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1.
Brain Commun ; 3(3): fcab197, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34514401

RESUMO

Biallelic pathogenic variants in PRKN (PARK2), encoding the E3 ubiquitin ligase parkin, lead to early-onset Parkinson's disease. Structural variants, including duplications or deletions, are common in PRKN due to their location within the fragile site FRA6E. These variants are readily detectable by copy number variation analysis. We studied four siblings with levodopa-responsive dystonia by exome sequencing followed by genome sequencing. Affected individuals developed juvenile levodopa-responsive dystonia with subsequent appearance of parkinsonism and motor fluctuations that improved by subthalamic stimulation. Exome sequencing and copy number variation analysis were not diagnostic, yet revealed a shared homozygous block including PRKN. Genome sequencing revealed an inversion within PRKN, with intronic breakpoints flanking exon 5. Breakpoint junction analysis implicated non-homologous end joining and possibly replicative mechanisms as the repair pathways involved. Analysis of cDNA indicated skipping of exon 5 (84 bp) that was replaced by 93 bp of retained intronic sequence, preserving the reading frame yet altering a significant number of residues. Balanced copy number inversions in PRKN are associated with a severe phenotype. Such structural variants, undetected by exome analysis and by copy number variation analysis, should be considered in the relevant clinical setting. These findings raise the possibility that PRKN structural variants are more common than currently estimated.

2.
EJNMMI Res ; 11(1): 86, 2021 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-34487268

RESUMO

BACKGROUND: 99mTc-labelled bisphosphonates are used for imaging assessment of patients with transthyretin cardiac amyloidosis (ATTR). Present study evaluates whether quantitative SPECT/CT measurement of absolute myocardial 99mTc-labelled 3,3-diphosphono-1,2-propanodicarboxylic acid (Tc-DPD) uptake can diagnose patients with suspected ATTR. METHODS: Twenty-eight patients (25 male, age 80.03 ± 6.99 years) with suspected ATTR referred for Tc-DPD imaging had planar and SPECT/CT imaging of the chest. Three operators independently obtained Tc-DPD myocardial SUVmax and SUVmean above threshold (SMaT) (20, 40 and 60% of SUVmax), using a semi-automated threshold segmentation method. Results were compared to visual grading (0-3) of cardiac uptake. RESULTS: Twenty-two patients (78%) had cardiac uptake (2 grade 1, 15 grade 2, 5 grade 3). SUVmax and SMaT segmentation thresholds enabled separating grades 2/3 from 0/1 with excellent inter- and intra-reader correlation. Cut-off values 6.0, 2.5, 3 and 4 for SUVmax, SMaT20,40,60, respectively, separated between grades 2/3 and 0 /1 with PPV and NPV of 100%. SMaT20,40,60(cardiac)/SUVmean (liver) and SMaT20,40,60(cardiac)/SUVmean(liver/lung) separated grades 2 and 3. CONCLUSION: Quantitative SPECT/CT parameters of cardiac Tc-DPD uptake are robust, enabling separation of patients with grades 2 and 3 cardiac uptake from grades 0 and 1. Larger patient cohorts will determine the incremental value of SPECT/CT quantification for ATTR management.

3.
EJNMMI Phys ; 8(1): 63, 2021 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-34436698

RESUMO

BACKGROUND: Following each cycle of peptide receptor radionuclide therapy (PRRT), absorbed doses by tumors and normal organs are typically calculated from three quantitative single-photon emission computed tomography (SPECT)/computed tomography (CT) studies acquired at t1 = 24 h, t2 = 96 h, t3 = 168 h after the first cycle of treatment and from a single study at t1 after the subsequent cycles. In the present study, we have assessed the feasibility of a single SPECT/CT study after each PRRT cycle using a trained multiple linear regression (MLR) model for absorbed dose calculation and have evaluated its impact on patient management. Quantitative [177Lu]-DOTA-TATE SPECT/CT data after PRRT of seventy-two consecutive metastatic neuroendocrine tumors patients were retrospectively evaluated. A set of 40 consecutive studies was used to train the MLR model. The two independent variables of the model included the time of imaging after administration of the treatment and the radiopharmaceutical activity concentration in a given  organ/tumor. The dependent variable was the dose absorbed by the organ/tumor obtained with the standard protocol. For bone marrow dosimetry, the independent variables included the time of imaging, and the blood and remainder of the body activity concentration. The model was evaluated in 32 consecutive patients. Absorbed doses were assessed for kidneys, bone marrow, liver, spleen and tumor sites. RESULTS: There was no difference in management decisions, whether PRRT can be safely continued or not because unsafe absorbed dose to risk organs between the standard and the MLR model-based protocol using a single SPECT/CT study performed at t3 = 168 h after the first cycle and at t1 = 24 h after the subsequent cycles. Cumulative absorbed doses were obtained with mean relative differences of - 0.5% ± 5.4%, 1.6% ± 15.1%, - 6.2% ± 7.3%, - 5.5% ± 5.8% and 2.9% ± 12.7% for kidneys, bone marrow, liver, spleen and tumors, respectively (Pearson's r correlation coefficient 0.99, 0.91, 0.99, 0.99 and 0.97, respectively). CONCLUSION: Dosimetry calculations using a MLR model with a single SPECT/CT study are in good agreement with the standard protocol, while avoiding the use of dosimetry software and enabling improved patient comfort and reduced scanner and staff time.

4.
J Nucl Med ; 2021 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-34301777

RESUMO

Anti-COVID-19 vaccination has created new challenges. Lymphadenopathy (LA) with increased uptake in patients undergoing PET/CT may mislead to unnecessary further evaluation. We have analyzed routinely performed PET/CT studies following Pfizer-BioNTech vaccination to familiarize with PET/CT appearances with various PET tracers and to prevent consequences of misinterpretation. Methods: 1281 PET/CT studies performed between January 01 2021 and February 15 2021 were analyzed. Information about dates and site of vaccination was collected. Visual and semi-quantitative analysis of axillary - neck LA and arm uptake was correlated with immunization data. Results: Increased uptake in unilateral axillary LA was observed in 66% vaccinated patients, in 55% vaccinated once and in 69% vaccinated twice. Intensity of uptake decreased over time. 64/315 patients (20%) had simultaneous increased activity in the posterior arm and ipsilateral axillary LA ("double sign" [DS]). Sensitivity, specificity, PPV and NPV of axillary LA and DS were 55.4%, 83.6%, 86.7%, 49.2% and 38.6%, 100%, 100% and 66.1%, respectively. No DS was observed later than 10 and 21 days after first and the second vaccinations, respectively. None of the non-vaccinated patients had arm uptake or DS. Conclusion: Anti-COVID-19 vaccination frequently causes non-specific axillary LA with increased PET tracer activity. In one fifth of our study population this was associated with increased uptake at the vaccination site, DS. DS was 100% specific with 100% PPV for p/vaccination LA hence enabling to avoid misinterpretation of PET/CT studies and further unnecessary evaluation.

5.
6.
Harefuah ; 160(7): 419-424, 2021 07.
Artigo em Hebraico | MEDLINE | ID: mdl-34263567

RESUMO

AIMS: The aim of this study was to evaluate the predictive power of the absorbed dose to kidneys after the first course of treatment with [177Lu]-DOTA-TATE on the cumulative kidney absorbed dose after 3 or 4 cycles of treatment. BACKGROUND: Peptide receptor radionuclide therapy (PRRT) with [177Lu]-DOTA-TATE is an effective treatment for somatostatin receptor positive neuroendocrine tumors (NETs). Post-treatment scans (PTS) are required after each cycle of treatment for personalized radiation dosimetry in order to calculate the dose to organs and tumors and to ensure a cumulative absorbed dose to kidneys under a safety threshold of 25 Gy. METHODS: A total of 187 patients who completed treatment and underwent PTS for dosimetry calculation were included in this retrospective study. The correlation between the cumulative absorbed dose to the kidneys after completion of treatment and the absorbed dose after the first cycle(s) was studied. Multilinear regression analysis was performed to predict the cumulative absorbed dose by the kidneys in the subsequent cycles. An algorithm for the follow-up of the kidney absorbed dose is proposed. RESULTS: When the absorbed dose to kidneys after the first cycle of treatment is below 5.6 Gy, four cycles of treatment can be safely administered with a cumulative dose less than 25 Gy (p < 0.1). For the remaining patients, the cumulative dose absorbed after 3 or 4 cycles of treatment can be predicted after the second cycle of treatment. This protocol enabled early decisions on the number of treatment cycles and reduced the number of post-treatment SPECT/CT studies for dosimetry in 34% of patients, as well as hospitalization time for 56% of the treatment cycles. CONCLUSIONS: Assessment of the kidney absorbed dose after PRRT can be simplified with the algorithm presented in this study. This approach enabled early decisions on the number of therapy cycles in 75% of patients. DISCUSSION: The validity of these results is limited to the protocol of dosimetry calculation used in our institution. Implementation in other centers may require standardization of the acquisition parameters and the dosimetry protocol.


Assuntos
Tumores Neuroendócrinos , Exposição à Radiação , Humanos , Tumores Neuroendócrinos/radioterapia , Radioisótopos , Radiometria , Estudos Retrospectivos
7.
J Nucl Med ; 2021 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-34049983

RESUMO

To assess the efficacy and safety of 177Lu-DOTATATE in patients with somatostatin receptor (SSR) positive lung neuroendocrine tumor (NET). Methods: This is a retrospective review of the outcome of patients with typical carcinoid (TC) and atypical carcinoid (AC), treated with 177Lu-DOTATATE at two ENETS Centres of Excellence. Morphological imaging (RECIST 1.1) and 68Ga-DOTATATE PET/CT responses were assessed at 3 months after completion of 177Lu-DOTATATE. Concordance between two response assessment methods was evaluated by Kappa statistics. Progression-free survival (PFS) and overall survival (OS) was estimated by Kaplan-Meier analysis and compared by Log-rank test. Treatment-related adverse events (AEs) were graded based on CTCAE version 5. Results: Of 48 patients (median age, 63 years, 13 female), 43 (90%) had AC and 5 (10%) TC. Almost all patients (47, 98%) were treated due to progression. Majority (40, 83%) received somatostatin analogs and 10 patients (20%) had prior everolimus, chemotherapy or both. All patients had high SSR expression (≥ modified Krenning score 3) on pre-treatment 68Ga-DOTATATE PET/CT. Patients received a median 4 (range 1-4) cycles of 177Lu-DOTATATE (33% with concurrent radiosensitizing chemotherapy) to a median cumulative activity of 27GBq (range 6-43GBq). At median follow-up of 42 months, the median PFS and OS were 23 months (95% CI 18-28 months) and 59 months (95% CI 50-not reached [NR]), respectively. Of 40 patients with RECIST-measurable disease and 39 patients with available 68Ga-DOTATATE PET/CT response categories were: partial response, 20% (95% CI 10-35%) and 44% (95% CI 30-59%); stable disease, 68% (95% CI 52-80%) and 44% (95% CI 30-59%) and progressive disease 12% (95% CI 5-27%) by both, respectively. There was a moderate concordance between response categories by RECIST and 68Ga-DOTATATE PET/CT, weighted Kappa of 0.51 (95% CI 0.21-0.68). Of patients with stable disease by RECIST, those with partial response on 68Ga-DOTATATE PET/CT had longer OS compared to those with no response, NR vs 52 months (95% CI 28-64), HR 0.2 (95% CI 0.1-0.6), p 0.001. Most grade 3/4 AEs were reversible and the most common was lymphopenia (14%) with no incidence of myelodysplasia/leukemia. Conclusion: In patients with advanced progressive lung NET and satisfactory SSR expression, 177Lu-DOTATATE is effective and safe with a high disease control rate and encouraging PFS and OS.

8.
Surg Oncol ; 38: 101567, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33866190

RESUMO

INTRODUCTION: Breast cancer outcome is dependent on disease stage. The aim of the study was to assess the role of PET/CT in the evaluation of axillary lymph node and distant metastases in women with newly diagnosed primary breast cancer. MATERIALS AND METHODS: We assessed, among patients with newly diagnosed primary breast cancer, associations of [18F] fluorodeoxyglucose (FDG) uptake (maximum standardized uptake value [SUVmax]) with clinical variables of the primary tumor, including regional nodal status and the presence of distant metastases. RESULTS: Of 324 patients, 265 (81.8%) had focal uptake of FDG that corresponded with the cancerous lesion, and 21 (6.5%) had no FDG-avid findings. The remaining 38 patients had diffuse or nonspecific uptake of FDG. Among patients with a focal uptake of FDG (n = 265), the mean tumor size was 2.6 ± 1.9 (range 0.5-13.5), and the mean SUVmax was 5.3 ± 4.9 (range 1.2-25.0). In 83 patients (25.6%), PET/CT demonstrated additional suspected foci in the same breast. FDG-avid lymphadenopathy was observed in 156 patients (48.1%). Further assessment of lymph node involvement was available for 55/156 patients (axillary lymph node dissection [n = 21]; core needle biopsy [n = 34]) and confirmed axillary lymph node metastases in 47 (85.5%)). Thirteen patients (4.0%) had FDG-avid supraclavicular lymph nodes and six (1.9%) had FDG-avid internal mammary lymph nodes. Distant FDG-avid lesions were detected in 33 patients (10.2%). CONCLUSION: PET/CT is a useful diagnostic tool for staging breast cancer patients, but its use should be limited to specific clinical situations; further evaluation is needed.

9.
Artigo em Inglês | MEDLINE | ID: mdl-33686849

RESUMO

BACKGROUND: Omission errors in medical imaging can lead to missed diagnosis and harm to patients. The subject has been studied in conventional imaging, but no data is available for functional imaging in general and for PET/CT in particular. In this work, we evaluated the frequency and characteristics of perceptual omission errors in the PET component of oncologic PET/CT imaging and we analyze the hazardous scenarios prone to such modality-specific errors. MATERIALS AND METHODS: Perceptual omission errors were collected in one tertiary center PET/CT clinic during routine PET/CT reporting over a 26-month period. The omissions were detected either in reporting follow-up PET/CT studies of the same patient or during multidisciplinary meetings. RESULTS: Significant omission errors were found in 1.2 % of the 2100 reports included in the study. The most common omissions were bone metastases and focal colon uptake. We identified six PET-specific causative factors contributing to the occurrence of omissions, and we propose solutions to minimize their influence. CONCLUSIONS: The data presented here can help to promote the awareness of interpreting physicians to body areas that require higher attention and to implement reading strategies for improving the accuracy of PET/CT interpretation.

10.
EJNMMI Phys ; 8(1): 13, 2021 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-33580359

RESUMO

BACKGROUND: Image quality and quantitative accuracy of positron emission tomography (PET) depend on several factors such as uptake time, scanner characteristics and image reconstruction methods. Ordered subset expectation maximization (OSEM) is considered the gold standard for image reconstruction. Penalized-likelihood estimation (PL) algorithms have been recently developed for PET reconstruction to improve quantitation accuracy while maintaining or even improving image quality. In PL algorithms, a regularization parameter ß controls the penalization of relative differences between neighboring pixels and determines image characteristics. In the present study, we aim to compare the performance of Q.Clear (PL algorithm, GE Healthcare) and OSEM (3 iterations, 8 subsets, 6-mm post-processing filter) for 68Ga-DOTATATE (68Ga-DOTA) PET studies, both visually and quantitatively. Thirty consecutive whole-body 68Ga-DOTA studies were included. The data were acquired in list mode and were reconstructed using 3D OSEM and Q.Clear with various values of ß and various acquisition times per bed position (bp), thus generating images with reduced injected dose (1.5 min/bp: ß = 300-1100; 1.0 min/bp: ß = 600-1400 and 0.5 min/bp: ß = 800-2200). An additional analysis adding ß values up to 1500, 1700 and 3000 for 1.5, 1.0 and 0.5 min/bp, respectively, was performed for a random sample of 8 studies. Evaluation was performed using a phantom and clinical data. Two experienced nuclear medicine physicians blinded to the variables assessed the image quality visually. RESULTS: Clinical images reconstructed with Q.Clear, set at 1.5, 1.0 and 0.5 min/bp using ß = 1100, 1300 and 3000, respectively, resulted in images with noise equivalence to 3D OSEM (1.5 min/bp) with a mean increase in SUVmax of 14%, 13% and 4%, an increase in SNR of 30%, 24% and 10%, and an increase in SBR of 13%, 13% and 2%. Visual assessment yielded similar results for ß values of 1100-1400 and 1300-1600 for 1.5 and 1.0 min/bp, respectively, although for 0.5 min/bp there was no significant improvement compared to OSEM. CONCLUSION: 68Ga-DOTA reconstructions with Q.Clear, 1.5 and 1.0 min/bp, resulted in increased tumor SUVmax and in improved SNR and SBR at a similar level of noise compared to 3D OSEM. Q.Clear with ß = 1300-1600 enables one-third reduction of acquisition time or injected dose, with similar image quality compared to 3D OSEM.

11.
J Alzheimers Dis ; 78(2): 777-788, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33044181

RESUMO

BACKGROUND: Family history of Alzheimer's disease (AD) is associated with increased dementia-risk. OBJECTIVE: The Israel Registry for Alzheimer's Prevention (IRAP) is a prospective longitudinal study of asymptomatic middle-aged offspring of AD patients (family history positive; FH+) and controls (whose parents have aged without dementia; FH-) aimed to unravel the contribution of midlife factors to future cognitive decline and dementia. Here we present the study design, methods, and baseline characteristics. METHODS: Participants are members of the Maccabi Health Services, 40-65 years of age, with exquisitely detailed laboratory, medical diagnoses and medication data available in the Maccabi electronic medical records since 1998. Data collected through IRAP include genetic, sociodemographic, cognitive, brain imaging, lifestyle, and health-related characteristics at baseline and every three years thereafter. RESULTS: Currently IRAP has 483 participants [mean age 54.95 (SD = 6.68) and 64.8% (n = 313) women], 379 (78.5%) FH+, and 104 (21.5%) FH-. Compared to FH-, FH+ participants were younger (p = 0.011), more often males (p = 0.003) and with a higher prevalence of the APOE E4 allele carriers (32.9% FH+, 22% FH-; p = 0.040). Adjusting for age, sex, and education, FH+ performed worse than FH-in global cognition (p = 0.027) and episodic memory (p = 0.022). CONCLUSION: Lower cognitive scores and higher rates of the APOE E4 allele carriers among the FH+ group suggest that FH ascertainment is good. The combination of long-term historical health-related data available through Maccabi with the multifactorial information collected through IRAP will potentially enable development of dementia-prevention strategies already in midlife, a critical period in terms of risk factor exposure and initiation of AD-neuropathology.


Assuntos
Doença de Alzheimer/diagnóstico por imagem , Doença de Alzheimer/epidemiologia , Testes Neuropsicológicos , Sistema de Registros , Projetos de Pesquisa/tendências , Adulto , Idoso , Doença de Alzheimer/psicologia , Estudos Transversais , Feminino , Humanos , Israel/epidemiologia , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Neuroimagem/tendências , Estudos Prospectivos , Fatores de Risco
13.
Oncologist ; 25(9): 787-792, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32430954

RESUMO

BACKGROUND: Prostate cancer is a common malignancy of the elderly, and with the aging of the population, the need is growing for therapies suitable for this age group. Lutetium-177-prostate-specific membrane antigen (Lu-PSMA), a radiolabeled small molecule, binds with high affinity to prostate-specific membrane antigen, enabling beta particle therapy targeted to metastatic castration-resistant prostate cancer (mCRPC). In a recent single-arm phase II trial and a subsequent expansion cohort, a prostate-specific antigen (PSA) decline of ≥50% was observed in approximately 60% of patients receiving Lu-PSMA. Taking into account the specific challenges and potential toxicities of Lu-PSMA administration in elderly men, we sought to retrospectively analyze the safety and activity of Lu-PSMA in men aged older than 75 years with mCRPC. PATIENTS AND METHODS: The electronic medical records of 24 patients aged older than 75 years treated with Lu-PSMA "off-trial" were reviewed, and clinical data were extracted. Clinical endpoints were toxicity and activity, defined as a PSA decline ≥50%. Descriptive statistics were performed using Excel. RESULTS: The median age at treatment start was 81.7 years (range 75.1-91.9). The median number of previous treatment lines was four. The number of treatment cycles ranged from one to four; the mean administered radioactivity was 6 GBq per cycle. Treatment was generally tolerable; side effects included fatigue (n = 8, 33%), anemia (n = 7, 29%), thrombocytopenia (n = 5, 21%), and anorexia/nausea (n = 3, 13%). Clinical benefit was observed in 12 of 22 patients (54%); PSA decline above 50% was observed in 11 patients (48%) and was associated with significantly longer overall survival. CONCLUSION: Our results indicate that Lu-PSMA is safe and active in elderly patients with mCRPC. IMPLICATIONS FOR PRACTICE: Lutetium-177-prostate-specific membrane antigen (Lu-PSMA), a radiolabeled small molecule, binds with high affinity to prostate-specific membrane antigen, enabling beta particle therapy targeted to metastatic castration-resistant prostate cancer (mCRPC). The recently published single-arm phase II trial with Lu-PSMA, describing its safety and activity, did not include patients aged older than 75 years. In this study, Lu-PSMA activity was retrospectively analyzed in patients aged older than 75 years and results indicate that treatment was tolerable and similarly active in this age group, with no new emerging safety signals. Despite the small cohort size, this analysis suggests that Lu-PSMA can serve as an advanced palliative treatment line in mCRPC in elderly patients.


Assuntos
Neoplasias de Próstata Resistentes à Castração , Idoso , Idoso de 80 Anos ou mais , Dipeptídeos , Compostos Heterocíclicos com 1 Anel , Humanos , Lutécio , Masculino , Neoplasias de Próstata Resistentes à Castração/radioterapia , Radioisótopos/uso terapêutico , Compostos Radiofarmacêuticos , Estudos Retrospectivos , Resultado do Tratamento
14.
Alzheimers Dement (N Y) ; 6(1): e12008, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32296731

RESUMO

Introduction: Type 2 diabetes (T2D) is a risk factor for dementia. Ischemia due to vascular pathology is hypothesized to be an underlying mechanism for this association. Hyperbaric oxygen therapy (HBOT) is a treatment in which oxygen-enriched air (up to 100%) is administered to patients in a chamber at a pressure above one atmosphere absolute. HBOT is approved for the treatment of T2D ischemic non-healing wounds. Evidence from animal studies and small clinical trials suggests that HBOT improves hypoxic/ischemic brain injuries, consequently inducing brain angiogensis, leading to cognitive improvement. Methods: We present the design of the first double-blind, placebo-controlled, clinical trial on brain and cognitive outcomes in elderly (n = 154) with T2D and mild cognitive impairment to compare the effects of HBOT versus sham (normal air with 1.1 ATA pressure in the first and last 5 minutes of the session). Eligible candidates are randomized with equal probability to HBOT and sham. Outcomes are assessed before and after treatment, and at 6- and 12-month follow-up. The primary cognitive outcome is global cognitive change, indexed by a composite sum of z-scores of four executive functions and four episodic memory tests. The primary neurobiological outcome is cerebral blood flow (CBF; via arterial spin labeling magnetic resonance imaging [ASL-MRI]) and cerebral glucose utilization via fluorodeoxyglucose positron emission tomography (FDG-PET). Secondary outcome measures are specific cognitive domains (executive function and episodic memory) and functional measures (Clinical Dementia Rating sum of boxes, activities of daily living). Efficacy analyses will be performed for the intent-to-treat sample. Discussion: Recent studies suggest that HBOT induces neuroplasticity and improves cognition in post-stroke and traumatic brain injury patients. However, its effect on cognition, cerebral blood flow, and brain glucose utilization in T2D patients at high dementia risk is yet to be determined. If effective, this study may provide strong evidence for the brain and cognitive benefits of HBOT in this population.

15.
Clin Lymphoma Myeloma Leuk ; 20(4): 252-259, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32115401

RESUMO

BACKGROUND: The value of positron emission tomography/computed tomography (PET/CT) in the staging and assessment of treatment response in marginal zone lymphoma (MZL) lymphomas remains controversial. We investigated radiologic characteristics of subcutaneous MZL as imaged on PET/CT scans. PATIENTS AND METHODS: From the records of a single medical center, for the years 2008 and 2017, we identified subcutaneous lesions in PET/CT scans of patients with histopathologically confirmed MZL in sites other than subcutaneous tissue. RESULTS: Of 571 scans of 178 patients, subcutaneous lesions were found in 20 (11%). Lesions were located in soft tissue structures, mainly along the lateral aspects of the buttocks, thighs and lower and upper back areas, the flank, and the shoulders. Median lengths of the long and short axes of the lesions were 2.0 (range, 1.1-6.0) cm and 0.8 (range, 0.3-2.0) cm, respectively. Median standardized maximum uptake value was 2.3 (range, 0.9-7.6). In 12 patients (60%), MZL was diagnosed at an early stage; 15 (75%) had lymph node involvement and 10 (50%) extranodal involvement. One had spleen and 2 had cutaneous involvement; none had gastric findings. CONCLUSION: The findings of this study support the usefulness of PET/CT in the detection of subcutaneous MZL as well as in staging and treatment decisions.


Assuntos
Fluordesoxiglucose F18/administração & dosagem , Linfoma de Zona Marginal Tipo Células B/diagnóstico por imagem , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
16.
J Nucl Med ; 61(9): 1326-1330, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32005769

RESUMO

Esthesioneuroblastoma is rare, with limited therapeutic options when unresectable or metastatic; however, expression of somatostatin receptors qualifies it for peptide receptor radionuclide therapy (PRRT). We report outcomes of PRRT in esthesioneuroblastoma from 2 referral centers. Methods: Using PRRT databases at 2 European Neuroendocrine Tumor Society Centers of Excellence, cases were sought between 2004 and 2018 of patients who had PRRT with recurrent or metastatic esthesioneuroblastoma deemed unsuitable for further conventional therapies. Evaluations of survival and of response using a composite reference standard were performed. Results: Of 7 patients, 4 had partial response, 2 had disease stabilization, and one had early progression. Possible side effects include worsening cerebrospinal fluid leaks. Median progression-free survival was 17 mo (range, 0-30 mo), and median overall survival was 32 mo (range, 4-53 mo). Conclusion: PRRT shows promising efficacy and moderate survival duration in unresectable locally advanced or metastatic esthesioneuroblastoma warranting larger cohort studies incorporating measures of quality of life.


Assuntos
Estesioneuroblastoma Olfatório/radioterapia , Receptores de Peptídeos/metabolismo , Adulto , Idoso , Estesioneuroblastoma Olfatório/metabolismo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento
17.
Endocrine ; 68(1): 222-229, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32036501

RESUMO

PURPOSE: The decreased life expectancy of MEN-1 patients is mainly related to pancreatic neuroendocrine tumors (pNETs). At best, limited data is available on the natural history of MEN-1-associated pNETs, as these tumors are rare and have a wide range of biologic behavior. Our study aims to explore the clinical course of patients with MEN-1-associated pNETs and the long-term outcomes. METHODS: This longitudinal study was conducted on the MEN-1 cohort treated at our referral center over a 22-year period (1996-2018). Relevant clinical data were retrospectively analysed. RESULTS: Among the 33 MEN-1 patients included in our study, pNETs were identified in 21 subjects with a penetrance of 48% by the age of 50. Non-functioning and functioning pNETs were diagnosed in sixteen (76%) and five (24%) patients, respectively. Two-thirds of the patients had multifocal tumors. The median number of pancreatic macroscopic lesions per individual was 4.0 ± 3.9 (range 1-8) with a mean size of 1.3 ± 2.1 cm (range 0.5-10). The metastatic rate according to the dominant pNET lesion reached 100%, 62% and 6% for tumors sized > 4 cm, 2.1-4 cm, and 1-2 cm, respectively. Over the study period, one or more therapeutic interventions for pNETs were required in 20 out of the 21 patients. pNET-related metastatic complication was the main cause of death within this MEN-1 cohort. The overall survival rate for the pNETs patients was 86% during a mean follow-up period of 8.0 ± 4.6 years. CONCLUSIONS: In our MEN-1 cohort, non-functioning pNETs were the most frequent type of pancreaticoduodenal tumor, and the tumor size correlated with the risks of metastasis and death. Increased awareness, early diagnosis, and a multidisciplinary approach may improve the associated morbidity and mortality in these patients.


Assuntos
Neoplasia Endócrina Múltipla Tipo 1 , Tumores Neuroendócrinos , Neoplasias Pancreáticas , Humanos , Estudos Longitudinais , Neoplasia Endócrina Múltipla Tipo 1/terapia , Tumores Neuroendócrinos/epidemiologia , Tumores Neuroendócrinos/terapia , Neoplasias Pancreáticas/epidemiologia , Neoplasias Pancreáticas/terapia , Estudos Retrospectivos
18.
EJNMMI Phys ; 7(1): 5, 2020 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-31975156

RESUMO

BACKGROUND: After each cycle of [177Lu]-DOTA-TATE peptide receptor radionuclide therapy (PRRT) dosimetry is performed to enable precise calculation of the radiation-absorbed dose to tumors and normal organs. Absorbed doses are routinely calculated from three quantitative single-photon emission computed tomography (SPECT) studies corrected by computed tomography (CT) acquired at t1 = 24 h, t2 = 96 h, and t3 = 168 h after the first cycle of treatment. After following cycles, a single SPECT/CT study is performed. The aim of the present study is to assess the feasibility of a "two time point" quantitative SPECT/CT protocol after the first PRRT cycle and its impact on patient management. Quantitative SPECT/CT data of 25 consecutive patients with metastatic neuroendocrine tumors after PRRT were retrospectively analyzed. Radiation-absorbed doses calculated using the standard protocol with three SPECT/CT studies acquired at (t1, t2, t3) were compared to those obtained from three different "two time point" protocols with SPECT/CT studies performed at (t1, t2), (t1, t3), or (t2, t3). RESULTS: The best agreement for the cumulative doses absorbed by the kidneys, bone marrow, liver, spleen, and tumors with the conventional protocol was obtained with the (t1, t3) protocol with mean relative differences of - 1.0% ± 2.4%, 0.4% ± 3.1%, - 0.9% ± 4.0%, - 0.8% ± 1.1%, and - 0.5% ± 2.0%, respectively, and correlation coefficients of r = 0.99 for all. In all patients, there was no difference in the management decision of whether or not to stop PRRT because of unsafe absorbed dose to risk organs using either the standard protocol or the (t1, t3) protocol. CONCLUSION: These preliminary results demonstrate that dosimetry calculations using two quantitative SPECT/CT studies acquired at 24 and 168 h after the first PRRT cycle are feasible and are in good agreement with the standard imaging protocol with no change in patient management decisions, while enabling improved patient comfort and reduced scanner and staff time.

19.
Endocr Pract ; 26(10): 1131-1142, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33471715

RESUMO

OBJECTIVE: Von Hippel-Lindau (VHL) syndrome is a rare and complex disease. In 1996, we described a 3 generation VHL 2A kindred with 11 mutation carriers. We aim to share our experience regarding the long-term follow-up of this family and the management of all our other VHL patients focusing on frequently encountered neuroendocrine neoplasms: pheochromocytoma/paraganglioma and pancreatic neuroendocrine neoplasms (PNEN). METHODS: All VHL patients in follow-up at our tertiary center from 1980 to 2019 were identified. Clinical, laboratory, imaging, and therapeutic characteristics were retrospectively analyzed. RESULTS: We identified 32 VHL patients in 16 different families, 7/16 were classified as VHL 2 subtype. In the previously described family, the 4 initially asymptomatic carriers developed a neuroendocrine tumor; 7 new children were born, 3 of them being mutation carriers; 2 patients died, 1 due to metastatic PNEN-related liver failure. Pheochromocytoma was frequent (22/32), bilateral (13/22;59%), often diagnosed in early childhood when active screening was timely performed, associated with paraganglioma in 5/22, rarely malignant (1/22), and recurred after surgery in some cases after more than 20 years. PNEN occurred in 8/32 patients (25%), and was metastatic in 3 patients. Surgery and palliative therapy allowed relatively satisfactory outcomes. Severe disabling morbidities due to central-nervous system and ophthalmologic hemangiomas, and other rare tumors as chondrosarcoma in 2 patients and polycythemia in 1 patient were observed. CONCLUSION: A multidisciplinary approach and long-term follow-up is mandatory in VHL patients to manage the multiple debilitating morbidities and delay mortality in these complex patients.


Assuntos
Neoplasias das Glândulas Suprarrenais , Tumores Neuroendócrinos , Neoplasias Pancreáticas , Doença de von Hippel-Lindau , Neoplasias das Glândulas Suprarrenais/epidemiologia , Neoplasias das Glândulas Suprarrenais/terapia , Criança , Pré-Escolar , Humanos , Recidiva Local de Neoplasia , Tumores Neuroendócrinos/epidemiologia , Tumores Neuroendócrinos/terapia , Neoplasias Pancreáticas/epidemiologia , Neoplasias Pancreáticas/terapia , Estudos Retrospectivos , Proteína Supressora de Tumor Von Hippel-Lindau , Doença de von Hippel-Lindau/epidemiologia , Doença de von Hippel-Lindau/genética
20.
Nucl Med Commun ; 40(9): 913-919, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31343612

RESUMO

OBJECTIVES: The purpose of this study was to evaluate the use of Gallium-68 prostatic-specific membrane antigen (PSMA) PET-computerized tomography (CT) in patients with prostate cancer undergoing imaging for initial staging, biochemical failure or the evaluation of metastatic disease. METHODS: This is a single institution retrospective study of 95 patients with prostate cancer who were referred for PSMA PET-CT scans. The National Comprehensive Cancer Network guidelines were used to generate treatment recommendations. Univariate and multivariate statistical analyses were performed to identify parameters associated with positive findings on a PET-CT PSMA scan. RESULTS: Mean age, Gleason score, and median prostate serum antigen (PSA) were: 72 years, 7.6 and 4 ng/ml, respectively. PSMA PET-CT was positive in 75.5% of the patients. A maximum standardized uptake value was 10.7 ± 8.8. PSMA avidity increased with rising PSA level: PSA ≤ 1 ng/ml: 5/15 patients (33%); PSA 1-5 ng/ml: 18/27 patients (67%), and PSA ≥ 5 ng/ml: 33/34 patients (97%). Following imaging in nine high-risk patients referred for staging, changes in treatment occurred in 6 (67%). Treatment recommendations changed in 27/35 (65%) patients referred due to biochemical failure; these included recurrences suitable for salvage therapy (n = 14), metastatic disease not suitable for salvage therapy (n = 10), and no lesion (n = 17). No changes in treatment occurred in any of the 35 patients referred to evaluate metastatic disease. DISCUSSION: PSMA PET-CT imaging may have a substantial impact on clinical management in prostate cancer patients at the time of initial staging or with biochemical failure; yet this modality does not appear useful in the management of patients with known metastatic disease.


Assuntos
Glicoproteínas de Membrana , Compostos Organometálicos , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Neoplasias da Próstata/diagnóstico por imagem , Idoso , Humanos , Masculino , Metástase Neoplásica , Estadiamento de Neoplasias , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/patologia , Estudos Retrospectivos
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