Childhood cancer has been a global public health scourge with considerably escalating incidence each year [1]. Although the incidence is relatively lower compared to adult malignancies, it remains the leading cause of disease-related death in children. The most frequent childhood cancer is acute lymphoblastic leukemia (ALL) with an annual incidence of 3.5 per 100,000 children in the United States [2]. Similarly, in Indonesia, ALL has the highest number of cancer cases in children [3]. The total incidence of ALL in Indonesia reaches 2.5-4.0 per 100,000 children with an estimated 2,000-3,200 annually [4]. Because of its high incidence and curability, ALL is a logical initial objective for childhood cancer program developments in Indonesia. As an indicator of successful treatment of childhood ALL, the 5-year survival rate shows contrasting figures between high-income (HIC) and lower-middle-income countries (LMIC). In the United States and most European countries, the survival rates are approximately 90% and 85% respectively. However, in Southeast Asian countries, the highest 5-year survival rate for children aged 0 to 14 was reported in Malaysia (69.4%), followed by Thailand (55.1%) [5]. Furthermore, more unfavorable results were reported in Indonesia. Studies from Dharmais Cancer Hospital and Dr. Sardjito Hospital reported the 5-year survival rate of 28.9% and 31.8% respectively [6,7]. The outcome difference between Indonesia and other countries is probably due to the high rate of relapse occurrence and toxic death during the treatment. Some studies revealed the factors that affecting the worst outcome of childhood ALL in LMIC include inadequate and delayed diagnosis, limited healthcare access, treatment abandonment, and suboptimal supportive care [8]. As pediatric oncologists in HIC have become more effective at treating childhood ALL, much of the research attempts concentrated on the risk stratification of the patients. The term “risk stratification” is used to allocate the patients into various risk groups based on the notable prognostic features for specific treatment administration. Patients with a high-risk assessment could be targeted for more aggressive treatments, while patients with lower risk could be treated less intensively to avoid the side effects and toxicities [9]. In Indonesia, risk stratification strategy encompasses clinical-hematologic parameters (age, leukocyte count, extramedullary involvement), and conventional morphological examination. These assessments represent the first step in the diagnostic pathway of ALL. Though helpful, in certain cases, the residual leukemic cells might be undetectable under bone marrow morphology examination. This led to more underdiagnosed cases, thus more patients were subjected to inadequate treatment. Fortunately, immunophenotyping is currently applied to improve the diagnosis of childhood ALL by grouping the patients based on the aberrant expression of leukemic cell antigen, even though its application is only available in several centers including Dharmais Cancer Hospital. The BCR-ABL1 fusion gene examination by PCR-based techniques has also routinely been implemented to predict the poor outcome since it was detected in 12% of childhood ALL patients [10]. However, the current above-mentioned strategy is insufficient to solve the accuracy of risk stratification of childhood ALL. In HIC, childhood ALL are classified by more comprehensive examination involving morphology, immunophenotyping, cytogenetics, and molecular techniques. The approach to classifying prognosis and to personalize treatment based on the underlying genetic biology has already implemented for understanding the pathogenesis of childhood ALL. According to studies, the molecular features of childhood ALL have been shown to have a significant prognostic value [11], and the survival rate was improved when genetic examinations are applied [12]. In recent years, high-resolution array-based genomic technologies have revolutionized the understanding of the genetic basis of childhood ALL. Several biomarkers have successfully been identified that are provenly associated with poor prognosis in childhood ALL, including the deletion/mutation of IKZF1 (IKAROS), CDKN2A, ETV6, EBF1, JAK2, and many more [13]. The majority of these genetic changes were originally identified by sophisticated methods such as single nucleotide polymorphism (SNP) arrays, gene expression profiling (GEP), array-based comparative genomic hybridization (aCGH), and more recently next-generation sequencing (NGS) [14]. Despite being highly sensitive for detection of multiple copy number changes, these approaches are not feasible for routine diagnostic use in LMIC which requires significant EDITORIAL Indonesian Journal of Cancer, Vol 14(4), 115–116, December 2020 DOI: http://dx.doi.org/10.33371/ijoc.v14i4.818 www.indonesianjournalofcancer.or.id P-ISSN: 1978-3744 E-ISSN: 2355-6811 116 | financial investment. Therefore, molecular techniques that suit available resources and infrastructure should be developed in LMIC, and most importantly the cost should be affordable for patients. One feasible method is Multiplex Ligation-dependent Probe Amplification (MLPA). MLPA is a rapid multiplex PCR-based technique that enables the comparative analysis of multiple mutation spots [15]. MLPA provides a low-cost, simple alternative to array-based techniques for much routine clinical practice, even though it is unsuitable for whole-genome analysis. Furthermore, one benefit compared to other quantitative PCR-based techniques is that MLPA allows 50 or more different genomic DNA to be analyzed in a single tube reaction. Several studies have demonstrated the implementation of specific MLPA probe mixes for hematological malignancies, including ALL, chronic lymphocytic leukemia (CLL), and myelodysplastic syndrome (MDS). These studies have also shown the sensitive and accurate identification of clinically significant diseasespecific copy number changes [16]. Currently, MLPA has been established as a routine diagnostic of childhood ALL patients in Dharmais Cancer Hospital by a research-based service setting. It reliably detects small focal deletions, even from the low amount of specimens. In general, the results demonstrated the concordance between mutated genes reported in highrisk patients (deletion of IKZF1, CDKN2A, CDKN2B, PAX5). These findings surely can guide the doctors in Dharmais Cancer Hospital to assign the specific patients for the intensive treatment protocol, which is expected to increase the patient’s survival. Therefore, concerning the future clinical application, the inclusion of mutation status by MLPA for childhood ALL risk stratification should be widely promoted to a large health community, especially the Indonesian Pediatric Society, which views this as a consideration for refinement of standard diagnosis protocol for childhood ALL in Indonesia.

Objective: Molecular testing of thyroid nodules becomes important for improving the accuracy of fine-needle aspiration biopsy (FNAB). This study aimed to investigate the diagnostic utility of BRAF, NRAS, and TERT promoter mutation in thyroid nodules at Dharmais Cancer Hospital. Methods: We performed a prospective diagnostic study involving 50 patients with thyroid nodules who needed surgery between September 2013 and August 2014. Mutational hotspots in BRAF exon 15, NRAS exon 3, and TERT promoter region were analyzed by Sanger sequencing from FNAB specimens. Cytology and molecular data were compared to histopathology results. Results: Of the 50 cases included in the analysis, 39 cases (78%) were thyroid malignancies. Mutations of BRAF, NRAS, and TERT promoter were detected in 31% (12/39), 18% (7/39), and 13% (5/39) cases, respectively. BRAF and NRAS mutations were found mutually exclusive, while all of TERT promoter mutation was found coexistent either with BRAF (40%) or NRAS (60%). The combination of FNAB cytology and molecular testing resulted in 69% sensitivity, 100% specificity, 100% positive predictive value, 48% negative predictive value, and 76% accuracy. Conclusion: Molecular testing of BRAF, NRAS, and TERT mutations improve the sensitivity of thyroid FNAB and is beneficial for more definitive treatment in selective cases. However, the NPV is relatively low to avoid the need for diagnostic surgery. Therefore, further studies to identify more sensitive methods and more comprehensive molecular markers in the diagnosis of thyroid nodules are needed.

Background: Osteosarcoma is the most common bone malignancy in childhood and adolescence. Despite significant advances in diagnostic and therapeutic modalities, osteosarcoma has generally poor prognosis. Several studies highlighted the prognostic significance of demographic and clinical parameters in the pediatric population. Controversy exists about which obvious factors of mortality in some institutions. Meanwhile, little is known about the overall survival (OS) of pediatric osteosarcoma in Dharmais Cancer Hospital.The aim of this study is to estimate the OS in pediatric osteosarcoma.Methods: This retrospective cohort study enrolled 41 children with osteosarcoma during the period of January 2010-September 2017. Patients were selected using inclusion and exclusion criteria. Overall survival (OS) and patient variables were plotted using Kaplan-Meier.Results: Our result showed that all patients admitted to our hospital in advanced stages (IIB and III). Their median OS was 23 months (12.3-33.7 months) with the survival probability was 29.4%.Conclusions: Median OS of pediatric osteosarcoma in our institution was 23 months and the survival probability was 29.4%. It can be used as evidence showing lack of cancer awareness and early detection in our country.

Background: BCR-ABL1 fusion gene, which originated from t (9;22), is an important biomarker for diagnosis, therapeutic approach, and prognosis in childhood leukemia. However, there are no data in Indonesia about the profile of BCR-ABL1 fusion gene for this disease. This study intends to demonstrate the profile of the BCR-ABL1 fusion gene in childhood leukemia at “Dharmais” Cancer Hospital.Methods: This descriptive retrospective study included 79 patients with childhood leukemia who performed the BCR-ABL1 examination in “Dharmais” Cancer Hospital during 2008–2018. Demographic data, leukemia types, BCR-ABL1 examination results, and protein isoforms developed by BCR-ABL1 fusion were obtained from Cancer Registry Data.Results: Among 79 patients’ data recorded in this study, 65.8% (52/79) were male and 34.2% (27/79) were female. A total of 74.7% (59/79) patients were diagnosed with Chronic Myelogenous Leukemia (CML), 21.5% (17/79) with Acute Lymphoblastic Leukemia (ALL), and 3.8% (3/79) with Acute Myelogenous Leukemia (AML). The profile of positive BCR-ABL1 in CML patients was 72.8% (43/59). About 97.7% (42/43) of CML patients with positive BCR-ABL1 fusion gene expressed 210-kDa protein, while only 2.3% (1/43) expressed 190-kDa protein.Conclusions: This study found that, from a total of 79 respondents, 45 of them showed a positive BCR-ABL result, with details of 43 in CML and 2 in ALL. Among the total of 43 CML patients with positive BCR-ABL1, 42 (97.7%) of them expressed 210-kDa protein isoform. Further research to investigate the relationship between protein isoforms and their clinical effects may also be important to discuss. The valuable recommendation suggests that BCR-ABL1 examination should be performed for all childhood leukemia patients in Indonesia, especially for CML and ALL.