Cancer Research and Treatment

Original Articles

Gastrointestinal cancer

Clinical Characteristics of and Treatment Pattern for EGFR-Amplified Colorectal Cancer: Seong-Eun Kim, Hyehyun Jeong, Sun Young Kim, Jeong Eun Kim, Yong Sang Hong, Deokhoon Kim, Jihun Kim, Ji Sung Lee, Tae Won Kim; Cancer Res Treat. 2025;57(4):1104-1114. Published online January 10, 2025; DOI: https://doi.org/10.4143/crt.2024.569

Abstract PDF Supplementary Material PubReader ePub: Purpose
This study aimed to compare clinicopathologic features and clinical outcomes of metastatic colorectal cancer (mCRC) based on epidermal growth factor receptor (EGFR) amplification status.
Materials and Methods
Patients with mCRC who underwent next-generation sequencing using a targeted 244-gene panel from 2016 to 2021 were identified and screened for EGFR copy numbers. Cases with at least five copies were reviewed for tumor purity adjustment, and those with an adjusted copy number of ≥ 6 were defined as EGFR-amplified (EGFR amp+). Their clinical characteristics were compared with those without EGFR amplification (EGFR amp–).
Results
Among 2,421 patients, 35 (1.4%) were EGFR amp+. Clinical characteristics did not significantly differ according to EGFR amplification status, but EGFR amp+ cases had fewer instances of peritoneal seeding (8.6% vs. 21.8%). Overall survival (OS) tended to be better in EGFR amp+ patients compared with EGFR amp– patients (median OS [mOS], 76 vs. 37 months; p=0.145). Among 572 patients who received anti-EGFR antibody–based chemotherapy (anti-EGFR CTx) during disease course, mOS tended to be better in 16 EGFR amp+ patients (79 months) compared with 556 EGFR amp– patients (39 months, p=0.048). Seven out of 35 EGFR amp+ patients were treated with front-line anti-EGFR CTx, and their progression-free survival did not differ from that of EGFR amp– patients treated with front-line anti-EGFR CTx (20 vs. 14 months, p=0.344).
Conclusion
This study may suggest a favorable predictive impact of EGFR amplification in patients treated with anti-EGFR CTx. However, the benefit of front-line anti-EGFR antibody treatment in this group was not notable.

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General

Phase 1/2a Study of Rivoceranib, a Selective VEGFR-2 Angiogenesis Inhibitor, in Patients with Advanced Solid Tumors: Yoon-Koo Kang, Min-Hee Ryu, Yong Sang Hong, Chang-Min Choi, Tae Won Kim, Baek-Yeol Ryoo, Jeong Eun Kim, John R. Weis, Rachel Kingsford, Cheol Hee Park, Seong Jang, Arlo McGinn, Theresa L. Werner, Sunil Sharma; Cancer Res Treat. 2024;56(3):743-750. Published online January 18, 2024; DOI: https://doi.org/10.4143/crt.2023.980

Abstract PDF Supplementary Material PubReader ePub

Purpose
This study aimed to report the results from an early-phase study of rivoceranib, an oral tyrosine kinase inhibitor highly selective for vascular endothelial growth factor receptor 2, in patients with advanced solid tumors.
Materials and Methods
In this open-label, single-arm, dose-escalating, multicenter three-part phase 1/2a trial, patients had advanced solid tumors refractory to conventional therapy. Part 1 evaluated the safety and pharmacokinetics of five ascending once-daily doses of rivoceranib from 81 mg to 685 mg. Part 2 evaluated the safety and antitumor activity of once-daily rivoceranib 685 mg. Part 3 was conducted later, due to lack of maximum tolerated dose determination in part 1, to evaluate the safety and preliminary efficacy of once-daily rivoceranib 805 mg in patients with unresectable or advanced gastric cancer.
Results
A total of 61 patients were enrolled in parts 1 (n=25), 2 (n=30), and 3 (n=6). In parts 1 and 2, patients were white (45.5%) or Asian (54.5%), and 65.6% were male. The most common grade ≥ 3 adverse events were hypertension (32.7%), hyponatremia (10.9%), and hypophosphatemia (10.9%). The objective response rate (ORR) was 15.2%. In part 3, dose-limiting toxicities occurred in two out of six patients: grade 3 febrile neutropenia decreased appetite, and fatigue. The ORR was 33%.
Conclusion
The recommended phase 2 dose of rivoceranib was determined to be 685 mg once daily, which showed adequate efficacy with a manageable safety profile (NCT01497704 and NCT02711969).

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Advances in Targeted and Systemic Therapy for Salivary Gland Carcinomas: Current Options and Future Directions
Sushanth Sreenivasan, Rahim Jiwani, Richard White, Veli Bakalov, Ryan Moll, Joseph Liput, Larisa Greenberg
Current Oncology.2025; 32(4): 232. CrossRef
Proteomics profiling reveals the potential targets of Apatinib inhibiting the proliferation of glioma U251 cell
Yuyu Zhang, Yunshan Li, Fang Xu, Liangyu Pan, Saihang Zhang, Panpan Zhang, Xia Qin, Zuxiao Yang, Wei Yang, Wei Zhang, Dezhi Kong
Biochemical and Biophysical Research Communications.2025; 775: 152148. CrossRef

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Gastrointestinal cancer

A Phase 1b/2a Study of GC1118 with 5-Fluorouracil, Leucovorin and Irinotecan (FOLFIRI) in Patients with Recurrent or Metastatic Colorectal Cancer: Keun-Wook Lee, Sae-Won Han, Tae Won Kim, Joong Bae Ahn, Ji Yeon Baek, Sang Hee Cho, Howard Lee, Jin Won Kim, Ji-Won Kim, Tae-You Kim, Yong Sang Hong, Seung-Hoon Beom, Yongjun Cha, Yoonjung Choi, Seonhui Kim, Yung-Jue Bang; Cancer Res Treat. 2024;56(2):590-601. Published online December 7, 2023; DOI: https://doi.org/10.4143/crt.2023.1117

Abstract PDF Supplementary Material PubReader ePub

Purpose
GC1118 is a novel antibody targeting epidermal growth factor receptor (EGFR) with enhanced blocking activity against both low- and high-affinity EGFR ligands. A phase 1b/2a study was conducted to determine a recommended phase 2 dose (RP2D) of GC1118 in combination with 5-fluorouracil, leucovorin, and irinotecan (FOLFIRI) (phase 1b) and to assess the safety and efficacy of GC1118 plus FOLFIRI as a second-line therapy for recurrent/metastatic colorectal cancer (CRC) (phase 2a).
Materials and Methods
Phase 1b was designed as a standard 3+3 dose-escalation study with a starting dose of GC1118 (3 mg/kg/week) in combination with biweekly FOLFIRI (irinotecan 180 mg/m²; leucovorin 400 mg/m²; 5-fluorouracil 400 mg/m² bolus and 2,400 mg/m² infusion over 46 hours) in patients with solid tumors refractory to standard treatments. The subsequent phase 2a part was conducted with objective response rate (ORR) as a primary endpoint. Patients with KRAS/NRAS/BRAF wild-type, EGFR-positive, recurrent/metastatic CRC resistant to the first-line treatment were enrolled in the phase 2a study.
Results
RP2D of GC1118 was determined to be 3 mg/kg/wk in the phase 1b study (n=7). Common adverse drug reactions (ADRs) observed in the phase 2a study (n=24) were acneiform rash (95.8%), dry skin (66.7%), paronychia (58.3%), and stomatitis (50.0%). The most common ADR of ≥ grade 3 was neutropenia (33.3%). ORR was 42.5% (95% confidence interval [CI], 23.5 to 62.0), and median progression-free survival was 6.7 months (95% CI, 4.0-8.0).
Conclusion
GC1118 administered weekly at 3 mg/kg in combination with FOLFIRI appears as an effective and safe treatment option in recurrent/metastatic CRC.

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Drug resistance-driven cytokine alterations in the immunosuppressive microenvironment of colorectal cancer
Yingying Shao, Zewen Zhang, Yu Wang, Chunze Zhang, Erwei Liu, Haiyang Yu
Targetome.2026;[Epub] CrossRef
Drug combinations of camptothecin derivatives promote the antitumor properties
Zhen Liu, Yajie Yuan, Ning Wang, Peng Yu, Yuou Teng
European Journal of Medicinal Chemistry.2024; 279: 116872. CrossRef

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General

Impact of Patient Sex on Adverse Events and Unscheduled Utilization of Medical Services in Cancer Patients Undergoing Adjuvant Chemotherapy: A Multicenter Retrospective Cohort Study: Songji Choi, Seyoung Seo, Ju Hyun Lee, Koung Jin Suh, Ji-Won Kim, Jin Won Kim, Se Hyun Kim, Yu Jung Kim, Keun-Wook Lee, Jwa Hoon Kim, Tae Won Kim, Yong Sang Hong, Sun Young Kim, Jeong Eun Kim, Sang-We Kim, Dae Ho Lee, Jae Cheol Lee, Chang-Min Choi, Shinkyo Yoon, Su-Jin Koh, Young Joo Min, Yongchel Ahn, Hwa Jung Kim, Jin Ho Baek, Sook Ryun Park, Jee Hyun Kim; Cancer Res Treat. 2024;56(2):404-413. Published online November 7, 2023; DOI: https://doi.org/10.4143/crt.2023.784

Abstract PDF Supplementary Material PubReader ePub

Purpose
The female sex is reported to have a higher risk of adverse events (AEs) from cytotoxic chemotherapy. Few studies examined the sex differences in AEs and their impact on the use of medical services during adjuvant chemotherapy. This sub-study aimed to compare the incidence of any grade and grade ≥ 3 AEs, healthcare utilization, chemotherapy completion rate, and dose intensity according to sex.
Materials and Methods
This is a sub-study of a multicenter cohort conducted in Korea that evaluated the impact of healthcare reimbursement on AE evaluation in patients who received adjuvant chemotherapy between September 2013 and December 2016 at four hospitals in Korea.
Results
A total of 1,170 patients with colorectal, gastric, or non–small cell lung cancer were included in the study. Female patients were younger, had fewer comorbidities, and experienced less postoperative weight loss of > 10%. Females had significantly higher rates of any grade AEs including nausea, abdominal pain, stomatitis, vomiting, and neutropenia, and experienced more grade ≥ 3 neutropenia, nausea, and vomiting. The dose intensity of chemotherapy was significantly lower in females, and they also experienced more frequent dose reduction after the first cycle. Moreover, female patients receiving platinum-containing regimens had significantly higher rates of unscheduled outpatient visits.
Conclusion
Our study found that females experienced a higher incidence of multiple any-grade AEs and severe neutropenia, nausea, and vomiting, across various cancer types, leading to more frequent dose reductions. Physicians should be aware of sex differences in AEs for chemotherapy decisions.

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Survival benefit of adjuvant chemotherapy for perihilar cholangiocarcinoma: Impact of log odds of metastatic lymph node count
Jun Kawashima, Miho Akabane, Odysseas P. Chatzipanagiotou, Diamantis I. Tsilimigras, Zayed Rashid, Mujtaba Khalil, Abdullah Altaf, Yutaka Endo, Kota Sahara, Federico Aucejo, Hugo P. Marques, Beatriz Chumbinho, Tom Hugh, Shishir K. Maithel, Bas Groot Koerk
Surgery.2026; 191: 109913. CrossRef
Sex-based prognosis in industry-sponsored advanced solid tumor trials: an individual participant data meta-analysis of survival and adverse events
Rakchha Chhetri, Natansh D Modi, Bradley D Menz, Erik Cornelisse, David Postma, Nicole M Kuderer, Gary H Lyman, Sandra M Swain, Lee X Li, Ahmad Y Abuhelwa, Ross A McKinnon, Sina Vatandoust, Ganessan Kichenadasse, Andrew Rowland, Michael J Sorich, Ashley M
JNCI: Journal of the National Cancer Institute.2026;[Epub] CrossRef
Toxicidad del esquema FOLFOX-6, asociado o no a bolo de 5-fluorouracilo, en cáncer colorrectal metastásico
María Teresa Garrido Martínez, María Rodríguez Jorge, Ignacio García Giménez, María Isabel Guzmán Ramos, Salvador Grutzmancher Sáiz, Victoria Aviñó Tarazona
Farmacia Hospitalaria.2025; 49(3): 154. CrossRef
Cancer care for transgender and gender‐diverse people: Practical, literature‐driven recommendations from the Multinational Association of Supportive Care in Cancer
Elizabeth J. Cathcart‐Rake, Alexandre Chan, Alvaro Menendez, Denise Markstrom, Carla Schnitzlein, Yee Won Chong, Don S. Dizon
CA: A Cancer Journal for Clinicians.2025; 75(1): 68. CrossRef
Characterisation of the effects of the chemotherapeutic agent paclitaxel on neuropathic pain-related behaviour, anxiodepressive behaviour, cognition, and the endocannabinoid system in male and female rats
Chiara Di Marino, Álvaro Llorente-Berzal, Alba M. Diego, Ariadni Bella, Laura Boullon, Esther Berrocoso, Michelle Roche, David P. Finn
Frontiers in Pharmacology.2025;[Epub] CrossRef
[Translated article] Toxicity of the FOLFOX-6 regimen, with or without 5-fluorouracil bolus, in metastatic colorectal cancer
María Teresa Garrido Martínez, María Rodríguez Jorge, Ignacio García Giménez, María Isabel Guzmán Ramos, Salvador Grutzmancher Sáiz, Victoria Aviñó Tarazona
Farmacia Hospitalaria.2025; 49(3): T154. CrossRef
The Influence of Tumor Burden Score and Lymph Node Metastasis on the Survival Benefit of Adjuvant Chemotherapy in Intrahepatic Cholangiocarcinoma
Jun Kawashima, Yutaka Endo, Selamawit Woldesenbet, Mujtaba Khalil, Miho Akabane, François Cauchy, Feng Shen, Shishir Maithel, Irinel Popescu, Minoru Kitago, Matthew J. Weiss, Guillaume Martel, Carlo Pulitano, Luca Aldrighetti, George Poultsides, Andrea Ru
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Neurobehavioral manifestations in female rats after intermittent exposure to an anticancer agent, paclitaxel
Deepika Pathak, K.P. Singh
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Gender‐Affirming Hormone Therapy: Pharmacokinetic Considerations for Oncology in Transgender Patients
Anna Carollo, Lavinia Piazza, Alessio Provenzani
Clinical and Translational Science.2025;[Epub] CrossRef

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Erratum

ERRATUM: Recommendations for the Use of Next-Generation Sequencing and the Molecular Tumor Board for Patients with Advanced Cancer: A Report from KSMO and KCSG Precision Medicine Networking Group: Shinkyo Yoon, Miso Kim, Yong Sang Hong, Han Sang Kim, Seung Tae Kim, Jihun Kim, Hongseok Yun, Changhoon Yoo, Hee Kyung Ahn, Hyo Song Kim, In Hee Lee, In-Ho Kim, Inkeun Park, Jae Ho Jeong, Jaekyung Cheon, Jin Won Kim, Jina Yun, Sun Min Lim, Yongjun Cha, Se Jin Jang, Dae Young Zang, Tae Won Kim, Jin Hyoung Kang, Jee Hyun Kim; Cancer Res Treat. 2023;55(3):1061-1061. Published online April 21, 2023; DOI: https://doi.org/10.4143/crt.2021.1115.E; Corrects: Cancer Res Treat 2022;54(1):1

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Real-World Data: Implementation and Outcomes of Next-Generation Sequencing in the MENA Region
Rami Mahfouz, Reine Abou Zeidane, Tasnim Diab, Ali Tarhini, Eman Sbaity, Houry Kazarian, Yomna El Zibaoui, Nour Sabiha Naji, Mounir Barake, Hazem I. Assi
Diagnostics.2025; 15(10): 1183. CrossRef

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Original Article

Gastrointestinal cancer

Histopathologic and Molecular Biomarkers of PD-1/PD-L1 Inhibitor Treatment Response among Patients with Microsatellite Instability‒High Colon Cancer: Jaewon Hyung, Eun Jeong Cho, Jihun Kim, Jwa Hoon Kim, Jeong Eun Kim, Yong Sang Hong, Tae Won Kim, Chang Ohk Sung, Sun Young Kim; Cancer Res Treat. 2022;54(4):1175-1190. Published online January 12, 2022; DOI: https://doi.org/10.4143/crt.2021.1133

Abstract PDF Supplementary Material PubReader ePub

Purpose
Recent clinical trials have reported response rates < 50% among patients treated with programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1) inhibitors for microsatellite instability‒high (MSI-H) colorectal cancer (CRC), and factors predicting treatment response have not been fully identified. This study aimed to identify potential biomarkers of PD-1/PD-L1 inhibitor treatment response among patients with MSI-H CRC.
Materials and Methods
MSI-H CRC patients enrolled in three clinical trials of PD-1/PD-L1 blockade at Asan Medical Center (Seoul, Republic of Korea) were screened and classified into two groups according to treatment response. Their histopathologic features and expression of 730 immune-related genes from the NanoString platform were evaluated, and a machine learning–based classification model was built to predict treatment response among MSI-H CRCs patients.
Results
A total of 27 patients (15 responders, 12 non-responders) were included. A high degree of lymphocytic/neutrophilic infiltration and an expansile tumor border were associated with treatment response and prolonged progression-free survival (PFS), while mucinous/signet-ring cell carcinoma was associated with a lack of treatment response and short PFS. Gene expression profiles revealed that the interferon-γ response pathway was enriched in the responder group. Of the top eight differentially expressed immune-related genes, PRAME had the highest fold change in the responder group. Higher expression of PRAME was independently associated with better PFS along with histologic subtypes in the multivariate analysis. The classification model using these genes showed good performance for predicting treatment response.
Conclusion
We identified histologic and immune-related gene expression characteristics associated with treatment response in MSI-H CRC, which may contribute to optimal patient stratification.

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Special Article

Recommendations for the Use of Next-Generation Sequencing and the Molecular Tumor Board for Patients with Advanced Cancer: A Report from KSMO and KCSG Precision Medicine Networking Group: Shinkyo Yoon, Miso Kim, Yong Sang Hong, Han Sang Kim, Seung Tae Kim, Jihun Kim, Hongseok Yun, Changhoon Yoo, Hee Kyung Ahn, Hyo Song Kim, In Hee Lee, In-Ho Kim, Inkeun Park, Jae Ho Jeong, Jaekyung Cheon, Jin Won Kim, Jina Yun, Sun Min Lim, Yongjun Cha, Se Jin Jang, Dae Young Zang, Tae Won Kim, Jin Hyoung Kang, Jee Hyun Kim; Cancer Res Treat. 2022;54(1):1-9. Published online December 13, 2021; DOI: https://doi.org/10.4143/crt.2021.1115; Correction in: Cancer Res Treat 2023;55(3):1061

Abstract PDF PubReader ePub

Next-generation sequencing (NGS) is becoming essential in the fields of precision oncology. With implementation of NGS in daily clinic, the needs for continued education, facilitated interpretation of NGS results and optimal treatment delivery based on NGS results have been addressed. Molecular tumor board (MTB) is multidisciplinary approach to keep pace with the growing knowledge of complex molecular alterations in patients with advanced solid cancer. Although guidelines for NGS use and MTB have been developed in western countries, there is limitation for reflection of Korea’s public health environment and daily clinical practice. These recommendations provide a critical guidance from NGS panel testing to final treatment decision based on MTB discussion.

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Clinical practice recommendations for the use of next-generation sequencing in patients with solid cancer: a joint report from KSMO and KSP
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Original Articles

Gastrointestinal cancer

Radiofrequency Ablation versus Stereotactic Body Radiation Therapy in the Treatment of Colorectal Cancer Liver Metastases: Jesang Yu, Dong Hwan Kim, Jungbok Lee, Yong Moon Shin, Jong Hoon Kim, Sang Min Yoon, Jinhong Jung, Jin Cheon Kim, Chang Sik Yu, Seok-Byung Lim, In Ja Park, Tae Won Kim, Yong Sang Hong, Sun Young Kim, Jeong Eun Kim, Jin-hong Park, So Yeon Kim; Cancer Res Treat. 2022;54(3):850-859. Published online October 13, 2021; DOI: https://doi.org/10.4143/crt.2021.674

Abstract PDF Supplementary Material PubReader ePub

Purpose
This study aimed to compare the treatment outcomes of radiofrequency ablation (RFA) and stereotactic body radiation therapy (SBRT) for colorectal cancer liver metastases (CRLM) and to determine the favorable treatment modality according to tumor characteristics.
Materials and Methods
We retrospectively analyzed the records of 222 colorectal cancer patients with 330 CRLM who underwent RFA (268 tumors in 178 patients) or SBRT (62 tumors in 44 patients) between 2007 and 2014. Kaplan–Meier method and Cox models were used by adjusting with inverse probability of treatment weighting (IPTW).
Results
The median follow-up duration was 30.5 months. The median tumor size was significantly smaller in the RFA group than in the SBRT group (1.5 cm vs 2.3 cm, p<0.001). In IPTW-adjusted analysis, difference in treatment modality was not associated with significant differences in 1-year and 3-year recurrence-free survival (35% vs 43%, 22% vs 23%; p=0.198), overall survival (96% vs 91%, 58% vs 56%; p=0.508), and freedom from local progression (FFLP; 90% vs 72%, 78% vs 60%; p=0.106). Significant interaction effect between the treatment modality and tumor size was observed for FFLP (p=0.001). In IPTW-adjusted subgroup analysis of patients with tumor size >2 cm, the SBRT group had a higher FFLP compared with the RFA group (HR, 0.153; p<0.001).
Conclusion
SBRT and RFA showed similar local control in the treatment of patients with CRLM. Tumor size was an independent prognostic factor for local control and SBRT may be preferred for larger tumors.

Citations

Citations to this article as recorded by

Radiotherapy for liver tumours⭑
Marin Guigo, Laure Parent, Nicolas Jaksic, Olivier Riou, Véronique Vendrely, Emmanuel Rio
Cancer/Radiothérapie.2026; 30(1): 104802. CrossRef
Isolated para-aortic lymph node recurrence from colorectal cancer treated by radiotherapy: a systematic review and meta-analysis
Seok-Joo Chun, Hyunkyung Kim, Jiyun Jung, Sun Hyun Bae, Mi-Sook Kim
Scientific Reports.2026;[Epub] CrossRef
Ablative techniques in colorectal liver metastases: A systematic review, descriptive summary of practice, and recommendations for optimal data reporting
Wee Han Ng, Catarina Machado, Alice Rooney, Robert Jones, Jonathan Rees, Samir Pathak
European Journal of Surgical Oncology.2025; 51(2): 109487. CrossRef
Effects of maximum dose on local control after stereotactic body radiotherapy for oligometastatic tumors of colorectal cancer
Su Jin Kang, Jongmoo Park, Gyu-Seog Choi, Jong Gwang Kim, Jun Seok Park, Hye Jin Kim, Jin Ho Baek, Byung Woog Kang, An Na Seo, Shin-Hyung Park, Bong Kyung Bae, Min Kyu Kang, Soo Yeun Park, Devarati Mitra
PLOS ONE.2025; 20(1): e0313438. CrossRef
Stereotactic ablative radiotherapy (SABR) for liver metastases: where we currently stand
S.H.R. Kim, M.K. Harrison
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Treatment of Oligometastatic GI Cancers
Clayton T. Marcinak, Patrick B. Schwartz, Mustafa M. Basree, Newton Hurst, Michael Bassetti, Jeremy D. Kratz, Nataliya V. Uboha
American Society of Clinical Oncology Educational Book.2024;[Epub] CrossRef
Stereotactic radiotherapy for liver oligometastases: a pooled analysis following the estro/eortc consensus recommendations
D. Pezzulla, G. Chiloiro, E. M. Lima, G. Macchia, C. Romano, S. Reina, G. Panza, S. Cilla, A. G. Morganti, F. Cellini, M. A. Gambacorta, F. Deodato
Clinical & Experimental Metastasis.2024; 41(5): 667. CrossRef
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Max Seidensticker
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Xiong Zhang, Hong-Yi Zhu, Ming Yuan
World Journal of Gastrointestinal Surgery.2024; 16(9): 2986. CrossRef
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Wen-Yu Huang, Sheng Zheng, Dan Zhu, Ying-Lang Zeng, Juan Yang, Xue-Li Zeng, Pei Liu, Shun-Ling Zhang, Ming Yuan, Zhi-Xia Wang
World Journal of Gastrointestinal Surgery.2024; 16(9): 2860. CrossRef
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Hwa Kyung Byun, Gyu Sang Yoo, Soo-Yoon Sung, Jin-Ho Song, Byoung Hyuck Kim, Yoo-Kang Kwak, Yeon Joo Kim, Yeon-Sil Kim, Kyung Su Kim
Radiation Oncology Journal.2024; 42(4): 247. CrossRef
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Vito Filbert Jayalie, Merinda, Herryanto Lumbantobing, Sudibio, Julius Oentario, Hendriyo, Sry Suryani Widjaja
Forum of Clinical Oncology.2024; 15(1): 61. CrossRef
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Kyungmi Yang, Jeong Eun Lee, Won Park, Yong Chan Ahn, Seung Jae Huh
Japanese Journal of Clinical Oncology.2023; 53(12): 1177. CrossRef
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Federica Borrelli de Andreis, Maria Alessandra Calegari, Angela Romano, Maria Gabriella Brizi, Luigi Sofo, Ivo Boskoski, Guido Costamagna, Fabia Attili
Current Problems in Cancer: Case Reports.2023; 9: 100216. CrossRef
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Chai Hong Rim, Jung Sue Lee, Soo Yeon Kim, Jinsil Seong
JHEP Reports.2023; 5(1): 100594. CrossRef
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Cancer Research and Treatment.2023; 55(3): 707. CrossRef
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Sara Mheid, Stefan Allen, Sylvia S. W. Ng, William A. Hall, Nina N. Sanford, Todd A. Aguilera, Ahmed M. Elamir, Rana Bahij, Martijn P. W. Intven, Ganesh Radhakrishna, Issa Mohamad, Jeremy De Leon, Hendrick Tan, Shirley Lewis, Cihan Gani, Teo Stanecu, Vero
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Koji Tomita, Yusuke Matsui, Mayu Uka, Noriyuki Umakoshi, Takahiro Kawabata, Kazuaki Munetomo, Shoma Nagata, Toshihiro Iguchi, Takao Hiraki
Japanese Journal of Radiology.2022; 40(10): 1035. CrossRef

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A Phase II Study of Avelumab Monotherapy in Patients with Mismatch Repair–Deficient/Microsatellite Instability–High or POLE-Mutated Metastatic or Unresectable Colorectal Cancer: Jwa Hoon Kim, Sun Young Kim, Ji Yeon Baek, Yong Jun Cha, Joong Bae Ahn, Han Sang Kim, Keun-Wook Lee, Ji-Won Kim, Tae-You Kim, Won Jin Chang, Joon Oh Park, Jihun Kim, Jeong Eun Kim, Yong Sang Hong, Yeul Hong Kim, Tae Won Kim; Cancer Res Treat. 2020;52(4):1135-1144. Published online April 24, 2020; DOI: https://doi.org/10.4143/crt.2020.218

Abstract PDF Supplementary Material PubReader ePub

Purpose
We evaluated the efficacy and safety of avelumab, an anti-PD-L1 antibody, in patients with metastatic or unresectable colorectal cancer (mCRC) with mismatch repair deficiency (dMMR)/microsatellite instability-high (MSI-H) or POLE mutations.
Materials and Methods
In this prospective, open-label, multicenter phase II study, 33 patients with mCRC harboring dMMR/MSI-H or POLE mutations after failure of ≥1st-line chemotherapy received avelumab 10 mg/kg every 2 weeks. dMMR/MSI-H was confirmed with immunohistochemical staining (IHC) by loss of expression of MMR proteins or polymerase chain reaction (PCR) for microsatellite sequences. POLE mutation was confirmed by next-generation sequencing (NGS). The primary endpoint was the objective response rate (ORR) by Response Evaluation Criteria in Solid Tumors ver. 1.1.
Results
The median age was 60 years, and 78.8% were male. Thirty patients were dMMR/MSI-H and three had POLE mutations. The ORR was 24.2%, and all of the responders were dMMR/MSI-H. For 21 patients with MSI-H by PCR or NGS, the ORR was 28.6%. At a median follow-up duration of 16.3 months, median progression-free survival and overall survival were 3.9 and 13.2 months in all patients, and 8.1 months and not reached, respectively, in patients with MSI-H by PCR or NGS. Dose interruption and discontinuation due to treatment-related adverse events occurred in 4 and 2 patients, respectively, with no treatment-related deaths.
Conclusion
Avelumab displayed antitumor activity with manageable toxicity in patients with previously treated mCRC harboring dMMR/MSI-H. Diagnosis of dMMR/MSI-H with PCR or NGS could be complementary to IHC to select patients who would benefit from immunotherapy.

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Prospective Validation of The Korean Cancer Study Group Geriatric Score (KG)-7, a Novel Geriatric Screening Tool, in Older Patients with Advanced Cancer Undergoing First-line Palliative Chemotherapy: Jin Won Kim, Se Hyun Kim, Yun-Gyoo Lee, In Gyu Hwang, Jin Young Kim, Su-Jin Koh, Yoon Ho Ko, Seong Hoon Shin, In Sook Woo, Soojung Hong, Tae-Yong Kim, Ji Yeon Baek, Hyun Jung Kim, Hyo Jung Kim, Myung Ah Lee, Jung Hye Kwon, Yong Sang Hong, Hun-Mo Ryoo, Kyung Hee Lee, Jee Hyun Kim; Cancer Res Treat. 2019;51(3):1249-1256. Published online January 2, 2019; DOI: https://doi.org/10.4143/crt.2018.451

Abstract PDF Supplementary Material PubReader ePub

Purpose
The purpose of this study was to prospectively validate the Korean Cancer Study Group Geriatric Score (KG)-7, a novel geriatric screening tool, in older patients with advanced cancer planned to undergo first-line palliative chemotherapy.
Materials and Methods
Participants answered the KG-7 questionnaire before undergoing geriatric assessment (GA) and first-line palliative chemotherapy. The performance of KG-7 was evaluated by calculating the sensitivity (SE), specificity (SP), positive and negative predictive value (PPV and NPV), balanced accuracy (BA), and area under the curve (AUC).
Results
The baseline GA and KG-7 results were collected from 301 patients. The median age was 75 years (range, 70 to 93 years). Abnormal GA was documented in 222 patients (73.8%). Based on the ≤ 5 cut-off value of KG-7 for abnormal GA, abnormal KG-7 score was shown in 200 patients (66.4%). KG-7 showed SE, SP, PPV, NPV, and BA of 75.7%, 59.7%, 84.4%, 46.0%, and 67.7%, respectively; AUC was 0.745 (95% confidence interval, 0.687 to 0.803). Furthermore, patients with higher KG-7 scores showed significantly longer survival (p=0.006).
Conclusion
KG-7 appears to be adequate in identifying patients with abnormal GA prospectively. Hence, KG-7 can be a useful screening tool for Asian countries with limited resources and high patient volume.

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Paired Primary and Metastatic Tumor Analysis of Somatic Mutations in Synchronous and Metachronous Colorectal Cancer: Kyu-pyo Kim, Jeong-Eun Kim, Yong Sang Hong, Sung-Min Ahn, Sung Min Chun, Seung-Mo Hong, Se Jin Jang, Chang Sik Yu, Jin Cheon Kim, Tae Won Kim; Cancer Res Treat. 2017;49(1):161-167. Published online July 4, 2016; DOI: https://doi.org/10.4143/crt.2015.490

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Purpose
Although the mutation status of KRAS is highly concordant in primary and metastatic lesions, it has not been generalized to other major pathway genes.
Materials and Methods
In this study, 41 genes were evaluated and the mutational profiles were compared in 46 colorectal cancer patients with paired surgical specimens of primary and metastatic lesions: synchronous (n=27) and metachronous (n=19) lesions. A high-throughput mass spectrometry-based genotyping platform validated by orthogonal chemistry, OncoMap v.4.4, was used to evaluate the formalin-fixed, paraffin-embedded surgical specimens. The patients’ demographics, tumor characteristics, and microsatellite instability status were analyzed by a retrospective chart review.
Results
In this study,with OncoMap, mutationswere identified in 80.4% of patientswith the following frequency: KRAS (39.1%), TP53 (28.3%), APC (28.3%), PIK3CA (6.5%), BRAF (6.5%), and NRAS (4.3%). Although 19.6% (9/46) of the patients showed no gene mutations, 43.5% (20/46) and 37.0% (17/46) had mutations in one and two or more genes, respectively. The synchronous and metachronous lesions showed similar mutational profiles. Paired samples between primary and metastatic tumors differed in 7.4% (2/27) and 10.5% (2/19) for synchronous and metachronous according to OncoMap.
Conclusion
These findings indicate the major pathway genes, including KRAS, TP53, APC, PIK3CA, BRAF, and NRAS, are often concordant between the primary and metastatic lesions regardless of the temporal relationship of metastasis.

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Use of a High-Throughput Genotyping Platform (OncoMap) for RAS Mutational Analysis to Predict Cetuximab Efficacy in Patients with Metastatic Colorectal Cancer: Dalyong Kim, Yong Sang Hong, Jeong Eun Kim, Kyu-pyo Kim, Jae-Lyun Lee, Sung-Min Chun, Jihun Kim, Se Jin Jang, Tae Won Kim; Cancer Res Treat. 2017;49(1):37-43. Published online April 27, 2016; DOI: https://doi.org/10.4143/crt.2016.069

Abstract PDF PubReader ePub

Purpose
Cetuximab demonstrates improved efficacy outcomes in patients with metastatic colorectal cancer (mCRC) harboring wild-type KRAS exon 2. Resistance to cetuximab is mediated by activating less frequent mutations in the RAS genes beyond KRAS exon 2. We performed extended RASmutational analysis using a high -throughput genotyping platform (OncoMap) and evaluated extended RAS analysis for predicting cetuximab efficacy in patients harboring wild-type KRAS exon 2 tumors following Sanger sequencing.
Materials and Methods
Extended RAS analysis was performed on 227 wild-type KRAS exon 2 mCRC patients who received cetuximab as salvage treatment using OncoMap ver. 4.0. Targeted genes included exon 2, exon 3, and exon 4, both in KRAS and NRAS, and included BRAF exon 15. We assessed efficacy by the new RAS mutation status.
Results
The OncoMap detected 57 additional mutations (25.1%): 25 (11%) in KRAS exon 2 and 32 (14.1%) beyond KRAS exon 2. Survival differences were observed after dividing patients into the wild-type RAS group (n=170) and mutant RAS group (n=57) using OncoMap. Progression-free survival was 4.8 months versus 1.8 months (hazard ratio [HR], 0.44; 95% confidence interval [CI], 0.32 to 0.61), and overall survival was 11.9 months versus 8.4 months (HR, 0.65; 95% CI, 0.47 to 0.88).
Conclusion
Sanger sequencing is not sufficient for selecting candidates for cetuximab treatment. High-throughput extended RAS genotyping is a feasible approach for this purpose and identifies patients who might benefit from cetuximab treatment.

Citations

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Cancers.2025; 18(1): 31. CrossRef
Metastatik Kolorektal Kanserli Hastaların RAS Mutasyon Durumuna Göre Klinik ve Patolojik Özellikleri
Mehmet SEZEN, Murat ARAZ
Uludağ Üniversitesi Tıp Fakültesi Dergisi.2019; 45(2): 131. CrossRef
Pan-Asian adapted ESMO consensus guidelines for the management of patients with metastatic colorectal cancer: a JSMO–ESMO initiative endorsed by CSCO, KACO, MOS, SSO and TOS
T. Yoshino, D. Arnold, H. Taniguchi, G. Pentheroudakis, K. Yamazaki, R.-H. Xu, T.W. Kim, F. Ismail, I.B. Tan, K.-H. Yeh, A. Grothey, S. Zhang, J.B. Ahn, M.Y. Mastura, D. Chong, L.-T. Chen, S. Kopetz, T. Eguchi-Nakajima, H. Ebi, A. Ohtsu, A. Cervantes, K.
Annals of Oncology.2018; 29(1): 44. CrossRef
Ligand-Independent Epidermal Growth Factor Receptor Overexpression Correlates with Poor Prognosis in Colorectal Cancer
Sumi Yun, Yoonjin Kwak, Soo Kyung Nam, An Na Seo, Heung-Kwon Oh, Duck-Woo Kim, Sung-Bum Kang, Hye Seung Lee
Cancer Research and Treatment.2018; 50(4): 1351. CrossRef
Primary tumor location predicts poor clinical outcome with cetuximab in RAS wild-type metastatic colorectal cancer
Dalyong Kim, Sun Young Kim, Ji Sung Lee, Yong Sang Hong, Jeong Eun Kim, Kyu-pyo Kim, Jihun Kim, Se Jin Jang, Young-Kwang Yoon, Tae Won Kim
BMC Gastroenterology.2017;[Epub] CrossRef

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