Toward Patient-Specific,Biologically Optimized Radiation Therapy Plans for the Treatment of Glioblastoma

Purpose

To demonstrate a method of generating patient-specific, biologically-guided radiotherapy dose plans and compare them to the standard-of-care protocol.

Methods and Materials

We integrated a patient-specific biomathematical model of glioma proliferation, invasion and radiotherapy with a multiobjective evolutionary algorithm for intensity-modulated radiation therapy optimization to construct individualized, biologically-guided plans for 11 glioblastoma patients. Patient-individualized, spherically-symmetric simulations of the standard-of-care and optimized plans were compared in terms of several biological metrics.

Results

The integrated model generated spatially non-uniform doses that, when compared to the standard-of-care protocol, resulted in a 67% to 93% decrease in equivalent uniform dose to normal tissue, while the therapeutic ratio, the ratio of tumor equivalent uniform dose to that of normal tissue, increased between 50% to 265%. Applying a novel metric of treatment response (Days Gained) to the patient-individualized simulation results predicted that the optimized plans would have a significant impact on delaying tumor progression, with increases from 21% to 105% for 9 of 11 patients.

Conclusions

Patient-individualized simulations using the combination of a biomathematical model with an optimization algorithm for radiation therapy generated biologically-guided doses that decreased normal tissue EUD and increased therapeutic ratio with the potential to improve survival outcomes for treatment of glioblastoma.     

Effect of anode angle on photon beam spectra and depth dose characteristics for X-RAD320 orthovoltage unit

Background

In radiation therapy with orthovoltage units, the tube design has a crucial effect on its dosimetric features.

Aim

In this study, the effect of anode angle on photon beam spectra, depth dose and photon fluence per initial electron was studied for a commercial orthovoltage unit of X-RAD320 biological irradiator.

Materials and methods

The MCNPX MC code was used for modeling in the current study. We used the Monte Carlo method to model the X-RAD320 X-ray unit based on the manufacturer provided information. The MC model was validated by comparing the MC calculated photon beam spectra with the results of SpekCalc software. The photon beam spectra were calculated for anode angles from 15 to 35 degrees. We also calculated the percentage depth doses for some angles to verify the impact of anode angle on depth dose. Additionally, the heel effect and its relation with anode angle were studied for X-RAD320 irradiator.

Results

Our results showed that the photon beam spectra and their mean energy are changed significantly with anode angle and the optimum anode angle of 30 degrees was selected based on less heel effect and appropriate depth dose and photon fluence per initial electron.

Conclusion

It can be concluded that the anode angle of 30 degrees for X-RAD320 unit used by manufacturer has been selected properly considering the heel effect and dosimetric properties.     

Biodosimetry and assessment of radiation dose

Aim

When investigating radiation accidents, it is very important to determine the exposition dose to the individuals. In the case of exposures over 1 Gy, clinicians may expect deterministic effects arising the following weeks and months, in these cases dose estimation will help physicians in the planning of therapy. Nevertheless, for doses below 1 Gy, biodosimetry data are important due to the risk of developing late stochastic effects. Finally, some accidental overexposures are lack of physical measurements and the only way of quantifying dose is by biological dosimetry.

Background

The analysis of chromosomal aberrations by different techniques is the most developed method of quantifying dose to individuals exposed to ionising radiations.^1,2 Furthermore, the analysis of dicentric chromosomes observed in metaphases from peripheral lymphocytes is the routine technique used in case of acute exposures to assess radiation doses.

Materials and methods

Solid stain of chromosomes is used to determine dicentric yields for dose estimation. Fluorescence in situ hybridization (FISH) for translocations analysis is used when delayed sampling or suspected chronically irradiation dose assessment. Recommendations in technical considerations are based mainly in the IAEA Technical Report No. 405.²

Results

Experience in biological dosimetry at Gregorio Marañón General Hospital is described, including own calibration curves used for dose estimation, background studies and real cases of overexposition.

Conclusion

Dose assessment by biological dosimeters requires a large previous standardization work and a continuous update. Individual dose assessment involves high qualification professionals and its long time consuming, therefore requires specific Centres. For large mass casualties cooperation among specialized Institutions is needed.     

Wax boluses and accuracy of EBT and RTQA radiochromic film detectors in radiotherapy with the JINR Phasotron proton beam

Aim

To present the results obtained using radiochromic films EBT and RTQA 1010P for the reconstruction the dose distributions for targets irradiated by proton beam and modified by wax boluses.

Background

In Medico-Technical Complex at the Joint Institute for Nuclear Research in Dubna implemented technology of wax boluses.

Materials and methods

Wax boluses are easier to make and they give better dose distributions than boluses made from modeling clay previously used at our center. We irradiated two imaginary targets, one shaped as a cylinder and the other one as two cuboids. The evaluated calibration curve was used for calculation of the dose distributions measured by the EBT and RTQA radiochromic film. In both cases, the measured dose distributions were compared to the dose distributions calculated by the treatment planning system (TPS). We also compared dose distributions using three different conformity indices at a 95% isodose.

Results

Better target coverage and better compliance of measurements (semiconductor detectors and radiochromic films) with calculated doses was obtained for cylindrical target than for cuboidal target. The 95% isodose covered well the tumor for both target shapes, while for cuboidal target larger volume around the target received therapeutic dose, due to the complicated target shape. The use wax boluses provided to be effective tool in modifying proton beam to achieve appropriate shape of isodose distribution.

Conclusion

EBT film yielded the best visual matching. Both EBT and RTQA films confirmed good conformity between calculated and measured doses, thus confirming that wax boluses used to modify the proton beam resulted in good dose distributions.     

Analyzing the performance of ArcCHECK diode array detector for VMAT plan

Aim

The aim of this study is to evaluate performance of ArcCHECK diode array detector for the volumetric modulated arc therapy (VMAT) patient specific quality assurance (QA). VMAT patient specific QA results were correlated with ion chamber measurement. Dose response of the ArcCHECK detector was studied.

Background

VMAT delivery technique improves the dose distribution. It is complex in nature and requires proper QA before its clinical implementation. ArcCHECK is a novel three dimensional dosimetry system.

Materials and methods

Twelve retrospective VMAT plans were calculated on ArcCHECK phantom. Point dose and dose map were measured simultaneously with ion chamber (IC-15) and ArcCHECK diode array detector, respectively. These measurements were compared with their respective TPS calculated values.

Results

The ion chamber measurements are in good agreement with TPS calculated doses. Mean difference between them is 0.50% with standard deviation of 0.51%. Concordance correlation coefficient (CCC) obtained for ion chamber measurements is 0.9996. These results demonstrate a strong correlation between the absolute dose predicted by our TPS and the measured dose. The CCC between ArcCHECK doses and TPS predictions on the CAX was found to be 0.9978. In gamma analysis of dose map, the mean passing rate was 98.53% for 3% dose difference and 3 mm distance to agreement.

Conclusions

The VMAT patient specific QA with an ion chamber and ArcCHECK phantom are consistent with the TPS calculated dose. Statistically good agreement was observed between ArcCHECK measured and TPS calculated. Hence, it can be used for routine VMAT QA.     

Correlation of Plasma FL Expression with Bone Marrow Irradiation Dose

Purpose

Ablative bone marrow irradiation is an integral part of hematopoietic stem cell transplantation. These treatment regimens are based on classically held models of radiation dose and the bone marrow response. Flt-3 ligand (FL) has been suggested as a marker of hematopoiesis and bone marrow status but the kinetics of its response to bone marrow irradiation has yet to be fully characterized. In the current study, we examine plasma FL response to total body and partial body irradiation in mice and its relationship with irradiation dose, time of collection and pattern of bone marrow exposure.

Materials/Methods

C57BL6 mice received a single whole body or partial body irradiation dose of 1–8 Gy. Plasma was collected by mandibular or cardiac puncture at 24, 48 and 72 hr post-irradiation as well as 1–3 weeks post-irradiation. FL levels were determined via ELISA assay and used to generate two models: a linear regression model and a gated values model correlating plasma FL levels with radiation dose.

Results

At all doses between 1–8 Gy, plasma FL levels were greater than control and the level of FL increased proportionally to the total body irradiation dose. Differences in FL levels were statistically significant at each dose and at all time points. Partial body irradiation of the trunk areas, encompassing the bulk of the hematopoietically active bone marrow, resulted in significantly increased FL levels over control but irradiation of only the head or extremities did not. FL levels were used to generate a dose prediction model for total body irradiation. In a blinded study, the model differentiated mice into dose received cohorts of 1, 4 or 8 Gy based on plasma FL levels at 24 or 72 hrs post-irradiation.

Conclusion

Our findings indicate that plasma FL levels might be used as a marker of hematopoietically active bone marrow and radiation exposure in mice.     

Immunogenicity is not improved by increased antigen dose or booster dosing of seasonal influenza vaccine in a randomized trial of HIV infected adults

Introduction

The risk of poor vaccine immunogenicity and more severe influenza disease in HIV necessitate strategies to improve vaccine efficacy.

Methods

A randomized, multi-centered, controlled, vaccine trial with three parallel groups was conducted at 12 CIHR Canadian HIV Trials Network sites. Three dosing strategies were used in HIV infected adults (18 to 60 years): two standard doses over 28 days, two double doses over 28 days and a single standard dose of influenza vaccine, administered prior to the 2008 influenza season. A trivalent killed split non-adjuvanted influenza vaccine (Fluviral™) was used. Serum hemagglutinin inhibition (HAI) activity for the three influenza strains in the vaccine was measured to assess immunogenicity.

Results

297 of 298 participants received at least one injection. Baseline CD4 (median 470 cells/µL) and HIV RNA (76% of patients with viral load <50 copies/mL) were similar between groups. 89% were on HAART. The overall immunogenicity of influenza vaccine across time points and the three influenza strains assessed was poor (Range HAI ≥40 = 31–58%). Double dose plus double dose booster slightly increased the proportion achieving HAI titre doubling from baseline for A/Brisbane and B/Florida at weeks 4, 8 and 20 compared to standard vaccine dose. Increased immunogenicity with increased antigen dose and booster dosing was most apparent in participants with unsuppressed HIV RNA at baseline. None of 8 serious adverse events were thought to be immunization-related.

Conclusion

Even with increased antigen dose and booster dosing, non-adjuvanted influenza vaccine immunogenicity is poor in HIV infected individuals. Alternative influenza vaccines are required in this hyporesponsive population.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00764998","term_id":"NCT00764998"}}NCT00764998     

Modelling the Time Evolution of Active Caspase-3 Protein in the Rat Lens after In Vivo Exposure to Ultraviolet Radiation-B

Purpose

To introduce a model for the time evolution of active caspase-3 protein expression in albino rat lens up to 24 hours after in vivo exposure to low dose UVR in the 300 nm wavelength region (UVR-300 nm).

Methods

Forty Sprague-Dawley rats were unilaterally exposed in vivo to 1 kJ/m² UVR-300 nm for 15 minutes. At 0.5, 8, 16, and 24 hours after the UVR exposure, the exposed and contralateral not-exposed lenses were removed and processed for immunohistochemistry. The differences in the probability of active caspase-3 expression at four different time points after exposure were used to determine the time evolution of active caspase-3 expression. A logistic model was introduced for the expression of active caspase-3. The parameters for the exposed and the not exposed lenses were estimated for the observation time points.

Results

The exposure to UVR-300 nm impacted on the parameters of the logistic model. Further, the parameters of the model varied with time after exposure to UVR-300 nm.

Conclusion

The logistic model predicts the impact of exposure to UVR-300 nm on the spatial distribution of probability of active caspase-3 protein expression, depending on time.     

Open label study of escalating doses of oral treprostinil diethanolamine in patients with systemic sclerosis and digital ischemia: pharmacokinetics and correlation with digital perfusion

Introduction

Treprostinil diethanolamine is an innovative salt form of the prostacyclin analogue, treprostinil sodium, developed as an oral sustained release (SR) osmotic tablet. The availability of a formulation permitting convenient systemic delivery might have applicability to scleroderma vascular complications. We evaluated pharmacokinetics and perfusion in scleroderma patients with digital ischemia following escalating twice-daily doses of treprostinil diethanolamine SR.

Methods

Scleroderma patients with digital ulcers were enrolled in this dual-center, open-label, phase I pharmacokinetic study. Drug concentrations and perfusion, quantified by laser Doppler imaging, were measured over 12 hours at the 2 mg and 4 mg (or maximally tolerated) doses. Pharmacokinetic parameters were determined from individual plasma concentration versus time profiles using non-compartmental analysis methods. Digital perfusion and skin temperature were modeled as a function of log-transformed drug concentration and other covariates by performing repeated measures analyses using random effects models.

Results

Nineteen scleroderma patients (84% female, 53% limited scleroderma) received treprostinil diethanolamine SR with dose titration up to 4 mg twice daily as tolerated. Peak concentrations (mean maximum plasma concentration (C_max) = 1,176 and 2,107 pg/mL) occurred approximately 3.6 hours after dose administration, and overall exposure (under the plasma concentration-time curve from time 0 to 12 hours post dose (AUC_0-12) = 7,187 and 12,992 hr*pg/mL) was linear between the 2 mg and 4 mg doses. Perfusion and digital skin temperature were positively associated with log-transformed plasma concentration at the 4 mg dose (P = 0.015 and P = 0.013, respectively). The most frequent adverse events were similar to those seen with prostacyclin analogues.

Conclusions

Oral treprostinil diethanolamine was effectively absorbed in patients with scleroderma. Drug administration was temporally associated with improved cutaneous perfusion and temperature. Treprostinil diethanolamine may provide a new therapeutic option for Raynaud''s phenomenon and the peripheral vascular disease of scleroderma.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00848939","term_id":"NCT00848939"}}NCT00848939.

Electronic supplementary material

The online version of this article (doi:10.1186/ar4216) contains supplementary material, which is available to authorized users.     

Measurement verification of dose distributions in pulsed-dose rate brachytherapy in breast cancer

Aim

The aim of the study was to verify the dose distribution optimisation method in pulsed brachytherapy.

Background

The pulsed-dose rate brachytherapy is a very important method of breast tumour treatment using a standard brachytheraphy equipment. The appropriate dose distribution round an implant is an important issue in treatment planning. Advanced computer systems of treatment planning are equipped with algorithms optimising dose distribution.

Materials and methods

The wax-paraffin phantom was constructed and seven applicators were placed within it. Two treatment plans (non-optimised, optimised) were prepared. The reference points were located at a distance of 5 mm from the applicators’ axis. Thermoluminescent detectors were placed in the phantom at suitable 35 chosen reference points.

Results

The dosimetry verification was carried out in 35 reference points for the plans before and after optimisation. Percentage difference for the plan without optimisation ranged from −8.5% to 1.4% and after optimisation from −8.3% to 0.01%. In 16 reference points, the calculated percentage difference was negative (from −8.5% to 1.3% for the plan without optimisation and from −8.3% to 0.8% for the optimised plan). In the remaining 19 points percentage difference was from 9.1% to 1.4% for the plan without optimisation and from 7.5% to 0.01% for the optimised plan.No statistically significant differences were found between calculated doses and doses measured at reference points in both dose distribution non-optimised treatment plans and optimised treatment plans.

Conclusions

No statistically significant differences were found in dose values at reference points between doses calculated by the treatment planning system and those measured by TLDs. This proves the consistency between the measurements and the calculations.     

Dependence of the safe rectum dose on the CTV–PTV margin size and treatment technique

Background

Late rectal injury is a common side effect of external beam radiotherapy for prostate cancer.

Aim

The aim of this study was to evaluate what total dose may be safely delivered for prostate patients for 3DCRT and IMRT techniques and the CTV–PTV margin.

Materials and methods

3DCRT and IMRT plans were prepared for 12 patients. For each patient PTV was defined with CTV–PTV margins of 0.4, 0.6, …, 1.0 cm, and total doses of 70, 72, …, 80 Gy, with 2 Gy dose fraction. NTCP values for the rectum were calculated using the Lyman model. Both techniques were compared in terms of population mean DVH.

Results

Significantly smaller NTCPs for IMRT were obtained. For both techniques diminishing the margin CTV–PTV of 2 mm leads to decreasing the NTCP of about 0.03. For total dose of 80 Gy the NTCP was smaller than 10% for the 4 mm margin only. The QUANTEC dose volume constraints were more frequently fulfilled for the IMRT technique than for the 3DCRT technique.

Conclusions

The IMRT technique is safer for prostate patients than the 3DCRT. If very high total doses are applied the CTV–PTV margin of 0.4 cm and the IMRT technique should be used. If the CTV–PTV margin of 0.6 cm is applied, the NTCP is smaller than 10% for the 3DCRT and IMRT techniques for the total doses smaller than 74 Gy and 78 Gy, respectively.     

Advances and future of Radiation Oncology

Aim

Review of recent advances and vision for future developments in clinical practice of Radiation Oncology.

Background

There have been substantial research and technological developments in Radiation Oncology over the past 40 years.

Materials and methods

The relevant literature was reviewed and the authors offer their perspective on future opportunities for advancement in Radiation Oncology.

Conclusions

Significant innovative technological developments have been introduced in the practice of Radiation Oncology, with more precise target delineation and tracking and three dimensional treatment planning, optimal delivery of radiation therapy to the target and lower doses to surrounding Organs at Risk. This dose optimization and adaptive therapy have enhanced the role of Radiation Therapy to more effectively treat patients with cancer. Further creativity and refinements will continue to advance the field into new applications of ionizing radiations in cancer therapy.     

Craniospinal radiotherapy in children: Electron- or photon-based technique of spinal irradiation

Background

The prone position and electron-based technique for craniospinal irradiation (CSI) have been standard in our department for many years. But this immobilization is difficult for the anaesthesiologist to gain airway access. The increasing number of children treated under anaesthesia led us to reconsider our technique.

Aim

The purpose of this study is to report our new photon-based technique for CSI which could be applied in both the supine and the prone position and to compare this technique with our electron-based technique.

Materials and methods

Between November 2007 and May 2008, 11 children with brain tumours were treated in the prone position with CSI. For 9 patients two treatment plans were created: the first one using photons and the second one using electron beams for spinal irradiation. We prepared seven 3D-conformal photon plans and four forward planned segmented field plans. We compared 20 treatment plans in terms of target dose homogeneity and sparing of organs at risk.

Results

In segmented field plans better dose homogeneity in the thecal sac volume was achieved than in electron-based plans. Regarding doses in organs at risk, in photon-based plans we obtained a lower dose in the thyroid but a higher one in the heart and liver.

Conclusions

Our technique can be applied in both the supine and prone position and it seems to be more feasible and precise than the electron technique. However, more homogeneous target coverage and higher precision of dose delivery for photons are obtained at the cost of slightly higher doses to the heart and liver.     

Progression of Cartilage Degradation, Bone Resorption and Pain in Rat Temporomandibular Joint Osteoarthritis Induced by Injection of Iodoacetate

Background

Osteoarthritis (OA) is an important subtype of temporomandibular disorders. A simple and reproducible animal model that mimics the histopathologic changes, both in the cartilage and subchondral bone, and clinical symptoms of temporomandibular joint osteoarthritis (TMJOA) would help in our understanding of its process and underlying mechanism.

Objective

To explore whether injection of monosodium iodoacetate (MIA) into the upper compartment of rat TMJ could induce OA-like lesions.

Methods

Female rats were injected with varied doses of MIA into the upper compartment and observed for up to 12 weeks. Histologic, radiographic, behavioral, and molecular changes in the TMJ were evaluated by light and electron microscopy, MicroCT scanning, head withdrawal threshold test, real-time PCR, immunohistochemistry, and TUNEL assay.

Results

The intermediate zone of the disc loosened by 1 day post-MIA injection and thinned thereafter. Injection of an MIA dose of 0.5 mg or higher induced typical OA-like lesions in the TMJ within 4 weeks. Condylar destruction presented in a time-dependent manner, including chondrocyte apoptosis in the early stages, subsequent cartilage matrix disorganization and subchondral bone erosion, fibrosis, subchondral bone sclerosis, and osteophyte formation in the late stages. Nociceptive responses increased in the early stages, corresponding to severe synovitis. Furthermore, chondrocyte apoptosis and an imbalance between anabolism and catabolism of cartilage and subchondral bone might account for the condylar destruction.

Conclusions

Multi-level data demonstrated a reliable and convenient rat model of TMJOA could be induced by MIA injection into the upper compartment. The model might facilitate TMJOA related researches.     

Is dose escalation achievable for esophageal carcinoma?

Aim

To investigate the feasibility of dose escalation using rapid arc (RA) and Helical Tomotherapy (HT) for patients with upper, middle and distal esophageal carcinomas, even for large tumor volumes.

Background

In esophageal cancer, for patients with exclusive radio-chemotherapy, local disease control remains poor. Planning study with dose escalation was done for two sophisticated modulated radiotherapy techniques: Rapid arc against Tomotherapy.

Materials and methods

Six patients treated with a RA simultaneous integrated boost (SIB) of 60 Gy were re-planned for RA and HT techniques with a SIB dose escalated to 70 Gy. Dose volume histogram statistics, conformity indices and homogeneity indices were analyzed. For a given set of normal tissue constraints, the capability of each treatment modality to increase the GTV dose to 70 Gy was investigated.

Results

Either HT or VMAT may be used to escalate the dose delivered in esophageal tumors while maintaining the spinal cord, lung and heart doses within tolerance. Adequate target coverage was achieved by both techniques. Typically, HT achieved better lung sparing and PTV coverage than did RA.

Conclusions

Dose escalation for esophageal cancer becomes clinically feasible with the use of RA and HT. This promising result could be explored in a carefully controlled clinical study which considered normal tissue complications and tumor control as endpoints.     

Application of IMRT in adjuvant treatment of soft tissue sarcomas of the thigh—Preliminary results

Background

Fracture of the femur is the most frequent late complication in patients with soft tissue sarcomas (STS) who receive external beam radiotherapy after limb-sparing surgery.

Aim

To reduce the risk of bone fracture following radiotherapy of STS of the thigh, we minimized the dose to the femur and to surrounding normal tissues by applying intensity modulated radiation therapy (IMRT). We report preliminary results of post-surgery IMRT of the thigh in patients with STS in this extremity.

Materials and methods

10 adult patients undergoing post-operative radiotherapy of STS of the thigh were treated using IMRT. Clinical IMRT plans with simultaneous integrated boost (SIB) and 3-phase three-dimensional conformal radiotherapy (3D-CRT) were designed to adequately treat the planning target volume and to spare the femur to the largest extent possible. Dose distributions and dose-volume histograms were compared.

Results

For either technique, a comparable target coverage was achieved; however, target volume was better covered and critical structures were better spared in IMRT plans. Mean and maximum doses to OAR structures were also significantly reduced in the IMRT plans. On average, the mean dose to the femur in 3D-CRT plans was about two times higher than that in IMRT plans.

Conclusion

Compared with 3D-CRT, the application of IMRT improves the dose distribution within the concave target volumes and reduces dose to the OAR structures without compromising target coverage.     

The Application of the Grey Disaster Model to Forecast Epidemic Peaks of Typhoid and Paratyphoid Fever in China

Objective

The objectives of this study were to forecast epidemic peaks of typhoid and paratyphoid fever in China using the grey disaster model, to evaluate its feasibility of predicting the epidemic tendency of notifiable diseases.

Methods

According to epidemiological features, the GM(1,1) model and DGM model were used to build the grey disaster model based on the incidence data of typhoid and paratyphoid fever collected from the China Health Statistical Yearbook. Model fitting accuracy test was used to evaluate the performance of these two models. Then, the next catastrophe date was predicted by the better model.

Results

The simulation results showed that DGM model was better than GM(1,1) model in our data set. Using the DGM model, we predicted the next epidemic peak time will occur between 2023 to 2025.

Conclusion

The grey disaster model can predict the typhoid and paratyphoid fever epidemic time precisely, which may provide valuable information for disease prevention and control.     

Radiotherapy dose enhancement using BNCT in conventional LINACs high-energy treatment: Simulation and experiment

Aim

To employ the thermal neutron background that affects the patient during a traditional high-energy radiotherapy treatment for BNCT (Boron Neutron Capture Therapy) in order to enhance radiotherapy effectiveness.

Background

Conventional high-energy (15–25 MV) linear accelerators (LINACs) for radiotherapy produce fast secondary neutrons in the gantry with a mean energy of about 1 MeV due to (γ, n) reaction. This neutron flux, isotropically distributed, is considered as an unavoidable undesired dose during the treatment. Considering the moderating effect of human body, a thermal neutron fluence is localized in the tumour area: this neutron background could be employed for BNCT by previously administering ¹⁰B-Phenyl-Alanine (¹⁰BPA) to the patient.

Materials and methods

Monte Carlo simulations (MCNP4B-GN code) were performed to estimate the total amount of neutrons outside and inside human body during a traditional X-ray radiotherapy treatment.Moreover, a simplified tissue equivalent anthropomorphic phantom was used together with bubble detectors for thermal and fast neutron to evaluate the moderation effect of human body.

Results

Simulation and experimental results confirm the thermal neutron background during radiotherapy of 1.55E07 cm⁻² Gy⁻¹.The BNCT equivalent dose delivered at 4 cm depth in phantom is 1.5 mGy-eq/Gy, that is about 3 Gy-eq (4% of X-rays dose) for a 70 Gy IMRT treatment.

Conclusions

The thermal neutron component during a traditional high-energy radiotherapy treatment could produce a localized BNCT effect, with a localized therapeutic dose enhancement, corresponding to 4% or more of photon dose, following tumour characteristics. This BNCT additional dose could thus improve radiotherapy, acting as a localized radio-sensitizer.     

Total skin electron beam (TSEB) therapy in pediatric patients: A review of the literature

Aim

A literature review was undertaken to identify current TSEB therapy in pediatric patients.

Background

Total skin electron beam (TSEB) therapy is a method of irradiation with low energy electron beam dedicated to patients who have superficial skin lesions all over their body. Such skin malignancies are sparse among adults and even more uncommon with pediatric population.

Materials and methods

In this study, all reported case reports were summed up with a special emphasis on techniques used, doses prescribed and special shielding of critical organs. Moreover, potential problems that were encountered during TSEB irradiation of very young patients were depicted.

Results

The literature has described only seven case reports of children undergoing TSEB therapy. Most of them were infants; however, two adolescents were also treated. For all infants, general anesthesia was provided to allow safe and accurate TSEB irradiation. The prescribed dose varied from 16 Gy to 28 Gy depending on the irradiation schedule and patient condition. Usually, boost fields were applied to the scalp and perineum. Typical shields for fingernails, toenails and lenses were usually used.

Conclusion

This paper revealed that TSEB therapy may be considered as a palliative treatment for pediatric patients with leukemia cutis. However, its role is still unclear and should be further investigated.     

Impact of Acetazolamide and CPAP on Cortical Activity in Obstructive Sleep Apnea Patients

Study Objectives

1) To investigate the impact of acetazolamide, a drug commonly prescribed for altitude sickness, on cortical oscillations in patients with obstructive sleep apnea syndrome (OSAS). 2) To examine alterations in the sleep EEG after short-term discontinuation of continuous positive airway pressure (CPAP) therapy.

Design

Data from two double-blind, placebo-controlled randomized cross-over design studies were analyzed.

Setting

Polysomnographic recordings in sleep laboratory at 490 m and at moderate altitudes in the Swiss Alps: 1630 or 1860 m and 2590 m.

Patients

Study 1: 39 OSAS patients. Study 2: 41 OSAS patients.

Interventions

Study 1: OSAS patients withdrawn from treatment with CPAP. Study 2: OSAS patients treated with autoCPAP. Treatment with acetazolamide (500–750 mg) or placebo at moderate altitudes.

Measurements and Results

An evening dose of 500 mg acetazolamide reduced slow-wave activity (SWA; approximately 10%) and increased spindle activity (approximately 10%) during non-REM sleep. In addition, alpha activity during wake after lights out was increased. An evening dose of 250 mg did not affect these cortical oscillations. Discontinuation of CPAP therapy revealed a reduction in SWA (5–10%) and increase in beta activity (approximately 25%).

Conclusions

The higher evening dose of 500 mg acetazolamide showed the “spectral fingerprint” of Benzodiazepines, while 250 mg acetazolamide had no impact on cortical oscillations. However, both doses had beneficial effects on oxygen saturation and sleep quality.