The aim of this study was to optimize the dosimetric approach and to review the absorbed doses delivered, taking into account radiobiology, in order to identify the optimal methodology for an ...individualized treatment planning strategy based on (99m)Tc-macroaggregated albumin (MAA) single photon emission computed tomography (SPECT) images.
We performed retrospective dosimetry of the standard TheraSphere® treatment on 52 intermediate (n = 17) and advanced (i.e. portal vein thrombosis, n = 35) hepatocarcinoma patients with tumour burden < 50% and without obstruction of the main portal vein trunk. Response was monitored with the densitometric radiological criterion (European Association for the Study of the Liver) and treatment-related liver decompensation was defined ad hoc with a time cut-off of 6 months. Adverse events clearly attributable to disease progression or other causes were not attributed to treatment. Voxel dosimetry was performed with the local deposition method on (99m)Tc-MAA SPECT images. The reconstruction protocol was optimized. Concordance of (99m)Tc-MAA and (90)Y bremsstrahlung microsphere biodistributions was studied in 35 sequential patients. Two segmentation methods were used, based on SPECT alone (home-made code) or on coregistered SPECT/CT images (IMALYTICS™ by Philips). STRATOS™ absorbed dose calculation was validated for (90)Y with a single time point. Radiobiology was used introducing other dosimetric variables besides the mean absorbed dose D: equivalent uniform dose (EUD), biologically effective dose averaged over voxel values (BEDave) and equivalent uniform biologically effective dose (EUBED). Two sets of radiobiological parameters, the first derived from microsphere irradiation and the second from external beam radiotherapy (EBRT), were used. A total of 16 possible methodologies were compared. Tumour control probability (TCP) and normal tissue complication probability (NTCP) were derived. The area under the curve (AUC) of the receiver-operating characteristic (ROC) curve was used as a figure of merit to identify the methodology which gave the best separation in terms of dosimetry between responding and non-responding lesions and liver decompensated vs non-decompensated liver treatment.
MAA and (90)Y biodistributions were not different (71% of cases), different in 23% and uncertain in 6%. Response correlated with absorbed dose (Spearman's r from 0.48 to 0.69). Responding vs non-responding lesion absorbed doses were well separated, regardless of the methodology adopted (p = 0.0001, AUC from 0.75 to 0.87). EUBED gave significantly better separation with respect to mean dose (AUC = 0.87 vs 0.80, z = 2.07). Segmentation on SPECT gave better separation than on SPECT/CT. TCP(50%) was at 250 Gy for small lesion volumes (<10 cc) and higher than 1,000 Gy for large lesions (>10 cc). Apparent radiosensitivity values from TCP were around 0.003/Gy, a factor of 3-5 lower than in EBRT, as found by other authors. The dose-rate effect was negligible: a purely linear model can be applied. Toxicity incidence was significantly larger for Child B7 patients (89 vs 14%, p < 0.0001), who were therefore excluded from dose-toxicity analysis. Child A toxic vs non-toxic treatments were significantly separated in terms of dose averaged on whole non-tumoural parenchyma (including non-irradiated regions) with AUC from 0.73 to 0.94. TD50 was ≈ 100 Gy. No methodology was superior to parenchyma mean dose, which therefore can be used for planning, with a limit of TD15 ≈ 75 Gy.
A dosimetric treatment planning criterion for Child A patients without complete obstruction of the portal vein was developed.
The potential impact of nuclear data uncertainties on a large number of performance parameters of reactor cores dedicated to the transmutation of radioactive wastes is discussed. An uncertainty ...analysis has been performed based on sensitivity theory, which underlines the cross sections, the energy range, and the isotopes that are responsible for the most significant uncertainties.
To provide guidelines on priorities for new evaluations or validation experiments, required accuracies on specific nuclear data have been derived, accounting for target accuracies on major design parameters. The required accuracies (mostly in the energy region below 20 MeV), in particular for minor actinide data, are of the same order of magnitude of the achieved accuracies on major actinides. Specific requirements also concern the improvement of minor actinide data related to decay heat and effective delayed-neutron fraction assessment.
Patient Electronic Health Records (EHRs) contain valuable clinical data that is useful for medical research and public health inquires. However, patient privacy regulation and improper resource ...sharing risks limit access to EHR medical data for research and public health purposes. In this paper, we introduce an end-to-end security solution that addresses both concerns and facilitates the sharing of patient EHR data over an unsecured third-party server using a leveled homomorphic encryption (LHE) scheme. Time testing for aggregating queries and linear computations was carried out using an HPE ProLiant DL580 Gen 10 server with an Intel Xeon Platinum 8280 Processor.
Neuroendocrine tumors over-express somatostatin receptors and literature data have demonstrated the efficacy of the peptide receptor radionuclide therapy with somatostatin analogues labelled with ...high activities of b-emitting radioisotopes, such as (90)Y and (177)Lu. Yttrium-90 is a pure high energy b-emitter while (177)Lu is a b/g emitter of medium energy. We decided to evaluate an original tandem treatment based on administration of radiolabeled DOTA(0),Tyr(3)octreotate (DOTA-TATE) alternating (177)Lu and 90Y. Aim of this study was to evaluate the feasibility, the efficacy and the toxicity of this treatment in neuroendocrine tumors expressing somatostatin receptors relapsed or refractory to conventional therapies.
Patients were treated with four therapeutic cycles alternating (177)LuDOTA-TATE (5.55 GBq) and (90)YDOTA-TATE (2.6 GBq). Dosimetric evaluation after administration of (177)LuDOTA-TATE allows to calculate the absorbed doses in healthy organs. Blood samples were collected at 5 min, 1, 6, 24, 48, 72, 96 h and scintigraphy was performed once a day for four days after administration. Toxicity was evaluated considering hematological parameters and renal toxicity was evaluated also by the glomerular filtration rate (GFR). Efficacy related with RECIST criteria.
Up to now 26 patients entered the study and 16 patients completed all cycles. Treatment was well tolerated with no adverse event registered. No damage to healthy organs was revealed in accordance with the calculated absorbed doses. We had a partial response in 10/15 patients evaluated three months after the fourth treatment.
Up to now only a few patients participated in and concluded this study; preliminary results are encouraging and indicate the feasibility of the study.
Medullary thyroid carcinoma (MTC) is a relatively rare neuroendocrine tumour originating from the parafollicular C cells and releases calcitonin (hCt), carcinoembryonic antigen (CEA) and occasionally ...other substances. In 20-30% of cases MTC presents a germline mutation of the RET proto-oncogene and occurs in 3 different hereditary forms: familial MTC, multiple endocrine neoplasia (MEN) 2A and MEN 2B syndrome. Prognosis of MTC is largely related to tumour extension at disease onset. Surgery remains the most effective therapy for potential cure. Overall survival is strictly linked to the occurrence of relapse. After surgery, serum hCt remains the most sensitive test for occult disease. Diagnostic imaging work-up includes ultrasound, computed tomography (CT), magnetic resonance imaging (MRI), bone scintigraphy, as the more frequent sites of recurrence or metastases are cervical and mediastinal lymph nodes, lungs, liver and bone. Nuclear medicine procedures include (111)In-labelled somatostatin analogs, radioiodinated metaiodobenzylguanidine (MIBG), and several PET radiopharmaceuticals. Experience with radionuclide therapy in MTC is restricted to few patients treated with (131)I-MIBG or (90)Y-DOTATOC. Since 1987, 1 027 diagnostic MIBG scans were performed in the Department Department of Diagnostic Imaging and Therapy of the Istituto Nazionale Tumori IRCCS Foundation (Milan, Italy), 85 of which for MTC, with a sensitivity of 38.7% in patients with evidence of disease and 30.7 % if all patients were considered. Since 1994, 13 MTC patients were treated with MIBG with 4 partial responses and 4 stable diseases. Patients with liver or bone involvement responded to therapy and showed long-term partial remission of disease, others showed stability of disease, which was apparently unrelated to therapy. Improvement of efficacy can be achieved through dosimetric calculation of administered activity.
Hypercalcaemia is found in more than 90% of the cases of primitive hyperparathyroidism and malignancies. Rarely, D hypervitaminosis, sarcoidosis, other granulomatous diseases, some drugs, and ...endocrine diseases may be responsible. Nine patients with systemic lupus erythematosus (SLE) and hypercalcaemia, without evidence of primary hyperparathyroidism, have been previously described. Here we report the 10th patient with SLE and hypercalcaemia, along with a brief review of the literature.
Abstract Evaluation of osteoporotic vertebral fracture risk is currently based on measurement of bone mineral density (BMD), but bone strength depends also on bone quality parameters. Aim of this ...study was to evaluate the validity of a new vertebral morphometric index, the Anterior Vertebral Heights sum (AHs) in discriminating women at high risk of vertebral fracture, comparing its diagnostic accuracy with that of BMD measured at lumbar spine (LS-BMD) and femoral neck (FN-BMD). Materials and methods A total of 163 Caucasian post-menopausal women (age range 46–74 years, mean age ± SD = 63.8 ± 7.1 years), who did not present prevalent fractures at baseline evaluation, were observed at longitudinal follow-up. X-ray of the thoracic and lumbar spine, LS-BMD and FN-BMD measurements were obtained in all patients at baseline and repeated at the second follow-up visit 18–24 months later (mean 21 ± 1.7 months). Radiographs of spine were analysed in order to identify vertebral fractures using a visual semiquantitative method (SQ) and vertebral morphometry as well as by calculating the AHs morphometric index. Results During follow-up, 21/163 patients (12.9%) sustained a new vertebral fracture; 95.2% (20/21) of fractured patients but only 4.9% (7/142) of non-fractured women had reduced AHs values. As regarding BMD, 66.6% (14/21) and 61.9% (13/21) of women with incident fracture were osteoporotic at lumbar spine and femoral neck baseline evaluation , whereas among non-fractured women, 38% (54/142) at LS-BMD and 33.1% (47/142) at FN-BMD were osteoporotic . Analyses of Receiver Operating Characteristic (ROC) curves showed that AHs discriminated vertebral fractures almost perfectly (AUC 0.97; 95% CI 0.95–0.99). On the other hand, the AUC for LS-BMD was only 0.73 (95% CI 0.64–0.81) and for FN-BMD was 0.72 (95%CI 0.63–0.80), showing that the diagnostic accuracy of AHs was significantly higher compared to that of LS-BMD ( p < 0.001) or FN-BMD ( p < 0.001). A modified Poisson regression model for binary data was used to assess the independent role of AHs in predicting vertebral fracture. The effect of AHs remained statistically significant ( p < 0.001) after adjusting by FN-BMD, age, weight and body height. Conclusions Results of this study indicate the validity of this new morphometric index in evaluating the risk of osteoporotic vertebral fractures thus suggesting that AHs should be considered a valid parameter in clinical practice to assess the need for primary prevention of vertebral fractures.
This paper compares the numerical results obtained from various nuclear codes and nuclear data libraries with the YALINA Booster subcritical assembly (Minsk, Belarus) experimental results. This ...subcritical assembly was constructed to study the physics and the operation of accelerator-driven subcritical systems (ADS) for transmuting the light water reactors (LWR) spent nuclear fuel. The YALINA Booster facility has been accurately modeled, with no material homogenization, by the Monte Carlo codes MCNPX (MCNP/MCB) and MONK. The MONK geometrical model matches that of MCNPX. The assembly has also been analyzed by the deterministic code ERANOS. In addition, the differences between the effective neutron multiplication factor and the source multiplication factors have been examined by alternative calculational methodologies. The analyses include the delayed neutron fraction, prompt neutron lifetime, generation time, neutron flux profiles, and spectra in various experimental channels. The accuracy of the numerical models has been enhanced by accounting for all material impurities and the actual density of the polyethylene material used in the assembly (the latter value was obtained by dividing the total weight of the polyethylene by its volume in the numerical model). There is good agreement between the results from MONK, MCNPX, and ERANOS. The ERANOS results show small differences relative to the other results because of material homogenization and the energy and angle discretizations.The MCNPX results match the experimental measurements of the
3He(n,p) reaction rates obtained with the californium neutron source.
Since the second half of the 1980s, (131)I-MIBG has been widely used for treatment of patients with malignant pheochromocytoma. In 1991, at the International Meeting in Rome, it was agreed that ...(131)I-MIBG therapy induces significant tumor responses in about 30-50% of cases, long-term stabilization of disease in several cases and significant reduction of cathecolamine-related symptoms in almost all patients. Nevertheless, more than 20 years later, its therapeutic use in malignant phaeochromocytoma has not yet been standardized. Aim of the present study was to compare the use of low versus intermediate activity of MIBG to achieve better results in a shorter time with higher activities.
Two different modalities of (131)I-MIBG therapy were performed: before 2001, 12 patients (Group 1) received a fixed activity of 5.55 GBq/session. From 2001 to 2009, 16 patients (Group 2) were treated with 9.25-12.95 GBq/session.
As expected, the overall response rate in Group 2 are slightly better. The most important result of increasing the single session activity was the shorter median time to achieve a significant response (7 versus 19 months), which was obtained with a lower median cumulative activity (11 versus 22 GBq) in a lower median number of sessions (2 versus 7).
We demonstrated that intermediate single session activity shortened to one third the global treatment time, with similar efficacy and a moderate increment of toxicity. Consequently, the increase of (131)I-MIBG activity, without reaching myeloablative levels, can be recommended for standard treatment of pheochromocytoma and paraganglioma patients.
This paper analyzes the available data on the dosimetric approach and describes the use of dosimetry in the Division of Nuclear Medicine of the National Cancer Institute in Milan. Dosimetry is rarely ...performed when planning radio-iodine activity, although most of the available guidelines do mention this possibility, without giving any well defined indication. Aim of the present research was to validate the usefulness of dosimetry in the management of metastatic thyroid cancer. Benua (1962) set the limit of blood absorbed dose at 2 Gy to avoid hematological toxicity. Maxon (1983) determined at 80 Gy the dose to achieve complete destruction of a metastatic lesion. Dorn (2003) combined red marrow and lesion dosimetry showing that high activity administrations with less that 3 Gy to the red marrow are a safe and more effective with respect to fixed activities administrations. Lee (2008) reported 50% responses with high activity administrations based on blood dosimetry, in 47 patients which were unsuccessfully previously treated with fixed activities. Sgouros (2005) and Song (2006) introduced key parameters as Biological Effective Dose and Uniform Equivalent Dose in order to describe the effects of continuous low dose rate irradiation and non uniform activity uptake, typical of nuclear medicine treatments.
Red marrow and lesion dosimetry (planar view) were performed during the treatment, without changing the fixed activity schema.
This experience demonstrate first of all, that dosimetry is feasible in the clinical routine, and that it can provide the clinician with important information, no matter its often quoted limited numerical accuracy. A total of 17/20 lesion doses below 80 Gy have been detected. Three/17 (doses between 40 and 80 Gy) disappeared in the follow-up scintigram. Two/17 were undetectable at computed tomography or nuclear magnetic resonance. These data suggest that repetition of treatment on a lesion drastically reduces its uptake, with a loss of therapeutic efficacy along the sequence of fixed activity administrations.
The usefulness of dosimetry should not be assessed only on the basis of patient survival or therapeutic efficacy; the possibility to avoid useless treatments should also be considered. According to the authors, individualized dosimetry could improve the management of metastatic differentiated thyroid cancer. Even post-therapeutic dosimetry, as performed at this institution, has a significant impact on clinical decision-making. The question for the future is how to include dosimetry into the patient management framework.
