Cancer Research and Treatment

Accepted and E-pub version articles are published online before they appear in a regular issue of the journal. Accepted articles are PDF versions of manuscripts that have been peer reviewed and accepted for publication, but not yet copyedited or typeset, allowing readers the most rapid access to accepted papers. The accepted article remains on this page until the final proof version of the paper is posted in Epub Ahead-of Print page.
Accepted article is given its own Doi, so it can be citable as it has been linked to PubMed.

It may be cited as shown in the following example:
Park IH, Im SA, Jung KH, Sohn JH, Park YH, Lee KS, et al. Randomized Open Label Phase III Trial of Irinotecan Plus Capecitabine versus Capecitabine Monotherapy in Patients with Metastatic Breast Cancer Previously Treated with Anthracycline and Taxane: PROCEED Trial (KCSG BR 11-01). Cancer Res Treat. 2018 Feb 14 [Epub]. https://doi.org/10.4143/crt.2017.562.

Original Articles

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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Pilot Study for Feasibility of Onco-Geriatric Intervention Model in Older Patients with Cancer in a Tertiary Academic Hospital: Jin Won Kim, Jung-Yeon Choi, Woochan Park, Minsu Kang, Jeongmin Seo, Eun Hee Jung, Koung Jin Suh, Ji-Won Kim, Se Hyun Kim, Yu Jung Kim, Keun-Wook Lee, Sang-A Kim, Ji Yun Lee, Jeong-Ok Lee, Soo-Mee Bang, Kwang-il Kim, Jee Hyun Kim; Received January 20, 2025 Accepted March 11, 2025 Published online March 12, 2025; DOI: https://doi.org/10.4143/crt.2025.079 [Accepted]

Abstract PDF: Purpose
Older cancer patients face unique challenges due to age-related physiological changes, increasing their vulnerability to treatment-related toxicities. Geriatric assessment (GA) is a validated tool for optimizing care, yet there is no consensus on integrating geriatric interventions into oncology. This study evaluates the feasibility of a tailored onco-geriatric intervention model incorporating the KG-7 screening tool.
Materials and Methods
This prospective study included 30 patients aged ≥70 years with solid tumors undergoing adjuvant or palliative chemotherapy. Patients scoring ≤5 of KG-7 were eligible. Tailored interventions incorporating KG-7 included polypharmacy, functional status, mobility, nutrition, cognition, emotional well-being, insomnia, social support, and medical problem. KG-7, GA, and quality of life (QoL) were followed at 12 weeks.
Results
Participants (median age: 79.5 years) had colon (43.3%), pancreatic (23.3%), or gastric cancer (23.3%). At baseline, most patients showed independent ADL (100%)/IALD (90%). However, 93.3% had abnormal GA. Particularly, 86.7% were either malnourished or at risk of malnutrition. The most frequently identified intervention needs included polypharmacy (70.0%), nutritional support (60.0%), and emotional well-being (50.0%) with high adherence (100.0%, 88.9%, and 46.7%, respectively). At 12 weeks, KG-7 scores improved in 43.8% of patients, and 69.2% of GA domains were improved. QoL analysis revealed modest improvement in Global Health Status (mean difference 6.3, p=0.176). One-year survival rates were 92.3% and 79.4% for adjuvant and palliative groups, respectively.
Conclusion
The onco-geriatric intervention model incorporating KG-7 demonstrated high feasibility and potential to enhance clinical outcomes. Future studies should validate this approach in randomized trials to optimize care for older cancer patients.

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Special Articles

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; Received March 6, 2025 Accepted March 10, 2025 Published online March 11, 2025; DOI: https://doi.org/10.4143/crt.2025.263 [Accepted]

Abstract PDF: 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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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; Received March 7, 2025 Accepted March 10, 2025 Published online March 11, 2025; DOI: https://doi.org/10.4143/crt.2025.264 [Accepted]

Abstract PDF: 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 (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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Original Articles

Elevated SLC3A2 Expression Promotes the Progression of Gliomas and Enhances Ferroptosis Resistance through the AKT/NRF2/GPX4 Axis: Yuqian Zheng, Shaolong Zhou, Yiran Tao, Zimin Shi, Xiang Li, Xudong Fu, Jian Ma, Weihua Hu, Wulong Liang, Xinjun Wang; Received September 26, 2024 Accepted March 7, 2025 Published online March 10, 2025; DOI: https://doi.org/10.4143/crt.2024.933 [Accepted]

Abstract PDF: Purpose
The aim of this study is to determine the impact of SLC3A2 on the malignant phenotype of gliomas and its role in regulating ferroptosis sensitivity.
Materials and Methods
The malignant phenotype of glioma was assessed by cell proliferation assay, colony formation assay, EdU assay, wound healing and transwell experiments.We further validated the impact of reduced SLC3A2 expression on the sensitivity to ferroptosis in glioma cells through CCK-8 assays, flow cytometry, Western blotting, and transmission electron microscopy. Western blot was used to explore how SLC3A2 affects glioma sensitivity to ferroptosis through the AKT/NRF2/GPX4 axis. By establishing a subcutaneous xenograft tumor model in BALB/c-Nude mice, we investigated the growth of tumors following the knockout of SLC3A2 in glioma cells.
Results
Downregulation of SLC3A2 suppressed the malignant phenotype of glioma by blocking the cell cycle and EMT processes. On the other hand, loss of SLC3A2 not only downregulated SLC7A11 but also prevented the activation of the AKT/NRF2/GPX4 axis. These lead to increased accumulation of ROS and lipid peroxides, ultimately enhancing the susceptibility of glioma to ferroptosis.
Conclusion
Our findings suggest that SLC3A2 is an oncogene in gliomas, promoting their occurrence and development. It plays a critical role in ferroptosis resistance through the AKT/NRF2/GPX4 axis.

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Ten-Year Follow-Up Clinical Outcomes and the Role of Adjuvant Chemotherapy in HER2-Positive Patients with Microinvasive Breast Cancer: Yeokyeong Shin, Soo-Young Lee, Hyehyun Jeong, Jin-Hee Ahn, Kyung Hae Jung, Sung-Bae Kim, Hee Jeong Kim, Jong Won Lee, Byung Ho Son, BeomSeok Ko, Ji Sun Kim, Il Yong Chung, Hee Jin Lee, Gyungyub Gong, Sae Byul Lee, Jae Ho Jeong; Received November 22, 2024 Accepted March 3, 2025 Published online March 5, 2025; DOI: https://doi.org/10.4143/crt.2024.1120 [Accepted]

Abstract PDF: Purpose
Although HER2 positivity is prevalent in microinvasive breast cancer (MIBC), data focused on HER2-positive MIBC are limited. We investigated the clinical course and long-term outcomes of HER2-positive MIBC and evaluated the role of adjuvant chemotherapy.
Materials and Methods
The study included patients with curatively resected pT1mi pN0 HER2-positive breast cancer between January 2000 and January 2020. Treatments and survival outcomes, including invasive breast cancer-free survival (IBCFS), distant recurrence-free survival (DRFS), and overall survival (OS) were analyzed.
Results
The analysis included 799 female patients. The median age was 51 years (range, 23–79), and 51.6% (n=412) were premenopausal. Multifocality was confirmed in 17.3% (n=138), and estrogen receptor (ER) positivity in 29.8% (n = 238). Adjuvant chemotherapy was administered to 17.5% (n=140), with doxifluridine in 96.4% of cases. One patient (0.1%) received trastuzumab. With a median follow-up of 119.0 months (95% CI, 114.0–127.0), the 8-year IBCFS, DRFS, and OS were 91.2% (95% CI, 89.1–93.3), 97.5% (95% CI, 96.4–98.7), and 98.8% (95% CI, 98.0–99.6), respectively. No significant differences were observed between patients with and without adjuvant chemotherapy. The lack of differences in IBCFS by chemotherapy was consistent across subgroups, including pre-/postmenopausal patients, grade 1-2/3 tumors, and ER-negative disease.
Conclusion
A clinically meaningful proportion of HER2-positive MIBC patients experience IBCFS events with long-term follow-up. Adjuvant chemotherapy did not improve survival, potentially due to the use of an outdated, ineffective regimen. The role of modern adjuvant regimens, particularly those incorporating HER2-targeted therapy, warrants further exploration.

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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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The Profile of Gut Microbiota in Carcinogenesis Driven by Mutant EGFR in Non-Small Cell Lung Cancer: Da-Som Kim, Eun Hye Kim, Ji Yong Kim, Dong Ha Kim, Yun Jung Choi, Jaeyi Jeong, Young Hoon Sung, Dong-Cheol Woo, Chong Jai Kim, Jae Cheol Lee, Miyong Yun, Jin-Yong Jeong, Jin Kyung Rho; Received December 9, 2024 Accepted March 2, 2025 Published online March 4, 2025; DOI: https://doi.org/10.4143/crt.2024.1177 [Accepted]

Abstract PDF: Purpose
Accumulating evidence has clarified that gut dysbiosis is involved in lung cancer development and progression. Although the relationship between tumors and gut microbiota has been extensively studied using clinical samples, no studies have examined the association between mutant EGFR-induced lung carcinogenesis and dysbiosis in gut microbiota. Therefore, we investigated the gut microbiota profiles in stool samples from human lung-specific conditional EGFR-mutant transgenic mice during lung tumor carcinogenesis.
Materials and Methods
Stool samples were collected before tamoxifen treatment (V1) and at each time point following mutant EGFR expression in lung tissue (V2) and lung tumor appearance (V3). Fecal 16S rRNA taxonomy was analyzed to assess microbial diversity, composition, and dynamic changes at each time point.
Results
We found that microbiota richness and diversity were significantly elevated when tumors developed and grew in the lung. Phylogenetic analysis of the microbial community revealed that Lachnospiraceae, Ruminococcaceae, Porphyromonadaceae, Rhodospirillaceae, Odoribacteraceae, and Desulfovibrionaceae showed a significant increase at the V3 stage compared to the V1 stage at the family level. In contrast, Lactobacillaceae, Bacteroidaceae, Muribaculaceae, Coriobacteriaceae, and Rikenellaceae significantly decreased at the V3 stage compared to the V1 stage. Furthermore, Lactobacillus species, also known as SCFA-producing bacteria, were relatively abundant at the V1 stage but were depleted with the occurrence of lung tumors at the V3 stage.
Conclusion
Changes in gut microbiota, such as Lactobacillus species, may be a predictive factor for the emergence and progression of tumors in an animal model of lung adenocarcinoma induced by mutant EGFR.

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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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Validating the Korean Geriatric Assessment Tool in Elderly Multiple Myeloma Patients: A Multicenter Study: Ji Yun Lee, Sang-A Kim, Youngil Koh, Ho-Young Yhim, Gyeong-Won Lee, Chang-Ki Min, Young Rok Do, Hyo Jung Kim, Sung Hwa Bae, Hyeon-Seok Eom, Sung-Hoon Jung, Hyunkyung Park, Seung-Hyun Nam, Ji Hyun Lee, Sung-Hyun Kim, Hyun Jung Lee, Young Seob Park, Soo-Mee Bang; Received January 15, 2025 Accepted February 20, 2025 Published online February 21, 2025; DOI: https://doi.org/10.4143/crt.2025.066 [Accepted]

Abstract PDF: Purpose
This study evaluates the Korean Cancer Study Group Geriatric Score-7 (KG-7) frailty screening tool's effectiveness in elderly multiple myeloma (MM) patients to prevent under and over-treatment.
Materials and Methods
This prospective pilot cohort study included 100 elderly patients aged 70 and older with newly diagnosed MM who had not undergone transplantation from August 2020 to January 2022.
Results
The median age was 77 years, and 73% of patients were classified at International Staging System (ISS) stages 2 or 3. Using a 5-point cutoff on the KG-7 index (non-frail, score ≥ 5; frail, score < 5), 31% were categorized as frail. After a median follow-up of 26.8 months, the 3-year overall survival rate was 73.0%. There was no statistically significant association between any frailty index and the risk of death. However, frail patients defined by the simplified frailty index (HR, 2.49; 95% CI, 1.09–5.95; p=0.030) and by KG-7 (HR, 2.43; 95% CI, 1.03–5.86; p=0.043) had a significantly higher risk of grade 3–4 non-hematologic toxicity, whereas the IMWG definition did not. Over a 24-month tracking period, vulnerability as measured by KG-7 either improved or deteriorated.
Conclusion
The pilot study, which had a limited number of participants, did not demonstrate KG-7’s effectiveness in predicting survival; however, it successfully predicted severe non-hematologic toxicities. We plan to conduct larger studies in elderly MM patients to determine whether KG-7 can help tailor their treatment regimens.

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Epidermal Growth Factor Receptor Aberrations Identified by Next-generation Sequencing in Patients with Metastatic Cancers: Minkyue Shin, Dae-Ho Choi, Jaeyun Jung, Deok geun Kim, Sung Hee Lim, Seung Tae Kim, Jung Yong Hong, Se Hoon Park, Joon Oh Park, Kyoung-Mee Kim, Jeeyun Lee; Received June 17, 2024 Accepted January 21, 2025 Published online February 21, 2025; DOI: https://doi.org/10.4143/crt.2024.564 [Accepted]

Abstract PDF: Purpose
The epidermal growth factor receptor (EGFR) is a therapeutic target with confirmed clinical efficacy for several cancer types. We aimed to identify EGFR aberrations and their associations with other genomic alterations in patients with metastatic diseases of various cancers.
Materials and Methods
We used real-world data from the next-generation sequencing (NGS) of 3,286 patients with metastatic cancer at the Samsung Medical Center. We analyzed the distribution of EGFR amplification, mutation, and fusion, as well as their correlations with microsatellite instability (MSI), tumor mutation burden (TMB), and other gene aberrations.
Results
A total of 3,286 patients were tested using NGS of a panel covering 523 cancer-related genes (TSO500, Illumina) as part of clinical practice between October 2019 and October 2022. Patients with lung cancer and gliomas were not included in the analysis. Of the 3,286 patients, 175 (5.3%) had EGFR amplification, 38 (1.2%) had EGFR mutations, and 8 (0.2%) had EGFR fusion. All 175 patients with EGFR amplifications had microsatellite-stable (MSS) tumors, but 102 had co-amplifications in other cancer-related genes, and 78 had mutations with clinical significance (tier I/II). Among the 38 patients with EGFR mutations, three (8%) showed MSI-high status, and eleven (29%) demonstrated high TMB (≥ 10 mutations/mb). Among eight patients with EGFR fusion, three exhibited possible functionalities of the EGFR gene.
Conclusion
EGFR aberrations, mainly amplification, followed by mutation and fusion, were present in 6.4% of patients with metastatic solid tumors.

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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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A Multicenter Phase II Study of Modified FOLFIRINOX for First-line Treatment for Advanced Urachal Cancer (ULTMA; KCSG GU20-03): Inkeun Park, Jae Lyun Lee, Shinkyo Yoon, Sang Joon Shin, Seong-Hoon Shin, Jung Hoon Kim, Kwonoh Park, Hyo Jin Lee; Received December 21, 2024 Accepted February 12, 2025 Published online February 13, 2025; DOI: https://doi.org/10.4143/crt.2024.1231 [Accepted]

Abstract PDF: Purpose
To assess the efficacy and safety of the first-line modified FOLFIRINOX in patients with advanced urachal cancer.
Materials and Methods
The ULTIMA trial (NCT04611724) is a single-arm, open-label, multicenter phase II study evaluating modified FOLFIRINOX (Oxaliplatin 85 mg/m² over 2 hours, Irinotecan 150 mg/m² over 1.5 hours, Leucovorin 400 mg/m² over 2 hours, and 5-FU 2400 mg/m² over 46 hours) plus prophylactic pegteograstim in patients with recurrent or metastatic urachal cancer every 2 weeks for up to 12 cycles, or until disease progression or unacceptable toxicity. The primary endpoint was the objective response rate (ORR). Secondary endpoints included progression-free survival (PFS), overall survival (OS), and the incidence of febrile neutropenia.
Results
Between April 2021 and November 2023, 21 patients with advanced urachal cancer were enrolled across five cancer centers. The median age was 50 (28–68), with 15 male patients. The most common metastatic site was the lung (47.6%), followed by lymph nodes (38.1%) and peritoneal seeding (33.3%). Two patients and 11 patients achieved a complete and partial response, respectively, yielding an ORR of 61.9%. The study met its primary endpoint in the first stage. With a median follow-up of 23.3 months, the median PFS was 9.3 months (95% CI, 6.7–11.9), and the median OS was 19.7 months (95% CI, 14.3–25.1). The treatment regimen was well tolerated, with no unexpected adverse events, and no instances of febrile neutropenia or grade 4 adverse events.
Conclusion
In this preliminary analysis of ULTIMA trial, Modified FOLFIRINOX demonstrated a promising ORR and PFS in patients with advanced urachal cancer. Completing the full study is essential to confirm the potential role of this regimen in the management of advanced urachal cancer.

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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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Significant Dissatisfaction with the Anachronistic System: A Survey on The Experience of Application for Off-Label Use of Anti-Cancer Drugs by Korean Society of Medical Oncology: Jae Lyun Lee, Dong-Hoe Koo, Young-Woong Won, Young Saing Kim, Hee Kyung Ahn, Seungtaek Lim; Received August 7, 2024 Accepted February 10, 2025 Published online February 11, 2025; DOI: https://doi.org/10.4143/crt.2024.749 [Accepted]

Abstract PDF: Purpose
This study evaluates the experiences and satisfaction levels of Korean medical oncologists with the prior authorization system for the off-label use of anti-cancer drugs. Conducted by the Korean Society of Medical Oncology (KSMO), the survey aimed to identify challenges and areas for improvement in the current regulatory framework.
Materials and Methods
A cross-sectional web-based survey was carried out between May 4 and May 14, 2023, targeting 261 active KSMO medical oncologists. Invitations were sent via email, and the survey, comprising 19 questions, was hosted on Microsoft Forms. The questions covered personal characteristics, work environment, experiences with the pre-application process, and post-approval experiences.
Results
For the 261 invitations sent, 110 responses (42.1%) were received. Most respondents had over 10 years of experience and worked in tertiary hospitals. Although 93.6% were familiar with the pre-application system, 67.3% expressed moderate to high dissatisfaction. The key issues included complex applications, long approval period, stringent criteria, and inconsistent reviews. Additionally, 74.4% respondents spent over 3 hours on first-time applications, with 68.3% experiencing rejections. Emotional responses to rejections were largely negative, with many feeling disregarded. Post-approval, patients of 96.8% respondents faced financial burdens leading to treatment discontinuation. Most oncologists (86.0%) supported selective reimbursement if the disease was controlled for a certain period.
Conclusion
The survey highlights significant dissatisfaction with the current system, suggesting the need for streamlining the application process, easing approval criteria, and reconsidering the financial aspects of post-approval treatments to support patient care and oncologists’ decision-making autonomy.

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Evaluation of Nomenclature of Fatty Liver Disease in Association with Hepatocellular Carcinoma: A 14.5-Year Cohort Study in Korea: Tung Hoang, Jeonghee Lee, Bo Hyun Kim, Yuri Cho, Jeongseon Kim; Received September 7, 2024 Accepted February 10, 2025 Published online February 11, 2025; DOI: https://doi.org/10.4143/crt.2024.876 [Accepted]

Abstract PDF: Purpose
New nomenclature has incorporated metabolic traits and/or alcohol intake history to replace nonalcoholic fatty liver disease (NAFLD). Concerning the performance of different terminologies in Asian population, this study aimed to investigate the risk of developing hepatocellular carcinoma (HCC) in persons meeting the criteria for subclasses of fatty liver disease.
Materials and Methods
Between 2002 and 2021, 28,749 participants from the cancer registry linkage, who had no prior history of HCC, were prospectively included. Fatty liver disease was defined using abdominal sonography and fatty liver index. Participants were classified as having NAFLD, metabolic dysfunction–associated fatty liver disease (MAFLD), metabolic dysfunction-associated steatotic liver disease (MASLD), steatotic liver disease with increased alcohol intake (MetALD), or alcohol-related liver disease (ALD) and their association with HCC risk was investigated using Cox regression models.
Results
During a median follow-up of 14.5 years, 166 HCC cases were newly diagnosed. The prevalences of NAFLD and MASLD were 19.7% and 18.7%, respectively, whereas MAFLD was observed in 35.2% of the study population. Given the low proportion of excessive alcohol consumption, we identified 3.3% MetALD and 3.5% ALD cases. Overall, MAFLD was suggestively associated with HCC risk (hazard ratio, 1.40; 95% confidence interval 0.99-1.98). In contrast, the results for other nomenclature were not significant.
Conclusion
Our results suggest the importance of both fatty liver and the presence of metabolic dysfunction in relation to HCC risk and the need to reconsider alcohol intake thresholds in the diagnostic criteria for NAFLD and MASLD within the Korean population.

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Association between Antipsychotic Drug and Survival in Patients with Lung Cancer Treated with Chemoradiotherapy: A Nationwide Korean Cohort Study: Dong-Yun Kim, In Gyu Hwang, Sun Mi Kim, Dae Ryong Kang, Tae-Hwa Go, Se Hwa Hong, Shin Young Park, Hyunho Lee, Jin Hwa Choi; Received June 12, 2024 Accepted February 5, 2025 Published online February 6, 2025; DOI: https://doi.org/10.4143/crt.2024.554 [Accepted]

Abstract PDF: Purpose
Antipsychotic drugs (APDs) can be used to relieve psychological symptoms in patients with cancer. We investigated the nationwide use of APDs during concurrent chemoradiotherapy (CCRT) for patients with lung cancer and its association with overall survival (OS).
Materials and Methods
The National Health Service database was used in this retrospective cohort study. Patients diagnosed with lung cancer between 2010 and 2020 who received cisplatin-based CCRT were included. The APDs included in the analysis were aripiprazole, quetiapine, olanzapine, risperidone, haloperidol, and chlorpromazine, and the APD prescription details included prescription time, dosage, and duration.
Results
Among the 23,099 patients with lung cancer treated with CCRT, 2,662 (11.5%) took APDs concurrently. Quetiapine (47.3%) and chlorpromazine (36.6%) were the frequently prescribed APDs. In the univariate analysis, patients prescribed APDs during CCRT had a significantly worse OS than those who did not take APDs. The 2-year OS rates for APD (+) and APD (-) patients were 20.4% and 36.4%, respectively (p < 0.001). Multivariable analyses revealed that APD prescription, male, age >80 years, and comorbidities, such as hypertension, myocardial infarction, and depressive disorder, significantly influenced OS. In patients who used APDs during CCRT, APD prescription timing (pre-CCRT vs. during CCRT), dosage (low vs. high) and duration (within 6 months vs. over 6 months) had no significant difference.
Conclusion
Overall, 11.5% of patients with lung cancer used APDs during CCRT. Patients who used APDs during CCRT had poorer survival than those who did not. Further studies are required to elucidate the effects of APDs on patients with cancer.

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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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Preoperative Prediction Model for Early Recurrence of Intrahepatic Cholangiocarcinoma After Surgical Resection: Development and External Validation Study: Dong Hwan Kim, Sang Hyun Choi, Sehee Kim, Hyungjin Rhee, Eun-Suk Cho, Suk-Keu Yeom, Sumi Park, Seung Soo Lee, Mi-Suk Park; Received December 10, 2024 Accepted February 4, 2025 Published online February 5, 2025; DOI: https://doi.org/10.4143/crt.2024.1187 [Accepted]

Abstract PDF: Purpose
We aimed to develop a preoperative risk scoring system to predict early recurrence (ER) of intrahepatic cholangiocarcinoma (ICCA) after resection, utilizing clinical and computed tomography (CT) features.
Materials and Methods
This multicenter study included 365 patients who underwent curative-intent surgical resection for ICCA at six institutions between 2009 and 2016. Of these, 264 patients from one institution constituted the development cohort, while 101 patients from the other institutions constituted the external validation cohort. Logistic regression models were constructed to predict ER based on preoperative variables and were subsequently translated into a risk-scoring system. The discrimination performance of the risk-scoring system was validated using external data and compared to the American Joint Committee on Cancer (AJCC) TNM staging system.
Results
Among the 365 patients (mean age, 62±10 years), 153 had ER. A preoperative risk scoring system that incorporated both clinical and CT features demonstrated superior discriminatory performance compared to the postoperative AJCC TNM staging system in both the development (area under the curve [AUC], 0.78 vs. 0.68; p=0.002) and validation cohorts (AUC, 0.69 vs. 0.66; p=0.641). The preoperative risk scoring system effectively stratified patients based on their risk for ER: the 1-year recurrence-free survival rates for the low, intermediate, and high-risk groups were 85.5%, 56.6%, and 15.6%, respectively (p<0.001) in the development cohort, and 87.5%, 58.5%, and 25.0%, respectively (p<0.001) in the validation cohort.
Conclusion
A preoperative risk scoring system that incorporates clinical and CT imaging features was valuable in identifying high-risk patients with ICCA for ER following 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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Differential Efficacy of Alpelisib by PIK3CA Mutation Site in Head and Neck Squamous Cell Carcinoma: An Analysis from the KCSG HN 15-16 TRIUMPH Trial: Kyoo Hyun Kim, Shinwon Hwang, Min Kyoung Kim, Keon-Uk Park, Tak Yun, Keun-Wook Lee, Joo Hang Kim, Bhumsuk Keam, Byoung Chul Cho, So Yeon Oh, Sang Hee Cho, Sangwoo Kim, Sung-Bae Kim, Min Hee Hong, Hye Ryun Kim; Received December 11, 2024 Accepted January 27, 2025 Published online January 31, 2025; DOI: https://doi.org/10.4143/crt.2024.1195 [Accepted]

Abstract PDF: Purpose
The TRIUMPH trial was a biomarker-driven umbrella trial for patients with recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC). This analysis focuses on the PIK3CAɑ inhibitor alpelisib (arm 1) in patients with phosphoinositide 3-kinase (PI3K) pathway alterations.
Materials and Methods
Patients with PI3K pathway altered tumors were enrolled in the alpelisib arm of the TRIUMPH study. We conducted a detailed analysis of the correlation between PI3K pathway mutations and treatment outcomes including disease control rate (DCR), overall survival (OS), and progression-free survival (PFS).
Results
From Oct 2017 and Aug 2020, 203 were enrolled, with 42 treated with alpelisib. Response evaluation was possible for 33 patients. Genomic profiles revealed PIK3CA amplifications in 26.2%, and point mutations in E542K (26.2%), E545K (23.8%), and H1047R (9.5%). Neither PIK3CA amplification nor co-occurring TP53 mutations had a notable influence on alpelisib response or survival outcomes. Although the overall response rates were similar between helical domain mutations (E542, E545) and kinase domain mutations (H1047), patients with H1047 mutations exhibited significantly poorer PFS compared to those with non-H1047 PIK3CA alterations (1.6 vs. 7.3 months, p=0.017). OS in patients with H1047 kinase domain mutations showed a trend toward being shorter compared to others, though this difference did not reach statistical significance.
Conclusion
Alpelisib showed differential efficacy based on PI3K pathway alterations in patients with R/M HNSCC and was well-tolerated. These findings suggest the usefulness of NGS testing-based decision-making when using the targeted agents in R/M HNSCC. We need to confirm results in larger cohorts.

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Literature-Guided 6-Gene Signature for the Stratification of High-Risk Acute Myeloid Leukemia: Jong Keon Song, Dong Hyeok Lee, Hyery Kim, Sang-Hyun Hwang; Received November 20, 2024 Accepted January 22, 2025 Published online January 24, 2025; DOI: https://doi.org/10.4143/crt.2024.1114 [Accepted]

Abstract PDF: Purpose
Acute myeloid leukemia (AML) shows significant heterogeneity in therapeutic responses. We aimed to develop a gene signature for the stratification of high-risk pediatric AML using publicly available AML datasets, with a focus on literature-based prognostic gene sets. Materials and Methods We identified 300 genes from 12 well-validated studies on AML-related gene signatures. Clinical and gene expression data were obtained from three datasets: TCGA-LAML, TARGET-AML, and BeatAML. Least absolute shrinkage and selection operator (LASSO)-Cox regression analysis was used to perform the initial gene selection and to construct a prognostic model using the TCGA database (n=132). The final gene signature was validated with two independent cohorts: BeatAML (n=411) and TARGET-AML (n=187).
Results
We identified a six-gene signature (ETFB, ARL6IP5, PTP4A3, CSK, HS3ST3B1, PLA2G4A), referred to as the literature-based signature 6 (LBS6), that was significantly associated with lower overall survival rates across the TCGA (HR=4.2, 95% CI: 2.59–6.81, p<0.0001), BeatAML (HR=1.52, 95% CI: 1.17–1.96, p=0.0013), and TARGET (HR=2.05, 95% CI: 1.36–3.08, p<0.001) datasets. The high-LBS6 score group exhibited significantly poorer five-year event-free survival compared to the low-LBS6 score group (HR=2.09, 95% CI: 1.38–3.15, p<0.001). After adjusting for key risk factors, including gene mutations (WT1, FLT3, and NPM1), protocol-based risk group, WBC count, and age, the LBS6 score was independently associated with worse survival rates in validation cohorts.
Conclusion
Our literature-driven approach identified a robust gene signature that stratifies AML patients into distinct risk groups. The LBS6 score shows promise in redefining initial risk stratification and identifying high-risk AML patients.

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Tracing Metastatic Evolutionary Patterns in Lung Adenocarcinoma: Prognostic Dissection Based on a Multi-state Model: Geewon Lee, Yang-Jin Kim, Insuk Sohn, Jong Hoon Kim, Ho Yun Lee; Received July 25, 2024 Accepted January 22, 2025 Published online January 24, 2025; DOI: https://doi.org/10.4143/crt.2024.700 [Accepted]

Abstract PDF: Purpose
After surgery for lung adenocarcinoma, a patient may experience various states of recurrence, with multiple factors potentially influencing the transitions between these states. Our purpose was to investigate the effects of clinical and pathological factors on tumor recurrence, death, and prognosis across various metastasizing pathways.
Materials and Methods
Our study group included 335 patients with all demographic and pathologic data available who underwent surgical resection for lung adenocarcinoma for more than 10 years. The following states of disease were defined: initial state, operation (OP); three intermediate states of local recurrence (LR), metastasis (Meta), and concurrent LR with metastasis (LR+Meta); and a terminal state, death. We identified 8 transitions representing various pathways of tumor progression. We employed a multi-state model (MSM) to separate the impacts of multiple prognostic factors on the transitions following surgery.
Results
After surgery, approximately half of patients experienced recurrence. Specifically, 142 (42.4%), 54 (16.1%), and 7 (2.1%) patients developed Meta, LR+Meta, and LR, respectively. Clinical and pathological factors associated with the transitions were different. Impact of pathological lymph node remained a risk factor for both OP to Meta (λ₀₂, p-value=0.001) and OP to LR+Meta (λ₀₃, p-value = 0.001).
Conclusion
Lung adenocarcinoma displays a broad spectrum of clinical scenarios even after curative surgery. Incidence, risk factors, and prognosis varied across different pathways of recurrence in lung adenocarcinoma patients. The greatest implication of this MSM is its ability to predict the timing and type of clinical intervention that will have the greatest impact on survival.

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Review Article

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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Original Articles

Prognostic Value of POST-Treatment Extent of Tumor (POSTTEXT) System in Patients with Hepatoblastoma: Hana Jeong, Hee Mang Yoon, Pyeong Hwa Kim, Ah Young Jung, Young Ah Cho, Jin Seong Lee, Kyung-Nam Koh, Jung-Man Namgoong; Received June 28, 2024 Accepted January 19, 2025 Published online January 20, 2025; DOI: https://doi.org/10.4143/crt.2024.600 [Accepted]

Abstract PDF: Purpose
To assess prognostic values of the POST-Treatment Extent of Tumor (POSTTEXT) system and clinical factors after neoadjuvant chemotherapy in hepatoblastoma patients and evaluate benefits of posttreatment imaging and clinical factors concomitant with Children’s Hepatic Tumors International Collaboration-Hepatoblastoma Stratification (CHIC-HS) system.
Materials and Methods
This single-center retrospective study of hepatoblastoma cases (2006–2022) included pediatric patients receiving ≥ 4 cycles of neoadjuvant chemotherapy, with pre- and post-treatment imaging and complete medical records. Clinical data included age, sex, and serum alpha-fetoprotein (AFP) levels. Cox regression analyses identified predictors of event-free survival (EFS). Time-dependent receiver operating characteristic curves assessed the predictive power of combining the CHIC-HS risk stratification with posttreatment factors. Inter-reader agreement was analyzed using weighted kappa.
Results
Among the 109 hepatoblastoma patients, 73 (mean age: 2.2 ± 2.7 years) met the inclusion criteria. Prognostic factors for EFS included AFP levels after the fourth cycle of neoadjuvant chemotherapy (HR, 1.233; 95% CI, 1.806–1.400; p=0.001), tumor size change ratio (HR, 0.654; 95% CI, 0.448–0.955; p=0.03), and POSTTEXT annotation factor M (HR, 5.209; 95% CI, 1.639–16.553; p=0.005). Incorporating AFP levels after the fourth cycle of neoadjuvant chemotherapy into the CHIC-HS improved predictive power (p=0.043). POSTTEXT system showed better inter-reader agreement than PRETEXT.
Conclusion
Predictors of EFS in hepatoblastoma include AFP levels after the fourth cycle of neoadjuvant chemotherapy, tumor size change ratio, and metastasis (POSTTEXT M). Combining AFP levels after the fourth cycle of neoadjuvant chemotherapy to the CHIC-HS improved the predictive ability.

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Lipid Metabolism Related Gene ACSL3 as a Biomarker for Predicting Immunotherapy Outcomes in Lung Adenocarcinoma: Taiping He, Jinhan Hu, Haoyue Guo, Meng Diao, Yuanyuan Wang, Yuhan Wu, Lei Cheng, Chao Zhao, Xuefei Li, Caicun Zhou; Received November 22, 2024 Accepted January 16, 2025 Published online January 20, 2025; DOI: https://doi.org/10.4143/crt.2024.1119 [Accepted]

Abstract PDF: Purpose
Investigate the role of lipid metabolism in the tumor immune microenvironment (TIME) of lung adenocarcinoma (LUAD) and identify vital lipid metabolism-related genes (LMRGs) that contribute to immunotherapy outcomes.
Materials and Methods
1130 LUAD patients were acquired utilizing public databases. Multiple algorithms were used to analyze the contribution of lipid metabolism in TIME. Importantly, cell lines, clinical samples (52 patients in surgery cohort and 36 in immunotherapy cohort), animal models, RNA-seq, experiments in protein and mRNA levels were conducted for identifying and validating key biomarker in LUAD immunotherapy.
Results
A prognostic signature comprising 33 LMRGs was developed and validated as an effective predictor of prognosis and TIME, with a C-index of 0.766 (95% CI: 0.729-0.804). Additionally, we identified Acyl-CoA Synthetase Long Chain Family Member 3 (ACSL3) as a potential biomarker for immunotherapy prognosis. The expression of ACSL3 was verified in 88 clinical tissues from LUAD patients, which indicated that elevated ACSL3 expression was correlated with worse progression-free survival (PFS) (p<0.001) and overall survival (OS) (p=0.008). Subsequent experiments revealed that knockdown of ACSL3 in vivo enhanced the efficacy of immunotherapy, potentially through increasing interferon α secretion, as indicated by Bulk RNA-seq and ELISA analysis, thereby promoting the infiltration of anti-tumor immune cells.
Conclusion
The study established a model that accurately predicts immunotherapy response, prognosis, and TIME dynamics in LUAD patients. Notably, the pivotal role of ACSL3 in driving tumor progression and immune evasion was uncovered, offering novel insights into the optimization of immunotherapy strategies for LUAD.

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