M.L.G. Janssen-Heijnen

Prevalence of co-morbidity and its relationship to treatment among unselected patients with Hodgkin's disease and non-Hodgkin's lymphoma, 1993-1996

Abstractu2002A 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 Hodgkins disease (HD) and on 904 patients with non-Hodgkins lymphoma (NHL) diagnosed between 1993 and 1996 were derived from the Eindhoven Cancer Registry. In the age-group below 60u2009years, 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 Hodgkins disease who were 60u2009years and over and 43% and 61% for non Hodgkin patients who were 60–69u2009years and 70u2009years 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 Hodgkins patients. For non-Hodgkins patients of 60–69u2009years and 70u2009years 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 Hodgkins disease and 10–15% less to elderly patients with non-Hodgkins lymphoma. The presence of co-morbidity was associated with a decreased overall survival within the first 4u2009months after diagnosis in both Hodgkins disease and non-Hodgkins lymphoma for all age-groups. In conclusion, serious co-morbidity was found for more than half of all lymphoma patients who were 60u2009years 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 4u2009months after diagnosis.

Treatment and survival of 38 female breast lymphomas: a population-based study with clinical and pathological reviews

Breast lymphomas are rare and consensus about their treatment is lacking. A population-based study of 38 breast lymphomas, registered in the databases of two Comprehensive Dutch Cancer Centers from 1981 to 1999, was performed. The median age of all female patients was 65xa0years (20–92): 25 patients had localized and 13 patients had disseminated lymphoma. The most common type was diffuse large B-cell lymphoma (DLBCL), which accounted for 17 of the localized and 4 of the disseminated cases. Burkitts lymphoma (BL), three being disseminated, was found in four patients. There were six extranodal marginal zone lymphomas (ENMZL), three being localized. Seven DLBCL and one BL showed additional histological features of mucosa-associated lymphoid tissue (MALT) lymphoma. Localized aggressive lymphomas treated with surgery and/or radiation therapy had relapse rates of 100% and 67%, respectively. Cyclophosphamide, hydroxydaunomycin, vincristine, and prednisone (CHOP)-like chemotherapy with or without local irradiation led to 17% relapses in patients with localized aggressive lymphoma. Median follow-up time was 32xa0months (0.6–218); 37% of the patients relapsed and 24% had progressive disease. Response to salvage regimens, given to 91% of the patients with recurrent disease, was poor. The 2-year overall survival rate was 63%, 72% for patients with localized disease, and 46% for patients with disseminated lymphoma. The majority of breast lymphomas are localized aggressive lymphomas that should be treated initially with CHOP-like chemotherapy with or without irradiation. The initial choice of treatment is very important because response to salvage regimens is poor.

Disease-specific mortality among stage I–III colorectal cancer patients with diabetes: a large population-based analysis

Aims/hypothesisThe aim of our study was to investigate overall and disease-specific mortality of colorectal cancer patients with diabetes.MethodsIn this population-based study, we included all colorectal cancer patients, newly diagnosed with stage I–III cancer, between 1997 and 2007 in the registration area of the Eindhoven Cancer Registry. Stage of cancer, cancer treatment and comorbidities were actively collected by reviewing hospital medical records. Data on patients with and without diabetes were linked to Statistics Netherlands to assess vitality, date of death and underlying cause of death. Follow-up of all patients was completed until 1 January 2009.ResultsWe included 6,974 patients with colon cancer and 3,888 patients with rectal cancer, of whom 820 (12%) and 404 (10%), respectively, had diabetes at the time of cancer diagnosis. During follow-up, death occurred in 611 (50%) of 1,224 cancer patients with diabetes and 3,817 (40%) of 9,638 cancer patients without diabetes. Multivariate Cox regression analyses, adjusted for age, sex, socioeconomic status, stage, lymph nodes examined, adjuvant therapy and year of diagnosis, showed that overall mortality was significantly higher for colon (HR 1.12, 95% CI 1.01, 1.25) and rectal (HR 1.21, 95% CI 1.03, 1.41) cancer patients with diabetes than for those without. Disease-specific mortality was only significantly increased for rectal cancer patients (HR 1.30, 95% CI 1.06, 1.60).Conclusions/interpretationDiabetes at the time of rectal cancer diagnosis was independently associated with an increased risk of colorectal cancer mortality compared with no diabetes, suggesting a specific interaction between diabetes and rectal cancer. Future in-depth studies including detailed diabetes- and cancer-related variables should elucidate pathways.

Significant improvement in survival of patients presenting with metastatic colon cancer in the south of The Netherlands from 1990 to 2004

BACKGROUNDnIn randomised controlled trials, the median overall survival (OS) for patients with metastatic colon cancer has improved. However, the results of randomised controlled trials should be interpreted with caution and cannot simply be extrapolated to the general practice. We retrospectively analysed population-based survival data of patients who presented with metastatic colon cancer at diagnosis.nnnPATIENTS AND METHODSnAll patients diagnosed with primary metastatic colon cancer from 1990 to 2004 in the registration area of the Eindhoven Cancer Registry were included. Date of diagnosis was divided into four periods (1990-1994, 1995-1999, 2000-2002, and 2003-2004) according to the availability of chemotherapy for metastatic colon cancer. We assessed OS according to chemotherapy use and period.nnnRESULTSnOf the 1769 patients, 30.6% received chemotherapy. Chemotherapy use over time increased from 24% in 1990-1994 to 55% in 2000-2004 for patients aged <70 years and from 2% to 22% in patients aged 70 years and older. Median survival for patients diagnosed in 1990-1994 was 26 [95% confidence interval (CI) 22-32] weeks, while patients diagnosed in 2003-2004 had a median survival of 39 (95% CI 31-48) weeks. Patients who did not receive chemotherapy had a survival of 22 (95% CI 20-25) weeks, while the survival for patients who did receive chemotherapy was 57 (95% CI 51-65) weeks. OS decreased with increasing age (P < 0.0001). In the multivariate survival analysis, chemotherapy use, increasing age, having multiple comorbid conditions, and having more than one tumour site significantly affect survival, with the strongest effect of chemotherapy use.nnnCONCLUSIONnPalliative chemotherapy significantly improved OS in unselected patients with metastatic colon cancer.

Two sides of the medallion: poor treatment tolerance but better survival by standard chemotherapy in elderly patients with advanced-stage diffuse large B-cell lymphoma

BACKGROUNDnWe investigated treatment of unselected elderly patients with diffuse large B-cell lymphoma (DLBCL) and its subsequent impact on treatment tolerance and survival.nnnPATIENTS AND METHODSnData from all 419 advanced-stage DLBCL patients, aged 75 or older and newly diagnosed between 1997 and 2004, were included from five regional population-based cancer registries in The Netherlands. Subsequent data on comorbidity, performance status, treatment, motives for adaptations or refraining from chemotherapy and toxic effects was collected from the medical records. Follow-up was completed until 1st January 2009.nnnRESULTSnOnly 46% of patients received the standard therapy [aggressive chemotherapy with cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP)-like chemotherapy]. Motives for withholding chemotherapy were refusal by patient/family, poor performance status or estimated short life expectancy. Of all patients receiving CHOP-like chemotherapy, only 56% could complete at least six cycles. Grade 3 or 4 toxicity occurred in 67% of patients receiving standard therapy. The independent effect of therapy on survival remained after correction for the age-adjusted International Prognostic Index.nnnCONCLUSIONSnStandard therapy was applied less often in elderly patients with a subsequent independent negative impact on survival. Furthermore, high toxicity rate and the impossibility of the majority of patients to complete treatment were seen. This implies that better treatment strategies should be devised including a proper selection of senior patients for this aggressive chemotherapy.BACKGROUNDnWe investigated treatment of unselected elderly patients with diffuse large B-cell lymphoma (DLBCL) and its subsequent impact on treatment tolerance and survival.nnnPATIENTS AND METHODSnData from all 419 advanced-stage DLBCL patients, aged 75 or older and newly diagnosed between 1997 and 2004, were included from five regional population-based cancer registries in The Netherlands. Subsequent data on comorbidity, performance status, treatment, motives for adaptations or refraining from chemotherapy and toxic effects was collected from the medical records. Follow-up was completed until 1st January 2009.nnnRESULTSnOnly 46% of patients received the standard therapy [aggressive chemotherapy with cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP)-like chemotherapy]. Motives for withholding chemotherapy were refusal by patient/family, poor performance status or estimated short life expectancy. Of all patients receiving CHOP-like chemotherapy, only 56% could complete at least six cycles. Grade 3 or 4 toxicity occurred in 67% of patients receiving standard therapy. The independent effect of therapy on survival remained after correction for the age-adjusted International Prognostic Index.nnnCONCLUSIONSnStandard therapy was applied less often in elderly patients with a subsequent independent negative impact on survival. Furthermore, high toxicity rate and the impossibility of the majority of patients to complete treatment were seen. This implies that better treatment strategies should be devised including a proper selection of senior patients for this aggressive chemotherapy.

Chronic Lymphocytic Leukaemia in the Netherlands: Trends in incidence, treatment and survival, 1989-2008

We present trends in incidence, early treatment and survival of Chronic Lymphocytic Leukaemia (CLL) between 1989 and 2008, based on population-based data from the Netherlands Cancer Registry. Incidence rates were stable at 5.1 per 100,000 person-years for males, but increased from 2.3 to 2.5 for females, especially for females aged 50-64 years (from 3.6 to 4.3). Patients were less likely to receive chemotherapy within six months, i.e. from 29% to 24% among males and from 25% to 21% among females. Five-year relative survival increased from 61% in 1989-1993 to 70% 2004-2008 for males, and from 71% to 76% for females. The relative excess risk of dying decreased in time to 0.7 (males) and 0.9 (females) in 2004-2008, reference 1989-1993, and increased with age to 2.9 (males) and 1.8 (females) in patients aged 75-94 years, reference 30-64 years. The increasing incidence among females aged 50-64 coincided with the introduction of mass screening for breast cancer, which resulted in a large group of women under increased surveillance and possibly led to increased detection of CLL. The increase in survival might be underestimated due to possible decreased or delayed registration of indolent cases and the retroactive effect of the introduction of new therapies.

Diverging trends in incidence and mortality, and improved survival of non-Hodgkin's lymphoma, in the Netherlands, 1989–2007

BACKGROUNDnWe studied progress in the fight against non-Hodgkins lymphoma (NHL) in the Netherlands by describing the changes in incidence, treatment, relative survival, and mortality during 1989-2007.nnnPATIENTS AND METHODSnWe included all adult patients with NHL [i.e. all mature B-, T-, and natural killer (NK) cell neoplasms, with the exception of plasma cell neoplasms], newly diagnosed in the period 1989-2007 and recorded in the Netherlands Cancer Registry (n = 55 069). Regular mortality data were derived from Statistics Netherlands. Follow-up was completed up to 1 January 2009. Annual percentages of change in incidence, mortality, and relative survival were calculated.nnnRESULTSnThe incidence of indolent B-cell and T- and NK-cell neoplasms rose significantly (estimated annual percentage change = 1.2% and 1.3%, respectively); incidence of aggressive B-cell neoplasms remained stable. Mortality due to NHL remained stable between 1989 and 2003, and has decreased since 2003. Five-year relative survival rates rose from 67% to 75%, and from 43% to 52%, respectively, for indolent and aggressive mature B-cell neoplasms, but 5-year survival remained stable at 48% for T- and NK-cell neoplasms.nnnCONCLUSIONSnIn the Netherlands, incidence of indolent mature B-cell and mature T- and NK-cell neoplasms has increased since 1989 but remained stable for aggressive neoplasms. Survival increased for all mature B-cell neoplasms, preceding a declining mortality and increased prevalence of NHL (17 597 on 1 January 2008).BACKGROUNDnWe studied progress in the fight against non-Hodgkins lymphoma (NHL) in the Netherlands by describing the changes in incidence, treatment, relative survival, and mortality during 1989-2007.nnnPATIENTS AND METHODSnWe included all adult patients with NHL [i.e. all mature B-, T-, and natural killer (NK) cell neoplasms, with the exception of plasma cell neoplasms], newly diagnosed in the period 1989-2007 and recorded in the Netherlands Cancer Registry (n=55 069). Regular mortality data were derived from Statistics Netherlands. Follow-up was completed up to 1 January 2009. Annual percentages of change in incidence, mortality, and relative survival were calculated.nnnRESULTSnThe incidence of indolent B-cell and T- and NK-cell neoplasms rose significantly (estimated annual percentage change=1.2% and 1.3%, respectively); incidence of aggressive B-cell neoplasms remained stable. Mortality due to NHL remained stable between 1989 and 2003, and has decreased since 2003. Five-year relative survival rates rose from 67% to 75%, and from 43% to 52%, respectively, for indolent and aggressive mature B-cell neoplasms, but 5-year survival remained stable at 48% for T- and NK-cell neoplasms.nnnCONCLUSIONSnIn the Netherlands, incidence of indolent mature B-cell and mature T- and NK-cell neoplasms has increased since 1989 but remained stable for aggressive neoplasms. Survival increased for all mature B-cell neoplasms, preceding a declining mortality and increased prevalence of NHL (17 597 on 1 January 2008).

Chemotherapy in elderly small-cell lung cancer patients: yes we can, but should we do it?

BACKGROUNDnTwenty percent of all newly diagnosed patients with small-cell lung cancer (SCLC) are >75 years. Elderly patients may show more toxicity due to co-morbidity. We evaluated motives for adherence to treatment guidelines, completion of treatment and toxicity.nnnPATIENTS AND METHODSnPopulation-based data from patients aged ≥75 years and diagnosed with SCLC in 1997-2004 in The Netherlands were used (368 limited disease and 577 extensive disease). Additional data on co-morbidity (Adult Co-morbidity Evaluation 27), World Health Organisation performance status (PS), treatment, motive for no chemotherapy, adaptations and underlying motive and grade 3 or 4 toxicity were gathered from the medical records.nnnRESULTSnForty-eight percent did not receive chemotherapy. The most common motives were refusal by the patient or family, short life expectancy or a combination of high age, co-morbidity and poor PS. Although only relatively fit elderly were selected for chemotherapy, 60%-75% developed serious toxicity, and two-thirds of all patients could not complete the full chemotherapy.nnnCONCLUSIONSnWe hypothesise that a better selection by proper geriatric assessments is needed to achieve a more favourable balance between benefit and harm.

Conditional survival for long-term colorectal cancer survivors in the Netherlands: who do best?

AIMnWith the increase in the number of long-term colorectal cancer (CRC) survivors, there is a growing need for subgroup-specific analysis of conditional survival.nnnMETHODSnAll 137,030 stage I-III CRC patients diagnosed in the Netherlands between 1989 and 2008 aged 15-89 years were selected from the Netherlands Cancer Registry. We determined conditional 5-year relative survival rates, according to age, subsite and tumour stage for each additional year survived up to 15 years after diagnosis as well as trends in absolute risks for and distribution of causes of death during follow-up.nnnRESULTSnMinimal excess mortality (conditional 5-year relative survival >95%) was observed 1 year after diagnosis for stage I colon cancer patients, while for rectal cancer patients this was seen after 6 years. For stage II and III CRC, minimal excess mortality was seen 7 years after diagnosis for colon cancer, while for rectal cancer this was 12years. The differences in conditional 5-year relative survival between colon and rectal cancer diminished over time for all patients, except for stage III patients aged 60-89 years. The absolute risk to die from CRC diminished sharply over time and was below 5% after 5 years. The proportion of patients dying from CRC decreased over time after diagnosis while the proportions of patients dying from other cancers, cardiovascular disease and other causes increased.nnnCONCLUSIONnPrognosis for CRC survivors improved with each additional year survived, with the largest improvements in the first years after diagnosis. Quantitative insight into conditional relative survival estimates is useful for caregivers to inform and counsel patients with stage I-III colon and rectal cancer during follow-up.

Treatment and complications in elderly stage III colon cancer patients in the Netherlands

BACKGROUNDnWe evaluated which patient factors were associated with treatment tolerance and outcome in elderly colon cancer patients.nnnDESIGNnPopulation-based data from five regions included in the Netherlands Cancer Registry were used. Patients with resected stage III colon cancer aged ≥75 years diagnosed in 1997-2004 who received adjuvant chemotherapy (N = 216) were included as well as a random sample (N = 341) of patients who only underwent surgery.nnnRESULTSnThe most common motives for withholding adjuvant chemotherapy were a combination of high age, co-morbidity and poor performance status (PS, 43%) or refusal by the patient or family (17%). In 57% of patients receiving chemotherapy, adaptations were made in treatment regimens. Patients who received adjuvant chemotherapy developed more complications (52%) than those with surgery alone (41%). For the selection of patients who had survived the first year after surgery, receiving adjuvant chemotherapy resulted in better 5-year overall survival (52% versus 34%), even after adjustment for differences in age, co-morbidity and PS.nnnCONCLUSIONnDespite high toxicity rates and adjustments in treatment regimens, elderly patients who received chemotherapy seemed to have a better survival. Prospective studies are needed for evaluating which patient characteristics predict the risks and benefits of adjuvant chemotherapy in elderly colon cancer patients.