxicity. A worse cosmetic outcome was recorded at the 2-year follow up for large breasts, but was not confirmed at the 5-year follow-up. These long-term data suggest that hypofractionated SIB-VMAT is a viable modality also in large-breasted patients.

MLC parameters from static fields to VMAT plans: an evaluation in a RT-dedicated MC environment (PRIMO).

BACKGROUND: PRIMO is a graphical environment based on PENELOPE Monte Carlo (MC) simulation of radiotherapy beams able to compute dose distribution in patients, from plans with different techniques. The dosimetric characteristics of an HD-120 MLC (Varian), simulated using PRIMO, were here compared with measurements, and also with Acuros calculations (in the Eclipse treatment planning system, Varian). MATERIALS AND METHODS: A 10 MV FFF beam from a Varian EDGE linac equipped with the HD-120 MLC was used for this work. Initially, the linac head was simulated inside PRIMO, and validated against measurements in a water phantom. Then, a series of different MLC patterns were established to assess the MLC dosimetric characteristics. Those tests included: i) static fields: output factors from MLC shaped fields (2 × 2 to 10 × 10 cm2), alternate open and closed leaf pattern, MLC transmitted dose; ii) dynamic fields: dosimetric leaf gap (DLG) evaluated with sweeping gaps, tongue and groove (TG) effect assessed with profiles across alternate open and closed leaves moving across the field. The doses in the different tests were simulated in PRIMO and then compared with EBT3 film measurements in solid water phantom, as well as with Acuros calculations. Finally, MC in PRIMO and Acuros were compared in some clinical cases, summarizing the clinical complexity in view of a possible use of PRIMO as an independent dose calculation check. RESULTS: Static output factor MLC tests showed an agreement between MC calculated and measured OF of 0.5%. The dynamic tests presented DLG values of 0.033 ± 0.003 cm and 0.032 ± 0.006 cm for MC and measurements, respectively. Regarding the TG tests, a general agreement between the dose distributions of 1-2% was achieved, except for the extreme patterns (very small gaps/field sizes and high TG effect) were the agreement was about 4-5%. The analysis of the clinical cases, the Gamma agreement between MC in PRIMO and Acuros dose calculation in Eclipse was of 99.5 ± 0.2% for 3%/2 mm criteria of dose difference/distance to agreement. CONCLUSIONS: MC simulations in the PRIMO environment were in agreement with measurements for the HD-120 MLC in a 10 MV FFF beam from a Varian EDGE linac. This result allowed to consistently compare clinical cases, showing the possible use of PRIMO as an independent dose calculation check tool.

Computed tomography based radiomic signature as predictive of survival and local control after stereotactic body radiation therapy in pancreatic carcinoma.

PURPOSE: To appraise the ability of a radiomics signature to predict clinical outcome after stereotactic body radiation therapy (SBRT) for pancreas carcinoma. METHODS: A cohort of 100 patients was included in this retrospective, single institution analysis. Radiomics texture features were extracted from computed tomography (CT) images obtained for the clinical target volume. The cohort of patients was randomly divided into two separate groups for the training (60 patients) and validation (40 patients). Cox regression models were built to predict overall survival and local control. The significant predictors at univariate analysis were included in a multivariate model. The quality of the models was appraised by means of area under the curve and concordance index. RESULTS: A clinical-radiomic signature associated with Overall Survival (OS) was found significant in both training and validation sets (p = 0.01 and 0.05 and concordance index 0.73 and 0.75 respectively). Similarly, a signature was found for Local Control (LC) with p = 0.007 and 0.004 and concordance index 0.69 and 0.75. In the low risk group, the median OS and LC in the validation group were 14.4 and 28.6 months while in the high-risk group were 9.0 and 17.5 months respectively. CONCLUSION: A CT based radiomic signature was identified which correlate with OS and LC after SBRT and allowed to identify low and high-risk groups of patients.

Radiomics based analysis to predict local control and survival in hepatocellular carcinoma patients treated with volumetric modulated arc therapy.

BACKGROUND: To appraise the ability of a radiomics based analysis to predict local response and overall survival for patients with hepatocellular carcinoma. METHODS: A set of 138 consecutive patients (112 males and 26 females, median age 66 years) presented with Barcelona Clinic Liver Cancer (BCLC) stage A to C were retrospectively studied. For a subset of these patients (106) complete information about treatment outcome, namely local control, was available. Radiomic features were computed for the clinical target volume. A total of 35 features were extracted and analyzed. Univariate analysis was used to identify clinical and radiomics significant features. Multivariate models by Cox-regression hazards model were built for local control and survival outcome. Models were evaluated by area under the curve (AUC) of receiver operating characteristic (ROC) curve. For the LC analysis, two models selecting two groups of uncorrelated features were analyzes while one single model was built for the OS analysis. RESULTS: The univariate analysis lead to the identification of 15 significant radiomics features but the analysis of cross correlation showed several cross related covariates. The un-correlated variables were used to build two separate models; both resulted into a single significant radiomic covariate: model-1: energy p < 0.05, AUC of ROC 0.6659, C.I.: 0.5585-0.7732; model-2: GLNU p < 0.05, AUC 0.6396, C.I.:0.5266-0.7526. The univariate analysis for covariates significant with respect to local control resulted in 9 clinical and 13 radiomics features with multiple and complex cross-correlations. After elastic net regularization, the most significant covariates were compacity and BCLC stage, with only compacity significant to Cox model fitting (Cox model likelihood ratio test p < 0.0001, compacity p < 0.00001; AUC of the model is 0.8014 (C.I. = 0.7232-0.8797)). CONCLUSION: A robust radiomic signature, made by one single feature was finally identified. A validation phases, based on independent set of patients is scheduled to be performed to confirm the results.

Use of PTW-microDiamond for relative dosimetry of unflattened photon beams.

PURPOSE: The increasing interest in SBRT treatments encourages the use of flattening filter free (FFF) beams. Aim of this work was to evaluate the performance of the PTW60019 microDiamond detector under 6MV and 10MVFFF beams delivered with the EDGE accelerator (Varian Medical System, Palo Alto, USA). A flattened 6MV beam was also considered for comparison. METHODS: Short term stability, dose linearity and dose rate dependence were evaluated. Dose per pulse dependence was investigated in the range 0.2-2.2mGy/pulse. MicroDiamond profiles and output factors (OFs) were compared to those obtained with other detectors for field sizes ranging from 40×40cm2 to 0.6×0.6cm2. In small fields, volume averaging effects were evaluated and the relevant correction factors were applied for each detector. RESULTS: MicroDiamond short term stability, dose linearity and dependence on monitor unit rate were less than 0.8% for all energies. Response variations with dose per pulse were found within 1.8%. MicroDiamond output factors (OF) values differed from those measured with the reference ion-chamber for less than 1% up to 40×40cm2 fields where silicon diodes overestimate the dose of ≈3%. For small fields (<3×3cm2) microDiamond and the unshielded silicon diode were in good agreement. CONCLUSIONS: MicroDiamond showed optimal characteristics for relative dosimetry even under high dose rate beams. The effects due to dose per pulse dependence up to 2.2mGy/pulse are negligible. Compared to other detectors, microDiamond provides accurate OF measurements in the whole range of field sizes. For fields <1cm correction factors accounting for fluence perturbation and volume averaging could be required.

Dosimetric trade-offs in breast treatment with VMAT technique.

OBJECTIVE: Breast planning with volumetric modulated arc therapy (VMAT) has been explored, especially for left-sided breast treatments, with the primary intent of lowering the heart dose and improving target dose homogeneity. As a trade-off, larger healthy tissue volumes would receive low dose levels, with the potential risk of increasing late toxicities and secondary cancer induction, although no clinical data are available today to confirm the risk level. The scope of this work is to explore the dosimetric trade-offs using two different VMAT plans. METHODS: Two planning strategies for dual-partial-arc VMAT, RA_avoid and RA_full, with and without avoidance sectors, were explored in a cohort of 20 patients, for whole left breast irradiation for 40.05 Gy to the mean target dose in 15 fractions. Common dose objectives included a stringent dose homogeneity, mean dose to the heart <5 Gy, ipsilateral lung (Ilung) <8 Gy, contralateral lung (Clung) <2 Gy and contralateral breast (Cbreast) <3 Gy. RESULTS: RA_full showed a better dose conformity, lower high-dose spillage in the healthy tissue and lower skin dose. RA_avoid presented a reduction of the mean doses for all critical structures: 51% to the heart, 12% to the Ilung, 81% to the Clung and 73% to the Cbreast. All differences were significant with p < 0.0001. CONCLUSION: The adaptation of VMAT options to planning objectives reduced significantly the healthy tissue dose levels at the price of some high-dose spillage. Evaluation of the trade-offs for application to the different critical structures should drive in improving the usage of the VMAT technique for breast cancer treatment. Advances in knowledge: Different planning strategies in the same VMAT technique could give significant variations in dose distributions. The choice of the trade-offs would affect the possible future late toxicity and secondary cancer induction risk.

Evaluation of the dose calculation accuracy for small fields defined by jaw or MLC for AAA and Acuros XB algorithms.

PURPOSE: Small field measurements are challenging, due to the physical characteristics coming from the lack of charged particle equilibrium, the partial occlusion of the finite radiation source, and to the detector response. These characteristics can be modeled in the dose calculations in the treatment planning systems. Aim of the present work is to evaluate the MU calculation accuracy for small fields, defined by jaw or MLC, for anisotropic analytical algorithm (AAA) and Acuros XB algorithms, relative to output measurements on the beam central axis. METHODS: Single point output factor measurement was acquired with a PTW microDiamond detector for 6 MV, 6 and 10 MV unflattened beams generated by a Varian TrueBeam STx equipped with high definition-MLC. Fields defined by jaw or MLC apertures were set; jaw-defined: 0.6 × 0.6, 0.8 × 0.8, 1 × 1, 2 × 2, 3 × 3, 4 × 4, 5 × 5, and 10 × 10 cm2; MLC-defined: 0.5 × 0.5 cm2 to the maximum field defined by the jaw, with 0.5 cm stepping, and jaws set to: 2 × 2, 3 × 3, 4 × 4, 5 × 5, and 10 × 10 cm2. MU calculation was obtained with 1 mm grid in a virtual water phantom for the same fields, for AAA and Acuros algorithms implemented in the Varian eclipse treatment planning system (version 13.6). Configuration parameters as the effective spot size (ESS) and the dosimetric leaf gap (DLG) were varied to find the best parameter setting. Differences between calculated and measured doses were analyzed. RESULTS: Agreement better than 0.5% was found for field sizes equal to or larger than 2 × 2 cm2 for both algorithms. A dose overestimation was present for smaller jaw-defined fields, with the best agreement, averaged over all the energies, of 1.6% and 4.6% for a 1 × 1 cm2 field calculated by AAA and Acuros, respectively, for a configuration with ESS = 1 mm for both X and Y directions for AAA, and ESS = 1.5 and 0 mm for X and Y directions for Acuros. Conversely, a calculated dose underestimation was found for small MLC-defined fields, with the best agreement averaged over all the energies, of -3.9% and 0.2% for a 1 × 1 cm2 field calculated by AAA and Acuros, respectively, for a configuration with ESS = 0 mm for both directions and both algorithms. CONCLUSIONS: For optimal setting applied in the algorithm configuration phase, the agreement of Acuros calculations with measurements could achieve the 3% for MLC-defined fields as small as 0.5 × 0.5 cm2. Similar agreement was found for AAA for fields as small as 1 × 1 cm2.

Phase II trial of hypofractionated VMAT-based treatment for early stage breast cancer: 2-year toxicity and clinical results.

BACKGROUND: To report toxicity and early clinical outcomes of hypofractionated simultaneous integrated boost (SIB) approach with Volumetric Modulated Arc Therapy (VMAT) as adjuvant treatment after breast-conserving surgery. METHODS: Patients presenting early-stage breast cancer were enrolled in a phase II trial. ELIGIBILITY CRITERIA: age > 18 years old, invasive cancer or ductal carcinoma in situ (DCIS), Stage I-II (T < 3 cm and N ≤ 3), breast-conserving surgery without oncoplastic reconstruction. Any systemic therapy was allowed in neoadjuvant or adjuvant setting. All patients underwent VMAT-SIB technique to irradiate the whole breast and the tumor bed. Doses to whole breast and surgical bed were 40.5 Gy and 48 Gy, respectively, delivered in 15 fractions over 3 weeks. Acute and late skin toxicities were recorded. Cosmetic outcome was assessed as excellent/good or fair/poor. RESULTS: The present study focused on results of a cohort of 144 patients with a minimum follow-up of 24 months (median 37, range 24-55 months). Median age was 62 years old (range 30-88). All patients had an invasive carcinoma (no patients with DCIS were present in this subset). At one year, the highest reported skin toxicity was G1, in 14 % of the patients; this data dropped to 4 % at the last follow-up, after more than 2 years. Breast pain was recorded in 21.6 % of the patients 6 months after treatment, while it was present in 3.5 % of the patients at the last follow-up, showing a significant improvement with time. Correlation between liponecrosis and boost target volume was found not significant. Breast pain was correlated with breast volume. No pulmonary or cardiological toxicities were recorded. After an early evaluation of clinical outcomes, only one case presented disease relapse, as liver metastases. CONCLUSIONS: The 3-week VMAT-SIB course as adjuvant treatment after breast-conserving surgery showed to be well tolerated and was associated with optimal local control. Long-term follow-up data are needed to assess late toxicity and clinical outcomes.

Small field correction factors for the IBA Razor.

The IBA Razor diode supersedes the IBA SFD and is intended for use in small fields. However, its behaviour in small fields has not yet been quantified. In this work, we examine the response of the Razor diode against the air core scintillation dosimeter (FOD) and Gafchromic film in photon beams from three Varian linac beams. Fields between 4mm and 30mm in width were measured, both with and without a flattening filter and at two energies. The Razor exhibited an over-response of up to 4.5% for MLC collimated fields and 7.1% for stereotactic cone collimated fields. The presence of the flattening filter altered the over-response by up to 1.5%. The small field correction factors are tabulated and agree with the mathematical relation of Liu et al. (2014). Four samples of the Razor were used, two having received a significant prior dose. The correction factors for the four samples differed and may depend on their dose history.

Can advanced new radiation therapy technologies improve outcome of high grade glioma (HGG) patients? analysis of 3D-conformal radiotherapy (3DCRT) versus volumetric-modulated arc therapy (VMAT) in patients treated with surgery, concomitant and adjuvant chemo-radiotherapy.

BACKGROUND: To assess the impact of volumetric-modulated arc therapy (VMAT) compared with 3D-conformal radiotherapy (3DCRT) in patients with newly diagnosed high grade glioma in terms of toxicity, progression free survival (PFS) and overall survival (OS). METHODS: From March 2004 to October 2014, 341 patients underwent surgery followed by concomitant and adjuvant chemo-radiotherapy. From 2003 to 2010, 167 patients were treated using 3DCRT; starting from 2011, 174 patients underwent VMAT. The quantitative evaluation of the treatment plans was performed by means of standard dose volume histogram analysis. Response was recorded using the Response Assessment in Neuro-Oncology (RANO) criteria and toxicities graded according to Common Terminology Criteria for Adverse Event version 4.0. RESULTS: Both techniques achieved an adequate dose conformity to the target. The median follow up time was 1.3 years; at the last observation 76 patients (23.4 %) were alive and 249 (76.6 %) dead (16 patients were lot to follow-up). For patients who underwent 3DCRT, the median PFS was 0.99 ± 0.07 years (CI95: 0.9-1.1 years); the 1 and 3 years PFS were, 49.6 ± 4 and 19.1 ± 3.1 %. This shall be compared, respectively, to 1.29 ± 0.13 years (CI95: 1.01-1.5 years), 60.8 ± 3.8, and 29.7 ± 4.6 % for patients who underwent VMAT (p = 0.02). The median OS for 3DCRT patients was 1.21 ± 0.09 years (CI95:1.03-1.3 years); 1 and 5 year OS was, 63.3 ± 3.8 and 21.5 ± 3.3 %. The corresponding results for 3DRCT patients were 1.56 ± 0.09 years (CI95:1.37-1.74 years), 73.4 ± 3.5, 30 ± 4.6 % respectively (p < 0.01). In both groups, prognostic factors conditioning PFS and OS were age, gender, KPS, histology and extent of resection (EOR). CONCLUSIONS: VMAT resulted superior to 3DCRT in terms of dosimetric findings and clinical results.