Comparative effectiveness of 6x R-CHOP21 versus 6x R-CHOP21 + 2 R for patients with advanced-stage diffuse large B-cell lymphoma

First-line treatment for advanced-stage diffuse large B-cell lymphoma (DLBCL) typically involves 6x R-CHOP21 or 6x R-CHOP21 with two additional rituximab administrations (6x R-CHOP21 + 2 R). In contemporary practice, this treatment choice might be guided by interim PET scan results. This nationwide, population-based study investigates the comparative effectiveness of these treatment regimens in an era where interim PET-guided treatment decisions were not standard practice. Utilizing the Netherlands Cancer Registry, we identified 1577 adult patients diagnosed with advanced-stage DLBCL between 2014–2018 who completed either 6x R-CHOP21 (43%) or 6x R-CHOP21 + 2 R (57%). We used propensity scores to assess differences in event-free survival (EFS) and overall survival (OS). At five years, EFS (hazard ratio of 6x R-CHOP21 + 2 R versus 6x R-CHOP21 [HR] = 0.89; 95% confidence interval [CI], 0.72–1.09) and OS (HR = 0.93; 95% CI, 0.73–1.18) were not significantly different between both regimens. In exploratory risk-stratified analysis according to the International Prognostic Index (IPI), high-IPI patients (i.e., scores of 4-5) benefit most from 6x R-CHOP21 + 2 R (5-year absolute risk difference of EFS = 16.8%; 95% CI, −0.4%−34.1% and OS = 12.1%; 95% CI, −5.4–29.6%). Collectively, this analysis reveals no significant differences on average in EFS and OS between the two treatments. However, the potential benefits for high-risk patients treated with 6x R-CHOP21 + 2 R underscore the need for future research.</p

Regional disparities in the use of intensive chemotherapy for AML in the Netherlands:Does it influence survival?

Objective Acute myeloid leukaemia (AML) prognosis is enhanced with intensive remission induction chemotherapy (ICT) in eligible patients. However, ICT eligibility perceptions may differ among healthcare professionals. This nationwide, population-based study aimed to explore regional variation in ICT application and its relation with overall survival (OS). Methods and analysis We compared nine Dutch regional networks using data from the Netherlands Cancer Registry. Regional variance was assessed for the entire population and age subgroups (ie, ≤60 years and &gt;60 years) using multivariable mixed effects logistic and Cox proportional hazard regression analyses, expressed via median OR (MOR) and median HR (MHR). Results Including all adult AML patients from 2014 to 2018 (N=4060 patients; 58% males; median age, 70 years), 1761 (43%) received ICT. ICT application varied from 36% to 57% (MOR 1.36 (95% CI 1.11 to 1.58)) across regions, with minor variations for patients aged ≤60 years (MOR 1.16 (95% CI 1.00 to 1.40)) and more extensive differences for those aged &gt;60 years (MOR 1.43 (95% CI 1.16 to 1.63)). Median OS spanned 4.9-8.4 months across regions (MHR 1.11 (95% CI 1.00 to 1.15)), with pronounced differences in older patients (MHR 1.12 (95% CI 1.08 to 1.20)) but negligible differences in the younger group (MHR 1.02 (95% CI 1.00 to 1.14)). Survival differences for the total population and the older patients decreased to respectively, MHR 1.09 (95% CI 1.00 to 1.13) and 1.10 (95% CI 1.04 to 1.18), after additional adjustment for the probability of receiving ICT within a region, indicating approximately 10% unexplained differences. Conclusion Regional disparities in ICT application and survival exist, especially in older AML patients. However, ICT application differences partially explain survival disparities, indicating the need for more standardised ICT eligibility criteria and a better understanding of underlying causes of outcome disparities.</p

Doxorubicin Exposure and Breast Cancer Risk in Survivors of Adolescent and Adult Hodgkin Lymphoma

PURPOSEFemale Hodgkin lymphoma (HL) survivors treated with chest radiotherapy (RT) at a young age have a strongly increased risk of breast cancer (BC). Studies in childhood cancer survivors have shown that doxorubicin exposure may also increase BC risk. Although doxorubicin is the cornerstone of HL chemotherapy, the association between doxorubicin and BC risk has not been examined in HL survivors treated at adult ages.METHODSWe assessed BC risk in a cohort of 1,964 female 5-year HL survivors, treated at age 15-50 years in 20 Dutch hospitals between 1975 and 2008. We calculated standardized incidence ratios, absolute excess risks, and cumulative incidences. Doxorubicin exposure was analyzed using multivariable Cox regression analyses.RESULTSAfter a median follow-up of 21.6 years (IQR, 15.8-27.1 years), 252 women had developed invasive BC or ductal carcinoma in situ. The 30-year cumulative incidence was 20.8% (95% CI, 18.2 to 23.4). Survivors treated with a cumulative doxorubicin dose of &gt;200 mg/m2 had a 1.5-fold increased BC risk (95% CI, 1.08 to 2.1), compared with survivors not treated with doxorubicin. BC risk increased 1.18-fold (95% CI, 1.05 to 1.32) per additional 100 mg/m2 doxorubicin (Ptrend =.004). The risk increase associated with doxorubicin (yes v no) was not modified by age at first treatment (hazard ratio [HR]age &lt;21 years, 1.5 [95% CI, 0.9 to 2.6]; HRage ≥21 years, 1.3 [95% CI, 0.9 to 1.9) or chest RT (HRwithout mantle/axillary field RT, 1.9 [95% CI, 1.06 to 3.3]; HRwith mantle/axillary field RT, 1.2 [95% CI, 0.8 to 1.8]).CONCLUSIONThis study shows that treatment with doxorubicin is associated with increased BC risk in both adolescent and adult HL survivors. Our results have implications for BC surveillance guidelines for HL survivors and treatment strategies for patients with newly diagnosed HL.</p

Doxorubicin Exposure and Breast Cancer Risk in Survivors of Adolescent and Adult Hodgkin Lymphoma

PURPOSEFemale Hodgkin lymphoma (HL) survivors treated with chest radiotherapy (RT) at a young age have a strongly increased risk of breast cancer (BC). Studies in childhood cancer survivors have shown that doxorubicin exposure may also increase BC risk. Although doxorubicin is the cornerstone of HL chemotherapy, the association between doxorubicin and BC risk has not been examined in HL survivors treated at adult ages.METHODSWe assessed BC risk in a cohort of 1,964 female 5-year HL survivors, treated at age 15-50 years in 20 Dutch hospitals between 1975 and 2008. We calculated standardized incidence ratios, absolute excess risks, and cumulative incidences. Doxorubicin exposure was analyzed using multivariable Cox regression analyses.RESULTSAfter a median follow-up of 21.6 years (IQR, 15.8-27.1 years), 252 women had developed invasive BC or ductal carcinoma in situ. The 30-year cumulative incidence was 20.8% (95% CI, 18.2 to 23.4). Survivors treated with a cumulative doxorubicin dose of &gt;200 mg/m2 had a 1.5-fold increased BC risk (95% CI, 1.08 to 2.1), compared with survivors not treated with doxorubicin. BC risk increased 1.18-fold (95% CI, 1.05 to 1.32) per additional 100 mg/m2 doxorubicin (Ptrend =.004). The risk increase associated with doxorubicin (yes v no) was not modified by age at first treatment (hazard ratio [HR]age &lt;21 years, 1.5 [95% CI, 0.9 to 2.6]; HRage ≥21 years, 1.3 [95% CI, 0.9 to 1.9) or chest RT (HRwithout mantle/axillary field RT, 1.9 [95% CI, 1.06 to 3.3]; HRwith mantle/axillary field RT, 1.2 [95% CI, 0.8 to 1.8]).CONCLUSIONThis study shows that treatment with doxorubicin is associated with increased BC risk in both adolescent and adult HL survivors. Our results have implications for BC surveillance guidelines for HL survivors and treatment strategies for patients with newly diagnosed HL.</p

Regional disparities in the use of intensive chemotherapy for AML in the Netherlands: Does it influence survival?

Objective Acute myeloid leukaemia (AML) prognosis is enhanced with intensive remission induction chemotherapy (ICT) in eligible patients. However, ICT eligibility perceptions may differ among healthcare professionals. This nationwide, population-based study aimed to explore regional variation in ICT application and its relation with overall survival (OS). Methods and analysis We compared nine Dutch regional networks using data from the Netherlands Cancer Registry. Regional variance was assessed for the entire population and age subgroups (ie, ≤60 years and >60 years) using multivariable mixed effects logistic and Cox proportional hazard regression analyses, expressed via median OR (MOR) and median HR (MHR). Results Including all adult AML patients from 2014 to 2018 (N=4060 patients; 58% males; median age, 70 years), 1761 (43%) received ICT. ICT application varied from 36% to 57% (MOR 1.36 (95% CI 1.11 to 1.58)) across regions, with minor variations for patients aged ≤60 years (MOR 1.16 (95% CI 1.00 to 1.40)) and more extensive differences for those aged >60 years (MOR 1.43 (95% CI 1.16 to 1.63)). Median OS spanned 4.9-8.4 months across regions (MHR 1.11 (95% CI 1.00 to 1.15)), with pronounced differences in older patients (MHR 1.12 (95% CI 1.08 to 1.20)) but negligible differences in the younger group (MHR 1.02 (95% CI 1.00 to 1.14)). Survival differences for the total population and the older patients decreased to respectively, MHR 1.09 (95% CI 1.00 to 1.13) and 1.10 (95% CI 1.04 to 1.18), after additional adjustment for the probability of receiving ICT within a region, indicating approximately 10% unexplained differences. Conclusion Regional disparities in ICT application and survival exist, especially in older AML patients. However, ICT application differences partially explain survival disparities, indicating the need for more standardised ICT eligibility criteria and a better understanding of underlying causes of outcome disparities

Doxorubicin Exposure and Breast Cancer Risk in Survivors of Adolescent and Adult Hodgkin Lymphoma

PURPOSEFemale Hodgkin lymphoma (HL) survivors treated with chest radiotherapy (RT) at a young age have a strongly increased risk of breast cancer (BC). Studies in childhood cancer survivors have shown that doxorubicin exposure may also increase BC risk. Although doxorubicin is the cornerstone of HL chemotherapy, the association between doxorubicin and BC risk has not been examined in HL survivors treated at adult ages.METHODSWe assessed BC risk in a cohort of 1,964 female 5-year HL survivors, treated at age 15-50 years in 20 Dutch hospitals between 1975 and 2008. We calculated standardized incidence ratios, absolute excess risks, and cumulative incidences. Doxorubicin exposure was analyzed using multivariable Cox regression analyses.RESULTSAfter a median follow-up of 21.6 years (IQR, 15.8-27.1 years), 252 women had developed invasive BC or ductal carcinoma in situ. The 30-year cumulative incidence was 20.8% (95% CI, 18.2 to 23.4). Survivors treated with a cumulative doxorubicin dose of >200 mg/m2 had a 1.5-fold increased BC risk (95% CI, 1.08 to 2.1), compared with survivors not treated with doxorubicin. BC risk increased 1.18-fold (95% CI, 1.05 to 1.32) per additional 100 mg/m2 doxorubicin (Ptrend =.004). The risk increase associated with doxorubicin (yes v no) was not modified by age at first treatment (hazard ratio [HR]age <21 years, 1.5 [95% CI, 0.9 to 2.6]; HRage ≥21 years, 1.3 [95% CI, 0.9 to 1.9) or chest RT (HRwithout mantle/axillary field RT, 1.9 [95% CI, 1.06 to 3.3]; HRwith mantle/axillary field RT, 1.2 [95% CI, 0.8 to 1.8]).CONCLUSIONThis study shows that treatment with doxorubicin is associated with increased BC risk in both adolescent and adult HL survivors. Our results have implications for BC surveillance guidelines for HL survivors and treatment strategies for patients with newly diagnosed HL

Conditional relative survival in Waldenström’s macroglobulinaemia: a population-based study in The Netherlands

Contemporary diagnosed WM patients, compared to the general population, continue to experience excess mortality regardless of having survived up to 15 years post-diagnosis. This gradual increase in excess mortality might result from the incurable nature of this disease characterized by multiple relapses throughout the disease course with limited efficacious treatment options in the released/refractory setting