Emmanuel Itti

Bone marrow involvement in diffuse large B-cell lymphoma: correlation between FDG-PET uptake and type of cellular infiltrate

PurposeTo assess, in patients with diffuse large B-cell lymphoma (DLBCL), whether the low sensitivity of 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) for bone marrow assessment may be explained by histological characteristics of the cellular infiltrate.MethodsFrom a prospective cohort of 110 patients with newly diagnosed aggressive lymphoma, 21 patients with DLBCL had bone marrow involvement. Pretherapeutic FDG-PET images were interpreted visually and semiquantitatively, then correlated with the type of cellular infiltrate and known prognostic factors.ResultsOf these 21 patients, 7 (33%) had lymphoid infiltrates with a prominent component of large transformed lymphoid cells (concordant bone marrow involvement, CBMI) and 14 (67%) had lymphoid infiltrates composed of small cells (discordant bone marrow involvement, DBMI). Only 10 patients (48%) had abnormal bone marrow FDG uptake, 6 of the 7 with CBMI and 4 of the 14 with DBMI. Therefore, FDG-PET positivity in the bone marrow was significantly associated with CBMI, while FDG-PET negativity was associated with DBMI (Fisher’s exact test, p=0.024). There were no significant differences in gender, age and overall survival between patients with CBMI and DBMI, while the international prognostic index was significantly higher in patients with CBMI.ConclusionOur study suggests that in patients with DLBCL with bone marrow involvement bone marrow FDG uptake depends on two types of infiltrate, comprising small (DBMI) or large (CBMI) cells. This may explain the apparent low sensitivity of FDG-PET previously reported for detecting bone marrow involvement.

Phase II study of sirolimus in treatment-naive patients with advanced hepatocellular carcinoma

BACKGROUNDnRapalogs are emerging as promising targeted anticancer drugs. Activation of the PI3K/Akt/mTOR pathway has been observed in 15-50% of hepatocellular carcinomas.nnnMETHODSnIn this phase II study, patients with advanced hepatocellular carcinoma and underlying cirrhosis received sirolimus (20 mg/week for 1 month then 30 mg/week). Tumour response was assessed every 8 weeks. The primary endpoint was the objective tumour response rate according to the Response Evaluation Criteria in Solid Tumours criteria. Secondary endpoints included the objective response according to the modified Response Evaluation Criteria in Solid Tumours criteria, safety, and pharmacokinetic parameters.nnnRESULTSnTwenty-five patients received sirolimus for a median of 20.6 weeks. Two patients had an objective response (8%, 95CI: 0.98-26.03), including one complete response, and 8 patients had stable disease. There were 2 cases of grade 5 toxicity (infections) and 5 cases of grade 3 toxicity. The main grade 1/2 toxicity was mild transient fatigue (76%). Median time to radiological progression and overall survival were 15.3 weeks (range: 8.2-173.9) and 26.4 weeks (range: 8.2-173.9) respectively. Use of the modified Response Evaluation Criteria in Solid Tumours criteria did not identify any further responders.nnnCONCLUSIONnThese data suggest that first-line sirolimus shows antitumoural efficacy in advanced hepatocellular carcinoma. Larger trials with Child A patients are needed.

Whole-body diffusion magnetic resonance imaging in the assessment of lymphoma.

Abstract The current evidence regarding the usefulness of whole-body diffusion-weighted magnetic resonance imaging (diffusion MRI) in the assessment of lymphoma is reviewed. Diffusion MRI combining both anatomical and bio-physiological information is currently under investigation as a valuable tool in the oncology field including lymphoma, not only for staging but also for the assessment of response. Representative images for each purpose are shown. Diffusion MRI requires no administration of contrast medium and does not use ionizing radiation, which could be particularly advantageous for repeat follow-up surveillance in lymphoma patients. Diffusion MRI may prove to be a useful biomarker in clinical decision making for patients with lymphoma. Large-scale prospective studies are warranted to further establish its complementary value to the current standard of care, [18F]fluorodeoxyglucose positron emission tomography/computed tomography.

Whole-body diffusion-weighted imaging in lymphoma.

Abstract The current evidence regarding the usefulness of whole-body diffusion-weighted magnetic resonance imaging (DWI) in lymphoma is reviewed. DWI is capable of combining anatomical and functional information and is becoming a valuable tool in oncology, in particular for staging purposes. DWI may prove to be a useful biomarker in clinical decision making for patients with lymphoma. Large-scaled prospective studies are needed to confirm these preliminary results.

Use of Model-Based Iterative Reconstruction (MBIR) in reduced-dose CT for routine follow-up of patients with malignant lymphoma: dose savings, image quality and phantom study

ObjectivesTo evaluate both in vivo and in phantom studies, dose reduction, and image quality of body CT reconstructed with model-based iterative reconstruction (MBIR), performed during patient follow-ups for lymphoma.MethodsThis study included 40 patients (mean age 49xa0years) with lymphoma. All underwent reduced-dose CT during follow-up, reconstructed using MBIR or 50xa0% advanced statistical iterative reconstruction (ASIR). All had previously undergone a standard dose CT with filtered back projection (FBP) reconstruction. The volume CT dose index (CTDIvol), the density measures in liver, spleen, fat, air, and muscle, and the image quality (noise and signal to noise ratio, SNR) (ANOVA) observed using standard or reduced-dose CT were compared both in patients and a phantom study (Catphan 600) (Kruskal Wallis).ResultsThe CTDIvol was decreased on reduced-dose body CT (4.06xa0mGy vs. 15.64xa0mGy pu2009<u20090.0001). SNR was higher in reduced-dose CT reconstructed with MBIR than in 50xa0% ASIR or than standard dose CT with FBP (patients, pu2009≤u20090.01; phantoms, pu2009=u20090.003). Low contrast detectability and spatial resolution in phantoms were not altered on MBIR-reconstructed CT (pu2009≥u20090.11).ConclusionReduced-dose CT with MBIR reconstruction can decrease radiation dose delivered to patients with lymphoma, while keeping an image quality similar to that obtained on standard-dose CT.Key Points• In lymphoma patients, CT dose reduction is a major concern.• Reduced-dose body CT provides a fourfold radiation dose reduction.• Optimized CT reconstruction techniques (MBIR) can maintain image quality.

[F-18]-Fluoro-2-deoxy-d-glucose positron emission tomography as a tool for early detection of immunotherapy response in a murine B cell lymphoma model

Abstract[F-18]-fluoro-2-deoxy-d-glucose positron emission tomography (FDG-PET) is a non-invasive imaging technique which has recently been validated for the assessment of therapy response in patients with aggressive non-Hodgkin’s lymphoma. Our objective was to determine its value for the evaluation of immunotherapy efficacy in immunocompetent Balb/c mice injected with the A20 syngeneic B lymphoma cell line. The high level of in vitro FDG uptake by A20 cells validated the model for further imaging studies. When injected intravenously, the tumour developed as nodular lesions mostly in liver and spleen, thus mimicking the natural course of an aggressive human lymphoma. FDG-PET provided three-dimensionnal images of tumour extension including non-palpable lesions, in good correlation with ex vivo macroscopic examination. When mice were pre-immunized with an A20 cell lysate in adjuvant before tumour challenge, their significantly longer survival, compared to control mice, were associated with a lower incidence of lymphoma visualized by PET at different time points. Estimation of tumour growth and metabolism using the calculated tumour volumes and maximum standardized uptake values, respectively, also demonstrated delayed lymphoma development and lower activity in the vaccinated mice. Thus, FDG-PET is a sensitive tool relevant for early detection and follow-up of internal tumours, allowing discrimination between treated and non-treated small animal cohorts without invasive intervention.

Breast Radiotherapy (RT) Using Tangential Fields (TgF): A Prospective Evaluation of the Dose Distribution in the Sentinel Lymph Node (SLN) Area as Determined Intraoperatively by Clip Placement

BackgroundRandomized trials have established that patients with limited involvement of sentinel lymph node (SLN) do not require axillary lymph node dissection (ALND). The similar outcome in patients with ≤2 positive SLN with or without additional ALND is attributed, in part, to tangential fields (TgF) RT.xa0We evaluated the dose distribution in the SLN biopsy area (SLNBa) as determined intraoperatively by clips placement for radiotherapy (RT) optimization.MethodsThis prospective study included 25 patients who had breast conservation. Titanium clips were used intraoperatively to mark the SLNBa. All patients had 3D-conformal RT using standard (STgF) or high tangential fields (HTgF). Axillary levels, SLNBa, and organs at risk were contoured on a CT scan. Dose distribution and overlap between TgF and target volumes were analyzed.ResultsThe average doses delivered to axilla levels I-III and SLNBa were 25, 5, 2, and 33xa0Gy, respectively. The average dose delivered to SLNBa was higher using HTgF with better coverage of the axilla. Only 12 of 25 patients (48xa0%) had their SLNBa completely covered by the TgF. There was no impact of TgF size on ipsilateral lung dose. The mean heart dose delivered using STgF was lower than HTgF.ConclusionsIn the era of SLNB, axilla and SNLBaxa0RT technique has to be standardized to deliver adequate dose. We recommend the use of HTgF or direct axillary RT techniques (such as in AMAROS trial)xa0in patients with metastases in SLN without ALND completion,xa0when only TgF are expected to cure potential residual disease in the axilla.

Clinical routine use of dopamine transporter imaging in 516 consecutive patients

Abstract[123I]-FP-CIT is a single photon emission computed tomography (SPECT) ligand showing in vivo the loss of dopaminergic terminals in the brain and is now available in the market. Despite several systematic studies in clinically inconclusive cases, the use of such imaging in clinical routine is scarcely reported. We analyzed 516 files of subjects with movement disorders who were consecutively examined using [123I]-FP-CIT scan and determined whether the use of imaging was appropriate and if it improved clinical diagnosis or care of the patient. In addition, we determined if appropriate use was related to subspecialties in Neurology, e.g., movement disorders’ specialists vs. general neurologists, and if appropriate use was increasing over time. Among the 516 scans, 18xa0% were in agreement with the license, 62xa0% were classified as appropriate and 37xa0% were considered inappropriate. A change of management was obvious in 60xa0% of patients, but in 92xa0% of those with an appropriate request vs. 13xa0% of patients with an inappropriate request. Movement disorders’ specialists had more appropriate requests than other practitioners. Eventually, comparing the first 100 vs. the last 100 quantified SPECT, performed more than 2.5xa0years apart, we found no difference for the appropriateness of the examination. The use of [123I]-FP-CIT imaging in clinical routine does not fit a restrictive license. An inappropriate use is seen in nearly 40xa0% of cases, which reduces the real cost-effectiveness of the technique suggesting a need for continuing medical education on the topic.

FDG-PET/CT Brain Findings in a Patient With Macrophagic Myofasciitis

Brain Positron Emission Tomography/Computed Tomography with 18F-fluorodeoxyglucose (FDG PET/CT) was performed in a 44-year-old woman with marked cognitive impairment, diffuse myalgias, sensory, memory and visual disorders, and chronic fatigue, presenting with histopathological features of macrophagic myofasciitis (MMF) at deltoid muscle biopsy. Cerebromedullary Magnetic Resonance Imaging (MRI), electromyography, ophthalmic examination, and cerebrospinal fluid analysis were normal. Visual analysis of FDG PET/CT images showed an atypical pattern of hypometabolism, involving symmetrically the occipital cortex, temporal lobes, and limbic system (including in particular amygdalo-hippocampal complexes), and the cerebellum. Posterior cingulate cortex and parietal areas were preserved. This pattern was confirmed by a voxel-based procedure using Statistical Parametric Mapping (SPM12) that compared a patient’s images to normal reference samples from six healthy subjects with adjustment to age obtained using the same PET/CT camera. These results provide a glucose metabolism substrate for cognitive complaints in patients with long-lasting aluminium hydroxide-induced MMF.

Automatic lesion detection and segmentation of 18F-FET PET in gliomas: A full 3D U-Net convolutional neural network study

Introduction Amino-acids positron emission tomography (PET) is increasingly used in the diagnostic workup of patients with gliomas, including differential diagnosis, evaluation of tumor extension, treatment planning and follow-up. Recently, progresses of computer vision and machine learning have been translated for medical imaging. Aim was to demonstrate the feasibility of an automated 18F-fluoro-ethyl-tyrosine (18F-FET) PET lesion detection and segmentation relying on a full 3D U-Net Convolutional Neural Network (CNN). Methods All dynamic 18F-FET PET brain image volumes were temporally realigned to the first dynamic acquisition, coregistered and spatially normalized onto the Montreal Neurological Institute template. Ground truth segmentations were obtained using manual delineation and thresholding (1.3 x background). The volumetric CNN was implemented based on a modified Keras implementation of a U-Net library with 3 layers for the encoding and decoding paths. Dice similarity coefficient (DSC) was used as an accuracy measure of segmentation. Results Thirty-seven patients were included (26 [70%] in the training set and 11 [30%] in the validation set). All 11 lesions were accurately detected with no false positive, resulting in a sensitivity and a specificity for the detection at the tumor level of 100%. After 150 epochs, DSC reached 0.7924 in the training set and 0.7911 in the validation set. After morphological dilatation and fixed thresholding of the predicted U-Net mask a substantial improvement of the DSC to 0.8231 (+ 4.1%) was noted. At the voxel level, this segmentation led to a 0.88 sensitivity [95% CI, 87.1 to, 88.2%] a 0.99 specificity [99.9 to 99.9%], a 0.78 positive predictive value: [76.9 to 78.3%], and a 0.99 negative predictive value [99.9 to 99.9%]. Conclusions With relatively high performance, it was proposed the first full 3D automated procedure for segmentation of 18F-FET PET brain images of patients with different gliomas using a U-Net CNN architecture.