IDENTIA Registry: Incidence of Deep Vein Thrombosis in Medically Ill Subjects at High Risk in Indonesia: A Prospective Study.

BACKGROUND: medically ill hospitalized patients are at risk of deep vein thrombosis (DVT) and consequentially have high chances of mortality. In Indonesia, there is disparity in healthcare facility and data on incidence of DVT in this multi-ethnic, geographically unique country with large population are limited. Hence, we determined the incidence of DVT and evaluated mean Wells score among medically ill hospitalized persons at increased risk. METHODS: in this multicenter, prospective, observational registry in Indonesia, subjects (age >40 years) with acute medical illness (like cancer, acute infection, or severe respiratory disease) confined to bed for >3 days were enrolled between January 2016 and November 2017. Data for medical history, Wells score, and DVT diagnosis with compression ultrasonography (CUS) were recorded. DVT incidence was analyzed in eligible and evaluable groups. Data were analyzed by descriptive method. RESULTS: out of 360 subjects enrolled, 334 were included in the eligible group for analyses. CUS could not be performed in 26 subjects. Thus, 308 subjects who completed the study were included in the evaluable group. Javanese were predominant in the eligible group and obesity was the most common medical history at presentation. Overall, incidence of DVT in eligible and evaluable patients was 37.1% and 40.3%, respectively. Mean (SD) Wells score and bedridden days were 3 (1.20) and 9 (6.89), respectively. CONCLUSION: this study indicated that the incidence of DVT is high in medically ill patients in Indonesia and will provide new insights and awareness about DVT in Indonesia.

Intercalated combination of chemotherapy and erlotinib for patients with advanced stage non-small-cell lung cancer (FASTACT-2): a randomised, double-blind trial.

BACKGROUND: The results of FASTACT, a randomised, placebo-controlled, phase 2 study, showed that intercalated chemotherapy and erlotinib significantly prolonged progression-free survival (PFS) in patients with advanced non-small-cell lung cancer. We undertook FASTACT-2, a phase 3 study in a similar patient population. METHODS: In this phase 3 trial, patients with untreated stage IIIB/IV non-small-cell lung cancer were randomly assigned in a 1:1 ratio by use of an interactive internet response system with minimisation algorithm (stratified by disease stage, tumour histology, smoking status, and chemotherapy regimen) to receive six cycles of gemcitabine (1250 mg/m(2) on days 1 and 8, intravenously) plus platinum (carboplatin 5 × area under the curve or cisplatin 75 mg/m(2) on day 1, intravenously) with intercalated erlotinib (150 mg/day on days 15-28, orally; chemotherapy plus erlotinib) or placebo orally (chemotherapy plus placebo) every 4 weeks. With the exception of an independent group responsible for monitoring data and safety monitoring board, everyone outside the interactive internet response system company was masked to treatment allocation. Patients continued to receive erlotinib or placebo until progression or unacceptable toxicity or death, and all patients in the placebo group were offered second-line erlotinib at the time of progression. The primary endpoint was PFS in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, number NCT00883779. FINDINGS: From April 29, 2009, to Sept 9, 2010, 451 patients were randomly assigned to chemotherapy plus erlotinib (n=226) or chemotherapy plus placebo (n=225). PFS was significantly prolonged with chemotherapy plus erlotinib versus chemotherapy plus placebo (median PFS 7·6 months [95% CI 7·2-8·3], vs 6·0 months [5·6-7·1], hazard ratio [HR] 0·57 [0·47-0·69]; p<0·0001). Median overall survival for patients in the chemotherapy plus erlotinib and chemotherapy plus placebo groups was 18·3 months (16·3-20·8) and 15·2 months (12·7-17·5), respectively (HR 0·79 [0·64-0·99]; p=0·0420). Treatment benefit was noted only in patients with an activating EGFR gene mutation (median PFS 16·8 months [12·9-20·4] vs 6·9 months [5·3-7·6], HR 0·25 [0·16-0·39]; p<0·0001; median overall survival 31·4 months [22·2-undefined], vs 20·6 months [14·2-26·9], HR 0·48 [0·27-0·84]; p=0·0092). Serious adverse events were reported by 76 (34%) of 222 patients in the chemotherapy plus placebo group and 69 (31%) of 226 in the chemotherapy plus erlotinib group. The most common grade 3 or greater adverse events were neutropenia (65 [29%] patients and 55 [25%], respectively), thrombocytopenia (32 [14%] and 31 [14%], respectively), and anaemia (26 [12%] and 21 [9%], respectively). INTERPRETATION: Intercalated chemotherapy and erlotinib is a viable first-line option for patients with non-small-cell lung cancer with EGFR mutation-positive disease or selected patients with unknown EGFR mutation status. FUNDING: F Hoffmann-La Roche.

Patient-reported outcomes and symptom clusters pattern of chemotherapy-induced toxicity in patients with early breast cancer.

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.

Chemotherapy-Induced Nausea and Vomiting in Patients With Breast Cancer: Risk Factor and Predictive Model Using Classification and Regression Tree (CART).

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.

Prognostic Value of Vimentin in Triple Negative Breast Cancer Patients Depends on Chemotherapy Regimen and p53 Mutant Expression.

Purpose: 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.

Sexual Dysfunction Following Breast Cancer Chemotherapy: A Cross-Sectional Study in Yogyakarta, Indonesia.

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/m2 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.

The occurrence and risk factors of chemotherapy-induced neutropenia in patients with breast cancer not receiving primary G-CSF prophylaxis.

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 × 103/mm3 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.

Multidisciplinary Team Meeting in the Core of Nasopharyngeal Cancer Management Improved Quality of Care and Survival of Patients.

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.

Vitamin D status in breast cancer cases following chemotherapy: A pre and post observational study in a tertiary hospital in Yogyakarta, Indonesia.

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.

Delays in the presentation and diagnosis of women with breast cancer in Yogyakarta, Indonesia: A retrospective observational study.

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.

Efficacy and safety of convalescent plasma therapy in patients with moderate-to-severe COVID-19: A non-randomized comparative study with historical control in a referral hospital in Indonesia.

BACKGROUND: Studies to confirm the efficacy and safety of convalescent plasma (CP) as an adjunctive treatment for COVID-19 are still required especially for the countries where standard treatments are unevenly distributed. METHODS: A non-randomized comparative study was done from June - September 2020 in Dr. Sardjito Hospital, Yogyakarta, Indonesia. Plasma with anti-SARS-CoV-2 specific IgG titer of >1:320 were used. Primary end points were clinical and laboratory parameters outcome including BGA, chest X-ray, CT value, CRP, procalcitonin, IL-6, D-Dimer and ALC examined on day 1, 2 and 7 post-transfusion. RESULTS: The experimental arm of this study consisted of 15 patients who received CP: 3 (20%) with moderate COVID-19 and 12 (80%) with severe COVID-19. There were 15 historical controls in this study. Ten recipients survived and 5 deceased (survival rate was 66.7%). There were higher rate of pneumonia resolution (OR 1.54, CI95% 0.33-7.23), ARDS resolution (OR 1.20, CI95% 0.25-5.84) and shorter median length of stay (20 vs 22 days, p = 0.41) among recipients compared to controls. Lower mortality rate was observed in recipients vs controls (33.3% vs 46.7% (OR 0.75, CI95% 0.17-3.33)). Median death onset was longer in recipient vs control (7th vs 1st day, p = 0.13). Survival analysis showed protective effect of CP (HR 0.69, CI 95% 0.21-2.27, p = 0.545). Higher CT value improvement (p = 0.51) and negative conversion rate (OR1.20, CI95% 0.25-5.84) were observed in recipients compared to controls. Sub-analysis showed more number of comorbidities, higher procalcitonin and higher D-Dimer among CP recipients who did not survive (p = 0.02 and p = 0.02 respectively). Lower CRP and procalcitonin, and higher ALC were found in survivors compared to non-survivors (p = 0.0437; p = 0.0049; and p = 0.0002 respectively). CONCLUSION: This study showed promising results for CP marked by improvements in clinical outcome, as well as significant reduction of inflammatory markers among recipients.

Concentration of serum HER-2/neu as a prognostic factor in locally advanced breast cancer (LABC) and metastatic breast cancer (MBC).

AIM: to determine whether serum HER-2/neu level could be used as a prognostic factor in locally advanced breast cancer (LABC) and metastatic breast cancer (MBC). METHODS: a prospective cohort study was done in LABC and MBC patients in dr. Sardjito Hospital Yogyakarta from April 2006 to March 2008. Serum concentration of HER-2/neu was measured by ELISA done before and after chemotherapy. HER-2/neu expression tissue examination was done by immunohistochemistry. The clinical responses on therapy, survival and progression were recorded. RESULTS: twenty seven cases were obtained. Average concentration of serum HER-2/neu was 21.02 ± 7.1 ng/ml. The level of serum HER-2/neu in LABC was lower than MBC (17.21 ng/ml vs 28.64 ng/ml; p=0.32). Average concentration of serum HER-2/neu in partial responders was 13.20 ng/ml (95% Cl 0.142 - 26.25), stable responders was 19.42 ng/ml (95% Cl -0.255 - 39.09) and 29.35 ng/ml(95% Cl 1.95 - 56.74) in progressors (p=0.468). Patients with better clinical response had a lower average HER-2/neu serum level (16.12 ng/ml vs 29.35 ng/ml; p=0.247). HER-2/neu over expression was found in 40.7% of the tissues, 44% of LABC and 33.3% of MBC tissues (p=0.692). Negative HER-2/neu tissue protein expression had better clinical response (75% vs 45.5% p=0.224), and longer survival (p=0.08). CONCLUSION: neither the expression of HER-2/neu in the tissue nor the level of serum HER-2/neu can be used as clinical prognosis factor on advanced stage breast cancer in our study population.

Molecular Analysis of Colorectal Cancers Suggests a High Frequency of Lynch Syndrome in Indonesia.

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_LyST) was used in this project. N_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.

Survival outcome and prognostic factors of patients with nasopharyngeal cancer in Yogyakarta, Indonesia: A hospital-based retrospective study.

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.

BCR-ABL Gene Transcript Types of Patients with Chronic Myelogenous Leukemia in Yogyakarta, Indonesia.

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.

Impressive Response to Capecitabine in a Patient with Obstructive Jaundice due to Metastatic Triple-Negative Breast Cancer.

BACKGROUND: Metastatic breast cancer with obstructive jaundice due to para-aortic lymph node enlargement is an unusual case that poses a therapeutic challenge in determining a chemotherapy regimen. CASE REPORT: A 61-year-old woman presented with triple-negative left invasive ductal breast carcinoma with liver and pulmonary metastases. After receiving gemcitabine and carboplatin as the 4th-line treatment, chemotherapy was postponed due to an increased bilirubin level. Abdominal imaging revealed para-aortic lymph node metastases compressing the distal common hepatic duct. The patient then received capecitabine along with ursodeoxycholic acid. This relieved her jaundice after 8 cycles of chemotherapy, and radiologic evaluation revealed a complete resolution of the obstructive jaundice. CONCLUSION: This finding emphasizes the success of capecitabine regimen as a salvage therapy in a metastatic breast cancer patient with hyperbilirubinemia and opens up the possibility of optimizing systemic chemotherapy for metastatic obstructive jaundice in the setting of limited facility resources.

Effects of oxaliplatin-containing adjuvant chemotherapy on short-term survival of patients with colon cancer in Dr. Sardjito Hospital, Yogyakarta, Indonesia.

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.

Clinicopathologic Significance of CXCL12 and CXCR4 Expressions in Patients with Colorectal Cancer.

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.

Analgesic Prescription Patterns and Pain Outcomes in Southeast Asia: Findings From the Analgesic Treatment of Cancer Pain in Southeast Asia Study.

PURPOSE: To identify patterns of analgesic prescription and to explore patient-reported pain intensity, sleep disturbance, and quality of life among cancer patients with pain in Southeast Asia (SEA). METHODS: This cross-sectional observational study included 465 adult outpatients prescribed analgesics for cancer pain for 1 month or longer at 22 sites in Indonesia, Malaysia, Philippines, Singapore, Thailand, and Vietnam. Data on analgesic prescription and cancer characteristics were extracted from medical records. Pain intensity, sleep disturbance, and quality of life measures were recorded via questionnaires. RESULTS: Most patients (84.4%) had stage III or IV cancer. A total of 419 patients (90.7%) were prescribed opioids; of these, 42.2% received only weak opioids, whereas 57.8% received at least one strong opioid. The mean worst pain intensity during the past 24 hours was 4.76 (standard deviation [SD], 2.47) on a scale of 0 (no pain) to 10 (worst possible pain); the mean current pain intensity was 4.10 (SD, 2.61). More than half of patients (54.8%) reported sleep disturbance caused by pain in the past 7 days. The majority of patients reported problems with pain/discomfort (82.3%), usual activities (65.8%), mobility (58.2%), and anxiety/depression (56.3%). The median daily dose prescribed in oral morphine equivalents was 30 mg for both morphine and tramadol. CONCLUSION: Despite unrelieved pain, sleep disturbance, and issues with quality of life, a notable proportion of patients were prescribed only weak opioids, and opioid doses prescribed were generally low. Efforts focused on encouragement of prescriptions with analgesic strength and/or doses proportional to the pain management needs of patients are vital to improve the status of cancer pain management in the region.

Correlation between vascular endothelial growth factor-A expression and tumor location and invasion in patients with colorectal cancer.

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.