Children with palliative care needs - the landscape of the nordic countries.

BACKGROUND: To strengthen palliative care for children in the Nordic countries, an updated status of current needs, resources, clinical services, education, and research is necessary to align and consolidate future research. A Nordic research collaboration initiative for children with palliative care needs was assembled in 2023. Building on this initiative, this paper presents an overview of pediatric palliative care (PPC) in the Nordic countries' (a) population characteristics, (b) care models and setting of care, (c) education and training, and (d) research. METHODS: The Nordic initiative researchers collaboratively gathered and assessed available data on the characteristics of PPC within Denmark, Finland, Greenland, Iceland, Norway, the Faroe Islands, Sweden, and Åland. Data were compiled in a matrix with population characteristics, models- and setting of care, education and training, and areas of research in a Nordic context. The findings are narratively and descriptively presented, providing an overview of Nordic PPC. RESULTS: In total, the Nordic child population comprises around six million children (0-19 years), of which about 41.200 are estimated to be living with a life-limiting and/or life-threatening condition. Healthcare services are provided through various care models, ranging from specialized care to homecare settings. Overall, there remain few opportunities for education and training with some exceptions. Also, Nordic research within PPC has been shown to be a growing field although much remains to be done. CONCLUSION: This overview is the first outline of the current PPC in Nordic countries. Although some differences remain important to acknowledge, overall, the strengths and challenges faced within PPC in the Nordic countries are comparable and call for joint action to increase evidence, services, and education to better serve the children, families, and healthcare personnel within PPC. Despite the varying structural premises for PPC, research endeavors aiming to provide evidence in this field seem increasing, timely and relevant for the Nordic countries, as well as the international context.

Treatment intensity affects immune reconstitution even after childhood cancer not treated with hematopoietic stem cell transplantation.

BACKGROUND: Only a few previous studies examine immune system recovery after completed cancer treatment. AIMS: The aim of this study was to analyze immune reconstitution after childhood cancer therapy in a non-hematopoietic stem cell transplantation setting. METHODS AND RESULTS: We analyzed children (N = 79) who received chemotherapy with/without irradiation for cancer diagnosed between 2014 and 2019 at Turku University Hospital, Finland. We retrospectively collected data on baseline parameters and post-treatment immunological recovery, namely neutrophil and lymphocyte counts, IgG levels, CD19, CD4 and natural killer cell counts. Immunological parameters were followed until their normalization. Treatment intensity was stratified according to the Intensity of Treatment Rating Scale (ITR-3). We analyzed the effects of treatment intensity on normalization of immunological parameters across the entire treatment range. Treatment intensity had a major effect on immune system recovery after completion of treatment. Most patients had normal immunological parameters 1-4 months post-treatment both in high- and low-intensity treatment groups, but patients classified in the high-intensity group had low parameters more often than patients in the low-intensity group. CONCLUSION: Our data suggest a fast recovery of studied immunological parameters after the majority of current pediatric oncologic treatments. Treatment for high-risk acute lymphoblastic leukemia, acute myeloid leukemia, medulloblastoma, and mature B-cell lymphoma was associated with prolonged recovery times for a substantial proportion of cases. High treatment intensity was associated with prolonged immunological recovery.

Use of electronic patient data storage for evaluating and setting the risk category of late effects in childhood cancer survivors.

BACKGROUND: Many of the late effects of cancer treatment in childhood may occur even decades after the treatment, and only a minority of the survivors remain as healthy as their peers. Providing appropriate long-term care for childhood cancer survivors after transition to primary health care is a challenge. Both survivors and primary care providers need information on potential late effects. The lack of a systematic late effect follow-up plan may lead to excessive use of health care services or delayed intervention. While manual compilation of individual follow-up plans is time consuming for experienced clinicians, electronic algorithms may be feasible. PROCEDURE: In Finland, international guidelines for determining the risk of late effects have been implemented. Nationally, Turku University Hospital was asked with developing an automatized system for calculating the risk of late effects, based on electronic patient records saved in the hospital data lake. An electronic algorithm that uses details from exposure-based health screening guidelines published by the Children's Oncology Group was created. The results were compared with those manually extracted by an experienced clinician. RESULTS: Significant concordance between the manual and algorithm-based risk classification was found. A total of 355 patients received a classification using the algorithm, and 325 of those matched with the manual categorization, producing a Cohen's coefficient of 0.91 (95% confidence interval 0.88-0.95). CONCLUSION: Automated algorithms can be used to categorize childhood cancer survivors efficiently and reliably into late effect risk groups. This further enables automatized compilation of appropriate individual late effect follow-up plan for all survivors.

Randomized controlled and double-blinded study of Caphosol versus saline oral rinses in pediatric patients with cancer.

BACKGROUND: Oral mucositis (OM) is a significant side effect of cancer treatment. The purpose of this study was to compare topically administered Caphosol to saline rinses in the prevention of mucositis in pediatric cancer patients. PROCEDURE: A controlled, double-blinded, and randomized clinical crossover study recruited patients between 2 to 17.99 years of age who were diagnosed with a malignancy and were receiving either high-dose methotrexate (≥1 g/m2 ), anthracycline, or cisplatin chemotherapy (NCT0280733). All patients received two 7-day cycles of the mouth rinses; that is, one cycle of Caphosol and one cycle of saline in a randomized order. Oral changes and symptoms were evaluated using the World Health Organisation (WHO) toxicity scale and the Children's International Mucositis Evaluation Scale (ChIMES). The primary endpoint was the frequency and severity of OM and oral symptoms. RESULTS: A total of 56 patients were recruited to the study, of whom 45 were randomized with a median age of 6.5 years (range 2.1-17.1 years). No cases of severe OM were observed. Grade ≥ 3 oral symptoms were present at least once in six (13%) patients during the Caphosol cycle and 13 (29%) patients during the saline cycle (P = .12). The peak of symptom scores was evident at around day 4-7 after administration of the chemotherapy with no marked differences between the rinse solutions. Multivariable regression analysis did not indicate a benefit of using Caphosol over the saline solution. CONCLUSIONS: No difference in prevention of oral mucositis was observed between the use of Caphosol or saline rinses.

Diseases of renal function and bone metabolism after treatment for early onset cancer: A registry-based study.

Modern cancer therapy has led to a growing number of pediatric and young adult cancer survivors, who are prone to increased morbidities caused by the late effects of therapy. The aim of our study was to investigate pediatric and young adult cancer survivors' morbidity due to renal and bone metabolism diseases and especially to study bone metabolism in cancer survivors with renal disease. Patients were identified from the Finnish Cancer Registry, and the cohort consisted of 13,860, 5-year survivors of cancer diagnosed below the age of 35 years. Healthy siblings were used as the comparison cohort. Information on the main outcomes was linked from the national Care Register for Health Care. Hazard ratios (HRs) comparing cancer survivors to siblings were calculated for various outcomes. The patient cohort was separated into two age groups, pediatric (0-19 years) and young adults (20-34 years). Significantly elevated HRs (p < 0.0001) in survivors were observed in both age groups for scoliosis (HR 1.6, 95% confidence interval [CI] 1.3-2.0), osteoporosis (HR 5.2, 95% CI 2.4-11.4), osteonecrosis (HR 12.7, 95% CI 5.4-29.7), nephritis (HR 1.9, 95% CI 1.5-2.2) and kidney failure (HR 3.6, 95% CI 2.4-5.3) for all. For cancer survivors with a renal outcome, the risk for developing any outcome of bone metabolism was increased (HR 2.3, 95% CI 1.4-3.6). These results show that pediatric and young adult cancer survivors have an elevated risk for long-term, adverse outcomes related to renal function and bone metabolism. These results suggest follow-up care for young cancer patients.

Use of endocrinological and neurological medication among 5-year survivors of young onset brain tumors.

The burden of late-effects for young onset brain tumor (BT) survivors needs more careful evaluation. Our aim was to assess the need for endocrinological and neurological medication among this specific group. We identified 5-year survivors diagnosed at the age of 0-24 years between 1988 and 2004 from the Finnish Cancer Registry (N = 602). Data on endocrinological and neurological drug purchases were collected from the Social Insurance Institution of Finland. Five years after diagnosis the most commonly purchased drugs had been: antiepileptics (44.8 %), systemic hydrocortisone (18.3 %), female sex hormones (17.6 %), thyroid hormones (11.2 %), and growth hormone (10.0 %). The survivors showed an increased hazard ratio (HR) for a need for new types of drugs still 5 years after diagnosis. Thyroid hormones (HR 10.6, 95 % CI 5.1-21.4), estrogens (HR 8.0, 95 % CI 2.1-25.7), and antiepileptics (HR 6.3, 95 % CI 3.4-11.2) were bought with high frequencies. Irradiation increased the hazard for drug-purchases other than antiepileptics. Cumulative incidence of purchases of estrogens or androgens increased still 15 years after diagnosis. The cumulative incidence of purchasing thyroid hormones and antiepileptics showed continuous increase for the youngest group, whereas survivors diagnosed at 15-24 years of age reached stable level before 15 years from diagnosis. The need for new medication continued more than a decade after BT diagnosis. Especially the need for new thyroid or sex hormone medication among childhood BT survivors may emerge long after diagnosis.

Late new morbidity in survivors of adolescent and young-adulthood brain tumors in Finland: a registry-based study.

BACKGROUND: Brain tumors (BTs) in adolescence and young adulthood (AYA) differ from those in childhood or late adulthood. However, research concerning late effects in this particular survivor group is limited. This study evaluates late morbidity of survivors diagnosed in AYAs. METHODS: We identified from the Finnish Cancer Registry all survivors diagnosed with BT at the ages 16-24 years between 1970 and 2004 (N = 315) and used data from the Hospital Discharge Registry to evaluate their late (≥5 y after diagnosis) morbidity requiring treatment in a specialized health care setting. A sibling cohort of BT patients diagnosed before the age of 25 years was used as a comparison cohort (N = 3615). RESULTS: The AYA BT survivors had an increased risk for late-appearing endocrine diseases (HR, 2.9; 95% CI, 1.1-8.0), psychiatric disorders (HR, 2.0; 95% CI, 1.2-3.2), diseases of the nervous system (HR, 9; 95% CI, 6.6-14.0), disorders of vision/hearing loss (HR, 3.6; 95% CI, 1.5-8.5), diseases of the circulatory system (HR, 4.9; 95% CI, 2.9-8.1), and diseases of the kidney (HR, 5.9; 95% CI, 2.5-14.1). Survivors with irradiation had an increased risk for diseases of the nervous system compared with non-irradiated survivors (HR, 3.3; 95% CI, 1.8-6.2). The cumulative prevalence for most of the diagnoses remained significantly increased for survivors even 20 years after cancer diagnosis. CONCLUSIONS: The AYA BT survivors have an increased risk of morbidity for multiple new outcomes for ≥5 years after their primary diagnosis. This emphasizes the need for structured late-effect follow-up for this patient group.

Late morbidity in long-term survivors of childhood brain tumors: a nationwide registry-based study in Finland.

BACKGROUND: The population of long-term survivors of childhood brain tumors (BTs) is growing. The aim of our study was to evaluate late-appearing morbidity in BT survivors. METHODS: Patients diagnosed with a BT at the age of 0-15 years between 1970 and 2004, and surviving at least 5 years, were identified from the Finnish Cancer Registry (n = 740). Their late new morbidity ≥ 5 years after cancer diagnosis was assessed using the Hospital Discharge Registry containing hospitalizations and outpatient visits in specialized health care settings. The morbidity of BT survivors was compared with that of the sibling cohort (n = 3615). RESULTS: The 5-year survivors had a significantly increased hazard ratio (HR) for endocrine diseases (HR, 14.7), psychiatric disorders (HR, 1.8), cognitive and developmental disorders (HR, 16.6), neurological diseases (HR, 9.8), disorders of vision and hearing (HR, 10.5), and diseases of the circulatory system (HR, 2.7) compared with the sibling cohort. The HRs for disorders of musculoskeletal system (HR, 1.4) and diseases of the kidney (HR, 2.1) were not significantly increased. Radiation treatment did not explain all of the excess morbidity. Female survivors had a higher risk for disorders of vision and hearing (P = .046). Age at diagnosis did not show an effect on HRs. The HRs for endocrine diseases and disorders of vision or hearing loss were highest for survivors treated in the 1980s or later. CONCLUSIONS: Pediatric BT survivors had significant neurocognitive consequences. This, together with the considerable risk for endocrine morbidity, will motivate us to organize systematic follow-up procedures for pediatric BT survivors.

[Solid tumors in children]. / Lasten kiinteät kasvaimet.

A quarter of cancers diagnosed in those under 18 years of age are leukemias, another quarter being tumors of the central nervous system. The remaining cancers are solid tumors occurring elswehere in the body, most commonly lymphomas, soft tissue and bone sarcomas, neuroblastomas and Wilms tumors. In almost all cases, the treatment of these solid tumors consists of combinations of surgery, cytotoxic drugs and radiotherapy. Although the prognoses have improved, they exhibit variation even within tumor groups. New targeted therapies are being developed, but for the time being they do not have any significant role.

Long-term follow-up of renal function after high-dose methotrexate treatment in children.

BACKGROUND: High-dose methotrexate (HD-MTX) is commonly used in treatment of pediatric leukemias and lymphomas. Transient deterioration in renal function is frequently noted during HD-MTX treatment, but possible long-term changes are less well known. In this study we aimed to study long-term renal prognosis after HD-MTX treatment, and to find possible underlying risk factors for reduced renal function. PROCEDURE: Medical records of pediatric cancer patients treated with HD-MTX were reviewed retrospectively after follow-up of 1-10 years. Renal function before and after chemotherapy was investigated in a total of 28 patients. Assessment of glomerular and tubular function was prospectively evaluated in each case. Glomerular function was evaluated by either (51)Cr-EDTA or (99m)Tc-DTPA clearance methods, and by urinary albumin excretion. Tubular function was assessed by measuring blood electrolyte levels and urinary alpha(1)- or beta(2)-microglobulin. RESULTS: A decrease in glomerular filtration rate (GFR) was statistically significant as follow-up time increased (P = 0.02). Age at the time of diagnosis and exposure to potentially nephrotoxic antibiotics during cancer treatment had no influence on GFR. However, albuminuria was observed more often in patients treated with amphotericin B or gentamycin (P = 0.04). No changes in tubular function were observed. CONCLUSIONS: Our results show that HD-MTX treatment significantly decreases GFR and may cause albuminuria in pediatric cancer patients several years after treatment. Long-term renal follow-up of these patients is therefore important.

Comparison of glomerular function tests in children with cancer.

Evaluation of renal function should be performed as part of the follow-up during and after chemotherapy in pediatric cancer patients. The aim of this study was to compare an isotope clearance method [isotope glomerular filtration rate (iGFR)] with alternative methods to determine GFR in such patients. Isotope GFR [(99m)Tc-labeled diethylene triaminopentoacetic acid (DTPA) or (51)Cr-labeled ethylenediaminetetra-acetate (EDTA)] was measured in 36 children (112 studies) and compared with simultaneously measured creatinine clearance (CrCl), serum creatinine (SCr), and cystatin C (CysC) concentrations, as well as the results of Schwartz, Counahan-Barratt, and Cockroft-Gault formulae, using general linear mixed models. Our results showed a significant association between iGFR and CysC concentrations (p < 0.001). No linear relationship was observed between CrCl and iGFR (p = 0.7). As expected, the results of height-based formulae (Counahan-Barratt and Schwartz) had significantly (p = 0.004) better correlation to iGFR than the results of a formula based on weight (Cockroft-Gault) (p = 0.19). Despite significant linear correlation, intraclass correlation coefficients showed poor agreement. Tests of similarity between iGFR estimates showed differences between average values of GFR. Therefore, determination of iGFR remains the method of choice in estimation of GFR in cancer patients. In our study population, assay of serum CysC was the most reliable alternative method to measure glomerular function.

Methotrexate induces cell swelling and necrosis in renal tubular cells.

BACKGROUND: The present study was carried out to investigate if methotrexate (MTX) has a direct lethal effect in renal tubular cells, and if so, to further clarify the mechanisms of cell death. MATERIALS AND METHODS: Renal tubular cells (LLC-PK(1) cells) were incubated with MTX (0.01 microM, 0.1 microM, and 1 microM), either alone or in combination with 0.1 microM amiloride (Na(+)/H(+) antiporter inhibitor) or 1 microM carbachol (M-cholinergic agonist). Cell viability was then determined by means of trypan blue (TB) exclusion tests and MTT assays. RESULTS: After 4 hr incubation with 0.1 microM MTX the number of viable cells was decreased by 18% in comparison with control cells, and the proportion of dead cells was increased by 38%. Cell death induced by MTX was time-dependent and did not show apoptotic features. On the contrary, cell swelling was discovered. This cell death was prevented by co-incubating the cells with amiloride or carbachol. CONCLUSIONS: MTX induces cell swelling and cell death in renal tubular LLC-PK(1) cells. The tubular cell death induced by MTX is time-dependent. Cell death can be prevented by co-incubating with amiloride, thus indicating that the Na(+)/H(+) antiporter and possibly other volume regulatory factors in renal tubular cells are involved in MTX-induced renal failure.