Cancer Research and Treatment

The Synergistic Effect of PARP Inhibitors and Irinotecan in Small Cell Lung Cancer Cells: Songji Oh, Soyeon Kim, Bhumsuk Keam, Jeonghwan Youk, Tae Min Kim, Dong-Wan Kim, Miso Kim; Received August 1, 2024 Accepted January 6, 2025 Published online January 7, 2025; DOI: https://doi.org/10.4143/crt.2024.728 [Accepted]

Abstract PDF: Purpose
This study focused on combining irinotecan with Poly (ADP-ribose) polymerase (PARP) inhibitors to explore the potential for novel combination therapeutics in small cell lung cancer (SCLC).
Materials and Methods
We selected 10 different SCLC cell lines with diverse mutational backgrounds in DNA damage response (DDR) pathway genes to evaluate the efficacy of the combination of three PARP inhibitors and irinotecan. After the cells were exposed to the drugs for seven days, cell viability was measured, and a combination index was calculated. Apoptotic signaling was assessed via western blot, and DNA damage was evaluated using an alkaline comet assay.
Results
We assessed the synergistic effects of PARP inhibitors and irinotecan in in vitro SCLC models, which revealed increased sensitivity, particularly in cells harboring BRCA mutations. However, even in cells lacking mutations in DNA damage response pathway genes, the combination of the two drugs exhibited a synergistic effect. When treated with 50 nM irinotecan, the IC₅₀ fold changes for PARP inhibitors were: olaparib, 1649 ± 4049; talazoparib, 25 ± 34.21; venadaparib, 336 ± 596.01. This combination enhanced apoptosis signaling and increased p-chk1 and p-p53 protein levels. Additionally, the treatment of PARP inhibitor with irinotecan increased DNA damage, as visualized by the alkaline comet assay.
Conclusion
This study provides preclinical evidence of the potential clinical benefits of combining irinotecan with PARP inhibitors in SCLC. Further clinical investigations are warranted to validate these findings for the development of more effective and personalized therapeutic strategies for SCLC patients.

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A Prospective, Single-Cohort, Open, Multi-Center, Observational Study of Sublingual Fentanyl for Breakthrough Cancer Pain: Effectiveness, Safety, and Tolerability in Korean Cancer Patients: Youn Seon Choi, Su-Jin Koh, Woo Kyun Bae, Se Hyung Kim, Seong Hoon Shin, So Yeon Oh, Sang Byung Bae, Yaewon Yang, Eun-Kee Song, Yoon Young Cho, Pyung Bok Lee, Ho-Suk Oh, MinYoung Lee, Jin Seok Ahn; Received June 13, 2024 Accepted December 24, 2024 Published online December 26, 2024; DOI: https://doi.org/10.4143/crt.2024.557 [Accepted]

Abstract PDF: Purpose
Fentanyl, a highly lipophilic opioid, was developed as a sublingual fentanyl tablet (SFT) for the management of breakthrough cancer pain (BTcP), and its efficacy and safety were confirmed in a randomized, controlled study. We investigated the effectiveness and safety of SFT administered to alleviate BTcP in a real-world setting.
Materials and Methods
In this prospective, open, single-cohort study, conducted in 13 referral hospitals in South Korea, opioid-tolerant cancer patients receiving around-the-clock opioids for persistent cancer pain were enrolled if the individual had BTcP ≥ 1 episode/day during the preceding week. The primary outcome was the SFT titration success rate.
Results
Among 113 patients evaluated for effectiveness, 103 patients (91.2%) had a successful titration of SFT, with an effective dose range between 100 µg and 400 µg. The most frequent dose was 100 µg, administered to 65.0%, 72.1%, and 81.8% of the patients at Week 1, 4, and 12, respectively. The proportion of patients achieving the personalized pain goal assessed in the first week was 75.2%. The mean change in pain intensity measured with a numeric rating scale at 30 and 60 minutes after taking SFT was -2.57 and -3.62, respectively (p<0.0001 for both). The incidence rate of adverse events related to SFT among 133 patients included for safety evaluation was 9.0% (12/133), which included vomiting (3.0%), nausea (2.3%), and headache (1.5%).
Conclusion
In a real-world setting, SFT provides rapid and effective analgesia in BTcP, even at the lowest dose (100 μg), and the safety profile was acceptable.

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Psychometric Validation of Sheffield Profile for Assessment and Referral to Care (SPARC) in Korean Cancer Patients: Hong Jun Kim, Eun Hee Jung, Jung Hye Kwon, Yu Jung Kim, Su-Jin Koh, Myung Ah Lee, Jung Hun Kang, Sun Young Rha, Eun Mi Nam, Sun Kyung Baek, Ha Yeon Lee, Hun Ho Song, Young-Woong Won, Hanbyul Lee; Received July 26, 2024 Accepted December 4, 2024 Published online December 5, 2024; DOI: https://doi.org/10.4143/crt.2024.706 [Accepted]

Abstract PDF: Purpose
Identifying the palliative care needs of patients with advanced cancer is important for maintaining quality of life and timely transition to palliative care. We aimed to validate the Korean Sheffield Profile for Assessment and Referral for Care (K-SPARC) in such patients and establish its psychometric properties, including reliability, validity, and responsiveness to change.
Materials and Methods
We used the forward-back translated version of SPARC, which was verified through a pilot study, to assess the palliative care needs of patients with advanced cancer. Reliability was evaluated by internal consistency using Cronbach's alpha coefficients and test-retest reliability. Criterion validity was analyzed against other questionnaires, including the Korean versions of the Functional Assessment of Cancer Therapy-General (FACT-G Korean) and Korean versions of the Edmonton Symptom Assessment System (K-ESAS). Factor analysis was used to assess construct validity.
Results
Two hundred fifty-nine patients were included from 2019 to 2022. Forty-nine percent of all patients were women, and the median age was 63 years. Cronbach’s alpha coefficient (range, 0.642–0.903) and test-retest reliability (range, 0.574–0.749) indicated acceptable reliability. The correlation coefficients between K-SPARC and FACT-G Korean suggested significant criterion validity. The correlation coefficients for the physical, social, emotional, and functional domains were 0.701, 0.249, 0.718, and 0.511, respectively (p-value <0.001, all). Factor analysis demonstrated satisfactory construct validity of the tool.
Conclusion
This study demonstrated the utility of K-SPARC as an evaluation tool for providing palliative care to patients with advanced cancer through psychometric validation; the tool had good internal consistency, reliability, and acceptable validity.

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Identifying Trends in Oncology Research through a Bibliographic Analysis of Cancer Research and Treatment: Choong-kun Lee, Jeong Min Choo, Yong Chan Ahn, Jin Kim, Sun Young Rha, Chai Hong Rim, On behalf of the 50th Anniversary Committee of the Korean Cancer Association; Cancer Res Treat. 2025;57(1):11-18. Published online December 5, 2024; DOI: https://doi.org/10.4143/crt.2024.688

Abstract PDF PubReader ePub: During the celebration of the 50th anniversary of the founding of the Korean Cancer Association, articles published in Cancer Research and Treatment from 2004 to 2023 were assessed based on the subject and design of each study. Based on this analysis, trends in domestic cancer research were inferred and directions were suggested for the future development of Cancer Research and Treatment.

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Normal Brain-Sparing Radiotherapy versus Whole Brain Radiotherapy for Multiple Brain Metastasis from Non-Small Cell Lung Cancer: Sangjoon Park, Jaeho Cho, Kyung Hwan Kim, Hong In Yoon, Chang Geol Lee; Received July 23, 2024 Accepted December 2, 2024 Published online December 3, 2024; DOI: https://doi.org/10.4143/crt.2024.679 [Accepted]

Abstract PDF: Purpose
The efficacy and lower neurotoxicity of normal brain-sparing radiotherapy (NBS-RT) with systemic therapy in treating multiple brain metastases from non-small cell lung cancer (NSCLC) is underexplored. This study compares whole-brain radiotherapy (WBRT) and NBS-RT for multiple brain metastases in NSCLC, focusing on treatment outcomes and leukoencephalopathy.
Materials and Methods
This retrospective study included 503 patients with NSCLC with multiple brain metastases at a single center, treated with either WBRT or NBS-RT. Post-RT treatments included chemotherapy, targeted therapy, or immunotherapy. Main outcomes measured were intracranial control, overall survival (OS), and leukoencephalopathy incidence.
Results
In this study, 441 patients received WBRT and 62 received NBS-RT, with median ages of 62 and 61 years, respectively. A significant portion of both groups, 77.3% in WBRT and 80.6% in NBS-RT, received post-RT systemic therapy. The median number of brain metastases was 10 for WBRT and 12 for NBS-RT, with median maximal diameters of 11.7 mm in WBRT and 14.4 mm in NBS-RT. After a median follow-up of 10.9 months for WBRT and 11.8 months for NBS-RT, there were no significant differences in intracranial progression (p=0.516) or OS (p=0.492) between the groups. However, WBRT patients had a higher incidence of leukoencephalopathy than NBS-RT patients (p=0.013).
Conclusion
NBS-RT combined with systemic therapy was as effective in treating multiple brain metastases as WBRT and was less toxic. NBS-RT-based strategies deserve further investigation in a prospective setting.

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Associations of Financial Toxicity with Employment Concerns and Cancer-Related Distress: A Cross-Sectional Survey among Korean Working-Age Cancer Survivors: Hyun-Ju Seo, Dal-Lae Jin, Young Ae Kim, Su Jung Lee, Seok-Jun Yoon; Received January 24, 2024 Accepted December 2, 2024 Published online December 3, 2024; DOI: https://doi.org/10.4143/crt.2024.090 [Accepted]

Abstract PDF: Purpose
Although South Korea’s health insurance has a co-payment-decreasing policy for cancer survivors, information on the extent of financial toxicity and its related factors is limited. We assessed the level of financial toxicity and the association of high levels of financial toxicity with employment concerns after diagnosis and cancer-related distress in working-age cancer survivors.
Materials and Methods
A cross-sectional study was conducted. Study participants were recruited from the National Cancer Survivorship Center between November and December 2022. Financial burden was assessed using the Korean version of the Comprehensive Score for Financial Toxicity, and cancer-related distress was measured using the NCCN Distress Thermometer. Multivariate logistic regression analyses were used to explore the associations between high financial toxicity, cancer-related distress, and changes in employment status after cancer diagnosis.
Results
Of 1,403 working-age cancer survivors, approximately 62% reported high levels of financial distress. Survivors reporting early retirement and taking time off work with the intent to return were more likely to report high financial toxicity (adjusted OR 1.69, 95% CI 1.14-2.5; and adjusted OR 2.82, 95% CI 1.24-6.43, respectively) than those with a full-time or part-time job. Moreover, cancer survivors with high distress levels were more likely to report high financial toxicity than those with low distress levels (adjusted OR 4.36, 95% CI 3.17-5.99).
Conclusion
High financial toxicity is associated with adverse employment concerns and cancer-related distress among working-age cancer survivors. Therefore, developing cancer survivorship interventions within the healthcare system is necessary to ensure improvements in financial well-being.

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Machine Learning-Based Prognostic Gene Signature for Early Triple Negative Breast Cancer: Ju Won Kim, Jonghyun Lee, Sung Hak Lee, Sangjeong Ahn, Kyong Hwa Park; Received September 26, 2024 Accepted November 18, 2024 Published online November 19, 2024; DOI: https://doi.org/10.4143/crt.2024.937 [Accepted]

Abstract PDF: Purpose
This study aimed to develop a machine learning-based approach to identify prognostic gene signatures for early-stage Triple Negative Breast Cancer (TNBC) using next-generation sequencing data from Asian populations.
Materials and Methods
We utilized next-generation sequencing data to analyze gene expression profiles and identify potential biomarkers. Our methodology involved integrating various machine learning techniques, including feature selection and model optimization. We employed logistic regression, Kaplan-Meier survival analysis, and receiver operating characteristic (ROC) curves to validate the identified gene signatures.
Results
We identified a gene signature significantly associated with relapse in TNBC patients. The predictive model demonstrated robustness and accuracy, with an area under the ROC curve (AUROC) of 0.9087, sensitivity of 0.8750, and specificity of 0.9231. The Kaplan-Meier survival analysis revealed a strong association between the gene signature and patient relapse, further validated by logistic regression analysis.
Conclusion
This study presents a novel machine learning-based prognostic tool for TNBC, offering significant implications for early detection and personalized treatment. The identified gene signature provides a promising approach for improving the management of TNBC, contributing to the advancement of precision oncology.

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Effectiveness and Safety of Regorafenib and TAS-102 in Patients with Metastatic Colorectal Cancer: A Nationwide Population-Based Study in Taiwan: Ya-Wen Chang, Chun-Nan Kuo, Chia-Lun Chang, Jason C. Hsu, Yu Ko; Received April 16, 2024 Accepted November 16, 2024 Published online November 18, 2024; DOI: https://doi.org/10.4143/crt.2024.376 [Accepted]

Abstract PDF: Purpose
This study aimed to examine the real-world effectiveness and safety of regorafenib and trifluridine/tipiracil (TAS-102) in metastatic colorectal cancer (mCRC) patients in Taiwan.
Materials and Methods
Data were extracted from Taiwan’s National Health Insurance Research Database to evaluate the clinical outcomes of mCRC patients treated with either regorafenib or TAS-102 between 2016 and 2019. Overall survival (OS) was compared using Kaplan-Meier curves and Cox’s proportional hazard models, adjusting for age, gender, Quan-CCI score, liver metastases, number of metastatic sites, and the use of anti-EGFR medications. Additionally, OS was compared between regorafenib monotherapy and TAS-102 monotherapy, excluding patients who had received both regorafenib and TAS-102.
Results
A total of 2,608 patients in the regorafenib group and 521 patients in the TAS-102 group were identified. The median OS was 6.5 months for regorafenib and 7.5 months for TAS-102, with a significant difference observed (p=0.001). The mean duration of treatment was similar for regorafenib and TAS-102 (108 days vs. 101 days) with no significant difference. The safety profiles of the two drugs were distinct; a higher proportion of patients in the regorafenib group had hypertension and hand-foot skin reaction while nausea and vomiting were more common in the TAS-102 group. In the subgroup analysis, patients receiving TAS-102 monotherapy showed significantly longer OS than those receiving regorafenib monotherapy.
Conclusion
The findings of this study indicated that TAS-102 had superior survival outcomes compared to regorafenib in mCRC patients. This study provides insights into the effectiveness and safety profiles of regorafenib and TAS-102 in Taiwan.

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Predictive Value of the nProfiler 1 Assay for the Efficacy of Adjuvant S-1-Based Doublet Chemotherapy in Stage III Gastric Cancer: A Post-Hoc Analysis of a Randomized Phase III Trial: Dong Ki Lee, Choong-kun Lee, Hyo Song Kim, Sun Jin Sym, Dae Young Zang, Ki Hyang Kim, Joo Han Lim, Hae Su Kim, Kyung Hee Lee, Heon Yung Gee, Sun Young Rha, Hyunki Kim, Minkyu Jung; Received July 25, 2024 Accepted November 9, 2024 Published online November 12, 2024; DOI: https://doi.org/10.4143/crt.2024.705 [Accepted]

Abstract PDF: Purpose
The nProfiler 1 Stomach Cancer Assay (nProfiler1), designed to predict responses to fluorouracil-based adjuvant chemotherapy, measures the expression of four gastric cancer target genes (GZMB, WARS, SFRP4, and CDX1). The randomized phase III POST trial aimed to compare the efficacies of two adjuvant S-1-based doublet chemotherapies: S-1 plus cisplatin (SP) and S-1 plus docetaxel (DS). This study aimed to validate the nProfiler1 assay using a distinct cohort from the POST trial.
Materials and Methods
The nProfiler1 assay stratifies patients into three groups (low-risk, intermediate-risk, and high-risk) using the prognostic single-patient classifier and two groups (chemotherapy-benefit and no-benefit) using the predictive single-patient classifier. The nProfiler1 assay was applied to formalin-fixed paraffin-embedded slides obtained from the POST trial. Disease-free survival (DFS) and overall survival (OS), including 5-year survival rates, were calculated for the enrolled patients.
Results
Of the 153 patients in the POST trial, 118 were included in the post-hoc analysis. With a median follow-up of 57.9 months, no significant difference in DFS or OS was observed between the SP and DS groups. The prognostic single-patient classifier predicted the OS in the SP group (p=0.0425) but not in the DS group (p=0.5940). The chemotherapy-benefit group exhibited numerically longer DFS than the no-benefit group in the SP and DS groups.
Conclusion
The nProfiler1 assay offers valuable insights into the prognosis and efficacy of adjuvant chemotherapy based on fluorouracil plus platinum doublet regimens but not docetaxel-containing regimens. Further validation with larger patient cohorts and different regimens is warranted.

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Unraveling the Impact of Sarcopenia-Induced Lymphopenia on Treatment Response and Prognosis in Patients with Stage III Non-Small Cell Lung Cancer: Insights for Optimizing Chemoradiation and Immune Checkpoint Inhibitor: Joongyo Lee, Kyung Hwan Kim, Jina Kim, Chang Geol Lee, Jaeho Cho, Hong In Yoon, Yeona Cho; Received May 23, 2024 Accepted October 29, 2024 Published online October 30, 2024; DOI: https://doi.org/10.4143/crt.2024.493 [Accepted]

Abstract PDF: Purpose
Sarcopenia is a poor prognostic factor in non-small cell lung cancer (NSCLC). However, its prognostic significance in patients with NSCLC receiving immune checkpoint inhibitors (ICIs) and its relationship with lymphopenia remain unclear. We aimed to investigate the prognostic role of sarcopenia and its effect on lymphocyte recovery in patients with stage III NSCLC treated with concurrent chemoradiotherapy (CCRT) followed by ICI.
Materials and Methods
We retrospectively evaluated 151 patients with stage III NSCLC who received definitive CCRT followed by maintenance ICI between January 2016 and June 2022. Sarcopenia was evaluated by measuring the skeletal muscle area at the L3 vertebra level using computed tomography scans. Lymphocyte level changes were assessed based on measurements taken before and during CCRT and at 1, 2, 3, 6, and 12 months post-CCRT completion.
Results
Even after adjusting for baseline absolute lymphocyte count through propensity score-matching, patients with pre-radiotherapy (RT) sarcopenia (n=86) exhibited poor lymphocyte recovery and a significantly high incidence of grade ≥3 lymphopenia during CCRT. Pre-RT sarcopenia and grade ≥3 lymphopenia during CCRT emerged as prognostic factors for overall survival and progression-free survival, respectively. Concurrent chemotherapy dose adjustments, objective response after CCRT, and discontinuation of maintenance ICI were also analyzed as independent prognostic factors.
Conclusion
Our results demonstrated an association between pre-RT sarcopenia and poor survival, concurrent chemotherapy dose adjustments, and impaired lymphocyte recovery after definitive CCRT. Moreover, CCRT-induced lymphopenia not only contributed to poor prognosis but may have also impaired the therapeutic efficacy of subsequent maintenance ICI, ultimately worsening treatment outcomes.

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Impact of TTF-1 Expression on the Prognostic Prediction of Patients with NSCLC with PD-L1 Expression Levels of 1% to 49%, Treated with Chemotherapy vs Chemoimmunotherapy: A Multicenter, Retrospective Study: Naoya Nishioka, Tae Hata, Tadaaki Yamada, Yasuhiro Goto, Akihiko Amano, Yoshiki Negi, Satoshi Watanabe, Naoki Furuya, Tomohiro Oba, Tatsuki Ikoma, Akira Nakao, Keiko Tanimura, Hirokazu Taniguchi, Akihiro Yoshimura, Tomoya Fukui, Daiki Murata, Kyoichi Kaira, Shinsuke Shiotsu, Makoto Hibino, Asuka Okada, Yusuke Chihara, Hayato Kawachi, Takashi Kijima, Koichi Takayama; Received August 7, 2024 Accepted October 24, 2024 Published online October 25, 2024; DOI: https://doi.org/10.4143/crt.2024.748 [Accepted]

Abstract PDF: Purpose
Thyroid transcription factor 1 (TTF-1) expression is a useful predictor of treatment efficacy in advanced non-squamous non-small-cell lung cancer (NSCLC). This study aimed to evaluate whether TTF-1 could predict the effectiveness of chemotherapy versus chemoimmunotherapy in patients with non-squamous NSCLC with programmed death ligand-1 (PD-L1) expression between 1% and 49%.
Materials and Methods
We conducted a retrospective study of patients with NSCLC who were treated with chemotherapy or chemoimmunotherapy between March 2016 and May 2023. The patients had histologically confirmed NSCLC, stage III-IV or postoperative recurrence, TTF-1 measurements, and PD-L1 expression levels between 1% and 49%. Clinical data were analyzed to evaluate the effect of TTF-1 expression on treatment efficacy.
Results
This study included 283 of 624 patients. TTF-1-positive patients showed longer progression-free survival (PFS) and overall survival (OS) (PFS: 6.4 months [95% confidence interval (CI): 5.0−9.4] vs 4.1 months [95% CI: 2.7−6.1], p=0.03, OS: 17.9 months [95% CI: 15.2−28.1] vs 9.4 months [95% CI: 6.3−17.0], p<0.01) in the chemotherapy cohorts (n=93). In the chemoimmunotherapy cohort (n=190), there was no significant difference in PFS and OS between TTF-1-positive and negative groups (PFS: 7.6 months [95% CI: 6.4−11.0] vs 6.0 months [95% CI: 3.6−12.6], p=0.59, OS: 25.0 months [95% CI: 18.0−49.2] vs 21.3 months [95% CI: 9.8−28.8], p=0.09).
Conclusion
In patients with NSCLC with PD-L1 expression between 1% and 49%, TTF-1 expression was a predictor of chemotherapeutic, but not chemoimmunotherapeutic, efficacy.

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Stage Evaluation of Cystic Duct Cancer: Yeseul Kim, You-Na Sung, Haesung Jung, Kyung Jin Lee, Daegwang Yoo, Sun-Young Jun, HyungJun Cho, Shin Hwang, Woohyung Lee, Seung-Mo Hong; Received July 16, 2024 Accepted September 15, 2024 Published online September 19, 2024; DOI: https://doi.org/10.4143/crt.2024.660 [Accepted]

Abstract PDF Supplementary Material: Purpose
Cystic duct cancers (CDCs) have been classified as extrahepatic bile duct cancers or gallbladder cancers (GBCs); however, it is unclear whether their clinical behavior is similar to that of distal extrahepatic bile duct cancers (DBDCs) or GBCs.
Materials and Methods
T category of the CDCs was classified using current T category scheme of the GBCs and DBDCs, and clinicopathological factors were compared among 38 CDCs, 345 GBCs, and 349 DBDCs. We modified Nakata’s classifications (type 1, confined within cystic duct (CD); combined types 2–4, extension beyond CD) and compared them.
Results
No significant overall survival (OS) difference was observed between the patients with CDC, GBC, and DBDC. The T category of GBC staging was more accurate at distinguishing OS in patients with CDC than the DBDC staging. Patients with T3 CDC and GBC showed a significant OS difference when using the T category for GBC staging, while those with T1–T2 CDC and GBC showed no significant difference. In contrast, the T category of DBDC staging did not show any significant OS difference between patients with T1–T2 CDC and DBDC or T3 CDC and DBDC. Patients with type 1 CDC had significantly better OS than those with combined types.
Conclusion
Unlike GBCs and DBDCs, CDCs exhibit distinct clinicopathological characteristics. The OS is better when the CDC confines within the CD, compared to when it extends beyond it. Therefore, we propose a new T category scheme (T1, confined to CD; T2, invaded beyond CD) for better classifying CDCs.

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Weight Change after Cancer Diagnosis and Risk of Diabetes Mellitus: A Population-Based Nationwide Study: Hye Yeon Koo, Kyungdo Han, Mi Hee Cho, Wonyoung Jung, Jinhyung Jung, In Young Cho, Dong Wook Shin; Received June 25, 2024 Accepted August 28, 2024 Published online August 29, 2024; DOI: https://doi.org/10.4143/crt.2024.586 [Epub ahead of print]

Abstract PDF Supplementary Material

Purpose
Cancer survivors are at increased risk of diabetes mellitus (DM). Additionally, the prevalence of obesity, which is also a risk factor for DM, is increasing in cancer survivors. We investigated the associations between weight change after cancer diagnosis and DM risk.
Materials and Methods
This retrospective cohort study used data from the Korean National Health Insurance Service. Participants who were newly diagnosed with cancer from 2010 to 2016 and received national health screening before and after diagnosis were included and followed until 2019. Weight change status after cancer diagnosis was categorized into four groups: sustained normal weight, obese to normal weight, normal weight to obese, or sustained obese. Cox proportional hazard analyses were performed to examine associations between weight change and DM.
Results
The study population comprised 264,250 cancer survivors. DM risk was highest in sustained obese (adjusted hazard ratios [aHR], 2.17; 95% confidence interval [CI], 2.08 to 2.26), followed by normal weight to obese (aHR, 1.66; 95% CI, 1.54 to 1.79), obese to normal weight (aHR, 1.29; 95% CI, 1.21 to 1.39), and then sustained normal weight group (reference). In subgroup analyses according to cancer type, most cancers showed the highest risks in sustained obese group.
Conclusion
Obesity at any time point was related to increased DM risk, presenting the highest risk in cancer survivors with sustained obesity. Survivors who changed from obese to normal weight had lower risk than survivors with sustained obesity. Survivors who changed from normal weight to obese showed increased risk compared to those who sustained normal weight. Our finding supports the significance of weight management among cancer survivors.

Citations

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Effects of smoking behavior change on diabetes incidence after cancer development: A nationwide cohort study
MI Hee Cho, Jinhyung Jung, Hye Yeon Koo, Wonyoung Jung, Kyungdo Han, In Young Cho, Dong Wook Shin
Diabetes & Metabolism.2025; 51(1): 101604. CrossRef

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Harnessing Institutionally Developed Clinical Targeted Sequencing to Improve Patient Survival in Breast Cancer: A Seven-Year Experience: Jiwon Koh, Jinyong Kim, Go-Un Woo, Hanbaek Yi, So Yean Kwon, Jeongmin Seo, Jeong Mo Bae, Jung Ho Kim, Jae Kyung Won, Han Suk Ryu, Yoon Kyung Jeon, Dae-Won Lee, Miso Kim, Tae-Yong Kim, Kyung-Hun Lee, Tae-You Kim, Jee-Soo Lee, Moon-Woo Seong, Sheehyun Kim, Sungyoung Lee, Hongseok Yun, Myung Geun Song, Jaeyong Choi, Jong-Il Kim, Seock-Ah Im; Received March 23, 2024 Accepted August 18, 2024 Published online August 21, 2024; DOI: https://doi.org/10.4143/crt.2024.296 [Epub ahead of print]

Abstract PDF Supplementary Material PubReader ePub: Purpose
Considering the high disease burden and unique features of Asian patients with breast cancer (BC), it is essential to have a comprehensive view of genetic characteristics in this population. An institutional targeted sequencing platform was developed through the Korea Research-Driven Hospitals project and was incorporated into clinical practice. This study explores the use of targeted next-generation sequencing (NGS) and its outcomes in patients with advanced/metastatic BC in the real world.
Materials and Methods
We reviewed the results of NGS tests administered to BC patients using a customized sequencing platform—FiRST Cancer Panel (FCP)—over 7 years. We systematically described clinical translation of FCP for precise diagnostics, personalized therapeutic strategies, and unraveling disease pathogenesis.
Results
NGS tests were conducted on 548 samples from 522 patients with BC. Ninety-seven point six percentage of tested samples harbored at least one pathogenic alteration. The common alterations included mutations in TP53 (56.2%), PIK3CA (31.2%), GATA3 (13.8%), BRCA2 (10.2%), and amplifications of CCND1 (10.8%), FGF19 (10.0%), and ERBB2 (9.5%). NGS analysis of ERBB2 amplification correlated well with human epidermal growth factor receptor 2 immunohistochemistry and in situ hybridization. RNA panel analyses found potentially actionable and prognostic fusion genes. FCP effectively screened for potentially germline pathogenic/likely pathogenic mutation. Ten point three percent of BC patients received matched therapy guided by NGS, resulting in a significant overall survival advantage (p=0.022), especially for metastatic BCs.
Conclusion
Clinical NGS provided multifaceted benefits, deepening our understanding of the disease, improving diagnostic precision, and paving the way for targeted therapies. The concrete advantages of FCP highlight the importance of multi-gene testing for BC, especially for metastatic conditions.

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Combination Therapy of Pyrotinib and Metronomic Vinorelbine in HER2+ Advanced Breast Cancer after Trastuzumab Failure (PROVE): A Prospective Phase 2 Study: Chunfang Hao, Xu Wang, Yehui Shi, Zhongsheng Tong, Shufen Li, Xiaodong Liu, Lan Zhang, Jie Zhang, Wenjing Meng, Li Zhang; Received April 3, 2024 Accepted August 8, 2024 Published online August 9, 2024; DOI: https://doi.org/10.4143/crt.2024.340 [Epub ahead of print]

Abstract PDF PubReader ePub: Purpose
Approximately 50%-74% of patients with metastatic human epidermal growth factor receptor 2 (HER2)–positive breast cancer do not respond to trastuzumab, with 75% of treated patients experiencing disease progression within a year. The combination of pyrotinib and capecitabine has showed efficacy in these patients. This study evaluates the efficacy and safety of pyrotinib combined with metronomic vinorelbine for trastuzumab-pretreated HER2-positive advanced breast cancer patients.
Materials and Methods
In this phase 2 trial, patients aged 18-75 years with HER2-positive advanced breast cancer who had previously failed trastuzumab treatment were enrolled to receive pyrotinib 400 mg daily in combination with vinorelbine 40mg thrice weekly. The primary endpoint was progression-free survival (PFS), while secondary endpoints included objective response rate (ORR), disease control rate (DCR), overall survival (OS), and safety.
Results
From October 21, 2019, to January 21, 2022, 36 patients were enrolled and received at least one dose of study treatment. At the cutoff date, 20 experienced disease progression or death. With a median follow-up duration of 35 months, the median PFS was 13.5 months (95% confidence interval [CI], 8.3 to 18.5). With all patients evaluated, an ORR of 38.9% (95% CI, 23.1 to 56.5) and a DCR of 83.3% (95% CI, 67.2 to 93.6) were achieved. The median OS was not reached. Grade 3 adverse events (AEs) were observed in 17 patients, with diarrhea being the most common (27.8%), followed by vomiting (8.3%) and stomachache (5.6%). There were no grade 4/5 AEs.
Conclusion
Pyrotinib combined with metronomic vinorelbine showed promising efficacy and an acceptable safety profile in HER2-positive advanced breast cancer patients after trastuzumab failure.

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Gastrointestinal cancer

Integrating Deep Learning–Based Dose Distribution Prediction with Bayesian Networks for Decision Support in Radiotherapy for Upper Gastrointestinal Cancer: Dong-Yun Kim, Bum-Sup Jang, Eunji Kim, Eui Kyu Chie; Cancer Res Treat. 2025;57(1):186-197. Published online August 2, 2024; DOI: https://doi.org/10.4143/crt.2024.333

Abstract PDF Supplementary Material PubReader ePub: Purpose
Selecting the better techniques to harbor optimal motion management, either a stereotactic linear accelerator delivery using TrueBeam (TBX) or magnetic resonance–guided gated delivery using MRIdian (MRG), is time-consuming and costly. To address this challenge, we aimed to develop a decision-supporting algorithm based on a combination of deep learning-generated dose distributions and clinical data.
Materials and Methods
We retrospectively analyzed 65 patients with liver or pancreatic cancer who underwent both TBX and MRG simulations and planning process. We trained three-dimensional U-Net deep learning models to predict dose distributions and generated dose volume histograms (DVHs) for each system. We integrated predicted DVH metrics into a Bayesian network (BN) model incorporating clinical data.
Results
The MRG prediction model outperformed the TBX model, demonstrating statistically significant superiorities in predicting normalized dose to the planning target volume (PTV) and liver. We developed a final BN prediction model integrating the predictive DVH metrics with patient factors like age, PTV size, and tumor location. This BN model an area under the receiver operating characteristic curve index of 83.56%. The decision tree derived from the BN model showed that the tumor location (abutting vs. apart of PTV to hollow viscus organs) was the most important factor to determine TBX or MRG. It provided a potential framework for selecting the optimal radiation therapy (RT) system based on individual patient characteristics.
Conclusion
We demonstrated a decision-supporting algorithm for selecting optimal RT plans in upper gastrointestinal cancers, incorporating both deep learning-based dose prediction and BN-based treatment selection. This approach might streamline the decision-making process, saving resources and improving treatment outcomes for patients undergoing RT.

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Trends in Cancer-Screening Rates in Korea: Findings from the National Cancer Screening Survey, 2004-2023: EunKyo Kang, Kui Son Choi, Jae Kwan Jun, Yeol Kim, Hyeon Ji Lee, Chang Kyun Choi, Tae Hee Kim, Sun Hwa Lee, Mina Suh; Cancer Res Treat. 2025;57(1):28-38. Published online August 2, 2024; DOI: https://doi.org/10.4143/crt.2024.325

Abstract PDF Supplementary Material PubReader ePub: Purpose
This study aimed to report the overall national trends in the rates of cancer screening based on recommendations and provide insights into the changing trends of these rates across different demographics.
Materials and Methods
This study used data from the Korean National Cancer Screening Survey (KNCSS), which surveys nationwide cancer-screening rates and includes 4,500 individuals meeting the Korean National Cancer Screening Program (NCSP) protocol age criteria. Cancer-screening rates were assessed using structured questionnaires; yearly trends were analyzed for both lifetime cancer-screening rates and rates of screening based on recommendations, and subgroup analyses were performed based on age and sex.
Results
The rates of cancer screening based on recommendations showed significant increments: the stomach cancer-screening rate increased from 39.2% in 2004 to 77.5% in 2023 (3.50% per year), the liver cancer-screening rate increased from 20.0% to 48.8% (4.30% per year), and the colorectal cancer, increased from 19.9% to 70.7% (5.15% per year). The breast cancer-screening rate increased from 33.2% to 72.7% (2.88% per year), and the cervical cancer, increased from 58.3% to 70.2% (1.08% per year). Despite some differences, particularly in relation to sociodemographic factors, screening rates increased significantly for all cancer types.
Conclusion
Cancer-screening rates in Korea increased consistently from 2004 to 2023, demonstrating the effectiveness of the national cancer-screening program. However, the increments in breast, cervical and lung cancer-screening rates were relatively lower, indicating the need for additional efforts and strategies.

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General

The Survival and Financial Benefit of Investigator-Initiated Trials Conducted by Korean Cancer Study Group: Bum Jun Kim, Chi Hoon Maeng, Bhumsuk Keam, Young-Hyuck Im, Jungsil Ro, Kyung Hae Jung, Seock-Ah Im, Tae Won Kim, Jae Lyun Lee, Dae Seog Heo, Sang-We Kim, Keunchil Park, Myung-Ju Ahn, Byoung Chul Cho, Hoon-Kyo Kim, Yoon-Koo Kang, Jae Yong Cho, Hwan Jung Yun, Byung-Ho Nam, Dae Young Zang; Cancer Res Treat. 2025;57(1):39-46. Published online July 10, 2024; DOI: https://doi.org/10.4143/crt.2024.421

Abstract PDF PubReader ePub: Purpose
The Korean Cancer Study Group (KCSG) is a nationwide cancer clinical trial group dedicated to advancing investigator-initiated trials (IITs) by conducting and supporting clinical trials. This study aims to review IITs conducted by KCSG and quantitatively evaluate the survival and financial benefits of IITs for patients.
Materials and Methods
We reviewed IITs conducted by KCSG from 1998 to 2023, analyzing progression-free survival (PFS) and overall survival (OS) gains for participants. PFS and OS benefits were calculated as the difference in median survival times between the intervention and control groups, multiplied by the number of patients in the intervention group. Financial benefits were assessed based on the cost of investigational products provided.
Results
From 1998 to 2023, KCSG conducted 310 IITs, with 133 completed and published. Of these, 21 were included in the survival analysis. The analysis revealed that 1,951 patients in the intervention groups gained a total of 2,558.4 months (213.2 years) of PFS and 2,501.6 months (208.5 years) of OS, with median gains of 1.31 months in PFS and 1.58 months in OS per patient. When analyzing only statistically significant results, PFS and OS gain per patients was 1.69 months and 3.02 months, respectively. Investigational drug cost analysis from six available IITs indicated that investigational products provided to 252 patients were valued at 10,400,077,294 won (approximately 8,046,481 US dollars), averaging about 41,270,148 won (approximately 31,930 US dollars) per patient.
Conclusion
Our findings, based on analysis of published research, suggest that IITs conducted by KCSG led to survival benefits for participants and, in some studies, may have provided financial benefits by providing investment drugs.

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Gastrointestinal cancer

Clinical Outcomes of Surgery after Neoadjuvant Chemotherapy in Locally Advanced Pancreatic Ductal Adenocarcinoma: Yoo Na Lee, Min Kyu Sung, Dae Wook Hwang, Yejong Park, Bong Jun Kwak, Woohyung Lee, Ki Byung Song, Jae Hoon Lee, Changhoon Yoo, Kyu-Pyo Kim, Heung-Moon Chang, Baek-Yeol Ryoo, Song Cheol Kim; Cancer Res Treat. 2024;56(4):1240-1251. Published online June 19, 2024; DOI: https://doi.org/10.4143/crt.2023.977

Abstract PDF PubReader ePub: Purpose
Clinical outcomes of surgery after neoadjuvant chemotherapy have not been investigated for locally advanced pancreatic cancer (LAPC), despite well-established outcomes in borderline resectable pancreatic cancer (BRPC). This study aimed to investigate the clinical outcomes of patients with LAPC who underwent curative resection following neoadjuvant chemotherapy.
Materials and Methods
We retrospectively reviewed the records of patients diagnosed with pancreatic adenocarcinoma between January 2017 and December 2020.
Results
Among 1,358 patients, 260 underwent surgery following neoadjuvant chemotherapy. Among 356 LAPC patients, 98 (27.5%) and 147 (35.1%) of 418 BRPC patients underwent surgery after neoadjuvant chemotherapy. Compared to resectable pancreatic cancer (resectable PC) with upfront surgery, both LAPC and BRPC exhibited higher rates of venous resection (28.6% vs. 49.0% vs. 4.0%), arterial resection (30.6% vs. 6.8% vs. 0.5%) and greater estimated blood loss (260.5 vs. 213.1 vs. 70.4 mL). However, hospital stay, readmission rates, and postoperative pancreatic fistula rates (grade B or C) did not differ significantly between LAPC, BRPC, and resectable PC. Overall and relapse-free survival did not differ significantly between LAPC and BRPC patients. The median overall survival was 37.3 months for LAPC and 37.0 months for BRPC. The median relapse-free survival was 22.7 months for LAPC and 26.0 months for BRPC.
Conclusion
Overall survival time and postoperative complications in LAPC patients who underwent curative resection following neoadjuvant chemotherapy showed similar results to those of BRPC patients. Further research is needed to identify specific sub-populations of LAPC patients who benefit most from conversion surgery and to minimize postoperative complications.

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General

Therapeutic Effect of Anti-inflammatory Tripeptide Cream in Hand-Foot Syndrome/Skin Reaction Related to Anticancer Drugs: A Randomized, Double-Blind, Placebo-Controlled Pilot Trial: Yaewon Yang, Jang-Hee Hahn, Min Seo Kim, Minkwan Jo, Yong-Pyo Lee, Hongsik Kim, Hee Kyung Kim, Jihyun Kwon, Ki Hyeong Lee, Hye Sook Han; Cancer Res Treat. 2024;56(4):1050-1057. Published online June 5, 2024; DOI: https://doi.org/10.4143/crt.2024.080

Abstract PDF Supplementary Material PubReader ePub: Purpose
Hand-foot syndrome (HFS) and hand-foot skin reaction (HFSR) are relatively common toxicities that interfere with the quality of life (QoL) of patients with cancer. Anti-inflammatory tripeptide cream (ATPC) is a complex formulation of anti-inflammatory tripeptides, the CD99-agonist Binterin and the Wnt-antagonist Winhibin. The present study aimed to assess the therapeutic effects of ATPC in HFS/HFSR associated with anticancer drugs.
Materials and Methods
This was a single-center, randomized, double-blind, placebo-controlled trial. Patients who developed grade 1 HFS/HFSR after systemic anticancer treatments were enrolled, and randomly assigned to receive either ATPC or placebo cream (PC) and followed up at 3-week intervals for up to 9 weeks. Primary endpoint was the development of grade ≥ 2 HFS/HFSR.
Results
Between April 2019 and July 2022, 60 patients (31 in the ATPC and 29 in the PC group) completed the study. The incidence of grade ≥ 2 HFS/HFSR was significantly lower in the ATPC than in the PC group (25.8% vs. 51.7%, p=0.039). The ATPC showed trends towards a better QoL score, assessed by a HFSR and QoL questionnaire at 9 weeks (26.0 vs. 29.9, p=0.574), and a lower frequency of discontinuation, interruption, or dose reduction of anticancer drugs (51.6% vs. 58.6%, p=0.586) than the PC group over 9 weeks, though without statistical significance.
Conclusion
Our results showed that ATPC significantly decreased the development of grade ≥ 2 HFS/HFSR in patients already with HFS/HFSR. Therefore, ATPC may be an effective treatment for HFS/HFSR associated with anticancer drugs.

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Precision Oncology Clinical Trials: A Systematic Review of Phase II Clinical Trials with Biomarker-Driven, Adaptive Design: Hyerim Ha, Hee Yeon Lee, Jee Hyun Kim, Do Yeun Kim, Ho Jung An, SeungJin Bae, Hye-sung Park, Jin Hyoung Kang; Cancer Res Treat. 2024;56(4):991-1013. Published online May 7, 2024; DOI: https://doi.org/10.4143/crt.2024.128

Abstract PDF Supplementary Material PubReader ePub: Novel clinical trial designs are conducted in the precision medicine era. This study aimed to evaluate biomarker-driven, adaptive phase II trials in precision oncology, focusing on infrastructure, efficacy, and safety. We systematically reviewed and analyzed the target studies. EMBASE and PubMed searches from 2015 to 2023 generated 29 eligible trials. Data extraction included infrastructure, biomarker screening methodologies, efficacy, and safety profiles. Government agencies, cancer hospitals, and academic societies with accumulated experiences led investigator-initiated precision oncology clinical trials (IIPOCTs), which later guided sponsor-initiated precision oncology clinical trials (SIPOCTs). Most SIPOCTs were international studies with basket design. IIPOCTs primarily used the central laboratory for biomarker screening, but SIPOCTs used both central and local laboratories. Most of the studies adapted next-generation sequencing and/or immunohistochemistry for biomarker screening. Fifteen studies included an independent central review committee for outcome investigation. Efficacy assessments predominantly featured objective response rate as the primary endpoint, with varying results. Nine eligible studies contributed to the United States Food and Drug Administration’s marketing authorization. Safety monitoring was rigorous, but reporting formats lacked uniformity. Health-related quality of life and patient-reported outcomes were described in some protocols but rarely reported. Our results reveal that precision oncology trials with adaptive design rapidly and efficiently evaluate anticancer drugs’ efficacy and safety, particularly in specified biomarker-driven cohorts. The evolution from IIPOCT to SIPOCT has facilitated fast regulatory approval, providing valuable insights into the precision oncology landscape.

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Gastrointestinal cancer

Longitudinal Comparative Analysis of Circulating Tumor DNA and Matched Tumor Tissue DNA in Patients with Metastatic Colorectal Cancer Receiving Palliative First-Line Systemic Anti-Cancer Therapy: Seung-been Lee, Ji-Won Kim, Hong-Geun Kim, Sung-Hyun Hwang, Kui-Jin Kim, Ju Hyun Lee, Jeongmin Seo, Minsu Kang, Eun Hee Jung, Koung Jin Suh, Se Hyun Kim, Jin Won Kim, Yu Jung Kim, Jee Hyun Kim, Nak-Jung Kwon, Keun-Wook Lee; Cancer Res Treat. 2024;56(4):1171-1182. Published online April 29, 2024; DOI: https://doi.org/10.4143/crt.2024.016

Abstract PDF Supplementary Material PubReader ePub: Purpose
This study aimed to compare tumor tissue DNA (ttDNA) and circulating tumor DNA (ctDNA) to explore the clinical applicability of ctDNA and to better understand clonal evolution in patients with metastatic colorectal cancer undergoing palliative first-line systemic therapy.
Materials and Methods
We performed targeted sequencing analysis of 88 cancer-associated genes using germline DNA, ctDNA at baseline (baseline-ctDNA), and ctDNA at progressive disease (PD-ctDNA). The results were compared with ttDNA data.
Results
Among 208 consecutively enrolled patients, we selected 84 (41 males; median age, 59 years; range, 35 to 90 years) with all four sample types available. A total of 202 driver mutations were found in 34 genes. ttDNA exhibited the highest mutation frequency (n=232), followed by baseline-ctDNA (n=155) and PD-ctDNA (n=117). Sequencing ctDNA alongside ttDNA revealed additional mutations in 40 patients (47.6%). PD-ctDNA detected 13 novel mutations in 10 patients (11.9%) compared to ttDNA and baseline-ctDNA. Notably, seven mutations in five patients (6.0%) were missense or nonsense mutations in APC, TP53, SMAD4, and CDH1 genes. In baseline-ctDNA, higher maximal variant allele frequency (VAF) values (p=0.010) and higher VAF values of APC (p=0.012), TP53 (p=0.012), and KRAS (p=0.005) mutations were significantly associated with worse overall survival.
Conclusion
While ttDNA remains more sensitive than ctDNA, our ctDNA platform demonstrated validity and potential value when ttDNA was unavailable. Post-treatment analysis of PD-ctDNA unveiled new pathogenic mutations, signifying cancer’s clonal evolution. Additionally, baseline-ctDNA’s VAF values were prognostic after treatment.

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Association between Endoscopist Volume and Interval Cancers after Colonoscopy: Results from the National Colorectal Cancer Screening Program in Korea: Dong Jun Kim, Nan-He Yoon, Jae Kwan Jun, Mina Suh, Sunhwa Lee, Seongju Kim, Ji Eun Kim, Hooyeon Lee; Cancer Res Treat. 2024;56(4):1164-1170. Published online April 16, 2024; DOI: https://doi.org/10.4143/crt.2024.009

Abstract PDF Supplementary Material PubReader ePub: Purpose
The rate of interval colorectal cancer (iCRC) is now accepted as a key performance indicator of organized colorectal cancer (CRC) screening programs. We aimed to examine the association between endoscopist volumes and the rate of iCRC among individuals with a positive fecal immunochemical test (FIT) within a nationwide population-based CRC screening program.
Materials and Methods
Individuals aged ≥ 50 years who underwent colonoscopy after a positive FIT from January 1, 2019 until December 31, 2020 in the Korean National Cancer Screening Program (KNCSP) were enrolled. We converted the data into per-endoscopist screening results, calculated the iCRC rates per endoscopist, and compared them to the previous year’s annual volume that was divided into five groups (V1, 1-9; V2, 10-29; V3, 30-59; V4, 60-119; V5, ≥ 120).
Results
A total of 10,412 endoscopists performed 216,907 colonoscopies. Overall, the average rate of iCRC per endoscopist was 8.46 per 1,000 examinations. Compared with the group with the highest volume (V5 group), the rate of iCRC was 2.21 times higher in the V1 group. Similar trends were observed in the other groups (V2: relative risks [RR], 2.15; 95% confidence interval [CI], 1.57 to 2.94; V3: RR, 1.56; 95% CI, 1.15 to 2.13; V4: RR, 1.18; 95% CI, 0.83 to 1.67).
Conclusion
The findings emphasize that endoscopists with lower procedure volumes have higher risks of interval cancer being missed or undetected. To maximize the preventative impact of colonoscopy for CRC, this issue should be addressed by monitoring endoscopist volumes and variations in performances.

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Identification of New Pathogenic Variants of Hereditary Diffuse Gastric Cancer: Seung-Young Oh, Giyong Jang, Jaeryuk Kim, Kyoung-Yun Jeong, Hyun Myong Kim, Yoon Jin Kwak, Seong-Ho Kong, Do Joong Park, Hyuk-Joon Lee, Sung-Yup Cho, Jong-Il Kim, Han-Kwang Yang; Cancer Res Treat. 2024;56(4):1126-1135. Published online April 11, 2024; DOI: https://doi.org/10.4143/crt.2024.328

Abstract PDF PubReader ePub

Purpose
Hereditary diffuse gastric cancer (HDGC) presents a significant genetic predisposition, notably linked to mutations in the CDH1 and CTNNA1. However, the genetic basis for over half of HDGC cases remains unidentified. The aim of this study is to identify novel pathogenic variants in HDGC and evaluate their protein expression.
Materials and Methods
Among 20 qualifying families, two were selected based on available pedigree and DNA. Whole genome sequencing (WGS) on DNA extracted from blood and whole exome sequencing on DNA from formalin-fixed paraffin-embedded tissues were performed to find potential pathogenic variants in HDGC. After selection of a candidate variant, functional validation, and enrichment analysis were performed.
Results
As a result of WGS, three candidate germline mutations (EPHA5, MCOA2, and RHOA) were identified in one family. After literature review and in-silico analyses, the RHOA mutation (R129W) was selected as a candidate. This mutation was found in two gastric cancer patients within the family. In functional validation, it showed RhoA overexpression and a higher GTP-bound state in the Rhoa^R129W mutant. Decreased phosphorylation at Ser127/397 suggested altered YAP1 regulation in the Rho-ROCK pathway. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses linked Rhoa^R129W overexpression to changed migration/adhesion in MKN1 cell line. However, this RHOA mutation (R129W) was not found in index patients in other families.
Conclusion
The RHOA mutation (R129W) emerges as a potential causative gene for HDGC, but only in one family, indicating a need for further studies to understand its role in HDGC pathogenesis fully.

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Current advances and challenges in Managing Hereditary Diffuse Gastric Cancer (HDGC): a narrative review
L. van der Sluis, J.M. van Dieren, R.S. van der Post, T.M. Bisseling
Hereditary Cancer in Clinical Practice.2024;[Epub] CrossRef

1,637 View
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1 Crossref

Applicability of Spatial Technology in Cancer Research: Sangjeong Ahn, Hye Seung Lee; Cancer Res Treat. 2024;56(2):343-356. Published online January 30, 2024; DOI: https://doi.org/10.4143/crt.2023.1302

Abstract PDF PubReader ePub

This review explores spatial mapping technologies in cancer research, highlighting their crucial role in understanding the complexities of the tumor microenvironment (TME). The TME, which is an intricate ecosystem of diverse cell types, has a significant impact on tumor dynamics and treatment outcomes. This review closely examines cutting-edge spatial mapping technologies, categorizing them into capture-, imaging-, and antibody-based approaches. Each technology was scrutinized for its advantages and disadvantages, factoring in aspects such as spatial profiling area, multiplexing capabilities, and resolution. Additionally, we draw attention to the nuanced choices researchers face, with capture-based methods lending themselves to hypothesis generation, and imaging/antibody-based methods that fit neatly into hypothesis testing. Looking ahead, we anticipate a scenario in which multi-omics data are seamlessly integrated, artificial intelligence enhances data analysis, and spatiotemporal profiling opens up new dimensions.

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Navigating the landscape of plant proteomics
Tian Sang, Zhen Zhang, Guting Liu, Pengcheng Wang
Journal of Integrative Plant Biology.2025;[Epub] CrossRef
Distinctive Phenotypic and Microenvironmental Characteristics of Neuroendocrine Carcinoma and Adenocarcinoma Components in Gastric Mixed Adenoneuroendocrine Carcinoma
Yoonjin Kwak, Soo Kyung Nam, Yujun Park, Yun-Suhk Suh, Sang-Hoon Ahn, Seong-Ho Kong, Do Joong Park, Hyuk-Joon Lee, Hyung-Ho Kim, Han-Kwang Yang, Hye Seung Lee
Modern Pathology.2024; 37(10): 100568. CrossRef
Effector Function Characteristics of Exhausted CD8+ T-Cell in Microsatellite Stable and Unstable Gastric Cancer
Dong-Seok Han, Yoonjin Kwak, Seungho Lee, Soo Kyung Nam, Seong-Ho Kong, Do Joong Park, Hyuk-Joon Lee, Nak-Jung Kwon, Hye Seung Lee, Han-Kwang Yang
Cancer Research and Treatment.2024; 56(4): 1146. CrossRef
Prognostic significance of CD8 and TCF1 double positive T cell subset in microsatellite unstable gastric cancer
Juhyeong Park, Soo Kyung Nam, Yoonjin Kwak, Hyeon Jeong Oh, Seong-Ho Kong, Do Joong Park, Hyuk-Joon Lee, Han-Kwang Yang, Hye Seung Lee
Scientific Reports.2024;[Epub] CrossRef

4,434 View
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4 Web of Science
4 Crossref

Lung and Thoracic cancer

Association of Immune-Related Adverse Events and the Efficacy of Anti–PD-(L)1 Monotherapy in Non–Small Cell Lung Cancer: Adjusting for Immortal-Time Bias: Ying Yu, Ning Chen, Sizhe Yu, Wanji Shen, Wanchen Zhai, Hui Li, Yun Fan; Cancer Res Treat. 2024;56(3):751-764. Published online January 2, 2024; DOI: https://doi.org/10.4143/crt.2023.1118

Abstract PDF Supplementary Material PubReader ePub

Purpose
The association between immune-related adverse events (irAEs) and survival outcomes in non–small cell lung cancer (NSCLC) patients treated with programmed death-(ligand) 1 [PD-(L)1] inhibitors remains controversial, partly due to variations in dealing with immortal-time bias (ITB).
Materials and Methods
We retrospectively enrolled 425 advanced NSCLC patients who received anti–PD-(L)1 monotherapy between January 2016 and June 2021, stratifying them into irAE (n=127) and non-irAE (n=298) groups. The primary endpoint was to assess the impact of irAEs on progression-free survival (PFS) and overall survival (OS). Landmark (2-, 3-, 6-, and 9-month) and time-dependent Cox analyses were performed to eliminate ITB.
Results
With a median follow-up of 38.8 months, the occurrence of overall irAEs was significantly associated with superior PFS (11.2 vs. 3.4 months, p < 0.001) and OS (31.4 vs. 14.0 months, p < 0.001), which persisted in landmark and time-dependent Cox analyses. For the main organ-specific irAEs, skin, thyroid, and hepatic irAEs, respectively, showed significantly improved survival compared to the non-irAE group, whereas pneumonitis did not. Single-organ irAEs had the best outcomes compared with multi-organ or no irAE, which also held across subgroups of skin, thyroid, and hepatic irAEs. Moreover, severe grade irAEs and immunotherapy discontinuation had a detrimental effect on survival, systemic steroid therapy showed little effect, while immunotherapy resumption had tolerable safety and a trend of improved survival.
Conclusion
After adequately adjusting ITB, the occurrence of overall irAEs predicts for favorable efficacy of anti–PD-(L)1 monotherapy in NSCLC, with better outcomes observed in patients with skin, thyroid, or hepatic irAEs, particularly those with single-organ involvement.

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Management, biomarkers and prognosis in people developing endocrinopathies associated with immune checkpoint inhibitors
Shintaro Iwama, Tomoko Kobayashi, Hiroshi Arima
Nature Reviews Endocrinology.2025;[Epub] CrossRef
Development of pituitary dysfunction and destructive thyroiditis is associated with better survival in non-small cell lung cancer patients treated with programmed cell death-1 inhibitors: a prospective study with immortal time bias correction
Koji Suzuki, Tomoko Kobayashi, Tetsushi Izuchi, Koki Otake, Masahiko Ando, Tomoko Handa, Takashi Miyata, Mariko Sugiyama, Takeshi Onoue, Daisuke Hagiwara, Hidetaka Suga, Ryoichi Banno, Tetsunari Hase, Megumi Inoue, Makoto Ishii, Hiroshi Arima, Shintaro Iw
Frontiers in Endocrinology.2024;[Epub] CrossRef
Associations between Immune-related Adverse Events and Prognosis in Cancer Patients Receiving Immune Checkpoint Inhibitor Therapy
Yusuke Inoue, Naoki Inui
Internal Medicine.2024;[Epub] CrossRef
The impact of immune-related adverse events on the outcome of advanced gastric cancer patients with immune checkpoint inhibitor treatment
Tianhang Zhang, Haitao Lv, Jiasong Li, Shasha Zhang, Jingjing Zhang, Siqi Wang, Yingnan Wang, Zhanjun Guo
Frontiers in Immunology.2024;[Epub] CrossRef

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Breast cancer

Trastuzumab Biosimilar (HLX02), Pertuzumab Plus Chemotherapy in Patients with HER2-Positive Metastatic Breast Cancer after Progression of Trastuzumab: A Prospective, Phase II Study: Ruyan Zhang, Xiaoran Liu, Guohong Song, Yan Zhang, Huiping Li; Cancer Res Treat. 2024;56(3):795-801. Published online December 20, 2023; DOI: https://doi.org/10.4143/crt.2023.1151

Abstract PDF PubReader ePub: Purpose
This study aims to evaluate the efficacy and safety of trastuzumab biosimilar (HLX02) in combination with pertuzumab and chemotherapy in patients with human epidermal growth factor receptor 2 (HER2)–positive metastatic breast cancer (MBC) after progression of trastuzumab.
Materials and Methods
In this prospective, single-arm, phase II study, patients with HER2-positive MBC after progression of trastuzumab received pertuzuamb, HLX02, and chemotherapy in Beijing Cancer Hospital from March 2020 to December 2022. The primary endpoint was progression-free survival (PFS), and secondary endpoints included objective response rate (ORR), disease control rate (DCR), overall survival (OS), and safety. The study was registered with ClinicalTrials.gov (NCT05188495).
Results
A total of 45 patients were included in this study. Twelve patients (26.7%) were treated in second-line and 33 patients (73.3%) were in third-line and later setting. Eighty percent and 15.5% patients had previously received pyrotinib/lapatinib and T-DM1, respectively. With a median follow-up of 24.4 months (range, 1.2 to 43.9 months), the median PFS was 7.6 months (95% confidence interval, 4.3 to 10.9), OS was not reached, the ORR was 31.1%, and DCR was 91.1%. The treatment was well tolerated.
Conclusion
The combination of trastuzumab biosimilar HLX02, pertuzumab, and chemotherapy exhibited promising efficacy and a favorable safety profile as second- and beyond-line treatment in HER2-positive MBC.

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Hematologic malignancy

Secondary Malignancies in Multiple Myeloma in Korean Patients: A Nationwide Population-Based Study: Boyoung Park, Eunyoung Lee, Junghyun Yoon, YoungJu Park, Hyeon-Seok Eom; Cancer Res Treat. 2024;56(3):936-944. Published online December 18, 2023; DOI: https://doi.org/10.4143/crt.2023.843

Abstract PDF Supplementary Material PubReader ePub: Purpose
This study investigated the incidence of secondary malignancy in multiple myeloma (MM) patients compared with that in the general population using a population-based database covering all residents in Korea.
Materials and Methods
Based on the national health insurance system in Korea, all people primarily diagnosed with MM between January 1, 2010 to December 31, 2018 were identified. A total of 9,985 MM patients aged ≥ 20 years in Korea were included.
Results
Among them, 237 (2.4%) developed secondary malignancies by 2018. The standardized incidence rates (SIRs) of all secondary malignancies in MM patients were 0.87 (95% confidence interval [CI], 0.76 to 0.98), with a higher incidence of hematologic malignancies than in the general population with an SIR of 3.80 (95% CI, 2.61 to 5.00). The incidence rates of both lymphoid malignancy (SIR, 3.56; 95% CI, 2.31 to 4.82) and myeloid malignancy (SIR, 3.78; 95% CI, 1.16 to 6.39) were higher in MM patients than in the general population. In contrast, a lower incidence of solid cancer was observed in MM patients than in the general population (SIR, 0.76, 95% CI, 0.65 to 0.86). There was no significant difference in survival in MM patients without secondary malignancies, with hematologic malignancy, and with solid cancer (p=0.413).
Conclusion
MM patients had a greater risk of secondary malignancies, especially hematologic malignancies, than the general population. Future studies with a focus on analyzing patients’ history, treatment details, and genetic information in various stages of MM patients are needed to better understand the mechanism behind this increased risk.

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Breast cancer

Assessment of Eligibility and Utilization of Accelerated Partial Breast Irradiation in Korean Breast Cancer Patients (KROG 22-15): Seok-Joo Chun, Ji Hwan Jo, Yong Bae Kim, Sangjoon Park, Sung-Ja Ahn, Su Ssan Kim, Kyubo Kim, Kyung Hwan Shin; Cancer Res Treat. 2024;56(2):549-556. Published online December 8, 2023; DOI: https://doi.org/10.4143/crt.2023.1109

Abstract PDF Supplementary Material PubReader ePub

Purpose
We investigated the proportions of patients eligible for accelerated partial breast irradiation (APBI) among those with pT1-2N0 breast cancer, based on the criteria set by the American Society for Radiation Oncology (ASTRO), the Groupe Européen de Curiethérapie and the European Society for Radiotherapy and Oncology (GEC-ESTRO), the American Brachytherapy Society (ABS), and the American Society of Breast Surgeons (ASBS). Additionally, we analyzed the rate of APBI utilization among eligible patients.
Materials and Methods
Patients diagnosed with pT1-2N0 breast cancer in 2019 were accrued in four tertiary medical centers in Korea. All patients had undergone breast conserving surgery followed by radiotherapy, either whole breast irradiation or APBI. To determine which guideline best predicts the use of APBI in Korea, the F1 score and Matthews Correlation Coefficient (MCC) were determined for each guideline.
Results
A total of 1,251 patients were analyzed, of whom 196 (15.7%) underwent APBI. The percentages of eligible patients identified by the ASTRO, GEC-ESTRO, ABS, and ASBS criteria were 13.7%, 21.0%, 50.5%, and 63.5%, respectively. APBI was used to treat 54.4%, 37.2%, 27.1%, and 23.7% of patients eligible by the ASTRO, GEC-ESTRO, ABS, and ASBS criteria, respectively. The ASTRO guideline exhibited the highest F1 score (0.76) and MCC (0.67), thus showing the best prediction of APBI utilization in Korea.
Conclusion
The proportion of Korean breast cancer patients who are candidates for APBI is substantial. The actual rate of APBI utilization among eligible patients may suggest there is a room for risk-stratified optimization in offering radiation therapy.

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Impact of the ASTRO 2024 Guideline on Partial Breast Irradiation Eligibility in Breast Cancer Patients (KROG 24-01)
Seok-Joo Chun, Sangjoon Park, Yong Bae Kim, Sung-Ja Ahn, Kyubo Kim, Kyung Hwan Shin
Practical Radiation Oncology.2024;[Epub] CrossRef

2,805 View
139 Download
1 Crossref

General

Health Inequities in Cancer Incidence According to Economic Status and Regions Are Still Existed Even under Universal Health Coverage System in Korea: A Nationwide Population Based Study Using the National Health Insurance Database: Youngs Chang, Soo-Hee Hwang, Sang-A Cho, Hyejin Lee, Eunbyul Cho, Jin Yong Lee; Cancer Res Treat. 2024;56(2):380-403. Published online December 6, 2023; DOI: https://doi.org/10.4143/crt.2023.650

Abstract PDF Supplementary Material PubReader ePub

Purpose
The purpose of this study is to determine the level of health equity in relation to cancer incidence.
Materials and Methods
We used the National Health Insurance claims data of the National Health Insurance Service between 2005 and 2022 and annual health insurance and medical aid beneficiaries between 2011 and 2021 to investigate the disparities of cancer incidence. We calculated age-sex standardized cancer incidence rates by cancer and year according to the type of insurance and the trend over time using the annual percentage change. We also compared the hospital type of the first diagnosis by cancer type and year and cancer incidence rates by cancer type and region in 2021 according to the type of insurance.
Results
The total cancer incidence increased from 255,971 in 2011 to 325,772 cases in 2021. The absolute difference of total cancer incidence rate between the NHI beneficiaries and the medical aid (MA) recipients increased from 510.1 cases per 100,000 population to 536.9 cases per 100,000 population. The odds ratio of total cancer incidence for the MA recipients increased from 1.79 (95% confidence interval [CI], 1.77 to 1.82) to 1.90 (95% CI, 1.88 to 1.93). Disparities in access to hospitals and regional cancer incidence were profound.
Conclusion
This study examined health inequities in relation to cancer incidence over the last decade. Cancer incidence was higher in the MA recipients, and the gap was widening. We also found that regional differences in cancer incidence still exist and are getting worse. Investigating these disparities between the NHI beneficiaries and the MA recipients is crucial for implementing of public health policies to reduce health inequities.

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