Radiomic- and dosiomic-based clustering development for radio-induced neurotoxicity in pediatric medulloblastoma.

BACKGROUND: Texture analysis extracts many quantitative image features, offering a valuable, cost-effective, and non-invasive approach for individual medicine. Furthermore, multimodal machine learning could have a large impact for precision medicine, as texture biomarkers can underlie tissue microstructure. This study aims to investigate imaging-based biomarkers of radio-induced neurotoxicity in pediatric patients with metastatic medulloblastoma, using radiomic and dosiomic analysis. METHODS: This single-center study retrospectively enrolled children diagnosed with metastatic medulloblastoma (MB) and treated with hyperfractionated craniospinal irradiation (CSI). Histological confirmation of medulloblastoma and baseline follow-up magnetic resonance imaging (MRI) were mandatory. Treatment involved helical tomotherapy (HT) delivering a dose of 39 Gray (Gy) to brain and spinal axis and a posterior fossa boost up to 60 Gy. Clinical outcomes, such as local and distant brain control and neurotoxicity, were recorded. Radiomic and dosiomic features were extracted from tumor regions on T1, T2, FLAIR (fluid-attenuated inversion recovery) MRI-maps, and radiotherapy dose distribution. Different machine learning feature selection and reduction approaches were performed for supervised and unsupervised clustering. RESULTS: Forty-eight metastatic medulloblastoma patients (29 males and 19 females) with a mean age of 12 ± 6 years were enrolled. For each patient, 332 features were extracted. Greater level of abstraction of input data by combining selection of most performing features and dimensionality reduction returns the best performance. The resulting one-component radiomic signature yielded an accuracy of 0.73 with sensitivity, specificity, and precision of 0.83, 0.64, and 0.68, respectively. CONCLUSIONS: Machine learning radiomic-dosiomic approach effectively stratified pediatric medulloblastoma patients who experienced radio-induced neurotoxicity. Strategy needs further validation in external dataset for its potential clinical use in ab initio management paradigms of medulloblastoma.

Characterization of a flexible a-Si:H detector for in vivo dosimetry in therapeutic x-ray beams.

BACKGROUND: The increasing use of complex and high dose-rate treatments in radiation therapy necessitates advanced detectors to provide accurate dosimetry. Rather than relying on pre-treatment quality assurance (QA) measurements alone, many countries are now mandating the use of in vivo dosimetry, whereby a dosimeter is placed on the surface of the patient during treatment. Ideally, in vivo detectors should be flexible to conform to a patient's irregular surfaces. PURPOSE: This study aims to characterize a novel hydrogenated amorphous silicon (a-Si:H) radiation detector for the dosimetry of therapeutic x-ray beams. The detectors are flexible as they are fabricated directly on a flexible polyimide (Kapton) substrate. METHODS: The potential of this technology for application as a real-time flexible detector is investigated through a combined dosimetric and flexibility study. Measurements of fundamental dosimetric quantities were obtained including output factor (OF), dose rate dependence (DPP), energy dependence, percentage depth dose (PDD), and angular dependence. The response of the a-Si:H detectors investigated in this study are benchmarked directly against commercially available ionization chambers and solid-state diodes currently employed for QA practices. RESULTS: The a-Si:H detectors exhibit remarkable dose linearities in the direct detection of kV and MV therapeutic x-rays, with calibrated sensitivities ranging from (0.580 ± 0.002) pC/cGy to (19.36 ± 0.10) pC/cGy as a function of detector thickness, area, and applied bias. Regarding dosimetry, the a-Si:H detectors accurately obtained OF measurements that parallel commercially available detector solutions. The PDD response closely matched the expected profile as predicted via Geant4 simulations, a PTW Farmer ionization chamber and a PTW ROOS chamber. The most significant variation in the PDD performance was 5.67%, observed at a depth of 3 mm for detectors operated unbiased. With an external bias, the discrepancy in PDD response from reference data was confined to ± 2.92% for all depths (surface to 250 mm) in water-equivalent plastic. Very little angular dependence is displayed between irradiations at angles of 0° and 180°, with the most significant variation being a 7.71% decrease in collected charge at a 110° relative angle of incidence. Energy dependence and dose per pulse dependence are also reported, with results in agreement with the literature. Most notably, the flexibility of a-Si:H detectors was quantified for sample bending up to a radius of curvature of 7.98 mm, where the recorded photosensitivity degraded by (-4.9 ± 0.6)% of the initial device response when flat. It is essential to mention that this small bending radius is unlikely during in vivo patient dosimetry. In a more realistic scenario, with a bending radius of 15-20 mm, the variation in detector response remained within ± 4%. After substantial bending, the detector's photosensitivity when returned to a flat condition was (99.1 ± 0.5)% of the original response. CONCLUSIONS: This work successfully characterizes a flexible detector based on thin-film a-Si:H deposited on a Kapton substrate for applications in therapeutic x-ray dosimetry. The detectors exhibit dosimetric performances that parallel commercially available dosimeters, while also demonstrating excellent flexibility results.

Fully automated volumetric modulated arc therapy technique for radiation therapy of locally advanced breast cancer.

BACKGROUND: This study aimed to evaluate an a-priori multicriteria plan optimization algorithm (mCycle) for locally advanced breast cancer radiation therapy (RT) by comparing automatically generated VMAT (Volumetric Modulated Arc Therapy) plans (AP-VMAT) with manual clinical Helical Tomotherapy (HT) plans. METHODS: The study included 25 patients who received postoperative RT using HT. The patient cohort had diverse target selections, including both left and right breast/chest wall (CW) and III-IV node, with or without internal mammary node (IMN) and Simultaneous Integrated Boost (SIB). The Planning Target Volume (PTV) was obtained by applying a 5 mm isotropic expansion to the CTV (Clinical Target Volume), with a 5 mm clip from the skin. Comparisons of dosimetric parameters and delivery/planning times were conducted. Dosimetric verification of the AP-VMAT plans was performed. RESULTS: The study showed statistically significant improvements in AP-VMAT plans compared to HT for OARs (Organs At Risk) mean dose, except for the heart and ipsilateral lung. No significant differences in V95% were observed for PTV breast/CW and PTV III-IV, while increased coverage (higher V95%) was seen for PTV IMN in AP-VMAT plans. HT plans exhibited smaller values of PTV V105% for breast/CW and III-IV, with no differences in PTV IMN and boost. HT had an average (± standard deviation) delivery time of (17 ± 8) minutes, while AP-VMAT took (3 ± 1) minutes. The average γ passing rate for AP-VMAT plans was 97%±1%. Planning times reduced from an average of 6 h for HT to about 2 min for AP-VMAT. CONCLUSIONS: Comparing AP-VMAT plans with clinical HT plans showed similar or improved quality. The implementation of mCycle demonstrated successful automation of the planning process for VMAT treatment of locally advanced breast cancer, significantly reducing workload.

Hydrogenated amorphous silicon high flux x-ray detectors for synchrotron microbeam radiation therapy.

Objective. Microbeam radiation therapy (MRT) is an alternative emerging radiotherapy treatment modality which has demonstrated effective radioresistant tumour control while sparing surrounding healthy tissue in preclinical trials. This apparent selectivity is achieved through MRT combining ultra-high dose rates with micron-scale spatial fractionation of the delivered x-ray treatment field. Quality assurance dosimetry for MRT must therefore overcome a significant challenge, as detectors require both a high dynamic range and a high spatial resolution to perform accurately.Approach. In this work, a series of radiation hard a-Si:H diodes, with different thicknesses and carrier selective contact configurations, have been characterised for x-ray dosimetry and real-time beam monitoring applications in extremely high flux beamlines utilised for MRT at the Australian Synchrotron.Results. These devices displayed superior radiation hardness under constant high dose-rate irradiations on the order of 6000 Gy s-1, with a variation in response of 10% over a delivered dose range of approximately 600 kGy. Dose linearity of each detector to x-rays with a peak energy of 117 keV is reported, with sensitivities ranging from (2.74 ± 0.02) nC/Gy to (4.96 ± 0.02) nC/Gy. For detectors with 0.8µm thick active a-Si:H layer, their operation in an edge-on orientation allows for the reconstruction of micron-size beam profiles (microbeams). The microbeams, with a nominal full-width-half-max of 50µm and a peak-to-peak separation of 400µm, were reconstructed with extreme accuracy. The full-width-half-max was observed as 55 ± 1µm. Evaluation of the peak-to-valley dose ratio and dose-rate dependence of the devices, as well as an x-ray induced charge (XBIC) map of a single pixel is also reported.Significance. These devices based on novel a-Si:H technology possess a unique combination of accurate dosimetric performance and radiation resistance, making them an ideal candidate for x-ray dosimetry in high dose-rate environments such as FLASH and MRT.

Updates on the APBI-IMRT-Florence Trial (NCT02104895) Technique: From the Intensity Modulated Radiation Therapy Trial to the Volumetric Modulated Arc Therapy Clinical Practice.

Several phase 3 trials have demonstrated partial breast irradiation noninferiority compared with whole breast irradiation in terms of local control and similar or reduced toxicity. During recent years, especially owing to the COVID-19 pandemic, a growing interest in 5-fraction regimens emerged. The APBI-IMRT-Florence trial (NCT02104895) schedule (30 Gy in 5 fractions) might represent an appealing treatment option, being both a safe and effective partial breast irradiation schedule, with long-term reported results. The aim of this report is to support planners interested in implementing this technique and to warrant equal access to postoperative radiation treatment for most early breast cancer patient candidates. We report the current delivery technique optimized from the original protocol and the updated dose constraints for plan optimization. We also report a statistical analysis of dosimetric parameters on 50 patients treated in consecutive fractions. Treatment-related toxic effects were assessed using the acute radiation morbidity scoring criteria and late radiation morbidity scoring scheme from the Radiation Therapy Oncology Group and the European Organisation for Research and Treatment of Cancer. The mean volume of ipsilateral breast was 731 cm3 (standard deviation ± 450; range, 151-2205) and the mean planning target volume (PTV) was 139 cm3 (standard deviation ± 48; range, 55-259). There was good correlation between ipsilateral breast V15Gy and the ratio between the PTV and ipsilateral breast volume (R2 = .911). At a median follow-up of 4.5 years, 32% of patients (n = 16) developed any grade 1 acute toxic effect. No grade >1 toxic effect was observed. Sixteen percent of patients (n = 8) developed any grade 1 late toxic effect. No grade >1 toxic effect was observed. Physician-assessed cosmesis was reported as excellent (84%), good (14%), and fair (2%). The schedule of 30 Gy in 5 consecutive fractions might represent a safe, easy-to-deliver, and cost-effective option for appropriately selected patients affected by early breast cancer.

High-Resolution Photoemission Study of Neutron-Induced Defects in Amorphous Hydrogenated Silicon Devices.

In this paper, by means of high-resolution photoemission, soft X-ray absorption and atomic force microscopy, we investigate, for the first time, the mechanisms of damaging, induced by neutron source, and recovering (after annealing) of p-i-n detector devices based on hydrogenated amorphous silicon (a-Si:H). This investigation will be performed by mean of high-resolution photoemission, soft X-Ray absorption and atomic force microscopy. Due to dangling bonds, the amorphous silicon is a highly defective material. However, by hydrogenation it is possible to reduce the density of the defect by several orders of magnitude, using hydrogenation and this will allow its usage in radiation detector devices. The investigation of the damage induced by exposure to high energy irradiation and its microscopic origin is fundamental since the amount of defects determine the electronic properties of the a-Si:H. The comparison of the spectroscopic results on bare and irradiated samples shows an increased degree of disorder and a strong reduction of the Si-H bonds after irradiation. After annealing we observe a partial recovering of the Si-H bonds, reducing the disorder in the Si (possibly due to the lowering of the radiation-induced dangling bonds). Moreover, effects in the uppermost coating are also observed by spectroscopies.

Clinical validation of an automatic atlas-based segmentation tool for male pelvis CT images.

PURPOSE: This retrospective work aims to evaluate the possible impact on intra- and inter-observer variability, contouring time, and contour accuracy of introducing a pelvis computed tomography (CT) auto-segmentation tool in radiotherapy planning workflow. METHODS: Tests were carried out on five structures (bladder, rectum, pelvic lymph-nodes, and femoral heads) of six previously treated subjects, enrolling five radiation oncologists (ROs) to manually re-contour and edit auto-contours generated with a male pelvis CT atlas created with the commercial software MIM MAESTRO. The ROs first delineated manual contours (M). Then they modified the auto-contours, producing automatic-modified (AM) contours. The procedure was repeated to evaluate intra-observer variability, producing M1, M2, AM1, and AM2 contour sets (each comprising 5 structures × 6 test patients × 5 ROs = 150 contours), for a total of 600 contours. Potential time savings was evaluated by comparing contouring and editing times. Structure contours were compared to a reference standard by means of Dice similarity coefficient (DSC) and mean distance to agreement (MDA), to assess intra- and inter-observer variability. To exclude any automation bias, ROs evaluated both M and AM sets as "clinically acceptable" or "to be corrected" in a blind test. RESULTS: Comparing AM to M sets, a significant reduction of both inter-observer variability (p < 0.001) and contouring time (-45% whole pelvis, p < 0.001) was obtained. Intra-observer variability reduction was significant only for bladder and femoral heads (p < 0.001). The statistical test showed no significant bias. CONCLUSION: Our atlas-based workflow proved to be effective for clinical practice as it can improve contour reproducibility and generate time savings. Based on these findings, institutions are encouraged to implement their auto-segmentation method.

Implementation of automatic plan optimization in Italy: Status and perspectives.

PURPOSE: To investigate and report on the diffusion and clinical use of automated radiotherapy planning systems in Italy and to assess the perspectives of the community of Italian medical physicists involved in radiotherapy on the use of these tools. MATERIALS AND METHODS: A survey of medical physicists (one per Institute) of 175 radiotherapy centers in Italy was conducted between February 21st and April 1st, 2021. The information collected included the institute's characteristics, plan activity, availability/use of automatic tools and related issues regarding satisfaction, criticisms, expectations, and perceived professional modifications. Responses were analysed, including the impact of a few variables such as the institute type and experience. RESULTS: 125 of the centers (71%) answered the survey, with regional variability (range: 47%-100%); among these, 49% have a TPS with some automatic option. Clinical use of automatic planning is present in 33% of the centers, with 13% applying it in >50% of their plans. Among the 125 responding centres the most used systems are Pinnacle (16%), Raystation (9%) and Eclipse (4%). The majority of participants consider the use of automated techniques to be beneficial, while only 1% do not see any advantage; 83% of respondents see the possibility of enriching their professional role as a potential benefit, while 3% see potential threats. CONCLUSIONS: Our survey shows that 49% of the responding centres have an automatic planning solution although clinically used in only 33% of the cases. Most physicists consider the use of automated techniques to be beneficial and show a prevalently positive attitude.

Validation of a secondary dose check tool against Monte Carlo and analytical clinical dose calculation algorithms in VMAT.

PURPOSE: Patient-specific quality assurance (QA) is very important in radiotherapy, especially for patients with highly conformed treatment plans like VMAT plans. Traditional QA protocols for these plans are time-consuming reducing considerably the time available for patient treatments. In this work, a new MC-based secondary dose check software (SciMoCa) is evaluated and benchmarked against well-established TPS (Monaco and Pinnacle3 ) by means of treatment plans and dose measurements. METHODS: Fifty VMAT plans have been computed using same calculation parameters with SciMoCa and the two primary TPSs. Plans were validated with measurements performed with a 3D diode detector (ArcCHECK) by translating patient plans to phantom geometry. Calculation accuracy was assessed by measuring point dose differences and gamma passing rates (GPR) from a 3D gamma analysis with 3%-2 mm criteria. Comparison between SciMoCa and primary TPS calculations was made using the same estimators and using both patient and phantom geometry plans. RESULTS: TPS and SciMoCa calculations were found to be in very good agreement with validation measurements with average point dose differences of 0.7 ± 1.7% and -0.2 ± 1.6% for SciMoCa and two TPSs, respectively. Comparison between SciMoCa calculations and the two primary TPS plans did not show any statistically significant difference with average point dose differences compatible with zero within error for both patient and phantom geometry plans and GPR (98.0 ± 3.0% and 99.0 ± 3.0% respectively) well in excess of the typical 95 % clinical tolerance threshold. CONCLUSION: This work presents results obtained with a significantly larger sample than other similar analyses and, to the authors' knowledge, compares SciMoCa with a MC-based TPS for the first time. Results show that a MC-based secondary patient-specific QA is a clinically viable, reliable, and promising technique, that potentially allows significant time saving that can be used for patient treatment and a per-plan basis QA that effectively complements traditional commissioning and calibration protocols.

Local treatment for relapsing glioblastoma: A decision-making tree for choosing between reirradiation and second surgery.

In case of circumscribed recurrent glioblastoma (rec-GBM), a second surgery (Re-S) and reirradiation (Re-RT) are local strategies to consider. The aim is to provide an algorithm to use in the daily clinical practice. The first step is to consider the life expectancy in order to establish whether the patient should be a candidate for active treatment. In case of a relatively good life expectancy (>3 months) and a confirmed circumscribed disease(i.e. without multiple lesions that are in different lobes/hemispheres), the next step is the assessment of the prognostic factors for local treatments. Based on the existing prognostic score systems, patients who should be excluded from local treatments may be identified; based on the validated prognostic factors, one or the other local treatment may be preferred. The last point is the estimation of expected toxicity, considering patient-related, tumor-related and treatment-related factors impacting on side effects. Lastly, patients with very good prognostic factors may be considered for receiving a combined treatment.

Methodological approach to create an atlas using a commercial auto-contouring software.

PURPOSE: The aim of this work was to establish a methodological approach for creation and optimization of an atlas for auto-contouring, using the commercial software MIM MAESTRO (MIM Software Inc. Cleveland OH). METHODS: A computed tomography (CT) male pelvis atlas was created and optimized to evaluate how different tools and options impact on the accuracy of automatic segmentation. Pelvic lymph nodes (PLN), rectum, bladder, and femurs of 55 subjects were reviewed for consistency by a senior consultant radiation oncologist with 15 yr of experience. Several atlas and workflow options were tuned to optimize the accuracy of auto-contours. The deformable image registration (DIR), the finalization method, the k number of atlas best matching subjects, and several post-processing options were studied. To test our atlas performances, automatic and reference manual contours of 20 test subjects were statistically compared based on dice similarity coefficient (DSC) and mean distance to agreement (MDA) indices. The effect of field of view (FOV) reduction on auto-contouring time was also investigated. RESULTS: With the optimized atlas and workflow, DSC and MDA median values of bladder, rectum, PLN, and femurs were 0.91 and 1.6 mm, 0.85 and 1.6 mm, 0.85 and 1.8 mm, and 0.96 and 0.5 mm, respectively. Auto-contouring time was more than halved by strictly cropping the FOV of the subject to be contoured to the pelvic region. CONCLUSION: A statistically significant improvement of auto-contours accuracy was obtained using our atlas and optimized workflow instead of the MIM Software pelvic atlas.

Validation of a commercial deformable image registration for surface-guided radiotherapy using an ad hoc-developed deformable phantom.

PURPOSE: The use of optical surface systems (OSSs) for patient setup verification in external radiation therapy is increasing. To manage potential deformations in a patient's anatomy, a novel deformable image registration (DIR) tool has been applied in a commercial OSS. In this study we investigate the accuracy of the DIR as compared to rigid image registration (RR). METHODS AND MATERIALS: The positioning accuracy of the DIR and RR implemented in the OSS was investigated using an ad hoc-developed anthropomorphic deformable phantom, named Mary. The phantom consists of 33 slices of expanded polystyrene slabs shaped thus to simulate part of a female body. Anatomical details, simulating the ribs and spinal cord, together with 10 inner targets at different depths are included in thorax and abdominal parts. Mary is capable of realistic body movements and deformations, such as head and arm rotations, body torsion and moderate breast/abdomen swelling. The accuracy of DIR and RR was investigated for four internal targets after deliberately deforming the phantom nine times. Breast and abdomen enlargements and torsions around x, y, and z axes were applied. For reference purposes, rigid displacements (where Mary's anatomy was kept intact) were included. The phantom was positioned on the linac couch under the OSS guidance and for each target and displacement a CBCT was acquired. The accuracy of DIR and RR was assessed evaluating the difference in means of absolute values between CBCT and the OSS registration parameters (lateral, longitudinal, vertical, rot, pitch, and roll), using both a reference surface extracted from CT (CTr) or acquired with the OSS (OSSr). A comparison of the four different combinations, DIR + OSSr, DIR + CTr, RR + OSSr, and RR + CTr, was carried out to evaluate the position accuracy for the various combinations. Finally, the positioning accuracy of the different target positions using only OSSr was investigated for the DIR. A paired sample Wilcoxon signed-rank test (P < 0.05) and a two-tailed Mann-Whitney test (P < 0.05) were carried out. RESULTS: The DIR in combination with OSSr showed significantly (P < 0.05) improved positioning accuracy in the lateral and longitudinal directions and in pitch, compared to RR, when deformations were applied to Mary. The positioning accuracy improved from 1.9 ± 1.5 mm, 1.1 ± 0.8 mm to 1.1 ± 1.2 mm, 0.6 ± 0.5 mm in lateral and longitudinal directions, respectively, and from 0.8 ± 0.6° to 0.4 ± 0.4° in pitch, using DIR compared to RR. Both the DIR and RR showed a similar positioning accuracy when rigid displacements of Mary were applied. For DIR, the OSSr generally showed improved calculation accuracy compared to CTr. Independent of the reference image used, the target position influenced the registration accuracy, and hence, one target could not be evaluated using RR due to its inability to calculate the correct position. CONCLUSIONS: Improved positioning accuracy was observed for DIR with respect to RR when deformations of Mary's anatomy were applied. For both DIR and RR, improved positioning accuracy was observed using OSSr as compared to CTr. The position of the target inside the phantom influenced the positioning accuracy for DIR.

Accelerated Partial-Breast Irradiation Compared With Whole-Breast Irradiation for Early Breast Cancer: Long-Term Results of the Randomized Phase III APBI-IMRT-Florence Trial.

PURPOSE: To report the long-term results of external-beam accelerated partial-breast irradiation (APBI) intensity-modulated radiation therapy (IMRT) Florence phase III trial comparing whole-breast irradiation (WBI) to APBI in early-stage breast cancer. PATIENTS AND METHODS: The primary end point was to determine the 5-year difference in ipsilateral breast tumor recurrence (IBTR) between 30 Gy in 5 once-daily fractions (APBI arm) and 50 Gy in 25 fractions with a tumor bed boost (WBI arm) after breast-conserving surgery. RESULTS: Five hundred twenty patients, more than 90% of whom had characteristics associated with low recurrence risk, were randomly assigned (WBI, n = 260; APBI, n = 260) between 2005 and 2013. Median follow-up was 10.7 years. The 10-year cumulative incidence of IBTR was 2.5% (n = 6) in the WBI and 3.7% (n = 9) in the APBI arm (hazard ratio [HR], 1.56; 95% CI, 0.55 to 4.37; P = .40). Overall survival at 10 years was 91.9% in both arms (HR, 0.95; 95% CI, 0.50 to 1.79; P = .86). Breast cancer-specific survival at 10 years was 96.7% in the WBI and 97.8% in the APBI arm (HR, 0.65; 95% CI, 0.21 to 1.99; P = .45). The APBI arm showed significantly less acute toxicity (P = .0001) and late toxicity (P = .0001) and improved cosmetic outcome as evaluated by both physician (P = .0001) and patient (P = .0001). CONCLUSION: The 10-year cumulative IBTR incidence in early breast cancer treated with external APBI using IMRT technique in 5 once-daily fractions is low and not different from that after WBI. Acute and late treatment-related toxicity and cosmesis outcomes were significantly in favor of APBI.

Comprehensive Analysis of Radiomic Datasets by RadAR.

Quantitative analysis of biomedical images, referred to as radiomics, is emerging as a promising approach to facilitate clinical decisions and improve patient stratification. The typical radiomic workflow includes image acquisition, segmentation, feature extraction, and analysis of high-dimensional datasets. While procedures for primary radiomic analyses have been established in recent years, processing the resulting radiomic datasets remains a challenge due to the lack of specific tools for doing so. Here we present RadAR (Radiomics Analysis with R), a new software to perform comprehensive analysis of radiomic features. RadAR allows users to process radiomic datasets in their entirety, from data import to feature processing and visualization, and implements multiple statistical methods for analysis of these data. We used RadAR to analyze the radiomic profiles of more than 850 patients with cancer from publicly available datasets and showed that it was able to recapitulate expected results. These results demonstrate RadAR as a reliable and valuable tool for the radiomics community. SIGNIFICANCE: A new computational tool performs comprehensive analysis of high-dimensional radiomic datasets, recapitulating expected results in the analysis of radiomic profiles of >850 patients with cancer from independent datasets.

Automated planning through robust templates and multicriterial optimization for lung VMAT SBRT of lung lesions.

PURPOSE: To develop and validate a robust template for VMAT SBRT of lung lesions, using the multicriterial optimization (MCO) of a commercial treatment planning system. METHODS: The template was established and refined on 10 lung SBRT patients planned for 55 Gy/5 fr. To improve gradient and conformity a ring structure around the planning target volume (PTV) was set in the list of objectives. Ideal fluence optimization was conducted giving priority to organs at risk (OARs) and using the MCO, which further pushes OARs doses. Segmentation was conducted giving priority to PTV coverage. Two different templates were produced with different degrees of modulation, by setting the Fluence Smoothing parameter to Medium (MFS) and High (HFS). Each template was applied on 20 further patients. Automatic and manual plans were compared in terms of dosimetric parameters, delivery time, and complexity. Statistical significance of differences was evaluated using paired two-sided Wilcoxon signed-rank test. RESULTS: No statistically significant differences in PTV coverage and maximum dose were observed, while an improvement was observed in gradient and conformity. A general improvement in dose to OARs was seen, which resulted to be significant for chest wall V30 Gy , total lung V20 Gy , and spinal cord D0.1 cc . MFS plans are characterized by a higher modulation and longer delivery time than manual plans. HFS plans have a modulation and a delivery time comparable to manual plans, but still present an advantage in terms of gradient. CONCLUSION: The automation of the planning process for lung SBRT using robust templates and MCO was demonstrated to be feasible and more efficient.

Dosimetric Predictors of Acute and Chronic Alopecia in Primary Brain Cancer Patients Treated With Volumetric Modulated Arc Therapy.

Purpose: To determine dose constraints that correlate with alopecia in patients treated with photon-based Volumetric Modulated Arc Therapy (VMAT) for primary brain tumors. Methods: During the treatment planning process, the scalp was drawn as a region of interest. Dose received by 0.1 cc (D0.1cc), mean dose (Dmean), absolute volumes receiving different doses (V16Gy, V20Gy, V25Gy, V30Gy, V35Gy, V40Gy, and V43Gy) were registered for the scalp. Alopecia was assessed according to Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Receiver operating characteristics (ROC) curve analysis was used to identify parameters associated with hair-loss. Results: One-hundred and one patients were included in this observational study. At the end of radiotherapy (RT), 5 patients did not develop alopecia (Dmean scalp 3.1 Gy). The scalp of the patients with G1 (n = 11) and G2 (n = 85) alopecia received Dmean of 10.6 Gy and 11.8 Gy, respectively. At ROC analysis, V16Gy20Gy ≥ 5.2 cc were the strongest predictors of acute alopecia risk. Chronic hair-loss assessment was available for 74 patients: median time to recovery from G2 alopecia was 5, 9 months. The actuarial rate of hair regrowth was 98.1% at 18 months after the end of RT. At ROC analysis, V40Gy43Gy ≥2.2 cc were the strongest predictors of chronic G2-alopecia risk. V20Gy, V40Gy, and D0,1cc were shown to be independent variables according to correlation coefficient r. Conclusions: V20Gy and V40Gy were the strongest predictors for acute and chronic G2 hair-loss, respectively. The low-dose bath typical of VMAT corresponds to large areas of acute but transient alopecia. However, the steep dose gradient of VMAT allows to reduce the areas of the scalp that receive higher doses, minimizing the risk of permanent alopecia. The application of our dosimetric findings for the scalp may help in reducing the alopecia risk and also in estimating the probability of hair-loss during patient counseling before starting radiotherapy.

Bearing Witness: Exploring the End-of-Life Needs of Homeless Persons and Barriers to Appropriate Care.

Traditional models of palliative care are largely inaccessible to homeless persons, and their preferences regarding end-of-life care are poorly understood. The purpose of the present scoping review is to summarize the burgeoning gray and academic literature on end-of-life care for homeless persons. Five medical databases, seven social science databases, and four gray literature databases were searched, resulting in 57 relevant titles. Six themes emerged: (a) Characteristics of homeless persons who require end-of-life care; (b) preferences and concerns of homeless persons approaching the end of life; (c) the role of spirituality for homeless persons at the end of life; (d) barriers to care at the patient, provider, and institutional or structural levels; (e) inclusive models of palliative care; and (f) implications for policy and practice. Practitioners and homeless persons must negotiate many obstacles in the provision and receipt of palliative care. However, there is tremendous potential and opportunity to improve the quality of life at the end of life for this vulnerable population.

Analysis of skin dose distribution for the prediction of severe radiation dermatitis in head and neck squamous cell carcinoma patients treated with concurrent chemo-radiotherapy.

BACKGROUND: We investigated whether the pattern of intensity-modulated radiotherapy (IMRT) dose distribution to the skin can be correlated with the development of G3/G4 radiation dermatitis (RD). METHODS: A frequency-matched cohort analysis was perfomed on patients treated with IMRT and concurrent cisplatin or cetuximab. Risk ratios were obtained by fitting Poisson regression models. RESULTS: The incidence of G3/G4 RD was 41.1% in 90 patients included (50% vs 36.6% in the cetuximab and cisplatin cohorts, respectively). In multivariate analysis, PS ≥ 1 and weight loss at RT completion >10 kg were the only factors that retained significance. The best dosimetric predictive accuracy was provided by 19.9 cc and 5.8 cc of skin ring 2 mm V50 and V60, respectively (AUC: 0.61 for both). CONCLUSION: Along with clinical factors, the pattern of dose distribution to a ring structure localized 2 mm below the patient's surface may help predict the development of severe RD.

ADAM phantom to test 4D medical imaging and dose delivery devices.

Radiotherapy treatment of moving lesions is a challenging task in which different strategies can be used. The clinical implementation of the variety of complex technical solutions pursued to treat cancer, while sparing healthy tissues, requires accurate quality assurance tests and adequate phantoms. The aim of this work is to report on the anthropomorphic dynamic breathing model (ADAM) and on its applications to test image quality and dose delivery for four-dimensional (4D) techniques used to compensate for breathing-induced tumor motion. ADAM reproduces a male torso containing realistic ribs and spinal cord. Lungs move along circular or elliptical paths lying on sagittal planes, while the anterior chest surface moves independently up and down. Lungs host radiochromic films, a diamond detector and objects of known shape and dimensions to test 4D scanners. Markers are embedded around a target and a specific tool, hosting orthogonal radiochromic films, has been provided to perform end-to-end tests of tracking systems. To demonstrate ADAM's performance in testing techniques and methods used to image and treat moving lesions we report the results of three experiments performed to evaluate the accuracy of 4D computed tomography reconstructed volumes, the repeatability of measured dose in volumetric modulated arc treatments and tracking performances of a robotic system. The results obtained show that the percentage differences of reconstructed volumes, with respect to the known volume, depend on the breathing pattern and the pitch size (maximum 5% for breathing rate > 10 breaths per minute). Repeatability of measured dose maps obtained comparing radiochromic films was demonstrated (GI3%/2 mm > 99%). Differences between planned and delivered point dose measurements were <1%. Tracking errors were all below the tolerance level (range 0.6-0.9 mm). The results of this study demonstrate that ADAM is suitable to test techniques and methods used to image and treat moving lesions.

A multiparametric method to assess the MIM deformable image registration algorithm.

A quantitative evaluation of the performances of the deformable image registration (DIR) algorithm implemented in MIM-Maestro was performed using multiple similarity indices. Two phantoms, capable of mimicking different anatomical bending and tumor shrinking were built and computed tomography (CT) studies were acquired after applying different deformations. Three different contrast levels between internal structures were artificially created modifying the original CT values of one dataset. DIR algorithm was applied between datasets with increasing deformations and different contrast levels and manually refined with the Reg Refine tool. DIR algorithm ability in reproducing positions, volumes, and shapes of deformed structures was evaluated using similarity indices such as: landmark distances, Dice coefficients, Hausdorff distances, and maximum diameter differences between segmented structures. Similarity indices values worsen with increasing bending and volume difference between reference and target image sets. Registrations between images with low contrast (40 HU) obtain scores lower than those between images with high contrast (970 HU). The use of Reg Refine tool leads generally to an improvement of similarity parameters values, but the advantage is generally less evident for images with low contrast or when structures with large volume differences are involved. The dependence of DIR algorithm on image deformation extent and different contrast levels is well characterized through the combined use of multiple similarity indices.