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Indonesia

Cancer Statistics
Population in 2012: 244.8m
People newly diagnosed with cancer (excluding NMSC) / yr: 299,700
Age-standardised rate, incidence per 100,000 people/yr: 133.5
Risk of getting cancer before age 75:14.0%
People dying from cancer /yr: 194,500
Data from IARC GlobalCan (2012)
Indonesia Cancer Organisations and Resources
Latest Research Publications Related to Indonesia

Indonesia Cancer Organisations and Resources (7 links)


Latest Research Publications Related to Indonesia

Youl Lee J, Taniguchi T, Zhang K, et al.
Report of the forth Asian Prostate Cancer (A-CaP) study meeting.
Jpn J Clin Oncol. 2019; 49(6):581-586 [PubMed] Related Publications
The Asian Prostate Cancer (A-CaP) Study is an Asia-wide prospective registry study for surveying the treatment outcome of prostate cancer patients who have received a histopathological diagnosis. The study aims to clarify the clinical situation for prostate cancer in Asia and use the outcomes for the purposes of international comparison. Following the first meeting in Tokyo on December 2015, the second meeting in Seoul, Korea 2016, the third meeting in Chiang Mai, Thailand, on October 2017, the fourth meeting was held in Seoul, again on August 2018 with the participation of members and collaborators from 13 countries and regions. In the meeting, participating countries and regions presented the current status of data collection and the A-CaP office presented a preliminary analysis of the registered cases received from each country and region. Participants discussed ongoing challenges relating to data cleaning and data up-dating which is the next step of the A-CaP study following the data collection phase between 2016 and 2018. There was specific difference in term of the patient characteristics, and initial treatment pattern among East Asia, Southeast Asia and Turkey, and Jordan. Finally, a close relationship between prevalence of PSA test and disease stage of the patients at diagnosis in Japan and Malaysia was discussed.

Karlowee V, Amatya VJ, Takayasu T, et al.
Immunostaining of Increased Expression of Enhancer of Zeste Homolog 2 (EZH2) in Diffuse Midline Glioma H3K27M-Mutant Patients with Poor Survival.
Pathobiology. 2019; 86(2-3):152-161 [PubMed] Related Publications
INTRODUCTION: The interaction of K27M mutation in histone H3 (H3K27M mutation) with polycomb repressive complex 2 (PRC2) is facilitated by the enhancer of zeste homolog 2 (EZH2). Subsequently, this interaction leads to the global reduction level of H3K27me3. We analyzed the EZH2 expression level in H3K27M mutation-positive tumors and revealed the association of high EZH2 expression with poor survival.
METHODS: Our study included 12 patients, with an age range of 6-56 years and treated between 2007 and 2016. All patients underwent MRI study for nonenhanced T1, T2, diffusion, gadolinium-enhanced T1-weighted imaging, and fluid-attenuated inversion recovery (FLAIR). Immunohistochemical staining was performed against H3K27M, H3K27me3, EZH2, EED, mutant isocitrate dehydrogenase 1 (IDH1), α-thalassemia X-linked intellectual disability (ATRX), p53, O6-methylguanine-DNA methyltransferase (MGMT), and Ki-67 antibodies.
RESULTS: All patients were negative for IDH1R132H and H3K27me3, but H3K27M-positive. Staining against EZH2 was negative in all histological features of grade II cases (3/12) and positive in grade III and IV cases; EZH2 positivity is associated with poor prognosis (p = 0.0082). EZH2 positivity was not associated with EED positivity. Retained ATRX staining was found mostly in grade III and IV cases (6/12). P53 was predominantly positive in cases of astrocytoma and glioblastoma (8/12). The labeling index of Ki-67 was 1.2-31.4% for grade II and III histological features and 11.2-24.8% for grade IV.
CONCLUSION: We suggest that the expression of EZH2 is not associated with the PRC2 pathway and increases in patients with H3K27M-mutant diffuse midline glioma and a poor prognosis. Further studies are necessary to understand the mechanism involved.

Sinaga ES, Ahmad RA, Shivalli S, Hutajulu SH
Age at diagnosis predicted survival outcome of female patients with breast cancer at a tertiary hospital in Yogyakarta, Indonesia.
Pan Afr Med J. 2018; 31:163 [PubMed] Free Access to Full Article Related Publications
Introduction: Breast cancer is the most common cancer in women in Indonesia. Patients' survival depends on various factors, namely patient-, tumor-, and treatment-related factors. Survival analysis on Indonesian patients has only been reported in a few studies. This study aimed to identify the factors that are associated with five-year overall survival (OS) among patients with breast cancer at a local tertiary hospital in Indonesia.
Methods: A retrospective cohort study was conducted at Dr Sardjito Hospital, Yogyakarta. Female patients diagnosed with breast cancer between January and December 2009 were studied. Socio-demographic and clinicopathological data were collected from the medical and pathological records. The five-year OS rate was assessed using Kaplan Meier method and prognostic factors were analyzed using Cox regression.
Results: A total of 213 eligible patients with breast cancer were recruited. The five-year OS probability of the breast cancer patient was 51.07%. The majority of the patients (151, 70.9%) presented an advanced stage at the time of diagnosis. In the bi-variable analysis, cases who were younger, of a lower educational status, at a more advanced stage, with a bigger tumor size, and a central tumor location showed a worse five-year OS compared to their counterparts (p = 0.005, 0.001, 0.004, 0.011 and 0.023, respectively). In the multivariable analysis, age was an independent predictor for the OS (HR = 3.73; 95% CI = 1.0-13.6, p = 0.046).
Conclusion: The five-year OS of breast cancer patients in the local tertiary hospital was 51.07%. The patients' age at diagnosis was the only significant prognostic factor for the patients' survival.

Kristina SA, Permitasari NPAL, Krisnadewi KI, Santosa KA
Incidence and Mortality of Cancers Related to Secondhand Smoking in Southeast Asia Countries
Asian Pac J Cancer Prev. 2019; 20(3):971-976 [PubMed] Related Publications
Background: Secondhand smoke has been a big problem for human being worldwide as it is well-established risk factors for cancers. ASEAN (Association of Southeast Asian Nations) bear high burden of cancers since the high prevalence of secondhand smoke. The objective of this study is to estimate the burden of cancer attributable to secondhand smoking in ASEAN. Methods: This research was using descriptive epidemiological incidence and prevalence-based research design, with cancers incidence and mortality data gained from GLOBOCAN 2012. Secondhand smoke attributable fractions (SAFs) of six cancers (lung, bladder, colorectal, stomach, pancreas and larynx) were estimated and burden of cancers caused by secondhand smoking in ASEAN were calculated in term of incidence and mortality. Results: Secondhand smoking estimated for 453,562 cancer cases and 323,284 of total cancer mortality in 2012. The number of incidence and death of lung cancer attributable to secondhand smoking show the highest number compared with other type of cancers. Furthermore, we found that the number of cancer cases and cancer deaths attributable to secondhand smoking varied by each countries due to differences in size of population, various background risk of the cancer, and prevalence of secondhand smoking in each country. Conclusion: Secondhand smoking has been a risk factor for about two-fifth of cancer incidence and mortality in ASEAN. Therefore, ASEAN member countries are strongly encouraged to put in place stronger tobacco control policies and to strengthen the existing tobacco control measure in order to decrease the number of secondhand smokers and more effectively control cancers.

Goud EVSS, Malleedi S, Ramanathan A, et al.
Association of Interleukin-10 Genotypes and Oral Cancer Susceptibility in Selected Malaysian Population: A Case- Control Study
Asian Pac J Cancer Prev. 2019; 20(3):935-941 [PubMed] Related Publications
Background: Interleukin-10 (IL10) genotypes have been closely correlated to the susceptibility for oral squamous cell carcinoma. More than half of oral cancers in the world occur in Asia with estimated 168,850 new cases were diagnosed in this geographical region alone. Considering the rising numbers of oral cancer cases in Malaysia, association of IL10 A1082G gene polymorphism was correlated. Methodology: 41 oral squamous cell carcinoma (OSCC) cases and 48 healthy controls of comparable age, gender, and with habits like smoking, alcohol consumption and betel quid chewing were selected. In this case-control study, samples were collected from the Oral Cancer Research and Coordinating Centre (OCRCC), Faculty of Dentistry, University of Malaya, Malaysia. Genotyping conditions were evaluated by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP). The PCR products were subjected to digestion by MnlI enzyme (NEB, UK) to screen for the IL10 A-1082G. Digested DNA products were analyzed by electrophoresis on 4% (w/v) agarose gel, stained with ethidium bromide and imaged under UV illumination. Chi-square test and Fisher’s Exact test were used in statistical analysis. Results: AG genotypes were present in 81.3% and 86.0% of healthy control and OSCC cases respectively (OR=0.468, 95% CI=0.133-1.653). No significant association was found between IL10 A1082G polymorphism with risk habits, clinico-pathological parameters and 5-years overall survival. The findings also show no significant correlation between the IL10 genotype and features of OSCC within the case group as measured by tumor size, lymph node involvement, stage, invasive front, grading, depth, pattern of invasion. Conclusion: This study suggests that functional polymorphism AG of IL10 A1082G may have no influence with OSCC susceptibility. However, further investigation with larger sample sizes can be conducted to provide additional evidence to support the lack of association of IL10 A1082G polymorphism in oral cancer.

Darwito D, Dharmana E, Riwanto I, et al.
Effects of Omega-3 Supplementation on Ki-67 and VEGF Expression Levels and Clinical Outcomes of Locally Advanced Breast Cancer Patients Treated with Neoadjuvant CAF Chemotherapy: A Randomized Controlled Trial Report
Asian Pac J Cancer Prev. 2019; 20(3):911-916 [PubMed] Related Publications
Background: Omega-3 is a polyunsaturated fatty acid with an ability to regulate cell proliferation and apoptosis through interaction with inflammatory mediators. The potential additional beneficial effects of Omega-3 on chemotherapy patients with breast cancer is not yet completely revealed. Methods: A double-blind randomized control trial (RCT) involving a total of 48 locally advanced breast cancer patients was conducted. Ki-67 and VEGF expressions, as well as overall survival of patients receiving neoadjuvant cyclophosphamide-doxorubicin-5’fluorouracyl (CAF) chemotherapy plus Omega-3 (intervention group) or placebo (control group), were compared. Kaplan-Meier curve and Cox-regression tests were used to assess conditional disease-free survival (DFS) and overall survival (OS) between the two groups. Results: Decreased Ki-67 expression was observed in the intervention group compared to control (42.4±4.8 versus 39.2±5.3; T-test p=0.032). Decreased Ki-67 expression was observed in intervention compared to control group (42.4±4.8 versus 39.2±5.3; T-test p=0.032). Decreased VEGF expression was also seen in the intervention group compared to control (32.7±5.2 versus 29.5±5.4; T-test p=0.041). VEGF expression positively correlated with Ki-67 expression (Spearman’s test p<0.001, R2=0.541). Overall survival in the intervention group was significantly longer in comparison to the control group (mean survival: 30.9 ± 3.71 versus 25.9 ± 3.6 weeks, Mantel-Cox test p=0.048; HR=0.411, 95%CI: 0.201-0.840). Disease-free survival was significantly longer in the intervention group compared to the control group (mean survival: 28.5 ± 3.3 versus 23.7 ± 3.6, respectively; Mantel-Cox test p=0.044, HR= 0.439, 95%CI: 0.222-0.869). Conclusion: Omega-3 fatty acid supplementation improved overall survival and progression-free survival of locally advanced breast cancer treated with CAF neoadjuvant chemotherapy and mastectomy.

Zaitun Hasibuan PA, Sumaiyah S
The Anti-Proliferative and Pro-Apoptotic Properties of Ethanol Plectranthus amboinicus (Lour.) Spreng. Leaves Ethanolic Extract Nanoparticles on T47D Cell Lines
Asian Pac J Cancer Prev. 2019; 20(3):897-901 [PubMed] Related Publications
Objectives: Plectranthus amboinicus (Lour.) Spreng. is a plant which has the potential as an anti-cancer agent. To enhance the bioavailability of an extract, it is necessary to transform the extract into nanoparticles. This research aimed to create nanoparticles of the extract and investigate the anti-proliferative and pro-apoptosis effects on T47D breast cancer cell lines. Materials and Methods: The extraction with ethanol was performed using maceration method. The nanoparticles were prepared by using the ionic gelation method. Cytotoxic assay method evaluation of the proliferation of T47D cell line (using doubling time) was carried out using the MTT assay. Apoptosis was observed using the flow cytometry assay. Results: Treatment with Plectranthus amboinicus (Lour.) Spreng. ethanolic extract nanoparticles (PAEEN) inhibited the proliferation of T47D cell lines after 48 hours and 72 hours of incubation at concentrations of 22.3 μg/mL, 44.6 μg/mL, and 89.2 μg/mL. The viable cells were 93%, 86%, 54% (48 hours), and 98%, 71%, 57% (72 hours), respectively. The nanoparticles of extract also induced apoptosis at concentrations of ¼ IC50 (2.16%), ½ IC50 (1.57%), and IC50 (2.43%). Conclusion: PAEEN exhibits the anti-proliferative effect on T47D breast cancer cells via apoptosis. Further study is required to confirm the mechanism of PAEEN in the cell cycle arrest and apoptosis induction on T47D cells.

Solikhah, Promthet S, Hurst C
Awareness Level about Breast Cancer Risk Factors, Barriers, Attitude and Breast Cancer Screening among Indonesian Women
Asian Pac J Cancer Prev. 2019; 20(3):877-884 [PubMed] Related Publications
Background: Globally, breast cancer is the second most common cancer in women and is a leading cause of mortality in Indonesia. Raising awareness of breast cancer is particularly important to help at risk women seek medical treatment for this disease. This study aimed to comprehensively investigate the Indonesian women’s level of knowledge about breast cancer risk factors, barriers, attitude and breast cancer screening. Methods: This population-based cross-sectional study administered the breast cancer awareness Indonesian scale (BCAS-I) to 856 Indonesian women. Samples were selected in rural and urban combinations from three provinces by stratified random sampling. The ordinal logistic model was used to investigate the clustering effect of the participant’s characteristics in this study. Results: Of the women, 62% lived in rural areas and 38% lived in urban areas. Living in an urban area was significantly associated with a lower knowledge of the risk factors. However, living in an urban area was significantly associated with better attitudes and healthier behaviours related to breast cancer awareness. Women with higher education levels had 70% worse attitudes toward breast cancer awareness. Women living South of Sumatera, women living in Yogyakarta, and unmarried women were 5.03, 3.84, and 1.56 times as likely to have higher perceived barriers, respectively. Conclusion: Urban women had a poorer level of knowledge of breast cancer risk factors compared to women living in more rural areas. The result of this study may reflect inadequate breast cancer awareness campaigns or a lack of breast cancer awareness campaigns. These findings suggest that additional education programs aiming to increase awareness and educate the public are needed.

Prabawa IPY, Bhargah A, Liwang F, et al.
Pretreatment Neutrophil-to-Lymphocyte ratio (NLR) and Platelet-to-Lymphocyte Ratio (PLR) as a Predictive Value of Hematological Markers in Cervical Cancer
Asian Pac J Cancer Prev. 2019; 20(3):863-868 [PubMed] Related Publications
Background: Inflammation represents a pivotal role in the progression of cervical cancer. The hematological markers of inflammation in complete blood count (CBC) panel are potentially useful in determining the prognosis of the disease. Objective: The aim of the study was to investigate whether the pretreatment neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) could be used as in predicting the stage of cervical cancer. Methods: A retrospective cross-sectional study involving 282 patients with cervical cancer was enrolled at Sanglah General Hospital for five years (2013-2017). The histopathological records and complete blood counts (CBC) of the patients were collected and analyzed using SPSS ver. 16 software. FIGO stage I–II and III-IV were classified as early and advance stage respectively. Results: The median NLR and PLR were significantly higher in the advance stage compared with early stage (7.58 (1.36-33.20) and 247.89 (97.10-707.11); p-value = 0.001). A strong positive correlation was found between the staging of cervical cancer and NLR (r=0.638) and PLR (r=0.668). The AUC, sensitivity, and specificity value of NLR and PLR were 0.803 (82%; 71%) and 0.716 (72%; 70%). Advanced stage of cervical cancer was found in high NLR (adjusted OR: 9.02; 95%CI=2.42-33.64; p=0.001) and PLR (adjusted OR = 2.47; 95% CI = 1.45-4.85; p = 0.032). Conclusion: Increased pretreatment NLR and PLR values may provide a useful information in predicting the staging of cervical cancer.

Setyowibowo H, Iskandarsyah A, Sadarjoen SS, et al.
A Self-Help Guided Psychoeducational Intervention for Indonesian Women with Breast Cancer Symptoms: Development and Pilot Feasibility Study
Asian Pac J Cancer Prev. 2019; 20(3):711-722 [PubMed] Related Publications
Background: Delay in the diagnosis of breast cancer (BC) may lead to an advanced stage of the disease and a poor prognosis. A psychoeducational intervention can be crucial in helping women with BC symptoms complete the examination procedures and reduce diagnosis delay of BC. Objective: To develop a psychoeducational intervention to reduce the delay of BC diagnosis among Indonesian women with BC symptoms. Methods: The development of the intervention included an inventory of crucial elements in developing psychoeducation through literature review as well as consultation with BC patients and healthcare providers. Additionally, we developed PERANTARA as the first pilot version of the self-help guided psychoeducational intervention. PERANTARA is an abbreviation for “Pengantar Perawatan Kesehatan Payadura”, which means an introduction to breast health treatment. The pilot feasibility study combined an expert review and a pilot testing in hospital settings. A semi-structured interview and the client satisfaction inventory were utilized to measure feasibility and acceptability of the intervention for Indonesian women with BC symptoms. Results: PERANTARA contained an oncologist’s explanation about BC and the BC survivors’ testimony to reduce the time to diagnosis. The pilot study results showed that most patients were satisfied with and trusted on PERANTARA. Conclusion: PERANTARA was feasible and acceptable for Indonesian patients with BC symptoms. The development framework suggested in this study can be applied to develop psychoeducational packages for other patients group, in particular, those interventional packages aimed at reducing diagnosis and treatment delays and nonadherence.

Nindrea RD, Aryandono T, Lazuardi L, Dwiprahasto I
Protective Effect of Omega-3 Fatty Acids in Fish Consumption Against Breast Cancer in Asian Patients: A Meta-Analysis
Asian Pac J Cancer Prev. 2019; 20(2):327-332 [PubMed] Related Publications
Objective: This systematic review and meta-analysis was performed to determine the protective effect of omega-3 fatty acids in fish consumption against breast cancer in Asian patients. Methods: The authors conducted a meta-analysis of published research articles on protective effect of omega-3 fatty acids in fish consumption against breast cancer in Asian patients published between January 2000 and July 2018 in online database of PubMed, ProQuest and EBSCO. Pooled odds ratios (OR) were calculated by using fixed and random-effect models. Publication bias was visually evaluated by using funnel plots and statistically assessed in Egger’s and Begg’s tests. Data were processed by Review Manager 5.3 (RevMan 5.3) and Stata version 14.2 (Stata Corporation). Results: This study reviewed 913 articles. There were 11 studies which conducted systematic review then continued by meta-analysis of relevant data with total number of samples were 130,365 patients. The results showed there was protective effect of omega-3 fatty acids in fish consumption against breast cancer in Asian patients (OR = 0.80 [95% CI 0.73-0.87, p <0.00001]). There was not any study with significant publication bias included. Conclusion: This analysis confirmed the protective effect of omega-3 fatty acids in fish consumption against breast cancer in Asian patients.

Kong TW, Ryu HS, Kim SC, et al.
Asian Society of Gynecologic Oncology International Workshop 2018.
J Gynecol Oncol. 2019; 30(2):e39 [PubMed] Free Access to Full Article Related Publications
The Asian Society of Gynecologic Oncology International Workshop 2018 on gynecologic oncology was held in the Ajou University Hospital, Suwon, Korea on the 24th to 25th August 2018. The workshop was an opportunity for Asian doctors to discuss the latest findings of gynecologic cancer, including cervical, ovarian, and endometrial cancers, as well as the future of fertility-sparing treatments, minimally invasive/radical/debulking surgery, radiotherapy, chemotherapy, targeted therapy, and immunotherapy. Clinical guidelines and position statement of Asian countries were presented by experts. Asian clinical trials for gynecologic cancers were reviewed and experts emphasized the point that original Asian study is beneficial for Asian patients. In Junior session, young gynecologic oncologists presented their latest research on gynecologic cancers.

Anwar SL, Raharjo CA, Herviastuti R, et al.
Pathological profiles and clinical management challenges of breast cancer emerging in young women in Indonesia: a hospital-based study.
BMC Womens Health. 2019; 19(1):28 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: Breast cancer diagnosed at a young age is often associated with aggressive biology, advanced stage, and unfavorable prognosis. The median age of breast cancer diagnosis in Indonesia is younger (48 vs. 68 years-old in Europe) with a relatively higher proportion of patients younger than 40 years old. Although prognosis and outcome of young breast cancer are well studied in developed nations, research evaluating biological characteristics, delivered treatment, and clinical outcomes is very limited in Indonesia.
METHODS: We analyzed all breast cancer patients who underwent surgery at Dr. Sardjito Hospital, Indonesia, in 2012-2017. Details of pathology profiles, treatment administrated, and outcomes, as well as reproductive factors among patients younger than 40 years old, were collected and analyzed. Kaplan-Meier curve was used to assess conditional survival based on baseline characteristics.
RESULTS: From the total of 1259 breast cancer patients (median age 51 years), 144 (11.4%) were younger than 40 years old (median age 37 years). Of these young patients, 19 (13.2%) were bilateral and 92 (64%) were diagnosed in advanced stages (stages IIIA-C and IV). Median tumor diameter was 5.5 cm and nodal infiltration was present in 73%. Distant metastasis was found in 16% at the time of diagnosis. Moderate and poor differentiation of tumor were 20.8 and 78.5%, respectively, and lymphovascular invasion was found in 90.3%. Around 40% were hormone receptor-positive, 30.6% human epidermal growth factor receptor 2 positive, and 38.2% triple negative. Patients underwent radical surgery in 121 cases (84%) and breast conserving surgery in 7 cases (4.9%). Adjuvant chemotherapy was administrated in 68% and hormonal therapy in 34%. Progression-free survival was significantly shorter in patients with advanced stage, skin and chest wall involvement (T4), positive lymph node infiltration, positive hormonal receptor, and triple negative subtype (log-rank Mantel-Cox tests, p < 0.05).
CONCLUSION: We found a high frequency of young breast cancer with biologically more aggressive tumors, late diagnosis, frequent relapse, and poor prognosis. Further actions to improve clinical management and meet psychosocial needs in young breast cancer patients are warranted.

Rozaliyani A, Sedono R, Jusuf A, et al.
A novel diagnosis scoring model to predict invasive pulmonary aspergillosis in the intensive care unit.
Saudi Med J. 2019; 40(2):140-146 [PubMed] Free Access to Full Article Related Publications
OBJECTIVES: To improve the quality of invasive pulmonary aspergillosis (IPA) management for intensive care unit (ICU) patients using a practical diagnostic scoring model.
METHODS: This nested case-control study aimed to determine the incidence of IPA in 405 ICU patients, between July 2012 and June 2014, at 6 hospitals in Jakarta, Indonesia. Phenotypic identifications and galactomannan (GM) tests of sera and lung excreta were performed in mycology laboratory, Parasitology Department, Faculty of Medicine, Universitas Indonesia in Jakarta, Indonesia.
RESULTS: The incidence of IPA in the ICUs was 7.7% (31 of 405 patients). A scoring model used for IPA diagnosis showed 4 variables as the most potential risk factors: lung excreta GM index (score 2), solid organ malignancy (score 2), pulmonary tuberculosis (score 2), and systemic corticosteroids (score 1). Patients were included in a high-risk group if their score was greater than 2, and in a low-risk group if their score was less than 2.
CONCLUSION: This study provides a novel diagnosis scoring model to predict IPA in ICU patients. Using this model, a more rapid diagnosis and treatment of IPA may be possible. The application of the diagnosis scoring should be preceded by specified pre-requisites.

Satibi S, Andayani TM, Endarti D, et al.
Comparison of Real Cost Versus the Indonesian Case Base Groups (INA-CBGs) Tariff Rates Among Patients of High- Incidence Cancers Under the National Health Insurance Scheme
Asian Pac J Cancer Prev. 2019; 20(1):117-122 [PubMed] Free Access to Full Article Related Publications
Background: The national health insurance of Indonesia has implemented the Indonesian Case Base Groups (INA-CBGs) tariff rates for healthcare payment. However, there is still problem of difference between the real cost of healthcare and the INA-CBGs tariff rates. This study aimed to evaluate the real cost of healthcare in comparison with the INA-CBG’s tariff rates and to analyze factors associating with the real cost. The study focus on healthcare cost of non-chemotherapy expenditure among patients of high-incidence cancers having chemotherapy covered by the national health insurance. Methods: The study was conducted from the perspective of healthcare provider. Costs data was obtained from hospital billing of Sanglah hospital, a referral hospital in Bali Provincein the period of January – July 2014. The data involved 383, 161, and 152 of in-patient breast cancer cases, cervical cancer cases, and nasopharyngeal cancer cases, respectively. Descriptive statistic was used to analyze patients characteristics, one sample t-test was used to analyze the mean difference of healthcare cost based on real cost and INA-CBG’s tariff rates, and finally, bivariate analysis was used to examine relationship between patients’ characteristics and the real cost. Results: The study shows there were significant differences of non-chemotherapy expenditures based on the real cost and INA-CBG’s tariff rates, in which the costs were lower for the real cost. Factors which significantly associated with the real cost were number of procedure, type of hospitalized room, and length of stay. Conclusions: The study supports the necessary of evaluation of the INA-CBG’s tariff rates to adjust to the real healthcare expenditure. On the other hand, the hospital needs to evaluate the service quality of patient treatment by optimizing budget allocated by the health insurance.

Riantoro BD, Kristina SA, Endarti D
Estimating Premature Mortality Cost of Cancers Attributable to Obesity in Indonesia
Asian Pac J Cancer Prev. 2019; 20(1):87-90 [PubMed] Free Access to Full Article Related Publications
Obesity is one of the risk factor of non-communicable diseases, one of them is cancer. It may lead to the escalation of mortality. Indonesia is the top 10 country with the highest prevalence of cancer burden due to obesity. The chance of cancer caused by obesity is estimated epidemiologic descriptive and prevalence-based estimation with obesity attributable cancer mortality and Premature Mortality Cost as indicators. Obesity-related cancer mortality is calculated by multiplying Obesity Attributable Fractions (OAFs) rate by cancer death rate, which OAFs rate obtained by calculating obesity prevalence data and relative risk of each disease. Premature Mortality Cost was calculated by multiplying obesity-related cancer mortality, life expectancy, and Indonesian average income. The highest total mortality’s rate for obesity-related cancer and overweight-related cancer are colon cancer (929 deaths), ovarian cancer (599 deaths), and pancreatic cancer (190 deaths). The highest value of Premature Mortality Cost are IDR 61,118 million for ovarian cancer, IDR 56,651 million for colon cancer, and IDR 15,472 million for pancreatic cancer. The estimation of cancer burden due to obesity shall be done to help the government determines the health programs and decrease the number of cancer burden due to obesity in Indonesia.

Loho IM, Siregar L, Waspodo AS, Hasan I
Current Practice of Hepatocellular Carcinoma Surveillance.
Acta Med Indones. 2018; 50(4):353-360 [PubMed] Related Publications
Hepatocellular carcinoma (HCC) is the second most common cause of cancer-related death worldwide. This is due to the heterogeneity of the tumor biology and lack of curative treatment options. The most significant prognostic factor is detection at early stage and thus, surveillance strategies are of high importance. High-risk patients should undergo ultrasound and tumor marker tests at six-month interval in order to detect HCC at the earlier stage. However, in real-life practice, ultrasound has several limitations and the adherence to HCC surveillance is suboptimal due to various provider, patient, and health-care system factors. In this paper, we will address current methods of HCC surveillance and obstacles found in real-life practice.

Widjaja FF, Kalista KF, Kurniawan J
Radiofrequency Ablation versus Resection in Large Single Nodule of Hepatocellular Carcinoma: an Evidence-based Case Report.
Acta Med Indones. 2018; 50(4):346-352 [PubMed] Related Publications
BACKGROUND: nowadays, radiofrequency ablation (RFA) is applied widely as an alternative therapy of resection in patient with hepatocellular carcinoma (HCC). Moreover, in single nodule with size of less than 2 cm, RFA can be the primary treatment. Although resection is the main treatment and one of the curative treatments in nodule meeting Milan criteria, it needs consideritation of the surgery risk stratification. This report was aimed to search evidence of RFA compared with RFA in term of survival in patient with HCC single nodule size of more than 5 cm.
METHODS: the searching was done using PubMed, Scopus, Web of Science, dan CINAHL from EBSCO with keyword of "hepatocellular carcinoma", "single nodule", "radiofrequency ablation", "resection", and "survival". The limitation of the article was English with clinical question of "In patient with HCC single nodule size of more than 5cm, was RFA more superior in resection in term of survival?".
RESULTS: there were three articles with retrospective study. One of the article combined RFA and percutaneous ethanol injection in the analysis, meanwhile another article combined RFA and transarterial chemoembolization. These articles showed conflicting data that showed absolute risk reduction of 33% till absolute risk increment of 60.6%.
CONCLUSION: all studies used RFA as the alternative of resection when the the tumor was irresectable which means the severity is higher in RFA group. Hence, we can not solely conclude that RFA resulted in worse survival.

Sutandyo N, Suratman E
Non-Small Cell Lung Carcinoma in Women: A Retrospective Cohort Study in Indonesia.
Acta Med Indones. 2018; 50(4):291-298 [PubMed] Related Publications
BACKGROUND: the increasing incidence of lung cancer in female patients has been observed in Indonesia. Lung cancer in female might have different biology process than male, but it has never been evaluated in Indonesia. This study aimed to know characteristics and survival of female patients with non-small-cell lung carcinoma (NSCLC) in Dharmais National Cancer Centre Hospital.
METHODS: a retrospective cohort study was performed among NSCLC female patients in Dharmais Cancer Hospital (DCH) between January 2005 and December 2015. Survival analysis was done using the Kaplan-Meir estimation curve with proportional assumption test. Independent prognostic factors were analyzed using the Cox proportional hazard model with a hazard ratio (HR) and its 95% confidence interval (CI).
RESULTS: a total of 956 NSCLC cases were retrieved during the study; 268 (28.0%) were female patients. Mean of age in female patients was 56.9 (11.87) years old. Among female patients, 21 (7.8%) were smokers, 244 (91.1%) had adenocarcinoma subtype, and 261 (98.0%) were in advanced stage (III-IV). Median survival was slightly longer in female than male patients (14.9 months vs. 12.2 months; log-rank p=0.055). Significant prognostic factors for survival were older age (>50 y.o) (HR = 0.681; 95% CI = 0.467 - 0.992; p= 0.045) and positive eGFR mutation (HR = 0.393; 95% CI = 0.251 - 0.615; p<0.001).
CONCLUSION: female patients contributed to about 28% of all NSCLC cases. They were mostly non-smokers, have more adenocarcinoma histopathology and eGFR mutation. Survival tended to be longer in female than male patients. Age over 50 years and the presence of eGFR mutation were good prognostic factors to survival in female lung cancer patients.

Wardhani LO, Matsushita M, Kuwamoto S, et al.
Expression of Notch 3 and Jagged 1 Is Associated With Merkel Cell Polyomavirus Status and Prognosis in Merkel Cell Carcinoma.
Anticancer Res. 2019; 39(1):319-329 [PubMed] Related Publications
BACKGROUND/AIM: Merkel cell carcinoma (MCC) is a rare, aggressive, neuroendocrine skin cancer and most MCCs are related to infection with Merkel cell polyomavirus (MCPyV). Notch signaling modulates cell fate in various tissues including the skin during development and homeostasis, and its aberrant activity relates to onset and progression of various malignancies. Therefore, association of NOTCH1/ NOTCH2/NOTCH3/jagged 1 (JAG1) expression with MCPyV status and prognosis in MCC was investigated.
MATERIALS AND METHODS: A total of 19 MCPyV-positive and 19 MCPyV-negative MCC samples from patients were stained immunohistochemically with antibodies against NOTCH1, NOTCH2, NOTCH3, and JAG1 and analyzed.
RESULTS: Expression of NOTCH1 and NOTCH2 was not associated with MCPyV status or prognosis. However, higher JAG1 expression was found in MCPyV-negative than in MCPyV-positive MCC (p<0.001), and NOTCH3 expression was higher in MCPyV-positive MCC (p=0.062). Kaplan-Meier and multivariate analyses showed that patients with MCC with higher NOTCH3 expression had better overall survival than otherwise (p=0.001 and p=0.033, respectively).
CONCLUSION: Expression of NOTCH3, as a tumor suppressor, is an independent predictor of MCC outcome.

Yang C, Chan KK, Xu G, et al.
Biodegradable Polymer-Coated Multifunctional Graphene Quantum Dots for Light-Triggered Synergetic Therapy of Pancreatic Cancer.
ACS Appl Mater Interfaces. 2019; 11(3):2768-2781 [PubMed] Related Publications
In this work, we reported the synthesis of an engineered novel nanocarrier composed of biodegradable charged polyester vectors (BCPVs) and graphene quantum dots (GQDs) for pancreatic cancer (MiaPaCa-2 cells) therapy applications. Such a nanocarrier was utilized to co-load doxorubicin (DOX) and small interfering ribonucleic acid (siRNA), resulting in the formation of GQD/DOX/BCPV/siRNA nanocomplexes. The resulting nanocomplexes have demonstrated high stability in physiologically mimicking media, excellent K-ras downregulation activity, and effective bioactivity inhibition for MiaPaCa-2 cells. More importantly, laser light was used to generate heat for the nanocomplexes via the photothermal effect to damage the cells, which was further employed to trigger the release of payloads from the nanocomplexes. Such triggered release function greatly enhanced the anticancer activity of the nanocomplexes. Preliminary colony formation study also suggested that GQD/DOX/BCPV/siRNA nanocomplexes are qualified carrier candidates in subsequent in vivo tests.

Sari DP, Basyuni M, Hasibuan PA, et al.
Cytotoxic and Antiproliferative Activity of Polyisoprenoids in Seventeen Mangroves Species Against WiDr Colon Cancer Cells
Asian Pac J Cancer Prev. 2018; 19(12):3393-3400 [PubMed] Free Access to Full Article Related Publications
Background: Secondary metabolites from the group of isoprenoid compounds are widely distributed in mangrove plants. Polyisoprenoids (dolichol and polyprenol) are known to have benefits as anticancer agents. The present study was conducted to determine the cytotoxic potential of polyisoprenoids in leaves from seventeen selected mangrove species against colon cancer (WiDr) cells. Methods: Cytotoxic activity was evaluated by MTT assay in vitro using WiDr human colon cancer cells and 3T3 fibroblasts from Swiss albino mouse embryo tissue as controls. Mechanisms of action were approached by assessing apoptosis and the cell cycle using flow cytometry and fluorescence microscopy with annexin V-FITC, as well as expression of Bcl-2 and cyclin D1 by immunocytochemistry. Results: Polyisoprenoids from N. fruticans leaves demonstrated the highest anticancer activity, with an IC50 of 180.2 μg/mL, as compared to 397.7 μg/mL against 3T3 normal cells. Significant decrease in the expression of Bcl-2 and cyclin D1 was also noted, facilitating apoptosis and arrest of the cell cycle in the G0-G1 phase in WiDr cells. The present study showed for the first time that polyisoprenoids from N. fruticans exhibit concrete anticancer activity in vitro, decreasing cell proliferation and inducing apoptosis in colon cancer cells. Conclusions: Polyisoprenoids isolated from N. fruticans leaves may have promise as a source of anticancer agents.

Yamaguchi S, Sasaki K, Kato H, et al.
Questionnaire-Based Survey on Management of Ulcerative Colitis-Associated Cancer in East Asian Countries.
Digestion. 2019; 99(1):86-94 [PubMed] Related Publications
BACKGROUND/AIMS: To elucidate the current management of ulcerative colitis (UC)-associated cancer, a questionnaire-based survey was conducted to gather current opinions on colitis-associated cancer in different East Asian countries.
METHODS: The questionnaire, based on physicians, contains 9 questions focused on UC management and cancer surveillance. In addition, the questionnaire based on neoplastic cases, which contains 17 questions, was collected and analyzed.
RESULTS: With regard to the diagnosis of UC-associated cancer, most respondents started surveillance colonoscopy within 10 years from onset, favored targeted biopsies, and thought advanced imaging was useful. As for morphology, the frequency of elevated lesion and type 4 lesions was most common in early and advanced cancer, respectively. Peritoneal metastasis was frequently observed, and undifferentiated tumor was frequently developed. Laparoscopic surgery was widely used because it is less invasive. The prognostic outcome was poor, particularly in stage III and undifferentiated type.
CONCLUSIONS: The current survey elucidated the current management in Asian countries and characteristics of colitis-associated cancer in these countries.

Wimardhani YS, Warnakulasuriya S, Subita GP, et al.
Public awareness of oral cancer among adults in Jakarta, Indonesia.
J Investig Clin Dent. 2019; 10(1):e12379 [PubMed] Related Publications
AIM: The aim of the present study was to investigate the awareness of oral cancer among adults in Jakarta, Indonesia, and explore the factors influencing it.
METHODS: A previously-tested questionnaire on 1000 adults in Jakarta was used in the present study. The data included sociodemographic factors and answers to assess the awareness of oral cancer, early signs and symptoms, risks factors, lifestyles, and history of dental visits.
RESULTS: Only 53.2% of participants were aware of oral cancer. The level of awareness significantly differed by level of education, occupation, and experience of dental visits. Only 30% of patients had been asked about their tobacco and alcohol habits, and had been informed about the hazards of these by their dentists. All of the smokers knew that tobacco increased the risk for oral cancer. However, only a few participants considered alcohol, betel quid chewing, UV light exposure, poor diet, and genetics to play role in the development of oral cancer. Health warnings were the main source of information about oral cancer; the role of health professionals is still quite low and needs to be emphasized.
CONCLUSION: Oral cancer awareness is still low among adults in Jakarta; this finding was consistent with other studies conducted in Asia. Educational material suited to particular communities is warranted.

Isnaini I, Permatasari N, Mintaroem K, et al.
Oxidants-Antioxidants Profile in the Breast Cancer Cell Line MCF-7
Asian Pac J Cancer Prev. 2018; 19(11):3175-3178 [PubMed] Free Access to Full Article Related Publications
Reactive oxygen species (ROS) have various biological effects and they are non-linear in characteristic. In high oxidative stress, they may cause cytotoxicity, inhibit cell proliferation, and induce cell death in the form of apoptosis/necrosis; while in low or medium oxidative stress, ROS may cause DNA damage, cell mutation, inflammation, cell proliferation, and eventually they may induce carcinogenesis. Antioxidants are compounds with the ability to reduce ROS. Cell line MCF-7 is one of the breast cancer cell lines that is known to have small amount of antioxidant MnSOD compared to the other cell lines. Low antioxidant MnSOD level in breast cancer cell line MCF-7 leads to low concentration of hydrogen peroxide, because antioxidant MnSOD will convert radical superoxide to hydrogen peroxide. The aim of this research was to analyze oxidants and antioxidants profile in breast cancer cell line MCF-7 and their relationship with cell number. Observations were conducted for 5 days. The cell number was counted with tryphan blue method and haematometer. The concentration of radical superoxide was measured with DHE staining using LSCM tipe Olympus Fluoview FV 1000-Ver 1.7. MnSOD activity, hydrogen peroxide concentration, and catalase activity were measured with ELISA. The results showed that the longer of observation, the greater concentration of oxidants and MnSOD activity, but there was no change in catalase activity. Conclusion the increase in cancer cells number is influenced by radical superoxide.

Arshita N, Lestari RV, Hutajulu SH, et al.
The Tendency of Having MSH2 and MSH6 Microsatellite Instability among Clinicopathological Features in Patients with Colorectal Cancer
Asian Pac J Cancer Prev. 2018; 19(11):3147-3152 [PubMed] Free Access to Full Article Related Publications
Objective: This study aimed to identify micro-satellite instability (MSI) based on the expression of MMRp (MSH2 and MSH6) and to evaluate the association of MSI and with clinicopathological features in patients with colorectal cancer (CRC). Methods: MMRp expression in 80 tissue samples from patients with adenocarcinoma CRC were evaluated by using anti-MSH2 and -MSH6 antibodies. Loss of MSH2 and/or MSH6 expression was stated as MSI. The association between MSI status and clinicopathological features were analyzed by using binary logistic regression (p<0.05). Results: The frequency of MSI in patients with CRC varied, corresponding to 8.3% (6/72) MSH2 MSI, 36.1% (26/72) MSH6 MSI and 6.9% (5/72) MSH2-MSH6 MSI. Male patients (OR=1.98), with tumor located in colon (OR=1.47) and late stage tumor (OR=1.48) have a tendency of having MSH2 MSI. Male patients (OR=1.4), with tumor located in colon (OR=2.53) and poor tumor differentiation (OR=3.02) have a tendency to encounter MSH6 MSI. Male patients (OR=4.93) with late stage tumor (OR=1.69) have a tendency of having MSH2-MSH6 MSI. Conclusion: Patients more likely to have MSH2 MSI are males, and/or having tumor located in colon, and /or having late stage tumor. Patients more likely to have MSH6 MSI are males, and/or having tumor located in colon, and/or having tumor with poor differentiation. Patients who have greater tendency to have MSH2 and MSH6 MSI are males, and/or having late stage tumor.

Kumasaka S, Nakajima T, Arisaka Y, et al.
Prognostic value of metabolic tumor volume of pretreatment
BMC Med Imaging. 2018; 18(1):46 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: This study aimed to determine the prognostic value of positron emission tomography (PET) metabolic parameters-namely metabolic tumor volume (MTV), total lesion glycolysis (TLG), and total lesion retention (TLR)-on fluorine-18 (
METHODS: The study group comprised 112 NSCLC patients who underwent
RESULTS: Higher TNM, higher clinical stage, inoperable status, and higher values for all PET parameters (both
CONCLUSIONS: MTV of

Ramayanti O, Verkuijlen SAWM, Novianti P, et al.
Vesicle-bound EBV-BART13-3p miRNA in circulation distinguishes nasopharyngeal from other head and neck cancer and asymptomatic EBV-infections.
Int J Cancer. 2019; 144(10):2555-2566 [PubMed] Free Access to Full Article Related Publications
Cell-free microRNA (miRNA) in biofluids released by tumors in either protein or vesicle-bound form, represent promising minimally-invasive cancer biomarkers. However, a highly abundant non-tumor background in human plasma and serum complicates the discovery and detection of tumor-selective circulating miRNAs. We performed small RNA sequencing on serum and plasma RNA from Nasopharyngeal Carcinoma (NPC) patients. Collectively, Epstein Barr virus-encoded miRNAs, more so than endogenous miRNAs, signify presence of NPC. However, RNAseq-based EBV miRNA profiles differ between NPC patients, suggesting inter-tumor heterogeneity or divergent secretory characteristics. We determined with sensitive qRT-PCR assays that EBV miRNAs BART7-3p, BART9-3p and BART13-3p are actively secreted by C666.1 NPC cells bound to extracellular vesicles (EVs) and soluble ribonucleoprotein complexes. Importantly, these miRNAs are expressed in all primary NPC tumor biopsies and readily detected in nasopharyngeal brushings from both early and late-stage NPC patients. Increased levels of BART7-3p, BART9-3p and particularly BART13-3p, distinguish NPC patient sera from healthy controls. Receiver operating characteristic curve analysis using sera from endemic NPC patients, other head and neck cancers and individuals with asymptomatic EBV-infections reveals a superior diagnostic performance of EBV miRNAs over anti-EBNA1 IgA serology and EBV-DNA load (AUC 0.87-0.96 vs 0.86 and 0.66 respectively). The high specificity of circulating EBV-BART13-3p (97%) for NPC detection is in agreement with active secretion from NPC tumor cells. We conclude EV-bound BART13-3p in circulation is a promising, NPC-selective, biomarker that should be considered as part of a screening strategy to identify NPC in endemic regions.

Jain M, Rojanaporn D, Chawla B, et al.
Retinoblastoma in Asia.
Eye (Lond). 2019; 33(1):87-96 [PubMed] Article available free on PMC after 01/01/2020 Related Publications
Asia-Pacific region bears a significant global burden of retinoblastoma (RB), therefore understanding RB in Asia-Pacific region is important. Based on the year 2013 population estimates, 43% (3452 of 8099 children) of the global burden of RB lives in 6 countries of Asia-Pacific region: 1486 children in India, 1103 children in China, 277 children in Indonesia, 260 children in Pakistan, 184 children in Bangladesh, 142 children in Philippines. There exists a wide disparity, technological and socio-economical, within countries in this region resulting in a varied pattern of clinical presentation and survival varies. Challenges in developing nations are not just technological, but also social. Opportunities emerge for research to study and understand the socio-economical aspects of the disease to develop interventions that are relevant culturally and feasible economically. Possible steps include disease education and counselling, universal screening, highly subsidized/free of cost treatment for low socioeconomic strata, raising funds through the government and non-governmental organizations, sensitization and training of man-power in screening, diagnosis and treatment, and developing new specialized centers with tele-ophthalmology services.

Yuniarti L, Mustofa M, Aryandono T, Haryana SM
Synergistic Action of 1,2-Epoxy-3 (3- (3,4-dimethoxyphenyl)- 4H-1-benzopiyran-4-on) Propane with Doxorubicin and Cisplatin through Increasing of p53, TIMP-3, and MicroRNA-34a in Cervical Cancer Cell Line (HeLa)
Asian Pac J Cancer Prev. 2018; 19(10):2955-2962 [PubMed] Article available free on PMC after 01/01/2020 Related Publications
Objective: Cervical cancer is the second most common cancer among women worldwide, with a high mortality rate especially in developing countries. Insufficient treatment for cervical cancer, multiple side effects, and high drug prices encourage researchers to look for effective and selective cancer drugs with appropriate molecular targets. This study explored the cytotoxicity of (1,2-epoxy-3(3-(3,4-dimethoxyphenyl)-4H-1-benzopyran-4-on) propane (EPI) synthesized from clove leaves oil on HeLa cells, its combination with doxorubicin (DOX) and cisplatin (CIS), and also their influence on p53, TIMP-3, and miR-34a as therapeutic targets. Materials and Methods: This research was an experimental in vitro study on cervical cancer uteri culture. The cytotoxicity was analyzed by MTT assay. The drug combination synergisms were indicated by the combination index (CI) (using CompuSyn 1.4). HeLa cells in 32 wells were divided into eight groups as negative control, which were given EPI ½IC50, EPI IC50, EPI 2IC50, DOX IC50, combination of EPI+DOX, CIS, and the combination of EPI+CIS. The p53 and TIMP-3 concentrations were measured using ELISA, and expressions of miR-34a with qRT-PCR. One-way ANOVA and post hoc Tukey tests were performed to determine the mean difference of all variables between the study groups. Results: IC50 for EPI was 33.24 (±3.01) μg/ml, while DOX and CIS were 4.8 μg/ml (±0.1), and 23.34 μg/ml (±3.01), respectively, while CI values for EPI-DOX were <0.1 and for EPI-CIS <0.9. Expression of p53 in group 6 (1.67±0.31) μg/ml and 8 (1.18±0.18) μg/ml, TIMP-3 6 (3.81±0.49) μg/ml and 8 (2.93±0.42) μg/ml were significantly higher compared to the control group (p<0.05). All treatment groups showed significantly increased miR-34a expressions compared to the control group (p<0.05). Conclusion: The combinations showed a very strong synergism and a moderate slight synergism for EPI-DOX and EPI-CIS. Both combinations were able to increase the expressions of p53, TIMP-3 proteins, and MiR-34a in the HeLa cells.

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