Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 439
Filtrar
1.
Oncology ; 98(5): 280-288, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32155643

RESUMO

BACKGROUND: Recent studies have reported that the occurrence of postoperative complications after esophagectomy for esophageal cancer has a negative impact on long-term survival. Although salvage esophagectomy is associated with higher rates of morbidity and mortality, the impact of postoperative complications on long-term survival following salvage esophagectomy has not been fully investigated. METHODS: We retrospectively analyzed 73 patients with thoracic esophageal cancer who underwent salvage esophagectomy between January 1997 and December 2017 after definitive chemoradiotherapy. We investigated the clinical impact of postoperative complications on long-term survival after salvage esophagectomy. RESULTS: Postoperative complications, pulmonary complications, and anastomotic leakage occurred in 34 (47%), 14 (13%), and 14 (19%) of the patients, respectively. Patients with complications had significantly poorer survival than patients who did not have complications (HR [hazard ratio], 2.06; p = 0.017), but there were no significant differences in overall survival between patients with and those without pulmonary complications or anastomotic leakage (HR, 1.48, p = 0.318, and HR, 1.37, p = 0.377, respectively). Multivariate analysis revealed that pathological T3-4 disease (HR, 4.63; p = 0.001), residual disease (HR, 5.09; p = 0.001), and postoperative complications (HR, 3.85; p = 0.001) were significant independent prognostic factors. In particular, the frequency of death from other diseases among patients with postoperative complications was nonsignificantly higher than among patients without postoperative complications (26 vs. 10%; p = 0.071). CONCLUSION: The occurrence of complications leads to a poor prognosis for patients with esophageal cancer after salvage esophagectomy. Prevention of postoperative complications and long-term postoperative general supportive care might be important for improving patients' prognosis.


Assuntos
Quimiorradioterapia/efeitos adversos , Neoplasias Esofágicas/patologia , Neoplasias Esofágicas/terapia , Esofagectomia/efeitos adversos , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/patologia , Terapia de Salvação/efeitos adversos , Terapia Combinada/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/terapia , Neoplasia Residual/patologia , Neoplasia Residual/terapia , Prognóstico , Modelos de Riscos Proporcionais , Estudos Prospectivos , Estudos Retrospectivos
2.
Medicine (Baltimore) ; 99(3): e18880, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32011515

RESUMO

INTRODUCTION: Pleomorphic xanthoastrocytomas (PXA) are rare, typically benign, slow-growing tumors that commonly occur in the cerebral hemispheres. We describe two cases of clinically aggressive PXA with uncommon locations; one was in the tectal plate, and the other had simultaneous multicentric lesions. PATIENT CONCERNS: The both cases presented with severe headache with no significant past medical history. DIAGNOSIS: PXA World Health Organization grade II were histopathologically diagnosed from surgically resected specimens, and immunohistochemical and sequence analysis revealed a high Ki-67 proliferative index and BRAF V600E mutation in both the cases. INTERVENTIONS: The first case presented with multicentric lesions and underwent partial resection, whereas the second case presented with a tectal plate tumor that was managed by gross total surgical resection. Strong 5-aminolevulinic acid (5-ALA)-induced fluorescence was observed in both the lesions. Postoperative radiotherapy plus concomitant and adjuvant temozolomide was administered to both the patients. OUTCOMES: Despite completing adjuvant chemo-radiotherapy, both the patients had local tumor recurrence at 2 and 5 months after the operation, respectively. CONCLUSION: The progressive clinical courses in our cases suggest that additional postoperative therapy should be considered during the treatment of PXA with a high Ki67 index, and that temozolomide with radiotherapy, followed by temozolomide maintenance therapy, may not prevent recurrence in such tumors. Importantly, our experience implies that unlike other subtypes of low grade gliomas, 5-ALA fluorescence is useful for intraoperative visualization of PXA.


Assuntos
Astrocitoma/patologia , Neoplasias Encefálicas/patologia , Astrocitoma/diagnóstico por imagem , Astrocitoma/genética , Astrocitoma/terapia , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/terapia , Terapia Combinada , Diagnóstico Diferencial , Progressão da Doença , Feminino , Humanos , Antígeno Ki-67/genética , Pessoa de Meia-Idade , Gradação de Tumores , Recidiva Local de Neoplasia , Neoplasia Residual/diagnóstico por imagem , Neoplasia Residual/genética , Neoplasia Residual/terapia , Proteínas Proto-Oncogênicas B-raf/genética , Adulto Jovem
3.
Turk Neurosurg ; 30(3): 366-370, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32020567

RESUMO

AIM: To discuss the optimal and recent treatment options based on clinical review of 16 chordoma patients. MATERIAL AND METHODS: Data of the patients diagnosed and treated between 1999 and 2017 in Gazi University School of Medicine has been collected through patients’ files and the electronic database of hospital records. Statistical analysis was applied to evaluate the correlation between the progression free survival and treatment modalities. RESULTS: Nine of the 16 patients were women (56.3%). Half of the patients had intracranially located tumors, whereas the other 50% of the sample had spinal (n=5) and sacral (n=3) chordomas. The median follow-up time was 51.7 months. Recurrence was observed in 50% of patients, while the median recurrence time equaled to 27.6 months. Multivariate analysis results showed that age, gender tumor size, intra or extracranial location of tumor, treatment modalities, subtotal or grosstotal resection of tumor, radiotherapy dose, and techniques were not associated with recurrence. On the other hand, 2 patients are still under chemoterapy (imatinib, bevacizumab) without evident of recurrent disease. CONCLUSION: Despite the fact that surgery remains to be the cornerstone of treatment, total resection is not reasonable for all patients with chordomas. For this reason, adjuvant treatment for ensuring local control is highly important. If the residual tumor is of a small volume, SBRT may provide more advantages. Targeted treatment or chemotheapeutic agents may also be benificial for maintanence therapy. As the clinical awareness about chordomas is based on our series, aggressive multi-modality treatment options should be applied in the adjuvant therapy.


Assuntos
Neoplasias Encefálicas/terapia , Cordoma/terapia , Neoplasias da Base do Crânio/terapia , Neoplasias da Coluna Vertebral/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Neoplasias Encefálicas/diagnóstico , Cordoma/diagnóstico , Terapia Combinada/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasia Residual/diagnóstico , Neoplasia Residual/terapia , Procedimentos Neurocirúrgicos/métodos , Sacro/patologia , Sacro/cirurgia , Neoplasias da Base do Crânio/diagnóstico , Neoplasias da Coluna Vertebral/diagnóstico , Resultado do Tratamento
4.
Pediatr Blood Cancer ; 67(4): e28149, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31981407

RESUMO

BACKGROUND: Accurate disease detection is integral to risk stratification in B-cell acute lymphoblastic leukemia (ALL). The gold standard used to evaluate response in the United States includes morphologic evaluation and minimal residual disease (MRD) testing of aspirated bone marrow (BM) by flow cytometry (FC). This MRD assessment is usually made on a single aspirate sample that is subject to variability in collection techniques and sampling error. Additionally, central nervous system (CNS) assessments for ALL include evaluations of cytopathology and cell counts, which can miss subclinical involvement. PROCEDURE: We retrospectively compared BM biopsy, aspirate, and FC samples obtained from children and young adults with relapsed/refractory ALL to identify the frequency and degree of disease discrepancies in this population. We also compared CNS FC and cytopathology techniques. RESULTS: Sixty of 410 (14.6%) BM samples had discrepant results, 41 (10%) of which were clinically relevant as they resulted in a change in the assignment of marrow status. Discrepant BM results were found in 28 of 89 (31.5%) patients evaluated. Additionally, cerebrospinal fluid (CSF) FC identified disease in 9.7% of cases where cytopathology was negative. CONCLUSIONS: These results support further investigation of the role of concurrent BM biopsy, with aspirate and FC evaluations, and the addition of FC to CSF evaluations, to fully assess disease status and response, particularly in patients with relapsed/refractory ALL. Prospective studies incorporating more comprehensive analysis to evaluate the impact on clinical outcomes are warranted.


Assuntos
Medula Óssea/patologia , Citometria de Fluxo/métodos , Transplante de Células-Tronco Hematopoéticas/métodos , Recidiva Local de Neoplasia/patologia , Neoplasia Residual/patologia , Leucemia-Linfoma Linfoblástico de Células Precursoras B/patologia , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Imunofenotipagem , Masculino , Recidiva Local de Neoplasia/terapia , Neoplasia Residual/terapia , Leucemia-Linfoma Linfoblástico de Células Precursoras B/terapia , Prognóstico , Estudos Retrospectivos , Adulto Jovem
5.
Leukemia ; 34(7): 1730-1740, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-31992840

RESUMO

The prognostic value of IL7-receptor pathway (IL7Rp) mutations in T-cell acute lymphoblastic leukemia (T-ALL) remains unclear. We performed a comprehensive study of 200 adult patients with T-ALL included in the GRAALL2003/2005 protocols to address the clinical significance of IL7Rp mutations. Next-generation sequencing of the IL7Rp (IL7R/JAK1/JAK3/STAT5B) revealed that IL7Rp mutations were frequent in adult T-ALL (28%) particularly in immature/early T-cell progenitor (ETP)-ALL. They were associated with mutations of NOTCH-pathway, PHF6, and PRC2 components but not with K/NRAS. IL7Rp mutated (IL7Rpmut) T-ALL were slow-responders, with a high rate of M2/M3 day-8 marrow compared with IL7Rp non-mutated (IL7RpWT) T-ALL (p = 0.002) and minimal residual disease positivity at 6-weeks (MRD1) (p = 0.008) but no difference in MRD2 positivity at 12-weeks. Despite this, no adverse prognosis was evidenced when censored for allogeneic hematopoietic stem cell transplantation (HSCT). In time-dependent analysis, HSCT did not benefit IL7Rpmut patients whereas it was of marked benefit to IL7RpWT cases. IL7Rp-mutations identify a subgroup of slow-responder T-ALLs which benefit from post-induction chemotherapy regimens but not from HSCT. Our data suggest that prior knowledge of the mutation status of IL7Rp may influence HSCT decision and help to guide therapy reduction.


Assuntos
Biomarcadores Tumorais/genética , Transplante de Células-Tronco Hematopoéticas/mortalidade , Mutação , Neoplasia Residual/patologia , Leucemia-Linfoma Linfoblástico de Células T Precursoras/patologia , Receptores de Interleucina-7/genética , Adolescente , Adulto , Feminino , Seguimentos , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasia Residual/genética , Neoplasia Residual/terapia , Leucemia-Linfoma Linfoblástico de Células T Precursoras/genética , Leucemia-Linfoma Linfoblástico de Células T Precursoras/terapia , Prognóstico , Taxa de Sobrevida , Transplante Homólogo , Adulto Jovem
6.
Pediatr Blood Cancer ; 67(2): e28079, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31724815

RESUMO

INTRODUCTION: Total body irradiation (TBI)-based conditioning is the standard of care in the treatment of acute lymphoblastic leukemia (ALL) that requires allogeneic hematopoietic stem cell transplantation (HSCT). However, TBI is known to be associated with an increased risk of late effects, and therefore, non-TBI regimens have also been utilized successfully. A recent study showed that patients that were next-generation sequencing-minimal residual disease (NGS-MRD) negative prior to allogeneic HSCT had a very low risk of relapse, and perhaps could avoid exposure to TBI without compromising disease control. We examined outcomes at our institution in patients that received a TBI or non-TBI regimen, as well as explored the impact of NGS-MRD status in predicting risk of relapse post transplant. PROCEDURES: This retrospective analysis included 57 children and young adults with ALL that received their first myeloablative allogeneic HSCT from 2012 to 2017 at the University of California San Francisco. Our primary endpoint was the cumulative incidence of relapse at 3 years post transplant. RESULTS: We demonstrated similar cumulative incidence of relapse for patients treated with either a TBI or non-TBI conditioning regimen, while NGS-MRD positivity prior to transplant was highly predictive of relapse. The presence of acute graft-versus-host disease was associated with decreased relapse rates, particularly among patients that received a TBI conditioning regimen and patients that were NGS-MRD positive prior to HSCT. CONCLUSIONS: Our data suggest that the decision to use either a TBI or non-TBI regimens in ALL should depend on NGS-MRD status, with conditioning regimens based on TBI reserved for patients that cannot achieve NGS-MRD negativity prior to allogeneic HSCT.


Assuntos
Doença Enxerto-Hospedeiro/mortalidade , Transplante de Células-Tronco Hematopoéticas/mortalidade , Recidiva Local de Neoplasia/mortalidade , Neoplasia Residual/mortalidade , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidade , Irradiação Corporal Total/mortalidade , Adolescente , Adulto , Biomarcadores Tumorais/análise , Criança , Pré-Escolar , Terapia Combinada , Feminino , Seguimentos , Doença Enxerto-Hospedeiro/patologia , Doença Enxerto-Hospedeiro/terapia , Humanos , Lactente , Recém-Nascido , Masculino , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/terapia , Neoplasia Residual/patologia , Neoplasia Residual/terapia , Leucemia-Linfoma Linfoblástico de Células Precursoras/patologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida , Condicionamento Pré-Transplante , Transplante Homólogo , Adulto Jovem
7.
Pediatr Blood Cancer ; 67(2): e28086, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31738008

RESUMO

INTRODUCTION: Pediatric adrenal cortical tumors are characterized by a wide spectrum of behavior. Questions remain regarding intermediate disease stages with isolated tumor rupture or relapse. OBJECTIVES: To describe clinical characteristics, treatment strategy, and outcome of patients depending on disease stage, tumor rupture, or in case of a refractory tumor, to discuss optimal management. MATERIAL AND METHODS: Pediatric patients with histological material reviewed and treated between 2000 and 2018 in 23 French oncology centers were included. RESULTS: Among 95 cases, 59% of patients had stage I tumors (n = 55), 16% had stage II tumors (n = 16), 19% had stage III tumors (n = 17), and 5% had stage IV tumors (n = 5) (missing data: 2). Overall, 27% of patients (n = 25) had an unfavorable histology. Initial tumor resection was performed for 90% of patients (n = 86). Systemic therapies included mitotane in 20 cases and chemotherapy in 13 cases. Among 17 stage III patients, 12 had microscopic residual tumor due to an initial biopsy (n = 5), intraoperative rupture (n = 8), or surgical resection with microscopic residue or tumor spillage surgery (n = 1) (two patients with two modalities). After a median follow-up of 96 months (25-119), four early progressions and two relapses occurred. A total of seven patients died, including five of disease. Stage III diseases due to microscopic residual disease correlated with a worse prognosis: 5-year progression-free survival 44% (95% CI, 22-87%) versus 82% (95% CI, 73-91%) for the whole cohort (P < .0001). Among the 14 patients with refractory disease, only 3 were alive and free of disease after multimodal second-line therapy. CONCLUSIONS: Stage III diseases due to a microscopic residual tumor have a dismal prognosis, arguing for the systematic use of adjuvant therapy. Patients with a relapsed disease should be included in experimental studies.


Assuntos
Neoplasias do Córtex Suprarrenal/classificação , Neoplasias do Córtex Suprarrenal/patologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Resistencia a Medicamentos Antineoplásicos , Recidiva Local de Neoplasia/patologia , Neoplasia Residual/patologia , Terapia de Salvação , Adolescente , Neoplasias do Córtex Suprarrenal/terapia , Criança , Pré-Escolar , Terapia Combinada , Feminino , Seguimentos , Humanos , Lactente , Masculino , Recidiva Local de Neoplasia/terapia , Neoplasia Residual/terapia , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida
8.
Blood ; 135(3): 159-166, 2020 01 16.
Artigo em Inglês | MEDLINE | ID: mdl-31738819

RESUMO

T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive malignancy that has historically been associated with a very poor prognosis. Nevertheless, despite a lack of incorporation of novel agents, the development of intensified T-ALL-focused protocols has resulted in significant improvements in outcome in children. Through the use of several representative cases, we highlight the key changes that have driven these advances including asparaginase intensification, the use of induction dexamethasone, and the safe omission of cranial radiotherapy. We discuss the results of recent trials to explore key topics including the implementation of risk stratification with minimal residual disease measurement and how to treat high-risk subtypes such as early T-cell precursor ALL. In particular, we address current discrepancies in treatment between different cooperative groups, including the use of nelarabine, and provide rationales for current treatment protocols for both T-ALL and T-lymphoblastic lymphoma.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Irradiação Craniana/métodos , Transplante de Células-Tronco Hematopoéticas/métodos , Neoplasia Residual/terapia , Leucemia-Linfoma Linfoblástico de Células T Precursoras/terapia , Criança , Pré-Escolar , Terapia Combinada , Feminino , Humanos , Masculino , Neoplasia Residual/patologia , Leucemia-Linfoma Linfoblástico de Células T Precursoras/patologia , Prognóstico
9.
Recent Results Cancer Res ; 214: 71-91, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31473849

RESUMO

Bispecific T cell engagers are antibody constructs directed to a tumor-specific target on the one hand and to CD3-positive T cells on the other hand. Blinatumomab is a compound with specificity for the pan-B cell marker CD19. Clinical activity was tested in relapsed and refractory (R/R) non-Hodgkin's Lymphoma (NHL), R/R acute lymphoblastic leukemia (ALL), and ALL patients with minimal residual disease. Trials have already been started in de novo ALL. The most clinically relevant toxicities are neurologic events and cytokine release syndrome as with other T cell-activating therapies. The mechanisms of resistance are not fully understood. Higher leukemia load and later stage disease represent unfavorable factors. Besides, an upregulation of regulatory T cells and inhibitory molecules like PD-1/PD-L1 may have a role as the loss of target by several mechanisms. The future will show whether the use of bispecifics in ALL can change the standard treatment algorithms and whether bispecific T cell engagers will also be successfully used in other malignant entities.


Assuntos
Anticorpos Biespecíficos/farmacologia , Linfoma não Hodgkin/terapia , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Linfócitos T/citologia , Antígenos CD19 , Ensaios Clínicos como Assunto , Humanos , Neoplasia Residual/terapia
10.
Radiat Oncol ; 14(1): 219, 2019 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-31801574

RESUMO

OBJECTIVE: The microscopic tumor spread (MS) beyond the macroscopic tumor borders of esophageal tumors is crucial for determining the clinical target volume (CTV) in radiotherapy. The question arises whether current voluminous CTV margins of 3-5 cm around the macroscopic gross tumor volume (GTV) to account for MS are still accurate when fiducial markers are used for GTV determination. We aimed to pathologically validate the use of fiducial markers placed on the (echo)endoscopically determined tumor border (EDTB) as a surrogate for macroscopic tumor borders and to analyse the MS beyond EDTBs. METHODS: Thirty-three consecutive esophageal cancer patients treated with neo-adjuvant chemoradiotherapy after (echo)endoscopic fiducial marker implantation at cranial and caudal EDTB were included in this study. Fiducial marker positions were detected in the surgical specimens under CT guidance and demarcated with beads, and subsequently analysed for macroscopic tumor spread and MS beyond the demarcations. A logistic regression analysis was performed to determine predicting factors for MS beyond EDTB. RESULTS: A total of 60 EDTBs were examined in 32 patients. In 50% of patients no or only partial regression of tumor in response to therapy (≥Mandard 3) or higher was seen (i.e., residual tumor group) and included for MS analysis. None had macroscopic tumor spread beyond EDTBs. In the residual tumor group, only 20 and 21% of the cranial and caudal EDTBs were crossed with a maximum of 9 mm and 16 mm MS, respectively. This MS was corrected for each individual determined contraction rate (mean: 93%). Presence of MS beyond EDTB was significantly associated with initial tumor length (p = 0.028). CONCLUSION: Our results validate the use of fiducial markers on EDTB as a surrogate for macroscopic tumor and indicate that CTV margins around the GTV to compensate for MS along the esophageal wall can be limited to 1-1.5 cm, when the GTV is determined with fiducial markers.


Assuntos
Quimiorradioterapia Adjuvante/mortalidade , Endoscopia/métodos , Neoplasias Esofágicas/patologia , Marcadores Fiduciais , Terapia Neoadjuvante/mortalidade , Neoplasia Residual/patologia , Adenocarcinoma/metabolismo , Adenocarcinoma/patologia , Adenocarcinoma/terapia , Neoplasias Esofágicas/metabolismo , Neoplasias Esofágicas/terapia , Carcinoma de Células Escamosas do Esôfago/metabolismo , Carcinoma de Células Escamosas do Esôfago/patologia , Carcinoma de Células Escamosas do Esôfago/terapia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasia Residual/metabolismo , Neoplasia Residual/terapia , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida , Carga Tumoral
11.
Clin Ter ; 170(5): e352-e356, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31612192

RESUMO

OBJECTIVE: Multiparameter flow cytometry is considered the gold standard to evaluate minimal residual disease in multiple myeloma (MM) and patients in complete remission can achieve "Flow MRD-negative" status (i.e. immunophenotypically abnormal plasma cells not detectable). In the current study we report the usefulness of an eight-color flow cytometric method with a 10-5 sensitivity, using monoclonal antibodies in dried formulation. MATERIALS AND METHODS: Forty-six patients with MM were treated with bortezomib-based regimens and, when eligible, with autologous stem cell transplantation. Response to therapy was assessed according to the criteria validated by the International Myeloma Working Group. Multiparameter flow cytometry was carried out with an 8-color panel validated by the Euroflow Consortium. A commercially available single 8-color tube in dried formulation was used and almost 2,000,000 events were acquired, in order to obtain a 10-5 sensitivity. RESULT: Sixteen patients achieved stringent complete remission and another three patients achieved complete remission. In these groups of patients, the "Flow MRD-negative" status was achieved in sixteen cases. In patients who had a different degree of response (very good partial response, partial response, minimal response) immunophenotypically abnormal plasma cells were always detected. CONCLUSION: Using a single eight-color tube in dried formulation, and an acquisition strategy able to obtain a 10-5 sensitivity, not only is it possible to detect a deep response to modern therapy in patients who obtained at least complete remission, but it is also always possible to detect minimal residual disease in patients with either complete remission or stringent complete remission.


Assuntos
Citometria de Fluxo/métodos , Transplante de Células-Tronco Hematopoéticas/métodos , Mieloma Múltiplo/terapia , Neoplasia Residual/terapia , Adulto , Anticorpos Monoclonais/uso terapêutico , Terapia Combinada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/diagnóstico , Neoplasia Residual/diagnóstico , Indução de Remissão , Transplante Autólogo
12.
Surg Pathol Clin ; 12(3): 671-686, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31352980

RESUMO

Increasing evidence supports the prognostic significance of measurable residual disease (MRD) in acute myeloid leukemia (AML). Dynamic MRD assessment for patients with AML complements baseline patient risk assessment factors in determining patient prognosis. MRD status may also be helpful in informing therapeutic decisions. The European Leukemia Net MRD working party recently issued consensus recommendations for the use of MRD in AML. The Food and Drug Administration also issued advice for using MRD in trials of hematologic malignancies. This article discusses MRD testing, highlights the challenges in adopting MRD testing in clinical practice, and provides insights into the future of the field.


Assuntos
Leucemia Mieloide Aguda/diagnóstico , Neoplasia Residual/diagnóstico , Biomarcadores Tumorais/metabolismo , Citometria de Fluxo/métodos , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Humanos , Imunofenotipagem/métodos , Leucemia Mieloide Aguda/terapia , Terapia de Alvo Molecular/métodos , Neoplasia Residual/terapia , Fenótipo , Reação em Cadeia da Polimerase em Tempo Real/métodos , Indução de Remissão/métodos , Sensibilidade e Especificidade , Manejo de Espécimes/métodos
13.
Urol Clin North Am ; 46(3): 419-427, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31277736

RESUMO

Growing teratoma syndrome (GTS) is a rare clinical phenomenon in patients with nonseminomatous germ cell cancer defined by growing metastatic mass during ongoing or directly after completed chemotherapy with timely decreasing tumor markers and postpubertal teratoma exclusively after resection. GTS was first described in 1982, and few reports have been published. The limited number of studies and the resulting lack of exact knowledge about development, differentiation, and treatment of GTS leaves several clinical problems regarding treatment and follow-up unsolved. This review provides an overview of clinical diagnosis and disease management and an approach to explain the molecular development of GTS.


Assuntos
Teratoma/patologia , Teratoma/terapia , Neoplasias Testiculares/patologia , Neoplasias Testiculares/terapia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores Tumorais/análise , Terapia Combinada , Diagnóstico Diferencial , Progressão da Doença , Humanos , Metástase Linfática , Masculino , Estadiamento de Neoplasias , Neoplasia Residual/patologia , Neoplasia Residual/terapia , Prognóstico , Neoplasias Retroperitoneais/secundário , Neoplasias Retroperitoneais/terapia , Síndrome
14.
Nutr Hosp ; 36(Spec No2): 44-49, 2019 Jul 01.
Artigo em Espanhol | MEDLINE | ID: mdl-31189321

RESUMO

Introduction: The efficient management of health services requires obtaining the highest level of health possible with the available resources. The health economy has developed in recent years under the pressure of a more demanding population, older and with more comorbidities, in an environment of limited resources and greater financing difficulties. The Economics of Nutrition was born as a new discipline that addresses aspects related to the role of economics and nutrition in the health of healthy and sick populations. The economic analyzes are part of the evaluation tools for health interventions. Cost-effectiveness studies are the most frequently used. Cost-effectiveness studies have shown that the use of oral nutritional supplements offer clinical advantages for undernourished patients (reduction of morbidity and mortality) and economic benefits for the system (reduction of hospital stay, lower re-entry rates and cost savings). Oral nutritional supplementation in the integral recovery of the patient with malnutrition related to the disease is cost effective.


Assuntos
Desnutrição/economia , Desnutrição/terapia , Neoplasia Residual/terapia , Terapia Nutricional/economia , Adulto , Idoso , Idoso de 80 Anos ou mais , Redução de Custos , Análise Custo-Benefício , Suplementos Nutricionais , Humanos , Desnutrição/complicações , Pessoa de Meia-Idade , Apoio Nutricional
15.
World Neurosurg ; 128: e1024-e1033, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31103758

RESUMO

OBJECTIVE: The management of residual nonfunctional pituitary tumors after surgical resection remains controversial. In this study, we compared the prognosis of postoperative radiation therapy and observation only in patients with residual nonfunctional pituitary adenoma and reviewed the long-term complications after radiation therapy. METHODS: We retrospectively analyzed 90 patients who underwent surgery for nonfunctional pituitary adenomas from January 2008 to April 2012. Residual tumors were classified by size, location, and pathologic staining. Tumor progression was defined as volume progression ≥15% with or without clinical symptoms. Postoperative radiation therapy was performed <1 year after the last surgery. We compared the progression and 3-year and 5-year progression-free survival between the observation group and postoperative radiation therapy group. Postradiation complications including hypopituitarism, diabetes insipidus, deterioration in visual field or acuity, cranial nerve palsy, and hydrocephalus were also analyzed. RESULTS: More of the patients who received postoperative radiation therapy had a tumor progression-free survival of ≥3 years than did those who did not receive postoperative radiation therapy. Postoperative radiation therapy was significantly beneficial for the patients with a tumor size ≥3 cm or with tumors in the cavernous sinus. The most frequent complication after radiation therapy was hypopituitarism and a few cases had third cranial nerve palsy; however, there were no significant relationships with radiation therapy. CONCLUSIONS: In this study, immediate radiation therapy after tumor resection was an effective and relatively safe treatment for residual or progressive nonfunctional pituitary adenomas. Moreover, the long-term complications of radiation therapy were mild.


Assuntos
Adenoma/terapia , Neoplasias Hipofisárias/terapia , Radioterapia Adjuvante , Adulto , Idoso , Idoso de 80 Anos ou mais , Progressão da Doença , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasia Residual/terapia , Complicações Pós-Operatórias , Prognóstico , Estudos Retrospectivos
16.
Pediatr Blood Cancer ; 66(8): e27812, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31111633

RESUMO

BACKGROUND: Approximately one-third of children with acute myeloid leukemia (AML) relapse, requiring re-treatment and allogeneic hematopoietic stem cell transplantation (HSCT). Although achieving second complete remission (CR2) prior to HSCT is desirable, once CR2 is attained, it is unclear if there is any benefit from further chemotherapy prior to HSCT. Moreover, although pre-HSCT minimal residual disease (MRD) has prognostic value in acute lymphoblastic leukemia, the benefit of MRD reduction after achieving CR prior to HSCT is less clear for AML. PROCEDURE: To address these questions, we analyzed data from pediatric transplant centers in Australia and New Zealand concerning relapsed childhood AML cases occurring between 1998 and 2013. Given the retrospective nature of our analysis and assay data available, we analyzed patients on the basis of measurable residual disease (MeRD) by any methodology, rather than MRD in the conventional sense. RESULTS: We observed improved overall survival (OS) in children receiving two chemotherapy cycles, compared to one cycle or three or more cycles pre-HSCT. Improved OS with two cycles remained significant for patients without MeRD after cycle 1. CONCLUSIONS: These data suggest that a second chemotherapy cycle pre-HSCT may improve survival by lowering disease burden. Prospective trials assessing strategies to reduce pre-HSCT MRD in relapsed childhood AML are warranted.


Assuntos
Transplante de Células-Tronco Hematopoéticas/mortalidade , Leucemia Mieloide Aguda/terapia , Recidiva Local de Neoplasia/terapia , Neoplasia Residual/terapia , Adolescente , Austrália , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Lactente , Recém-Nascido , Leucemia Mieloide Aguda/patologia , Masculino , Recidiva Local de Neoplasia/patologia , Neoplasia Residual/patologia , Prognóstico , Sistema de Registros , Indução de Remissão , Estudos Retrospectivos , Taxa de Sobrevida
17.
Am J Hematol ; 94(8): 902-912, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31124175

RESUMO

In acute myeloid leukemia (AML), the assessment of post-treatment minimal residual disease (MRD) may inform a more effective management approach. We investigated the prognostic utility of next-generation sequencing (NGS)-based MRD detection undertaken before hematopoietic stem cell transplantation (HSCT). Forty-two AML subjects underwent serial disease monitoring both by standard methods, and a targeted 42-gene NGS assay, able to detect leukemia-specific mutant alleles (with >0.5% VAF) (mean 5.1 samples per subject). The prognostic relevance of any persisting diagnostic mutation before transplant (≤27 days) was assessed during 22.1 months (median) of post-transplant follow-up. The sensitivity of the NGS assay (27 MRD-positive subjects) exceeded that of the non-molecular methods (morphology, FISH, and flow cytometry) (11 positive subjects). Only one of the 13 subjects who relapsed after HSCT was NGS MRD-negative (92% assay sensitivity). The cumulative incidence of post-transplant leukemic relapse was significantly higher in the pre-transplant NGS MRD-positive (vs MRD-negative) subjects (P = .014). After adjusting for TP53 mutation and transplant conditioning regimen, NGS MRD-positivity retained independent prognostic significance for leukemic relapse (subdistribution hazard ratio = 7.3; P = .05). The pre-transplant NGS MRD-positive subjects also had significantly shortened progression-free survival (P = .038), and marginally shortened overall survival (P = .068). In patients with AML undergoing HSCT, the pre-transplant persistence of NGS-defined MRD imparts a significant, sensitive, strong, and independent increased risk for subsequent leukemic relapse and death. Given that NGS can simultaneously detect multiple leukemia-associated mutations, it can be used in the majority of AML patients to monitor disease burdens and inform treatment decisions.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Leucemia Mieloide Aguda/genética , Neoplasia Residual/genética , Adulto , Idoso , Estudos de Coortes , Feminino , Humanos , Leucemia Mieloide Aguda/epidemiologia , Leucemia Mieloide Aguda/terapia , Masculino , Pessoa de Meia-Idade , Mutação , Neoplasia Residual/epidemiologia , Neoplasia Residual/terapia , Recidiva , Estudos Retrospectivos , Condicionamento Pré-Transplante/métodos
18.
Nanomedicine ; 20: 102020, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31125675

RESUMO

Local recurrence is common among patients with advanced cancer who have undergone surgery. Here, we developed a new surgical treatment for cancer based on a nanoparticle that loaded a near-infrared dye (IR780 iodide) and perfluorooctyl bromide into liposomes (NP-IR780). In an orthotopic breast cancer mouse model, NP-IR780 was demonstrated to have excellent tumor-targeting ability due to the selective tumor accumulation of IR780 iodide and the enhanced permeation and retention effect of the nanoparticle. With the excellent targeting ability, concurrent computed tomography and photoacoustic imaging were achieved for preoperative planning. In particular, NP-IR780 could serve as a tumor indicator for near-infrared fluorescence image-guided precise resection of lesions during surgery. Importantly, residual tumors could be ablated through intraoperative photothermal therapy without obvious recurrence. This work provides a theranostic strategy that significantly improved the survival of mice through pre/intraoperative image-guided tumor resection and subsequent photothermal therapy of residual lesions.


Assuntos
Hipertermia Induzida , Nanopartículas/química , Neoplasia Residual/terapia , Fototerapia , Espectroscopia de Luz Próxima ao Infravermelho , Cirurgia Assistida por Computador , Animais , Linhagem Celular Tumoral , Feminino , Humanos , Indóis/química , Camundongos Endogâmicos BALB C , Nanopartículas/ultraestrutura , Metástase Neoplásica , Neoplasia Residual/patologia , Antígeno Nuclear de Célula em Proliferação/metabolismo
19.
Am J Hematol ; 94(8): 853-861, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31074033

RESUMO

The value of minimal residual disease (MRD) status by bone marrow and imaging analysis as independent prognostic factors has been well established in multiple myeloma (MM). Nevertheless data about their potential complementarity for a more accurate assessment are limited. With this aim, we retrospectively analyzed the prediction of outcome with the combination of PET-CT and MRD, assessed by multiparameter flow cytometry (MFC) in 103 patients with newly diagnosed MM. We confirmed the benefit in terms of progression-free survival (PFS), linked to the achievement of negativity by MFC (hazard ratio [HR] 0.53; 95% confidence interval [CI]: 0.28-0.98), and PET-CT (HR 0.18; 95% CI: 0.09-0.36) individually. By combining both techniques, patients who became MRD-/PET-, with a median of PFS 92 months, had significant prolonged median PFS (P < .001). This is compared with MRD+/PET- and PET+ patients (median PFS of 45 and 28 months, respectively). We observed a significant difference (P = .003) in overall survival (OS) outcomes between MRD-/PET- and MRD+/PET- patients (4-year OS 94.2% and 100%, respectively), vs PET+ patients (4-year OS 73.8%). All survival results were confirmed in a conditional landmark analysis. These findings support the potential complementarity between PET-CT and MFC, and highlight their better predictive capability when improving sensitivity.


Assuntos
Medula Óssea/patologia , Mieloma Múltiplo/diagnóstico por imagem , Neoplasia Residual/diagnóstico por imagem , Imagem Corporal Total , Medula Óssea/diagnóstico por imagem , Citometria de Fluxo , Humanos , Estimativa de Kaplan-Meier , Mieloma Múltiplo/mortalidade , Mieloma Múltiplo/patologia , Mieloma Múltiplo/terapia , Neoplasia Residual/mortalidade , Neoplasia Residual/patologia , Neoplasia Residual/terapia , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Intervalo Livre de Progressão , Modelos de Riscos Proporcionais , Estudos Retrospectivos
20.
Pediatr Blood Cancer ; 66(8): e27780, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31034759

RESUMO

BACKGROUND: Assessment of minimal residual disease (MRD) is an integral component for response monitoring and treatment stratification in acute lymphoblastic leukemia (ALL). We aimed to evaluate the genomic ETV6-RUNX1 fusion sites as a single marker for MRD quantification. PROCEDURE: In a representative, uniformly treated cohort of pediatric relapsed ALL patients (n = 52), ETV6-RUNX1 fusion sites were compared to the current gold standard, immunoglobulin/T-cell receptor (Ig/TCR) gene rearrangements. RESULTS: Primer/probe sets designed to ETV6-RUNX1 fusions achieved significantly more frequent a sensitivity and a quantitative range of at least 10-4 compared to the gold standard with 100% and 73% versus 76% and 47%, respectively. The breakpoint sequence was identical at diagnosis and relapse in all tested cases. There was a high degree of concordance between quantitative MRD results assessed using ETV6-RUNX1 and the highest Ig/TCR marker (Spearman's 0.899, P < .01) with differences >½ log-step in only 6% of patients. A high proportion of ETV6-RUNX1-positive ALL relapses (40%) in our cohort showed a poor response to induction treatment at relapse, and therefore had an indication for hematopoietic stem cell transplantation, demonstrating the need of accurate identification of this subgroup. CONCLUSIONS: ETV6-RUNX1 fusion sites are highly sensitive and reliable MRD markers. Our data confirm that they are unaffected by clonal evolution and selection during front-line and second-line chemotherapy in contrast to Ig/TCR rearrangements, which require several markers per patient to compensate for the observed loss of target clones. In future studies, the genomic ETV6-RUNX1 fusion can be used as single MRD marker.


Assuntos
Biomarcadores Tumorais/genética , Evolução Clonal , Subunidade alfa 2 de Fator de Ligação ao Core/genética , Genômica/métodos , Transplante de Células-Tronco Hematopoéticas , Neoplasia Residual/patologia , Proteínas de Fusão Oncogênica/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/patologia , Seguimentos , Humanos , Neoplasia Residual/genética , Neoplasia Residual/terapia , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Prognóstico , Estudos Prospectivos , Curva ROC
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA