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.

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.

Hypofractionated stereotactic radiation therapy in skull base meningiomas.

To investigate the role of hypo-fractionated stereotactic radiation treatment (HSRT) in the management of skull base meningioma. Twenty-six patients were included in the study and treated with a dose of 30 Gy in 5 fractions with volumetric modulated arc therapy (RapidArc). Eighteen patients were symptomatic before treatment. Endpoints were local toxicity and relief from symptoms. Tumors were located in anterior skull base in 4/27 cases, in middle skull base in 12/27 and in posterior skull base in 11/27. HSRT was performed as first treatment in 17 (65 %) patients, in 9 (35 %) patients it followed a previous partial resection. Median follow up was 24.5 months (range 5-57 months). clinical remission of symptoms, complete or partial, was obtained in the vast majority of patients after treatment. Out of the 18 symptomatic patients, partial remission occurred in 9 (50 %) patients and complete remission in 9 (50 %). All asymptomatic patients retained their status after treatment. No severe neurologic toxicity grade III-IV was recorded. No increase of meningioma in the same site of treatment occurred; 16 (62 %) patients had stable disease and 9 (38 %) patients had tumor reduction. The mean tumor volume after treatment was 10.8 ± 17.8 cm(3) compared with 13.0 ± 19.1 cm(3) before treatment (p = 0.02). The mean actuarial OS was 54.4 ± 2.8 months. The 1- and 2-years OS was 92.9 ± 0.7 %. HSRT proved to be feasible for these patients not eligible to full surgery or to ablative radiation therapy. Local control and durability of results suggest for a routine application of this approach in properly selected cases.

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.

Dosimetric comparison between VMAT with different dose calculation algorithms and protons for soft-tissue sarcoma radiotherapy.

BACKGROUND: To appraise the potential of volumetric modulated arc therapy (VMAT, RapidArc) and proton beams to simultaneously achieve target coverage and enhanced sparing of bone tissue in the treatment of soft-tissue sarcoma with adequate target coverage. MATERIAL AND METHODS: Ten patients presenting with soft-tissue sarcoma of the leg were collected for the study. Dose was prescribed to 66.5 Gy in 25 fractions to the planning target volume (PTV) while significant maximum dose to the bone was constrained to 50 Gy. Plans were optimised according to the RapidArc technique with 6 MV photon beams or for intensity modulated protons. RapidArc photon plans were computed with: 1) AAA; 2) Acuros XB as dose to medium; and 3) Acuros XB as dose to water. RESULTS: All plans acceptably met the criteria of target coverage (V95% >90-95%) and bone sparing (D(1 cm3) <50 Gy). Significantly higher PTV dose homogeneity was found for proton plans. Near-to-maximum dose to bone was similar for RapidArc and protons, while volume receiving medium/low dose levels was minimised with protons. Similar results were obtained for the remaining normal tissue. Dose distributions calculated with the dose to water option resulted ~5% higher than corresponding ones computed as dose to medium. CONCLUSION: High plan quality was demonstrated for both VMAT and proton techniques when applied to soft-tissue sarcoma.

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.

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.

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.

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.

Can volumetric modulated arc therapy with flattening filter free beams play a role in stereotactic body radiotherapy for liver lesions? A volume-based analysis.

PURPOSE: To compare volumetric modulated arc therapy with flattening filter free (FFF) and flattening filter (FF) beams in patients with hepatic metastases subject to hypofractionated radiotherapy (RT). METHODS: A planning study on 13 virtual lesions of increasing volume was performed. Two single arc plans were optimized with the RapidArc technique using either FFF or FF beams. A second planning study was performed on ten patients treated for liver metastases to validate conclusions. In all cases, a dose of 75 Gy in 3 fractions was prescribed to the planning target volume (PTV) and plans were evaluated in terms of coverage, homogeneity, conformity, mean dose to healthy liver and to healthy tissue. For each parameter, results were expressed in relative terms as the percentage ratio between FFF and FF data. RESULTS: In terms of PTV coverage, conformity index favored FFF for targets of intermediate size while FF resulted more suitable for small (<100 cm(3)) and large (>300 cm(3)) targets. Plans optimized with FFF beams resulted in increased sparing of healthy tissue in ≈85% of cases. Despite the qualitative results, no statistically significant differences were found between FFF and FF results. Plans optimized with un-flattened beams resulted in higher average MU∕Gy than plans with FF beams. A remarkable and significant difference was observed in the beam-on time (BOT) needed to deliver plans. The BOT for FF plans was 8.2 ± 1.0 min; for FFF plans BOT was 2.2 ± 0.2 min. CONCLUSIONS: RapidArc plans optimized using FFF were dosimetrically equivalent to those optimized using FF beams, showing the feasibility of SBRT treatments with FFF beams. Some improvement in healthy tissue sparing was observed when using the FFF modality due to the different beam's profile. The main advantage was a considerable reduction of beam-on time, relevant for SBRT techniques.

Anatomy driven optimization strategy for total marrow irradiation with a volumetric modulated arc therapy technique.

The purpose of this study was to evaluate the possibility of dose distribution optimization for total marrow irradiation (TMI) employing volumetric-modulated arc therapy (VMAT) with RapidArc (RA) technology setting isocenter's positions and jaw's apertures according to patient's anatomical features. Plans for five patients were generated with the RA engine (PROIII): eight arcs were distributed along four isocenters and simultaneously optimized with collimator set to 90°. Two models were investigated for geometrical settings of arcs: (1) in the "symmetric" model, isocenters were equispaced and field apertures were set the same for all arcs to uniformly cover the entire target length; (2) in the "anatomy driven" model, both field sizes and isocenter positions were optimized in order to minimize the target volume near the field edges (i.e., to maximize the freedom of motion of MLC leaves inside the field aperture (for example, avoiding arcs with ribs and iliac wings in the same BEV)). All body bones from the cranium to mid of the femurs were defined as PTV; the maximum length achieved in this study was 130 cm. Twelve (12) Gy in 2 Gy/fractions were prescribed in order to obtain the covering of 85% of the PTV by 100% of the prescribed dose. For all organs at risk (including brain, optical structures, oral and neck structures, lungs, heart, liver, kidneys, spleen, bowels, bladder, rectum, genitals), planning strategy aimed to maximize sparing according to ALARA principles, looking to reach a mean dose lower than 6 Gy (i.e., 50% of the prescribed dose). Mean MU/fraction resulted 3184 ± 354 and 2939 ± 264 for the two strategies, corresponding to a reduction of 7% (range -2% to 13%) for (1) and (2). Target homogeneity, defined as D(2%)-D(98%) was 18% better for (2). Mean dose to the healthy tissue, defined as body minus PTV, had 10% better reduction with (2). The isocenter's position and the jaw's apertures are significant parameters in the optimization of the TMI with RA technique, giving the medical physicist a crucial role in driving the optimization and thus obtaining the best plan. A clinical protocol started in our department in October 2010.

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.

Stereotactic body radiation therapy (SBRT) for adrenal metastases : a feasibility study of advanced techniques with modulated photons and protons.

PURPOSE: To compare advanced treatment techniques with photons and protons as a stereotactic body radiation therapy (SBRT) for adrenal glands metastases. MATERIALS AND METHODS: Planning computer tomographic (CT) scans of 10 patients were selected. A total dose of 45 Gy in 7.5 Gy fractions was prescribed. Organs at risk (OAR) were liver and kidneys. Dose-volume metrics were defined to quantify quality of plans assessing target coverage and sparing of organs at risk. Plans for RapidArc, intensity-modulated radiotherapy (IMRT), dynamic conformal arcs, 3D conformal static fields, and intensity modulated protons were compared. The main planning objective for the clinical target volume (CTV) was to cover 100% of the volume with 95% (V(95%) = 100%) and to keep the maximum dose below 107% of the prescribed dose (V(107%) = 0%). Planning objective for planning target volume (PTV) was V(95%) > 80%. For kidneys, the general planning objective was V(15Gy) < 35% and for liver V(15Gy) < (liver volume-700 cm(3)). RESULTS: All techniques achieved the minimum and maximum dose objective for CTV and PTV, D(5-95%) ranged from 1 Gy (protons) to 1.6 Gy (conformal static fields) on CTV. Maximal organ at risk sparing was achieved by protons. RapidArc presented the second lowest dose bath (V(10Gy) and integral dose) after protons and the best conformality together with IMRT. CONCLUSIONS: Stereotactic body radiation therapy (SBRT) to adrenal glands metastases is achievable with several advanced techniques with either photons or protons. The intensity modulated approaches using either static fields, dynamic arcs or protons are superior to the other conformal solutions. For their simplicity, IMRT or RapidArc should be considered as the first option radiation treatment for those patients not eligible for proton treatment.

Semiautomatic method to identify the best phase for gated RT in lung region by 4D-PET/CT acquisitions.

PURPOSE: Delineating tumor motion by four-dimensional positron emission tomography/computed tomography (4D-PET/CT) is a crucial step for gated radiotherapy (RT). This article quantitatively evaluates semiautomatic algorithms for tumor shift estimation in the lung region due to patient respiration by 4D-PET/CT, in order to support the selection of the best phases for gated RT, by considering the most stable phases of the breathing cycle. METHODS: Three mobile spheres and ten selected lesions were included in this study. 4D-PET/CT data were reconstructed and classified into six/ten phases. The semiautomatic algorithms required the generation of single sets of images representative of the full target motion, used as masks for segmenting the phases. For 4D-CT, a pre-established HU range was used, whereas three thresholds (100%, 80%, and 40%) were evaluated for 4D-PET. By using these segmentations, the authors estimated the lesion motion from the shifting centroids, and the phases with the least motion were also deduced including the phases with a curve slope less than 2 mm/ delta phase. The proposed algorithms were validated by comparing the results to those generated entirely by manual contouring. RESULTS: In the phantom study, the mean difference between the manual contour and the semiautomatic technique was 0.1 +/- 0.1 mm for 4D-CT and 0.2 +/- 0.1 mm for the 4D-PET based on 40% threshold. In the patients' series, the mean difference was 0.9 +/- 0.6 mm for 4D-CT and 0.8 +/- 0.2 mm for the 4D-PET based on 40% threshold. CONCLUSIONS: Estimation of lesion motion by the proposed semiautomatic algorithm can be used to evaluate tumor motion due to breathing.

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.

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.

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.

Cone beam CT pre- and post-daily treatment for assessing geometrical and dosimetric intrafraction variability during radiotherapy of prostate cancer.

The purpose of this study was to quantify the relationship between treatment time and dose uncertainty due to intrafraction organ motion in prostate cancer radiotherapy (RT). Ten consecutive patients with prostate cancer treated by radical RT by volumetric modulated arc therapy (RapidArc) were considered. For each patient, pre- and post-treatment cone beam computed tomography (CBCT) was performed in 10 fractions. The prostate, rectum and bladder were contoured on each CBCT. The change in organ position, volume and dosimetric uncertainty induced by organ motion were evaluated. Interval time between the two CBCTs ranged between 4 and 16 min (mean 7.3 ± 0.7 min). Treatment with intrafraction prostate motion >3mm and > 5 mm were 24% and 5%, respectively. Regarding change in centroid position and volume, a poor time correlation was found for target and rectum, while a constant increase was obtained for bladder. The agreement index was highly correlated to time (r = -0.89 for bladder, r = -0.95 for rectum, and r= -0.84 for prostate). In terms of difference in dose volume histogram between pre- and post-CBCT, the dose uncertainties for the targets and rectum amplified with the increasing time. The increasing intrafraction dose uncertainty with time requires the use of an RT technique with minimization of treatment time to improve confidence in planning dose distribution.

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.