Adults aged =80 years (the oldest-old) comprise the fastest growing age group in Western populations. Yet little is known about their cancer burden. In this nation-wide study, we assessed their... Show moreAdults aged =80 years (the oldest-old) comprise the fastest growing age group in Western populations. Yet little is known about their cancer burden. In this nation-wide study, we assessed their trends in incidence, treatment and survival over a 30-year period, and predicted their future cancer incidence. All 2 468 695 incident cancer cases during 1990 to 2019 were selected from the Netherlands Cancer Registry, of whom 386 611 were diagnosed in the oldest-old (16%). The incidence of the oldest-old was predicted until 2032. Net and overall survival (OS) were calculated. Patients were divided into four age groups (<80, 80-84, 85-89 and =90 years). The incidence of the oldest-old doubled between 1990 and 2019 and is expected to grow annually with 5% up to 2032. In virtually all cancers the share of oldest-old patients grew, but declined for prostate cancer (25% in 1990-1994 vs 13% in 2015-2019). The proportion of undetermined disease stage increased with age in most cancers. The application of systemic therapy increased, albeit less pronounced in the oldest-old than their younger counterparts (1990 vs 2019: 12%-34%, 3%-15%, 2%-7% and 1%-3% in <80, 80-84, 85-89 and =90 years old). Five-year OS of the oldest-old patients increased by 7 percentage points (to 26%) between 1990 to 1994 and 2015 to 2019 compared to 19 percentage points (to 63%) in <80 years old. The oldest-old cancer patients are a rapidly growing group who benefitted less from improvements in cancer treatment than younger patients, reflecting the multiple challenges faced in the care of the oldest-old. Show less
Straten, L. van der; Levin, M.D.; Dinnessen, M.A.W.; Visser, O.; Posthuma, E.F.M.; Doorduijn, J.K.; ... ; Dinmohamed, A.G. 2023
The longevity of patients with chronic lymphocytic leukemia (CLL) has improved progressively over the past decades, making it essential to understand long-term health outcomes, such as second... Show moreThe longevity of patients with chronic lymphocytic leukemia (CLL) has improved progressively over the past decades, making it essential to understand long-term health outcomes, such as second primary malignancies (SPMs). Therefore, this nationwide, population-based study assessed the risk of SPM development in CLL patients diagnosed during 1989-2019 in the Netherlands compared to the expected number of malignancies in an age-, sex-, and period-matched group from the general Dutch population. In 24,815 CLL patients followed for 162,698.49 person-years, 4369 SPMs were diagnosed with a standardized incidence ratio (SIR) of 1.63 (95% confidence interval [CI] 1.59-1.68). This elevated risk was observed for solid (SIR, 1.67; 95% CI, 1.65-1.75) and hematological SPMs (SIR 1.42; 95% CI, 1.24-1.62). The highest risk for SPMs was noted beyond five years post-diagnosis (SIR, 1.70; 95% CI, 1.62-1.77), for male individuals (SIR, 1.70; 95% CI, 1.64-1.77), and patients aged 18-69 years (SIR, 1.92; 95% CI, 1.79-2.05). The risk of SPMs was higher in CLL patients who received anti-neoplastic therapy (SIR, 2.12; 95% CI, 1.96-2.28), as compared with those who did not (SIR, 1.58; 95% CI, 1.53-1.63). Routine surveillance activities and tailored interventions to counteract the increased morbidity and excess mortality associated with SPMs are essential for improving long-term outcomes in CLL patients. Show less
Meeuwes, F.O.; Brink, M.; Poel, M.W.M. van der; Kersten, M.J.; Wondergem, M.; Mutsaers, P.G.N.J.; ... ; Nijland, M. 2022
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... Show moreBackground: 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. Sur-vival 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 pa-tients 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 multi -variable 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. 2022 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). Show less
Brink, M.; Meeuwes, F.O.; Poel, M.W.M. van der; Kersten, M.J.; Wondergem, M.; Mutsaers, P.G.N.J.; ... ; Nijland, M. 2022
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... Show morePatients 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. Show less
Leeuwen, R.W.F.V.; Comte, M. le; Reyners, A.K.L.; Tweel, A. van den; Vlijmen, B. van; Kwee, W.; ... ; Jansman, F.G.A. 2022
Drug-drug interactions (DDIs) with anticancer drugs are common and can significantly affect efficacy and toxicity of treatment. Therefore, a Dutch Multidisciplinary Expert group is assessing the... Show moreDrug-drug interactions (DDIs) with anticancer drugs are common and can significantly affect efficacy and toxicity of treatment. Therefore, a Dutch Multidisciplinary Expert group is assessing the clinical signifi-cance of DDIs in oncology and provides recommendations for the management of these DDIs. We present an overview of methodology and outcome of an evidence-and consensus-based assessment of DDIs be-tween anticancer drugs and non-anticancer drugs.A literature search was performed through PubMed and EMA and FDA assessment reports, to iden-tify potential DDI's involving anticancer drugs. For each potential DDI a concept report for risk analysis and practical advice for management was created. Subsequently, this risk analysis and the corresponding advice were assessed and weighed.A total of 290 potential DDIs have been identified in the literature thus far. Of these 290 potential DDIs, the Expert Group has identified 94 (32%) DDIs as clinically relevant, with a need for an automated alert and a suggested intervention. Furthermore, 110 DDIs have been identified as clinically not relevant. For 86 potential DDIs evidence supporting a relevant DDI was insufficient and in these cases neither an alert nor advice regarding a suggested intervention were formulated.A transparent risk analysis is presented for identification of clinically relevant DDIs with anticancer drugs. Integration of DDI guidelines into the national electronic prescribing system is essential to achieve optimal efficacy and minimal toxicity in patients receiving anticancer therapy. A clear overview of clin-ically relevant DDIs with anticancer therapy provides clinicians with a structured, evidence-based and consensus-built tool for anticancer therapy surveillance. (c) 2022 The Author(s). Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/) Show less
Background Among sarcomas, which are rare cancers, many types are exceedingly rare; however, a definition of ultra-rare cancers has not been established. The problem of ultra-rare sarcomas is... Show moreBackground Among sarcomas, which are rare cancers, many types are exceedingly rare; however, a definition of ultra-rare cancers has not been established. The problem of ultra-rare sarcomas is particularly relevant because they represent unique diseases, and their rarity poses major challenges for diagnosis, understanding disease biology, generating clinical evidence to support new drug development, and achieving formal authorization for novel therapies.Methods The Connective Tissue Oncology Society promoted a consensus effort in November 2019 to establish how to define ultra-rare sarcomas through expert consensus and epidemiologic data and to work out a comprehensive list of these diseases. The list of ultra-rare sarcomas was based on the 2020 World Health Organization classification, The incidence rates were estimated using the Information Network on Rare Cancers (RARECARENet) database and NETSARC (the French Sarcoma Network's clinical-pathologic registry). Incidence rates were further validated in collaboration with the Asian cancer registries of Japan, Korea, and Taiwan.Results It was agreed that the best criterion for a definition of ultra-rare sarcomas would be incidence. Ultra-rare sarcomas were defined as those with an incidence of approximately <= 1 per 1,000,000, to include those entities whose rarity renders them extremely difficult to conduct well powered, prospective clinical studies. On the basis of this threshold, a list of ultra-rare sarcomas was defined, which comprised 56 soft tissue sarcoma types and 21 bone sarcoma types.conclusions Altogether, the incidence of ultra-rare sarcomas accounts for roughly 20% of all soft tissue and bone sarcomas. This confirms that the challenges inherent in ultra-rare sarcomas affect large numbers of patients. Show less
Oud, J.A.; Evers, D.; Middelburg, R.A.; Vooght, K.M.K. de; Kerkhof, D. van de; Visser, O.; ... ; Zwaginga, J.J. 2020
Background Renal failure and renal replacement therapy (RRT) affect the immune system and could therefore modulate red blood cell (RBC) alloimmunization after transfusion.Study Design and Methods... Show moreBackground Renal failure and renal replacement therapy (RRT) affect the immune system and could therefore modulate red blood cell (RBC) alloimmunization after transfusion.Study Design and Methods We performed a nationwide multicenter case-control study within a source population of newly transfused patients between 2005 and 2015. Using conditional multivariate logistic regression, we compared first-time transfusion-induced RBC alloantibody formers (N = 505) with two nonalloimmunized recipients with similar transfusion burden (N = 1010).Results Renal failure was observed in 17% of the control and 13% of the case patients. A total of 41% of the control patients and 34% of case patients underwent acute RRT. Renal failure without RRT was associated with lower alloimmunization risks after blood transfusion (moderate renal failure: adjusted relative rate [RR], 0.82 [95% confidence interval (CI), 0.67-1.01]); severe renal failure, adjusted RR, 0.76 [95% CI, 0.55-1.05]). With severe renal failure patients mainly receiving RRT, the lowest alloimmunization risk was found in particularly these patients [adjusted RR 0.48 (95% CI 0.39-0.58)]. This was similar for patients receiving RRT for acute or chronic renal failure (adjusted RR, 0.59 [95% CI, 0.46-0.75]); and adjusted RR, 0.62 [95% CI 0.45-0.88], respectively).Conclusion These findings are indicative of a weakened humoral response in acute as well as chronic renal failure, which appeared to be most pronounced when treated with RRT. Future research should focus on how renal failure and RRT mechanistically modulate RBC alloimmunization. Show less
Patients with MYC-rearrangement positive large B-cell lymphoma (MYC+ LBCL) have an inferior prognosis following standard first-line therapy with rituximab, cyclophosphamide, doxorubicin,... Show morePatients with MYC-rearrangement positive large B-cell lymphoma (MYC+ LBCL) have an inferior prognosis following standard first-line therapy with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP) compared to patients withoutMYC rearrangement. Although intensive chemotherapy regimens yield higher remission rates, toxicity remains a concern. Lenalidomide is an oral immunomodulatory drug which downregulates MYC and its target genes thereby providing support using lenalidomide as additional therapeutic option for MYC+ LBCL. A phase II trial was conducted evaluating the efficacy of lenalidomide (15 mg day 1-14) in combination with R-CHOP (R2CHOP) in newly diagnosed MYC+ LBCL patients identified through a nationwide MYCFISH screening program. The primary endpoint was complete metabolic response (CMR) on centrally reviewed F-18-fluorodeoxyglucose (F-18-FDG) positron emission tomography (PET)-computer tomography (CT)-scan at end-of-treatment. Secondary endpoints were overall survival (OS), disease free survival (DFS) and event-free survival (EFS). Eighty-two patients with stage II-IV MYC+ LBCL were treated with six cycles of R2CHOP. At end of treatment, 67% (95% Confidence interval [CI]: 58-75) of the patients reached CMR. With a median follow-up of 25.4 months, 2-year estimates for OS, DFS, EFS were 73% (95% CI: 62-82), 75% (95% CI: 63-84) and 63% change to: (95% CI: 52-73) respectively. In this prospective trial for newly diagnosed MYC+ LBCL patients, we found that administering R2CHOP was safe, and yields comparable CMR and survival rates as in studies applying more intensive chemotherapy regimens. Hence, these findings offer new prospects for MYC+ LBCL patients and warrant comparison in prospective randomized clinical trials. This trial was registered at www.clinicaltrialsregister.eu (#2014-002654-39). Show less
IMPORTANCE Early plasma transfusion for women with severe postpartum hemorrhage (PPH) is recommended to prevent coagulopathy. However, there is no comparative, quantitative evidence on the... Show moreIMPORTANCE Early plasma transfusion for women with severe postpartum hemorrhage (PPH) is recommended to prevent coagulopathy. However, there is no comparative, quantitative evidence on the association of early plasma transfusion with maternal outcomes.OBJECTIVE To compare the incidence of adverse maternal outcomes among women who received plasma during the first 60 minutes of persistent PPH vs women who did not receive plasma for similarly severe persistent PPH.DESIGN, SETTING, AND PARTICIPANTS This multicenter cohort study used a consecutive sample of women with persistent PPH, defined as PPH refractory to first-line measures to control bleeding, between January 1, 2011, and January 1, 2013. Time-dependent propensity score matching was used to select women who received plasma during the first 60 minutes of persistent PPH and match each of them with a woman who had shown the same severity and received the same treatment of PPH but who had not received plasma at the moment of matching. Transfusions were not guided by coagulation tests. Statistical analysis was performed from June 2018 to June 2019.EXPOSURES Transfusion of plasma during the first 60 minutes of persistent PPH vs no or later plasma transfusion.MAIN OUTCOMES AND MEASURES Incidence of adverse maternal outcomes, defined as a composite of death, hysterectomy, or arterial embolization.RESULTS This study included 1216 women (mean [SD] age, 31.6 [5.0] years) with persistent PPH, of whom 932 (76.6%) delivered vaginally and 780 (64.1%) had PPH caused by uterine atony. Seven women (0.6%) died because of PPH, 62 women (5.1%) had a hysterectomy, and 159 women (13.1%) had arterial embolizations. Among women who received plasma during the first 60 minutes of persistent PPH, 114 women could be matched with a comparable woman who had not received plasma at the moment of matching. The incidence of adverse maternal outcomes was similar between the women, with adverse outcomes recorded in 24 women (21.2%) who received early plasma transfusion and 23 women (19.9%) who did not receive early plasma transfusion (odds ratio, 1.09; 95% CI, 0.57-2.09). Results of sensitivity analyses were comparable to the primary results.CONCLUSIONS AND RELEVANCE In this cohort study, initiation of plasma transfusion during the first 60 minutes of persistent PPH was not associated with adverse maternal outcomes compared with no or later plasma transfusion, independent of severity of PPH. Show less
Henriquez, D.D.C.A.; Gillissen, A.; Smith, S.M.; Cramer, R.A.; Akker, T. van den; Zwart, J.J.; ... ; TeMpOH-1 Study Grp 2019
Background The absence of a uniform and clinically relevant definition of severe postpartum haemorrhage hampers comparative studies and optimization of clinical management. The concept of... Show moreBackground The absence of a uniform and clinically relevant definition of severe postpartum haemorrhage hampers comparative studies and optimization of clinical management. The concept of persistent postpartum haemorrhage, based on refractoriness to initial first-line treatment, was proposed as an alternative to common definitions that are either based on estimations of blood loss or transfused units of packed red blood cells (RBC). We compared characteristics and outcomes of women with severe postpartum haemorrhage captured by these three types of definitions. Methods In this large retrospective cohort study in 61 hospitals in the Netherlands we included 1391 consecutive women with postpartum haemorrhage who received either >= 4 units of RBC or a multicomponent transfusion. Clinical characteristics and outcomes of women with severe postpartum haemorrhage defined as persistent postpartum haemorrhage were compared to definitions based on estimated blood loss or transfused units of RBC within 24 h following birth. Adverse maternal outcome was a composite of maternal mortality, hysterectomy, arterial embolisation and intensive care unit admission. Results One thousand two hundred sixty out of 1391 women (90.6%) with postpartum haemorrhage fulfilled the definition of persistent postpartum haemorrhage. The majority, 820/1260 (65.1%), fulfilled this definition within 1 h following birth, compared to 819/1391 (58.7%) applying the definition of >= 1 L blood loss and 37/845 (4.4%) applying the definition of >= 4 units of RBC. The definition persistent postpartum haemorrhage captured 430/471 adverse maternal outcomes (91.3%), compared to 471/471 (100%) for >= 1 L blood loss and 383/471 (81.3%) for >= 4 units of RBC. Persistent postpartum haemorrhage did not capture all adverse outcomes because of missing data on timing of initial, first-line treatment. Conclusion The definition persistent postpartum haemorrhage identified women with severe postpartum haemorrhage at an early stage of haemorrhage, unlike definitions based on blood transfusion. It also captured a large majority of adverse maternal outcomes, almost as large as the definition of >= 1 L blood loss, which is commonly applied as a definition of postpartum haemorrhage rather than severe haemorrhage. Show less
Teepen, J.C.; Kremer, L.C.; Heiden-van der Loo, M. van der; Tissing, W.J.; Pal, H.J. van der; Heuvel-Eibrink, M.M. van den; ... ; DCOG-LATER Study Grp 2019
Purpose Childhood cancer survivors are at increased risk of developing subsequent malignant neoplasms (SMNs). We compared survival and clinical characteristics of survivors with SMNs (sarcoma,... Show morePurpose Childhood cancer survivors are at increased risk of developing subsequent malignant neoplasms (SMNs). We compared survival and clinical characteristics of survivors with SMNs (sarcoma, breast cancer, or melanoma) and a population-based sample of similar first malignant neoplasm (FMN) patients. Methods We assembled three case series of solid SMNs observed in a cohort of 5-year Dutch childhood cancer survivors diagnosed 1963-2001 and followed until 2014: sarcoma (n = 45), female breast cancer (n = 41), and melanoma (n = 17). Each SMN patient was sex-, age-, and calendar year-matched to 10 FMN patients in the population-based Netherlands Cancer Registry. We compared clinical and histopathological characteristics by Fisher's exact tests and survival by multivariable Cox regression and competing risk regression analyses. Results Among sarcoma-SMN patients, overall survival [hazard ratio (HR) 1.88, 95% confidence interval (CI) 1.23-2.87] and sarcoma-specific mortality (HR 1.91, 95% CI 1.16-3.13) were significantly worse compared to sarcoma-FMN patients (foremost for soft-tissue sarcoma), with 15-year survival rates of 30.8% and 61.6%, respectively. Overall survival did not significantly differ for breast-SMN versus breast-FMN patients (HR 1.14, 95% CI 0.54-2.37), nor for melanoma-SMN versus melanoma-FMN patients (HR 0.71, 95% CI 0.10-5.00). No significant differences in tumor characteristics were observed between breast-SMN and breast-FMN patients. Breast-SMN patients were treated more often with mastectomy without radiotherapy/chemotherapy compared to breast-FMN patients (17.1% vs. 5.6%). Conclusions Survival of sarcoma-SMN patients is worse than sarcoma-FMN patients. Although survival and tumor characteristics appear similar for breast-SMN and breast-FMN patients, treatment differs; breast-SMN patients less often receive breast-conserving therapy. Larger studies are necessary to substantiate these exploratory findings. Show less
