Whole-Exome Sequencing Reveals Novel Candidate Driver Mutations and Potential Druggable Mutations in Patients with High-Risk Neuroblastoma.

Neuroblastoma is the most prevalent solid tumor in early childhood, with a 5-year overall survival rate of 40-60% in high-risk cases. Therefore, the identification of novel biomarkers for the diagnosis, prognosis, and therapy of neuroblastoma is crucial for improving the clinical outcomes of these patients. In this study, we conducted the whole-exome sequencing of 48 freshly frozen tumor samples obtained from the Biobank. Somatic variants were identified and selected using a bioinformatics analysis pipeline. The mutational signatures were determined using the Mutalisk online tool. Cancer driver genes and druggable mutations were predicted using the Cancer Genome Interpreter. The most common mutational signature was single base substitution 5. MUC4, MUC16, and FLG were identified as the most frequently mutated genes. Using the Cancer Genome Interpreter, we identified five recurrent cancer driver mutations spanning MUC16, MUC4, ALK, and CTNND1, with the latter being novel and containing a missense mutation, R439C. We also identified 11 putative actionable mutations including NF1 Q1798*, Q2616*, and S636X, ALK F1174L and R1275Q, SETD2 P10L and Q1829E, BRCA1 R612S, NOTCH1 D1670V, ATR S1372L, and FGFR1 N577K. Our findings provide a comprehensive overview of the novel information relevant to the underlying molecular pathogenesis and therapeutic targets of neuroblastoma.

Co-stimulation of CD28/CD40 signaling molecule potentiates CAR-T cell efficacy and stemness.

CD19 chimeric antigen receptor T (CD19CAR-T) cells have achieved promising outcomes in relapsed/refractory B cell malignancies. However, recurrences occur due to the loss of CAR-T cell persistence. We developed dual T/B cell co-stimulatory molecules (CD28 and CD40) in CAR-T cells to enhance intense tumoricidal activity and persistence. CD19.28.40z CAR-T cells promoted pNF-κB and pRelB downstream signaling while diminishing NFAT signaling upon antigen exposure. CD19.28.40z CAR-T cells demonstrated greater proliferation, which translated into effective anti-tumor cytotoxicity in long-term co-culture assay. Repetitive weekly antigen stimulation unveiled continuous CAR-T cell expansion while preserving central memory T cell subset and lower expression of exhaustion phenotypes. The intrinsic genes underlying CD19.28.40z CAR-T cell responses were compared with conventional CARs and demonstrated the up-regulated genes associated with T cell proliferation and memory as well as down-regulated genes related to apoptosis, exhaustion, and glycolysis pathway. Enrichment of genes toward T cell stemness, particularly SELL, IL-7r, TCF7, and KLF2, was observed. Effective and continuing anti-tumor cytotoxicity in vivo was exhibited in both B cell lymphoblastic leukemia and B cell non-Hodgkin lymphoma xenograft models while demonstrating persistent T cell memory signatures. The functional enhancement of CD37.28.40z CAR-T cell activities against CD37+ tumor cells was further validated. The modification of dual T/B cell signaling molecules remarkably maximized the efficacy of CAR-T cell therapy.

Targeting pediatric solid tumors in the new era of RNA therapeutics.

Despite substantial progress in pediatric cancer treatment, poor prognosis remained for patients with recurrent or metastatic disease, given the limitations of approved targeted treatments and immunotherapies. RNA therapeutics offer significant potential for addressing a broad spectrum of diseases, including cancer. Advances in manufacturing and delivery systems are paving the way for the rapid development of therapeutic RNAs for clinical applications. This review summarizes therapeutic RNA classifications and the mechanisms of action, highlighting their potential in manipulating major cancer-related pathways and biological effects. We also focus on the pre-clinical investigation of RNA molecules with efficient delivery systems for their therapeutic potential targeting pediatric solid tumors.

Proteomic Analysis of Butyrate-Resistant Colorectal Cancer-Derived Exosomes Reveals Potential Resistance to Anti-Cancer Drugs.

BACKGROUND: Butyrate-resistant (BR) cells play an important role in acquiring chemoresistance in colorectal cancer (CRC). Our previous study demonstrated that BR CRC cells showed cross-resistance to chemotherapy drugs, including 5-fluorouracil and oxaliplatin, in both monolayer and spheroid cultures. The mechanisms underlying drug resistance were also elucidated. However, the link between parental (PT) and BR cells remains unclear. Extracellular vesicles (EVs) are key cell-cell communications that transport various molecules, including DNA, RNA, and proteins, between the donor and target cells. EVs contribute to drug resistance in cancers, such as melanoma and lung cancer. Recently, we focused on the correlation of proteomic profiles of EVs from different cell types. METHODS: In this study, we analyzed the proteomic profiles of EVs derived from PT and BR cells to investigate the mechanisms underlying the butyrate- and chemo-resistant phenotypes. EVs were isolated from PT and BR cells using ultracentrifugation. The characteristics of the EVs were evaluated using western blot and transmission electron microscopy. The EV proteomic data were further analyzed using liquid chromatography-mass spectrometry. RESULTS: We identified a unique protein expressed in BR cells related to the chemoresistant phenotype. Functional enrichment analysis showed that BR cells had higher protein catalytic activity, binding, and transcription activity. The STITCH database showed a greater correlation between protein-drug interactions in BR cells than in PT cells. Moreover, our findings support the hypothesis that EVs promote tumor progression and metastasis and affect the tumor microenvironment. CONCLUSIONS: Proteomic analysis of EVs from BR CRC cells reveals insights into drug resistance mechanisms, including protein-mediated carcinogenesis and reduced drug uptake, offering potential strategies to overcome resistance in clinical practice.

Establishment, characterization, and genetic profiling of patient-derived osteosarcoma cells from a patient with retinoblastoma.

Osteosarcoma is the most common malignant bone cancer in pediatric patients. Patients who respond poorly to chemotherapy experience worse clinical outcomes with a high mortality rate. The major challenge is the lack of effective drugs for these patients. To introduce new drugs for clinical approval, preclinical studies based on in vitro models must demonstrate the potency of the tested drugs, enabling the drugs to enter phase 1 clinical trials. Patient-derived cell culture is a promising testing platform for in vitro studies, as they more accurately recapitulate cancer states and genetic profiles compared to cell lines. In the present study, we established patient-derived osteosarcoma cells (PDC) from a patient who had previously been diagnosed with retinoblastoma. We identified a new variant of a germline mutation in the RB1 gene in the tissue of the patient. The biological effects of this PDC were studied to observe whether the cryopreserved PDC retained a feature of fresh PDC. The cryopreserved PDC preserved the key biological effects, including cell growth, invasive capability, migration, and mineralization, that define the conserved phenotypes compared to fresh PDC. From whole genome sequencing analysis of osteosarcoma tissue and patient-derived cells, we found that cryopreserved PDC was a minor population in the origin tissue and was selectively grown under the culture conditions. The cryopreserved PDC has a high resistance to conventional chemotherapy. This study demonstrated that the established cryopreserved PDC has the aggressive characteristics of osteosarcoma, in particular the chemoresistance phenotype that might be used for further investigation in the chemoresistant mechanism of osteosarcoma. In conclusion, the approach we applied for primary cell culture might be a promising method to generate in vitro models for functional testing of osteosarcoma.

Geographic variation of mutagenic exposures in kidney cancer genomes.

International differences in the incidence of many cancer types indicate the existence of carcinogen exposures that have not yet been identified by conventional epidemiology make a substantial contribution to cancer burden1. In clear cell renal cell carcinoma, obesity, hypertension and tobacco smoking are risk factors, but they do not explain the geographical variation in its incidence2. Underlying causes can be inferred by sequencing the genomes of cancers from populations with different incidence rates and detecting differences in patterns of somatic mutations. Here we sequenced 962 clear cell renal cell carcinomas from 11 countries with varying incidence. The somatic mutation profiles differed between countries. In Romania, Serbia and Thailand, mutational signatures characteristic of aristolochic acid compounds were present in most cases, but these were rare elsewhere. In Japan, a mutational signature of unknown cause was found in more than 70% of cases but in less than 2% elsewhere. A further mutational signature of unknown cause was ubiquitous but exhibited higher mutation loads in countries with higher incidence rates of kidney cancer. Known signatures of tobacco smoking correlated with tobacco consumption, but no signature was associated with obesity or hypertension, suggesting that non-mutagenic mechanisms of action underlie these risk factors. The results of this study indicate the existence of multiple, geographically variable, mutagenic exposures that potentially affect tens of millions of people and illustrate the opportunities for new insights into cancer causation through large-scale global cancer genomics.

Discovery of Novel Potential Prognostic Markers and Targeted Therapy to Overcome Chemotherapy Resistance in an Advanced-Stage Wilms Tumor.

Wilms tumor (WT), the most prevalent type of renal cancer in children, exhibits overall survival rates exceeding 90%. However, chemotherapy resistance, which occurs in approximately 10% of WT cases, is a major challenge for the treatment of WT, particularly for advanced-stage patients. In this study, we aimed to discover potential mutation markers and drug targets associated with chemotherapy resistance in advanced-stage WT. We performed exome sequencing to detect somatic mutations and molecular targets in 43 WT samples, comprising 26 advanced-stage WTs, of which 7 cases were chemotherapy-resistant. Our analysis revealed four genes (ALPK2, C16orf96, PRKDC, and SVIL) that correlated with chemotherapy resistance and reduced disease-free survival in advanced-stage WT. Additionally, we identified driver mutations in 55 genes within the chemotherapy-resistant group, including 14 druggable cancer driver genes. Based on the mutation profiles of the resistant WT samples, we propose potential therapeutic strategies involving platinum-based agents, PARP inhibitors, and antibiotic/antineoplastic agents. Our findings provide insights into the genetic landscape of WT and offer potential avenues for targeted treatment, particularly for patients with chemotherapy resistance.

Exome Sequencing Reveals Novel Germline Variants in Breast Cancer Patients in the Southernmost Region of Thailand.

Germline carriers of pathogenic variants in cancer susceptibility genes are at an increased risk of breast cancer (BC). We characterized germline variants in a cohort of 151 patients diagnosed with epithelial BC in the southernmost region of Thailand, where the predominant ethnicity differs from that of the rest of the country. Whole exome sequencing was used to identify and subsequently filter variants present in 26 genes known to be associated with cancer predisposition. Of the 151 individuals assessed, 23, corresponding to 15.2% of the sample, exhibited the presence of one or more pathogenic or likely pathogenic variants associated with BC susceptibility. We identified novel germline truncating variants in BRIP1, CHEK2, MSH6, PALB2, and PTEN and annotated variants of uncertain significance (VUSs), both novel and previously documented. Therefore, it is advisable to use genetic testing as an additional risk screening method for BC in this area.

Population-based prevalence study of common congenital malformations of the alimentary tract and abdominal wall in Thailand: a study using data from the National Health Security Office.

Background: The study aimed to estimate the prevalence of major congenital anomalies of the alimentary system and the abdominal wall in Thailand using a nationwide hospital discharge database from the National Health Security Office (2017-2020). Methods: The study extracted data from records with International Classification of Diseases-10 (ICD-10) codes related to esophageal malformation (ESO), congenital duodenal obstruction (CDO), jejunoileal atresia (INTES), Hirschsprung's disease (HSCR), anorectal malformation (ARM), abdominal wall defects (omphalocele (OMP) and gastroschisis (GAS)), and diaphragmatic hernia from the database with patient age selection set to less than 1 year. Results: A total of 2539 matched ICD-10 records were found in 2376 individuals over the 4-year study period. Concerning foregut anomalies, the prevalence of ESO was 0.88/10 000 births, while that of CDO was 0.54/10 000 births. The prevalence figures of INTES, HSCR, and ARM were 0.44, 4.69, and 2.57 cases per 10 000 births, respectively. For abdominal wall defects, the prevalences of OMP and GAS were 0.25 and 0.61 cases/10 000 births, respectively. The mortality in our cases was 7.1%, and survival analysis found that associated cardiac defects had a statistically significant influence on survival in most anomalies studied. In HSCR, both Down syndrome (DS) (hazard ratio (HR)=7.57, 95% confidence interval (CI)=4.12 to 13.91, p<0.001) and cardiac defects (HR=5.82, 95% CI=2.85 to 11.92, p<0.001) were significantly associated with poorer survival outcomes. However, only DS (adjusted HR=5.55, 95% CI=2.63 to 11.75, p<0.001) independently predicted worse outcomes by multivariable analysis. Conclusions: Our analysis of the hospital discharge database found that the prevalence of gastrointestinal anomalies in Thailand was lower than that reported in other countries, except for HSCR and anorectal malformations. Associated Down syndrome and cardiac defects influence the survival outcomes of these anomalies.

Proteome Analysis of the Antiproliferative Activity of the Novel Chitooligosaccharide-Gallic Acid Conjugate against the SW620 Colon Cancer Cell Line.

Chitooligosaccharide (COS) and gallic acid (GA) are natural compounds with anti-cancer properties, and their conjugate (COS-GA) has several biological activities. Herein, the anti-cancer activity of COS-GA in SW620 colon cancer cells was investigated. MTT assay was used to evaluate cell viability after treatment with 62.5, 122, and 250 µg/mL of COS, GA, and COS-GA for 24 and 48 h. The number of apoptotic cells was determined using flow cytometry. Proteomic analysis was used to explore the mechanisms of action of different compounds. COS-GA and GA showed a stronger anti-cancer effect than COS by reducing SW620 cell proliferation at 125 and 250 µg/mL within 24 h. Flow cytometry revealed 20% apoptosis after COS-GA treatment for 24 h. Thus, GA majorly contributed to the enhanced anti-cancer activity of COS via conjugation. Proteomic analysis revealed alterations in protein translation and DNA duplication in the COS group and the structural constituents of the cytoskeleton, intermediate filament organization, the mitochondrial nucleoid, and glycolytic processes in the COS-GA group. Anti-cancer-activity-related proteins were altered, including CLTA, HSPA9, HIST2H2BF, KRT18, HINT1, DSP, and VIM. Overall, the COS-GA conjugate can serve as a potential anti-cancer agent for the safe and effective treatment of colon cancer.

A Clinical Prediction Model for Breast Cancer in Women Having Their First Mammogram.

BACKGROUND: Digital mammography is the most efficient screening and diagnostic modality for breast cancer (BC). However, the technology is not widely available in rural areas. This study aimed to construct a prediction model for BC in women scheduled for their first mammography at a breast center to prioritize patients on waiting lists. METHODS: This retrospective cohort study analyzed breast clinic data from January 2013 to December 2017. Clinical parameters that were significantly associated with a BC diagnosis were used to construct predictive models using stepwise multiple logistic regression. The models' discriminative capabilities were compared using receiver operating characteristic curves (AUCs). RESULTS: Data from 822 women were selected for analysis using an inverse probability weighting method. Significant risk factors were age, body mass index (BMI), family history of BC, and indicated symptoms (mass and/or nipple discharge). When these factors were used to construct a model, the model performance according to the Akaike criterion was 1387.9, and the AUC was 0.82 (95% confidence interval: 0.76-0.87). CONCLUSION: In a resource-limited setting, the priority for a first mammogram should be patients with mass and/or nipple discharge, asymptomatic patients who are older or have high BMI, and women with a family history of BC.

Genomics-Driven Precision Medicine in Pediatric Solid Tumors.

Over the past decades, several study programs have conducted genetic testing in cancer patients to identify potential genetic targets for the development of precision therapeutic strategies. These biomarker-driven trials have demonstrated improved clinical outcomes and progression-free survival rates in various types of cancers, especially for adult malignancies. However, similar progress in pediatric cancers has been slow due to their distinguished mutation profiles compared to adults and the low frequency of recurrent genomic alterations. Recently, increased efforts to develop precision medicine for childhood malignancies have led to the identification of genomic alterations and transcriptomic profiles of pediatric patients which presents promising opportunities to study rare and difficult-to-access neoplasms. This review summarizes the current state of known and potential genetic markers for pediatric solid tumors and provides perspectives on precise therapeutic strategies that warrant further investigations.

Survival Outcome in Critically Ill Patients Receiving Extracorporeal Membrane Oxygenation Support: Early Experience from a University Hospital in Thailand.

Objective Extracorporeal membrane oxygenation (ECMO) is a relatively new technology used for life support in patients with cardiopulmonary failure from various causes. The objective of this study is to review the first 5-year experience in adopting this technology in a teaching hospital in southern Thailand. Methods The data of ECMO-supported patients in Songklanagarind Hospital, from the years 2014 to 2018, were retrospectively reviewed. Data sources were from electronic medical records and the database of the perfusion service. Parameters in focus included prior conditions and indications of ECMO, type of ECMO and cannulation method, complications during and after the treatment, and discharge statuses. Results A total of 83 patients received ECMO life support during the 5-year period and the number of cases per year increased. The proportion of venovenous: venoarterial ECMO in our institute was 49:34 cases and there were three cases who used ECMO as a part of cardiopulmonary resuscitation. Moreover, there were 57 cases who used ECMO for cardiac failure and 26 cases were for respiratory causes, while premature withdrawal was decided in 26 cases (31.3%). Overall survival from ECMO was 35/83 cases (42.2%) and survival to discharge was 32/83 (38.6%). During therapy, ECMO could restore serum pH to the normal range in all cases. Furthermore, those who used ECMO for respiratory failure had significantly higher survival probability (57.7%) when compared to the cardiac counterpart (29.8%, p -value = 0.03). Patients with younger ages also had significantly better survival outcomes. The most common complications were cardiac (75 cases, 85.5%), followed by renal (45 cases, 54.2%), and hematologic systems (38 cases, 45.8%). In those who survived to discharge, average ECMO duration was 9.7 days. Conclusion Extracorporeal life support is a technology that bridges the patients with cardiopulmonary failure to their recovery or definitive surgery. Despite the high complication rate, survival can be expected, especially in respiratory failure cases and relatively young patients.

Prevalence of Pathogenic Germline Mutations in 13 Hereditary Cancer-Related Genes in Breast Cancer Patients in Narathiwat Province, Thailand.

BACKGROUND: BRCA1 and BRCA2 genes are known to increase breast cancer's lifetime risk. Early identification of women with this inherited risk can potentially reduce the risk of breast and/or ovarian cancer and, together with early screening, decrease the mortality rate. OBJECTIVE: This study explored the frequency and distribution of genetic variants in consecutive cases of breast cancer in Narathiwat province, one of the three provinces in the southernmost Thai border. MATERIAL & METHOD: A series of 64 consecutive breast cancer patients who underwent treatment in two general hospitals in the province during the period from the year 2021 to 2022. Genotyping studies were performed using a whole exome sequencing platform. Moderate to high penetrance variants recommended by the National Comprehensive Cancer Network (NCCN) guidelines 2022 (ATM, BARD1, BRCA1, BRCA2, CDH1, CHEK2, NF1, PALB2, PTEN, RAD51C, RAD51D, STK11, TP53) were annotated and filtered for pathogenic, likely pathogenic, or high-impact variants. RESULTS: Pathogenic germline variants were found in 8/64 cases (12.5%), namely BRCA1 in 3 (4.7%), BRCA2 in 4 (6.3%), ATM in 1 (1.6%), and PALB2 in 1 (1.6%). One patient had two concomitant germline mutations in BRCA2 and ATM. CONCLUSION: This is the first study on the frequency of germline mutations in BRCA1/2 and other breast cancer-predisposing genes in the southernmost provinces of Thailand. At least one pathogenic germline mutation was identified in 12.5% of the study patients, which suggests that genetic testing in this population has a high potential to provide benefits.

Correlation between image-defined risk factors and surgical complications in patients with neuroblastoma: a retrospective study.

BACKGROUND: Image-defined risk factor (IDRF) is a common tool used for neuroblastoma risk group classification. We speculated that anatomical evaluation by IDRF might be correlated with surgical complications and the oncologic outcome. Here, we investigated correlation between IDRF with outcomes of surgery of neuroblastoma patients. METHODS: Medical records and computed tomography images of neuroblastoma patients who underwent a surgery at Songklanagarind Hospital between 2002 and 2019 were retrospectively reviewed. IDRFs were analyzed for correlation with surgical complications, overall survival, progression-free survival and local recurrence within 2 years. RESULTS: Forty-five patients were enrolled in the study. Sixteen (35%) patients had low IDRF score at diagnosis (score ≤ 5). Other 29 (64%) patients had high IDRF score (score ≥ 6). High IDRF group significantly had higher incidence of organ injury and more intraoperative blood loss. At post-chemotherapy, high IDRF was not only associated with higher operative complications, but also associated with 2-year overall survival and progress-free survival. CONCLUSIONS: Neuroblastoma patients whose IDRF score, either at diagnosis or after neoadjuvant therapy, was 6 or higher had increased risk of surgical complication. This evidence prompts pediatric surgeons to prepare more for safe surgery in this group of patients.

Enrichment of T-cell proliferation and memory gene signatures of CD79A/CD40 costimulatory domain potentiates CD19CAR-T cell functions.

CD19 chimeric antigen receptor (CAR) T-cells have demonstrated remarkable outcomes in B-cell malignancies. Recently, the novel CD19CAR-T cells incorporated with B-cell costimulatory molecules of CD79A/CD40 demonstrated superior antitumor activity in the B-cell lymphoma model compared with CD28 or 4-1BB. Here, we investigated the intrinsic transcriptional gene underlying the functional advantage of CD19.79A.40z CAR-T cells following CD19 antigen exposure using transcriptome analysis compared to CD28 or 4-1BB. Notably, CD19.79A.40z CAR-T cells up-regulated genes involved in T-cell activation, T-cell proliferation, and NF-κB signaling, whereas down-regulated genes associated with T-cell exhaustion and apoptosis. Interestingly, CD19.79A.40z CAR- and CD19.BBz CAR-T cells were enriched in almost similar pathways. Furthermore, gene set enrichment analysis demonstrated the enrichment of genes, which were previously identified to correlate with T-cell proliferation, interferon signaling pathway, and naïve and memory T-cell signatures, and down-regulated T-cell exhaustion genes in CD79A/CD40, compared with the T-cell costimulatory domain. The CD19.79A.40z CAR-T cells also up-regulated genes related to glycolysis and fatty acid metabolism, which are necessary to drive T-cell proliferation and differentiation compared with conventional CD19CAR-T cells. Our study provides a comprehensive insight into the understanding of gene signatures that potentiates the superior antitumor functions by CD19CAR-T cells incorporated with the CD79A/CD40 costimulatory domain.

Stuttering priapism in a pediatric patient with pheochromocytoma-induced thrombocytosis.

Priapism is an erection of more than 4 h without sexual stimulation. Ischemic priapism may lead to irreversible erectile dysfunction after a long-lasting period. Stuttering priapism is characterized by a pattern of recurrence that may progress to an unrelenting ischemic crisis, which is a urological emergency. Few reports have revealed that priapism is associated with essential thrombocythemia. The reactive thrombocytosis is uncommonly manifested by pheochromocytoma and rarely causes thrombotic events even if the platelet count is extremely high. We presented priapism related to reactive severe thrombocytosis in a 12-year-old male with pheochromocytoma. The cornerstone of care was prompt medical and surgical intervention by a multidisciplinary team approach to save life and preserve erectile function.

An evaluation of the association between radiological parameters and survival outcomes in pediatric patients with hepatoblastoma.

BACKGROUND: We evaluated the survival outcomes following hepatic resection as a treatment modality in pediatric patients with hepatoblastoma at a single institution, and to identify radiological parameters associated with poorer survival outcomes. METHODS: This was a retrospective cohort study. Medical records were reviewed, pertaining to pediatric patients diagnosed with hepatoblastoma who underwent surgical resection at a university hospital in Thailand between 2004 and 2021. Radiological parameters, clinical factors, and pathological data were also collected. Survival analysis was performed, and prognostic factors were identified using logistic regression analysis. RESULTS: Forty-two suitable patients were identified. Three cases with incomplete data were excluded, resulting in 39 cases being analyzed. Except for two, all patients received preoperative chemotherapy following the Thai Pediatric Oncology Group regimen. The two- and five-year overall survival rates were 78.0% and 70.9%, respectively. Upon analysis, the radiological parameters associated with poorer survival were poor response to neoadjuvant chemotherapy, presence of metastasis, post-chemotherapy tumor diameter, Post treatment extent of disease (POSTTEXT) Stage IV disease, presence of portal vein involvement, and presence of residual disease; poor neoadjuvant-response, portal vein involvement, and metastasis were independently associated with worse outcomes. In patients with non-metastatic hepatoblastoma who had at least a 25% reduction in size following neoadjuvant chemotherapy, the 5-year survival rate was 90.9% (95% CI 50.8-98.6%). CONCLUSIONS: Although preoperative evaluation of the tumor extent staging did not significantly affect survival, portal vein involvement as per POSTTEXT staging, stable or increasing tumor size, and metastasis following neoadjuvant chemotherapy were associated with poor overall survival. LEVEL OF EVIDENCE: IIB.

Inferior Clinical Outcomes of Pediatric Rhabdomyosarcoma in Thailand: A 16-Year Experience in a Single Tertiary Institution.

INTRODUCTION: There is limited data available on the treatment outcomes of pediatric rhabdomyosarcoma (RMS) in Asian populations. Therefore, we aimed to review the baseline characteristics, clinical outcomes, and prognostic factors in children with RMS from Thailand. METHODS: The data of children under 15 years of age diagnosed with RMS between 2003 and 2019 from a large tertiary hospital in Southern Thailand were retrospectively reviewed. Descriptive statistics were utilized to describe the clinical characteristics. The Kaplan-Meier method was utilized to estimate survival. Cox proportional hazards regression analysis was utilized to determine prognostic factors that affect survival. RESULTS: A total of 42 children RMS were included in this study. The median age at diagnosis was 6.4 years (IQR, 2.4-10.2). Among these patients, 11 (26%) were older than 10 years, and 13 (31%) presented with metastatic disease at diagnosis. The 5-year overall survival (OS) rate was 39% for all children. Age greater than 10 years (hazard ratio (HR): 3.3, 95% CI: 1.2-9.2) and metastatic disease at diagnosis (hazard ratio (HR): 2.8, 95% CI: 1.1-7.5) were independently associated with poorer survival. The 3-year OS for children with metastatic disease (stage IV) was 15% (95% CI: 4.3-55). CONCLUSION: The percentage of metastatic disease in our cohort was higher than that in previous reports and may have contributed to a poorer outcome. Age greater than 10 years and metastatic disease at diagnosis were noted as adverse prognostic factors.