Background/Aims: Biliary tract cancer (BTC) is a rare malignancy with poor prognosis. We investigated genomic determinants of clinical benefit from gemcitabine, cisplatin, and nab-paclitaxel (GAP) versus gemcitabine and cisplatin (GC) in advanced BTC. Methods: Clinical and genomic data using TruSight Oncology 500 were analyzed from patients treated with GAP (N=198) or GC (N=89) as first-line therapy. Results: With a median follow-up of 33.0 months, GAP modestly improved progression-free survival (PFS) (hazard ratio [HR] 0.764; 95% confidence interval [CI] 0.591–0.989) without significant overall survival (OS) difference compared to GC. Genomic profiling revealed frequent alterations in TP53 (35.2%), KRAS (16.4%), SMAD4 (10.5%), and TNFRSF14 (10.5%), involving RTK/RAS (44.3%), TP53 (41.8%), and PI3K (20.2%) pathways. Single-gene mutations did not predict treatment benefit. However, pathway-level analysis identified PI3K pathway activation as significantly associated with inferior PFS (HR 2.148; 95% CI 1.478–3.124) and OS (HR 2.096; 95% CI 1.413–3.109) in patients receiving GAP, an effect not observed with GC. Importantly, GAP conferred clinical benefit only in patients without PI3K pathway activation, while no survival advantage was seen in those with such alterations (Pinteraction=0.023 for PFS, Pinteraction=0.003 for OS). Similar results were obtained in the independent validation cohort treated with GAP (N=103) or GC (N=64) for BTC. Conclusions Genomic profiling using next-generation sequencing identified PI3K pathway activation as key molecular determinant that differentiates patient outcomes between GAP and GC treatments in advanced BTC.

Background: and Purpose Treatments for neuromyelitis optica spectrum disorder (NMOSD) such as eculizumab, ravulizumab, satralizumab, and inebilizumab have significantly advanced relapse prevention, but they remain expensive. Rituximab is an off-label yet popular alternative that offers a cost-effective solution, but its real-world efficacy needs better quantification for guiding the application of newer approved NMOSD treatments (ANTs). This study aimed to determine real-world rituximab failure rates to anticipate the demand for ANTs and aid in resource allocation. Methods: We conducted a nationwide retrospective study involving 605 aquaporin-4-antibody-positive NMOSD patients from 22 centers in South Korea that assessed the efficacy and safety of rituximab over a median follow-up of 47 months. Results: The 605 patients treated with rituximab included 525 (87%) who received continuous therapy throughout the follow-up period (median=47 months, interquartile range=15–87 months). During this period, 117 patients (19%) experienced at least 1 relapse. Notably, 68 of these patients (11% of the total cohort) experienced multiple relapses or at least 1 severe relapse.Additionally, 2% of the patients discontinued rituximab due to adverse events, which included severe infusion reactions, neutropenia, and infections. Conclusions This study has confirmed the efficacy of rituximab in treating NMOSD, as evidenced by an 87% continuation rate among patients over a 4-year follow-up period. Nevertheless, the occurrence of at least one relapse in 19% of the cohort, including 11% who experienced multiple or severe relapses, and a 2% discontinuation rate due to adverse events highlight the urgent need for alternative therapeutic options.

Purpose: To assess the effectiveness of the prostate health index (PHI) in patients with no index lesions on multiparametric magnetic resonance imaging (mpMRI) or with negative findings on past prostate biopsy if there was an index lesion on mpMRI. Materials and Methods: Patients without an index lesion on MRI or with a negative result on combined biopsy for index lesions were assessed. Patients who underwent transperineal mapping biopsy among those suspected of having prostate cancer (PCa) due to persistently elevated prostate-specific antigen (PSA) levels were analyzed. Results: Of the 291 patients, 82 (28.2%) were diagnosed with PCa. Sixty-five of 291 patients had negative finding in previous combined biopsy. In total, 226 patients did not have any index lesions. The mean age of the PCa group was 64.33±8.88 years and that of the non-cancer group was 59.88±10.26 years (p<0.001). The PHI was 46.75±28.22 in the PCa group and 37.74±17.37 in the noncancer group (p=0.001), and the prostate volume was 41.52±15.77 mL in the PCa group and 50.78±23.97 mL in the non-cancer group (p=0.001). In multivariate analysis, age (odds ratio [OR] 1.096, p<0.001), PHI (OR 1.021, p=0.005), and prostate volume (OR 0.954, p<0.001) were identified as significant factors for PCa detection. The optimal cutoff value of the PHI for PCa detection was 44.6 and the PHI density (PHID) was 0.88. Conclusions In patients with elevated PSA levels but no index lesions on mpMRI or negative biopsy findings, PHI and PHID demonstrated significant potential for improving PCa detection.

Purpose: Prostate cancer ranks as the second most common cancer in men globally, representing a significant cause of cancer-related mortality. Metastasis, the spread of cancer cells from the primary site to distant organs, remains a major challenge in managing prostate cancer. Pyruvate dehydrogenase kinase 4 (PDK4) is implicated in the regulation of aerobic glycolysis, emerging as a potential player in various cancers. However, its role in prostate cancer remains unclear. This study aims to analyze PDK4 expression in prostate cancer cells and human samples, and to explore the gene's clinical significance. Materials and Methods: PDK4 expression was detected in cell lines and human tissue samples. Migration ability was analyzed using Matrigel-coated invasion chambers. Human samples were obtained from the Kyungpook National University Chilgok Hospital. Results: PDK4 expression was elevated in prostate cancer cell lines compared to normal prostate cells, with particularly high levels in DU145 and LnCap cell lines. PDK4 knockdown in these cell lines suppressed their invasion ability, indicating a potential role of PDK4 in prostate cancer metastasis. Furthermore, our results revealed alterations in epithelial-mesenchymal transition markers and downstream signaling molecules following PDK4 suppression, suggesting its involvement in the modulation of invasion-related pathways. Furthermore, PDK4 expression was increased in prostate cancer tissues, especially in castration-resistant prostate cancer, compared to normal prostate tissues, with PSA and PDK4 expression showing a significantly positive correlation. Conclusions PDK4 expression in prostate cancer is associated with tumor invasion and castration status. Further validation is needed to demonstrate its effectiveness as a therapeutic target.

Background: and Purpose Treatments for neuromyelitis optica spectrum disorder (NMOSD) such as eculizumab, ravulizumab, satralizumab, and inebilizumab have significantly advanced relapse prevention, but they remain expensive. Rituximab is an off-label yet popular alternative that offers a cost-effective solution, but its real-world efficacy needs better quantification for guiding the application of newer approved NMOSD treatments (ANTs). This study aimed to determine real-world rituximab failure rates to anticipate the demand for ANTs and aid in resource allocation. Methods: We conducted a nationwide retrospective study involving 605 aquaporin-4-antibody-positive NMOSD patients from 22 centers in South Korea that assessed the efficacy and safety of rituximab over a median follow-up of 47 months. Results: The 605 patients treated with rituximab included 525 (87%) who received continuous therapy throughout the follow-up period (median=47 months, interquartile range=15–87 months). During this period, 117 patients (19%) experienced at least 1 relapse. Notably, 68 of these patients (11% of the total cohort) experienced multiple relapses or at least 1 severe relapse.Additionally, 2% of the patients discontinued rituximab due to adverse events, which included severe infusion reactions, neutropenia, and infections. Conclusions This study has confirmed the efficacy of rituximab in treating NMOSD, as evidenced by an 87% continuation rate among patients over a 4-year follow-up period. Nevertheless, the occurrence of at least one relapse in 19% of the cohort, including 11% who experienced multiple or severe relapses, and a 2% discontinuation rate due to adverse events highlight the urgent need for alternative therapeutic options.

Background: and Purpose Treatments for neuromyelitis optica spectrum disorder (NMOSD) such as eculizumab, ravulizumab, satralizumab, and inebilizumab have significantly advanced relapse prevention, but they remain expensive. Rituximab is an off-label yet popular alternative that offers a cost-effective solution, but its real-world efficacy needs better quantification for guiding the application of newer approved NMOSD treatments (ANTs). This study aimed to determine real-world rituximab failure rates to anticipate the demand for ANTs and aid in resource allocation. Methods: We conducted a nationwide retrospective study involving 605 aquaporin-4-antibody-positive NMOSD patients from 22 centers in South Korea that assessed the efficacy and safety of rituximab over a median follow-up of 47 months. Results: The 605 patients treated with rituximab included 525 (87%) who received continuous therapy throughout the follow-up period (median=47 months, interquartile range=15–87 months). During this period, 117 patients (19%) experienced at least 1 relapse. Notably, 68 of these patients (11% of the total cohort) experienced multiple relapses or at least 1 severe relapse.Additionally, 2% of the patients discontinued rituximab due to adverse events, which included severe infusion reactions, neutropenia, and infections. Conclusions This study has confirmed the efficacy of rituximab in treating NMOSD, as evidenced by an 87% continuation rate among patients over a 4-year follow-up period. Nevertheless, the occurrence of at least one relapse in 19% of the cohort, including 11% who experienced multiple or severe relapses, and a 2% discontinuation rate due to adverse events highlight the urgent need for alternative therapeutic options.

Purpose: Esophagojejunostomy leakage (EJL) remains one of the most critical complications following total gastrectomy for gastric cancer. This study aimed to evaluate the evolving therapeutic approaches and clinical outcomes of EJL using data from a large-scale multicenter retrospective cohort. Methods: Among 6,577 patients who underwent total gastrectomy or proximal gastrectomy with double tract reconstruction at nine institutions from 2003 to 2024, 196 (3.0%) developed EJL. Of these, 162 patients with comprehensive clinical data were included in the final analysis. The study examined treatment modalities, changes in management over time, patient characteristics, surgical variables, and clinical outcomes. Four groups were defined according to treatment approach: conservative, endoscopic, reoperation, and multimodal (combined) therapy. Results: Endoscopic therapy was first introduced in 2011 and has progressively supplanted reoperation, now comprising 32.5% of cases. The average time to EJL diagnosis was 8.4 days after surgery. Overall in-hospital mortality was 6.1% (10/162). When conservative management was excluded, endoscopic treatment demonstrated the highest rate of therapeutic success (94.3%, p = 0.004). Both the duration until diet resumption and length of hospital stay were notably reduced in the endoscopic and conservative groups compared with reoperation and multimodal therapy (p < 0.001). Moreover, although the highest post-leakage hospitalization costs were observed with multimodal treatment (p < 0.001), overall hospitalization expenses were significantly lower for patients managed conservatively or with endoscopic intervention (p < 0.001). Conclusion Over the past two decades, management of EJL has shifted toward endoscopic approaches. Endoscopic therapies yield superior clinical outcomes and should be considered a primary option for appropriate candidates.

Background: In patients with metastatic renal cell carcinoma (mRCC), sites of metastatic involvement have been reported to be associated with a difference in survival. However, the frequency and survival according to different sites of metastases in Korean patients with mRCC remain unclear. Therefore, this study aimed to assess the frequency of metastatic site involvement and the association between sites of metastatic involvement and survival in Korean patients with mRCC. Methods: This retrospective study used the multicenter cohort of the Korean Renal Cancer Study Group mRCC database to identify patients who started targeted therapy between December 2005 and March 2018. Data on the frequency of metastatic organ involvement at the time of mRCC diagnosis and oncologic outcomes according to different sites of metastasis were analyzed. Results: A total of 1,761 patients were eligible for analysis. Of the 1,761 patients, 1,564 (88.8%) had clear cell RCC, and 1,040 (59.1%) had synchronous metastasis. The median number of metastasis sites was 2 (interquartile range [IQR], 1–6). The median age at the initiation of systemic therapy was 60 years (IQR, 29–88), 1,380 (78.4%) were men, and 1,341 (76.1%) underwent nephrectomy. Based on the International Metastatic Renal Cell Carcinoma Database Consortium model, patients were stratified into favorable-, intermediate-, and poor-risk groups with 359 (20.4%), 1,092 (62.0%), and 310 (17.6%) patients, respectively. The lung (70.9%), lymph nodes (37.9%), bone (30.7%), liver (12.7%), adrenal gland (9.8%), and brain (8.2%) were the most common sites of metastasis, followed by the pancreas, pleura, peritoneum, spleen, thyroid, and bowel. Among the most common sites of metastasis (> 5%), the median cancer-specific survival (CSS) ranged from 13.9 (liver) to 29.1 months (lung). An association was observed between liver, bone, and pleural metastases and the shortest median CSS (< 19 months). Conclusion In Korean patients with mRCC, metastases to the lung, lymph nodes, bone, liver, adrenal gland, and brain were more frequent than those to other organs. Metastases to the liver, bone, and pleura were associated with poor CSS. The findings of this study may be valuable for patient counseling and guiding future study designs.

Background: In patients with metastatic renal cell carcinoma (mRCC), sites of metastatic involvement have been reported to be associated with a difference in survival. However, the frequency and survival according to different sites of metastases in Korean patients with mRCC remain unclear. Therefore, this study aimed to assess the frequency of metastatic site involvement and the association between sites of metastatic involvement and survival in Korean patients with mRCC. Methods: This retrospective study used the multicenter cohort of the Korean Renal Cancer Study Group mRCC database to identify patients who started targeted therapy between December 2005 and March 2018. Data on the frequency of metastatic organ involvement at the time of mRCC diagnosis and oncologic outcomes according to different sites of metastasis were analyzed. Results: A total of 1,761 patients were eligible for analysis. Of the 1,761 patients, 1,564 (88.8%) had clear cell RCC, and 1,040 (59.1%) had synchronous metastasis. The median number of metastasis sites was 2 (interquartile range [IQR], 1–6). The median age at the initiation of systemic therapy was 60 years (IQR, 29–88), 1,380 (78.4%) were men, and 1,341 (76.1%) underwent nephrectomy. Based on the International Metastatic Renal Cell Carcinoma Database Consortium model, patients were stratified into favorable-, intermediate-, and poor-risk groups with 359 (20.4%), 1,092 (62.0%), and 310 (17.6%) patients, respectively. The lung (70.9%), lymph nodes (37.9%), bone (30.7%), liver (12.7%), adrenal gland (9.8%), and brain (8.2%) were the most common sites of metastasis, followed by the pancreas, pleura, peritoneum, spleen, thyroid, and bowel. Among the most common sites of metastasis (> 5%), the median cancer-specific survival (CSS) ranged from 13.9 (liver) to 29.1 months (lung). An association was observed between liver, bone, and pleural metastases and the shortest median CSS (< 19 months). Conclusion In Korean patients with mRCC, metastases to the lung, lymph nodes, bone, liver, adrenal gland, and brain were more frequent than those to other organs. Metastases to the liver, bone, and pleura were associated with poor CSS. The findings of this study may be valuable for patient counseling and guiding future study designs.

Purpose: Oligoprogressive lesions are observed in a subset of patients who progress to castration-resistant prostate cancer (CRPC), while other lesions remain controlled by systemic therapy. This study evaluates the impact of progression-directed therapy (PDT) on these oligoprogressive lesions. Materials and Methods: This retrospective study included 40 patients diagnosed with oligoprogressive CRPC. PDT was performed for treating all progressive sites using radiotherapy. Fifteen patients received PDT using radiotherapy for all progressive sites (PDT group) while 25 had additional first-line systemic treatments (non-PDT group). In PDT group, 7 patients underwent PDT and unchanged systemic therapy (PDT-A group) and 8 patients underwent PDT with additional new line of systemic therapy on CRPC (PDT-B group). The Kaplan–Meier method was used to assess treatment outcomes. Results: The prostate specific antigen (PSA) nadir was significantly lower in PDT group compare to non-PDT group (p=0.007). A 50% PSA decline and complete PSA decline were observed in 13 patients (86.7%) and 10 patients (66.7%) of PDT group and in 18 patients (72.0%) and 11 patients (44.0%) of non-PDT group, respectively. The PSA-progression free survival of PDT-B group was significantly longer than non-PDT group. The median time to failure of first-line systemic therapy on CRPC was 30.2 months in patients in PDT group and 14.9 months in non-PDT group (p=0.014). PDT-B group showed a significantly longer time to progression than non-PDT group (p=0.025). Minimal PDT-related adverse events were observed. Conclusions PDT can delay progression of disease and enhance treatment efficacy with acceptable tolerability in oligoprogressive CRPC.