Cancer Research and Treatment

Original Articles

Clinical Impact of TP53 Mutations in Patients with Head and Neck Cancer Who Were Treated with Targeted Therapies or Immunotherapy: Eun Joo Kang, Shinwon Hwang, Yun-Gyoo Lee, Jong-Kwon Choi, Seong Hoon Shin, Yoon Hee Choi, Keun-Wook Lee, Hyun Woo Lee, Min Kyoung Kim, Seung Taek Lim, Hwan Jung Yun, Sang-Gon Park, Sangwoo Kim, Sung-Bae Kim, Hye Ryun Kim; Received August 28, 2024 Accepted December 21, 2024 Published online December 23, 2024; DOI: https://doi.org/10.4143/crt.2024.836 [Epub ahead of print]

Abstract PDF PubReader ePub: Purpose
Tumor suppressor p53 (TP53) mutations are common in head and neck squamous cell carcinoma (HNSCC). We evaluated their clinical impact in patients treated with targeted agents or immunotherapy in the KCSG HN15-16 TRIUMPH trial.
Materials and Methods
We analyzed clinical characteristics and outcomes of patients with TP53 mutations in the TRIUMPH trial, a multicenter, biomarker-driven umbrella trial in Korea. Patients were assigned to treatment groups based on genomic profiles: group 1, alpelisib; group 2, poziotinib; group 3, nintedanib; and group 4, abemaciclib. If there was no identifiable target, the patients were allocated to group 5 (durvalumab±tremelimumab).
Results
TP53 mutations were detected in 116/179 patients (64.8%), more frequently in human papillomavirus–negative and non-oropharyngeal cancers. Patients with TP53 mutations exhibited shorter progression-free survival than TP53 wild-type in all the patients (1.7 vs. 3.8 months, p=0.002) and in those who received targeted treatments (2.5 vs. 7.3 months, p=0.009). Furthermore, TP53 mutations were strongly associated with poor overall survival than TP53 wild-type in all the patients (11.1 vs. 28.8 months, p=0.005) and in group 5 (8.1 vs. 33.0 months, p=0.001).
Conclusion
TP53 mutations were associated with aggressive clinical characteristics and poor survival, particularly in HNSCC patients treated with immunotherapy.

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Hematologic malignancy

Long-term Psychiatric and Endocrine Complications Following Hematopoietic Stem Cell Transplantation in Hematologic Disease in Korea: A Nation-Wide Cohort Study: Min Ji Jeon, Eunjin Noh, Seok Joo Moon, Eun Sang Yu, Chul Won Choi, Dae Sik Kim, Eun Joo Kang; Cancer Res Treat. 2024;56(4):1262-1269. Published online May 9, 2024; DOI: https://doi.org/10.4143/crt.2024.047

Abstract PDF PubReader ePub: Purpose
Numerous patients experience long-term complications after hematopoietic stem cell transplantation (HSCT). This study aimed to identify the frequency and risk factors for psychiatric and endocrine complications following HSCT through big data analyses.
Materials and Methods
We established a cohort of patients with hematologic disease who underwent HSCT in Korea between 2010 and 2012 using the Health Insurance Review & Assessment Service data. A total of 3,636 patients were identified, and insurance claims were tracked using psychiatric and endocrine diagnostic International Classification of Diseases, 10th Revision codes for the ensuing decade. We identified the incidence rates of long-term complications based on the baseline disease and HSCT type. Prognostic factors for each complication were scrutinized using logistic regression analysis.
Results
A total of 1,879 patients underwent allogeneic HSCT and 1,757 patients received autologous HSCT. Post-HSCT, 506 patients were diagnosed with depression, 465 with anxiety disorders, and 659 with diabetes. The highest incidence of long-term complications occurred within the first year post-HSCT (12.2%), subsequently decreasing over time. Risk factors for depressive disorders after allogeneic HSCT included female sex, a total body irradiation–based conditioning regimen, and cyclosporine. Identified risk factors for diabetes mellitus comprised old age, total body irradiation–based conditioning regimen, and non-antithymocyte globulin protocol. Regarding autologous HSCT, only female sex was identified as a risk factor for depressive disorders, whereas elderly patients and those with multiple myeloma were identified as poor prognostic factors for diabetes mellitus.
Conclusion
The incidence of long-term psychiatric and endocrine complications post-HSCT remains high, and patients with risk factors for these complications require vigilant follow-up.

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Head and Neck cancer

Analysis of Response and Progression Patterns of Tyrosine Kinase Inhibitors in Recurrent or Metastatic Adenoid Cystic Carcinoma: A Post Hoc Analysis of Two KCSG Phase II Trials: Youjin Kim, Bhumsuk Keam, Eun Joo Kang, Jin-Soo Kim, Hye Ryun Kim, Keun-Wook Lee, Jung Hye Kwon, Kyoung Eun Lee, Yaewon Yang, Yoon Hee Choi, Min Kyoung Kim, Jun Ho Ji, Tak Yun, Moon Young Choi, Ki Hyeong Lee, Sung-Bae Kim, Myung-Ju Ahn; Cancer Res Treat. 2024;56(4):1068-1076. Published online April 15, 2024; DOI: https://doi.org/10.4143/crt.2024.008

Abstract PDF Supplementary Material PubReader ePub: Purpose
In this study, we evaluated 66 patients diagnosed with adenoid cystic carcinoma (ACC) enrolled in two Korean Cancer Study Group trials to investigate the response and progression patterns in recurrent and/or metastatic ACC treated with vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR-TKIs).
Materials and Methods
We evaluated 66 patients diagnosed with ACC who were enrolled in the Korean Cancer Study Group trials. The tumor measurements, clinical data, treatment outcomes, and progression patterns of therapy were analyzed.
Results
In the 66 patients (53 receiving axitinib and 13 receiving nintedanib), the disease control rate was 61%, and three patients achieved partial response. The median follow-up, median progression-free survival (PFS), overall survival, and 6-month PFS rate were 27.6%, 12.4%, and 18.1% months and 62.1%, respectively. Among 42 patients who experienced progression, 27 (64.3%) showed target lesion progression. Bone metastasis was an independent poor prognostic factor.
Conclusion
Overall, most patients demonstrated stable disease with prolonged PFS; however, prominent target lesion progression occurred in some patients. Thus, PFS may capture VEGFR-TKI efficacy better than the objective response rate.

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General

Comparison of the Data of a Next-Generation Sequencing Panel from K-MASTER Project with That of Orthogonal Methods for Detecting Targetable Genetic Alterations: Yoon Ji Choi, Jung Yoon Choi, Ju Won Kim, Ah Reum Lim, Youngwoo Lee, Won Jin Chang, Soohyeon Lee, Jae Sook Sung, Hee-Joon Chung, Jong Won Lee, Eun Joo Kang, Jung Sun Kim, Taekyu Lim, Hye Sook Kim, Yu Jung Kim, Mi Sun Ahn, Young Saing Kim, Ji Hyun Park, Seungtaek Lim, Sung Shim Cho, Jang Ho Cho, Sang Won Shin, Kyong Hwa Park, Yeul Hong Kim; Cancer Res Treat. 2022;54(1):30-39. Published online May 20, 2021; DOI: https://doi.org/10.4143/crt.2021.218

Abstract PDF PubReader ePub

Purpose
K-MASTER project is a Korean national precision medicine platform that screened actionable mutations by analyzing next-generation sequencing (NGS) of solid tumor patients. We compared gene analyses between NGS panel from the K-MASTER project and orthogonal methods.
Materials and Methods
Colorectal, breast, non–small cell lung, and gastric cancer patients were included. We compared NGS results from K-MASTER projects with those of non-NGS orthogonal methods (KRAS, NRAS, and BRAF mutations in colorectal cancer [CRC]; epidermal growth factor receptor [EGFR], anaplastic lymphoma kinase [ALK] fusion, and reactive oxygen species 1 [ROS1] fusion in non–small cell lung cancer [NSCLC], and Erb-B2 receptor tyrosine kinase 2 (ERBB2) positivity in breast and gastric cancers).
Results
In the CRC cohort (n=225), the sensitivity and specificity of NGS were 87.4% and 79.3% (KRAS); 88.9% and 98.9% (NRAS); and 77.8% and 100.0% (BRAF), respectively. In the NSCLC cohort (n=109), the sensitivity and specificity of NGS for EGFR were 86.2% and 97.5%, respectively. The concordance rate for ALK fusion was 100%, but ROS1 fusion was positive in only one of three cases that were positive in orthogonal tests. In the breast cancer cohort (n=260), ERBB2 amplification was detected in 45 by NGS. Compared with orthogonal methods that integrated immunohistochemistry and in situ hybridization, sensitivity and specificity were 53.7% and 99.4%, respectively. In the gastric cancer cohort (n=64), ERBB2 amplification was detected in six by NGS. Compared with orthogonal methods, sensitivity and specificity were 62.5% and 98.2%, respectively.
Conclusion
The results of the K-MASTER NGS panel and orthogonal methods showed a different degree of agreement for each genetic alteration, but generally showed a high agreement rate.

Citations

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Genomic Profiling of Driver Gene Alterations in Patients With Non–Small Cell Lung Cancer, Patterns of Treatment and Impact on Survival Outcomes: A Single Center Experience of More Than 1200 Patients
Minit Shah, Vanita Noronha, Vijay Patil, Ajay Kumar Singh, Nandini Menon, Supriya Goud, Srushti Shah, Sucheta More, Akhil Kapoor, Bal Krishna Mishra, Pratik Chandrani, Anuradha Chougule, Vinod Gupta, Priyanka Pange, Omshree Shetty, Trupti Pai, Rajiv Kaush
Clinical Lung Cancer.2025;[Epub] CrossRef
Integrated clinical and genomic models using machine-learning methods to predict the efficacy of paclitaxel-based chemotherapy in patients with advanced gastric cancer
Yonghwa Choi, Jangwoo Lee, Keewon Shin, Ji Won Lee, Ju Won Kim, Soohyeon Lee, Yoon Ji Choi, Kyong Hwa Park, Jwa Hoon Kim
BMC Cancer.2024;[Epub] CrossRef
Supporting Biomarker-Driven Therapies in Oncology: A Genomic Testing Cost Calculator
Albrecht Stenzinger, Brian Cuffel, Noman Paracha, Eric Vail, Jesus Garcia-Foncillas, Clifford Goodman, Ulrik Lassen, Gilles Vassal, Sean D Sullivan
The Oncologist.2023; 28(5): e242. CrossRef
Genomic analysis of plasma circulating tumor DNA in patients with heavily pretreated HER2 + metastatic breast cancer
Kyoungmin Lee, Jongwon Lee, Jungmin Choi, Sung Hoon Sim, Jeong Eun Kim, Min Hwan Kim, Yeon Hee Park, Jee Hyun Kim, Su-Jin Koh, Kyong Hwa Park, Myoung Joo Kang, Mi Sun Ahn, Kyoung Eun Lee, Hee-Jun Kim, Hee Kyung Ahn, Han Jo Kim, Keon Uk Park, In Hae Park
Scientific Reports.2023;[Epub] CrossRef
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
Cancer Research and Treatment.2022; 54(1): 1. CrossRef

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Head and Neck cancer

Induction Chemotherapy as a Prognostication Index and Guidance for Treatment of Locally Advanced Head and Neck Squamous Cell Carcinoma: The Concept of Chemo-Selection (KCSG HN13-01): Yun-Gyoo Lee, Eun Joo Kang, Bhumsuk Keam, Jin-Hyuk Choi, Jin-Soo Kim, Keon Uk Park, Kyoung Eun Lee, Hyo Jung Kim, Keun-Wook Lee, Min Kyoung Kim, Hee Kyung Ahn, Seong Hoon Shin, Hye Ryun Kim, Sung-Bae Kim, Hwan Jung Yun; Cancer Res Treat. 2022;54(1):109-117. Published online April 27, 2021; DOI: https://doi.org/10.4143/crt.2020.1329

Abstract PDF PubReader ePub

Purpose
Certain patient subgroups who do not respond to induction chemotherapy (IC) show inherent chemoresistance in locally advanced head and neck squamous cell carcinoma (LA-HNSCC). This study aimed to assess the prognostic value of IC, and role of IC in guiding the selection of a definitive locoregional therapy.
Materials and Methods
Out of the 445 patients in multi-institutional LA-HNSCC cohort, 158 (36%) receiving IC were enrolled. The study outcome was to assess overall survival (OS) through IC responsiveness and its role to select subsequent treatments.
Results
Among 135 patients who completed subsequent treatment following IC, 74% responded to IC (complete response in 17% and partial response in 58%). IC-non-responders showed 4.5 times higher risk of mortality than IC-responders (hazard ratio, 4.52; 95% confidence interval, 2.32 to 8.81; p < 0.001). Among IC-responders, 84% subsequently received definitive concurrent chemoradiotherapy (CCRT) and OS was not differed by surgery or CCRT (p=0.960). Regarding IC-non-responders, 54% received CCRT and 46% underwent surgery, and OS was poor in CCRT (24-month survival rate of 38%) or surgery (24-month survival rate of 63%).
Conclusion
Response to IC is a favorable prognostic factor. For IC-responders, either surgery or CCRT achieved similar survival probabilities. For IC-non-responder, multidisciplinary approach was warranted reflecting patients’ preference, morbidity, and prognosis.

Citations

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Circulating tumor DNA determines induction chemotherapy response in HPV associated oropharyngeal squamous cell carcinoma: A pilot study
Zachary M. Huttinger, Emile Gogineni, Sujith Baliga, Dukagjin M. Blakaj, Priyanka Bhateja, Marcelo Bonomi, Stephen Y. Kang, Matthew O. Old, Nolan B. Seim, Kyle K. VanKoevering, Amit Agrawal, Enver Ozer, James W. Rocco, Catherine T. Haring
Oral Oncology.2025; 161: 107179. CrossRef
Clinical decision pathway and management of locally advanced head and neck squamous cell carcinoma: A multidisciplinary consensus in Asia-Pacific
Ye Guo, Torahiko Nakashima, Byoung Chul Cho, Darren W.-T. Lim, Muh-Hwa Yang, Pei-Jen Lou, June Corry, Jin Ching Lin, Guo Pei Zhu, Kyung Hwan Kim, Bin Zhang, Zhiming Li, Ruey-Long Hong, Junice Yi Siu Ng, Ee Min Tan, Yan Ping Liu, Con Stylianou, Carmel Spit
Oral Oncology.2024; 148: 106657. CrossRef
Neoadjuvant programmed cell death 1 blockade combined with chemotherapy for locally advanced head and neck squamous cell carcinoma
Ping Han, Faya Liang, Pan Song, Taowei Wu, Yangyang Li, Ming Gao, Peiliang Lin, Jianming Fan, Xiaoming Huang
Holistic Integrative Oncology.2024;[Epub] CrossRef
Clinical prognostic factors to guide treatment strategy for HPV‑positive oropharyngeal cancer using treatment outcomes of induction chemotherapy: A real‑world experience
Hyun Bang, Hyeon-Jong Kim, Seung Lee, Hyun Shim, Jun Hwang, Woo Bae, Ik-Joo Chung, Sang-Hee Cho
Oncology Letters.2024;[Epub] CrossRef
Role of induction chemotherapy in advanced‐stage olfactory neuroblastoma
Sung‐Woo Cho, Bhumsuk Keam, Keun‐Wook Lee, Ji‐Won Kim, Doo Hee Han, Hyun Jik Kim, Jeong‐Whun Kim, Dong‐Young Kim, Chae‐Seo Rhee, Yun Jung Bae, Ji‐Hoon Kim, Keun‐Yong Eom, Hong‐Gyun Wu, Yong Hwy Kim, Chae‐Yong Kim, Sun Ha Paek, Hyojin Kim, Tae‐Bin Won
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Intra-Arterial Chemotherapy for Locally Advanced Oral Cavity Cancer
B. B. Vyzhigina, M. A. Kropotov, B. I. Dolgushin, D. A. Safarov, I. V. Pogrebnyakov, S. B. Alieva
Journal of oncology: diagnostic radiology and radiotherapy.2024; 7(3): 62. CrossRef
Response to induction chemotherapy as a prognostic indicator in locally advanced head and neck squamous cell carcinoma
Francesca Huwyler, Roland Giger, Ruben Bill, Daniel Rauch, Simon Haefliger
Journal of Cancer Research and Clinical Oncology.2024;[Epub] CrossRef
Response to induction chemotherapy in sinonasal malignancies: A single‐institutional experience
Sarah C. Nyirjesy, Rachel Fenberg, Margaret A. Heller, Ryan T. Judd, Michael M. Li, Brandon Koch, Marcelo Bonomi, Ricardo L. Carrau, Kyle K. VanKoevering
Head & Neck.2023; 45(6): 1445. CrossRef
Human Papillomavirus-Related Non-Metastatic Oropharyngeal Carcinoma: Current Local Treatment Options and Future Perspectives
Michaela Svajdova, Pavol Dubinsky, Tomas Kazda, Branislav Jeremic
Cancers.2022; 14(21): 5385. CrossRef

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Investigating the Feasibility of Targeted Next-Generation Sequencing to Guide the Treatment of Head and Neck Squamous Cell Carcinoma: Sun Min Lim, Sang Hee Cho, In Gyu Hwang, Jae Woo Choi, Hyun Chang, Myung-Ju Ahn, Keon Uk Park, Ji-Won Kim, Yoon Ho Ko, Hee Kyung Ahn, Byoung Chul Cho, Byung-Ho Nam, Sang Hoon Chun, Ji Hyung Hong, Jung Hye Kwon, Jong Gwon Choi, Eun Joo Kang, Tak Yun, Keun-Wook Lee, Joo-Hang Kim, Jin Soo Kim, Hyun Woo Lee, Min Kyoung Kim, Dongmin Jung, Ji Eun Kim, Bhumsuk Keam, Hwan Jung Yun, Sangwoo Kim, Hye Ryun Kim; Cancer Res Treat. 2019;51(1):300-312. Published online May 9, 2018; DOI: https://doi.org/10.4143/crt.2018.012

Abstract PDF Supplementary Material PubReader ePub

Purpose
Head and neck squamous cell carcinoma (HNSCC) is a deadly disease in which precision medicine needs to be incorporated. We aimed to implement next-generation sequencing (NGS) in determining actionable targets to guide appropriate molecular targeted therapy in HNSCC patients.
Materials and Methods
Ninety-three tumors and matched blood samples underwent targeted sequencing of 244 genes using the Illumina HiSeq 2500 platform with an average depth of coverage of greater than 1,000×. Clinicopathological data from patients were obtained from 17 centers in Korea, and were analyzed in correlation with NGS data.
Results
Ninety-two of the 93 tumors were amenable to data analysis. TP53 was the most common mutation, occurring in 47 (51%) patients, followed by CDKN2A (n=23, 25%), CCND1 (n=22, 24%), and PIK3CA (n=19, 21%). The total mutational burden was similar between human papillomavirus (HPV)–negative vs. positive tumors, although TP53, CDKN2A and CCND1 gene alterations occurred more frequently in HPV-negative tumors. HPV-positive tumors were significantly associated with immune signature-related genes compared to HPV-negative tumors. Mutations of NOTCH1 (p=0.027), CDKN2A (p < 0.001), and TP53 (p=0.038) were significantly associated with poorer overall survival. FAT1 mutations were highly enriched in cisplatin responders, and potentially targetable alterations such as PIK3CA E545K and CDKN2A R58X were noted in 14 patients (15%).
Conclusion
We found several targetable genetic alterations, and our findings suggest that implementation of precision medicine in HNSCC is feasible. The predictive value of each targetable alteration should be assessed in a future umbrella trial using matched molecular targeted agents.

Citations

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Personalized Biomarker-Based Umbrella Trial for Patients With Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma: KCSG HN 15-16 TRIUMPH Trial
Bhumsuk Keam, Min Hee Hong, Seong Hoon Shin, Seong Gu Heo, Ji Eun Kim, Hee Kyung Ahn, Yun-Gyoo Lee, Keon-Uk Park, Tak Yun, Keun-Wook Lee, Sung-Bae Kim, Sang-Cheol Lee, Min Kyoung Kim, Sang Hee Cho, So Yeon Oh, Sang-Gon Park, Shinwon Hwang, Byung-Ho Nam, S
Journal of Clinical Oncology.2024; 42(5): 507. CrossRef
A Phase II Trial of Nintedanib in Patients with Metastatic or Recurrent Head and Neck Squamous Cell Carcinoma: In-Depth Analysis of Nintedanib Arm from the KCSG HN 15-16 TRIUMPH Trial
Kyoo Hyun Kim, Sun Min Lim, Hee Kyung Ahn, Yun-Gyoo Lee, Keun-Wook Lee, Myung-Ju Ahn, Bhumsuk Keam, Hye Ryun Kim, Hyun Woo Lee, Ho Jung An, Jin-Soo Kim
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Han Na Kang, Jae-Hwan Kim, A-Young Park, Jae Woo Choi, Sun Min Lim, Jinna Kim, Eun Joo Shin, Min Hee Hong, Kyoung-Ho Pyo, Mi Ran Yun, Dong Hwi Kim, Hanna Lee, Sun Och Yoon, Da Hee Kim, Young Min Park, Hyung Kwon Byeon, Inkyung Jung, Soonmyung Paik, Yoon W
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Ana Carolina de Carvalho, Sandra Perdomo, Wellington dos Santos, Gabriela Carvalho Fernandes, Lais Machado de Jesus, Raiany Santos Carvalho, Cristovam Scapulatempo-Neto, Gisele Caravina de Almeida, Bruna Pereira Sorroche, Lidia Maria Rebolho Batista Arant
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Case Report

Bladder and Liver Involvement of Visceral Larva Migrans May Mimic Malignancy: Eun Joo Kang, Yoon Ji Choi, Jung Sun Kim, Byung Hyun Lee, Ka-Won Kang, Hong Jun Kim, Eun Sang Yu, Yeul Hong Kim; Cancer Res Treat. 2014;46(4):419-424. Published online July 18, 2014; DOI: https://doi.org/10.4143/crt.2013.104

Abstract PDF PubReader ePub

Visceral larva migrans (VLM) syndrome is a clinical manifestation of systemic organ involvement by Toxocara species. VLM with involvement of the bladder and liver is a rare finding. A 62-year-old woman presented with diffuse bladder wall thickening and multiple liver masses with peripheral eosinophilia and urinary symptoms. We considered malignancy or eosinophilic cystitis through clinical manifestations and imaging findings. However, no suspicious malignant lesions were observed on cystoscopy and liver mass biopsy revealed the presence of eosinophilic necrotizing granuloma without malignant cells. Anti-Toxocara antibodies were detected by western blotting and the patient was diagnosed with VLM syndrome. After taking prednisolone, urinary symptoms disappeared. On abdominal CT scan taken after three months, the size of multiple liver masses and bladder wall thickening had decreased. VLM syndrome should be suspected in patients with an atypical imaging pattern and peripheral eosinophilia.

Citations

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