RESUMEN

Total metabolic tumor volume (TMTV) is prognostic in lymphoma. However, cutoff values for risk stratification vary markedly, according to the tumor delineation method used. We aimed to create a standardized TMTV benchmark dataset allowing TMTV to be tested and applied as a reproducible biomarker. Methods: Sixty baseline 18F-FDG PET/CT scans were identified with a range of disease distributions (20 follicular, 20 Hodgkin, and 20 diffuse large B-cell lymphoma). TMTV was measured by 12 nuclear medicine experts, each analyzing 20 cases split across subtypes, with each case processed by 3-4 readers. LIFEx or ACCURATE software was chosen according to reader preference. Analysis was performed stepwise: TMTV1 with automated preselection of lesions using an SUV of at least 4 and a volume of at least 3 cm3 with single-click removal of physiologic uptake; TMTV2 with additional removal of reactive bone marrow and spleen with single clicks; TMTV3 with manual editing to remove other physiologic uptake, if required; and TMTV4 with optional addition of lesions using mouse clicks with an SUV of at least 4 (no volume threshold). Results: The final TMTV (TMTV4) ranged from 8 to 2,288 cm3, showing excellent agreement among all readers in 87% of cases (52/60) with a difference of less than 10% or less than 10 cm3 In 70% of the cases, TMTV4 equaled TMTV1, requiring no additional reader interaction. Differences in the TMTV4 were exclusively related to reader interpretation of lesion inclusion or physiologic high-uptake region removal, not to the choice of software. For 5 cases, large TMTV differences (>25%) were due to disagreement about inclusion of diffuse splenic uptake. Conclusion: The proposed segmentation method enabled highly reproducible TMTV measurements, with minimal reader interaction in 70% of the patients. The inclusion or exclusion of diffuse splenic uptake requires definition of specific criteria according to lymphoma subtype. The publicly available proposed benchmark allows comparison of study results and could serve as a reference to test improvements using other segmentation approaches.

Asunto(s)

Benchmarking , Fluorodesoxiglucosa F18 , Linfoma , Tomografía Computarizada por Tomografía de Emisión de Positrones , Carga Tumoral , Humanos , Linfoma/diagnóstico por imagen , Linfoma/metabolismo , Femenino , Masculino , Persona de Mediana Edad , Adulto , Anciano , Procesamiento de Imagen Asistido por Computador , Internacionalidad , Adulto Joven , Anciano de 80 o más Años

RESUMEN

PURPOSE: Artificial intelligence can reduce the time used by physicians on radiological assessments. For 18F-fluorodeoxyglucose-avid lymphomas, obtaining complete metabolic response (CMR) by end of treatment is prognostic. METHODS: Here, we present a deep learning-based algorithm for fully automated treatment response assessments according to the Lugano 2014 classification. The proposed four-stage method, trained on a multicountry clinical trial (ClinicalTrials.gov identifier: NCT01287741) and tested in three independent multicenter and multicountry test sets on different non-Hodgkin lymphoma subtypes and different lines of treatment (ClinicalTrials.gov identifiers NCT02257567, NCT02500407; 20% holdout in ClinicalTrials.gov identifier NCT01287741), outputs the detected lesions at baseline and follow-up to enable focused radiologist review. RESULTS: The method's response assessment achieved high agreement with the adjudicated radiologic responses (eg, agreement for overall response assessment of 93%, 87%, and 85% in ClinicalTrials.gov identifiers NCT01287741, NCT02500407, and NCT02257567, respectively) similar to inter-radiologist agreement and was strongly prognostic of outcomes with a trend toward higher accuracy for death risk than adjudicated radiologic responses (hazard ratio for end of treatment by-model CMR of 0.123, 0.054, and 0.205 in ClinicalTrials.gov identifiers NCT01287741, NCT02500407, and NCT02257567, compared with, respectively, 0.226, 0.292, and 0.272 for CMR by the adjudicated responses). Furthermore, a radiologist review of the algorithm's assessments was conducted. The radiologist median review time was 1.38 minutes/assessment, and no statistically significant differences were observed in the level of agreement of the radiologist with the model's response compared with the level of agreement of the radiologist with the adjudicated responses. CONCLUSION: These results suggest that the proposed method can be incorporated into radiologic response assessment workflows in cancer imaging for significant time savings and with performance similar to trained medical experts.

Asunto(s)

Aprendizaje Profundo , Fluorodesoxiglucosa F18 , Linfoma no Hodgkin , Humanos , Linfoma no Hodgkin/diagnóstico por imagen , Linfoma no Hodgkin/metabolismo , Tomografía de Emisión de Positrones/métodos , Radiofármacos , Femenino , Masculino

RESUMEN

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.

Asunto(s)

Protocolos de Quimioterapia Combinada Antineoplásica , Enfermedad de Hodgkin , Enfermedades Pulmonares , Humanos , Enfermedad de Hodgkin/epidemiología , Enfermedad de Hodgkin/tratamiento farmacológico , Femenino , Masculino , Adulto , Dinamarca/epidemiología , Persona de Mediana Edad , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Enfermedades Pulmonares/inducido químicamente , Enfermedades Pulmonares/epidemiología , Enfermedades Pulmonares/etiología , Anciano , Bleomicina/efectos adversos , Bleomicina/administración & dosificación , Adulto Joven , Incidencia , Procarbazina/efectos adversos , Procarbazina/administración & dosificación , Vincristina/efectos adversos , Vincristina/uso terapéutico , Vincristina/administración & dosificación , Estudios de Cohortes , Ciclofosfamida/efectos adversos , Ciclofosfamida/uso terapéutico , Ciclofosfamida/administración & dosificación , Adolescente , Doxorrubicina/efectos adversos , Doxorrubicina/uso terapéutico , Doxorrubicina/administración & dosificación

RESUMEN

Purpose: Most adult patients diagnosed with acute lymphoblastic leukemia (ALL) are below retirement age. The overall survival of patients with ALL has improved with implementation of high intensity pediatric-inspired treatment protocols. However, this treatment comes with a risk of long-term complications, which could affect the ability to work. The aim of this study was to investigate the risk of disability pension (DP) and return to work (RTW) for patients with ALL. Patients and Methods: Patients aged 18-60 years diagnosed with ALL between 2005 and 2019 were identified in the Danish National Acute Leukemia Registry. Each patient was matched with five comparators from the general population on birth year, sex, and Charlson Comorbidity Index. The Aalen-Johansen estimator was used to calculate the cumulative risk of DP for patients and comparators from index date (defined as 1 year after diagnosis) with competing events (transplantation or relapse, death, retirement pension, or early retirement pension). Differences in cumulative incidences were calculated using Gray's test. RTW was calculated as proportions one, three, and five years after the index date for patients holding a job before diagnosis. Results: A total of 154 patients with ALL and 770 matched comparators were included. The 5-year cumulative risk of DP was increased fivefold for patients with ALL compared with the general population. RTW was 41.7%, 65.7%, and 60.7% one, three, and five years after the index date, respectively. Conclusion: The risk of DP in patients with ALL increased significantly compared with the general population. Five years after the index date, RTW was 60.7% for patients with ALL.

Asunto(s)

Nitrilos , Mielofibrosis Primaria , Pirazoles , Pirimidinas , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Método Doble Ciego , Nitrilos/uso terapéutico , Mielofibrosis Primaria/tratamiento farmacológico , Pirazoles/uso terapéutico , Pirimidinas/uso terapéutico , Resultado del Tratamiento

RESUMEN

INTRODUCTION: Treatment of lymphoma can be associated with cognitive challenges, and some patients may fear development of dementia as long-term complication. Studies report a lower risk of dementia after cancer. Some believe this difference to be a protective mechanism of cancer, others believe it to be driven by bias. The risk of developing dementia after lymphoma has not been investigated in a population-based setting. The aim of this study was to identify the risk of being diagnosed with dementia after lymphoma treatment. MATERIALS AND METHODS: This Danish nationwide matched cohort study included patients aged ≥65 years with a first-time diagnosis of a non-central nervous system lymphoma between 2005 and 2018 in complete remission after treatment with chemotherapy. Patients diagnosed with dementia or treated with dementia medication before lymphoma diagnosis were excluded. Each patient was matched 1:5 on sex, year of birth, and a modified Charlson comorbidity index. Patients and matched comparators were followed from the corresponding patient's date of complete remission. The risk of developing dementia was calculated using cause-specific hazard ratios (HR), and the cumulative risk was estimated by Aalen-Johansen with death as the competing risk. RESULTS: A total of 3,244 patients and 16,220 matched comparators were included in the study. There was no difference in risk of all-cause dementia among patients with lymphoma compared to matched comparators with cause-specific HR of 0.85 (95% confidence interval [CI]: 0.70;1.04). The risk of both Alzheimer's disease and non-Alzheimer's dementia was equal among patients and comparators: HR 0.89 (95% CI: 0.66;1.21) and 0.82 (95% CI: 0.63;1.07), respectively. Stratified by lymphoma subtype, age, or year of diagnosis, the risk of all-cause dementia remained equal among patients and matched comparators. The cumulative risk of all-cause dementia was significantly lower among patients with lymphoma compared to matched comparators (Gray's test p < 0.001), probably reflecting higher mortality in patients with lymphoma. DISCUSSION: The risk of all-cause dementia, Alzheimer's disease, and non-Alzheimer's dementia was equal among older patients with lymphoma compared to matched comparators. Our data suggests that risk of developing dementia is not changed after lymphoma treatment.

Asunto(s)

Enfermedad de Alzheimer , Linfoma , Humanos , Estudios de Cohortes , Linfoma/epidemiología , Dinamarca/epidemiología

RESUMEN

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.

Asunto(s)

Protocolos de Quimioterapia Combinada Antineoplásica , Clorhidrato de Bendamustina , Densidad Ósea , Linfoma Folicular , Fracturas de la Columna Vertebral , Humanos , Persona de Mediana Edad , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Clorhidrato de Bendamustina/efectos adversos , Fracturas por Compresión/tratamiento farmacológico , Linfoma Folicular/tratamiento farmacológico , Prednisona/efectos adversos , Rituximab/efectos adversos , Fracturas de la Columna Vertebral/tratamiento farmacológico , Vincristina/efectos adversos

RESUMEN

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.

Asunto(s)

Enfermedades Cardiovasculares , Trasplante de Células Madre Hematopoyéticas , Linfoma , Humanos , Masculino , Resultado del Tratamiento , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Trasplante Autólogo , Trasplante de Células Madre , Dinamarca

RESUMEN

PURPOSE: CNS progression or relapse is an uncommon but devastating complication of aggressive B-cell lymphoma. There is no consensus regarding the optimal approach to CNS prophylaxis. This study was designed to determine whether high-dose methotrexate (HD-MTX) is effective at preventing CNS progression in patients at high risk of this complication. PATIENTS AND METHODS: Patients age 18-80 years with aggressive B-cell lymphoma and high risk of CNS progression, treated with curative-intent anti-CD20-based chemoimmunotherapy, were included in this international, retrospective, observational study. Cause-specific hazard ratios (HRs) and cumulative risks of CNS progression were calculated according to use of HD-MTX, with time to CNS progression calculated from diagnosis for all patients (all-pts) and from completion of frontline systemic lymphoma induction therapy, for patients in complete response at completion of chemoimmunotherapy (CR-pts). RESULTS: Two thousand four hundred eighteen all-pts (HD-MTX; n = 425) and 1,616 CR-pts (HD-MTX; n = 356) were included. CNS International Prognostic Index was 4-6 in 83.4% all-pts. Patients treated with HD-MTX had a lower risk of CNS progression (adjusted HR, 0.59 [95% CI, 0.38 to 0.90]; P = .014), but significance was not retained when confined to CR-pts (adjusted HR, 0.74 [95% CI, 0.42 to 1.30]; P = .29), with 5-year adjusted risk difference of 1.6% (95% CI, -1.5 to 4.4; all-pts) and 1.4% (95% CI, -1.5 to 4.1; CR-pts). Subgroups were underpowered to draw definitive conclusions regarding the efficacy of HD-MTX in individual high-risk clinical scenarios; however, there was no clear reduction in CNS progression risk with HD-MTX in any high-risk subgroup. CONCLUSION: In this large study, high-risk patients receiving HD-MTX had a 7.2% 2-year risk of CNS progression, consistent with the progression risk in previously reported high-risk cohorts. Use of HD-MTX was not associated with a clinically meaningful reduction in risk of CNS progression.

Asunto(s)

Neoplasias del Sistema Nervioso Central , Linfoma de Células B , Metotrexato , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Humanos , Persona de Mediana Edad , Adulto Joven , Neoplasias del Sistema Nervioso Central/tratamiento farmacológico , Neoplasias del Sistema Nervioso Central/patología , Neoplasias del Sistema Nervioso Central/prevención & control , Linfoma de Células B/tratamiento farmacológico , Metotrexato/administración & dosificación , Estudios Retrospectivos

RESUMEN

BACKGROUND: Second primary malignancies (SPMs) are known complications after chemotherapy, but the risk is not well characterised for patients with lymphoma treated with high-dose chemotherapy and autologous haematopoietic stem-cell transplantation (HSCT). We aimed to investigate the rate of SPMs in this population relative to matched control individuals from the general population. METHODS: In this retrospective, population-based cohort study, patients aged 18 years or older with an aggressive lymphoma who received high-dose chemotherapy and autologous HSCT in Denmark between Jan 1, 2001, and Dec 31, 2017, were included from the Danish Lymphoma Registry and matched (1:5) to control individuals from the general population on birth year and sex via the Danish Civil Registration System. Patients were eligible if they had a registered date of autologous HSCT and patients with primary CNS lymphoma were excluded. Exclusion criteria for both patients and matched control individuals were HIV infection, organ transplantation, or other malignancies before inclusion. The key endpoint was the incidence of SPMs assessed in all study participants. The effect of treatment on SPMs was also investigated in patients who were followed up from first lymphoma diagnosis, with high-dose chemotherapy and autologous HSCT as a time-dependent exposure. FINDINGS: Of 910 patients with lymphoma assessed, 803 were included (537 [67%] were male and 266 [33%] were female); 4015 matched control individuals were included (2685 [67%] were male and 1330 [33%] were female). Ethnicity data were not available. Median follow-up was 7·76 years (IQR 4·77-11·73). The SPM rate was higher among patients receiving high-dose chemotherapy and autologous HSCT than matched control individuals (adjusted hazard ratio [HR] 2·35, 95% CI 1·93-2·87, p<0·0001). Patients receiving high-dose chemotherapy and autologous HSCT had a higher rate of non-melanoma skin cancer (2·94, 2·10-4·11, p<0·0001) and of myelodysplastic syndrome or acute myeloid leukaemia (AML; 41·13, 15·77-107·30, p<0·0001) than matched control individuals, but there was no significant difference in the rate of solid tumours (1·21, 0·89-1·64, p=0·24). The cumulative risk of SPMs at 10 years was 20% (95% CI 17-23) in patients compared with 14% (13-15) in matched control individuals. High-dose chemotherapy and autologous HSCT was associated with an increased risk of SPMs when analysed as a time-dependent exposure from first lymphoma diagnosis (adjusted HR 1·58, 95% CI 1·14-2·17, p=0·0054). INTERPRETATION: High-dose chemotherapy and autologous HSCT was associated with an increased risk of non-melanoma skin cancer and myelodysplastic syndrome or AML but not with increased risk of solid tumours in patients treated for lymphoma. These findings are relevant for future individualised risk-benefit assessments when choosing between high-dose chemotherapy and autologous HSCT and chimeric antigen receptor T-cell therapy in this setting. FUNDING: Danish Cancer Society.

RESUMEN

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.

Asunto(s)

Linfoma no Hodgkin , Niño , Humanos , Masculino , Femenino , Suecia/epidemiología , Estudios de Cohortes , Linfoma no Hodgkin/tratamiento farmacológico , Sobrevivientes , Reproducción , Dinamarca/epidemiología

RESUMEN

Time to progression of disease (POD) after first-line (1L) therapy is prognostic in mantle cell lymphoma (MCL), although studies have included a broad range of 1L, second-line (2L), and subsequent lines of therapy. The purpose of this study was to evaluate the factors predicting outcomes in patients with relapsed/refractory (R/R) MCL exclusively initiating 2L Bruton's tyrosine kinase inhibitors (BTKis) after 1L rituximab-containing therapy. Patients were accrued from 8 international centers (7 main, 1 validation cohort). Multivariable models evaluating the association between time to POD and clinical/pathologic factors were constructed and converted into nomograms and prognostic indexes predicting outcomes in this population. A total of 360 patients were included, including 160 in the main cohort and 200 in the validation cohort. Time to POD, Ki67 ≥ 30%, and MCL International Prognostic Index (MIPI) were associated with progression-free survival (PFS2) and overall survival (OS2) from the start of 2L BTKis. C-indexes were consistently ≥0.68 in both cohorts. Web/application-based calculators based on nomograms and prognostic indexes to estimate PFS2 and OS2 were constructed. The 2L BTKi MIPI identifies 3 groups with distinct 2-year PFS2, including high risk (14%), intermediate risk (50%), and low risk (64%). Time to POD, Ki67, and MIPI are associated with survival outcomes in patients with R/R MCL receiving 2L BTKis. Simple clinical models incorporating these variables may assist in planning for alternative therapies such as chimeric antigen receptor T-cell therapy, allogeneic stem cell transplantation, or novel agents with alternative mechanisms of action.

Asunto(s)

Trasplante de Células Madre Hematopoyéticas , Linfoma de Células del Manto , Adulto , Humanos , Linfoma de Células del Manto/patología , Antígeno Ki-67 , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Pronóstico

RESUMEN

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.

Asunto(s)

Enfermedad de Hodgkin , Femenino , Niño , Humanos , Masculino , Enfermedad de Hodgkin/tratamiento farmacológico , Enfermedad de Hodgkin/epidemiología , Doxorrubicina/uso terapéutico , Bleomicina/efectos adversos , Suecia/epidemiología , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Estudios de Cohortes , Vinblastina/uso terapéutico , Dacarbazina , Vincristina/uso terapéutico , Ciclofosfamida/uso terapéutico , Etopósido , Reproducción , Prednisona/uso terapéutico , Dinamarca

RESUMEN

Purpose: Many patients diagnosed with lymphoma are of working age. Cancer patients are known to have a higher risk of sick leave and disability pension, but this has only been delineated for certain subtypes of lymphoma. Therefore, this study aimed at investigating the overall risk of disability pension for all lymphoma subtypes and at quantifying return to work for patients with lymphoma in work before diagnosis. Patients and Methods: Patients aged 18-60 years with lymphoma in complete remission (CR) diagnosed between 2000 and 2019 were included in the study. Using national registers, each patient was matched with five comparators from the general population with same sex, birth year, and level of Charlson Comorbidity Index. Risk of disability pension was calculated from 90 days after CR or end of treatment with competing events (death, retirement pension, early retirement pension, relapse for patients, or lymphoma diagnosis for comparators). Return to work for patients was calculated annually until 5 years after diagnosis for patients employed before diagnosis. Results: In total, 4072 patients and 20,360 comparators were included. There was a significant increased risk of disability pension for patients with all types of lymphoma compared to the general population (5-year risk difference: 5.3 (95% confidence interval (CI): 4.4;6.2)). Patients with non-Hodgkin lymphoma were more likely to get disability pension than patients with Hodgkin lymphoma (sex- and age-adjusted 10-year risk difference: 2.9 (95% CI: 0.3;5.5)). One year after diagnosis, 24.5% of the relapse-free patients were on sick leave. Return to work was highest 2 years after diagnosis (82.1%). Conclusion: Patients with lymphoma across all subtypes have a significantly higher risk of disability pension. Return to work peaks at 2 years after diagnosis.

RESUMEN

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.

Asunto(s)

Leucemia Linfocítica Crónica de Células B , Linfoma Folicular , Adulto , Humanos , Femenino , Masculino , Adolescente , Adulto Joven , Persona de Mediana Edad , Anciano , Anciano de 80 o más Años , Incidencia , Estudios de Cohortes , Caracteres Sexuales

RESUMEN

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.

Asunto(s)

Neoplasias del Sistema Nervioso Central , Linfoma de Células B Grandes Difuso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias del Sistema Nervioso Central/tratamiento farmacológico , Neoplasias del Sistema Nervioso Central/patología , Neoplasias del Sistema Nervioso Central/prevención & control , Humanos , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Linfoma de Células B Grandes Difuso/patología , Metotrexato/uso terapéutico , Recurrencia Local de Neoplasia/patología

RESUMEN

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.

Asunto(s)

Trasplante de Células Madre Hematopoyéticas , Linfoma de Células B Grandes Difuso , Linfoma no Hodgkin , Receptores Quiméricos de Antígenos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Humanos , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Linfoma no Hodgkin/tratamiento farmacológico , Receptores Quiméricos de Antígenos/uso terapéutico , Recurrencia , Trasplante Autólogo

RESUMEN

Remarkable improvements in outcomes for many haematological malignancies have been driven primarily by a proliferation of novel therapeutics over the past two decades. Targeted agents, immune and cellular therapies, and combination regimens have adverse event profiles distinct from conventional finite cytotoxic chemotherapies. In 2018, a Commission comprising patient advocates, clinicians, clinical investigators, regulators, biostatisticians, and pharmacists representing a broad range of academic and clinical cancer expertise examined issues of adverse event evaluation in the context of both newer and existing therapies for haematological cancers. The Commission proposed immediate actions and long-term solutions in the current processes in adverse event assessment, patient-reported outcomes in haematological malignancies, toxicities in cellular therapies, long-term toxicity and survivorship in haematological malignancies, issues in regulatory approval from an international perspective, and toxicity reporting in haematological malignancies and the real-world setting. In this follow-up report, the Commission describes progress that has been made in these areas since the initial report.

Asunto(s)

Antineoplásicos , Neoplasias Hematológicas , Neoplasias , Neoplasias Hematológicas/complicaciones , Neoplasias Hematológicas/tratamiento farmacológico , Humanos

Asunto(s)

Trasplante de Células Madre Hematopoyéticas , Linfoma , Hematopoyesis Clonal , Humanos , Linfocitos T , Trasplante Autólogo

RESUMEN

PURPOSE: Rituximab with cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP) represents the standard of care for first-line treatment of diffuse large B-cell lymphoma (DLBCL). However, many patients are unable to tolerate R-CHOP and have inferior outcomes. This study aimed to develop a practical tool to help physicians identify patients with newly diagnosed DLBCL unlikely to tolerate a full course of R-CHOP. METHODS: We developed a predictive model (Tolerability of R-CHOP in Aggressive Lymphoma [TRAIL]) on the basis of a training data set from the phase III GOYA trial (obinutuzumab with CHOP v R-CHOP in 1L DLBCL) using a composite binary end point, identifying patients who prematurely stopped or required reductions of R-CHOP. Candidate predictive variables were selected on the basis of known baseline characteristics that contribute to patient frailty, comorbidity, and/or chemotherapy toxicity. TRAIL was developed using an iterative trial-and-error modeling process to fit a logistic regression model. The final model was evaluated for robustness using a GOYA holdout data set and the phase III MAIN (R-CHOP with or without bevacizumab in 1L DLBCL) R-CHOP-21 data set as external validation. RESULTS: TRAIL includes four simple predictors available in the routine clinical setting: Charlson Comorbidity Index, presence of cardiovascular disease or diabetes, serum albumin, and creatinine clearance. Model generalization performance estimated by the area under the curve was around or above 0.70 across GOYA training, GOYA holdout, and MAIN data sets. Classifying patients into low-, intermediate- and high-risk categories, the proportion of patients experiencing a tolerability event was 3.3%, 12.4%, and 32.9%, respectively, in GOYA holdout, and 9.7%, 9.7%, and 34.2%, respectively, in MAIN. CONCLUSION: TRAIL may be useful as a clinical decision support tool for treatment decisions in patients with DLBCL who may not tolerate standard chemoimmunotherapies.

Asunto(s)

Protocolos de Quimioterapia Combinada Antineoplásica , Linfoma de Células B Grandes Difuso , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Ensayos Clínicos Fase III como Asunto , Ciclofosfamida/uso terapéutico , Doxorrubicina/uso terapéutico , Humanos , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Prednisona/uso terapéutico , Rituximab/uso terapéutico , Vincristina/uso terapéutico