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2.
J Nucl Med ; 2024 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-38514088

RESUMO

Advanced neuroendocrine tumors (NETs) are associated with a poor prognosis. A regimen of 4 cycles of 177Lu-DOTATATE has been shown to improve both progression-free survival (PFS) and overall survival (OS) in patients with advanced NETs. To the best of our knowledge, this is the first study in the United States to evaluate the effectiveness and safety of additional cycles of 177Lu-DOTATATE therapy in patients with progressive NETs. Methods: This was a retrospective chart review of adults with advanced NETs. The patients had undergone initial treatment with up to 4 cycles of 177Lu-DOTATATE and, after disease progression and a period of at least 6 mo since the end of the initial treatment, were retreated with at least 1 additional cycle at a single center (2010-2020). Patient characteristics, treatment patterns, and clinical outcomes were evaluated descriptively. Response was evaluated according to RECIST 1.1; toxicity was defined using criteria from Common Terminology Criteria for Adverse Events, version 5.0. Kaplan-Meier plots were used to evaluate PFS and OS. Results: Of the 31 patients who received 177Lu-DOTATATE retreatment, 61% were male and 94% were White. Overall, patients received a median of 6 cycles (4 initial cycles and 2 retreatment cycles), and the mean administered activity was 41.9 GBq. Two patients also went on to receive additional retreatment (1 and 2 cycles, individually) after a second period of at least 6 mo and progression after retreatment. Best responses of partial response and stable disease were observed in 35% and 65% of patients after the initial treatment and 23% and 45% of patients after retreatment, respectively. The median PFS after the initial treatment was 20.2 mo and after retreatment was 9.6 mo. The median OS after the initial treatment was 42.6 mo and after retreatment was 12.6 mo. Hematologic parameters decreased significantly during both the initial treatment and retreatment but recovered such that there was little difference between the values before the initial treatment and before the retreatment. Clinically significant hematotoxicity occurred in 1 and 3 patients after the initial treatment and retreatment, respectively. No grade 3 or 4 nephrotoxicity was observed. Conclusion: Retreatment with 177Lu-DOTATATE after progression appeared to be well tolerated and offered disease control in patients with progressive NETs after initial 177Lu-DOTATATE treatment.

3.
J Nucl Med ; 63(9): 1326-1333, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-34992153

RESUMO

Peptide receptor radiotherapy with somatostatin analogs has been successfully used for years as a treatment for somatostatin-overexpressing tumors. Treatment of neuroendocrine tumors (NETs) with the ß-particle emitter 177Lu-DOTATATE is currently considered the standard of care for subjects with gastroenteropancreatic NETs. Despite the success of 177Lu-DOTATATE, there remains significant room for improvement in terms of both safety and efficacy. Targeted α-emitter therapy with isotopes such as 212Pb has the potential to improve both. Here, we present the preliminary results of the phase 1 first-in-humans dose-escalation trial evaluating 212Pb-DOTAMTATE (a bifunctional metal chelator [DOTAM] and the SSTR-targeting peptide [TATE]) in patients with somatostatin receptor-positive NETs. Methods: Twenty subjects with histologically confirmed NETs, prior positive somatostatin analog scans, and no prior history of 177Lu/90Y/111In peptide receptor radiotherapy, with different primary sites of the disease, were enrolled. Treatment began with single ascending doses of 212Pb-DOTAMTATE, with subsequent cohorts receiving an incremental 30% dose increase, which was continued until a tumor response or a dose-limiting toxicity was observed. This was followed by a multiple ascending dose regimen. The recommended phase 2 dose regimen consisted of 4 cycles of 2.50 MBq/kg (67.6 µCi/kg) of 212Pb-DOTAMTATE administered at 8-wk intervals, intravenously. Results: Ten subjects received the highest dose, 2.50 MBq/kg/cycle (67.6 µCi/kg/cycle). Treatment was well tolerated, with the most common treatment-emergent adverse events being nausea, fatigue, and alopecia. No serious treatment-emergent adverse events were related to the study drug, and no subjects required treatment delay or a dose reduction. An objective radiologic response of 80% was observed for the first 10 subjects treated at the recommended phase 2 dose. Conclusion: Targeted α-therapy with 212Pb-DOTAMTATE has been shown to be well tolerated. Preliminary efficacy results are highly promising. If these results are confirmed in a larger, multicenter clinical trial, 212Pb-DOTAMTATE would provide a substantial benefit over currently Food and Drug Administration-approved therapies for patients with metastatic or inoperable SSTR-expressing NETs regardless of the grade and location of the primary tumor.


Assuntos
Tumores Neuroendócrinos , Compostos Organometálicos , Quelantes/efeitos adversos , Humanos , Chumbo , Radioisótopos de Chumbo , Tumores Neuroendócrinos/diagnóstico por imagem , Tumores Neuroendócrinos/tratamento farmacológico , Tumores Neuroendócrinos/radioterapia , Octreotida/efeitos adversos , Compostos Organometálicos/efeitos adversos , Tomografia por Emissão de Pósitrons , Cintilografia , Compostos Radiofarmacêuticos/efeitos adversos , Receptores de Somatostatina , Somatostatina/efeitos adversos
4.
Clin Neuropsychol ; 36(2): 367-387, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34429015

RESUMO

The present study investigated the contribution of health risk factors (using the Charlson Comorbidity Index [CCI]) on cognitive outcomes in a sample of 380 HIV-positive (HIV+; n = 221) and HIV-seronegative (HIV-; n = 159) African American and European American adults aged 50+.Participants were recruited from HIV clinics and community advertisements. HIV status was confirmed by serological testing. Self-report and chart history review was used to gather information about medical ssscomorbidities. The Charlson Comorbidity Index (CCI) was used to create a comorbidity score. Participants were administered a brief cognitive test battery.As expected, health risks were greater among those with HIV. There was a HIV × Race interaction on CCI scores, such that in the HIV + group, European Americans had significantly higher CCI scores (M = 3.74; SD = 2.1) than African American HIV + participants (M = 2.70; SD = 1.9). However, in the HIV - group, African Americans had significantly higher CCI scores (M = 2.20; SD = 1.1) than HIV - European American participants (M = 1.80; SD = 1.2). Also, consistent with hypotheses, across the entire sample CCI score was significantly associated with global cognition (ß = -.24, p = .02).Study results underscore the importance of considering HIV serostatus in studies examining racial disparities in health, and how multiple medical risks relate to cognitive outcomes. Neuropsychologists evaluating patients living with HIV should consider how the presence of multiple medical comorbidities may contribute to the course of cognitive decline as people age.


Assuntos
Infecções por HIV , População Branca , Idoso , Cognição , Comorbidade , Infecções por HIV/complicações , Infecções por HIV/psicologia , Humanos , Testes Neuropsicológicos , Fatores Raciais
5.
Psychosom Med ; 83(3): 218-227, 2021 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-33793453

RESUMO

OBJECTIVE: This cross-sectional study examined the effects of socioeconomic status (SES) mobility from childhood to adulthood on psychological and cognitive well-being in African American and non-Hispanic White HIV-positive (HIV+) and HIV-seronegative (HIV-) adults who are part of an ongoing study investigating psychosocial and neurobehavioral effects of HIV. METHODS: Participants (N = 174, 24.1% female, 59.2% African American, 67.8% HIV+) were categorized into four groups (upward mobility, downward mobility, stable-not-poor, chronic-poverty) based on self-reported childhood and current community SES (which were correlated with objective measures of SES and proxies of childhood SES). SES groups were compared on self-report measures of psychological well-being, subjective executive functioning ratings, and performance across six cognitive domains. Primary analyses were stratified by HIV status. RESULTS: For the HIV+ group, SES mobility was associated with psychological well-being (chronic burden of stress: F(7,101) = 3.17, mean squared error [MSE] = 49.42, p = .030, η2 = 0.14; depressive symptoms: F(7,101) = 4.46, MSE = 70.49, p = .006,η2 = 0.14), subjective ratings of executive dysfunction (F(7,101) = 6.11, MSE = 114.29, p = .001,η2 = 0.18), and objective performance in executive functioning (F(9,99) = 3.22, MSE = 249.52, p = .030, η2 = 0.15) and learning (F(9,99) = 3.01, MSE = 220.52, p = .034, η2 = 0.13). In the control group, SES mobility was associated with chronic stress burden (F(5,49) = 4.677, p = .025, η2 = 0.15); however, no other relationships between SES mobility and outcomes of interest were observed (all p values > .20). In general, downward mobility and chronic poverty were associated with worse ratings across psychological well-being measures and cognitive performance. CONCLUSIONS: Findings within the HIV+ group are consistent with previous studies that report downward mobility to be associated with poor psychological outcomes. People living with HIV may be particularly vulnerable to the adverse effects of socioeconomic instability.


Assuntos
Infecções por HIV , Classe Social , Adulto , Cognição , Estudos Transversais , Feminino , Humanos , Masculino , População Branca , Adulto Jovem
6.
Eur J Nucl Med Mol Imaging ; 48(6): 1864-1875, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33210240

RESUMO

PURPOSE: Postoperative infection still constitutes an important complication of spine surgery, and the optimal imaging modality for diagnosing postoperative spine infection has not yet been established. The aim of this prospective multicenter study was to assess the diagnostic performance of three imaging modalities in patients with suspected postoperative spine infection: MRI, [18F]FDG PET/CT, and SPECT/CT with 99mTc-UBI 29-41. METHODS: Patients had to undergo at least 2 out of the 3 imaging modalities investigated. Sixty-three patients enrolled fulfilled such criteria and were included in the final analysis: 15 patients underwent all 3 imaging modalities, while 48 patients underwent at least 2 imaging modalities (MRI + PET/CT, MRI + SPECT/CT, or PET/CT + SPECT/CT). Final diagnosis of postoperative spinal infection was based either on biopsy or on follow-up for at least 6 months. The MRI, PET/CT, and SPECT/CT scans were read blindly by experts at designated core laboratories. Spine surgery included metallic implants in 46/63 patients (73%); postoperative spine infection was diagnosed in 30/63 patients (48%). RESULTS: Significant discriminants between infection and no infection included fever (P = 0.041), discharge at the wound site (P < 0.0001), and elevated CRP (P = 0.042). There was no difference in the frequency of infection between patients who underwent surgery involving spinal implants versus those who did not. The diagnostic performances of MRI and [18F]FDG PET/CT analyzed as independent groups were equivalent, with values of the area under the ROC curve equal to 0.78 (95% CI: 0.64-0.92) and 0.80 (95% CI: 0.64-0.98), respectively. SPECT/CT with 99mTc-UBI 29-41 yielded either unacceptably low sensitivity (44%) or unacceptably low specificity (41%) when adopting more or less stringent interpretation criteria. The best diagnostic performance was observed when combining the results of MRI with those of [18F]FDG PET/CT, with an area under the ROC curve equal to 0.938 (95% CI: 0.80-1.00). CONCLUSION: [18F]FDG PET/CT and MRI both possess equally satisfactory diagnostic performance in patients with suspected postoperative spine infection, the best diagnostic performance being obtained by combining MRI with [18F]FDG PET/CT. The diagnostic performance of SPECT/CT with 99mTc-UBI 29-41 was suboptimal in the postoperative clinical setting explored with the present study.


Assuntos
Discite , Fluordesoxiglucose F18 , Discite/diagnóstico por imagem , Humanos , Imageamento por Ressonância Magnética , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Estudos Prospectivos , Cintilografia , Compostos Radiofarmacêuticos , Sensibilidade e Especificidade
7.
Curr Opin Endocrinol Diabetes Obes ; 27(3): 162-169, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32250976

RESUMO

PURPOSE OF REVIEW: Pheochromocytomas and paragangliomas represent less than 1% of all endocrine tumors. Approximately 15-20% of these tumors are malignant. The definition of malignancy relies on the presence of metastasis. Metastatic pheochromocytomas and paragangliomas are usually advanced, incurable tumors with limited therapeutic options. About 50-60% of these tumors express the noradrenaline transporter in their cell membranes. Recently, the United States Food and Drug Administration approved high-specific-activity iodine 131 metaiodobenzylguanidine (HSA-I-131-MIBG) for the treatment of metastatic pheochromocytomas and paragangliomas that express the noradrenaline transporter. This review reports the benefits and toxicity of HSA-I-131-MIBG, its physical and dosimetric aspects, and radiation safety precautions, as well as its potential therapeutic value for other malignancies (neuroblastoma, gastroenteropancreatic neuroendocrine tumors, and medullary thyroid carcinoma). RECENT FINDINGS: A phase 2 clinical trial with HSA-I-131-MIBG reported an impressive clinical benefit rate, acceptable toxicity and long-term benefits. SUMMARY: HSA-I-131-MIBG is an effective medication for metastatic pheochromocytomas and paragangliomas that express the noradrenaline transporter.


Assuntos
3-Iodobenzilguanidina/uso terapêutico , Neoplasias das Glândulas Suprarrenais/radioterapia , Radioisótopos do Iodo/uso terapêutico , Paraganglioma/radioterapia , Feocromocitoma/radioterapia , Doenças Raras/radioterapia , Neoplasias das Glândulas Suprarrenais/patologia , Carcinoma Neuroendócrino/patologia , Carcinoma Neuroendócrino/radioterapia , Humanos , Neoplasias Intestinais/patologia , Neoplasias Intestinais/radioterapia , Metástase Neoplásica , Neuroblastoma/patologia , Neuroblastoma/radioterapia , Tumores Neuroendócrinos/patologia , Tumores Neuroendócrinos/radioterapia , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/radioterapia , Paraganglioma/patologia , Feocromocitoma/patologia , Neoplasias Gástricas/patologia , Neoplasias Gástricas/radioterapia , Terapias em Estudo/métodos , Neoplasias da Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/radioterapia
8.
J Nucl Med ; 61(6): 890-896, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-31924723

RESUMO

Studies demonstrate that the investigational 64Cu-DOTATATE radiopharmaceutical may provide diagnostic and logistical benefits over available imaging agents for patients with somatostatin receptor (SSTR)-positive neuroendocrine tumors (NETs). Accordingly, we aimed to prospectively determine the lowest dose of 64Cu-DOTATATE that facilitates diagnostic-quality scans and evaluated the diagnostic performance and safety in a phase III study of patients with SSTR-expressing NETs. Methods: A dose-ranging study was conducted on 12 patients divided into 3 dose groups (111 MBq [3.0 mCi], 148 MBq [4.0 mCi], and 185 MBq [5.0 mCi] ± 10%) to determine the lowest dose of 64Cu-DOTATATE that produced diagnostic-quality PET/CT images. Using the 64Cu-DOTATATE dose identified in the dose-ranging study, 3 independent nuclear medicine physicians who were masked to all clinical information read PET/CT scans from 21 healthy volunteers and 42 NET-positive patients to determine those with disease or no disease, as well as those with localized versus metastatic status. Masked-reader evaluations were compared with a patient-specific standard of truth, which was established by an independent oncologist who used all previously available pathology, clinical, and conventional imaging data. Diagnostic performance calculated for 64Cu-DOTATATE included sensitivity, specificity, negative predictive value, positive predictive value, and accuracy. Inter- and intrareader reliability, as well as ability to differentiate between localized and metastatic disease, was also determined. Adverse events were recorded from 64Cu-DOTATATE injection through 48 h after injection. Results: The dose-ranging study identified 148 MBq (4.0 mCi) as the optimal dose to obtain diagnostic-quality PET/CT images. After database lock, diagnostic performance from an initial majority read of the 3 independent readers showed a significant 90.9% sensitivity (P = 0.0042) and 96.6% specificity (P < 0.0001) for detecting NETs, which translated to a 100.0% sensitivity and 96.8% specificity after correcting for an initial standard-of-truth misread. Excellent inter- and intrareader reliability, as well as ability to distinguish between localized and metastatic disease, was also noted. No adverse events were related to 64Cu-DOTATATE, and no serious adverse events were observed. Conclusion:64Cu-DOTATATE PET/CT is a safe imaging technique that provides high-quality and accurate images at a dose of 148 MBq (4.0 mCi) for the detection of somatostatin-expressing NETs.


Assuntos
Tumores Neuroendócrinos/diagnóstico por imagem , Octreotida/análogos & derivados , Compostos Organometálicos , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Compostos Radiofarmacêuticos , Receptores de Somatostatina/análise , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Tumores Neuroendócrinos/química , Octreotida/efeitos adversos , Compostos Organometálicos/efeitos adversos , Estudos Prospectivos
9.
J Int Neuropsychol Soc ; 24(10): 1038-1046, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30165914

RESUMO

OBJECTIVES: People living with HIV (PLWH) are more likely to report sleep difficulties and cognitive deficits. While cognitive impairment associated with sleep problems have been found in healthy and medical populations, less is known about the effects of poor sleep health (SH) on cognition among PLWH. This study examined differences in cognitive performance among participants classified based upon their HIV status and reported SH. METHODS: One hundred sixteen (N=116) adults recruited from the Greater Los Angeles community were administered a comprehensive cognitive test battery and completed a questionnaire about SH. Participants were classified into the following HIV/SH groups: [HIV+/good sleep health (SH+; n=34); HIV-/SH+ (n=32); HIV-/poor sleep health (SH-; n=18) and HIV+/SH- (n=32)]. RESULTS: For both HIV+ and HIV- individuals, poor SH was associated with lower cognitive performance, with the domains of learning and memory driving the overall relationship. The HIV+/SH- group had poorer scores in domains of learning and memory compared to the SH+ groups. Additionally, the HIV-/SH- group demonstrated poorer learning compared to the HIV-/SH+ group. CONCLUSIONS: Our findings suggest that sleep problems within medical populations are relevant to cognitive functioning, highlighting the clinical and scientific importance of monitoring sleep health and cognition to help identify individuals at greatest risk of poor health outcomes. Longitudinal investigations using both objective and subjective measures of sleep are needed to determine the robustness of the current findings and the enduring effects of poor SH in the context of chronic disease. (JINS, 2018, 24, 1038-1046).


Assuntos
Cognição , Soronegatividade para HIV , Soropositividade para HIV/psicologia , Sono , Adulto , Disfunção Cognitiva , Feminino , Soropositividade para HIV/complicações , Soropositividade para HIV/imunologia , Nível de Saúde , Humanos , Aprendizagem , Masculino , Memória , Pessoa de Meia-Idade , Testes Neuropsicológicos , Transtornos do Sono-Vigília/etiologia , Transtornos do Sono-Vigília/psicologia , Fatores Socioeconômicos , Inquéritos e Questionários
10.
J Womens Health (Larchmt) ; 27(9): 1177-1185, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-30070959

RESUMO

BACKGROUND: In Los Angeles County, the rates of sexually transmitted infections and diseases among African Americans represent a significant public health disparity. Older African American women are at particular risk as they are more likely to engage in high-risk sexual behaviors and report social isolation and loneliness than their younger counterparts. However, the literature on the relationship between sexual health and mental health in this group is limited. The purpose of this study was to use a community-based participatory research (CBPR) approach to better understand sexual health behaviors and mental health among African American women over 50 years of age who reside in South Los Angeles. MATERIALS AND METHODS: This project was divided into two phases. Phase I (January-March 2017) of the project consisted of four dialog/focus groups (N = 45) (ages: 50-80; Mage = 67). The purpose of Phase II (April 2017) was to present study results from Phase I to the community via a community-based conference, as well as gather feedback and generate discussion about the next steps for community prevention/intervention. RESULTS: Women reported that they did not feel comfortable discussing sexual practices with their physician, partners, and friends. Most women identified depression, loneliness, and self-esteem issues as reasons for engaging in high-risk sexual behaviors. During Phase II, potential intervention avenues emerged to address issues such as lack of physician-patient communication, lack of community support, and dialogs about sex. CONCLUSIONS: The use of CBPR greatly enhanced our knowledge of the core issues surrounding sexual health and mental health among older African American women.


Assuntos
Negro ou Afro-Americano/estatística & dados numéricos , Saúde Mental/etnologia , Comportamento Sexual/etnologia , Saúde Sexual/etnologia , Sexualidade/etnologia , Negro ou Afro-Americano/psicologia , Idoso , Idoso de 80 Anos ou mais , Pesquisa Participativa Baseada na Comunidade , Feminino , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Pessoa de Meia-Idade , Relações Profissional-Paciente , Comportamento Sexual/psicologia , Infecções Sexualmente Transmissíveis/epidemiologia , Estados Unidos
11.
Hum Brain Mapp ; 39(6): 2532-2540, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29488278

RESUMO

OBJECTIVE: HIV infection and aging are both associated with neurodegeneration. However, whether the aging process alone or other factors associated with advanced age account for the progression of neurodegeneration in the aging HIV-positive (HIV+) population remains unclear. METHODS: HIV+ (n = 70) and HIV-negative (HIV-, n = 34) participants underwent diffusion tensor imaging (DTI) and metrics of microstructural properties were extracted from regions of interest (ROIs). A support vector regression model was trained on two independent datasets of healthy adults across the adult life-span (n = 765, Cam-CAN = 588; UiO = 177) to predict participant age from DTI metrics, and applied to the HIV dataset. Predicted brain age gap (BAG) was computed as the difference between predicted age and chronological age, and statistically compared between HIV groups. Regressions assessed the relationship between BAG and HIV severity/medical comorbidities. Finally, correlation analyses tested for associations between BAG and cognitive performance. RESULTS: BAG was significantly higher in the HIV+ group than the HIV- group F (1, 103) = 12.408, p = .001). HIV RNA viral load was significantly associated with BAG, particularly in older HIV+ individuals (R2 = 0.29, F(7, 70) = 2.66, p = .021). Further, BAG was negatively correlated with domain-level cognitive function (learning: r = -0.26, p = .008; memory: r = -0.21, p = .034). CONCLUSIONS: HIV infection is associated with augmented white matter aging, and greater brain aging is associated with worse cognitive performance in multiple domains.


Assuntos
Envelhecimento/patologia , Encéfalo/patologia , Infecções por HIV/patologia , Substância Branca/patologia , Adulto , Distribuição por Idade , Idoso , Idoso de 80 Anos ou mais , Análise de Variância , Encéfalo/diagnóstico por imagem , Encéfalo/virologia , Antígenos CD4/metabolismo , Cognição/fisiologia , Feminino , Infecções por HIV/diagnóstico por imagem , Infecções por HIV/fisiopatologia , Humanos , Processamento de Imagem Assistida por Computador , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Escalas de Graduação Psiquiátrica , Estatísticas não Paramétricas , Carga Viral , Substância Branca/diagnóstico por imagem , Substância Branca/virologia
12.
Artigo em Inglês | MEDLINE | ID: mdl-28884520

RESUMO

The relative pressure difference across stenotic blood vessels serves as an important clinical index for the diagnosis of many cardiovascular diseases. While the clinical gold standard for relative pressure difference measurements is invasive catheterization, Phase-Contrast Magnetic Resonance Imaging has emerged as a promising tool for enabling a noninvasive quantification, by linking highly spatially resolved velocity measurements with relative pressures via the incompressible Navier-Stokes equations. In this work, we provide a review and analysis of current methods for relative pressure estimation and propose 3 additional techniques. Methods are compared using synthetic data from numerical examples, and sensitivity to subsampling and noise was explored. Through our analysis, we verify that the newly proposed approaches are more robust with respect to spatial subsampling and less sensitive to noise and therefore provide improved means for estimating relative pressure differences noninvasively.


Assuntos
Velocidade do Fluxo Sanguíneo/fisiologia , Pressão Sanguínea/fisiologia , Modelos Teóricos , Vasos Sanguíneos/diagnóstico por imagem , Humanos , Imageamento por Ressonância Magnética
13.
Skeletal Radiol ; 41(8): 899-909, 2012 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-22101865

RESUMO

OBJECTIVE: Our purposes were to explore the epidemiology of metastases to skeletal muscle and their detection on fused positron emission tomography and computed tomography. MATERIALS AND METHODS: We evaluated the epidemiology of skeletal muscle metastases in the literature and among cases from our hospital and studied the prevalence and appearance of skeletal muscle metastases among 433 patients undergoing fused positron emission tomography and computed tomography for non-small-cell lung cancer. RESULTS: We found 264 cases of skeletal muscle metastases in 151 articles. Mean age was 57.8 years with 67% men. At our hospital we studied 70 cases. Mean patient age was 55.7 years with 63% men. The most common source was lung cancer, and the most common site of involvement was the muscles of the trunk. Among our lung cancer patients undergoing fused positron emission tomography and computed tomography, we found 7 (1.6%) with skeletal muscle metastases. In only one of these seven patients was the metastasis first discovered by another imaging modality. In one patient discovery of the metastasis at fused positron emission tomography and computed tomography changed management. CONCLUSION: Skeletal muscle metastases are not rare. They may be more apparent at fused positron emission tomography and computed tomography than at other staging examinations, particularly contrast-enhanced CT scanning. Radiologists need to be alert to their presence when interpreting staging examinations in cancer patients.


Assuntos
Carcinoma/epidemiologia , Carcinoma/secundário , Neoplasias Pulmonares/epidemiologia , Imagem Multimodal/estatística & dados numéricos , Neoplasias Musculares/epidemiologia , Neoplasias Musculares/secundário , Tomografia por Emissão de Pósitrons , Tomografia Computadorizada por Raios X/estatística & dados numéricos , Carcinoma/diagnóstico , Comorbidade , Feminino , Humanos , Neoplasias Pulmonares/diagnóstico , Masculino , Pessoa de Meia-Idade , Neoplasias Musculares/diagnóstico , Prevalência , Doenças Raras , Fatores de Risco
14.
J Clin Oncol ; 29(23): 3126-32, 2011 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-21730275

RESUMO

PURPOSE: Trastuzumab resistance has been linked to activation of the phosphoinositol 3-kinase (PI3K) pathway. Phosphatase and tensin homolog (PTEN) is a dual phosphatase that counteracts the PI3K function; PTEN loss leads to activation of the Akt cascade and the downstream mammalian target of rapamycin (mTOR). Preclinical studies demonstrated that mTOR inhibition sensitized the response to trastuzumab in mice with HER2 overexpressing and PTEN-deficient breast xenografts. Our trial evaluated the safety and efficacy of the combination of everolimus and trastuzumab in women with HER2-overexpressing metastatic breast cancer (MBC) that progressed on trastuzumab-based therapy. PATIENTS AND METHODS: This represents a pooled analysis (n = 47), stemming from two trials that occurred concurrently in The University of Texas MD Anderson Cancer Center, Beth Israel Deaconess Medical Center, and Dana-Farber Cancer Institute. Patients with HER2-overexpressing MBC who had progressed on trastuzumab-based therapy received trastuzumab every 3 weeks in combination with daily everolimus. RESULTS: Among 47 patients, the combination of everolimus and trastuzumab provided partial responses in seven patients (15%) and persistent stable disease (lasting 6 months or longer) in nine patients (19%), resulting in a clinical benefit rate of 34%. The median progression-free survival (PFS) was 4.1 month. Fatigue, infection, and mucositis were the predominant nonhematologic toxicities. Trastuzumab did not have significant influence on the pharmacokinetic profile of everolimus. Patients with PTEN loss demonstrated decreased overall survival (P = .048). However, PFS was not affected by PTEN loss. CONCLUSION: Inhibition of mTOR results in clinical benefit and disease response in patients with trastuzumab-resistant HER2-overexpressing MBC.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Receptor ErbB-2/biossíntese , Sirolimo/análogos & derivados , Adulto , Idoso , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais/farmacocinética , Anticorpos Monoclonais Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/farmacocinética , Biomarcadores Tumorais/análise , Neoplasias da Mama/metabolismo , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Intervalo Livre de Doença , Everolimo , Feminino , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Metástase Neoplásica , PTEN Fosfo-Hidrolase/metabolismo , Terapia de Salvação/métodos , Sirolimo/administração & dosagem , Sirolimo/efeitos adversos , Sirolimo/farmacocinética , Sirolimo/uso terapêutico , Serina-Treonina Quinases TOR/metabolismo , Trastuzumab
16.
Endocrine ; 37(1): 209-12, 2010 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-20963572

RESUMO

We present a patient with metastatic pheochromocytoma, who developed progressive and fatal hypoglycemia most likely secondary to direct tumor glucose consumption that did not respond to high-dose glucose infusion, corticosteroids, or glucagon therapy. The pattern of glucose uptake on (18)F-2-fluoro-2-deoxy-D-glucose positron emission tomography, with preferential tumor glucose uptake in association with a marked reduction in normal uptake in the heart, muscles, and brain, is highly suggestive of direct consumption of glucose by the tumor rather than insulin-like growth factor-2 mediated hypoglycemia. In patients with large-volume metastatic malignancies, direct tumor glucose consumption should be considered in the differential diagnosis of hypoglycemia. Nuclear medicine imaging techniques can illustrate the pathophysiology of hypoglycemia in such cases.


Assuntos
Neoplasias das Glândulas Suprarrenais/metabolismo , Neoplasias das Glândulas Suprarrenais/fisiopatologia , Glucose/metabolismo , Hipoglicemia/etiologia , Feocromocitoma/metabolismo , Feocromocitoma/fisiopatologia , Neoplasias das Glândulas Suprarrenais/patologia , Neoplasias das Glândulas Suprarrenais/terapia , Neoplasias Ósseas/secundário , Progressão da Doença , Evolução Fatal , Fluordesoxiglucose F18 , Humanos , Neoplasias Hepáticas/secundário , Masculino , Feocromocitoma/patologia , Feocromocitoma/terapia , Tomografia por Emissão de Pósitrons , Tomografia Computadorizada de Emissão de Fóton Único , Carga Tumoral , Adulto Jovem
17.
J Pediatr Hematol Oncol ; 32(2): 160-2, 2010 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-20168252

RESUMO

Choroid plexus tumors are rare brain tumors which account for 0.4% to 0.6% among brain tumors. Tumor resection is known to be of large prognostic impact, and re-resection of residual tumors is a part of standard care. However, after multiple resections it can become difficult to differentiate tumor from reactive tissue. 99mTC-sestamibi scans may assist in differentiating neoplastic (99mTC-sestamibi positive) from non-neoplastic tissue (99mTC-sestamibi negative). Previous literature showed sestamibi to be helpful in detecting residual choroid plexus tumors resulting in further resection. Here, we report the first case to show that sestamibi scans can also help with the opposite decision.


Assuntos
Neoplasias do Plexo Corióideo/diagnóstico por imagem , Compostos Radiofarmacêuticos , Tecnécio Tc 99m Sestamibi , Tomografia Computadorizada de Emissão , Barreira Hematoencefálica , Neoplasias do Plexo Corióideo/patologia , Neoplasias do Plexo Corióideo/cirurgia , Feminino , Humanos , Lactente , Tecnécio Tc 99m Sestamibi/farmacocinética
18.
Mol Imaging Biol ; 12(2): 110-38, 2010 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-20049543

RESUMO

INTRODUCTION: Single photon emission computed tomography/computed tomography (SPECT/CT) delivers in a single imaging modality the functional-metabolic information from the SPECT image, combined with the detailed anatomical information from a diagnostic quality CT scanner. METHOD: In this review, we provide the details for the acquisition, processing, and display of the SPECT, as well as the CT, and the fused SPECT/CT images, with one of the newest devices that combines a dual-headed gamma camera with a multislice CT scanner. Also, we go over the performance characteristics, including the planning and installation requirements for this type of scanners. In addition, we describe what are the current and feasible near-future applications of this new and exciting hybrid imaging modality. DISCUSSION: The ability to combine an optimized state-of-the-art SPECT image, with resolutions down to 5 mm, with a diagnostic quality CT image-using slices as thin as 1.25 mm-provides a diagnostic advantage that potentially can deliver a more convenient and faster diagnosis, with clinical implications in a significant percentage of patients. This imaging technique has been investigated in a wide range of studies for the oncologic patient, including but not limited to bone scintigraphy, (111)In-pentetreotide scintigraphy, lymphoscintigraphy, (67)Ga and labeled leukocyte infection imaging, (131)I-metaiodobenzylguanidine, parathyroid scintigraphy, (131)I diagnostic scintigraphy, and (111)In ProstaScint, and for planning of radionuclide therapy. CONCLUSION: Therefore, this evolving and exciting imaging modality will continue to grow and define its place as an integral part of the evaluation of the cancer patient.


Assuntos
Neoplasias/diagnóstico por imagem , Tomografia Computadorizada de Emissão de Fóton Único/instrumentação , Tomografia Computadorizada por Raios X/instrumentação , Humanos , Processamento de Imagem Assistida por Computador
19.
Skeletal Radiol ; 39(2): 131-40, 2010 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-19760279

RESUMO

OBJECTIVE: To determine if the location of the point of maximum standardized uptake value (SUVmax) being included in or not included in the histopathologic slab section corresponded to tumor necrosis or survival. MATERIALS AND METHODS: Twenty-nine osteosarcoma patients underwent post-chemotherapy [fluorine-18]-fluoro-2-deoxy-D: -glucose (FDG) positron-emission tomography-computed tomography (PET/CT) prior to resection. PET/CT images were correlated with slab-section location as determined by photographs or knowledge of specimen processing. The location of the point of SUVmax was then assigned as being 'in' or 'out' of the slab section. Cox's proportional hazard regression was used to evaluate relationships between the location and value of SUVmax and survival. Logistic regression was employed to evaluate tumor necrosis. RESULTS: No correlation was found between the SUVmax location and survival or tumor necrosis. High SUVmax correlated to poor survival. CONCLUSION: High SUVmax value correlated to poor survival. Minimal viable tumor (> 10%) following chemotherapy is a known indicator of poor survival. No correlation was found between the location of SUVmax and survival or tumor necrosis. Therefore, the SUVmax value either does not correspond to a sufficient number of tumor cells to influence tumor necrosis measurement or it was included in the out-of-slab samples that were directed to viable-appearing areas of the gross specimen. Since high SUVmax has been previously found to correspond to poor tumor necrosis, and tumor necrosis is simply an estimate of the amount of viable tumor, SUVmax likely represents many viable tumor cells. Therefore, when not in the slab section, SUVmax was likely included in the tumor necrosis measurement through directed sampling, validating our current method of osteosarcoma specimen analysis.


Assuntos
Neoplasias Ósseas/diagnóstico , Neoplasias Ósseas/mortalidade , Fluordesoxiglucose F18 , Interpretação de Imagem Assistida por Computador/métodos , Osteossarcoma/diagnóstico , Osteossarcoma/mortalidade , Tomografia por Emissão de Pósitrons/estatística & dados numéricos , Neoplasias Ósseas/metabolismo , Fluordesoxiglucose F18/farmacocinética , Necrose , Osteossarcoma/metabolismo , Prevalência , Compostos Radiofarmacêuticos/farmacocinética , Reprodutibilidade dos Testes , Medição de Risco , Fatores de Risco , Sensibilidade e Especificidade , Análise de Sobrevida , Taxa de Sobrevida , Texas , Tomografia Computadorizada por Raios X/estatística & dados numéricos
20.
World J Surg ; 33(3): 412-6, 2009 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-19148701

RESUMO

BACKGROUND: A uniform and reliable description of the exact locations of adenomatous parathyroid glands is necessary for accurate communications between surgeons and other specialists. We developed a nomenclature that provides a precise means of communicating the most frequently encountered parathyroid adenoma locations. METHODS: This classification scheme is based on the anatomic detail provided by imaging and can be used in radiology reports, operative records, and pathology reports. It is based on quadrants and anterior-posterior depth relative to the course of the recurrent laryngeal nerve and the thyroid parenchyma. The system uses the letters A-G to describe exact gland locations. RESULTS: A type A parathyroid gland is a gland that originates from a superior pedicle, lateral to the recurrent laryngeal nerve compressed within the capsule of the thyroid parenchyma. A type B gland is a superior gland that has fallen posteriorly into the tracheoesophageal groove and is in the same cross-sectional plane as the superior portion of the thyroid parenchyma. A type C gland is a gland that has fallen posteriorly into the tracheoesophageal groove and on a cross-sectional view lies at the level of or below the inferior pole of the thyroid gland. A type D gland lies in the midregion of the posterior surface of the thyroid parenchyma, near the junction of the recurrent laryngeal nerve and the inferior thyroid artery or middle thyroidal vein; because of this location, dissection is difficult. A type E gland is an inferior gland close to the inferior pole of the thyroid parenchyma, lying in the lateral plane with the thyroid parenchyma and anterior half of the trachea. A type F gland is an inferior gland that has descended (fallen) into the thyrothymic ligament or superior thymus; it may appear to be "ectopic" or within the superior mediastinum. An anterior-posterior view shows the type F gland to be anterior to the trachea. A type G gland is a rare, truly intrathyroidal parathyroid gland. CONCLUSIONS: A reproducible nomenclature can provide a means of consistent communication about parathyroid adenoma location. If uniformly adopted, it has the potential to reliably communicate exact gland location without lengthy descriptions. This system may be beneficial for surgical planning as well as operative and pathology reporting.


Assuntos
Comunicação Interdisciplinar , Neoplasias das Paratireoides/classificação , Humanos , Neoplasias das Paratireoides/patologia , Neoplasias das Paratireoides/cirurgia , Terminologia como Assunto
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