Variation in guideline adherence in non-Hodgkin's lymphoma care: impact of patient and hospital characteristics.

BACKGROUND: The objective of this observational study was to assess the influence of patient, tumor, professional and hospital related characteristics on hospital variation concerning guideline adherence in non-Hodgkin's lymphoma (NHL) care. METHODS: Validated, guideline-based quality indicators (QIs) were used as a tool to assess guideline adherence for NHL care. Multilevel logistic regression analyses were used to calculate variation between hospitals and to identify characteristics explaining this variation. Data for the QIs regarding diagnostics, therapy, follow-up and organization of care, together with patient, tumor and professional related characteristics were retrospectively collected from medical records; hospital characteristics were derived from questionnaires and publically available data. RESULTS: Data of 423 patients diagnosed with NHL between October 2010 and December 2011 were analyzed. Guideline adherence, as measured with the QIs, varied considerably between the 19 hospitals: >20 % variation was identified in all 20 QIs and high variation between the hospitals (>50 %) was seen in 12 QIs, most frequently in the treatment and follow-up domain. Hospital variation in NHL care was associated more than once with the characteristics age, extranodal involvement, multidisciplinary consultation, tumor type, tumor aggressiveness, LDH level, therapy used, hospital region and availability of a PET-scanner. CONCLUSION: Fifteen characteristics identified at the patient level and at the hospital level could partly explain hospital variation in guideline adherence for NHL care. Particularly age was an important determinant: elderly were less likely to receive care as measured in the QIs. The identification of determinants can be used to improve the quality of NHL care, for example, for standardizing multidisciplinary consultations in daily practice.

Trends in incidence, treatment and survival of aggressive B-cell lymphoma in the Netherlands 1989-2010.

Only a small number of patients with aggressive B-cell lymphoma take part in clinical trials, and elderly patients in particular are under-represented. Therefore, we studied data of the population-based nationwide Netherlands Cancer Registry to determine trends in incidence, treatment and survival in an unselected patient population. We included all patients aged 15 years and older with newly diagnosed diffuse large B-cell lymphoma or Burkitt lymphoma in the period 1989-2010 and mantle cell lymphoma in the period 2001-2010, with follow up until February 2013. We examined incidence, first-line treatment and survival. We calculated annual percentage of change in incidence and carried out relative survival analyses. Incidence remained stable for diffuse large B-cell lymphoma (n=23,527), while for mantle cell lymphoma (n=1,634) and Burkitt lymphoma (n=724) incidence increased for men and remained stable for women. No increase in survival for patients with aggressive B-cell lymphoma was observed during the period 1989-1993 and the period 1994-1998 [5-year relative survival 42% (95%CI: 39%-45%) and 41% (38%-44%), respectively], but increased to 46% (43%-48%) in the period 1999-2004 and to 58% (56%-61%) in the period 2005-2010. The increase in survival was most prominent in patients under 65 years of age, while there was a smaller increase in patients over 75 years of age. However, when untreated patients were excluded, patients over 75 years of age had a similar increase in survival to younger patients. In the Netherlands, survival for patients with aggressive B-cell lymphoma increased over time, particularly in younger patients, but also in elderly patients when treatment had been initiated. The improvement in survival coincided with the introduction of rituximab therapy and stem cell transplantation into clinical practice.

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.

Improvement of hospital care for patients with non-Hodgkin's lymphoma: protocol for a cluster randomized controlled trial (PEARL study).

BACKGROUND: Malignant lymphomas constitute a diverse group of cancers of lymphocytes. One well-known disease is Hodgkin's lymphoma; the others are classified as non-Hodgkin's lymphoma (NHL). NHLs are the most common hematologic neoplasms in adults worldwide, and in 2012 over 170,000 new cases were estimated in the United States and Europe.In previous studies, several practice gaps in hospital care for patients with NHL have been identified. To decrease this variation in care, the present study aims to perform a problem analysis in which barriers to and facilitators for optimal NHL care will be identified and, based on these findings, to develop (tailored) improvement strategies. Subsequently, we will assess the effectiveness, feasibility and costs of the improvement strategies. METHODS/DESIGN: Barriers and facilitators will be explored using the literature, using interviews and questionnaires among physicians involved in NHL care, and patients diagnosed with NHL. The results will be used to develop a tailored improvement strategy. A cluster randomized controlled trial involving 19 Dutch hospitals will be conducted. Hospitals will be randomized to receive either an improvement strategy tailored to the barriers and facilitators found or, a standard strategy of audit and feedback.The effects of both strategies will be evaluated using previously developed quality indicators. Adherence to the indicators will be measured before and after the intervention period based on medical records from newly diagnosed NHL patients. To study the feasibility of both strategies, a process evaluation will be additionally performed. Data about exposure to the different elements of the strategies will be collected using questionnaires. Economic evaluation from a healthcare perspective will compare the two implementation strategies, where the costs of the implementation strategy and changes in healthcare consumption will be assessed. DISCUSSION: The presence of variation in the use of diagnostic tests, treatment, and follow-up between different physicians in different hospitals in the Netherlands is important for patients. To reduce the existing variation in care, implementation of tailored interventions to improve NHL care is necessary. TRIAL REGISTRATION: This trial is registered at ClinicalTrial.gov as the PEARL study, registration number NCT01562509.

Trends in incidence, therapy and outcome of localized nodal and extranodal marginal zone lymphomas: declining incidence and inferior outcome for gastrointestinal sites.

Population-based series analyzing clinical implications of nodal versus extranodal presentation of marginal zone lymphoma (MZL) are lacking. We studied clinical differences and trends in incidence, therapy and survival of nodal and extranodal MZL, and of MZL at different extranodal sites, in a population-based cohort. All patients with localized (Ann Arbor stage I and II) nodal (n = 211), splenic (n = 54) and extranodal (n = 1449) MZL, diagnosed between 1994 and 2010, were selected from The Netherlands Cancer Registry. Between 1994 and 2010 the incidence of nodal and extranodal MZL increased. The incidence of gastric MZL decreased. Patients with nodal MZL received more chemotherapy and targeted therapies than their extranodal counterparts. A trend in time toward less chemotherapy and more irradiation was observed. Overall survival (OS) curves for nodal and extranodal MZL overlapped (5-year OS 76% and 77%, respectively). Patients with a primary gastrointestinal (GI) localization had inferior OS compared to patients with non-GI extranodal MZL (5-year OS 71% and 85%, p < 0.0001). Patients with localized extranodal MZL presented more commonly with stage I disease, but their clinical presentation and survival were otherwise similar to patients with localized nodal MZL. MZL arising in the GI tract does not have a good prognosis and requires a different treatment approach.

Undertreatment of patients with localized extranodal compared with nodal diffuse large B-cell lymphoma.

Population-based studies analyzing clinical implications of nodal versus extranodal (EN) presentation of diffuse large B-cell lymphoma (DLBCL) are scarce. We studied clinical differences and trends in incidence, treatment and survival of nodal and EN DLBCL in a population-based cohort. All patients newly diagnosed with localized (Ann Arbor stage [AAS] I and II) nodal (n = 5124) and EN (n = 4776) DLBCL, and primary mediastinal B-cell lymphoma (PMBL; n = 88), diagnosed between 1989 and 2010, were selected from the Netherlands Cancer Registry. Primary EN disease was correlated with older age and more favorable clinical stage (AAS I). The age standardized incidence rates for men with localized EN DLBCL, and for men and women with localized PMBL, increased significantly, whereas the age standardized incidence rates of all other subgroups remained stable. The stomach was the most common EN localization. Patients with EN disease received less chemotherapy and targeted therapy than their nodal counterparts, irrespective of age and period of diagnosis. Their 5-year overall survival (OS) was 48% vs. 54% in the nodal group, but in multivariate analysis primary extranodal presentation was not independently associated with inferior survival. This population-based study shows clinically relevant differences between localized nodal and EN DLBCL and PMBL. Since patients with EN were significantly less often optimally treated, we advocate better interaction between medical disciplines.

Modest improvement in 20 years of kidney cancer care in the Netherlands.

AIM: For an evaluation of the progress achieved in the field of kidney cancer care in the Netherlands in the last decades, we described trends in incidence, treatment, mortality and relative survival. METHODS: All adult patients newly diagnosed with kidney cancer between 1989 and 2009 (N=32,545) were selected from the Netherlands Cancer Registry. Age-standardised incidence and mortality rates were calculated. Follow-up was completed until January 2010. In order to assess trends estimated annual percentages of change (EAPC) were estimated. RESULTS: The incidence of kidney cancer has been fairly stable between 1989 and 2001 with a European Standardised Rate of approximately 11 per 100,000 person years (PY). Since 2001 the incidence increased to 13 per 100,000 PY in 2009 (EAPC: 2.4%; 95%confidence interval (CI): 1.5 to 3.4%). The mortality rate decreased slightly over time, from 6.2 per 100,000 PY in 1989 to 5.6 in 2010. No changes in treatment were observed, except for the introduction of targeted therapies for stage IV disease, since 2005. The 5-year relative survival improved from 51% in 1989-1994 to 58% in 2005-2009 (EAPC: 0.9%; 95%CI 0.7 to 1.2%). Improvement in survival was especially seen in males, younger age groups and low stages. CONCLUSIONS: The incidence of kidney cancer has increased slightly, and survival improved modestly, resulting in a decreasing mortality. A positive effect of the introduction of targeted therapies for metastatic kidney cancer was observed in 1-year relative survival. For progress in kidney cancer care, effective prevention strategies and new therapies remain warranted.

Improving relative survival, but large remaining differences in survival for non-Hodgkin's lymphoma across Europe and the United States from 1990 to 2004.

PURPOSE: Non-Hodgkin's lymphoma (NHL) is the most common hematologic malignant neoplasm in adults. Monitoring differential changes in population-based survival is across Europe and the United States (US) could point to progress attained and impact of application of novel treatments. PATIENTS AND METHODS: We examined trends in age-specific 5-year relative survival among patients with NHL age 15 years or older between 1990 and 1994 and 2000 and 2004, on the basis of follow-up data from 12 population-based cancer registries across Europe, using period analysis techniques and compared the results with similar trends of patients with NHL in the US, as recorded in the Surveillance, Epidemiology, and End Results database. RESULTS: By 2000 to 2004, overall 5-year relative survival of patients with NHL across Europe was between 37% and 62%, achieved by overall increases in 5-year relative survival ranging from 4% to 12% units between 1990 and 1994 and 2000 and 2004. Changes in age-specific survival ranged from -1% to 43% units during the same time interval. For patients with NHL older than age 55 years, relative survival in individual European registries for the whole period was between 8% and 36% units lower than in the US, theoretically representing a lag of 4 to 10 years of progress. CONCLUSION: Our analyses disclosed a strong and ongoing increase in long-term survival for patients with NHL in European populations. The geographic differences potentially indicate that further improvements could be possible, especially for patients age 55 years or older. The presumptive delay in improvement in survival among elderly patients with NHL in Europe remains to be clarified.

Diabetes alone should not be a reason for withholding adjuvant chemotherapy for stage III colon cancer.

BACKGROUND: With increasing prevalence of diabetes mellitus and colon cancer, the number of patients suffering from both diseases is growing, and physicians are being faced with complicated treatment decisions. OBJECTIVE: To investigate the association between diabetes and treatment/course of stage III colon cancer and the association between colon cancer and course of diabetes. MATERIALS AND METHODS: Additional information was collected from the medical records of all patients with both stage III colon cancer and diabetes (n=201) and a random sample of stage III colon cancer patients without diabetes (n=206) in the area of the population-based Eindhoven Cancer Registry (1998-2007). RESULTS: Colon cancer patients without diabetes were more likely to receive adjuvant chemotherapy compared with diabetic colon cancer patients (OR 1.8; 95% CI 1.2-2.7). After adjustment for age, this difference was borderline significant (OR 1.6; 95% CI 1.0-2.6). Diabetic patients did not have: significantly more side-effects from surgery or adjuvant chemotherapy; more recurrence from colon cancer; significantly shorter time interval until recurrence; or a poorer disease-free survival or overall survival. Age and withholding of adjuvant chemotherapy were most predictive of all-cause mortality. After colon cancer diagnosis, the dose of antiglycaemic medications was increased in 22% of diabetic patients, resulting in significantly lower glycaemic indexes than before colon cancer diagnosis. CONCLUSIONS: Since diabetic patients did not have more side-effects of adjuvant chemotherapy, and adjuvant chemotherapy had a positive effect on survival for both patients with and without diabetes, diabetes alone should not be a reason for withholding adjuvant chemotherapy. Journal of Comorbidity 2011;1:19-27.

Excess of autoimmune and chronic inflammatory disorders in patients with lymphoma compared with all cancer patients: a cancer registry-based analysis in the south of the Netherlands.

OBJECTIVE: We investigated the association between autoimmune and chronic inflammatory disorders and several cancer types including lymphomas. METHODS: All cancer patients diagnosed between 1995 and 2007, aged 15 to 90 years, and registered in the Eindhoven Cancer Registry were included in this study. Co-morbidity at diagnosis was recorded by qualified registry personnel who obtained the information from the clinical record. We determined the prevalence of rheumatoid arthritis (RA), chronic inflammatory bowel diseases, connective and vascular tissue diseases, ulcers of the stomach and duodenum, hepatitis, human immunodeficiency virus (HIV), and tuberculosis (TBC) among newly diagnosed patients with lymphoma and compared this with the prevalence among patients with all other cancers. RESULTS: The prevalence of most of these co-morbidities was higher in patients with lymphomas than those with other malignancies. RA was more often present in newly diagnosed patients with most lymphomas, ulcers of stomach and duodenum in patients with marginal zone lymphoma, hepatitis in case of diffuse large B-cell lymphoma, HIV with aggressive B-cell lymphoma, and TBC with mantle cell lymphoma. CONCLUSION: This study confirms the positive association between autoimmune and chronic inflammatory disorders and the various lymphoproliferative malignancies, suggesting either a shared etiology or pathogenesis or a direct causal relation. This is a fairly new method to study aetiological questions about cancers in a population-based cancer registry.

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 1(st), 2008. Multiple imputations for missing covariates were used. Validity was assessed by comparing observed survival in our cohort with predicted survival according to the original Mantle cell lymphoma International Prognostic Index. A revised model was constructed with Cox regression analysis. Discrimination was assessed by a concordance statistic ('c'). RESULTS: The original Mantle cell lymphoma International Prognostic Index could stratify our cohort into three distinct risk groups based on Eastern Cooperative Group performance status, white blood cell count, lactate dehydrogenase level, and age, with the discrimination being nearly as good as in the original cohort (c 0.65 versus 0.63). A modified model including performance status in five categories (0/1/2/3/4) instead of two (0-1/2-4), the presence of B-symptoms (yes/no) and sex (male/female) in addition to the original variables resulted in a better prognostic index (c 0.75). CONCLUSIONS: The Mantle cell lymphoma International Prognostic Index is a valid tool for risk stratification, comparison of prognosis, and treatment decisions in an unselected Dutch population-based setting. Although the index can be significantly improved, external validation on an independent data set is warranted before broad application of the modified instrument could be recommended.

Conditional relative survival in head and neck squamous cell carcinoma: Permanent excess mortality risk for long-term survivors.

BACKGROUND: Dynamic predictions on head and neck cancer survival could offer, besides improved patient counseling, insight into long-term effects of tumor- and patient-based characteristics on survival. Theoretically, there could be a certain time period after diagnosis after which the patient returns to a population risk on survival. METHODS: In all, 7255 patients with a primary head and neck squamous cell carcinoma (HNSCC) aged 25 to 90 years, diagnosed between January 1980 and January 2004 in The Netherlands, were included. Conditional 5-year relative survival for every additional year survived was computed. RESULTS: The overall conditional relative prognosis reached a plateau after approximately 4 years; a permanent 20% to 25% excess mortality for long-term HNSCC survivors remained. CONCLUSIONS: Conditional 5-year relative survival for patients with HNSCC remains poorer compared to age- and sex-matched counterparts in the general population, even when alive at 15 years after diagnosis. We assume that this is caused by an excess comorbidity in these patients, mainly due to smoking and alcohol abuse.

Cancer patients with cardiovascular disease have survival rates comparable to cancer patients within the age-cohort of 10 years older without cardiovascular morbidity.

UNLABELLED: Due to aging of the population the prevalence of both cardiovascular diseases (CVDs) and cancer is increasing. Elderly patients are often under-represented in clinical trials, resulting in limited guidance about treatment and outcome. This study gives insight into the prevalence of CVD among unselected patients with colon, rectum, lung, breast and prostate cancer and its effects on cancer treatment and outcome. Over one fourth (N=11,200) of all included cancer patients aged 50 or older (N=41,126) also suffered from CVD, especially those with lung (34%) or colon cancer (30%). These patients were often treated less aggressively, especially in case COPD or diabetes was also present. CVD had an independent prognostic effect among patients with colon, rectum and prostate cancer. This prognostic effect could not be fully explained by differences in treatment. CONCLUSIONS: Many cancer patients with severe CVD have a poorer prognosis. More research is needed for explaining the underlying factors for the decreased survival. Such research should lead to treatment guidelines for these patients.