Cancer Research and Treatment

Original Articles

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

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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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The Relationship of PRAME Expression with Clinicopathologic Parameters and Immunologic Markers in Melanomas: In Silico Analysis
Yasemin Cakir, Banu Lebe
Applied Immunohistochemistry & Molecular Morphology.2025; 33(2): 117. CrossRef
Exploration of the regulatory mechanism of norcantharidin on sine oculis homeobox homolog 4 in colon cancer using transcriptome sequencing and bioinformatic
Fanqin Zhang, Chao Wu, Jingyuan Zhang, Zhihong Huang, Antony Stalin, Yiyan Zhai, Shuqi Liu, Jiarui Wu
Journal of Traditional Chinese Medical Sciences.2025;[Epub] CrossRef
Biomarkers to predict efficacy of immune checkpoint inhibitors in colorectal cancer patients: a systematic review and meta-analysis
Hang Yu, Qingquan Liu, Keting Wu, Shuang Tang
Clinical and Experimental Medicine.2024;[Epub] CrossRef
An Insight into the Peculiarities of Signet-Ring Cell Carcinoma of the Colon – a Narrative Review
Loredana Farcaș, Diana Voskuil-Galoș
Journal of Medical and Radiation Oncology.2024; 4(7): 1. CrossRef
High serum IL-6 correlates with reduced clinical benefit of atezolizumab and bevacizumab in unresectable hepatocellular carcinoma
Hannah Yang, Beodeul Kang, Yeonjung Ha, Sung Hwan Lee, Ilhwan Kim, Hyeyeong Kim, Won Suk Lee, Gwangil Kim, Sanghoon Jung, Sun Young Rha, Vincent E. Gaillard, Jaekyung Cheon, Chan Kim, Hong Jae Chon
JHEP Reports.2023; 5(4): 100672. CrossRef
Identification of ZBTB4 as an immunological biomarker that can inhibit the proliferation and invasion of pancreatic cancer
Zhe Yang, Feiran Chen, Feng Wang, Xiubing Chen, Biaolin Zheng, Xiaomin Liao, Zhejun Deng, Xianxian Ruan, Jing Ning, Qing Li, Haixing Jiang, Shanyu Qin
BMC Cancer.2023;[Epub] CrossRef
PD-L1 Expression in Colorectal Carcinoma: A Comparison of 3 Scoring Methods in a Cohort of Jordanian Patients
Heyam A. Awad, Maher A. Sughayer, Jumana M. Obeid, Yaqoot N. Heilat, Ahmad S. Alhesa, Reda M. Yousef, Nabil M. Hasasna, Shafiq A. Masoud, Tareq Saleh
Applied Immunohistochemistry & Molecular Morphology.2023; 31(6): 379. CrossRef
Systemic Delivery of a STING Agonist‐Loaded Positively Charged Liposome Selectively Targets Tumor Immune Microenvironment and Suppresses Tumor Angiogenesis
Eun‐Jin Go, Hannah Yang, Wooram Park, Seung Joon Lee, Jun‐Hyeok Han, So Jung Kong, Won Suk Lee, Dong Keun Han, Hong Jae Chon, Chan Kim
Small.2023;[Epub] CrossRef
Review of the Immune Checkpoint Inhibitors in the Context of Cancer Treatment
Norah A. Alturki
Journal of Clinical Medicine.2023; 12(13): 4301. CrossRef
Enhancing head and neck tumor management with artificial intelligence: Integration and perspectives
Nian-Nian Zhong, Han-Qi Wang, Xin-Yue Huang, Zi-Zhan Li, Lei-Ming Cao, Fang-Yi Huo, Bing Liu, Lin-Lin Bu
Seminars in Cancer Biology.2023; 95: 52. CrossRef
Artificial intelligence for prediction of response to cancer immunotherapy
Yuhan Yang, Yunuo Zhao, Xici Liu, Juan Huang
Seminars in Cancer Biology.2022; 87: 137. CrossRef

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Lung and Thoracic cancer

Selection Strategies and Practical Application of BRAF V600E-Mutated Non–Small Cell Lung Carcinoma: Inwoo Hwang, Yoon-La Choi, Hyunwoo Lee, Soohyun Hwang, Boram Lee, Hobin Yang, Chaithanya Chelakkot, Joungho Han; Cancer Res Treat. 2022;54(3):782-792. Published online November 23, 2021; DOI: https://doi.org/10.4143/crt.2021.843

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Purpose
The incidence of BRAF V600E mutation in non-small cell lung carcinoma (NSCLC) is lower than 2%, which poses difficulties in finding legitimate patients for targeted therapy. We investigated the predictive factors pertaining to BRAF V600E and the effectiveness of the VE1 antibody as a screening method for patient selection.
Materials and Methods
The study was designed into two steps. In a first group, BRAF-mutated NSCLCs were identified from sequencing data to determine the features of BRAF V600E mutation. The results of the first group helped the collection of adenocarcinomas with a papillary or micropapillary pattern but without EGFR or ALK alterations as a second group so that the frequency of BRAF V600E mutation could be calculated. The sensitivity and specificity of the VE1 were compared with BRAF V600E status.
Results
Among 39 BRAF-mutated NSCLCs in the first group, 20 (51%) were V600E. BRAF V600E mutation was more common in female patients and showed no significant correlation with smoking status. Nineteen cases were adenocarcinomas without EGFR and ALK alterations. The most common patterns of invasion were papillary and micropapillary along with central fibrosis. The sensitivity and specificity of the VE1 were 90.0% and 92.3%, respectively. In the second group, 6.7% of cases were VE1-positive, indicating that the prevalence was significantly higher than that reported in previous studies (0.3-1.8%).
Conclusion
BRAF V600E-mutated NSCLCs could be enriched with the application of clinicopathologic parameters, which are not perfect. Therefore, additional VE1 immunohistochemistry may be useful as a screening method.

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The rapidly changing field of predictive biomarkers of non-small cell lung cancer
László József Tóth, Attila Mokánszki, Gábor Méhes
Pathology and Oncology Research.2024;[Epub] CrossRef
BRAF V600E Mutation of Non-Small Cell Lung Cancer in Korean Patients
Hyo Yeong Ahn, Chang Hun Lee, Min Ki Lee, Jung Seop Eom, Yeon Joo Jeong, Yeong Dae Kim, Jeong Su Cho, Jonggeun Lee, So Jeong Lee, Dong Hoon Shin, Ahrong Kim
Medicina.2023; 59(6): 1085. CrossRef
The Impact of Liquid Biopsies Positive for EGFR Mutations on Overall Survival in Non-Small Cell Lung Cancer Patients
Jonnathan Roldan Ruiz, Marta Fuentes Gago, Luis Chinchilla Tabora, Idalia Gonzalez Morais, José Sayagués, Mar Abad Hernández, Maria Cordovilla Pérez, Maria Ludeña de la Cruz, Edel del Barco Morillo, Marta Rodriguez Gonzalez
Diagnostics.2023; 13(14): 2347. CrossRef
Usefulness of BRAF VE1 immunohistochemistry in non–small cell lung cancers: a multi-institutional study by 15 pathologists in Korea
Sunhee Chang, Yoon-La Choi, Hyo Sup Shim, Geon Kook Lee, Seung Yeon Ha
Journal of Pathology and Translational Medicine.2022; 56(6): 334. CrossRef

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Head and Neck cancer

Re-irradiation with Moderate Hypo-fractionation Using Intensity Modulated Photon or Proton Radiation Therapy in Locally Recurrent Squamous Cell Carcinoma of Nasopharynx: Heerim Nam, Yong Chan Ahn, Kyungmi Yang, Dongryul Oh, Jae Myoung Noh; Cancer Res Treat. 2022;54(1):96-108. Published online March 26, 2021; DOI: https://doi.org/10.4143/crt.2020.1349

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Purpose
This study aimed to analyze the treatment outcomes of locally recurrent nasopharyngeal cancer (NPC) patients following moderate hypo-fractionation re-irradiation (re-RT).
Materials and Methods
Sixty locally recurrent NPC patients underwent hypo-fractionation re-RT. Forty-eight point three percentage had rT3-4, and 30.0% did keratinizing squamous cell carcinoma. Intensity-modulated radiation therapy (IMRT), with or without intensity-modulated proton therapy (IMPT), was used in 66.7% of patients.
Results
With the median follow-up of 22 months (range, 2 to 254 months), 31 patients (51.7%) died, 38 (63.3%) developed further treatment failure, and 30 (50.0%) developed ≥ grade 3 toxicity (including seven grade 5) at time of analysis. The 2- and 5-year rates of overall survival, local failure-free survival, and ≥ grade 3 toxicity-free survival were 57.9% and 45.8%, 64.1% and 52.5%, and 54.8% and 44.9%, respectively. In multivariate analyses, worse factors for overall survival (OS) were iT3-4 (p=0.010) and age at re-RT ≥ 53 years (p=0.003), those for local failure-free survival (LFFS) were rT3-4 (p=0.022) and rN0-1 (p=0.035), and those for toxicity-free survival (TFS) were iT3-4 (p=0.020) and re-IMRT/IMPT (p=0.030), respectively. Cumulative dose or fraction size ≥ 3 Gy at re-RT, however, showed no significance for OS, LFFS and TFS.
Conclusion
Current re-RT with modern RT techniques by moderate hypo-fractionation scheme seemed feasible in treating locally recurrent NPC patients.

Citations

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Case Report: Unresectable recurrent nasopharyngeal cancer treated with immuno oncology
Fabiano Flauto, Rosa Maria Di Crescenzo, Vincenzo Damiano
Frontiers in Oncology.2025;[Epub] CrossRef
Envisioning an Italian Head and Neck Proton Therapy Model-Based Selection: Challenge and Opportunity
Giulia Fontana, Matteo Pepa, Anna Maria Camarda, Mimoza Strikchani, Michela Meregaglia, Alessandro Vai, Alfredo Mirandola, Barbara Vischioni, Andrea Pella, Guido Baroni, Barbara Alicja Jereczek-Fossa, Marta Scorsetti, Marco Cianchetti, Elisa D’Angelo, Pie
International Journal of Particle Therapy.2025; 16: 100745. CrossRef
Radiation oncology for the rhinologist
Helena Levyn, Fan Yang, Nancy Y. Lee
Current Opinion in Otolaryngology & Head & Neck Surgery.2024; 32(1): 5. CrossRef
Identifying the prognostic value of MRI-based tumor response and predicting the risk of radio-resistance in re-radiotherapy for locally recurrent nasopharyngeal carcinoma
Zi-Jian Lu, Ting Liu, Jie-Yi Lin, Sheng-Ting Pei, Ling Guo, Sai-Lan Liu, Hai-Qiang Mai
Radiotherapy and Oncology.2023; 183: 109635. CrossRef
Low-dose radiotherapy effects the progression of anti-tumor response
Lei Gao, Anqi Zhang
Translational Oncology.2023; 35: 101710. CrossRef
The Role of Hypofractionation in Proton Therapy
Alexandre Santos, Scott Penfold, Peter Gorayski, Hien Le
Cancers.2022; 14(9): 2271. CrossRef
Toxicity Profiles and Survival Outcomes Among Patients With Nonmetastatic Nasopharyngeal Carcinoma Treated With Intensity-Modulated Proton Therapy vs Intensity-Modulated Radiation Therapy
Xingzhe Li, Sarin Kitpanit, Anna Lee, Dennis Mah, Kevin Sine, Eric J. Sherman, Lara A. Dunn, Loren S. Michel, James Fetten, Kaveh Zakeri, Yao Yu, Linda Chen, Jung Julie Kang, Daphna Y. Gelblum, Sean M. McBride, Chiaojung J. Tsai, Nadeem Riaz, Nancy Y. Lee
JAMA Network Open.2021; 4(6): e2113205. CrossRef

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6 Web of Science
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Long-term Outcome of Chondrosarcoma: A Single Institutional Experience: Srimanth Bindiganavile, Ilkyu Han, Ji Yeon Yun, Han-Soo Kim; Cancer Res Treat. 2015;47(4):897-903. Published online February 12, 2015; DOI: https://doi.org/10.4143/crt.2014.135

Abstract PDF PubReader ePub

Purpose
The prognostic factors of chondrosarcoma remain uncertain as only a few large studies with long-term follow-up have been reported. The aim of this study was to analyze oncological outcomes and prognostic factors.
Materials and Methods
A retrospective review of oncological outcomes and prognostic factors was performed on 125 consecutive chondrosarcoma patients who underwent surgery at our institution.
Results
Overall survival was 91.6%±2.5%, 84.1%±3.8%, and 84.1%±3.8% at 5, 10, and 15 years respectively. Among the histological types, dedifferentiated type showed the worst survival (p < 0.001). As for conventional type chondrosarcoma, histologic grade and anatomical location predicted outcome, with high-grade with axial location having the worst outcome (p < 0.001). In contrast, low-grade chondrosarcoma of appendicular skeleton could be treated safely by intralesional curettage.
Conclusion
Histological type was significantly associated with the outcome of chondrosarcoma. For the conventional type, histologic grade and anatomical location predicted outcome, with highgrade with axial location having the worst outcome.

Citations

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