Cancer Research and Treatment

Distinct Evolutionary Dynamics of HER2-Ultralow Versus HER2-Null from Residual to Metastatic Disease in Non-pCR Breast Cancer: Shunan Wang, Jingjing Liu, Tong Liu, Shichao Zhang, Xinyu Liu, Yu Liu, Jin Zhang; Received March 22, 2026 Accepted May 11, 2026 Published online May 12, 2026; DOI: https://doi.org/10.4143/crt.2026.0302 [Accepted]

Abstract PDF: Purpose
In breast cancer (BC) patients without pathological complete response (pCR) after neoadjuvant therapy, residual disease drives recurrence. The HER2 spectrum now includes HER2-low and HER2-ultralow. HER2-low tumors are eligible for HER2-targeted antibody-drug conjugates (ADCs), while T-DXd is approved for HR-positive HER2-ultralow metastatic BC after endocrine therapy. Evolution patterns of HER2-ultralow versus HER2-null from residual to metastatic disease remain unclear.
Materials and Methods
We retrospectively studied 488 non-pCR patients with refined HER2 classification; 92 with HER2-0 residual disease formed the analytic cohort for HER2-ultralow/HER2-null comparison. HER2 status was tested in paired residual and metastatic lesions. Logistic regression was used to identify factors linked to HER2 evolution.
Results
In the 92‑patient HER2‑0 analytic cohort, HER2-ultralow (46.7% of HER2-0) converted more frequently to HER2-low than HER2-null (51.2% vs 30.6%, p=0.045). This difference remained statistically significant in the multivariable logistic regression model. In the full 517-patient contextual cohort, HER2 expression gain in recurrent/metastatic lesions was independently associated with poorer post-recurrence survival (PRS) (adjusted HR=1.74, p=0.009). In the 488-patient primary cohort, conversion from HER2-0 to HER2-low was also associated with poorer PRS (adjusted HR=2.18, p<0.001). The broader HER2 expression evolution in the full 517‑patient cohort and the primary 488‑patient refined HER2 cohort was consistent with the core finding from the 92‑patient HER2‑0 analytic cohort and supported its biological plausibility.
Conclusion
HER2-ultralow shows distinct evolution and high HER2-low conversion potential, affecting ADC eligibility. Routine HER2-0 subclassification and metastatic HER2 reassessment appear clinically useful and warrant prospective validation.

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Genetic Variant at 6p21.1 Impairs APOBEC2 in Hypoxic Mitophagy via HIF-1α/BNIP3 in Gastric Cancer: Zhonghua Zheng, Qian Li, Yuanliang Gu, Xinxiang Gao, Xinya Wang, Yan Zhang, Fangmei An, Qiang Zhan, Shuangshuang Yin, Yun Gao, Rui Peng, Li Liu, Erbao Zhang, Meng Zhu, Xiaofeng Chen, Gang Li, Hao Xu, Guangfu Jin, Caiwang Yan; Received October 30, 2025 Accepted May 8, 2026 Published online May 12, 2026; DOI: https://doi.org/10.4143/crt.2025.1194 [Accepted]

Abstract PDF: Purpose
Genome-wide association studies (GWASs) have identified single-nucleotide polymorphisms (SNPs) at the 6p21.1 locus associated with gastric cancer (GC) risk. However, the underlying biological mechanisms remain poorly understood.
Materials and Methods
We conducted fine-mapping analysis of the 6p21.1 region using large-scale GC GWAS data (10,254 cases and 10,914 controls). Functional annotation, luciferase reporter assays, Electrophoretic mobility shift assay (EMSA) and chromatin immunoprecipitation (ChIP) experiments were performed to identify functional variants. The eQTL and colocalization analyses were used to determine the susceptibility gene. Mechanistic investigations included phenotypic assays under normoxic and hypoxic conditions, along with seahorse, immunofluorescence and ATP assays to assess mitochondrial function.
Results
We identified rs9381024 as the independent association signal at 6p21.1, with rs2235679, in strong linkage disequilibrium with rs9381024, emerging as a potential causative SNP. The T risk allele of rs2235679 reduced APOBEC2 expression by enhancing the binding of transcriptional repressor MZF1, thereby suppressing promoter activity. Expression analysis revealed a progressive decrease in APOBEC2 levels with gastric lesions severity, becoming nearly undetectable in GC tissues. Functionally, reduced APOBEC2 expression significantly promoted the proliferation of GC cells under hypoxic conditions but not under normoxia. Mechanistically, downregulation of APOBEC2 activated mitophagy to maintain mitochondria homeostasis via HIF-1α/BNIP3 pathway under hypoxia, ultimately driving tumor growth.
Conclusion
Our findings provide novel mechanistic insights into how genetic variants at 6p21.1 contribute to GC risk and progression, highlighting the tumor-suppressive role of APOBEC2.

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Gaps between Supportive Care Needs and Services in Korea: Experiences and Preferences of Patients with Advanced Cancer and Their Caregivers in the Hospital and at Home: Min Seol Jang, In Gyu Hwang, Shin Hye Yoo, Belong Cho, Bhumsuk Keam, Yu Jung Kim, Sun Kyung Baek, Min Sun Kim, Sun Young Lee; Received October 23, 2025 Accepted May 4, 2026 Published online May 7, 2026; DOI: https://doi.org/10.4143/crt.2025.1162 [Accepted]

Abstract PDF: Purpose
With longer survivals in advanced cancer, the need for supportive care is increasing. However, in Korea, these services remain limited, and many patients rely on long-term care hospitals. We investigated the supportive care experiences of patients with advanced cancer and their caregivers, and preferred place of care (pPOC) by performance status (PS).
Materials and Methods
A cross-sectional survey was conducted at a tertiary hospital in Seoul, Korea, targeting patients hospitalized only for supportive care and their caregivers. PS was assessed using the Eastern Cooperative Oncology Group scale [good (0–1) or poor (2–4)]. Hospital and home care experiences and pPOC were compared by PS. Logistic regression analysis was used to identify factors associated with pPOC.
Results
This study included 200 participants (117 patients, 83 caregivers). Among patients, 72% had good PS and 28% had poor PS. Main reasons for hospitalization were symptom control (51.2%), assistance with daily living (36.5%), and device or wound management (22.5%). Overall, 60.5% of participants reported discomfort during hospitalization, mostly related to hospital life, and 34.5% noted that care was insufficient at home, particularly those in the poor PS group (27.1% vs. 53.6%). Concern about emergencies was the most common home-care difficulty. Despite these challenges, 60% of participants chose home as their future pPOC, with no significant differences by PS or other demographic/clinical factors.
Conclusion
Although most patients with advanced cancer and their caregivers preferred home for supportive care, many relied on hospitals. Structured home-based medical care programs are urgently required in South Korea.

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A Phase Ib/II Study of Pemigatinib in Combination with Paclitaxel in Patients with Gastric Cancer with FGFs/FGFRs Alterations: Minkyu Jung, Soo Hyun Park, Hyoyoung Kim, Youhyun Kim, Un-Jung Yun, Jiwoo Hwang, Hyo Song Kim, Choong-kun Lee, Hyunki Kim, Chung Lee, Dong-Hoe Koo, Hei-Cheul Jeung, Dae Young Zang, Eun-Kee Song, Sun Young Rha; Received December 10, 2025 Accepted May 1, 2026 Published online May 4, 2026; DOI: https://doi.org/10.4143/crt.2025.1352 [Accepted]

Abstract PDF: Purpose
Pemigatinib is a selective inhibitor of fibroblast growth factor receptors (FGFR) 1–3 with demonstrated activity in tumors harboring FGFR2 fusions or amplifications. This phase Ib/II trial assessed the efficacy and safety of pemigatinib in combination with paclitaxel in patients with recurrent or advanced gastric cancer exhibiting FGFs/FGFRs alterations.
Materials and Methods
Patients with gastric cancer harboring FGFs/FGFRs aberrations who experienced progression following first-line therapy were enrolled. The phase Ib component established the recommended phase II dose (RP2D); the phase II component evaluated clinical efficacy.
Results
Twelve patients were enrolled. The RP2D was determined as pemigatinib 13.5 mg/day (days 1–21) plus paclitaxel 80 mg/m² (days 1, 8, 15) every 4 weeks. Median progression-free and overall survival were 4.4 and 10.5 months, respectively. Patients with FGFR2 amplification (n=6) exhibited prolonged progression-free survival (6.5 vs. 3.5 months, p=0.049), while overall survival did not differ significantly. The objective response and disease control rates were 33.3% and 91.7%, respectively. The most frequent treatment-related adverse events were neutropenia (83.3%, grade ≥3: 58.3%) and hyperphosphatemia (83.3%, grade ≥3: 33.3%).
Conclusion
Pemigatinib plus paclitaxel demonstrated antitumor activity with an acceptable safety profile in FGFR2-amplified gastric cancer. Further investigation is warranted to elucidate resistance mechanisms and validate these findings in larger cohorts.

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Is Adjuvant Chemotherapy Necessary for All Patients with pT3N0 Rectal Cancer after Upfront Surgery? A Multicenter Retrospective Study: Kyong-Min Kang, Ho Yung Lee, Hong-min Ahn, Heung-Kwon Oh, Duck-Woo Kim, Sung-Bum Kang, Dong Woon Lee, Sung Chan Park, Jae Hwan Oh, Min Jung Kim, Ji Won Park, Seung-Bum Ryoo, Seung-Yong Jeong, Kyu Joo Park; Received November 27, 2025 Accepted April 30, 2026 Published online May 4, 2026; DOI: https://doi.org/10.4143/crt.2025.1308 [Accepted]

Abstract PDF: Purpose
The role of adjuvant chemotherapy (ACT) in pathologic T3N0 (pT3N0) rectal cancer, which has a favorable prognosis, remains controversial because high-risk groups for recurrence are not well defined. This study investigated prognostic factors for survival in this patient group and evaluated the benefit of ACT based on these factors.
Materials and Methods
This retrospective study analyzed 352 patients with pT3N0 rectal cancer who underwent upfront radical surgery at three referral hospitals between November 2003 and December 2020. A multivariable Cox regression model was used to identify the prognostic factors for 5-year recurrence-free survival (RFS). Patients were categorized as high or low risk based on these factors, and survival outcomes were compared between those who received ACT and those who did not, using the log-rank test.
Results
Median follow-up was 52.8 months. 193 (54.8%) patients received ACT. Multivariable analysis revealed that ACT, circumferential resection margin (CRM) ≤ 2mm, vascular invasion, and perineural invasion were independent predictors of 5-year RFS. In patients with ≥ 1 risk factor, ACT significantly improved RFS (92.5% vs. 72.8%, hazard ratio [HR] 0.247, 95% confidence interval [CI] 0.090–0.683, p < 0.01). In those without risk factors, no significant benefit was observed (98.0% vs. 91.6%, HR 0.272, 95% CI 0.057–1.313, p=0.082).
Conclusion
This study identified CRM ≤ 2mm, vascular invasion, and perineural invasion as high-risk features for recurrence in pT3N0 rectal cancer. ACT improved RFS only in patients with these features. While these findings support risk-based ACT administration in this patient population, further validation of our risk stratification system is needed.

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Concurrent Chemoradiotherapy with or without Induction Chemoimmunotherapy in Unresectable Esophageal Squamous Cell Carcinoma: A Multicenter Real-World Study: Biqi Chen, Peiying Cen, Qi Cheng, Tiejun Wang, Zimeng Li, Chen Yi, Xingyuan Cheng, Dongmei Chi, Shiliang Liu, Yujia Zhu, Hao Zhang, Mian Xi, Baoqing Chen, Yujin Xu, Qiaoqiao Li; Received November 7, 2025 Accepted April 27, 2026 Published online April 28, 2026; DOI: https://doi.org/10.4143/crt.2025.1224 [Accepted]

Abstract PDF: Purpose
This study aimed to compare the efficacy and safety of concurrent chemoradiotherapy (CCRT) with or without induction chemoimmunotherapy (CI) in unresectable esophageal squamous cell carcinoma (ESCC).
Materials and Methods
The study included patients with unresectable ESCC who received CCRT with or without induction CI at three cancer centers. Patients receiving concurrent immunotherapy were excluded. Propensity score matching (PSM) balanced baseline characteristics between groups.
Results
A total of 519 patients were included. After PSM, 183 patients per group were selected. Induction CI significantly improved OS and PFS compared to CCRT alone, consistently. The median OS for CCRT and induction CI groups were 29.9 months (95% CI: 18.8-41.0) and not reached (HR: 0.57, 95% CI: 0.42-0.77, p < 0.001). The median PFS was 17.6 months (IQR: 13.7-21.4) versus 30.6 months (IQR: 17.3-43.8) (HR: 0.66, 95% CI: 0.51-0.86, p = 0.002). Responders to the induction CI had significantly better OS (HR: 0.22, 95%CI: 0.14-0.36, p < 0.001) than nonresponders. Subgroup analysis showed radiation dose escalation or consolidation immunotherapy did not further improve survival in the induction CI group.
Conclusion
The addition of induction chemoimmunotherapy to CCRT was associated with improved survival in patients with locally advanced unresectable ESCC, particularly in responders to induction chemoimmunotherapy, with acceptable toxicity. These findings warrant confirmation in prospective randomized trials.

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Toward Sustainable Care in HER2-Positive Metastatic Breast Cancer: Emerging Evidence for Treatment De-escalation: Matilda Xinwei Lee, Soo Chin Lee; Received October 16, 2025 Accepted April 23, 2026 Published online April 23, 2026; DOI: https://doi.org/10.4143/crt.2025.1131 [Accepted]

Abstract PDF: Major advances in the management of HER2-positive (HER2+) metastatic breast cancer (MBC) have been achieved through treatment intensification with novel HER2-targeted agents and combination strategies, resulting in substantial survival gains. However, indefinite exposure to systemic therapy imposes cumulative toxicity, financial strain, and quality-of-life burdens. In contrast, the concept of treatment de-escalation, aimed at maintaining disease control with less intensive therapy, has only recently emerged as a complementary paradigm. This review highlights two evolving avenues of treatment de-escalation. First, in hormone receptor-positive (HR+)/ HER2+ disease, randomized trials have demonstrated that combining HER2 blockade with endocrine therapy and CDK4/6 inhibitors can overcome endocrine resistance, offering a chemotherapy-sparing approach with outcomes comparable to chemotherapy or antibody-drug conjugates. Second, in long-term responders, retrospective analyses and ongoing prospective trials are evaluating whether discontinuation of prolonged maintenance HER2 therapy can safely reduce treatment burden while preserving disease control, with the added potential for effective rechallenge upon relapse. Together, these developments suggest that treatment de-escalation represents a rational and necessary treatment strategy. Future progress will depend on biomarker-driven patient selection and prospective validation. Redefining success in HER2+ MBC to include not only survival but also quality of life and sustainability represents an important step toward patient-centered cancer care.

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Is Complete Mesocolic Excision with Central Vascular Ligation Necessary for Suspected Early-stage Right-sided Colon Cancer?: Mi Jeong Choi, Duck-Woo Kim, Yu Kyung Jun, Ji Ae Lee, Jeehye Lee, Hong-Min Ahn, Heung-Kwon Oh, Sung-Bum Kang; Received September 29, 2025 Accepted April 13, 2026 Published online April 15, 2026; DOI: https://doi.org/10.4143/crt.2025.1065 [Accepted]

Abstract PDF: Purpose
To assess lymph node status in patients undergoing additional surgery after endoscopic resection to evaluate the need for complete mesocolic excision with central vascular ligation for clinically suspected early-stage right-sided colon cancer.
Materials and Methods
This retrospective study, conducted at a single institution using a prospectively collected database, comprised patients who underwent additional surgery following endoscopic intervention between May 2003 and March 2022. The primary outcomes were the rate and location of lymph node metastases, including peritumoral, pericolic, and superior mesenteric lymph nodes. The secondary outcome was recurrence-free survival.
Results
Among 119 patients, pathological examination identified 5 (4.2%) with Tis requiring surgery owing to uncheckable margins or tumor depth, 106 (89.1%) with stage T1 tumors, and 8 (6.7%) with stage T2 tumors. The nodal stage was N0 in 107 patients (89.9%) and N1 in 12 (10.1%) patients. The mean number of harvested lymph nodes was 39.7, including 7.6 ± 6.9 peritumoral, 31.5 ± 14.4 pericolic, and 4.0 ± 3.8 superior mesenteric nodes. All metastatic lymph nodes were in the peritumoral and pericolic regions. At a mean follow-up of 48.2 months, recurrence occurred in one (0.8%) patient, who developed liver metastases 24 months postoperatively.
Conclusion
For patients with clinically suspected early-stage right-sided colon cancer who initially underwent endoscopic resection, the risk of superior mesenteric node metastases is very low. D2 lymph node dissection alone may be sufficient rather than routine application of complete mesocolic excision with central vascular ligation, which might be reconsidered in these patients.

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Cancer Statistics in Korea: Incidence, Mortality, Survival, and Prevalence in 2023: Eun Hye Park, Kyu-Won Jung, Seo Hyun Choi, Nam Ju Park, Mee Joo Kang, E Hwa Yun, Hye-Jin Kim, Jeong-Eun Kim, Kui Son Choi, Han-Kwang Yang, The Community of Population-Based Regional Cancer Registries; Cancer Res Treat. 2026;58(2):349-367. Published online March 23, 2026; DOI: https://doi.org/10.4143/crt.2026.298

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 2023, with international comparisons.
Materials and Methods
Cancer incidence, survival, and prevalence rates were calculated using the Korea National Cancer Incidence Database (1999-2023), with survival follow-up until December 31, 2024. Mortality data were obtained from the Ministry of Data and Statistics, while international comparisons were based on GLOBOCAN data.
Results
In 2023, 288,613 newly diagnosed cancer cases (age-standardized rate [ASR], 288.6 per 100,000) and 85,271 deaths from cancer (ASR, 64.3 per 100,000) were reported. Among the incident cases, 145,452 (50.4%) were aged 65 years or older. Prostate cancer became the most common cancer among men for the first time. The proportion of localized-stage cancers increased from 45.6% in 2005 to 51.8% in 2023. Korea had the lowest cancer mortality among countries with similar incidence rates and the lowest mortality-to-incidence ratios for stomach, colorectal, and breast cancer. The 5-year relative survival rate (2019-2023) was 73.7% overall and 92.7% for localized-stage cancers. Over 2.73 million prevalent cases were identified in 2023, representing 5.3% of the Korean population.
Conclusion
These findings indicate that Korea’s cancer control efforts have contributed to early detection and improved survival outcomes. As Korea enters a super-aged society in 2025, cancer burden will continue to increase, requiring sustained and adaptive cancer control strategies.

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Prediction of Cancer Incidence and Mortality in Korea, 2026: Kyu-Won Jung, Mee Joo Kang, Eun Hye Park, E Hwa Yun, Hye-Jin Kim, Jeong-Eun Kim, Kui Sun Choi, Han-Kwang Yang; Cancer Res Treat. 2026;58(2):368-375. Published online March 23, 2026; DOI: https://doi.org/10.4143/crt.2026.289

Abstract PDF PubReader ePub: Purpose
This study aimed to project cancer incidence and mortality for 2026 to estimate Korea’s current cancer burden.
Materials and Methods
Cancer incidence data from 1999 to 2023 were obtained from the Korea National Cancer Incidence Database, while cancer mortality data from 1993 to 2024 were acquired from the Ministry of Data and Statistics. 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 the projected age-specific rates by the anticipated age-specific population for 2026. 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 308,876 new cancer cases and 86,317 cancer deaths are expected in Korea in 2026. 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 63.5% of all newly diagnosed cancers. Lung cancer is expected to be the leading cause of cancer-related deaths, followed by liver, colorectal, pancreatic, gallbladder, and stomach cancers, together comprising 65.9% of all cancer deaths.
Conclusion
Korea’s cancer burden continues to shift toward malignancies prevalent in older populations. The sustained increase in prostate cancer among men and the rising mortality impact of pancreatic cancer reflect structural changes in the national cancer profile amid rapid population aging.

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Spatial Interactions of CD103+ Tissue-Resident Memory T Cells in the Tumor Periphery Are Associated with Clinical Outcomes in Triple-Negative Breast Cancer Following Neoadjuvant Chemotherapy: Hyun Lee, Byung-Kwan Jeong, Gyungyub Gong, Miseon Lee, Hee Jin Lee; Received December 29, 2025 Accepted March 14, 2026 Published online March 18, 2026; DOI: https://doi.org/10.4143/crt.2025.1416 [Accepted]

Abstract PDF Supplementary Material: Purpose
Triple-negative breast cancer (TNBC) is an aggressive subtype with poor prognosis. CD103+ tissue-resident memory T (TRM) cells are crucial for anti-tumor immunity in TNBC. We investigated whether their spatial interactions with other T-cells influence clinical outcomes, particularly following neoadjuvant chemotherapy (NAC).
Materials and Methods
This retrospective study analyzed 182 TNBC patients (98 NAC-treated; 84 non-NAC). Using Opal™ multiplex immunohistochemistry data and the Spatial Image Analysis of Tissues (SPIAT) R package, we analysed spatial interactions between CD103+ cells and other T cell subsets (CD45RO, CD8, CD4, PD-1) in central/peripheral tumor regions. Normalized mixing score (NMS) quantified spatial interactions.
Results
NMS-based clustering revealed two distinct CD103+ cell interaction patterns—Cluster 1 (low NMS) characterized by weaker and Cluster 2 (high NMS) by stronger spatial interactions between CD103+ and other T cell subsets. In the NAC group, Cluster 2 in the tumor periphery was associated with lower pathologic stage (p=0.002), higher stromal tumor-infiltrating lymphocyte level (p=0.031), and significantly improved recurrence-free survival (p=0.028) and overall survival (p=0.018) compared to Cluster 1. Central tumor region clustering patterns had no association with prognosis. No significant survival-related differences were observed in the non-NAC group according to NMS-based clustering.
Conclusion
Spatial interaction patterns between CD103+ and other T cell subsets in the tumor periphery influence clinical outcomes in NAC-treated TNBC patients. Analysing such spatial relationships between T cells, rather than their presence alone, may provide additional prognostic information for patients undergoing NAC.

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Korean Colorectal Cancer Screening Guidelines for Asymptomatic, average-Risk Adults: The 2025 Revision: EunKyo Kang, Jae Myung Cha, Seo Young Kang, Kiheon Lee, Su Young Kim, Younghoon Kim, An Na Seo, Hyo-Jin Kang, Jong Keon Jang, Kwang-Pil Ko, Aesun Shin, Dae Kyung Sohn, Youngki Hong, Eun-Jung Cho, Minje Han, Soo Young Kim, Hyeon Ji Lee, Chang Kyun Choi, Mina Suh; Received January 5, 2026 Accepted February 27, 2026 Published online March 13, 2026; DOI: https://doi.org/10.4143/crt.2026.014 [Accepted]

Abstract PDF: Purpose
To develop the 2025 update to the Korean colorectal cancer (CRC) screening guidelines by systematically assessing recent evidence, integrating domestic data, and addressing changes since the 2015 guideline revision, and accordingly, provide an evidence-based standard for clinicians and policymakers.
Materials and Methods
A multidisciplinary committee developed the guidelines using the Grading of Recommendations, Assessment, Development and Evaluation methodology. The process involved establishing three Key Questions (KQs) focused on efficacy, accuracy, and optimal age and interval for screening. A systematic review of international guidelines and primary literature (327 studies included) was conducted. A utility-based analysis using the Markov model was also performed to determine optimal screening ages and intervals.
Results
The review identified high-certainty evidence for Fecal Immunochemical Test (FIT) in reducing CRC mortality and moderate-certainty evidence for colonoscopy. Evidence for CT colonography (CTC) and stool DNA testing showed very low certainty. Based on this synthesis and cost-utility analysis, the committee conditionally recommends screening for asymptomatic, average-risk adults aged 45–74 years using either colonoscopy every 10 years or FIT every 1–2 years. CTC and stool DNA testing were not recommended owing to insufficient evidence.
Conclusion
The 2025 Korean Guidelines for Colorectal Cancer Screening provide the latest evidence-based recommendations tailored to the domestic context. By conditionally adopting both colonoscopy and FIT for individuals aged 45–74 years, these guidelines aim to optimize public health outcomes and reduce the colorectal cancer burden in South Korea.

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Conditional Relative Survival and Competing Mortality in Surgically Treated Patients with Localized and Regional Kidney Cancer in Korea: A Nationwide Cohort Study: Hyun Bin Shin, Dong Wook Shin, In Young Cho, Junhee Park, Jung Jin Hyung, Kyungdo Han, Jinsung Park; Received May 24, 2025 Accepted March 5, 2026 Published online March 9, 2026; DOI: https://doi.org/10.4143/crt.2025.557 [Accepted]

Abstract PDF: Purpose
To investigate the 5-year conditional relative survival and competing mortality in surgically treated patients with localized and regional kidney cancer.
Materials and Methods
Using a nationwide population-based database, the Korea Clinical Data Utilization Network for Research Excellence, conditional relative survival conditioned on 1 to 3 years of survival after diagnosis was measured. These rates were stratified by age, sex, socioeconomic status, comorbidities, and treatment received. Cause of death and estimated cause-specific mortality were also described and considered with competing risks.
Results
This study included a total of 19,749 newly diagnosed patients with kidney cancer who underwent surgical treatment from 2013 to 2019. The baseline conditional relative survival rates for the entire cohort, patients with localized disease, and patients with regional disease were 97.2%, 99.4%, and 82.6%, respectively. After one year, these rates increased to 99.4%, 100.0%, and 95.3%, respectively. Patients who underwent surgery only had the highest baseline conditional relative survival rates (99.3%) compared with those who received surgery with radiotherapy (74.0%), with chemotherapy (38.9%), and with chemotherapy and radiotherapy (16.2%). Specifically, patients who underwent robotic surgery or partial nephrectomy showed higher baseline conditional relative survival rates (>100%) than others. Furthermore, kidney cancer was the leading cause of death (49.6%), followed by other types of cancer and cardiovascular disease. Over time, kidney cancer-specific mortality decreased.
Conclusion
Conditional survival after surgery for localized or regional kidney cancer was high and improved over time. These findings indicate that long-term prognosis varies by stage and patient characteristics and should inform postoperative surveillance.

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Effect of Smoking Cessation Duration on Lung Cancer Incidence: A Nationwide Retrospective Cohort Study in Korea: Myeong Geun Choi, Min-Ho Kim, Hong Jin Kim, Eun Mi Chun; Received October 10, 2025 Accepted February 25, 2026 Published online February 26, 2026; DOI: https://doi.org/10.4143/crt.2025.1099 [Accepted]

Abstract PDF: Purpose
While smoking cessation is known to reduce lung cancer risk, the extent to which smoking cessation duration mitigates lung cancer risk remains unclear. This study aimed to analyze the association between smoking cessation duration and the reduction in lung cancer incidence using large-scale health insurance data from Korea.
Materials and Methods
In this retrospective cohort study, we utilized the cohort from the Korea National Health Insurance Corporation. Approximately 50% of the adults aged ≥50 years who underwent health examinations in 2009–2013 were randomly sampled and followed using medical and health examination records. The participants were classified into three groups: never-smokers, former smokers, and current smokers, and the incidence rates of lung cancer were compared among these groups.
Results
We analyzed 165,512 individuals selected through propensity score matching (82,756 never-smokers, 41,378 former smokers, and 41,378 current smokers). Lung cancer risk significantly decreased after two years of smoking cessation (2–3 years after cessation: hazard ratio 0.760, p<0.001) but remained higher than that of never-smokers for up to 10 years. Subgroup analyses revealed similar tendencies among males, whereas no consistent patterns were observed among females. Moreover, a longer duration of smoking cessation was generally required for heavy smokers (≥20 pack-years) than for light smokers (<20 pack-years).
Conclusion
This nationwide cohort study highlights the significant impact of smoking cessation duration on lung cancer risk, emphasizing the substantial benefits of even short-term cessation regardless of prior smoking history.

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Assessing Radiation Pneumonitis Through Functional Lung Imaging: A Single Photon Emission Computed Tomography (SPECT)-Based Approach in Lung Cancer: Joo-Hyun Chung, Soo Jin Lee, Ji Young Kim, Hae Jin Park; Received November 13, 2025 Accepted February 18, 2026 Published online February 19, 2026; DOI: https://doi.org/10.4143/crt.2025.1248 [Accepted]

Abstract PDF: Purpose
To develop models to assess the risk of symptomatic radiation pneumonitis (SRP) (Common Terminology Criteria for Adverse Events 4.03 grade ≥ 2) in lung cancer patients by utilizing single-photon emission computed tomography (SPECT) for functional lung volume identification and dosimetric analysis.
Materials and Methods
This retrospective study included 71 lung cancer patients who underwent SPECT before radiotherapy from 2018 to 2024. Perfusion and ventilation SPECT images were co-registered with planning CT to define functional and anatomical lung volumes. Functional lung was defined as voxels with ≥ 20% of the maximum intensity on SPECT. Models to assess the risk of SRP were constructed using Cox regression and evaluated using corrected Akaike Information Criterion (AICc) and time-dependent receiver operating characteristic analysis.
Results
At a median follow-up of 16.8 months, 19 of 71 patients (26.8%) developed SRP. Factors significantly associated with SRP risk included planning target volume ≥ 150 mL, percentage of total perfusion-defined functional lung receiving ≥ 10 Gy (pVf10) exceeding that of total anatomical lung receiving ≥ 10 Gy (V10), percentage of total ventilation-defined lung receiving ≥ 10 Gy (vVf10) ≥ 45%, and ipsilateral vVf10 ≥ 60% (p=0.004, 0.004, 0.024, and 0.007, respectively). Among the three models, the model incorporating additional ventilation-based parameters demonstrated the best performance (AICc = 85.81, area under the curve = 0.819).
Conclusion
SPECT-based dosimetric parameters derived from perfusion and ventilation are significantly associated with the risk of SRP. Incorporating SPECT may improve risk stratification and enable lung-sparing strategies.

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A Phase I/II Trial to Evaluate the Safety and Efficacy of Continuous Positive Airway Pressure in Volumetric Modulated Arc Therapy for Breast Cancer: Jung Bin Park, Tosol Yu, Jaeman Son, Chul-Won Choi, Seho Kwon, Hyun-Woo Shin, Hak Jae Kim, Ji Hyun Chang; Received November 22, 2025 Accepted January 25, 2026 Published online January 26, 2026; DOI: https://doi.org/10.4143/crt.2025.1281 [Accepted]

Abstract PDF: Purpose
This phase I/II study aimed to evaluate the tolerability and the organ-sparing effects of continuous positive airway pressure (CPAP) in breast cancer radiotherapy (RT).
Materials and Methods
We conducted a prospective, single-institutional trial approved by the Ministry of Food and Drug Safety of South Korea. Patients with breast cancer who received postoperative RT underwent 4D-CT simulation and treatment planning under both free breathing (FB) and CPAP-assisted breathing (WC), with a target pressure of 20 cm H₂O. Adverse events (AEs) were evaluated, and dosimetric parameters of organs at risk and heart position change were compared between the FB and WC arms.
Results
Among 20 enrolled patients, four withdrew due to discomfort during simulation. During the trial, no CPAP-related AEs greater than grade 2 were observed. Compared to FB, CPAP reduced the mean heart dose by 33.8% (p < 0.001), as well as V₅–V₃₀ for both the left ventricle and left anterior descending artery (all p < 0.05). It also led to significant reductions in V₅–V₄₀ and the mean ipsilateral lung dose, including a 4.4% reduction in V₂₀ (all p < 0.001). The heart centroid shifted rightward (4.8 mm), ventrally (8.1 mm), and caudally (16.3 mm) with CPAP, displacing the heart away from the RT field.
Conclusion
CPAP demonstrated both safety and efficacy for breast cancer RT, achieving significant reductions in cardiac and pulmonary radiation exposure. These findings support further investigation of CPAP as a novel respiratory motion management strategy. Future studies are warranted to identify optimal CPAP pressure levels to facilitate broader clinical implementation.

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Salidroside-Loaded, TMTP1-Modified CSC-Exosomes Reprogram the PI3K/AKT/mTOR Axis to Overcome PD-1 Resistance in Breast Cancer: Faxiang Yin, Xin Jin, Ligong Zhang, Qiang Xie, Jun Qian; Received August 8, 2025 Accepted January 11, 2026 Published online January 14, 2026; DOI: https://doi.org/10.4143/crt.2025.849 [Accepted]

Abstract PDF: Purpose
To elucidate how Salidroside-loaded, oligopeptide-modified tumor exosomes (Salidroside@T-exo) rewire the PI3K/AKT/mTOR axis to remodel the immune microenvironment (IME) and reverse acquired PD-1 resistance in breast cancer.
Materials and Methods
CSC-exosomes were surface-engineered with TMTP1 peptide and electroporated with Salidroside. PD-1-resistant MA782/5s-8101-R cells and an orthotopic mouse model were used. Multi-omics, flow cytometry, ELISA, immunofluorescence, in vivo imaging, and molecular assays examined immune and signaling outcomes.
Results
Salidroside@T-exo restored T-cell IFN-γ and GZMB secretion, suppressed CD8+ T-cell apoptosis, and inhibited p-PI3K/p-AKT/p-mTOR in T cells. CSC migration, invasion, and stemness (OCT4, NANOG, SOX2) were markedly reduced. Tumor growth, Ki-67 index, and CSC frequency dropped while TUNEL-positive cells rose.
Conclusion
Salidroside@T-exo reverses PD-1 blockade resistance by simultaneously inhibiting PI3K/AKT/mTOR signaling in T cells and eradicating breast CSCs, offering a clinically translatable strategy for refractory breast cancer immunotherapy.

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Radiomics-Based Prediction of Lymphedema after Radiotherapy in Breast Cancer: Integrating Clinical and Dosimetric Features: Jae Sik Kim, Seung Hyuck Jeon, Bum-Sup Jang, Jin Ho Kim, Ji Hyun Chang, Dowook Kim, Kyung Hwan Shin; Received September 9, 2025 Accepted January 11, 2026 Published online January 13, 2026; DOI: https://doi.org/10.4143/crt.2025.985 [Accepted]

Abstract PDF: Purpose
Arm lymphedema is a common, debilitating complication in patients with breast cancer undergoing postoperative radiotherapy (PORT). Although clinical and dosimetric factors have been used for risk prediction, radiomics offers a novel approach for improving the predictive accuracy.
Materials and Methods
We designed a predictive model for lymphedema using clinical, dosimetric, and radiomic features. We included 532 patients (399 training and 133 testing) who underwent breast cancer surgery followed by PORT. Radiomic features were extracted from axillary levels I, II, III, and supraclavicular regions, which were automatically contoured on PORT-planning computed tomography scans. Least absolute shrinkage and selection operator regression was used for feature selection. Model performance was evaluated using the area under the curve (AUC), accuracy, sensitivity, and specificity.
Results
The Combined model integrating clinical, dosimetric, and radiomic features showed higher predictive performance (AUC: training 0.783, test 0.767, total 0.779) than the Clinical/Dosimetric (AUC: training 0.730, test 0.671, total 0.717) and Radiomics-only (AUC: training 0.721, test 0.668, total 0.708) models. The Combined model also achieved a higher accuracy (training 78.9%, test 78.2%, total 78.8%), sensitivity (training 74.6%, test 62.5%, total 72.0%), and specificity (training 79.7%, test 80.3%, total 79.9%) than the other models. DeLong’s test confirmed that the Combined model significantly outperformed the Clinical/Dosimetric model (p=0.036 in training and p=0.010 in all datasets).
Conclusion
Integrating radiomic features with clinical and dosimetric factors showed potential to enhance lymphedema prediction in patients with breast cancer receiving PORT. This model can potentially guide personalized treatment strategies and improve patient outcomes.

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Unplanned Readmission among Patients with Advanced Cancer on Active Treatment: Multi-Center, Retrospective Study: Sun Young Lee, Hong Jun Kim, Shin Hye Yoo, In Gyu Hwang, Beodeul Kang, Yu Jung Kim, Dalyong Kim, Chung Ryul Oh, Sun Kyung Baek, Eun Hee Jung, Go-Un Woo, Woohyeon Cho, In Young Hwang, Kyae Hyung Kim, Min Sun Kim, Belong Cho; Received March 19, 2025 Accepted December 30, 2025 Published online January 2, 2026; DOI: https://doi.org/10.4143/crt.2025.330 [Accepted]

Abstract PDF: Purpose
Unplanned readmissions of patients with cancer increase healthcare costs and disrupt care. Although well-studied in surgical oncology, data on patients receiving active treatment for advanced cancer remain limited. This study examined the causes, clinical characteristics, and outcomes of unplanned readmissions.
Materials and Methods
This retrospective, multicenter study included patients with advanced solid tumors from six South Korean university hospitals who had unplanned readmissions within 1 month of prior hospitalization in 2019. Patients with terminal cancer who did not receive active treatment were excluded. Readmissions were categorized as Cancer Progression (e.g., worsening symptoms), treatment-related (e.g., therapy complications), or other (e.g., non-cancer conditions). Additional unplanned hospital use within 1 month post-discharge was analyzed in survivors with 6-month follow-up data.
Results
Among the 542 patients, readmissions were classified as cancer progression (42.6%), treatment-related (37.3%), or other (20.1%). The cancer progression group had the longest hospital stay (median, 12 days) and the highest mortality (23.4%). The Treatment-Related group had shorter stays (8 days) and lower mortality (8.4%). Among the 445 survivors, 24.9% had unplanned hospital visits within 1 month post-discharge. Home discharge increased the likelihood of these events (adjusted odds ratio: 4.82 for readmissions, 2.65 for emergency department visits).
Conclusion
Cancer progression was the leading cause of readmission and was associated with prolonged hospital stays and high mortality rates. Home discharge is a key predictor of early additional unplanned hospital visits, indicating the need for careful post-discharge monitoring in this population.

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Smoking, Alcohol, and Abdominal Obesity Increase Gastric Cancer Risk after Helicobacter pylori Eradication: Joo Hyun Lim, Cheol Min Shin, Kyungdo Han, Jin-Hyung Jung, Jinju Choi, Eun Hyo Jin, Seung Joo Kang, Dong Ho Lee; Received November 3, 2025 Accepted December 30, 2025 Published online January 2, 2026; DOI: https://doi.org/10.4143/crt.2025.1200 [Accepted]

Abstract PDF: Purpose
Helicobacter pylori is the single most important risk factor for gastric cancer (GC). However, H. pylori eradication (HPE) does not eliminate risk of GC. To clarify the association of lifestyle factors with GC risk after HPE.
Materials and Methods
Using the Korean National Health Insurance Services (NHIS) database, adult individuals who claimed HPE between 2010 and 2016 were analyzed. The adjusted hazard ratios (aHR) for GC were analyzed according to the lifestyle status including smoking (never; light [<10PY]; moderate [10-20PY]; heavy [≥20PY]), alcohol (none; mild [<30g/day]; heavy [30g/day]), and abdominal obesity by using Cox proportional hazard model.
Results
During a median follow-up period of 6.7 years, 9,754 individuals were newly diagnosed with GC among the total of 1,282,702 subjects. Compared with never smokers, moderate (aHR 1.12 [95%CI 1.04-1.20]) and heavy smokers (1.34 [1.27-1.42]) had greater risks of post-HPE GC with dose-response manner. Heavy drinkers had increased risk of GC (1.23 [1.15-1.32]) compared with non-drinkers, and those with abdominal obesity had slightly elevated GC risk compared with those without that (1.11 [1.06-1.15]). In subgroup analyses, those who had HPE at age ≥ 55 were shown to be more affected by the unhealthy lifestyles (smoking [p-for-interaction <0.01], alcohol [0.03], and abdominal obesity [0.03]). Also, male showed greater risk increase by smoking habit [p-for-interaction 0.02] than female.
Conclusion
Unhealthy lifestyles like smoking, alcohol, and abdominal obesity were shown as risk factors for post-HPE GC. Those with late HPE were more likely to be affected by unhealthy lifestyles.

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Identification of Tumor Doubling Time-Related Subtypes and Construction of Risk Models to Predict Prognosis and Immunological Features in Breast Cancer: Yuehong Xu, Hongbo Li, Lulu Yang, Rongfei Wang; Received August 27, 2025 Accepted December 30, 2025 Published online December 31, 2025; DOI: https://doi.org/10.4143/crt.2025.948 [Accepted]

Abstract PDF: Purpose
Breast cancer (BRCA)'s molecular heterogeneity complicates prognosis and treatment. Tumor Doubling Time (TDT), a critical growth rate metric with clinical and prognostic significance, offers untapped potential as a biomarker to decode heterogeneity and improve therapeutic strategies.
Materials and Methods
Based on transcriptomic and clinical data from TCGA and GEO, this study analyzed BRCA. Through differential expression and survival analyses, differentially expressed tumor doubling time-related genes (TDTRGs) with prognostic significance were identified. Consensus clustering using these genes defined two molecular subtypes. A prognostic risk model was constructed and validated through LASSO and multivariate Cox regression. Comprehensive evaluation was performed on these molecular subtypes and risk groups, encompassing immune infiltration (ssGSEA, CIBERSORT, ESTIMATE), mutational burden, response to immunotherapy (IMvigor210), and drug sensitivity (CellMiner, pRRophetic).
Results
This study constructed and validated an 8 gene prognostic risk model demonstrating robust predictive performance in both training (AUCs: 1-year=0.703, 3-year=0.693, 5-year=0.671) and validation cohorts. The low-risk group showed significantly enhanced immune cell infiltration, elevated immune checkpoint expression, and improved response to immunotherapy. Conversely, the high-risk group displayed increased tumor purity, metabolic reprogramming (e.g., respiratory electron transport), genomic instability, higher tumor mutational burden, and differential drug sensitivity (e.g., resistance to Gemcitabine/Tamoxifen).
Conclusion
This study establishes a novel TDTRGs framework for BRCA molecular classification and validated prognostic stratification. It reveals key disparities in immune microenvironment and genomic stability, enhancing understanding and guiding personalized therapeutic strategies.

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Redefining HER2 in Breast Cancer: From Conventional Positivity to Low and Ultralow in the New Era of Antibody-Drug Conjugates: Jiwon Koh, Seock-Ah Im; Cancer Res Treat. 2026;58(1):15-25. Published online December 18, 2025; DOI: https://doi.org/10.4143/crt.2025.1182

Abstract PDF PubReader ePub

Human epidermal growth factor receptor 2 (HER2) has evolved from a poor prognostic factor to one of the most impactful predictive biomarkers in oncology. The introduction of trastuzumab established HER2 as a binary determinant of therapy, with HER2 immunohistochemistry (IHC) becoming the treatment-guiding diagnostic assay. However, the emergence of antibody-drug conjugates (ADCs), particularly trastuzumab deruxtecan, has challenged this paradigm by demonstrating activity in tumors with low and even ultralow HER2 expression. This review outlines the evolution of HER2 testing, from its historical discovery and early assay variability to the ADC era, where categories such as HER2-low and HER2-ultralow have emerged. We highlight key challenges: poor reproducibility at the lower end of IHC scoring, instability of HER2 status across timepoints and between primary and metastatic tumors, and no consistent biological distinction between low, ultralow, and null. Efforts to improve reliability—including structured training, high-sensitivity assays, RNA-based methods, and artificial intelligence-assisted pathology—are summarized. Finally, we reconsider the therapeutic implications of ADCs, with the question of whether the benefit parallels HER2 expression or extends into HER2-null disease. HER2 exemplifies how biomarker interpretation evolves with drug development. As new ADCs target additional antigens, pathologists must balance trial-driven categories with biologic reproducibility to ensure diagnostics remain aligned with therapeutic advances.

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Mechanisms of Resistance and Synergy: The Role of Tumor Microenvironment in HER2-Low Breast Cancer Therapy
Youssef Basem, Alamer Ata, Abanoub Sherif, Shaimaa Abdel-Ghany, Borros Arneth, Hussein Sabit
Pharmaceuticals.2026; 19(4): 541. CrossRef

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1 Crossref

Immunosuppressive Tumor Microenvironment in Colorectal Cancer Lung Metastases: Implications for Recurrence After Metastasectomy: Minsuk Kwon, Min-Kyue Shin, Minae An, Yeong Jeong Jeon, Tae Hee Hong, Jung Kyong Shin, Sung Hee Lim, Yoonah Park, Yong Beom Cho, Seung Tae Kim, Yong Soo Choi, Jeeyun Lee; Received July 3, 2025 Accepted December 8, 2025 Published online December 17, 2025; DOI: https://doi.org/10.4143/crt.2025.691 [Accepted]

Abstract PDF Supplementary Material: Purpose
Colorectal cancer (CRC) lung metastases exhibit high recurrence rates after resection, underscoring the need for improved therapeutic strategies. This study aimed to characterize the tumor microenvironment (TME) of CRC lung metastases and identify the factors associated with recurrence.
Materials and Methods
Fifteen CRC patients who underwent lung metastasectomy were enrolled. Multiplex immunohistochemistry (IHC), whole exome sequencing, transcriptome profiling, and single-cell RNA sequencing (scRNA-seq) were conducted on matched tumor, adjacent and distant normal lung tissues. Immune cell populations and gene expression profiles were analyzed and correlated with clinical recurrence outcomes.
Results
Exome and transcriptome analyses revealed frequent TP53, KRAS, and APC mutations. Most tumors corresponded to consensus molecular subtypes 2 and 4, characterized by immune-depleted and fibrotic features. Tumors showed downregulation of effector T and NK cell signatures. IHC revealed reduced density and increased distance of CD8+ T cells and macrophages from the epithelial cells. scRNA-seq demonstrated increased regulatory T cells and decreased NK and effector T cells in tumor. Tumor-associated macrophages (TAMs), particularly SPP1 (osteopontin)-expressing subsets, were markedly enriched in tumor and correlated with suppressed effector T cella activity. High SPP1 expression was associated with early recurrence and poor overall survival. Patients with recurrence had higher proportion of PD-1+ CD8+ T cells in adjacent normal tissues.
Conclusion
Immunosuppressive features including enrichment of SPP1+ TAMs and depletion of effector T and NK cells contribute to recurrence after CRC lung metastasectomy. Therapeutic strategies targeting both TAMs and T cells may enhance clinical outcomes in this patient population.

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Silence of Transmembrane Channel-Like 5 Inhibits Cell Proliferation, Migration, and Invasion While Promoting Apoptosis Via Deactivating the AKT Pathway in Breast Cancer: Jinnan Wan, Yang Li, Zhimin Liu; Received July 30, 2025 Accepted December 7, 2025 Published online December 9, 2025; DOI: https://doi.org/10.4143/crt.2025.805 [Accepted]

Abstract PDF: Purpose
Transmembrane channel-like 5 (TMC5) plays a tumor-promoting role in the progression of various tumors. However, its effect on regulating breast cancer cell function remains scarce. The current study aimed to evaluate the effect of TMC5 silence on the proliferation, apoptosis, migration, and invasion of breast cancer cell lines.
Materials and Methods
TMC5-specific small interfering RNA (siTMC5) and siNC were transfected into MDA-MB-231 and MCF-7 cell lines; subsequently, the 740Y-P was co-cultured. Then, the proliferation, apoptosis, migration, invasion, and p-AKT expression were determined.
Results
In MDA-MB-231 and MCF-7 cell lines, silence of TMC5 could reduce the proliferation rate at 48 hours (h) and 72 h, migration rate, and invasion rate, while elevate the apoptosis rate. Besides, silence of TMC5 could decrease the p-AKT/AKT expression. The combination of 740Y-P with the silence of TMC5 could reversely increase the proliferation rate at 48h and 72h, migration rate, and invasion rate compared with the silence of TMC5 only. The apoptosis rate showed the opposite trend.
Conclusion
The silence of TMC5 could inhibit the proliferation, migration, and invasion while promoting the apoptosis of breast cancer, while more in vivo validation is needed to explore its potential to be a treatment target for patients with breast cancer.

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Zolbetuximab Plus Chemotherapy as First-Line Treatment in Patients with Claudin 18.2-Positive, HER2-Negative, Locally Advanced Unresectable or Metastatic Gastric or Gastroesophageal Junction Adenocarcinoma: Korean Population Subgroup—Combined Efficacy and Safety Analysis from SPOTLIGHT and GLOW: Keun-Wook Lee, Sang Cheul Oh, Jong Gwang Kim, Sun Jin Sym, Byoung Yong Shim, Seok Yun Kang, In-Ho Kim, Jwa Hoon Kim, Hong Jae Chon, Sang-Hee Cho, Eun-Kee Song, Do-Youn Oh, Jin-Soo Kim, Young Iee Park, Won Ki Kang, Hyung-Don Kim, Janise Lee, Miri Yi, Min-Hee Ryu; Received August 28, 2025 Accepted December 4, 2025 Published online December 5, 2025; DOI: https://doi.org/10.4143/crt.2025.935 [Accepted]

Abstract PDF: Purpose
The phase 3 SPOTLIGHT and GLOW trials, in patients with claudin 18 isoform 2–positive, human epidermal growth factor receptor 2–negative, locally advanced unresectable or metastatic gastric or gastroesophageal junction adenocarcinoma, demonstrated statistically significant and clinically meaningful improvement in progression-free survival (PFS) and overall survival (OS) with first-line zolbetuximab plus chemotherapy versus placebo plus chemotherapy. This analysis evaluated efficacy and safety in the Korean subgroup from SPOTLIGHT and GLOW.
Materials and Methods
Patients were randomized 1:1 to receive zolbetuximab plus chemotherapy or placebo plus chemotherapy (mFOLFOX6 [modified folinic acid, 5-fluorouracil, and oxaliplatin] or CAPOX [capecitabine and oxaliplatin]). Primary endpoint was PFS, assessed per RECIST v1.1 by independent review committee. Other efficacy and safety parameters were assessed.
Results
The Korean subgroup consisted of 49 patients in the zolbetuximab group and 47 in the placebo group. Median PFS (95% confidence interval [CI]) was 12.3 months (7.3-15.3), and median OS was 30.5 months (16.1-45.5) with zolbetuximab versus 8.1 months (4.2-10.4) and 15.8 months (11.8-19.7) with placebo, respectively. Most common TEAEs in patients who received zolbetuximab versus placebo were nausea (79.6% vs. 53.2%), vomiting (55.1% vs. 21.3%), and decreased appetite (53.1% vs. 23.4%). Treatment-related TEAEs led to discontinuation of zolbetuximab and placebo in 4.1% and 2.1% of patients, respectively.
Conclusion
Zolbetuximab plus chemotherapy demonstrated favorable PFS and OS versus placebo plus chemotherapy in the Korean subgroup, with numerically greater efficacy compared with the overall pooled population. This may be potentially attributable to low rates of zolbetuximab discontinuation and toxicity management.

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Association between FGFR2b Positivity and Survival Outcomes of Patients with Gastric Cancer Treated with First-Line Nivolumab Plus Chemotherapy: Hyung-Don Kim, Heonwoo Lee, Hyungeun Lee, Meesun Moon, Jaewon Hyung, Jungeun Ma, Young Soo Park, Min-Hee Ryu; Received June 6, 2025 Accepted November 22, 2025 Published online November 24, 2025; DOI: https://doi.org/10.4143/crt.2025.598 [Accepted]

Abstract PDF: Purpose
Fibroblast growth factor receptor 2b (FGFR2b) is a promising therapeutic target in gastric cancer; however, its clinical relevance in immune checkpoint inhibitor (ICI)-based chemotherapy remains unclear. Therefore, this study aims to evaluate the expression pattern and predictive value of FGFR2b in patients undergoing first-line nivolumab plus chemotherapy.
Materials and Methods
This single-center study included 503 patients diagnosed with gastric cancer. Among them, 296 underwent nivolumab-chemotherapy, while 207 underwent chemotherapy alone. FGFR2b expression was assessed via immunohistochemistry using samples collected after mid-2022. FGFR2b positivity was defined as membranous staining intensity of 2+/3+ in ≥ 1% of tumor cells, with ≥ 10% as overexpression, and 1–9% as low expression.
Results
FGFR2b overexpression and positivity were identified in 9.3% and 18.7% of cases, respectively. Discordance between paired biopsy and surgical samples was observed (20.0% and 40.0% for overexpression and positivity, respectively), indicating marked intratumoral heterogeneity. Among patients who underwent nivolumab-chemotherapy, FGFR2b overexpression and low expression were associated with favorable survival trends compared to those of FGFR2b-negative cases. These associations were not observed in patients treated with chemotherapy alone. Compared to chemotherapy alone, nivolumab-chemotherapy was associated with a greater survival benefit in patients with FGFR2b positivity. Multivariate interaction analyses revealed a significant interaction between FGFR2b expression and nivolumab-based chemotherapy.
Conclusion
FGFR2b expression exhibits substantial intratumoral heterogeneity in gastric cancer and may be linked to favorable outcomes in patients undergoing first-line ICI plus chemotherapy. Therefore, future studies should validate this finding, along with mechanistic investigations.

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Kidney Failure–Related Mortality in Patients with Cancer: Insights from the Cancer Public Library Database in South Korea: Chang Seong Kim, Sang Heon Suh, Hong Sang Choi, Eun Hui Bae, Seong Kwon Ma, Jin Hyung Jung, Bongseong Kim, Kyung-Do Han, Soo Wan Kim; Received April 29, 2025 Accepted November 22, 2025 Published online November 24, 2025; DOI: https://doi.org/10.4143/crt.2025.466 [Accepted]

Abstract PDF Supplementary Material

Purpose
Kidney failure is associated with an increased risk of death. However, since the impact of kidney failure on overall and cancer-related mortality among individuals with cancer remains unclear, we investigated kidney failure–related mortality in patients with cancer, stratified by various cancer types.
Materials and Methods
A total of 1,307,680 participants newly diagnosed with cancer were identified from the Cancer Public Library Database. We analyzed data from patients with preexisting kidney failure before cancer diagnosis and compared their mortality risk with patients without kidney failure using multivariable Cox proportional hazard models.
Results
All-cause and cancer-related mortality was significantly higher in the kidney failure group. Preexisting kidney failure was associated with an increased risk of mortality in all cancer types after adjusting for comorbidities and treatment modalities (adjusted hazard ratio [aHR] of all-cause death 1.75, 95% CI 1.70–1.81; aHR of cancer-related death 1.27, 95% CI 1.22–1.32). Among specific cancer types, thyroid and breast cancers showed the highest mortality risks of kidney failure, with thyroid cancer presenting the greatest risk. However, the risk of death was attenuated in liver, gallbladder, and lung cancers. Furthermore, aHRs were lower for mortality in metastatic cancer compared to localized and regional stages.
Conclusion
Preexisting kidney failure significantly increases the risk of all-cause and cancer-related death among cancer patients, particularly in localized cancer and specific cancer types.

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Adverse Renal Outcomes in Patients With Mesothelioma—A Territory‐Wide Real‐World Data
Wang Chun Kwok, James Chung Man Ho, Isaac Sze Him Leung, Desmond Yat Hin Yap
Cancer Medicine.2026;[Epub] CrossRef

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Skeletal Muscle Index to Red Cell Distribution Width Ratio: A Novel Prognostic Indicator for Patients with Stage I-III Colorectal Cancer: Jiahn Choi, Jeonghyun Kang; Received August 15, 2025 Accepted November 12, 2025 Published online November 17, 2025; DOI: https://doi.org/10.4143/crt.2025.884 [Accepted]

Abstract PDF: Purpose
Herein, a novel prognostic marker based on the skeletal muscle index (SMI) and red cell distribution width (RDW) for patients with colorectal cancer (CRC) was developed.
Materials and Methods
585 Patients with stage I–III CRC who underwent surgery between January 2004 and April 2011 were included. The ratio of SMI to RDW (SRR) was calculated, and patients were grouped into sex-specific quartiles (G1 to G4) based on SRR. The Kaplan-Meier method was employed to estimate survival differences, and the Cox proportional hazards model was applied to evaluate the association between SRR and overall survival (OS). The Concordance Index (C-index) was calculated to assess the individual and combined effects of SMI and RDW on survival.
Results
There was a significant difference in OS across SRR quartiles (G1: 65.0%, G2: 82.9%, G3: 84.1%, G4: 89.8%, p<0.001). G1 had worse OS compared to the other groups, and SRR was confirmed as an independent prognostic factor for OS (G1 vs. G2, HR=0.531, 95% CI=0.320-0.882, p=0.014; G1 vs. G3, HR=0.534, 95% CI=0.302-0.942, p=0.030; G1 vs. G4, HR=0.419, 95% CI=0.212-0.827, p=0.012). SRR demonstrated greater prognostic power for OS than SMI or RDW alone.
Conclusion
SRR is a novel and significant predictor of overall survival in patients with stages I–III CRC demonstrating greater prognostic power than either SMI or RDW alone.

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Dual-Functional PTX@Fe₃O₄ Nanobubbles: A Novel Theranostic Platform for Enhanced Ultrasound Imaging and Controlled Drug Delivery in Breast Cancer: Weiyang Lv, Xiaomei Ning, Chunxin Huang, Xing Li, Lianjie Bai, Xiaotong Wang, Zihan Wang, Yunna Song, Huilin Liu; Received September 26, 2025 Accepted November 16, 2025 Published online November 17, 2025; DOI: https://doi.org/10.4143/crt.2025.1055 [Accepted]

Abstract PDF: Purpose
This study aimed to develop a novel theranostic nanoplatform that integrates ultrasound imaging and controlled drug delivery for the treatment of breast cancer.
Methods
PTX@Fe₃O₄ nanobubbles (NBs) were synthesised via microfluidics. Characterisation included transmission electron microscopy, dynamic light scattering, drug release kinetics, phantom imaging and biocompatibility assays in vitro and in mice.
Results
The NBs exhibited uniform size (178 ± 12 nm), high drug loading (8.3%) and pH/ultrasound-responsive release (68.2% at pH 5.5+US). Ultrasound signal enhancement correlated linearly with concentration (R² = 0.988), with imaging duration three times longer than SonoVue. The system exhibited minimal haemolysis (<2%) and low cytotoxicity and induced S-phase arrest (68.2%) in MCF-7 cells. No significant toxicity was observed in mice at 10 mg Fe/kg.
Conclusion
PTX@Fe₃O₄ NBs represent a promising, biocompatible theranostic platform for image-guided breast cancer therapy.

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Changes in Uptake, Participant Disparities, and Screening Outcomes of the Korean National Lung Cancer Screening Program: A Five-Year Experience: Chang Kyun Choi, Na-Young Lee, Mina Suh, Kui Son Choi, Yeol Kim; Received January 15, 2025 Accepted November 6, 2025 Published online November 10, 2025; DOI: https://doi.org/10.4143/crt.2025.067 [Accepted]

Abstract PDF: Purpose
Low-dose computed tomography (LDCT) is effective in reducing lung cancer mortality among high-risk smokers. The Korean National Lung Cancer Screening Program (KNLCS), the world’s first nationwide lung cancer screening initiative using LDCT, was launched in 2019. This study aimed to evaluate the KNLCS uptake rates in relation to participants’ economic status and changes in positive screening rates across screening rounds.
Materials and Methods
Data from the National Health Insurance Service (NHIS) and National Cancer Screening Information System for 2019–2023 were analyzed. Eligible participants in the KNLCS were current smokers aged 54–74 years with a smoking history of at least 30 pack-years. The KNLCS provides counseling by physicians on screening results and smoking cessation. Screening uptake rates, counseling rates, and Lung CT Screening Reporting and Data System (Lung-RADS) distributions were assessed.
Results
Screening uptake rates increased from 24.7% in 2019 to 51.2% in 2023 (p < 0.001). Economic disparities were observed, with higher-income groups showing consistently higher uptake rates than lower-income group. Screening positive rates has been decreased from 9.1% in 2019 to 7.0% in 2023 according to increasing the proportion of subsequent screening participants. The inter-institutional variance in Lung-RADS category 4 decreased significantly over the years (p < 0.001).
Conclusion
The KNLCS rapidly increased screening uptake rates by systematically inviting eligible participants. Positive screening rates decreased primarily due to a reduction in Lung-RADS category 3 findings in subsequent rounds.

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