Plastic scintillator-based dosimeters for ultra-high dose rate (UHDR) electron radiotherapy.

This paper reports the development of dosimeters based on plastic scintillating fibers imaged by a charge-coupled device camera, and their performance evaluation through irradiations with the electron Flash research accelerator located at the Centro Pisano Flash Radiotherapy. The dosimeter prototypes were composed of a piece of plastic scintillating fiber optically coupled to a clear optical fiber which transported the scintillation signal to the readout systems (an imaging system and a photodiode). The following properties were tested: linearity, capability to reconstruct the percentage depth dose curve in solid water and to sample in time the single beam pulse. The stem effect contribution was evaluated with three methods, and a proof-of-concept one-dimensional array was developed and tested for online beam profiling. Results show linearity up to 10 Gy per pulse, and good capability to reconstruct both the timing and spatial profiles of the beam, thus suggesting that plastic scintillating fibers may be good candidates for low-energy electron Flash dosimetry.

IOeRT conventional and FLASH treatment planning system implementation exploiting fast GPU Monte Carlo: The case of breast cancer.

Partial breast irradiation for the treatment of early-stage breast cancer patients can be performed by means of Intra Operative electron Radiation Therapy (IOeRT). One of the main limitations of this technique is the absence of a treatment planning system (TPS) that could greatly help in ensuring a proper coverage of the target volume during irradiation. An IOeRT TPS has been developed using a fast Monte Carlo (MC) and an ultrasound imaging system to provide the best irradiation strategy (electron beam energy, applicator position and bevel angle) and to facilitate the optimisation of dose prescription and delivery to the target volume while maximising the organs at risk sparing. The study has been performed in silico, exploiting MC simulations of a breast cancer treatment. Ultrasound-based input has been used to compute the absorbed dose maps in different irradiation strategies and a quantitative comparison between the different options was carried out using Dose Volume Histograms. The system was capable of exploring different beam energies and applicator positions in few minutes, identifying the best strategy with an overall computation time that was found to be completely compatible with clinical implementation. The systematic uncertainty related to tissue deformation during treatment delivery with respect to imaging acquisition was taken into account. The potential and feasibility of a GPU based full MC TPS implementation of IOeRT breast cancer treatments has been demonstrated in-silico. This long awaited tool will greatly improve the treatment safety and efficacy, overcoming the limits identified within the clinical trials carried out so far.

Perspectives in linear accelerator for FLASH VHEE: Study of a compact C-band system.

PURPOSE: In order to translate the FLASH effect in clinical use and to treat deep tumors, Very High Electron Energy irradiations could represent a valid technique. Here, we address the main issues in the design of a VHEE FLASH machine. We present preliminary results for a compact C-band system aiming to reach a high accelerating gradient and high current necessary to deliver a Ultra High Dose Rate with a beam pulse duration of 3µs. METHODS: The proposed system is composed by low energy high current injector linac followed by a high acceleration gradient structure able to reach 60-160 MeV energy range. To obtain the maximum energy, an energy pulse compressor options is considered. CST code was used to define the specifications RF parameters of the linac. To optimize the accelerated current and therefore the delivered dose, beam dynamics simulations was performed using TSTEP and ASTRA codes. RESULTS: The VHEE parameters Linac suitable to satisfy FLASH criteria were simulated. Preliminary results allow to obtain a maximum energy of 160 MeV, with a peak current of 200 mA, which corresponds to a charge of 600 nC. CONCLUSIONS: A promising preliminary design of VHEE linac for FLASH RT has been performed. Supplementary studies are on going to complete the characterization of the machine and to manufacture and test the RF prototypes.

Absolute dose measurements by means of a small cylindrical ionization chamber for very high dose per pulse high energy electron beams.

Very high dose per pulse (3-13 cGy/pulse) high energy electron beams are currently produced by special linear accelerators (linac) dedicated to Intra Operative Radiation Therapy (IORT). The electron beams produced by such linacs are collimated by special Perspex applicators of various size and cylindrically shaped. The biggest problems from the dosimetric point of view are caused by the high dose-per-pulse values and the use of inclined applicators. In this work measurements of absolute dose for the inclined applicators were done by using a small cylindrical ionization chamber, type CC01 (Wellhofer), a parallel plane ionization chamber type Markus (PTW 23343) and radiochromic films type EBT. We show a method which allows calculating the quality correction factors for CC01 chamber with an uncertainty of 1% and the absolute dose value for the inclined applicators using CC01 with an uncertainty of 3.1% for electron beams of energy of 6 and 7 MeV produced by the linac dedicated to IORT Novac7.

A dosimetric algorithm for patient-specific 131I therapy of thyroid cancer based on a prescribed target-mass reduction.

(131)I therapy is used in the treatment of differentiated thyroid cancer both to ablate the post-surgical thyroid remnant and to treat recurrent or metastatic cancer. The optimum administered activity for ablation remains controversial: the most commonly used method is the administration of a fixed radioiodine activity (1110-3700 MBq or more); an alternative is the administration of an activity individually calculated to deliver a prescribed absorbed dose (usually 300 Gy for remnant ablation and 80 Gy for treatment of metastasis). Neither of these two approaches is based on a theoretical model and for this reason the debate on the optimization of (131)I therapy of thyroid cancer could have a weak grounding. In this paper, the meaning of the fixed value of target absorbed dose (Gy) is discussed and a mathematical model for remnant/metastasis optimum absorbed dose calculation is presented. This model is based on the desired reduction of the volume of the target (remnant or metastasis) and allows one to calculate individually the value of the optimum target absorbed dose (Gy) and consequently the optimum therapeutic activity to administer to the patient.

Ion recombination correction for very high dose-per-pulse high-energy electron beams.

The parallel-plate ionization chamber is the recommended tool for the absorbed dose measurement in pulsed high-energy electron beams. Typically, the electron beams used in radiotherapy have a dose-per-pulse value less then 0.1 cGy/pulse. In this range the factor to correct the response of an ionization chamber for the lack of complete charge collection due to ion recombination (ksat) can be properly evaluated with the standard "two voltage" method proposed by the international dosimetric reports. Very high dose-per-pulse electron beams are employed in some special Linac dedicated to the Intra-Operatory-Radiation-Therapy (IORT). The high dose-per-pulse values (3-13 cGy/pulse) characterizing the IORT electron beams allow to deliver the therapeutic dose (10-20 Gy) in less than a minute. This considerably reduces the IORT procedure time, but some dosimetric problems arise because the standard method to evaluate ksat overestimates its value by 20%. Moreover, if the dose-per-pulse value >1 cGy/pulse, the dependence of ksat on the dose-per-pulse value cannot be neglected for relative dosimetry. In this work the dependence of ksat on the dose-per-pulse value is derived, based on the general equation that describes the ion recombination in the Boag theory. A new equation for ksat, depending on known or measurable quantities, is presented. The new ksat equation is experimentally tested by comparing the absorbed doses to water measured with parallel-plate ionization chambers (Roos and Markus) to that measured using dose-per-pulse independent dosimeters, such as radiochromic films and chemical Fricke dosimeters. These measurements are performed in the high dose-per-pulse (3-13 cGy/pulse) electron beams of the IORT dedicated Linac Hitesys Novac7 (Aprilia-Latina, Italy). The dose measurements made using the parallel-plate chambers and those made using the dose-per-pulse independent dosimeters are in good agreement (<3%). This demonstrates the possibility of using the parallel-plate ionization chambers also for the very high dose-per-pulse (> 1 cGy/pulse) electron-beam dosimetry.

Oxidative and genotoxic damage after radio-iodine therapy of Graves' hyperthyroidism.

PURPOSE: To evaluate genetic damage and oxidative stress following a single therapeutic dose of 131I in Graves' disease patients monitored up to 180 days after treatment. MATERIALS AND METHODS: Genetic damage induction was estimated as the increase in micronuclei in peripheral lymphocytes of patients. As indicators of radiogenic oxidative stress, vitamin E and lipoperoxide levels were assessed in the plasma of patients, as well as the release of plasmic clastogenic factors measured by the induction of micronuclei in vitro in peripheral lymphocytes of a healthy donor. RESULTS: Vitamin E depletion lasted at least 3 days and the basal level was restored within 7 days. No statistically significant variations were observed in lipoperoxide plasma levels. A sharp increase of micronuclei in the peripheral lymphocytes of patients was correlated (p < 0.001) with the release of clastogenic factor in the plasma. The highest micronucleus value was negatively correlated (p < 0.03) with the lowest vitamin E level observed in each patient. CONCLUSIONS: Micronuclei induction was the direct consequence not only of the energy deposition of 131I on the genetic material, but also of oxidative stress, likely via the release of clastogenic factor.

Influence of thyroid volume reduction on calculated dose in radioiodine therapy of Graves' hyperthyroidism.

Administration of radioactive iodine (131I) is an effective treatment for hyperthyroidism due to Graves' disease. Recently several investigators have shown that the success of this therapy may depend on the absorbed dose to the thyroid. Thyroid dose varies inversely with the mass of the gland. Much experimental evidence demonstrates that a reduction of the thyroid volume (mass) may occur after radioiodine therapy. In this work we evaluate the influence of the volume reduction on the calculation of the absorbed dose to the thyroid. A mathematical model of thyroid mass reduction after 131I therapy is presented, based on masses evaluated with ultrasonography of ten patients treated in the endocrinology department of our hospital. This model was applied to the general formula for calculation of the thyroid doses in these patients. The dose values obtained considering a reduction of thyroid mass after the treatment are often quite different from those obtained without considering change in mass (from 9% to 30% greater). We conclude that the consideration of thyroid mass reduction is important for an accurate estimation of the calculated dose.

A theoretical model for prescription of the patient-specific therapeutic activity for radioiodine therapy of Graves' disease.

A fundamental function of the thyroid is to extract iodine from the blood, synthesize it into thyroid hormones, and release it into the circulation under feedback control by pituitary-secreted hormones. This capability of the thyroid, termed as functionality, can in principle be related to the severity of hyperthyroidism in individual patients. In this paper the uptake and release of 131I by the thyroid following the administration of 131I therapy for Graves' disease has been theoretically studied. The kinetics of iodine in the thyroid and blood have been evaluated using a two-compartment model. This simplified model appears to be adequate for dosimetry purposes and allows one to correlate levels of increased thyroid functionality (hyperthyroidism) with clinically measurable kinetic parameters. An expression has been derived for the rate of change of thyroid mass following therapy; this has the same form as an empirical relationship described in an earlier work. A method is presented for calculation of the amount of radioiodine activity to be administered to individual patients in order to achieve the desired final functionality of the gland. The activity to be administered is based on measurements of 131I kinetics after the administration of a 'low-activity' (1850 kBq) tracer for treatment planning.

Use of surgical gamma probe for the detection of lymph node metastases in differentiated thyroid cancer.

BACKGROUND: Patients with differentiated thyroid cancer (DTC) after total or near-total thyroidectomy require 131I therapy. After surgery the persistence of lymph node metastases in our series of patients was frequent (30%). Such patients are preferentially treated with radioiodine and shifted to surgical reintervention when the nodal lesions persist after two 131I treatments. AIM: Use of an intraoperative radioactive probe (C-TraK) to allow a more radical surgical approach in thyroid cancer patients submitted to surgery for lymph node metastases. METHODS AND RESULTS: After adequate withdrawal of L-thyroxine suppressive therapy six patients were given high 131I doses followed by post-therapy WBS which demonstrated cervical activity in 5 patients and peri-jugular activity in 1. Surgery with the help of a gamma probe allowed to detect and remove all metastatic nodes. After excision all surgical specimens showed higher radioactive counts with respect to the background. The post-surgical scan showed the disappearance of all areas of 131I uptake. Histology confirmed the presence of metastatic lesions from papillary thyroid cancer. CONCLUSIONS: We conclude that the use of a gamma probe can be successful in patients with metastatic neck lesions resistant to 131I treatment, particularly in patients with nonpalpable lesions.

Study of the correlation between administered activity and radiation committed dose to the thyroid in 131I therapy of Graves' disease.

Substantial reduction in the thyroid volume (up to 70-80%) after 131I therapy of Graves' disease has been demonstrated and reported in the literature. Recently a mathematical model of thyroid mass reduction during the first month after therapy has been developed and a new algorithm for the radiation committed dose calculation has been proposed. Reduction of the thyroid mass and the radiation committed dose to the gland depend on a parameter k, defined for each subject. The calculation of k allows the prediction of the activity to administer, depending on the radiation committed dose chosen by the physician. In this paper a method for calculating k is proposed. The calculated values of k are compared to values derived from measurements of the changes in thyroid mass in twenty-six patients treated by 131I for Graves' disease. The radiation committed dose to the thyroid can be predicted within 21%, and the radioiodine activity to administer to the patient can be predicted within 22% using the calculated values of k. The thyroid volume reduction during the first month after therapy administration can be also predicted with good accuracy using the calculated values of k. The radiation committed dose and the radioiodine activity to administer were calculated using a new, very simple algorithm. A comparison between the values calculated by this new algorithm and the old, classical Marinelli-Quimby algorithm shows that the new method is more accurate.

A minimally invasive method to evaluate 131I kinetics in blood.

The dose limiting factor for 131I therapy in patients with thyroid cancer is myelotoxicity, thus an accurate determination of radioiodine activity in the red marrow is of paramount importance. The reference method for red marrow dosimetry in radiometabolic therapy is based on the measurement of radioiodine kinetics, particularly the activity/time curve in blood. Such a measurement requires withdrawal of blood samples at various times after 131I administration. This procedure involves some potential risk from the radiation protection point of view, such as possible contamination of personnel with blood and disposal of the radioactive blood samples (and syringes). We present here a minimally invasive method to evaluate radioiodine kinetics in the blood, which only requires one blood sample and a set of measurements on the patient's thigh made with a collimated NaI(Tl) probe. The method has been validated in four patients treated with 131I for thyroid cancer.

Ion recombination correction for very high dose-per-pulse high-energy electron beams.

The parallel-plate ionization chamber is the recommended tool for the absorbed dose measurement in pulsed high-energy electron beams. Typically, the electron beams used in radiotherapy have a dose-per-pulse value less then 0.1cGy∕pulse. In this range the factor to correct the response of an ionization chamber for the lack of complete charge collection due to ion recombination (ksat) can be properly evaluated with the standard "two voltage" method proposed by the international dosimetric reports. Very high dose-per-pulse electron beams are employed in some special Linac dedicated to the Intra-Operatory-Radiation-Therapy (IORT). The high dose-per-pulse values (3-13cGy∕pulse) characterizing the IORT electron beams allow to deliver the therapeutic dose (10-20Gy) in less than a minute. This considerably reduces the IORT procedure time, but some dosimetric problems arise because the standard method to evaluate ksat overestimates its value by 20%. Moreover, if the dose-per-pulse value >1cGy∕pulse, the dependence of ksat on the dose-per-pulse value cannot be neglected for relative dosimetry. In this work the dependence of ksat on the dose-per-pulse value is derived, based on the general equation that describes the ion recombination in the Boag theory. A new equation for ksat, depending on known or measurable quantities, is presented. The new ksat equation is experimentally tested by comparing the absorbed doses to water measured with parallel-plate ionization chambers (Roos and Markus) to that measured using dose-per-pulse independent dosimeters, such as radiochromic films and chemical Fricke dosimeters. These measurements are performed in the high dose-per-pulse (3-13cGy∕pulse) electron beams of the IORT dedicated Linac Hitesys Novac7 (Aprilia-Latina, Italy). The dose measurements made using the parallel-plate chambers and those made using the dose-per-pulse independent dosimeters are in good agreement (<3%). This demonstrates the possibility of using the parallel-plate ionization chambers also for the very high dose-per-pulse (>1cGy∕pulse) electron-beam dosimetry.

Location of functioning metastases from differentiated thyroid carcinoma by simultaneous double isotope acquisition of I-131 whole body scan and bone scan.

In a young patient with differentiated thyroid carcinoma (DTC), previously submitted to total thyroidectomy and I-131 therapy for ablation of thyroid remnant, a follow-up 1-131 diagnostic whole body scan (WBS) demonstrated four small abnormal I-131 uptake areas. Two of these were projected over the thoracic region and corresponded to lung nodules, as later demonstrated by lung computerized tomography (CT)-scan. The remaining two areas were found in the lumbar-pelvic region, but their precise location could not be determined. Standard bone Rx examination and bone scan were negative. After I-131 therapy, we simultaneously acquired a I-131 WBS and a Tc-99m oxidronate bone scan by setting a dual window on the gamma camera. Comparing the I-131 and bone images we were able to identify the 4th lumbar vertebra and right ilium as the bone segments to be studied by a radiological approach. Eventually, the thin slice CT-scan demonstrated the presence of two small osteolytic lesions in these areas. In conclusion, the simultaneous acquisition of images both from I-131 and a bone-seeking agent may be useful to locate functioning bone metastases from DTC.