Cancer Research and Treatment

Original Articles

Gastrointestinal cancer

Efficacy of Lenvatinib Combined with Anti–PD-1 Antibodies Plus Transcatheter Arterial Chemoembolization for Hepatocellular Carcinoma with Portal Vein Tumor Thrombus: A Retrospective, Multicenter Study: Xiangye Ou, Junyi Wu, Jiayi Wu, Yangkai Fu, Zhenxin Zeng, Shuqun Li, Yinan Li, Deyi Liu, Han Li, Bin Li, Jianyin Zhou, Shaowu Zhuang, Shuqun Cheng, Zhibo Zhang, Kai Wang, Shuang Qu, Maolin Yan; Cancer Res Treat. 2024;56(4):1207-1218. Published online April 30, 2024; DOI: https://doi.org/10.4143/crt.2023.1165

Abstract PDF Supplementary Material PubReader ePub

Purpose
The prognosis of patients with hepatocellular carcinoma (HCC) and portal vein tumor thrombus (PVTT) is extremely poor, and systemic therapy is currently the mainstream treatment. This study aimed to assess the efficacy and safety of lenvatinib combined with anti–programmed cell death-1 antibodies and transcatheter arterial chemoembolization (triple therapy) in patients with HCC and PVTT.
Materials and Methods
This retrospective multicenter study included patients with HCC and PVTT who received triple therapy, were aged between 18 and 75 years, classified as Child-Pugh class A or B, and had at least one measurable lesion. The overall survival (OS), progression-free survival (PFS), objective response rates, and disease control rates were analyzed to assess efficacy. Treatment-related adverse events were analyzed to assess safety profiles.
Results
During a median follow-up of 11.23 months (range, 3.07 to 34.37 months), the median OS was greater than 24 months, and median PFS was 12.53 months. The 2-year OS rate was 54.9%. The objective response rate and disease control rate were 69.8% (74/106) and 84.0% (89/106), respectively; 20.8% (22/106) of the patients experienced grade 3/4 treatment-related adverse events and no treatment-related deaths occurred. The conversion rate to liver resection was 31.1% (33/106), with manageable postoperative complications. The median OS was not reached in the surgery group, but was 19.08 months in the non-surgery group. The median PFS in the surgery and non-surgery groups were 20.50 and 9.00 months, respectively.
Conclusion
Triple therapy showed promising survival benefits and high response rates in patients with HCC and PVTT, with manageable adverse effects.

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A real-world study of the efficacy of second-line treatment of unresectable hepatocellular carcinoma with esophagogastric varices after progression on first-line lenvatinib combined with PD-1 inhibitor
Saifeng Li, Qin Wen, Wenwu Huang, Zeyu Qiu, Long Feng, Fengming Yi
World Journal of Surgical Oncology.2025;[Epub] CrossRef

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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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Lung and Thoracic cancer

EGFR-TKI Combined with Pemetrexed versus EGFR-TKI Monotherapy in Advanced EGFR-Mutated NSCLC: A Prospective, Randomized, Exploratory Study: Weiguang Gu, Hua Zhang, Yiyu Lu, Minjing Li, Shuang Yang, Jianmiao Liang, Zhijian Ye, Zhihua Li, Minhong He, Xiaoliang Shi, Fei Wang, Dong You, Weiquan Gu, Weineng Feng; Cancer Res Treat. 2023;55(3):841-850. Published online February 13, 2023; DOI: https://doi.org/10.4143/crt.2022.1438

Abstract PDF Supplementary Material PubReader ePub

Purpose
We aimed to evaluate whether the addition of pemetrexed is effective in improving progression-free survival (PFS) in epidermal growth factor receptor (EGFR)–mutated patients with or without concomitant alterations.
Materials and Methods
This multicenter clinical trial was conducted in China from June 15, 2018, to May 31, 2019. A total of 92 non–small cell lung cancer (NSCLC) patients harboring EGFR-sensitive mutations were included and divided into concomitant and non-concomitant groups. Patients in each group were randomly treated with EGFR–tyrosine kinase inhibitor (TKI) monotherapy or EGFR-TKI combined with pemetrexed in a ratio of 1:1. PFS was recorded as the primary endpoint.
Results
The overall median PFS of this cohort was 10.1 months. There were no significant differences in PFS between patients with and without concomitant and between patients received TKI monotherapy and TKI combined with pemetrexed (p=0.210 and p=0.085, respectively). Stratification analysis indicated that patients received TKI monotherapy had a significantly longer PFS in non-concomitant group than that in concomitant group (p=0.002). In concomitant group, patients received TKI combined with pemetrexed had a significantly longer PFS than patients received TKI monotherapy (p=0.013). Molecular dynamic analysis showed rapidly emerging EGFR T790M in patients received TKI monotherapy. EGFR mutation abundance decreased in patients received TKI combined chemotherapy, which supports better efficacy for a TKI combined chemotherapy as compared to TKI monotherapy. A good correlation between therapeutic efficacy and a change in circulating tumor DNA (ctDNA) status was found in 66% of patients, supporting the guiding role of ctDNA minimal residual disease (MRD) in NSCLC treatment.
Conclusion
EGFR-TKI monotherapy is applicable to EGFR-sensitive patients without concomitant alterations, while a TKI combined chemotherapy is applicable to EGFR-sensitive patients with concomitant alterations. CtDNA MRD may be a potential biomarker for predicting therapeutic efficacy.

Citations

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Prognostic factors influencing overall survival in stage IV EGFR-mutant NSCLC patients treated with EGFR-TKIs
Linwu Kuang, Yuchen Zhang, Hao Wang, Peng Wang, Yangkai Li
BMC Pulmonary Medicine.2025;[Epub] CrossRef
SP3-induced Timeless transcription contributes to cell growth of lung adenocarcinoma cells
Ping Tian, Dajun Du, Li Yang, Nan Zhou, Ling Tao, Divijendra Natha Reddy Sirigiri
PLOS ONE.2024; 19(2): e0298295. CrossRef
PIK3CA mutation as an acquired resistance driver to EGFR-TKIs in non-small cell lung cancer: Clinical challenges and opportunities
Xiaohong Liu, Wuxuan Mei, Pengfei Zhang, Changchun Zeng
Pharmacological Research.2024; 202: 107123. CrossRef
Risk factors for interstitial lung disease in patients with non-small cell lung cancer with epidermal growth factor receptor-tyrosine kinase inhibitors: A systematic review and meta-analysis
Yosuke Fukuda, Yoshitaka Uchida, Koichi Ando, Ryo Manabe, Akihiko Tanaka, Hironori Sagara
Respiratory Investigation.2024; 62(3): 481. CrossRef
Concomitant genomic features stratify prognosis to patients with advanced EGFR mutant lung cancer
Xiao Liang, Jiali Xu, Yuqin Jiang, Yuqian Yan, Hongshuai Wu, Jiali Dai, Yanan Cui, Chen Zhang, Wei Chen, Zhihong Zhang, Renhua Guo
Molecular Carcinogenesis.2024; 63(9): 1643. CrossRef
Identification and Application of Emerging Biomarkers in Treatment of Non-Small-Cell Lung Cancer: Systematic Review
Juan Carlos Restrepo, Darly Martínez Guevara, Andrés Pareja López, John Fernando Montenegro Palacios, Yamil Liscano
Cancers.2024; 16(13): 2338. CrossRef

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Hematologic malignancy

Clinical Impact of Drug Adherence of Tyrosine Kinase Inhibitors in Children with Ph-Positive Acute Lymphoblastic Leukemia: Jun-Xia Wang, Miao-Miao Yang, Li-Peng Liu, Hui-Min Zhang, Meng-Chuan Wang, Yu-Wen Chen, Xiao-Ying Zang, Fang Hu; Cancer Res Treat. 2023;55(3):1023-1030. Published online February 6, 2023; DOI: https://doi.org/10.4143/crt.2022.1618

Abstract PDF PubReader ePub: Purpose
This study aimed to explore the impact of ABL1–tyrosine kinase inhibitors (TKIs) adherence on the survival of chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL) children and clarify the potential predictors of patients’ prognosis from TKIs intake practices.
Materials and Methods
Ninety newly diagnosed Ph+ ALL patients who received TKIs were enrolled. We collected the baseline characteristics and adverse events in all children; moreover, TKIs adherence was measured by an eight-item Morisky medication adherence scale (MMAS-8). Progression-free survival (PFS) and overall survival (OS) analysis were performed, and risk factors for PFS and OS were evaluated.
Results
Among all patients, 69 cases were regarded as adherers, while 21 were non-adherers. The median duration of TKIs interruption was significantly prolonged in the non-adherence group than in the adherence group (13 [0-101] vs. 56 [11-128], p < 0.001). Additionally, dose reduction occurred in 55.2% of non-adherers versus 23.0% of adherers (p=0.002). The PFS and OS in adherers were significantly higher versus non-adherers (p=0.020 and p=0.039). MMAS-8 score was an independent risk factor for PFS (p=0.010) and OS (p=0.031). Among non-adherers, the median OS was only 23.1% (4.2%-42%) in patients aged ≤ 10 years versus 54.4% (38.8%-70%) in adolescents. Most of the patients who experienced TKIs non-adherence suffered pancytopenia.
Conclusion
TKIs adherence during treatment significantly influenced the survival of pediatric Ph+ ALL patients, and non-adherers with age ≤ 10 years were more vulnerable to TKIs disruption. The cumulative TKIs dose should be especially emphasized to patients with age ≤ 10 years, which may result in an inferior achievement of relevant treatment milestones.

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Impact of Pulmonary Tuberculosis on the EGFR Mutational Status and Clinical Outcome in Patients with Lung Adenocarcinoma: In Kyoung Hwang, Seung Sook Paik, Seung Hyeun Lee; Cancer Res Treat. 2019;51(1):158-168. Published online April 2, 2018; DOI: https://doi.org/10.4143/crt.2018.084

Abstract PDF Supplementary Material PubReader ePub

Purpose
Although it has been suggested that pulmonary tuberculosis (TB) is associated with increased risk of lung cancer, the exact mechanism is not clearly identified. We investigated the effect of pulmonary TB on the epidermal growth factor receptor (EGFR) mutational status and clinical outcome in patients with pulmonary adenocarcinoma.
Materials and Methods
We reviewed data of patients diagnosed with pulmonary adenocarcinoma harboring EGFR mutations and treated at our institution from 2008 to 2015. We divided our population into two groups: patients with pre-existing TB lesions on chest computed tomography scan (TB group) and those without the lesions (non-TB group). We compared the differences in EGFR mutational status, response to tyrosine kinase inhibitors (TKIs) and survival between the two groups.
Results
A total of 477 patients with pulmonary adenocarcinoma were analyzed. One hundred eighty-three patients (39%) had EGFR-mutated tumors and 100 (21%) patients had pre-existing TB lesions. The frequency of EGFR mutation was significantly higher in the TB group compared with the non-TB group (56% vs. 34%, p=0.038). Pre-existing TB lesions were independently associated with more frequent EGFR mutations in multivariate analysis (odds ratio, 1.43). In addition, both the progression-free survival (9.1 months vs. 11.6 months, p=0.020) and the overall survival (19.4 months vs. 24.5 months, p=0.014) after first-line EGFR-TKIs were significantly shorter in the TB group than in the non-TB group.
Conclusion
Previous pulmonary TB may be associated with more frequent EGFR mutations and poorer treatment response to EGFR-TKIs in patients with pulmonary adenocarcinoma.

Citations

Citations to this article as recorded by

A DNA Methylation Signature From Buccal Swabs to Identify Tuberculosis Infection
Lovisa Karlsson, Isabelle Öhrnberg, Shumaila Sayyab, David Martínez-Enguita, Mika Gustafsson, Patricia Espinoza, Melissa Méndez-Aranda, Cesar Ugarte-Gil, Lameck Diero, Ronald Tonui, Jakob Paues, Maria Lerm
The Journal of Infectious Diseases.2025; 231(1): e47. CrossRef
Contagious illness of tuberculosis and correlation with various types of cancer
Karthikeyan Sundaram, Venkataraman Prabhu
Medicine in Microecology.2025; 24: 100123. CrossRef
Coexistent Pulmonary Tuberculosis and Lung Cancer: An Analysis of Incidence Trends, Financial Burdens and Influencing Factors
Fei Qi, Hongjie Yang, Yi Han, Yujie Dong, Fan Zhang, Yishuo Wang, Juan Du, Yuan Gao, Xueguang Hu, Liqun Zhang, Tongmei Zhang
Cancer Innovation.2025;[Epub] CrossRef
Progress in mechanism-based diagnosis and treatment of tuberculosis comorbid with tumor
Chuan Wang, Rong-Qi Zou, Guo-Zhong He
Frontiers in Immunology.2024;[Epub] CrossRef
Lung cancer and pulmonary tuberculosis: key features of molecular mechanisms of concomitant disease
G. M. Agafonov, G. G. Kudriashov, U. S. Krylova, T. S. Zubareva, I. M. Kvetnoy, P. K. Yablonskiy
Uspehi fiziologičeskih nauk.2024; 55(3): 58. CrossRef
Antimicrobial peptides as drugs with double response against Mycobacterium tuberculosis coinfections in lung cancer
Giulia Polinário, Laura Maria Duran Gleriani Primo, Maiara Alane Baraldi Cerquetani Rosa, Freddy Humberto Marin Dett, Paula Aboud Barbugli, Cesar Augusto Roque-Borda, Fernando Rogério Pavan
Frontiers in Microbiology.2023;[Epub] CrossRef
Mycobacterium Tubercular Mediated Inflammation and Lung Carcinogenesis: Connecting Links
Abhay Vashishth, Mohd Shuaib, Tanya Bansal, Shashank Kumar
OBM Genetics.2023; 07(02): 1. CrossRef
Prevalence of Lung Cancer with a History of Tuberculosis
Nadira Putri Nastiti, Laksmi Wulandari, Sulistiawati Sulistiawati, Anna Febriani, Wiwin Is Effendi
Jurnal Respirasi.2023; 9(2): 87. CrossRef
Previous pulmonary tuberculosis enhances the risk of lung cancer: systematic reviews and meta-analysis
Hossein Abdeahad, Maryam Salehi, Atieh Yaghoubi, Amir Hossein Aalami, Farnoosh Aalami, Saman Soleimanpour
Infectious Diseases.2022; 54(4): 255. CrossRef
Pulmonary Tuberculosis and Risk of Lung Cancer: A Systematic Review and Meta-Analysis
Soo Young Hwang, Jong Yeob Kim, Hye Sun Lee, Sujee Lee, Dayeong Kim, Subin Kim, Jong Hoon Hyun, Jae Il Shin, Kyoung Hwa Lee, Sang Hoon Han, Young Goo Song
Journal of Clinical Medicine.2022; 11(3): 765. CrossRef
Clinical and pathological characteristics associated with the presence of the IS6110 Mycobacterim tuberculosis transposon in neoplastic cells from non-small cell lung cancer patients
Oscar Arrieta, Camilo Molina-Romero, Fernanda Cornejo-Granados, Brenda Marquina-Castillo, Alejandro Avilés-Salas, Gamaliel López-Leal, Andrés F. Cardona, Alette Ortega-Gómez, Mario Orozco-Morales, Adrián Ochoa-Leyva, Rogelio Hernandez-Pando
Scientific Reports.2022;[Epub] CrossRef
Lung cancer occurrence after an episode of tuberculosis: a systematic review and meta-analysis
Javier Cabrera-Sanchez, Vicente Cuba, Victor Vega, Patrick Van der Stuyft, Larissa Otero
European Respiratory Review.2022; 31(165): 220025. CrossRef
Proteomic profile of vitreous in patients with tubercular uveitis
Reema Bansal, Mohd M. Khan, Surendra Dasari, Indu Verma, David R. Goodlett, Nathan P. Manes, Aleksandra Nita-Lazar, Surya P. Sharma, Aman Kumar, Nirbhai Singh, Anuradha Chakraborti, Vishali Gupta, M.R. Dogra, Jagat Ram, Amod Gupta
Tuberculosis.2021; 126: 102036. CrossRef
Epidermal growth factor receptor-mutant pulmonary adenocarcinoma coexisting with tuberculosis
Ning Liu, Lingnan Zheng, Min Yu, Shuang Zhang
Medicine.2021; 100(8): e24569. CrossRef
Quantitative analysis of cell-free DNA by droplet digital PCR reveals the presence of EGFR mutations in non-malignant lung pathologies
Rajesh Venkataram, Srividya Arjuna, Giridhar Belur Hosmane, Anirban Chakraborty
Monaldi Archives for Chest Disease.2021;[Epub] CrossRef
Concomitant Pulmonary Tuberculosis Impair Survival in Advanced Epidermal Growth Factor Receptor (EGFR) Mutant Lung Adenocarcinoma Patients Receiving EGFR-Tyrosine Kinase Inhibitor
Yalin Xie, Ning Su, Wei Zhou, An Lei, Xiang Li, Weiwei Li, Zhan Huang, Wenchang Cen, Jinxing Hu
Cancer Management and Research.2021; Volume 13: 7517. CrossRef
A Case of Delayed Diagnostic Pulmonary Tuberculosis during Targeted Therapy in an EGFR Mutant Non-Small Cell Lung Cancer Patient
Caibao Jin, Bin Yang
Case Reports in Oncology.2021; 14(1): 659. CrossRef
Follow‐up of an occult tuberculosis scar cancer after resection of metastatic lesions
Mengyao Sun, Yinghui Xu, Xu Wang, Chao Sun, Ye Guo, Guoguang Shao, Zhiguang Yang, Yunpeng Liu, Peng Zhang, Shi Qiu, Kewei Ma
Thoracic Cancer.2020; 11(8): 2347. CrossRef

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Incorporating Neutrophil-to-lymphocyte Ratio and Platelet-to-lymphocyte Ratio in Place of Neutrophil Count and Platelet Count Improves Prognostic Accuracy of the International Metastatic Renal Cell Carcinoma Database Consortium Model: Pawel Chrom, Rafal Stec, Lubomir Bodnar, Cezary Szczylik; Cancer Res Treat. 2018;50(1):103-110. Published online March 3, 2017; DOI: https://doi.org/10.4143/crt.2017.033

Abstract PDF Supplementary Material PubReader ePub

Purpose
The study investigated whether a replacement of neutrophil count and platelet count by neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) within the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) model would improve its prognostic accuracy.
Materials and Methods
This retrospective analysis included consecutive patients with metastatic renal cell carcinoma treated with first-line tyrosine kinase inhibitors. The IMDC and modified-IMDC models were compared using: concordance index (CI), bias-corrected concordance index (BCCI), calibration plots, the Grønnesby and Borgan test, Bayesian Information Criterion (BIC), generalized R², Integrated Discrimination Improvement (IDI), and continuous Net Reclassification Index (cNRI) for individual risk factors and the three risk groups.
Results
Three hundred and twenty-one patients were eligible for analyses. The modified-IMDC model with NLR value of 3.6 and PLR value of 157 was selected for comparison with the IMDC model. Both models were well calibrated. All other measures favoured the modified-IMDC model over the IMDC model (CI, 0.706 vs. 0.677; BCCI, 0.699 vs. 0.671; BIC, 2,176.2 vs. 2,190.7; generalized R², 0.238 vs. 0.202; IDI, 0.044; cNRI, 0.279 for individual risk factors; and CI, 0.669 vs. 0.641; BCCI, 0.669 vs. 0.641; BIC, 2,183.2 vs. 2,198.1; generalized R², 0.163 vs. 0.123; IDI, 0.045; cNRI, 0.165 for the three risk groups).
Conclusion
Incorporation of NLR and PLR in place of neutrophil count and platelet count improved prognostic accuracy of the IMDC model. These findings require external validation before introducing into clinical practice.

Citations

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Manjun Ye, Lixia Zhang
International Journal of General Medicine.2024; Volume 17: 2289. CrossRef
Evaluating the Prognostic Variables for Overall Survival in Patients with Metastatic Renal Cell Carcinoma: A Meta-Analysis Of 29,366 Patients
Bruce Li, Swati Sood, Melissa J. Huynh, Nicholas E. Power
JU Open Plus.2024;[Epub] CrossRef
The relationship between complete blood cell count-derived inflammatory biomarkers and benign prostatic hyperplasia in middle-aged and elderly individuals in the United States: Evidence from NHANES 2001–2008
Chengdong Shi, Hongliang Cao, Guoqiang Zeng, Lei Yang, Yuantao Wang, Alaa A. A. Aljabali
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Diana Voskuil-Galoş, Tudor Călinici, Andra Piciu, Adina Nemeş
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Jinliang Ni, Ziye Li, Wei Song, Houliang Zhang, Yidi Wang, Yifan Zhang, Haipeng Zhang, Guangcan Yang, Jun Xie, Keyi Wang, Bo Peng, Weipu Mao
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Yasser Ged, Alejandro Sanchez, Sujata Patil, Andrea Knezevic, Emily Stein, Stacey Petruzella, Kate Weiss, Cihan Duzgol, Joshua Chaim, Oguz Akin, Marina Mourtzakis, Michael T. Paris, Jessica Scott, Fengshen Kuo, Ritesh Kotecha, A. Ari Hakimi, Chung-Han Lee
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Ruotao Xiao, Chuxiao Xu, Wei He, Lei Liu, Hongxian Zhang, Cheng Liu, Lulin Ma
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External validation of the systemic immune-inflammation index as a prognostic factor in metastatic renal cell carcinoma and its implementation within the international metastatic renal cell carcinoma database consortium model
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