Aims/hypothesis
The aim of this study was to examine the prospective associations between objectively measured physical activity energy expenditure (PAEE), sedentary time, ...moderate-to-vigorous-intensity physical activity (MVPA), cardiorespiratory fitness (CRF) and cardiometabolic risk factors over 4 years in individuals with recently diagnosed diabetes.
Methods
Among 308 adults (mean age 61.0 SD 7.2 years; 34% female) with type 2 diabetes from the Anglo–Danish–Dutch Study of Intensive Treatment in People with Screen Detected Diabetes in Primary Care (ADDITION)-Plus study, we measured physical activity using individually calibrated combined heart rate and movement sensing. Multivariable linear regression models were constructed to examine the associations between baseline PAEE, sedentary time, MVPA, CRF and cardiometabolic risk factors and clustered cardiometabolic risk (CCMR) at follow-up, and change in these exposures and change in CCMR and its components over 4 years of follow-up.
Results
Individuals who increased their PAEE between baseline and follow-up had a greater reduction in waist circumference (−2.84 cm, 95% CI −4.84, −0.85) and CCMR (−0.17, 95% CI −0.29, −0.04) compared with those who decreased their PAEE. Compared with individuals who decreased their sedentary time, those who increased their sedentary time had a greater increase in waist circumference (3.20 cm, 95% CI 0.84, 5.56). Increases in MVPA were associated with reductions in systolic blood pressure (−6.30 mmHg, 95% CI −11.58, −1.03), while increases in CRF were associated with reductions in CCMR (−0.23, 95% CI −0.40,−0.05) and waist circumference (−3.79 cm, 95% CI −6.62, −0.96). Baseline measures were generally not predictive of cardiometabolic risk at follow-up.
Conclusions/interpretation
Encouraging people with recently diagnosed diabetes to increase their physical activity and decrease their sedentary time may have beneficial effects on their waist circumference, blood pressure and CCMR.
To investigate whether bioelectrical impedance analysis could be used to identify overweight individuals at increased cardiometabolic risk, defined as the presence of metabolic syndrome and/or ...diabetes.
Cross-sectional study of a Scottish population including 1210 women and 788 men. The diagnostic performance of thresholds of percentage body fat measured by bioelectrical impedance analysis to identify people at increased cardiometabolic risk was assessed using receiver-operating characteristic curves. Odds ratios for increased cardiometabolic risk in body mass index categories associated with values above compared to below sex-specific percentage body fat thresholds with optimal diagnostic performance were calculated using multivariable logistic regression analyses. The validity of bioelectrical impedance analysis to measure percentage body fat in this population was tested by examining agreement between bioelectrical impedance analysis and dual-energy X-ray absorptiometry in a subgroup of individuals.
Participants were aged 16-91 years and the optimal bioelectrical impedance analysis cut-points for percentage body fat for identifying people at increased cardiometabolic risk were 25.9% for men and 37.1% for women. Stratifying by these percentage body fat cut-points, the prevalence of increased cardiometabolic risk was 48% and 38% above the threshold and 24% and 19% below these thresholds for men and women, respectively. By comparison, stratifying by percentage body fat category had little impact on identifying increased cardiometabolic risk in normal weight and obese individuals. Fully adjusted odds ratios of being at increased cardiometabolic risk among overweight people with percentage body fat ≥ 25.9/37.1% compared with percentage body fat <25.9/37.1% as a reference were 1.93 (95% confidence interval: 1.20-3.10) for men and 1.79 (1.10-2.92) for women.
Percentage body fat measured using bioelectrical impedance analysis above a sex-specific threshold could be used in overweight people to identify individuals at increased cardiometabolic risk, who could benefit from risk factor management.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
ObjectiveTo examine mortality and morbidity patterns before and after premalignancy diagnosis in individuals with monoclonal gammopathy of undetermined significance (MGUS) and monoclonal B-cell ...lymphocytosis (MBL) and compare their secondary healthcare activity to that of the general population.DesignPopulation-based patient cohort, within which each patient is matched at diagnosis to 10 age-matched and sex-matched individuals from the general population. Both cohorts are linked to nationwide information on deaths, cancer registrations and Hospital Episode Statistics.SettingThe UK’s Haematological Malignancy Research Network, which has a catchment population of around 4 million served by 14 hospitals and a central diagnostic laboratory.ParticipantsAll patients newly diagnosed during 2009–2015 with MGUS (n=2193) or MBL (n=561) and their age and sex-matched comparators (n=27 538).Main outcome measuresMortality and hospital inpatient and outpatient activity in the 5 years before and 3 years after diagnosis.ResultsIndividuals with MGUS experienced excess morbidity in the 5 years before diagnosis and excess mortality and morbidity in the 3 years after diagnosis. Increased rate ratios (RRs) were evident for nearly all clinical specialties, the largest, both before and after diagnosis, being for nephrology (before RR=4.29, 95% CI 3.90 to 4.71; after RR=13.8, 95% CI 12.8 to 15.0) and rheumatology (before RR=3.40, 95% CI 3.18 to 3.63; after RR=5.44, 95% CI 5.08 to 5.83). Strong effects were also evident for endocrinology, neurology, dermatology and respiratory medicine. Conversely, only marginal increases in mortality and morbidity were evident for MBL.ConclusionsMGUS and MBL are generally considered to be relatively benign, since most individuals with monoclonal immunoglobulins never develop a B-cell malignancy or any other monoclonal protein-related organ/tissue-related disorder. Nonetheless, our findings offer strong support for the view that in some individuals, monoclonal gammopathy has the potential to cause systemic disease resulting in wide-ranging organ/tissue damage and excess mortality.
Hodgkin lymphoma is usually detected in primary care with early signs and symptoms, and is highly treatable with standardised chemotherapy. However, late presentation is associated with poorer ...outcomes.
To investigate the relationship between markers of advanced disease, emergency admission, and survival following a diagnosis of classical Hodgkin lymphoma (CHL).
The study was set within a sociodemographically representative UK population-based patient cohort of ~4 million, within which all patients were tracked through their care pathways, and linked to national data obtained from Hospital Episode Statistics (HES) and deaths.
All 971 patients with CHL newly diagnosed between 1 September 2004-31 August 2015 were followed until 18th December 2018.
The median diagnostic age was 41.5 years (range 0-96 years), 55.2% of the patients were male, 31.2% had stage IV disease, 43.0% had a moderate-high or high risk prognostic score, and 18.7% were admitted via the emergency route prior to diagnosis. The relationship between age and emergency admission was U-shaped: more likely in patients aged <25 years and ≥70 years. Compared to patients admitted via other routes, those presenting as an emergency had more advanced disease and poorer 3-year survival (relative survival 68.4% 95% confidence interval {CI} = 60.3 to 75.2 versus 89.8% 95% CI = 87.0 to 92.0, respectively
<0.01). However, after adjusting for clinically important prognostic factors, no difference in survival remained.
These findings suggest that CHL survival as a whole could be increased by around 4% if the cancer in patients who presented as an emergency had been detected at the same point as in other patients.
Associations between previous joint replacement and B‐cell lymphoid malignancies have been reported, but despite numerous reports, associations with the disease subtypes have received little ...attention. Using a UK‐based register of haematological malignancies and a matched general population‐based cohort, joint replacements from linked hospital inpatient records were examined. Cases diagnosed 2009–2015 who were aged 50 years or more were included; 8,013 mature B‐cell neoplasms comprising myeloma (n = 1,763), diffuse large B‐cell lymphoma (DLBCL, n = 1,676), chronic lymphocytic leukaemia (CLL, n = 1,594), marginal zone lymphoma (MZL, n = 957), follicular lymphoma (FL, n = 725) and classical Hodgkin lymphoma (CHL, n = 255), together with monoclonal gammopathy of uncertain significance (MGUS, n = 2,138) and monoclonal B‐cell lymphocytosis (MBL, n = 632). Odds ratios (OR) and 95% confidence intervals (95%CI) were calculated relative to 10 age‐ and sex‐matched controls using conditional logistic regression. Having had a joint replacement before diagnosis was associated with myeloma (OR = 1.3, 95% CI 1.1–1.5, p = 0.008) and MGUS (OR = 1.3, 95% CI 1.1–1.5, p < 0.001). Excluding replacements in the year before diagnosis, the MGUS risk remained, elevated where two or more joints were replaced (OR = 1.5, 95% CI 1.2–2.0, p = 0.001), with hip (OR = 1.2, 95% CI 1.0–1.5, p = 0.06) or knee replacements (OR = 1.5, 95% CI 1.2–1.8, p < 0.001). Associations with CHL and two or more replacements (OR = 2.7, 95% CI 1.3–5.6, p = 0.005) or hip replacements (OR = 1.9, 95% CI 1.0–3.4, p = 0.04); and between DLBCL and knee replacements (OR = 1.3, 95% CI 1.0–1.6, p = 0.04) were also observed. Our study reports for the first time a relationship between joint replacements and MGUS; while absolute risks of disease are low and not of major public health concern, these findings warrant further investigation.
What's new?
While lymphoid malignancies are increased in persons with previous joint replacements, data on associations with particular diagnostic subtypes is lacking. Here, the authors investigated the relationship between joint replacement and mature B‐cell neoplasms and their precursor conditions in an established cohort of patients with hematological malignancies linked to national healthcare records. Previous joint replacement was associated with subsequent elevated risk of myeloma, monoclonal gammopathy of uncertain significance, and Hodgkin lymphoma subtypes of hematological disease. While the findings indicate that absolute risks are low, joint replacement procedures are increasing and disentangling the underlying reasons behind these associations warrants further investigation.
Population-based information on cancer incidence and outcome are required to inform clinical practice and research; but contemporary data are lacking for many lymphoid cancer subtypes.
Set within a ...socio-demographically representative UK population of ∼4 million, data are from an established UK patient cohort (N = 22,414 diagnoses). Information on incidence (crude and age-standardised) and survival (overall and net) is presented for > 40 subtypes.
The median diagnostic age was 69.9 years (interquartile range 59.1–78.3), but unlike many other cancers, lymphoid malignancies can be diagnosed at any age; different subtypes dominating at different ages. Males were more likely to be diagnosed than females (age-standardised sex rate ratio: 1.55 (95% Confidence Interval: 1.50,1.59)), and most subtypes had a male predominance, some more than three-fold (e.g. Burkitt lymphoma 3.26 (2.42, 4.40)). Five-year net survival estimates varied hugely, ranging from 97.4% (95% CI: 56.5, 99.9) in patients with hairy cell leukaemia to 31.6% (95% CI: 2.5, 69.8) in those with T-cell prolymphocytic leukaemia. No significant sex difference in survival were observed for the majority of diagnoses; one exception being classical Hodgkin lymphoma, where males had a higher mortality (Excess Mortality Ratio: 1.44 (95% CI: 1.11, 1.87)). An improvement in survival over time was observed for some, but not all, of the major diagnostic groups.
Marked incidence and survival variations by subtype, sex and age confirm the heterogeneity of lymphoid neoplasms and highlight the importance of accurately characterising disease entities. Despite recent improvements, routine cancer registration of lymphoid neoplasms remains challenging and new issues continue to emerge; including the lack of an international consensus on classification and the recording of progressions and transformations. Furthermore, the increasing need for additional molecular and genomic information required for accurate classification is likely to impact negatively on the quality of cancer registration data, especially in low income countries.
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•Distinct patterns by age at diagnosis were seen across lymphoid malignancy subtypes.•Incidence was higher in males; although the reasons for this are unknown.•Survival varied by subtype with some patients having a near normal life expectancy.•For most diagnostic groups there was no difference in survival by sex.•Improvement in survival over time was seen for some of the major diagnostic groups.
Introduction
Since the advent of chemo-immunotherapy, diffuse large B-cell lymphoma (DLBCL) is one of the few haematological malignancies that is considered potentially curable, with the ...life-expectancy of patients who respond to therapy returning to background general population levels. Few studies have, however, examined the veracity of this assumption. With centralised diagnostics and a unified clinical network covering a catchment population of 4 million people, the UK's Haematological Malignancy Research Network (HMRN) was specifically established to provide timely real-world data to answer such questions; and findings from this unique population-based cohort are reported here.
Methods
Demographic, prognostic, treatment and outcome data were examined for all patients (18+ years) newly diagnosed 2004-15 with de novo DLBCL (n= 2,893, excluding those with primary CNS DLBCL). Two approaches were used to examine whether the long-term mortality of patients who responded to first-line therapy varied from that of the general population:Relative Survival (RS, which adjusts for the age and sex specific mortality in the general population) was estimated using UK life tables to measure disease-specific survival.For all patients diagnosed 2009-15 (cases, n=1,875), 10 people without DLBCL from the HMRN catchment population, matched on sex and year of birth, were selected (controls, n=18,750). Overall survival (OS) was estimated using standard statistical methods for both cases and controls. For controls the date of diagnosis of their matched case was used.
Mortality data (date and cause of death) for cases and controls were obtained from the Office for National Statistics - subjects were followed-up until June 2018 (median 6.8 years: range 2.8-13.7 years).
Results
Median age at diagnosis was 70.3 years, 68% of patients had an ECOG score of 0/1, 48% were diagnosed with stage IV disease and 28% had high risk disease as defined by the International Prognostic Index (IPI). The majority of patients were treated with intensive chemotherapy (n=2,355), predominantly R-CHOP (n=2,116); the remaining patients received non-intensive chemotherapy (2.2%), radiotherapy only (2%), or were managed with a supportive/palliative strategy (13.3%). As expected, those not treated curatively were, on average, older with a poorer performance status compared to those treated intensively (median age 80 years vs. 68 years, ECOG 0/1: 20% vs. 78% respectively).
For the 1,919/2,355 intensively treated patients who had either a complete or partial response their corresponding 1, 5, 10-year RS estimates from the time of diagnosis were 96%, 86% and 82% respectively (Figure A - purple marker). By contrast, the 1-year RS was 17% for those who did not achieve a response, either due to refractory disease or as a consequence of discontinuing first-line treatment (for any reason). The analyses were repeated to estimate RS for patients surviving 2-years (n=1,622) and 5-years (n=1,088) - ‘conditional survival’. The corresponding 10-year RS estimates were 91% and 95% respectively.
Figures B-D show the Kaplan-Meier plots for cases diagnosed 2009-15 who achieved a response following intensive chemotherapy (n=1,254), as well as that of their corresponding age-sex matched controls (n= 12,540); 5-year OS was 75% and 88% respectively. The gap in 5-year OS between cases and controls narrowed when the analyses were repeated for cases and controls who survived 1 year after diagnosis: 79% (n=1,172) and 86% (n=12,218). The corresponding 2-year conditional survival estimates were closer still at 87% (n=1,006) and 89% (n=11,122) respectively.
Conclusion
In contrast to the small proportion of patients who did not respond to first-line therapy, the long term outlook for patients who responded to therapy were largely good, and any deaths that occurred were generally not attributable to lymphoma. Furthermore, encouragingly for patients who survived for at least 2 years after diagnosis, mortality almost returned to the background rate seen in the general population. These findings demonstrate that most patients diagnosed with DLBCL who are fit enough for treatment will be cured of their disease, regardless of their age at diagnosis.
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Patmore:Gilead Sciences: Consultancy; Roche: Consultancy. Smith:Johnson & Johnson: Research Funding; Jazz Pharmaceuticals: Research Funding; Novartis: Research Funding; Gilead Sciences: Consultancy. Burton:NHS: Employment; Takeda: Honoraria; Roche: Honoraria; Takeda: Consultancy; Roche: Consultancy; Bristol-Myers Squibb: Consultancy.
Introduction
Anaplastic large-cell lymphoma (ALCL) is a rare subtype of T-cell non-Hodgkin lymphoma, characterized by uniformly strong CD30 expression and further delineated by expression of the Alk ...protein.
Standard first-line (1L) therapy is CHOP-based chemotherapy, with or without consolidative autologous stem cell transplant (ASCT) (Schmitz, Blood, 2010). Despite intensive chemotherapy approaches, 40-65% of patients experience relapsed/refractory disease, for which brentuximab vedotin (BV) as monotherapy has established efficacy (Pro, Blood, 2017)
Recent results from ECHELON-2 (E2), led to FDA approval of BV in combination with CHP (CHP+A) as first-line treatment for CD30+ PTCL, based on a 34% reduction in risk of death compared to CHOP, an effect only demonstrable in ALCL (70% of the E2 cohort) (Horwitz, Lancet, 2019). Given this renewed treatment landscape, we investigated outcomes of unselected patients with ALCL treated in routine clinical practice.
Methods/Study Population
Consecutively diagnosed patients with systemic ALCL from 6 UK and Australian centres (n=166) were studied (Dec 2004-Dec 2018). Patients ≥16 years with ALCL were included irrespective of Alk status. Treatment allocation was clinician choice and included best supportive care (BSC). Post-mortem diagnosis and 10 patients treated on E2 were excluded. Principal outcomes were PFS and OS following 1L treatment. Additional outcome measures included frequency of ASCT and use of BV for r/r ALCL. Data were retrospectively collected following GDPR guidelines and in accordance with the declaration of Helsinki.
Results
Median age at diagnosis was 57.5 years (range 16-93), 62% were male, 19% had ECOG ≥3 and 53 (35%) patients were ALK positive. Median lines of therapy was 1 (range 0-6). Baseline patient characteristics are shown in table 1.
The most frequent 1L treatment regimen was CHOP in 104 pts (67%), 26 (18%) received intensified regimens (CHOEP, CHOP/IVE/MTX, CODOX-M, ALCL99), 4 received other regimens (2.6%) and 14 had best supportive care (9%). Treatment-related mortality was 5.6% (8/142). 12 (8%) patients underwent ASCT in first response, of whom 10 had received intensified induction regimens.
Of 141 evaluable pts, ORR was 71% and CR rate was 52%. Median follow up of all patients was 40 months, 3-year PFS and OS for 1L of treatment were 46% and 58% respectively. For the CHOP-treated cohort (n=104), 3-year PFS and OS were 47% and 57%. Outcomes for ALK-negative patients treated with CHOP (n=78) were inferior to ALK-positive; 3-year PFS, OS of 35% and 44% vs 66% and 82% respectively (p=0.003 for both, figure 1).
BV was given to 24 pts (15%), mostly for second (16/24) line of therapy. Median doses received were 5 (range 1-14). ORR to BV was 11/24 (45%) and CR rate was 7/24 (30%). Median follow up after BV was 18 months, at which point the PFS and OS rates were 33% and 35% respectively (Figure 1). Bridging to ASCT or alloSCT occurred in 3 and 4 pts respectively, of whom 6 remain alive at data cutoff.
41 patients were staged with both CT and PET-CT, with concordant staging in 63%. 9/41 patients were upstaged by PET, 3 of which resulted in upgraded IPI score (extranodal sites not found on CT). 52 patients had PET-CT after first-line therapy. At data cutoff, 26/35 patients did not progress after PET-defined CR (74%), whereas 6/12 patients progressed after PET-defined PR (50%).
Conclusions
This study describes a large unselected cohort of ALCL treated in routine clinical practice prior to publication of the E2 study, observing a comparable baseline Alk pos/neg distribution. Notably, survival outcomes of our CHOP-treated cohort are similar to those in the E2 control arm, notwithstanding 28% of our patients with ECOG ≥3 (an E2 exclusion criterion) and also comparable to data from the prospective international T-cell lymphoma project (Shustov, Haematol Oncol, 2019). A minority of pts received intensified regimens and only 8% underwent ASCT consolidation. Achievement of CMR by PET-CT was still associated with a significant proportion of relapses. Outcomes of r/r ALCL treated with single-agent BV were inferior in our cohort as compared to the pivotal Phase 2 data (Pro, Blood, 2017). Our data represent an important benchmark as an unselected ALCL population treated with conventional chemotherapy in routine clinical practice; future studies of CHP+A in the real-world setting will be crucial in assessing the wider impact of the E2 study.
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Martinez-Calle:ABBVIE: Other: Travel support. Manos:Janssen: Honoraria; Novo Nordisk Pharmaceuticals: Other: Travel. Bishton:Takeda: Other: Travel support, Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees; Celgene: Research Funding; AbbVie: Research Funding; Celltrion: Membership on an entity's Board of Directors or advisory committees, Other: travel support; Roche: Other: Travel support, Research Funding. Hawkes:Bristol-Myers Squibb: Research Funding, Speakers Bureau; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Mundi pharma: Research Funding; Merck Sharp & Dohme: Membership on an entity's Board of Directors or advisory committees; Roche/Genentech: Membership on an entity's Board of Directors or advisory committees, Other: Travel expenses, Speakers Bureau; Roche: Research Funding; Astra Zeneca: Research Funding; Merck KgA: Research Funding; Janssen-Cilag: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Gilead: Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Speakers Bureau. Osborne:Gilead: Consultancy; Pfizer: Honoraria, Speakers Bureau; Takeda: Consultancy, Honoraria, Other: Travel, Speakers Bureau; Novartis: Other: Travel; Servier: Consultancy; MSD: Consultancy; Roche: Consultancy, Honoraria, Other: Travel, Speakers Bureau. Collins:Gilead: Consultancy, Honoraria. Burton:Celgene: Membership on an entity's Board of Directors or advisory committees; Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees; Bristol-Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees. Fox:AbbVie: Consultancy; Gilead: Consultancy; Janssen: Consultancy; Celgene: Consultancy; Sunesis: Consultancy; Takeda Pharmaceuticals: Consultancy; Atara Biotherapeutics: Consultancy; Adienne: Other: Travel Support.
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