Bilateral Sudden Hearing Loss in Iron Deficiency Anemia.

The present study describes an unusual case of bilateral sudden hearing loss associated with iron deficiency anemia. Although hematologic disorders such as anemia or leukemia have been reported to be associated with sudden hearing loss, bilateral sudden hearing loss, which was presented as the first manifestation of iron deficiency anemia, has not been reported. A 74-year-old man presented with simultaneous bilateral sudden hearing loss without vertigo. A complete blood count test revealed a hemoglobin level of 6.4 g/dL and a ferritin level of 14.5 mg/mL, indicating iron deficiency anemia. Postcontrast 3D FLAIR MRI showed enhancement of the bilateral cochlea, vestibules, and lateral semicircular and posterior semicircular canals. After treatment, the patient's hearing loss partially improved.

Transcriptome-based deep learning analysis identifies drug candidates targeting protein synthesis and autophagy for the treatment of muscle wasting disorder.

Sarcopenia, the progressive decline in skeletal muscle mass and function, is observed in various conditions, including cancer and aging. The complex molecular biology of sarcopenia has posed challenges for the development of FDA-approved medications, which have mainly focused on dietary supplementation. Targeting a single gene may not be sufficient to address the broad range of processes involved in muscle loss. This study analyzed the gene expression signatures associated with cancer formation and 5-FU chemotherapy-induced muscle wasting. Our findings suggest that dimenhydrinate, a combination of 8-chlorotheophylline and diphenhydramine, is a potential therapeutic for sarcopenia. In vitro experiments demonstrated that dimenhydrinate promotes muscle progenitor cell proliferation through the phosphorylation of Nrf2 by 8-chlorotheophylline and promotes myotube formation through diphenhydramine-induced autophagy. Furthermore, in various in vivo sarcopenia models, dimenhydrinate induced rapid muscle tissue regeneration. It improved muscle regeneration in animals with Duchenne muscular dystrophy (DMD) and facilitated muscle and fat recovery in animals with chemotherapy-induced sarcopenia. As an FDA-approved drug, dimenhydrinate could be applied for sarcopenia treatment after a relatively short development period, providing hope for individuals suffering from this debilitating condition.

Deep learning algorithm for automatically measuring Cobb angle in patients with idiopathic scoliosis.

PURPOSE: The Cobb angle is a standard measurement to qualify and track the progression of scoliosis. However, the Cobb angle has high inter- and intra-observer variability. Consequently, its measurement varies with vertebrae and may even differ when the same vertebra is measured. Therefore, it is not constant and differs with measurements. This study aimed to develop a deep learning model that automatically measures the Cobb angle. The deep learning model for identifying vertebrae on spine radiographs was developed. METHODS: The dataset consisted of 297 images that were divided into two subsets for training and validation. Two hundred and twenty-seven images (76.4%) were used to train the model, while 70 images (23.6%) were used as the validation dataset. Absolut error between the measurements by the observer and developed deep learning model and intraclass correlation coefficient (ICC). RESULTS: The average absolute error between the measurements was 1.97° with a standard deviation of 1.57°. In addition, 95.9% of the angles had an absolute error of less than 5°. The ICC was calculated to assess the model's reliability further. The ICC was 0.981, indicating excellent reliability. CONCLUSIONS: The authors believe the model will be useful in clinical practice by relieving clinicians of the burden of having to manually compute the Cobb angle. Further studies are needed to enhance the accuracy and versatility of this deep learning model.

Targeting the m6A RNA methyltransferase METTL3 attenuates the development of kidney fibrosis.

Kidney fibrosis is a major mechanism underlying chronic kidney disease (CKD). N6-methyladenosine (m6A) RNA methylation is associated with organ fibrosis. We investigated m6A profile alterations and the inhibitory effect of RNA methylation in kidney fibrosis in vitro (TGF-ß-treated HK-2 cells) and in vivo (unilateral ureteral obstruction [UUO] mouse model). METTL3-mediated signaling was inhibited using siRNA in vitro or the METTL3-specific inhibitor STM2457 in vivo and in vitro. In HK-2 cells, METTL3 protein levels increased in a dose- and time-dependent manner along with an increase in the cellular m6A levels. In the UUO model, METTL3 expression and m6A levels were significantly increased. Transcriptomic and m6A profiling demonstrated that epithelial-to-mesenchymal transition- and inflammation-related pathways were significantly associated with RNA m6A methylation. Genetic and pharmacologic inhibition of METTL3 in HK-2 cells decreased TGF-ß-induced fibrotic marker expression. STM2457-induced inhibition of METTL3 attenuated the degree of kidney fibrosis in vivo. Furthermore, METTL3 protein expression was significantly increased in the tissues of CKD patients with diabetic or IgA nephropathy. Therefore, targeting alterations in RNA methylation could be a potential therapeutic strategy for treating kidney fibrosis.

Bi-directional regulation of AIMP2 and its splice variant on PARP-1-dependent neuronal cell death; Therapeutic implication for Parkinson's disease.

BACKGROUND: Parthanatos represents a critical molecular aspect of Parkinson's disease, wherein AIMP2 aberrantly activates PARP-1 through direct physical interaction. Although AIMP2 ought to be a therapeutic target for the disease, regrettably, it is deemed undruggable due to its non-enzymatic nature and predominant localization within the tRNA synthetase multi-complex. Instead, AIMP2 possesses an antagonistic splice variant, designated DX2, which counteracts AIMP2-induced apoptosis in the p53 or inflammatory pathway. Consequently, we examined whether DX2 competes with AIMP2 for PARP-1 activation and is therapeutically effective in Parkinson's disease. METHODS: The binding affinity of AIMP2 and DX2 to PARP-1 was contrasted through immunoprecipitation. The efficacy of DX2 in neuronal cell death was assessed under 6-OHDA and H2O2 in vitro conditions. Additionally, endosomal and exosomal activity of synaptic vesicles was gauged in AIMP2 or DX2 overexpressed hippocampal primary neurons utilizing optical live imaging with VAMP-vGlut1 probes. To ascertain the role of DX2 in vivo, rotenone-induced behavioral alterations were compared between wild-type and DX2 transgenic animals. A DX2-encoding self-complementary adeno-associated virus (scAAV) was intracranially injected into 6-OHDA induced in vivo animal models, and their mobility was examined. Subsequently, the isolated brain tissues were analyzed. RESULTS: DX2 translocates into the nucleus upon ROS stress more rapidly than AIMP2. The binding affinity of DX2 to PARP-1 appeared to be more robust compared to that of AIMP2, resulting in the inhibition of PARP-1 induced neuronal cell death. DX2 transgenic animals exhibited neuroprotective behavior in rotenone-induced neuronal damage conditions. Following a single intracranial injection of AAV-DX2, both behavior and mobility were consistently ameliorated in neurodegenerative animal models induced by 6-OHDA. CONCLUSION: AIMP2 and DX2 are proposed to engage in bidirectional regulation of parthanatos. They physically interact with PARP-1. Notably, DX2's cell survival properties manifest exclusively in the context of abnormal AIMP2 accumulation, devoid of any tumorigenic effects. This suggests that DX2 could represent a distinctive therapeutic target for addressing Parkinson's disease in patients.

Brain-targeted delivery of neuroprotective survival gene minimizing hematopoietic cell contamination: implications for Parkinson's disease treatment.

BACKGROUND: Neurodegenerative diseases, including Parkinson's disease, Amyotropic Lateral Sclerosis (ALS) and Alzheimer's disease, present significant challenges for therapeutic development due to drug delivery restrictions and toxicity concerns. Prevailing strategies often employ adeno-associated viral (AAV) vectors to deliver neuroprotective survival genes directly into the central nervous system (CNS). However, these methods have been limited by triggering immunogenic responses and risk of tumorigenicity, resulting from overexpression of survival genes in peripheral blood mononuclear cells (PBMC), thereby increasing the risk of tumorigenicity in specific immune cells. Thus, by coding selectively suppressive microRNA (miRNA) target sequences in AAV genome, we designed CNS-targeted neuroprotective gene expression vector system without leakage to blood cells. METHODS: To minimize the potential for transgene contamination in the blood, we designed a CNS-specific AAV system. Our system utilized a self-complementary AAV (scAAV), encoding a quadruple repeated target sequence of the hematopoietic cell-specific miR142-3p at the 3' untranslated region (UTR). As a representative therapeutic survival gene for Parkinson's disease treatment, we integrated DX2, an antagonistic splice variant of the apoptotic gene AIMP2, known to be implicated in Parkinson's disease, into the vector. RESULTS: This configuration ensured that transgene expression was stringently localized to the CNS, even if the vector found its way into the blood cells. A single injection of scAAV-DX2 demonstrated marked improvement in behavior and motor activity in animal models of Parkinson's disease induced by either Rotenone or 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Importantly, comprehensive preclinical data adhering to Good Laboratory Practice (GLP) standards revealed no adverse effects in the treated animals. CONCLUSIONS: Our CNS-specific vector system, which encodes a survival transgene DX2, signifies a promising avenue for safe gene therapy, avoiding unintended expression of survival gene in blood cells, applicable to various neurodegenerative diseases.

Comparative study between Embosphere® and Marine gel® as embolic agents for chemoembolization of hepatocellular carcinoma.

BACKGROUND: While gelatin sponge particles and calibrated microspheres are commonly used as embolic materials in conventional transarterial chemoembolization (cTACE), direct comparisons between these embolic agents are rare. AIM: To compare the efficacy and safety of superselective cTACE using Embosphere® or Marine gel® in patients with early-stage hepatocellular carcinoma (HCC). METHODS: This retrospective study included 70 patients with small (< 4 cm) HCC who underwent cTACE with Embosphere® (n = 33) or Marine gel® (n = 37) as the embolic agent at a single center between March 2021 and July 2022. The radiologic images and clinical data were retrospectively reviewed, with an emphasis on tumor response, procedure-related complications, and local tumor recurrence. The primary index tumor was assessed on a 1-mo follow-up image, and local progression-free survival was obtained using the Kaplan-Meier method and was compared by the log-rank test. RESULTS: The median tumor size of both groups was 1.5 cm, and 69 patients achieved a complete response one month after cTACE. The cumulative local recurrence rate at 12 mo was 15.5% in the Embosphere® group and 14.4% in the Marine gel® group. The local progression-free survival was not significantly different between the two groups (P = 0.83). In the multivariate analysis, high serum alpha-fetoprotein was the only significant poor prognostic factor for local tumor progression (P = 0.01). Postembolization syndrome occurred in 36.4% of the Embosphere® group and 35.1% of the Marine gel® group, and there were no cases of biloma, biliary duct dilation, or liver abscess in either group. CONCLUSION: Calibrated gelatin sponge particles (Marine gel®) and calibrated microspheres (Embosphere®) have similar outcomes in terms of tumor response for superselective cTACE of small HCC.

Radiation Major Hepatectomy Using Ablative Dose Yttrium-90 Radioembolization in Patients with Hepatocellular Carcinoma 5 cm or Larger.

PURPOSE: To evaluate the safety and effectiveness of ablative radioembolization for large hepatocellular carcinoma (HCC) while preserving a small future liver remnant (FLR). MATERIALS AND METHODS: Twenty-five patients with large HCC of ≥5 cm requiring treatment for >60% of the total liver volume and having well-preserved liver function were treated with ablative glass microsphere radioembolization at a single institution from January 2017 to December 2021. Radioembolization was performed with a mean absorbed dose of >150 Gy, and the FLR per nontumor liver volume (NTLV) was set at >30%. Changes in liver function, adverse events, duration of response (DoR) in a treated area, time-to-progression (TTP), and overall survival (OS) were retrospectively investigated. RESULTS: The largest tumor diameter and planned dose per treated volume were 11.4 cm ± 3.9 and 242.3 Gy ± 63.6 (169.4 Gy ± 45.9 per whole liver volume), respectively. All patients remained at Child-Pugh Class A for 90 days. No patient experienced Grade 3‒4 hyperbilirubinemia or new ascites. One patient (lung dose, 27.8 Gy) developed radiation pneumonitis requiring transient steroid treatment. According to the posttreatment dosimetry, the tumorous and nontumorous liver absorbed doses were 418.8 Gy ± 227.4 and 69.0 Gy ± 32.1, respectively. The median DoR in a treated area and TTP were 22.0 and 17.1 months, respectively. The 5-year OS rate was 83.2%. CONCLUSIONS: Ablative radioembolization of large HCC of ≥5 cm can be performed safely and effectively in patients with preserved liver function when FLR/NTLV exceeds 30%.

Transarterial Chemoembolization Using Idarubicin Versus Doxorubicin Chemoemulsion in Patients with Hepatocellular Carcinoma (IDADOX): Protocol for a Randomized, Non-inferiority, Double-Blind Trial.

PURPOSE: This study aims to test the hypothesis that idarubicin-based transarterial chemoembolization (IDA-TACE), using one of the most potent chemotherapeutic agents, could yield oncologic outcomes equivalent to or marginally improved over doxorubicin-based TACE (DOX-TACE). MATERIALS AND METHODS: This single-center, prospective, phase II, randomized controlled, non-inferiority, double-blind trial will enroll 128 treatment-naïve patients with HCC (≤ 5 tumors, 1-5 cm in diameter) for conventional TACE. Participants will be randomly assigned (1:1) to either IDA-TACE or DOX-TACE, with stratification by Child-Pugh class. Superselective conventional TACE will be performed using cone-beam CT and small-bore microcatheters. Patient evaluations, including dynamic imaging and blood tests, will occur at 1, 3, and 6 months post-initial treatment. The primary outcome measure is the objective response rate (ORR) according to mRECIST at 6 months. Secondary outcomes include 3-month and 6-month tumor responses, time-to-progression, the incidence of treatment-related serious adverse events within 30 days, and the incidence and severity of any adverse events. STATISTICS: Non-inferiority will be claimed if the upper limit of a one-sided 97.5% confidence interval for the proportion difference (i.e., "6-month ORR of DOX-TACE" - "6-month ORR of IDA-TACE") falls below 0.15 in both intention-to-treat and per-protocol analyses. The proportion difference and its confidence interval will be calculated by the Cochran-Mantel-Haenszel method to obtain a weighted average of stratum-specific proportion differences. EXPECTED GAIN OF KNOWLEDGE: If IDA-TACE demonstrates outcomes comparable to DOX-TACE, this study could provide compelling evidence that various cytotoxic agents yield similar contributions in TACE, considering the minor role of chemotherapeutic agents in TACE. TRIAL REGISTRATION: ClinicalTrials.gov ( https://clinicaltrials.gov/ ). Identifier: NCT06114082. World Health Organization International Clinical Trials Registry Platform (WHO ICTRP) ( https://trialsearch.who.int/Default.aspx ). Identifier: KCT0008166.

Experience from a single-center study on multimodal medication therapy for patients with complex regional pain syndrome.

BACKGROUND: Despite the application of various therapeutic methods, pain caused by complex regional pain syndrome (CRPS) is not sufficiently managed and often progresses to a chronic stage. For the systematic and effective treatment of CRPS, we developed an algorithm for multimodal medication therapy based on the established pathophysiology of CRPS to control CRPS-related pain. OBJECTIVE: In this study, we present the outcomes of our novel algorithm for multimodal medication therapy for patients with CRPS, consisting of three major components: multimodal oral medication, intravenous ketamine, and intravenous lidocaine therapy. METHODS: We retrospectively investigated patients with CRPS who received multimodal therapy. Pain severity scores were evaluated using a numerical rating scale at four time points (P1, pain at initial consultation; P2, pain after oral medication; P3, pain after ketamine treatment; and P4, pain after lidocaine treatment). The effect of the multimodal medication therapy algorithm on pain management was evaluated at each time point. RESULTS: In patients with CRPS, multimodal oral medication, intravenous ketamine, and intravenous lidocaine therapies led to significantly improved pain control (p< 0.05). Additionally, the combination of these three therapies (through the multimodal medication therapy algorithm) resulted in significant pain relief in patients with CRPS (p< 0.05). CONCLUSIONS: Our multimodal medication therapy algorithm effectively controlled pain in patients with CRPS. However, further prospective studies with large sample sizes and randomized controlled trials are needed for more accurate generalization.

Prognostic value of collateral perfusion estimation by arterial spin labeling for acute anterior circulation ischemic stroke.

PURPOSE: This study aimed to verify the value of arterial spin labeling (ASL) collateral perfusion estimation for predicting functional outcomes in acute anterior circulation ischemic stroke. METHODS: This secondary analysis of an ongoing prospective observational study included data from participants with acute ischemic stroke due to steno-occlusion of the internal carotid artery and/or the middle cerebral artery within 8 h of symptom onset. We compared the collateral map, which is a 5-phase collateral imaging derived from dynamic contrast-enhanced magnetic resonance angiography, and ASL to validate the ASL collateral perfusion estimation. Multiple logistic regression analyses were conducted to identify independent predictors of favorable functional outcomes. RESULTS: One hundred forty-eight participants (68 ± 13 years, 96 men) were evaluated. The ASL collateral perfusion grade was positively correlated with the collateral perfusion grade of the collateral map (P < .001). Younger age (OR = 0.53, 95% CI = 0.36-0.78, P = .002), lower baseline NIHSS score (OR = 0.85, 95% CI = 0.78-0.92, P < .001), intermediate ASL collateral perfusion grade (OR = 4.02, 95% CI = 1.43-11.26, P = .008), good ASL collateral perfusion grade (OR = 26.37, 95% CI = 1.06-655.01, P = .046), and successful reperfusion (OR = 5.84, 95% CI = 2.08-16.42, P < .001) were independently associated with favorable functional outcomes. CONCLUSION: ASL collateral perfusion estimation provides prognostic information, which can be helpful in guiding management decisions.

C-Arm Computed Tomographic Image Fusion for Repetitive Transarterial Chemoembolization of Hepatocellular Carcinoma.

OBJECTIVE: The aim of this study was to evaluate the potential implications of fusion imaging with C-arm computed tomography (CACT) scans for repetitive conventional transarterial chemoembolization (cTACE) for hepatocellular carcinoma. MATERIALS AND METHODS: Fifty-six cTACE sessions were performed using fusion CACT images from September 2020 to June 2021 in a tertiary referral center, and the data were retrospectively analyzed. Fusion of unenhanced and enhanced CACT images was considered when previously accumulated iodized oil hampered the identification of local tumor progression or intrahepatic distant metastasis (indication A), when a tumor was supplied by multiple arteries with different origins from the aorta and missing tumor enhancement was suspected (indication B), or when iodized oil distribution on immediate post-cTACE CACT images needed to be precisely compared with the pre-cTACE images (indication C). Fusion image quality, initial tumor response, time to local progression (TTLP) of index tumors, and time to progression (TTP) were evaluated. RESULTS: The fusion quality was satisfactory with a mean misregistration distance of 1.4 mm. For the 40 patients with indication A, the initial tumor responses at 3 months were nonviable, equivocal, and viable in 27 (67.5%), 4 (10.0%), and 9 (22.5%) index tumors, respectively. The median TTLP and TTP were 14.8 months and 4.5 months, respectively. For 10 patients with indication B, the median TTLP and TTP were 8.3 months and 2.6 months, respectively. Among the 6 patients with indication C, 2 patients were additionally treated at the same cTACE session after confirming incomplete iodized oil uptake on fusion imaging. CONCLUSIONS: Fusion CACT images are useful in patients with hepatocellular carcinoma undergoing repetitive cTACE.

Transarterial Chemoembolization for Hepatocellular Carcinoma: 2023 Expert Consensus-Based Practical Recommendations of the Korean Liver Cancer Association.

Transarterial chemoembolization (TACE) was introduced in 1977 with the administration of chemotherapeutic agent to gelatin sponge particles through the hepatic artery in patients with hepatocellular carcinoma (HCC) and was established as conventional TACE using Lipiodol in the 1980s. In the 2000s, drug-eluting beads were developed and applied clinically. Currently, TACE is a commonly used non-surgical treatment modality for patients with HCC who are unsuitable for curative treatment. Considering the vital role of TACE in the management of HCC, it is crucial to organize current knowledge and expert opinions regarding patient preparation, procedural techniques, and post-treatment care in TACE, which can enhance therapeutic efficacy and safety. A group of 12 experts in the fields of interventional radiology and hepatology, convened by the Research Committee of the Korean Liver Cancer Association (KLCA), has developed expert consensus-based practical recommendations in TACE. These recommendations have been endorsed by the Korean Society of Interventional Radiology and provide useful information and direction in performing TACE procedure as well as pre- and post-procedural patient care.

Transarterial chemoembolization for hepatocellular carcinoma: 2023 Expert consensus-based practical recommendations of the Korean Liver Cancer Association.

Transarterial chemoembolization (TACE) was introduced in 1977 with the administration of chemotherapeutic agent to gelatin sponge particles through the hepatic artery in patients with hepatocellular carcinoma (HCC) and was established as conventional TACE using Lipiodol in the 1980s. In the 2000s, drug-eluting beads were developed and applied clinically. Currently, TACE is a commonly used non-surgical treatment modality for patients with HCC who are unsuitable for curative treatment. Considering the vital role of TACE in the management of HCC, it is crucial to organize current knowledge and expert opinions regarding patient preparation, procedural techniques, and post-treatment care in TACE, which can enhance therapeutic efficacy and safety. A group of 12 experts in the fields of interventional radiology and hepatology, convened by the Research Committee of the Korean Liver Cancer Association (KLCA), has developed expert consensus-based practical recommendations in TACE. These recommendations have been endorsed by the Korean Society of Interventional Radiology and provide useful information and direction in performing TACE procedure as well as pre- and post- procedural patient care.

Transarterial chemoembolization for hepatocellular carcinoma: 2023 expert consensus-based practical recommendations of the Korean Liver Cancer Association.

Transarterial chemoembolization (TACE) was introduced in 1977 with the administration of chemotherapeutic agent to gelatin sponge particles through the hepatic artery in patients with hepatocellular carcinoma (HCC) and was established as conventional TACE using Lipiodol in the 1980s. In the 2000s, drug-eluting beads were developed and applied clinically. Currently, TACE is a commonly used non-surgical treatment modality for patients with HCC who are unsuitable for curative treatment. Considering the vital role of TACE in the management of HCC, it is crucial to organize current knowledge and expert opinions regarding patient preparation, procedural techniques, and post-treatment care in TACE, which can enhance therapeutic efficacy and safety. A group of 12 experts in the fields of interventional radiology and hepatology, convened by the Research Committee of the Korean Liver Cancer Association (KLCA), has developed expert consensus-based practical recommendations in TACE. These recommendations have been endorsed by the Korean Society of Interventional Radiology and provide useful information and direction in performing TACE procedure as well as pre- and post- procedural patient care.

Safety of Radioembolization via the Cystic Artery in Patients with Hepatocellular Carcinoma and Parasitized Arterial Supply.

PURPOSE: To evaluate the safety and effectiveness of radioembolization through the cystic artery supplying hepatocellular carcinoma (HCC) adjacent to the gallbladder. MATERIALS AND METHODS: This retrospective, single-center study included 24 patients who underwent radioembolization via the cystic artery between March 2017 and October 2022. The median tumor size was 8.3 cm (range, 3.4-20.4 cm). Twenty-two (92%) patients had Child-Pugh Class A disease, and 2 (8%) patients had Class B cirrhosis. Technical issues, adverse events, and tumor response were analyzed. RESULTS: Infusion of radioactive microspheres was performed from the main cystic artery (n = 6), the deep cystic artery (n = 9), and small feeders from the cystic artery (n = 9). The cystic artery supplied the primary index tumor in 21 patients. The median radiation activity delivered via the cystic artery was 0.19 GBq (range, 0.02-0.43 GBq). The median total radiation activity administered was 4.1 GBq (range, 0.9-10.8 GBq). There was no case of symptomatic cholecystitis requiring invasive intervention. One patient experienced abdominal pain during injection of radioactive microspheres via the cystic artery. Eleven (46%) patients received pain medication during or within 2 days of the procedure. Twelve (50%) patients had gallbladder wall thickening on a 1-month follow-up computed tomography scan. Based on follow-up imaging, 23 (96%) patients showed an objective response (complete or partial response) of the tumor supplied by the cystic artery. CONCLUSION: Radioembolization via the cystic artery may be safe in patients with HCC partially supplied by the cystic artery.

Prognostication and risk factor stratification for survival of patients with hepatocellular carcinoma: a nationwide big data analysis.

This study was conducted to identify risk factors affecting overall survival (OS) and provide prognostication for patients with hepatocellular carcinoma (HCC) using nationwide big data. Between January 2008 and December 2014, 10,573 adult patients with new HCC were registered in a nationwide database. Among them, 6830 patients without missing data were analyzed to construct a prognostication system. A validation cohort of 4580 patients was obtained from a tertiary hospital. All patients were assumed to have received the best treatment. A conditional inference tree analysis was performed to establish a prognostic system. The C-index and calibration plot for 5-year survival were estimated for validation. As a result, the tumor burden (TB) grade was the most significant factor in determining OS, and the cutoff was TB3 (TB1‒3 versus TB4). The patients were ultimately divided into 13 prognosis groups. The C-indexes were 0.714 and 0.737 (95% confidence interval, 0.733-0.742) in the nationwide (derivation) and hospital (validation) cohorts, respectively. In the calibration plot, the 5-year survival of the validation cohort largely matched the 45-degree line. In conclusion, the proposed prognostication system with a simple tree structure enabled the detailed stratification of patient prognosis and visualized the strata of risk factors affecting OS.