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2.
Radiology ; 282(1): 160-170, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-27479640

RESUMO

Purpose To evaluate the frequency, patterns, and prognostic importance of metastatic hepatic involvement in serous ovarian cancer. Materials and Methods This institutional review board-approved retrospective study, with waived informed consent, included 244 patients with pathologically proven serous ovarian cancer (mean age ± standard deviation, 59 years ± 10.7; range 19-93 years). Electronic medical records and all available imaging studies over a median follow-up of 44 months (interquartile range [IQR], 27-70) were reviewed to identify the frequency of liver parenchymal invasion (LPI) from perihepatic peritoneal metastasis and hematogenous liver metastases. The associations and prognostic importance of LPI and hematogenous metastases were studied by using univariate and multivariate Cox proportional analysis. Results Eighty-four of 244 patients (34%) developed perihepatic metastases, of whom 55 (23%) developed LPI after median of 43 months (IQR, 25-63). Hematogenous hepatic metastases developed in 38 of 244 patients (16%) after median of 42 months (IQR, 26-64). At multivariate analysis, age (P = .008; hazard ratio [HR]: 1.03; 95% confidence interval [CI]: 1.009, 1.07) and suboptimal cytoreduction (P = .03; HR, 2.13; 95% CI: 1.12, 4.07) were associated with LPI. Increasing age (P = .01; HR, 1.04; 95% CI: 1.008, 1.08), high-grade tumor (P = .01; HR, 6.75; 95% CI: 1.44, 120.5), and advanced stage (P = .03; HR, 3.16; 95% CI: 1.94, 4.56) were associated with hematogenous metastases. Overall survival with and without LPI was similar (median, 80 months; IQR, 50-not reached vs 123 months; IQR, 49-279; P = .6). Hematogenous metastases were associated with significantly shorter survival at univariate (median 63 months, IQR 43-139 vs 145 months, IQR 50-not reached; P = .006) and multivariate analyses (P = .03; HR, 1.88; 95% CI: 1.14, 3.28). Conclusion Differentiating hematogenous metastases and LPI is important for radiologists; hematogenous metastases are associated with shorter survival, while LPI does not adversely affect survival and prognostically behaves like peritoneal disease. © RSNA, 2016.


Assuntos
Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/secundário , Neoplasias Ovarianas/patologia , Tomografia Computadorizada por Raios X/métodos , Idoso , Meios de Contraste , Feminino , Humanos , Iohexol , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Interpretação de Imagem Radiográfica Assistida por Computador , Estudos Retrospectivos
3.
J Neurooncol ; 130(3): 495-503, 2016 12.
Artigo em Inglês | MEDLINE | ID: mdl-27576699

RESUMO

Glioblastoma (GBM) is an incurable brain tumor characterized by the expression of pro-angiogenic cytokines. A recent phase II clinical trial studied VEGF Trap in adult patients with temozolomide-resistant GBM. We sought to explore changes in [18F]Fluorodeoxyglucose positron emission tomography (FDG-PET) or magnetic resonance imaging (MRI) in trial participants correlating these changes with disease response. FDG-PET and MRI images obtained before and after the first dose of VEGF Trap were spatially co-registered. Regions of interest on each image slice were combined to produce a volume of interest representative of the entire tumor. Percent and absolute changes in maximum FDG-avidity, mean apparent diffusion coefficient (ADC), Ktrans, and Ve were calculated per lesion. Among the 12 participants that underwent dynamic contrast enhanced MRI (DCE-MRI), there were large, statistically significant reductions in Ktrans and Ve (median difference = -41.8 %, p < 0.02 and -42.6 %, p < 0.04, respectively). In contrast, there were no significant reductions in ADC or FDG-PET SUVmax values. DCE-MRI is a useful measure of early pharmacodynamic effects of VEGF Trap on tumor vasculature. The absence of significant changes in FDG-PET and DW-MRI suggest that the early pharmacodynamic effects are specific to tumor perfusion and/or permeability and do not directly inhibit metabolism or induce cell death. DCE-MRI in conjunction with standard imaging may be promising for the identification of anti-angiogenic effects in this patient population with this therapeutic target. Further studies are needed to evaluate the relationship between DCE-MRI response and clinical outcome.


Assuntos
Antineoplásicos/uso terapêutico , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/tratamento farmacológico , Glioblastoma/diagnóstico por imagem , Glioblastoma/tratamento farmacológico , Imageamento por Ressonância Magnética , Receptores de Fatores de Crescimento do Endotélio Vascular/uso terapêutico , Proteínas Recombinantes de Fusão/uso terapêutico , Feminino , Fluordesoxiglucose F18/metabolismo , Humanos , Masculino , Tomografia por Emissão de Pósitrons , Estatísticas não Paramétricas , Análise de Sobrevida , Resultado do Tratamento , Fator A de Crescimento do Endotélio Vascular/metabolismo
4.
Cancer ; 121(22): 4007-15, 2015 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-26264378

RESUMO

BACKGROUND: Patients with mucosal and acral melanomas have limited treatment options and a poor prognosis. Mutations of the KIT oncogene in these melanoma subtypes provide a potential therapeutic target. METHODS: A multicenter phase 2 trial of sunitinib was conducted in patients with unresectable stage III or IV melanoma of a mucosal or acral primary origin. Patients were treated in 2 cohorts: cohort A received sunitinib at a dose of 50 mg daily for 4 weeks of a 6-week cycle, and cohort B received sunitinib at a dose of 37.5 mg daily on a continuous basis. Dose reductions were permitted for treatment-related toxicities, and tumor assessments were performed every 2 months. RESULTS: Fifty-two patients were enrolled: 21 in cohort A and 31 in cohort B. Four patients had confirmed partial responses, which lasted 5 to 10 months (1 with a KIT mutation). In both cohorts, the proportion of patients alive and progression-free at 2 months was 52% (95% confidence interval, 38%-66%); this was significantly larger than the hypothesized null of 5%. There was no significant difference in response or overall survival between the 25% of patients with a KIT mutation and those without one (response rate, 7.7% vs 9.7%; overall survival, 6.4 vs 8.6 months). The overall disease control rate was 44%, and a high rate of toxicity was associated with the treatment. CONCLUSIONS: Sunitinib showed activity in the treatment of mucosal and acral melanoma that was not dependent on the presence of a KIT mutation. However, the medication was poorly tolerated, and there were no prolonged responses. Cancer 2015;121:4007-4015. © 2015 American Cancer Society.


Assuntos
Antineoplásicos/uso terapêutico , Indóis/uso terapêutico , Melanoma/tratamento farmacológico , Pirróis/uso terapêutico , Neoplasias Cutâneas/tratamento farmacológico , Antineoplásicos/efeitos adversos , Feminino , Humanos , Indóis/efeitos adversos , Masculino , Melanoma/genética , Melanoma/mortalidade , Melanoma/secundário , Mucosa/patologia , Mutação , Proteínas Proto-Oncogênicas c-kit/genética , Pirróis/efeitos adversos , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/mortalidade , Sunitinibe
5.
Radiology ; 277(3): 733-40, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26053310

RESUMO

PURPOSE: To study the frequency, timing, and associations of thoracic metastases in advanced (stage III and IV) high-grade serous ovarian cancer (HGSC) to help optimize the use of cross-sectional chest imaging. MATERIALS AND METHODS: This institutional review board-approved retrospective study with waived informed consent included 186 consecutive patients with pathologically proven advanced HGSC after primary cytoreduction (mean age ± standard deviation, 60 years ± 9.7) who underwent imaging at our tertiary cancer institution from January 2012 to December 2012 with at least 1 year of follow-up, unless there was thoracic metastasis or death. Electronic medical records and all available imaging studies were reviewed to record patient and tumor characteristics, frequency and timing of abdominal and thoracic metastases, and visibility of the first thoracoabdominal metastasis on abdominal images. Patient and tumor characteristics associated with thoracic metastases were studied by using univariate and multivariate Cox proportional analysis. RESULTS: After median follow-up of 57 months (interquartile range [IQR], 38-93), 175 patients (94%) developed metastatic disease; each had abdominal disease, and 76 (41%) had thoracic metastases. The first thoracoabdominal metastasis was visible on abdominal images in all 175 patients. The thoracic metastasis-free interval was longer than the abdominal disease-free interval (median, 85 months [IQR, 28-131] vs 14 months [IQR, 7-27], respectively; P < .0001). Presence of disease on abdominal images (hazard ratio, 2.56; 95% confidence interval: 1.35, 4.76) was the only factor independently associated with thoracic metastases. CONCLUSION: Thoracic metastases in advanced HGSC rarely occur before abdominal disease, and first thoracoabdominal metastases are invariably visible on abdominal images. Therefore, cross-sectional chest imaging may be deferred until development of abdominal disease, with minimal risk of missing thoracic metastases.


Assuntos
Neoplasias Ovarianas/patologia , Neoplasias Torácicas/secundário , Adulto , Feminino , Humanos , Pessoa de Meia-Idade , Neoplasias Ovarianas/diagnóstico por imagem , Terminologia como Assunto , Tomografia Computadorizada por Raios X
6.
Radiographics ; 35(2): 424-37, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25763727

RESUMO

Cancer immunotherapy is changing the imaging evaluation of cancer treatment response and treatment-related toxic effects. New emerging patterns of treatment response and treatment-related toxic effects after treatment with immunomodulating agents have been observed. Treatment response after immunomodulatory therapy can be associated with significantly delayed decrease in tumor size, and new or enlarging tumors observed soon after completion of treatment may not reflect disease progression. In addition, activation of the immune system to fight cancer may lead to unwanted autoimmune-mediated toxic effects that could be mistaken for metastatic disease or misdiagnosed as a non-treatment-related process and delay appropriate clinical management. Radiologists must recognize the novel treatment response patterns and the wide range of autoimmune toxic effects, which should not be mistaken for treatment failure or metastatic disease progression.


Assuntos
Diagnóstico por Imagem , Imunoterapia/efeitos adversos , Neoplasias/diagnóstico , Neoplasias/terapia , Humanos , Resultado do Tratamento
7.
Cancer ; 120(5): 711-21, 2014 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-24264883

RESUMO

BACKGROUND: Alternative response criteria have been proposed in patients with metastatic renal cell carcinoma (mRCC) who are receiving vascular endothelial growth factor (VEGF)-targeted therapy, including 10% tumor shrinkage as an indicator of response/outcome. However, to the authors' knowledge, intraobserver and interobserver measurement variability have not been defined in this setting. The objective of the current study was to determine intraobserver and interobserver agreement of computed tomography (CT) size and attenuation measurements to establish reproducible response indicators. METHODS: Seventy-one patients with mRCC with 179 target lesions were enrolled in phase 2 and phase 3 trials of VEGF-targeted therapies and retrospectively studied with Institutional Review Board approval. Two radiologists independently measured the long axis diameter and mean attenuation of target lesions at baseline and on follow-up CT. Concordance correlation coefficients and Bland-Altman plots were used to assess intraobserver and interobserver agreement. RESULTS: High concordance correlation coefficients (range, 0.8602-0.9984) were observed in all types of measurements. The 95% limits of agreement for the percentage change of the sum longest diameter was -7.30% to 7.86% for intraobserver variability, indicating that 10% tumor shrinkage represents a true change in tumor size when measured by a single observer. The 95% limits of interobserver variability were -16.3% to 15.4%. On multivariate analysis, the location of the lesion was found to significantly contribute to interobserver variability (P = .048). The 95% limits of intraobserver agreement for the percentage change in CT attenuation were -18.34% to 16.7%. CONCLUSIONS: In patients with mRCC who are treated with VEGF inhibitors, 10% tumor shrinkage is a reproducible radiologic response indicator when baseline and follow-up studies are measured by a single radiologist. Lesion location contributes significantly to measurement variability and should be considered when selecting target lesions.


Assuntos
Inibidores da Angiogênese/uso terapêutico , Carcinoma de Células Renais/diagnóstico por imagem , Carcinoma de Células Renais/tratamento farmacológico , Neoplasias Renais/diagnóstico por imagem , Neoplasias Renais/tratamento farmacológico , Tomografia Computadorizada por Raios X , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/diagnóstico por imagem , Neoplasias/tratamento farmacológico , Variações Dependentes do Observador , Resultado do Tratamento
8.
Oncologist ; 19(5): 507-14, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24755461

RESUMO

Vascular endothelial growth factor (VEGF)-targeted agents are standard therapies for metastatic renal cell carcinoma (mRCC), associated with variable tumor shrinkage. Response Evaluation Criteria in Solid Tumors (RECIST) is of limited utility in this setting, and other imaging changes are sought to reliably predict outcome early. We aim to validate 10% tumor shrinkage as the best early indicator of outcome. Methods. In this institutional review board-approved, Health Insurance Portability and Accountability Act-compliant study, 66 mRCC patients with 165 lesions on clinical trials of VEGF-targeted agents underwent thoracic and abdominal computed tomography at baseline and at first follow-up after therapy. Measurements were performed according to RECIST and tumor shrinkage of ≥10% decrease in sum of the longest diameter (-10%SLD). Correlation with time-to-treatment failure (TTF) and overall survival (OS) were compared and stratified by response to the radiologic criteria. Receiver-operating characteristics (ROC) analysis yielded the optimal threshold change in SLD, defining patients with prolonged survival. Results. More than -10%SLD significantly differentiated responders from nonresponders (median TTF 8.4 vs. 4.1 months, p = .001), whereas partial response by RECIST did not (median TTF 6.9 vs. 5.5 months in responders vs. nonresponders, p = .34). -10%SLD was also significantly predictive of OS (median OS 35.1 vs. 15.0 months in responders vs. nonresponders, p = .003). ROC curve analysis yielded -9.3% in SLD as the optimal threshold for response/no response. Conclusion. Ten percent tumor shrinkage is validated as a reliable early predictor of outcome in mRCC patients receiving VEGF-targeted therapies and may provide a practical measure to guide therapeutic decisions.


Assuntos
Inibidores da Angiogênese/uso terapêutico , Carcinoma de Células Renais/tratamento farmacológico , Neoplasias Renais/tratamento farmacológico , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Renais/diagnóstico por imagem , Carcinoma de Células Renais/mortalidade , Feminino , Humanos , Neoplasias Renais/diagnóstico por imagem , Neoplasias Renais/mortalidade , Masculino , Pessoa de Meia-Idade , Terapia de Alvo Molecular/métodos , Curva ROC , Critérios de Avaliação de Resposta em Tumores Sólidos , Estudos Retrospectivos , Tomografia Computadorizada por Raios X , Resultado do Tratamento
10.
Blood ; 119(20): 4597-607, 2012 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-22383795

RESUMO

Mantle cell lymphoma (MCL) carries an unfavorable prognosis and requires new treatment strategies. The associated t(11:14) translocation results in enhanced cyclin D1 expression and cyclin D1-dependent kinase activity to promote cell-cycle progression. A pharmacodynamic study of the selective CDK4/6 inhibitor PD0332991 was conducted in 17 patients with relapsed disease, using 2-deoxy-2-[(18)F]fluoro-D-glucose (FDG) and 3-deoxy-3[(18)F]fluorothymidine (FLT) positron emission tomography (PET) to study tumor metabolism and proliferation, respectively, in concert with pre- and on-treatment lymph node biopsies to assess retinoblastoma protein (Rb) phosphorylation and markers of proliferation and apoptosis. Substantial reductions in the summed FLT-PET maximal standard uptake value (SUV(max)), as well as in Rb phosphorylation and Ki-67 expression, occurred after 3 weeks in most patients, with significant correlations among these end points. Five patients achieved progression-free survival time of > 1 year (range, 14.9-30.1+ months), with 1 complete and 2 partial responses (18% objective response rate; 90% confidence interval, 5%-40%). These patients demonstrated > 70%, > 90%, and ≥ 87.5% reductions in summed FLT SUV(max) and expression of phospho-Rb and Ki67, respectively, parameters necessary but not sufficient for long-term disease control. The results of the present study confirm CDK4/6 inhibition by PD0332991 at a well-tolerated dose and schedule and suggest clinical benefit in a subset of MCL patients. This study is registered at www.clinicaltrials.gov under identifier NCT00420056.


Assuntos
Linfoma de Célula do Manto/tratamento farmacológico , Piperazinas/uso terapêutico , Piridinas/uso terapêutico , Adulto , Idoso , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Antineoplásicos/uso terapêutico , Quinase 4 Dependente de Ciclina/antagonistas & inibidores , Quinase 6 Dependente de Ciclina/antagonistas & inibidores , Feminino , Humanos , Linfoma de Célula do Manto/sangue , Linfoma de Célula do Manto/diagnóstico , Linfoma de Célula do Manto/metabolismo , Masculino , Pessoa de Meia-Idade , Piperazinas/administração & dosagem , Piperazinas/efeitos adversos , Piperazinas/farmacocinética , Prognóstico , Inibidores de Proteínas Quinases/administração & dosagem , Inibidores de Proteínas Quinases/efeitos adversos , Inibidores de Proteínas Quinases/farmacocinética , Inibidores de Proteínas Quinases/uso terapêutico , Piridinas/administração & dosagem , Piridinas/efeitos adversos , Piridinas/farmacocinética , Especificidade por Substrato , Resultado do Tratamento
11.
Comput Med Imaging Graph ; 111: 102312, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-38141568

RESUMO

Accurate lymph node size estimation is critical for staging cancer patients, initial therapeutic management, and assessing response to therapy. Current standard practice for quantifying lymph node size is based on a variety of criteria that use uni-directional or bi-directional measurements. Segmentation in 3D can provide more accurate evaluations of the lymph node size. Fully convolutional neural networks (FCNs) have achieved state-of-the-art results in segmentation for numerous medical imaging applications, including lymph node segmentation. Adoption of deep learning segmentation models in clinical trials often faces numerous challenges. These include lack of pixel-level ground truth annotations for training, generalizability of the models on unseen test domains due to the heterogeneity of test cases and variation of imaging parameters. In this paper, we studied and evaluated the performance of lymph node segmentation models on a dataset that was completely independent of the one used to create the models. We analyzed the generalizability of the models in the face of a heterogeneous dataset and assessed the potential effects of different disease conditions and imaging parameters. Furthermore, we systematically compared fully-supervised and weakly-supervised methods in this context. We evaluated the proposed methods using an independent dataset comprising 806 mediastinal lymph nodes from 540 unique patients. The results show that performance achieved on the independent test set is comparable to that on the training set. Furthermore, neither the underlying disease nor the heterogeneous imaging parameters impacted the performance of the models. Finally, the results indicate that our weakly-supervised method attains 90%- 91% of the performance achieved by the fully supervised training.


Assuntos
Imageamento Tridimensional , Redes Neurais de Computação , Humanos , Imageamento Tridimensional/métodos , Tomografia Computadorizada por Raios X/métodos , Linfonodos/diagnóstico por imagem , Estadiamento de Neoplasias , Processamento de Imagem Assistida por Computador/métodos
12.
Radiographics ; 33(7): 2003-17, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24224593

RESUMO

Inflammatory breast cancer (IBC) is a rare breast cancer with a highly virulent course and low 5-year survival rate. Trimodality treatment that includes preoperative chemotherapy, mastectomy, and radiation therapy is the therapeutic mainstay and has been shown to improve prognosis. Proper diagnosis and staging of IBC is critical to treatment planning and requires a multidisciplinary approach that includes imaging. Patients with IBC typically present with rapid onset of breast erythema, edema, and peau d'orange. Both tissue diagnosis of malignancy and clinical findings of inflammatory disease are required to confirm diagnosis of IBC. Imaging is used to identify a biopsy target; direct biopsy; stage IBC; differentiate curable from incurable (stage IV) disease; and help plan chemotherapy, surgical management, and radiation therapy. Comparison of baseline and posttreatment images helps confirm and quantitate disease response. When imaging is used early in the course of therapy to noninvasively predict treatment response, optimal tailored strategies for management of IBC can be implemented. Imaging is vital to diagnosis and treatment planning for patients with IBC, and radiologists are an integral part of the multidisciplinary patient care team.


Assuntos
Neoplasias Inflamatórias Mamárias/diagnóstico , Neoplasias Inflamatórias Mamárias/terapia , Mamografia/métodos , Equipe de Assistência ao Paciente , Ultrassonografia Mamária/métodos , Adulto , Idoso , Diagnóstico Diferencial , Feminino , Humanos , Pessoa de Meia-Idade
13.
J Nucl Med Technol ; 51(3): 204-210, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37316304

RESUMO

In a prospective clinical trial, [18F]fluoro-5α-dihydrotestosterone ([18F]FDHT), the radiolabeled analog of the androgen dihydrotestosterone, was used as a PET/CT imaging agent for in vivo assessment of metastatic androgen receptor-positive breast cancer in postmenopausal women. To our knowledge, this article presents the first report of PET/CT image-based radiation dosimetry of [18F]FDHT in women. Methods: [18F]FDHT PET/CT imaging was performed on a cohort of 11 women at baseline before the start of therapy and at 2 additional time points during selective androgen receptor modulator (SARM) therapy for androgen receptor-positive breast cancer. Volumes of interest (VOIs) were placed over the whole body and within source organs seen on the PET/CT images, and the time-integrated activity coefficients of [18F]FDHT were derived. The time-integrated activity coefficients for the urinary bladder were calculated using the dynamic urinary bladder model in OLINDA/EXM software, with biologic half-life for urinary excretion derived from VOI measurements of the whole body in postvoid PET/CT images. The time-integrated activity coefficients for all other organs were calculated from VOI measurements in the organs and the physical half-life of 18F. Organ dose and effective dose calculations were then performed using MIRDcalc, version 1.1. Results: At baseline before SARM therapy, the effective dose for [18F]FDHT in women was calculated as 0.020 ± 0.0005 mSv/MBq, and the urinary bladder was the organ at risk, with an average absorbed dose of 0.074 ± 0.011 mGy/MBq. Statistically significant decreases in liver SUV or uptake of [18F]FDHT were found at the 2 additional time points on SARM therapy (linear mixed model, P < 0.05). Likewise, absorbed dose to the liver also decreased by a small but statistically significant amount at the 2 additional time points (linear mixed model, P < 0.05). Neighboring abdominal organs of the gallbladder wall, stomach, pancreas, and adrenals also showed statistically significant decreases in absorbed dose (linear mixed model, P < 0.05). The urinary bladder wall remained the organ at risk at all time points. Absorbed dose to the urinary bladder wall did not show statistically significant changes from baseline at any of the time points (linear mixed model, P ≥ 0.05). Effective dose also did not show statistically significant changes from baseline (linear mixed model, P ≥ 0.05). Conclusion: Effective dose for [18F]FDHT in women before SARM therapy was calculated as 0.020 ± 0.0005 mSv/MBq. The urinary bladder wall was the organ at risk, with an absorbed dose of 0.074 ± 0.011 mGy/MBq.


Assuntos
Neoplasias da Mama , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Humanos , Feminino , Receptores Androgênicos , Di-Hidrotestosterona , Estudos Prospectivos , Tomografia por Emissão de Pósitrons/métodos , Radiometria/métodos
14.
J Clin Oncol ; 41(31): 4829-4836, 2023 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-37890277

RESUMO

PURPOSE: Most gastrointestinal stromal tumors (GISTs) express constitutively activated mutant isoforms of KIT or kinase platelet-derived growth factor receptor alpha (PDGFRA) that are potential therapeutic targets for imatinib mesylate. The relationship between mutations in these kinases and clinical response to imatinib was examined in a group of patients with advanced GIST. PATIENTS AND METHODS: GISTs from 127 patients enrolled onto a phase II clinical study of imatinib were examined for mutations of KIT or PDGFRA. Mutation types were correlated with clinical outcome. RESULTS: Activating mutations of KIT or PDGFRA were found in 112 (88.2%) and six (4.7%) GISTs, respectively. Most KIT mutations involved exon 9 (n = 23) or exon 11 (n = 85). All KIT mutant isoforms, but only a subset of PDGFRA mutant isoforms, were sensitive to imatinib, in vitro. In patients with GISTs harboring exon 11 KIT mutations, the partial response rate (PR) was 83.5%, whereas patients with tumors containing an exon 9 KIT mutation or no detectable mutation of KIT or PDGFRA had PR rates of 47.8% (P = .0006) and 0.0% (P < .0001), respectively. Patients whose tumors contained exon 11 KIT mutations had a longer event-free and overall survival than those whose tumors expressed either exon 9 KIT mutations or had no detectable kinase mutation. CONCLUSION: Activating mutations of KIT or PDGFRA are found in the vast majority of GISTs, and the mutational status of these oncoproteins is predictive of clinical response to imatinib. PDGFRA mutations can explain response and sensitivity to imatinib in some GISTs lacking KIT mutations.

15.
AJR Am J Roentgenol ; 199(2): 367-72, 2012 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-22826398

RESUMO

OBJECTIVE: The purpose of the study was to retrospectively review the frequency, sites, and patterns of atypical metastases from prostate cancer and to determine whether any correlation exists between the atypical sites and biochemical or histologic variables. MATERIALS AND METHODS: All available imaging studies of 620 consecutive patients with biopsy-proven prostate carcinoma seen at our institute between 1999 and 2009 were reviewed. Eighty-two patients (mean age, 72 years; age range, 58-87 years) with atypical sites of metastases were identified. Patients were separated into groups on the basis of the presence or absence of concurrent osseous metastasis and high or low Gleason grade, and metastatic patterns were compared using the Fisher exact test. The maximum prostate-specific antigen (PSA) level for each patient was recorded and correlated with metastatic pattern using the Mann-Whitney test. RESULTS: The most frequent sites of atypical metastases were the lungs and pleura (40%, 33/82), liver (37%, 30/82), supradiaphragmatic lymph nodes (34%, 28/82), and adrenal glands (15%, 12/82). Supradiaphragmatic lymphadenopathy was more common in patients with osseous metastases (45%, 25/56) than in patients without concurrent osseous involvement (12%, 3/26; p < 0.05). There was no significant correlation between the other atypical metastatic sites and osseous metastases. Abdominal visceral metastasis occurred more frequently in patients with a high Gleason grade (25/43, 58%) than in patients with a low Gleason grade (9/29, 31%; p < 0.05). There was no significant correlation between metastatic pattern and PSA level. CONCLUSION: The lungs and pleura, liver, supradiaphragmatic lymph nodes, and adrenal glands are the most common extranodal metastatic sites of prostate cancer. Supradiaphragmatic lymphadenopathy was strongly associated with concurrent osseous metastases.


Assuntos
Metástase Neoplásica/diagnóstico por imagem , Neoplasias da Próstata/patologia , Tomografia Computadorizada por Raios X , Idoso , Idoso de 80 Anos ou mais , Biópsia , Humanos , Masculino , Pessoa de Meia-Idade , Antígeno Prostático Específico/sangue , Estatísticas não Paramétricas
16.
J Nucl Med ; 63(1): 22-28, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34049982

RESUMO

Most breast cancers express androgen receptors (ARs). This prospective imaging substudy explored imaging of ARs with 18F-fluoro-5α-dihydrotestosterone (18F-FDHT) PET in patients with metastatic breast cancer (MBC) receiving selective AR modulation (SARM) therapy (GTx-024). Methods: Eleven postmenopausal women with estrogen receptor-positive MBC underwent 18F-FDHT PET/CT at baseline and at 6 and 12 wk after starting SARM therapy. Abnormal tumor 18F-FDHT uptake was quantified using SUVmax AR status was determined from tumor biopsy specimens. 18F-FDHT SUVmax percentage change between scans was calculated. Best overall response was categorized as clinical benefit (nonprogressive disease) or progressive disease using RECIST 1.1. Results: The median baseline 18F-FDHT SUVmax was 4.1 (range, 1.4-5.9) for AR-positive tumors versus 2.3 (range, 1.5-3.2) for AR-negative tumors (P = 0.22). Quantitative AR expression and baseline 18F-FDHT uptake were weakly correlated (Pearson ρ = 0.39, P = 0.30). Seven participants with clinical benefit at 12 wk tended to have larger declines in 18F-FDHT uptake than did those with progressive disease both at 6 wk after starting GTx-024 (median, -26.8% [range, -42.9% to -14.1%], vs. -3.7% [range,-31% to +29%], respectively; P = 0.11) and at 12 wk after starting GTx-024 (median, -35.7% [range, -69.5% to -7.7%], vs. -20.1% [range, -26.6% to +56.5%], respectively; P = 0.17). Conclusion: These hypothesis-generating data suggest that 18F-FDHT PET/CT is worth further study as an imaging biomarker for evaluating the response of MBC to SARM therapy and reiterate the feasibility of including molecular imaging in multidisciplinary therapeutic trials.


Assuntos
Di-Hidrotestosterona
17.
Cancer ; 117(16): 3860-6, 2011 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-21319153

RESUMO

BACKGROUND: Incidence of pulmonary embolism (PE) for different cancer types in oncology outpatients is unknown. The purposes of the current study is to determine the incidence of PE in oncology outpatients and to investigate whether the incidence for PE is higher in certain cancers. METHODS: A cohort of oncology outpatients who had imaging studies at Dana-Farber Cancer Institute, a tertiary outpatient cancer institute, from January 2004 through December 2009 was identified using research patient data registry. Radiology reports were reviewed to identify patients who developed PE. Incidences of PE in the total population and in each of 16 predefined cancer groups were calculated. Risk of PE for each cancer was compared using Fisher exact test. RESULTS: A total of 13,783 patients was identified, of which 395 (2.87%; 95% confidence interval [CI], 2.59-3.16) developed PE. The incidence of PE was highest in the central nervous system ([CNS] 12.90%; 95% CI, 8.45-18.59), hepatobiliary (6.85%; 95% CI, 3.33-12.24), pancreatic (5.81%; 95% CI, 3.59-8.84), and upper gastrointestinal (5.81%; 95% CI, 3.96-8.20) malignancies. The risk of PE was significantly higher for CNS (P < .0001; odds ratio [OR], 5.28), pancreatic (P = .0027; OR, 2.15), upper gastrointestinal (P = .0002; OR, 2.18), and lung/pleural malignancies (P = .0028; OR, 1.45). There was significantly lower risk of PE for hematologic (incidence, 1.16%; 95% CI, 0.79-1.64; P < .0001; OR, 0.35) and breast malignancies (incidence, 1.50%; 95% CI, 1.02-2.11; P < .0001; OR, 0.47). CONCLUSIONS: The incidence of PE in oncology outpatients in a tertiary cancer center during a 6-year period was 2.87%. CNS, pancreatic, upper gastrointestinal, and lung/pleural malignancies had a significantly higher risk for PE than other malignancies, whereas hematologic and breast malignancies had a significantly lower risk.


Assuntos
Neoplasias/complicações , Embolia Pulmonar/complicações , Embolia Pulmonar/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Pacientes Ambulatoriais
18.
AJR Am J Roentgenol ; 197(6): W1001-7, 2011 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-22109313

RESUMO

OBJECTIVE: The purpose of this article is to present the important malignancies associated with the most common hereditary cancer syndromes. CONCLUSION: Hereditary cancer syndromes comprise 5% of all cancers and have an increased risk of early onset and of multiple or bilateral malignancies. Radiologists should be familiar with various hereditary cancer syndromes and their common associations because early detection of these neoplasms may help decrease patient morbidity and mortality.


Assuntos
Diagnóstico por Imagem , Predisposição Genética para Doença , Síndromes Neoplásicas Hereditárias/diagnóstico , Neoplasias Colorretais Hereditárias sem Polipose/diagnóstico , Neoplasias Colorretais Hereditárias sem Polipose/genética , Meios de Contraste , Humanos , Síndrome de Li-Fraumeni/diagnóstico , Síndrome de Li-Fraumeni/genética , Neoplasia Endócrina Múltipla/diagnóstico , Neoplasia Endócrina Múltipla/genética , Síndromes Neoplásicas Hereditárias/genética , Neurofibromatoses/diagnóstico , Neurofibromatoses/genética , Doença de von Hippel-Lindau/diagnóstico , Doença de von Hippel-Lindau/genética
19.
AJR Am J Roentgenol ; 196(1): 117-22, 2011 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-21178055

RESUMO

OBJECTIVE: The purpose of this study was to evaluate the metastatic pattern of muscle-invasive bladder cancer and to correlate the findings with the characteristics of the primary tumor. MATERIALS AND METHODS: From a clinic population of 392 patients with muscle-invasive (pT2-4) bladder cancer seen at our institution from January 2004 through December 2009, we studied the cases of 150 consecutively registered patients with pathologically proven metastatic disease. The metastasis-free intervals and metastatic patterns of different T categories were compared by Kruskal-Wallis test and Freeman-Halton extension of Fisher's exact test. Patients were divided into two histologic categories, those with transitional cell carcinoma and those with atypical histologic features. The metastasis-free interval and metastatic pattern of these two groups were compared by Mann-Whitney test and Fisher's exact test. RESULTS: The study group consisted of 150 patients (116 men [77%], 34 women [23%]; median age, 64 years). The transitional cell carcinoma group consisted of 94 (63%) patients and the atypical histologic features group of 56 (37%) patients. The most common metastatic sites were lymph nodes (104 patients, 69%), bone (71 patients, 47%), lung (55 patients, 37%), liver (39 patients, 26%), and peritoneum (24 patients, 16%). Patients with tumors of a more advanced T category had shorter metastasis-free intervals (p = 0.001, df = 2). There was no significant difference in the metastatic patterns of tumors in the different T categories. Patients with atypical histologic features had a shorter median metastasis-free interval (3 months; range, 0-29 months) than patients with transitional cell carcinoma (12 months; range, 0-192 months) (p = 0.0001). Patients with atypical histologic features had a significantly higher incidence of peritoneal metastasis (p < 0.0002). CONCLUSION: Lymph nodes, bones, lung, liver, and peritoneum are the most common sites of metastasis from bladder cancer. Tumors in a more advanced T category and those with atypical histologic features metastasize earlier. Tumors with atypical histologic features also have a higher frequency of peritoneal metastasis.


Assuntos
Músculos/patologia , Invasividade Neoplásica/patologia , Neoplasias da Bexiga Urinária/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica/patologia , Estudos Retrospectivos , Estatísticas não Paramétricas , Tomografia Computadorizada por Raios X
20.
J Comput Assist Tomogr ; 35(2): 217-22, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21412093

RESUMO

OBJECTIVE: To study the metastatic pattern of upper urinary tract urothelial cancer and to correlate it with tumor histopathology and location. METHODS: After approval by the institutional review board, we studied patients with pathologically proven metastatic urothelial cancers of renal pelvis or ureter, who presented between January 2003 and December 2009. The metastasis-free interval and metastatic pattern were compared for T stage, histopathological subtype (transitional cell carcinoma versus atypical histology), and location (renal pelvis versus ureter). RESULTS: The study group consisted of 52 patients (33 men and 19 women: transitional cell carcinoma, 69% [36/52]; atypical histology, 31% [16/52]; renal pelvis, 73% [38/52]; ureter, 27% [14/52]). Lymph nodes (75% [39/52]), lung (65% [34/52]), liver (54% [28/52]), bone (39% [20/52]), and peritoneum (19% [10/52]) were the most common metastatic sites. There was no difference in the metastatic pattern for different T stages, histologic groups, or locations. CONCLUSION: Lymph nodes, lung, liver, bone, and peritoneum are the most common metastatic sites of upper urinary tract urothelial cancers. Tumor histology and location within the upper urinary tract have no effect on metastatic pattern.


Assuntos
Neoplasias Renais/diagnóstico por imagem , Neoplasias Renais/patologia , Reconhecimento Automatizado de Padrão/métodos , Neoplasias Ureterais/diagnóstico por imagem , Neoplasias Ureterais/patologia , Urotélio/diagnóstico por imagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Radiografia , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Estatística como Assunto
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