Cancer Research and Treatment

Original Articles

Risk Stratification in T4 or N3 Nasopharyngeal Carcinoma: Lin-Feng Guo, Lu-Chao Zhu, Yi-Feng Yu, Zhen-Zhen Lu, Qin Lin, San-Gang Wu; Received May 28, 2025 Accepted August 11, 2025 Published online August 12, 2025; DOI: https://doi.org/10.4143/crt.2025.573 [Epub ahead of print]

Abstract PDF PubReader ePub: Purpose
This study aimed to investigate the prognostic heterogeneity among stage III nasopharyngeal carcinoma (NPC) patients according to the 9th edition of the American Joint Committee on Cancer (AJCC)/Union for International Cancer Control (UICC) staging system to identify potential subgroups requiring tailored therapeutic strategies.
Materials and Methods
We retrospectively included stage III patients (T1-3N3 or T4N0-3) who were diagnosed with NPC between January 2015 and December 2021 according to the 9th edition of the AJCC/UICC staging system. Kaplan-Meier method and multivariable Cox regression analyses were used for statistical analysis.
Results
A total of 309 patients were included in this study. A total of 92/309 (29.8%) patients developed locoregional recurrence and/or distant metastasis with a median follow-up of 52.9 months. Those with T4N3 disease had significantly lower distant metastasis-free survival (DMFS), progression-free survival (PFS), and overall survival (OS) but comparable locoregional relapse-free survival (LRFS) to those with T1-3N3 and T4N0-2 disease. Those with T4N3 disease had comparable LRFS but significantly lower 5-year DMFS (78.7% vs. 44.7%, p < 0.001), PFS (65.7% vs. 27.6%, p < 0.001), and OS (77.1% vs. 45.9%, p < 0.001) compared to those with stage T4N0-2 and T1-3N3 diseases. Similar results were confirmed using the multivariate analysis.
Conclusion
Our study demonstrates the prognostic heterogeneity of stage III disease within the 9th edition NPC staging system. T4N3 category should be considered separately and treated as a distinct entity regardless of the staging editions.

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Breast cancer

Sex Disparities in Breast Cancer Survival According to Clinical Treatment Score Post-5 Years (CTS5) Risk Stratification: Ke Liu, Zhen-Zhen Lu, Zhen-Yu He, San-Gang Wu; Cancer Res Treat. 2026;58(2):525-533. Published online May 27, 2025; DOI: https://doi.org/10.4143/crt.2025.361

Abstract PDF PubReader ePub: Purpose
The role of the Clinical Treatment Score post-5 years (CTS5) in male breast cancer (MBC) remains unclear. This study aimed to investigate the characteristics and prognosis of CTS5 between MBC and female breast cancer (FBC).
Materials and Methods
Patients diagnosed with human epidermal growth factor receptor 2–negative/estrogen receptor–positive breast cancer between 2010 and 2015 were identified from the Surveillance, Epidemiology, and End Results (SEER) database. The chi-square test, Kaplan-Meier analysis, and multivariate Cox proportional hazard model were used for statistical analysis.
Results
This study included 169,869 patients, comprising 168,422 (99.1%) FBC and 1,447 (0.9%) MBC patients. More MBC patients had intermediate risk (IR)/high risk (HR) disease compared to FBC patients (17.7% vs. 8.7%, p < 0.001). MBC patients had an inferior overall survival (OS) but similar breast cancer-specific survival compared to those with FBC. Sensitivity analyses showed that sex was an independent prognostic factor associated with OS but not breast cancer-specific survival (BCSS) in both the low-risk (LR) and IR/HR cohorts. Those with MBC exhibited significantly worse OS (p < 0.001) than FBC patients in both cohorts. In MBC patients, those with IR/HR disease had significantly worse OS (p < 0.001) and BCSS (p < 0.001) compared to those with LR disease. For FBC patients, the IR/HR group had also significantly worse OS (p < 0.001) and BCSS (p < 0.001) compared to the LR group.
Conclusion
Our findings highlight critical differences in clinical characteristics, treatment patterns, and outcomes between MBC and FBC, suggesting the need for sex-tailored approaches in breast cancer management.

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Correspondence

Reply to Commentary on “Metronomic S-1 Adjuvant Chemotherapy Improves Survival in Patients with Locoregionally Advanced Nasopharyngeal Carcinoma”: San-Gang Wu; Cancer Res Treat. 2025;57(1):291-292. Published online November 4, 2024; DOI: https://doi.org/10.4143/crt.2024.1048

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Original Articles

Head and Neck cancer

Metronomic S-1 Adjuvant Chemotherapy Improves Survival in Patients with Locoregionally Advanced Nasopharyngeal Carcinoma: Yi-Feng Yu, Peng Wu, Rui Zhuo, San-Gang Wu; Cancer Res Treat. 2024;56(4):1058-1067. Published online February 19, 2024; DOI: https://doi.org/10.4143/crt.2023.1343

Abstract PDF PubReader ePub

Purpose
This study aimed to investigate the efficacy and safety of using metronomic S-1 adjuvant chemotherapy in locoregionally advanced nasopharyngeal carcinoma (LANPC).
Materials and Methods
We retrospectively collected data on patients diagnosed with LANPC between January 2016 and December 2021. All patients were treated with induction chemotherapy and concurrent chemoradiotherapy with or without metronomic chemotherapy (MC). Toxicities during MC were recorded. The chi-square test, Kaplan-Meier methods, propensity score matching (PSM), and Cox proportional hazards model were used for statistical analyses.
Results
A total of 474 patients were identified, including 64 (13.5%) and 410 (83.5%) patients with or without receiving MC, respectively. Patients who received metronomic S-1 had significantly better 3-year locoregional recurrence-free survival (LRFS) (100% vs. 90.9%, p=0.038), distant metastasis-free survival (DMFS) (98.5% vs. 84.1%, p=0.002), disease-free survival (DFS) (98.4% vs. 77.5%, p < 0.001), and overall survival (OS) (98.0% vs. 87.7%, p=0.008) compared to those without metronomic S-1. The multivariate prognostic analysis revealed that metronomic S-1 was identified as an independent prognostic factor associated with better DMFS (hazard ratio [HR], 0.074; p=0.010), DFS (HR, 0.103; p=0.002) and OS (HR, 0.127; p=0.042), but not in LRFS (p=0.071). Similar results were found using PSM. Common adverse events observed in the metronomic S-1 group included leukopenia, neutropenia, increased total bilirubin, anorexia, rash/desquamation, and hyperpigmentation. All patients with adverse events were grade 1-2.
Conclusion
It is worth conducting a randomized controlled trial to assess the effect of metronomic S-1 on survival outcomes and toxicities of LANPC.

Citations

Citations to this article as recorded by

Reply to Commentary on “Metronomic S-1 Adjuvant Chemotherapy Improves Survival in Patients with Locoregionally Advanced Nasopharyngeal Carcinoma”
San-Gang Wu
Cancer Research and Treatment.2025; 57(1): 291. CrossRef
Commentary on “Metronomic S-1 Adjuvant Chemotherapy Improves Survival in Patients with Locoregionally Advanced Nasopharyngeal Carcinoma”
Erkan Topkan, Efsun Somay, Nilufer Kılıc Durankus, Ugur Selek
Cancer Research and Treatment.2025; 57(1): 289. CrossRef
Two or three cycles of induction chemotherapy in locoregionally advanced nasopharyngeal carcinoma?
Lin-Feng Guo, Yi-Feng Yu, Zhen-Zhen Lu, Qin Lin, San-Gang Wu
BMC Cancer.2025;[Epub] CrossRef
Comment on “Ten-year survival outcomes of concurrent chemoradiotherapy with or without adjuvant chemotherapy for locoregionally advanced nasopharyngeal carcinoma in the IMRT era: A retrospective cohort study stratified by high- and low-risk profiles”
Erkan Topkan, Efsun Somay, Duriye Ozturk, Ugur Selek
Clinical and Translational Radiation Oncology.2025; 54: 101025. CrossRef
Genetic algorithm-optimized neural network outperforms TNM staging in predicting rapidly progressive nasopharyngeal carcinoma: Reassessing adjuvant chemotherapy benefit via propensity score matching
Li-ting Ling, Wang-jian Li, Yue Yao, Kai-qing Tan, Bo-lin Zhu, Li-Qing Zhou, Song Qu, Ling Li, Ying Guan, Xiao-dong Zhu, Ling-hui Pan, Zhong-guo Liang
European Journal of Cancer.2025; 230: 115787. CrossRef
Metronomic chemotherapy in locoregionally advanced nasopharyngeal carcinoma with residual EBV-DNA after induction chemotherapy
Lin-Feng Guo, Liu-Yun Gong, Qin Lin, San-Gang Wu
Infectious Agents and Cancer.2025;[Epub] CrossRef
Risk Stratification in T4 or N3 Nasopharyngeal Carcinoma
Lin-Feng Guo, Lu-Chao Zhu, Yi-Feng Yu, Zhen-Zhen Lu, Qin Lin, San-Gang Wu
Cancer Research and Treatment.2025;[Epub] CrossRef
Short-term versus long-term metronomic adjuvant chemotherapy in locally advanced nasopharyngeal carcinoma: A propensity score-matched real-world study
Shuhui Dong, Weixin Bei, Lanfeng Lin, Yaofei Jiang, Nian Lu, Guoying Liu, Yanqun Xiang, Weixiong Xia
Oral Oncology.2024; 156: 106908. CrossRef

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Impact of 21-Gene Recurrence Score on Chemotherapy Decision in Invasive Ductal Carcinoma of Breast with Nodal Micrometastases: Wei-Rong Chen, Jia-Peng Deng, Jun Wang, Jia-Yuan Sun, Zhen-Yu He, San-Gang Wu; Cancer Res Treat. 2019;51(4):1437-1448. Published online March 4, 2019; DOI: https://doi.org/10.4143/crt.2018.611

Abstract PDF PubReader ePub

Purpose
The purpose of this study was to investigate the effect of 21-gene recurrence score (RS) on predicting prognosis and chemotherapy decision in node micrometastases (N1mi) breast invasive ductal carcinoma (IDC).
Methods
Patients with stage T1-2N1mi and estrogen receptor-positive IDC diagnosed between 2004 and 2015 were included. The associations of 21-gene RS with breast cancer-specific survival (BCSS), chemotherapy decision, and benefit of chemotherapy were analyzed.
Results
We identified 4,758 patients including 1,403 patients (29.5%) treated with adjuvant chemotherapy. In the traditional RS cutoffs, 2,831 (59.5%), 1,634 (34.3%), and 293 (6.2%) patients were in the low-, intermediate-, and high-risk RS groups, respectively. In 3,853 patients with human epidermal growth factor receptor-2 (HER2) status available, most patients were HER2-negative disease (98.3%). A higher RS was independently related to chemotherapy receipt, and 14.0%, 47.7%, and 77.8% of patients in the low-, intermediate-, and high-risk RS groups received chemotherapy, respectively. The multivariate analysis indicated that a higher RS was related to worse BCSS (p < 0.001). The 5-year BCSS rates were 99.3%, 97.4%, and 91.9% in patients with low-, intermediate-, and high-risk RS groups, respectively (p < 0.001). However, chemotherapy receipt did not correlate with better BCSS in low-, intermediate-, or high-risk RS groups. There were similar trends using Trial Assigning Individualized Options for Treatment RS cutoffs.
Conclusion
The 21-gene RS does predict outcome and impact on chemotherapy decision of N1mi breast IDC. Large cohort and long-term outcomes studies are needed to identify the effects of chemotherapy in N1mi patients by different 21-gene RS groups.

Citations

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21-gene recurrence score predictive of the benefit of postoperative radiotherapy after breast-conserving surgery for elderly patients with T1N0 and luminal breast cancer
Run-Jie Wang, Hai-Ying Liu, Lin-Feng Guo, De Yu, San-Gang Wu
Breast Cancer.2024; 31(6): 1156. CrossRef
Evaluation of adjuvant therapy for T1-2N1miM0 breast cancer without further axillary lymph node dissection
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Molecular Diagnosis & Therapy.2020; 24(5): 621. CrossRef

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KIF11 Functions as an Oncogene and Is Associated with Poor Outcomes from Breast Cancer: Juan Zhou, Wei-Rong Chen, Li-Chao Yang, Jun Wang, Jia-Yuan Sun, Wen-Wen Zhang, Zhen-Yu He, San-Gang Wu; Cancer Res Treat. 2019;51(3):1207-1221. Published online December 27, 2018; DOI: https://doi.org/10.4143/crt.2018.460

Abstract PDF Supplementary Material PubReader ePub

Purpose
The study aimed to search and identify genes that were differentially expressed in breast cancer, and their roles in cancer growth and progression.
Materials and Methods
The Gene Expression Omnibus (Oncomine) and The Cancer Genome Atlas databases (https://cancergenome.nih.gov/) were screened for genes that were expressed differentially in breast cancer and were closely related to a poor prognosis. Gene expressions were verified by quantitative real-time polymerase chain reaction, and genes were knocked down by a lentivirus-based system. Cell growth and motility were evaluated and in vivo nude mice were used to confirm the in vitro roles of genes. Markers of epithelial-to-mesenchymal transition and the associations of KIF11 with the classical cancer signaling pathways were detected by Western blot.
Results
A series of genes expressed differentially in patients with breast cancer. The prognosis associated with high KIF11 expression was poor, and the expression of KIF11 increased significantly in high stage and malignant tumor cells. Inhibiting KIF11 expression in lentivirus-suppressed cells revealed that KIF11 inhibition significantly reduced cell viability and colony formation, inhibited migration and invasion, but promoted apoptosis. The sizes and weights of KIF11-inhibited tumors in nude mice were significantly lower than in the negative controls. Western blot showed that E-cadherin in breast cancer was significantly upregulated in KIF-inhibited cells and tumor tissues, whereas N-cadherin and vimentin were significantly downregulated. BT549 and MDA231 cells with KIF11 knockdown exhibited decreased ERK, AMPK, AKT, and CREB phosphorylation.
Conclusion
KIF11 acts as a potential oncogene that regulates the development and progression of breast cancer.

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Using the Lymph Node Ratio to Evaluate the Prognosis of Stage II/III Breast Cancer Patients Who Received Neoadjuvant Chemotherapy and Mastectomy: San-Gang Wu, Qun Li, Juan Zhou, Jia-Yuan Sun, Feng-Yan Li, Qin Lin, Huan-Xin Lin, Xun-Xing Gaun, Zhen-Yu He; Cancer Res Treat. 2015;47(4):757-764. Published online December 8, 2014; DOI: https://doi.org/10.4143/crt.2014.039

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Purpose
This study was conducted to investigate the prognostic value of lymph node ratio (LNR) in stage II/III breast cancer patients who undergo mastectomy after neoadjuvant chemotherapy.
Materials and Methods
Clinical and pathological data describing stage II/III breast cancer patients were included in this retrospective study. The primary outcomes were locoregional recurrence-free survival (LRFS), distant metastasis-free survival (DMFS), disease-free survival (DFS), and overall survival (OS).
Results
Among 277 patients, there were 43 ypN0, 64 ypN1, 89 ypN2, and 81 ypN3 cases. Additionally, there were 43, 57, 92 and 85 cases in the LNR 0, 0.01-0.20, 0.21-0.65, and > 0.65 groups, respectively. The median follow-up was 49.5 months. Univariate analysis showed that both ypN stage and LNR were prognostic factors of LRFS, DMFS, DFS, and OS (p < 0.05). Multivariate analysis showed that LNR was an independent prognostic factor of LRFS, DMFS, DFS, and OS (p < 0.05), while ypN stage had no effect on prognosis (p > 0.05).
Conclusion
The integrated use of LNR and ypN may be suitable for evaluation the prognosis of stage II/III breast cancer patients who undergo mastectomy after neoadjuvant chemotherapy.

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Association of lymph node ratio with adjuvant radiotherapy benefit in human papillomavirus-positive oropharyngeal squamous cell carcinoma: a population-based analysis
Zhen-Zhen Lu, Xin-Jia Chen, Zi-Qing You, Yi-Min Li, San-Gang Wu
Infectious Agents and Cancer.2026;[Epub] CrossRef
Axillary staging in post-neoadjuvant chemotherapy breast cancer patients: prognostic analysis and validation of axillary nodal metrics and comparison of the pathological node staging versus the lymph node ratio systems in a 169-case series
Amin Safavi, Narjes Mohammadzadeh, Ahmad Kaviani, Anita Dadashi, Atousa Dadashi
BMC Cancer.2026;[Epub] CrossRef
Machine learning-based prediction of disease-free survival in breast cancer patients with non-pathological complete response after neoadjuvant chemotherapy: a retrospective multicenter cohort study
Zi-Ran Zhang
American Journal of Cancer Research.2025; 15(6): 2482. CrossRef
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Lingfeng Tang, Linshan Jiang, Xiujie Shu, Yudi Jin, Haochen Yu, Shengchun Liu
Scientific Reports.2024;[Epub] CrossRef
Prognostic disparities in young patients based on breast cancer subtype: A population-based study from the SEER database
Bing Chen, Xiaojuan Zhang, Yi Liu, Chuandong Wang
Medicine.2023; 102(13): e33416. CrossRef
The Effect of Lymph Node Harvest on Prognosis in Locally Advanced Middle-Low Rectal Cancer After Neoadjuvant Chemoradiotherapy
Zhuangbin Lin, Xiaobo Li, Jianyuan Song, Rong Zheng, Cheng Chen, Anchuan Li, Benhua Xu
Frontiers in Oncology.2022;[Epub] CrossRef
Breast Cancer Patients With Positive Apical or Infraclavicular/Ipsilateral Supraclavicular Lymph Nodes Should Be Excluded in the Application of the Lymph Node Ratio System
Zhe Wang, Wei Chong, Huikun Zhang, Xiaoli Liu, Yawen Zhao, Zhifang Guo, Li Fu, Yongjie Ma, Feng Gu
Frontiers in Cell and Developmental Biology.2022;[Epub] CrossRef
Is Pathologic Axillary Staging Valid If Lymph Nodes Are Less than 10 with Axillary Lymph Node Dissection after Neoadjuvant Chemotherapy?
Hee Jun Choi, Jai Min Ryu, Jun Ho Lee, Yoonju Bang, Jongwook Oh, Byung-Joo Chae, Seok Jin Nam, Seok Won Kim, Jeong Eon Lee, Se Kyung Lee, Jonghan Yu
Journal of Clinical Medicine.2022; 11(21): 6564. CrossRef
A novel nomogram for predicting locoregional recurrence risk in breast cancer patients treated with neoadjuvant chemotherapy and mastectomy
Zhou Huang, Mei Shi, Wei-Hu Wang, Liang-Fang Shen, Yu Tang, Qing-Lin Rong, Li Zhu, Xiao-Bo Huang, Jian Tie, Jia-Yi Chen, Jun Zhang, Hong-Fen Wu, Jing Cheng, Min Liu, Chang-Ying Ma, Shu-Lian Wang, Ye-Xiong Li
Radiotherapy and Oncology.2021; 161: 191. CrossRef
Lymph node ratio as best prognostic factor in triple‐negative breast cancer patients with residual disease after neoadjuvant chemotherapy
Gabriel A. De la Cruz‐Ku, Diego Chambergo‐Michilot, Bryan Valcarcel, Pamela Rebaza, Mecker Möller, Jhajaira M. Araujo, Daniel Enriquez, Zaida Morante, Cesar Razuri, Renato Luque, Antonella Saavedra, Eduardo Eyzaguirre, Maria Lujan, Naysha Noel, Joseph Pin
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Development and validation of a nomogram incorporating axillary lymph node ratio to predict survival in node-positive breast cancer patients after neoadjuvant chemotherapy
Jianguo Lai, Zihao Pan, Peixian Chen, Guolin Ye, Kai Chen, Fengxi Su
Japanese Journal of Clinical Oncology.2019; 49(1): 22. CrossRef
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Dong Hui Cho, Soo Youn Bae, Ji Young You, Hong Kyu Kim, Young Woo Chang, Yoo Jin Choi, Sang Uk Woo, Gil Soo Son, Jae Bok Lee, Jeoung Won Bae, Seung Pil Jung
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Cirugía Española.2017; 95(9): 536. CrossRef
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Manel Cremades, Mireia Torres, Montse Solà, Jordi Navinés, Icíar Pascual, Antonio Mariscal, Albert Caballero, Eva Castellà, Miguel Ángel Luna, Joan Francesc Julián
Cirugía Española (English Edition).2017; 95(9): 536. CrossRef
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Liang Huang, Sheng Chen, Wentao T. Yang, Zhiming Shao
Oncotarget.2017; 8(24): 39703. CrossRef
Lymph Node Ratio Analysis After Neoadjuvant Chemotherapy is Prognostic in Hormone Receptor-Positive and Triple-Negative Breast Cancer
Jacqueline Tsai, Danielle Bertoni, Tina Hernandez-Boussard, Melinda L. Telli, Irene L. Wapnir
Annals of Surgical Oncology.2016; 23(10): 3310. CrossRef
Number of negative lymph nodes as a prognostic factor for ypN0-N1 breast cancer patients undergoing neoadjuvant chemotherapy
Fei Xin, Yue Yu, Zheng-Jun Yang, Li-Kun Hou, Jie-Fei Mao, Li Xia, Xin Wang, Xu-Chen Cao
Tumor Biology.2016; 37(6): 8445. CrossRef

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Ovarian Ablation Using Goserelin Improves Survival of Premenopausal Patients with Stage II/III Hormone Receptor-Positive Breast Cancer without Chemotherapy-Induced Amenorrhea: Juan Zhou, San-Gang Wu, Jun-Jie Wang, Jia-Yuan Sun, Feng-Yan Li, Qin Lin, Huan-Xin Lin, Zhen-Yu He; Cancer Res Treat. 2015;47(1):55-63. Published online August 21, 2014; DOI: https://doi.org/10.4143/crt.2013.165

Abstract PDF PubReader ePub

Purpose
The purpose of this study was to assess the value of ovarian ablation using goserelin in premenopausal patients with stage II/III hormone receptor-positive breast cancer without chemotherapy-induced amenorrhea (CIA). Materials and Methods We retrospectively reviewed the data of breast patients treated between October 1999 and November 2007 without CIA. The Kaplan-Meier method was used for calculation of the survival rate. Log rank method and Cox regression analysis were used for univariate and multivariate prognostic analysis. Results The median follow-up period was 61 months. Initially, 353 patients remained without CIA after chemotherapy and 98 among those who received goserelin and tamoxifen (TAM). In univariate analysis, goserelin improved locoregional recurrence-free survival (LRFS) (98.9% vs. 94.1%, p=0.041), distant metastasis-free survival (DMFS) (85.4% vs. 71.9%, p=0.006), disease-free survival (DFS) (85.4% vs. 71.6%, p=0.005), and overall survival (OS) (93.5% vs. 83.5%, p=0.010). In multivariate analysis, goserelin treatment was an independent factor influencing DMFS (hazard ratio [HR], 1.603; 95% confidence interval [CI], 1.228 to 2.092; p=0.001), DFS (HR, 1.606; 95% CI, 1.231 to 2.096; p=0.001), and OS (HR, 3.311; 95% CI, 1.416 to 7.742; p=0.006). In addition, treatment with goserelin resulted in significantly improved LRFS (p=0.039), DMFS (p=0.043), DFS (p=0.036), and OS (p=0.010) in patients aged < 40 years. In patients aged ≥ 40 years, goserelin only improved DMFS (p=0.028) and DFS (p=0.027). Conclusion Ovarian ablation with goserelin plus TAM resulted in significantly improved therapeutic efficacy in premenopausal patients with stage II/III hormone receptor-positive breast cancer without CIA.

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Lin Qiu, Fangmeng Fu, Meng Huang, Yuxiang Lin, Yazhen chen, Minyan Chen, Chuan Wang
Scientific Reports.2016;[Epub] CrossRef
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Meagan E Brennan, Frances M Boyle, Phyllis N Butow, Andrew J Spillane
Breast Cancer Management.2015; 4(3): 145. CrossRef
More Options for Fertility Preservation for Patients With Cancer
Pamela N. Munster
Journal of Clinical Oncology.2015; 33(22): 2413. CrossRef

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