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Ibnu Purwanto,1,* Benedreky Leo,2,* Susanna Hilda Hutajulu,1 Johan Kurnianda,1 Kartika Widayati Taroeno-Hariadi,1 Mardiah Suci Hardianti,1 Amanda Dania Satiti,1 Ery Kus Dwianingsih,3 Didik Setyo Heriyanto,3 Irianiwati Widodo,3 Teguh Aryandono4 1Division of Hematology and Medical Oncology, Department of Internal Medicine, Faculty of Medicine, Public Health, and Nursing, Gadjah Mada University/Dr Sardjito Hospital, Yogyakarta, Indonesia; 2Department of Internal Medicine, Faculty of Medicine, Public Health, and Nursing, Gadjah Mada University/Dr Sardjito Hospital, Yogyakarta, Indonesia; 3Department of Anatomical Pathology, Faculty of Medicine, Public Health, and Nursing, Gadjah Mada University/Dr Sardjito Hospital, Yogyakarta, Indonesia; 4Division of Surgical Oncology, Department of Surgery, Faculty of Medicine, Public Health, and Nursing, Gadjah Mada University/Dr Sardjito Hospital, Yogyakarta, Indonesia*These authors contributed equally to this workCorrespondence: Ibnu Purwanto, Jalan Farmako, Sekip Utara, Yogyakarta, 55281, Indonesia, Tel/Fax +62 274 560300, Email ibnupurwanto@ugm.ac.idPurpose: To determine the prognostic value of vimentin in triple negative breast cancer (TNBC) patients, specifically in relation to chemotherapy regimen and p53 mutant expression.Patient and Methods: We retrospectively analyzed the association of pre-treatment tumor expression of vimentin with 48-month overall survival (OS) of 72 all stages TNBC patients diagnosed between 2014 and 2018 in relation to chemotherapy regimen and expression of p53 mutant. Vimentin and p53 mutant expressions were examined using immunohistochemistry. Analysis was conducted on all patients collectively, then repeated on two cohorts divided according to the chemotherapy regimen. Sub-analysis was performed to determine the effect of p53 mutant expression on the prognostic value of vimentin.Results: Vimentin was expressed in 43.1% of patients and was not associated with clinicopathologic characteristics. Vimentin was associated with improved 48-month OS in all patients in univariate analysis but not significant in multivariate analysis. When analyzed according to chemotherapy regimen, vimentin was independently associated with improved 48-month OS in patients receiving non-platinum-based chemotherapy (80% vs 15.8%; HR: 0.17, 95% CI: 0.05– 0.58, p: 0.005). Other independent prognostic factors include T (HR: 6.18, 95% CI: 1.38– 27.7, p: 0.017) and M (HR: 5.64, 95% CI: 1.2– 26.33, p: 0.028). On subanalysis, vimentin was significantly associated with improved 48-month OS in patients expressing p53 mutant (69.2% vs 22.2%, p: 0.006) but was not significant in patients not expressing p53 mutant.Conclusion: Vimentin expression was independently associated with improved 48-month OS in TNBC patients treated with non–platinum–based chemotherapy. Expression of p53 mutant significantly affected the prognostic value of vimentin.Keywords: vimentin, p53 mutant, chemotherapy, platinum resistance, TNBC, prognostic factor

Susanna Hilda Hutajulu,1 Johan Kurnianda,1 I Bing Tan,2,3 Jaap M Middeldorp4 1Department of Internal Medicine, Faculty of Medicine Universitas Gadjah Mada/Dr Sardjito General Hospital, Yogyakarta, Indonesia; 2Department of Ear, Nose and Throat, The Netherlands Cancer Institute/Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands; 3Department of Ear, Nose and Throat, Faculty of Medicine Universitas Gadjah Mada/Dr Sardjito General Hospital, Yogyakarta, Indonesia; 4Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands Abstract: Nasopharyngeal carcinoma (NPC) is highly endemic in certain regions including the People's Republic of China and Southeast Asia. Its etiology is unique and multifactorial, involving genetic background, epigenetic, and environment factors, including Epstein–Barr virus (EBV) infection. The presence of EBV in all tumor cells, aberrant pattern of antibodies against EBV antigens in patient sera, and elevated viral DNA in patient circulation as well as nasopharyngeal site underline the role of EBV during NPC development. In NPC tumors, EBV expresses latency type II, where three EBV-encoded proteins, Epstein–Barr nuclear antigen 1, latent membrane protein 1 and 2 (LMP1, 2), are expressed along with BamH1-A rightward reading frame 1, Epstein–Barr virus-encoded small nuclear RNAs, and BamH1-A rightward transcripts. Among all encoded proteins, LMP1 plays a central role in the propagation of NPC. Standard treatment of NPC consists of radiotherapy with or without chemotherapy for early stage, concurrent chemoradiotherapy in locally advanced tumors, and palliative systemic chemotherapy in metastatic disease. However, this standard care has limitations, allowing recurrences and disease progression in a certain proportion of cases. Although the pathophysiological link and molecular process of EBV-induced oncogenesis are not fully understood, therapeutic approaches targeting the virus may increase the cure rate and add clinical benefit. The promising results of early phase clinical trials on EBV-specific immunotherapy, epigenetic therapy, and treatment with viral lytic induction offer new options for treating NPC. Keywords: immunotherapy, epigenetic therapy, viral lytic induction therapy

Purpose: Chemotherapy-induced peripheral neuropathy (CIPN) poses a substantial challenge in breast cancer (BC) chemotherapy, affecting the patient's quality of life. Recent studies have focused on exploring predictors and patterns of CIPN occurrence. We aimed to develop a prediction model for CIPN occurrence using a classification and regression tree (CART) algorithm., Methods: In this prospective study of 170 patients with BC undergoing chemotherapy, patient-reported adaptation of the Common Terminology Criteria for Adverse Events version 4.0 was used to assess CIPN occurrence. Multivariable analysis using the CART model was tuned using 10-fold cross-validation to identify baseline predictors for CIPN throughout chemotherapy. A receiver operating characteristic curve analysis was conducted for the CART model. A multivariable logistic regression was conducted from the variables included in the CART model to assess the strength and direction of the association., Results: The prevalence of CIPN was 64.7% (n = 110). The most decisive predictor of CIPN occurrence in the CART model was the subject's C-reactive protein (CRP) level. CRP level >3.91 mg/dL, BMI >21.85 kg/m 2 , and a marital status of unmarried have predicted a probability of 100% in CIPN occurrence. The CART model showed an accuracy of 65.9%, sensitivity of 51.7%, specificity of 73.2%, and an area under the curve of 0.705. A CRP level of >3.91 mg/dL and a neutrophil-to-lymphocyte ratio (NLR) of >2.82 are significantly associated with the occurrence of CIPN (odds ratio [OR], 2.01 [95% CI, 1.01 to 4.01]; P = .046, OR, 2.09 [95%, CI, 1.02 to 4.24]; P = .042, respectively)., Conclusion: Baseline CRP, NLR, BMI level, and marital status are significant predictors of CIPN occurrence throughout chemotherapy. Our CART model was better at ruling out individuals who would not experience CIPN. The CART model may provide insight into the future development of individualized patient care and prevention strategies.

Objectives: To assess the feasibility, acceptability, and preliminary effectiveness of implementing a home-based aerobic and resistance exercise for patients with breast cancer receiving endocrine treatment in Indonesia., Methods: This is a mixed methods study with concurrent design consisting of quantitative single-arm pre-post intervention and qualitative study. We recruited patients with breast cancer ( N  = 36) receiving endocrine treatment and assigned 12 weeks of home-based pedometer-driven walking and resistance exercises using therapeutic bands. Descriptive statistics were used to assess the feasibility (recruitment, retention, and adherence) and safety. The modified Bruce treadmill test was used to measure predicted aerobic capacity (V̇O 2 peak). Quality of life and fatigue were assessed using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire and fatigue severity scale. Measurements were performed at baseline and post-intervention and analyzed with the paired t -test or Wilcoxon test. Semi-structured interviews and thematic analysis were conducted post-intervention to explore patients' acceptability., Results: The results showed a recruitment rate of 75%, retention rate of 89%, and adherence rates were 53% for aerobic and 78% for resistance exercise. No severe adverse events were reported. Post-intervention interviews identified positive attitudes toward the intervention, with low burden and high perceived benefit. Exercise duration and predicted V̇O 2  peak increased significantly (+1.1 min, p  = 0.001 and +2.3 ml/kg/min, p  = 0.043), but no significant change was detected for Quality of Life ( p  > 0.050) or fatigue severity ( p  = 0.299)., Conclusions: A home-based aerobic and resistance exercise was feasible when implemented in the context of routine care in our study population, improving predicted aerobic capacity. Further research is required to understand limited changes to Quality of Life and fatigue and adaptations to support implementation in additional sites in Indonesia., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2024.)

Background: Early colorectal cancer (CRC) symptom recognition and prompt diagnosis are crucial for the identification of cases in the earliest stage and for improving survival. This study investigates the incidence of presentation and diagnosis delays, their contributing determinants and their impact on the cancer stage at diagnosis., Methods: This cross-sectional study recruited 227 CRC patients between November 2022 and October 2023. We developed a semi-structured questionnaire to collect information on the factors related to delays in the presentation and diagnosis. Presentation delay was defined as the time between the initial symptoms and the first consultation exceeding 1 month, while diagnosis delay was defined as the time between presentation and the pathological diagnosis confirmation exceeding 4 months. We examined the impact of these delays on the status of the metastatic disease and identified the determinants of the presentation and diagnosis delays., Results: The median values for presentation and diagnosis delay are 1 and 4 months, respectively. Patients aged ≥60 years were less likely to experience diagnosis delays odds ratio (OR = 0.52, 95% confidence interval (CI) 0.28-0.95, p = 0.035), as opposed to those who were younger. The absence of red flag symptoms at presentation (OR = 2.73, 95% CI 1.47-5.10, p = 0.002), the utilisation of complementary and alternative medicine (OR = 2.01, 95% CI 1.12-3.61, p = 0.019) and ≥3 distinct healthcare facility visits before diagnosis (OR = 3.51, 95% CI 1.95-6.29, p < 0.001) were associated with an increased risk of diagnosis delays. Diagnosis delays were also correlated with a higher risk of metastatic disease at diagnosis (OR = 2.04, 95% CI 1.17-3.53, p = 0.011)., Conclusion: Our CRC patients experience considerable delays in their presentation and diagnosis. Diagnosis delays were observed to increase the likelihood of presenting with metastatic disease. Given the determinants and the patients' perspectives revealed in this study, future research to explore evidence-based approaches to reducing these delays is warranted., Competing Interests: The author(s) declare that they have no conflict of interest., (© the authors; licensee ecancermedicalscience.)

Purpose: There has been a global increase in early-onset colorectal cancer (EOCRC), yet there has been very limited exploration of its impact in Indonesia. This study aimed to determine the clinicopathologic characteristics and the overall survival (OS) of EOCRC compared with those of average-onset colorectal cancer (AOCRC)., Methods: Medical records were retrospectively reviewed from all patients presenting with colorectal cancer (CRC) at Dr Sardjito General Hospital (Yogyakarta, Indonesia) between 2016 and 2019. Sociodemographic, clinicopathologic, and treatment variables were extracted. t Tests were used to compare characteristics of EOCRC and AOCRC patient groups. The Cox proportional hazards regression model was used to analyze age and other potential prognostic factors., Results: The total population (N = 1,276) comprised EOCRC (n = 149; 11.7%) and AOCRC (n = 1,127; 88.3%) patients. EOCRC patients were more likely to have a higher education level, be single, have out-of-pocket insurance, be underweight, and have signet ring histology (all P values <.05), compared with AOCRC patients. EOCRC and AOCRC groups had a comparable estimated 5-year OS of 34.2% and 36.9%, respectively. In multivariable analyses, performance status (Eastern Cooperative Oncology Group), hemoglobin level, cancer stage, and treatment intention were independent prognostic factors for OS (all P values <.05)., Conclusion: To our knowledge, this first major study of EOCRC in Indonesia highlights its role in the overall burden of CRC and its connection with social determinants of health. Patients with EOCRC are more commonly underweight and generally have a higher proportion of signet ring histology than AOCRC, yet OS in both groups is similar. Future research is required to identify risk factors to inform the content and focus of public health education activities, alongside delineating the biology and causes of early and average onset of the disease.

Background: In Indonesia incidence of colorectal cancer (CRC) remains high. Information about early symptoms that can offer clinicians insights for timely diagnosis, prompt referral and quick treatment decisions is very limited. This study aims to examine the pattern of CRC early symptoms and its association with tumor laterality, age at onset, metastatic status, and symptom-to-treatment initiation (STI) duration and delay., Method: This cross-sectional study recruits 258 patients diagnosed with CRC between November 2022 and October 2023 from two distinct study databases. Patient baseline characteristics were also obtained from medical records and through interviews at baseline. Symptom-to-treatment initiation (STI) duration was defined as the number of days between the date of the symptom's onset and the date of the first treatment's initiation. Relative risk estimation for metastatic disease and the STI delay, based on tumor laterality and the age at onset group, were estimated using a log-binomial regression for each early symptom., Result: Experiencing abdominal mass as an early symptom is significantly associated with metastatic disease, specifically in right-sided CRC cases (relative risk/RR=2.08, 95% confidence interval/CI 1.29-3.37, p=0.003). In all study subjects, the median STI duration was 182 days (2-5,082 days), with more than half of the subjects experiencing an STI delay of >180 days. Experiencing rectal mass as an early symptom is significantly associated with a higher risk of STI delay >180 days in early onset CRC (RR=1.97, 95% CI 1.27-3.06, p=0.003) and left sided-CRC cases (RR=1.54, 95% CI 1.13-2.08, p=0.005). The non-specific early symptom of weight loss is associated with a higher risk of STI delay >180 days in right-sided CRC cases (RR=1.73, 95% CI 1.06-2.84, p=0.029)., Conclusion: The findings underlined the importance of maintaining a high clinical suspicion, particularly in patients with rectal masses and unexplained weight loss, as they might experience STI delay.

Background: In Indonesia, early-onset colorectal cancer (EOCRC) rates are higher in patients < 50 years old compared to Western populations, possibly due to a higher frequency of Lynch syndrome (LS) in CRC patients. We aimed to examine the association of KRAS and PIK3CA mutations with LS., Methods: In this retrospective cross-sectional single-center study, the PCR-HRM-based test was used for screening of microsatellite instability (MSI) mononucleotide markers (BAT25, BAT26, BCAT25, MYB, EWSR1), MLH1 promoter methylation, and oncogene mutations of BRAF (V600E), KRAS (exon 2 and 3), and PIK3CA (exon 9 and 20) in FFPE DNA samples., Results: All the samples (n = 244) were from Dr. Sardjito General Hospital Yogyakarta, Indonesia. KRAS and PIK3CA mutations were found in 151/244 (61.88%) and 107/244 (43.85%) of samples, respectively. KRAS and PIK3CA mutations were significantly associated with MSI status in 32/42 (76.19%) and 25/42 (59.52%) of samples, respectively. KRAS mutation was significantly associated with LS status in 26/32 (81.25%) of samples. The PIK3CA mutation was present in a higher proportion in LS samples of 19/32 (59.38%), but not statistically significant. Clinicopathology showed that KRAS mutation was significantly associated with right-sided CRC and higher histology grade in 39/151 (25.83%) and 24/151 (16.44%) samples, respectively. PIK3CA mutation was significantly associated with female sex and lower levels of tumor-infiltrating lymphocytes in 62/107 (57.94%) and 26/107 (30.23%) samples, respectively. KRAS and PIK3CA mutations did not significantly affect overall survival (120 months) in LS and non-LS patients., Conclusions: The high probability of LS in Indonesian CRC patients is associated with KRAS and PIK3CA mutations., Competing Interests: MI was appointed as specialist committee member to the Diagnostics Assessment Committee of the National Institute for Health and Care Excellence (NICE), which produced the guidance DG27 on Lynch Syndrome testing. DSH, AMR, and MI are unpaid scientific advisors of PathGen Diagnostik Teknologi. Other authors have no competing interest to declare., (Copyright 2024, Heriyanto et al.)

Objectives: Colon and rectal cancer are associated with different risk factors and prognostic. However, this discrepancy has not been widely explored in the local population. This study aimed to investigate the site-specific likelihood of colorectal cancer (CRC) incidence in the Yogyakarta province, Indonesia., Methods: This cross-sectional study analyses 1,295 CRC cases diagnosed in 2008-2019 registered in the Yogyakarta population-based cancer registry (PBCR) database. Cases were grouped into colon and rectal cancer. Log-binomial regression was used to determine the relative risk of either colon or rectal cancer across different gender, age group, and rurality of residence. The age-specific rates were calculated by age group and temporal trend for each group were analyzed using joinpoint regression., Results: Females displayed higher odds of colon cancer (relative risk/RR = 1.20, 95%CI = 1.02-1.41) and lower odds of rectal cancer (RR = 0.92, 95%CI = 0.85-0.99). Elevated odds of colon cancer were observed in younger age group, especially 30-39 (RR = 1.87, 95%CI = 1.10-3.19), while decreased odds of rectal cancer was apparent in age group 30-39 and 40-49 (RR = 0.75, 95%CI = 0.60-0.93 and RR = 0.82, 95%CI = 0.69-0.98, respectively). Living in urban or rural areas did not significantly influence the odds of either having colon (RR = 0.98, 95%CI = 0.82-1.17) or rectal cancer (RR = 1.01, 95%CI = 0.93-1.10). During 2008-2019, trends of colon cancer in age <50 increased by 8.15% annually while rectal cancer displayed a 9.71% increase annually prior to 2017, followed by a 17.23% decrease until 2019., Conclusions: Yogyakarta population shows higher odds of young-onset colon cancer, especially between age 30-39 years old. Overall observation of trend shows increasing incidence in young-onset colon cancer, and non-significant decrease in rectal cancer., Competing Interests: The authors have declared that no competing interests exixst., (Copyright: © 2024 Puspitaningtyas et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objective: This study aims to characterize patient-reported chemotherapy-induced toxicity in patients with breast cancer, determine its association with treatment regimens and patient characteristics, identify toxicity symptom clusters within a specific chemotherapy timeframe and analyze the correlation between symptom clusters within and between the timeframe to understand the changes and influences across chemotherapy., Methods: Forty-six patient-reported toxicities during neoadjuvant/adjuvant chemotherapy for breast cancer were evaluated using adapted CTCAE version 4.0. Chi-Square/Fisher's Exact test was performed to analyze the difference in the incidence of toxicity symptoms by chemotherapy regimens. Poisson regression performed to assess factors associated with patient's total chemotherapy toxicity. Exploratory factor analysis (EFA) conducted to identify symptom clusters at T1 (first half) and T2 (second half of planned cycle). Factor scores were generated and Spearman correlation performed to explore the factor scores correlation between symptom clusters., Results: A total of 142 patients with stage I-III breast cancer were included. The incidence of several toxicities differed significantly among three chemotherapy regimens. Subjects age ≥51 years are associated with lower number of reported toxicity (IRR/incidence rate ratio = 0.94, 95% confidence interval/CI 0.88 to 0.99, p = 0.042). Receiving more chemotherapy cycles are associated with higher number of reported toxicity (IRR = 1.06, 95% CI 1.03 to 1.10, p<0.001). Two symptom clusters identified at T1 (psychoneurological-pain/PNP-T1 and gastrointestinal-psychological/GIP-T1 cluster) and three at T2 (psychoneurological-pain/PNP-T2, epithelial/EPI-T2, and gastrointestinal cluster/GI-T2), with moderate-strong positive correlation between PNP-T1 and GIP-T2 (p<0.001), PNP-T1 and PNP-T2 (p<0.001), and GIP-T1 and PNP-T2 (p<0.001)., Conclusions: This study investigated 46 patient-reported toxicities prospectively during adjuvant/neoadjuvant chemotherapy for early breast cancer. Anthracycline-taxane combination regimen had higher proportions of toxicity incidence. Subject's age and number of chemotherapy cycles significantly associated with total number of toxicity symptoms. Two symptom clusters at T1 and three at T2 were identified, with significant correlation between symptom clusters within and between chemotherapy timeframe., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Wiranata et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Nasopharyngeal carcinoma (NPC) is the most prevalent geographically-specific head and neck cancer. Its incidence was high in the Asian population, especially in certain parts such as Southern China and South East Asia. Most patients with NPC are presented with intermediate-stage or locally advanced disease requiring chemoradiation as the primary treatment of choice. Epidermal Growth Factor Receptor (EGFR) was found overexpressed in most patients with NPC associated with poor prognosis making its inhibitor one of the most plausible treatment options in addition to chemoradiation. In EGFR-positive NPC patients, nimotuzumab, a humanized anti-EGFR monoclonal antibody will bind the extracellular domain of EGFR leading to tumor growth suppressions. This study's objective was to assess the real-world clinical efficacy of nimotuzumab for patients with intermediate-stage and locally advanced NPC when in combination with concurrent chemoradiation., Methods: This retrospective real-world study examined a sample of intermediate-stage and locally advanced NPC patients who were treated with or without adding nimotuzumab to concurrent chemoradiation at Dr. Cipto Mangunkusumo General Hospital in Indonesia from January 2009 to December 2017. The outcomes were patients' real-world five-year overall survival (rwOS) and progression-free survival (rwPFS) compared using Kaplan-Meier analysis and Cox proportional hazard models adjusting for age, gender, comorbidities, clinical staging, staging based on Tumor status (T), staging based on Nodes status (N), and types of radiotherapy.  Results: A total of 407 patients were included in the analysis, 61 patients receiving concurrent nimotuzumab and chemoradiation and 346 patients receiving chemoradiation alone. Patients receiving concurrent nimotuzumab and chemoradiation tended to have less aggressive NPC than patients receiving chemoradiation alone. Multivariate-adjusted Cox models revealed that combining nimotuzumab with chemoradiation was associated with a statistically significant longer rwOS gain (hazard ratio (HR)=0.46 (95% CI: 0.26-0.82, p=0.008)) and a trend of longer rwPFS (hazard ratio (HR)=0.67 (95% CI: 0.41-1.09, p=0.109)) in comparison to chemoradiation alone.  Conclusion: In this retrospective real-world study, concurrent nimotuzumab and chemoradiation usage was associated with a significant overall survival benefit than chemoradiation alone for intermediate-stage and locally advanced NPC patients. Hence, adding nimotuzumab to patients' chemoradiation should be considered in patients with intermediate-stage and locally advanced NPC., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Rachman et al.)

Background: Chemotherapy-induced neutropenia (CIN) is a substantial side effect in chemotherapy of breast cancer patients. Administration of granulocyte colony stimulating factor (G-CSF) that may reduce CIN occurrence is not commonly available to many local cases., Objectives: To investigate the occurrence of grade 4 CIN and the influencing factors in breast cancer patients not receiving G-CSF prophylaxis., Methods: One-hundred and eighty-six newly diagnosed breast cancer patients who received a 3-weekly (neo)adjuvant or palliative chemotherapy without primary G-CSF prophylaxis were included. Grade 4 CIN was defined as absolute neutrophil count (ANC) <0.5 × 10 3 /mm 3 during any chemotherapy cycle. We used logistic regression to explore the association of clinical, pathological and treatment factors with the risk of grade 4 CIN in the first cycle and in any given cycle., Results: Fifty-seven (30.6%) patients experienced grade 4 CIN in the first cycle and 145 (78%) had it at least once during chemotherapy. In the first cycle, haemoglobin, ANC, and albumin levels were associated with grade 4 CIN (OR = 1.48, p = 0.031; OR = 0.68, p = 0.006; and OR = 2.07, p = 0.042). In any cycle, pre-treatment ANC levels and anthracycline-taxane combination regimen were associated with grade 4 CIN (OR = 0.78, p = 0.032 and OR = 3.64, p = 0.012)., Conclusions: A significant proportion of the local breast cancer cases undergoing chemotherapy without primary G-CSF prophylaxis experienced grade 4 CIN. Haemoglobin, ANC, and albumin levels are the risk factors for first cycle CIN, while pre-treatment ANC levels and anthracycline-taxane chemotherapy regimen are associated with CIN in any given cycle. These risk factors may be used to direct a recommendation of G-CSF prophylaxis to the most at-risk individuals in the local setting or other settings in similar situations., Competing Interests: The authors declare no conflict of interest for this manuscript., (© the authors; licensee ecancermedicalscience.)

Nasopharyngeal cancer (NPC) cases are often diagnosed in advanced stages. The complexity of clinical management for advanced-stage NPC requires thorough communication and shared decisions between medical professionals and allied teams. Incorporating a multidisciplinary team meeting (MDTM) for newly diagnosed NPC patients was chosen to facilitate collaboration and communication between physicians. This retrospective study aimed to compare the quality of care, clinical responses and survival between NPC patients treated with and without MDTM. Data on clinical responses, assessment visits, date of progression and death with progression-free survival (PFS), overall survival (OS), and hazard ratio (HR) were collected and analyzed with 95% confidence interval (CI) and significance set as P  < .05. There were 87 of 178 NPC patients treated with MDTM. Revisions of diagnosis and stage occurred in 5.7% and 52.9% of cases during the MDTM. More clinical responses were achieved by patients treated with MDTM (69.0%vs 32.0%, P  < .00). NPC patients who received MDTM treatment recommendation had a lower risk for progression (median PFS 59.89 months vs 12.68 months; HR 0.267, 95% CI: 0.17-0.40, P  < .00) and mortality (median OS was not reached vs 13.44 months; HR 0.134, 95% CI: 0.08-0.24, P  < .00) compared to patients without MDTM. Incorporating the MDTM approach into NPC management improves patients' clinical responses and survival., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2023.)

BACKGROUND Cerebral ischemia and hemorrhages were reported to be the main complications of polycythemia vera (PV). The relationship between PV and increased risk of the cerebrovascular events has been established. Some patients with secondary polycythemia have thromboembolic events comparable to those of PV. However, secondary polycythemia that leads to cerebrovascular events is uncommon. CASE REPORT A 35-year-old man without any prior medical history presented with mild clinical acute ischemic stroke and polycythemia. The patient then showed worsening neurological deficits that were later attributed to the concurrent cerebral venous thrombosis, which led to malignant cerebral infarction with hemorrhagic transformation, and subarachnoid hemorrhage. His polycythemia appeared to be secondary to bacterial infection. The treatments for the secondary polycythemia were first phlebotomy and intravenous hydration, followed by intravenous broad-spectrum antibiotics. PV was excluded because the JAK2 V617F mutation was absent, the patient's peripheral blood smear suggested secondary polycythemia due to bacterial infection, and there were improvements in hemoglobin, erythrocyte count, and hematocrit after intravenous antibiotics. At the 1-month follow-up, he was moderately dependent, and hemoglobin, erythrocyte count, and hematocrit were within normal limits, without receiving any further phlebotomy or cytoreductive agents. CONCLUSIONS This case highlights the plausible causation of secondary polycythemia that could lead to concomitant cerebral thrombosis and hemorrhagic events. The diagnosis of cerebral venous thrombosis should be considered in a patient who presents with headache, focal neurological deficits, polycythemia, and normal head computed tomography scan.

Introduction Triple assessment, consisting of clinical breast examination, breast imaging, and fine-needle aspiration biopsy (FNAB), is the gold standard for breast lump diagnosis to avoid diagnostic errors. However, current diagnostic practices for breast lump cases in Indonesia are widely variable and evidence for triple assessment implementation is lacking. We aimed to explore the implementation of diagnostic assessments in breast lump cases, its influencing factors, and its association with diagnostic error. Methods This cross-sectional study consecutively recruited 364 females with breast lumps who underwent surgery in Soehadi Prijonegoro Public Hospital, Sragen, Indonesia. Data were retrospectively collected from patient's medical records. Diagnostic assessments were classified as single assessment with clinical breast examination, double assessment with clinical breast examination and breast ultrasonography (USG) or fine-needle aspiration biopsy (FNAB), and triple assessment. Diagnostic error was defined as a discrepancy between pre- and post-surgery diagnosis or repeated surgery without neoadjuvant chemotherapy. Factors associated with diagnostic assessment implementation, diagnostic error, and repeated surgery were analyzed using the chi-square test. Results The choice of diagnostic assessment was influenced by patients' age and health insurance (p<0.001). Triple assessment was only implemented in 21 (5.8%) breast lump cases. It was more frequently applied in patients ≥40 years (57.1%) and patients with contributory health insurance (76.2%). Diagnostic errors were observed in 84 cases (23.1%) and 47 patients out of them (47%) experienced repeated surgery. The implementation of diagnostic assessments was not associated with diagnostic error (p=0.257) but was significantly associated with repeated surgery in breast cancer (p<0.001). Repeated surgery rates were significantly lowered in cases receiving double assessment with FNAB (p<0.001). Conclusions The implementation of triple assessment in the local setting was very low. The choice of diagnostic assessment was influenced by patients' age and health insurance. Further, double assessment applying clinical breast examination and FNAB significantly decreased repeated surgery rates and thus may serve as an alternative to triple assessment in the limited resource setting., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Guntersah et al.)

Introduction Chemotherapy-induced nausea and vomiting (CINV) is a common and debilitating adverse effect of breast cancer chemotherapy. The incidence of CINV in the first cycle of chemotherapy is essential, as it sets the tone for anticipatory CINV and the overall patients' treatment experience. We aimed to investigate the risk factors of first cycle CINV in breast cancer patients and to develop a classification and regression tree (CART) model to predict its occurrence. Methods This is a cross-sectional study that nested in a prospective cohort. One hundred and thirty-seven female breast cancer patients receiving highly emetogenic chemotherapy were included. We used the Common Toxicity Criteria for Adverse Events (CTCAE) version 4.0 to assess patient-reported nausea and vomiting in the first chemotherapy cycle. The proportional difference of CINV between sociodemographic and clinicopathologic variables was analyzed using chi-square, and the strength and direction of the relationship with CINV were analyzed using bivariable logistic regression analysis. Multivariable logistic regression and CART analysis included variables with a p-value <0.250. Results The incidence of first-cycle CINV was 43.1%. The chi-square test revealed a significant association between insurance status and CINV (p<0.001) and between the stage at diagnosis and CINV (p<0.001). Underweight to normal body mass index (BMI) patients are significantly associated with an increased risk of first-cycle CINV (OR =2.17, 95% CI 1.03-4.56, p =0.041). In hierarchical order, three variables (stage at diagnosis, BMI, and age) were included in the CART model, which significantly influenced the probability of first cycle CINV. With an accuracy of 61.3%, the CART model had a sensitivity of 28.8%, a specificity of 85.9%, a positive predictive value of 60.7%, a negative predictive value of 61.5%, and an area under curve (AUC) of 0.602.  Conclusion Breast cancer patients with an underweight to normal BMI have a higher risk of developing first-cycle CINV. Our CART model was better at identifying patients who would not develop CINV than those who would. The CART model may provide a simple and effective way to individualize patient care for first-cycle CINV., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Ng et al.)

Background: The utilization of a multidisciplinary team (MDT) strategy is a beneficial approach in integrating the knowledge and proficiencies of various fields to produce thorough and advantageous cancer treatment plans for patients. Nevertheless, MDT has yet to be widely adopted in Indonesia. In this study, the authors examined an early form of MDT in Indonesia that does not involve dedicated meetings, referred as independent multidisciplinary work (IMW). The objective is to investigate the differences in survival rates of nasopharyngeal cancer (NPC) patients who underwent treatment with and without IMW., Materials and Methods: This study has a retrospective cohort design. Data were collected from the medical records of newly diagnosed stage 3 and 4 NPC patients between 2016 and 2018. The subjects were divided into two groups: the IMW group and the non-IMW group. The primary end point of the study is overall survival rate between the two groups. Kaplan-Meier survival analysis, log-rank test, and cox proportional hazard analysis were used for statistical analysis., Results: This study included a total of 124 patients with NPC, 81 patients in the IMW group and 43 patients in the non-IMW group. At the end of the 36-month follow-up period, the median survival of the IMW group was not reached, while in the non-IMW, it was 12 months [95% confidence intervals (95% CI), 8.78-15.22], hazard ratio (HR): 0.47 (95% CI, 0.28-0.78; P <0.01). The 1-year survival rate was 66.7% in the IMW group versus 46.5% in the non-IMW group (HR=0.7, 95% CI 0.49-0.99; P =0.03); the 2-year survival rate was 40.7% in the IMW group versus 16.3% in the non-IMW group (HR=0.4, 95% CI 0.19-0.83; P <0.01). Daniel Rizky, Vina Yunarvika, and Yasjudan Rastrama Putra, these authors contributed equally to this work. In the multivariate analysis, the IMW approach, ECOG (The Eastern Cooperative Oncology Group) status, distant metastasis, and treatment approach were significantly associated with survival outcome., Conclusion: The use of IMW approach in the treatment of NPC was associated with a better survival outcome compared to non-IMW treatment., Competing Interests: The authors declare that there are no conflicts of interest.Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Introduction Sexual dysfunction is rarely studied in Indonesian patients with breast cancer. We aimed to assess the prevalence of sexual dysfunction symptoms following chemotherapy, as well as the pattern and the associated factors. Methods This cross-sectional study included 135 female breast cancer patients receiving primary chemotherapy. The present study measured the prevalence of sexual dysfunction symptoms using an e-questionnaire containing Common Toxicity Criteria for Adverse Events (CTCAE) version 4 at different time points. Other data included sociodemography, clinicopathology, treatment, and other concurrent symptom characteristics. Bivariate and multivariate logistic regression tests were used to analyze any association among variables. Results In the whole panel, 86 (63.7%) of 135 cases experienced sexual dysfunction. The most common symptom was vaginal dryness (45.9%), followed by decreased libido (45.2%), dyspareunia (13.3%), delayed orgasm (11.1%), and anorgasmia (8.9%). When observed at five different time points, the frequency of symptoms increased during chemotherapy and persisted until six months after completing treatment. Chemotherapy duration of >120 days was associated with a higher probability of vaginal dryness (p=0.012) and decreased libido (p=0.033). Spouse age ≥55 years old and body mass index (BMI) ≥23 kg/m 2 were associated with a reduced probability of decreased libido (p=0.033 and 0.025, respectively). The presence of comorbidity was associated with a reduced probability of delayed orgasm (p=0.034). Conclusions A significant proportion of patients with breast cancer had sexual dysfunction following chemotherapy. Vaginal dryness, decreased libido, and dyspareunia were the commonest symptoms observed. Duration of chemotherapy, spouse age, BMI, and comorbidity were associated with the risk of sexual dysfunction occurrence., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Haris et al.)

Background: Breast cancer is a significant public health concern worldwide, including in Indonesia. Little is known about the spatial and temporal patterns of breast cancer incidence in Indonesia. This study aimed to analyze temporal and spatial variations of breast cancer incidence in Yogyakarta Province, Indonesia., Methods: The study used breast cancer case data from the Yogyakarta Population-Based Cancer Registry (PBCR) from 2008 to 2019. The catchment areas of the PBCR included the 48 subdistricts of 3 districts (Sleman, Yogyakarta City, and Bantul). Age-standardized incidence rates (ASR) were calculated for each subdistrict. Joinpoint regression was used to detect any significant changes in trends over time. Global Moran's and Local Indicators of Spatial Association (LISA) analyses were performed to identify any spatial clusters or outliers., Results: The subdistricts had a median ASR of 41.9, with a range of 15.3-70.4. The majority of cases were diagnosed at a late stage, with Yogyakarta City having the highest proportion of diagnoses at stage 4. The study observed a significant increasing trend in breast cancer incidence over the study period the fastest of which is in Yogyakarta City with an average annual percentage change of 18.77%, with Sleman having an 18.21% and Bantul having 8.94% average changes each year (p <0.05). We also found a significant positive spatial autocorrelation of breast cancer incidence rates in the province (I = 0.581, p <0.001). LISA analysis identified 11 subdistricts which were high-high clusters in the central area of Yogyakarta City and six low-low clusters in the southeast region of the catchment area in the Bantul and Sleman Districts. No spatial outliers were identified., Conclusions: We found significant spatial clustering of BC ASR in the Yogyakarta Province, and there was a trend of increasing ASR across the region. These findings can inform resource allocation for public health efforts to high-risk areas and develop targeted prevention and early detection strategies. Further res is needed to understand the factors driving the observed temporal and spatial patterns of breast cancer incidence in Yogyakarta Province, Indonesia., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Ng et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

We aimed to explore the district-level temporal dynamics and sub-district level geographical variations of colorectal cancer (CRC) incidence in the Special Region of Yogyakarta Province. We performed a cross-sectional study using data from the Yogyakarta population-based cancer registry (PBCR) comprised of 1,593 CRC cases diagnosed in 2008-2019. The age-standardized rates (ASRs) were determined using 2014 population data. The temporal trend and geographical distribution of cases were analysed using joinpoint regression and Moran's I statistics. During 2008-2019, CRC incidence increased by 13.44% annually. Joinpoints were identified in 2014 and 2017, which were also the periods when annual percentage change (APC) was the highest throughout the observation periods (18.84). Significant APC changes were observed in all districts, with the highest in Kota Yogyakarta (15.57). The ASR of CRC incidence per 100,000 person- years was 7.03 in Sleman, 9.20 in Kota Yogyakarta, and 7.07 in Bantul district. We found a regional variation of CRC ASR with a concentrated pattern of hotspots in the central sub-districts of the catchment areas and a significant positive spatial autocorrelation of CRC incidence rates in the province (I=0.581, p<0.001). The analysis identified four high-high clusters sub-districts in the central catchment areas. This is the first Indonesian study reported from PBCR data, showing an increased annual CRC incidence during an extensive observation period in the Yogyakarta region. A heterogeneous distribution map of CRC incidence is included. These findings may serve as basis for CRC screening implementation and healthcare services improvement.

BACKGROUND Chemotherapy based on 5-fluorouracil (5-FU) is a well-established treatment for solid cancers, including metastatic or advanced colon cancer. Despite its efficacy, 5-FU can cause rare but serious adverse events such as acute neurotoxicity, which presents as symptoms similar to stroke. CASE REPORT We report the case of a patient who was diagnosed with stage IV colorectal cancer and who underwent chemotherapy with a high dose of 5-FU as part of the FOLFIRI (Folinic Acid, Fluorouracil, Irinotecan) treatment plan. During the seventh, eighth, and ninth cycles of chemotherapy, the patient suffered from severe encephalopathy, and the cause of this condition was determined to the 46-hour continuous intravenous infusion of 5-FU, which was part of the FOLFIRI regimen. CONCLUSIONS 5-FU-induced hyperammonemic encephalopathy is a rare but serious adverse event that requires immediate recognition and treatment. The first step in managing this condition is to halt the 5-FU infusion and provide the patient with high volumes of fluid. Although most cases of 5-FU-induced encephalopathy resolve spontaneously, recurrence is possible if the drug is re-administered to the same patient. Therefore, it is crucial for healthcare providers to closely monitor patients receiving 5-FU chemotherapy and be aware of the signs and symptoms of hyperammonemic encephalopathy. Early intervention can prevent further complications and ensure the best possible outcome for the patient. It is important to note that while 5-FU-induced hyperammonemic encephalopathy is rare, it highlights the importance of closely monitoring patients receiving chemotherapy to identify and treat adverse events promptly. This can help improve patient outcomes and prevent serious long-term complications.

Background: Lung cancer is the second most common cancer and leading cause of cancer mortality worldwide. Recent advances in molecular testing and targeted therapy have improved survival among patients with metastatic non-small-cell lung cancer (NSCLC). We sought to quantify and describe molecular testing among metastatic non-squamous NSCLC cases in selected Southeast Asian countries and describe first-line therapy chosen., Patients and Methods: A retrospective study was conducted based on incident lung cancer cases diagnosed between 2017 and 2019 in Lampang (Thailand), Penang (Malaysia), Singapore and Yogyakarta (Indonesia). Cases (n = 3413) were defined using the International Classification of Diseases for Oncology third edition. In Singapore, a clinical series obtained from the National Cancer Centre was used to identify patients, while corresponding population-based cancer registries were used elsewhere. Tumor and clinical information were abstracted by chart review according to a predefined study protocol. Molecular testing of epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK) gene rearrangement, ROS1 gene rearrangement and BRAF V600 mutation was recorded., Results: Among 2962 cases with a specified pathological diagnosis (86.8%), most patients had non-squamous NSCLC (75.8%). For cases with staging information (92.1%), the majority presented with metastatic disease (71.3%). Overall, molecular testing rates in the 1528 patients with stage IV non-squamous NSCLC were 67.0% for EGFR, 42.3% for ALK, 39.1% for ROS1, 7.8% for BRAF and 36.1% for PD-L1. Among these patients, first-line systemic treatment included chemotherapy (25.9%), targeted therapy (35.6%) and immunotherapy (5.9%), with 31% of patients having no record of antitumor treatment. Molecular testing and the proportion of patients receiving treatment were highly heterogenous between the regions., Conclusions: This first analysis of data from a clinically annotated registry for lung cancer from four settings in Southeast Asia has demonstrated the feasibility of integrating clinical data within population-based cancer registries. Our study results identify areas where further development could improve patient access to optimal treatment., Competing Interests: Disclosure RS is involved in advisory boards for Amgen, AstraZeneca, Bayer, BMS, Boehringer Ingelheim, Janssen, Lily, Merck, Merck Serono, Novartis, Pfizer, Puma, Roche, Taiho, Takeda, Yuhan and has received research grants from AstraZeneca and Boehringer Ingelheim. RK has been an advisor/speaker or received honorarium from AstraZeneca, Pfizer, Merck, MSD, BMS, J&J, Ipsen, Eisai, Amgen, Novartis, Lucence Therapeutics and Astellas. NP has consulting or advisory roles with AstraZeneca, Novartis and Roche. SP has consulting/advisory roles with AbbVie, Amgen, Arcus, AstraZeneca, Bayer, Beigene, Biocartis, BioInvent, Blueprint Medicines, Boehringer Ingelheim, Bristol-Myers Squibb, Clovis, Daiichi Sankyo, Debiopharm, ecancer, Eli Lilly, Elsevier, F-Star, Fishawack, Foundation Medicine, Genzyme, Gilead, GSK, Illumina, Imedex, IQVIA, Incyte, iTeos, Janssen, Medscape, Merck Sharp and Dohme, Merck Serono, Merrimack, Novartis, Novocure, Oncology Education, Pharma Mar, Phosplatin Therapeutics, PER, Pfizer, PRIME, Regeneron, RMEI, Roche/Genentech, RTP, Sanofi, Seattle Genetics, Takeda and Vaccibody; has talked in organized public events for AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, ecancer, Eli Lilly, Foundation Medicine, Illumina, Imedex, Medscape, Merck Sharp and Dohme, Mirati, Novartis, PER, Pfizer, Prime, Roche/Genentech, RTP, Sanofi and Takeda; has been a principal investigator in trials (institutional financial support for clinical trials) sponsored by Amgen, AstraZeneca, Beigene, Bristol-Myers Squibb, GSK, Merck Sharp and Dohme, and Roche/Genentech. RSt has been an invited speaker for Amgen, AstraZeneca, Blueprint, Bristol-Myers Squibb, Boehringer Ingelheim, GSK, MSD, Novartis and Roche; has been on advisory boards for AstraZeneca, BMS, Boehringer Ingelheim, GSK, MSD, Pfizer, Roche, Sandoz, Seattle Genetics and Takeda; has received institutional support (ETOP, IBCSG) from AstraZeneca, Bristol-Myers Squibb, Daiichi Sankyo, Celgene, Ipsen, Janssen, Mirati, MSD, Novartis, Pfizer, Pierre Fabre and Roche. All other authors have declared no conflicts of interest. Where authors are identified as personnel of the International Agency for Research on Cancer/World Health Organization, the authors alone are responsible for the views expressed in this article, and they do not necessarily represent the decisions, policy, or views of the International Agency for Research on Cancer/World Health Organization., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Objectives: To observe pre- and post-treatment vitamin D level and its association with treatment and concomitant factors in breast cancer patients treated with chemotherapy., Methods: We performed a pre-post observational analysis that nested in an ongoing prospective cohort study of breast cancer patients at Dr. Sardjito General Hospital, Yogyakarta, Indonesia. 136 subjects were recruited from the main study. Information on subjects' socio-demographic characteristics clinical status, and tumour profile was assessed at baseline. Number of chemotherapy cycles and chemotherapy-induced nausea vomiting (CINV) were also recorded. Vitamin D concentration was measured using ELISA methods at baseline and post-treatment. Vitamin D level of <20 ng/ml and <12 ng/ml were defined as deficiency and severe deficiency. Correlation between socio-demographic and clinical profile with baseline vitamin D was tested using Spearman correlation. Paired t-test was used to evaluate changes in post-treatment vitamin D concentration. The odds ratio for a subject to experience post-treatment vitamin D decrease was assessed based on number of chemotherapy cycles and CINV severity., Results: The mean vitamin D level before chemotherapy was very low (8.80±3.64 ng/ml) in the whole panel. Higher AST level were associated with lower vitamin D level at baseline (r = -0.188, p = 0.028). Severe deficiency was found in 82.4% subjects at baseline and the rate increased to 89.0% after chemotherapy. Eighty-five cases showed a decrease level whereas 51 showed a slight improvement. Overall, a significant decrease of the vitamin D level was observed after chemotherapy (median change 3.13±4.03 ng/ml, p <0.001). Subjects who received >6 cycles of chemotherapy were less likely to experience a decreased level of post-treatment vitamin D (OR = 0.436, 95% CI = 0.196-0.968, p = 0.039)., Conclusions: Indonesian breast cancer patients showed pre-existing severe vitamin D deficiency and deterioration of vitamin D after chemotherapy. Future research is needed to explore its implication towards patients' survival in the local setting. Evidence-based approach also needs to be taken to address this modifiable condition, including increasing awareness of the importance of maintaining vitamin D sufficiency both in patients and the general population., Competing Interests: The authors have declared that no competing interests exist.

Introduction: Limited research exists exploring the experience of living with advanced breast cancer in Indonesia. We sought to explore the narratives of women with breast cancer across the illness trajectory to understand their experiences from diagnosis to accessing and undergoing cancer treatments to inform the development of cancer care., Methods: A nested, exploratory study adopting a qualitative approach. We conducted in-depth face-to-face interviews with women living with advanced breast cancer in Yogyakarta, Indonesia. We purposively sampled participants by age, education and marital status. All interviews were transcribed verbatim with thematic analysis used to identify, analyse and report patterns and themes within the data., Findings: Four main themes were derived: 1) Early experiences, prior to accessing health care; 2) Navigating the system to access treatment; 3) Enduring chemotherapy and advancing disease, with crucial family support; 4) Seeking normalcy and belief in treatment. From initial symptoms through to undergoing treatments, the experience of participants was punctuated by barriers and challenges., Discussion: Presentation delays were driven by dismissing initial symptoms, seeking alternative medicines, and fear of surgery. Access to healthcare required participants to contend with long-distance travel to facilities, tiered and convoluted referral processes, and adverse effects and financial impact of treatments. Individual determination, belief in God, and the role of families were critical throughout the disease trajectory. Adopting a focus across the disease trajectory facilitated the identification of enduring and persistent challenges to care delivery that can inform targeted development and optimisation of care delivery for women with breast cancer., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Chemotherapy is a commonly used cancer treatment. However, it causes physical side effects and psychological side effects such as distress. Providing prechemotherapy education using audiovisual methods can reduce distress, but not all research about the use of educational videos have the same conclusions. This study aimed to evaluate the effect of prechemotherapy education using audio visual methods on distress of patients with cancer. This study was a quasi-experiment using pre-test and posttest design with a control group. Eighty-two cancer patients who undergo chemotherapy for the first time were divided into 2 groups with forty-one patients in the control group and forty-one patients in the intervention group. Patients in the control group received education with a booklet (usual care), while the intervention group received prechemotherapy education using audio visual materials. Patients completed a distress thermometer before and 1-2 weeks after chemotherapy. The analysis used the Wilcoxon test in each group before and 1-2 weeks after prechemotherapy education. The Mann-Whitney tests were used to determine the difference in distress scores between the two groups. Statistical significance was defined as p value < 0.05. The effect of prechemotherapy education in each group was in the control group (p = 0.004) and the intervention group (p = 0.000). The control group had a mean decrease of 1.69 points, and the intervention group had a mean decrease of 1.29 points. There was a significant difference of distress between control group and intervention group with a p value of 0.037. The conclusion is the prechemotherapy education using audio visual method can reduce distress in patients with cancer in addition to the usual method., (© 2020. American Association for Cancer Education.)

Purpose: To investigate factors associated with delays in presentation and diagnosis of women with confirmed breast cancer (BC)., Methods: A cross-sectional study nested in an ongoing prospective cohort study of breast cancer patients at Dr Sardjito Hospital, Yogyakarta, Indonesia, was employed. Participants (n = 150) from the main study were recruited, with secondary information on demographic, clinical, and tumor variables collected from the study database. A questionnaire was used to gather data on other socioeconomic variables, herbal consumption, number of healthcare visits, knowledge-attitude-practice of BC, and open-ended questions relating to initial presentation. Presentation delay (time between initial symptom and first consultation) was defined as ≥3 months. Diagnosis delay was defined as ≥1 month between presentation and diagnosis confirmation. Impact on disease stage and determinants of both delays were examined. A Kruskal-Wallis test was used to assess the length and distribution of delays by disease stage. A multivariable logistic regression analysis was conducted to explore the association between delays, cancer stage and factors., Results: Sixty-five (43.3%) patients had a ≥3-month presentation delay and 97 (64.7%) had a diagnosis confirmation by ≥1 month. Both presentation and diagnosis delays increased the risk of being diagnosed with cancer stage III-IV (odds ratio/OR 2.21, 95% CI 0.97-5.01, p = 0.059 and OR 3.03, 95% CI 1.28-7.19, p = 0.012). Visit to providers ≤3 times was significantly attributed to a reduced diagnosis delay (OR 0.15, 95% CI 0.06-0.37, p <0.001), while having a family history of cancer was significantly associated with increased diagnosis delay (OR 2.28, 95% CI 1.03-5.04, p = 0.042). The most frequent reasons for delaying presentation were lack of awareness of the cause of symptoms (41.5%), low perceived severity (27.7%) and fear of surgery intervention (26.2%)., Conclusions: Almost half of BC patients in our setting had a delay in presentation and 64.7% experienced a delay in diagnosis. These delays increased the likelihood of presentation with a more advanced stage of disease. Future research is required in Indonesia to explore the feasibility of evidence-based approaches to reducing delays at both levels, including educational interventions to increase awareness of BC symptoms and reducing existing complex and convoluted referral pathways for patients suspected of having cancer., Competing Interests: The authors have declared that no competing interests exist.

The highest prevalence of breast cancer in Indonesia is in the Province of Yogyakarta. dr. Sardjito General Hospital has quite complete clinical data on breast cancer patients. Characteristics of the population in various regions in Indonesia are different from one another. This problem is the basis for doing this research. Statistical data analysis needs to be done in each area for better diagnosis and treatment of cancer. Data recording is carried out continuously during outpatient treatment at dr. Sardjito General Hospital. Data for breast cancer patients was taken from July 2018 to June 2020. The data obtained were grouped into four categories: laboratory investigation, socio-demographic, clinical examination, and pathology. Descriptive and correlation analysis aims to determine the characteristics of breast cancer patients seeking treatment at dr. Sardjito General Hospital and anticipate their possibility of developing neutropenia after chemotherapy. The results of the descriptive analysis are significant to determine patient characteristics and treatment steps that can be taken. Correlation analysis variables closely related to neutrophils included leucocyte count, lymphocyte, monocyte, albumin, age at first diagnosis, and height. These variables can be a severe concern of medical personnel before undergoing chemotherapy, especially lymphocytes, which have the largest (negative) correlation and can be an early sign of neutropenia., (© 2021 The Authors.)

There is about three times higher incidence of young patients <50 years old with colorectal cancer, termed EOCRC, in Indonesia as compared to Europe, the UK and USA. The aim of this study was to investigate the frequency of Lynch Syndrome (LS) in Indonesian CRC patients. The previously described Nottingham Lynch Syndrome Test (N&#95;LyST) was used in this project. N&#95;LyST is a robust high-resolution melting (HRM)-based test that has shown 100% concordance with standard reference methods, including capillary electrophoresis and Sanger sequencing. The test consisted of five mononucleotide microsatellite markers (BAT25, BAT26, BCAT25, MYB, EWSR1), BRAF V600E mutation and MLH1 region C promoter for methylation (using bisulphite-modified DNA). A total of 231 archival (2016-2019) formalin-fixed, paraffin-embedded (FFPE) tumour tissues from CRC patients collected from Dr. Sardjito General Hospital Yogyakarta, Indonesia, were successfully tested and analysed. Among those, 44/231 (19.05%) were MSI, 25/231 (10.82%) were harbouring BRAF V600E mutation and 6/231 (2.60%) had MLH1 promoter methylation. Almost all-186/197 (99.45%)-MSS cases were MLH1 promoter unmethylated, while there were only 5/44 (11.36%) MSI cases with MLH1 promoter methylation. Similarly, only 9/44 (20.45%) of MSI cases were BRAF mutant. There were 50/231 (21.65%) EOCRC cases, with 15/50 (30%) regarded as MSI, as opposed to 29/181 (16.02%) within the older group. In total, 32/231 patients (13.85%) were classified as "Probable Lynch" (MSI, BRAF wildtype and MLH1 promoter unmethylated), which were enriched in EOCRC as compared to older patients (24% vs. 11.05%, p = 0.035). Nonetheless, 30/50 (76.00%) cases among the EOCRC cases were non-LS (sporadic) and were significantly associated with a left-sided tumour. The overall survival of both "Probable Lynch" and non-LS (sporadic) groups ( n = 227) was comparable ( p = 0.59), with follow up period of 0-1845 days/61.5 months. Stage, node status, histological grading and ECOG score were significantly associated with patient overall survival ( p < 0.005), yet only ECOG was an independent factor for OS (HR: 4.38; 95% CI: 1.72-11.2; p = 0.002). In summary, this study is the first to reveal a potentially higher frequency of LS among CRC patients in Indonesia, which may partially contribute to the reported much higher number of EOCRC as compared to the incidence in the West.

Purpose: This study aimed to determine the survival outcome and prognostic factors of patients with nasopharyngeal cancer accessing treatment in Yogyakarta, Indonesia., Methods: Data on 759 patients with NPC diagnosed from 2007 to 2016 at Dr Sardjito General Hospital were included. Potential prognostic variables included sociodemographic, clinicopathology and treatment parameters. Multivariable analyses were implemented using semi-parametric Cox proportional hazards modelling and fully parametric survival analysis., Results: The median time of observation was 14.39 months. In the whole cohort the median observed survival was 31.08 months. In the univariable analysis, age, education status, insurance type, BMI, ECOG index, stage and treatment strategy had an impact on overall survival (OS) (p values <0.01). Semi-parametric multivariable analyses with stage stratification showed that education status, ECOG index, and treatment modality were independent prognostic factors for OS (p values <0.05). In the fully parametric models age, education status, ECOG index, stage, and treatment modality were independent prognostic factors for OS (p values <0.05). For both multivariable analyses, all treatment strategies were associated with a reduced hazard (semi-parametric models, p values <0.05) and a better OS (parametric models, p values <0.05) compared with no treatment. Furthermore, compared with radiation alone or chemotherapy alone, a combination of chemotherapy and radiation either in a form of concurrent chemoradiotherapy (CCRT), sequential chemotherapy and radiation, or induction chemotherapy followed by CCRT demonstrated a reduced hazard (hazard ratio/HR 0.226, 95% confidence interval/CI 0.089-0.363, and HR 0.390, 95%CI 0.260-0.519) and a better OS (time ratio/TR 3.108, 95%CI 1.274-4.942 and TR 2.531, 95%CI 1.829-3.233) (p values < 0.01)., Conclusions: Median OS for the cohort was low compared to those reported in both endemic and non-endemic regions. By combining the findings of multivariable analyses, we showed that age, education status, ECOG index, stage and first treatment modality were independent predictors for the OS., Competing Interests: The authors have declared that no competing interests exist.

Introduction: The incidence of cancer and its prevalence are increasing in Indonesia. It is crucial to ensure national cancer policies are evidence-based and promote research. While cancer research is being conducted across Indonesia, the extent and focus of research activities are not known, with no existing synthesis of the cancer research landscape. We seek to address this gap by characterising trends in the extent and types of cancer research conducted in Indonesia., Methods: Scientometric study using descriptive analyses to determine annual growth patterns in publications across all cancer research literature from Indonesia. We developed a classification system for both research type and study design which was applied to all included publications. A visualisation software tool (VOSviewer) was used to explore the geographical distribution of research activity. The Wilcoxon rank-sum test was used to determine the influence of international collaboration on the impact factor of journals in which articles were published., Results: We retrieved 1773 cancer-related articles published by Indonesia-affiliated authors from 1961 to 2020, with notable year-on-year increases in the annual total number of published articles since 2015. Most articles (84.0%) were published by authors affiliated with institutions on Java Island. The most commonly published article type was basic research and discovery science (28.8%), using a one-group analytical study design (28.8%). International collaboration was significantly correlated with a higher h-index of the journal in which research was published (P < .0001, r = .317)., Conclusion: An increase in the number and range of topics explored in cancer-related publications over time was identified. The summary of the current corpus of cancer-related research for Indonesia can be used to direct the development of the national cancer control plan alongside informing the national cancer research strategy. Our novel and feasible scientometric approach can be used to direct future national and regional mapping of cancer research.

The aim of this study was analyzing the BCR-ABL transcript types of patients with chronic myeloid leukemia (CML) in Dr Sardjito General Hospital, Yogyakarta, Indonesia. This study is very relevant because the data concerning BCR-ABL gene transcript types is very limited in Indonesia. Furthermore, it is important for patient's management, particularly in defining the tyrosine kinase inhibitors (TKIs) therapy and monitoring after therapy. The introduction of TKIs has become a major advance in the management of patients with CML, especially in the chronic phase (CML-CP), in which most patients are diagnosed., Methods: One hundred eighty five (185) of 370 recruited patients were included in this study (2010-2014). RNA samples were isolated from mononuclear cells of peripheral blood of the subjects taken at primary diagnosis. Detection of BCR-ABL gene transcript types was done using multiplex reverse transcriptase PCR (multiplex RT-PCR) and/or nested PCR following the cDNA synthesis. When the first PCR set failed to amplify the BCR-ABL gene, RT-conventional PCR and/or nested PCR would be applied. The proportion of each transcript type was calculated among the BCR-ABL positive CML patients., Results: Approximately 99% (183/185) of CML patients are BCR-ABL positive, with the most common type is major b3a2 (136/183; 74.3%), followed by major b2a2 (41/183; 22.4%). Two samples (1.1%) showed co-expression of b3a2 and b2a2; 1 sample showed co-expression of b3a2 and fragment at 500bp; and 3 samples showed uncommon fragments., Conclusion: Ninety nine percent (99%) of CML patients in Yogyakarta, Indonesia are BCR-ABL positive, with 74.3% have b3a2 transcript, 22.4% have b2a2 trascript, 1.1% have co-expression of b3a2 and b2a2 transcript, and the rest (2.2%) have uncommon bands that still need to be confirmed.

Background: The Indonesian government has applied the cancer "see and treat" method which involves a visual inspection using acetic acid (VIA), followed by a cryotherapy procedure, to reduce the incidence of cervical cancer. However, compliance with the program is still low in the targeted population. This study aims to see what factors influence women to receive cryotherapy treatment if they have positive VIA result., Methods: This cross-sectional study was conducted among 356 VIA positive women, aged 30-50 years old, registered at Temanggung District Health Office, Central Java, Indonesia between March 29 and April 31, 2018. Data on whether subjects underwent cryotherapy, their demographic profile, education, knowledge about cryotherapy, and family support were collected in a direct interview using a structured questionnaire. A statistical analysis was carried out to observe the influence of all the variables on subjects' decisions on cryotherapy., Results: In our study, 217 women (60.69%) received cryotherapy, while 139 women (39.04%) did not. Among all the variables analyzed, the factors affecting the subjects' likelihood to undergo cryotherapy are their knowledge about cervical cancer and screening (PR=0.776;95%CI=0.660-0.913;p=0.003), their residences distance from health centre (PR=0.795;95%CI=0.650-0.971;p=0.016), permission from their family (PR=0.675;95%CI=0.556-0.820;p=0.018), and being accompanied by their family (PR=0.824;95%CI=0.700-0.970;p=0.026). Age, marital status, occupation, and education background did not show a significant correlation with the women's decisions to receive cryotherapy., Conclusions: Interestingly, the result of our study indicates that women are less willing to undergo the cryotherapy procedure if they have good knowledge about the cryotherapy procedure and its importance in cervical cancer's prevention. Providing higher quality and more accessible health facilities with cryotherapy services are important in influencing women's willingness to receive cryotherapy. Family support, in the form of permission given by spouses, and if they accompanied the patient to seek cryotherapy care are observed as factors influencing women's willingness to have the procedure., .

Background: Oxaliplatin-based adjuvant chemotherapy has been applied as standard treatment for high risk stages II and III colon cancer in many countries. There was no comprehensive report of oxaliplatin use in Indonesia. This research aimed to evaluate the short-term survival of patients with colon cancer treated with such strategy and the prognostic factors., Methods: Medical records of patients with colon cancer receiving oxaliplatin-containing adjuvant chemotherapy were retrospectively reviewed. Demography, clinicopathological, and treatment data were collected. Two-year overall survival (OS) and disease-free survival (DFS) were calculated using Kaplan-Meier method and survival predictors were estimated using Cox proportional hazard models., Results: Data of 81 patients had been included with a median follow-up of 25.2 months. The estimated OS and DFS at 2 years were 75.8% and 72.7%. In multivariate analyses, the Eastern Cooperative Oncology Group (ECOG) 2 performance status [hazard ratio (HR) =2.967; 95% confidence interval (CI), 1.265 to 6.957; P=0.012], T4 stage (HR =2.669; 95% CI, 1.087 to 6.557; P=0.032), and less cycles of chemotherapy administration (HR =3.280; 95% CI, 1.333 to 8.070; P=0.010) were significant independent factors for an increased risk of death. Cases with moderately to poorly differentiated tumors had significantly worse DFS compared with those with well differentiated tumors (HR =3.503; 95% CI, 1.403 to 8.744; P=0.007)., Conclusions: Colon cancer patients receiving oxaliplatin-based adjuvant regimens in our clinical practice had 2-year OS rate of 75.8% and 2-year DFS rate of 72.7%. ECOG 2 performance status, T4 stage, and less cycles of chemotherapy administration significantly predicted a poor OS and moderately to poorly histological grade significantly predicted a poor DFS., Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare.

Background: Vascular endothelial growth factor-A (VEGF-A) has been observed as the predominant angiogenic factor in colorectal cancer (CRC) and the assessment of microvessel density (MVD) has been used to quantify tumor neoangiogenesis. This study aimed to determine clinicopathological and prognostic significance of both angiogenic markers in the local CRC patients., Methods: We analyzed tissue samples obtained from 81 cases with CRC. VEGF-A expression and MVD counts were immunohistochemically detected using anti VEGF-A and CD31. The assessments of both markers were classified as low and high. Correlation between VEGF-A expression and MVD value and clinicopathological characteristics were examined using Chi-square test. The overall survival (OS) was plotted using the Kaplan-Meier method., Results: High VEGF-A expression was found more frequently in the rectal location (P=0.042) and T4 tumors (P=0.041) compared to their counterparts. Older patients tended to show a higher MVD value compared to younger cases (P=0.062). In addition, survival analysis showed that males had a worse OS compared to females (P=0.029), and VEGF-A expression and MVD count did not correlate with patients' survival., Conclusions: There were significant differences of VEGF-A expression according to tumor location and T invasion. Sex, but not angiogenic markers, had an influence on the survival of CRC patients., Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare.

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., (Creative Commons Attribution License)

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.

Background: Colorectal cancer (CRC) is both a global and national burden, being the third most common malignancy in men and the second in women, worldwide. The prognosis of CRC is affected by various factors like the histological grade, angiolymphatic invasion, and distant metastases. Metastasis is an intricate process; one of the possible mechanisms is through the interaction of the chemokines CXCL12 and CXCR4. This study aims to reveal the expression patterns of CXCL12 and CXCR4 in CRC., Methods: The quantitative expressions of CXCL12 and CXCR4 messenger RNA (mRNA) were evaluated in 32 patients with adenocarcinoma-type CRC. Real-time polymerase chain reaction (qRT-PCR) was performed on formalin-fixed tissues. CXCL12 and CXCR4's expressions, clinicopathologic features, and the treatment response to the CRC were analysed., Results: All tumour tissues showed higher levels of both chemokines compared to normal colonic tissue. The expression of CXCL12 mRNA was higher in rectal location ( p = 0.04) with a tendency to be higher in later stages ( p = 0.15), while the expression of CXCR4 was lower in tumours with a lymphatic invasion ( p = 0.02), compared to their counterparts. There was no difference in the expression of CXCL12 and CXCR4 according to the patients' ages, gender, tumour differentiation, or response to chemotherapy., Conclusion: Our study demonstrated that the mRNA expression of CXCL12 was significantly correlated with rectal location. CXCR4 mRNA expression was inversely correlated in tumours with a lymphatic invasion.

Background: Cancer screening awareness and participation may be lower in low- and middle-income countries that lack established national screening programmes compared with those that do. We evaluated potential determinants of awareness about and participation in breast and cervical cancer screening, and breast self-examination (BSE) in women using survey data from Indonesia., Methods: From the fifth Indonesian Family Life Survey (2014-2015), a total of 5397 women aged 40 and older without any history of cancer who responded to questionnaires concerning Pap smears, mammography, and BSE were included. Multilevel modelling was used to assess potential determinants in relation to awareness about Pap smears and mammography, and participation in Pap smears and BSE practice. Multivariable analyses were performed to identify independent predictors of cancer screening., Results: Of the 5397 respondents, 1058 (20%) women were aware of Pap smears, of which 297 had never had the procedure. Only 251 (5%) participants were aware of mammography. A total of 605 (12%) of women reported they performed BSE. Higher education and household expenditure were consistently associated with higher odds of awareness about Pap smears and mammography (e.g. odds ratio [OR] of being aware of Pap smear and mammography: 7.82 (95% CI: 6.30-9.70) and 7.70 (6.19-9.58), respectively, for high school graduates compared to women with less educational attainment in the multivariable models), and participation in Pap smears and BSE. We also identified enabling factors linked with greater cancer screening awareness and participation, including health insurance, shorter distance to health services, and social participation., Conclusion: There are socioeconomic disparities in cancer screening awareness and participation among Indonesian women. Our findings may help inform targeted health promotion and screening for cancer in the presence of limited resources.

Epstein-Barr (EBV) infection and presence of a nasopharyngeal cancer (NPC) case in the family increases the risk of developing NPC. Aberrant anti-EBV immunoglobulin A (IgA) antibodies (EBV-IgA) may be present in the sera of non-cancer individuals and predict NPC. Limited studies report the presence of EBV-IgA antibodies within non-cancer individuals in Indonesia where the disease is prevalent. This study aimed at exploring whether EBV-IgA was found more frequently among first degree relatives of NPC patients and individuals presenting with chronic symptoms in the head and neck area compared to healthy controls. A total of 967 non-cancer subjects were recruited, including 509 family members of NPC cases, 196 individuals having chronic complaints in the head and neck region, and 262 healthy donors of the local blood bank. Sera were analyzed using a standardized peptide-based EBV-IgA ELISA. Overall, 61.6% of all individuals had anti-EBV IgA reactivity equal to or below cut off value (CoV). Seroreactivity above CoV was significantly higher in females (38.7%) compared to males (28.7%) (p = 0.001). Older individuals had more seroreactivity above CoV (42.5%) than the younger ones (26.4%) (p< 0.001). Seroprevalence was significantly higher in family members of NPC patients (41.7%), compared to 32.7% of individuals with chronic head and neck problems (p = 0.028) and 16.4% healthy blood donors (p< 0.001). As conclusion, this study showed a significant higher seroprevalence in healthy family members of NPC cases and subjects presenting with chronic symptoms in the head and neck area compared to healthy individuals from the general community. This finding indicates that both groups have elevated risk of developing NPC and may serve as targets for a regional NPC screening program.

Background: Polymorphic bases in several exons of the BCR gene have been found in several studies of the BCR-ABL fusion gene . Most of the polymorphisms do not have any implications for the primary structure of the BCR-ABL protein. Nucleotide changes are often located in the area close to the fusion region, and therefore may influence primer annealing. Our previous work failed to amplify 15 of 200 samples from BCR-ABL positive chronic myelogenous leukemia (CML) patients using multiplex PCR, the standard method to detect BCR-ABL transcripts used in our institution. The failure was considered due to problems in primer annealing caused by sequence variations. Sequence analysis of BCR-ABL fusion gene breakpoint types in CML patients has never been hitherto performed in Indonesia. Therefore, the aim of this study was to perform sequence analysis of several samples that did not show amplification using the standard method. Methods: Fifteen samples were qualitatively amplified by two-step PCR using inner primers in the 2nd PCR to determine the breakpoint type of the BCR-ABL fusion gene. The 2nd PCR products were used as templates to perform sequence analysis, and the results were compared to those in genbank. Result: Seven and 5 of 15 samples were confirmed as major b3a2 and major b2a2, respectively. One sample featured a combination of b3a2 and b2a2, and 2 samples a combination of b3a2 and b2a2 with an additional fragment at 500bp. Sequence analysis showed 3 sequence variations in the major b3a2 breakpoint. One had been reported earlier (c.3296T>C) but the others (c.3245C>T and c.3359T>C) were novel. Fragments at 500bp were confirmed as b3a2 and similar sequence b3a2 in genbank. Conclusion: This study found two new genetic variations in the BCR gene in BCR-ABL fusion cases., (Creative Commons Attribution License)

Epstein-Barr virus (EBV) infection and family history are significant risk factors associated with undifferentiated nasopharyngeal carcinoma. The presence of aberrant immunoglobulin A (IgA) antibodies against specific EBV antigens in healthy individuals can be predictive of the disease. Very limited reports explored the EBV IgA antibody presence within families of sporadic cases of nasopharyngeal carcinoma. This study aimed to determine whether EBV IgA was observed more frequently among family members of sporadic cases of nasopharyngeal carcinoma compared to community controls and evaluated the non-viral factors as determinants of antibody level. First-degree relatives of nasopharyngeal carcinoma patients (n = 520) and case-matched community controls (n = 86) were recruited. Sera from all individuals were tested in standardized peptide-based EBV IgA ELISA. Data on demographic variables and other exogenous factors were collected using a questionnaire through face-to-face interviews. A similar frequency of EBV IgA (cut-off value/CoV 0.354) was observed in the first-degree relatives of cases and in community controls (41.2% vs. 39.5%, P = 0.770). However, with a higher antibody level (OD(450)  = 1.000; about three times standard CoV), the relatives showed significantly higher frequency (36.9% vs. 14.7%, P = 0.011). When adjusted for all exogenous factors, the strongest factors associated with seropositivity are being a father (odds ratio/OR = 4.36; 95% confidence interval/CI = 1.56-12.21) or a sibling (OR = 1.89; 95% CI = 1.06-3.38) of a case of nasopharyngeal carcinoma. The higher level of EBV IgA seroreactivity in first-degree relatives of sporadic cases of nasopharyngeal carcinoma compared to the general population supports the use of EBV IgA ELISA for screening among family members., (Copyright © 2012 Wiley Periodicals, Inc.)

Increasing evidence demonstrated that inactivation of tumor suppressor genes (TSGs) by aberrant promoter methylation is an early event during carcinogenesis. Aiming at developing early diagnostic or prognostic tools for various tumors, we took an EBV-associated tumor, nasopharyngeal carcinoma (NPC), as a model and developed a powerful assay based on "multiplex methylation specific-PCR (MMSP)". The MMSP assay was designed to detect tumor-specific methylation status of several NPC-related genes and was capable of acquiring multiplex information simultaneously through a single PCR reaction with the tiny tumor DNA derived from the direct body fluid close to the primary tumor. In this study, we collected paired nasopharyngeal (NP) swabs and NPC biopsies from 49 NPC patients and twenty noncancerous controls. A panel of markers including two EBV, and two cellular TSG markers were applied in this NPC-specific-MMSP assay. We optimized the working condition of MMSP so that it provides information equal to that from the corresponding separate PCRs. The results showed that MMSP patterns of NPC swab were largely consistent with those of corresponding biopsies and significantly distinguished themselves from those of 20 noncancerous volunteers. Among the 69 samples (49 NPCs and 20 normal controls), the sensitivity of detecting NPC from NP swabs is 98%. The specificity is as high as 100%. In conclusion, being characterized by its noninvasiveness, high reproducibility and informativeness, MMSP assay is a reliable and potential diagnostic tool for NPC. It paves the way for the development of population screening and early diagnosis approaches for various tumor types.

Background: Undifferentiated nasopharyngeal carcinoma (NPC) is strongly related to Epstein-Barr virus (EBV) infection, allowing aberrant antibodies against EBV and viral DNA load as screening tools in high risk populations. Methylation analysis in the promoter of tumor suppressor genes (TSGs) may serve as a complementary marker for identifying early cases. This study determined methylation status of multiple TSGs and evaluated whether it may improve early detection., Methods: Nasopharyngeal brushings were taken from 53 NPC patients, 22 high risk subjects and 25 healthy EBV carriers. Corresponding NPC paraffin tissue was included. DNA was bisulfite-modified preceding analysis by methylation-specific PCR (MSP). Ten TSGs were studied., Results: NPC paraffin and brushing DNA revealed an 81.8% concordance so that MSP analysis was done using either one of both specimens. NPC samples showed methylation for individual TSGs (DAPK1 79.2%, CDH13 77.4%, DLC1 76.9%, RASSF1A 75.5%, CADM1 69.8%, p16 66.0%, WIF1 61.2%, CHFR 58.5%, RIZ1 56.6% and RASSF2A 29.2%). High risk individuals, having elevated EBV IgA and viral load, showed high frequency of methylation of CDH13, DAPK1, DLC1 and CADM1, but low frequency of methylation of p16 and WIF1 and undetectable methylation of RASSF1A, CHFR, RIZ1 and RASSF2A. Healthy subjects showed similar patterns as high risk individuals. A combination of RASSF1A and p16 gave good discrimination between NPC and non-NPC, but best results were combined analysis of five methylation markers (RASSF1A, p16, WIF1, CHFR and RIZ1) with detection rate of 98%., Conclusion: Multiple marker MSP is proposed as a complementary test for NPC risk assessment in combination with EBV-based markers.

WHO type III nasopharyngeal carcinoma (NPC) is highly prevalent in Indonesia and 100% associated with Epstein-Barr virus (EBV). NPC tumor cells express viral proteins, including BARF1, which is secreted and is considered to have oncogenic and immune-modulating properties. Recently, we found conserved mutations in the BARF1 gene in NPC isolates. This study describes the expression and purification of NPC-derived BARF1 and analyzes humoral immune responses against prototype BARF1 (B95-8) and purified native hexameric BARF1 in sera of Indonesian NPC patients (n = 155) compared to healthy EBV-positive (n = 56) and EBV-negative (n = 16) individuals. BARF1 (B95-8) expressed in Escherichia coli and baculovirus, as well as BARF1-derived peptides, did not react with IgG or IgA antibodies in NPC. Purified native hexameric BARF1 protein isolated from culture medium was used in enzyme-linked immunosorbent assay (ELISA) and revealed relatively weak IgG and IgA responses in human sera, although it had strong antibody responses to other EBV proteins. Higher IgG reactivity was found in NPC patients (P = 0.015) than in regional Indonesian controls or EBV-negative individuals (P < 0.001). IgA responses to native BARF1 were marginal. NPC sera with the highest IgG responses to hexameric BARF1 in ELISA showed detectable reactivity with denatured BARF1 by immunoblotting. In conclusion, BARF1 has low immunogenicity for humoral responses and requires native conformation for antibody binding. The presence of antibodies against native BARF1 in the blood of NPC patients provides evidence that the protein is expressed and secreted as a hexameric protein in NPC patients.