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.

Rapid Malignant Transformation of Tubulovillous Adenoma, Initially Presenting as McKittrick-Wheelock Syndrome: A Case Report.

Most cases of colorectal cancer develop from adenomatous polyps, slowly progressing within an average period of 8-10 years. McKittrick-Wheelock syndrome (MKWS) is a rare manifestation of tubulovillous adenoma. It generally presents as hypersecretory diarrhea with severe electrolyte and fluid depletion. Roughly, 5% of the published cases have reported malignant histopathology associated with MKWS, with little to no data regarding the malignant transformation process of those patients. Our patient was a 53-year-old Asian woman suffering from chronic secretory diarrhea, resulting in severe volume, electrolyte depletion, and prerenal azotemia, consistent for MKWS. Her symptoms initially improved with sulfasalazine but eventually worsened. She demonstrated signs of systemic (elevated leukocyte, CRP, and LDH) and local inflammation (dense lymphocyte infiltration in colorectal tissue) throughout the course of her disease. Serial pathological results showed rapid neoplastic progression of adenomatous polyp to adenocarcinoma within 1 year period. Surgical resection resulted in complete symptom resolution. Molecular examination showed a favorable profile of exon 4 Kirsten rat sarcoma viral oncogene homolog mutation, normal NRAS, BRAF, CDX2, and CK20 expressions. Her molecular pattern did not reflect the profile of an aggressive disease, suggesting the possibility of oncogenic processes outside the major pathways of adenoma to carcinoma progression. Chronic inflammation is a well-established risk factor for colorectal cancer, and prostaglandin E2 (PGE2) has been observed as one of the key regulators of tumor initiation and growth. PGE2 is also responsible for hypersecretory diarrhea associated with MKWS.

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.

Impact of independent multidisciplinary work on the survival rate of stage 3 and 4 nasopharyngeal cancer in Indonesia: a retrospective cohort study.

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.

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.

Malaria as Potential Aetiology and Treatment Complicating Factor in DLBCL Patient: A Case Report.

Malaria is known to be a significant risk factor and also a potential complicating factor during the treatment of lymphoid malignancy. There has not been a reported case of malaria reactivation that occurred weeks after cytotoxic chemotherapy completion, especially in non-endemic regions. Our patient was a 47-year-old man with a history of repeated falciparum malaria infection experiencing 2 months of progressive unilateral nasal blockage and recurrent anterior epistaxis, which was diagnosed as diffuse large B-cell lymphoma (DLBCL) through pathological examination. He was treated with six cycles of classical R-CHOP, resulting in complete remission. One month after remission, he experienced shivering, fever, sweating, and a return to normal temperature, which repeated irregularly for roughly 1 week. His laboratory result showed anaemia, leucopenia, and profound thrombocytopenia. Immunochromatographic testing (ICT) confirmed the diagnosis of falciparum malaria. This case was considered a relapse since our centre is not in the malaria-endemic region. He was cured with a combination of dihydroartemisinin-piperaquine and primaquine. Our case demonstrated the duality of malaria as potential aetiology and treatment complicating factor in DLBCL.

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.

Stromal Tumor Infiltrating Lymphocytes (sTILs) Were Associated with a Higher Grade and a Lower Stage of Indonesian Triple Negative Breast Cancers.

OBJECTIVE: This study aimed to investigate the association of sTILs with clinicopathological parameters and overall survival (OS) in patients with triple negative breast cancer (TNBC). METHODS: One hundred and twenty-five paraffin embedded tissue of patients with TNBC, collected from Dr. Sardjito General Hospital Yogyakarta, Indonesia, between 2008-2017, were used in this study. Stromal TILs were examined from hematoxylin and eosin (H&E)-stained samples, and classified as either low or high score using 20% cut-off. Analysis of the association of sTILs with clinicopathological parameters, relative risk (RR) and OS used 95% confidence interval (CI) with significance set as p<0.05. RESULTS: The higher proportion of TNBC patients in this study were ≥40 years old (83.3%), high tumor grade (68%), tumor stage >IIIa (56%), alive (50.4%), and with low sTILs (54.4%). The results showed significant association between sTILs and a higher grade or a lower stage of tumor (B = 0.259, 95%CI = 0.090-0.468, p = 0.004 and B = -0.255, 95%CI = -0.433 - -0.080, p = 0.005, respectively ). Meanwhile sTILs were not associated with age at diagnosis (B = 0.027, 95%CI = -0.193 - 0.264  p = 0.758 nor 3-year OS of patients (HR = 0.342, 95%CI = 0.41 - 1.43  p = 0.402). CONCLUSION: The results indicate that sTILs may serve as an additional pathological parameter for TNBC.

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.

Characteristics of breast cancer patients at dr. Sardjito Hospital for early anticipation of neutropenia: Cross-sectional study.

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.

Two Cases of Hemophagocytic Lymphohistiocytosis Associated with Disseminated Histoplasmosis Presented with Transient Pancytopenia.

Transient pancytopenia due to reactive bone marrow suppression often occurs in hemophagocytic lymphohistiocytosis (HLH), a syndrome resulting from excessive immune activation following a severe infection. We reported two cases with pancytopenia and disseminated histoplasmosis accompanied by HLH, initially suspected to be blood malignancies. Our first case documented the relevance between the improvement of pancytopenia and the clearance of Histoplasma capsulatum in serial bone marrow aspirations. The second case showed immense Histoplasma engulfment by the macrophage in relation to a severe clinical condition, followed by improvement of clinical symptoms in accordance with the recovery of pancytopenia. These two cases highlighted the importance of comprehensive and critical analysis for cases with concurrent pancytopenia and severe infection, since it may be that the pancytopenia underlies the severe infection or vice versa.

A Complicated Case of Diffuse Large B-Cell Lymphoma in an Elderly Presenting with Massive Gastrointestinal Bleeding Successfully Treated with R-mini CHOP.

Gastrointestinal lymphoma accounts for up to 20% of all extranodal lymphoma cases. Among them, the ileum is the second most commonly affected site after the stomach. The majority of gastrointestinal lymphoma originates from the B cell lineage. We report the case of 60-year-old male with persistent anemia, hematochezia, and poor performance status (PS). After thorough workup, imaging, and pathological study, the patient was diagnosed with diffuse large B-cell lymphoma of the terminal ileum. He was treated with R-CHOP based chemotherapy with dose tailoring to accommodate his poor PS. His symptoms promptly subsided after the first chemotherapy cycle. After eight cycles of chemotherapy, terminal ileum wall thickening was gone and the patient was disease-free for 6 months. This case report shows that chemotherapy can be beneficial in patients with gastrointestinal lymphoma despite poor PS. Therefore, it should be given when possible with proper dose tailoring.

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.

MicroRNA-223 is Associated with Resistance Towards Platinum-based Chemotherapy and Worse Prognosis in Indonesian Triple-negative Breast Cancer Patients.

PURPOSE: Determining the optimal strategy to implement systemic treatment modalities has been challenging in triple-negative breast cancer (TNBC). We aim to investigate the role of microRNA-223 (miR-223) as prognostic factor and predictor of response toward chemotherapy in TNBC. PATIENTS AND METHODS: We retrospectively analyzed the association of pretreatment miR-223 expression with clinicopathologic characteristics and 36-month overall survival (OS) of 53 all stages TNBC patients. Tumor level of miR-223 was measured using real-time quantitative polymerase chain reaction (expressed in fold change). Cutoff value for miR-223 was determined by using receiver operating curve (ROC). Kaplan-Meier curve was used to perform survival analysis. RESULTS: The optimum cutoff value for miR-223 was 23.435 (AUC: 0.706, 95%CI: 0.565-0.848; p:0.01; sensitivity: 78.6%; specificity: 56%) and was used to categorize mir-223 expression into over- and underexpressed group. Overexpression of miR-223 was associated with increased expression of EGFR (69.7% vs 35%, p: 0.022) and lower 36-month OS (33.3% vs 70%; median OS±SE (months): 25.66±1.58 vs 30.23±1.99; log rank p<0.05). Worse survival is observed in miR-223 overexpressed group receiving platinum-based chemotherapy compared to miR-223 underexpressed group (mean OS (95%CI) months: 24.7 (20.3-29.1) vs 34.3 (31.2-37.4); p<0.01), while no significant difference observed in non-platinum containing regimen. No significant association was observed between miR-223 expression with other clinicopathologic characteristics. CONCLUSION: Overexpression of miR-223 is associated with increased expression of EGFR, worse prognosis, and resistance toward platinum-based chemotherapy in Indonesian TNBC patients.

Overexpression of Programmed Death-Ligand 1 Receptor mRNA as an Independent Negative Prognostic Factor for Triple Negative Breast Cancer.

BACKGROUND: Triple negative breast cancer (TNBC) (represents roughly 25% of all breast cancers in Yogyakarta) still has the worst survival compared to other breast cancer subtypes. Results from recent studies have shown that inhibition of programmed death-ligand 1 receptor (PD-L1) in TNBC patients is associated with better prognosis. Currently, data on PD-L1 expression and its prognostic value in Indonesian TNBC patients are still relatively unknown. This study aimed to investigate the expression of PD-L1 in Indonesian TNBC patients as preliminary proof to support PD-L1 inhibitor as a possible treatment option near in the future. METHODS: We retrospectively included stage I-III TNBC patients diagnosed between 2014 and 2017 in Dr. Sardjito Hospital, Yogyakarta, Indonesia. Clinical variables were collected from medical record. Paraffin blocks of biopsy specimen were retrieved to examine mRNA level of PD-L1. RESULTS: We included 48 subjects with mean age of 51.09 years and mean body mass index (BMI) of 24.58. The 3-year overall survival (OS) was 58.3%. Overexpression of PD-L1 mRNA in TNBC patients is associated with worse prognosis (P < 0.01). There were no statistically significant associations between PD-L1 mRNA expression and any of the clinicopathologic variables examined. CONCLUSIONS: In summary, PD-L1 mRNA overexpression is associated with worse survival in Indonesian TNBC patients, independent of other established risk factors. PD-L1 mRNA is expressed in all of our samples, presenting as a feasible alternative or complementary method in deciding which patient might benefit from receiving PD-L1 inhibitor.

Complete Remission of Relapsed Hodgkin's Lymphoma following Brentuximab Vedotin and Gemcitabine Combination Therapy with Severe Hypotension as Possible Treatment-Related Adverse Event: A Case Report.

A 40-year-old Asian female with heavily treated relapsed Hodgkin's lymphoma showed complete remission (CR) after receiving 8 cycles of brentuximab vedotin (BV) in combination with gemcitabine as 4th line treatment. The patient remained in CR at the 18-month post-treatment follow-up. She developed severe hypotension (50/36 mm Hg) with upper and lower limb petechiae and edema after the addition of gemcitabine on the 6th cycle of BV. This adverse event resolved after 3 days of treatment with vasopressor and high-dose corticosteroid. The addition of dexamethasone for the subsequent 2 cycles successfully prevented this adverse event from recurring.

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.