Clinical Validation of Siemens' Syngo.via Automatic Contouring System.

Purpose: The manual delineation of organs at risk is a process that requires a great deal of time both for the technician and for the physician. Availability of validated software tools assisted by artificial intelligence would be of great benefit, as it would significantly improve the radiation therapy workflow, reducing the time required for segmentation. The purpose of this article is to validate the deep learning-based autocontouring solution integrated in syngo.via RT Image Suite VB40 (Siemens Healthineers, Forchheim, Germany). Methods and Materials: For this purpose, we have used our own specific qualitative classification system, RANK, to evaluate more than 600 contours corresponding to 18 different automatically delineated organs at risk. Computed tomography data sets of 95 different patients were included: 30 patients with lung, 30 patients with breast, and 35 male patients with pelvic cancer. The automatically generated structures were reviewed in the Eclipse Contouring module independently by 3 observers: an expert physician, an expert technician, and a junior physician. Results: There is a statistically significant difference between the Dice coefficient associated with RANK 4 compared with the coefficient associated with RANKs 2 and 3 (P < .001). In total, 64% of the evaluated structures received the maximum score, 4. Only 1% of the structures were classified with the lowest score, 1. The time savings for breast, thorax, and pelvis were 87.6%, 93.5%, and 82.2%, respectively. Conclusions: Siemens' syngo.via RT Image Suite offers good autocontouring results and significant time savings.

Machine learning-based automated planning for hippocampal avoidance prophylactic cranial irradiation.

PURPOSE: Design and evaluate a knowledge-based model using commercially available artificial intelligence tools for automated treatment planning to efficiently generate clinically acceptable hippocampal avoidance prophylactic cranial irradiation (HA-PCI) plans in patients with small-cell lung cancer. MATERIALS AND METHODS: Data from 44 patients with different grades of head flexion (range 45°) were used as the training datasets. A Rapid Plan knowledge-based planning (KB) routine was applied for a prescription of 25 Gy in 10 fractions using two volumetric modulated arc therapy (VMAT) arcs. The 9 plans used to validate the initial model were added to generate a second version of the RP model (Hippo-MARv2). Automated plans (AP) were compared with manual plans (MP) according to the dose-volume objectives of the PREMER trial. Optimization time and model quality were assessed using 10 patients who were not included in the first 44 datasets. RESULTS: A 55% reduction in average optimization time was observed for AP compared to MP. (15 vs 33 min; p = 0.001).Statistically significant differences in favor of AP were found for D98% (22.6 vs 20.9 Gy), Homogeneity Index (17.6 vs 23.0) and Hippocampus D mean (11.0 vs 11.7 Gy). The AP met the proposed objectives without significant deviations, while in the case of the MP, significant deviations from the proposed target values were found in 2 cases. CONCLUSION: The KB model allows automated planning for HA-PCI. Automation of radiotherapy planning improves efficiency, safety, and quality and could facilitate access to new techniques.

DNA Damage Protection for Enhanced Bacterial Survival Under Simulated Low Earth Orbit Environmental Conditions in Escherichia coli.

Some organisms have shown the ability to naturally survive in extreme environments, even outer space. Some of these have natural mechanisms to resist severe DNA damage from conditions such as ionizing and non-ionizing radiation, extreme temperatures, and low pressures or vacuum. A good example can be found in Deinococcus radiodurans, which was exposed to severe conditions such as those listed in the Exposure Facility of the International Space Station (ISS) for up to three years. Another example are tardigrades (Ramazzottius varieornatus) which are some of the most resilient animals known. In this study, the survival under simulated Low earth Orbit (LEO) environmental conditions was tested in Escherichia coli. The radiation resistance of this bacteria was enhanced using the Dsup gene from R. varieornatus, and two more genes from D. radiodurans involved in DNA damage repair, RecA and uvrD. The enhanced survival to wide ranges of temperatures and low pressures was then tested in the new strains. This research constitutes a first step in the creation of new bacterial strains engineered to survive severe conditions and adapting existing species for their survival in remote environments, including extra-terrestrial habitats. These strains could be key for the development of environments hospitable to life and could be of use for ecological restoration and space exploration. In addition, studying the efficacy and the functioning of the DNA repair mechanisms used in this study could be beneficial for medical and life sciences engineering.

Ex-Press P50 device filtering failure due to non-visible intraluminal blockages.

PURPOSE: To describe Ex-Press P50 failures due to an internal blockage. METHODS: A retrospective series of 248 eyes of 219 patients with Ex-Press P50 surgery was conducted. Of these cases, 18 (7.2%) required surgical revision due to filtration failure with no visible blockages in the gonioscopy and no filtering bleb in the slit lamp examination. In all of these cases, we found fibrosis on the edges of the scleral flap. After dissecting the scleral flap, filtration through the implant was restored spontaneously in 10 (4.0%) cases. In two cases fibrous tissue was observed on the tip of the implant and was necessary to remove it. In 6 (2.4%) cases, there was no filtration despite no visible obstruction and attempts to restore the flow were unsuccessful, requiring extraction of the implant and reconverting to trabeculectomy. Two of the removed devices were sanded until the lumen was visible to ascertain the nature of the obstruction. RESULTS: In our series, the most common cause of failure was episcleral fibrosis. In 2.4% of the cases, the blockage was intraluminal and aqueous flow could not be restored. CONCLUSION: In the Ex-Press P50 implant an internal blockage, that is not visible through the proximal or distal orifices, may be the cause of failure. Unblocking by surgical maneuvers is not feasible due to the intraluminal design. These cases can be solved by extraction of the implant and conversion to trabeculectomy.

Validation of 3D printing materials for high dose-rate brachytherapy using ionisation chamber and custom phantom.

Methods.Measurements were taken with the Exradin A20 (Standard Imaging) ionisation chamber, and the 'homemade' MARM phantom was made with the 3D Ultimaker 2+ printer using PLA material. The material used for validation was ABS Medical from Smart Materials 3D. The irradiation was undertaken with a192Ir source by means of Varian's GammaMed Plus iX HDR equipment. EBT3 films were used to run additional tests. We compared different measurements for PLA, ABS Medical, and water. Additional validation methods, described in the bibliography, were also compared.Results.The measurements with the ionisation chamber that we obtained using the MARM phantom with PLA and ABS within the clinically relevant range (0.5-1.5 cm) differ with respect to the measures in the water reference, by 2.3% and 0.94%, respectively.Discussion.The literature describes highly heterogeneous validation methods, complicating the performance of systematic reviews and comparisons between materials. Thus, creating a phantom represents a single effort that will quickly pay off. This system enables comparisons, ensuring that geometric conditions remain stable-something that is not always possible with radiochromic films. The use of a calibrated ionisation chamber in the corresponding energy range, combined with the 'homemade' MARM phantom applied according to the proposed methodology, allows a differentiation between the attenuation of the material itself and the drop in the dose due to distance.Conclusion.The validation method for 3D printing materials, using an ionisation chamber and the MARM PLA phantom, represents an accessible, standardisable solution for manufacturing brachytherapy applicators.

Prevention of radiochemotherapy-induced esophagitis with glutamine: results of a pilot study.

PURPOSE: To assess the usefulness of oral glutamine to prevent radiochemotherapy-induced esophagitis in patients with lung cancer, and to determine the dosimetric parameter predictive of esophagitis. METHODS AND MATERIALS: Seventy-five patients were enrolled; 34.7% received sequential radiochemotherapy, and 65.3% received concomitant radiochemotherapy. Every patient received prophylactic glutamine powder in doses of 10 g/8 h. Prescribed radiation doses were 45-50 Gy to planning target volume (PTV)1 (gross tumor volume plus wide margins) and 65-70 Gy to PTV2 (reduced margins). The primary endpoint was the incidence of Grade 2 or greater acute esophagitis. RESULTS: No patient experienced glutamine intolerance or glutamine-related toxicity. Seventy-three percent of patients who received sequential chemotherapy and 49% of those who received concomitant chemotherapy did not present any form of esophagitis. V50 was the dosimetric parameter with better correlation between esophagitis and its duration. A V50 of or=2, which increased to 71% with a V50 of >30% (p = 0.0009). CONCLUSIONS: The use of oral glutamine may have an important role in the prevention of esophageal complications of concomitant radiochemotherapy in lung cancer patients. However, randomized trials are needed to corroborate that effect. V50 is the dosimetric parameter with better correlation with esophagitis grade and duration.

Multicentre validation of IMRT pre-treatment verification: comparison of in-house and external audit.

BACKGROUND AND PURPOSE: We performed a multicentre intercomparison of IMRT optimisation and dose planning and IMRT pre-treatment verification methods and results. The aims were to check consistency between dose plans and to validate whether in-house pre-treatment verification results agreed with those of an external audit. MATERIALS AND METHODS: Participating centres used two mock cases (prostate and head and neck) for the intercomparison and audit. Compliance to dosimetric goals and total number of MU per plan were collected. A simple quality index to compare the different plans was proposed. We compared gamma index pass rates using the centre's equipment and methodology to those of an external audit. RESULTS: While for the prostate case, all centres fulfilled the dosimetric goals and plan quality was homogeneous, that was not the case for the head and neck case. The number of MU did not correlate with the plan quality index. Pre-treatment verifications results of the external audit did not agree with those of the in-house measurements for two centres: being within tolerance for in-house measurements and unacceptable for the audit or the other way round. CONCLUSIONS: Although all plans fulfilled dosimetric constraints, plan quality is highly dependent on the planner expertise. External audits are an excellent tool to detect errors in IMRT implementation and cannot be replaced by intercomparison using results obtained by centres.

Relationship between radiation-induced apoptosis of T lymphocytes and chronic toxicity in patients with prostate cancer treated by radiation therapy: a prospective study.

PURPOSE: To assess the correlation of radiation-induced apoptosis in vitro of CD4 and CD8 T lymphocytes with late toxicity of prostate cancer patients treated with radiation therapy. METHODS AND MATERIALS: 214 patients were prospectively included in the study. Peripheral blood was drawn from patients before treatment and irradiated with 8 Gy. The percentage of CD4+ and CD8+ T lymphocytes that underwent radiation-induced apoptosis was assessed by flow cytometry. Toxicity and mortality were correlated in 198 cases with pretreatment apoptosis and clinical and biological variables by use of a Cox proportional hazards model. RESULTS: The mean percentage of CD4+ and CD8+ T lymphocyte radiation-induced apoptosis was 28.58% (±14.23) and 50.76% (±18.9), respectively. Genitourinary (GU) toxicity was experienced by 39.9% of patients, while gastrointestinal (GI) toxicity was experienced by 19.7%. The probability of development of GU toxicity was nearly doubled (hazard ratio [HR] 1.99, P=.014) in those patients in whom the percentage of in vitro radiation-induced apoptosis of CD4+ T-lymphocytes was ≤28.58%. It was also almost double in patients who received doses ≥50 Gy in 65% of the bladder volume (V65 ≥50) (HR 1.92, P=.048). No correlation was found between GI toxicity and any of the variables studied. The probability of death during follow-up, after adjustment for different variables, was 2.7 times higher in patients with a percentage of CD8+ T lymphocyte apoptosis ≤50.76% (P=.022). CONCLUSIONS: In conclusion, our study shows, in the largest prospective cohort of prostate cancer patients undergoing radiation therapy, that in vitro radiation-induced apoptosis of CD4+ T lymphocytes assessed before radiation therapy was associated with the probability of developing chronic GU toxicity. In addition, the radiation dose received in the urinary bladder (V65 ≥50) affected the occurrence of GU toxicity. Finally, we also demonstrate that radiation-induced apoptosis of CD8+ T lymphocytes was associated with overall survival, although larger series are needed to confirm this finding.

Five-year outcomes, cosmesis, and toxicity with 3-dimensional conformal external beam radiation therapy to deliver accelerated partial breast irradiation.

PURPOSE: To report the interim results from a study comparing the efficacy, toxicity, and cosmesis of breast-conserving treatment with accelerated partial breast irradiation (APBI) or whole breast irradiation (WBI) using 3-dimensional conformal external beam radiation therapy (3D-CRT). METHODS AND MATERIALS: 102 patients with early-stage breast cancer who underwent breast-conserving surgery were randomized to receive either WBI (n=51) or APBI (n=51). In the WBI arm, 48 Gy was delivered to the whole breast in daily fractions of 2 Gy, with or without additional 10 Gy to the tumor bed. In the APBI arm, patients received 37.5 Gy in 3.75 Gy per fraction delivered twice daily. Toxicity results were scored according to the Radiation Therapy Oncology Group Common Toxicity Criteria. Skin elasticity was measured using a dedicated device (Multi-Skin-Test-Center MC-750-B2, CKelectronic-GmbH). Cosmetic results were assessed by the physician and the patients as good/excellent, regular, or poor. RESULTS: The median follow-up time was 5 years. No local recurrences were observed. No significant differences in survival rates were found. APBI reduced acute side effects and radiation doses to healthy tissues compared with WBI (P<.01). Late skin toxicity was no worse than grade 2 in either group, without significant differences between the 2 groups. In the ipsilateral breast, the areas that received the highest doses (ie, the boost or quadrant) showed the greatest loss of elasticity. WBI resulted in a greater loss of elasticity in the high-dose area compared with APBI (P<.05). Physician assessment showed that >75% of patients in the APBI arm had excellent or good cosmesis, and these outcomes appear to be stable over time. The percentage of patients with excellent/good cosmetic results was similar in both groups. CONCLUSIONS: APBI delivered by 3D-CRT to the tumor bed for a selected group of early-stage breast cancer patients produces 5-year results similar to those achieved with conventional WBI.

Long-term results and prognostic factors of patients with cervical carcinoma treated with concurrent chemoradiotherapy.

AIMS AND BACKGROUND: To evaluate the predictive factors of recurrence in cervical cancer treated with radical radiochemotherapy. METHODS: A retrospective analysis of 56 women was performed. Response was assessed using the RECIST response. Overall survival and disease-free survival curves were estimated by the Kaplan-Meier method and the Cox proportional hazards model was used to analyse predictors of recurrence. RESULTS: Local recurrence was documented in 16 patients and distant metastases in 15. The Kaplan-Meier survival probabilities were 95.1 ± 6.4% at 3 years and 80.4 ± 13.1% at 5 years and the Kaplan-Meier curve values for disease-free survival were 60.3 ± 14.3% at 3 years and 53.0 ± 15.7% at 5 years. Thirty-five patients were alive and 21 patients died, 19 from metastatic disease and 2 from other causes. Complete response after chemoradiation therapy, squamous cell carcinoma and tumour size ≤ 4 cm were significantly associated with outcome. In the Cox regression model, tumour size > 4 cm (hazard ratio 7.48; 95% CI 2.71-20.6; p < 0.001) and partial response (hazard ratio 7.09; 95% CI 2.82-17.8; p < 0.001) were predictive factors for disease-free survival and partial response (hazard ratio 3.7; 95% CI 1.3-10.1; p < 0.001) and non-squamous cell carcinoma (hazard ratio 3.5; 95% CI 1.2-9.7; p < 0.001) were predictive factors for overall survival. CONCLUSIONS: Non-squamous histology and partial response were independent prognostic factors for overall survival and tumour size and partial response were independent prognostic variables for 5-year disease survival.

Irradiación completa de la mama y sobreimpresión del lecho tumoral hipofraccionadas en el cáncer de mama: valoración de la toxicidad / Whole-breast and tumor boost hypofractionated irradiation in breast carcinoma: toxicity results

Introducción. Presentamos los resultados de tolerancia de la adición de sobreimpresión hipofraccionada después de irradiación global hipofraccionada de la mama. Material y método. Se incluyeron pacientes con cirugía conservadora y tratadas mediante hipofraccionamiento de 2,67Gy/día hasta 40Gy sobre la mama. La sobreimpresión del lecho tumoral se realizó a dosis de 16 o 8Gy según los criterios de riesgo para recaída local: tamaño tumoral, grado, márgenes o presencia de carcinoma ductal in situ, o nada en ausencia de dichos factores. Resultados. Se trataron 110 pacientes. Los grupos de riesgo se distribuyeron en alto, medio o bajo, con 51, 54 y 5 pacientes, respectivamente. Un 4,5% no presentaron toxicidad aguda. Las pacientes presentaron dermitis grado i o ii en el 38,2 y 47,3% de los casos, respectivamente. No se observaron diferencias en la toxicidad aguda dependiendo de la dosis de sobreimpresión. Tras un seguimiento medio de 2 años, en 79 casos (71,8%) no hubo cambios cutáneos crónicos. Apareció fibrosis leve en 24 pacientes (21,8%) y de grado ii en 7 pacientes. Conclusiones. La sobreimpresión hipofraccionada parece bien tolerada y las toxicidades aguda y crónica son leves. No parece haber impacto de la dosis total acumulada en la incidencia de fibrosis(AU)

Introduction. We present the results of adding a hypofractionated boost after whole-breast hypofractionated radiotherapy and report patient tolerance of this procedure. Material and method. Patients were included after conservative surgery and underwent adjuvant therapy. The whole breast was treated at 2.67Gy per fraction up to 40Gy. The boost was performed at different dose levels (16 or 8Gy) according to the presence of risk factors for local recurrence (tumor size, histologic grade, margin status or the presence of carcinoma in situ) or nothing in case of their absence. Results. A total of 110 patients were treated. The distribution into high-, middle- and low-risk groups was 51, 54 and 5 patients, respectively. There was no toxicity in 4.5% of the patients. Grade i or ii dermatitis was found in 38.2 and 47.3%, respectively. No differences were observed in acute dermatitis depending on boost doses. After a follow-up of 2 years, there were no chronic skin or subcutaneous changes in 79 patients (71.8%). Mild fibrosis occurred in 24 patients (21.8%) and grade ii fibrosis occurred in 7 patients. Conclusions. Hypofractionated boost seems to be well tolerated. Acute and chronic toxicities are mild. The cumulative dose does not seem to increase the incidence of fibrosis at the boost area compared with the whole breast(AU)