Publications by authors named "Emilio Mezzenga"

15 Publications

  • Page 1 of 1

Exploratory Analysis of F-3'-deoxy-3'-fluorothymidine (F-FLT) PET/CT-Based Radiomics for the Early Evaluation of Response to Neoadjuvant Chemotherapy in Patients With Locally Advanced Breast Cancer.

Front Oncol 2021 24;11:601053. Epub 2021 Jun 24.

Nuclear Medicine Unit, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) "Dino Amadori," Meldola, Italy.

Purpose: The objective of this study was to evaluate a set of radiomics-based advanced textural features extracted from F-FLT-PET/CT images to predict tumor response to neoadjuvant chemotherapy (NCT) in patients with locally advanced breast cancer (BC).

Materials And Methods: Patients with operable (T2-T3, N0-N2, M0) or locally advanced (T4, N0-N2, M0) BC were enrolled. All patients underwent chemotherapy (six cycles every 3 weeks). Surgery was performed within 4 weeks of the end of NCT. The MD Anderson Residual Cancer Burden calculator was used to evaluate the pathological response. F-FLT-PET/CT was performed 2 weeks before the start of NCT and approximately 3 weeks after the first cycle. The evaluation of PET response was based on EORTC criteria. Standard uptake value (SUV) statistics (SUV, SUV, SUV), together with 148 textural features, were extracted from each lesion. Indices that are robust against contour variability (ICC test) were used as independent variables to logistically model tumor response. LASSO analysis was used for variable selection.

Results: Twenty patients were included in the study. Lesions from 15 patients were evaluable and analyzed: 9 with pathological complete response (pCR) and 6 with pathological partial response (pPR). Concordance between PET response and histological examination was found in 13/15 patients. LASSO logistic modelling identified a combination of SUV and the textural feature index IVH_VolumeIntFract_90 as the most useful to classify PET response, and a combination of PET response, ID range, and ID_Coefficient of Variation as the most useful to classify pathological response.

Conclusions: Our study suggests the potential usefulness of FLT-PET for early monitoring of response to NCT. A model based on PET radiomic characteristics could have good discriminatory capacity of early response before the end of treatment.
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http://dx.doi.org/10.3389/fonc.2021.601053DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8264651PMC
June 2021

Geometric contour variation in clinical target volume of axillary lymph nodes in breast cancer radiotherapy: an AIRO multi-institutional study.

Br J Radiol 2021 Jul 21;94(1123):20201177. Epub 2021 Apr 21.

Radiation Oncology Unit, Istituti Clinici Scientifici Maugeri IRCCS, Pavia, Italy.

Objectives: To determine interobserver variability in axillary nodal contouring in breast cancer (BC) radiotherapy (RT) by comparing the clinical target volume of participating single centres (SC-CTV) with a gold-standard CTV (GS-CTV).

Methods: The GS-CTV of three patients (P1, P2, P3) with increasing complexity was created in DICOM format from the median contour of axillary CTVs drawn by BC experts, validated using the simultaneous truth and performance-level estimation and peer-reviewed. GS-CTVs were compared with the correspondent SC-CTVs drawn by radiation oncologists, using validated metrics and a total score (TS) integrating all of them.

Results: Eighteen RT centres participated in the study. Comparative analyses revealed that, on average, the SC-CTVs were smaller than GS-CTV for P1 and P2 (by -29.25% and -27.83%, respectively) and larger for P3 (by +12.53%). The mean Jaccard index was greater for P1 and P2 compared to P3, but the overlap extent value was around 0.50 or less. Regarding nodal levels, L4 showed the highest concordance with the GS. In the intra-patient comparison, L2 and L3 achieved lower TS than L4. Nodal levels showed discrepancy with GS, which was not statistically significant for P1, and negligible for P2, while P3 had the worst agreement. DICE similarity coefficient did not exceed the minimum threshold for agreement of 0.70 in all the measurements.

Conclusions: Substantial differences were observed between SC- and GS-CTV, especially for P3 with altered arm setup. L2 and L3 were the most critical levels. The study highlighted these key points to address.

Advances In Knowledge: The present study compares, by means of validated geometric indexes, manual segmentations of axillary lymph nodes in breast cancer from different observers and different institutions made on radiotherapy planning CT images. Assessing such variability is of paramount importance, as geometric uncertainties might lead to incorrect dosimetry and compromise oncological outcome.
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http://dx.doi.org/10.1259/bjr.20201177DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8248216PMC
July 2021

Targeted Alpha Therapy in mCRPC (Metastatic Castration-Resistant Prostate Cancer) Patients: Predictive Dosimetry and Toxicity Modeling of Ac-PSMA (Prostate-Specific Membrane Antigen).

Front Oncol 2020 5;10:531660. Epub 2020 Nov 5.

Nuclear Medicine Unit, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy.

Radioligand therapy is a type of internal radiotherapy combining a short-range radioisotope labeled to a carrier with a high affinity for a specific receptor expressed on tumor cells. Targeted alpha therapy (TAT) combines a high-linear energy transfer (LET) emitter (Ac) with a prostate-specific membrane antigen (PSMA) carrier, specifically binding tumor cells in patients with metastatic castration-resistant prostate cancer. Although the antitumor activity of Ac-PSMA is well-documented, this treatment is nowadays only used as salvage therapy because the high incidence of xerostomia limits the therapeutic window. Thus, methods to reduce salivary toxicity and models able to describe xerostomia incidence are needed. We recently studied the efficacy of salivary gland protectors administered in combination with Lu-PSMA therapy. Starting from these data, we performed a predictive dosimetric evaluation of Ac-PSMA to assess the impact of salivary gland protectors in TAT. Ac-PSMA predictive dosimetry was performed in 13 patients treated with Lu-PSMA. Sequential whole-body planar images were acquired 0.5-1, 16-24, 36-48, and 120 h post-injection. Lu time-activity curves were corrected for Ac physical decay and assumed in equilibrium for all daughters. The OLINDA/EXM spherical model was used for dose estimation of the parotid and submandibular glands. The dose for each daughter was calculated and summed for the total dose estimation. The biologically effective dose formalism was extended to high-LET emitters. For the total biologically effective dose formalism extended to high-LET emitters, including the contribution of all daughter isotopes, the brachytherapy formalism for a mixture of radionuclides was implemented. Equivalent doses in 2 Gy/fraction (EQD2) were then calculated and compared with the normal tissue complication probability model derived from external beam radiotherapy for grade ≥2 xerostomia induction. Median predictive doses were 0.86 Bd/MBq for parotid glands and 1.05 Bd/MBq for submandibular glands, with a 53% reduction compared with previously published data. The results show that the radiobiological model implemented is conservative, as it overestimates the complication rate with respect to the clinical data. Our data shows the possibility of reducing salivary gland uptake in TAT with the coadministration of organ protectors, but these results should be confirmed for TAT with Ac-PSMA by carrying out prospective trials with defined toxicity endpoints and dosimetry procedures.
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http://dx.doi.org/10.3389/fonc.2020.531660DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7674768PMC
November 2020

A Whole Body Dosimetry Protocol for Peptide-Receptor Radionuclide Therapy (PRRT): 2D Planar Image and Hybrid 2D+3D SPECT/CT Image Methods.

J Vis Exp 2020 04 24(158). Epub 2020 Apr 24.

Medical Physics Unit, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy.

Peptide-receptor-radionuclide-therapy (PPRT) is a targeted therapy that combines a short-range energy radionuclide with a substrate with high specificity for cancer cell receptors. After injection, the radiotracer is distributed throughout the entire body, with a higher uptake in tissues where targeted receptors are overexpressed. The use of beta/gamma radionuclide emitters enables therapy imaging (beta-emission) and post-therapy imaging (gamma-emission) to be performed at the same time. Post-treatment sequential images permit absorbed dose calculation based on local uptake and wash-in/wash-out kinetics. We implemented a hybrid method that combines information derived from both 2D and 3D images. Serial whole-body images and blood samples are acquired to estimate the absorbed dose to different organs at risk and to lesions disseminated throughout the body. A single 3D-SPECT/CT image, limited to the abdominal region, overcomes projection overlap on planar images of different structures such as the intestines and kidneys. The hybrid 2D+3D-SPECT/CT method combines the effective half-life information derived from 2D planar images with the local uptake distribution derived from 3D images. We implemented this methodology to estimate the absorbed dose for patients undergoing PRRT with Lu-PSMA-617. The methodology could, however, be implemented with other beta-gamma radiotracers. To date, 10 patients have been enrolled into the dosimetry study with Lu-PSMA-617 combined with drug protectors for kidneys and salivary glands (mannitol and glutamate tablets, respectively). The median ratio between kidney uptake at 24 h evaluated on planar images and 3D-SPECT/CT is 0.45 (range:0.32-1.23). The comparison between hybrid and full 3D approach has been tested on one patient, resulting in a 1.6% underestimation with respect to full 3D (2D: 0.829 mGy/MBq, hybrid: 0.315 mGy/MBq, 3D: 0.320 mGy/MBq). Treatment safety has been confirmed, with a mean absorbed dose of 0.73 mGy/MBq (range:0.26-1.07) for kidneys, 0.56 mGy/MBq (0.33-2.63) for the parotid glands and 0.63 mGy/MBq (0.23-1.20) for submandibular glands, values in accordance with previously published data.
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http://dx.doi.org/10.3791/60477DOI Listing
April 2020

SUV as a Reliable Alternative to SUV for Determining Renal Uptake in [Ga] PSMA PET/CT.

Mol Imaging Biol 2020 08;22(4):1070-1077

Medical Physics Unit, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy.

Purpose: Widely used in clinical practice, the maximum standardized uptake value (SUV) is a statistical index highly prone to physical and biological variations, which can lead to unpredictable errors. This study has a methodological aim: to identify a more robust SUV-based index representing the tracer accumulation. In particular, the new metric was tested to confirm the potential of mannitol to reduce renal uptake Ga-68 prostate-specific membrane antigen ([Ga]PSMA).

Procedures: To this aim, our previously published work, proving the efficacy of mannitol, was considered as a background study. Renal SUV was calculated in nine patients undergoing [Ga]PSMA positron emission tomography (PET)/X-ray computed tomography (CT) at baseline (b-PET/CT) and at follow-up after intravenous infusion of 500 ml of 10 % mannitol (m-PET/CT). SUV values of kidney volumes were extracted by a new 3D segmentation method. A new parameter, the median computed on the upper 10% of the SUV distribution (SUV), was introduced to better characterize the tracer accumulation. A comparison between SUV and SUV was also performed. Kruskal-Wallis test was used to assess the statistical significance of the differences in SUV between b-PET/CT and m-PET/CT.

Results: SUV not only confirmed the efficacy of mannitol as demonstrated in the previous study but improved the separability of b-PET/CT and m-PET/CT examinations, overturning SUV findings in two cases. The outcomes of the Kruskal-Wallis test computed for each kidney proved that differences between b-PET/CT and m-PET/CT SUV values were significant (p value < 0.001).

Conclusions: Our findings indicate that SUV is a more robust index to assess high uptake level, representing a reliable alternative to SUV. Independently from the segmentation method, the superiority of SUV and its easy computation could make its clinical impact decisive. The results obtained with SUV, more representative of tracer uptake than those with SUV suggest, in our opinion, that mannitol infusion could be used to reduce the adsorbed dose to the kidneys during [Ga]PSMA PET/CT and Lu-177 or Ac-225 therapy. Our future goal will be confirming this effect in a larger cohort of patients, also verifying the role of SUV in the evaluation of tumor response to therapy.
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http://dx.doi.org/10.1007/s11307-019-01451-1DOI Listing
August 2020

Departmental action limits for TQA energy variations defined by means of statistical process control methods.

Australas Phys Eng Sci Med 2019 Aug 26. Epub 2019 Aug 26.

Queensland University of Technology Science and Engineering Faculty, Brisbane, 4000, Australia.

The purpose of this study is to define departmental action limits for energy percentage variation measured by means of step-wedge helical Tomotherapy quality assurance module. Individual charts using the Statistical Process Control techniques have been used to identify retrospectively out-of-control situations ascribable to documented actions performed on the Tomotherapy system. Using the in-control data of our analysis process capability indices (c, c, c and c) are calculated in order to document the real working condition of the Tomotherapy system. Our findings indicate use of an action limit of 1.0% for energy percentage variation difference between the measured and reference output is a good working condition of a Tomotherapy system. c and c indices are suggested as good indices that correctly report the system capability. A method for calculating and reporting Tomotherapy action limits for the integrated self-checking TQA energy check was shown in this study. SPC technique has proven to be efficient in defining departmental action limits from retrospective data for TQA energy measurements, hence optimally enabling corrective improvements in the process of quality assurance.
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http://dx.doi.org/10.1007/s13246-019-00791-0DOI Listing
August 2019

Texture analysis in 177Lu SPECT phantom images: Statistical assessment of uniformity requirements using texture features.

PLoS One 2019 31;14(7):e0218814. Epub 2019 Jul 31.

Nuclear Medicine Unit, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Forli-Cesena, Italy.

The purpose of this study was to apply texture analysis (TA) to evaluate the uniformity of SPECT images reconstructed with the 3D Ordered Subsets Expectation Maximization (3D-OSEM) algorithm. For this purpose, a cylindrical homogeneous phantom filled with 177Lu was used and a total of 24 spherical volumes of interest (VOIs) were considered inside the phantom. The location of the VOIs was chosen in order to define two different configurations, i.e. gravity and radial configuration. The former configuration was used to investigate the uniformity of distribution of 177Lu inside the phantom, while the latter configuration was used to investigate the lack of uniformity from center towards edge of the images. For each VOI, the trend of different texture features considered as a function of 3D-OSEM updates was investigated in order to evaluate the influence of reconstruction parameters. TA was performed using CGITA software. The equality of the average texture feature trends in both spatial configurations was assumed as the null hypothesis and was tested by functional analysis of variance (fANOVA). With regard to the gravity configuration, no texture feature rejected the null hypothesis when the number of subsets increased. For the radial configuration, the statistical analysis revealed that, depending on the 3D-OSEM parameters used, a few texture features were capable of detecting the non-uniformity of 177Lu distribution inside the phantom moving from the center of the image towards its edge. Finally, cross-correlation coefficients were calculated to better identify the features that could play an important role in assessing quality assurance procedures performed on SPECT systems.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0218814PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6668785PMC
February 2020

Dosimetry of Lu-PSMA-617 after Mannitol Infusion and Glutamate Tablet Administration: Preliminary Results of EUDRACT/RSO 2016-002732-32 IRST Protocol.

Molecules 2019 Feb 11;24(3). Epub 2019 Feb 11.

Nuclear Medicine Unit, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, 47014 Meldola, Italy.

Radio-ligand therapy (RLT) withLu-PSMA-617 is a promising option for patients with metastatic castration-resistant prostate-cancer (mCRPC). A prospective phase-II study (EUDRACT/RSO,2016-002732-32) on mCRPC is ongoing at IRST (Meldola, Italy). A total of 9 patients (median age: 68 y, range: 53⁻85) were enrolled for dosimetry evaluation of parotid glands (PGs), kidneys, red marrow (RM) and whole body (WB). Folic polyglutamate tablets were orally administered as PGs protectors and 500 mL of a 10% mannitol solution was intravenously infused to reduce kidney uptake. The whole body planar image (WBI) and blood samples were acquired at different times post infusion (1 h, 16⁻24 h, 36⁻48 h and 120 h). Dose calculation was performed with MIRD formalism (OLINDA/EXM software). The median effective half-life was 33.0 h (range: 25.6⁻60.7) for PGs, 31.4 h (12.2⁻80.6) for kidneys, 8.2 h (2.5⁻14.7) for RM and 40.1 h (31.6⁻79.7) for WB. The median doses were 0.48 mGy/MBq (range: 0.33⁻2.63) for PGs, 0.70 mGy/MBq (0.26⁻1.07) for kidneys, 0.044 mGy/MBq (0.023⁻0.067) for RM and 0.04 mGy/MBq (0.02⁻0.11) for WB. A comparison with previously published dosimetric data was performed and a significant difference was found for PGs while no significant difference was observed for the kidneys. For PGs, the possibility of reducing uptake by administering glutamate tablets during RLT seems feasible while further research is warranted for a more focused evaluation of the reduction in kidney uptake.
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http://dx.doi.org/10.3390/molecules24030621DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6385027PMC
February 2019

Quantitative accuracy of 177Lu SPECT imaging for molecular radiotherapy.

PLoS One 2017 14;12(8):e0182888. Epub 2017 Aug 14.

Medical Physics Unit, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy.

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.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0182888PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5564164PMC
October 2017

Reduction of Ga-PSMA renal uptake with mannitol infusion: preliminary results.

Eur J Nucl Med Mol Imaging 2017 Dec 11;44(13):2189-2194. Epub 2017 Aug 11.

Nuclear Medicine Unit, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy.

Purpose: Urea-based prostate-specific membrane antigen (PSMA) ligands labelled with Ga or Lu are new tracers with great potential for theranostic approaches in prostate cancer. However, clinical studies have shown that the kidneys are one of the off-target organs along with the salivary and lacrimal glands. In the kidneys, PSMA is physiologically expressed in the apical epithelium of the proximal tubules, and mannitol acts as an osmotic diuretic in these tubules. We investigated the potential of mannitol to reduce renal uptake of Ga-PSMA.

Methods: Kidney uptake (SUVmax) was calculated in nine patients undergoing Ga-PSMA PET/CT at baseline (b-PET/CT) and after intravenous infusion of 500 ml of 10% mannitol (m-PET/CT). Two different infusion schemes for mannitol were used: (1) 500 ml mannitol was infused over 40 min after Ga-PSMA administration (A-infusion) and (2) 250 ml mannitol was infused over 15 min before and again after Ga-PSMA administration (B-infusion).

Results: In patients receiving the A-infusion, mean SUV increased by 11.9% and 7.4% in the right and left kidney, respectively. In patients receiving the B-infusion, mean SUV decreased by 24.3% and 22.4% in the right and left kidney, respectively.

Conclusion: Our preliminary findings indicate that mannitol may play a role in reducing off-target Ga-PSMA renal uptake. Administration of the osmotic diuretic should be rapid and start before Ga-PSMA injection. These results warrant dosimetric studies in patients treated with Lu-PSMA to find the best scheme for mannitol administration.
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http://dx.doi.org/10.1007/s00259-017-3791-4DOI Listing
December 2017

Investigating output and energy variations and their relationship to delivery QA results using Statistical Process Control for helical tomotherapy.

Phys Med 2017 Jun 24;38:105-110. Epub 2017 May 24.

Cancer Care Services, Royal Brisbane and Women's Hospital, Brisbane, Australia; Queensland University of Technology, Brisbane, Australia.

The aims of this study were to investigate machine beam parameters using the TomoTherapy quality assurance (TQA) tool, establish a correlation to patient delivery quality assurance results and to evaluate the relationship between energy variations detected using different TQA modules. TQA daily measurement results from two treatment machines for periods of up to 4years were acquired. Analyses of beam quality, helical and static output variations were made. Variations from planned dose were also analysed using Statistical Process Control (SPC) technique and their relationship to output trends were studied. Energy variations appeared to be one of the contributing factors to delivery output dose seen in the analysis. Ion chamber measurements were reliable indicators of energy and output variations and were linear with patient dose verifications.
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http://dx.doi.org/10.1016/j.ejmp.2017.05.052DOI Listing
June 2017

MR Spectroscopy in Prostate Cancer: New Algorithms to Optimize Metabolite Quantification.

PLoS One 2016 10;11(11):e0165730. Epub 2016 Nov 10.

Medical Physics Unit, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, FC, Italy.

Prostate cancer (PCa) is the most common non-cutaneous cancer in male subjects and the second leading cause of cancer-related death in developed countries. The necessity of a non-invasive technique for the diagnosis of PCa in early stage has grown through years. Proton magnetic resonance spectroscopy (1H-MRS) and proton magnetic resonance spectroscopy imaging (1H-MRSI) are advanced magnetic resonance techniques that can mark the presence of metabolites such as citrate, choline, creatine and polyamines in a selected voxel, or in an array of voxels (in MRSI) inside prostatic tissue. Abundance or lack of these metabolites can discriminate between pathological and healthy tissue. Although the use of magnetic resonance spectroscopy (MRS) is well established in brain and liver with dedicated software for spectral analysis, quantification of metabolites in prostate can be very difficult to achieve, due to poor signal to noise ratio and strong J-coupling of the citrate. The aim of this work is to develop a software prototype for automatic quantification of citrate, choline and creatine in prostate. Its core is an original fitting routine that makes use of a fixed step gradient descent minimization algorithm (FSGD) and MRS simulations developed with the GAMMA libraries in C++. The accurate simulation of the citrate spin systems allows to predict the correct J-modulation under different NMR sequences and under different coupling parameters. The accuracy of the quantifications was tested on measurements performed on a Philips Ingenia 3T scanner using homemade phantoms. Some acquisitions in healthy volunteers have been also carried out to test the software performance in vivo.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0165730PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5104319PMC
June 2017

Long-term follow-up and role of FDG PET in advanced pancreatic neuroendocrine patients treated with Lu-D OTATATE.

Eur J Nucl Med Mol Imaging 2017 Mar 4;44(3):490-499. Epub 2016 Oct 4.

Nuclear Medicine Unit, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy.

Purpose: Lu-DOTATATE (Lu-PRRT) is a valid therapeutic option in differentiated pancreatic neuroendocrine tumors (P-NETs). FDG PET seems to be an important prognostic factor in P-NETs. We evaluated the efficacy of Lu-PRRT and the role of FDG PET in 60 patients with advanced P-NETs.

Methods: From March 2008 to June 2011, 60 consecutive patients with P-NETs were enrolled in the study. Follow-up lasted until March 2016. Eligible patients were treated with two different total cumulative activities (18.5 or 27.8 GBq in 5 cycles every 6-8 weeks), according to kidney and bone marrow parameters.

Results: Twenty-eight patients received a mean full activity (FA) of 25.9 GBq and 32 a mean reduced activity (RA) of 18.5 GBq. The disease control rate (DCR), defined as the sum of CR+PR+SD was 85.7 % in the FA group and 78.1 % in the RA group. Median progression-free survival (mPFS) was 53.4 months in the FA group and 21.7 months in the RA group (P = 0.353). Median overall survival (mOS) was not reached (nr) in FA patients and was 63.8 months in the RA group (P = 0.007). Fifty-five patients underwent an FDG PET scan before Lu-PRRT, 32 (58 %) showing an increased FDG uptake in tumor sites. mPFS was 21.1 months in FDG PET-positive patients and 68.7 months in the FDG PET-negative group (P < 0.0002), regardless of the total activity administered.

Conclusion: Both FA and RA are active in patients undergoing Lu-PRRT. However, an FA of 27.8 GBq of Lu-PRRT prolongs PFS and OS compared to an RA of 18.5 GBq. Our results indicate that FDG PET is an independent prognostic factor in this patient setting.
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http://dx.doi.org/10.1007/s00259-016-3533-zDOI Listing
March 2017

Preliminary Retrospective Analysis of Daily Tomotherapy Output Constancy Checks Using Statistical Process Control.

PLoS One 2016 5;11(2):e0147936. Epub 2016 Feb 5.

Medical Physics Department, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, FC, Italy.

The purpose of this study was to retrospectively evaluate the results from a Helical TomoTherapy Hi-Art treatment system relating to quality controls based on daily static and dynamic output checks using statistical process control methods. Individual value X-charts, exponentially weighted moving average charts, and process capability and acceptability indices were used to monitor the treatment system performance. Daily output values measured from January 2014 to January 2015 were considered. The results obtained showed that, although the process was in control, there was an out-of-control situation in the principal maintenance intervention for the treatment system. In particular, process capability indices showed a decreasing percentage of points in control which was, however, acceptable according to AAPM TG148 guidelines. Our findings underline the importance of restricting the acceptable range of daily output checks and suggest a future line of investigation for a detailed process control of daily output checks for the Helical TomoTherapy Hi-Art treatment system.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0147936PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4746057PMC
July 2016
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