Cancer Research and Treatment

Original Articles

Lung and Thoracic cancer

Comparison of the Predictive Power of a Combination versus Individual Biomarker Testing in Non–Small Cell Lung Cancer Patients Treated with Immune Checkpoint Inhibitors: Hyojin Kim, Hyun Jung Kwon, Eun Sun Kim, Soohyeon Kwon, Kyoung Jin Suh, Se Hyun Kim, Yu Jung Kim, Jong Seok Lee, Jin-Haeng Chung; Cancer Res Treat. 2022;54(2):424-433. Published online July 7, 2021; DOI: https://doi.org/10.4143/crt.2021.583

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Purpose
Since tumor mutational burden (TMB) and gene expression profiling (GEP) have complementary effects, they may have improved predictive power when used in combination. Here, we investigated the ability of TMB and GEP to predict the immunotherapy response in patients with non–small cell lung cancer (NSCLC) and assessed if this combination can improve predictive power compared to that when used individually.
Materials and Methods
This retrospective cohort study included 30 patients with NSCLC who received immune checkpoint inhibitors (ICI) therapy at the Seoul National University Bundang Hospital. programmed cell death-ligand-1 (PD-L1) protein expression was assessed using immunohistochemistry, and TMB was measured by targeted deep sequencing. Gene expression was determined using NanoString nCounter analysis for the PanCancer IO360 panel, and enrichment analysis were performed.
Results
Eleven patients (36.7%) showed a durable clinical benefit (DCB), whereas 19 (63.3%) showed no durable benefit (NDB). TMB and enrichment scores (ES) showed significant differences between the DCB and NDB groups (p=0.044 and p=0.017, respectively); however, no significant correlations were observed among TMB, ES, and PD-L1. ES was the best single biomarker for predicting DCB (area under the curve [AUC], 0.794), followed by TMB (AUC, 0.679) and PD-L1 (AUC, 0.622). TMB and ES showed the highest AUC (0.837) among other combinations (AUC [TMB and PD-L1], 0.777; AUC [PD-L1 and ES], 0.763) and was similar to that of all biomarkers used together (0.832).
Conclusion
The combination of TMB and ES may be an effective predictive tool to identify patients with NSCLC patients who would possibly benefit from ICI therapies.

Citations

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Microdroplet-enhanced chip platform for high-throughput immunotherapy marker screening from extracellular vesicle RNAs and membrane proteins
Chuanhao Tang, Zaizai Dong, Shi Yan, Bing Liu, Zhiying Wang, Long Cheng, Feng Liu, Hong Sun, Yimeng Du, Lu Pan, Yuhao Zhou, Zhiyuan Jin, Libo Zhao, Nan Wu, Lingqian Chang, Xiaojie Xu
Biosensors and Bioelectronics.2025; 267: 116748. CrossRef
Exploring the ferroptosis-related gene lipocalin 2 as a potential biomarker for sepsis-induced acute respiratory distress syndrome based on machine learning
Jiayi Zhan, Junming Chen, Liyan Deng, Yining Lu, Lianxiang Luo
Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease.2024; 1870(4): 167101. CrossRef
Evaluation of Blood Tumor Mutation Burden for the Efficacy of Second-Line Atezolizumab Treatment in Non-Small Cell Lung Cancer: BUDDY Trial
Cheol-Kyu Park, Ha Ra Jun, Hyung-Joo Oh, Ji-Young Lee, Hyun-Ju Cho, Young-Chul Kim, Jeong Eun Lee, Seong Hoon Yoon, Chang Min Choi, Jae Cheol Lee, Sung Yong Lee, Shin Yup Lee, Sung-Min Chun, In-Jae Oh
Cells.2023; 12(9): 1246. CrossRef
Unveiling the role of regulatory T cells in the tumor microenvironment of pancreatic cancer through single-cell transcriptomics and in vitro experiments
Wei Xu, Wenjia Zhang, Dongxu Zhao, Qi Wang, Man Zhang, Qiang Li, Wenxin Zhu, Chunfang Xu
Frontiers in Immunology.2023;[Epub] CrossRef
Facilitating “Omics” for Phenotype Classification Using a User-Friendly AI-Driven Platform: Application in Cancer Prognostics
Uraquitan Lima Filho, Tiago Alexandre Pais, Ricardo Jorge Pais
BioMedInformatics.2023; 3(4): 1071. CrossRef
Current state and challenges of emerging biomarkers for immunotherapy in hepatocellular carcinoma (Review)
Mo Cheng, Xiufeng Zheng, Jing Wei, Ming Liu
Experimental and Therapeutic Medicine.2023;[Epub] CrossRef

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The Prognostic Values of Preoperative Tumor Volume and Tumor Diameter in T1N0 Papillary Thyroid Cancer: Seung Taek Lim, Ye Won Jeon, Young Jin Suh; Cancer Res Treat. 2017;49(4):890-897. Published online December 13, 2016; DOI: https://doi.org/10.4143/crt.2016.325

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Purpose
The current TNM staging system for papillary thyroid cancer (PTC), which is based on tumor diameter, may not precisely reflect the true tumor burden. Therefore, we investigated whether preoperative tumor volume might more accurately reflect tumor burden and predict prognosis in patients with T1N0 PTC than preoperative tumor diameter.
Materials and Methods
We retrospectively reviewed data from 1,659 patients with T1N0 PTC, and after exclusion, a total of 1,081 patients were ultimately included. Tumor volume (V) was calculated for all patients using preoperative ultrasonography, and patientswere grouped according to tumor diameter (T1a vs. T1b) and tumor volume (V1a vs. V1b). The recurrence-free survival (RFS) rates were then compared for these groups.
Results
The mean follow-up time was 66.12±28.75 months, and 97.2% of the cohort experienced RFS. The optimal volume cut-off was defined as 0.545 cm³. There were no differences in RFS rates between T1a/T1b groups (all ages) and V1a/V1b groups (< 45 years of age). However, ≥ 45-year-old patients in the V1b group had a significantly poorer RFS rate than those in the V1a group. These results were confirmed by multivariate analysis.
Conclusion
Our results indicate that preoperative tumor volume may be more useful for predicting prognosis than tumor diameter in ≥ 45-year-old patients with T1N0 PTC.

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Recommendation for Clinical T Staging in Patients with Non-Small Cell Lung Cancer: Volumetric Measurement: A Retrospective Study from Turkey
Muhammet Sayan, Aykut Kankoc, Muhammet Tarik Aslan, Irmak Akarsu, İsmail Cuneyt Kurul, Ali Celik
Journal of Chest Surgery.2025; 58(2): 51. CrossRef
Tumour volume is a predictor of lymphovascular invasion in differentiated small thyroid cancer
Krishna Vikneson, Tariq Haniff, May Thwin, Ahmad Aniss, Alex Papachristos, Mark Sywak, Anthony Glover
Endocrine Oncology.2022; 2(1): 42. CrossRef
Prognostic impact of dimensional factors in pT1 gastric cancer
Chikara Kunisaki, Masazumi Takahashi, Sho Sato, Nobuhiro Tsuchiya, Jun Watanabe, Tsutomu Sato, Kazuhisa Takeda, Yusaku Tanaka, Kohei Kasahara, Takashi Kosaka, Hirotoshi Akiyama, Itaru Endo
Surgical Oncology.2021; 38: 101584. CrossRef
Total thyroidectomy with and without prophylactic central compartment neck dissection in early papillary thyroid cancer: A comparative study
Hisham Omran, Ehab Mohammed Ali Fadl, Ahmed Abd El Aal Sultan
International Journal of Surgery Open.2021; 37: 100411. CrossRef
MicroRNA‑30a suppresses papillary thyroid cancer cell proliferation, migration and invasion by directly targeting E2F7
Haiyan Guo, Linyun Zhang
Experimental and Therapeutic Medicine.2019;[Epub] CrossRef
Periostin silencing suppresses the aggressive phenotype of thyroid carcinoma cells by suppressing the Akt/thyroid stimulating hormone receptor axis
Min Wang, Chunyi Gui, Shenglong Qiu, Jingdong Tang, Zhihai Peng
Cytotechnology.2018; 70(1): 275. CrossRef
Comparison of incidental versus palpable thyroid nodules presenting for fine‐needle aspiration biopsy
Ayaka J. Iwata, Arti Bhan, Sharon Lahiri, Amy M. Williams, Andrew R. Taylor, Steven S. Chang, Michael C. Singer
Head & Neck.2018; 40(7): 1508. CrossRef
Prognostic influence of 3-dimensional tumor volume on breast cancer compared to conventional 1-dimensional tumor size
Ki-Tae Hwang, Wonshik Han, Sang Mok Lee, Jaewoo Choi, Jongjin Kim, Jiyoung Rhu, Young A Kim, Dong-Young Noh
Annals of Surgical Treatment and Research.2018; 95(4): 183. CrossRef
Measurement of tumor volume is not superior to diameter for prediction of lymph node metastasis in early gastric cancer with minute submucosal invasion
Jeung Hui Pyo, Sun-Ju Byeon, Hyuk Lee, Yang Won Min, Byung-Hoon Min, Jun Haeng Lee, Kyoung-Mee Kim, Hyeon Seon Ahn, Kyunga Kim, Yoon-Ho Choi, Jae J. Kim
Oncotarget.2017; 8(69): 113758. CrossRef

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Clinical Features of Male Breast Cancer: Experiences from Seven Institutions Over 20 Years: Ji Hyung Hong, Kyung Sun Ha, Yun Hwa Jung, Hye Sung Won, Ho Jung An, Guk Jin Lee, Donghoon Kang, Ji Chan Park, Sarah Park, Jae Ho Byun, Young Jin Suh, Jeong Soo Kim, Woo Chan Park, Sang Seol Jung, Il Young Park, Su-Mi Chung, In Sook Woo; Cancer Res Treat. 2016;48(4):1389-1398. Published online April 11, 2016; DOI: https://doi.org/10.4143/crt.2015.410

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Purpose
Breast cancer treatment has progressed significantly over the past 20 years. However, knowledge regarding male breast cancer (MBC) is sparse because of its rarity. This study is an investigation of the clinicopathologic features, treatments, and clinical outcomes of MBC.
Materials and Methods
Clinical records of 59 MBC patients diagnosed during 1995-2014 from seven institutions in Korea were reviewed retrospectively.
Results
Over a 20-year period, MBC patients accounted for 0.98% among total breast cancer patients, and increased every 5 years. The median age of MBC patientswas 66 years (range, 24 to 87 years). Forty-three patients (73%) complained of a palpable breast mass initially. The median symptom duration was 5 months (range, 1 to 36 months). Mastectomy was performed in 96% of the patients. The most frequent histology was infiltrating ductal carcinoma (75%). Ninety-one percent of tumors (38/43) were estrogen receptor–positive, and 28% (11/40) showed epidermal growth factor receptor 2 (HER-2) overexpression. After curative surgery, 42% of patients (19/45) received adjuvant chemotherapy; 77% (27/35) received hormone therapy. Five out of ten patients with HER-2 overexpressing tumors did not receive adjuvant anti–HER-2 therapy, while two out of four patients with HER-2 overexpressing tumors received palliative trastuzumab for recurrent and metastatic disease. Letrozole was used for one patient in the palliative setting. The median overall survival durations were 7.2 years (range, 0.6 to 17.0 years) in patients with localized disease and 2.9 years (range, 0.6 to 4.3 years) in those with recurrent or metastatic disease.
Conclusion
Anti–HER-2 and hormonal therapy, except tamoxifen, have been underutilized in Korean MBC patients compared to female breast cancer patients. With the development of precision medicine, active treatment with targeted agents should be applied. Further investigation of the unique pathobiology of MBC is clinically warranted.

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Setup Error and Effectiveness of Weekly Image-Guided Radiation Therapy of TomoDirect for Early Breast Cancer: Mi Joo Chung, Guk Jin Lee, Young Jin Suh, Hyo Chun Lee, Sea-Won Lee, Songmi Jeong, Jeong Won Lee, Sung Hwan Kim, Dae Gyu Kang, Jong Hoon Lee; Cancer Res Treat. 2015;47(4):774-780. Published online February 13, 2015; DOI: https://doi.org/10.4143/crt.2014.189

Abstract PDF PubReader ePub

Purpose
This study investigated setup error and effectiveness of weekly image-guided radiotherapy (IGRT) of TomoDirect for early breast cancer. Materials and Methods One hundred and fifty-one breasts of 147 consecutive patients who underwent breast conserving surgery followed by whole breast irradiation using TomoDirect in 2012 and 2013 were evaluated. All patients received weekly IGRT. The weekly setup errors from simulation to each treatment in reference to chest wall and surgical clips were measured. Random, systemic, and 3-dimensional setup errors were assessed. Extensive setup error was defined as 5 mm above the margin in any directions.
Results
All mean errors were within 3 mm of all directions. The mean angle of gantry shifts was 0.6°. The mean value of absolute 3-dimensional setup error was 4.67 mm. In multivariate analysis, breast size (odds ratio, 2.82; 95% confidence interval, 1.00 to 7.90) was a significant factor for extensive error. The largest significant deviation of setup error was observed in the first week of radiotherapy (p < 0.001) and the deviations gradually decreased with time. The deviation of setup error was 5.68 mm in the first week and within 5 mm after the second week. Conclusion In this study, there was a significant association between breast size and significant setup error in breast cancer patients who received TomoDirect. The largest deviation occurred in the first week of treatment. Therefore, patients with large breasts should be closely observed on every fraction and fastidious attention is required in the first fraction of IGRT.

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Evidence-Based Complementary and Alternative Medicine.2015; 2015: 1. CrossRef

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Predictors of Axillary Lymph Node Metastases (ALNM) in a Korean Population with T1-2 Breast Carcinoma: Triple Negative Breast Cancer has a High Incidence of ALNM Irrespective of the Tumor Size: Jong Hoon Lee, Sung Hwan Kim, Young Jin Suh, Byoung Yong Shim, Hoon Kyo Kim; Cancer Res Treat. 2010;42(1):30-36. Published online March 31, 2010; DOI: https://doi.org/10.4143/crt.2010.42.1.30

Abstract PDF PubReader ePub

Purpose

We estimated the likelihood of breast cancer patients having axillary lymph node metastases (ALNM) based on a variety of clinical and pathologic factors.

Materials and Methods

Three hundred sixty-one breast cancer patients without distant metastases and who underwent breast conserving surgery and axillary lymph node dissection (ALND) (level I and II) or modified radical mastectomy (MRM) were identified, and we retrospectively reviewed their pathology records and treatment charts.

Results

Positive axillary lymph nodes were detected in 104 patients for an overall incidence of 28.8%: 2 patients (5%) with T1a tumor, 5 (9.2%) with T1b tumor, 24 (21.8%) with T1c tumor and 73 (44.2%) with T2 tumor. On the multivariate analysis, an increased tumor size (adjusted OR=11.87, p=0.02), the presence of lymphovascular invasion (adjusted OR=7.41, p<0.01), a triple negative profile (ER/PR-, Her2-) (adjusted OR=2.09, p=0.04) and a palpable mass at the time of diagnosis (adjusted OR=2.31, p=0.03) were all significant independent factors for positive ALNM.

Conclusion

In our study, the tumor size, the presence of lymphovascular invasion, a triple negative profile and a palpable mass were the independent predictive factors for ALNM. The tumor size was the strongest predictor of ALNM. Thus, the exact estimation of the extent of tumor is necessary for clinicians to optimize the patients' care. Patients with a triple negative profile have a high incidence of ALNM irrespective of the tumor size.

Citations

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Restoration of Hormone Dependency in Estrogen Receptor - Lipofected MDA-MB-231 Human Breast Cancer Cells: Young Jin Suh, Jae Hee Chang, Chung Soo Chun; J Korean Cancer Assoc. 1999;31(3):473-482.

Abstract PDF: PURPOSE
The loss of estrogen and progesterone receptors appeats to be associated with a progression to less differentiated and hormone-independent tumors. The gain of hormone independency over time even in estrogen receptor-positive tumors has become another obstacle to endocrine therapy for breast cancer. We tried to regain the hormone dependency in estrogen receptor-negative breast cancer cells by lipofecting estmgen receptor cDNA.
MATERIALS AND METHODS
The mutant human estrogen receptor cDNA (pSGS-HEO) was lipofected into estrogen receptor-negative human breast cancer cell line MDA-MB-231, in an attempt to restore their sensitivity to antiestrogen. Then the effects of 17p-estradiol and tamoxifen were studied by counting viable cell numbers after treating the lipofected cell line with either one or together.
RESULTS
Culture medium cantaining phenol red, a weak estrogen, has growth advantages compared with culture medium without it. In both culture conditions, cell growth was most profoundly inhibited in 4 days after lipofection with mutant human estrogen receptor cDNA, which was overcome after that day. Tamoxifen, as an antiestrogen, showed a growth inhibitory effect slightly stronger tban combined conditions of tamoxifen and 17- estradiol compared to estrogen-treated group and to control, and the inhibitory effect was lasted 4 days.
CONCLUSION
The temporary induction of estrogen receptor by lipofection with pSGS-HEO on estrogen receptor-negative human breast cancer cell line MDA-MB-231 showed negative growth control on these cells by tamoxifen, indicating that liposome-mediated estrogen receptor transfection may be used as a novel therapeutic strategy for hormane independent human breast cancers in the near future.

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Identification of Estrogen Receptor Gene in Breast Cancer: Young Jin Suh, In Chul Kim, Sang Seol Jung; J Korean Cancer Assoc. 1996;28(5):796-806.

Abstract PDF: Background
The initiation and progression of breast carcinoma are profoundly influenced by hormonal factors. Breast tumors that express the estrogen receptor (ER) are slower growing, associated with better long-term disease-free survival, and amenable to endocrine therapy with agents such as the antiestrogen. But only 60% of the ER-positive breast cancer patients respond to endocrine manipulation. In addition, many ER-positive cancers that initially respond to endocrine therapy ultimately progress to a more aggressive hormone-independent phenotype. Loss of estrogen receptor expression is an important means of hormone resistance, but the mechanisms involved are poorly understood. Materials & Method: We examined the ER by dextran-coated charcoal assay and the ER cDNA by reverse transcription-palymerase chain reaction in 19 primary breast cancers to determine if alterations of the gene are associated with the ER-negative status. Results: From this study, we could see the expression of the ER gene in all of the ER- positive specimens, but ER-negative group showed inconsistent results. Four out of 9 ER- negative specimens expressed ER gene. Three of these four were progesterone receptor-positive. Conclusion: This results suggest that ER expression may be determined at the transcription level and that genomic analysis of the ER may be more accurate than conventional ER assays in clinical setting.

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