The Importance of Uncertainty Analysis and Traceable Measurements in Routine Quantitative 90Y-PET Molecular Radiotherapy: A Multicenter Experience.

Molecular Radiation Therapy (MRT) is a valid therapeutic option for a wide range of malignancies, such as neuroendocrine tumors and liver cancers. In its practice, it is generally acknowledged that there is a need to evaluate the influence of different factors affecting the accuracy of dose estimates and to define the actions necessary to maintain treatment uncertainties at acceptable levels. The present study addresses the problem of uncertainty propagation in 90Y-PET quantification. We assessed the quantitative accuracy in reference conditions of three PET scanners (namely, Siemens Biograph mCT, Siemens Biograph mCT flow, and GE Discovery DST) available at three different Italian Nuclear Medicine centers. Specific aspects of uncertainty within the quantification chain have been addressed, including the uncertainty in the calibration procedure. A framework based on the Guide to the Expression of Uncertainty in Measurement (GUM) approach is proposed for modeling the uncertainty in the quantification processes, and ultimately, an estimation of the uncertainty achievable in clinical conditions is reported.

Modelling a new approach for radio-ablation after resection of breast ductal carcinoma in-situ based on the BAT-90 medical device.

The majority of local recurrences, after conservative surgery of breast cancer, occurs in the same anatomical area where the tumour was originally located. For the treatment of ductal carcinoma in situ (DCIS), a new medical device, named BAT-90, (BetaGlue Technologies SpA) has been proposed. BAT-90 is based on the administration of 90Y ß-emitting microspheres, embedded in a bio-compatible matrix. In this work, the Geant4 simulation toolkit is used to simulate BAT-90 as a homogenous cylindrical 90Y layer placed in the middle of a bulk material. The activity needed to deliver a 20 Gy isodose at a given distance z from the BAT-90 layer is calculated for different device thicknesses, tumour bed sizes and for water and adipose bulk materials. A radiobiological analysis has been performed using both the Poisson and logistic Tumour Control Probability (TCP) models. A range of radiobiological parameters (α and ß), target sizes, and densities of tumour cells were considered. Increasing α values, TCP increases too, while, for a fixed α value, TCP decreases as a function of clonogenic cell density. The models predict very solid results in case of limited tumour burden while the activity/dose ratio could be further optimized in case of larger tumour beds.

Role of radiation therapy in mycosis fungoides refractory to systemic therapy.

The long natural history of early stage mycosis fungoides (MF) makes its management a difficult problem. Skin lesions are sensitive to different therapies and a variety of treatment modalities have been used, such as topical nitrogen mustard, puvatherapy, UV-B, retinoids, radiation therapy, extracorporal photopheresis and systemic chemotherapy. For patients with refractory early stage MF, treatment selection is made by clinical parameters such as the age, sex and performance status of the patients, as well as the institutional expertise and the toxicity profiles of the different therapeutic approaches. We report radiation therapy in a relapsed/resistant stage IB patient with mycosis fungoides treated with local radiation therapy for symptomatic progression unresponsive to bexarotene therapy. Total skin electron beam therapy has been employed in early stage and for limited skin failure MF, while the role of local radiation therapy in MF is less defined. In our experience local radiotherapy has proved to be a very efficient, tolerable and cost effective approach in patients with MF unresponsive to systemic approaches.

Assessment of the SARS-CoV-2 basic reproduction number, R 0, based on the early phase of COVID-19 outbreak in Italy.

As of March 12th Italy has the largest number of SARS-CoV-2 cases in Europe as well as outside China. The infections, first limited in Northern Italy, have eventually spread to all other regions. When controlling an emerging outbreak of an infectious disease it is essential to know the key epidemiological parameters, such as the basic reproduction number R 0, i.e. the average number of secondary infections caused by one infected individual during his/her entire infectious period at the start of an outbreak. Previous work has been limited to the assessment of R 0 analyzing data from the Wuhan region or Mainland China. In the present study the R 0 value for SARS-CoV-2 was assessed analyzing data derived from the early phase of the outbreak in Italy. In particular, the spread of SARS-CoV-2 was analyzed in 9 cities (those with the largest number of infections) fitting the well-established SIR-model to available data in the interval between February 25-March 12, 2020. The findings of this study suggest that R 0 values associated with the Italian outbreak may range from 2.43 to 3.10, confirming previous evidence in the literature reporting similar R 0 values for SARS-CoV-2.

Evaluation of the uncertainty associated with the ion recombination correction in high dose-per-pulse electron beam dosimetry: an MC approach.

The high dose and dose-per-pulse rates (up to 130 mGy/pulse) produced by some intraoperative radiation therapy (IORT) accelerators pose specific dosimetric problems due to the high density of electric charge per pulse produced in the ionization chamber cavity. In particular, the correction factor for ion recombination, ks , calculated with the traditional two-voltage method is significantly overestimated and three alternative models have been proposed in the literature allowing for the presence of a free-electron component. However, at present there is no general consensus on the best model to assess the ion recombination correction and controversy remains on the uncertainty associated with k s . In the present work we adopted a Monte Carlo (MC) approach to assess the uncertainty associated with the ion recombination correction in plane-parallel chambers used in high dose-per-pulse electron beam dosimetry. The uncertainty associated with k s was calculated for the following plane-parallel ionization chambers: Scanditronix/Wellhofer Parallel Plate Chamber PPC05 and PPC40, PTW Advanced Markus Model 34 045 and PTW Roos Model 34 001. Input variables for MC calculations were derived from experimental data at 28 and 73 mGy/pulse. Taken together, the results of this study indicate that ks values calculated according to the three ion recombination models do not overlap within their standard uncertainties, suggesting that an additional type-B uncertainty component would be necessary to take into account possible differences between the models. Our results indicate that the combined relative standard uncertainty in k s should be calculated as the sum in quadrature of a (type-A) MC-based uncertainty component and a (type-B) uncertainty contribution evaluated assuming a uniform distribution between k s values obtained from the two extreme models.

Absorbed dose measurements from a 90Y radionuclide liquid solution using LiF:Mg,Cu,P thermoluminescent dosimeters.

In the last few years there has been an increasing interest in the measurement of the absorbed dose from radionuclides, with special attention devoted to molecular radiotherapy treatments. In particular, the determination of the absorbed dose from beta emitting radionuclides in liquid solution poses a number of issues when dose measurements are performed using thermoluminescent dosimeters (TLD). Finite volume effect, i.e. the exclusion of radioactivity from the volume occupied by the TLD is one of these. Furthermore, TLDs need to be encapsulated into some kind of waterproof envelope that unavoidably contributes to beta particle attenuation during the measurement. The purpose of this study is twofold: I) to measure the absorbed dose to water, Dw, using LiF:Mg,Cu,P chips inside a PMMA cylindrical phantom filled with a homogenous 90YCl3 aqueous solution II) to assess the uncertainty budget related to Dw measurements. To this purpose, six cylindrical PMMA phantoms were manufactured at ENEA. Each phantom can host a waterproof PMMA stick containing 3 TLD chips encapsulated by a polystyrene envelope. The cylindrical phantoms were manufactured so that the radioactive liquid environment surrounds the whole stick. Finally, Dw measurements were compared with Monte Carlo (MC) calculations. The measurement of absorbed dose to water from 90YCl3 radionuclide solution using LiF:Mg,Cu,P TLDs turned out to be a viable technique, provided that all necessary correction factors are applied. Using this method, a relative combined standard uncertainty in the range 3.1-3.7% was obtained on each Dw measurement. The major source of uncertainty was shown to be TLDs calibration, with associated uncertainties in the range 0.7-2.2%. Comparison of measured and MC-calculated absorbed dose per emitted beta particle provided good results, with the two quantities being in the ratio 1.08.

The effects of terahertz radiation on human keratinocyte primary cultures and neural cell cultures.

Terahertz (THz) frequencies are found in a previously underexploited region of the radiation spectrum. This non-ionising energy is now being employed in medical imaging, so the possibility of adverse effects on human skin was evaluated. Primary cultures of normal human keratinocytes (NHKs) express adhesion molecules that comprise part of the natural barrier function of the skin. The effects of exogenous agents on this barrier function can be measured. The ND7/23 cell line, which displays the characteristics of sensory neurones, can proliferate in the undifferentiated state, but can be induced to differentiate and develop neurite-like projections. Previous studies with NHK and neural cell cultures produced no evidence of the inability of these cells to differentiate and form a barrier following THz exposure. The cells were exposed to 0.14THz radiation for times varying from 10 minutes to 24 hours. For each 80-nanosecond pulse, the cells were exposed to a peak power of between 24 and 62mW/cm(2), i.e. a total energy at peak power of 345J, or 86J at average power over 24 hours. No changes in cell activity occurred, as monitored with the resazurin reduction assay, or with the barrier function of the human corneal cells, as measured with the fluorescein leakage assay. The monitoring of differentiation by using an assay for cornified envelope formation, revealed no adverse effects. Glutathione (GSH) and heat shock protein 70 levels were examined before and after differentiation, to determine the degree of the stress response, with the effects of UVB radiation as a control. UVB induced a stress response, as did heat shock treatment at 43 degrees C, whilst 0.15THz radiation, even after 24 hours of exposure, did not. Repeated exposure to THz radiation at this level, also resulted in no detectable adverse reactions.

Permeability changes induced by 130 GHz pulsed radiation on cationic liposomes loaded with carbonic anhydrase.

The effects of pulsed 130 GHz radiations on lipid membrane permeability were investigated by using cationic liposomes containing dipalmitoyl phosphatidylcholine (DPPC), cholesterol, and stearylamine. Carbonic anhydrase (CA) was loaded inside the liposomes and the substrate p-nitrophenyl acetate (p-NPA) added in the bulk aqueous phase. Upon permeation across the lipid bilayer, the trapped CA catalyzes the conversion of the p-NPA molecules into products. Because the self-diffusion rate of p-NPA across intact liposomes is very low the CA reaction rate, expressed as Delta A/min, is used to track membrane permeability changes. The effect of 130 GHz radiation pulse-modulated at low frequencies of 5, 7, or 10 Hz, and at time-averaged incident intensity (I(AV)) up to 17 mW/cm(2) was studied at room temperature (22 degrees C), below the phase transition temperature of DPPC liposomes. At all the tested values of I(AV) a significant enhancement of the enzyme reaction rate in CA-loaded liposomes occurred when the pulse repetition rate was 7 Hz. Typically, an increase from Delta A/min = 0.0026 +/- 0.0010 (n = 11) to Delta A/min = 0.0045 +/- 0.0013 (n = 12) (P < 0.0005) resulted at I(AV) = 7.7 mW/cm(2). The effect of 130 GHz pulse-modulated at 7 Hz was also observed on cationic liposomes formed with palmitoyloleoyl phosphatidylcholine (POPC), at room temperature (22 degrees C), above the phase transition temperature of POPC liposomes.

Uncertainty Analysis in the Calibration of an Emission Tomography System for Quantitative Imaging.

It is generally acknowledged that calibration of the imaging system (be it a SPECT or a PET scanner) is one of the critical components associated with in vivo activity quantification in nuclear medicine. The system calibration is generally performed through the acquisition of a source with a known amount of radioactivity. The decay-corrected calibration factor is the "output" quantity in a measurement model for the process. This quantity is a function of a number of "input" variables, including total counts in the volume of interest (VOI), radionuclide activity concentration, source volume, acquisition duration, radionuclide half-life, and calibration time of the radionuclide. Uncertainties in the input variables propagate through the calculation to the "combined" uncertainty in the output quantity. In the present study, using the general formula given in the GUM (Guide to the Expression of Uncertainty in Measurement) for aggregating uncertainty components, we derive a practical relation to assess the combined standard uncertainty for the calibration factor of an emission tomography system. At a time of increasing need for accuracy in quantification studies, the proposed approach has the potential to be easily implemented in clinical practice.

Quantitative accuracy of 177Lu SPECT imaging for molecular radiotherapy.

The purpose of this study is to investigate the optimal reference geometry for gamma camera calibration. Yet another question of interest was to assess the influence of the number of 3D Ordered Subsets Expectation Maximization (3D-OSEM) updates on activity quantification for SPECT imaging with 177Lu. The accuracy of 177Lu activity quantification was assessed both in small and in large objects. Two different reference geometries, namely a cylindrical homogeneous phantom and a Jaszczak 16 ml sphere surrounded by cold water, were used to determine the gamma camera calibration factor of a commercial SPECT/CT system. Moreover, the noise level and the concentration recovery coefficient were evaluated as a function of the number of 3D-OSEM updates by using the SPECT/CT images of the reference geometry phantoms and those of a cold Jaszczak phantom with three hot spheres (16ml, 8ml and 4ml), respectively. The optimal choice of the number of 3D-OSEM updates was based on a compromise between the noise level achievable in the reconstructed SPECT images and the concentration recovery coefficients. The quantitative accuracy achievable was finally validated on a test phantom, where a spherical insert composed of two concentric spheres was used to simulate a lesion in a warm background. Our data confirm and extend previous observations. Using the calibration factor obtained with the cylindrical homogeneous phantom and the Jaszczak 16 ml sphere, the recovered activity in the test phantom was underestimated by -16.4% and -24.8%, respectively. Our work has led us to conclude that gamma camera calibration performed with large homogeneous phantom outperforms calibration executed with the Jaszczak 16ml sphere. Furthermore, the results obtained support the assumption that approximately 50 OSEM updates represent a good trade-off to reach convergence in small volumes, meanwhile minimizing the noise level.

Phantom validation of quantitative Y-90 PET/CT-based dosimetry in liver radioembolization.

BACKGROUND: PET/CT has recently been shown to be a viable alternative to traditional post-infusion imaging methods providing good quality images of 90Y-laden microspheres after selective internal radiation therapy (SIRT). In the present paper, first we assessed the quantitative accuracy of 90Y-PET using an anthropomorphic phantom provided with lungs, liver, spine, and a cylindrical homemade lesion located into the hepatic compartment. Then, we explored the accuracy of different computational approaches on dose calculation, including (I) direct Monte Carlo radiation transport using Raydose, (II) Kernel convolution using Philips Stratos, (III) local deposition algorithm, (IV) Monte Carlo technique (MCNP) considering a uniform activity distribution, and (V) MIRD (Medical Internal Radiation Dose) analytical approach. Finally, calculated absorbed doses were compared with those obtained performing measurements with LiF:Mg,Cu,P TLD chips in a liquid environment. RESULTS: Our results indicate that despite 90Y-PET being likely to provide high-resolution images, the 90Y low branch ratio, along with other image-degrading factors, may produce non-uniform activity maps, even in the presence of uniform activity. A systematic underestimation of the recovered activity, both for the tumor insert and for the liver background, was found. This is particularly true if no partial volume correction is applied through recovery coefficients. All dose algorithms performed well, the worst case scenario providing an agreement between absorbed dose evaluations within 20%. Average absorbed doses determined with the local deposition method are in excellent agreement with those obtained using the MIRD and the kernel-convolution dose calculation approach. Finally, absorbed dose assessed with MC codes are in good agreement with those obtained using TLD in liquid solution, thus confirming the soundness of both calculation approaches. This is especially true for Raydose, which provided an absorbed dose value within 3% of the measured dose, well within the stated uncertainties. CONCLUSIONS: Patient-specific dosimetry is possible even in a scenario with low true coincidences and high random fraction, as in 90Y-PET imaging, granted that accurate absolute PET calibration is performed and acquisition times are sufficiently long. Despite Monte Carlo calculations seeming to outperform all dose estimation algorithms, our data provide a strong argument for encouraging the use of the local deposition algorithm for routine 90Y dosimetry based on PET/CT imaging, due to its simplicity of implementation.

Usefulness of dual-time point imaging after carbonated water for the fluorodeoxyglucose positron emission imaging of peritoneal carcinomatosis in colon cancer.

BACKGROUND: Fluorodeoxygluose (FDG) positron emission/computed tomography (PET/CT) is emerging as a useful tool for the diagnosis of peritoneal carcinomatosis (PC). In this study, we assessed whether dual-time point imaging can improve the accuracy of FDG PET/CT for the diagnosis of PC after colon rectal cancer (CRC). METHODS: Thirty-nine patients with past history of CRC were evaluated. Whole-Body PET/CT scan was acquired 1 hour after tracer injection. If one or more focal areas of increased FDG uptake (standardized uptake value, SUV max>2.5) were found in the abdomen, 1 L of carbonated water was orally administered to patients and a delayed scan of the abdominal region was acquired at 2 hours. The SUV max and the mean Delta (Δ) SUV were calculated. The scintigraphic results were compared with the results of colonoscopy and histology and with the clinical follow-up. RESULTS: Thirteen out of the 39 patients did not show any significant area of FDG uptake at the whole-body scan. The remaining 26 patients showed an overall number of 27 sites of focal increased uptake, showing a mean SUV max of 6.5+3.3. Late scan of the abdomen showed vanishing spots in 11 cases. Focal and increasing FDG uptake was found in 15 subjects (for an overall number of 16 sites) with SUV max of 15.6+4 and mean Δ SUV of +26.3%±7.5%. In these cases, final diagnosis was PC in 10 patients (according to cytology or histology) and dysplastic polyp in 5 cases. No significant difference in Δ SUV was found between patients with PC and those with polypoid formations. CONCLUSIONS: According to our results, dual-time point imaging after carbonated water may increase the accuracy of FDG PET/CT for the imaging of PC in patients affected by CRC.

Absorbed dose to lesion and clinical outcome after liver radioembolization with 90Y microspheres: a case report of PET-based dosimetry.

A 54-year-old woman with metastatic colorectal carcinoma underwent liver radioembolization with (90)Y resin microspheres. Microsphere biodistribution was assessed 2 h after the treatment through a 20-min long (90)Y PET scan. Isodose map and lesion dose-volume histogram (DVH) were then evaluated using a MATLAB-based code. Response to therapy was assessed performing a (18)F-FDG PET 6 months after the treatment. At (90)Y PET the patient showed a well-defined horseshoe-shaped hepatic lesion with hot margins and a cold core. The lesion presented a heterogeneous DVH with a hot margin receiving an average radiation dose as high as 287 Gy and a cold area receiving an average radiation dose of 70 Gy approximately. Six months after the treatment the patient reported a complete remission of tumour areas which received a high radiation dose, while progression of metastases was observed in the area that presented scarce microsphere localization at (90)Y PET. According to our experience, the use of (90)Y PET voxel dosimetry may provide a useful tool to assess possible correlations between microsphere biodistribution and clinical outcome of the treatment. In agreement with current literature findings, an average radiation dose greater than approximately 100 Gy may be required to sterilize liver metastases.

Quantification of dose nonuniformities by voxel-based dosimetry in patients receiving 90Y-ibritumomab-tiuxetan.

UNLABELLED: Abstract Objective: To assess the impact of nonuniform dose distribution within lesions and tumor-involved organs of patients receiving Zevalin(®), and to discuss possible implications of equivalent uniform biological effective doses (EU-BED) on treatment efficacy and toxicity. MATLAB™ -based software for voxel-based dosimetry was adopted for this purpose. METHODS: Eleven lesions from seven patients with either indolent or aggressive non-Hodgkin lymphoma were analyzed, along with four organs with disease. Absorbed doses were estimated by a direct integration of single-voxel kinetic data from serial tomographic images. After proper corrections, differential BED distributions and surviving cell fractions were estimated, allowing for the calculation of EU-BED. To quantify dose uniformity in each target area, a heterogeneity index was defined. RESULTS: Average doses were below those prescribed by conventional radiotherapy to eradicate lymphoma lesions. Dose heterogeneity and effect on tumor control varied among lesions, with no apparent relation to tumor mass. Although radiation doses to involved organs were safe, unexpected liver toxicity occurred in one patient who presented with a pattern of diffuse infiltration. CONCLUSION: Voxel-based dosimetry and radiobiologic modeling can be successfully applied to lesions and tumor-involved organs, representing a methodological advance over estimation of mean absorbed doses. However, effects on tumor control and organ toxicity still cannot be easily predicted.

Three-dimensional patient-specific dosimetry in radioimmunotherapy with 90Y-ibritumomab-tiuxetan.

Aim of the present article was to perform three-dimensional (3D) single photon emission tomography-based dosimetry in radioimmunotherapy (RIT) with (90)Y-ibritumomab-tiuxetan. A custom MATLAB-based code was used to elaborate 3D images and to compare average 3D doses to lesions and to organs at risk (OARs) with those obtained with planar (2D) dosimetry. Our 3D dosimetry procedure was validated through preliminary phantom studies using a body phantom consisting of a lung insert and six spheres with various sizes. In phantom study, the accuracy of dose determination of our imaging protocol decreased when the object volume decreased below 5 mL, approximately. The poorest results were obtained for the 2.58 mL and 1.30 mL spheres where the dose error evaluated on corrected images with regard to the theoretical dose value was -12.97% and -18.69%, respectively. Our 3D dosimetry protocol was subsequently applied on four patients before RIT with (90)Y-ibritumomab-tiuxetan for a total of 5 lesions and 4 OARs (2 livers, 2 spleens). In patient study, without the implementation of volume recovery technique, tumor absorbed doses calculated with the voxel-based approach were systematically lower than those calculated with the planar protocol, with average underestimation of -39% (range from -13.1% to -62.7%). After volume recovery, dose differences reduce significantly, with average deviation of -14.2% (range from -38.7.4% to +3.4%, 1 overestimation, 4 underestimations). Organ dosimetry in one case overestimated, in the other underestimated the dose delivered to liver and spleen. However, both for 2D and 3D approach, absorbed doses to organs per unit administered activity are comparable with most recent literature findings.

90Y-PET for the assessment of microsphere biodistribution after selective internal radiotherapy.

OBJECTIVES: To demonstrate the feasibility of 90Y-PET imaging for biodistribution assessment after selective internal radiotherapy treatments with 90Y-microspheres, comparing the results with 99mTc-macroaggregated albumin (MAA) images obtained with single-photon emission computed tomography. METHODS: Preliminary studies were performed with the aim of evaluating the imaging system spatial resolution and scanner sensitivity for detecting annihilation photons. Subsequently, microsphere distribution was evaluated in 10 patients who underwent liver selective internal radiotherapy treatment. 99mTc-MAA and 90Y-microsphere were simultaneously injected for immediate monitoring after treatment. For each patient, the metastases detected with 90Y-PET and 99mTc-MAA were assessed and compared with 18F-fluorodeoxyglucose-PET (18F-FDG-PET) obtained before treatment and used as an imaging benchmark procedure. The correlation between these techniques was thus investigated in terms of matching lesions. Lesions were considered true positive in the case of matching with 18F-FDG-PET. The sensitivity of both techniques was evaluated as the true-positive fraction of detected spots in the treated liver sectors. RESULTS: With our experimental setup, a maximum scanner sensitivity of 0.577 and 0.077 cps/MBq was obtained for three-dimensional and two-dimensional acquisitions, respectively. A good correlation was obtained between images obtained before and after treatment, with 90Y-PET being by far the most accurate technique in detecting microsphere distribution and tumor nonhomogeneity areas. A sensitivity as high as 0.91 was obtained with 90Y-PET, whereas 99mTc-MAA imaging showed a SE of 0.75. CONCLUSION: 90Y-PET is a promising and reliable technique for microsphere biodistribution evaluation after liver selective internal radiotherapy treatment. Because of the better resolution and the possibility to perform computed tomography fusion, 90Y-PET images are more accurate than 99mTc-MAA single-photon emission computed tomography, which is now considered the gold standard for biodistribution assessment.

Integral dose and radiation-induced secondary malignancies: comparison between stereotactic body radiation therapy and three-dimensional conformal radiotherapy.

The aim of the present paper is to compare the integral dose received by non-tumor tissue (NTID) in stereotactic body radiation therapy (SBRT) with modified LINAC with that received by three-dimensional conformal radiotherapy (3D-CRT), estimating possible correlations between NTID and radiation-induced secondary malignancy risk. Eight patients with intrathoracic lesions were treated with SBRT, 23 Gy × 1 fraction. All patients were then replanned for 3D-CRT, maintaining the same target coverage and applying a dose scheme of 2 Gy × 32 fractions. The dose equivalence between the different treatment modalities was achieved assuming α/ß = 10 Gy for tumor tissue and imposing the same biological effective dose (BED) on the target (BED = 76 Gy(10)). Total NTIDs for both techniques was calculated considering α/ß = 3 Gy for healthy tissue. Excess absolute cancer risk (EAR) was calculated for various organs using a mechanistic model that includes fractionation effects. A paired two-tailed Student t-test was performed to determine statistically significant differences between the data (p ≤ 0.05). Our study indicates that despite the fact that for all patients integral dose is higher for SBRT treatments than 3D-CRT (p = 0.002), secondary cancer risk associated to SBRT patients is significantly smaller than that calculated for 3D-CRT (p = 0.001). This suggests that integral dose is not a good estimator for quantifying cancer induction. Indeed, for the model and parameters used, hypofractionated radiotherapy has the potential for secondary cancer reduction. The development of reliable secondary cancer risk models seems to be a key issue in fractionated radiotherapy. Further assessments of integral doses received with 3D-CRT and other special techniques are also strongly encouraged.

90Y PET-based dosimetry after selective internal radiotherapy treatments.

OBJECTIVES: The decay of 90Y has a minor branch to the O+ first excited state of 89Zr, the de-excitation of which to the fundamental state is followed by a ß+­ß- emission that has been used recently for biodistribution assessment after selective internal radiotherapy (SIRT) treatments. The purpose of the present study is to demonstrate the feasibility of 90Y PET imaging for dose assessment after radioembolization with 90Y microspheres. METHODS: Activity quantification was validated through preliminary phantom studies using a cylindrical body phantom composed of six inserts of different volumes filled with a calibrated amount of 90Y microspheres. A GE Discovery ST PET/CT scanner provided with bismuth germinate (BGO) crystals was used for image acquisition. Images were reconstructed with an ordered subset expectation­maximization method. The effect of object size and the effect of the number of iterations on dose evaluation and volume recovery were investigated. Microsphere dose distribution was then evaluated on one patient (one lesion) who underwent liver SIRT treatment. Dose calculations were made with a MATLAB-based code developed in our department. Dedicated Monte Carlo calculations were executed to evaluate dose S-values for the 90Y source. The activity distribution derived from 90Y PET acquisitions was convolved with the voxel S-values to obtain a three-dimensional absorbed dose distribution and dose­volume histograms. RESULTS: Dosimetry studies carried out on the body phantom with ordered subset expectation­maximization algorithm, three iterations, provided an accuracy of 7.62% in determining the absorbed dose in the largest insert. The dose difference increases as the insert size reduces. Preliminary results on a patient provided a high-resolution absorbed dose distribution map. An average dose of 139.3 Gy was evaluated for the tumor area, with a maximum dose as high as 237.9 Gy. The absorbed dose to the healthy liver was below the tolerance dose of 35 Gy (33.8 Gy). A clear correlation between absorbed dose and tumor response was observed at 18F-fluorodeoxyglucose PET acquired 6 months after treatment. CONCLUSION: According to our experience, 90Y PET is a promising and reliable technique for microsphere dose assessment and might pave the way for a patient-specific PET-based dosimetry after liver SIRT treatments.

Intensity modulated radiotherapy in early stage Hodgkin lymphoma patients: is it better than three dimensional conformal radiotherapy?

BACKGROUND: Cure rate of early Hodgkin Lymphoma are high and avoidance of late toxicities is of paramount importance. This comparative study aims to assess the normal tissue sparing capability of intensity-modulated radiation therapy (IMRT) versus standard three-dimensional conformal radiotherapy (3D-CRT) in terms of dose-volume parameters and normal tissue complication probability (NTCP) for different organs at risk in supradiaphragmatic Hodgkin Lymphoma (HL) patients. METHODS: Ten HL patients were actually treated with 3D-CRT and all treatments were then re-planned with IMRT. Dose-volume parameters for thyroid, oesophagus, heart, coronary arteries, lung, spinal cord and breast were evaluated. Dose-volume histograms generated by TPS were analyzed to predict the NTCP for the considered organs at risk, according to different endpoints. RESULTS: Regarding dose-volume parameters no statistically significant differences were recorded for heart and origin of coronary arteries. We recorded statistically significant lower V30 with IMRT for oesophagus (6.42 vs 0.33, p = 0.02) and lungs (4.7 vs 0.1 p = 0.014 for the left lung and 2.59 vs 0.1 p = 0.017 for the right lung) and lower V20 for spinal cord (17.8 vs 7.2 p = 0.02). Moreover the maximum dose to the spinal cord was lower with IMRT (30.2 vs 19.9, p <0.001). Higher V10 with IMRT for thyroid (64.8 vs 95, p = 0.0019) and V5 for lungs (30.3 vs 44.8, p = 0.03, for right lung and 28.9 vs 48.1, p = 0.001 for left lung) were found, respectively. Higher V5 and V10 for breasts were found with IMRT (V5: 4.14 vs 20.6, p = 0.018 for left breast and 3.3 vs 17, p = 0.059 for right breast; V10: 2.5 vs 13.6 p = 0.035 for left breast and 1.7 vs 11, p = 0.07 for the right breast.) As for the NTCP, our data point out that IMRT is not always likely to significantly increase the NTCP to OARs. CONCLUSIONS: In HL male patients IMRT seems feasible and accurate while for women HL patients IMRT should be used with caution.

Fractionated stereotactic radiotherapy for skull base tumors: analysis of treatment accuracy using a stereotactic mask fixation system.

BACKGROUND: To assess the accuracy of fractionated stereotactic radiotherapy (FSRT) using a stereotactic mask fixation system. PATIENTS AND METHODS: Sixteen patients treated with FSRT were involved in the study. A commercial stereotactic mask fixation system (BrainLAB AG) was used for patient immobilization. Serial CT scans obtained before and during FSRT were used to assess the accuracy of patient immobilization by comparing the isocenter position. Daily portal imaging were acquired to establish day to day patient position variation. Displacement errors along the different directions were calculated as combination of systematic and random errors. RESULTS: The mean isocenter displacements based on localization and verification CT imaging were 0.1 mm (SD 0.3 mm) in the lateral direction, 0.1 mm (SD 0.4 mm) in the anteroposterior, and 0.3 mm (SD 0.4 mm) in craniocaudal direction. The mean 3D displacement was 0.5 mm (SD 0.4 mm), being maximum 1.4 mm. No significant differences were found during the treatment (P=0.4). The overall isocenter displacement as calculated by 456 anterior and lateral portal images were 0.3 mm (SD 0.9 mm) in the mediolateral direction, -0.2 mm (SD 1 mm) in the anteroposterior direction, and 0.2 mm (SD 1.1 mm) in the craniocaudal direction. The largest displacement of 2.7 mm was seen in the cranio-caudal direction, with 95% of displacements<2 mm in any direction. CONCLUSIONS: The results indicate that the setup error of the presented mask system evaluated by CT verification scans and portal imaging are minimal. Reproducibility of the isocenter position is in the best range of positioning reproducibility reported for other stereotactic systems.