Cancer Research and Treatment

Malignant Hepatocellular Neoplasm, not Otherwise Specified, Displays Poorer Chemoresponsiveness and Postoperative Prognosis than Hepatoblastoma: In Hye Song, Sujin Gang, Hee Mang Yoon, Pyeong Hwa Kim, Bokyung Ahn, Jihun Kim, Deok Hoon Kim, Jung-Man Namgoong, Kyung-Nam Koh; Received February 1, 2025 Accepted April 27, 2025 Published online May 12, 2025; DOI: https://doi.org/10.4143/crt.2025.117 [Accepted]

Abstract PDF Supplementary Material: Purpose
Malignant hepatocellular neoplasm, not otherwise specified (HCN-NOS) is a provisional diagnostic entity, characterised by intermediate or a combination of hepatoblastoma and paediatric hepatocellular carcinoma (p-HCC) features. We compared the characteristics of HCN-NOS with hepatoblastoma and p-HCC.
Materials and Methods
The records of 148 paediatric patients diagnosed with hepatocellular malignancy after resection were retrieved from the institutional database. Clinical parameters and histopathology slides were reviewed to re-establish each patient’s diagnosis. Molecular analyses were conducted in 37 patients.
Results
Patients were profiled as 21 (14.2%) with HCN-NOS, 109 (73.6%) with hepatoblastoma, and 18 (12.2%) with p-HCC. The median age was 8.6 years in HCN-NOS, 1.2 years in hepatoblastoma, and 7.9 years in p-HCC. Background liver disease was frequently observed in p-HCC (11/18, 61%) but infrequent in HCN-NOS (4/21, 19%) and hepatoblastoma (4/109, 3.7%). HCN-NOS presented with a more advanced PRETEXT stage (p=0.012), metastasis (p<0.001), and lymphovascular invasion (p<0.001) than hepatoblastoma and p-HCC. Patients with HCN-NOS received longer cycles of preoperative chemotherapy; however, they reported a lower decrease in serum alpha-fetoprotein and tumour size than hepatoblastoma (p=0.043, 0.004, 0.044, respectively). HCN-NOS was an independent poor prognostic factor for event-free survival (hazard ratio, 4.968; 95% confidence interval, 2.004–12.32; p<0.001).
Conclusion
The possibility of HCN-NOS should be considered in paediatric patients with liver cancer, especially those ≥ 5 years old with no background liver disease. Because HCN-NOS exhibits poor chemo-responsiveness and unfavourable postoperative prognosis, liver transplantation should be strongly considered.

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Comparative Study of Mastectomy Using Conventional Techniques, Multiport and Single-Port Robotic Surgical Systems: Jeea Lee, Jieon Go, Suk Jun Lee, Yonghan Kwon, Nam Hee Kim, Jee Ye Kim, Hyung Seok Park; Received January 31, 2025 Accepted May 6, 2025 Published online May 7, 2025; DOI: https://doi.org/10.4143/crt.2025.115 [Accepted]

Abstract PDF: Purpose
Oncologic and surgical outcomes of robot-assisted nipple-sparing mastectomy (RNSM) compared to conventional NSM (CNSM) is under investigation. This study compared the clinical outcomes of recurrence-free survival and postoperative complication after RNSM and CNSM.
Materials and Methods
We retrospectively reviewed data of 401 patients who underwent da Vinci Si/Xi/SP-assisted RNSM or CNSM with immediate reconstruction between November 2016 and November 2020 at a single institute. Oncological outcomes were collected until March 2022. Primary endpoints were long-term outcomes, such as local recurrence, distant metastasis, disease-free survival, overall survival, and postoperative complications, while secondary endpoints were pathology results, and oncological outcomes.
Results
Patients underwent RNSM (n=162) or CNSM (n=239). Of RNSM cases, 9 (5.6%) were performed using the da Vinci Si System, 96 (59.3%) using the da Vinci Xi System, and 57 (35.2%) using the da Vinci SP System. No significant difference in recurrence-free survival was found between the RNSM and CNSM group, and both groups had a median follow-up of 37 months. The recurrence rate in RNSM patients after a median follow-up of 24.5 months was 3.8%, compared with 5.9% in CNSM patients after a median follow-up of 42 months. No difference in recurrence was seen among RNSM patients with respect to surgical systems (multiport vs. SP, p =0.136). In addition, grade III postoperative complication rate was lower in patients with RNSM than in those with CNSM. Transfusion was only applied in 6.2% of patients.
Conclusion
Robot-assisted surgical systems can be safely used to perform NSM in patients with early breast cancer.

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Neoadjuvant Sintilimab Combined with Gemcitabine and Cisplatin (GP) for Muscle-Invasive Bladder Cancer (MIBC) Patients Followed by Selective Bladder Sparing Surgery: A Phase 2 Trial: Zhou Tong, Guanghou Fu, Feng Zhou, Xiaoyan Liu, Xing Xue, Hangyu Zhang, Yimin Wang, Xudong Zhu, Yang Gao, Lulu Liu, Xuanwen Bao, Yi Zheng, Weijia Fang, Peng Zhao, Baiye Jin; Received February 24, 2025 Accepted April 22, 2025 Published online April 28, 2025; DOI: https://doi.org/10.4143/crt.2025.214 [Accepted]

Abstract PDF: Purpose
To evaluate the safety and efficacy of GP regimen in combination with immune checkpoint inhibitor sintilimab as neoadjuvant therapy for MIBC patients and the feasibility of the following selective bladder sparing surgery.
Materials and Methods
Patients with histopathological confirmed urothelial carcinoma without distant metastases (T2-4a, N≤1, M0, AJCC 8th) and with adequate organ function will be enrolled. The therapeutic regimen was sintilimab 200 mg once on day 8, gemcitabine 1,000 mg/m2 and cisplatin 35 mg/m2 once on days 1 and 8, every 21 days for four cycles. The primary endpoint was pathologic complete response (pCR, pT0N0) rate. The secondary end points were ypT<2 rate, R0 resection rate, event free survival and safety.
Results
From May 4, 2020, to May 20, 2023, 55 patients were enrolled. Forty-six patients were evaluated for efficacy. Among the 42 patients who underwent surgery, 16 patients (38.0%) achieved pCR. 33 patients (78.6%) achieved pT<2. With a median follow-up of 15.7 months, the 1-year EFS was 91.3%. Notwithstanding the poor pathological baseline characteristic of a high T3-T4a proportion (39.1%), a promising bladder preservation (including 22 patients TURBT, 5 patients partial cystectomy and 4 surveillances) rate was achieved (67.4%). The most common grade ≥3 TRAEs was neutropenia (n=15, 27.3%), which was related to chemotherapy. There were no grade 3 immune-related AEs.
Conclusion
Neoadjuvant GP plus sintilimab is a promising regimen for MIBC patients, with relatively high pT<2 rate and triggering the emerging roles for the MDT decision-making for bladder sparing surgery.

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Safety and Effectiveness of Eribulin in Patients with Advanced or Metastatic Breast Cancer Previously Treated with Anthracyclines and Taxanes in Real-World Clinical Practice: A 6-Year Post-Marketing Surveillance Study in South Korea: Yee Soo Chae, Kyung A Kwon, Moon Hee Lee, Mi Sun Ahn, Kyung-Hun Lee, Su-Jin Koh, Joohyuk Sohn, Keon Uk Park, Min Young Kim, Youngji Pyo, Bo Young Kim, Kyung Hae Jung; Received November 27, 2024 Accepted April 26, 2025 Published online April 28, 2025; DOI: https://doi.org/10.4143/crt.2024.1142 [Accepted]

Abstract PDF: Purpose
This 6-year post-marketing surveillance (PMS) study was conducted in South Korea to evaluate the real-world safety and effectiveness of eribulin in patients with advanced or metastatic breast cancer previously treated with anthracyclines and taxanes.
Materials and Methods
During the study period (17 August 2012 to 16 August 2018), case-report files (CRFs) of patients receiving eribulin were collected. The main study endpoint was to assess the safety of eribulin. Evaluation of the effectiveness of eribulin was an exploratory endpoint. Patients were followed for 1 year after eribulin initiation.
Results
CRFs were collected from 64 investigators at 64 sites for 1079 patients. The safety analysis set (SAS) included 1,001 eribulin recipients; effectiveness was assessed in 244 patients. In the SAS, patients were predominantly female (99.6%), with a median age of 53.0 years, and diagnosed with metastatic breast cancer (92.0%). Eribulin was administered as a median 4th line chemotherapy. A total of 2,124 TEAEs were reported in 661 patients (66.0%). Neutropenia was the most common TEAE (32.5% of patients), occurring at a median of 9–11 days from initial eribulin administration. Overall response and disease control rates were 31.7% and 95.6%, respectively, and the median duration of eribulin use (time to treatment failure) was 3.0 months.
Conclusion
This large real-world PMS analysis in patients with advanced or metastatic breast cancer demonstrated the effectiveness of eribulin and found no new safety concerns relative to safety information from prior clinical and real-world studies, and approvals in South Korea and other countries.

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Adjuvant Chemotherapy in Breast Cancer After Neoadjuvant Therapy: Essential or Optional?: Di Zhang, Luo Yang, Yuan Zheng, Qi Zhou; Received December 31, 2024 Accepted April 20, 2025 Published online April 24, 2025; DOI: https://doi.org/10.4143/crt.2024.1254 [Accepted]

Abstract PDF: Purpose
This study aimed to evaluate the impact of postoperative adjuvant chemotherapy (AC) on survival outcomes in breast cancer (BC) patients who have already undergone neoadjuvant chemotherapy (NAC) followed by surgery.
Materials and Methods
Data from a population-based cohort (2010-2020) were analyzed for BC patients treated with NAC and surgery. Univariate and multivariate Cox regression identified prognostic factors for overall survival (OS), and a nomogram was developed and validated. Personalized scores from the nomogram were used for risk stratification to assess the effect of postoperative AC.
Results
A total of 15,921 BC patients were analyzed, with 11,144 in the training cohort and 4,777 in the validation cohort. The key prognostic indicators for OS included age, race, marital status, histological grade, breast cancer subtype, T stage, N stage, type of surgery, and response to NAC (all p<0.05). The nomogram effectively predicted individualized OS rates and stratified patients into various risk categories. Postoperative AC was found to significantly enhance OS in the high-risk subgroup (p=0.011 in the training cohort, p=0.012 in the overall population). However, for the low-risk subgroup, there was no significant survival benefit from postoperative AC (p=0.130 for the training cohort, p=0.588 for the overall population), suggesting that some patients might safely forgo unnecessary postoperative AC.
Conclusion
This study efficiently differentiates between varying levels of risk, enabling clinicians to identify patients unlikely to benefit from postoperative AC and thus reduce the likelihood of overtreatment.

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IARC Group 1 Pharmaceuticals and Associated Cancer Risks: A Nationwide Population-Based Cohort Study in Korea: Woojin Lim, Na Rae Lee, Ho Gyun Shin, Su-Yeon Yu, Sue K. Park; Received December 12, 2024 Accepted April 23, 2025 Published online April 24, 2025; DOI: https://doi.org/10.4143/crt.2024.1201 [Accepted]

Abstract PDF: Purpose
The aim of this study is to summarize cancer risk among patients with clinical indications of immunosuppressive and antineoplastic drugs in Korea, which are pharmaceuticals defined as group 1 by International Agency for Research on Cancer (IARC).
Materials and Methods
We conducted a nationwide population-based retrospective cohort study using the Korean National Health Insurance Service (NHIS) claims data from 2002 to 2018. Patients with clinical indications for group 1 pharmaceuticals from 2002 to 2017 were selected as baseline population, and followed up until 2018. Cox proportional hazards regression model was used to analyze the risk of cancer and dose-response relationship between group 1 pharmaceuticals and cancer.
Results
Azathioprine use increased the risk of skin and hematologic cancer (HR 4.63, 95% CI 2.91-7.39; HR 3.15, 95% CI 2.41-4.13). Cyclosporine use increased the risk of skin and hematologic cancer (HR 2.30, 95% CI 1.79-2.95; HR 2.96, 95% CI 2.59-3.40). Cyclophosphamide use increased the risk of bladder and hematologic cancer (HR 2.69, 95% CI 1.92-3.78; HR 3.83, 95% CI 3.20-4.59). Chlorambucil use increased the risk of hematologic cancer (HR 3.51, 95% CI 2.53-4.87) and melphalan use increased the risk of hematologic cancer (HR 16.31, 95% CI 13.41-19.85). Methoxsalen use increased the risk of skin cancer (HR 2.32, 95% CI 1.36-3.95).
Conclusion
Group 1 pharmaceuticals were associated with increased risk of cancer. The results are expected to help establish alternative clinical strategies and policies for patients with clinical indications of group 1 pharmaceuticals, by continuous risk analysis and discussions on the surveillance systems.

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Differences in Responses to Neoadjuvant Anti-HER2 Therapy between HER2 2+ISH+ and HER2 3+ in HER2-Positive Breast Cancer: Lingjun Ma, Ran Zheng, Lingyun Xu, Ying Zhu, Hong Yin, Xiaoqing Zhang, Rong Deng, Jue Wang, Xiaoming Zha; Received December 12, 2024 Accepted April 18, 2025 Published online April 21, 2025; DOI: https://doi.org/10.4143/crt.2024.1200 [Accepted]

Abstract PDF: Purpose
Dual anti-HER2 drugs has become the standard regimen for neoadjuvant systematic treatment (NST) to HER2-positive breast cancer patients. However, the efficacy varies greatly among patients with different HER2 protein expression levels
Materials and Methods
A total of 575 HER2-positive breast cancer patients from multiple centers throughout China from 2013 to 2022 were retrospectively analyzed. We compared clinicopathological features in different HER2 IHC classes (HER2 2+ISH+ or HER2 3+), and their difference in response to NST and survival with single or dual anti-HER2 drugs. Drug sensitivity assays were used to evaluate different efficacy of anti-HER2 drugs in vitro.
Results
Compared to HER2 3+ subgroup, the HER2 2+ISH+ group had a higher proportion of HR+ status (48.7% vs. 76.1%; p < 0.001), more HER2 protein loss after NST, lower pCR rate (46.07% vs. 16.24%; p < 0.001), and tended to have worse DFS. In HER2 2+ISH+ patients, treated with pertuzumab and trastuzumab in combination had no significant improvement in pCR (19.12% vs. 12.24%; p=0.287) and DFS (p=0.908) than using alone. Drug sensitivity assay showed poor efficacy with dual anti-HER2 drugs in HER2 2+ISH+ cell lines, however, T-Dxd drugs had a satisfactory effect.
Conclusion
Owing to the differences in clinicopathological features and treatment efficacy, we considered the HER2 2+ISH+ group to be a distinct subtype and defined it as the HER2-moderate-positive (HER2-mod) subgroup. In this subgroup, dual anti-HER2 drugs did not exert significant improvement in pCR and DFS. Therefore, treatment optimization is warranted, with ADC drugs as potential options.

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RASSF4 Suppresses Gastric Tumor Growth through Activation of Chk2-p53 Signaling Axis: Soon-Ki Park, Min-Ju Kang, Kyung-Phil Ko, Sung-Gil Chi; Received February 5, 2025 Accepted April 17, 2025 Published online April 18, 2025; DOI: https://doi.org/10.4143/crt.2025.135 [Accepted]

Abstract PDF: Purpose
Ras association domain family 4 (RASSF4) is a putative tumor suppressor that is frequently inactivated in multiple human cancers. However, its candidacy as a suppressor in gastric tumorigenesis remains undefined. To understand the role for RASSF4 in gastric tumorigenesis, we investigated its expression status in cancer cell lines and tissues and regulatory role in tumor growth.
Materials and Method
RASSF4 expression was analyzed in 13 cancer cell lines and 20 carcinoma tissues using PCR and immunoblot assays. RASSF4 effect on cell proliferation and apoptosis was examined by flow cytometry, colony formation, and [³H]thymidine incorporation assays and its regulation of p53 was determined using cycloheximide chase, promoter reporter, and immunoprecipitation assays. Mouse xenograft assay was performed to verify RASSF4 effect on tumor growth and therapeutic response.
Results
RASSF4 expression is epigenetically inactivated in 8 of 13 (61.5%) cancer cell lines and 15 of 20 (75%) primary carcinomas. RASSF4 suppresses cell proliferation by inducing a G2/M cell-cycle arrest and enhances apoptotic response to therapeutic drugs. RASSF4 is induced in response to genotoxic agents to facilitate stress-induced apoptosis in a highly p53-dependent fashion. Mechanistically, RASSF4 stabilizes p53 through Chk2 activation and its apoptotic function is profoundly impaired by depletion of either p53 or Chk2. RASSF4 attenuates xenograft tumor growth and enhances tumor response to 5-FU. Clinically, RASSF4 expression correlates strongly with the overall survival of gastric cancer patients.
Conclusion
RASSF4 suppresses gastric tumor growth through the activation of the Chk2-p53 axis, illuminating the mechanistic consequence of its inactivation in gastric tumorigenesis.

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Deciphering the Risk of Developing Lung Cancer After the Diagnosis of Gastric Cancer with Genetic Evidence: A European and East Asian Populations-Based Mendelian Randomization Analysis: Jiansheng Chen, Aiming Zeng, Yunzhe Yu, Sida Sun, Liqun Liao, Siwei Huang, Zhongshan Yang, Junfeng Zhou, Weijie Wu; Received September 6, 2024 Accepted April 16, 2025 Published online April 18, 2025; DOI: https://doi.org/10.4143/crt.2024.875 [Accepted]

Abstract PDF Supplementary Material: Purpose
Lung cancer is frequently observed as a second primary malignancy following gastric cancer, yet the genetic causality between them remains uncertain. This study aims to evaluate the causal relationship between gastric and lung cancers using Mendelian randomization (MR) analysis.
Materials and Methods
Single nucleotide polymorphisms associated with gastric and lung cancers were selected from Genome-Wide Association Study in East Asian and European populations as instrumental variables. The causal effects between gastric and lung cancers were evaluated using univariable and multivariable MR analysis, with the inverse variance weighted (IVW) method serving as the primary criterion. Heterogeneity and sensitivity analyses were performed to ensure the robustness of the findings.
Results
Univariable MR analysis demonstrated that genetic susceptibility to gastric cancer in the European population was significantly associated with an increased risk of lung cancer (IVW: OR:1.285, 95%CI:1.072-1.541, p=6.83E-03), which was consistently validated in the East Asian population (IVW:OR:1.356, 95% CI:1.114-1.651, p=2.40E-03). Multivariable MR analysis further indicated that the significant positive causal relationship between gastric cancer and lung cancer persisted in both populations after adjusting for confounding factors (all p<0.05). Conversely, no significant causal relationship was observed for the risk of developing gastric cancer following the diagnosis of lung cancer diagnosis in either population (p>0.05).
Conclusion
This study confirms that genetic susceptibility to gastric cancer increases the risk of lung cancer. This finding provides a theoretical basis for exploring the underlying biological mechanisms and suggests that enhancing lung cancer screening in patients with gastric cancer may be necessary to improve patient prognosis.

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Survival Rates of Patients with Gastric Cancer According to Age and Sex: A Large-Scale Study Using Data from 14,739 Patients: Yonghoon Choi, Nayoung Kim, Ji Hyun Kim, Hyeong Ho Jo, Hyeon Jeong Oh, Hye Seung Lee, Yu Kyung Jun, Hyuk Yoon, Cheol Min Shin, Young Soo Park, Dong Ho Lee, So Hyun Kang, Young Suk Park, Sang-Hoon Ahn, Yun-Suhk Suh, Do Joong Park, Hyung Ho Kim, Ji-Won Kim, Jin Won Kim, Keun-Wook Lee, Won Chang, Yoon Jin Lee, Kyoung Ho Lee, Young Hoon Kim; Received February 9, 2025 Accepted April 15, 2025 Published online April 16, 2025; DOI: https://doi.org/10.4143/crt.2025.149 [Accepted]

Abstract PDF: Purpose
The male predominance in the incidence of gastric cancer (GC) is established; however, sex differences in the prognosis of GC remain controversial. As such, this study analyzed the prognosis of patients with GC based on age and sex.
Materials and Methods
Data from 14,739 patients diagnosed with GC at Seoul National University Bundang Hospital between 2003 and 2023 were analyzed. Baseline characteristics, histological types of GC, overall and GC-specific survival rates (age and stage stratification), and associated risk factors were analyzed.
Results
Females were significantly younger (p < 0.001) and exhibited more gastric body cancers (p < 0.001) and tumors with diffuse-type or poorly differentiated histology (p < 0.001) than males. Females exhibited an advantage over males in terms of overall survival (p=0.004), but not in GC-specific survival. However, age stratification revealed significant sex differences, that females < 50 years of age exhibited survival disadvantages (p < 0.001); however, this trend was reversed with age, and females > 60 years exhibited survival advantages (p < 0.001) for both overall and GC-specific survival. This may be explained by the lower ratio of diffuse-type GC as females age. Furthermore, in the analysis according to stage, females with stage IV disease exhibited significant survival disadvantages, with significantly younger age and a higher proportion of diffuse-type GC which exhibits aggressive features, resulting in poorer survival than in males.
Conclusion
Age and stage stratification revealed significant differences in survival between the sexes, which can be helpful for public health strategies.

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The Impact of Obesity on Treatment Outcomes in Patients with Hormone Receptor-Positive HER2-Negative Metastatic Breast Cancer Receiving CDK 4/6 Inhibitors: Yoo Bin Jung, Hee Kyung Ahn, Hyun-Young Shin, Ji Hyung Hong, Chai Hong Rim; Received January 25, 2025 Accepted April 13, 2025 Published online April 15, 2025; DOI: https://doi.org/10.4143/crt.2025.110 [Accepted]

Abstract PDF: Purpose
Guidelines from the aromatase inhibitor era for early breast cancer (EBC) treatment recommend maintaining a body mass index (BMI) below 25. In the current era of CDK 4/6 inhibitors, now standard in metastatic breast cancer (MBC), limited data exist on treatment outcomes in obese patients. This study investigates how adiposity affects the treatment outcome of CDK 4/6 inhibitors in patients with hormone receptor (HR)-positive, HER2-negative MBC.
Materials and Methods
We searched PubMed, MEDLINE, and Embase databases, assessing efficacy outcomes such as progression-free survival (PFS) based on obesity markers, including BMI and visceral adipose tissue (VAT) index.
Results
Twelve studies were reviewed, with seven studies and 1,812 patients included in a pooled meta-analysis. Among patients with BMI ≥25, modest improvement in PFS was observed, with a pooled hazard ratio (HR) of 0.944 (95% CI, 0.909-0.980; p = 0.003). Besides, add-on analysis using VAT to define obesity revealed a notable PFS improvement, with a pooled HR of 0.452 (95% CI, 0.256-0.798; p = 0.006).
Conclusion
While BMI-defined obesity showed slight PFS improvement with CDK 4/6 inhibitors and endocrine therapy, using VAT to define obesity revealed significant PFS gains. This highlights the need for further research on biomarker to clarify the role of adiposity in MBC, which may differ from its impact in EBC.

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Spatial Transcriptomic Landscape of Brain Metastases from Triple-Negative Breast Cancer: Comparison of Primary Tumor and Brain Metastases Using Spatial Analysis: Jihwan Yoo, Inho Park, Hyun Jung Kim, Hun Ho Park, Sora Lee, Jee Hung Kim, Yoon Jin Cha; Received January 8, 2025 Accepted April 13, 2025 Published online April 15, 2025; DOI: https://doi.org/10.4143/crt.2025.033 [Accepted]

Abstract PDF: Purpose
Triple-negative breast cancer (TNBC) is a particularly aggressive subtype of breast cancer, with approximately 30% of patients eventually developing brain metastases (BM), which result in poor outcomes. An understanding of the tumor microenvironment (TME) at both primary and metastatic sites offers insights into the mechanisms underlying BM and potential therapeutic targets.
Materials and Method
Spatial RNA sequencing (spRNA-seq) was performed on primary TNBC and paired BM tissues from three patients, one of whom had previously received immune checkpoint inhibitors before BM diagnosis. Specimen regions were categorized into tumor, proximal, and distal TME based on their spatial locations. Gene expression differences across these zones were analyzed, and immune cell infiltration was estimated using TIMER. A gene module analysis was conducted to identify key gene clusters associated with BM.
Results
Distinct gene expression profiles were noted in the proximal and distal TMEs. In BM, the proximal TME exhibited neuronal gene expression, suggesting neuron-tumor interactions compared to tumor, and upregulation of epithelial genes compared to the distal TME. Immune cell analysis revealed dynamic changes in CD8+ T cells and macrophages across the tumor and TME zones. Gene module analysis identified five key modules, including one related to glycolysis, which correlated with patient survival. Drug repurposing analysis identified potential therapeutic targets, including VEGFA, RAC1, EGLN3, and CAMK1D.
Conclusion
This study provides novel insights into the transcriptional landscapes in TNBC BM using spRNA-seq, emphasizing the role of neuron-tumor interactions and immune dynamics. These findings suggest new therapeutic strategies and underscore the importance of further research.

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Comparison of Long-term Oncological Outcome of Sentinel Lymph Node Mapping Methods (Dye-Only versus Dye and Radioisotope) in Breast Cancer Patients Following Neoadjuvant Chemotherapy: Jinyoung Byeon, Changjin Lim, Eunhye Kang, Ji-Jung Jung, Hong-Kyu Kim, Han-Byoel Lee, Hyeong-Gon Moon, Wonshik Han; Received December 30, 2024 Accepted April 13, 2025 Published online April 15, 2025; DOI: https://doi.org/10.4143/crt.2024.1253 [Accepted]

Abstract PDF: Purpose
Sentinel lymph node biopsy (SLNB) using dye and isotope (DUAL) is recommended over the dye-only (DYE) method after neoadjuvant chemotherapy (NCT) due to potentially lower false-negative rates. However, the long-term outcome of either method is unclear. We aimed to compare the long-term oncological outcomes of DYE versus DUAL SLNB methods in patients who received NCT.
Materials and Methods
In this retrospective cohort study, 893 patients who underwent SLNB following NCT and had pathologically negative lymph nodes were included. After propensity score matching for cT, cN, and pT stages, 280 patients were in the DYE group and 560 in the DUAL group. Indigo carmine was used for dye and Tc-99m antimony trisulfate for isotope mapping.
Results
Median follow-up was 75.6 months in the DYE group and 83.0 months in the DUAL group. Mean (±SD) number of harvested sentinel nodes was 6.7 (±3.4) and 6.7 (±3.8) in the DYE and DUAL groups (p=0.51). Five-year distant metastasis-free survival was 95.2% in DYE group and 93.3% in DUAL group (HR=1.45; 95% CI, 0.82–2.57; p=0.19). Disease-free survival (HR=0.97; 95% CI, 0.69–1.50; p=0.91) and overall survival (HR=0.98; 95% CI, 0.56–1.69; p=0.95) were not significantly different. Axillary recurrence rate was 1.8% and 2.5% in DYE and DUAL groups(p=0.64).
Conclusion
Long-term oncological outcomes did not significantly differ between DYE and DUAL SLNB methods. The dye-only method can be safely recommended for breast cancer patients who received NCT.

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Reduced Dose and Selective Neck Irradiation Policy in Treating Oropharynx Cancer: Excellent Oncological Outcomes with very Low Risk of Locoregional Failure: Eunyeong Yang, Seung Gyu Park, Kyungmi Yang, Dongryul Oh, Yong Chan Ahn; Received December 13, 2024 Accepted April 9, 2025 Published online April 10, 2025; DOI: https://doi.org/10.4143/crt.2024.1204 [Accepted]

Abstract PDF: Purpose
To evaluate the risk of locoregional failure after reduced dose selective neck irradiation (RD-SNI) in patients with oropharyngeal cancer (OPC).
Materials and Methods
Between 2008 and 2022, 342 OPC patients underwent definitive radiation therapy (with or without concurrent systemic therapy). The doses of 67.2–68.4 Gy to gross tumor volume (GTV), 56–60 Gy to high risk clinical target volumes (CTV-HR), and 32–36 Gy to low risk clinical target volumes (CTV-LR) were irradiated. The same target delineation and dosing policy were applied to all patients regardless of human papillomavirus (HPV) status. Oncological outcomes including failure patterns were also investigated.
Results
With a median follow-up of 60.3 months (range: 1.4-196.6 months), the 3- and 5-year locoregional control, distant metastasis-free survival (DMFS), disease-free survival, and overall survival rates were 91.6%/90.7%, 83.7%/80.7%, 78.7%/74.8%, and 91.0%/85.8%, respectively. The HPV-positive patients exhibited significantly better outcomes. Treatment failure occurred in 61 patients (17.8%); 37 (10.8%) had distant metastasis, 22 (6.4%) had local failure, and 8 (2.3%) had regional failure. GTV failure was significantly more common in HPV-negative patients (p=0.003). Among the 27 patients with locoregional failure, either GTV and/or CTV-HR failure occurred in 22 (81.5%), with CTV-LR failure in 1 (3.7%), and out-target regional (OTR) failure in 5 (18.5%). Only five failures (1.5%) could be attributed to the current RD-SNI policy: one CTV-LR failure (0.3%) reflecting the RD policy and four OTR failures (1.2%) reflecting the SNI policy.
Conclusion
Excellent oncological outcomes were achieved with the current RD-SNI policy.

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The Effect of Alcohol Consumption Behavior Changes on Gastric Cancer Risks Stratified by Sex in South Korea: Yonghoon Choi, Jieun Jang, Hyeong Ho Jo, Nayoung Kim; Received June 24, 2024 Accepted March 31, 2025 Published online April 1, 2025; DOI: https://doi.org/10.4143/crt.2024.591 [Accepted]

Abstract PDF: Purpose
The effect of behavior changes in alcohol drinking on gastric cancer (GC) development, and the sex differences in those effects have not yet been fully elucidated. This study investigated the effect of behavior changes in alcohol drinking on the GC risk by sex.
Materials and Methods
The cohort was consisted of 310,192 Koreans (≥ 40 years) from the National Health Insurance Service–Health Screening Cohort with a median follow-up period of 12 years. Subjects were classified according to alcohol consumption behavior changes (non-drinker, quitter, reducer, sustainer, and increaser). The independent effect of changes in alcohol drinking patterns or concurrent effect of alcohol on GC risk were evaluated using the Cox proportional hazard regression.
Results
In males, non-drinkers showed a lower risk of developing GC (hazard ratio [HR], 0.91; 95% confidence interval [CI], 0.84–0.98), whereas increasers showed a higher risk of GC than sustainers (HR, 1.11; 95% CI, 1.02–1.20). Starting to drink alcohol, even at a mild level, was associated with an increased GC risk, while a decreased GC risk was induced when alcohol consumption dose decreases to a mild from a moderate level among males. However, in females, only substantial change of alcohol consumption dose from non- to heavy-drinking was associated with increased GC risk (HR, 1.97; 95% CI, 0.98–3.96).
Conclusion
These results suggest that alcohol abstinence can reduce the risk of developing GC, particularly among males.

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Efficacy of Chemotherapy Following Prior PARP-Inhibitor Treatment in Patients with Ovarian Cancer: Jung Chul Kim, Junsik Park, Yong Jae Lee, Eun Ji Nam, Sang Wun Kim, Sung-Hoon Kim, Young Tae Kim, Se Ik Kim, Jae-Weon Kim, Byoung-Gie Kim, Jung-Yun Lee; Received December 23, 2024 Accepted March 16, 2025 Published online March 19, 2025; DOI: https://doi.org/10.4143/crt.2024.1202 [Accepted]

Abstract PDF: Purpose
Considering the current lack of consensus on post-poly (adenosine diphosphate-ribose) polymerase inhibitor (PARPi) treatment strategies, this study aimed to evaluate the efficacy of subsequent therapy and compare the outcomes of regimes in patients with recurrent ovarian cancer after PARPi treatment.
Materials and Methods
This multi-center retrospective cohort study analyzed data on patients diagnosed with ovarian cancer between January 2012 and June 2023 who had previously used PARPi after first- to fourth-line platinum-based chemotherapy. The primary endpoint was progression-free survival (PFS), which was the interval between recurrence after using PARPi and subsequent recurrence in the case of recurrence.
Results
Of 318 patients, 147/318 (46.2%) recurred after the PARPi maintenance. Patients were categorized into groups based on subsequent therapy except non-treated (11/147, 7.5%): platinum-based chemotherapy (89/147, 60.5%), non-platinum-based chemotherapy (21/147, 14.3%), other treatments (26/147, 17.7%), and the median PFS (mPFS) for each group were 7.3, 4.8 and 11.4 months, respectively. Among the platinum-based chemotherapy group, the gemcitabine + carboplatin regimen demonstrated a longer mPFS (10.1 months) than the other regimens (6.6 months, p=0.0194). In non-platinum-based chemotherapy, no statistically significant differences were observed among the regimens. And, in the other therapy group, where the proportion of patients with oligometastasis was as high as 88.5%, no significant differences were observed among the therapies, including other modalities.
Conclusion
In the subsequent chemotherapy of recurrent ovarian cancer after platinum-based chemotherapy and PARPi, the gemcitabine + carboplatin regimen demonstrated a potential to delay recurrence more effectively compared to other therapies.

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Cancer Statistics in Korea: Incidence, Mortality, Survival, and Prevalence in 2022: Eun Hye Park, Kyu-Won Jung, Nam Ju Park, Mee Joo Kang, E Hwa Yun, Hye-Jin Kim, Jeong-Eun Kim, Hyun-Joo Kong, Kui-Son Choi, Han-Kwang Yang, The Community of Population-Based Regional Cancer Registries; Cancer Res Treat. 2025;57(2):312-330. Published online March 11, 2025; DOI: https://doi.org/10.4143/crt.2025.264

Abstract PDF Supplementary Material PubReader ePub: Purpose
The current study provides national cancer statistics and their secular trends in Korea, including incidence, mortality, survival, and prevalence in 2022, with international comparisons.
Materials and Methods
Cancer incidence, survival, and prevalence rates were calculated using the Korea National Cancer Incidence Database (1999-2022), with survival follow-up until December 31, 2023. Mortality data obtained from Statistics Korea, while international comparisons were based on GLOBOCAN data.
Results
In 2022, 282,047 newly diagnosed cancer cases (age-standardized rate [ASR], 287.0 per 100,000) and 83,378 deaths from cancer (ASR, 65.7 per 100,000) were reported. The proportion of localized-stage cancers increased from 45.6% in 2005 to 50.9% in 2022. Stomach, colorectal, and breast cancer showed increased localized-stage diagnoses by 18.1, 18.5, and 9.9 percentage points, respectively. Compared to 2001-2005, the 5-year relative survival (2018-2022) increased by 20.4 percentage points for stomach cancer, 7.6 for colorectal cancer, and 5.6 for breast cancer. Korea had the lowest cancer mortality among countries with similar incidence rates and the lowest mortality-to-incidence (M/I) ratios for these cancers. The 5-year relative survival (2018-2022) was 72.9%, contributing to over 2.59 million prevalent cases in 2022.
Conclusion
Since the launch of the National Cancer Screening Program in 2002, early detection has improved, increasing the diagnosis of localized-stage cancers and survival rates. Korea recorded the lowest M/I ratio among major comparison countries, demonstrating the effectiveness of its National Cancer Control Program.

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Prediction of Cancer Incidence and Mortality in Korea, 2025: Kyu-Won Jung, Mee Joo Kang, Eun Hye Park, E Hwa Yun, Hye-Jin Kim, Jeong-Eun Kim, Hyun-Joo Kong, Kui Son Choi, Han-Kwang Yang; Cancer Res Treat. 2025;57(2):331-338. Published online March 11, 2025; DOI: https://doi.org/10.4143/crt.2025.263

Abstract PDF PubReader ePub: Purpose
This study aimed to project cancer incidence and mortality for 2025 to estimate Korea’s current cancer burden.
Materials and Methods
Cancer incidence data from 1999 to 2022 were obtained from the Korea National Cancer Incidence Database, while cancer mortality data from 1993 to 2023 were acquired from Statistics Korea. Cancer incidence and mortality were projected by fitting a linear regression model to observed age-specific cancer rates against their respective years and then by multiplying the projected age-specific rates by the anticipated age-specific population for 2025. A joinpoint regression model was applied to identify significant changes in trends, using only the most recent trend data for predictions.
Results
A total of 304,754 new cancer cases and 84,019 cancer deaths are expected in Korea in 2025. The most commonly diagnosed cancer is projected to be thyroid cancer, followed by the colorectal, lung, breast, prostate and stomach cancers. These six cancers are expected to account for 63.8% of the total cancer burden. Lung cancer is expected to be the leading cause of cancer-related deaths, followed by liver, colorectal, pancreatic, stomach, and gallbladder cancers, together comprising 66.6% of total cancer deaths.
Conclusion
The increasing incidence of female breast cancer and the rise in prostate and pancreatic cancers are expected to continue. As aging accelerates, cancer commonly found in older adults are projected to rise significantly.

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Detection Ability of Quality of Life Changes and Responsiveness of the KOQUSS-40 and the EORTC QLQ-C30/STO22 in Patients Who Underwent Gastrectomy: A Prospective Comparative Study: Bang Wool Eom, Keun Won Ryu, Ji Yeong An, Yun-Suhk Suh, In Cho, Sung Geun Kim, Ji-Ho Park, Hoon Hur, Hyung-Ho Kim, Sang-Hoon Ahn, Sun-Hwi Hwang, Hong Man Yoon, Ki Bum Park, Hyoung-Il Kim, In-Gyu Kwon, Han-Kwang Yang, Byoung-Jo Suh, Sang-Ho Jeong, Tae-Han Kim, Oh Kyoung Kwon, Hye-Seong Ahn, Ji Yeon Park, Ki Young Yoon, Myoung Won Son, Seong-Ho Kong, Young-Gil Son, Geum Jong Song, Jong Hyuk Yun, Jung-Min Bae, Do Joong Park, Sol Lee, Jun-Young Yang, Kyung Won Seo, You-Jin Jang, So Hyun Kang, Joongyub Lee, Hyuk-Joon Lee, on behalf of KOrean QUality of life in Stomach cancer patients Study group (KOQUSS); Received November 20, 2024 Accepted February 28, 2025 Published online March 5, 2025; DOI: https://doi.org/10.4143/crt.2024.1104 [Accepted]

Abstract PDF: Purpose
The aim of this study is to compare the detection ability of quality of life (QoL) changes and responsiveness of the KOrean QUality of life in Stomach cancer patients Study group (KOQUSS)-40 and European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ).
Materials and Methods
A multicenter prospective observational study was conducted to evaluate QoL changes after various gastrectomies between January 2021 and April 2022. Participants were instructed to complete the KOQUSS-40 and EORTC QLQ-C30/STO22 preoperatively and at 1, 3, 6, and 12 months postoperatively. QoL changes over time and QoL responsiveness were assessed for each questionnaire.
Results
Data from 491 patients who underwent curative gastrectomy for gastric cancer at 22 institutions were analyzed. The summary scores of the KOQUSS-40 and EORTC QLQ-STO22 showed significant differences between the total and proximal gastrectomy groups (p=0.044 and 0.038, respectively), but no difference was observed for the EORTC QLQ-C30. Dysphagia on the KOQUSS-40 was significantly different between the total and proximal gastrectomy groups (p=0.044); however, dysphagia on the EORTC QLQ-STO22 did not differ. The responsiveness of the KOQUSS-40 was similar to that of the EORTC QLQ in patients who experienced ≥10% body weight loss, but approximately 10% less in patients receiving adjuvant chemotherapy than the EORTC QLQ.
Conclusion
KOQUSS-40 has several advantages over EORTC QLQ-C30/STO22 when comparing QoL between the total and proximal gastrectomy groups. The findings provide information for researchers investigating the QoL of patients who have undergone curative gastrectomy for gastric cancer.

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Association Between Benign Thyroid Disorders and Breast Cancer Risk in Korean Women: Boyoung Park, Thi Xuan Mai Tran; Received August 16, 2024 Accepted February 25, 2025 Published online February 26, 2025; DOI: https://doi.org/10.4143/crt.2024.787 [Accepted]

Abstract PDF: Purpose
This study aimed to investigate the potential association between thyroid disorders and breast cancer (BC) risk in a cohort of Korean women.
Materials and Methods
Data for this retrospective cohort study were obtained from the Korean National Health Insurance database, including all women aged ≥ 40 who underwent BC screening from 2009 to 2010 in Korea. Thyroid disorders were identified using medical records from 2009 to 2010 and extracted using the ICD-10 codes for thyroid nodules, hypothyroidism, and hyperthyroidism. BC cases were defined using the ICD-10 codes and tracked until December 2021. A Cox regression model was used to evaluate the association between thyroid disorders and the risk of BC. Additionally, we evaluated the association between well-known risk factors of BC and thyroid disorders using logistic regression analysis.
Results
Among 5,051,633 women, the mean (standard deviation) age was 55.2 (10.7) years, and the median follow-up was 11.6 years, with 87,784 BC cases recorded. The proportions of patients with thyroid nodules, hypothyroidism, and hyperthyroidism were 2.5, 1.8, and 0.9%, respectively. The hazard ratio (HR) for BC risk associated with thyroid nodules was 1.16 (95% CI 1.11–1.20), for hypothyroidism was 0.98 (95% CI 0.93–1.03), and for hyperthyroidism was 1.13 (95% CI 1.06–1.21). In both premenopausal and postmenopausal women, an increased risk of BC was significantly associated with thyroid nodules (aHR 1.16 and 1.13) and hyperthyroidism (aHR 1.11 and 1.16). History of benign breast disease, oral contraceptive use, breastfeeding, menopausal status, and hormone replacement therapy were associated with thyroid nodules and hyperthyroidism.
Conclusion
Our findings suggest an increased risk of BC in women with a history of thyroid nodules and hyperthyroidism, whereas no such association was found in women with hypothyroidism.

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Novel Bronchoscopy Method for Molecular Profiling of Lung Cancer: Targeted Washing Technique: Mi-Hyun Kim, Hayoung Seong, Hyojin Jang, Saerom Kim, Wanho Yoo, Soo Han Kim, Jeongha Mok, Kwangha Lee, Ki Uk Kim, Min Ki Lee, Jung Seop Eom; Received November 25, 2024 Accepted February 25, 2025 Published online February 26, 2025; DOI: https://doi.org/10.4143/crt.2024.1128 [Accepted]

Abstract PDF: Purpose
There have been efforts to find alternative samples other than standard samples of tissue or plasma for mutational analyses for lung cancer patients. However, no other sample or technique has replaced the mutational analyses using standard samples. In this prospective study, we assessed a novel bronchoscopy method, named as targeted washing technique, for detecting the EGFR mutation.
Materials and Methods
A 3.0-mm ultrathin bronchoscope was precisely navigated to the target lung lesion with the assistance of virtual bronchoscopic navigation and fluoroscopy. Once the bronchoscope is placed in front of target lung lesion, 0.9% normal saline was instilled for targeted washing. EGFR testing using targeted washing fluid (TWF) was compared to standard methods using plasma or tumor tissue.
Results
In 41 TWF samples, the T790M mutation was detected in tissue, plasma, and TWF samples at rates of 22%, 10%, and 29%, respectively. The overall EGFR T790M detection rate using tissue, plasma, or TWF samples was 37%, with TWF samples increasing the T790M mutation detection rate by up to 10%. The accuracy of T790M mutation detection using TWF sample was 83% compared with standard samples. Four patients were found to have the EGFR T790M mutation solely through EGFR testing using TWF, which repeated rebiopsies using either plasma or tissue finally confirmed to have the T790M mutation.
Conclusion
We demonstrated the clinical potential of targeted washing technique for molecular testing, which can be a good option to overcome spatial heterogeneity, low sensitivity of plasma sample or technical limitations in collecting tumor tissues.

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Molecular Mosaics: Unveiling Heterogeneity in Synchronous Colorectal Cancers: Hyun Gu Lee, Yeseul Kim, Mi-Ju Kim, Yeon Wook Kim, Sun-Young Jun, Deokhoon Kim, In Ja Park, Seung-Mo Hong; Received September 30, 2024 Accepted February 17, 2025 Published online February 18, 2025; DOI: https://doi.org/10.4143/crt.2024.947 [Accepted]

Abstract PDF: Purpose
Molecular characteristics of synchronous colorectal cancers (SCRCs) remain incompletely elucidated, despite their importance in targeted therapy selection. We compared the molecular characteristics and somatic mutations between SCRCs.
Materials and Methods
This retrospective study (2012-2014) included 98 consecutive patients with surgically resected SCRCs. Molecular characteristics, including microsatellite instability (MSI) and tumor-infiltrating lymphocytes (TILs), were analyzed for all cancer lesions. The intertumoral heterogeneity of SCRCs was evaluated using whole-exome sequencing (WES) for 18 cancers from 9 patients with at least one MSI-high (MSI-H) tumor.
Results
Twelve patients had at least one MSI-H tumor; five showed discordant MSI status. Mucinous adenocarcinoma frequency and TIL density were higher in patients with at least one MSI-H tumor than in those with only microsatellite-stable tumors. WES revealed that, except one patient (6.5%), most synchronous cancers shared few variants in each patient (0.09–0.36%). The concordance rates for BRAF, KRAS, NRAS, and PIK3CA in synchronous cancers from each patient were 66.7%, 66.7%, 66.7%, and 55.6%, respectively.
Conclusion
Although synchronous cancers shared a mutated gene, the mutation subtypes differed. SCRCs exhibited 5.1% MSI status discordance rate and a high discordance rate in somatic mutational variants. As intertumoral heterogeneity may affect the targeted therapy response, molecular analysis of all tumors is recommended for patients with SCRCs.

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Validation of 2023 FIGO Stage IA1–IIIC2 Endometrial Carcinoma: A Retrospective Analysis of Two Tertiary Centers in South Korea and Taiwan: Myeong-Seon Kim, Yen-Ling Lai, Yurimi Lee, Hyun-Soo Kim, Yu-Li Chen, Yoo-Young Lee; Received December 11, 2024 Accepted February 10, 2025 Published online February 17, 2025; DOI: https://doi.org/10.4143/crt.2024.1190 [Accepted]

Abstract PDF: Purpose
As understanding of the molecular pathogenesis of endometrial carcinoma (EC) advanced, the International Federation of Gynecology and Obstetrics (FIGO) staging system was revised in 2023. This study compared EC survival outcomes using the 2009 and 2023 FIGO staging systems.
Materials and Methods
We retrospectively analyzed 3,029 patients diagnosed with 2009 FIGO stage I–III EC between 1985 and 2022 in South Korea, and between 2020 and 2022 in Taiwan. All patients were reclassified using the 2023 FIGO staging, and survival and risk factors were examined under both systems.
Results
Transitioning from the 2009 to 2023 FIGO resulted in 549 (18.0%) patients being upstaged and their survival curves being diversified, indicating significant prognostic value of the 2023 FIGO. Re-classification using the 2023 FIGO upstaged the 2009 FIGO stage IA high-risk ECs, allowing more intensive treatment and potentially improving survival outcomes. The most significant changes occurred in the 2009 FIGO stages IA, IB, and IIIA ECs: upstaging in 16.5%, 49.0%, and 2.0% of IA, IB, and IIIA tumors, respectively, and downstaging 0.3% and 40.8% of IB and IIIA tumors, respectively. The risk factors for poor survival included old age (≥60), menopause, diabetes, substantial lymphovascular space invasion, aberrant p53 expression, and some aggressive histological types (carcinosarcoma, undifferentiated carcinoma, mesonephric-like adenocarcinoma, and neuroendocrine carcinoma).
Conclusion
The 2023 FIGO staging provides more refined stratification of early-stage EC than the 2009 version. Thus, the 2023 FIGO may more accurately guide prognosis and therapeutic decision-making.

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Long-term Immunogenicity of the 13-valent Pneumococcal Conjugate Vaccine during Adjuvant Chemotherapy in Patients with Gastric and Colorectal Cancer: A 5-year Follow-up of a Randomized Controlled Trial: Hyeon-Jong Kim, Hyunjin Bang, Hyun-Jung Shim, Jun Eul Hwang, Sang-Hee Cho, Ik-Joo Chung, Seung Ji Kang, Jong Gwang Kim, Seung-Hoon Beom, A-Yeung Jang, Joon Young Song, Woo Kyun Bae; Received November 12, 2024 Accepted February 11, 2025 Published online February 12, 2025; DOI: https://doi.org/10.4143/crt.2024.1083 [Accepted]

Abstract PDF: Purpose
Current guidelines recommend vaccination at least two weeks before chemotherapy initiation to optimize the immune response despite limited evidence. Our previous study indicated no differences in short-term immune response for the 13-valent pneumococcal conjugate vaccine (PCV13) according to the vaccination timing. This study aims to investigate the long-term efficacy of PCV13 and clinical factors associated with the respective antibody response.
Materials and Methods
Patients with gastric or colorectal cancer who received adjuvant chemotherapy were enrolled and divided into two groups: vaccinated two weeks before chemotherapy (arm A) and vaccinated concurrently with chemotherapy (arm B). Serum samples were collected before vaccination and in one month, three years, and five years. Immune responses were measured using ELISA and multiplex opsonophagocytosis assay.
Results
Including 63 patients, both groups showed an initial increase in the geometric mean titers (GMTs) of opsonophagocytic activity and the geometric mean concentrations (GMCs) of serotype-specific IgG levels after one month, followed by a decline at three and five years, particularly for serotypes 1, 14, 18C, and 19A. Despite the decline, global protection was maintained for five years, although global response decreased. The two arms did not show significant differences in immunogenicity nor in factors such as vaccination timing, age, cancer type, or chemotherapy regimen.
Conclusion
Vaccination timing is not a significant factor for the immunogenicity of PCV13 in cancer patients undergoing adjuvant chemotherapy. Global protection against pneumococcal infection was sustained for >5 years, and global response remained in over half of patients.

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Stereotactic Ablative Radiotherapy Versus Surgery in Patients with Pulmonary Metastases from Colorectal Cancer: Byung min Lee, Ha Eun Kim, Young Ho Yang, Seung Yoon Yang, Han Sang Kim, Seo Hee Choi, Woong Sub Koom, Byung Jo Park, Jee Suk Chang; Received October 29, 2024 Accepted February 5, 2025 Published online February 6, 2025; DOI: https://doi.org/10.4143/crt.2024.1040 [Accepted]

Abstract PDF: Purpose
We compared the local control rate and toxicity of stereotactic ablative radiotherapy (SABR) versus wedge resection for colorectal pulmonary metastases.
Materials and Methods
We retrospectively reviewed medical charts and imaging of patients treated with SABR or wedge resection between 2010 and 2017 at a single institution.
Results
There were 404 patients who were treated with local therapy for 528 pulmonary metastatic lesions. While surgery was frequently used upfront for smaller, solitary metastases without other site involvement, SABR was often used for larger, multiple lesions and disease burdens beyond the lungs. The 3-year local control rate was 88.6% following surgery, which was not significantly different from that with SABR at 86.7% (p=0.174). No major postoperative complications or mortality were observed in the surgery group, and 2.8% of patients in the SABR group experienced grade 3-4 radiation pneumonitis.
Conclusion
SABR was used in patients with a higher risk of progression compared to those undergoing surgery, yet it has similar local control rates to wedge resection.

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ALYREF-Mediated Regulation of TBL1XR1 and KMT2E Synergistically Upregulates APOC1, Contributing to Oxaliplatin Resistance in Esophageal Cancer: Jie Hu, Qilong Liu, Bi Feng, Yanling Lu, Kai Chen; Received November 15, 2024 Accepted February 3, 2025 Published online February 4, 2025; DOI: https://doi.org/10.4143/crt.2024.1091 [Accepted]

Abstract PDF: Purpose
Esophageal cancer (EC) is a rapidly progressing malignancy characterized by a low survival rate and limited treatment success, largely due to late-stage detection, frequent recurrence, and a high propensity for metastasis, despite ongoing advances in therapeutic strategies. While oxaliplatin (L-OHP) is a potent chemotherapeutic agent that induces apoptosis in EC cells, its effectiveness is significantly hindered by the development of resistance.
Materials and Methods
The assessment of gene and protein expression was conducted through a combination of RT-qPCR, Western blot, and IHC staining. Cell viability was assessed using the CCK-8 assay. The interactions among ALYREF, TBL1XR1, KMT2E, and APOC1 were investigated through RIP, ChIP, ChIP-reChIP, RNA pulldown, and dual-luciferase assays. An in vivo mouse model of EC was established.
Results
Expression levels of both APOC1 and ALYREF were elevated in L-OHP-resistant EC tissues and cell lines, and their silencing enhanced sensitivity to L-OHP. TBL1XR1 and KMT2E synergistically upregulated APOC1 expression. Moreover, ALYREF recognized the m5C sites on TBL1XR1 and KMT2E mRNAs, stabilizing these transcripts and promoting APOC1 expression. The regulatory role of these interactions was further validated in vivo.
Conclusion
This study demonstrated that ALYREF interacted with the m5C sites on TBL1XR1 and KMT2E mRNAs, enhancing their stability and leading to increased transcription of APOC1, which in turn contributed to L-OHP resistance in EC. These findings suggest that targeting APOC1 could be a promising strategy for overcoming L-OHP resistance in EC.

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Dose-response Association Between Alcohol Consumption and Kidney Cancer Risk Differs According to Glycemic Status: A Nationwide Cohort Study of 9.4 Million Individuals: Joo-Hyun Park, Jung Yong Hong, Kyungdo Han, Jay J. Shen, Se Hoon Park; Received October 15, 2024 Accepted January 30, 2025 Published online January 31, 2025; DOI: https://doi.org/10.4143/crt.2024.996 [Accepted]

Abstract PDF: Purpose
Previous studies suggested an association between alcohol consumption and reduced kidney cancer risk. Given a potential interaction between alcohol's insulin-sensitizing effect and hyperglycemia-related insulin resistance, we aimed to assess whether the dose-response association between alcohol intake and kidney cancer risk varies based on glycemic status.
Materials and Methods
This nationwide cohort study analyzed data from 9,492,331 adults who underwent a national health screening program in 2009 and were followed until 2018. Multivariable-adjusted Cox regression models were applied to estimate the hazard ratios (aHRs) and 95% confidence intervals (CIs).
Results
Over a median follow-up period of 8.3 years, 12,381 participants were diagnosed with kidney cancer. A U-shaped relationship between alcohol consumption and kidney cancer risk was observed among individuals with normoglycemia (light-to-moderate; HR, 0.94; 95% CI, 0.89–0.99 and heavy; HR, 1.00; 95% CI, 0.91–1.09, respectively). In prediabetic individuals, alcohol consumption was not significantly associated with kidney cancer risk. In individuals with diabetes, a dose-dependent increase in kidney cancer risk was noted with higher alcohol consumption (light-to-moderate consumption: HR, 1.12; 95% CI, 1.03–1.22; heavy consumption: HR, 1.24; 95% CI, 1.09–1.42; P for trend <0.01).
Conclusion
A modest U-shaped dose-response association between alcohol consumption and kidney cancer risk was observed exclusively in individuals with normoglycemia. Individuals with diabetes demonstrated a dose-dependent increased risk of kidney cancer with higher alcohol consumption. Tailored patient education and personalized risk assessments regarding alcohol consumption and kidney cancer risk should be emphasized over a generalized 'one-size-fits-all' approach.

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Novel Breast Cancer Risk Assessment Tools for Pre- and Post-Menopausal Asian Women: Development and Validation in a Nationwide Mammographic Screening Cohort: Wonyoung Jung, Yong-Moon Mark Park, Sang Hyun Park, Kyungdo Han, Junhee Park, Yohwan Yeo, Jung Kwon Lee, Dale P. Sandler, Dong Wook Shin; Received September 4, 2024 Accepted January 30, 2025 Published online January 31, 2025; DOI: https://doi.org/10.4143/crt.2024.861 [Accepted]

Abstract PDF: Purpose
Widely used breast cancer risk-prediction tools are based on data from Western countries, but risk factors may differ for Asian women. Hence, we aimed to develop a risk assessment tool for breast cancer in Asian women using a nationwide, population-based mammographic screening cohort.
Materials and Methods
Women aged ≥40 years who underwent breast cancer screening and general health examination in 2009 were included. Age, body mass index (BMI), breast density, lifestyle and reproductive factors, and comorbidities were used to develop 5-year breast cancer risk-prediction models for premenopausal (n=771,856) and postmenopausal (n=1,108,047) women at baseline. The best-fit risk prediction model was constructed using backward stepwise selection in a Cox proportional hazards model and was transformed into a risk score nomogram. The performance was assessed by discrimination and calibration.
Results
In premenopausal women, high BMI, low parity, short breastfeeding period, early age at menarche, high breast density, a history of benign breast masses, and family history of breast cancer contributed to the risk prediction of breast cancer. In postmenopausal women, age, diabetes mellitus, dyslipidemia, late-onset menopause, and hormone replacement therapy use were additional risk predictors of breast cancer. Our risk-prediction model showed a concordant statistic of 0.58 (0.57–0.59) for premenopausal women and 0.64 (0.63–0.65) for postmenopausal women. The calibration plot demonstrated good correlations for both models.
Conclusion
Our breast cancer risk-prediction model demonstrated performance comparable to that of Western countries, especially among postmenopausal women. This provides a foundation for implementing risk-based screening recommendations in Asian women.

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The Current Evidence and Future Direction of Adjuvant Treatment for Gastric Cancer in the Era of Precision Medicine: Jong Hyuk Yun, Yoon Young Choi, Jae-Ho Cheong; Received December 18, 2024 Accepted January 22, 2025 Published online January 23, 2025; DOI: https://doi.org/10.4143/crt.2024.1222 [Accepted]

Abstract PDF: Although gastric cancer remains a significant global health burden, its treatment strategies vary across different geographical regions, leading to distinct guidelines. In Asia, particularly in Korea, D2 gastrectomy followed by adjuvant chemotherapy has been established as the standard treatment for stage II/III gastric cancer based on landmark clinical trials. However, this "one-size-fits-all" approach requires refinement as emerging evidence suggests heterogeneous outcomes even within the same stage. This review discusses the evolving landscape of adjuvant treatment in gastric cancer, emphasizing the transition towards precision medicine. Recent molecular characterization of gastric cancer has revealed distinct subtypes with varying prognoses and chemotherapy responses, exemplified by the favorable outcomes of microsatellite instability-high tumors without adjuvant chemotherapy. Additionally, clinical factors including sub-stages within stage II/III, patient performance status, comorbidities, and personal preferences should be considered in treatment decisions. The integration of these molecular and clinical factors, along with shared decision-making between physicians and patients, represents a crucial step toward personalized treatment approaches. Looking ahead, the field is poised for further evolution with the emergence of immune checkpoint inhibitors, growing evidence for neoadjuvant chemotherapy in selected cases, and the potential of circulating tumor DNA as a biomarker for minimal residual disease. This comprehensive approach to treatment decision-making, considering both tumor biology and patient factors, will be essential for realizing precision medicine in gastric cancer care.

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The Roles of Ninjurin1 and Estrogen in Modulating AOM/DSS-Induced Colitis-Associated Colorectal Cancer in Male Mice: Chin-Hee Song, Nayoung Kim, Ryoung Hee Nam, Jae Young Jang, Eun Hye Kim, Sungchan Ha, Eun Shin, Ha-Na Lee, Hoon Choi, Kyu-Won Kim, Sejin Jeon, Goo Taeg Oh; Received October 2, 2024 Accepted January 10, 2025 Published online January 13, 2025; DOI: https://doi.org/10.4143/crt.2024.959 [Accepted]

Abstract PDF: Purpose
Ninjury-induced protein 1 (Ninj1) is associated with inflammation and tumor progression and shows increased expression in various cancers. This study aimed to investigate the role of Ninj1 in colitis-associated colorectal cancer (CRC) by focusing on its interaction with 17β-estradiol (E2).
Materials and Methods
Using an azoxymethane (AOM)/dextran sodium sulfate (DSS) mouse model of colitis-associated CRC, wild-type (WT) and Ninj1 knockout (KO) male mice were treated with or without E2.
Results
At week 2, Ninj1 KO mice exhibited attenuated colitis symptoms than WT mice following AOM/DSS treatment. E2 administration significantly alleviated these symptoms in both WT and Ninj1 KO mice, with reductions in the disease activity index (DAI), colon length shortening, and histopathological damage. The levels of pro-inflammatory mediators were reduced by E2 treatment in both groups, with the Ninj1 KO group showing a more pronounced response. At week 13, tumor development in Ninj1 KO mice was significantly lower than that in WT mice, particularly in the distal colon. E2 treatment inhibited tumor formation in WT mice and had a stronger inhibitory effect on distal colon tumorigenesis in Ninj1 KO mice. Immune cell populations, including the populations of macrophages and T cells, were also modulated by E2 in WT mice; however, these effects were diminished in Ninj1 KO mice.
Conclusion
These findings suggest that Ninj1 plays a role in modulating colitis and CRC progression, with E2 exerting anti-inflammatory and anti-tumorigenic effects that are influenced by Ninj1 status.

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