Changes in income and employment after diagnosis among patients with multiple myeloma in The Netherlands.

OBJECTIVE: Due to new treatment options, survival rates in multiple myeloma (MM) are improving. Consequently, maintaining work and income is becoming more important for patients and society. Therefore, we aimed to explore the change in income and employment in patients with MM. METHODS: Data from the Netherlands Cancer Registry of MM patients diagnosed between 2012 and 2017 were merged with socioeconomic data from Statistics Netherlands. Descriptive statistics were used to analyse total income, income from employment, and accumulated income before and after diagnosis. RESULTS: Income from employment decreased by 45% in MM patients, between 1 year before and 4 years after diagnosis Four years after diagnosis, 35% of the patients were still employed, with an accumulated 5-year productivity loss of €121 million. Higher income loss from employment and job loss was observed in female patients, patients with more extensive disease, or those not treated with autologous stem cell transplant. CONCLUSION: Loss of (income from) employment among patients with MM was high, causing financial burden on the patient and society. With improving survival in MM, more research and awareness are needed to better assess the importance of income and work for MM patients and society.

Treatment strategies and outcome in relapsed peripheral T-cell lymphoma: results from the Netherlands Cancer Registry.

Optimal treatment in patients with refractory or relapsed peripheral T-cell lymphomas (R/R T-NHL) is unknown. In this population-based study, outcome in R/R PTCL not otherwise specified (PTCL NOS), angioimmunoblastic T-cell lymphoma (AITL) and ALK+ and ALK- anaplastic large cell lymphoma (ALCL) was evaluated. Patients with PTCL NOS, AITL, ALK+ ALCL and ALK- ALCL (≥18 years) diagnosed in 2014-2019 were identified using the Netherlands Cancer Registry. Endpoints were overall response rate (ORR), progression-free survival (PFS) and overall survival (OS). The 2-year PFS of 821 patients was 57%. Among 311 patients with a relapse, 243 received second-line treatment: 44% salvage chemotherapy, 20% brentuximab vedotin (BV) and 36% other treatment. In third-line, BV was most commonly used (38%). ORR following second-line treatment was 47%. Two-year PFS and OS after relapse were 25% and 34%, respectively. Risk of second relapse was negatively affected by early relapse (<12 months post-diagnosis), while BV reduced this risk compared to salvage chemotherapy (HR 0.55; 0.35-0.87; p=0.01). Reduced risk of relapse was independent of histological subtype. The best outcomes were observed for patients treated with salvage chemotherapy receiving consolidative autologous and allogeneic stem cell transplantation (SCT) (2-year OS 68%), patients treated with BV achieving a second complete remission (2-year OS 74%) and patients with allogeneic SCT (2-year OS 60%). The risk of second relapse was significantly lower for R/R T-NHL patients treated with BV compared to patients treated with salvage chemotherapy, and this was irrespective of subtype. Therefore, the use of salvage chemotherapy for R/R T-NHL patients is challenged.

Outcome of combined modality treatment in first-line for stage I(E) peripheral T-cell lymphoma; a nationwide population-based cohort study from the Netherlands.

Peripheral T-cell lymphomas (PTCL) comprise a heterogeneous group of mature T-cell neoplasms with an unfavorable prognosis; presentation with stage I(E) disease is uncommon. In clinical practice, an abbreviated chemotherapy treatment regimen combined with radiotherapy (combined modality treatment [CMT]) is commonly used, although evidence from clinical trials is lacking. The aim of this nationwide population-based cohort study is to describe first-line treatment and outcome of patients with stage I(E) PTCL. All newly diagnosed patients ≥18 years with stage I(E) anaplastic large cell lymphoma (ALCL), angioimmunoblastic T-cell lymphoma (AITL) and peripheral T-cell lymphoma NOS (PTCL not otherise specified [NOS]) in 1989-2020 were identified in the Netherlands Cancer Registry. Patients were categorized according to treatment regimen, i.e., chemotherapy (CT), radiotherapy (RT), CMT, other therapy and no treatment. The primary endpoint was overall survival (OS). Patients with stage I(E) ALCL, AITL and PTCL NOS (n=576) were most commonly treated with CMT (28%) or CT (29%), 2% underwent SCT. RT only was given in 18%, and 8% received other therapy and 16% no treatment. Overall, the 5-year OS was 59%. According to subtype, 5-year OS was superior for ALCL as compared to PTCL NOS and AITL (68% vs. 55% and 52%, respectively; P=0.03). For patients treated with CMT, 5-year OS was significantly higher (72%) as compared to patients treated with either CT or RT alone (55% and 55%, respectively; P<0.01). In multivariable analysis, age per year increment (hazard ratio [HR] =1.06, 95% confidence interval [CI]: 1.05-1.07), male sex (HR=1.53, 95% CI: 1.23-1.90), and CT, or no treatment (HR=1.64, 95% CI: 1.21-2.21, and HR=1.55, 95% CI: 1.10-2.17, respectively) were associated with a higher risk of mortality. For stage I(E) ALCL, AITL and PTCL NOS, 5-year OS is 59%, comparing favorably to historical outcome in advanced-stage disease. Superior outcome estimates were observed in patients treated with CMT.

A population-based study of transformed marginal zone lymphoma: identifying outcome-related characteristics.

Histological transformation of marginal zone lymphoma (tMZL) into diffuse large B-cell lymphoma is associated with poor outcomes. Clinical characteristics associated with transformation risk and outcome after transformation are largely unknown due to scarcity of data. In this population-based study, competing risk analyses were performed to elucidate clinical characteristics associated with developing transformation among 1793 MZL patients using the Netherlands Cancer Registry. Cox regression analyses were performed to elucidate clinical characteristics associated with risk of relapse and mortality after transformation. Transformation occurred in 75 (4%) out of 1793 MZL patients. Elevated LDH and nodal MZL subtype at MZL diagnosis were associated with an increased risk, and radiotherapy with a reduced risk of developing tMZL. Most tMZL patients received R-(mini)CHOP (n = 53, 71%). Age >60 years and (immuno)chemotherapy before transformation were associated with an increased risk of relapse and mortality after transformation. Two-year progression-free survival (PFS) and overall survival (OS) were 66% (95% CI 52-77%) and 75% (95% CI 62-85%) for R-(mini)CHOP-treated tMZL patients, as compared to a PFS and OS both of 41% (95% CI 19-63%) for patients treated otherwise. Our study offers comprehensive insights into characteristics associated with transformation and survival after transformation, thereby optimizing guidelines and patient counseling.

Impact of rituximab on treatment outcomes of patients with angioimmunoblastic T-cell lymphoma; a population-based analysis.

BACKGROUND: Patients with angioimmunoblastic T-cell lymphoma (AITL) are treated with cyclophosphamide, doxorubicin, vincristine and prednisone with or without etoposide (CHO(E)P). In the majority of cases, Epstein-Barr virus (EBV)-positive B-cells are present in the tumour. There is paucity of research examining the effect of rituximab when added to CHO(E)P. In this nationwide, population-based study, we analysed the impact of rituximab on overall response rate (ORR), progression-free survival (PFS) and overall survival (OS) of patients with AITL. METHODS: Patients with AITL diagnosed between 2014 and 2020 treated with ≥one cycle of CHO(E)P with or without rituximab were identified in the Netherlands Cancer Registry. Survival follow-up was up to 1st February 2022. Baseline characteristics, best response during first-line treatment and survival were collected. PFS was defined as the time from diagnosis to relapse or to all-cause-death. OS was defined as the time from diagnosis to all-cause-death. Multivariable analysis for the risk of mortality was performed using Cox regression. FINDINGS: Out of 335 patients, 146 patients (44%) received R-CHO(E)P. Rituximab was more frequently used in patients with a B-cell infiltrate (71% versus 89%, p < 0·01). The proportion of patients who received autologous stem cell transplantation (ASCT) was similar between CHO(E)P and R-CHO(E)P (27% versus 30%, respectively). The ORR and 2-year PFS for patients who received CHO(E)P and R-CHO(E)P were 71% and 78% (p = 0·01), and 40% and 45% (p = 0·12), respectively. The 5-year OS was 47% and 40% (p = 0·99), respectively. In multivariable analysis, IPI-score 3-5, no B-cell infiltrate and no ASCT were independent prognostic factors for risk of mortality, whereas the use of rituximab was not. INTERPRETATION: Although the addition of rituximab to CHO(E)P improved ORR for patients with AITL, the PFS and OS did not improve.

Impact of etoposide and ASCT on survival among patients aged <65 years with stage II to IV PTCL: a population-based cohort study.

Patients aged <65 years with peripheral T-cell lymphoma (PTCL) are treated with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP). Although the addition of etoposide (CHOEP) and consolidation with autologous stem cell transplantation (ASCT) are preferred in some countries, randomized trials are lacking. This nationwide population-based study assessed the impact of etoposide and ASCT on overall survival (OS) among patients aged 18 to 64 years with stage II to IV anaplastic large-cell lymphoma (ALCL), angioimmunoblastic T-cell lymphoma (AITL), or PTCL not otherwise specified (NOS) diagnosed between 1989 and 2018 using the Netherlands Cancer Registry. Patients were categorized into 2 calendar periods, representing pre- and post-eras of etoposide and ASCT, respectively. A total of 1427 patients were identified (ALCL, 35%; AITL, 21%; and PTCL NOS, 44%). OS increased from 39% in the period from 1989 to 2009 to 49% in the period of 2009 to 2018 (P < .01). Five-year OS was superior for patients treated with CHOEP vs CHOP (64% and 44%, respectively; P < .01). When adjusted for subtype, International Prognostic Index score, and ASCT, the risk of mortality was similar between the 2 groups, except for patients with ALK+ ALCL, for whom the risk of mortality was 6.3 times higher when treated with CHOP vs CHOEP. Patients undergoing consolidation with ASCT had superior 5-year OS of 81% compared with 39% for patients not undergoing ASCT (P < .01), regardless of whether complete remission was achieved. In patients aged <65 years with advanced-stage ALK- ALCL, AITL, or PTCL, the use of ASCT consolidation, but not the addition of etoposide, was associated with improved OS.

Primary therapy and relative survival in patients with lymphoplasmacytic lymphoma/Waldenström macroglobulinaemia: a population-based study in the Netherlands, 1989-2018.

It is unclear how treatment advances impacted the population-level survival of patients with lymphoplasmacytic lymphoma/Waldenström macroglobulinaemia (LPL/WM). Therefore, we assessed trends in first-line therapy and relative survival (RS) among patients with LPL/WM diagnosed in the Netherlands between 1989 and 2018 (N = 6232; median age, 70 years; 61% males) using data from the nationwide Netherlands Cancer Registry. Patients were grouped into three age groups (<65, 66-75 and >75 years) and four calendar periods. Overall, treatment with anti-neoplastic agents within 1 year post-diagnosis gradually decreased over time, following a broader application of an initial watch-and-wait approach. Approximately 40% of patients received anti-neoplastic therapy during 2011-2018. Furthermore, use of chemotherapy alone decreased over time, following an increased application of chemoimmunotherapy. Detailed data among 1596 patients diagnosed during 2014-2018 revealed that dexamethasone-rituximab-cyclophosphamide was the most frequently applied regimen; its use increased from 14% to 39% between 2014 and 2018. The 5-year RS increased significantly over time, particularly since the introduction of rituximab in the early-mid 2000s. The 5-year RS during 1989-1995 was 75%, 65%, and 46% across the age groups compared to 93%, 85%, and 79% during 2011-2018. However, the survival improvement was less pronounced after 2011. Collectively, the impressive survival improvement may be accounted for by broader application of rituximab-containing therapy. The lack of survival improvement in the post-rituximab era warrants studies across multiple lines of therapy to further improve survival in LPL/WM.

Decrease in early mortality for newly diagnosed multiple myeloma patients in the Netherlands: a population-based study.

Identification of risk factors for early mortality (EM) in multiple myeloma (MM) patients may contribute to different therapeutic approaches in patients at risk for EM. This population-based study aimed to assess trends in EM and risk factors for EM among MM patients diagnosed in the Netherlands. All MM patients, newly diagnosed between 1989 and 2018, were identified in the Netherlands Cancer Registry. Patients were categorized into three calendar periods (1989-1998, 1999-2008, 2009-2018) and into five age groups (≤65, 66-70, 71-75, 76-80, >80 years). EM was defined as death by any cause ≤180 days post-diagnosis. We included 28,328 MM patients (median age 70 years; 55% males). EM decreased from 22% for patients diagnosed in 1989-1998 to 13% for patients diagnosed in 2009-2018 (P < 0.01) and this decrease was observed among all age groups. Exact causes of death could not be elucidated. Besides patient's age, we found that features related to a more aggressive disease presentation, and patient characteristics reflecting patients' physical condition were predictive of EM. In summary, EM decreased from 1999 onwards. Nevertheless, EM remains high, especially for patients aged >70 years. Therefore, novel strategies should be explored to improve the outcome of patients at risk for EM.

Impact of rituximab biosimilars on overall survival in diffuse large B-cell lymphoma: a Dutch population-based study.

In 2017, the European Medicines Agency approved rituximab biosimilars (R-biosimilars) for treatment of diffuse large B-cell lymphoma (DLBCL). Thereafter, the Netherlands was one of the first countries to implement R-biosimilars, given lower costs compared with rituximab originator (R-originator). This study's objective was to investigate whether overall survival (OS) of patients with DLBCL receiving R-biosimilars is similar to patients treated with R-originator. DLBCL patients ≥18 years, diagnosed between 2014 and 2018, who received at least 1 cycle of rituximab combined with cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP) were identified in the Netherlands Cancer Registry. Patients were categorized into R-originator or R-biosimilars groups based on data from a central repository of the Dutch medicinal drug market. The primary end point was 3-year OS, defined as the time between diagnosis and all-cause death. By the end of 2018, 91% of purchased rituximab were biosimilars. In total, 4429 patients were identified with 876 in the R-biosimilars group and 3553 in the R-originator group. Patients in the R-biosimilars group less frequently received >6 cycles of R-CHOP compared with patients treated with R-originator (24% vs 30%, P = .003). The 3-year OS did not differ between patients treated with R-originator or R-biosimilars (73% vs 73%, P = .855). This was confirmed with a multivariable Cox regression analysis accounting for sex, age, International Prognostic Index score, and number of R-CHOP cycles. In conclusion, the 3-year OS is similar for patients treated with CHOP in combination with R-originator or R-biosimilars and, therefore, favors the use of R-biosimilars in DLBCL treatment management.

Doctors' reports about palliative systemic treatment: A medical record study.

BACKGROUND: Decisions about palliative systemic treatment are key elements of palliative and end-of-life care. Such decisions must often be made in complex, clinical situations. AIM: To explore the content of medical records of patients with advanced non-small cell lung cancer and pancreatic cancer with specific emphasis on doctors' notes about decisions on palliative systemic treatment. DESIGN: Medical record review (2009-2012) of 147 cancer patients containing 276 notes about palliative systemic treatment. We described the proportion of notes/medical records containing pre-specified items relevant to palliative systemic treatment. We selected patients using the nationwide Netherlands Cancer Registry. SETTING: Hospital based. RESULTS: About 75% of all notes reported doctors' considerations to start/continue palliative systemic treatment, including information about the prognosis (47%), possible survival gain (22%), patients' wish for palliative systemic treatment (33%), impact on quality of life (8%), and patient's age (3%). Comorbidity (82%), smoking status (78%) and drinking behaviour (63%) were more often documented than patients' performance status (16%). Conversations with the patient/family about palliative systemic treatment were reported in 49% of all notes. Response measurements and dose adaptations were documented in 75% and 71% of patients who received palliative systemic treatment respectively. CONCLUSION: Medical records provide insight into the decision-making process about palliative systemic treatment. The content and detail of doctors' notes, however, widely varies especially concerning their palliative systemic treatment considerations. Registries that aim to measure the quality of (end-of-life) care must be aware of this outcome. Future research should further explore how medical records can best assist in evaluating the quality of the decision-making process in the patient's final stage of life.

Adherence to cancer treatment guidelines: influence of general and cancer-specific guideline characteristics.

Background: Guideline adherence remains a challenge in clinical practice, despite guidelines' ascribed potential to improve patient outcomes. We studied the level of adherence to recommendations from Dutch national cancer treatment guidelines, and the influence of general and cancer-specific guideline characteristics on adherence. Methods: Based on data from a national cancer registry, adherence was evaluated for 15 treatment recommendations for breast, colorectal, prostate and lung cancer, and melanoma. Recommendations were selected by representatives of the medical specialist associations responsible for developing and implementing the guidelines. We used multivariable multilevel analysis to calculate mean adherence and variation between individual hospitals. Results: Mean adherence to the different treatment recommendations ranged from 40 to 99%. Adherence differed only slightly between older and newer guidelines and between recommendations with low, moderate or high levels of evidence (range 79-84% and 77-91%, respectively), while adherence differed more between recommendations for different cancer types (range 54-99%), different treatment modalities (adherence ranged from 40 to 92%) or recommendations that advised against or recommended in favour of particular treatment (adherence ranged from 75 to 98%). Conclusion: We found significant variation in adherence between different cancer treatment guidelines. While some guideline characteristics that seem to explain this variation may be considered difficult to modify, the potential for variance across cancer types and treatment modalities suggests that adherence could be further improved. At the same time, these results warrant tailored strategies for the improvement of adherence to clinical practice guidelines.

Markedly increased incidence and improved survival of testicular cancer in the Netherlands.

BACKGROUND: Worldwide marked changes have been observed in the incidence and survival of testicular cancer (TC) during the last decades. We conducted a study on trends in TC incidence, treatment, survival, and mortality in the Netherlands during the period 1970-2009 with specific focus on trends according to age, histology and stage of disease. METHODS: Data from the Eindhoven cancer registry, the Netherlands cancer registry and Statistics Netherlands was used. Age-standardized incidence and mortality rates and five-year relative survival were calculated. Treatment was categorized into five major groups. RESULTS: TC incidence showed a substantial annual increase of 3.9% in the period 1989-2009. The incidence increased for all stages of both seminoma and non-seminoma TC. Stage distribution for the non-seminoma patients shifted towards more localized disease. Most patients received primary treatment according to the guidelines. Five-year relative survival improved (non-significantly) for most groups of stage and histology. TC mortality dropped sharply in the 1970s and 1980s and remained relatively stable thereafter. CONCLUSION: This study shows that incidence of TC has increased sharply in the Netherlands. Relative survival is high and improved in most disease stages. There is a growing demand for medical care of newly diagnosed TC patients and for the rapidly increasing number of prevalent TC patients.

Prevalence of multiple malignancies in the Netherlands in 2007.

As the number of cancer survivors increases in the Netherlands, there is a concomitant increase in patients with multiple malignancies (MMs), the prevalence of which needs to be assessed to estimate care needs. This study analyzed incidence data on all malignant cancers diagnosed between 1989 and 2006 retrieved from the population-based Netherlands Cancer Registry. The point prevalence of MMs was determined on January 1, 2007. Of all cancer survivors in 2007, 30,064 (7% of the total) were patients with MMs. Their median age was 74 (interquartile range 71-76) years. Ninety two percent (i.e., 27,660) of these patients had two cancer diagnoses. The most common subsequent cancers being squamous cell skin cancer (5,468), colorectal cancer (4,634), and breast cancer (3,959). High frequency of combinations included: (i) female breast and genital cancers (any order), (ii) urinary tract and prostate cancers (any order), (iii) Hodgkin's lymphoma and subsequent female breast cancer and (iv) non-Hodgkin's lymphoma and subsequent squamous cell skin cancer. As the number of cancer survivors continues to increase and their survival improves, MMs are becoming more important in the field of cancer surveillance.

Dietary fat and risk of colon and rectal cancer with aberrant MLH1 expression, APC or KRAS genes.

OBJECTIVE: To investigate baseline fat intake and the risk of colon and rectal tumors lacking MLH1 (mutL homolog 1, colon cancer, nonpolyposis type 2) repair gene expression and harboring mutations in the APC (adenomatous polyposis coli) tumor suppressor gene and in the KRAS (v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog) oncogene. METHODS: After 7.3 years of follow-up of the Netherlands Cohort Study (n = 120,852), adjusted incidence rate ratios (RR) and 95% confidence intervals (CI) were computed, based on 401 colon and 130 rectal cancer patients. RESULTS: Total, saturated and monounsaturated fat were not associated with the risk of colon or rectal cancer, or different molecular subgroups. There was also no association between polyunsaturated fat and the risk of overall or subgroups of rectal cancer. Linoleic acid, the most abundant polyunsaturated fatty acid in the diet, was associated with increased risk of colon tumors with only a KRAS mutation and no additional truncating APC mutation or lack of MLH1 expression (RR = 1.41, 95% CI 1.18-1.69 for one standard deviation (i.e., 7.5 g/day) increase in intake, p-trend over the quartiles of intake <0.001). Linoleic acid intake was not associated with risk of colon tumors without any of the gene defects, or with tumors harboring aberrations in either MLH1 or APC. CONCLUSION: Linoleic acid intake is associated with colon tumors with an aberrant KRAS gene, but an intact APC gene and MLH1 expression, suggesting a unique etiology of tumors with specific genetic aberrations.

Meat and fish consumption, APC gene mutations and hMLH1 expression in colon and rectal cancer: a prospective cohort study (The Netherlands).

OBJECTIVE: The aim of this study was to investigate the associations between meat and fish consumption and APC mutation status and hMLH1 expression in colon and rectal cancer. METHODS: The associations were investigated in the Netherlands Cohort Study, and included 434 colon and 154 rectal cancer patients on whom case-cohort analyses (subcohort n = 2948) were performed. RESULTS: Total meat consumption was not associated with the endpoints studied. Meat product (i.e. processed meat) consumption showed a positive association with colon tumours harbouring a truncating APC mutation, whereas beef consumption was associated with an increased risk of colon tumours without a truncating APC mutation (incidence rate ratio (RR) highest versus lowest quartile of intake 1.61, 95% confidence interval (CI) 0.96-2.71, p-trend = 0.04 and 1.58, 95% CI 1.10-2.25, p-trend = 0.01, respectively). Consumption of other meat (horsemeat, lamb, mutton, frankfurters and deep-fried meat rolls) was associated with an increased risk of rectal cancer without a truncating APC mutation (RR intake versus no intake 1.79, 95% CI 1.10-2.90). No associations were observed for meat consumption and tumours lacking hMLH1 expression. CONCLUSIONS: Our data indicate that several types of meat may contribute differently to the aetiology of colon and rectal cancer, depending on APC mutation status but not hMLH1 expression of the tumour.

Dietary folate intake and k-ras mutations in sporadic colon and rectal cancer in The Netherlands Cohort Study.

We studied the association between dietary folate and specific K-ras mutations in colon and rectal cancer in The Netherlands Cohort Study on diet and cancer. After 7.3 years of follow-up, 448 colon and 160 rectal cancer patients and 3,048 sub-cohort members (55-69 years at baseline) were available for data analyses. Mutation analysis of the K-ras gene was carried out on all archival adenocarcinoma specimens. Case-cohort analyses were used to compute adjusted incidence rate ratios (RR) and 95% confidence intervals (CI) for colon and rectal cancer overall and for K-ras mutation status subgroups according to 100 mug/day increased intake in dietary folate. Dietary folate intake was not significantly associated with colon cancer risk for men or women, neither overall nor with K-ras mutation status. For rectal cancer, folate intake was associated with a decreased disease risk in men and was most pronounced for K-ras mutated tumors, whereas an increased association was observed for women. Regarding the K-ras mutation status in women, an increased association was observed for both wild-type and mutated K-ras tumors. Specifically, folate intake was associated with an increased risk of G>T and G>C transversions in rectal tumors (RR = 2.69, 95% CI = 1.43-5.09), but inversely associated with G>A transitions (RR = 0.08, 95% CI = 0.01-0.53). Our data suggest that the effect of folate on rectal cancer risk is different for men and women and depends on the K-ras mutation status of the tumor.