Dose and DNA damage modelling of diffusing alpha-emitters radiation therapy using Geant4.

PURPOSE: Diffusing alpha-emitters radiation therapy (DaRT) is a brachytherapy technique using α-particles to treat solid tumours. The high linear energy transfer (LET) and short range of α-particles make them good candidates for the targeted treatment of cancer. Treatment planning of DaRT requires a good understanding of the dose from α-particles and the other particles released in the 224Ra decay chain. METHODS: The Geant4 Monte Carlo toolkit has been used to simulate a DaRT seed to better understand the dose contribution from all particles and simulate the DNA damage due to this treatment. RESULTS: Close to the seed α-particles deliver the majority of dose, however at radial distances greater than 4 mm, the contribution of ß-particles is greater. The RBE has been estimated as a function of number of double strand breaks (DSBs) and complex DSBs. A maximum seed spacing of 5.5 mm and 6.5 mm was found to deliver at least 20 Gy RBE weighted dose between the seeds for RBEDSB and RBEcDSB respectively. CONCLUSIONS: The DNA damage changes with radial distance from the seed and has been found to become less complex with distance, which is potentially easier for the cell to repair. Close to the seed α-particles contribute the majority of dose, however the contribution from other particles cannot be neglected and may influence the choice of seed spacing.

Electron contamination suppression in transmission detectors for radiotherapy.

Objective.Higher energy and intensity radiotherapy beams are being used, in part, due to the increased spatial accuracy of treatments. However, higher intensity beams can result in a larger total dose error, motivating the increasing need for real-time dose monitoring. We are developing a thin, real-time upstream monolithic active pixel sensor based system for beam monitoring with excellent precision on measuring the beam shape. Here we present a method to additionally provide dosimetry by adding thin conversion material in strips to the surface of the detector, a grating structure.Approach.By modulating the thickness of the conversion material to minimally disturb the contamination electron signal while enhancing the photon signal, the difference in these signals can be used to extract a photon-only signal, and hence dose. The simulation software Gate, based on Geant4, is utilised to study whether well functioning gratings can be better made from aluminium or copper and to optimise the thickness of a copper grating.Main results.It is possible to enhance the photon signal by a factor 6.7 (7.7) compared to the bare sensor for a 5.8 (6.7) MV beam, without modulation of the signal due to beam electrons.Significance.The grating can be used to perform dosimetry in real-time using a thin upstream detector.

In-silico calculations of DNA damage induced by α-particles in the 224Ra DaRT decay chain for a better understanding of the radiobiological effectiveness of this treatment.

Diffusing alpha-emitters radiation Therapy (DaRT) is an interstitial brachytherapy technique using 224Ra seeds. For accurate treatment planning a good understanding of the early DNA damage due to α-particles is required. Geant4-DNA was used to calculate the initial DNA damage and radiobiological effectiveness due to α-particles with linear energy transfer (LET) values in the range 57.5-225.9 keV/µm from the 224Ra decay chain. The impact of DNA base pair density on DNA damage has been modelled, as this parameter varies between human cell lines. Results show that the quantity and complexity of DNA damage changes with LET as expected. Indirect damage, due to water radical reactions with the DNA, decreases and becomes less significant at higher LET values as shown in previous studies. As expected, the yield of complex double strand breaks (DSBs), which are harder for a cell to repair, increases approximately linearly with LET. The level of complexity of DSBs and radiobiological effectiveness have been found to increase with LET as expected. The quantity of DNA damage has been shown to increase for increased DNA density in the expected base pair density range of human cells. The change in damage yield as a function of base pair density is largest for higher LET α-particles, an increase of over 50% for individual strand breaks between 62.7 and 127.4 keV/µm. This change in yield shows that the DNA base pair density is an important parameter for modelling DNA damage particularly at higher LET where the DNA damage is greatest and most complex.

Performance of a Full-Scale Upstream MAPS-Based Verification Device for Radiotherapy.

Intensity-modulated radiotherapy is a widely used technique for accurately targeting cancerous tumours in difficult locations using dynamically shaped beams. This is ideally accompanied by real-time independent verification. Monolithic active pixel sensors are a viable candidate for providing upstream beam monitoring during treatment. We have already demonstrated that a Monolithic Active Pixel Sensor (MAPS)-based system can fulfill all clinical requirements except for the minimum required size. Here, we report the performance of a large-scale demonstrator system consisting of a matrix of 2 × 2 sensors, which is large enough to cover almost all radiotherapy treatment fields when affixed to the shadow tray of the LINAC head. When building a matrix structure, a small dead area is inevitable. Here, we report that with a newly developed position algorithm, leaf positions can be reconstructed over the entire range with a position resolution of below ∼200 µm in the centre of the sensor, which worsens to just below 300 µm in the middle of the gap between two sensors. A leaf position resolution below 300 µm results in a dose error below 2%, which is good enough for clinical deployment.

"Starry liver" - Von Meyenburg complex clinical case presentation and differential diagnosis discussion: A case report.

BACKGROUND: Von Meyenburg complex (VMC) (i.e., biliary hamartoma) is a rare congenital disorder characterized by multiple dilated cystic bile ducts, without clear trends in sex or age predominance. Due to the low number of published cases and the lack of recognized guidelines, the management of such patients remains a clinical challenge. CASE SUMMARY: We present a case of symptomatic VMC that was diagnosed after imaging and histopathological examinations. Considering the patient's condition, a conservative treatment strategy was chosen. Instrumental, laboratory, and clinical follow-up demonstrated the stable condition of the patient receiving conservative treatment. CONCLUSION: VMC is a potentially non-life threatening condition, but its recognition is crucial for the management of patients.

Telemedicine for screening diabetic retinopathy: The NO BLIND Italian multicenter study.

AIMS: Diabetic retinopathy (DR) represents the main cause of blindness among adults in the industrialized Countries. Use of telemedicine could offer an easy, smart specialist fundus oculi examination, as well as putting in a screening programme many patients who otherwise would be excluded. MATERIALS AND METHODS: The NO BLIND is a transversal, multicentre, observational study. Its pilot phase involved nine public outpatient clinics for 6 months. As endpoint of the study, we assessed the prevalence of DR by retinography in a subset of the Italian population. Patients' fundus oculi photos were performed by trained diabetologists through a digital smart ophthalmoscope. RESULTS: According to our endpoint, in the final study population (n = 1461), obtained excluding patients for whom retinography was not able to provide any diagnosis, DR prevalence was equal to 15.5%. According to the receiver operating characteristic (ROC) curve performed, we can observe how retinography appears a highly accurate method to detect DR (AUROC 0.971, 95% confidence interval, 0.954-0.989), with a specificity of the 100% and a sensitivity of the 94.3%. CONCLUSIONS: Our findings, in an Italian setting, confirm main data in the literature about DR prevalence. Hence, telemedicine could represent an accurate, fast, and cheap method for screening of DR.

Optimized contrast-enhanced ultrasonography for characterization of focal liver lesions in cirrhosis: A single-center retrospective study.

BACKGROUND: Hepatocellular carcinoma (HCC) is the leading cause of death amongst cirrhotic patients. Its diagnosis and discrimination from non-HCC malignant lesions in cirrhosis includes contrast enhanced computed tomography (CECT), contrast enhanced magnetic resonance imaging (CEMRI), or, in selected cases, liver biopsy. The role of contrast-enhanced ultrasonography (CEUS) is still controversial. AIMS: To evaluate whether, by selecting an appropriate 'time to wash-out' cut-off value, CEUS capability of discriminating between HCC and non-HCC malignancies in cirrhotic patients may be enhanced. METHODS: We enrolled 282 cirrhotic patients who underwent CEUS at our institute, from January 2008 to January 2012, for focal liver lesions (FLLs) detected at ultrasound (US). We used liver biopsy and subsequent histological evaluation as the gold standard for correct classification of FLLs. We calculated the area under receiver operator characteristic curves for CEUS to distinguish patients with HCC from those with non-HCC malignancies. The best 'time to wash-out' cut-off values were selected. RESULTS: HISTOLOGICAL DIAGNOSIS OF FLLS WAS AS FOLLOWS: 34 benign lesions (i.e. 25 regenerative nodules and 9 dysplastic nodules) and 248 malignant lesions (223 well-to-moderately differentiated HCCs; 7 poorly-differentiated HCCs; 5 intrahepatic colangiocellular carcinomas (ICCs); 5 primary non-Hodgkin B-cell lymphomas (NHBLs); and 8 metastatic liver tumors). A time to wash-out > 55 s identified patients with HCC with the highest level of accuracy (92.7%). Similarly, a time to wash-out ≤ 55 s correctly identified the vast majority of the non-HCC malignancies (100% sensitivity, 98.2% specificity and diagnostic accuracy of 98.3%). CONCLUSIONS: CEUS is an accurate and safe procedure for discriminating FLLs in cirrhotic patients, especially when a cut-off time to wash-out of 55 s is chosen as a reference value.

Liver failure in an obese middle-aged woman after biliointestinal bypass.

Obesity is considered an emerging epidemic that is often associated with non-alcoholic fatty liver disease. Among the therapeutic options for morbid obesity, bariatric surgery plays an important role when conventional therapies fail. The effects of bariatric surgery on liver function and morphology are controversial in the literature. Liver failure has been reported after jejunoileal bypass (JIB), biliopancreatic diversion and gastric bypass. Biliointestinal bypass (BIB) is considered an effective procedure among recently introduced bariatric surgery techniques. It is a clinically safe, purely malabsorptive operation in which the blind intestinal loop of the JIB is anastomosed to the gallbladder, allowing a portion of bile to transit into excluded intestinal tract. BIB is the only procedure, to our knowledge, to have no liver side effects reported in the literature. We report the case of a young obese woman who developed liver failure 8 mo after BIB. She had a rapid weight loss (70 kg) with a reduction in body mass index of 41% from January to September 2012. Because of a severe hepatic decompensation, she was referred to a transplantation centre. We strongly believe that the most important pathogenetic mechanism involved in the development of liver injury is the rapid weight loss that produced a significant fatty liver infiltration.