Quality indicators for hyperthermia treatment: Italian survey analysis.

AIM: Nowadays, no Quality Indicators (QI) have been proposed for Hyperthermia treatments. Starting from radiotherapy experience, the aim of this work is to adapt radiotherapy indicators to Hyperthermia and to propose a new specific set of QI in Hyperthermia field. MATERIAL AND METHODS: At first, radiotherapy quality indicators published in literature have been adapted to hyperthermia setting. Moreover, new specific indicators for the treatment of hyperthermia have been defined. To obtain the standard reference values of quality indicators, a questionnaire was sent to 7 Italian hyperthermia Institutes with a list of questions on physical and clinical hyperthermia treatment in order to highlight the different therapeutic approaches. RESULTS: Three structure, five process and two outcome QI were selected. It has been possible to adapt seven indicators from radiotherapy, while three indicators have been defined as new specific indicators for hyperthermia. Average values used as standard reference values have been obtained and proposed. CONCLUSION: The survey performed on 7 Italian centres allowed to derive the standard reference value for each indicator. The proposed indicators are available to be investigated and applied by a larger number of Institutes in which hyperthermia treatment is performed in order to monitor the operational procedures and to confirm or modify the reference standard value derived for each indicator.

Predicting locally advanced rectal cancer response to neoadjuvant therapy with 18F-FDG PET and MRI radiomics features.

PURPOSE: Pathological complete response (pCR) following neoadjuvant chemoradiotherapy or radiotherapy in locally advanced rectal cancer (LARC) is reached in approximately 15-30% of cases, therefore it would be useful to assess if pretreatment of 18F-FDG PET/CT and/or MRI texture features can reliably predict response to neoadjuvant therapy in LARC. METHODS: Fifty-two patients were dichotomized as responder (pR+) or non-responder (pR-) according to their pathological tumor regression grade (TRG) as follows: 22 as pR+ (nine with TRG = 1, 13 with TRG = 2) and 30 as pR- (16 with TRG = 3, 13 with TRG = 4 and 1 with TRG = 5). First-order parameters and 21 second-order texture parameters derived from the Gray-Level Co-Occurrence matrix were extracted from semi-automatically segmented tumors on T2w MRI, ADC maps, and PET/CT acquisitions. The role of each texture feature in predicting pR+ was assessed with monoparametric and multiparametric models. RESULTS: In the mono-parametric approach, PET homogeneity reached the maximum AUC (0.77; sensitivity = 72.7% and specificity = 76.7%), while PET glycolytic volume and ADC dissimilarity reached the highest sensitivity (both 90.9%). In the multiparametric analysis, a logistic regression model containing six second-order texture features (five from PET and one from T2w MRI) yields the highest predictivity in distinguish between pR+ and pR- patients (AUC = 0.86; sensitivity = 86%, and specificity = 83% at the Youden index). CONCLUSIONS: If preliminary results of this study are confirmed, pretreatment PET and MRI could be useful to personalize patient treatment, e.g., avoiding toxicity of neoadjuvant therapy in patients predicted pR-.

Impact of a rectal and bladder preparation protocol on prostate cancer outcome in patients treated with external beam radiotherapy.

PURPOSE AND OBJECTIVE: To test the hypothesis that a rectal and bladder preparation protocol is associated with an increase in prostate cancer specific survival (PCSS), clinical disease free survival (CDFS) and biochemical disease free survival (BDFS). PATIENTS AND METHODS: From 1999 to 2012, 1080 prostate cancer (PCa) patients were treated with three-dimensional conformal radiotherapy (3DCRT). Of these patients, 761 were treated with an empty rectum and comfortably full bladder (RBP) preparation protocol, while for 319 patients no rectal/bladder preparation (NRBP) protocol was adopted. RESULTS: Compared with NRBP patients, patients with RBP had significantly higher BDFS (64% vs 48% at 10 years, respectively), CDFS (81% vs 70.5% at 10 years, respectively) and PCSS (95% vs 88% at 10 years, respectively) (log-rank test p < 0.001). Multivariate analysis (MVA) indicated for all treated patients and intermediate high-risk patients that the Gleason score (GS) and the rectal and bladder preparation were the most important prognostic factors for PCSS, CDFS and BDFS. With regard to high- and very high-risk patients, GS, RBP, prostate cancer staging and RT dose were predictors of PCSS, CDFS and BDFS in univariate analysis (UVA). CONCLUSION: We found strong evidence that rectal and bladder preparation significantly decreases biochemical and clinical failures and the probability of death from PCa in patients treated without daily image-guided prostate localization, presumably since patients with RBP are able to maintain a reproducibly empty rectum and comfortably full bladder across the whole treatment compared with NRPB patients.

Use of the FLUKA Monte Carlo code for 3D patient-specific dosimetry on PET-CT and SPECT-CT images.

Patient-specific absorbed dose calculation for nuclear medicine therapy is a topic of increasing interest. 3D dosimetry at the voxel level is one of the major improvements for the development of more accurate calculation techniques, as compared to the standard dosimetry at the organ level. This study aims to use the FLUKA Monte Carlo code to perform patient-specific 3D dosimetry through direct Monte Carlo simulation on PET-CT and SPECT-CT images. To this aim, dedicated routines were developed in the FLUKA environment. Two sets of simulations were performed on model and phantom images. Firstly, the correct handling of PET and SPECT images was tested under the assumption of homogeneous water medium by comparing FLUKA results with those obtained with the voxel kernel convolution method and with other Monte Carlo-based tools developed to the same purpose (the EGS-based 3D-RD software and the MCNP5-based MCID). Afterwards, the correct integration of the PET/SPECT and CT information was tested, performing direct simulations on PET/CT images for both homogeneous (water) and non-homogeneous (water with air, lung and bone inserts) phantoms. Comparison was performed with the other Monte Carlo tools performing direct simulation as well. The absorbed dose maps were compared at the voxel level. In the case of homogeneous water, by simulating 10(8) primary particles a 2% average difference with respect to the kernel convolution method was achieved; such difference was lower than the statistical uncertainty affecting the FLUKA results. The agreement with the other tools was within 3­4%, partially ascribable to the differences among the simulation algorithms. Including the CT-based density map, the average difference was always within 4% irrespective of the medium (water, air, bone), except for a maximum 6% value when comparing FLUKA and 3D-RD in air. The results confirmed that the routines were properly developed, opening the way for the use of FLUKA for patient-specific, image-based dosimetry in nuclear medicine.

A free database of radionuclide voxel S values for the dosimetry of nonuniform activity distributions.

The increasing availability of SPECT/CT devices with advanced technology offers the opportunity for the accurate assessment of the radiation dose to the biological target volume during radionuclide therapy. Voxel dosimetry can be performed employing direct Monte Carlo radiation transport simulations, based on both morphological and functional images of the patient. On the other hand, for voxel dosimetry calculations the voxel S value method can be considered an easier approach than patient-specific Monte Carlo simulations, ensuring a good dosimetric accuracy at least for anatomic regions which are characterized by uniform density tissue. However, this approach has been limited because of the lack of tabulated S values for different voxel dimensions and radionuclides. The aim of this work is to provide a free dataset of values which can be used for voxel dosimetry in targeted radionuclide studies. Seven different radionuclides (89Sr, 90Y, 131I, 153Sm, 177Lu, 186Re, 188Re), and 13 different voxel sizes (2.21, 2.33, 2.4, 3, 3.59, 3.9, 4, 4.42, 4.8, 5, 6, 6.8 and 9.28 mm) are considered. Voxel S values are calculated performing simulations of monochromatic photon and electron sources in two different homogeneous tissues (soft tissue and bone) with DOSXYZnrc code, and weighting the contributions on the basis of the radionuclide emission spectra. The outcomes are validated by comparison with Monte Carlo simulations obtained with other codes (PENELOPE and MCNP4c) performing direct simulation of the radionuclide emission spectra. The differences among the different Monte Carlo codes are of the order of a few per cent when considering the source voxel and the bremsstrahlung tail, whereas the highest differences are observed at a distance close to the maximum continuous slowing down approximation range of electrons. These discrepancies would negligibly affect dosimetric assessments. The dataset of voxel S values can be freely downloaded from the website www.medphys.it.

Calculation of electron and isotopes dose point kernels with FLUKA Monte Carlo code for dosimetry in nuclear medicine therapy.

PURPOSE: The calculation of patient-specific dose distribution can be achieved by Monte Carlo simulations or by analytical methods. In this study, FLUKA Monte Carlo code has been considered for use in nuclear medicine dosimetry. Up to now, FLUKA has mainly been dedicated to other fields, namely high energy physics, radiation protection, and hadrontherapy. When first employing a Monte Carlo code for nuclear medicine dosimetry, its results concerning electron transport at energies typical of nuclear medicine applications need to be verified. This is commonly achieved by means of calculation of a representative parameter and comparison with reference data. Dose point kernel (DPK), quantifying the energy deposition all around a point isotropic source, is often the one. METHODS: FLUKA DPKS have been calculated in both water and compact bone for monoenergetic electrons (10-3 MeV) and for beta emitting isotopes commonly used for therapy (89Sr, 90Y, 131I 153Sm, 177Lu, 186Re, and 188Re). Point isotropic sources have been simulated at the center of a water (bone) sphere, and deposed energy has been tallied in concentric shells. FLUKA outcomes have been compared to PENELOPE v.2008 results, calculated in this study as well. Moreover, in case of monoenergetic electrons in water, comparison with the data from the literature (ETRAN, GEANT4, MCNPX) has been done. Maximum percentage differences within 0.8.RCSDA and 0.9.RCSDA for monoenergetic electrons (RCSDA being the continuous slowing down approximation range) and within 0.8.X90 and 0.9.X90 for isotopes (X90 being the radius of the sphere in which 90% of the emitted energy is absorbed) have been computed, together with the average percentage difference within 0.9.RCSDA and 0.9.X90 for electrons and isotopes, respectively. RESULTS: Concerning monoenergetic electrons, within 0.8.RCSDA (where 90%-97% of the particle energy is deposed), FLUKA and PENELOPE agree mostly within 7%, except for 10 and 20 keV electrons (12% in water, 8.3% in bone). The discrepancies between FLUKA and the other codes are of the same order of magnitude than those observed when comparing the other codes among them, which can be referred to the different simulation algorithms. When considering the beta spectra, discrepancies notably reduce: within 0.9.X90, FLUKA and PENELOPE differ for less than 1% in water and less than 2% in bone with any of the isotopes here considered. Complete data of FLUKA DPKS are given as Supplementary Material as a tool to perform dosimetry by analytical point kernel convolution. CONCLUSIONS: FLUKA provides reliable results when transporting electrons in the low energy range, proving to be an adequate tool for nuclear medicine dosimetry.

Recent issues on dosimetry and radiobiology for peptide receptor radionuclide therapy.

Peptide receptor radionuclide therapy (PRRT) has been constantly evolving over the last decade, providing successful results in the treatment of tumors expressing somatostatin receptors, especially with 90Y -- and 177Lu -- radiolabelled peptides. Recent and/or ongoing studies assure new perspectives to come. Dosimetry represents a precious guide for the selection of radionuclides and peptides, for protocol settings, for toxicity prevention and therapy optimization. Thus, reliable and personalized dosimetry is more and more requested. This paper reviews the important advances recently obtained in the dosimetric methods that have been applied to this therapy. Special emphasis has been given to the impact derived (or derivable in the next future) from more refined dose evaluations focused on the kidneys and the red marrow. The possibility of improving the accuracy of dosimetry represents a further challenge for this therapy. Following the preliminary correlation observed between the biological effective dose and the probability of renal injury, more reliable dose estimates could definitively enhance the predicitivity of the radiobiological effects, for toxicity prevention as well as for tumor control.

Dosimetry for treatment with radiolabelled somatostatin analogues. A review.

Peptide Receptor Radionuclide Therapy (PRRT) has proven its efficacy in the treatment of neuroendocrine and other somatostatin receptor expressing tumours (SR-tumours). Several clinical trials have confirmed that adverse effects are represented by possible renal impairment, which is the major concern, and low but not absent hematological toxicity. High kidney irradiation is a constant, despite the sparing of dose obtained by renal protectors. Hematological toxicity, although low, needs to be monitored. The clinical and dosimetry results collected in more than a decade have recognized weak points to unravel, increased knowledge, offering new views. When planning therapy with radiopeptides, the large patients' variability as for biodistribution and tumour uptake must be taken into account in order to tailor the therapy, or at least to avoid foreseeable gross treatments. Reliable and personalized dosimetry is more and more requested. This paper reviews through the literature the methods to study the biokinetics, the dosimetry outcomes, some clue information and correlations obtained once applying the radiobiological models. Special focus is given on recent improvements and indications for critical organ protection that light up challenging perspectives for PRRT.

IART (Intra-Operative Avidination for Radionuclide Therapy) for accelerated radiotherapy in breast cancer patients. Technical aspects and preliminary results of a phase II study with 90Y-labelled biotin.

BACKGROUND: Breast conserving surgery (BCS) plus external beam radiotherapy (EBRT) is considered the standard treatment for early breast cancer. We have investigated the possibility of irradiating the residual gland, using an innovative nuclear medicine approach named IART(®) (Intra-operative Avidination for Radionuclide Therapy). AIM: The objective of this study was to determine the optimal dose of avidin with a fixed activity (3.7 GBq) of (90)Y-biotin, in order to provide a boost of 20 Gy, followed by EBRT to the whole breast (WB) at the reduced dose of 40 Gy. Local and systemic toxicity, patient's quality of life, including the cosmetic results after the combined treatment with IART(®) and EBRT, were assessed. METHODS: After tumour excision, the surgeon injected native avidin diluted in 30 ml of saline solution into and around the tumour bed (see video). Patients received one of three avidin dose levels: 50 mg (10 pts), 100 mg (15 pts) and 150 mg (10 pts). Between 12 to 24 h after surgery, 3.7 GBq (90)Y-biotin spiked with 185 MBq (111)In-biotin was administered intravenously (i.v.). Whole body scans and SPECT images were performed up to 30 h post-injection for dosimetric purposes. WB-EBRT was administered four weeks after the IART(®) boost. Local toxicity and quality of life were evaluated. RESULTS: Thirty-five patients were evaluated. No side effects were observed after avidin administration and (90)Y-biotin infusion. An avidin dose level of 100 mg resulted the most appropriate in order to deliver the required radiation dose (19.5 ± 4.0 Gy) to the surgical bed. At the end of IART(®), no local toxicity occurred and the overall cosmetic result was good. The tolerance to the reduced EBRT was also good. The highest grade of transient local toxicity was G3, which occurred in 3/32 pts following the completion of WB-EBRT. The combination of IART(®)+EBRT was well accepted by the patients, without any changes to their quality of life. CONCLUSIONS: These preliminary results support the hypothesis that IART(®) may represent a valid approach to accelerated WB irradiation after BCS. We hope that this nuclear medicine technique will contribute to a better management of breast cancer patients.

SPECT/CT 90Y-Bremsstrahlung images for dosimetry during therapy.

BACKGROUND: the characteristics of (90)Y, suitable for therapy, are denoted by the lack of γ-emission. Alternative methods, using analogues labelled with (111)In or (86)Y, are generally applied to image (90)Y-conjugates, with some inevitable drawbacks. New generation SPECT/CT image systems offer improved Bremsstrahlung images. The intent of this brief communication is to show that high quality (90)Y-Bremsstrahlung SPECT-CT images can be obtained, allowing the biodistribution of pure ß-emitter therapeutical agents to be evaluated, also during the course of therapy. METHODS: the hybrid system Siemens Symbia-T2 was used for the acquisition of images of a patient given 1.7 GBq of (90)Y-DOTATATE. The following parameters were set for SPECT: 80 (50%) and 120 (30%) keV energy windows; medium energy collimators; 128 × 128 matrix, 64 projections (40s/step). Low-dose CT was acquired (80 mAs) for attenuation correction. Images were reconstructed with the OSEM 3D-Fast algorithm. RESULTS: post-therapy SPECT-CT (90)Y-Bremsstrahlung images of a patient undergoing receptor peptide radionuclide therapy are presented. (90)Y-Bremsstrahlung images obtained are suitable for tumour and normal organ dosimetry, providing detailed information on biodistribution, comparable to (111)In-diagnostic images. CONCLUSIONS: the improved Bremsstrahlung images means that the diagnostic examinations can be used for patient recruitment and that dosimetry evaluation can be restricted only to treated patients. This could avoid the need for a different radionuclide or isotope to mimic therapy. The clinical impact might be notable, as dosimetry and toxicity information are essential in radionuclide therapy, especially in patients with risk factors.