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PURPOSE: Haemorrhage and calcification can be qualitatively distinguished on susceptibility-weighted imaging (SWI) using phase information, but it is unclear how to make this distinction in a subset of lesions with ambiguous phase, containing a mixture of positive and negative values. This work investigates the validity of qualitative phase assessment at the cranial or caudal margins in classifying such lesions as haemorrhagic or calcific, when quantitative susceptibility mapping is not available to the neuroradiologist. METHODS: In a retrospective review of magnetic resonance imaging examinations acquired between July 2015 and November 2019, 87 lesions with ambiguous phase which could be confidently determined to be haemorrhagic or calcific were identified. Two blinded neuroradiologists independently classified these lesions as haemorrhagic or calcific using 3 approaches: qualitative phase assessment at the lesions' cranial or caudal margins, dominant phase, and in-plane margins. Combined sensitivities and specificities of these analyses were calculated using a generalised linear mixed model with random effects for reader. RESULTS: Assessment at the cranial or caudal margins achieved a sensitivity of 100% for haemorrhage and calcification, which was significantly superior (pâ¯< 0.05) to dominant phase assessment with sensitivities of 52% for haemorrhage (95% confidence interval, CI 43-61%) and 54% for calcification (95% CI 42-66%), as well as in-plane margin assessment with 28% (95% CI 18-38%) and 46% (95% CI 36-56%). CONCLUSION: Haemorrhage and calcification can be reliably distinguished in lesions with ambiguous phase on SWI by qualitative review of the phase signal at the cranial or caudal margins.
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Calcinose , Imageamento por Ressonância Magnética , Hemorragia , Humanos , Estudos Retrospectivos , Sensibilidade e EspecificidadeRESUMO
BACKGROUND: Peripheral T-cell lymphomas (PTCLs) are uncommon and their frequency is regionally heterogeneous. Several studies have been conducted to evaluate the clinical features and treatment outcomes of this disease entity, but the majority of these were conducted in limited areas, making it difficult to comprehensively analyze their relative frequency and clinical features. Furthermore, no consensus treatment for PTCLs has been established. Therefore, we conducted an Asia-specific study to understand the relative frequency of PTCLs and assess treatments and their outcomes in Asian patients. METHODS: We performed a multinational, multicenter, prospective registry of adult patients with PTCLs that was named as the International Cooperative non-Hodgkin T-cell lymphoma prospective registry study where thirty-two institutes from six Asian countries and territories (Korea, China, Taiwan, Singapore, Malaysia, and Indonesia) participated. FINDINGS: A total of 486 patients were registered between April 2016 and February 2019, and more than a half of patients (57%) had stage III or IV. Extranodal natural killer (NK)/T- cell lymphoma was the most common subtype (n = 139,28.6%), followed by angioimmunoblastic T-cell lymphoma (AITL, n = 120,24.7%), PTCL-not otherwise specified (PTCL-NOS, n = 101,20.8%), ALK-positive anaplastic large cell lymphoma (ALCL, n = 34,6.9%), and ALK-negative ALCL (n = 30,6.2%). The median progression-free survival (PFS) and overall survival (OS) were 21.1 months (95% CI,10.6-31.6) and 83.6 months (95% CI, 56.7-110.5), respectively. Upfront use of combined treatment with chemotherapy and radiotherapy showed better PFS than chemotherapy alone in localized ENKTL whereas consolidation with upfront autologous stem cell transplantation (SCT) provided longer PFS in advance stage ENKTL. In patients with PTCLs other than ENKTL, anthracycline-containing chemotherapies were widely used, but the outcome of those regimens was not satisfactory, and upfront autologous SCT was not significantly associated with survival benefit, either. The treatment outcome of salvage chemotherapy was disappointing, and none of the salvage strategies showed superiority to one another. INTERPRETATION: This multinational, multicenter study identified the relative frequency of each subtype of PTCLs across Asian countries, and the survival outcomes according to the therapeutic strategies currently used. FUNDING: Samsung Biomedical Research Institute.
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PURPOSE: To propose a framework for optimal pairing of radiologists when reading mammograms based on their search patterns. MATERIALS AND METHODS: Four experienced and four less-experienced radiologists were asked to assess 120 cases (59 with cancers) while their eye positions were tracked. Fourteen eye-tracking metrics were extracted to quantify the differences among radiologists' visual search pattern. For each radiologist and metric, less-experienced radiologists and expert readers were ranked based on the level of similarities in gaze patterns (from the most different to the most similar). Less-experienced readers and experts were also ranked based on the values of area under the receiver operating characteristic curve (AUC) after pairing (the best possible way of ranking). Using the Kendall's tau distance, rankings based on different metrics were compared with the best possible ranking. Using paired Wilcoxon signed-rank test, the AUC values when pairing in the best way were compared with pairing based on different metrics. Finally, we investigated the robustness of pairing strategies against the small sample size. RESULTS: For ranking the experienced radiologists, results from eight metrics were as good as the best possible ranking. For the less-experienced ones, only one metric resulted in a ranking comparable to the best possible way of ranking. The AUC values of pairings based on these metrics did not differ significantly from the best pairing scenario. Compared to the pairings based on the cognitive metrics, the ranking based on AUC values varied more greatly with the sample size, suggesting that it is less robust against the small sample size compared to the cognitive metrics. CONCLUSION: Different pairings may have different effects on performance; some are detrimental while some improve the performance of the pair. Using the suggested cognitive metrics, we can optimize the pairings even with a small dataset.
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Movimentos Oculares , Mamografia , Radiologistas , Neoplasias da Mama/diagnóstico por imagem , Reações Falso-Positivas , Feminino , HumanosRESUMO
PURPOSE: The purpose of this study was to Propose a classifier based on recurrence quantification analysis (RQA) metrics for distinguishing experts' scanpaths from those of less-experienced readers and to explore the association of spatiotemporal dynamics of the mammographic scanpaths with the characteristics of cases and radiologists using RQA metrics. MATERIALS AND METHODS: Eye movements were recorded from eight radiologists (two cohorts: four experienced and four less-experienced) while reading 120 mammograms (59 cancer, 61 normal). Ten RQA measures were extracted for each recorded scanpath. The measures described the temporal distribution of recurrent fixations as well as laminar and deterministic eye movements. Recurrent fixations are fixations that are located close to a previously fixated point in a scanpath. Deterministic eye movements represent looking back and forth between two locations, while laminar eye movements indicate detailed scanning of an area with consecutive fixations. The RQA metrics along with six conventional eye-tracking parameters were used to construct a classifier for distinguishing experts' scanpaths from those of less-experienced readers. Leave-one-out cross validation was used for evaluating the classifier. For each reader cohort, the ANOVA analysis was done to study the relationship of RQA measures with breast density, case pathology, readers' expertise, and readers' decisions on the case. The proportions of laminar and deterministic movements involved fixations in the location of lesions were also compared for two reader cohorts using two proportion z-tests. RESULTS: All RQA measures differed significantly between scanpaths of experienced readers and those of less-experienced readers. The classifier achieved an area under the receiver operating characteristic curve of 0.89 (0.87-0.91) for detecting experts' scanpaths. Proportionately more refixations and laminar and deterministic sequences were in the location of the lesion for the experienced cohort compared to the less-experienced cohort (all P-values < 0.001). Eight and four RQA measures differed between normal and cancer cases for the experienced and less experienced readers, respectively. None of metrics differed between fatty and dense breasts for the less experienced readers, while two measures resulted into a significant difference for the experienced readers. For experts, six measures differed significantly between true negatives and false positives and nine were significantly different between true positives and false negatives. For the less-experienced cohort, the corresponding figures were seven and one measures, respectively. CONCLUSION: The RQA measures can quantify the differences among experienced and less experienced radiologists. They also capture differences among experts' scanpaths related to case pathology and radiologists' decisions on the case.
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Competência Clínica , Interpretação de Imagem Assistida por Computador/métodos , Mamografia , Radiologistas , Neoplasias da Mama/diagnóstico por imagem , Movimentos Oculares , Humanos , RecidivaRESUMO
This study introduces an individualized tool for identifying mammogram interpretation errors, called eye-Computer Assisted Perception (iCAP). iCAP consists of two modules, one which processes areas marked by radiologists as suspicious for cancer and classifies these as False Positive (FP) or True Positive (TP) decisions, while the second module classifies fixated but not marked locations as False Negative (FN) or True-Negative (TN) decisions. iCAP relies on both radiologists' gaze-related parameters, extracted from eye tracking data, and image-based features. In order to evaluate iCAP, eye tracking data from eight breast radiologists reading 120 two-view digital mammograms were collected. Fifty-nine cases had biopsy proven cancer. For each radiologist, a user-specific support vector machine model was built to classify the radiologist' s reported areas as TPs or FPs and fixated locations as TNs or FNs. The performances of the classifiers were evaluated by utilizing leave-one-out cross validation. iCAP was tested retrospectively in a simulated scenario in which it was assumed that the radiologists would accept all iCAP decisions. Using iCAP led to an average increase of 12%±6% in the number of correctly localized cancer and an average decrease of 44.5%±22.7% in the number of FPs per image.
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Mamografia , Biópsia , Neoplasias da Mama , Humanos , RadiologistasRESUMO
AIM: Brain metastasis is rare in sarcoma. Prognostic factors, optimal management strategies and therapeutic outcomes of such patients are not well studied. We aimed to evaluate the incidence, clinical characteristics and treatment outcomes of parenchymal brain metastasis in sarcoma patients. METHODS: This is a single center retrospective analysis. Overall survival (OS) was calculated from the time of diagnosis of brain metastasis to time of death. RESULTS: Sixteen patients (2.1%) with complete electronic medical records treated at our institution from 2002 to 2010 were identified. Median age was 52 years; 88% had additional sites of metastases. Eight different subtypes of soft tissue and bone sarcoma were identified. Eighty-one percent of the patients developed metachronous brain metastasis at a median of 14 months after initial sarcoma diagnosis. Thirty-eight percent of patients had solitary brain metastasis and 44% underwent aggressive therapy for brain metastasis, defined as either surgical resection or multimodality treatment. The remaining 56% received conservative treatment (either whole brain radiation alone, chemotherapy alone or best supportive care). Median OS for the entire cohort was 3.5 months (95% CI 1.1-6.3 months). A trend toward improved OS was observed with an aggressive treatment approach, 3.7 months versus 1.2 months (P = 0.077) and the usage of chemotherapy (P = 0.071). CONCLUSION: Brain metastasis in sarcoma is rare, usually coexists with significant systemic disease and is associated with a grave prognosis. Use of chemotherapy and an aggressive treatment approach in well-selected patients may be associated with improved survival. Prospective studies are needed to confirm these findings.
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Neoplasias Encefálicas/secundário , Neoplasias Encefálicas/terapia , Terapia Combinada/métodos , Metastasectomia/métodos , Sarcoma/secundário , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Ósseas/mortalidade , Neoplasias Ósseas/patologia , Neoplasias Ósseas/terapia , Neoplasias Encefálicas/mortalidade , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Sarcoma/tratamento farmacológico , Sarcoma/mortalidade , Neoplasias de Tecidos Moles/mortalidade , Neoplasias de Tecidos Moles/patologia , Neoplasias de Tecidos Moles/terapia , Resultado do TratamentoRESUMO
BACKGROUND: Patients with relapsed or refractory peripheral T-cell lymphoma have a poor prognosis after conventional chemotherapy. Approved novel agents have only modest single-agent activity in most subtypes of peripheral T-cell lymphoma. Panobinostat is a potent oral pan-deacetylase inhibitor. Findings of many preclinical studies have shown synergistic antilymphoma activity when panobinostat is combined with the proteasome inhibitor bortezomib. We aimed to study the effect of panobinostat and bortezomib in patients with relapsed or refractory peripheral T-cell lymphoma. METHODS: In this open-label, multicentre phase 2 trial, we recruited patients aged 21 years or older with relapsed or refractory peripheral T-cell lymphoma who had received at least one previous line of systemic therapy from five tertiary hospitals in Singapore, Malaysia, and South Korea. Patients received 20 mg oral panobinostat three times a week and 1·3 mg/m(2) intravenous bortezomib two times a week, both for 2 of 3 weeks for up to eight cycles. The primary endpoint was the proportion of patients who achieved an objective response in accordance with the International Working Group revised response criteria; analyses were by intention to treat. The study is completed and is registered with ClinicalTrials.gov, number NCT00901147. FINDINGS: Between Nov 9, 2009, and Nov 26, 2013, we enrolled 25 patients with various histological subtypes of peripheral T-cell lymphoma. Of 23 patients assessable for responses, ten (43%, 95% CI 23-63) patients had an objective response, of which five were complete responses. Serious adverse events were reported in ten (40%) of 25 patients. Common treatment-related grade 3-4 adverse events included thrombocytopenia (17 [68%]), neutropenia (ten [40%]), diarrhoea (five [20%]), and asthenia or fatigue (two [8%]). We recorded peripheral neuropathy of any grade in ten (40%) patients. INTERPRETATION: Combined proteasome and histone deacetylase inhibition is safe and feasible and shows encouraging activity for patients with peripheral T-cell lymphoma. Our findings validate those of preclinical studies showing synergism in the combination and represent a rational way forward in harnessing the full potential of novel agents in peripheral T-cell lymphoma. FUNDING: Novartis Pharmaceuticals, Janssen Pharmaceuticals, and Singhealth Foundation.
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Antineoplásicos/uso terapêutico , Bortezomib/uso terapêutico , Ácidos Hidroxâmicos/uso terapêutico , Indóis/uso terapêutico , Linfoma de Células T Periférico/tratamento farmacológico , Adulto , Idoso , Antineoplásicos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bortezomib/administração & dosagem , Feminino , Humanos , Ácidos Hidroxâmicos/administração & dosagem , Indóis/administração & dosagem , Malásia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Panobinostat , República da Coreia , Singapura , Resultado do TratamentoRESUMO
Vasculitis is an inflammation that can present as acute or chronic in nature, which causes changes in the walls of blood vessels, including thickening, weakening, narrowing and scarring. Gemcitabine, an antimetabolite chemotherapeutic agent, is generally well tolerated with a favorable side effect profile. However, there is increasing evidence that it is associated with vasculitis, which can affect small and large vessels. In this case report, we report a patient who has experienced fever with severe tenderness over right carotid artery, which occurred on the fifth day after the administration of gemcitabine. The exact mechanism of gemcitabine-induced vasculitis is unknown but cessation of gemcitabine and initiation of anti-inflammatory treatment appears to aid in the resolution of the clinical syndrome.
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Antimetabólitos Antineoplásicos/efeitos adversos , Arterite/induzido quimicamente , Doenças das Artérias Carótidas/induzido quimicamente , Desoxicitidina/análogos & derivados , Neoplasias da Bexiga Urinária/tratamento farmacológico , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Arterite/diagnóstico , Artérias Carótidas/efeitos dos fármacos , Desoxicitidina/administração & dosagem , Desoxicitidina/efeitos adversos , Docetaxel , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Taxoides/administração & dosagem , Taxoides/efeitos adversos , Tomografia Computadorizada por Raios X , Vasculite/induzido quimicamente , Vasculite/terapia , GencitabinaRESUMO
Second lymphoid neoplasms are an uncommon but recognized feature of non-Hodgkin's lymphomas, putatively arising secondary to common genetic or environmental risk factors. Previous limited evaluations of clonal relatedness between successive mature B-cell malignancies have yielded mixed results. We describe the case of a man with intravascular large B-cell lymphoma involving the central nervous system who went into clinical remission following immunochemotherapy and brain radiation, only to relapse 2 years later with a plasmacytoma of bone causing cauda equina syndrome. The plasmacytoma stained strongly for the cell cycle regulator cyclin D1 on immunohistochemistry, while the original intravascular large cell lymphoma was negative, a disparity providing no support for clonal identity between the 2 neoplasms. Continued efforts atcataloging and evaluating unique associations of B-cell malignancies are critical to improving understanding of overarching disease biology in B-cell malignancies.
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This study aimed to describe the epidemiology and risk factors for cytomegalovirus (CMV) infection and end-organ disease in patients with lymphoma undergoing potentially curative or salvage therapy. We retrospectively reviewed 534 patients with lymphoma treated at an Asian tertiary cancer center between January 2007 and December 2010. Overall, 48 patients (9.0%) experienced CMV infection, with 12 patients (25.0%) being further diagnosed with CMV end-organ disease. Many patients with CMV infection were male, with poor performance status, non-Hodgkin lymphoma and advanced disease, and received rituximab use. Moreover, patients receiving rituximab and HyperCVAD (hyperfractionated cyclophosphamide, vincristine, doxorubicin and dexamethasone) regimens had a high rate of CMV end-organ disease. In Asian patients with lymphoma receiving curative or salvage therapy, CMV infection was relatively common (9.0%). Most of these were likely to be reactivation in nature. A small group, especially those on rituximab or HyperCVAD, developed CMV end-organ disease (12/534). Such patients should be monitored closely for CMV end-organ disease. Alternatively, prophylaxis should be studied.
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Povo Asiático , Infecções por Citomegalovirus/complicações , Linfoma/complicações , Linfoma/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Antivirais/uso terapêutico , Citomegalovirus/classificação , Infecções por Citomegalovirus/diagnóstico , Infecções por Citomegalovirus/tratamento farmacológico , Feminino , Humanos , Linfoma/diagnóstico , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Estudos Retrospectivos , Fatores de Risco , Terapia de Salvação , Sorotipagem , Índice de Gravidade de Doença , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND: The gastrointestinal (GI) tract is one of the most common extranasal sites in extranodal NK/T-cell lymphoma (ENKTL). However, data regarding ENKTL involving the GI tract are relatively scarce. Thus, we performed a multicenter, multinational retrospective study to analyze clinical features and treatment outcomes of ENKTL involving the GI tract. PATIENTS AND METHODS: Patients with ENKTL involving the GI tract diagnosed in twelve participating centers between 1991 and 2012 were retrospectively analyzed from five Asian countries. RESULTS: The analysis of 81 patients with ENKTL involving the GI tract revealed that more than 60% of patients presented as advanced disease with B symptoms. 55 patients (68%) had GI manifestations including abdominal pain (n = 26, 32%), GI tract bleeding (n = 17, 21%) and bowel perforation (n = 12, 15%). The most common GI site was the small intestine, including the jejunum and ileum (n = 57, 70.3%). There were 34 patients (42%) who received systemic chemotherapy while 33 patients (41%) underwent surgery plus chemotherapy. However, 35 patients (43%) died due to disease progression, and treatment-related mortality including sepsis occurred in 17 patients (21%). Thus, the median overall survival was 7.8 months (95% Confidence interval: 3.9 - 11.7 months). Patients who could undergo surgery plus chemotherapy showed a trend of better survival than those treated with chemotherapy alone. CONCLUSION: Overall, the data indicated that ENKTL involving the GI tract has a dismal prognosis despite active treatment including chemotherapy and surgery. Thus, more effective treatment strategies are required for this disease entity.
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Neoplasias Gastrointestinais/patologia , Neoplasias Gastrointestinais/terapia , Linfoma Extranodal de Células T-NK/patologia , Linfoma Extranodal de Células T-NK/terapia , Adolescente , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Análise de Sobrevida , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND: Hepatitis B virus (HBV) reactivation is increasing, as rituximab has become widely used for B-cell lymphoma. Thus, prevention and management of HBV reactivation are important in HBV-endemic areas. METHODS: Hepatitis B virus (HBV) reactivation in HBV surface antigen (HBsAg)-positive patients and HBsAg-negative/HBV core antibody (HBcAb)-positive patients who received rituximab-containing chemotherapy was investigated by the Asia Lymphoma Study Group via retrospective (n=340), and the results were compared to cross-sectional analysis with patients who were prospectively monitored in a single institute (n=127). The goal of the study was to define the frequency of HBV reactivation and the efficacy of antiviral prophylaxis. RESULTS: HBV reactivation was found in 27.8% of HBsAg-positive patients (45/162) in the retrospective analysis, being significantly less frequent in patients receiving antiviral prophylaxis than those not (22.9%, 32/140 versus 59.1%, 13/22; p<0.001). Lamivudine was most commonly used (96/162, 59.3%), but more than 20% of HBsAg-positive patients showed breakthrough HBV reactivation. In the cross-sectional analysis, a reduced rate of HBV reactivation occurred for entecavir as compared with lamivudine prophylaxis (6.3% versus 39.3%; p<0.05). HBV DNA monitoring of HBsAg-negative/HBcAb-positive patients in the cross-sectional analysis showed HBV reactivation in only 2.4% of cases. CONCLUSIONS: This is the largest study of HBV reactivation in patients receiving rituximab-containing chemotherapy to date, and we defined the probability of HBV reactivation in an HBV-endemic region.
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Anticorpos Monoclonais Murinos/efeitos adversos , Antineoplásicos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Vírus da Hepatite B/efeitos dos fármacos , Hepatite B/epidemiologia , Linfoma de Células B/tratamento farmacológico , Ativação Viral/efeitos dos fármacos , Antivirais/uso terapêutico , Ásia/epidemiologia , Biomarcadores/sangue , Estudos Transversais , DNA Viral/sangue , Doenças Endêmicas , Feminino , Hepatite B/sangue , Hepatite B/diagnóstico , Hepatite B/prevenção & controle , Antígenos de Superfície da Hepatite B/sangue , Vírus da Hepatite B/genética , Vírus da Hepatite B/imunologia , Vírus da Hepatite B/fisiologia , Humanos , Incidência , Estimativa de Kaplan-Meier , Linfoma de Células B/epidemiologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Estudos Retrospectivos , Rituximab , Resultado do Tratamento , Carga ViralRESUMO
At the National Cancer Centre Singapore, which is currently the largest ambulatory cancer centre in Singapore, clinical pharmacists have taken upon responsibilities to provide direct pharmaceutical care in the center's lymphoma team since 2006. Given the complexity and intricacies of lymphoma treatments, clinical pharmacists are often positioned to ensure supportive care is optimized among these patients. Besides management of chemotherapy-related and supportive care issues, clinical pharmacists play a pivotal role in guiding cost-effective and safe prescribing. In collaboration with the medical team, they are also involved in conducting practice research in order to optimize the delivery of pharmaceutical care. In this report, the dedicated services and research activities conducted by clinical pharmacists of a lymphoma team will be discussed.
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Antineoplásicos/uso terapêutico , Institutos de Câncer , Linfoma/tratamento farmacológico , Farmacêuticos , Serviço de Farmácia Hospitalar , Antineoplásicos/efeitos adversos , Antineoplásicos/economia , Pesquisa Biomédica/métodos , Institutos de Câncer/economia , Análise Custo-Benefício , Monitoramento de Medicamentos , Custos Hospitalares , Humanos , Prescrição Inadequada/prevenção & controle , Linfoma/economia , Linfoma/terapia , Oncologia/métodos , Equipe de Assistência ao Paciente , Farmacologia Clínica/métodos , Serviço de Farmácia Hospitalar/economia , Papel Profissional , Singapura , Recursos HumanosRESUMO
AIMS: The entity 'B cell lymphoma, unclassifiable, with features intermediate between diffuse large B cell lymphoma (DLBCL) and Burkitt lymphoma (BL)' refers to B cell neoplasms that share overlapping characteristics of BL and DLBCL. A subset of these 'grey-zone lymphomas' possesses C-MYC and IGH translocations but, in addition, contains additional rearrangements of BCL2 and/or BCL6 genes. The aim of this study was to investigate if the proliferation fraction by Ki67 immunostaining can be used to identify such double-/triple-hit lymphomas. METHODS AND RESULTS: We studied 492 cases of mature aggressive B cell neoplasms by histology, immunohistochemistry and interphase fluorescence in-situ hybridization (FISH) using break-apart probes against C-MYC, BCL2, BCL6, IGH, MALT1, PAX5 and CCND1. Forty Burkitt lymphomas and 28 cases of MYC(+) double-/triple-hit lymphomas were identified. Of the latter, 77% and 54% displayed proliferation fractions exceeding 75% and 90%, respectively. With a cut-off of >75% by Ki67 immunostaining, the sensitivity and specificity for detection of MYC(+) double/triple translocations was 0.77 and 0.36. Raising the proliferation fraction criterion to >90% improved the specificity to 0.62 at the expense of a low sensitivity of 0.54. CONCLUSIONS: Immunostaining for Ki67 is not a useful approach to prescreen B cell lymphomas for MYC(+) double/triple translocations.
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Linfoma de Burkitt/genética , Linfoma de Burkitt/patologia , Proliferação de Células , Linfoma de Células B/patologia , Linfoma Difuso de Grandes Células B/genética , Linfoma Difuso de Grandes Células B/patologia , Translocação Genética/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Linfoma de Burkitt/diagnóstico , Diagnóstico Diferencial , Detecção Precoce de Câncer/métodos , Feminino , Testes Genéticos/métodos , Humanos , Cadeias Pesadas de Imunoglobulinas/genética , Antígeno Ki-67/metabolismo , Linfoma de Células B/metabolismo , Linfoma Difuso de Grandes Células B/diagnóstico , Masculino , Pessoa de Meia-Idade , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-6/genética , Proteínas Proto-Oncogênicas c-myc/genética , Estudos Retrospectivos , Sensibilidade e EspecificidadeRESUMO
UNLABELLED: The molecular pathogenesis of natural killer/T-cell lymphoma (NKTCL) is not well understood. We conducted whole-exome sequencing and identified Janus kinase 3 (JAK3) somatic-activating mutations (A572V and A573V) in 2 of 4 patients with NKTCLs. Further validation of the prevalence of JAK3 mutations was determined by Sanger sequencing and high-resolution melt (HRM) analysis in an additional 61 cases. In total, 23 of 65 (35.4%) cases harbored JAK3 mutations. Functional characterization of the JAK3 mutations support its involvement in cytokine-independent JAK/STAT constitutive activation leading to increased cell growth. Moreover, treatment of both JAK3-mutant and wild-type NKTCL cell lines with a novel pan-JAK inhibitor, CP-690550, resulted in dose-dependent reduction of phosphorylated STAT5, reduced cell viability, and increased apoptosis. Hence, targeting the deregulated JAK/STAT pathway could be a promising therapy for patients with NKTCLs. SIGNIFICANCE: Gene mutations causing NKTCL have not been fully identified. Through exome sequencing, we identified activating mutations of JAK3 that may play a significant role in the pathogenesis of NKTCLs. Our findings have important implications for the management of patients with NKTCLs.
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Janus Quinase 3/genética , Linfoma de Células T/genética , Mutação , Células T Matadoras Naturais/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Western Blotting , Linhagem Celular Tumoral , Proliferação de Células , Análise Mutacional de DNA , Ativação Enzimática/genética , Feminino , Humanos , Janus Quinase 3/antagonistas & inibidores , Janus Quinase 3/metabolismo , Linfoma de Células T/metabolismo , Linfoma de Células T/patologia , Masculino , Pessoa de Meia-Idade , Células T Matadoras Naturais/patologia , Fosforilação , Piperidinas , Pirimidinas/farmacologia , Pirróis/farmacologia , Interferência de RNA , Fator de Transcrição STAT5/metabolismoRESUMO
AIM: Recently, a number of studies have demonstrated the effectiveness of a single reduced dose of rasburicase for the management of tumor lysis syndrome (TLS) in adults. Whether Asian lymphoma patients similarly respond to a single dose of rasburicase is currently unknown. We aim to assess the efficacy of a single dose rasburicase in preventing TLS in Asian lymphoma patients. METHODS: This was a single-center case series of adult lymphoma patients at high risk of TLS who received a single fixed dose of rasburicase. Patients had to have their uric acid, serum creatinine, lactate dehydrogenase and electrolytes monitored for at least 24-48 h post-administration. RESULTS: Eleven patients were identified. Majority were Chinese (91%), male (64%) and with a median age of 61 years (range 41-84). All had at least two risk factors for developing TLS. Ten patients received a 6-mg dose and one received 4.5 mg. Prior to rasburicase administration, the mean uric acid level was 835 µmol/L (range 318-1237 µmol/L) and the level 24-h post-administration was 186 µmol/L (range 30-653 µmol/L) (P < 0.001). Eight patients (73%) experienced an improvement of renal function 72-h post-rasburicase. Normalization of serum electrolytes was achieved within 96 h. CONCLUSION: Among Asian lymphoma patients who manifested at least two risk factors for developing TLS, a single fixed dose of rasburicase at 6 mg is deemed to be effective for rapidly lowering uric acid levels as well as sustaining reduced levels for up to 72 h.
Assuntos
Linfoma de Burkitt/patologia , Linfoma Difuso de Grandes Células B/patologia , Síndrome de Lise Tumoral/tratamento farmacológico , Urato Oxidase/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Ásia , Linfoma de Burkitt/sangue , Creatinina/sangue , Feminino , Humanos , L-Lactato Desidrogenase/sangue , Linfoma Difuso de Grandes Células B/sangue , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Síndrome de Lise Tumoral/sangue , Síndrome de Lise Tumoral/patologia , Ácido Úrico/sangueRESUMO
AIM: Febrile neutropenia (FN) is a highly prevalent complication of chemotherapy, particularly in patients with non-Hodgkin's lymphoma. This study aimed to compare the efficacy of filgrastim and pegfilgrastim in Asian lymphoma patients by evaluating the incidence of FN and associated complications. METHODS: This was a single-center, retrospective cohort study in Asian lymphoma patients who received chemotherapy with primary prophylactic granulocyte colony-stimulating factors support between January 2008 and August 2009. Data were analyzed using an intent-to-treat approach, which aimed to reflect actual prescribing practices. RESULTS: A total of 204 Asian lymphoma patients were included in this study, with 81 patients in the filgrastim arm and 123 patients in the pegfilgrastim arm. Overall, the incidence of breakthrough FN was similar between the two groups of patients (13.6%: filgrastim arm vs 16.3%: pegfilgrastim arm; P=0.69). Neutropenic complications such as chemotherapy treatment delay and chemotherapy dose reduction were similar between the two arms. CONCLUSION: In Asian patients, pegfilgrastim prophylaxis did not show a therapeutic advantage for preventing neutropenic outcomes compared with filgrastim prophylaxis.
Assuntos
Antineoplásicos/efeitos adversos , Fator Estimulador de Colônias de Granulócitos/uso terapêutico , Linfoma não Hodgkin/tratamento farmacológico , Neutropenia/prevenção & controle , Ásia , Estudos de Coortes , Feminino , Filgrastim , Humanos , Masculino , Pessoa de Meia-Idade , Neutropenia/induzido quimicamente , Polietilenoglicóis , Prognóstico , Proteínas Recombinantes , Estudos Retrospectivos , Taxa de SobrevidaAssuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Linfoma Extranodal de Células T-NK/tratamento farmacológico , Linfoma de Células T/tratamento farmacológico , Adulto , Ácidos Borônicos/administração & dosagem , Bortezomib , Desoxicitidina/administração & dosagem , Desoxicitidina/análogos & derivados , Feminino , Humanos , Ifosfamida/administração & dosagem , Compostos Organoplatínicos/administração & dosagem , Oxaliplatina , Pirazinas/administração & dosagem , Resultado do Tratamento , GencitabinaRESUMO
INTRODUCTION: Protoplasmic astrocytomas are a poorly recognized and uncommon subtype of astrocytoma. While usually categorized with other low-grade gliomas, there is literature to suggest that protoplasmic astrocytomas have differences in biology compared to other gliomas in this group. This paper presents the MR imaging characteristics of a series of eight protoplasmic astrocytomas. METHODS: We retrospectively reviewed MR images and histopathology of eight consecutive cases of histologically proven protoplasmic astrocytomas. RESULTS: Patients ranged from 17 to 51 years of age with a 5:3 male to female ratio. The tumors were located in the frontal or temporal lobes and tended to be large, well defined, and had a very high signal on T2 (close to cerebrospinal fluid). Generally, a large proportion of the tumor showed substantial signal suppression on T2 fluid-attenuated inversion recovery (FLAIR). Six of the eight lesions also demonstrated a partial or complete rim of reduced apparent diffusion coefficient (ADC) around the T2 FLAIR suppressing portion. CONCLUSIONS: The possibility that a primary cerebral neoplasm represents a protoplasmic astrocytoma should be considered in a patient with a large frontal or temporal tumor that has a very high signal on T2 with a large proportion of the tumor showing substantial T2 FLAIR suppression. A further clue is a partial or complete rim of reduced ADC.