RESUMO
BACKGROUND: Primary pulmonary diffuse large B-cell lymphoma (PP-DLBCL) is a rare extranodal non-Hodgkin's lymphoma (EN-NHL). Its prognosis as an aggressive lymphoma is abysmal, and predictive models are still lacking. METHODS: We screened patients diagnosed with PP-DLBCL between 2010 and 2019 from the Surveillance, Epidemiology, and End Results (SEER) database. Then, univariate and multivariate COX regression analyses were used to identify independent risk factors affecting patient prognosis. Finally, a novel nomogram was constructed and the model was evaluated by looking at three dimensions. RESULTS: A total of 831 patients were included in this study. Most of the patients were elderly (526 (63.8%)) and female (428 (51.9%)). The included patients were randomized in a 7:3 ratio into a training group (577 (70%)) and a validation group (248 (30%)). We concluded that the independent risk factors of prognosis were age, extrapulmonary metastasis, radiotherapy, chemotherapy, and surgical intervention. The results of receiver operating characteristic curves, calibration curves, and decision curve analysis in the training and validation groups confirmed that the risk prediction nomogram could accurately predict the survival of PP-DLBCL. CONCLUSION: This study is the first large population-based clinical data study on PP-DLBCL. A novel predictive model about prognosis has been developed to help clinical decision-making.
Primary pulmonary diffuse large B-cell lymphoma (PP-DLBCL), a rare extranodal non-Hodgkin's lymphoma (EN-NHL), has a very poor prognosis as an aggressive lymphoma.We screened individuals from the Surveillance, Epidemiology, and End Results (SEER) database who were diagnosed with PP-DLBCL between 2010 and 2019. Then, univariate and multivariate COX regression analyses were used to identify independent risk factors affecting patient prognosis.Finally, we built a new predictive model to aid in clinical decision making.
Assuntos
Neoplasias Pulmonares , Linfoma Difuso de Grandes Células B , Nomogramas , Humanos , Linfoma Difuso de Grandes Células B/terapia , Linfoma Difuso de Grandes Células B/diagnóstico , Linfoma Difuso de Grandes Células B/epidemiologia , Linfoma Difuso de Grandes Células B/mortalidade , Feminino , Masculino , Pessoa de Meia-Idade , Idoso , Prognóstico , Neoplasias Pulmonares/terapia , Neoplasias Pulmonares/epidemiologia , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/mortalidade , Fatores de Risco , Programa de SEER , Adulto , Idoso de 80 Anos ou maisRESUMO
Primary diffuse large B-cell lymphoma of the bone (PB-DLBCL) is an extremely rare type of extra-nodal lymphoma. The clinical characteristics, management, and survival outcomes of adult PB-DLBCL patients remain poorly defined. To explore the clinical manifestations, staging, therapeutic options, prognostic factors and outcomes of adult patients with PB-DLBCL and to create a model to predict survival outcomes. Data of adult PB-DLBCL patients were obtained from the Surveillance, Epidemiology, and End Results (SEER) Program 18 registries database from 2000 to 2018. The Kaplan-Meier survival analysis was conducted to calculate survival rates. Univariate Cox regression, best subset selection (BESS), and least absolute shrinkage and selection operator (LASSO), followed by backward stepwise multivariable Cox regression, were used to construct the nomogram. The nomograms were evaluated using the concordance index (C-index), calibration curves and decision curve analysis (DCA). Diffuse large B-cell lymphoma (DLBCL) (67.51%) was the most frequent type of primary bone lymphoma. The most involved sites were the spine and lower-limb long bones. For the whole cohort, the 3-, 5-, 10- and 15-year overall survival (OS) rates were 74.9%, 70.5%, 60.0%, and 49.9%, and corresponding disease-specific survival (DSS) rates were 79.7%, 77.8%, 75.1%, and 71.4%, respectively. For OS, age, Ann Arbor stage, primary site and therapy were confirmed as final factors to develop the nomogram in adult PB-DLBCL patients, whereas for DSS, Age, marital status, Ann Arbor stage, number of bone lesions, therapy and year of diagnosis were confirmed as final factors in developing the nomogram. The nomograms demonstrated good accuracy and clinical utility. Established nomograms can accurately predict the survival of patients with PB-DLBCL and help clinicians optimize treatment.
Assuntos
Neoplasias Ósseas , Linfoma Difuso de Grandes Células B , Nomogramas , Programa de SEER , Humanos , Linfoma Difuso de Grandes Células B/mortalidade , Linfoma Difuso de Grandes Células B/epidemiologia , Linfoma Difuso de Grandes Células B/terapia , Linfoma Difuso de Grandes Células B/patologia , Masculino , Feminino , Pessoa de Meia-Idade , Neoplasias Ósseas/mortalidade , Neoplasias Ósseas/epidemiologia , Neoplasias Ósseas/terapia , Neoplasias Ósseas/patologia , Adulto , Idoso , Estimativa de Kaplan-Meier , Prognóstico , Taxa de Sobrevida , Estadiamento de Neoplasias , Adulto JovemRESUMO
Background: Beta-2 microglobulin (ß2M) is acknowledged as a prognostic biomarker for B-cell malignancies. However, insights into the impact of ß2M on B-cell malignancy risk, and vice versa, are limited. Methods: We conducted a genome-wide meta-analysis (GWMA), bidirectional two-sample Mendelian randomization (TSMR) analysis, and pathway enrichment analysis to explore the causal relationship between ß2M and B-cell malignancies and the underlying biological processes. Results: The GWMA identified 55 lead SNPs across five genomic regions (three novel: WDR72, UMOD, and NLRC5) associated with ß2M. In the UKB, genetically predicted ß2M showed a positive association with diffuse large B-cell lymphoma (DLBCL; odds ratio [OR]: 1.742 per standard deviation increase in ß2M; 95% confidence interval [CI]: 1.215-2.498; P = 3.00 × 10-3; FDR = 7.50× 10-3) and Hodgkin lymphoma (HL; OR: 2.270; 95% CI: 1.525-3.380; P = 5.15 × 10-5; FDR =2.58 × 10-4). However, no associations were found with follicular lymphoma (FL), chronic lymphoid leukemia (CLL), or multiple myeloma (MM). Reverse TSMR analysis revealed no association between genetically predicted B-cell malignancies and ß2M. In FinnGen, ß2M was found to be associated with an increased risk of DLBCL (OR: 2.098; 95% CI: 1.358-3.242; P = 8.28 × 10-4; FDR = 4.14 × 10-3), HL (OR: 1.581; 95% CI: 1.167-2.142; P = 3.13 × 10-3; FDR = 5.22 × 10-3), and FL (OR: 2.113; 95% CI: 1.292-3.455; P = 2.90 × 10-3; FDR = 5.22 × 10-3). However, no association was found with CLL or MM. Reverse TSMR analysis indicated that genetically predicted DLBCL, FL, and MM may perturb ß2M levels. Pathway enrichment analysis suggested that the innate immune system represents a convergent biological process underlying ß2M, DLBCL, and HL. Conclusions: Our findings suggested that elevated levels of ß2M were associated with an increased risk of DLBCL and HL, which is potentially linked to dysfunction of the innate immune system.
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Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Análise da Randomização Mendeliana , Polimorfismo de Nucleotídeo Único , Microglobulina beta-2 , Humanos , Microglobulina beta-2/genética , Linfoma Difuso de Grandes Células B/genética , Linfoma Difuso de Grandes Células B/epidemiologiaRESUMO
The prognostic influence of socioeconomic status (SES) on the survival of diffuse large B-cell lymphoma (DLBCL) patients remains controversial. This observational study examines the potential impact of regional SES inequalities on overall survival (OS) among DLBCL patients in Germany. We analyzed data from the German nationwide population-based dataset spanning 2004-2019 sourced from the German Center for Cancer Registry Data (n = 49,465). The primary objective was to assess the 5-year OS among patients with low SES compared to those living in middle and high SES areas. SES was grouped according to quintiles of the German Index of Socioeconomic Deprivation, which summarized nine indicators covering aspects of regional education, employment, and income. DLBCL patients in low SES areas had significantly impaired 5-year OS compared to those in middle and high SES regions (59.2% vs. 61.8% vs. 64.1%, p < 0.0001). Yet, additionally accounting for regional premature mortality removed the impact of SES on survival (Hazard Ratio 0.94, 95% CI 0.87-1.01). Our findings indicate that the prognostic impact of socioeconomic deprivation on long-term survival is not due to variations in diagnosis and treatment of DLBCL itself but rather a higher comorbidity burden.
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Linfoma Difuso de Grandes Células B , Classe Social , Humanos , Linfoma Difuso de Grandes Células B/epidemiologia , Linfoma Difuso de Grandes Células B/mortalidade , Linfoma Difuso de Grandes Células B/terapia , Alemanha/epidemiologia , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Prognóstico , Sistema de Registros , Adulto , Idoso de 80 Anos ou mais , Fatores Socioeconômicos , Taxa de SobrevidaRESUMO
INTRODUCTION: The diffuse large B-cell lymphoma (Dlbcl) is the most common non-Hodgkin lymphoma and at highest incidence among the elderly. Despite the improved outcomes of patients treated with the first-line (1L) standard of care until the end of 2022, composed by rituximab and polychemotherapy (R-Chop), during the last 20 years, the rate of relapsed and refractory Dlbcl (rrDlbcl) remains elevated. This study has identified and analyzed patients newly diagnosed with Dlbcl and treated with 1L, from the perspective of the Italian National Health Service (Ssn). METHODS: From the administrative database of Fondazione Ricerca e Salute (ReS) including ~5.5 million inhabitants/year in Italy, adults with a new in-hospital Dlbcl diagnosis (index date) and treated with 1L in 2018, 2019, 2020 and 2021 were identified and characterized in terms of demographics and comorbidities during a period (from 4 to 8 years) preceding index date. From 1 to 4 years following index date (follow-up), overall survival (Kaplan-Meier curves), percentage distribution of patients by line of therapy including dispensation/administration of chemo-immunotherapy, hemopoietic stem cell transplantation (Hsct), and direct healthcare costs charge to the Ssn, were evaluated. RESULTS: Overall, from the ReS database, 206 patients newly diagnosed with Dlbcl and treated with 1L from 2018 to 2021 in Italy (incidence from 0.9 to 1.7 x100,000 adult inhabitants) were identified. They were mainly older (median age 68 [56; 75] years), males (56%) and affected by ≥2 comorbidities (52%), mostly cardiometabolic. During 4 years of follow-up, 56% of cases in 2018 survived. During the first follow-up year: 73%, 80%, 100% and 35% of cases in 2018, 2019, 2020 and 2021, respectively, received a 2L; 42% and 64% of cases in 2018 and 2020, respectively, received a 3L. At least one Hsct was found as a 2L among cases in 2018, 2020 and 2021. On average, each patient newly diagnosed with Dlbcl and treated with 1L from 2018 to 2021 caused a total expenditure directly charged to the Ssn ranging from 20,000 to 30,000 during the first follow-up year (chemo-immunotherapy accounted for 40-53%), which reduced with time in favor of other drugs and Hsct. CONCLUSIONS: This analysis confirms the high rate of rrDlbcl and the high economic impact charged to the SSN to support first the chemo-immunotherapy, then the chronic care and the absence of standardized further lines of therapy for patients with rrDlbcl.
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Protocolos de Quimioterapia Combinada Antineoplásica , Bases de Dados Factuais , Linfoma Difuso de Grandes Células B , Humanos , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/terapia , Linfoma Difuso de Grandes Células B/epidemiologia , Itália , Masculino , Idoso , Feminino , Pessoa de Meia-Idade , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/economia , Idoso de 80 Anos ou mais , Adulto , Rituximab/administração & dosagem , Estimativa de Kaplan-Meier , Transplante de Células-Tronco Hematopoéticas , Custos de Cuidados de Saúde/estatística & dados numéricos , Vincristina/administração & dosagem , Seguimentos , Ciclofosfamida/administração & dosagem , Ciclofosfamida/uso terapêutico , Doxorrubicina/administração & dosagem , Prednisona/administração & dosagem , Prednisona/uso terapêuticoRESUMO
Diffuse large B-cell Lymphoma (DLBCL) is an aggressive subtype of non-Hodgkin lymphoma (NHL). The disease generally occurs in older patients. Although at a lower prevalence, the disease also occurs in the adolescent and young adult group (AYA). There is paucity of data in the literature on racial and ethnic disparities in the incidence and survival outcomes of DLBCL in the AYA group. The objective of our study is to demonstrate the disparities in these outcomes. Utilizing SEER, we obtained data on patient demographics, incidence, and survival from 2000 to 2020. We observed statistically significant reduced incidence of DLBCL in all racial groups, except the non-Hispanic Asian and Pacific Islander group (NHAPI). The non-Hispanic Black group (NHB) had one of the lowest survival despite showing the largest decrease in incidence in DLBCL. The differences in the survival could be secondary to socioeconomic factors, however other reasons need to be explored. The increased incidence among the NHAPI group mirrors that of large population-based studies in East Asian countries, however, underlying reasons have not been elucidated.
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Linfoma Difuso de Grandes Células B , Programa de SEER , Humanos , Linfoma Difuso de Grandes Células B/mortalidade , Linfoma Difuso de Grandes Células B/epidemiologia , Linfoma Difuso de Grandes Células B/terapia , Linfoma Difuso de Grandes Células B/etnologia , Incidência , Adolescente , Masculino , Feminino , Adulto Jovem , Adulto , Grupos Raciais , Disparidades nos Níveis de Saúde , Estados Unidos/epidemiologia , EtnicidadeRESUMO
Colon lymphoma is a rare type of gastrointestinal lymphoma and represents 0.2% to -1.2% of all primary colon cancers. This study aimed to retrospectively examine the general characteristics, treatment methods, and survival characteristics of patients with colon lymphoma who were followed-up at our center. This retrospective study included patients diagnosed with colon lymphoma who were followed up at Ankara Numune Training and Research Hospital and Ankara Bilkent City Hospital between December 2005 and June 2023. Clinicopathological features, radiological findings, treatments, and modalities of patients were obtained from their medical records. Fourteen patients with primary colon lymphoma were included in the study. Thirteen patients (92.9%) were diagnosed with diffuse large B-cell lymphoma. The median age of the patients was 55 (28-84) years. The tumor location was the terminal ileum/cecum in 50% of the patients. At the time of diagnosis, 10 patients (7 with stage 1E-2E disease, 2 with stage 3E disease, and 1 with stage 4E disease due to tumor obstruction) underwent surgery. Twelve patients received chemotherapy (6 patients as adjuvant and 6 patients as first-line treatment). The median overall survival (OS) was 10 years (0.1-21.5) years, the 5-year median OS was 71%, and the 10-year median OS was 53%. Primary colon lymphoma is a rare disease and its optimal treatment is not clearly defined. The primary treatment for primary colon lymphoma is a combination of surgery and chemotherapy. A clear consensus on the treatment can be established through prospective studies.
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Neoplasias do Colo , Humanos , Pessoa de Meia-Idade , Masculino , Idoso , Feminino , Estudos Retrospectivos , Neoplasias do Colo/terapia , Neoplasias do Colo/patologia , Neoplasias do Colo/mortalidade , Adulto , Idoso de 80 Anos ou mais , Linfoma/terapia , Linfoma/epidemiologia , Linfoma/diagnóstico , Linfoma/mortalidade , Linfoma Difuso de Grandes Células B/terapia , Linfoma Difuso de Grandes Células B/epidemiologia , Linfoma Difuso de Grandes Células B/diagnóstico , Linfoma Difuso de Grandes Células B/mortalidade , Linfoma Difuso de Grandes Células B/patologia , Estadiamento de NeoplasiasRESUMO
INTRODUCTION: The histological transformation (HT) of follicular lymphoma (FL) is a crucial biological event. The study aimed to evaluate the incidence, clinicial characteristics, prognosis and impact of HT time on survival of FL transforming to diffuse large B-cell lymphoma in population-based large-scale cohorts. METHODS: A retrospective cohort study of FL with HT was performed in the Surveillance, Epidemiology, and End Results database. The Hematological Malignancy Research Network FL cohort and Aristotle study FL cohort were used to assess the external validity. RESULTS: Among 44,127 FL cases from the Surveillance, Epidemiology, and End Results database, 1311 cases were pathology-proven recorded to transform to diffuse large B-cell lymphoma. The cumulative rates of HT at 5, 10, and 15 years after FL diagnosis were estimated to be 1.19%, 2.93%, and 5.01%, respectively. Significantly worse overall survival and cancer-specific survival were exhibited in patients with HT than those without HT. Early HT (transformation of FL within 48 months after FL diagnosis [TOD48]) was an independent predictor for adverse overall survival of HT patients, regardless of treatment modalities before transformation. The adverse prognostic effect of TOD48 was validated in the Hematological Malignancy Research Network cohort and Aristotle study cohort. Older age (>75 years) and B symptoms within FL at diagnosis were the independent risk factors of TOD48. Furthermore, a novel prognostic model combining TOD48 with Follicular Lymphoma International Prognostic Index (TOD48-FLIPI) was constructed and validated for risk stratification. CONCLUSION: TOD48 was a risk indicator of HT, and the novel prognostic model "TOD48-FLIPI" for HT patients was proposed.
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Linfoma Folicular , Linfoma Difuso de Grandes Células B , Humanos , Linfoma Folicular/mortalidade , Linfoma Folicular/patologia , Linfoma Folicular/epidemiologia , Linfoma Difuso de Grandes Células B/patologia , Linfoma Difuso de Grandes Células B/mortalidade , Linfoma Difuso de Grandes Células B/epidemiologia , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Estudos Retrospectivos , Prognóstico , Programa de SEER , Transformação Celular Neoplásica/patologia , Adulto , Idoso de 80 Anos ou maisRESUMO
BACKGROUND: Histological transformation (HT) to diffuse large B-cell lymphoma (DLBCL) is a common complication of follicular lymphoma (FL) and is usually associated with a dismal outcome. However, the survival rate of these patients has improved over the last 20 years with the introduction of rituximab. This study aimed to access the outcome of transformation to DLBCL (t-DLBCL) from FL in a retrospective series that began after the widespread use of rituximab use. In addition, we also compared survival between t-DLBCL and primary DLBCL (p-DLBCL) in the same timeframe. METHODS: We utilized the Surveillance, Epidemiology, and End Results (SEER) database to identify patients with primary FL and patients with p-DLBCL between 2000 and 2020. Patients who had a subsequent diagnosis of DLBCL at least 2 months after FL diagnosis were identified as t-DLBCL. RESULTS: Finally, we identified 50,332 FL and 95,933 p-DLBCL. With a median follow-up of 119 months, 1631 patients developed t-DLBCL. The median time from FL diagnosis to t-DLBCL was approximately 4 years. The post-transformation survival (PTS) rate at 5 years was 49.6%, with a median PTS of 56 months. Older age, advanced stage, and early transformation were associated with worse PTS. Furthermore, t-DLBCL receiving chemotherapy or combined modality as initial therapy before HT was also associated with worse PTS, while the result was inverse when taking the impact of initial management strategy at HT into account. Taking t-DLBCL and p-DLBCL as a whole, comparable survival was observed between p-DLBCL and t-DLBCL receiving radiation or watch-and-wait as initial therapy prior to HT. CONCLUSION: The outcome of t-DLBCL in the rituximab era was better than historical series before the rituximab era. Due to the good prognosis, we did not recommend autologous stem cell transplantation for t-DLBCL receiving watch-and-wait or radiation as initial therapy before HT.
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Transplante de Células-Tronco Hematopoéticas , Linfoma Folicular , Linfoma Difuso de Grandes Células B , Humanos , Rituximab/uso terapêutico , Linfoma Folicular/tratamento farmacológico , Linfoma Folicular/epidemiologia , Estudos Retrospectivos , Transplante Autólogo , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/epidemiologia , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversosRESUMO
BACKGROUND: The full potential of competing risk modeling approaches in the context of diffuse large B-cell lymphoma (DLBCL) patients has yet to be fully harnessed. This study aims to address this gap by developing a sophisticated competing risk model specifically designed to predict specific mortality in DLBCL patients. METHODS: We extracted DLBCL patients' data from the SEER (Surveillance, Epidemiology, and End Results) database. To identify relevant variables, we conducted a two-step screening process using univariate and multivariate Fine and Gray regression analyses. Subsequently, a nomogram was constructed based on the results. The model's consistency index (C-index) was calculated to assess its performance. Additionally, calibration curves and receiver operator characteristic (ROC) curves were generated to validate the model's effectiveness. RESULTS: This study enrolled a total of 24,402 patients. The feature selection analysis identified 13 variables that were statistically significant and therefore included in the model. The model validation results demonstrated that the area under the receiver operating characteristic (ROC) curve (AUC) for predicting 6-month, 1-year, and 3-year DLBCL-specific mortality was 0.748, 0.718, and 0.698, respectively, in the training cohort. In the validation cohort, the AUC values were 0.747, 0.721, and 0.697. The calibration curves indicated good consistency between the training and validation cohorts. CONCLUSION: The most significant predictor of DLBCL-specific mortality is the age of the patient, followed by the Ann Arbor stage and the administration of chemotherapy. This predictive model has the potential to facilitate the identification of high-risk DLBCL patients by clinicians, ultimately leading to improved prognosis.
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Linfoma Difuso de Grandes Células B , Humanos , Estudos Retrospectivos , Linfoma Difuso de Grandes Células B/epidemiologia , Nomogramas , Curva ROCRESUMO
Primary gastrointestinal follicular lymphoma (PGI-FL) is a rare extra-nodal lymphoma. Its epidemiology and prognosis remain unclear. We performed a retrospective analysis of eligible patients with 1648 PGI-FL and 34 892 nodal FL (N-FL) in the Surveillance, Epidemiology and End Results (SEER) database. The age-adjusted average annual incidence of PGI-FL was 0.111/100000. The median overall survival (OS) for PGI-FL and N-FL patients was 207 and 165 months respectively. The 5-year diffuse large B-cell lymphoma (DLBCL) transformation rates were 2.1% and 2.6% respectively. Age, sex, grade, Ann Arbor stage, primary site and radiation were independent prognostic factors (p < 0.05). Nomograms were constructed to predict 1-, 5- and 10-year OS and disease-specific survival (DSS). The receiver operating characteristic curves and calibration plots showed the established nomograms had robust and accurate performance. Patients were classified into three risk groups according to nomogram score. In conclusion, the incidence of PGI-FL has increased over the past 40 years, and PGI-FL has a better prognosis and a lower DLBCL transformation rate than N-FL. The nomograms were developed and validated as an individualized tool to predict survival. Patients were divided into three risk groups to assist clinicians in identifying high-risk patients and choosing the optimal individualized treatments.
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Neoplasias Gastrointestinais , Linfoma Folicular , Programa de SEER , Humanos , Linfoma Folicular/mortalidade , Linfoma Folicular/epidemiologia , Linfoma Folicular/terapia , Linfoma Folicular/diagnóstico , Feminino , Masculino , Pessoa de Meia-Idade , Idoso , Neoplasias Gastrointestinais/epidemiologia , Neoplasias Gastrointestinais/mortalidade , Neoplasias Gastrointestinais/diagnóstico , Neoplasias Gastrointestinais/terapia , Adulto , Estudos Retrospectivos , Prognóstico , Idoso de 80 Anos ou mais , Nomogramas , Incidência , Linfoma Difuso de Grandes Células B/epidemiologia , Linfoma Difuso de Grandes Células B/mortalidade , Linfoma Difuso de Grandes Células B/diagnóstico , Linfoma Difuso de Grandes Células B/terapia , Adolescente , Adulto JovemRESUMO
BACKGROUND: The introduction of rituximab significantly improved the prognosis of diffuse large B-cell lymphoma (DLBCL), emphasizing the importance of evaluating the long-term consequences of exposure to radiotherapy, alkylating agents and anthracycline-containing (immuno)chemotherapy among DLBCL survivors. METHODS: Long-term risk of subsequent malignant neoplasms (SMNs) was examined in a multicenter cohort comprising 2373 5-year DLBCL survivors treated at ages 15-61 years in 1989-2012. Observed SMN numbers were compared with expected cancer incidence to estimate standardized incidence ratios (SIRs) and absolute excess risks (AERs/10 000 person-years). Treatment-specific risks were assessed using multivariable Cox regression. RESULTS: After a median follow-up of 13.8 years, 321 survivors developed one or more SMNs (SIR 1.5, 95% CI 1.3-1.8, AER 51.8). SIRs remained increased for at least 20 years after first-line treatment (SIR ≥20-year follow-up 1.5, 95% CI 1.0-2.2, AER 81.8) and were highest among patients ≤40 years at first DLBCL treatment (SIR 2.7, 95% CI 2.0-3.5). Lung (SIR 2.0, 95% CI 1.5-2.7, AER 13.4) and gastrointestinal cancers (SIR 1.5, 95% CI 1.2-2.0, AER 11.8) accounted for the largest excess risks. Treatment with >4500 mg/m2 cyclophosphamide/>300 mg/m2 doxorubicin versus ≤2250 mg/m2/≤150 mg/m2, respectively, was associated with increased solid SMN risk (hazard ratio 1.5, 95% CI 1.0-2.2). Survivors who received rituximab had a lower risk of subdiaphragmatic solid SMNs (hazard ratio 0.5, 95% CI 0.3-1.0) compared with survivors who did not receive rituximab. CONCLUSION: Five-year DLBCL survivors have an increased risk of SMNs. Risks were higher for survivors ≤40 years at first treatment and survivors treated with >4500 mg/m2 cyclophosphamide/>300 mg/m2 doxorubicin, and may be lower for survivors treated in the rituximab era, emphasizing the need for studies with longer follow-up for rituximab-treated patients.
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Linfoma Difuso de Grandes Células B , Segunda Neoplasia Primária , Humanos , Rituximab/efeitos adversos , Segunda Neoplasia Primária/epidemiologia , Segunda Neoplasia Primária/etiologia , Sobreviventes , Ciclofosfamida , Doxorrubicina , Linfoma Difuso de Grandes Células B/epidemiologiaRESUMO
The aim of this study was to describe the impact of marginalization on DLBCL overall survival (OS) within the Canadian setting. We conducted a population-based retrospective cohort study of adult patients with newly diagnosed DLBCL in Ontario between 1 January 2005 and 31 December 2017 receiving a rituximab-containing chemotherapy regimen with curative intent followed until 1 March 2020. Our primary exposure of interest was the Ontario Marginalization Index (ON-Marg). The primary outcome was 2-year OS, accounting for patient age, sex, cancer characteristics, comorbidity burden, and rural dwelling status. While two-year overall survival was inferior for individuals in the most deprived marginalization quintile (70.4% Q5 vs. 76.0% Q1), after adjustment for relevant covariates neither the composite ON-Marg nor any of its dimensions had a significant effect. Within the Canadian context, among patients who receive chemotherapy, marginalization may not have a significant association with overall survival when accounting for key patient covariates, lending support for preserved outcomes.
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Linfoma Difuso de Grandes Células B , Humanos , Masculino , Feminino , Linfoma Difuso de Grandes Células B/mortalidade , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/epidemiologia , Estudos Retrospectivos , Idoso , Pessoa de Meia-Idade , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Adulto , Ontário/epidemiologia , Marginalização Social , Idoso de 80 Anos ou mais , Prognóstico , Taxa de Sobrevida , Rituximab/uso terapêutico , Rituximab/administração & dosagem , Adulto JovemRESUMO
Secondary central nervous system involvement (sCNSi) in diffuse large B-cell lymphoma (DLBCL) is fatal. However, its features in patients with sCNSi who are categorized as lower risk by international prognostic index (IPI) or CNS-IPI are not yet fully understood. In the present analysis, we evaluated DLBCL patients who developed sCNSi at their first progression and who participated in JCOG0601, most of whom were lower risk by IPI. Of 409 patients, 21 (5.1%) developed sCNSi during a median follow-up of 4.9 years. Five-year cumulative incidence of sCNSi were 5.1%; and 4.0%, 5.3%, and 11.5% at low, intermediate, and high risk of CNS-IPI, respectively. The most common locations of extranodal lesions at the time of registration in patients with sCNSi were the stomach (n = 4), paranasal cavity (n = 3), and bone marrow (n = 2). In univariable analysis, paranasal cavity lesion was a high-risk factor for sCNSi (subdistribution hazard ratio, 4.34 [95% confidence interval 1.28-14.73]). Median overall survival after sCNSi was 1.3 years, with a 2-year overall survival rate of 39.3%. The incidence of sCNSi in DLBCL patients at lower risk of CNS-IPI was low, as previously reported, but paranasal cavity lesion might indicate high risk for organ involvement. CLINICAL TRIAL REGISTRATION: JCOG0601 was registered in the UMIN Clinical Trials Registry (UMIN000000929, date of registration; December 04, 2007) and the Japan Registry of Clinical Trials (jRCTs031180139, date of registration; February 20, 2019).
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Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias do Sistema Nervoso Central , Ciclofosfamida , Doxorrubicina , Linfoma Difuso de Grandes Células B , Prednisona , Rituximab , Vincristina , Humanos , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/epidemiologia , Rituximab/uso terapêutico , Masculino , Feminino , Vincristina/uso terapêutico , Vincristina/administração & dosagem , Pessoa de Meia-Idade , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Idoso , Doxorrubicina/uso terapêutico , Ciclofosfamida/uso terapêutico , Ciclofosfamida/administração & dosagem , Neoplasias do Sistema Nervoso Central/tratamento farmacológico , Adulto , Prednisona/uso terapêutico , Prednisona/administração & dosagem , Idoso de 80 Anos ou mais , Seguimentos , Taxa de SobrevidaRESUMO
OBJECTIVE: We aimed to identify critical clinical features to develop an accurate webbased prediction model for estimating the overall survival (OS) of primary breast diffuse large Bcell lymphoma (PB-DLBCL) adult patients. METHODS: We first included all PB-DLBCL cases with available covariates retrieved from the Surveillance, Epidemiology, and End Results database. We sequentially performed univariate and multivariate Cox regression approaches to identify the predictors independently associated with prognosis, and all the predictors that passed these tests were then constructed to build a nomogram for predicting 3-, 5-, and 10-year survival rates of patients. The C-index and the receiver operating characteristic curve (ROC) were used to evaluate the prediction discrimination, and the calibration curve was applied to estimate the calibration. RESULTS: A total of PB-DLBCL adult patients were included (median age was 69 with the interquartile range [IQR] of 57-79 years), of which 466 (70%) were randomly allocated to the development cohort, and the remaining cases were collected for validation. Using three identified independent predictors (i.e., age, stage, and radiation), an accurate nomogram for predicting OS was developed and validated. The C-indices of our nomogram were both relatively acceptable, with 0.74 (95% CI: 0.71-0.78) and 0.72 (95% CI: 0.70-0.75) for the development and validation cohorts, respectively. The calibration curves also accurately predicted the prognosis of PB-DLBCL in all cases. In addition, ROC curves showed our nomogram to possess superior predictive ability compared to any single variable. To visually present this prediction model, a convenient webbased tool was implemented based on our prognostic nomogram. CONCLUSION: For patients with PB-DLBCL, a more convenient and accurate web-based prediction model was developed and validated, which showed relatively good performances in both discrimination and calibration during model development and validation. External evaluation and validation are warranted by further independent studies.
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Linfoma Difuso de Grandes Células B , Idoso , Humanos , Pessoa de Meia-Idade , Bases de Dados Factuais , Linfoma Difuso de Grandes Células B/diagnóstico , Linfoma Difuso de Grandes Células B/epidemiologia , Nomogramas , PrognósticoRESUMO
Diffuse large B-cell lymphoma (DLBCL) is one of the malignancies at high risk for the development of venous thromboembolism (VTE). We aimed to evaluate the incidence of VTE and the predictive ability of the age-adjusted international prognostic index (aaIPI) for the prediction of VTE among DLBCL patients. This was a retrospective cohort study including adult patients with newly diagnosed DLBCL. Differences in VTE occurrence within one year after diagnosis of DLBCL were estimated across aaIPI groups using the Kaplan-Meier model, Cox's model, and Gray's model with deaths regarded as competing events. Five hundred and ninety-one newly diagnosed DLBCL patients with a median age of 58 (range 16-93) years were included in this study. At a median follow-up time of 365 (range 2-365) days, VTE events were objectively diagnosed in 32 patients, giving a one-year cumulative incidence of VTE of 5.4% (95% confidence interval [CI], 3.7-7.6). Patients with aaIPI ≥ 2 had a significantly higher risk of VTE than patients with aaIPI < 2 (hazard ratio, 3.5; 95% CI, 1.6-7.8; p = 0.001 based on Cox's model and sub-distribution hazard ratio, 3.0; 95% CI, 1.3-6.7; p = 0.007 using Gray's model). The C-statistic of aaIPI was 0.65 (95% CI, 0.58-0.72). We demonstrated that the incidence of VTE in Asian DLBCL patients was not uncommon. The aaIPI was effective in determining the risk of VTE in DLBCL patients, even when including death as a competing event. aaIPI may be helpful in identifying patients at higher risk of VTE in DLBCL patients.
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Linfoma Difuso de Grandes Células B , Tromboembolia Venosa , Adulto , Humanos , Adolescente , Adulto Jovem , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Tromboembolia Venosa/diagnóstico , Tromboembolia Venosa/epidemiologia , Tromboembolia Venosa/etiologia , Incidência , Fatores de Risco , Prognóstico , Estudos Retrospectivos , Linfoma Difuso de Grandes Células B/complicações , Linfoma Difuso de Grandes Células B/diagnóstico , Linfoma Difuso de Grandes Células B/epidemiologiaRESUMO
With the outbreak of coronavirus disease 2019 (COVID-19), there has been an increasing focus on exploring the relationship between SARS-CoV-2 infection and tumors. However, there is no consensus on the association between COVID-19 and lymphoma. In this study, genome-wide association study (GWAS) summary data sets for COVID-19 and lymphoma were obtained from the OPEN GWAS website. Single nucleotide polymorphisms (SNPs) were selected as genetic instrument variants for fulling P < 5 × 10-8 and linkage disequilibrium [LD] r2 < 0.001. Both palindromic and outlier SNPs were removed. Cochran's Q test, the MRâEgger intercept test, and leave-one-out analysis were employed to assess the sensitivity of the effect of COVID-19 on lymphoma. The results showed that COVID-19 patients with very severe respiratory symptoms have an increased risk of developing diffuse large B-cell lymphoma (IVW, OR = 1.765, 95% CI 1.174-2.651, P = 0.006). There was no association between COVID-19 with very severe respiratory symptoms and Hodgkin's lymphoma or other types of non-Hodgkin's lymphoma. No horizontal or directional pleiotropy was observed in the Mendelian randomization analysis. In conclusion, SARS-CoV-2 infection with very severe respiratory symptoms may be a potential risk factor for diffuse large B-cell lymphoma (DLBCL), and follow-up studies with larger samples are needed.
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COVID-19 , Linfoma Difuso de Grandes Células B , Humanos , Estudo de Associação Genômica Ampla , Análise da Randomização Mendeliana , COVID-19/genética , SARS-CoV-2 , Linfoma Difuso de Grandes Células B/epidemiologia , Linfoma Difuso de Grandes Células B/genéticaRESUMO
Hysterectomy is associated with an increased risk for adverse health outcomes. However, its connection to the risk of non-Hodgkin's lymphoma (NHL) remains unclear. The aims of our study were to investigate the associations between hysterectomy, oophorectomy and risk of NHL and its major subtypes (eg, diffuse large B-cell lymphoma [DLBCL]), and whether these associations were modified by exogenous hormone use. Postmenopausal women (n = 141,621) aged 50-79 years at enrollment (1993-1998) from the Women's Health Initiative were followed for an average of 17.2 years. Hysterectomy and oophorectomy were self-reported at baseline. Incident NHL cases were confirmed by central review of medical records and pathology reports. During the follow-up period, a total of 1719 women were diagnosed with NHL. Hysterectomy, regardless of oophorectomy status, was associated with an increased risk of NHL (hazard ratio [HR] = 1.23, 95% confidence interval [CI]: 1.05-1.44). Oophorectomy was not independently associated with NHL risk after adjusting for hysterectomy. When stratified by hormone use, the association between hysterectomy and NHL risk was confined to women who had never used hormone therapy (HR = 1.35, 95% CI: 1.06-1.71), especially for DLBCL subtype (P for interaction = .01), and to those who had undergone hysterectomy before the age of 55. Our large prospective study showed that hysterectomy was a risk factor of NHL. Findings varied by hormone use. Future studies incorporating detailed information on the types and indications of hysterectomy may deepen our understanding of the mechanisms underlying DLBCL development and its potential interactions with hormone use.
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Linfoma Difuso de Grandes Células B , Linfoma não Hodgkin , Feminino , Humanos , Estudos Prospectivos , Linfoma não Hodgkin/epidemiologia , Linfoma não Hodgkin/etiologia , Histerectomia/efeitos adversos , Ovariectomia/efeitos adversos , Fatores de Risco , Linfoma Difuso de Grandes Células B/epidemiologia , Linfoma Difuso de Grandes Células B/etiologia , HormôniosRESUMO
Background: The aim of the study was to investigate the impact of nutritional status, comorbidity, and performance status on patients with diffuse large B-cell lymphoma (DLBCL). Methods: A retrospective study was conducted on 112 DLBCL patients who were diagnosed at our center between 2009 and 2018. Demographic and disease characteristics and laboratory test results were recorded. Assessments were made using the age-adjusted Charlson comorbidity index (CCI-A) for comorbidity, albumin level for nutritional status, and Eastern Cooperative Oncology Group (ECOG) score for performance status. Results: The mean age of the patients was found to be 62.63 ± 15.16 years. The ECOG score of 65 patients (69.1%) was in the range of 0-1. The mean follow-up time of the patients was determined to be 25.24 ± 25.11 months, and at the end of the follow-up period, 64 patients (57.1%) were survivors. The progression-free survival (PFS), overall survival (OS), and 5-year OS rates of those with CCI-A > 4 were found to be significantly lower than those with CCI-A score ≤4 (P < 0.05). As a result of the Cox-Regression (Backward: LR method) analysis, ECOG and albumin levels were found to be independent risk factors for both OS and PFS (P < 0.05). Conclusion: This study demonstrated that CCI-A, ECOG, and nutritional status are independent prognostic markers for DLBCL patients. Initial evaluation of these patients should include all these parameters, which are easily available at the time of diagnosis.
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Linfoma Difuso de Grandes Células B , Humanos , Pessoa de Meia-Idade , Idoso , Prognóstico , Estudos Retrospectivos , Comorbidade , Linfoma Difuso de Grandes Células B/epidemiologia , Linfoma Difuso de Grandes Células B/patologia , AlbuminasRESUMO
Biopsy is recommended for patients with primary intracranial lymphoma to confirm the diagnosis, but the effect of tumor resection is still controversial. We conducted this retrospective study to better understand the epidemiology of primary intracranial lymphoma in the USA and explore the relationship between surgical resection and prognosis. Data regarding primary intracranial lymphoma, including incidence, were extracted from the SEER database. We analyzed the difference in incidence between different groups of people. We explored the effect of surgery on the survival of patients by the Kaplan-Meier method and evaluated the possible prognostic indicators by multivariate Cox proportional hazards models. The incidence significantly increased with age. The non-Hispanic Asian or Pacific Islander population exhibited the highest incidence, and the incidence was significantly higher in males than females. A total of 6428 cases were included in the cohort study, and most of the patients were diagnosed in the sixth to seventh decade of life. Sixty percent of tumors were supratentorial tumors. Surgery, especially total resection, significantly improved overall survival and cancer-specific survival. The survival of female patients, patients diagnosed before reaching 60 years of age, patients diagnosed after 2010, and patients with supratentorial lymphomas was better than that of their counterparts. The survival of patients with diffuse large B-cell lymphoma was worse than that of their counterparts. We conducted a comprehensive retrospective analysis of patients with primary intracranial lymphoma. We analyzed the difference in incidence between different groups of people. Surgery significantly improved overall and cancer-specific survival. The results of our research can help clinicians and patients better understand the epidemiology and management of primary intracranial lymphoma.