In a predominantly biomedical healthcare model focused on cure, providing optimal, person-centred palliative care is challenging. The general public, patients, and healthcare professionals are often ...unaware of palliative care's benefits. Poor interdisciplinary teamwork and limited communication combined with a lack of early identification of patients with palliative care needs contribute to sub-optimal palliative care provision. We aimed to develop a national quality framework to improve availability and access to high-quality palliative care in a mixed generalist-specialist palliative care model. We hypothesised that a whole-sector approach and a modified Delphi technique would be suitable to reach this aim. Analogous to the international AGREE guideline criteria and employing a whole-sector approach, an expert panel comprising mandated representatives for patients and their families, various healthcare associations, and health insurers answered the main question: 'What are the elements defining high-quality palliative care in the Netherlands?'. For constructing the quality framework, a bottleneck analysis of palliative care provision and a literature review were conducted. Six core documents were used in a modified Delphi technique to build the framework with the expert panel, while stakeholder organisations were involved and informed in round-table discussions. In the entire process, preparing and building relationships took one year and surveying, convening, discussing content, consulting peers, and obtaining final consent from all stakeholders took 18 months. A quality framework, including a glossary of terms, endorsed by organisations representing patients and their families, general practitioners, elderly care physicians, medical specialists, nurses, social workers, psychologists, spiritual caregivers, and health insurers was developed and annexed with a summary for patients and families. We successfully developed a national consensus-based patient-centred quality framework for high-quality palliative care in a mixed generalist-specialist palliative care model. A whole-sector approach and a modified Delphi technique are feasible structures to achieve this aim. The process we reported may guide other countries in their initiatives to enhance palliative care.
Half the patients with acute myeloid leukemia (AML) who achieve complete remission (CR), ultimately relapse. Residual treatment-surviving leukemia is considered responsible for the outgrowth of AML. ...In many retrospective studies, detection of minimal residual disease (MRD) has been shown to enable identification of these poor-outcome patients by showing its independent prognostic impact. Most studies focus on molecular markers or analyze data in retrospect. This study establishes the value of immunophenotypically assessed MRD in the context of a multicenter clinical trial in adult AML with sample collection and analysis performed in a few specialized centers.
In adults (younger than age 60 years) with AML enrolled onto the Dutch-Belgian Hemato-Oncology Cooperative Group/Swiss Group for Clinical Cancer Research Acute Myeloid Leukemia 42A study, MRD was evaluated in bone marrow samples in CR (164 after induction cycle 1, 183 after cycle 2, 124 after consolidation therapy).
After all courses of therapy, low MRD values distinguished patients with relatively favorable outcome from those with high relapse rate and adverse relapse-free and overall survival. In the whole patient group and in the subgroup with intermediate-risk cytogenetics, MRD was an independent prognostic factor. Multivariate analysis after cycle 2, when decisions about consolidation treatment have to be made, confirmed that high MRD values (> 0.1% of WBC) were associated with a higher risk of relapse after adjustment for consolidation treatment time-dependent covariate risk score and early or later CR.
In future treatment studies, risk stratification should be based not only on risk estimation assessed at diagnosis but also on MRD as a therapy-dependent prognostic factor.
Adolescents and young adults (AYAs) occupy a unique place within the hematologic malignancy community due to the challenges they face related to their disease biology and physical, psychosocial, and ...economic circumstances, as well as issues related to access to care and long-term follow-up. Efforts to define age-specific (supportive) care needs and targets for intervention in these areas are evolving. This review discusses the psychosocial issues AYAs with hematologic malignancies are dealing with, how these might affect their health-related quality of life, and the challenges in delivering high-quality supportive care to this underserved population.
We conducted an international, randomized, phase III trial to evaluate the efficacy and safety of consolidation with yttrium-90 ((90)Y)-ibritumomab tiuxetan in patients with advanced-stage follicular ...lymphoma in first remission.
Patients with CD20(+) stage III or IV follicular lymphoma, who achieved a complete response (CR)/unconfirmed CR (CRu) or partial response (PR) after first-line induction treatment, were randomly assigned to receive (90)Y-ibritumomab tiuxetan (rituximab 250 mg/m(2) on day -7 and day 0 followed on day 0 by (90)Y-ibritumomab tiuxetan 14.8 MBq/kg; maximum of 1,184 MBq) or no further treatment (control). The primary end point was progression-free survival (PFS), which was calculated from the time of random assignment.
A total of 414 patients (consolidation, n = 208; control, n = 206) were enrolled at 77 centers. (90)Y-ibritumomab tiuxetan consolidation significantly prolonged median PFS (after a median observation time of 3.5 years) in all patients (36.5 v 13.3 months in control arm; hazard ratio HR = 0.465; P < .0001) and regardless of whether patients achieved PR (29.3 v 6.2 months in control arm; HR = 0.304; P < .0001) or CR/CRu (53.9 v 29.5 months in control arm; HR = 0.613; P = .0154) after induction treatment. Median PFS with consolidation was prolonged in all Follicular Lymphoma International Prognostic Index risk subgroups. After (90)Y-ibritumomab tiuxetan consolidation, 77% of patients in PR after induction converted to CR/CRu, resulting in a final CR rate of 87%. The most common toxicity with (90)Y-ibritumomab tiuxetan was hematologic, and grade 3 or 4 infections occurred in 8% of patients.
Consolidation of first remission with (90)Y-ibritumomab tiuxetan in advanced-stage follicular lymphoma is highly effective with no unexpected toxicities, prolonging PFS by 2 years and resulting in high PR-to-CR conversion rates regardless of type of first-line induction treatment.
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.
The treatment of acute myeloid leukemia (AML) in first relapse is associated with unsatisfactory rates of complete responses that usually are short lived. Therefore, a clinically useful prognostic ...index can facilitate therapeutic decision making and evaluation of investigational treatment strategies at relapse of AML.
A prognostic score is presented based on the multivariate analysis of 667 AML patients in first relapse among 1,540 newly diagnosed non-M3 AML patients (age 15 to 60 years) entered onto three successive Dutch-Belgian Hemato-Oncology Cooperative Group and the Swiss Group for Clinical Cancer Research Collaborative Group trials.
Four clinically relevant parameters are included in this index (ie, length of relapse-free interval after first complete remission, cytogenetics at diagnosis, age at relapse, and whether previous stem-cell transplantation was performed). Using this stratification system, three risk groups were defined: a favorable prognostic group A (overall survival OS of 70% at 1 year and 46% at 5 years), an intermediate-risk group B (OS of 49% at 1 year and 18% at 5 years), and a poor-risk group C (OS of 16% at 1 year and 4% at 5 years).
The prognostic index estimates the outcome of AML patients in first relapse using four commonly applied clinical parameters and might identify patients who are candidates for salvage and investigational therapy.
We report the results of a prospective, randomized phase 3 trial evaluating autologous peripheral blood stem cell transplantation (ASCT) versus intensive consolidation chemotherapy in newly diagnosed ...AML patients in complete remission (CR1). Patients with AML (16-60 years) in CR1 after 2 cycles of intensive chemotherapy and not eligible for allogeneic SCT were randomized between intensive chemotherapy with etoposide and mitoxantrone or ASCT ater high-dose cyclophosphamide and busulfan. Of patients randomized (chemotherapy, n = 259; ASCT, n = 258), more than 90% received their assigned treatment. The 2 groups were comparable with regard to prognostic factors. The ASCT group showed a markedly reduced relapse rate (58% vs 70%, P = .02) and better relapse-free survival at 5 years (38% vs 29%, P = .065, hazard ratio = 0.82; 95% confidence interval, 0.66-1.1) with nonrelapse mortality of 4% versus 1% in the chemotherapy arm (P = .02). Overall survival was similar (44% vs 41% at 5 years, P = .86) because of more opportunities for salvage with second-line chemotherapy and stem cell transplantation in patients relapsing on the chemotherapy arm. This large study shows a relapse advantage for ASCT as postremission therapy but similar survival because more relapsing patients on the chemotherapy arm were salvaged with a late transplantation for relapse. This trial is registered at www.trialregister.nl as #NTR230 and #NTR291.
Many cancer survivors are facing difficulties in getting a life insurance; raised premiums and declinatures are common. We generated a prediction model estimating the conditional extra mortality risk ...of breast cancer patients in the Netherlands. This model can be used by life insurers to accurately estimate the additional risk of an individual patient, conditional on the years survived.
All women diagnosed with stage I-III breast cancer in 2005-2006, treated with surgery, were selected from the Netherlands Cancer Registry. For all stages separately, multivariable logistic regression was used to estimate annual mortality risks, conditional on the years survived, until 10 years after diagnosis, resulting in 30 models. The conditional extra mortality risk was calculated by subtracting mortality rates of the general Dutch population from the patient mortality rates, matched by age, gender and year. The final model was internally and externally validated, and tested by life insurers.
We included 23,234 patients: 10,101 stage I, 9,868 stage II and 3,265 stage III. The final models included age, tumor stage, nodal stage, lateralization, location within the breast, grade, multifocality, hormonal receptor status, HER2 status, type of surgery, axillary lymph node dissection, radiotherapy, (neo)adjuvant systemic therapy and targeted therapy. All models showed good calibration and discrimination. Testing of the model by life insurers showed that insurability using the newly-developed model increased with 13%, ranging from 0%-24% among subgroups.
The final model provides accurate conditional extra mortality risks of breast cancer patients, which can be used by life insurers to make more reliable calculations. The model is expected to increase breast cancer patients' insurability and transparency among life insurers.
The Dutch-Belgian Hemato-Oncology Cooperative Group and the Swiss Group for Clinical Cancer Research (HOVON-SAKK) collaborative study group evaluated outcome of patients (pts) with acute myeloid ...leukemia (AML) in first remission (CR1) entered in 3 consecutive studies according to a donor versus no-donor comparison. Between 1987 and 2004, 2287 pts were entered in these studies of whom 1032 pts (45%) without FAB M3 or t(15;17) were in CR1 after 2 cycles of chemotherapy, received consolidation treatment, and were younger than 55 years of age and therefore eligible for allogeneic hematopoietic stem cell transplantation (allo-SCT). An HLA-identical sibling donor was available for 326 pts (32%), whereas 599 pts (58%) lacked such a donor, and information was not available in 107 pts. Compliance with allo-SCT was 82% (268 of 326). Cumulative incidences of relapse were, respectively, 32% versus 59% for pts with versus those without a donor (P < .001). Despite more treatment-related mortality (TRM) in the donor group (21% versus 4%, P < .001), disease-free survival (DFS) appeared significantly better in the donor group (48% ± 3% versus 37% ± 2% in the no-donor group, P < .001). Following risk-group analysis, DFS was significantly better for pts with a donor and an intermediate- (P = .01) or poor-risk profile (P = .003) and also better in pts younger than 40 years of age (P < .001). We evaluated our results and those of the previous MRC, BGMT, and EORTC studies in a meta-analysis, which revealed a significant benefit of 12% in overall survival (OS) by donor availability for all patients with AML in CR1 without a favorable cytogenetic profile.
•Three cases with self-reported healing after prayer demonstrated mismatches between subjective experiences and objective findings.•No measurable improvements were found in audiological testing ...methods, but in-depth interviews, hetero-anamnesis and a validated questionnaire all confirmed the healings.•A paradox was noticed: ‘objective’ measurements did not reflect hearing abilities in daily life whereas ‘subjective’ experiential data did.•The mismatches were not well understood, but they do raise questions about high-low distinctions in science between ‘objective’ and ‘subjective’ data.•The healing experiences of the participants involved their entire being with profound positive effects in different domains of their lives, and a perception of a benevolent God. Labeled as healings of ‘mind, soul and body‘.
to enhance the understanding of documented mismatches between ‘subjective’ experiences and ‘objective’ data in three cases of self-reported instantaneous healing of hearing impairment upon prayer.
description of three cases taken out of a larger retrospective case-based study of prayer healing in the Netherlands. In this larger study multiple reported healings were investigated using both medical files and patients’ narratives through in-depth interviews. A subset of three cases with dramatic subjective reduction of hearing impairment upon prayer was studied. These patients underwent extensive additional investigations at the audiology center of the Amsterdam University Medical Centre. All data was evaluated by an interdisciplinary medical assessment team, subsequent analysis was transdisciplinary.
the three case histories with self-reported healing after prayer demonstrated a clear mismatch between subjective experiences and objective findings. No measurable improvements were found in four different audiological testing methods. However, in-depth interviews, hetero-anamnesis and a validated questionnaire all confirmed the healings. The medical assessment team could not label these healings as ‘medically remarkable’ because of absence of measurable ‘objective’ changes, but they did consider them as ‘remarkable in a broader sense’. On expert consultation no equivalents of mismatches to this extent could be found. The healing experiences of our participants involved their entire being with profound positive effects in different domains of their lives, and a perception of a benevolent God who acted upon them. There was a distinctive pattern, labelled by the participants as a healing of mind, soul and body.
The subjective-objective incongruities that were found were not well understood. We noticed a paradox: the ‘objective’ measurements did not reflect hearing abilities in daily life where-as ‘subjective experiential’ data did. The latter could be ‘objectified’ and validated in various ways. In fact, a rigid distinction between ‘objective’ and ‘subjective’ was not relevant here, nor a hierarchy among them. A model leaving room for different causations (horizontal epistemology) complied best with the multi dimensionality we came across.
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