RESUMO
Standard CHOP treatment includes a high cumulative dose of prednisone, and studies have shown increased fracture risk following CHOP. It is unclear whether reductions in bone mineral density (BMD) are caused by glucocorticoids or by the combination with chemotherapy. Our objective was to determine the effect of obinutuzumab (G)/rituximab (R)-bendamustine versus G/R-CHOP on BMD in follicular lymphoma patients. Patients in this GALLIUM post hoc study were ≥60 years old and in complete remission at induction treatment completion (ITC), following treatment with G or R in combination with bendamustine or CHOP. To assess BMD, Hounsfield units (HU) were measured in lumbar vertebra L1 on annual computed tomography. Furthermore, vertebral compression fractures were recorded. Of 173 patients included, 59 (34%) received CHOP and 114 (66%) received bendamustine. At baseline, there was no difference in HU between groups. The mean HU decrease from baseline to ITC was 27.8 after CHOP and 17.3 after bendamustine, corresponding to a difference of 10.4 (95% CI: 3.2-17.6). Vertebral fractures were recorded in 5/59 patients receiving CHOP and in 2/114 receiving bendamustine. CHOP was associated with a significant greater decrease in BMD and more frequent fractures. These results suggest that prophylaxis against BMD loss should be considered.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Cloridrato de Bendamustina , Densidade Óssea , Linfoma Folicular , Fraturas da Coluna Vertebral , Humanos , Pessoa de Meia-Idade , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Cloridrato de Bendamustina/efeitos adversos , Fraturas por Compressão/tratamento farmacológico , Linfoma Folicular/tratamento farmacológico , Prednisona/efeitos adversos , Rituximab/efeitos adversos , Fraturas da Coluna Vertebral/tratamento farmacológico , Vincristina/efeitos adversosRESUMO
Late toxicities can impact survivorship in patients with classical Hodgkin lymphoma (cHL) with pulmonary toxicity after bleomycin-containing chemotherapy being a concern. The incidence of pulmonary diseases was examined in this Danish population-based study. A total of 1474 adult patients with cHL treated with ABVD (doxorubicin, bleomycin, vinblastine and dacarbazine) or BEACOPP (bleomycin, vincristine, etoposide, doxorubicin, cyclophosphamide, procarbazine and prednisone) between 2000 and 2018 were included along with 7370 age- and sex-matched comparators from the background population. Median follow-up was 8.6 years for the patients. Patients with cHL had increased risk of incident pulmonary diseases (HR 2.91 [95% CI 2.30-3.68]), with a 10-year cumulative risk of 7.4% versus 2.9% for comparators. Excess risks were observed for interstitial lung diseases (HR 15.84 [95% CI 9.35-26.84]) and chronic obstructive pulmonary disease (HR 1.99 [95% CI 1.43-2.76]), with a 10-year cumulative risk of 4.1% and 3.5% respectively for patients. No excess risk was observed for asthma (HR 0.82 [95% CI 0.43-1.56]). Risk factors for interstitial lung diseases were age ≥60 years, the presence of B-symptoms and low albumin. These findings document a significant burden of pulmonary diseases among patients with cHL and emphasize the importance of diagnostic work-up of pulmonary symptoms.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Doença de Hodgkin , Pneumopatias , Humanos , Doença de Hodgkin/epidemiologia , Doença de Hodgkin/tratamento farmacológico , Feminino , Masculino , Adulto , Dinamarca/epidemiologia , Pessoa de Meia-Idade , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Pneumopatias/induzido quimicamente , Pneumopatias/epidemiologia , Pneumopatias/etiologia , Idoso , Bleomicina/efeitos adversos , Bleomicina/administração & dosagem , Adulto Jovem , Incidência , Procarbazina/efeitos adversos , Procarbazina/administração & dosagem , Vincristina/efeitos adversos , Vincristina/uso terapêutico , Vincristina/administração & dosagem , Estudos de Coortes , Ciclofosfamida/efeitos adversos , Ciclofosfamida/uso terapêutico , Ciclofosfamida/administração & dosagem , Adolescente , Doxorrubicina/efeitos adversos , Doxorrubicina/uso terapêutico , Doxorrubicina/administração & dosagemRESUMO
Cardiovascular diseases, especially congestive heart failure (CHF), are known complications of anthracyclines, but the risk for patients undergoing high-dose chemotherapy and autologous stem cell transplant (HDT-ASCT) is not well established. With T-cell therapies emerging as alternatives, studies of long-term complications after HDT-ASCT are warranted. Danish patients treated with HDT-ASCT for aggressive lymphoma between 2001 and 2017 were matched 1:5 on sex, birth year and Charlson comorbidity score to the general population. Events were captured using nationwide registers. A total of 787 patients treated with HDT-ASCT were identified. Median follow-up was 7.6 years. The risk of CHF was significantly increased in the HDT-ASCT population compared to matched comparators with an adjusted hazard ratio (HR) of 5.5 (3.8-8.1). The 10-year cumulative incidence of CHF was 8.0% versus 2.0% (p < 0.001). Male sex, ≥2 lines of therapy, hypertension and cumulative anthracycline dose (≥300 mg/m2 ) were risk factors for CHF. In a separate cohort of 4089 lymphoma patients, HDT-ASCT was also significantly associated with increased risk of CHF (adjusted HR of 2.6 [1.8-3.8]) when analysed as a time-dependent exposure. HDT-ASCT also increased the risk of other cardiac diseases. These findings are applicable for the benefit/risk assessment of HDT-ASCT versus novel therapies.
Assuntos
Doenças Cardiovasculares , Transplante de Células-Tronco Hematopoéticas , Linfoma , Humanos , Masculino , Resultado do Tratamento , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Transplante Autólogo , Transplante de Células-Tronco , DinamarcaRESUMO
Childbirth rates in classical Hodgkin lymphoma (cHL) survivors have historically been reduced compared to the general population. Understanding if contemporary treatment protocols are associated with reduced fertility is crucial as treatment guidelines shift toward more liberal use of intensive chemotherapy. We identified 2834 individuals aged 18-40 years with cHL in Swedish and Danish lymphoma registers, and in the clinical database at Oslo University Hospital diagnosed 1995-2018, who were linked to national medical birth registers. Cox regression adjusted for stage, performance status, year, and age at diagnosis was used to estimate hazard ratios (HRs) and 95% confidence intervals (CI) contrasting time to first childbirth by treatment groups (ABVD, 2-4 BEACOPP, 6-8 BEACOPP) up to 10 years after diagnosis. Overall, 74.8% of patients were treated with ABVD, 3.1% with 2-4 BEACOPP and 11.2% with 6-8 BEACOPP. Adjusted HRs comparing childbirth rates in individuals treated with 6-8 BEACOPP, and 2-4 BEACOPP to ABVD were 0.53 (CI: 0.36-0.77) and 0.33 (CI: 0.12-0.91) for males, and 0.91 (CI: 0.61-1.34) and 0.38 (CI: 0.12-1.21) for females. Cumulative incidence of childbirths after 10 years was 19.8% (CI: 14.5%-27.0%) for males and 34.3% (CI: 25.8%-45.6%) for females treated with 6-8 BEACOPP. Proportions of children born after assisted reproductive technique (ART) treatments were 77.4% (CI: 60.2-88.6%) for males following 6-8 BEACOPP, and <11% for females. Among ABVD treated patients the corresponding proportions were 12.2% (CI: 8.5%-17.3%) and 10.6% (CI: 7.4%-14.9%). BEACOPP treatment is associated with decreased childbirth rates compared to ABVD in male, but not female, cHL patients, despite widespread access to ART in the Nordics.
Assuntos
Doença de Hodgkin , Feminino , Criança , Humanos , Masculino , Doença de Hodgkin/tratamento farmacológico , Doença de Hodgkin/epidemiologia , Doxorrubicina/uso terapêutico , Bleomicina/efeitos adversos , Suécia/epidemiologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Estudos de Coortes , Vimblastina/uso terapêutico , Dacarbazina , Vincristina/uso terapêutico , Ciclofosfamida/uso terapêutico , Etoposídeo , Reprodução , Prednisona/uso terapêutico , DinamarcaRESUMO
Previous studies concerning reproductive patterns among non-Hodgkin lymphoma (NHL) survivors are scarce and those available have reported conflicting results. Treatment regimens vary considerably between aggressive and indolent NHL and studies of reproductive patterns by subtypes are warranted. In this matched cohort study, we identified all NHL patients aged 18-40 years and diagnosed between 2000 and 2018 from the Swedish and Danish lymphoma registers, and the clinical database at Oslo University Hospital (n = 2090). Population comparators were matched on sex, birth year and country (n = 19 427). Hazard ratios (HRs) were estimated using Cox regression. Males and females diagnosed with aggressive lymphoma subtypes had lower childbirth rates (HRfemale : 0.43, 95% CI: 0.31-0.59, HRmale : 0.61, 95% CI: 0.47-0.78) than comparators during the first 3 years after diagnosis. For indolent lymphomas, childbirth rates were not significantly different from comparators (HRfemale : 0.71, 95% CI: 0.48-1.04, HRmale : 0.94, 95% CI: 0.70-1.27) during the same period. Childbirth rates reached those of comparators for all subtypes after 3 years but the cumulative incidence of childbirths was decreased throughout the 10-year follow-up for aggressive NHL. Children of NHL patients were more likely to be born following assisted reproductive technology than those of comparators, except for male indolent lymphoma patients. In conclusion, fertility counselling is particularly important for patients with aggressive NHL.
Assuntos
Linfoma não Hodgkin , Criança , Humanos , Masculino , Feminino , Suécia/epidemiologia , Estudos de Coortes , Linfoma não Hodgkin/tratamento farmacológico , Sobreviventes , Reprodução , Dinamarca/epidemiologiaRESUMO
It is well established that the male sex is associated with increased risk for, as well as poorer survival of, most cancers. A similar pattern has been described in lymphomas but has not yet been comprehensively assessed. In this nationwide population-based cohort study, we used the Swedish Lymphoma Register to investigate sex differences in lymphoma subtype incidence and excess mortality in adults (age 18-99) diagnosed in 2000-2019. Male-to-female incidence rate ratios (IRRs) and excess mortality ratios (EMRs) adjusted for age and calendar year were predicted using Poisson regression. We identified 36 795 lymphoma cases, 20 738 (56.4%) in men and 16 057 (43.6%) in women. Men were at significantly higher risk of 14 out of 16 lymphoma subtypes with IRRs ranging from 1.15 (95% confidence interval [CI] 1.09-1.22) in follicular lymphoma to 5.95 (95% CI 4.89-7.24) in hairy cell leukemia. EMRs >1 were seen in 13 out of 16 lymphoma subtypes indicating higher mortality in men, although only statistically significant for classical Hodgkin lymphoma 1.26 (95% CI 1.04-1.54), aggressive lymphoma not otherwise specified 1.29 (95% CI 1.08-1.55), and small lymphocytic lymphoma 1.52 (95% CI 1.11-2.07). A corresponding analysis using data from the Danish Lymphoma Register was performed with comparable results. In conclusion, we demonstrate a significantly higher incidence and trend toward higher mortality in men for most lymphoma subtypes. Future studies with large patient material that include detailed clinicopathological prognostic factors are warranted to further delineate and explain sex differences in lymphoma survival to enable optimal management of lymphoma patients regardless of sex.
Assuntos
Leucemia Linfocítica Crônica de Células B , Linfoma Folicular , Adulto , Humanos , Feminino , Masculino , Adolescente , Adulto Jovem , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Incidência , Estudos de Coortes , Caracteres SexuaisRESUMO
CNS relapse in the brain parenchyma, eyes, or leptomeninges is an uncommon but devastating complication of diffuse large B-cell lymphoma. CNS prophylaxis strategies, typically involving intrathecal or high-dose antimetabolites, have been developed in the front-line treatment setting with the aim to reduce this subsequent risk. Clinical and biological features associated with elevated risk are increasingly well defined and are discussed in this Review. This Review summarises both the historical and current developments in this challenging field, provides a nuanced discussion regarding current reasons for and against standard prophylactic measures, outlines evidence for the timing of prophylactic measures when delivered, and reflects on possible future developments.
Assuntos
Neoplasias do Sistema Nervoso Central , Linfoma Difuso de Grandes Células B , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias do Sistema Nervoso Central/tratamento farmacológico , Neoplasias do Sistema Nervoso Central/patologia , Neoplasias do Sistema Nervoso Central/prevenção & controle , Humanos , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/patologia , Metotrexato/uso terapêutico , Recidiva Local de Neoplasia/patologiaRESUMO
Several recently published trials investigate novel therapies for relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL). To estimate the benefit of these therapies in the real-world setting, comprehensive data on patients treated in clinical routine are needed. We report outcomes for 736 R/R DLBCL patients identified among all curatively treated DLBCL patients in Sweden in the period 2007-2014. Survival and associations with disease characteristics, second-line treatment and fulfilment of chimaeric antigen receptor (CAR) T-cell trial criteria were assessed. Median overall survival (OS) was 6.6 months (≤70 years 9.6 months, >70 years 4.9 months). Early relapse (≤12 months) was strongly associated with selection of less intensive treatment and poor survival. Among patients of at most 70 years of age, 63% started intensive second-line treatment and 34% received autologous stem cell transplantation (ASCT). Two-year OS among transplanted patients was 56% (early relapse ≤12 months 40%, late relapse >12 months 66%). A minority of patients 76 years (n = 178/506, 35%) fitted CAR T trial criteria. Median progression-free survival (PFS) for patients with early relapse fitting trial criteria was 4.8 months. In conclusion, most R/R DLBCL manifest early and are often ineligible for or cannot complete intensive regimens resulting in dismal survival. Real-world patients eligible for CAR T trials also did poorly, providing a benchmark for efficacy of novel therapies.
Assuntos
Transplante de Células-Tronco Hematopoéticas , Linfoma Difuso de Grandes Células B , Linfoma não Hodgkin , Receptores de Antígenos Quiméricos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Humanos , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma não Hodgkin/tratamento farmacológico , Receptores de Antígenos Quiméricos/uso terapêutico , Recidiva , Transplante AutólogoRESUMO
There is a lack of data regarding treatment and prognosis for the growing group of oldest old patients with lymphoma. Therefore, we studied 2347 patients aged ≥85 years from the Danish and Swedish lymphoma registers 2000-2016 (Denmark) and 2007-2013 (Sweden). Outcome was assessed using relative survival (RS). The 2-year RS overall for patients with aggressive lymphomas was 38% [95% confidence interval (CI) 35-42%], of whom 845 (66%) patients received active treatment (chemotherapy, radiotherapy, immunotherapy, other). For aggressive lymphomas, not receiving active treatment was associated with an inferior 2-year RS of 12% (95% CI 9-17%) compared to 49% (95% CI 45-53%) for patients who received active treatment (excess mortality rate ratio 2·84, 95% CI 2·3-3·5; P < 0·0001). For patients with indolent lymphoma, the 2-year RS was 77% (95% CI 72-82%). Here, 383 (46%) patients received active treatment at diagnosis, but did not have better 2-year RS (75%, 95% CI 67-81%) compared to those who did not receive active treatment (83%, 95% CI 74-89%). We conclude that outcomes for the oldest old patients with lymphoma are encouraging for several subtypes and that active treatment is associated with improved outcome amongst the oldest old patients with aggressive lymphomas, indicating that age itself should not be a contraindication to treatment.
Assuntos
Linfoma/diagnóstico , Linfoma/terapia , Fatores Etários , Idoso de 80 Anos ou mais , Dinamarca/epidemiologia , Tratamento Farmacológico , Feminino , Humanos , Imunoterapia , Linfoma/epidemiologia , Masculino , Prognóstico , Radioterapia , Análise de Sobrevida , Suécia/epidemiologia , Resultado do TratamentoRESUMO
Radiotherapy (RT) can be curative in patients with localized follicular lymphoma (FL), with historical series showing a 10-year disease-free survival of 40 to 50%. As 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography with computerized tomography (PET-CT) upstages 10 to 60% of patients compared to CT, we sought to evaluate outcomes in patients staged by PET-CT, to determine if more accurate staging leads to better patient selection and results. We conducted a multicenter retrospective study under the direction of the International Lymphoma Radiation Oncology Group (ILROG). Inclusion criteria were: RT alone for untreated stage I to II FL (grade 1-3A) with dose equivalent ≥24 Gy, staged by PET-CT, age ≥18 years, and follow-up ≥3 months. End points were freedom from progression (FFP), local control, and overall survival (OS). A total of 512 patients treated between 2000 and 2017 at 16 centers were eligible for analysis; median age was 58 years (range, 20-90); 410 patients (80.1%) had stage I disease; median RT dose was 30 Gy (24-52); and median follow-up was 52 months (3.2-174.6). Five-year FFP and OS were 68.9% and 95.7%. For stage I, FFP was 74.1% vs 49.1% for stage II (P < .0001). Eight patients relapsed in-field (1.6%). Four had marginal recurrences (0.8%) resulting in local control rate of 97.6%. On multivariable analysis, stage II (hazard ratio [HR], 2.11; 95% confidence interval [CI], 1.44-3.10) and BCL2 expression (HR, 1.62; 95% CI, 1.07-2.47) were significantly associated with less favorable FFP. Outcome after RT in PET-CT staged patients appears to be better than in earlier series, particularly in stage I disease, suggesting that the curative potential of RT for truly localized FL has been underestimated.
Assuntos
Fluordesoxiglucose F18 , Linfoma Folicular/patologia , Recidiva Local de Neoplasia/patologia , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/normas , Compostos Radiofarmacêuticos , Radioterapia/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Humanos , Linfoma Folicular/diagnóstico por imagem , Linfoma Folicular/radioterapia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/diagnóstico por imagem , Recidiva Local de Neoplasia/radioterapia , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida , Adulto JovemRESUMO
Disease progression after frontline therapy for Diffuse large B-cell lymphoma (DLBCL) is a clinically significant event. Patients who experience early progression or have refractory disease have especially poor outcomes. Simple, clinically applicable prognostic tools are needed for selecting patients for consideration for novel therapies and prognostication in the relapsed/refractory (R/R) setting. Model building was performed in patients from the Surrogate endpoints in aggressive lymphoma (SEAL) consortium with disease progression after frontline immunochemotherapy. The primary endpoint was overall survival (OS) measured from date of progression. Validation was performed in the University of Iowa/Mayo Clinic SPORE Molecular Epidemiology Resource (MER) and Danish National Lymphoma Register (LYFO) cohorts. Model performance was assessed using time-dependent concordance indices (c-statistic) and calibration with metrics evaluated at 2 years from progression. Note, 1234 of 5112 patients treated with frontline immunochemotherapy in the SEAL consortium developed progressive disease. Time to progression on immunochemotherapy and age at progression were strongly associated with post-progression OS (both p < 0.001). A prognostic model was developed incorporating spline fit for both variables. The model had good concordance in the discovery (0.67) and validation sets (LYFO c = 0.64, MER c = 0.68) with generally good calibration. Time to progression on frontline therapy is strongly associated with post-progression OS in DLBCL. We developed and validated a simple to apply clinical prognostic tool in the R/R setting. The useful prediction of expected outcomes in R/R DLBCL and can inform treatment decisions such as considerations for CAR-T therapy as well as trial designs. The model is available in smartphone-based point of care applications.
Assuntos
Linfoma Difuso de Grandes Células B/mortalidade , Índice de Gravidade de Doença , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Estudos de Coortes , Terapia Combinada , Progressão da Doença , Resistencia a Medicamentos Antineoplásicos , Feminino , Humanos , Imunoterapia , Estimativa de Kaplan-Meier , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/terapia , Masculino , Pessoa de Meia-Idade , Aplicativos Móveis , Modelos Teóricos , Sistemas Automatizados de Assistência Junto ao Leito , Prognóstico , Recidiva , Risco , Smartphone , Resultado do TratamentoRESUMO
Aim: To estimate current real-world costs of drugs and supportive care for the treatment of multiple myeloma in a tax-based health system. Methods: Forty-one patients were included from a personalized medicine study (2016-2019). Detailed information was collected from patient journals and hospital registries to estimate the total and mean costs using inverse probability weighting of censored data. Results: Total observed (censored) costs for the 41 patients was 8.84 million during 125 treatment years, with antineoplastic drugs as the main cost driver (5.6 million). Individual costs showed large variations. Mean 3-year cost per patient from first progression was 182,103 (131,800-232,405). Conclusion: Prediction of real-world costs is hindered by the availability of detailed costing data. Micro-costing analyses are needed for budgeting and real-world evaluation of cost-effectiveness.
Lay abstract In recent years, there has been a dramatic improvement in the treatment of multiple myeloma due to the introduction of new drugs. These drugs have significantly increased survival but have also had an immense impact on healthcare budgets. In this study, we used detailed treatment information for multiple myeloma patients in combination with billing data from the hospital pharmacy at a Danish hospital to calculate individual cost histories for both drugs and supportive care. Using these data, we estimated the mean 3-year cost of a multiple myeloma patient to be 182.103, but we also found large variation between patients, causing an uncertainty of 50.000 in either direction. We believe that detailed costing studies, similar to the present one, are necessary for evaluation of cost-effectiveness of drugs in clinical practice.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/economia , Efeitos Psicossociais da Doença , Custos de Cuidados de Saúde/estatística & dados numéricos , Mieloma Múltiplo/economia , Cuidados Paliativos/economia , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Análise Custo-Benefício/estatística & dados numéricos , Dinamarca/epidemiologia , Progressão da Doença , Feminino , Seguimentos , Humanos , Masculino , Oncologia/economia , Oncologia/normas , Oncologia/estatística & dados numéricos , Pessoa de Meia-Idade , Mieloma Múltiplo/mortalidade , Mieloma Múltiplo/terapia , Programas Nacionais de Saúde/economia , Programas Nacionais de Saúde/normas , Programas Nacionais de Saúde/estatística & dados numéricos , Cuidados Paliativos/estatística & dados numéricos , Guias de Prática Clínica como Assunto , Intervalo Livre de Progressão , Sistema de Registros/estatística & dados numéricos , Fatores de TempoRESUMO
With rising life expectancy, the importance of patient-related prognostic factors and how to integrate such data into clinical decision-making becomes increasingly important. The aim of this study was to evaluate the prognostic impact of smoking status in patients with acute myeloid leukaemia (AML) treated with intensive chemotherapy. We conducted a nationwide cohort study based on data obtained from the Danish National Leukaemia Registry (DNLR). The study comprised Danish patients aged 18-75 years, diagnosed with AML between 1 January 2000 and 31 December 2012. Medical records were reviewed and data on smoking status were collected. A total of 1040 patients (median age 59 years) were included, and 602 patients (58·9%) were categorised as ever-smokers and the remaining as never-smokers. Kaplan-Meier survival estimates revealed that ever-smokers had a significant shorter median overall survival (OS) at 17·2 months [95% CI (14·9;19·1)] compared to never-smokers at 24·5 months (95% CI [19·2;30·7]). Multivariate analysis revealed smoking status as a significant prognostic factor for inferior OS with a hazard ratio (HR) of 1·22 [95% CI (1·04;1·44)]. In conclusion, smoking status was found to be associated with inferior OS in intensively treated AML patients.
Assuntos
Leucemia Mieloide Aguda/complicações , Fumar/efeitos adversos , Adolescente , Adulto , Idoso , Dinamarca , Feminino , Humanos , Leucemia Mieloide Aguda/mortalidade , Masculino , Pessoa de Meia-Idade , Prognóstico , Análise de Sobrevida , Resultado do Tratamento , Adulto JovemRESUMO
Non-endemic Burkitt lymphoma (BL) is a rare germinal centre B-cell-derived malignancy with the genetic hallmark of MYC gene translocation and with rapid tumour growth as a distinct clinical feature. To investigate treatment outcomes, loss of lifetime and relapse risk in adult BL patients treated with intensive immunochemotherapy, retrospective clinic-based and population-based lymphoma registries from six countries were used to identify 264 real-world patients. The median age was 47 years and the majority had advanced-stage disease and elevated LDH. Treatment protocols were R-CODOX-M/IVAC (47%), R-hyper-CVAD (16%), DA-EPOCH-R (11%), R-BFM/GMALL (25%) and other (2%) leading to an overall response rate of 89%. The two-year overall survival and event-free survival were 84% and 80% respectively. For patients in complete remission/unconfirmed, the two-year relapse risk was 6% but diminished to 0·6% for patients reaching 12 months of post-remission event-free survival (pEFS12). The loss of lifetime for pEFS12 patients was 0·4 (95% CI: -0·7 to 2) months. In conclusion, real-world outcomes of adult BL are excellent following intensive immunochemotherapy. For pEFS12 patients, the relapse risk was low and life expectancy similar to that of a general population, which is important information for developing meaningful follow-up strategies with increased focus on survivorship and less focus on routine disease surveillance.
Assuntos
Linfoma de Burkitt/tratamento farmacológico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Linfoma de Burkitt/mortalidade , Linfoma de Burkitt/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Análise de Sobrevida , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND: The mortality risk among cancer patients measured from the time of diagnosis is often elevated in comparison to the general population. However, for some cancer types, the patient mortality risk will over time reach the same level as the general population mortality risk. The time point at which the mortality risk reaches the same level as the general population is called the cure point and is of great interest to patients, clinicians, and health care planners. In previous studies, estimation of the cure point has been handled in an ad hoc fashion, often without considerations about margins of clinical relevance. METHODS: We review existing methods for estimating the cure point and discuss new clinically relevant measures for quantifying the mortality difference between cancer patients and the general population, which can be used for cure point estimation. The performance of the methods is assessed in a simulation study and the methods are illustrated on survival data from Danish colon cancer patients. RESULTS: The simulations revealed that the bias of the estimated cure point depends on the measure chosen for quantifying the excess mortality, the chosen margin of clinical relevance, and the applied estimation procedure. These choices are interdependent as the choice of mortality measure depends both on the ability to define a margin of clinical relevance and the ability to accurately compute the mortality measure. The analysis of cancer survival data demonstrates the importance of considering the confidence interval of the estimated cure point, as these may be wide in some scenarios limiting the applicability of the estimated cure point. CONCLUSIONS: Although cure points are appealing in a clinical context and has widespread applicability, estimation remains a difficult task. The estimation relies on a number of choices, each associated with pitfalls that the practitioner should be aware of.
Assuntos
Neoplasias do Colo , Neoplasias do Colo/diagnóstico , Neoplasias do Colo/terapia , Simulação por Computador , Humanos , Fatores de RiscoRESUMO
Molecular genetic studies of lymphoma have led to refinements in disease classification in the most recent World Health Organization update. Nevertheless, a 'one-size-fits-most' treatment strategy based on morphology remains widely used for lymphoma despite significant molecular heterogeneity within histopathologically-defined subtypes. Precision medicine aims to improve patient outcomes by leveraging disease- and patient-specific information to optimise treatment strategies, but implementation of precision medicine strategies is challenged by the biological diversity and rarity of lymphomas. In this review, we explore existing and emerging real-world data sources that can be used to facilitate the development of precision medicine strategies in lymphoma. We provide illustrative examples of the use of real-world analyses to refine treatment strategies, provide comparators for clinical trials, improve risk-stratification to identify patients with unmet clinical needs and describe long-term and rare toxicities.
Assuntos
Neoplasias Hematológicas/epidemiologia , Medicina de Precisão , Análise de Dados , HumanosAssuntos
Nitrilas , Mielofibrose Primária , Pirazóis , Pirimidinas , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Método Duplo-Cego , Nitrilas/uso terapêutico , Mielofibrose Primária/tratamento farmacológico , Pirazóis/uso terapêutico , Pirimidinas/uso terapêutico , Resultado do TratamentoRESUMO
BACKGROUND: Within cancer care, dynamic evaluations of the loss in expectation of life provides useful information to patients as well as physicians. The loss of lifetime function yields the conditional loss in expectation of life given survival up to a specific time point. Due to the inevitable censoring in time-to-event data, loss of lifetime estimation requires extrapolation of both the patient and general population survival function. In this context, the accuracy of different extrapolation approaches has not previously been evaluated. METHODS: The loss of lifetime function was computed by decomposing the all-cause survival function using the relative and general population survival function. To allow extrapolation, the relative survival function was fitted using existing parametric relative survival models. In addition, we introduced a novel mixture cure model suitable for extrapolation. The accuracy of the estimated loss of lifetime function using various extrapolation approaches was assessed in a simulation study and by data from the Danish Cancer Registry where complete follow-up was available. In addition, we illustrated the proposed methodology by analyzing recent data from the Danish Lymphoma Registry. RESULTS: No uniformly superior extrapolation method was found, but flexible parametric mixture cure models and flexible parametric relative survival models seemed to be suitable in various scenarios. CONCLUSION: Using extrapolation to estimate the loss of lifetime function requires careful consideration of the relative survival function outside the available follow-up period. We propose extensive sensitivity analyses when estimating the loss of lifetime function.
Assuntos
Algoritmos , Expectativa de Vida , Modelos Teóricos , Neoplasias/terapia , Idoso , Humanos , Pessoa de Meia-Idade , Neoplasias/mortalidade , Avaliação de Resultados em Cuidados de Saúde/métodos , Avaliação de Resultados em Cuidados de Saúde/estatística & dados numéricos , Sistema de Registros/estatística & dados numéricos , Análise de SobrevidaRESUMO
Cardiotoxicity is a known risk of anthracycline treatment. However, the relative contribution of anthracyclines to the development of congestive heart failure (CHF), when included in a poly-chemotherapy regimen, is unclear. We examined cardiotoxicity in adult patients with diffuse large B-cell lymphoma and follicular lymphoma undergoing first-line immunochemotherapy from 2000-2012. In total, 2440 patients without previous heart disease were identified from the Danish Lymphoma Registry, of which 1994 (81·7%) were treated with anthracycline-containing chemotherapy [R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisolone) or R-CHOEP (R-CHOP + etoposide)] and 446 (18·3%) were treated without anthracyclines (reference group). Compared to the reference group, the adjusted hazard ratio of CHF after 3-5 cycles of R-CHOP/CHOEP was 5·0 [95% confidence interval (CI) 1·4; 18·5], 6 cycles 6·8 (95% CI 2·0; 23·3) and >6 cycles 13·4 (95% CI 4·0; 45·0). The cumulative 5-year risk of CHF with all-cause mortality as competing risk was 4·6% after 3-5 cycles of R-CHOP/CHOEP, 4·5% after 6 and 7·9% after more than 6 cycles. Cumulative 5-year risk for patients treated without anthracyclines was 0·8%. Using anthracyclines in first-line lymphoma treatment increases risk of CHF in patients without previous history of heart disease. In particular, treatment with >6 cycles of R-CHOP/CHOEP is associated with a significant increase in CHF rate.
Assuntos
Antraciclinas/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Arritmias Cardíacas/induzido quimicamente , Insuficiência Cardíaca/induzido quimicamente , Adolescente , Adulto , Idoso , Anticorpos Monoclonais Murinos/administração & dosagem , Anticorpos Monoclonais Murinos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Arritmias Cardíacas/mortalidade , Cardiotoxicidade/etiologia , Cardiotoxicidade/mortalidade , Ciclofosfamida/administração & dosagem , Ciclofosfamida/efeitos adversos , Dinamarca/epidemiologia , Doxorrubicina/administração & dosagem , Doxorrubicina/efeitos adversos , Feminino , Insuficiência Cardíaca/mortalidade , Humanos , Imunoterapia/efeitos adversos , Linfoma Folicular/tratamento farmacológico , Linfoma Folicular/mortalidade , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/mortalidade , Masculino , Pessoa de Meia-Idade , Prednisona/administração & dosagem , Prednisona/efeitos adversos , Sistema de Registros , Estudos Retrospectivos , Fatores de Risco , Rituximab , Vincristina/administração & dosagem , Vincristina/efeitos adversos , Adulto JovemRESUMO
The use of routine imaging for patients with classical Hodgkin lymphoma (HL) in complete remission (CR) is controversial. In a population-based study, we examined the post-remission survival of Danish and Swedish HL patients for whom follow-up practices were different. Follow-up in Denmark included routine imaging, usually for a minimum of 2 years, whereas clinical follow-up without routine imaging was standard in Sweden. A total of 317 Danish and 454 Swedish comparable HL patients aged 18-65 years, diagnosed in the period 2007-2012 and having achieved CR following ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine)/BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, prednisone) therapy, were included in the study. The cumulative progression rates in the first 2 years were 4% (95% confidence interval [CI] 1-7) for patients with stage I-II disease vs. 12% (95% CI 6-18) for patients with stage III-IV disease. An imaging-based follow-up practice was not associated with a better post-remission survival in general (P = 0·2) or in stage-specific subgroups (P = 0·5 for I-II and P = 0·4 for III-IV). Age ≥45 years was the only independent adverse prognostic factor for survival. In conclusion, relapse of HL patients with CR is infrequent and systematic use of routine imaging in these patients does not improve post-remission survival. The present study supports clinical follow-up without routine imaging, as encouraged by the recent Lugano classification.