Pierre Vera

Strategies of Radioiodine Ablation in Patients with Low-Risk Thyroid Cancer

BACKGROUND It is not clear whether the administration of radioiodine provides any benefit to patients with low-risk thyroid cancer after a complete surgical resection. The administration of the smallest possible amount of radioiodine would improve care. METHODS In our randomized, phase 3 trial, we compared two thyrotropin-stimulation methods (thyroid hormone withdrawal and use of recombinant human thyrotropin) and two radioiodine ((131)I) doses (i.e., administered activities) (1.1 GBq and 3.7 GBq) in a 2-by-2 design. Inclusion criteria were an age of 18 years or older; total thyroidectomy for differentiated thyroid carcinoma; tumor-node-metastasis (TNM) stage, ascertained on pathological examination (p) of a surgical specimen, of pT1 (with tumor diameter ≤1 cm) and N1 or Nx, pT1 (with tumor diameter >1 to 2 cm) and any N stage, or pT2N0; absence of distant metastasis; and no iodine contamination. Thyroid ablation was assessed 8 months after radioiodine administration by neck ultrasonography and measurement of recombinant human thyrotropin-stimulated thyroglobulin. Comparisons were based on an equivalence framework. RESULTS There were 752 patients enrolled between 2007 and 2010; 92% had papillary cancer. There were no unexpected serious adverse events. In the 684 patients with data that could be evaluated, ultrasonography of the neck was normal in 652 (95%), and the stimulated thyroglobulin level was 1.0 ng per milliliter or less in 621 of the 652 patients (95%) without detectable thyroglobulin antibodies. Thyroid ablation was complete in 631 of the 684 patients (92%). The ablation rate was equivalent between the (131)I doses and between the thyrotropin-stimulation methods. CONCLUSIONS The use of recombinant human thyrotropin and low-dose (1.1 GBq) postoperative radioiodine ablation may be sufficient for the management of low-risk thyroid cancer. (Funded by the French National Cancer Institute [INCa] and the French Ministry of Health; ClinicalTrials.gov number, NCT00435851; INCa number, RECF0447.).

SUVmax reduction improves early prognosis value of interim positron emission tomography scans in diffuse large B-cell lymphoma.

The prognostic value of interim positron emission tomography (PET) interpreted according to visual criteria is a matter of debate in diffuse large B-cell lymphoma (DLBCL). Maximal standardized uptake value reduction (ΔSUVmax) may better predict outcome. To compare the prognostic value of both methods, we analyzed PET done at baseline (PET0) and after 2 (PET2) and 4 (PET4) cycles in 85 patients with high-risk DLBCL enrolled on a prospective multicenter trial. All images were centrally reviewed and interpreted visually according to the International Harmonization Project criteria and by computing ΔSUVmax between PET0 and PET2 (ΔSUVmaxPET0-2) or PET4 (ΔSUVmaxPET0-4). Optimal cutoff to predict progression or death was 66% for ΔSUVmaxPET0-2 and 70% for ΔSUVmaxPET0-4. Outcomes did not differ significantly whether PET2 and PET4 were visually positive or negative. Inversely, ΔSUVmaxPET0-2 analysis (> 66% vs ≤ 66%) identified patients with significantly different 2-year progression-free survival (77% vs 57%; P = .0282) and overall survival (93% vs 60%; P < .0001). ΔSUVmaxPET0-4 analysis (> 70% vs ≤ 70%) seemed even more predictive for 2-year progression-free survival (83 vs 40%; P < .0001) and overall survival (94% vs 50%; P < .0001). ΔSUVmax analysis of sequential interim PET is feasible for high-risk DLBCL and better predicts outcome than visual analysis. The trial was registered at http://clinicaltrials.gov as NCT00498043.

Interim [18F]Fluorodeoxyglucose Positron Emission Tomography Scan in Diffuse Large B-Cell Lymphoma Treated With Anthracycline-Based Chemotherapy Plus Rituximab

PURPOSE The prognostic value of [(18)F]fluorodeoxyglucose-positron emission tomography (PET), interpreted according to visual criteria, is a matter of debate for diffuse large B-cell lymphoma (DLBCL). Moreover, most published studies do not differentiate between patients treated with or without rituximab. We retrospectively investigated the prognostic value of PET performed in patients with DLBCL receiving chemotherapy plus rituximab. Images were interpreted both visually and by computing maximum standardized uptake value (SUV(max)) between PET performed at baseline and after two cycles of chemotherapy. PATIENTS AND METHODS One hundred twelve patients newly diagnosed with DLBCL were treated with an anthracycline-based regimen plus rituximab. A PET was performed after two cycles of treatment. PET positivity or negativity was related to progression-free survival (PFS) and overall survival (OS) using Kaplan-Meier analysis. RESULTS Visual analysis showed that 70 patients (62.5%) presented with a negative PET scan after two cycles of treatment. The 3-year PFS and OS rates were 84% and 88%, respectively, in patients with PET-negative results versus 47% and 62%, respectively, in patients with PET-positive results (P < .0001 and P < .003, respectively). A second analysis was performed on 85 patients by using interim PET in a quantitative approach on the basis of a ΔSUV(max) evaluation of more than 66%. The 3-year PFS was 77% for patients with PET-negative results and 37.5% for patients with PET-positive results (P = .002). CONCLUSION An early PET scan after two cycles of treatment can effectively predict the outcome in patients with DLBCL treated with rituximab and anthracycline-based chemotherapy by using either a visual or quantitative approach.

Impact of [18F]Fluorodeoxyglucose Positron Emission Tomography Response Evaluation in Patients With High–Tumor Burden Follicular Lymphoma Treated With Immunochemotherapy: A Prospective Study From the Groupe d'Etudes des Lymphomes de l'Adulte and GOELAMS

PURPOSE [(18)F]Fluorodeoxyglucose positron emission tomography (PET) is widely used for the staging and restaging of patients with aggressive lymphoma, but less is known about the utility of PET in patients with follicular lymphoma (FL). In a prospective study, we evaluated the prognostic value of PET performed during treatment and at the end of treatment in 121 patients with FL treated with first-line immunochemotherapy. PATIENTS AND METHODS Patients with previously untreated high-tumor burden FL were treated with six cycles of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) plus two cycles of rituximab, without rituximab maintenance. PET was performed before treatment, after four cycles of R-CHOP (interim PET), and at the end of treatment (final PET). PET scans were centrally reviewed. RESULTS The total number of patients included was 121. Median age was 57 years. After central review, interim PET (n = 111) was negative in 76% of patients, and final PET (n = 106) was negative in 78%. With a median follow-up of 23 months, 2-year progression-free survival rates were 86% for interim PET-negative versus 61% for interim PET-positive patients (P = .0046) and 87% for final PET-negative versus 51% for final PET-positive patients (P < .001), respectively. Two-year overall survival also significantly differed according to final PET results: 100% versus 88% (P = .0128). CONCLUSION PET performed either after four cycles of R-CHOP or at the end of therapy was strongly predictive of outcome in this prospective study. Therapeutic intervention based on PET results during or after inductive treatment should be evaluated.

Simultaneous positron emission tomography (PET) assessment of metabolism with 18F-fluoro-2-deoxy-d-glucose (FDG), proliferation with 18F-fluoro-thymidine (FLT), and hypoxia with 18fluoro-misonidazole (F-miso) before and during radiotherapy in patients with non-small-cell lung cancer (NSCLC): A pilot study

OBJECTIVES To investigate the changes in tumour proliferation (using FLT), metabolism (using FDG), and hypoxia (using F-miso) during curative (chemo-) radiotherapy (RT) in patients with non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS Thirty PET scans were performed in five patients (4 males, 1 female) that had histological proof of NSCLC and were candidates for curative-intent RT. Three PET-CT (Biograph S16, Siemens) scans were performed before (t(0)) and during (around dose 46 Gy, t(46)) RT with minimal intervals of 48 h between each PET-CT scan. The tracers used were (18)fluoro-2deoxyglucose (FDG) for metabolism, (18)fluorothymidine (FLT) for proliferation, and (18)F-misonidasole (F-miso) for hypoxia. The 3 image sets obtained at each time point were co-registered (rigid: n=9, elastic: n=1, Leonardo, TrueD, Siemens) using FDG PET-CT as reference. VOIs were delineated (40% SUV(max) values were used as a threshold) for tumours and lymph nodes on FDG PET-CT, and they were automatically pasted on FLT and F-miso PET-CT images. ANOVA and correlation analyses were used for comparison of SUV(max) values. RESULTS Four tumours and twelve nodes were identified on initial FDG PET-CT images. FLT SUV(max) values were significantly lower (p<0.0006) at t(46) in both tumours and nodes. The decrease in FDG SUV(max) values had a trend towards significance (p=0.048). F-Miso SUV(max) values were significantly higher in tumours than in nodes (p=0.02) and did not change during radiotherapy (p=0.39). A significant correlation was observed between FLT and FDG uptake (r=0.56, p<10(-4)) when all data were pooled together, and they remained similar when the before and during RT data were analysed separately. FDG and F-miso uptakes were significantly correlated (r=0.59, p=0.0004) when all data were analysed together. The best fit was obtained after adjusting for lesion type (tumour vs. node). This correlation was observed for the SUV(max) measured during RT (r=0.70, p=0.008) but not for the pre-RT data (r=0.19, p=0.35). The weak correlation between FLT and F-miso uptakes only became significant (r=0.66, p=0.002) when the analysis was restricted to the data acquired during RT. CONCLUSION Three different PET acquisitions can be performed quasi-simultaneously (4-7 days) before and during radiotherapy in patients with NSCLC. Our results at 46 Gy suggest that a fast decrease in the proliferation of both tumours and nodes exists during radiotherapy with differences in metabolism (borderline significant decrease) and hypoxia (stable).

Development of a generic thresholding algorithm for the delineation of 18FDG-PET-positive tissue: application to the comparison of three thresholding models

An iterative generic algorithm has been developed to compare three thresholding models used to delineate gross tumour volume on (18)F-FDG PET images. 3D volume was extracted and characteristic parameters were measured. Three fitting models using different parameters were studied: model 1 (volume, contrast), model 2 (contrast) and model 3 (SUV). The calibration was performed using a cylindrical phantom filled with hot spheres. To validate the models, two other phantoms were used. The calibration procedure showed a better fitting model for model 1 (R(2) from 0.94 to 1.00) than for model 3 (0.95) and model 2 (0.69). The validation study shows that model 3 yielded large volume measurement errors. Models 1 and 2 gave close results with no significant differences. Model 2 was preferred because it presents less error dispersion and needs fewer characteristic parameters, making it easier to implement. Our results show the importance of developing a generic algorithm to compare the performances of fitting models objectively and to validate results on other phantoms than the ones used during the calibration process to avoid methodological biases.

Frontal Assessment Battery is a marker of dorsolateral and medial frontal functions: A SPECT study in frontotemporal dementia

The objective of this study is to identify the cerebral regions that are assessed by the Frontal Assessment Battery (FAB). Using SPM voxel-based analysis, we looked for correlations between FAB performance and brain SPECT perfusion in 47 patients with the frontal variant of frontotemporal dementia (fv-FTD) recruited by the French FTD research network, a multicentre initiative of French University hospitals with expertise in the field of dementia. A significant correlation was found between FAB performance and perfusion in the medial and dorsolateral frontal cortex bilaterally, independently of age, gender and MMSE. No correlations were observed with orbital frontal or parietal perfusion, in spite of the presence of hypoperfusion in these areas, or with perfusion of any other cortical or subcortical region. These findings confirm that the FAB is an adequate tool for assessing functions related to the dorsolateral and medial frontal cortex, and is thus useful for the evaluation of diseases associated with frontal dysfunction.

Validation of the Monte Carlo simulator GATE for indium-111 imaging

Monte Carlo simulations are useful for optimizing and assessing single photon emission computed tomography (SPECT) protocols, especially when aiming at measuring quantitative parameters from SPECT images. Before Monte Carlo simulated data can be trusted, the simulation model must be validated. The purpose of this work was to validate the use of GATE, a new Monte Carlo simulation platform based on GEANT4, for modelling indium-111 SPECT data, the quantification of which is of foremost importance for dosimetric studies. To that end, acquisitions of (111)In line sources in air and in water and of a cylindrical phantom were performed, together with the corresponding simulations. The simulation model included Monte Carlo modelling of the camera collimator and of a back-compartment accounting for photomultiplier tubes and associated electronics. Energy spectra, spatial resolution, sensitivity values, images and count profiles obtained for experimental and simulated data were compared. An excellent agreement was found between experimental and simulated energy spectra. For source-to-collimator distances varying from 0 to 20 cm, simulated and experimental spatial resolution differed by less than 2% in air, while the simulated sensitivity values were within 4% of the experimental values. The simulation of the cylindrical phantom closely reproduced the experimental data. These results suggest that GATE enables accurate simulation of (111)In SPECT acquisitions.

Evaluation of a Rigid Registration Method of Lung Perfusion SPECT and Thoracic CT

OBJECTIVE The objective of our study was to evaluate a rigid registration method in lung perfusion SPECT using thoracic CT as a standard. MATERIALS AND METHODS The reproducibility of markers selection and the robustness of the method were assessed on a torso phantom. The accuracy of registration regarding the number and location of markers and the breathing state during CT was evaluated on eight patients using 10 external markers placed around the thorax before SPECT and CT acquisitions. The accuracy of registration was assessed using the mean errors (ME) between 10 markers after registration. RESULTS Registration using external markers on a phantom was accurate (ME, < 3 mm) when rotation was less than 40 degrees (p = 0.02). The accuracy of registration improved markedly from four to six markers for phantom (5.5-3.6 mm) and patients (11.2-9.5 mm) and then remained constant up to 10 markers. The ME was less when using markers that well encompassed the thorax for phantom and patients (p = 0.02 and p = 0.05, respectively). The use of four anatomic markers was not accurate (ME, 20 mm). CONCLUSION The registration method is reproducible and accurate, and six external markers were required to get an ME of less than 10 mm in patients.

Leukocyte SPECT/CT for Detecting Infection of Left-Ventricular-Assist Devices: Preliminary Results

We report our experience with using integrated molecular and anatomic hybrid imaging to assess infection in patients who have a left-ventricular-assist device (LVAD). Methods: Thirteen 99mTc-exametazime-leukocyte planar and SPECT/CT scans were obtained for 8 consecutive patients who had an implanted LVAD. SPECT/CT was used to assess suspected device-related infections (n = 8) and to evaluate the efficiency of current antibiotic therapy (n = 5). Results: Device-related infection was seen on 8 of the 13 scans. SPECT/CT was positive for infection in all 8 patients, whereas planar scans were positive in 6 of 8. SPECT/CT provided relevant information on the extent of infection and its exact location in all patients. Additional distant infectious foci were demonstrated in 3 of 13 patients. Conclusion: SPECT/CT led to an accurate diagnosis of LVAD-related infection, revealing both anatomic location and extent. This noninvasive approach could lead to improved therapeutic strategies.