Prevalence of co-morbidity and its relationship to treatment among unselected patients with Hodgkin's disease and non Hodgkin's lymphoma, 1993-l996

A population-based series of patients with cancer is likely to comprise more patients with serious co-morbidity than clinical trials because of restrictive eligibility criteria for the latter. Since co-morbidity may influence decision-making, we studied the age-specific prevalence of co-morbidity and its relationship to applied treatment. Data on all 194 patients with Hodgkin's disease (HD) and on 904 patients with non-Hodgkin's lymphoma (NHL) diagnosed between 1993 and 1996 were derived from the Eindhoven Cancer Registry. In the age-group below 60 years, 87% of patients with HD and 80% with NHL did not have a co-morbid condition. The prevalence of serious co-morbidity was 56% for patients with Hodgkin's disease who were 60 years and over and 43% and 61% for non Hodgkin patients who were 60-69 years and 70 years and over, respectively. The most common co-morbid conditions were cardiovascular disease (18%), hypertension (13%), chronic obstructive pulmonary disease (COPD; 13%), and diabetes mellitus (10%) for elderly Hodg kin's patients. For non-Hodgkin's patients of 60-69 years and 70 years and over, cardiovascular disease (15 and 22%, respectively), hypertension (14 and 14%, respectively), COPD (6 and 10% respectively), and diabetes mellitus (8 and 10% respectively) were the most prevalent co-morbid conditions. The presence of co-morbidity was not related to stage or grade of disease at diagnosis. In the presence of co-morbidity, 50% less chemotherapy was administered to elderly patients with Hodgkin's disease and 10-15% less to elderly patients with non-Hodgkin's lymphoma. The presence of co-morbidity was associated with a decreased overall survival within the first 4 months after diagnosis in both Hodgkin's disease and non-Hodgkin's lymphoma for all age-groups. In conclusion, serious co-morbidity was found for more than half of all lymphoma patients who were 60 years and older. Elderly patients with serious co-morbidity received chemotherapy less often, which is likely to affect survival adversely, as was indicated by a decreased survival within the first 4 months after diagnosis

Small but significant excess mortality compared with the general population for long-term survivors of breast cancer in the Netherlands

Background: Coinciding with the relatively good and improving prognosis for patients with stage I-III breast cancer, late recurrences, new primary tumours and late side-effects of treatment may occur. We gained insight into prognosis for long-term breast cancer survivors. Patients and methods: Data on all 205 827 females aged 15-89 diagnosed with stage I-III breast cancer during 1989-2008 were derived from the Netherlands Cancer Registry. Conditional 5-year relative survival was calculated for every subsequent year from diagnosis up to 15 years. Results: For stage I, conditional 5-year relative survival remained ~95% up to 15 years after diagnosis (a stable 5-year excess mortality rate of 5%). For stage II, excess mortality remained 10% for those aged 15-44 or 45-59 and 15% for those aged 60-74. For stage III, excess mortality decreased from 35% at diagnosis to 10% at 15 years for those aged 15-44 or 45-59, and from ~40% to 30% for those aged ≥60. Conclusions: Patients with stage I or II breast cancer had a (very) good long-term prognosis, albeit exhibiting a small but significant excess mortality at least up to 15 years after diagnosis

Long-Term Cause-Specific Mortality in Hodgkin Lymphoma Patients

BACKGROUND: Few studies have examined the impact of treatment-related morbidity on long-term, cause-specific mortality in Hodgkin lymphoma (HL) patients. METHODS: This multicenter cohort included 4919 HL patients, treated before age 51 years between 1965 and 2000, with a median follow-up of 20.2 years. Standardized mortality ratios, absolute excess mortality (AEM) per 10 000 person-years, and cause-specific cumulative mortality by stage and primary treatment, accounting for competing risks, were calculated. RESULTS: HL patients experienced a 5.1-fold (AEM = 123 excess deaths per 10 000 person-years) higher risk of death due to causes other than HL. This risk remained increased in 40-year survivors (standardized mortality ratio = 5.2, 95% confidence interval [CI] = 4.2 to 6.5, AEM = 619). At age 54 years, HL survivors experienced similar cumulative mortality (20.0%) from causes other than HL to 71-year-old individuals from the general population. Whereas HL mortality statistically significantly decreased over the calendar period (P < .001), solid tumor mortality did not change in the most recent treatment era. Patients treated in 1989-2000 had lower 25-year cardiovascular disease mortality than patients treated in 1965-1976 (4.3% vs 5.7%; subdistribution hazard ratio = 0.65, 95% CI = 0.46 to 0.93). Infectious disease mortality was not only increased after splenectomy but also after spleen irradiation (hazard ratio = 2.81, 95% CI = 1.55 to 5.07). For stage I-II, primary treatment with chemotherapy (CT) alone was associated with statistically significantly higher HL mortality (P < .001 for CT vs radiotherapy [RT]; P = .04 for CT vs RT+CT) but lower 30-year mortality from causes other than HL (15.8%, 95% CI = 9.7% to 23.3%) compared with RT alone (36.9%, 95% CI = 34.0% to 39.8%, P = .001) and RT and CT combined (29.8%, 95% CI = 26.8% to 32.9%, P = .02). CONCLUSIONS: Compared with the general population, HL survivors have a substantially reduced life expectancy. Optimal selection of patients for primary CT is crucial, weighing risks of HL relapse and long-term toxicity

Prognostic factors, survival and late mortality of patients with hodgkin's lymphoma

This thesis presents prognostic factors, survival and late mortality of patients with Hodgkin's lymphoma diagnosed in South-East Netherlands. Chapter 1 consists of an overview of epidemiology, pathogenesis, clinical presentation, management and its complications of Hodgkin's lymphoma (HL). ... Zie: Summary

Validation, revision and extension of the Mantle Cell Lymphoma International Prognostic Index in a population-based setting

Background The aim of this study was to validate the Mantle Cell Lymphoma International Prognostic Index in a population-based cohort and to study the relevance of its revisions. Design and Methods We analyzed data from 178 unselected patients with stage III or IV mantle cell lymphoma, registered between 1994 and 2006 in the Eindhoven Cancer Registry. Follow-up was completed up to January 1st, 2008. Multiple imputations for missing

Actual prognosis during follow-up of survivors of B-cell non-Hodgkin lymphoma in the Netherlands

Survival rates determined at diagnosis are often too negative for cancer survivors. Conditional relative survival reflects actual prognosis during follow-up better. Data from all 54,015 patients newly diagnosed in the Netherlands with B-cell non-Hodgkin lymphoma during 1989-2008, aged 15-89 years (Netherlands Cancer Registry), were used. Five-year conditional relative survival was computed for every additional year of survival up to 16 years after diagnosis, according to entity, grade, gender, age, and Ann Arbor stage. The prognosis for survivors of indolent B-cell non-Hodgkin lymphoma improved slightly with each additional year survived up to 91%. For patients with aggressive non-Hodgkin lymphoma conditional relative survival improved strongly during the first year after diagnosis (from 48% to 68%) and gradually thereafter to 93% after 16 years. There were differences between morphological entities. Initial differences in conditional relative survival at diagnosis between groups with different disease stages became smaller with increasing number of years survived. Age remained a prognostic indicator, also after prolonged follow-up. These results help caregivers to plan optimal surveillance and inform patients about their actual prognosis during follow-up. Long-lasting excess mortality among patients with B-cell non-Hodgkin lymphoma indicates the need for additional care long after their diagnosis

Validation, revision and extension of the follicular lymphoma international prognostic index (FLIPI) in a population-based setting

Background: The aim of this study was to validate the Follicular Lymphoma International Prognostic Index (FLIPI) in a population-based cohort and to study the relevance of revision and extension of the FLIPI. Patients and methods: Data of 353 unselected patients, 1993-2002, in the Eindhoven Cancer Registry, were collected. Follow-up was completed up to 1 January 2006. Multiple imputations for missing covariates were used. Validity was assessed by comparing observed to predicted survival of the original model and of a revised model with other prognostic variables. Results: The original FLIPI stratified our cohort into three different risk groups based on stage, Hb, lactate dehydrogenase, nodal involvement and age. The discrimination between risk groups was not as good as in the original cohort. A model including age in three categories (≤60/ 61-70/>70 years) and presence of cardiovascular disease (CVD) (yes/ no) resulted in a better prognostic index. The 5-year overall survival rates were 79%, 59% and 28% in the low-, intermediate- and high-risk groups for the extended FLIPI compared with 81%, 66% and 47% for the original FLIPI, respectively. Conclusions: The performance of the FLIPIwas validated in a population-based setting, but could significantly be improved by a more refined coding of age and by including the presence of CVD

Impairment of cognitive functioning during Sunitinib or Sorafenib treatment in cancer patients: a cross sectional study

Impairment of cognitive functioning has been reported in several studies in patients treated with chemotherapy. So far, no studies have been published on the effects of the vascular endothelial growth factor receptor (VEGFR) inhibitors on cognitive functioning. We investigated the objective and subjective cognitive function of patients during treatment with VEGFR tyrosine kinase inhibitors (VEGFR TKI). Three groups of participants, matched on age, sex and education, were enrolled; 1. metastatic renal cell cancer (mRCC) or GIST patients treated with sunitinib or sorafenib (VEGFR TKI patients n = 30); 2. patients with mRCC not receiving systemic treatment (patient controls n = 20); 3. healthy controls (n = 30). Sixteen neuropsychological tests examining the main cognitive domains (intelligence, memory, attention and concentration, executive functions and abstract reasoning) were administered by a neuropsychologist. Four questionnaires were used to assess subjective cognitive complaints, mood, fatigue and psychological wellbeing. No significant differences in mean age, sex distribution, education level or IQ were found between the three groups. Both patient groups performed significantly worse on the cognitive domains Learning & Memory and Executive Functions (Response Generation and Problem Solving) compared to healthy controls. However only the VEGFR TKI patients showed impairments on the Executive subdomain Response Generation. Effect sizes of cognitive dysfunction in patients using VEGFR TKI were larger on the domains Learning & Memory and Executive Functions, compared to patient controls. Both patients groups performed on the domain Attention & Concentration the same as the healthy controls. Longer duration of treatment on VEGFR TKI was associated with a worse score on Working Memory tasks. Our data suggest that treatment with VEGFR TKI has a negative impact on cognitive functioning, specifically on Learning & Memory, and Executive Functioning. We propose that patients who are treated with VEGFR TKI are monitored and informed for possible signs or symptoms associated with cognitive impairment. ClinicalTrials.gov Identifier: NCT0124684

Towards an evidence-based model of fear of cancer recurrence for breast cancer survivors

In order to understand the multidimensional mechanism of fear of cancer recurrence (FCR) and to identify potential targets for interventions, it is important to empirically test the theoretical model of FCR. This study aims at assessing the validity of Lee-Jones et al.'s FCR model. A total of 1205 breast cancer survivors were invited to participate in this study. Participants received a questionnaire booklet including questionnaires on demographics and psychosocial variables including FCR. Data analysis consisted of the estimation of direct and indirect effects in mediator models. A total of 460 women (38 %) participated in the study. Median age was 55.8 years (range 32-87). Indirect effects of external and internal cues via FCR were found for all mediation models with limited planning for the future (R (2) = .28) and body checking (R (2) = .11-.15) as behavioral response variables, with the largest effects for limited planning for the future. A direct relation was found between feeling sick and seeking professional advice, not mediated by FCR. In the first tested models of FCR, all internal and external cues were associated with higher FCR. In the models with limited planning for the future and body checking as behavioral response, an indirect effect of cues via FCR was found supporting the theoretical model of Lee-Jones et al. An evidence-based model of FCR may facilitate the development of appropriate interventions to manage FCR in breast cancer survivor

Future steps in cardio-oncology—a national multidisciplinary survey among healthcare professionals in the Netherlands

Background: The awareness of cancer therapy–related adverse cardiac effects is fueled by recent literature on cardiotoxicity incidence and detection strategies. Although this influences the sense of urgency, in current practice, cardiotoxicity monitoring and treatment is not structurally performed. With this study, we aimed to evaluate current perspectives on cardio-oncology and to assess needs, ultimately to determine an agenda for improvements in current practice. Material and methods: A national multidisciplinary 36-question survey was conducted. The survey was developed by a multidisciplinary team, theoretically based on an implementation checklist and distributed by email, through cardiology and oncology societies as well as social media. Results: One hundred ninety professionals completed the survey, of which 66 were cardiologists, 66 radiation oncologists, and 58 medical oncologists and hematologists. Many professionals were unaware of their specialisms’ cardio-oncology guidelines: 62.1% of cardiologists and 29.3% of the hematologists and medical oncologists respectively. Many cardiologists (N = 46; 69.7%), radiation oncologists (N = 45; 68.2%), and hematologists and medical oncologists (N = 38; 65.5%) expressed that they did not have sufficient knowledge to treat cardio-oncology patients and would either refer a patient or aspire to gain more knowledge on the topic. Conclusion: The field of cardio-oncology is advancing rapidly, with progress in stratification and detection strategies leading to the development of new guidelines and consensus statements. However, the application of these guidelines in current practice appears to be lagging. Professionals express a need for additional training and a practical guideline including risk stratification, monitoring, and treatment strategies. Multidisciplinary discussion and consensus on cardio-oncology care is vital to improve implementation of cardio-oncology guidelines, ultimately to improve cardiac care for oncology patients