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BACKGROUND/AIM: Central nervous system (CNS) involvement in aggressive B-cell lymphoma, either as a primary or secondary event to systemic disease, portends a poor prognosis. This study sought to identify patients at high risk for CNS relapse by analyzing their human leukocyte antigen (HLA) genotypes. PATIENTS AND METHODS: We retrospectively examined the HLA genotypes of 164 patients with systemic lymphoma, primary CNS lymphoma, and CNS relapse of systemic lymphoma. Patient records were analyzed, and HLA typing was performed by the Finnish Red Cross Blood Service. After excluding patients who received CNS prophylaxis, 131 patients were included in the final analysis. RESULTS: A strong association was found between the HLA-A*31 genotype and CNS disease (p=0.001). Additionally, various HLA genotypes were linked to lactate dehydrogenase levels, extranodal disease, International Prognostic Index score, and disease stage. CONCLUSION: The patient's genetic constitution, rather than solely disease-related factors, plays a role in the tropism of lymphoma for the CNS. If confirmed in a larger study, defining the HLA genotype of a lymphoma patient could provide valuable information for predicting CNS relapse.
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Neoplasias del Sistema Nervioso Central , Genotipo , Antígenos HLA , Linfoma de Células B Grandes Difuso , Humanos , Linfoma de Células B Grandes Difuso/genética , Linfoma de Células B Grandes Difuso/patología , Femenino , Neoplasias del Sistema Nervioso Central/genética , Neoplasias del Sistema Nervioso Central/patología , Masculino , Persona de Mediana Edad , Anciano , Adulto , Estudios Retrospectivos , Antígenos HLA/genética , Anciano de 80 o más Años , Adulto Joven , Pronóstico , Factores de Riesgo , Predisposición Genética a la EnfermedadRESUMEN
BACKGROUND: Social relationships are important health resources and may be investigated as social networks. We measured cancer patients' social subnetworks divided into generic social networks (people known to the patients) and disease-specific social networks (the persons talked to about the cancer) during 3 years after diagnosis. METHOD: Newly diagnosed patients with localized breast cancer (n = 222), lymphoma (n = 102), and prostate cancer (n = 141) completed a questionnaire on their social subnetworks at 2-5 months after diagnosis and 9, 18, and 36 months thereafter. Generic and cancer-specific numbers of persons of spouse/partner; other family; close relatives, in detail; and friends were recorded as well as cancer-specific numbers of persons in acquaintances; others with cancer; work community; healthcare professionals; and religious, hobby, and civic participation. The data was analyzed with regression models. RESULTS: At study entry, most patients had a spouse/partner, all had close relatives (the younger, more often parents; and the older, more often adult children with families) and most also friends. The cancer was typically discussed with them, and often with acquaintances and other patients (74-86%). Only minor usually decreasing time trends were seen. However, the numbers of distant relatives and friends were found to strongly increase by the 9-month evaluation (P < 0.001). CONCLUSION: Cancer patients have multiple social relationships and usually talk to them about their cancer soon after diagnosis. Most temporal changes are due to the natural course of life cycle. The cancer widened the patients' social networks by including other patients and healthcare professionals and by an increased number of relatives and friends.
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BACKGROUND: The modern-day therapeutic landscape for follicular lymphoma (FL) includes a number of highly effective therapies. PATIENTS AND METHODS: We set out to determine progression-free survival (PFS) after front line, second line, and third line of therapy on the basis of relevant biological characteristics and therapeutic choices. Patients (n = 743, 51% females, median 60 years old) diagnosed with grade 1-2 FL between 1997 and 2016 in nine institutions were included. RESULTS: The median PFS1, PFS2, and PFS3 were 8.1 years (95% confidence interval [CI]: 7-9.3 years), 4.2 years (95% CI: 2.8-5.6 years) and 2.2 years (95% CI 1.7-2.8 years). We found longer PFS1 for (1) females, (2) younger age, (3) lower-risk follicular lymphoma international prognostic index (FLIPI), (4) standard intensity (over low intensity) regimens and (5) immunochemotherapy strategies and (6) maintenance rituximab. We found a shorter PFS2 for patients who received front-line immunochemotherapy. Older age at diagnosis correlated with a shorter PFS3. Intensity of front-line chemotherapy, maintenance, or POD24 status did not correlate with PFS2 or PFS3 in this dataset. INTERPRETATION: With current immunochemotherapy strategies, the natural course of FL is characterized by shorter-lasting remissions after each relapse. It will be interesting to see whether new therapies can alter this pattern.
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Protocolos de Quimioterapia Combinada Antineoplásica , Linfoma Folicular , Supervivencia sin Progresión , Humanos , Linfoma Folicular/mortalidad , Linfoma Folicular/tratamiento farmacológico , Linfoma Folicular/terapia , Femenino , Persona de Mediana Edad , Masculino , Anciano , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Anciano de 80 o más Años , Rituximab/uso terapéutico , Estudios Retrospectivos , Adulto Joven , PronósticoRESUMEN
BACKGROUND: Rituximab-based combinations are the standard of care in diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL). Despite being on market for over 20 years, some of the adverse effects associated with the use of rituximab are not well known. Drug-induced interstitial pneumonitis (DIP) is a potentially fatal complication of the treatment. Granulocyte colony-stimulating factors (G-CSF) are supportive agents commonly used to prevent neutropenic infections. G-CSF are reported to have pulmonary toxicity, but the risk of DIP is greater when used in combination with other potentially pulmotoxic agents. METHODS: In this retrospective study, we reported the G-CSF use and risk of DIP in 234 DLBCL patients and 87 FL patients receiving R-CHOP-type immunochemotherapy. RESULTS: In 72% of patients, the treatment included a G-CSF support. The overall incidence of treatment-induced pneumonitis was 6.9% in this patient group. All the DIP cases (n = 16) were among patients receiving G-CSF support (p = 0.03). Older age (over 60 years) and higher disease stage (Ann Arbor 3-4) also increased the risk of DIP. CONCLUSIONS: These findings suggest that the use of G-CSF increases the risk of DIP, when used in combination with rituximab-containing regimen.
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Protocolos de Quimioterapia Combinada Antineoplásica , Ciclofosfamida , Doxorrubicina , Factor Estimulante de Colonias de Granulocitos , Linfoma Folicular , Linfoma de Células B Grandes Difuso , Prednisona , Rituximab , Vincristina , Humanos , Rituximab/efectos adversos , Rituximab/uso terapéutico , Rituximab/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Masculino , Factor Estimulante de Colonias de Granulocitos/uso terapéutico , Factor Estimulante de Colonias de Granulocitos/administración & dosificación , Femenino , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Persona de Mediana Edad , Vincristina/efectos adversos , Vincristina/uso terapéutico , Ciclofosfamida/efectos adversos , Ciclofosfamida/uso terapéutico , Anciano , Estudios Retrospectivos , Prednisona/uso terapéutico , Prednisona/efectos adversos , Prednisona/administración & dosificación , Doxorrubicina/efectos adversos , Doxorrubicina/uso terapéutico , Adulto , Linfoma Folicular/tratamiento farmacológico , Enfermedades Pulmonares Intersticiales/inducido químicamente , Anciano de 80 o más Años , Neumonía/inducido químicamente , Factores de Riesgo , Adulto JovenRESUMEN
BACKGROUND: We report here the first population-based incidence rates and prognosis of primary central nervous system lymphoma (PCNSL) in Finland. METHODS: Finnish Cancer Registry data by histological diagnosis and tumor location (2007-2017) for cases with diffuse large B-cell lymphoma. RESULTS: During 2007-2017, 392 new cases of PCNSL were reported (195 males, 197 females). The average age-adjusted incidence was 0.68/100,000 person-years. Incidence for males was 0.74/100,000 and for females 0.63/100,000, respectively. The incidence was highest, 2.93/100,000, among people aged 75-79 years. Concerning all cases in 2007-2017 the 2-year age-adjusted relative survival rate was 33% and the corresponding 5-year survival rate was 26%. Among patients under the age of 70, the age-adjusted 5-year relative survival rate increased from 36% in 2007-2012 to 43% for 2013-2017. Among patients aged 70+ the corresponding survival rates were poor, 7 and 9%. CONCLUSIONS: PCNSL incidence in Finland is among the highest reported in the world. The annual increase in incidence was 2.4%. The prognosis is still dismal, especially in elderly patients.
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Neoplasias del Sistema Nervioso Central/epidemiología , Linfoma/epidemiología , Adulto , Distribución por Edad , Anciano , Femenino , Finlandia/epidemiología , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Pronóstico , Sistema de Registros , Tasa de SupervivenciaRESUMEN
Follicular T-cell lymphoma (FTCL) is a rare subtype of mature T-cell lymphoma. It was recently recognized as a separate lymphoma entity in the 2017 revised fourth edition of the World Health Organization classification. The main goals of the present study were to gain better knowledge of the incidence and histopathological and clinical features of FTCL in Finland. In this study, we reviewed all angioimmunoblastic T-cell (AITL) and peripheral T-cell lymphomas, not otherwise specified, from the patient records in three hospital districts in Finland over a 10-year period, to identify FTCL cases and estimate its incidence. Five patients rediagnosed with FTCL and 34 with AITL were analyzed. Hodgkin/Reed-Sternberg (HRS)-like cells were observed in 24 of the 34 AITL cases and four of the five FTCL cases. We found that the main features that differentiated FTCL from AITL were rosetting of T-cells around HRS-like cells, the absence of clear cells, follicular dendritic cell meshwork and T-cell monoclonality. Our estimated incidence of FTCL is 0.20 per 100,000 people in Finland.
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Linfoma de Células T Periférico/epidemiología , Linfoma de Células T Periférico/patología , Adulto , Anciano , Femenino , Finlandia/epidemiología , Humanos , Inmunohistoquímica , Incidencia , Masculino , Persona de Mediana EdadRESUMEN
Although treatment for diffuse large B-cell lymphoma (DLBCL) has taken some notable steps in the 2000s, there are still subgroups of patients suffering from high mortality and relapse rates. To further improve treatment outcomes, it is essential to discover new mechanisms of chemotherapy resistance and create new treatment approaches to overcome them. In the present study, we analyzed the expression of chemokines and their ligands in systemic and testicular DLBCL. From our biopsy sample set of 21 testicular and 28 systemic lymphomas, we were able to demonstrate chemokine profile differences and identify associations with clinical risk factors. High cytoplasmic CXCL13 expression had correlations with better treatment response, lower disease-related mortality, and limited stage. This study suggests that active CXCR5/CXCL13 signaling could overtake the CXCR4/CXCL12 axis, resulting in a better prognosis.
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Linfoma de Células B Grandes Difuso , Neoplasias Testiculares , Adulto , Humanos , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Masculino , Recurrencia Local de Neoplasia , Pronóstico , Transducción de Señal , Neoplasias Testiculares/terapiaRESUMEN
The application of positron emission tomography (PET)-computed tomography (CT) in treatment response evaluation has increased in diffuse large B-cell lymphoma (DLBCL), although its predictive value is controversial. We retrospectively analyzed the rate of false-positive PET-CTs performed as interim (n = 94) and end-of-treatment (n = 8) assessments among 102 DLBCL patients treated during 2010-2017 at Oulu University Hospital. In PET-CT Deauville score ≥4 was regarded as positive. A biopsy was performed on 35 patients, and vital lymphoma tissue was detected from nine patients. Positive biopsy findings were associated with poor disease outcomes in this study. This difference was statistically significant: 2-year failure-free survival (FFS) was 44% in patients with a positive biopsy versus 83% for those with a negative biopsy (p = 0.003). The corresponding overall survival (OS) rates were 53% versus 95% (p = 0.010). In the multivariate analyses, a negative biopsy was an independent protective factor in FFS (Hazard Ratio (HR) 0.093 (95% confidence interval [CI] 0.017-0.511); p = 0.006) unrelated to the International Prognostic Index (IPI) (HR 1.139 [95% CI 0.237-5.474] p = 0.871) or stage (HR 1.365 [95% CI 0.138-13.470]; p = 0.790). There was no statistically significant difference in OS according to the PET results, but the FFS rate was significantly higher in patients with a negative PET. The value of PET-CT as an evaluation method suffers from a high false-positive rate, and it is inadequate alone for the justification of treatment decisions. Biopsy results provide more reliable prognostic information for the evaluation of treatment response and outcome and should be used to assess patients with positive PET-CT scans.
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Biopsia , Linfoma de Células B Grandes Difuso/diagnóstico por imagen , Linfoma de Células B Grandes Difuso/patología , Tomografía Computarizada por Tomografía de Emisión de Positrones/estadística & datos numéricos , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Biopsia/estadística & datos numéricos , Toma de Decisiones Clínicas , Intervalos de Confianza , Ciclofosfamida/administración & dosificación , Doxorrubicina/administración & dosificación , Epirrubicina/administración & dosificación , Etopósido/administración & dosificación , Reacciones Falso Positivas , Femenino , Humanos , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Linfoma de Células B Grandes Difuso/mortalidad , Masculino , Análisis Multivariante , Prednisona/administración & dosificación , Modelos de Riesgos Proporcionales , Rituximab/administración & dosificación , Tasa de Supervivencia , Resultado del Tratamiento , Vincristina/administración & dosificaciónRESUMEN
DLBCL is the most common type of non-Hodgkin lymphoma with a substantial group of patients suffering a poor prognosis. Therefore more specific markers are required for better understanding of disease biology and treatment. This study demonstrates that testis-specific antioxidant enzymes TXNDC2, TXNDC3, and TXNDC6 alongside oxidative stress marker 8-OHdG are expressed in both testicular and systemic DLBCL, and their presence or absence has correlations with clinical risk factors such as the number of extranodal effusion, the appearance of B-symptoms, and treatment response. Biopsy samples were collected from 28 systemic and 21 testicular male DLBCL patients. The samples were histostained with TXNDC2, TXNDC3, TXNDC6, and 8-OHdG, then graded by a hematopathologist blinded to clinical data. Immunoelectron microscopy was used as a second method to confirm the reliability of the acquired immunohistochemistry data. The absence of nuclear TXNDC2 expression in testicular DLBCL cells correlated with worse primary treatment response, cytoplasmic TXNDC3 expression in testicular and systemic DLBCL associated with lower frequency of B-symptoms, and TXNDC6 expression in cytoplasm in systemic DLBCL had a clinical significance with higher LD levels suggesting a role in the biological nature of these lymphomas. Overall, TXNDC3 cytoplasmic expression is correlated with a more positive outcome in both testicular and systemic DLBCL, while TXNDC6 cytoplasmic expression is associated with a negative outcome in systemic DLBCL.
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Linfoma de Células B Grandes Difuso/metabolismo , Linfoma de Células B Grandes Difuso/patología , Proteínas de la Membrana/metabolismo , Neoplasias Testiculares/metabolismo , Neoplasias Testiculares/patología , Testículo/metabolismo , Tiorredoxinas/metabolismo , 8-Hidroxi-2'-Desoxicoguanosina/metabolismo , Línea Celular Tumoral , Humanos , Linfoma de Células B Grandes Difuso/ultraestructura , Masculino , Persona de Mediana Edad , Especificidad de Órganos , Neoplasias Testiculares/ultraestructura , Testículo/patología , Testículo/ultraestructuraRESUMEN
Although overall survival in diffuse large B cell lymphomas (DLBCL) has improved, central nervous system (CNS) relapse is still a fatal complication of DLBCL. For this reason, CNS prophylaxis is recommended for patients at high risk of CNS disease. However, no consensus exists on definition of high-risk patient and optimal CNS prophylaxis. Systemic high-dose methotrexate in combination with R-CHOP has been suggested as a potential prophylactic method, since methotrexate penetrates the blood-brain barrier and achieves high concentration in the CNS. In this retrospective analysis, we report treatment outcome of 95 high-risk DLBCL/FL grade 3B patients treated with R-CHOP or its derivatives with (N = 57) or without (N = 38) CNS prophylaxis. At a median follow-up time (51 months), CNS relapses were detected in twelve patients (12.6%). Ten out of twelve (83%) of CNS events were confined to CNS system only. Median overall survival after CNS relapse was 9 months. Five-year isolated CNS relapse rates were 5% in the prophylaxis group and 26% in the group without prophylaxis. These findings suggest that high-dose methotrexate-containing prophylaxis decreases the risk of CNS failure.
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Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Neoplasias del Sistema Nervioso Central/prevención & control , Linfoma de Células B Grandes Difuso/prevención & control , Metotrexato/administración & dosificación , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias del Sistema Nervioso Central/mortalidad , Ciclofosfamida/administración & dosificación , Doxorrubicina/administración & dosificación , Femenino , Humanos , Incidencia , Linfoma de Células B Grandes Difuso/mortalidad , Masculino , Persona de Mediana Edad , Prednisona/administración & dosificación , Recurrencia , Rituximab/administración & dosificación , Vincristina/administración & dosificaciónRESUMEN
ABSTRACT Objectives: To investigate the protein expression of the epithelial-mesenchymal transition-inducing transcription factors (TFs) Twist, ZEB1 and Slug in peripheral T-cell lymphomas (PTCL) and their correlation with clinical parameters. Methods: The expression of these TFs was studied in 53 diagnostic biopsy specimens of several different PTCL subtypes with immunohistochemistry. Patient data were retrospectively collected from patient records and a statistical analysis was performed. Results: All three TFs were widely expressed. ZEB1 and Slug had correlations with clinical outcome. In all PTCL cases, high nuclear ZEB1 percentage correlated with a favorable progression-free survival (PFS) (3-year PFS: 70% vs. 34%; P = 0.010) and strong nuclear Slug intensity correlated with an unfavorable PFS (3-year PFS: 17% vs. 62%; P = 0.036). Discussion: The correlations between PFS and ZEB1 or Slug protein expression have not previously been established in PTCLs. The impact of ZEB1 and Slug expression on prognosis differed from our findings in DLBCL and the impact of ZEB1 expression was in line with current studies on mycosis fungoides and sézary syndrome. The findings may be explained by the roles these TFs play in hematopoiesis. Conclusion: ZEB1 and Slug may have potential clinical value for evaluating prognosis in PTCLs. The study size was small and heterogenous, and larger studies are warranted.
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Linfoma de Células T Periférico/genética , Factores de Transcripción de la Familia Snail/metabolismo , Proteína 1 Relacionada con Twist/metabolismo , Homeobox 1 de Unión a la E-Box con Dedos de Zinc/metabolismo , Femenino , Humanos , Masculino , Persona de Mediana Edad , PronósticoRESUMEN
OBJECTIVE: In diffuse large B-cell lymphoma (DLBCL), there is an unmet medical need to select patients who would benefit from intensified frontline treatments such as adding etoposide to an R-CHOP regimen. METHODS: The present work included a retrospective clinical analysis of two patient cohorts and an in vitro study. Primary biopsy samples from DLBCL patients treated with an etoposide-containing high-dose regimen (n = 37) and etoposide-containing frontline treatment (n = 69, R-CHOEP) were studied using immunohistochemical thioredoxin-1 (Trx1) staining. Two DLBCL cell lines expressing Trx1 were cultured, and their expression was silenced using the small interfering RNA knockdown technique. Chemoresistance was tested with doxorubicin, etoposide, vincristine, prednisolone and carboplatin. RESULTS: Thioredoxin-1 knockdown sensitised DLBCL cells to doxorubicin (P < .0001) but decreased etoposide-induced cell death (P < .00001). In DLBCL patients who received etoposide-containing frontline treatment, low cytoplasmic Trx1 expression was associated with inferior 5-year overall survival (46% vs 76%, P = .026) and disease-specific survival (68% vs 90%, P = .026). CONCLUSIONS: Strong Trx1 expression appears to increase drug resistance to doxorubicin but sensitises cells to etoposide. This implies that Trx1 expression might be the first predictive biological marker to select the patients who might benefit from adding etoposide to R-CHOP immunochemotherapy.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Biomarcadores , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Tiorredoxinas/metabolismo , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Línea Celular Tumoral , Ciclofosfamida/efectos adversos , Ciclofosfamida/uso terapéutico , Doxorrubicina/efectos adversos , Doxorrubicina/uso terapéutico , Etopósido/administración & dosificación , Femenino , Expresión Génica , Técnicas de Inactivación de Genes , Humanos , Inmunofenotipificación , Linfoma de Células B Grandes Difuso/diagnóstico , Linfoma de Células B Grandes Difuso/etiología , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Prednisona/efectos adversos , Prednisona/uso terapéutico , Pronóstico , Estudios Retrospectivos , Factores de Riesgo , Rituximab/efectos adversos , Rituximab/uso terapéutico , Tiorredoxinas/genética , Resultado del Tratamiento , Vincristina/efectos adversos , Vincristina/uso terapéuticoRESUMEN
Bulky and residual tumor are considered to increase the risk of relapse in diffuse large B-cell lymphoma (DLBCL) patients. Radiotherapy is conventionally used to reduce the risk, but the evidence is controversial. We performed a retrospective analysis to evaluate the significance of bulky and residual tumor treated with or without radiotherapy in DLBCL patients. We analyzed 312 DLBCL patients treated from 2010-2017 in Oulu University Hospital. A bulky tumor was detected in 123 patients and 55 of these patients (44.3%) received consolidative radiation therapy (RT) to the bulky tumor. Residual tumor meeting the required criteria was found in 138 (39.3%) patients, and 65 (45.5%) of these patients received consolidative RT to the site of residual tumor. iPET-CT scans were performed in 102 patients. In multivariate analyses, bulky was an independent risk factor in limited stage patients in progression free survival (HR 6.43 [95%CI 1.609-25.710]; P = .008) not related to International prognostic index (HR 1.35 [95% CI 0.256-7.124]; P = .724) or age (HR 1.62 [95% CI 0.468-5.638]; P = .445). This was not seen in advanced stage patients or in patients with residual tumor. Radiotherapy to the bulky or residual tumor was not able to improve the long-term PFS of patients. In this study, it appears that performing iPET is the most convincing method in improving evaluation and in finding patients with increased risk of relapse. Evidently, patients with negative iPET will not benefit from including RT in the treatment after metabolic complete response (CR), and patients with primary refractory disease are most likely in the group of positive iPET.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Quimioradioterapia/estadística & datos numéricos , Linfoma de Células B Grandes Difuso/terapia , Recurrencia Local de Neoplasia/epidemiología , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/farmacología , Biopsia , Médula Ósea/diagnóstico por imagen , Médula Ósea/patología , Supervivencia sin Enfermedad , Resistencia a Antineoplásicos , Femenino , Estudios de Seguimiento , Humanos , Linfoma de Células B Grandes Difuso/diagnóstico , Linfoma de Células B Grandes Difuso/mortalidad , Linfoma de Células B Grandes Difuso/patología , Masculino , Recurrencia Local de Neoplasia/prevención & control , Neoplasia Residual , Tomografía Computarizada por Tomografía de Emisión de Positrones , Supervivencia sin Progresión , Estudios Retrospectivos , Medición de Riesgo/estadística & datos numéricos , Carga TumoralRESUMEN
BACKGROUND/AIM: Tyrosine kinase inhibitors are important in the treatment of metastatic renal cell cancer (mRCC). The aim of the study was to evaluate the costs and effects of sunitinib in mRCC. PATIENTS AND METHODS: A total of 81 mRCC patients who received first-line sunitinib therapy between 2010 and 2014 were recruited. Drug doses, laboratory and imaging studies, outpatient visits and inpatient stays were recorded. Health-related quality of life (HRQoL) was measured (15D- and EQ-5D - 3L questionnaires). RESULTS: The cost of sunitinib (mean 22,268 /patient range 274 to 105,121 ) covered 73% of the total costs during the treatment period. The total treatment cost was 30,530 /patient (range=1,661-111,516 ). The median overall survival was 17.9 months. HRQoL decreased during treatment. CONCLUSION: The main cost during sunitinib treatment of mRCC was the drug itself (73% of the total costs). Drug costs and HRQoL should be considered when choosing treatment for mRCC.
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Carcinoma de Células Renales/tratamiento farmacológico , Carcinoma de Células Renales/economía , Neoplasias Renales/tratamiento farmacológico , Neoplasias Renales/economía , Sunitinib/economía , Sunitinib/uso terapéutico , Adulto , Anciano , Anciano de 80 o más Años , Antineoplásicos/economía , Antineoplásicos/uso terapéutico , Análisis Costo-Beneficio/métodos , Femenino , Costos de la Atención en Salud , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Calidad de VidaRESUMEN
BACKGROUND/AIM: Diffuse large B-cell lymphoma (DLBCL) is an aggressive malignancy where antioxidant enzyme peroxiredoxin 6 (Prx6) has previously been associated with adverse outcomes. Its systemic effects in DLBCL are unknown. MATERIALS AND METHODS: This study included 53 patients with DLBCL, five patients with primary central nervous system lymphoma (PCNSL) and 20 healthy controls. The expression of Prx6 was evaluated immunohistochemically in DLBCL tissue samples and compared to its expression in blood serum. RESULTS: Prx6 expression was the highest in healthy controls, followed by DLBCL patients and PCNSL patients. Febrile neutropenic infection after the first treatment course was associated with low pre-treatment Prx6 serum levels (<14 ng/ml) (p=0.025, OR=8.615, 95% confidence interval=1.032-71.933). Serum levels of Prx6 recovered after treatment (p=0.006). CONCLUSION: Patients with low Prx6 levels might be more prone to treatment-related adverse effects through elevated levels of oxidative stress.
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Infecciones/etiología , Linfoma de Células B Grandes Difuso/sangre , Linfoma de Células B Grandes Difuso/complicaciones , Neutropenia/complicaciones , Neutropenia/etiología , Peroxiredoxina VI/sangre , Adulto , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Biomarcadores , Femenino , Humanos , Linfoma de Células B Grandes Difuso/diagnóstico , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Medición de Riesgo , Factores de RiesgoRESUMEN
Introduction: Patients with follicular lymphoma (FL) have classically had a higher risk of solid cancers than the general population, but there is little data available in patients diagnosed and treated with modern day regimens.Material and methods: We conducted a retrospective multicenter study assessing the cumulative incidence of solid cancers other than nonmelanoma skin cancer in patients with FL between 1997 and 2016 and determined the standardized incidence ratio (SIR) to compare the incidence of solid cancers with that of the general populationResults: Among 1002 FL patients with 7 years of median follow-up, we found 74 solid cancers (most common breast [n = 19], lung and colon [n = 9 each]). The cumulative incidence was 3.8% at 5 years (95%CI 2.6-5.2) from the time of diagnosis and 4.4% at 5 years (95%CI 3.1-5.9%) from the time of front-line treatment. Although a comparison of all front-line strategies did not reveal differences in the risk of solid cancers, patients treated with anthracycline-based regimens appeared to have a lower incidence than those treated with bendamustine-based strategies (2.8% vs. 6.9%). However, patients receiving the former regimen were younger than the latter. On multivariable analysis, older age was correlated with the incidence of solid cancer and bendamustine-based treatment was of borderline significance. SIR for any solid cancer was 1.22 (95%CI 0.91-1.64), indicating no increased risk of solid cancer in patients with FL over that of the general population. However, on subgroup analyses, female patients treated with bendamustine-based strategies appeared to have a greater risk (SIR 3.85 [95%CI 1.45-10.27])Discussion: The incidence of solid cancer in this cohort of patients with FL was low and not greater than in the general population. However, the risk may be greater in female patients treated with bendamustine.
Asunto(s)
Linfoma Folicular/epidemiología , Neoplasias Primarias Secundarias/epidemiología , Factores de Edad , Anciano , Femenino , Humanos , Incidencia , Linfoma Folicular/patología , Linfoma Folicular/terapia , Masculino , Persona de Mediana Edad , Neoplasias Primarias Secundarias/patología , Neoplasias Primarias Secundarias/terapia , Estudios Retrospectivos , Factores SexualesRESUMEN
Follicular lymphoma (FL) is the most common indolent lymphoma. Currently there are many comparable treatment options available for FL. When selecting the most optimal therapy it is important to consider possible late effects of the treatment as well as survival. Secondary haematological malignancy (SHM) is a severe late effect of treatments, but the incidence of SHMs is still largely unknown. The goal of the present study was to determine the incidence of SHMs and how therapeutic decisions interfere with this risk. The study included 1028 FL patients with a median follow-up time of 5·6 years. The 5-year risk of SHM was 1·1% and the risk was associated with multiple lines of treatment (P = 0·016). The 5-year risk of SHM was 0·5% after the first-line treatment and 1·6% after the second-line. The standardized incidence ratio (SIR) was 6·2 (95% confidence interval 3·4-10·5) for SHM overall. This retrospective study found that the risk of SHM was low after first-line treatment in FL patients from the rituximab era. However, the risk of SHM increases with multiple lines of treatment. Therapeutic approaches should aim to achieve as long a remission as possible with first-line treatment, thereby postponing the added risk of SHM.
Asunto(s)
Neoplasias Hematológicas , Linfoma Folicular , Neoplasias Primarias Secundarias , Sistema de Registros , Rituximab/administración & dosificación , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Supervivencia sin Enfermedad , Femenino , Estudios de Seguimiento , Neoplasias Hematológicas/tratamiento farmacológico , Neoplasias Hematológicas/mortalidad , Humanos , Linfoma Folicular/tratamiento farmacológico , Linfoma Folicular/mortalidad , Masculino , Persona de Mediana Edad , Neoplasias Primarias Secundarias/tratamiento farmacológico , Neoplasias Primarias Secundarias/mortalidad , Estudios Retrospectivos , Factores de Riesgo , Tasa de SupervivenciaRESUMEN
AIMS: Oxidative stress markers and antioxidant enzymes have previously been shown to have prognostic value and associate with adverse outcome in patients with diffuse large B cell lymphoma (DLBCL). Nuclear factor erythroid 2-related factor 1 (Nrf1) and factor 2 (Nrf2) are among the principal inducers of antioxidant enzyme production. Kelch ECH associating protein 1 (Keap1) is a negative regulator of Nrf2, and BTB (BR-C, ttk and bab) domain and CNC homolog 1 (Bach1) represses the function of both factors. Their significance in DLBCL prognosis is unknown. METHODS: Diagnostic biopsy samples of 76 patients with high-risk DLBCL were retrospectively stained with immunohistochemistry for Nrf1, Nrf2, Keap1 and Bach1, and correlated with clinical data and outcome. RESULTS: Nuclear Nrf2 and nuclear Bach1 expression were associated with adverse clinical features (anaemia, advanced stage, high IPI, high risk of neutropaenic infections), whereas cytoplasmic Nrf1 and Nrf2 were associated with favourable clinical presentation (normal haemoglobin level, no B symptoms, limited stage). None of the evaluated factors could predict survival alone. However, when two of the following parameters were combined: high nuclear score of Nrf2, low nuclear score of Nrf1, high cytoplasmic score of Nrf1 and low cytoplasmic score of Keap1 were associated with significantly worse overall survival. CONCLUSIONS: Nrf1 and Nrf2 are relevant in disease presentation and overall survival in high-risk DLBCL. Low nuclear expression of Nrf1, high cytoplasmic expression of Nrf1, high nuclear expression of Nrf2 and low cytoplasmic expression of Keap1 are associated with adverse outcome in this patient group.
Asunto(s)
Antineoplásicos Inmunológicos/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Biomarcadores de Tumor/análisis , Linfoma de Células B Grandes Difuso/química , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Factor 1 Relacionado con NF-E2/análisis , Factor 2 Relacionado con NF-E2/análisis , Rituximab/administración & dosificación , Adulto , Anciano , Antineoplásicos Inmunológicos/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Factores de Transcripción con Cremalleras de Leucina de Carácter Básico/análisis , Núcleo Celular/química , Núcleo Celular/patología , Ciclofosfamida/administración & dosificación , Ciclofosfamida/efectos adversos , Citoplasma/química , Citoplasma/patología , Doxorrubicina/administración & dosificación , Doxorrubicina/efectos adversos , Etopósido/administración & dosificación , Etopósido/efectos adversos , Femenino , Humanos , Inmunohistoquímica , Proteína 1 Asociada A ECH Tipo Kelch/análisis , Linfoma de Células B Grandes Difuso/mortalidad , Linfoma de Células B Grandes Difuso/patología , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Valor Predictivo de las Pruebas , Prednisolona/administración & dosificación , Prednisolona/efectos adversos , Estudios Retrospectivos , Medición de Riesgo , Factores de Riesgo , Rituximab/efectos adversos , Resultado del Tratamiento , Vincristina/administración & dosificación , Vincristina/efectos adversos , Adulto JovenAsunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Doxorrubicina/efectos adversos , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Ciclofosfamida/administración & dosificación , Doxorrubicina/administración & dosificación , Sustitución de Medicamentos , Epirrubicina/administración & dosificación , Epirrubicina/efectos adversos , Etopósido/administración & dosificación , Etopósido/efectos adversos , Femenino , Estudios de Seguimiento , Cardiopatías/inducido químicamente , Cardiopatías/prevención & control , Humanos , Estimación de Kaplan-Meier , Masculino , Análisis por Apareamiento , Prednisona/administración & dosificación , Supervivencia sin Progresión , Estudios Retrospectivos , Rituximab/administración & dosificación , Vincristina/administración & dosificaciónRESUMEN
Diffuse large B-cell lymphoma (DLBCL) is an aggressive lymphoma with diverse outcomes. Concurrent translocation of MYC and BCL-2 and/or BCL-6, and concurrent immunohistochemical (IHC) high expression of MYC and BCL-2, have been linked to unfavorable treatment responses. TP53-mutated DLBCL has also been linked to worse outcome. Our aim was to evaluate the aforementioned issues in a cohort of 155 patients uniformly treated with R-CHOP-like therapies. We performed direct sequencing of TP53 exons 5, 6, 7 and 8 as well as fluorescence in-situ hybridization (FISH) of MYC, BCL-2 and BCL-6, and IHC of MYC, BCL-2 and BCL-6. In multivariate analysis, TP53 mutations in L3 and loop-sheet helix (LSH) associated with a risk ratio (RR) of disease-specific survival (DSS) of 8.779 (p = 0.022) and a RR of disease-free survival (DFS) of 10.498 (p = 0.011). In IHC analysis BCL-2 overexpression was associated with inferior DFS (p = 0.002) and DSS (p = 0.002). DLBCL with BCL-2 and MYC overexpression conferred inferior survival in all patients (DSS, p = 0.038 and DFS, p = 0.011) and in patients with non-GC phenotype (DSS (p = 0.013) and DFS (p = 0.010). Our results imply that in DLBCL, the location of TP53 mutations and IHC analysis of BCL-2 and MYC might have a role in the assessment of prognosis.