Analysis of high–dose rate brachytherapy dose distribution resemblance in CyberKnife hypofractionated treatment plans of localized prostate cancer

The present study is to analyze the CyberKnife hypofractionated dose distribution of localized prostate cancer in terms of high–dose rate (HDR) brachytherapy equivalent doses to assess the degree of HDR brachytherapy resemblance of CyberKnife dose distribution. Thirteen randomly selected localized prostate cancer cases treated using CyberKnife with a dose regimen of 36.25 Gy in 5 fractions were considered. HDR equivalent doses were calculated for 30 Gy in 3 fractions of HDR brachytherapy regimen. The D_5% of the target in the CyberKnife hypofractionation was 41.57 ± 2.41 Gy. The corresponding HDR fractionation (3 fractions) equivalent dose was 32.81 ± 1.86 Gy. The mean HDR fractionation equivalent dose, D_98%, was 27.93 ± 0.84 Gy. The V_100% of the prostate target was 95.57% ± 3.47%. The V_100% of the bladder and the rectum were 717.16 and 79.6 mm³, respectively. Analysis of the HDR equivalent dose of CyberKnife dose distribution indicates a comparable resemblance to HDR dose distribution in the peripheral target doses (D_98% to D_80%) reported in the literature. However, there is a substantial difference observed in the core high-dose regions especially in D_10% and D_5%. The dose fall-off within the OAR is also superior in reported HDR dose distribution than the HDR equivalent doses of CyberKnife.     

The biologically equivalent dose (BED): how solid is the calculation of this factor? A consideration of margins of error of biologically equivalent dose

To predict the effect on tumours in radiotherapy, especially relating to irreversible effects, but also to realize the retrospective assessment the so called L-Q-model is relied on at present. Internal specific organ parameters, such as alpha, beta, gamma, Tp, Tk, and rho, as well as external parameters, so as D, d, n, V, and Vref, were used for determination of the biologically equivalent dose BED. While the external parameters are determinable with small deviations, the internal parameters depend on biological varieties and dispersions: in some cases the lowest value is assumed to be delta = +/- 25%. This margin of error goes on to the biologically equivalent dose by means of the principle of superposition of errors. In some selected cases (lung, kidney, skin, rectum) these margins of error were calculated exemplarily. The input errors especially of the internal parameters cause a mean error delta on the biologically equivalent dose and a dispersion of the single fraction dose d dependent on the organ taking into consideration, of approximately 8-30%. Hence it follows only a very critical and cautious application of those L-Q-algorithms in expert proceedings, and in radiotherapy more experienced based decisions are recommended, instead of acting only upon simple two-dimensional mechanistic ideas.     

Influence of magnesium chloride on the dose–response of polyacrylamide-type gel dosimeters

We investigated the effect of magnesium chloride (MgCl₂) on the nuclear magnetic resonance dose–response of polyacrylamide-type (PAGAT, NIPAM, and VIPET) gel dosimeters containing acrylamide, N-isopropylacrylamide, and N-vinylpyrrolidone as a monomer, respectively. The dose-transverse relaxation rates (1/T₂?=?R₂) obtained from magnetic resonance imaging data revealed that a substantial increase in the dose–R₂ response occurred as the concentration of MgCl₂ in the gel dosimeters increased. The sensitivity of the PAGAT gel with 1.0 M MgCl₂ was found to be approximately one order higher than that of the same gel without MgCl₂. In addition, the water equivalences of the gels with MgCl₂ were evaluated over a wide range of photon energies. The results indicated that MgCl₂ acts as a powerful sensitizer to radiation-induced free-radical polymerization in polyacrylamide-type gel dosimeters, but does not interfere with the desirable properties of basic polyacrylamide-type gel dosimeters (i.e., the dose rate and dose integration).     

High or low dose radioiodine ablation of thyroid remnants?

The need for high dose radioiodine for ablation of remnants in patients with thyroid cancer is still in question. We compared the effectiveness of high and low dose 131I for ablation in patients in a prospective randomized study after surgical thyroidectomy. Twenty patients with differentiated pT2-3NoMo thyroid cancer were studied. The uptake was 5%-10% at 24 h. Ten patients received 100 mCi, the others 30 mCi 131I. Three months later all patients received a therapeutic dose of 150 mCi 131I. Another twenty patients with known distant metastases (pulmonary and/or bone) of differentiated thyroid cancer were studied. The remnant uptake was between 4%-10%. Ten patients received 300 mCi and ten 30 mCi 131I as ablation dose. Three months later all received 300 mCi 131I. The uptake at day seven was calculated for the same metastases from a whole body scan after both treatments. If effective ablation was defined as 24 h uptake in the remnant of less than 1%, then the ablation was effective in eight out of ten of the high dose and in seven out of ten of the low dose group. In pT2-3, N X M1 patients the ablation was effective in seven out of ten cases in both groups. If "effective" ablation was defined as an uptake of less than 0.5%, then the ablation was effective both in NoMo and in N X M1 patients in five out of ten with low dose and in six out of ten with high dose ablation treatment.(ABSTRACT TRUNCATED AT 250 WORDS)     

High or low dose radioiodine ablation of thyroid remnants?

The need for high dose radioiodine for ablation of remnants in patients with thyroid cancer is still in question. We compared the effectiveness of high and low dose¹³¹I for ablation in patients in a prospective randomized study after surgical thyroidectomy. Twenty patients with differentiatedpT2-3NoMo thyroid cancer were studied. The uptake was 5%–10% at 24 h. Ten patients received 100 mCi, the others 30 mCi¹³¹I. Three months later all patients received a therapeutic dose of 150 mCi¹³¹I. Another twenty patients with known distant metastases (pulmonary and/or bone) of differentiated thyroid cancer were studied. The remnant uptake was between 4%–10%. Ten patients received 300 mCi and ten 30 mCi¹³¹I as ablation dose. Three months later all received 300 mCi¹³¹I. The uptake at day seven was calculated for the same metastases from a whole body scan after both treatments. If effective ablation was defined as 24h uptake in the remnant of less than 1%, then the ablation was effective in eight out of ten of the high dose and in seven out of ten of the low dose group. In pT2-3, NxM1 patients the ablation was effective in seven out of ten cases in both groups. If effective ablation was defined as an uptake of less than 0.5%, then the ablation was effective both in NoMo and in NxM1 patients in five out of ten with low dose and in six out of ten with high dose ablation treatment. Seventh day uptake in 20 metastases after the second dose was at mean 3.6 times (range 2.8–4.3) higher than after the first, while there was no significant difference in TSH levels. In two patients,¹³¹I kinetics over a bone metastasis were recorded continuously during 300 mCi ablation treatment and 300 mCi therapeutic treatment without any significant difference. We therefore recommend a 30 mCi ablation dose for all patients with differentiated thyroid cancer after surgical thyroidectomy, followed by a 300 mCi treatment dose in pT2-3N1M x or pT2-3N x M1 patients, while in pT2-3NoMo low dose ablation will be a sufficient treatment.Supported in part by Deutsche Forschungsgemeinschaft (grant Cr 52/4-1)     

Age-dependent changes in oxygen tension,radiation dose and sensitivity within normal and diseased coronary arteries–Part A: Dose from radon and thoron

Purpose: There is mounting evidence that a significant fraction of radiation-induced mortality and years-life lost are non-cancerous in nature. This study quantifies the radon dose to the coronary artery walls, especially the intimal layer, vunerable to the development of atherosclerosis, and associated cardiovascular disease (CVD). Two accompanying papers determine the oxygen levels (Part B) in coronary arteries and the oxygen effect for radon and other exposures (Part C).

Materials and methods: The alpha-radiation dose to coronary artery walls was calculated from the proportion of inhaled radon (²²²Rn), thoron (²²⁰Rn) and their short-lived progeny, which was not deposited in the lung and passed into blood. Age- and gender-dependent morphology and composition for the wall layers of coronary arteries were developed from published data for a normal population and also for individuals with cardiovascular disease. The alpha particle dose to the coronary artery walls was evaluated taking account the diffusion of radon from blood and the solubility of radon-gas in tissues.

Results: Diseased arteries exhibited a moderate increase in the solubility of lipophylic radon (190%) in arteries with 88% luminal narrowing, as the high Rn solubility in fat was partially offset by the lower solubility in calcium deposits. The average worldwide dose rate to the diseased intimal layer from ²²²Rn and its short-lived progeny was estimated to be as high as 68 μSv y^?1 per 40 Bq m^?3 in air, whereas the corresponding dose rate from ²²⁰Rn per 0.3 Bq m^?3 in air was ≤0.1% in comparison. Gender had little influence on the dose.

Conclusion: The Rn dose to the coronary arteries is significant, but has a large uncertainty due to poor knowledge of Rn and its progeny concentrations in the body.     

Single dose planning for radioiodine-131 therapy of Graves’ disease

Objective  Patients with Graves’ disease were studied one year after radioiodine-131 therapy to assess the relationship between the effectiveness of the therapy and the radioiodine doses used.Methods: Patients were classified into three groups according to thyroid function as hyperthyroidism, euthyroidism and hypothyroidism at one year after I-131 therapy. In these groups we compared the mean values of dose, dose per thyroid weight calculated with I-123 uptake before the therapy (pre D/W), dose per thyroid weight calculated with therapeutic I-131 uptake (post D/W), and absorbed dose. Results  No significant differences were found between the three groups in terms of dose or pre D/W. The mean values of post D/W and absorbed dose in the non-hyperthyroid (euthyroid and hypothyroid) group were significantly greater than those in the hyperthyroid group. Post D/W of 6.3 MBq/g was a threshold separating the non-hyperthyroid group from the hyperthyroid group. There was no correlation between pre D/W and post D/W; however, the mean post D/W was significantly greater than the mean pre D/W. All patients with pre D/W above 6.3 MBq/g showed non-hyperthyroidism at one year after the radioiodine treatment. Conclusions  No indicators before the radioiodine therapy had significant relationships with the effectiveness of the therapy at one year after the treatment. However, the single therapy planned for setting the pre D/W above 6.3 MBq/g will certainly make the patients non-hyperthyroid. As this proposal of dose planning is based on a small number of patients, further study is needed.     

The dynamic range of digital radiographic systems: dose reduction or risk of overexposure?

OBJECTIVES: To investigate the range of diagnostically acceptable digital radiographs and film as a function of exposure time, as well as the relationship to dose reduction and consequences for dental practice. METHODS: Five systems for intraoral radiography were used to take a series of radiographs, with increasing exposure times, of five different dry bone specimens. Seven observers evaluated the 25 series of radiographs. The observers had to determine which radiographs of each series were acceptable for dental diagnostics and which radiograph of each series they preferred. RESULTS: For Ektaspeed Plus film, the exposure time for the preferred radiograph was 0.52 s, with a range of diagnostically acceptable radiographs from 0.23-1.02 s. The preferred radiograph of the solid-state systems required less radiation than film (Sirona, 0.13 s; MPDx 0.35 s). The exposure range of these systems is narrow. In contrast, the exposure range of the phosphor plate systems is very wide. The preferred radiograph of the phosphor plate systems required high exposure (Digora, 1.21 s; Gendex DenOptix, 1.16 s). CONCLUSIONS: All digital systems require less exposure than film for diagnostically acceptable radiographs, but this is less obvious for preferred radiographs. Solid-state systems alert the dentist when a too long exposure time is used by a lack of image quality; phosphor plate systems, however, produce good quality radiographs even at high exposure times, which may result in an unnecessarily high dose.     

Two year evolution of radon emission and tectonic movements in Tuzla Fault,Seferihisar-İzmir

Previous studies showed that tectonic movement and meteorological events are accompanied with radon release. In this study soil gas radon and tectonic movements were investigated with meteorological factors taking into account. Soil gas radon measurements were collected over a-two year period (2008–2010) at the Tuzla Fault in Turkey. The relationship between radon anomalies and seismic activities was evaluated using Dobrovolsky's form. It is shown that not only magnitude of earthquake but also distance from the measurement site should be used for identifying radon anomalies.     

Survey of computed tomography techniques and absorbed dose in Italian hospitals: a comparison between two methods to estimate the dose–length product and the effective dose and to verify fulfilment of the diagnostic reference levels

The aim of this study was the production of the first Italian survey of radiation dose in computed tomography (CT) prior to the widespread adoption of multislice CT, in order to have a reference point to facilitate later investigation of dose exposure changes brought by this new CT modality. The collected dose data were compared with diagnostic reference levels (DRLs). The agreement between experimental dose evaluation and Monte Carlo (MC) simulations was investigated. The survey was carried out in 29 Italian hospitals, covered 48 CT scanners and 232 examinations. The dose–length product (DLP) and effective dose (E) values were estimated based on MC simulations for seven clinical protocols using the CT-Dose program. Statistical analysis showed a significant difference (p<0.01) in the DLP between the two methods, with MC values being greater than the experimental ones. For E, the MC values were greater in routine head (8.2%), cervical spine (2.7%) and lumbar spine (2.9%) studies. The weighted CT dose index, the DLP and E were always below the DRLs set by the European Community. This dose survey gives a good but incomplete picture of the Italian CT dose situation and may be useful as a reference baseline for defining clinical multislice protocols in the near future.     

Predicting adherence of dose–volume constraints for personalized partial-breast irradiation technique

PurposeMulticatheter interstitial brachytherapy (MIB) and external-beam (EB) radiotherapy are established partial-breast irradiation (PBI) techniques. Although EB-PBI is widely available, it requires extra irradiated margins for target uncertainties. We examined the impact of EB-PBI on dose–volume constraints as compared to MIB-PBI.Methods and MaterialsAmong 653 patients receiving MIB-PBI between October 2008 and April 2020, consequent 159 patients after September 2018 were examined. Clinical target volume (CTV) included the lumpectomy cavity plus 1.0 cm. Planning target volume (PTV) for EB-PBI was defined as CTV with 1.0-cm expansion. Because the ratio of PTV to breast volume (RPB) was related to cosmesis, <25% of RPB was defined as suitable for the ipsilateral breast constraints. Preoperative breast size was classified as very small (<350 cm³), small (350–699 cm³), and medium or large (≥700 cm³). According to each category, the dose–volume constraints of the organs at risk were compared between the two PBI techniques.ResultsPatients including 84 very small, 59 small, and 16 moderate to large breasts were examined. Although RPB was suitable in all patients receiving MIB-PBI, it was achieved in 74 patients (46.5%) receiving EB-PBI (p < 0.0001). The suitable RPB in patients with very small, small, and moderate to large breast was 32.1%, 55.9%, and 100%, respectively (p < 0.0001). Normal-tissue constraints for the other organs could be satisfied in patients with moderate to large breasts.ConclusionAlthough EB-PBI may be an appropriate option for patients with moderate to large breasts, MIB-PBI could still be a crucial technique, especially for patients with small breasts.     

Is there a specific mutation of p53 gene due to radon exposure? A systematic review

Purpose: To review the existing literature analysing the influence of radon exposure on mutations in tumour protein 53 gene (TP53) in lung cancer patients.

Material and methods: Medline and EMBASE databases along with the International Agency for Research on Cancer (IARC) monographies were revised. Studies that had radon concentration as exposure variable and TP53 mutations as a result variable were included.

Results: Eight studies were obtained, with a total of 578 individuals. They had been carried out on miners and on general population. A 26% of the miners' tumours had a mutation in gene TP53, versus a 24% in the population exposed to residential radon. A predominance of the AGG^ARG→ ATG^MET (Arginine to Methionine) mutation in miners was observed.

Conclusions: The available results are not consistent in order to support the existence of a radon hotspot in TP53 gene. Future research should focus at least on exons 5 to 8, where most of the mutation clusters in lung tumours are observed.     

Does selective pleural irradiation of malignant pleural mesothelioma allow radiation dose escalation?

Background

After lung-sparing radiotherapy for malignant pleural mesothelioma (MPM), local failure at sites of previous gross disease represents the dominant form of failure. Our aim is to investigate if selective irradiation of the gross pleural disease only can allow dose escalation.

Materials and methods

In all, 12 consecutive stage I–IV MPM patients (6 left-sided and 6 right-sided) were retrospectively identified and included. A magnetic resonance imaging-based pleural gross tumor volume (GTV) was contoured. Two sets of planning target volumes (PTV) were generated for each patient: (1) a “selective” PTV (S-PTV), originating from a 5-mm isotropic expansion from the GTV and (2) an “elective” PTV (E-PTV), originating from a 5-mm isotropic expansion from the whole ipsilateral pleural space. Two sets of volumetric modulated arc therapy (VMAT) treatment plans were generated: a “selective” pleural irradiation plan (SPI plan) and an “elective” pleural irradiation plan (EPI plan, planned with a simultaneous integrated boost technique [SIB]).

Results

In the SPI plans, the average median dose to the S?PTV was 53.6?Gy (range 41–63.6?Gy). In 4 of 12 patients, it was possible to escalate the dose to the S?PTV to >58?Gy. In the EPI plans, the average median doses to the E?PTV and to the S?PTV were 48.6?Gy (range 38.5–58.7) and 49?Gy (range 38.6–59.5?Gy), respectively. No significant dose escalation was achievable.

Conclusion

The omission of the elective irradiation of the whole ipsilateral pleural space allowed dose escalation from 49?Gy to more than 58?Gy in 4 of 12 chemonaive MPM patients. This strategy may form the basis for nonsurgical radical combined modality treatment of MPM.

     

Do low dose-rate bystander effects influence domestic radon risks?

PURPOSE: Radon risks derive from exposure of bronchio-epithelial cells to high-linear energy transfer (LET) alpha-particles. alpha-particle exposure can result in bystander effects, where irradiated cells emit signals resulting in damage to nearby unirradiated bystander cells. This can result in non-linear dose-response relations, and inverse dose-rate effects. Domestic radon risk estimates are currently extrapolated from miner data, which are at both higher doses and higher dose-rates, so bystander effects on unhit cells could play a large role in the extrapolation of risks from mines to homes. Therefore, we extend an earlier quantitative mechanistic model of bystander effects to include protracted exposure, with the aim of quantifying the significance of the bystander effect for very prolonged exposures. MATERIALS AND METHODS: A model of high-LET bystander effects, originally developed to analyse oncogenic transformation in vitro, is extended to low dose-rates. The model considers radiation response as a superposition of bystander and linear direct e It attributes bystander effects to a small subpopulation of hypersensitive cells, with the bystander contribution dominating the direct contribution at very low acute doses but saturating as the dose increases. Inverse dose-rate effects are attributed to the replenishment of the hypersensitive subpopulation during prolonged irradiation. RESULTS: The model was fitted to dose- and dose-rate-dependent radon-exposed miner data, suggesting that one directly hit target bronchio-epithelial cell can send bystander signals to about 50 neighbouring target cells. The model suggests that a na?ve linear extrapolation of radon miner data to low doses, without accounting for dose-rate, would result in an underestimation of domestic radon risks by about a factor of 4, a value comparable with the empirical estimate applied in the recent BEIR-VI report on radon risk estimation. CONCLUSIONS: Bystander effects represent a plausible quantitative and mechanistic explanation of inverse dose-rate effects by high-LET radiation, resulting in non-linear dose-response relations and a complex interplay between the effects of dose and exposure time. The model presented provides a potential mechanistic underpinning for the empirical exposure-time correction factors applied in the recent BEIR-VI for domestic radon risk estimation.