Intra thyroid thymic carcinoma: A case report and literature review.

INTRODUCTION AND IMPORTANCE: Intrathyroid thymic carcinoma (ITC) is a malignant epithelial tumor with thymic differentiation within the thyroid gland. Its frequency is up to 0.15 % of all malignant thyroid tumors. It is frequently a low-grade tumor. The clinical status is often misleading to other more advanced tumors like cervical lymph node metastasis of nonkeratinizing squamous cell carcinoma, undifferentiated variant, dedifferentiated carcinoma, and medullary carcinoma of the thyroid. CASE PREPARATION: The patient came to us with the diagnosis of cervical lymph node metastasis of undifferentiated carcinoma. This patient was first diagnosed with cervical lymph node metastasis in the previous hospital. After having an ITC diagnosis, the patient was operated on the rennet of thyroid glands and had a low dose of radio-chemotherapy for recurrent prevention purposes. It is the first case of such a disease diagnosed at our hospital and also the first case reported in Vietnam. CLINICAL DISCUSSION: ITC is rare and appears similar to all thymic carcinoma variants. The most popular type is squamous carcinoma. Immunohistochemical stains are typical for thymic origin tumors with CD5, CD117 positive. ITC is often negative for monoclonal PAX8 but positive in this case (MRQ-50 clone, Sigma-Aldrich). This finding is an exciting one that should considered. CONCLUSION: Reporting the case increases the awareness of the disease, especially among Vietnam Doctors and patients.

Plain language summary of the HIMALAYA study: tremelimumab and durvalumab for unresectable hepatocellular carcinoma (liver cancer).

WHAT IS THIS SUMMARY ABOUT?: This is a summary of results from a phase 3 clinical study called HIMALAYA. HIMALAYA looked at treatment with one dose of a medication called tremelimumab combined with multiple doses of a medication called durvalumab (the STRIDE regimen) or multiple doses of durvalumab alone. These treatments were compared with a medication called sorafenib in participants with unresectable hepatocellular carcinoma (HCC). HCC is a type of liver cancer that is difficult to treat because it is often diagnosed when it is unresectable, meaning it can no longer be removed with surgery. Sorafenib has been the main treatment for unresectable HCC since 2007. However, people who take sorafenib may experience side effects that can reduce their quality of life, so alternative medicines are being trialed. Tremelimumab and durvalumab are types of drugs called immunotherapies, and they both work in different ways to help the body's immune system fight cancer. WHAT WERE THE RESULTS OF THE STUDY?: Participants who took STRIDE lived longer than participants who took sorafenib, whilst participants who took durvalumab alone lived a similar length of time as participants who took sorafenib. Participants who took STRIDE or durvalumab had a lower relative risk of experiencing worsening in their quality of life than participants who took sorafenib. The side effects that participants who received STRIDE or durvalumab experienced were expected for these types of treatments and could mostly be managed. WHAT DO THE RESULTS OF THE STUDY MEAN?: Overall, STRIDE is more effective than sorafenib for people with unresectable HCC.

Durvalumab Plus Olaparib in Previously Untreated, Platinum-Ineligible Patients With Metastatic Urothelial Carcinoma: A Multicenter, Randomized, Phase II Trial (BAYOU).

PURPOSE: Homologous recombination repair gene mutations (HRRm) are common in urothelial carcinoma (UC), rendering tumor cells sensitive to poly (ADP-ribose) polymerase (PARP) inhibition. We assessed efficacy and safety of durvalumab (anti-programmed cell death ligand-1) plus olaparib (PARP inhibitor) in patients with metastatic UC (mUC). METHODS: This randomized, multicenter, double-blind, phase II trial enrolled untreated, platinum-ineligible patients with mUC. Patients (N = 154) were randomly assigned 1:1 to receive durvalumab (1,500 mg intravenously once every 4 weeks) plus olaparib (300 mg orally, twice daily) or durvalumab plus placebo. The primary end point was progression-free survival (PFS) assessed by investigators per RECIST version 1.1. Secondary end points included overall survival in all patients and PFS in patients with HRRm. RESULTS: Overall, median PFS was 4.2 months (95% CI, 3.6 to 5.6) for durvalumab plus olaparib and 3.5 months (95% CI, 1.9 to 5.1) for durvalumab plus placebo (hazard ratio [HR], 0.94; 95% CI, 0.64 to 1.39; log-rank P value, .789). Median overall survival was 10.2 months (95% CI, 7.0 to 13.9) and 10.7 months (95% CI, 7.2 to 17.3), respectively (HR, 1.07; 95% CI, 0.72 to 1.61). In the 20% of patients with HRRm, median PFS was 5.6 months (95% CI, 1.9 to 8.1) and 1.8 months (95% CI, 1.7 to 2.2), respectively (HR, 0.18; 95% CI, 0.06 to 0.47). Treatment-related grade 3 or 4 adverse events occurred in 18% and 9% of patients, respectively. CONCLUSION: Adding olaparib to durvalumab did not improve survival outcomes in an unselected mUC population. Efficacy outcomes with durvalumab were similar to those reported for other anti-programmed cell death-1/programmed cell death ligand-1 agents. However, the results of secondary analyses suggest a potential role for PARP inhibition in patients with UC harboring HRRm.

Menstrual and Reproductive Factors in Association With Breast Cancer Risk in Vietnamese Women: A Case-Control Study.

OBJECTIVES: Though menstrual and reproductive factors have been associated with the risk of breast cancer in many populations, very few studies have been conducted among Vietnamese women. This study aimed to assess the association between menstrual and reproductive factors and the risk of breast cancer in Vietnamese women. METHODS: A retrospective case-control study of 490 breast cancer cases and 468 controls was conducted in Northern Vietnam. Unconditional logistic regression models adjusting for confounders were used to estimate odds ratios (ORs) and their 95% confidence intervals (CIs) for the associations of menstrual and reproductive factors with the risk of breast cancer; overall and by cancer subtype. RESULTS: Among breast cancer patients, the luminal B subtype was the most frequent (48.6%), followed by HER2-overexpressing (24.5%), luminal A (16.7%), and triple-negative breast cancer (TNBC; 10.2%). Among menopausal women, menopausal age at 50 years or older (OR = 1.71, 95% CI: 1.15-2.57 vs. <50 y) was associated with an increased risk of breast cancer. Earlier age at menarche (<13 y) was associated with a significantly increased risk of breast cancer (OR = 2.66, 95% CI: 1.08-7.51) among premenopausal women only and the luminal A subtype of breast cancer (OR = 3.06, 95% CI: 1.04-8.16). Having more than two children was associated with a reduced risk of premenopausal (OR = .42, 95%CI: .21-.83), luminal B (OR = .43, 95% CI: .24-.79), and TNBC (OR = .34, 95% CI: .14-.89). Later menopause was positively associated with the risk of breast cancer with HER2 overexpression (OR = 2.19, 95% CI: 1.14-4.23). CONCLUSION: Associations of menstrual and reproductive factors with breast cancer among Vietnamese women, particularly for among premenopausal women and for the luminal A subtype, are generally consistent with those reported from other countries. These findings suggest that changes in menstrual and reproductive patterns among young Vietnamese women may contribute to the recent rising incidence of breast cancer in Vietnam.

Real-World Treatment Patterns and Clinical Outcomes in Patients With Stage III Non-Small-Cell Lung Cancer: Results of KINDLE-Vietnam Cohort.

Objective: KINDLE-Vietnam was a part of a real-world KINDLE study with an aim to characterise treatment patterns and clinical outcomes of patients with stage III non-small cell lung cancer (NSCLC). Materials and Methods: Retrospective data from patients diagnosed with stage III NSCLC (American Joint Committee on Cancer, 7th edition) between January 2013 and December 2017 with at least 9 months of follow-up were collected from 2 centres in Vietnam. Descriptive statistics were used to summarise demographics, disease characteristics and treatment modalities. Kaplan-Meier methodology evaluated survival estimates; 2-sided 95% confidence intervals (CIs) were computed. Inferential statistics were used to correlate clinical and treatment variables with median progression-free survival (mPFS) and median overall survival (mOS). Results: A total of 150 patients (median age: 60 years [range 26-82]) were enrolled; 75.3% were male, 62.0% had smoking history, 56.4% had stage IIIB disease and 62.5% had adenocarcinoma. The majority of the cases (97.3%) were not discussed at a multidisciplinary team meeting. Overall, chemotherapy alone (43.3%), radiotherapy alone (17.0%), sequential chemoradiation (13.5%) and concurrent chemoradiation (12.8%) were preferred as initial therapy. Surgery-based treatment was administered in limited patients (stage IIIA, 10%; stage IIIB, 1.3%). Palliative therapy was the most commonly administered treatment upon relapse in the second-and third-line setting. The mPFS and mOS for the Vietnam cohort were 8.7 months (95% CI, 7.59-9.72) and 25.7 months (95% CI, 19.98-42.61), respectively. The mPFS and mOS for stage IIIA were 11.9 months (95% CI, 8.64-14.95) and 28.2 months (95% CI, 24.15-not-calculable) and for stage IIIB were 7.8 months (95% CI, 6.64-8.71) and 20.0 months (95% CI, 13.01-42.61). Conclusions: KINDLE-Vietnam offers insights into the clinical findings of stage III NSCLC. There is a high unmet need for identifying patients in the early stages of NSCLC. Strategies for improving clinical outcomes in this patient population include physician education, multidisciplinary management and catering to increased access to novel agents like immunotherapy and targeted therapy.

Tremelimumab plus Durvalumab in Unresectable Hepatocellular Carcinoma.

BACKGROUND: A single, high priming dose of tremelimumab (anti-cytotoxic T lymphocyte­associated antigen 4) plus durvalumab (anti­programmed cell death ligand-1), an infusion regimen termed STRIDE (Single Tremelimumab Regular Interval Durvalumab), showed encouraging clinical activity and safety in a phase 2 trial of unresectable hepatocellular carcinoma. METHODS: In this global, open-label, phase 3 trial, the majority of the patients we enrolled with unresectable hepatocellular carcinoma and no previous systemic treatment were randomly assigned to receive one of three regimens: tremelimumab (300 mg, one dose) plus durvalumab (1500 mg every 4 weeks; STRIDE), durvalumab (1500 mg every 4 weeks), or sorafenib (400 mg twice daily). The primary objective was overall survival for STRIDE versus sorafenib. Noninferiority for overall survival for durvalumab versus sorafenib was a secondary objective. RESULTS: In total, 1171 patients were randomly assigned to STRIDE (n=393), durvalumab (n=389), or sorafenib (n=389). The median overall survival was 16.43 months (95% confidence interval [CI], 14.16 to 19.58) with STRIDE, 16.56 months (95% CI, 14.06 to 19.12) with durvalumab, and 13.77 months (95% CI, 12.25 to 16.13) with sorafenib. Overall survival at 36 months was 30.7%, 24.7%, and 20.2%, respectively. The overall survival hazard ratio for STRIDE versus sorafenib was 0.78 (96.02% CI, 0.65 to 0.93; P=0.0035). Overall survival with durvalumab monotherapy was noninferior to sorafenib (hazard ratio, 0.86; 95.67% CI, 0.73 to 1.03; noninferiority margin, 1.08). Median progression-free survival was not significantly different among all three groups. Grade 3/4 treatment-emergent adverse events occurred for 50.5% of patients with STRIDE, 37.1% with durvalumab, and 52.4% with sorafenib. CONCLUSIONS: STRIDE significantly improved overall survival versus sorafenib. Durvalumab monotherapy was noninferior to sorafenib for patients with unresectable hepatocellular carcinoma. (Funded by AstraZeneca; ClinicalTrials.gov number, NCT03298451.)

Risk factors of Pancreatic Cancer in Vietnam: A Matched Case-Control Hospital-Based Study.

BACKGROUND: Data about the risk factors and pancreatic cancer in developing countries remain limited. We investigated for the first time the role of a number of risk factors (family cancer history, smoking, alcohol consumption, diabetes, inflammation disease, HBV infection) associated with pancreatic cancer among Vietnamese patients. METHODS: We included all patients hospitalized at 4 Northern Vietnamese hospitals (Vietnam National Cancer Hospital, Bach Mai, Viet Duc, Thai Nguyen) and diagnosed with pancreatic cancer during the period from 2017 to 2019. Risk factors of eligible patients were collected and assessed the associations using a matched control study and logistic regression model analysis. RESULTS: We identified 196 patients with diagnosis of pancreatic cancer of which 114 males and 82 females. The average age of the patient at the time of diagnosis was 58.28 years (standard deviation of 12.94, ranging from 25 to 87). Most of patients were diagnosed at advanced stage (85%). Smoking, diabetes, inflammation disease significantly increased the cancer risks (OR and 95% CI were 2.42 (1.38-4.37), 3.09 (1.54-6.68), 2.21 (1.42-3.45), respectively). HBV infection demonstrated a significant link with pancreatic cancer in univariate model (OR = 2.94 (1.08-9.36)), but not in multivariate model. However, cancer family history and alcohol drinkers did not show any significantly increased risk related to pancreatic cancer. CONCLUSIONS: Our finding showed smoking, diabetes, inflammation disease significantly increased the risk of pancreatic cancer in Vietnam.

Evaluation of Tumor Budding in Predicting Survival for Gastric Carcinoma Patients in Vietnam.

BACKGROUND: Tumor budding (Bd) has been demonstrated to be a promising prognostic factor in many carcinomas and in gastric cancer. It may represent an optimal additional parameter that is helpful for risk stratification in gastric adenocarcinoma. Hence, the present research was designed to predict the survival outcomes of gastric cancer in Vietnam, applying the tumor budding criteria of the International Tumor Budding Consensus Conference (ITBCC) 2016. METHODS: The present study was conducted on 109 gastric cancer patients who underwent surgery but did not receive neo-adjuvant chemotherapy from 2012 to 2015. The patients' clinicopathological features were recorded. Bd was evaluated according to the 2016 ITBCC criteria and classified as Bd1 (0-4 buds), Bd2 (5-9 buds), and Bd3 (≥10 buds) grades, in addition to being categorized into 2 main Bd groups: low (<10 buds) and high (≥10 buds) Bd. Kaplan-Meier and log-rank models were applied to analyze survival proportions. RESULTS: Of all the patients, 22.9% were classified as Bd1, 31.2% as Bd2, and 45.9% as Bd3 grades. Furthermore, 54.1% patients were categorized into the low and 45.9% into the high Bd groups. Patients with Bd1 and Bd2 grades (the low Bd group) exhibited the best prognosis, with 5-year overall survival (OS) rates of 85.7%, 90.8%, and90.3%, respectively. Patients with Bd3 grade (the high Bd group exhibited the worst prognosis, and none of them lived for 5 years (p < 0.001). Similar to OS rates, disease-free survival (DFS) rates markedly reduced from the Bd1 to Bd3 grade: Bd1, 95.0%; Bd2, 84.7%; and Bd3, 0% (p < 0.001). CONCLUSION: Patients with different gastric cancer Bd grades exhibited significantly different OS and DFS rates. The present study findings suggest that the ITBCC criteria can be used to stratify Bd for the treatment and prognosis of gastric cancer patients in Vietnam.

Expression of angiopoietin-like 4 fibrinogen-like domain (cANGPTL4) increases risk of brain metastases in women with breast cancer.

BACKGROUND: Brain metastases challenge daily clinical practice, and the mechanisms by which cancer cells cross the blood-brain barrier remain largely undeciphered. Angiopoietin-like 4 (ANGPTL4) proteolytic fragments have controversial biological effects on endothelium permeability. Here, we studied the link between ANGPTL4 and the risk of brain metastasis in cancer patients. MATERIALS AND METHODS: From June 2015 to June 2016, serum samples from 113 cancer patients were prospectively collected, and ANGPTL4 concentrations were assessed. Using a murine model of brain metastases, we investigated the roles of nANGPTL4 and cANGPTL4, the two cleaved fragments of ANGPTL4, in the occurrence of brain metastases. RESULTS: An ANGPTL4 serum concentration over 0.1 ng/mL was associated with decreased overall-survival. Multivariate analyses found that only breast cancer brain metastases were significantly associated with elevated ANGPTL4 serum concentrations. 4T1 murine breast cancer cells were transfected with either nANGPTL4- or cANGPTL4-encoding cDNAs. Compared to mice injected with wild-type 4T1 cells, mice injected with nANGPTL4 cells had shorter median survival (p < 0.05), while mice injected with cANGPTL4 had longer survival (p < 0.01). On tissue sections, compared to wild-type mice, mice injected with nANGPTL4 cells had significantly larger surface areas of lung metastases (p < 0.01), and mice injected with cANGPTL4 had significantly larger surface areas of brain metastases (p < 0.01). CONCLUSIONS: In this study, we showed that a higher expression of Angiopoietin-like 4 Fibrinogen-Like Domain (cANGPTL4) was associated with an increased risk of brain metastases in women with breast cancer.

Ubiquitin carboxyl-terminal esterase L1 (UCHL1) is associated with stem-like cancer cell functions in pediatric high-grade glioma.

Pediatric high-grade gliomas represent 8-12% of all primary tumors of the nervous system in children. Five-year survival for these pediatric aggressive tumors is poor (15-35%) indicating the need to develop better treatments for pediatric high-grade gliomas. In this work we used SF188 and SJ-GBM2 cell lines to study the function of the ubiquitin carboxyl-terminal esterase L1 (UCHL1), a deubiquitinase de-regulated in several cancers, in pediatric high-grade gliomas. UCHL1 depletion in SF188 and SJ-GBM2 glioma cells was associated with decreased cell proliferation and invasion, along with a reduced ability to grow in soft agar and to form spheres (i.e. self-renewal measure). A 70% reduction in Wnt signaling was also observed in the SF188 and SJ-GBM2 UCHL1 knockdowns (KDs) using a TCF-dependent TOPflash reporter assay. Transcriptome comparisons of UCHL1 KDs versus vector control identified a list of 306 differentially expressed genes (at least 2-fold change; p <0.05) which included genes known to be involved in cancer like ACTA2, POSTN, LIF, FBXL7, FBXW11, GDF15, HEY2, but also potential novel genes such us IGLL5, ABCA4, AQP3, AQP4, CALB1, and ALK. Bioinformatics gene ontology (GO) analysis of these 306 genes revealed significant enrichment in "signal peptides", "extracellular matrix"and "secreted proteins" GO Terms. "Angiogenesis and blood vessel development", "neuron differentiation/development", cell adhesion", and "cell migration" also showed significant enrichment in our GO analysis. Top canonical pathways identified by Ingenuity Pathway Analysis (IPA) included "Clathrin-mediated Endocytosis Signaling" (p = 5.14x10-4), "Virus Entry via Endocytic Pathways" (p = 6.15x 10-4), and "High Mobility Group-Box 1 (HMGB1) Signaling" (p = 6.15x10-4). While FGF2, IL1B, TNF and PDGFB were predicted as top upstream regulators (p < 2x10-16) of the UCHL1 KD-associated transcriptome. Aberrant expression of UCHL1 in pediatric high-grade gliomas may promote cell invasion, transformation, and self-renewal properties, at least in part, by modulating Wnt/Beta catenin activity. UCHL1 might act as an oncogene in glioma within the gene network that imparts stem-like characteristics to these cancer cells.