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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

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: 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.)

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.)

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: Several studies showed the superiority of aromatase inhibitor (AI) as first-line therapy for patients with hormone-receptor (HR)-positive breast cancer (BC). For the clinician, studies in the real world are warranted to determine treatment based on the efficacy of each drug. We compared a 5-y disease-free survival (DFS) of each AI in terms of survival benefit. Materials and Methods: We evaluated 450 medical records of postmenopausal women who were diagnosed with HR-positive HER2-negative BC (stage I - III) at Dr. Sardjito General Hospital from January to December 2019. All patients had undergone surgery and chemotherapy or radiation therapy. Moreover, study participants received anastrozole, letrozole, or exemestane for at least one year. Kaplan Meier estimation survival curve was used to analyze the survival rate. Result: Of 79 patients meeting inclusion criteria, there were 21.52% distant metastases documented. Time to disease progression of anastrozole, letrozole, and exemestane was 49 months, 58 months, and 53 months, respectively. Letrozole was found better than anastrozole (hazard ratio (HR)=4.342, 95% CI 0.95-19.95; p=0.038). Letrozole versus exemestane (HR=2.757, 95% CI 0.53-14.33; p=0,206) and anastrozole versus exemestane (HR=1.652, 95% CI 0.56-4.84; p=0.351) were found not significantly different. 5-y DFS rate of letrozole was better found (87.5%) than exemestane (73.7%) and anastrozole (61.4%). Conclusion: 5-year letrozole administration could be proposed as first-line therapy for postmenopausal women with HR-positive HER2-negative BC. A considerable subject and long-term follow-up are needed for validation., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2023 Tehran University of Medical Sciences.)

Background: Obesity and metabolic syndrome (MetS) have been linked to the risk of developing certain cancers. This study aimed to analyze the association between obesity markers, MetS and survival outcomes of patients with breast cancer., Methods: This study retrospectively investigated patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative (HR+/HER2-), nonmetastatic breast cancer diagnosed between January 2010 and December 2019. Data on clinical conditions, body mass index (BMI), waist-to-hip ratio (WHR), MetS, time of metastasis and death were collected., Results: A total of 223 breast cancer patient records were eligible for analysis. Obesity (BMI ≥ 25) was found in 38.1% of cases. Abdominal obesity measured as WHR ≥ 0.85 was found in 48.9%. Metabolic syndrome was detected in 56.1% of patients and was associated with older age (OR = 2.196, p = 0.005), postmenopausal status (OR = 2.585, p = 0.001), obesity (OR = 5.684, p = 0.001) and abdominal obesity (OR = 2.612, p = 0.001). Obesity was not associated with poor disease-free survival (DFS) or overall survival (OS), while abdominal obesity was modestly associated with poor DFS (HR = 1.539, p = 0.083) and OS (HR = 3.117; p = 0.019). Multivariate analysis revealed that WHR ≥ 0.85 was independently associated with unfavorable DFS (HR = 1.907, p = 0.027). Patients with MetS had a similar survival rate to those with normal metabolism., Conclusion: In Indonesian women with HR+/HER2- breast cancers, obesity and MetS were not associated with poor survival outcomes. The abdominal obesity marker (WHR) was more accurate in predicting unfavorable DFS.

Objective: Breast cancer is the most common cancer in Indonesia, with Indonesia's breast cancer mortality rate being the highest among Southeast Asian countries. This study aims to evaluate the cost-effectiveness and budget impacts of adding trastuzumab to chemotherapy versus chemotherapy alone for HER2-positive breast cancer patients in Indonesia., Methods: We performed a Markov model-based economic evaluation to assess cost-effectiveness, cost-utility, and budget impact. Utility data, direct medical costs, and indirect costs were obtained primarily from interviewing patients. Clinical effectiveness data, on the other hand, were obtained from systematic reviews and real-world data and represented through progression free survival, overall survival, and quality-adjusted life years (QALYs)., Result: From a healthcare provider's perspective, the total costs for the combined group were USD 14,516, while chemotherapy alone cost USD 7,489. While the cost-effectiveness analysis showed that the combination group had a higher total cost by USD 7,027, PFS was longer in the chemotherapy alone group, with a difference of 2.2 months. The ICER was USD 17,307 for every QALY gained. The total cost of adding trastuzumab over a 5-year period was USD 589 million., Conclusion: In conclusion, this economic evaluation suggests that the addition of trastuzumab to standard chemotherapy is not cost-effective in terms of PFS and OS compared with chemotherapy alone., .

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.

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.

Purpose: Long-term estrogen inhibition may cause fatty liver disease (non-alcoholic fatty liver disease; NAFLD) among other adverse conditions such as osteoporosis, climacteric symptoms, thromboembolism, dyslipidemia, and metabolic syndrome. The prevalence of NAFLD among breast cancer patients ranges from 2.3%-45.2%. This study aimed to determine the risk factors for newly developed NAFLD among breast cancer patients after hormonal treatment and whether it influences survival outcomes., Methods: This retrospective study investigated hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative (HR+/HER2-), nonmetastatic breast cancer patients diagnosed between January 2010 and December 2018. All patients received adjuvant hormonal treatment for at least 6 months. Clinical data on metabolic profile indicators such as body mass index (BMI), waist circumference, serum cholesterol, triglycerides, low-density lipoprotein-cholesterol (LDL-C), high-density lipoprotein-cholesterol (HDL-C), diabetes, and presence of metabolic syndrome (MetS) were collected. In total, 160 eligible patients with complete covariate data and survival follow-up were included., Results: NAFLD was diagnosed in 35% of patients. There were significant associations of being overweight (BMI ≥ 25 kg/m²), waist circumference > 80 cm, triglycerides ≥ 150 mg/dL, HDL-C ≤ 50 mg/dL, LDL-C < 150 mg/dL, and presence of MetS with the development of NAFLD. However, unlike other factors, MetS and HDL-C were not independently associated with NAFLD. Patients with breast cancer who developed NAFLD had longer disease-free survival (DFS). The median DFS was not reached in the NAFLD group, whereas it was 59.3 (45.6-73.0) months in the non-NAFLD group. No worsening of overall survival was observed in patients with breast cancer and NAFLD., Conclusion: The development of NAFLD during treatment in patients with HR+/HER2- breast cancer was associated with several independent risk factors: being overweight, waist circumference, triglycerides, and LDL-C. Interestingly, breast cancer patients with NAFLD during treatment had longer DFS than those without NAFLD., Competing Interests: The authors declare that they have no competing interests., (© 2021 Korean Breast Cancer Society.)

Objectives: Breast cancer (BC) in women could decrease health-related quality of life (HRQoL). HRQoL becomes important to be assessed to design a relevant treatment that could improve patient outcomes. Furthermore, assessing HRQoL by measuring health state utilities becomes pivotal for health economic evaluation. This study aimed to describe the HRQoL of postmenopausal women with hormone responsive (HR+) HER2- BC using the EQ5D5L instrument in Indonesia., Methods: A cross-sectional study was conducted among 126 patients in Dr. Sardjito Hospital in Indonesia. The HRQoL was assessed by interviewing BC patients using the EQ5D5L questionnaire, and the utility index was calculated using the Indonesian value set. Information regarding clinical characteristic and socio-demographic were gained from patient medical records. One-way ANOVA and post-hoc Scheffe's test was performed to compare the utility score within the health state., Results: Of the 126 patients, a mean ± SD for the age of 59.2 ± 6.1 years. The major problems of patients were pain/discomfort (75.4%) followed by anxiety/depression (54.8%). The mean (SD) of EQ5D VAS was 76.64 (14.91). Mean (SD) of utility score was 0.87 (0.10), 0.77 (0.19) and 0.58 (0.44) for free metastasis (FM), locoregional metastasis (LM) and distant metastasis (DM), respectively. Poor QoL was observed at DM health state (p<0.05)., Conclusions: HRQoL of postmenopausal women with HR+ HER2- BC was low. The major reported problems were pain/discomfort and anxiety/depression., (© 2021 Walter de Gruyter GmbH, Berlin/Boston.)

Objective: Since 2016, bevacizumab has been widely used to treat metastatic colorectal cancer (mCRC) in Indonesia. Nevertheless, the high cost of bevacizumab has raised the question of whether the therapy is considered cost-effective and should be included in the national health insurance system. This study aimed to assess the cost-effectiveness of bevacizumab plus chemotherapy versus chemotherapy alone for the treatment of mCRC patients., Methods: A Markov model was applied using the perspective of the Indonesian healthcare system to assess cost-effectiveness. The health outcomes were expressed in terms of quality-adjusted life years (QALY) using the validated EuroQoL-5D-5L instrument. Data for medical costs were collected from hospital billings in four hospitals located in three different cities in Indonesia. Meanwhile, data for utility were obtained from interviewing 90 patients who came to the hospital. We compared those mCRC patients who received chemotherapy alone either with FOLFOX or FOLFIRI, versus patients who received the addition of bevacizumab., Results: With the perspective of societal, the incremental cost-effectiveness ratio (ICER) of adding bevacizumab was USD 49,312 per QALY gained using secondary data and USD 28,446 per QALY using real world data., Conclusion: Using either a healthcare or societal perspective, the addition of bevacizumab for mCRC treatment was considered not cost-effective.

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.

Obesity and Metabolic Syndrome have been associated with cardiovascular, diabetes and cancer incidence. Obesity is a state of inflammation. There are cross-talks between adipocyte, adipokines, pro-inflammatory cytokines, insulin, leptin, and other growth factors to initiate signals for proliferation, anti-apoptosis, and angiogenesis. Those networks lead to cancer initiation, promotion, progression, and metastasis. Post menopause women with breast cancer commonly have overweight, obesity, and metabolic syndrome, which are previously reported as conditions to be associated with breast cancer prognosis. MicroRNAs (miRNAs), small non-coding RNA that regulate gene expression, are known to play important roles either in metabolic or carcinogenesis process in patients with breast cancer. Some miRNAs expressions are deregulated in persons either with obesity, breast cancer, or breast cancer with co-morbid obesity. This literature review aimed at reviewing recent publications on the role of obesity, leptin, and microRNA deregulation in adverse prognosis of breast cancer. Understanding the influence of deregulated miRNAs and their target genes in patients with breast cancer and obesity will direct more studies to explore the potential prognostic role of obesity in breast cancer from epigenetic points of view.

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.

Objective: Multiple myeloma (MM) with bone metastases causes a skeletal-related event (SRE), and decreases health-related quality of life (HRQoL). HRQoL needs to be evaluated for health technology assessment (HTA). Furthermore, HRQoL is calculated as a health state utility and is used in the Markov Model for HTA. Therefore, this study aimed to describe the HRQoL of MM patients with bone metastases, using The EuroQol five-dimension five levels (EQ -5D-5L) in Indonesia., Methods: a cross-sectional, multicenter study for MM patients with bone metastases (aged over 18 years old) that consulted a physician between November 2018 - May 2019 was conducted. The calculated HRQoL illustrated the health state utility, which was assessed using the EQ-5D-5L questionnaire, with the Indonesian value set. In addition, Mann-Whitney analyses were performed to determine the difference in utility scores at different points within the Durie-Salmon staging system and skeletal condition., Results: in 93 patients who completed the questioner, pain was their major concern with prevalence of over 60% (all levels inclusive). Moreover, the mean utility of patients in stage II and III were 0.735 (SD = 0.205) and 0.383 (SD = 0.555), and those without SRE was 0.753 (SD = 0.213) while patients with SRE was 0.302 (SD = 0.562). Therefore, the lessened values were observed at stage III and SRE condition (p<0.05)., Conclusion: MM patients with bone metastases have poor HRQoL, with pain as the most frequently reported challenge, which is associated with an advanced stage of MM and SRE event.

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.

Introduction: Nasopharyngeal Carcinoma (NPC) is a major health problem in southern and eastern Asia. In Indonesia NPC is the most frequent cancer in the head and neck area. NPC is very sensitive to radiotherapy resulting in 3-year disease-free and overall survival of approximately 70% and 80%, respectively. Here we present routine treatment results in a prospective study on NPC in a top referral; university hospital in Indonesia., Methods: All NPC patients presenting from September 2008 till January 2011 at the ear, nose and throat (ENT) department of the Dr. Sardjito General Hospital, Universitas Gadjah Mada, Yogyakarta, Indonesia, were possible candidates. Patients were included if the biopsy was a histological proven NPC without distant metastasis and were assessed during counselling sessions prior to treatment, as being able to complete the entire treatment., Results: In total 78 patients were included for treatment analysis. The median time between diagnosis and start of radiotherapy is 120 days. Forty-eight (62%) patients eventually finished all fractions of radiotherapy. The median duration of the radiotherapy is 62 days for 66 Gy. Median overall survival is 21 months (95% CI 18-35) from day of diagnosis., Conclusion: The results presented here reveal that currently the treatment of NPC at an Indonesian hospital is not sufficient and cannot be compared to the treatment results in literature. Main reasons for these poor treatment results are (1) a long waiting time prior to the start of radiotherapy, (2) the extended overall duration of radiotherapy and (3) the advanced stage of disease at presentation.

Studies on the role of vascular endothelial growth factor (VEGF) as the most potent angiogenic factor in disease progression of nasopharyngeal carcinoma (NPC) remain limited, partly be due to the geographical distribution of the disease. However, it has never been reported from Indonesian population despite its common incidence. Therefore, we aimed to study the possible prognostic value of VEGF in Indonesian advanced stage NPC. A clinical examination, CT scan, and the tumor tissue and plasma collection were performed before a combined therapy, and a local control rate was reassessed every 3 months to determine progression-free survival (PFS). Plasma VEGF-A was measured in 40 patients by ELISA, and VEGF and vWF expressions were examined in 30 patients by immunohistochemistry. Survival curves were plotted based on plasma VEGF-A level, VEGF, and microvessel density (MVD) count indicated by vWF expressions vs PFS. The median follow up was 16 months. Patients with high VEGF-A level (≥ 834pg/ml) presented shorter survival rate, as compared to those of low level (< 834pg/ml) (41.2% vs 82.6%; p=0.009, log rank 6.81). Patients with overexpressed VEGF (≥ 25%) showed shorter survival than those with low expression (<25%) (45.5% vs 79.6%; p=0.05, log rank 3.84). Patients with higher MVD count (≥ 25%) also had shorter survival than those with lower MVD count (53.4% vs 80%; p=0.101, log rank=2.70). In conclusion, an elevated plasma VEGF level predicts shorter survival for Indonesian advanced stage NPC in this study. However, more samples may be required to draw a better conclusion on a possible role of VEGF as a prognostic factor in the disease progression of NPC. This data is also substantial for the development of anti-VEGF as a possible targeted therapy for NPC.