Discovering needs for palliative care in children with cancer in Indonesia.

BACKGROUND: Although most children with cancer die in low- and middle-income countries, palliative care receives limited attention in these settings. This study explores parents' perspectives on experiences and needs of children dying from cancer. METHODS: Home visits were conducted to interview parents of children, who were treated for cancer at an Indonesian academic hospital and died between 2019 and 2020, using semi-structured questionnaires. RESULTS: Parents of 49 children (response rate 74%) were interviewed. While all children died in hospital, 37% of parents stated their child preferred to die at home. The most common symptoms during final illness were breathing difficulties (82%), pain (80%), and appetite loss (80%). Psychological symptoms received the least support from the medical team. No intervention was given to 46% of children with depression, 45% of children with anxiety, and 33% with sadness. Boys suffered more often from anxiety (68%) than girls (37%; p = .030). Parents (57%) were not always informed about their child's condition, and doctors gave confusing information (43%). The families' choice of treatment while dying was relieving pain or discomfort (39%) and extending life (33%), while for 29% it was unknown. However, many parents (51%) did not discuss these treatment wishes with doctors. Many children (45%) felt lonely wanting more interactions with school (71%), friends (63%), and family (57%). CONCLUSION: Relieving suffering of children with cancer requires regular physical, psychological, social, and spiritual needs assessment. Families should actively participate in deciding whether to extend life or relieve pain and discomfort. This can importantly improve the quality of life of children and families.

A cross-sectional study of nutritional status and dietary intake of paediatric oncology patients in Indonesia: Comparison between cancer aetiologies.

Background: Adequate energy and protein intakes are required to maintain nutritional status and prevent clinical deterioration in paediatric oncology patients. There are limited investigations of malnutrition and dietary intake adequacy during treatment in developing countries. Aim: This study aimed to assess the nutritional status and macro- and micronutrient intake adequacy in paediatric oncology patients undergoing therapy. Methods: This cross-sectional study was conducted at Dr Sardjito Hospital, Indonesia. Sociodemographic, anthropometry, dietary intake, and anxiety status were collected. Patients were grouped based on cancer aetiology (haematological malignancy (HM) or solid tumour (ST). Variables between groups were compared. P-values of <0.05 were considered statistically significant. Results: 82 patients aged 5-17 years (65.9% HM) were analysed. The prevalence of underweight was 24.4% (ST vs HM: 26.9% vs 23.2%), overweight 9.8% (ST vs HM: 11.5% vs 8.5%), and obesity 6.1% (ST vs HM: 0.0% vs 8.5%) according to BMI-for-age z-score. Mid-upper-arm circumference identified undernutrition in 55.7% and overnutrition in 3.7% of the patients. Stunted growth was found in 20.8% of the patients. Percentages of children with inadequate energy and protein intake were 43.9% and 26.8%, respectively. The percentages of participants meeting the national micronutrient requirements were low, ranging from 3.8% to 56.1%, with the highest adherence rate observed for vitamin A and the lowest for vitamin E. Appetite loss was associated with lower overall intake. Conclusion: This study confirmed that malnutrition is prevalent in paediatric patients treated for cancer. Inadequate intakes of macro- and micro-nutrients were also common, highlighting the need for early nutritional assessment and intervention.

Childhood acute lymphoblastic leukemia: Four years evaluation of protocols 2013 and 2016 in a single center in Indonesia, a lower-middle-income country.

BACKGROUND: The prognosis of childhood acute lymphoblastic leukemia (ALL) in Indonesia, a lower-middle-income country (LMIC), is lower than in high income countries (HICs). The Indonesian ALL2013 protocol resulted in too many toxic deaths (21%) and abandonments (11%). Therefore, we drafted an adapted protocol, ALL2016. Main changes: no anthracyclines in standard risk (SR), prednisone replaced dexamethasone at induction in high risk (HR), and anthracyclines and cyclophosphamide were rescheduled in HR. PROCEDURE: Patients (aged: 1-18 years) were stratified into SR and HR. HR was defined as age over 10 years, leucocyte count over 50 × 109 /L, central nervous system (CNS) involvement, mediastinal mass, T-cell phenotype, testicular involvement, or poor prednisone response. RESULTS: ALL2013 included 174 patients (106 SR and 68 HR) and ALL2016 188 (91 SR and 97 HR). Although the number of HR patients was significantly higher in ALL2016 (51.6% vs. 39.1%; p = .017), the outcome of ALL2016 improved over ALL2013 (4-year-probable overall survival (pOS) 60.1% vs. 50.0%; p = .042 and 4-year-probable event-free survival (pEFS) 49.5% vs. 36.8%; p = .018). ALL2016 showed a nonsignificant advantage for SR patients (4-year-pEFS 56.0% vs. 47.2%; p = .220 and 4-year-pOS 70.3% vs. 61.3%; p = .166), but less toxic deaths (7% vs. 20%; p = .011). In HR group, the outcomes were significantly better in ALL2016 (4-year-pEFS 43.3% vs. 20.6%; p = .004; 4-year-pOS 50.5% vs. 32.4%; p = .014) especially due to less relapses (31% vs. 62%; p = .001). Isolated CNS relapses went down from 18 to 8% in HR (p = .010) and 11 to 5% in SR (p = .474). Both SR and HR showed lower numbers of abandonment in ALL2016 (6% vs. 14%; p = .039). CONCLUSIONS: Overall ALL2016 results improved over ALL2013. Modest changes in protocol resulted in less initial toxicity and abandonments.

Anti-Mullerian hormone and puberty development in girls and adolescents who underwent cancer treatment.

BACKGROUND: High survival rates of children diagnosed with cancer have led to a growing population of women with premature ovarian failure (POF) due to chemotherapy and radiotherapy. The POF process occurs due to the disruption of the hypothalamic-pituitary and gonadal axis followed by the delay of puberty development. Evaluation of reproductive function in children with cancer is essential to determine the fertility preservation plan. This study aimed to describe reproductive functions in children and adolescents with cancer who received chemotherapy based on Tanner stage evaluation, menstrual cycle, and anti-Mullerian hormone (AMH) examination using electro-chemiluminescence immunoassay kit. RESULTS: Twenty-three girls aged 12-18 years old and had menarche who underwent cancer therapy in January-August 2019 in Dr. Sardjito General Hospital were included in the study. Among them, 61% had low AMH levels and were defined as diminished ovarian reserve (DOR). Two subjects with DOR experienced delayed puberty. Regular menstrual cycle was reported in 65.2% of subjects and irregular menstrual cycle in 34.8%, while 21.7% with irregular menstrual cycle encountered secondary amenorrhea. CONCLUSION: Chemotherapy exposure affected DOR occurrence in 60.9% of patients with childhood and adolescence cancer. Moreover, it also altered menstrual regularity in 34.8% and delayed puberty development in 8.7% subjects.

Impact of universal health coverage on childhood cancer outcomes in Indonesia.

BACKGROUND: Starting from 2014, the Indonesian government has implemented Universal Health Coverage (UHC) with the aim to make healthcare services accessible and affordable to all Indonesian citizens. A major reason for childhood cancer treatment failure in low- and middle-income countries, particularly among families with low socioeconomic status (SES), is abandonment of expensive cancer treatment. Our study compared childhood cancer treatment outcomes of the overall, low, and high SES population before and after introduction of UHC at a large Indonesian academic hospital. METHODS: Medical records of 1040 patients diagnosed with childhood cancer before (2011-2013, n = 506) and after (2014-2016, n = 534) introduction of UHC were abstracted retrospectively. Data on treatment outcome, SES, and health-insurance status at diagnosis were obtained. FINDINGS: After introduction of UHC, the number of insured patients increased from 38% to 82% (P < 0.001). Among low SES population, insurance coverage increased from 40% to 85% (P < 0.001), and among high SES population from 33% to 77% (P < 0.001). In the overall population, treatment abandonment decreased from 36% to 22% (P < 0.001). Event-free survival estimates at four years after diagnosis of overall population improved from 16% to 22% (P < 0.001). Hazard ratio for treatment failure was 1.26 (CI: 1.07-1.48, P = 0.006) for uninsured versus insured patients. In the low SES population, treatment abandonment decreased from 36% to 19% (P < 0.001). Event-free survival estimates at four years after diagnosis of low SES population improved from 14% to 22% (P < 0.001). INTERPRETATION: Introduction of UHC in Indonesia contributed significantly to better treatment outcome and event-free survival of children with cancer from low SES families.

Molecular Scanning of ß-Thalassemia in the Southern Region of Central Java, Indonesia; a Step Towards a Local Prevention Program.

Thalassemia is the most prevalent genetic blood disorder worldwide, and particularly prevalent in Indonesia. The purpose of this study was to determine the spectrum of ß-thalassemia (ß-thal) mutations found in the southern region of Central Java, Indonesia. The subjects of the study included 209 ß-thal Javanese patients from Banyumas Residency, a southwest region of Central Java Province. DNA analysis was performed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), amplification refractory mutation system (ARMS), and the direct sequencing method. The results showed that 14 alleles were found in the following order: IVS-I-5 (G > C) (HBB: c.92 + 5G > C) 43.5%, codon 26 (Hb E; HBB: c.79G > A) 28.2%, IVS-I-1 (G > A) (HBB: c.92 + 1G > A) 5.0%, codon 15 (TGG > TAG) (HBB: c.47G > A) 3.8%, IVS-I-1 (G > T) (HBB: c.92 + 1G > T) 3.1%, codon 35 (-C) (HBB: c.110delC) 2.4%. The rest, including codons 41/42 (-TTCT) (HBB: c.126_129delCTTT), codons 8/9 (+G) (HBB: c.27_28insG), codon 19 (AAC > AGC) (HBB: c.59A > G), codon 17 (AAG > TAG) (HBB: c.52A > T), IVS-I-2 (T > C) (HBB: c.92 + 2T > C), codons 123/124/125 (-ACCCCACC) (HBB: c.370_378delACCCCACCA), codon 40 (-G) (HBB: c.123delG) and Cap +1 (A > C) (HBB: c.-50A > C), accounted for up to 1.0% each. The most prevalent alleles would be recommended to be used as part of ß-thal screening for the Javanese, one of the major ethnic groups in the country.

Treatment Outcome of Children with Retinoblastoma in a Tertiary Care Referral Hospital in Indonesia.

Background: Although survival rates for retinoblastoma (RB) are over 95% in high-income countries, its high mortality rate in low and middle-income countries remains a great concern. Few studies investigated treatment outcome and factors contributing to RB survival in these latter settings. Aims of this study are to determine treatment outcome of Indonesian children diagnosed with RB and to explore factors predictive of treatment outcome. Methods: This study was a retrospective medical records review combined with an illustrative case report. Children newly diagnosed with RB between January 2011 and December 2016 at a tertiary care referral hospital in Indonesia were included. A home visit was conducted to perform an in-depth interview with a mother of two children affected by RB. Results: Of all 61 children with RB, 39% abandoned treatment, 21% died, 20% had progressive or relapsed disease and 20% event-free survival. Progressive or relapsed disease was more common in older (≥ 2 years at diagnosis, 29%) than young (<2 years at diagnosis, 0%) children (P=0.012). Event-free survival estimate at 5 years was higher in young (42%) than older (6%) children (P=0.045). Odds-ratio for event-free survival was 6.9 (95% CI: 1.747 ­ 27.328, P=0.006) for young versus older children. Other clinical and socio-demographic characteristics had no significant correlation with treatment outcome or event-free survival. The case report elucidated conditions and obstacles that Indonesian families face when their children are diagnosed with RB. Conclusion: Survival of children with RB in Indonesia is much lower compared to high-income and many other low and middle-income countries. Abandonment of treatment is the most common cause of treatment failure. Older age at diagnosis is associated with more progressive or relapsed disease and worse survival. Interventions to improve general public and health-care providers' awareness, early detection and treatment adherence are required.

Effect of music therapy on cortisol as a stress biomarker in children undergoing IV-line insertion.

OBJECTIVE: An IV-line insertion can often provoke stress that can lead to an increase in cortisol levels. Complementary medication such as music therapy is needed to overcome the increase in cortisol levels. We conducted this study to determine the effect of music therapy on salivary cortisol levels in children with leukaemia undergoing IV-line insertion. METHOD: This was a pre-experimental study with a pre- and post-test design. We analysed the salivary cortisol levels in 30 children with leukaemia undergoing IV-Line insertion from January until February 2018. Music was played using earphones after the completion of the IV-line insertion procedure. The salivary cortisol levels were analysed by an enzyme-linked immunosorbent assay (ELISA) test. Changes in cortisol levels were considered clinically significant if the differences were ≥0.05 ng/ml. The Wilcoxon test was used to test the effect of music therapy on cortisol levels and a p-value of <0.05 was considered statistically significant. RESULT: Levels of cortisol before and after the music therapy had a median (min-max) of 4.14 (0.25-9.89) and 3.47 (0.16-15.31), respectively. The median difference of cortisol levels was 0.67 ng/ml. This change of ≥0.05 ng/ml indicates the clinical effect of music therapy on cortisol levels. Though the music therapy did not significantly affect salivary cortisol levels (p = 0.99), this study revealed the clinical effect of music therapy in reducing cortisol levels. CONCLUSIONS: This study did not indicate a statistically significant effect of music therapy on cortisol levels of children with leukaemia during an IV-line insertion. However, the study findings reflect the clinical effect of music therapy in reducing cortisol levels.

Implementation of Medication Safety Practice in Childhood Acute Lymphoblastic Leukemia Treatment

Objective: Medical Safety Practice (MSP) is a safe procedure in medication process. It is important to investigate the use of MSP among childhood cancer patients because pediatric oncology is a high-risk area for potentially harmful adverse events. The purpose of this study is to determine the effects of the implementation of MSP in chemotherapy on the incidence of medication errors in childhood ALL patient at Dr. Sardjito Hospital, including in 1) transcribing, 2) administering, 3) monitoring, 4) the incidence of adverse drugs events. (ADEs). Methods: The study design is a quasi-experimental study with pre- and post-intervention without control. The sample consists of ALL patients who are taken care of at an academic hospital in Indonesia from 2012 to 2013. The sample was consecutively collected during the period of study. The data were collected through medical records, research form, observation, and discussion with the nurse. The intervention given is training and implementation of medical safety practice in chemotherapy. Result: Based on the analysis of the effect of the implementation of MSP (75 and 106 medical records of pre- and post-intervention), it is obtained: 1) the adherence of chemotherapy transcribing post-intervention increases significantly compared to pre-intervention (p<0.05), 2) the adherence of chemotherapy administering increases significantly in almost every aspect (p<0.05), except in preparing drugs by two different health worker, patient's confirmation of ADEs management, and verification of drug's expired date, 3) The adherence of chemotherapy monitoring improved significantly post-intervention (p<0.05), 4) Adverse Drug Events (ADE) decreased significantly post-intervention (p<0.05), from 52.1% to 30.5%. Conclusion: The implementation of MSP decreased the incidence of medication errors in ALL patients at Dr. Sardjito Hospital in ordering, dispensing, transcribing, administering, and monitoring chemotherapy. It also reduced the incidence of ADEs related to chemotherapy. Specific training for nurses are needed in order to improve the knowledge and skills, especially for medication error and skill in patients' care.

Modifying effect of XmnI, BCL11A, and HBS1L-MYB on clinical appearances: A study on ß-thalassemia and hemoglobin E/ß-thalassemia patients in Indonesia.

OBJECTIVE/BACKGROUND: Thalassemia is a monogenic hematologic disease that has the highest prevalence globally. In addition, there is complexity of the genetic background associated with a variety of phenotypes presented among patients. Genetic heterogeneity related to fetal hemoglobin (HbF) production has been reported as an influencing phenotypic factor of ß-thalassemia (ß-thal). Therefore, this study aimed to find the effect of these genetic modifiers, especially in the XmnI locus, rs11886868, rs766432 (BCL11A), and rs9399137 (HBS1L-MYB), among ß-thal and HbE/ß-thal patients in Indonesia, according to laboratory and clinical outcomes, including HbF levels and clinical scores. This study was also designed to compare these modifying effects among ß-thal and HbE/ß-thal patients in Indonesia. METHODS: A total of 189 patients with genotyping of ß-thal and HbE/ß-thal were included in this study. The erythrocytes index and Hb electrophoresis measurements were calculated using appropriate methods. The severity of ß-thal and HbE/ß-thal was classified based on the Mahidol score. Polymorphism of the XmnI locus, rs11886868, rs766432 (BCL11A), and rs9399137 (HBS1L-MYB) was determined using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and amplification refractory mutation system (ARMS) methods. RESULTS: The distributions of minor allele in the XmnI locus, rs11886868, rs766432, and rs9399137 were 14%, 22%, 19% and 18% respectively. The variation allele in the XmnI locus, rs11886868, and rs766432 showed a significant value for modifying HbF and clinical score in HbE/ß-thal patients, but rs9399137 did not demonstrate such features. In ß-thal patients, however, no correlation was found for any single-nucleotide polymorphisms and clinical appearance. CONCLUSION: The XmnI locus, rs11886868, and rs766432 have a modifying effect on HbF and clinical score in HbE/ß-thal patients in Indonesia, but not in ß-thal patients.

Status of Superoxide Dismutase in Transfusion Dependent Thalassaemia.

BACKGROUND: Thalassemia is a collection of genetic impairments in beta and alpha genes causing various states of anemia. Severe types of the disease need lifelong transfusions, leading to oxidant-antioxidant disturbance due to massive iron deposits. AIMS: The aim of this study was to assess the antioxidant enzyme Superoxide Dismutase (SOD) and ferritin levels of thalassemia major patients in a peripheral health facility. MATERIALS AND METHODS: Two hundred and nine probands were recruited and performed laboratory experiments for SOD and Ferritin levels. Chelation administration and clinical score were taken from interviewing the family and from medical report data. RESULTS: The study showed that SOD intensity was lower (162.41 u/ml) compared to the normal cutoff point (P = 0.001), while the mean of Ferritin levels was ten times over the normal value (4226,67 ng/dl). Observations also reported that chelation medicine was not administrated properly. CONCLUSIONS: The data indicates that thalassemic patients have oxidant-antioxidant uproar due to oxidative stress. Monitored chelating administration, selective antioxidant, and a well-balanced diet may prevent oxidative injury.

Yogyakarta Pediatric Cancer Registry: an international collaborative project of University Gadjah Mada, University of Saskatchewan, and the Saskatchewan Cancer Agency.

INTRODUCTION: In July 2001, a 'twinning' project was undertaken between University Gadjah Mada, Indonesia, and the Saskatchewan Cancer Agency, Canada to create a computerised Pediatric Cancer Registry at Sardjito Hospital, Yogyakarta city. OBJECTIVES: To analyse information from the Yogyakarta Pediatric Cancer Registry (YPCR) in order to i) determine the prevalence of pediatric cancers in Yogyakarta Special Region and, ii) compare the demographics of pediatric malignancies in the Special Region (population: 3.3 million), with those of the Saskatchewan Cancer Registry in the province of Saskatchewan (population: 1 million). METHODOLOGY: In May 2001, a computer dedicated to the YPCR was installed at Sardjito Hospital. Bilingual (English/Indonesian) data capture forms were developed for data extraction from hospital health records. Data items were then entered into a data base using the Statistical Package For Social Sciences (SPSS) program. Two projects were initiated: i) a prospective study from 2000-2009 of pediatric cancer cases from the YPCR, and ii) a comparison of demographics from both Cancer Registries during the time period 1996-2003. Comparative data were obtained for age, sex, diagnoses, and referral patterns. Results were analysed using the SPSS software program. RESULTS: i) In the 10 year prospective study, 1,124 pediatriccancer cases were accrued in the Yogyakarta Registry, the majority being in the age group 0-5 years. Male:female: 7:1. Leukemias were the most common diagnosis, followed by retinoblastoma and neuroblastoma. The majority of patients (68%) were referred from outside the catchment area of Yogyakarta Special Region. ii) In the 8 year archival comparative analysis, the most striking contrasts were a higher proportion of children with retinoblastoma and negligible numbers of pediatric brain tumors in the Yogyakarta Registry. CONCLUSION: This is the first published report of a computerised pediatric cancer registry in Indonesia. The differences in diagnostic frequencies noted above may, in part, be due to comparisons between the population-based Saskatchewan Cancer Registry versus the hospital-based Yogyakarta Pediatric Cancer Registry. The contrasts in demographics are multifactorial, and require further investigation.