Absorbed Dose Threshold Research Articles

TCP post-radioembolization and TCP post-EBRT in HCC are similar and can be predicted using the in vitro radiosensitivity

BackgroundTumor equivalent uniform dose (EUD) is proposed as a predictor of patient outcome after liver radioembolization (RE) of hepatocellular carcinoma (HCC) and can be evaluated with 90Y-TOF-PET. The aim is to evaluate the correlation between PET-based tumors EUD and the clinical response evaluated with dual molecular tracer (11C-acetate and 18F-FDG) PET/CT post-RE.Methods34 HCC tumors in 22 patients were prospectively evaluated. The metabolic response was characterized by the total lesion metabolism variation (ΔTLM) between baseline and follow-up. This response allowed to compute a tumor control probability (TCP) as a function of the tumor EUD.ResultsThe absorbed dose response correlation was highly significant (R = 0.72, P < 0.001). With an absorbed dose threshold of 40 Gy, the metabolic response was strongly different in both groups (median response 35% versus 100%, P < 0.001). Post-RE TCP as a function of the EUD was very similar to that observed in external beam radiation therapy (EBRT), with TCP values equal to 0.5 and 0.95 for a EUD of 51 Gy and 100 Gy, respectively. The TCP was perfectly predicted by the Poisson model assuming an inter tumor radiosensitivity variation of 30% around the HCC cell in vitro value.ConclusionsEUD-based 90Y TOF-PET/CT predicts the metabolic response post-RE in HCC assessed using dual molecular PET tracers and provides a similar TCP curve to that observed in EBRT. In vivo and in vitro HCC radiosensitivities are similar. Both TCPs show that a EUD of 100 Gy is needed to control HCC for the three devices (resin spheres, glass spheres, EBRT). Observed absorbed doses achieving this 100 Gy-EUD ranged from 190 to 1800 Gy!

Effect of synchrotron X-ray radiation damage on phase transitions in coordination polymers at high pressure.

The high-pressure phase-transition behaviour of metal-organic frameworks and coordination polymers upon varying degrees of X-ray irradiation are highlighted with four example studies. These show that, in certain cases, the radiation damage, while not extreme in changing unit-cell values, can impact the existence of a phase transition. In particular, pressure-induced phase transitions are suppressed after a certain absorbed dose threshold is reached for the sample. This is thought to be due to partial amorphization and/or defect formation in the sample, hindering the co-operative structural distortions needed for a phase transition. The high-pressure experiments were conducted with several crystals within the sample chamber in order to measure crystals with minimal X-ray irradiation at the highest pressures, which are compared with the crystals measured continuously upon pressure increase. Ways to minimize radiation damage are also discussed within the frame of high-pressure experiments.

Assessment of Organ and Effective Doses Received by Paediatric Patients Undergoing Computed Tomography Examinations in Three Hospitals in Brazzaville, Congo Republic: An Urgent Necessity for Regulatory Control

The present study aimed at estimating organ and effective doses from computed tomography (CT) scans of paediatric patients in three hospitals in Brazzaville, Congo Republic. A total of 136 data on paediatric patients, from 0.25 (3 months) to 15 years old, who underwent head, chest, abdomen – pelvis (AP) and chest – abdomen – pelvis (CAP) CT scans was considered. The approach followed in the present study to compute organ doses was to use pre-calculated volume CT dose index (CTDIvol) – and 100 milliampere-second (mAs) – normalized organ doses determined by Monte Carlo (MC) simulation. Effective dose were then derived using the international commission on radiological protection (ICRP) publications 60 and 103 formalism. For comparison purposes, effective dose were also computed using dose-length product (DLP) – to – effective dose conversion factors. A relatively high variation in organ and effective doses was observed in each age group due to the dependence of patient dose on the practice of technicians who perform the CT scan within the same facility or from one facility to another, patient size and lack of adequate training of technicians. In the particular case of head scan, the brain and the eye lens were delivered maximum absorbed doses of 991.81 mGy and 1176.51 mGy, respectively (age group 10-15 y). The maximum absorbed dose determined for the red bone marrow was 246.08 mGy (age group 1-5 y). This is of concern as leukaemia and brain tumours are the most common childhood cancers and as the ICRP recommended absorbed dose threshold for induction of cataract is largely exceeded. Effective doses derived from MC calculations and ICRP publications 60 and 103 tissues weighting factors showed a 0.40-17.61 % difference while the difference between effective doses derived by the use of k- factors and those obtained by MC calculations ranges from 0.06 to 224.87 %. The study has shown that urgent steps should be taken in order to significantly reduce doses to paediatric patients to levels observed in countries where dose reduction techniques are successfully applied.

The use of in vitro transcriptional data to identify thresholds of effects in a human lens epithelial cell-line exposed to ionizing radiation

Purpose: The International Commission on Radiological Protection (ICRP) recently recommended reducing the occupational equivalent dose limit for the lens of the eye. Based primarily on a review of epidemiological data, the absorbed dose threshold is now considered to be 0.5 Gy independent of dose-rate and severity of opacification, reduced from the previous threshold of 2 Gy. However, direct mechanistic evidence to support an understanding of the underlying molecular mechanisms of damage is still lacking. To this end, we explored the effects of a broad dose-range of ionizing radiation exposure on gene expression changes in a human lens epithelial (HLE) cell-line in order to better understand the shape of the dose–response relationship and identify transcriptional thresholds of effects.Methods: HLE cells were exposed to doses of 0, 0.01, 0.05, 0.25, 0.5, 2, and 5 Gy of X-ray radiation at two dose rates (1.62 cGy/min and 38.2 cGy/min). Cell culture lysates were collected 20 h post-exposure and analyzed using whole-genome RNA-sequencing. Pathways and dose-thresholds of biological effects were identified using benchmark dose (BMD) modeling.Results: Transcriptional responses were minimal at doses less than 2 Gy. At higher doses, there were a significant number of differentially expressed genes (DEGs) (p≤.05, fold change≥|1.5|) at both dose rates, with 1308 DEGs for the low dose rate (LDR) and 840 DEGs for the high dose rate (HDR) exposure. Dose–response modeling showed that a number of genes exhibited non-linear bi-phasic responses, which was verified by digital droplet PCR. BMD analysis showed the majority of the pathways responded at BMD median values in the dose range of 1.5–2.5 Gy, with the lowest BMD median value being 0.6 Gy for the HDR exposure. The minimum pathway BMD median value for LDR exposure, however, was 2.5 Gy. Although the LDR and HDR exposures shared pathways involved in extracellular matrix reorganization and collagen production with BMD median value of 2.9 Gy, HDR exposures were more effective in activating pathways associated with DNA damage response, apoptosis, and cell cycling relative to LDR exposure.Conclusions: Overall, the results suggest that radiation induces complex non-linear transcriptional dose–response relationships that are dose-rate dependent. Pathways shared between the two dose rates may be important contributors to radiation-induced cataractogenesis. BMD analysis suggests that the majority of pathways are activated above 0.6 Gy, which supports current ICRP identified dose thresholds for deterministic effects to the lens of the eye of 0.5 Gy.

A dosimetry procedure for organs-at-risk in 177Lu peptide receptor radionuclide therapy of patients with neuroendocrine tumours

PurposePeptide receptor radionuclide therapy with 177Lu-DOTATATE has become a standard treatment modality in neuroendocrine tumours (NETs). No consensus has yet been reached however regarding the absorbed dose threshold for lesion response, the absorbed dose limit to organs-at-risk, and the optimal fractionation and activity to be administered. This is partly due to a lack of uniform and comparable dosimetry protocols. The present article details the development of an organ-at-risk dosimetry procedure, which could be implemented and used routinely in a clinical context. MethodsForty-seven patients with NETs underwent 177Lu-DOTATATE therapy. Three SPECT/CT images were acquired at 4, 24 and 144–192 h post-injection. Three blood samples were obtained together with the SPECT/CT acquisitions and 2 additional samples were obtained around 30 min and 1 h post-injection. A bi-exponential fit was used to compute the source organ time-integrated activity coefficients. Coefficients were introduced into OLINDA/EXM software to compute organ-at-risk absorbed doses. Median values for all patients were computed for absorbed dose coefficient D/A0 and for late effective half-life T1/2eff for kidneys, spleen and red marrow. ResultsDosimetry resulted in a median[interquartile range] of 0.78[0.35], 1.07[0.58] and 0.028[0.010] Gy/GBq for D/A0 and of 55[9], 71[9] and 52[18] h for T1/2eff for kidneys, spleen and red marrow respectively. ConclusionsA dosimetry procedure for organs-at-risk in 177Lu-DOTATATE therapy based on serial SPECT/CT images and blood samples can be implemented routinely in a clinical context with limited patient burden. The results obtained were in accordance with those of other centres.

Radiotherapeutic implications of the updated ICRP thresholds for tissue reactions related to cataracts and circulatory diseases.

Radiation therapy of cancer patients involves a trade-off between a sufficient tumour dose for a high probability of local control and dose to organs at risk that is low enough to lead to a clinically acceptable probability of toxicity. The International Commission on Radiological Protection (ICRP) reviewed epidemiological evidence and provided updated estimates of 'practical' threshold doses for tissue injury, as defined at the level of 1% incidence, in ICRP Publication 118. Particular attention was paid to cataracts and circulatory diseases. ICRP recommended nominal absorbed dose threshold for these outcomes as low as 0.5 Gy. Threshold doses for tissue reactions can be reached in some patients during radiation therapy. Modern treatment planning systems do not account for such low doses accurately, and doses to therapy patients from associated imaging procedures are not generally accounted for. While local control is paramount, the observations of ICRP Publication 118 suggest that radiation therapy plans and processes should be examined with particular care. The research needs are discussed in this paper.

124I PET Assessment of Response of Bone Metastases to Initial Radioiodine Treatment of Differentiated Thyroid Cancer.

Before and after initial radioiodine therapy, patients underwent serial PET/CT scanning after administration of 20-40 MBq of 124I. The pretherapy PET data were used to segment BM volumes and to predict the average ADs after administration of dosimetry-guided 131I activity. The lower volume limit of determinability of the applied segmentation method was a sphere volume of 0.16 mL. This volume limit classified the BMs into known-volume and fixed-volume groups with their respective average and minimum ADs. Follow-up 124I and 18F-FDG PET/CT data after treatment were analyzed to assess lesion-based therapy response. Response rates at different AD thresholds were calculated and were expressed as the percentage of completely responding BMs above the respective AD threshold. BMs with a maximum extent greater than twice the PET spatial resolution were visually scored for nonuniformity. In total, 61 BMs in 10 patients were included, of which 46 and 15 comprised the known-volume group and the fixed-volume group, respectively. The median follow-up time was 5.6 mo (range, 3.7-23.2 mo). The median average and median minimum ADs in therapy were 183 Gy (range, 39-3,600 Gy) and 270 Gy (range, 63-1,300 Gy), respectively. A range of response rate of 70%-80% was achieved at an AD threshold range of 350-650 Gy. There were 26 BMs that were amenable to visual assessment of nonuniformity, of which two thirds (17/26) were scored as clearly nonuniform, and the majority (11/17) of these nonuniform BMs responded incompletely. Both the high AD threshold associated with high response rates and the low median AD per unit of 131I activity elucidate the difficulty in achieving therapeutic efficacy for BMs when a single standard activity is administered. The relatively high AD threshold range is possibly a result of distinct levels of spatial nonuniformity in ADs.

Implications in medical imaging of the new ICRP thresholds for tissue reactions.

The International Commission on Radiological Protection (ICRP) statement on tissue reactions, issued by the Commission in April 2011, reviewed epidemiological evidence and suggested that there are some tissue reactions where threshold doses are or may be lower than those previously considered. For the lens of the eye, the threshold is now considered to be 0.5 Gy. The absorbed dose threshold for circulatory disease in the heart and brain may be as low as 0.5 Gy. These values can be reached in some patients during interventional cardiology or neuroradiology procedures. They may also be of concern for repeated computed tomography examinations of the head. The new thresholds should be considered in optimisation strategies for clinical procedures, especially in patients likely to require repeated interventions. The new dose thresholds also affect occupational protection for operators and staff. Some operators do not protect their eyes or their brain adequately. After several years of work without proper protection, the absorbed doses to the lens of the eye and the brain of staff can exceed 0.5 Gy. More research is needed to understand the biological effects of cumulative incident air kerma and the instantaneous air kerma rates currently used in medical imaging. The new thresholds, and the need for specific occupational dosimetry related to lens doses, should be considered in radiation protection programmes, and should be included in the education and training of professionals involved in fluoroscopy guided procedures and computed tomography.

Lowest effective 131I activity for thyroid remnant ablation of differentiated thyroid cancer patients. Dosimetry-based model for estimation.

A theoretical dosimetry-based model was applied to estimate the lowest effective radioiodine activity for thyroid remnant ablation of low-risk differentiated thyroid cancer patients. The model is based on the distribution of the absorbed (radiation) dose per administered radioiodine activity and the absorbed dose threshold of 300 Gy for thyroid remnants, the level believed to destroy most thyroid remnants. For this purpose, ¹²⁴I PET/CT images of 49 thyroidectomised patients were retrospectively analysed to measure the distribution of the (average) absorbed doses to thyroid remnant per administered ¹³¹I activity. The fraction of thyroid remnants that received at least 300 Gy was determined for standard activities between 0.37 and 5.55 GBq. The lower activity was considered to be equally effective to that obtained with higher activity if the (absolute) fraction difference was below 5%. A total of 62 thyroid remnants were included. The medians and ranges (in parentheses) for the absorbed dose per unit 131I activity were 359 Gy/GBq (34 to 1825 Gy/GBq). The fractions of thyroid remnants receiving more than 300 Gy at different therapy activities (within parentheses) were 60% (1.11 GBq), 76% (1.85 GBq), 79% (2.22 GBq), and 81-82% for activities between 2.59 and 3.70 GBq. The therapy activity of 1.11 GBq is considerably less effective than that of 1.85 or 2.22 GBq; therapy activities were equally effective in the range between 2.22 to 3.70 GBq. On the basis of the model and the patients' data included, the lowest effective therapy activity appears to be approximately 2.2 GBq to ablate thyroid remnants. The results of this study may help to guide the design of prospective clinical studies.

Calibration of an eye lens dosemeter in terms of Hp(3) to be used in interventional radiology

Recently, the International Commission on Radiological Protection has reviewed epidemiological evidences suggesting that there were tissue reaction effects in the eye lens below the previously considered absorbed dose threshold. A new statement related to the eye lens was issued that changed the absorbed dose threshold and reduced the dose limits for occupationally exposed persons. As consequence, some planned exposures require eye lens dosimetry and a debate was raised on the adequacy of the dosimetric quantity and on its method of measurement. The aim of this work was to study the methodology for calibrating the EYE-D TM holder with a TLD-100H Harshaw chip detector and to determine its angular and energy dependences in terms of personal dose equivalent, H p (3). • Results of calibration of the eye lens dosemeters, in terms of H p (3). • The proposal of phantoms and specific dosemeters for eye lens have proved viable. • The tests carried out met the limits of acceptance proposed by ISO. • The good performance of the tests may suggest a reduction in the acceptance limits.

Emission of weak electrons: Dosimetry of nanovolumes

Modern radiation therapy (RT) technologies and the needs of molecular and micro radiobiology have necessitated the detection of radiation absorbed by micro/nano volumes. The possibility of developing a nano/micro-scale dosimeter is demonstrated via the use of prethreshold photoelectron and exoelectron emission from solid-state nanolayers (Si, bone) and nanofilms (ZrO2:PbS). The experiments indicate that the absorbed dose threshold depends on the detector origin. • Molecular radiobiology requires radiation detection in micro/nano volumes. • The escape length of weak electrons (several eV) of solids is at the nanometer scale. • Therefore, a solid-state dosimeter at the nanoscale could be developed. • Photo and exoelectron emissions (P-EE) have demonstrated dose detection in nanovolumes. • Nanolayers (Si, bone) and nanofilms (ZrO2:PbS) can be used for P-EE-based dosimeters.

Identification of In Vitro Electropermeabilization Equivalent Pulse Protocols

Exposure of cells to an external sufficiently strong electric field results in the formation of pores across the membrane. This phenomenon, termed electropermeabilization, permits the transport of poorly permeant molecules into cytosol. In clinical practice, cell membrane permeabilization for drug electrotransfer is achieved using the ESOPE pulse protocol (1000 V/cm, 8 pulses, 100 μs, 5 kHz). The aim of this study was to investigate several combinations of electric field amplitude and pulse number able to induce electropermeabilization as the one observed when the ESOPE protocol was applied. Decreasing electric field amplitudes (1000 to 300 V/cm) in combination with increasing number of pulses (8 to 320) were applied to in vitro MG63 cells. Propidium iodide and Calcein blue AM uptake were used to evaluate cell electropermeabilization and viability. Results showed that the threshold of local electric field needed to obtain electropermeabilization decreased exponentially with increasing the number of pulses delivered (r2 5 0.92, p<0.0001). The absorbed dose threshold was dependent on the number of pulses for each voltage applied (r2 5 0.96, p<0.0001). In conclusion, the possibility of applying an increased number of pulses rather than increasing the electric field amplitude to perform electropermeabilization, may become an important tool for electropermeabilization-related clinical applications.

Dosimetric evaluation and therapeutic response to internal radiation therapy of hepatocarcinomas using iodine-131-labelled lipiodol

Vectorized internal radiation therapy using lipiodol-labelled with iodine-131 (131 I-lipiodol) is an effective treatment for inoperable hepatocellular carcinomas. However, few dosimetric data are available based on this approach. We have developed a dosimetric protocol based on scintiscan imaging and that is designed to calculate the tumoural absorbed dose during the treatment of hepatocarcinoma by 131 I-lipiodol. This concept was developed on a gamma-camera coupled to a computed tomography scanner. It integrates corrections for attenuation phenomena, scattering and dead time. The tumoural absorbed dose calculation was carried out according to the Medical Internal Radiation Dose Committee formalism. This protocol was applied to a series of 41 patients in the framework of a retrospective study. The mean tumoural absorbed dose with the first treatment is 248 Gy (+/-176), as opposed to 152 Gy (+/-122) during the second. We highlighted a correlation between the tumoural absorbed dose, calculated in tomographic mode, and the morphological response to the first treatment (P=0.0071). Moreover, a tumoural absorbed dose of 280 Gy seems to be an effective absorbed dose threshold in our population. Above this absorbed dose, 84% of the patients are responders after the first treatment, whereas no responses are recorded below this threshold. These results are promising because, for the first time, they allow us to predict the effectiveness of a treatment by 131 I-lipiodol. They are required to be validated on a broader exploratory trial, including a dosimetric study of the critical organs, so an individualized dosimetry can be defined for each patient.

TH‐C‐230A‐05: Neutron Scattered Dose Equivalent to a Fetus From Proton Radiotherapy of the Mother

Scattered neutron dose equivalent to a representative point for a fetus is evaluated in an anthropomorphic phantom of the mother undergoing proton radiotherapy. The effect on scattered neutron dose equivalent to the fetus of changing the incident proton beam energy, aperture size, beam location, and air gap between the beam delivery snout and skin was studied for both a small field snout and a large field snout. Measurements of the fetus scattered neutron dose equivalent were made by placing a neutron bubble detector 10 cm below the umbilicus of an anthropomorphic Rando® phantom enhanced by a wax bolus to simulate a second trimester pregnancy. The neutron dose equivalent in milliSieverts per proton treatment Gray increased with incident proton energy and decreased with aperture size, distance of the fetus representative point from the field edge, and increasing air gap. Neutron dose equivalent to the fetus varied from 0.025 to 0.450 mSv per proton Gray for the small field snout and from 0.097 to 0.871 mSv per proton Gray for the large field snout. There is likely to be no excess risk to the fetus of severe mental retardation for a typical proton treatment of 80 Gray to the mother since the scattered neutron dose to the fetus of 69.7 mSv is well below the estimated radiation absorbed dose threshold of 600 mGy observed for the occurrence of severe mental retardation in prenatally exposed Japanese atomic bomb survivors. However based on the linear no threshold hypothesis and this same typical treatment for the mother, the excess risk to the fetus of radiation induced cancer death in the first 10 years of life is 17.4 per 10,000 children.

Prompt Effects of Radiation on the Heart Rate on a Mammalian Embryo

The prompt effects of radiation on the heart rates of 18 rat embryos were studied in vitro by culturing Sprague-Dawley rat embryos at day 11 of gestation in a circulating life support system. While in the life support system the embryos were exposed to either 1316 ± 76, 1750 ± 101 or 2200 ± 127 R/min of 250 kVp X-rays. The heart rates were continuously monitored and recorded from at least 15 min before the irradiation started until the heart rates dropped below 30 beats/min. Statistically significant changes in the heart rates during irradiation were found as measured by the slopes of the linear regressions. No statistically significant trend in the heart rates was observed until the onset of severe bradycardia. This response led to a cessation of the heart beat in all embryos. After the initial stopping, 45% recovered heart beats to an average level equal to 66% of the initial rate. The results suggest that there exists a total absorbed dose threshold and that the embryonic heart is more sensitive to the...