Cancer Research and Treatment

Original Articles

Normal Brain-Sparing Radiotherapy versus Whole Brain Radiotherapy for Multiple Brain Metastasis from Non-Small Cell Lung Cancer: Sangjoon Park, Jaeho Cho, Kyung Hwan Kim, Hong In Yoon, Chang Geol Lee; Received July 23, 2024 Accepted December 2, 2024 Published online December 3, 2024; DOI: https://doi.org/10.4143/crt.2024.679 [Accepted]

Abstract PDF: Purpose
The efficacy and lower neurotoxicity of normal brain-sparing radiotherapy (NBS-RT) with systemic therapy in treating multiple brain metastases from non-small cell lung cancer (NSCLC) is underexplored. This study compares whole-brain radiotherapy (WBRT) and NBS-RT for multiple brain metastases in NSCLC, focusing on treatment outcomes and leukoencephalopathy.
Materials and Methods
This retrospective study included 503 patients with NSCLC with multiple brain metastases at a single center, treated with either WBRT or NBS-RT. Post-RT treatments included chemotherapy, targeted therapy, or immunotherapy. Main outcomes measured were intracranial control, overall survival (OS), and leukoencephalopathy incidence.
Results
In this study, 441 patients received WBRT and 62 received NBS-RT, with median ages of 62 and 61 years, respectively. A significant portion of both groups, 77.3% in WBRT and 80.6% in NBS-RT, received post-RT systemic therapy. The median number of brain metastases was 10 for WBRT and 12 for NBS-RT, with median maximal diameters of 11.7 mm in WBRT and 14.4 mm in NBS-RT. After a median follow-up of 10.9 months for WBRT and 11.8 months for NBS-RT, there were no significant differences in intracranial progression (p=0.516) or OS (p=0.492) between the groups. However, WBRT patients had a higher incidence of leukoencephalopathy than NBS-RT patients (p=0.013).
Conclusion
NBS-RT combined with systemic therapy was as effective in treating multiple brain metastases as WBRT and was less toxic. NBS-RT-based strategies deserve further investigation in a prospective setting.

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Unraveling the Impact of Sarcopenia-Induced Lymphopenia on Treatment Response and Prognosis in Patients with Stage III Non-Small Cell Lung Cancer: Insights for Optimizing Chemoradiation and Immune Checkpoint Inhibitor: Joongyo Lee, Kyung Hwan Kim, Jina Kim, Chang Geol Lee, Jaeho Cho, Hong In Yoon, Yeona Cho; Received May 23, 2024 Accepted October 29, 2024 Published online October 30, 2024; DOI: https://doi.org/10.4143/crt.2024.493 [Accepted]

Abstract PDF: Purpose
Sarcopenia is a poor prognostic factor in non-small cell lung cancer (NSCLC). However, its prognostic significance in patients with NSCLC receiving immune checkpoint inhibitors (ICIs) and its relationship with lymphopenia remain unclear. We aimed to investigate the prognostic role of sarcopenia and its effect on lymphocyte recovery in patients with stage III NSCLC treated with concurrent chemoradiotherapy (CCRT) followed by ICI.
Materials and Methods
We retrospectively evaluated 151 patients with stage III NSCLC who received definitive CCRT followed by maintenance ICI between January 2016 and June 2022. Sarcopenia was evaluated by measuring the skeletal muscle area at the L3 vertebra level using computed tomography scans. Lymphocyte level changes were assessed based on measurements taken before and during CCRT and at 1, 2, 3, 6, and 12 months post-CCRT completion.
Results
Even after adjusting for baseline absolute lymphocyte count through propensity score-matching, patients with pre-radiotherapy (RT) sarcopenia (n=86) exhibited poor lymphocyte recovery and a significantly high incidence of grade ≥3 lymphopenia during CCRT. Pre-RT sarcopenia and grade ≥3 lymphopenia during CCRT emerged as prognostic factors for overall survival and progression-free survival, respectively. Concurrent chemotherapy dose adjustments, objective response after CCRT, and discontinuation of maintenance ICI were also analyzed as independent prognostic factors.
Conclusion
Our results demonstrated an association between pre-RT sarcopenia and poor survival, concurrent chemotherapy dose adjustments, and impaired lymphocyte recovery after definitive CCRT. Moreover, CCRT-induced lymphopenia not only contributed to poor prognosis but may have also impaired the therapeutic efficacy of subsequent maintenance ICI, ultimately worsening treatment outcomes.

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Impact of TTF-1 Expression on the Prognostic Prediction of Patients with NSCLC with PD-L1 Expression Levels of 1% to 49%, Treated with Chemotherapy vs Chemoimmunotherapy: A Multicenter, Retrospective Study: Naoya Nishioka, Tae Hata, Tadaaki Yamada, Yasuhiro Goto, Akihiko Amano, Yoshiki Negi, Satoshi Watanabe, Naoki Furuya, Tomohiro Oba, Tatsuki Ikoma, Akira Nakao, Keiko Tanimura, Hirokazu Taniguchi, Akihiro Yoshimura, Tomoya Fukui, Daiki Murata, Kyoichi Kaira, Shinsuke Shiotsu, Makoto Hibino, Asuka Okada, Yusuke Chihara, Hayato Kawachi, Takashi Kijima, Koichi Takayama; Received August 7, 2024 Accepted October 24, 2024 Published online October 25, 2024; DOI: https://doi.org/10.4143/crt.2024.748 [Accepted]

Abstract PDF: Purpose
Thyroid transcription factor 1 (TTF-1) expression is a useful predictor of treatment efficacy in advanced non-squamous non-small-cell lung cancer (NSCLC). This study aimed to evaluate whether TTF-1 could predict the effectiveness of chemotherapy versus chemoimmunotherapy in patients with non-squamous NSCLC with programmed death ligand-1 (PD-L1) expression between 1% and 49%.
Materials and Methods
We conducted a retrospective study of patients with NSCLC who were treated with chemotherapy or chemoimmunotherapy between March 2016 and May 2023. The patients had histologically confirmed NSCLC, stage III-IV or postoperative recurrence, TTF-1 measurements, and PD-L1 expression levels between 1% and 49%. Clinical data were analyzed to evaluate the effect of TTF-1 expression on treatment efficacy.
Results
This study included 283 of 624 patients. TTF-1-positive patients showed longer progression-free survival (PFS) and overall survival (OS) (PFS: 6.4 months [95% confidence interval (CI): 5.0−9.4] vs 4.1 months [95% CI: 2.7−6.1], p=0.03, OS: 17.9 months [95% CI: 15.2−28.1] vs 9.4 months [95% CI: 6.3−17.0], p<0.01) in the chemotherapy cohorts (n=93). In the chemoimmunotherapy cohort (n=190), there was no significant difference in PFS and OS between TTF-1-positive and negative groups (PFS: 7.6 months [95% CI: 6.4−11.0] vs 6.0 months [95% CI: 3.6−12.6], p=0.59, OS: 25.0 months [95% CI: 18.0−49.2] vs 21.3 months [95% CI: 9.8−28.8], p=0.09).
Conclusion
In patients with NSCLC with PD-L1 expression between 1% and 49%, TTF-1 expression was a predictor of chemotherapeutic, but not chemoimmunotherapeutic, efficacy.

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Lung and Thoracic cancer

Association of Immune-Related Adverse Events and the Efficacy of Anti–PD-(L)1 Monotherapy in Non–Small Cell Lung Cancer: Adjusting for Immortal-Time Bias: Ying Yu, Ning Chen, Sizhe Yu, Wanji Shen, Wanchen Zhai, Hui Li, Yun Fan; Cancer Res Treat. 2024;56(3):751-764. Published online January 2, 2024; DOI: https://doi.org/10.4143/crt.2023.1118

Abstract PDF Supplementary Material PubReader ePub

Purpose
The association between immune-related adverse events (irAEs) and survival outcomes in non–small cell lung cancer (NSCLC) patients treated with programmed death-(ligand) 1 [PD-(L)1] inhibitors remains controversial, partly due to variations in dealing with immortal-time bias (ITB).
Materials and Methods
We retrospectively enrolled 425 advanced NSCLC patients who received anti–PD-(L)1 monotherapy between January 2016 and June 2021, stratifying them into irAE (n=127) and non-irAE (n=298) groups. The primary endpoint was to assess the impact of irAEs on progression-free survival (PFS) and overall survival (OS). Landmark (2-, 3-, 6-, and 9-month) and time-dependent Cox analyses were performed to eliminate ITB.
Results
With a median follow-up of 38.8 months, the occurrence of overall irAEs was significantly associated with superior PFS (11.2 vs. 3.4 months, p < 0.001) and OS (31.4 vs. 14.0 months, p < 0.001), which persisted in landmark and time-dependent Cox analyses. For the main organ-specific irAEs, skin, thyroid, and hepatic irAEs, respectively, showed significantly improved survival compared to the non-irAE group, whereas pneumonitis did not. Single-organ irAEs had the best outcomes compared with multi-organ or no irAE, which also held across subgroups of skin, thyroid, and hepatic irAEs. Moreover, severe grade irAEs and immunotherapy discontinuation had a detrimental effect on survival, systemic steroid therapy showed little effect, while immunotherapy resumption had tolerable safety and a trend of improved survival.
Conclusion
After adequately adjusting ITB, the occurrence of overall irAEs predicts for favorable efficacy of anti–PD-(L)1 monotherapy in NSCLC, with better outcomes observed in patients with skin, thyroid, or hepatic irAEs, particularly those with single-organ involvement.

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Development of pituitary dysfunction and destructive thyroiditis is associated with better survival in non-small cell lung cancer patients treated with programmed cell death-1 inhibitors: a prospective study with immortal time bias correction
Koji Suzuki, Tomoko Kobayashi, Tetsushi Izuchi, Koki Otake, Masahiko Ando, Tomoko Handa, Takashi Miyata, Mariko Sugiyama, Takeshi Onoue, Daisuke Hagiwara, Hidetaka Suga, Ryoichi Banno, Tetsunari Hase, Megumi Inoue, Makoto Ishii, Hiroshi Arima, Shintaro Iw
Frontiers in Endocrinology.2024;[Epub] CrossRef
Associations between Immune-related Adverse Events and Prognosis in Cancer Patients Receiving Immune Checkpoint Inhibitor Therapy
Yusuke Inoue, Naoki Inui
Internal Medicine.2024;[Epub] CrossRef

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Intrathoracic Progression Is Still the Most Dominant Failure Pattern after First-Line Chemo-immunotherapy in Extensive-Stage Small-Cell Lung Cancer: Implications for Thoracic Radiotherapy: Dowook Kim, Hak Jae Kim, Hong-Gyun Wu, Joo Ho Lee, Suzy Kim, Tae Min Kim, Jin-Soo Kim, Byoung Hyuck Kim; Cancer Res Treat. 2024;56(2):430-441. Published online November 6, 2023; DOI: https://doi.org/10.4143/crt.2023.931

Abstract PDF Supplementary Material PubReader ePub

Purpose
This study aimed to compare the failure patterns before and after the introduction of immunotherapy and to determine the role of thoracic radiotherapy (TRT) in extensive-stage small-cell lung cancer (ES-SCLC) treatment.
Materials and Methods
We retrospectively reviewed 294 patients with ES-SCLC, of which 62.2% underwent chemotherapy alone, 13.3% underwent chemotherapy followed by consolidative TRT (TRT group), and 24.5% underwent chemotherapy with immune checkpoint inhibitor (ICI group). We performed propensity-score matching (PSM) to compare each treatment group.
Results
The median follow-up duration was 10.4 months. At the first relapse, in the cohort showing objective response, the proportion of cases showing intrathoracic progression was significantly lower in the TRT group (37.8%) than in the chemotherapy-alone (77.2%, p < 0.001) and the ICI (60.3%, p=0.03) groups. Furthermore, in the subgroup analysis, TRT showed benefits related to intrathoracic progression-free survival (PFS) in comparison with ICI in patients with less than two involved extrathoracic sites (p=0.008) or without liver metastasis (p=0.02) or pleural metastasis (p=0.005) at diagnosis. After PSM, the TRT group showed significantly better intrathoracic PFS than both chemotherapy-alone and ICI groups (p < 0.001 and p=0.04, respectively), but showed no significant benefit in terms of PFS and overall survival in comparison with the ICI group (p=0.17 and p=0.31, respectively).
Conclusion
In ES-SCLC, intrathoracic progression was the most dominant failure pattern after immunotherapy. In the era of chemoimmunotherapy, consolidative TRT can still be considered a useful treatment strategy for locoregional control.

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Clinical outcomes and synergistic effect between radiotherapy and immunotherapy in patients with extensive-stage small cell lung cancer: a real-world study
Meiling Sun, Huaijun Ji, Fang Deng, Jingyi Li, Ning Xu, Yu Li
BMC Cancer.2024;[Epub] CrossRef

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Combination of the LARS1 Inhibitor, BC-LI-0186 with a MEK1/2 Inhibitor Enhances the Anti-Tumor Effect in Non–Small Cell Lung Cancer: Sang Hoon Lee, Eun Young Kim, Jung Min Han, Gyoonhee Han, Yoon Soo Chang; Cancer Res Treat. 2023;55(3):851-864. Published online March 20, 2023; DOI: https://doi.org/10.4143/crt.2022.1527

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Purpose
The mammalian target of rapamycin complex 1 (mTORC1) regulates cell growth and proliferation by growth factor coordination and amino acid availability. Leucyl-tRNA synthetase 1 (LARS1) senses the intracellular leucine concentration and mediates amino acid-induced activation of mTORC1. Thus, LARS1 inhibition could be useful in cancer treatment. However, the fact that mTORC1 can be stimulated by various growth factors and amino acids suggests that LARS1 inhibition alone has limitations in inhibiting cell growth and proliferation. We investigated the combined effects of BC-LI-0186, a LARS1 inhibitor, and trametinib, an MEK inhibitor, on non–small cell lung cancer (NSCLC).
Materials and Methods
Protein expression and phosphorylation were observed by immunoblotting, and genes differentially expressed between BC-LI-0186–sensitive and –resistant cells were identified by RNA sequencing. The combined effect of the two drugs was inferred from the combination index values and a xenograft model.
Results
LARS1 expression was positively correlated with mTORC1 in NSCLC cell lines. BC-LI-0186 treatment of A549 and H460 cells maintained in media supplemented with fetal bovine serum revealed paradoxical phosphorylation of S6 and activation of mitogen- activated protein kinase (MAPK) signaling. Compared with BC-LI-0186–sensitive cells, –resistant cells showed enrichment of the MAPK gene set. The combination of trametinib and BC-LI-0186 inhibited the phosphorylation of S6, MEK, and extracellular signal-regulated kinase and their synergistic effects were confirmed in a mouse xenograft model.
Conclusion
The combination of BC-LI-0186 and trametinib inhibited the non-canonical mTORC1-activating function of LARS1. Our study demonstrated a new therapeutic approach for NSCLC without targetable driver mutations.

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LARS1 is a Prognostic Biomarker and Exhibits a Correlation with Immune Infiltrates in Hepatocellular Carcinoma
Longfei Fan, Zhongqiang Qin, Di Wu, Yunchuan Yang, Yigang Zhang, Bo Xie, Jingyu Qian, Jianzhu Wei, Zhaoying Wang, Peipei Yang, Zhen Qian, Mu Yuan, Ziyi Zhu, Yulin Tan, Yi Tan
International Journal of General Medicine.2024; Volume 17: 2203. CrossRef
Personalizing Therapy Outcomes through Mitogen-Activated Protein Kinase Pathway Inhibition in Non-Small Cell Lung Cancer
Hasan Alsharoh, Paul Chiroi, Ekaterina Isachesku, Radu Andrei Tanasa, Ovidiu-Laurean Pop, Radu Pirlog, Ioana Berindan-Neagoe
Biomedicines.2024; 12(7): 1489. CrossRef
UCHL1 Overexpression Is Related to the Aggressive Phenotype of Non-small Cell Lung Cancer
Chi Young Kim, Eun Hye Lee, Se Hyun Kwak, Sang Hoon Lee, Eun Young Kim, Min Kyoung Park, Yoon Jin Cha, Yoon Soo Chang
Tuberculosis and Respiratory Diseases.2024; 87(4): 494. CrossRef

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Diagnostic Performance of Endosonography to Detect Mediastinal Lymph Node Metastasis in Patients with Radiological N1 Non–Small Cell Lung Cancer: Bo-Guen Kim, Jong Ho Cho, Sun Hye Shin, Kyungjong Lee, Sang-Won Um, Hojoong Kim, Jhingook Kim, Young Mog Shim, Byeong-Ho Jeong; Cancer Res Treat. 2023;55(3):832-840. Published online March 2, 2023; DOI: https://doi.org/10.4143/crt.2022.1428

Abstract PDF Supplementary Material PubReader ePub

Purpose
Guidelines recommend that non–small cell lung cancer (NSCLC) patients with suspected hilar lymph node (LN) metastases should undergo invasive mediastinal LN staging prior to surgical treatment via endosonography. We evaluated the diagnostic performance of endosonography for detecting occult mediastinal metastases (OMM) and determined the factors associated with OMM in NSCLC patients with radiological N1.
Materials and Methods
Patients with confirmed primary NSCLC with radiological N1 who underwent endosonography for nodal staging assessment from January 2013 to December 2019 were retrospectively analyzed.
Results
The prevalence of OMM was found to be 83/279 (29.7%) and only 38.6% (32/83) were diagnosed via endosonography. However, five of them were confirmed as N3 by endosonography. The overall diagnostic sensitivity, negative predictive value, accuracy, and area under the curve of endosonography were 38.6%, 79.4%, 81.7%, and 0.69, respectively. In multivariable analysis, central tumor (adjusted odds ratio [aOR], 2.05; 95% confidence interval [CI], 1.15 to 3.68; p=0.016), solid tumor (aOR, 10.24; 95% CI, 1.32 to 79.49; p=0.026), and adenocarcinoma (aOR, 3.01; 95% CI, 1.63 to 5.55; p < 0.001) were related to OMM in radiological N1 NSCLC patients.
Conclusion
Although the sensitivity of endosonography for detecting OMM was only 40%, the prevalence of OMM was not low (30%) and some cases even turned out to be N3 diseases. Clinicians should be aware that OMM may be more likely in patients with central, solid, and adenocarcinomatous tumor when performing nodal staging in radiological N1 NSCLC via endosonography.

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EBUS‐TBNA for mediastinal staging of centrally located T1N0M0 non‐small cell lung cancer clinically staged with PET/CT
Pere Serra Mitjà, Bruno García‐Cabo, Ignasi Garcia‐Olivé, Joaquim Radua, Ramón Rami‐Porta, Lluís Esteban, Bienvenido Barreiro, Sergi Call, Carmen Centeno, Felipe Andreo, Carme Obiols, Juan Manuel Ochoa, Mireia Martínez‐Palau, Nina Reig, Mireia Serra, José
Respirology.2024; 29(2): 158. CrossRef
Clinical Effect of Endosonography on Overall Survival in Patients with Radiological N1 Non–Small Cell Lung Cancer
Bo-Guen Kim, Byeong-Ho Jeong, Goeun Park, Hong Kwan Kim, Young Mog Shim, Sun Hye Shin, Kyungjong Lee, Sang-Won Um, Hojoong Kim, Jong Ho Cho
Cancer Research and Treatment.2024; 56(2): 502. CrossRef
Clinical utility of artificial intelligence–augmented endobronchial ultrasound elastography in lymph node staging for lung cancer
Yogita S. Patel, Anthony A. Gatti, Forough Farrokhyar, Feng Xie, Waël C. Hanna
JTCVS Techniques.2024; 27: 158. CrossRef
Artificial Intelligence Algorithm Can Predict Lymph Node Malignancy from Endobronchial Ultrasound Transbronchial Needle Aspiration Images for Non-Small Cell Lung Cancer
Yogita S. Patel, Anthony A. Gatti, Forough Farrokhyar, Feng Xie, Waël C. Hanna
Respiration.2024; : 1. CrossRef

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MLL4 Regulates the Progression of Non–Small-Cell Lung Cancer by Regulating the PI3K/AKT/SOX2 Axis: Yang Yang, Rongfang Qiu, Qiaoyou Weng, Ziwei Xu, Jingjing Song, Siyu Zhao, Miaomiao Meng, Dengke Zhang, Chunli Kong, Hailin Wang, Min Xu, Zhongwei Zhao, Jiansong Ji; Cancer Res Treat. 2023;55(3):778-803. Published online January 26, 2023; DOI: https://doi.org/10.4143/crt.2022.1042

Abstract PDF Supplementary Material PubReader ePub

Purpose
Mixed-lineage leukemia protein 4 (MLL4/KMT2D) is a histone methyltransferase, and its mutation has been reported to be associated with a poor prognosis in many cancers, including lung cancer. We investigated the function of MLL4 in lung carcinogenesis.
Materials and Methods
RNA sequencing (RNA-seq) in A549 cells transfected with control siRNA or MLL4 siRNA was performed. Also, we used EdU incorporation assay, colony formation assays, growth curve analysis, transwell invasion assays, immunohistochemical staining, and in vivo bioluminescence assay to investigate the function of MLL4 in lung carcinogenesis.
Results
We found that MLL4 expression was downregulated in non–small cell lung cancer (NSCLC) tissues compared to adjacent normal tissues and tended to decrease with disease stage progression. We analyzed the transcriptomes in control and MLL4- deficient cells using high-throughput RNA deep sequencing (RNA-seq) and identified a cohort of target genes, such as SOX2, ATF1, FOXP4, PIK3IP1, SIRT4, TENT5B, and LFNG, some of which are related to proliferation and metastasis. Our results showed that low expression of MLL4 promotes NSCLC cell proliferation and metastasis and is required for the maintenance of NSCLC stem cell properties.
Conclusion
Our findings identify an important role of MLL4 in lung carcinogenesis through transcriptional regulation of PIK3IP1, affecting the PI3K/AKT/SOX2 axis, and suggest that MLL4 could be a potential prognostic indicator and target for NSCLC therapy.

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Role and potential therapeutic value of histone methyltransferases in drug resistance mechanisms in lung cancer
Linxiang Zhang, Xueying Zhang, Yan Shi, Yuhan Ni, Jiaojiao Fei, Zhixin Jin, Wenjuan Li, Xiaojing Wang, Nan Wu
Frontiers in Oncology.2024;[Epub] CrossRef
The multifaceted role of SOX2 in breast and lung cancer dynamics
Kiavash Hushmandi, Seyed Hassan Saadat, Seyedalireza Mirilavasani, Salman Daneshi, Amir Reza Aref, Noushin Nabavi, Rasoul Raesi, Afshin Taheriazam, Mehrdad Hashemi
Pathology - Research and Practice.2024; 260: 155386. CrossRef
PIK3IP1: structure, aberration, function, and regulation in diseases
Yingjie Jia, Pengxing He, Xubin Ma, Kaili Lv, Ying Liu, Yichao Xu
European Journal of Pharmacology.2024; 977: 176753. CrossRef
UBQLN4 promotes the proliferation and invasion of non-small cell lung cancer cell by regulating PI3K/AKT pathway
Li He, Heng Chen, Bin Ruan, Li He, Ming Luo, Yulun Fu, Rui Zou
Journal of Cancer Research and Clinical Oncology.2024;[Epub] CrossRef
Role of histone methyltransferase KMT2D in BMSC osteogenesis via AKT signaling
Zhichun Zhang, Yanyan Guo, Xuejun Gao, Xiaoyan Wang, Chanyuan Jin
Regenerative Therapy.2024; 26: 775. CrossRef
Landscape of targeted therapies for lung squamous cell carcinoma
Qiuxuan Chen, Xiaoshuo Zheng, Weiting Cheng, Jian Li
Frontiers in Oncology.2024;[Epub] CrossRef

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Genomic Characteristics and the Potential Clinical Implications in Oligometastatic Non–Small Cell Lung Cancer: Rongxin Liao, Kehong Chen, Jinjin Li, Hengqiu He, Guangming Yi, Mingfeng Huang, Rongrong Chen, Lu Shen, Xiaoyue Zhang, Zaicheng Xu, Zhenzhou Yang, Yuan Peng; Cancer Res Treat. 2023;55(3):814-831. Published online January 12, 2023; DOI: https://doi.org/10.4143/crt.2022.1315

Abstract PDF Supplementary Material PubReader ePub

Purpose
Oligometastatic non–small cell lung cancer (NSCLC) patients have been increasingly regarded as a distinct group that could benefit from local treatment to achieve a better clinical outcome. However, current definitions of oligometastasis are solely numerical, which are imprecise because of ignoring the biological heterogeneity caused by genomic characteristics. Our study aimed to profile the molecular alterations of oligometastatic NSCLC and elucidate its potential difference from polymetastasis.
Materials and Methods
We performed next-generation sequencing to analyze tumors and paired peripheral blood from 77 oligometastatic and 21 polymetastatic NSCLC patients to reveal their genomic characteristics and assess the genetic heterogeneity.
Results
We found ERBB2, ALK, MLL4, PIK3CB, and TOP2A were mutated at a significantly lower frequency in oligometastasis compared with polymetastasis. EGFR and KEAP1 alterations were mutually exclusive in oligometastatic group. More importantly, oligometastasis has a unique significant enrichment of apoptosis signaling pathway. In contrast to polymetastasis, a highly enriched COSMIC signature 4 and a special mutational process, COSMIC signature 14, were observed in the oligometastatic cohort. According to OncoKB database, 74.03% of oligometastatic NSCLC patients harbored at least one actionable alteration. The median tumor mutation burden of oligometastasis was 5.00 mutations/Mb, which was significantly associated with smoking, DNA damage repair genes, TP53 mutation, SMARCA4 mutation, LRP1B mutation, ABL1 mutation.
Conclusion
Our results shall help redefine oligometastasis beyond simple lesion enumeration that will ultimately improve the selection of patients with real oligometastatic state and optimize personalized cancer therapy for oligometastatic NSCLC.

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Prognostic and Predictive Biomarkers of Oligometastatic NSCLC: New Insights and Clinical Applications
Mandy Jongbloed, Martina Bortolot, Leonard Wee, Jarno W.J. Huijs, Murillo Bellezo, Rianne D.W. Vaes, Frank Aboubakar Nana, Koen J. Hartemink, Dirk K.M. De Ruysscher, Lizza E.L. Hendriks
JTO Clinical and Research Reports.2024; 5(12): 100740. CrossRef

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The Role of Brain Radiotherapy before First-Line Afatinib Therapy, Compared to Gefitinib or Erlotinib, in Patients with EGFR-Mutant Non–Small Cell Lung Cancer: Hyun Ae Jung, Sehhoon Park, Se-Hoon Lee, Jin Seok Ahn, Myung-Ju Ahn, Jong-Mu Sun; Cancer Res Treat. 2023;55(2):479-487. Published online December 27, 2022; DOI: https://doi.org/10.4143/crt.2022.1344

Abstract PDF Supplementary Material PubReader ePub

Purpose
Brain metastasis is common in patients with epidermal growth factor receptor (EGFR)–mutant non–small cell lung cancer (NSCLC) at initial presentation. A previous study showed that brain radiotherapy (RT) before first-generation (first-G) EGFR–tyrosine kinase inhibitor (TKI) therapy is associated with longer overall survival than TKI therapy alone. However, there is no data regarding the role of additional brain RT before afatinib therapy.
Materials and Methods
Between October 2014 and June 2019, EGFR-mutant NSCLC patients with brain metastases who started first-G EGFR-TKIs (gefitinib or erlotinib) or afatinib as first-line therapy were retrospectively analyzed. This study compared overall survival and intracranial progression-free survival (PFS) between patients who received EGFR-TKIs alone and EGFR-TKIs with brain RT and either a first-G EGFR-TKI or afatinib, respectively.
Results
The median follow-up duration was 29.6 months (range, 1.5 to 116.9 months). In the first-G EGFR-TKI group (n=155), 94 patients (60.6%) received the first-G EGFR-TKI alone and 61 patients (39.4%) received brain RT prior to their first-G EGFR-TKI. In the afatinib group (n=204), 126 patients (61.8%) received afatinib alone and 78 patients (38.2%) received brain RT prior to afatinib. There was no difference in overall survival rates between the groups with RT (35.6 months: 95% confidence interval [CI], 27.9 to 43.3) and without RT (31.4 months: 95% CI, 23.9 to 38.9) in the afatinib group (p=0.58), but there was a significant difference in overall survival in the first-G EGFR-TKI group in a manner favoring additional brain RT (41.1 months: 95% CI, 30.5 to 51.7 vs. 25.8 months: 95% CI, 20.1 to 31.5; p=0.02). Meanwhile, median intracranial PFS was not different between patients who received EGFR-TKI therapy alone vs. EGFR-TKI therapy with brain RT in both the first-G EGFR-TKI (p=0.39) and afatinib (p=0.24) groups.
Conclusion
Afatinib therapy alone showed comparable survival outcomes to those of afatinib with brain RT. The current study suggests that brain RT could be an optional, not mandatory, treatment modality when afatinib therapy is considered in patients with EGFR-mutant NSCLC.

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Radiation Recall Pneumonitis: The Open Challenge in Differential Diagnosis of Pneumonia Induced by Oncological Treatments
Francesca Grassi, Vincenza Granata, Roberta Fusco, Federica De Muzio, Carmen Cutolo, Michela Gabelloni, Alessandra Borgheresi, Ginevra Danti, Carmine Picone, Andrea Giovagnoni, Vittorio Miele, Nicoletta Gandolfo, Antonio Barile, Valerio Nardone, Roberta G
Journal of Clinical Medicine.2023; 12(4): 1442. CrossRef
Dacomitinib in EGFR-mutant non-small-cell lung cancer with brain metastasis: a single-arm, phase II study
H.A. Jung, S. Park, S.-H. Lee, J.S. Ahn, M.-J. Ahn, J.-M. Sun
ESMO Open.2023; 8(6): 102068. CrossRef
Recent advances progress of targeted drugs combined with radiotherapy for advanced non-small cell lung cancer: a review
Jiamin Xu, Zhongming Wang
Frontiers in Oncology.2023;[Epub] CrossRef

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Real-World Study of Osimertinib in Korean Patients with Epidermal Growth Factor Receptor T790M Mutation–Positive Non–Small Cell Lung Cancer: Jang Ho Lee, Eun Young Kim, Cheol-Kyu Park, Shin Yup Lee, Min ki Lee, Seong-Hoon Yoon, Jeong Eun Lee, Sang Hoon Lee, Seung Joon Kim, Sung Yong Lee, Jun Hyeok Lim, Tae-Won Jang, Seung Hun Jang, Kye Young Lee, Seung Hyeun Lee, Sei Hoon Yang, Dong Won Park, Chan Kwon Park, Hye Seon Kang, Chang Dong Yeo, Chang-Min Choi, Jae Cheol Lee; Cancer Res Treat. 2023;55(1):112-122. Published online July 19, 2022; DOI: https://doi.org/10.4143/crt.2022.381

Abstract PDF Supplementary Material PubReader ePub

Purpose
Although osimertinib is the standard-of-care treatment of epidermal growth factor receptor (EGFR) T790M mutation–positive non–small cell lung cancer, real-world evidence on the efficacy of osimertinib is not enough to reflect the complexity of the entire course of treatment. Herein, we report on the use of osimertinib in patients with EGFR T790M mutation–positive non–small cell lung cancer who had previously received EGFR tyrosine kinase inhibitor (TKI) treatment in Korea.
Materials and Methods
Patients with confirmed EGFR T790M after disease progression of prior EGFR-TKI were enrolled and administered osimertinib 80 mg daily. The primary effectiveness outcome was progression-free survival, with time-to-treatment discontinuation, treatment and adverse effects leading to treatment discontinuation, and overall survival being the secondary endpoints.
Results
A total of 558 individuals were enrolled, and 55.2% had investigator-assessed responses. The median progression-free survival was 14.2 months (95% confidence interval [CI], 13.0 to 16.4), and the median time-to-treatment discontinuation was 15.0 months (95% CI, 14.1 to 15.9). The median overall survival was 36.7 months (95% CI, 30.9 to not reached). The benefit with osimertinib was consistent regardless of the age, sex, smoking history, and primary EGFR mutation subtype. However, hepatic metastases at the time of diagnosis, the presence of plasma EGFR T790M, and the shorter duration of prior EGFR-TKI treatment were poor predictors of osimertinib treatment. Ten patients (1.8%), including three with pneumonitis, had to discontinue osimertinib due to severe adverse effects.
Conclusion
Osimertinib demonstrated its clinical effectiveness and survival benefit for EGFR T790M mutation–positive in Korean patients with no new safety signals.

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The importance of re-biopsy in the era of molecular therapy for lung cancer
Nensi Lalic, Daliborka Bursac, Marko Bojovic, Marko Nemet, Ivan Ergelasev
Srpski arhiv za celokupno lekarstvo.2024; 152(3-4): 209. CrossRef
Detection of EGFR exon 20 insertion mutations in non-small cell lung cancer: implications for consistent nomenclature in precision medicine
Jieun Park, Boram Lee, Ji-Young Song, Minjung Sung, Mi Jeong Kwon, Chae Rin Kim, Sangjin Lee, Young Kee Shin, Yoon-La Choi
Pathology.2024; 56(5): 653. CrossRef
Real‐world study of lazertinib as second‐line or greater treatment in advanced non‐small cell lung cancer
Jeong Uk Lim, Kyuhwan Kim, Kyu Yean Kim, Hye Seon Kang, Ah. Young Shin, Chang Dong Yeo, Sung Kyoung Kim, Chan Kwon Park, Sang Haak Lee, Seung Joon Kim
Thoracic Cancer.2024; 15(19): 1513. CrossRef
Comparative effectiveness of lazertinib in patients with EGFR T790M-positive non-small-cell lung cancer using a real-world external control
Ha-Lim Jeon, Meesong Kwak, Sohee Kim, Hye-Yeon Yu, Ju-Young Shin, Hyun Ae Jung
Scientific Reports.2024;[Epub] CrossRef
A Randomized, Multi-Center, Open Label Study to Compare the Safety and Efficacy between Afatinib Monotherapy and Combination Therapy with HAD-B1 for the Locally Advanced or Metastatic NSCLC Patients with EGFR Mutations
Eunbin Kwag, Soo-Dam Kim, Seong-Hoon Shin, Chulho Oak, So-Jung Park, Jun-Yong Choi, Seong Hoon Yoon, In-Cheol Kang, Mi-Kyung Jeong, Hyun Woo Lee, Sun-Hwi Bang, Ji Woong Son, Sanghun Lee, Seung Joon Kim, Hwa-Seung Yoo
Integrative Cancer Therapies.2024;[Epub] CrossRef
Clinical utility of repeated rebiopsy for EGFR T790M mutation detection in non-small cell lung cancer
Eun Hye Lee, Se Hyun Kwak, Kyeong Yeon Kim, Chi Young Kim, Sang Hoon Lee, Seok-Jae Heo, Yoon Soo Chang, Eun Young Kim
Frontiers in Oncology.2024;[Epub] CrossRef
Real-world evidence of osimertinib in Chinese patients with EGFR T790M-positive non-small cell lung cancer: a subgroup analysis from ASTRIS study
Qing Zhou, He-Long Zhang, Li-Yan Jiang, Yuan-Kai Shi, Yuan Chen, Jin-Ming Yu, Cai-Cun Zhou, Yong He, Yan-Ping Hu, Zong-An Liang, Yue-Yin Pan, Wen-Lei Zhuo, Yong Song, Gang Wu, Gong-Yan Chen, You Lu, Cui-Ying Zhang, Yi-Ping Zhang, Ying Cheng, Shun Lu, Chan
Journal of Cancer Research and Clinical Oncology.2023; 149(12): 10771. CrossRef

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Clinical Efficacy of Immune Checkpoint Inhibitors in Non–Small Cell Lung Cancer Patients with Liver Metastases: A Network Meta-Analysis of Nine Randomized Controlled Trials: Qing Yin, Longguo Dai, Ruizhu Sun, Ping Ke, Liya Liu, Bo Jiang; Cancer Res Treat. 2022;54(3):803-816. Published online October 25, 2021; DOI: https://doi.org/10.4143/crt.2021.764

Abstract PDF Supplementary Material PubReader ePub

Purpose
This network meta-analysis (NMA) was conducted to compare the efficacy of immune checkpoint inhibitors in advanced non–small cell lung cancer (NSCLC) patients with liver metastases.
Materials and Methods
English literature was retrieved from the PubMed, American Society of Clinical Oncology, and European Society for Medical Oncology databases from January 2015 to January 2021. We pooled the overall survival (OS) and progression-free survival (PFS) hazard ratios (HRs) using an NMA and ranked treatments by the surface under the cumulative ranking curve. Publication bias was evaluated by Begg’s and Egger’s tests. STATA 15.0 was used for the sensitivity analysis, and the remaining statistical analyses were performed using R 4.0.2.
Results
Nine eligible phase III randomized controlled trials were included, including 1,141 patients with liver metastases. Pembrolizumab+chemotherapy ranked highest, followed by atezolizumab+bevacizumab+chemotherapy and nivolumab. However, no significant difference in OS rates was observed across these three treatments (HR, 0.98; 95% confidence interval [CI], 0.43 to 2.22 for pembrolizumab+chemotherapy vs. atezolizumab+bevacizumab+chemotherapy; HR, 0.91; 95% CI, 0.52 to 1.57 for pembrolizumab+chemotherapy vs. nivolumab). Regarding the PFS rate, atezolizumab+bevacizumab+chemotherapy and pembro-lizumab+chemotherapy ranked highest and no significant difference was observed between them (HR, 0.79; 95% CI, 0.36 to 1.70 for atezolizumab+bevacizumab+chemotherapy vs. pembrolizumab+chemotherapy).
Conclusion
Pembrolizumab+chemotherapy, atezolizumab+bevacizumab+chemotherapy, and nivolumab were superior to other treatments in NSCLC patients with liver metastases. These new findings may help clinicians better select therapeutic strategies for NSCLC patients with liver metastases.

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Progress of immune checkpoint inhibitors therapy for non-small cell lung cancer with liver metastases
Fan-jie Qu, Yi Zhou, Shuang Wu
British Journal of Cancer.2024; 130(2): 165. CrossRef
Effectiveness and Safety of Immune Checkpoint Inhibitors Alone or in Combination With Chemotherapy in Pulmonary Sarcomatoid Carcinoma
Daisuke Hazama, Kenji Nakahama, Hiroaki Kodama, Akito Miyazaki, Koichi Azuma, Yosuke Kawashima, Yuki Sato, Kentaro Ito, Yoshimasa Shiraishi, Keita Miura, Takayuki Takahama, Satoshi Oizumi, Yoshinobu Namba, Satoshi Ikeda, Hiroshige Yoshioka, Asuka Tsuya, Y
JTO Clinical and Research Reports.2024; 5(1): 100613. CrossRef
Evolving landscape of treatments targeting the microenvironment of liver metastases in non-small cell lung cancer
Lingling Zhu, Xianzhe Yu, Xiaojun Tang, Chenggong Hu, Lei Wu, Yanyang Liu, Qinghua Zhou
Chinese Medical Journal.2024; 137(9): 1019. CrossRef
Treatment Options for Patients with Non-Small Cell Lung Cancer and Liver Metastases
Vesna Ćeriman Krstić, Natalija Samardžić, Milija Gajić, Milan Savić, Biljana Šeha, Marina Roksandić Milenković, Dragana Jovanović
Current Issues in Molecular Biology.2024; 46(12): 13443. CrossRef
Assessing the Relationship Between Liver Metastases and the Survival of Patients With Non-Small Cell Lung Cancer After Immune Checkpoint Inhibitors Treatment: A Systematic Review and Meta-Analysis
Huilin Xu, Pingpo Ming, Zhenyu Zhao, Nan Zhao, Dingjie Zhou, Xixian Tang, Dedong Cao
Integrative Cancer Therapies.2023;[Epub] CrossRef
Liver metastases and the efficacy of immune checkpoint inhibitors in advanced lung cancer: A systematic review and meta-analysis
Handai Xia, Wengang Zhang, Yuqing Zhang, Xiaoling Shang, Yanguo Liu, Xiuwen Wang
Frontiers in Oncology.2022;[Epub] CrossRef

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The Feasibility of Using Biomarkers Derived from Circulating Tumor DNA Sequencing as Predictive Classifiers in Patients with Small-Cell Lung Cancer: Yu Feng, Yutao Liu, Mingming Yuan, Guilan Dong, Hongxia Zhang, Tongmei Zhang, Lianpeng Chang, Xuefeng Xia, Lifeng Li, Haohua Zhu, Puyuan Xing, Hongyu Wang, Yuankai Shi, Zhijie Wang, Xingsheng Hu; Cancer Res Treat. 2022;54(3):753-766. Published online October 5, 2021; DOI: https://doi.org/10.4143/crt.2021.905

Abstract PDF Supplementary Material PubReader ePub

Purpose
To investigate the feasibility of biomarkers based on dynamic circulating tumor DNA (ctDNA) to classify small cell lung cancer (SCLC) into different subtypes.
Materials and Methods
Tumor and longitudinal plasma ctDNA samples were analyzed by next-generation sequencing of 1,021 genes. PyClone was used to infer the molecular tumor burden index (mTBI). Pre-treatment tumor tissues [T1] and serial plasma samples were collected (pre-treatment [B1], after two [B2], six [B3] cycles of chemotherapy and at progression [B4]).
Results
Overall concordance between T1 and B1 sequencing (n=30) was 66.5%, and 89.5% in the gene of RB1. A classification method was designed according to the changes of RB1 mutation, named as subtype Ⅰ (both positive at B1 and B2), subtype Ⅱ (positive at B1 but negative at B2), and subtype Ⅲ (both negative at B1 and B2). The median progressive-free survival for subtype Ⅰ patients (4.5 months [95%CI: 2.6-5.8]) was inferior to subtype Ⅱ (not reached, p<0.0001) and subtype Ⅲ (10.8 months [95%CI: 6.0-14.4], p=0.002). The median overall survival for subtype Ⅰ patients (16.3 months [95%CI: 5.3-22.9]) was inferior to subtype Ⅱ (not reached, p=0.01) and subtype Ⅲ (not reached, p=0.02). Patients with a mTBI dropped to zero at B2 had longer median overall survival (not reached vs. 19.5 months, p=0.01). The changes of mTBI from B4 to B1 were sensitive to predict new metastases, with a sensitivity of 100% and a specificity of 85.7%.
Conclusion
Monitoring ctDNA based RB1 mutation and mTBI provided a feasible tool to predict the prognosis of SCLC.

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Cell-free and extrachromosomal DNA profiling of small cell lung cancer
Roya Behrouzi, Alexandra Clipson, Kathryn L. Simpson, Fiona Blackhall, Dominic G. Rothwell, Caroline Dive, Florent Mouliere
Trends in Molecular Medicine.2024;[Epub] CrossRef
Circulating tumor DNA as liquid biopsy in lung cancer: Biological characteristics and clinical integration
Changshu Li, Jun Shao, Peiyi Li, Jiaming Feng, Jingwei Li, Chengdi Wang
Cancer Letters.2023; 577: 216365. CrossRef
Prognostic and predictive impact of molecular tumor burden index in non‐small cell lung cancer patients
Fan Yang, Min Tang, Liang Cui, Jing Bai, Jiangyong Yu, Jiayi Gao, Xin Nie, Xu Li, Xuefeng Xia, Xin Yi, Ping Zhang, Lin Li
Thoracic Cancer.2023; 14(31): 3097. CrossRef
Genomic and Gene Expression Studies Helped to Define the Heterogeneity of Small-Cell Lung Cancer and Other Lung Neuroendocrine Tumors and to Identify New Therapeutic Targets
Ugo Testa, Elvira Pelosi, Germana Castelli
Onco.2022; 2(3): 186. CrossRef

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4 Crossref

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

Abstract PDF Supplementary Material PubReader ePub

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.

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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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Lung Cancer

Inhibition of lncRNA KCNQ1OT1 Improves Apoptosis and Chemotherapy Drug Response in Small Cell Lung Cancer by TGF-β1 Mediated Epithelial-to-Mesenchymal Transition: Deyu Li, Qin Tong, Yuane Lian, Zhizhong Chen, Yaru Zhu, Weimei Huang, Yang Wen, Qiongyao Wang, Shumei Liang, Man Li, Jianjing Zheng, Zhenhua Liu, Huanxin Liu, Linlang Guo; Cancer Res Treat. 2021;53(4):1042-1056. Published online March 9, 2021; DOI: https://doi.org/10.4143/crt.2020.1208

Abstract PDF Supplementary Material PubReader ePub

Purpose
Drug resistance is one of the main causes of chemotherapy failure in patients with small cell lung cancer (SCLC), and extensive biological studies into chemotherapy drug resistance are required.
Materials and Methods
In this study, we performed lncRNA microarray, in vitro functional assays, in vivo models and cDNA microarray to evaluate the impact of lncRNA in SCLC chemoresistance.
Results
The results showed that KCNQ1OT1 expression was upregulated in SCLC tissues and was a poor prognostic factor for patients with SCLC. Knockdown of KCNQ1OT1 inhibited cell proliferation, migration, chemoresistance and promoted apoptosis of SCLC cells. Mechanistic investigation showed that KCNQ1OT1 can activate transforming growth factor-β1 mediated epithelial-to-mesenchymal transition in SCLC cells.
Conclusion
Taken together, our study revealed the role of KCNQ1OT1 in the progression and chemoresistance of SCLC, and suggested KCNQ1OT1 as a potential diagnostic and prognostic biomarker in SCLC clinical management.

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Mechanistic insights on the role of competing endogenous RNA regulatory networks (ceRNETs) in small cell lung cancer
Sachin Kumar
Advances in Cancer Biology - Metastasis.2024; 10: 100117. CrossRef
A review on the role of KCNQ1OT1 lncRNA in human disorders
Mohammad Taheri, Zeinab Shirvani-Farsani, Atefeh Harsij, Mohadeseh Fathi, Sheyda Khalilian, Soudeh Ghafouri-Fard, Aria Baniahmad
Pathology - Research and Practice.2024; 255: 155188. CrossRef
Hydroquinidine Demonstrates Remarkable Antineoplastic Effects on Non-small Cell Lung Cancer Cells
Mervenur Yavuz, Turan Demircan
Current Molecular Medicine.2024; 24(9): 1159. CrossRef
Overcoming multi-drug resistance in SCLC: a synergistic approach with venetoclax and hydroxychloroquine targeting the lncRNA LYPLAL1-DT/BCL2/BECN1 pathway
Shuxin Li, Jianyi Lv, Zhihui Li, Qiuyu Zhang, Jing Lu, Xueyun Huo, Meng Guo, Xin Liu, Changlong Li, Jinghui Wang, Hanping Shi, Li Deng, Zhenwen Chen, Xiaoyan Du
Molecular Cancer.2024;[Epub] CrossRef
Non-coding RNAs in lung cancer: molecular mechanisms and clinical applications
Ying Liu, Wei Ding, Jianxun Wang, Xiang Ao, Junqiang Xue
Frontiers in Oncology.2023;[Epub] CrossRef
Biological role of long non-coding RNA KCNQ1OT1 in cancer progression
Kai Zhan, Huafeng Pan, Zhang Zhou, Wenqian Tang, Zhining Ye, Shaogang Huang, Lei Luo
Biomedicine & Pharmacotherapy.2023; 169: 115876. CrossRef
Non-coding genome in small cell lung cancer between theoretical view and clinical applications
Xiaomeng Yin, Jiqiao Yang, Hang Wang, Yuling Luo, Zeyi Qin, Lei Deng, Xuelei Ma
Seminars in Cancer Biology.2022; 86: 237. CrossRef
KCNQ1OT1: An Oncogenic Long Noncoding RNA
Patrice Cagle, Qi Qi, Suryakant Niture, Deepak Kumar
Biomolecules.2021; 11(11): 1602. CrossRef

7,103 View
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Lung cancer

Phase II Study of Pemetrexed as a Salvage Chemotherapy for Thymidylate Synthase–Low Squamous Cell Lung Cancer: Mihong Choi, Heung Tae Kim, Ji-Youn Han, Geon Kook Lee, Soo-Hyun Lee, Kun Young Lim, Jungnam Joo, Hye Jin Won, Jin Soo Lee, Youngjoo Lee; Cancer Res Treat. 2021;53(1):87-92. Published online August 13, 2020; DOI: https://doi.org/10.4143/crt.2020.741

Abstract PDF Supplementary Material PubReader ePub

Purpose
Squamous cell carcinomas (SqCC) of the lung often express high levels of thymidylate synthase (TS), which is associated with primary resistance to pemetrexed. We explored the efficacy of pemetrexed in a selected population of patients with lung SqCC with low TS expression.
Materials and Methods
In this single-arm phase II trial, we enrolled 32 previously-treated patients with advanced lung SqCC exhibiting low immunohistochemical staining for TS (i.e., in 10% or less of tumor cells). The primary endpoint was 12-week progression-free survival (PFS) rate.
Results
Of 32 patients, eight patients (25%) had an Eastern Cooperative Oncology Group performance status of 2, and seven patients (22%) had previously received three or more lines of chemotherapy. The disease control rate from pemetrexed treatment was 30%, and no objective response was observed. The 12-week PFS rate was 24.5% (95% confidence interval [CI], 13.0 to 46.1). Median PFS was 1.3 months (95% CI, 1.3 to 2.7), and median overall survival was 11.8 months (95% CI, 8.1 to not applicable). Most of adverse events were grade 1 or 2.
Conclusion
Pemetrexed demonstrated modest activity as a salvage chemotherapy in patients with advanced lung SqCC with low TS expression, although its toxicity was generally manageable.

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Bioengineered miR-7-5p modulates non-small cell lung cancer cell metabolism to improve therapy
Gavin M. Traber, Mei-Juan Tu, Su Guan, Neelu Batra, Ai-Ming Yu
Molecular Pharmacology.2024; : 100006. CrossRef

6,898 View
127 Download
1 Crossref

Case Report

EGFR C797S as a Resistance Mechanism of Lazertinib in Non-small Cell Lung Cancer with EGFR T790M Mutation: Sehhoon Park, Bo Mi Ku, Hyun Ae Jung, Jong-Mu Sun, Jin Seok Ahn, Se-Hoon Lee, Keunchil Park, Myung-Ju Ahn; Cancer Res Treat. 2020;52(4):1288-1290. Published online June 22, 2020; DOI: https://doi.org/10.4143/crt.2020.278

Abstract PDF PubReader ePub

The non-small cell lung cancer with activating epidermal growth factor receptor (EGFR) mutation eventually acquires resistant to either first or second-generation EGFR tyrosine kinase inhibitor (TKI). As the following option, targeting EGFR T790M with third-generation EGFR TKI is now established as a standard treatment option. In this study, we are reporting the first case of resistance mechanism to the novel third-generation EGFR TKI, lazertinib, which showed promising clinical efficacy in phase 1-2 study. The patients showed resistance to the treatment by acquiring the additional EGFR C797S mutation in cis which is also confirmed from the patient-derived cell lines.

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Research Advances of Small Molecule EGFR-TKIs in NSCLC
亚南胡
Pharmacy Information.2024; 13(01): 1. CrossRef
An assessment of EGFR and HER2 inhibitors with structure activity relationship of fused pyrimidine derivatives for breast cancer: a brief review
Prasad Sanjay Dhiwar, Gurubasavaraja Swamy Purawarga Matada, Rohit Pal, Ekta Singh, Abhishek Ghara, Lalmohan Maji, Sindhuja Sengupta, Ganesh Andhale
Journal of Biomolecular Structure and Dynamics.2024; 42(3): 1564. CrossRef
The efficacy of almonertinib and anlotinib combination therapy for advanced non‐small‐cell lung cancer patients who continued to experience cancer progression during third‐generation EGFR‐TKI treatment: a retrospective study
Yu Zhang, Chengmeng Wang, Jing Zhao, Meng Wang
Thoracic Cancer.2024; 15(23): 1757. CrossRef
Successful treatment of a patient with advanced lung adenocarcinoma (EGFR-T790M and C797S cis) with lazertinib: A case report and literature review
Yue Fang, Qiankun Zhang, Weimin Wang, Juanjuan Tong, Xialin Li
Frontiers in Oncology.2023;[Epub] CrossRef
A Review on Fused Pyrimidine Systems as EGFR Inhibitors and Their Structure–Activity Relationship
Tanuja T. Yadav, Gulam Moin Shaikh, Maushmi S. Kumar, Meena Chintamaneni, Mayur YC
Frontiers in Chemistry.2022;[Epub] CrossRef
Structural Basis for Inhibition of Mutant EGFR with Lazertinib (YH25448)
David E. Heppner, Florian Wittlinger, Tyler S. Beyett, Tatiana Shaurova, Daniel A. Urul, Brian Buckley, Calvin D. Pham, Ilse K. Schaeffner, Bo Yang, Blessing C. Ogboo, Earl W. May, Erik M. Schaefer, Michael J. Eck, Stefan A. Laufer, Pamela A. Hershberger
ACS Medicinal Chemistry Letters.2022; 13(12): 1856. CrossRef
Potentiating Therapeutic Effects of Epidermal Growth Factor Receptor Inhibition in Triple-Negative Breast Cancer
Kyu Sic You, Yong Weon Yi, Jeonghee Cho, Jeong-Soo Park, Yeon-Sun Seong
Pharmaceuticals.2021; 14(6): 589. CrossRef
Paired analysis of tumor mutation burden calculated by targeted deep sequencing panel and whole exome sequencing in non-small cell lung cancer
Sehhoon Park, Chung Lee, Bo Mi Ku, Minjae Kim, Woong-Yang Park, Nayoung K. D. Kim, Myung-Ju Ahn
BMB Reports.2021; 54(7): 386. CrossRef

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Original Articles

Lung cancer

Real-World Experience of Nivolumab in Non-small Cell Lung Cancer in Korea: Sun Min Lim, Sang-We Kim, Byoung Chul Cho, Jin Hyung Kang, Myung-Ju Ahn, Dong-Wan Kim, Young-Chul Kim, Jin Soo Lee, Jong-Seok Lee, Sung Yong Lee, Keon Uk Park, Ho Jung An, Eun Kyung Cho, Tae Won Jang, Bong-Seog Kim, Joo-Hang Kim, Sung Sook Lee, Im-II Na, Seung Soo Yoo, Ki Hyeong Lee; Cancer Res Treat. 2020;52(4):1112-1119. Published online May 15, 2020; DOI: https://doi.org/10.4143/crt.2020.245

Abstract PDF Supplementary Material PubReader ePub

Purpose
The introduction of immune checkpoint inhibitors represents a major advance in the treatment of lung cancer, allowing sustained recovery in a significant proportion of patients. Nivolumab is a monoclonal anti–programmed death cell protein 1 antibody licensed for the treatment of locally advanced or metastatic non-small cell lung cancer (NSCLC) after prior chemotherapy. In this study, we describe the demographic and clinical outcomes of patients with advanced NSCLC treated with nivolumab in the Korean expanded access program.
Materials and Methods
Previously treated patients with advanced non-squamous and squamous NSCLC patients received nivolumab at 3 mg/kg every 2 weeks up to 36 months. Efficacy data including investigator-assessed tumor response, progression data, survival, and safety data were collected.
Results
Two hundred ninety-nine patients were treated across 36 Korean centers. The objective response rate and disease control rate were 18% and 49%, respectively; the median progression-free survival was 2.1 months (95% confidence interval [CI], 1.87 to 3.45), and the overall survival (OS) was 13.2 months (95% CI, 10.6 to 18.9). Patients with smoking history and patients who experienced immune-related adverse events showed a prolonged OS. Cox regression analysis identified smoking history, presence of immune-related adverse events as positive factors associated with OS, while liver metastasis was a negative factor associated with OS. The safety profile was generally comparable to previously reported data.
Conclusion
This real-world analysis supports the use of nivolumab for pretreated NSCLC patients, including those with an older age.

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Advances in reprogramming of energy metabolism in tumor T cells
Liu Xuekai, Song Yan, Chu Jian, Song Yifei, Wu Xinyue, Zhang Wenyuan, Han Shuwen, Yang Xi
Frontiers in Immunology.2024;[Epub] CrossRef
Effectiveness and Safety of PD-1 Inhibitors’ Treatment for Patients with Non-Small-Cell Lung Cancer in China: A Real-World Study
Ning Wan, Yongbang Chen, Liqing Lu, Bing Wang, Liuliu He, Hongyi Liang, Fei Xie, Xiaoshun Jian, Bo Ji, Jianping Zhang, Hammoda Abu-Odah
European Journal of Cancer Care.2024; 2024: 1. CrossRef
Optimization of treatment strategies for elderly patients with advanced non-small cell lung cancer
Qiang Chen, Shuo Ying, Jianwen Qin, Li Zhang
Frontiers in Oncology.2024;[Epub] CrossRef
Real-World Data on Pembrolizumab for Pretreated Non-Small-Cell Lung Cancer: Clinical Outcome and Relevance of the Lung Immune Prognostic Index
Ana Ortega-Franco, Clare Hodgson, Haseem Raja, Mathew Carter, Colin Lindsay, Sarah Hughes, Laura Cove-Smith, Paul Taylor, Yvonne Summers, Fiona Blackhall, Raffaele Califano
Targeted Oncology.2022; 17(4): 453. CrossRef
Liver metastases and the efficacy of immune checkpoint inhibitors in advanced lung cancer: A systematic review and meta-analysis
Handai Xia, Wengang Zhang, Yuqing Zhang, Xiaoling Shang, Yanguo Liu, Xiuwen Wang
Frontiers in Oncology.2022;[Epub] CrossRef
Immune-Related Adverse Events Predict the Efficacy of Immune Checkpoint Inhibitors in Lung Cancer Patients: A Meta-Analysis
Donghui Wang, Cen Chen, Yanli Gu, Wanjun Lu, Ping Zhan, Hongbing Liu, Tangfeng Lv, Yong Song, Fang Zhang
Frontiers in Oncology.2021;[Epub] CrossRef
Broad-Spectrum Antibiotic Regimen Affects Survival in Patients Receiving Nivolumab for Non-Small Cell Lung Cancer
Min Jung Geum, Chungsoo Kim, Ji Eun Kang, Jae Hee Choi, Jae Song Kim, Eun Sun Son, Sun Min Lim, Sandy Jeong Rhie
Pharmaceuticals.2021; 14(5): 445. CrossRef
Nivolumab

Reactions Weekly.2021; 1855(1): 269. CrossRef
Immune-Related Adverse Events Associated With Outcomes in Patients With NSCLC Treated With Anti-PD-1 Inhibitors: A Systematic Review and Meta-Analysis
Zhe Zhao, Xinfeng Wang, Jinghan Qu, Wei Zuo, Yan Tang, Huijuan Zhu, Xiaoguang Chen
Frontiers in Oncology.2021;[Epub] CrossRef

10,451 View
308 Download
15 Web of Science
9 Crossref

Caspase Recruitment Domain Containing Protein 9 Suppresses Non-Small Cell Lung Cancer Proliferation and Invasion via Inhibiting MAPK/p38 Pathway: Linyue Pan, Yuting Tan, Bin Wang, Wenjia Qiu, Yulei Yin, Haiyan Ge, Huili Zhu; Cancer Res Treat. 2020;52(3):867-885. Published online March 11, 2020; DOI: https://doi.org/10.4143/crt.2019.606

Abstract PDF Supplementary Material PubReader ePub

Purpose
Caspase recruitment domain containing protein 9 (CARD9) has been demonstrated to be a pro-tumor factor in various cancers. However, our previous study found a significant decrease of CARD9 in malignant pleural effusion compared with benign pleural effusion. So we investigated the role of CARD9 in non-small cell lung cancer (NSCLC) and its working mechanism.
Materials and Methods
Immunohistochemistry, western blot, and quantitative real-time polymerase chain reaction were used to detect the expression of CARD9 in specimens of NSCLC patients. The Cancer Genome Atlas (TCGA) databasewas also used to analyze the expression of CARD9 in NSCLC and its predicting value for prognosis. Immunofluorescence was used for CARD9 cellular location. Cell growth assay, clonal formation assay, wound healing assay, matrigel invasion assay, and flow cytometry were used to test cell proliferation, migration, invasion, apoptosis, and cycle progression of NSCLC cells with CARD9 knockdown or CARD9 overexpression. Co-immunoprecipitation was used to identify the interaction between CARD9 and B-cell lymphoma 10 (BCL10). SB203580 was used to inhibit p38 activation.
Results
CARD9 was decreased in NSCLC tissues compared with normal tissues; low CARD9 expression was associated with poor survival. CARD9 was expressed both in tumor cells and macrophages. Downregulation of CARD9 in NSCLC cells enhanced the abilities of proliferation, invasion and migration via activated MAPK/p38 signaling, while overexpression of CARD9 presented antitumor effects. BCL10 was identified to interact with CARD9.
Conclusion
We demonstrate that CARD9 is an independent prognostic factor in NSCLC patients and inhibits proliferation, migration, and invasion by suppressing MAPK/p38 pathway in NSCLC cells.

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CARD9 regulates myocardial inflammation, oxidative stress, and vascular dysfunction in hypertensive rats by activating MAPK/p38 pathway in combination with NOD2
XiangBin Xin, Jing Zhang, YanQin Du, XiaoTing Jang, XinYi Tian, Fu Ma, Fang Chen
Molecular & Cellular Toxicology.2024;[Epub] CrossRef
The implication of microbiome in lungs cancer: mechanisms and strategies of cancer growth, diagnosis and therapy
Yasmin Bano, Abhinav Shrivastava, Piyush Shukla, Anis Ahmad Chaudhary, Salah-Ud-Din Khan, Shahanavaj Khan
Critical Reviews in Microbiology.2024; : 1. CrossRef
Transcriptome Analysis of the Inhibitory Effects of 20(S)-Protopanaxadiol on NCI-H1299 Non-Small Cell Lung Cancer Cells
Zhongyi Cong, Xinmin Zhang, Zeqi Lv, Jingyuan Jiang, Lei Wang, Jiapeng Li, Jie Wang, Jianjun Zhao
Molecules.2023; 28(15): 5746. CrossRef
Sericin enhances ammonia detoxification by promotes urea cycle enzyme genes and activates hepatic autophagy in relation to CARD-9/MAPK pathway
Sumate Ampawong, Napatara Tirawanchai, Tapanee Kanjanapruthipong, Kamonpan Fongsodsri, Khwanchanok Tuentam, Duangnate Isarangkul, Pornanong Aramwit
Heliyon.2023; 9(11): e21563. CrossRef
Mycobiota and C-Type Lectin Receptors in Cancers: Know thy Neighbors
Lilong Zhang, Dongqi Chai, Chen Chen, Chunlei Li, Zhendong Qiu, Tianrui Kuang, Mungur Parveena, Keshuai Dong, Jia Yu, Wenhong Deng, Weixing Wang
Frontiers in Microbiology.2022;[Epub] CrossRef
Alpha1B-adreneroceptor is involved in norepinephrine-induced pulmonary artery smooth muscle cell proliferation via p38 signaling
Xiaolin Xiao, Ying Zhang, Shuaihu Tian, Xiaoyan Wang, Qianlong Zhang, Lixin Zhang, Xiufeng Yu, Cui Ma, Xiaodong Zheng, Yiying Li, Junting Zhang, Lihui Qu
European Journal of Pharmacology.2022; 931: 175159. CrossRef
Proteomic analysis provides insights into the function of Polian vesicles in the sea cucumber Apostichopus japonicus post-evisceration
Jinlin Ji, Zhenhui Wang, Wei Zhu, Qiang Li, Yinan Wang
Journal of Oceanology and Limnology.2022; 40(5): 2028. CrossRef
CARD9 as a potential therapeutic target in lung cancer
Ruanmei Sheng, Zhiwen Yang
Frontiers in Bioscience-Landmark.2021;[Epub] CrossRef

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Clinical Characteristics and Outcomes of Non-small Cell Lung Cancer Patients with HER2 Alterations in Korea: Kangkook Lee, Hyun Ae Jung, Jong-Mu Sun, Se-Hoon Lee, Jin Seok Ahn, Keunchil Park, Myung-Ju Ahn; Cancer Res Treat. 2020;52(1):292-300. Published online July 26, 2019; DOI: https://doi.org/10.4143/crt.2019.186

Abstract PDF Supplementary Material PubReader ePub

Purpose
Human epidermal growth factor receptor 2 (HER2) alterations are found in approximately 1%-3% of non-small cell lung cancers (NSCLCs). We evaluated the clinical features and outcomes of NSCLC harboring HER2 alteration detected by next-generation sequencing (NGS) in Korea.
Materials and Methods
A total of 1,108 patients who were diagnosed with NSCLC between December 2015 and December 2017 were screened and analyzed by NGS. Medical records were reviewed retrospectively to analyze the clinical characteristics and outcomes from various treatments.
Results
HER2 alterations were identified in 36 NSCLC patients. Of the patients, 22 (61.1%) had an exon 20 in-frame insertion mutation, 15 (41.7%) had HER2 amplification, and one had both. The median patient age was 58 years, 55.6% were male, and 50.0% were never-smokers. Adenocarcinoma was predominant (88.9%). The most common metastatic site was bone (58.3%), and 66.7% of patients were stage IV at initial diagnosis. Six patients (16.7%) had a coexistent sensitizing epidermal growth factor receptor (EGFR) mutation, and two patients (5.6%) had anaplastic lymphoma kinase (ALK) rearrangement. With a median 14 months of follow-up, the median progression-free survival of first-line treatment was 6 months (95% confidence interval, 4.172 to 7.828), and median overall survival was not reached. The proportions of adenocarcinoma, never-smokers, and metastasis to the liver were higher in the exon 20 in-frame insertion mutation group, whereas coexistence of EGFR mutation was more frequently found in the HER2 amplification group.
Conclusion
HER2-altered NSCLC showed distinct clinical features. Moreover, different characteristics were identified between the HER2 in-frame insertion mutation group and the HER2 amplification group.

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Clinicopathologic and Molecular Characteristics of HER2 (ERBB2)-Altered Non–Small Cell Lung Cancer: Implications for Precision Medicine
Yurimi Lee, Boram Lee, Yoon-La Choi, Dong-Wook Kang, Joungho Han
Modern Pathology.2024; 37(6): 100490. CrossRef
The frequency of EGFR gene mutations in a cohort of Romanian patients with non-small cell lung cancer and their association with PD-L1 expression level and ALK rearrangements
Ester-Andreea Cohn, Ortansa Csutak, Ecaterina Tataru
Revista Romana de Medicina de Laborator.2024; 32(3): 237. CrossRef
Antibody–Drug Conjugates for the Treatment of Non-Small Cell Lung Cancer with Central Nervous System Metastases
David J. H. Bian, Sara F. Cohen, Anna-Maria Lazaratos, Nathaniel Bouganim, Matthew Dankner
Current Oncology.2024; 31(10): 6314. CrossRef
ERBB2 mutation landscape in non-small cell lung cancer patients in Northeast China
Hui Li, Xiang Li, Shaowei Lan, Xuerong Zuo, Tianying Du, Ying Liu, Caixia Zhang, Jing Zhu, Ying Cheng
Tumori Journal.2023; 109(3): 276. CrossRef
Clinical characteristics and prognostic factors of patients with non-small cell lung cancer having HER2 alterations
Xiaoli Zhuo, Honglin Guo, Jun Ma, Jingjiang Lai, Lei Liu, Ke Yin, Jing Zhao, Jingliang Wang, Fengxian Jiang, Wei Xu, Xiaotian Yuan, Xiaoyan Lin, Guobin Fu
Journal of Cancer Research and Clinical Oncology.2023; 149(5): 2029. CrossRef
Real World Characteristics and Clinical Outcomes of HER2-Mutant Non–Small Cell Lung Cancer Patients Detected by Next-Generation Sequencing
Beung-Chul Ahn, Ye-Jeong Han, Hye Ryun Kim, Min Hee Hong, Byoung Chul Cho, Sun Min Lim
Cancer Research and Treatment.2023; 55(2): 488. CrossRef
Prevalence and clinicopathological associations of HER2 expression in non-small cell lung cancer: a retrospective study in Jordanian patients
Ola Abu Al Karsaneh, Arwa Al Anber, Mohammad ALQudah, Sahar Al-Mustafa, Hussien AlMa’aitah, Maher Sughayer
Diagnostic Pathology.2023;[Epub] CrossRef
Exploring the correlation between HER2 alterations and 18F-FDG PET/CT metabolic parameters and their prognostic value in EGFR-negative non-small-cell lung cancer patients
Maomei Ruan, Cheng Chang, Jianwen Sun, Liu Liu, Lihua Wang, Bei Lei, Hui Yan, He Zhang, Wenhui Xie, Yuetao Wang
Journal of Cancer Research and Clinical Oncology.2023; 149(16): 14493. CrossRef
Pyrotinib in Patients with HER2-Amplified Advanced Non–Small Cell Lung Cancer: A Prospective, Multicenter, Single-Arm Trial
Zhengbo Song, Dongqing Lv, Shi-Qing Chen, Jianjin Huang, Yuping Li, Shenpeng Ying, Xiaoyu Wu, Feng Hua, Wenxian Wang, Chunwei Xu, Ting Bei, Chan Gao, Zhijian Sun, Yiping Zhang, Shun Lu
Clinical Cancer Research.2022; 28(3): 461. CrossRef
Consensus for HER2 alterations testing in non-small-cell lung cancer
S. Ren, J. Wang, J. Ying, T. Mitsudomi, D.H. Lee, Z. Wang, Q. Chu, P.C. Mack, Y. Cheng, J. Duan, Y. Fan, B. Han, Z. Hui, A. Liu, J. Liu, Y. Lu, Z. Ma, M. Shi, Y. Shu, Q. Song, X. Song, Y. Song, C. Wang, X. Wang, Z. Wang, Y. Xu, Y. Yao, L. Zhang, M. Zhao,
ESMO Open.2022; 7(1): 100395. CrossRef
Deciphering the Impact of HER2 Alterations on Non-Small-Cell Lung Cancer: From Biological Mechanisms to Therapeutic Approaches
Christophe Bontoux, Jonathan Benzaquen, Véronique Hofman, Simon Heeke, Paul Hannetel, Pierre Capela-Brosseau-Laborde, Charles-Hugo Marquette, Marius Ilié, Paul Hofman
Journal of Personalized Medicine.2022; 12(10): 1651. CrossRef
Predictors for survival in patients with bone metastasis of small cell lung cancer
MingFeng Xue, Gang Chen, XingGuang Chen, JunYu Hu
Medicine.2021; 100(34): e27070. CrossRef
Advances in systemic therapy for non-small cell lung cancer
Meagan Miller, Nasser Hanna
BMJ.2021; : n2363. CrossRef
Genetic Markers in Lung Cancer Diagnosis: A Review
Katarzyna Wadowska, Iwona Bil-Lula, Łukasz Trembecki, Mariola Śliwińska-Mossoń
International Journal of Molecular Sciences.2020; 21(13): 4569. CrossRef
Exploration of estrogen receptor‑associated hub genes and potential molecular mechanisms in non‑smoking females with lung adenocarcinoma using integrated bioinformatics analysis
Hao Wang, Zhihong Zhang, Ke Xu, Song Wei, Lailing Li, Lijun Wang
Oncology Letters.2019;[Epub] CrossRef

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Dummy Run of Quality Assurance Program before Prospective Study of Hippocampus-Sparing Whole-Brain Radiotherapy and Simultaneous Integrated Boost for Multiple Brain Metastases from Non-small Cell Lung Cancer: Korean Radiation Oncology Group (KROG) 17-06 Study: Eunah Chung, Jae Myoung Noh, Kyu Chan Lee, Jin Hee Kim, Weon Kuu Chung, Yang-Gun Suh, Jung Ae Lee, Ki Ho Seol, Hong Gyun Wu, Yeon Sil Kim, O Kyu Noh, Jae Won Park, Dong Soo Lee, Jihae Lee, Young Suk Kim, Woo-Yoon Park, Min Kyu Kang, Sunmi Jo, Yong Chan Ahn; Cancer Res Treat. 2019;51(3):1001-1010. Published online October 15, 2018; DOI: https://doi.org/10.4143/crt.2018.415

Abstract PDF PubReader ePub

Purpose
Lung Cancer Subcommittee of Korean Radiation Oncology Group (KROG) has recently launched a prospective clinical trial (KROG 17-06) of hippocampus-sparing whole brain radiotherapy (HS-WBRT) with simultaneous integrated boost (SIB) in treating multiple brain metastases from non-small cell lung cancer. In order to improve trial quality, dummy run studies among the participating institutions were designed. This work reported the results of two-step dummy run procedures of the KROG 17-06 study.
Materials and Methods
Two steps tested hippocampus contouring variability and radiation therapy planning compliance. In the first step, the variation of the hippocampus delineation was investigated for two representative cases using the Dice similarity coefficients. In the second step, the participating institutions were requested to generate a HS-WBRT with SIB treatment plan for another representative case. The compliance of the treatment plans to the planning protocol was evaluated.
Results
In the first step, the median Dice similarity coefficients of the hippocampus contours for two other dummy run cases changed from 0.669 (range, 0.073 to 0.712) to 0.690 (range, 0.522 to 0.750) and from 0.291 (range, 0.219 to 0.522) to 0.412 (range, 0.264 to 0.598) after providing the hippocampus contouring feedback. In the second step, with providing additional plan priority and extended dose constraints to the target volumes and normal structures, we observed the improved compliance of the treatment plans to the planning protocol.
Conclusion
The dummy run studies demonstrated the notable inter-institutional variability in delineating the hippocampus and treatment plan generation, which could be decreased through feedback from the trial center.

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Radiotherapy trial quality assurance processes: a systematic review
Chloe Brooks, Elizabeth Miles, Peter J Hoskin
The Lancet Oncology.2024; 25(3): e104. CrossRef
Durvalumab with chemoradiotherapy for limited-stage small-cell lung cancer
Sehhoon Park, Jae Myoung Noh, Yoon-La Choi, Sang Ah Chi, Kyunga Kim, Hyun Ae Jung, Se-Hoon Lee, Jin Seok Ahn, Myung-Ju Ahn, Jong-Mu Sun
European Journal of Cancer.2022; 169: 42. CrossRef
Region-Specific Effects of Fractionated Low-Dose Versus Single-Dose Radiation on Hippocampal Neurogenesis and Neuroinflammation
Zoé Schmal, Claudia E. Rübe
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Non–coplanar whole brain radiotherapy is an effective modality for parotid sparing
Jaehyeon Park, Jae Won Park, Ji Woon Yea
Yeungnam University Journal of Medicine.2019; 36(1): 36. CrossRef

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Clinical Outcomes of EGFR Exon 20 Insertion Mutations in Advanced Non-small Cell Lung Cancer in Korea: Seonggyu Byeon, Youjin Kim, Sung Won Lim, Jang Ho Cho, Sehoon Park, Jiyun Lee, Jong-Mu Sun, Yoon-La Choi, Se-Hoon Lee, Jin Seok Ahn, Keunchil Park, Myung-Ju Ahn; Cancer Res Treat. 2019;51(2):623-631. Published online July 23, 2018; DOI: https://doi.org/10.4143/crt.2018.151

Abstract PDF Supplementary Material PubReader ePub

Purpose
Epidermal growth factor receptor (EGFR) exon 20 insertion mutations account for approximately 4% of all EGFR mutations. Given the rarity of this mutation, its clinical outcomes are not fully established.
Materials and Methods
Between 2009 and 2017, non-small cell lung cancer (NSCLC) patients who showed an exon 20 insertion were retrospectively reviewed for clinical characteristics and outcomes, including responses to chemotherapy (CTx) or targeted therapy.
Results
Of 3,539 NSCLC patients who harbored an activating EGFR mutation, 56 (1.6%) had an exon 20 insertion. Of the advanced NSCLC patients, 27 of 1,479 (1.8%) had an exon 20 insertion. The median overall survival was 29.4 months (95% confidence interval 9.3 to 49.6) for 27 advancedNSCLC patients. The 22 patientswho received systemic CTx achieved a 50.0% response rate and a 77.2% disease control rate, with 4.2 months of progressionfree survival. Six patients received EGFR tyrosine kinase inhibitors (TKIs). Three of the four patients that had only an exon 20 insertion showed progressive disease, while one showed stable disease. The othertwo patients had an exon 20 insertion and another EGFR mutation and achieved a partial response.
Conclusion
The incidence of an exon 20 insertion mutation is rare in Korea and occasionally accompanied by other common EGFR mutations. Although the response to systemic CTx. in these patients is comparable to that of patients with other mutations, the response rate to firstor second-generation EGFR TKIs is quite low. Therefore, the development of a more efficient agent is urgently needed.

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Journal of Cancer Research and Clinical Oncology.2023; 149(2): 865. CrossRef
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Sai-Hong I. Ou, Huamao M. Lin, Jin-Liern Hong, Yu Yin, Shu Jin, Jianchang Lin, Minal Mehta, Pingkuan Zhang, Danny Nguyen, Joel W. Neal
Lung Cancer.2023; 179: 107186. CrossRef
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Ramakrishna R. Sompallae, Bilge Dundar, Natalya V. Guseva, Aaron D. Bossler, Deqin Ma
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Ya Gao, Wies R. Vallentgoed, Pim J. French
Cancers.2018; 10(12): 489. CrossRef

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EGFR Mutation Is Associated with Short Progression-Free Survival in Patients with Stage III Non-squamous Cell Lung Cancer Treated with Concurrent Chemoradiotherapy: Song Ee Park, Jae Myoung Noh, You Jin Kim, Han Sang Lee, Jang Ho Cho, Sung Won Lim, Yong Chan Ahn, Hongryull Pyo, Yoon-La Choi, Joungho Han, Jong-Mu Sun, Se Hoon Lee, Jin Seok Ahn, Keunchil Park, Myung-Ju Ahn; Cancer Res Treat. 2019;51(2):493-501. Published online June 18, 2018; DOI: https://doi.org/10.4143/crt.2018.125

Abstract PDF PubReader ePub

Purpose
This study was conducted to evaluate the relationship between epidermal growth factor receptor (EGFR) mutation and clinical outcomes in patients with stage III non-squamous cell lung cancer treated with definitive concurrent chemoradiotherapy (CCRT).
Materials and Methods
From January 2008 to December 2013, the medical records of 197 patients with stage III non- squamous non-small cell lung cancer treated with definitive CCRT were analyzed to determine progression-free survival (PFS) and overall survival (OS) according to EGFR mutation status.
Results
Among 197 eligible patients, 81 patients were EGFR wild type, 36 patients had an EGFR mutation (exon 19 Del, n=18; L858R, n=9, uncommon [G719X, L868, T790M], n=9), and 80 patients had unknown EGFR status. The median age was 59 years (range, 28 to 80 years) and 136 patients (69.0%) were male. The median follow-up duration was 66.5 months (range, 1.9 to 114.5 months). One hundred sixty-four patients (83.2%) experienced disease progression. Median PFS was 8.9 months for the EGFR mutation group, 11.8 months for EGFR wild type, and 10.5 months for the unknown EGFR group (p=0.013 and p=0.042, respectively). The most common site of metastasis in the EGFR mutant group was the brain. However, there was no significant difference in OS among the three groups (34.6 months for EGFR mutant group vs. 31.9 months for EGFR wild type vs. 22.6 months for EGFR unknown group; p=0.792 and p=0.284). A total of 29 patients (80.6%) with EGFR mutation were treated with EGFR tyrosine kinase inhibitor (gefitinib, n=24; erlotinib, n=3; afatinib, n=2) upon progression.
Conclusion
EGFR mutation is associatedwith short PFS and the brain is the most common site of distant metastasis in patients with stage III non- squamous cell lung cancer treated with CCRT.

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Randomized Phase II Study of Pemetrexed Versus Gefitinib in Previously Treated Patients with Advanced Non-small Cell Lung Cancer: Young Saing Kim, Eun Kyung Cho, Hyun Sun Woo, Junshik Hong, Hee Kyung Ahn, Inkeun Park, Sun Jin Sym, Sun Young Kyung, Shin Myung Kang, Jeong-Woong Park, Sung Hwan Jeong, Jinny Park, Jae Hoon Lee, Dong Bok Shin; Cancer Res Treat. 2016;48(1):80-87. Published online March 2, 2015; DOI: https://doi.org/10.4143/crt.2014.307

Abstract PDF PubReader ePub

Purpose
This study aimed to evaluate the efficacy and safety of pemetrexed versus gefitinib in patients with advanced non-small cell lung cancer (NSCLC) previously treated with chemotherapy. Materials and Methods Patients with advanced (stage IIIB or IV) or recurrent NSCLC were randomly assigned to receive either 500 mg/m² of pemetrexed intravenously every 3 weeks or gefitinib 250 mg/day orally. The primary end point was progression-free survival (PFS) at 6 months.
Results
A total of 95 patients were enrolled (47 for pemetrexed and 48 for gefitinib). Most patients were male (72%) and current/ex-smokers (69%), and 80% had non-squamous cell carcinoma. The epidermal growth factor receptor (EGFR) mutation status was determined in 38 patients (40%); one patient per each arm was positive for EGFRmutation. The 6-month PFS rates were 22% and 15% for pemetrexed and gefitinib, respectively (p=0.35). Both arms showed an identical median PFS of 2.0 months and a median overall survival (OS) of 8.5 months. In EGFR wild-type patients, higher response rate (RR) and longer PFS as well as OS were achieved via pemetrexed compared with gefitinib, although there were no significant differences (RR: 39% vs. 9%, p=0.07; median PFS: 6.6 months vs. 3.1 months, p=0.45; median OS: 29.6 months vs. 12.9 months, p=0.62). Toxicities were mild in both treatment arms. Frequently reported toxicities were anemia and fatigue for pemetrexed, and skin rash and anorexia for gefitinib. Conclusion Both pemetrexed and gefitinib had similar efficacy with good tolerability as second-line treatment in unselected patients with advanced NSCLC. However, pemetrexed is considered more effective than gefitinib for EGFR wild-type patients.

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A network meta-analysis of immunotherapy-based treatments for advanced nonsquamous non-small cell lung cancer
Himani Aggarwal, Kerigo Ndirangu, Katherine B Winfree, Catherine Elizabeth Muehlenbein, Emily Zhu, Vanita Tongbram, Howard Thom
Journal of Comparative Effectiveness Research.2023;[Epub] CrossRef
Toxicity profile of epidermal growth factor receptor tyrosine kinase inhibitors for patients with lung cancer: A systematic review and network meta-analysis
Yi Zhao, Bo Cheng, Zisheng Chen, Jianfu Li, Hengrui Liang, Ying Chen, Feng Zhu, Caichen Li, Ke Xu, Shan Xiong, Weixiang Lu, Zhuxing Chen, Ran Zhong, Shen Zhao, Zhanhong Xie, Jun Liu, Wenhua Liang, Jianxing He
Critical Reviews in Oncology/Hematology.2021; 160: 103305. CrossRef
Efficacy and Safety of Pemetrexed and Gefitinib in the Treatment of Non-Small-Cell Lung Cancer: A Meta-Analysis
Zhihao Zhang, Xiyong Wang, Huaiqing Xiao, Dongqiang Wu, Dongliang Zhang, Qun Yu, Linna Yuan, Tao Huang
Computational and Mathematical Methods in Medicine.2021; 2021: 1. CrossRef
A meta-analysis of the safety and effectiveness of pemetrexed compared with gefitinib for pre-treated advanced or metastatic NSCLC
Xiaoxin Lu, Shengshu Li, Weizong Chen, Dongyang Zheng, Yuzhu Li, Fang Li
Medicine.2020; 99(29): e21170. CrossRef
Pemetrexed versus Gefitinib as Second-line Treatment for Advanced Non-small Cell Lung Cancer: A Meta-analysis Based on Randomized Controlled Trials
Huiyu Wang, Zunjing Zhang, Feng Liu, Miaoying Zhou, Handi Lv
Pteridines.2019; 30(1): 171. CrossRef
Gefitinib for advanced non-small cell lung cancer
Esther HA Sim, Ian A Yang, Richard Wood-Baker, Rayleen V Bowman, Kwun M Fong
Cochrane Database of Systematic Reviews.2018;[Epub] CrossRef
Pneumonitis in advanced non-small-cell lung cancer patients treated with EGFR tyrosine kinase inhibitor: Meta-analysis of 153 cohorts with 15,713 patients
Chong Hyun Suh, Hye Sun Park, Kyung Won Kim, Junhee Pyo, Hiroto Hatabu, Mizuki Nishino
Lung Cancer.2018; 123: 60. CrossRef
Second-Line Treatment of NSCLC—The Pan-ErbB Inhibitor Afatinib in Times of Shifting Paradigms
Jens Köhler
Frontiers in Medicine.2017;[Epub] CrossRef

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Pemetrexed-Erlotinib, Pemetrexed Alone, or Erlotinib Alone as Second-Line Treatment for East Asian and Non-East Asian Never-Smokers with Locally Advanced or Metastatic Nonsquamous Non-small Cell Lung Cancer: Exploratory Subgroup Analysis of a Phase II Trial: Dae Ho Lee, Jung Shin Lee, Jie Wang, Te-Chun Hsia, Xin Wang, Jongseok Kim, Mauro Orlando; Cancer Res Treat. 2015;47(4):616-629. Published online November 24, 2014; DOI: https://doi.org/10.4143/crt.2014.051

Abstract PDF PubReader ePub

Purpose
This subgroup analysis of a phase II trial was conducted to assess possible ethnicity-based trends in efficacy and safety in East Asian (EA) and non-EA populations with nonsquamous non-small cell lung cancer (NSCLC).
Materials and Methods
Never-smoker patients (n=240) with locally advanced or metastatic nonsquamous NSCLC included 133 EA patients randomized to pemetrexed supplemented with dexamethasone, folic acid, and vitamin B12 plus erlotinib (pemetrexed-erlotinib) (n=41), erlotinib (n=49), or pemetrexed (n=43), and 107 non-EA patients randomized to pemetrexed-erlotinib (n=37), erlotinib (n=33), or pemetrexed (n=37). The primary endpoint, progression-free survival (PFS), was analyzed using a multivariate Cox model.
Results
Consistent with the results of the overall study, a statistically significant difference in PFS among the three arms was noted in the EA population favoring pemetrexed-erlotinib (overall p=0.003) as compared with either single-agent arm (hazard ratio [HR], 0.48; 95% confidence interval [CI], 0.29 to 0.79; p=0.004 vs. erlotinib; HR, 0.40; 95% CI, 0.23 to 0.70; p=0.001 vs. pemetrexed). The EA patients treated with pemetrexed-erlotinib achieved a longer median PFS (7.4 months) compared with erlotinib (4.5 months) and pemetrexed (4.0 months). The PFS results also numerically favored pemetrexed-erlotinib in the non-EA population (overall p=0.210) (HR, 0.62; 95% CI, 0.37 to 1.05; p=0.078 vs. erlotinib; HR, 0.75; 95% CI, 0.42 to 1.32; p=0.320 vs. pemetrexed) (median PFS: pemetrexed-erlotinib, 6.7 months; erlotinib, 3.0 months; pemetrexed, 4.4 months).
Conclusion
The PFS results from this subset analysis in both EA and non-EA populations are consistent with the results in the overall population. The PFS advantage for pemetrexed-erlotinib is significant compared with the single agents in EA patients.

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Elisabeth Smolle, Martin Pichler
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Pemetrexed versus Gefitinib as Second-line Treatment for Advanced Non-small Cell Lung Cancer: A Meta-analysis Based on Randomized Controlled Trials
Huiyu Wang, Zunjing Zhang, Feng Liu, Miaoying Zhou, Handi Lv
Pteridines.2019; 30(1): 171. CrossRef
A Review of Regimens Combining Pemetrexed With an Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor in the Treatment of Advanced Nonsquamous Non–Small-Cell Lung Cancer
James Chih-Hsin Yang, Tony Mok, Baohui Han, Mauro Orlando, Tarun Puri, Keunchil Park
Clinical Lung Cancer.2018; 19(1): 27. CrossRef
Randomized Phase 2 Trial of Pharmacodynamic Separation of Pemetrexed and Intercalated Erlotinib Versus Pemetrexed Alone for Advanced Nonsquamous, Non–small-cell Lung Cancer
Tianhong Li, Bilal Piperdi, William V. Walsh, Mimi Kim, Laurel A. Beckett, Rasim Gucalp, Missak Haigentz, Venu G. Bathini, Huiyu Wen, Kaili Zhou, Patricia B. Pasquinelli, Srikanth Gajavelli, Meera Sreedhara, Xianhong Xie, Primo N. Lara, David R. Gandara,
Clinical Lung Cancer.2017; 18(1): 60. CrossRef
Erlotinib intercalating pemetrexed/cisplatin versus erlotinib alone in Chinese patients with brain metastases from lung adenocarcinoma: a prospective, non-randomised, concurrent controlled trial (NCT01578668)
Haihong Yang, Qiuhua Deng, Yuan Qiu, Jun Huang, Yubao Guan, Fengnan Wang, Xin Xu, Xinyun Yang
ESMO Open.2017; 2: e000112. CrossRef
Gene mutation discovery research of non-smoking lung cancer patients due to indoor radon exposure
Jung Ran Choi, Seong Yong Park, O Kyu Noh, Young Wha Koh, Dae Ryong Kang
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Epidermal Growth Factor Receptor Mutation Status in the Treatment of Non-small Cell Lung Cancer: Lessons Learned
Dae Ho Lee, Vichien Srimuninnimit, Rebecca Cheng, Xin Wang, Mauro Orlando
Cancer Research and Treatment.2015; 47(4): 549. CrossRef

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Review Article

Stereotactic Body Radiotherapy for Early Stage Lung Cancer: Yasushi Nagata; Cancer Res Treat. 2013;45(3):155-161. Published online September 30, 2013; DOI: https://doi.org/10.4143/crt.2013.45.3.155

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Stereotactic body radiation therapy (SBRT) is a newly developed technique currently in clinical use. SBRT originated from stereotactic radiosurgery for intracranial tumors. SBRT has been widely used clinically for lung cancer. The practice of SBRT demands different kinds of patient fixation, breathing control, target determination, treatment planning, and verifications. The history and current standard technique are reviewed. Clinical studies of lung cancer showed high local control rates with acceptable toxicities. Past and on-going clinical trials are reviewed.

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Radiation Oncology Journal.2015; 33(4): 265. CrossRef
Stereotactic Body Radiotherapy Using a Radiobiology-Based Regimen for Stage I Non–Small-Cell Lung Cancer: Five-Year Mature Results
Yuta Shibamoto, Chisa Hashizume, Fumiya Baba, Shiho Ayakawa, Akifumi Miyakawa, Taro Murai, Taiki Takaoka, Yukiko Hattori, Ryuji Asai
Journal of Thoracic Oncology.2015; 10(6): 960. CrossRef
Radiobiological basis of SBRT and SRS
Chang W. Song, Mi-Sook Kim, L. Chinsoo Cho, Kathryn Dusenbery, Paul W. Sperduto
International Journal of Clinical Oncology.2014; 19(4): 570. CrossRef
Recent advances in radiation oncology
Yasushi Nagata
International Journal of Clinical Oncology.2014; 19(4): 563. CrossRef
Current and emerging strategies to increase the efficacy of ionizing radiation in the treatment of cancer
Anthony J Berdis
Expert Opinion on Drug Discovery.2014; 9(2): 167. CrossRef
Radiation Oncology: Physics Advances that Minimize Morbidity
Ron R Allison, Rajen M Patel, Robert A McLawhorn
Future Oncology.2014; 10(15): 2329. CrossRef

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Original Articles

An Association Study of Polymorphisms in JAK3 Gene with Lung Cancer in the Korean Population: Wonbeak Yoo, Hae-Yun Jung, Seungjoon Lim, Jae Sook Sung, Kyong Hwa Park, Jeong Seon Ryu, Sang Won Shin, Jun Suk Kim, Jae Hong Seo, Yeul Hong Kim; Cancer Res Treat. 2011;43(2):108-116. Published online June 30, 2011; DOI: https://doi.org/10.4143/crt.2011.43.2.108

Abstract PDF PubReader ePub

PURPOSE
The genetic alteration of the janus kinases (JAKs), non-receptor tyrosine kinase, is related to the development of human cancers. However, little is known about how the sequence variation of JAK3 contributes to the development of lung cancer. This study investigated whether polymorphisms at the promoter region of the JAK3 gene are associated with the risk of lung cancer in the Korean population.
MATERIALS AND METHODS
A total of 819 subjects, including 409 lung cancer patients and 410 healthy controls were recruited. The SNaPshot assay and polymerase chain reaction-restriction fragment length polymorphism analysis were used, and logistic regression analyses were performed to characterize the association between polymorphisms of JAK3 and lung cancer risk.
RESULTS
Three polymorphisms (-672 G>A, +64 A>G and +227 G>A) of JAK3 were analyzed for large-scale genotyping (n=819). Statistical analyses revealed that polymorphisms and haplotypes in the JAK3 gene were not significantly associated with lung cancer.
CONCLUSION
JAK3 gene was not significantly associated with the risk of lung cancer in the Korean population.

Citations

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Association Analysis of Polymorphic Gene Variants in the JAK/STAT Signaling Pathway with Aging and Longevity
V. V. Erdman, T. R. Nasibullin, I. A. Tuktarova, R. Sh. Somova, O. E. Mustafina
Russian Journal of Genetics.2019; 55(6): 728. CrossRef

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Clinical Responses and Prognostic Indicators of Concurrent Chemoradiation for Non-small Cell Lung Cancer: Dong-Soo Lee, Yeon-Sil Kim, Jin-Hyoung Kang, Sang-Nam Lee, Young-Kyoun Kim, Myung-Im Ahn, Dae-Hee Han, Ie-Ryung Yoo, Young-Pil Wang, Jae-Gil Park, Sei-Chul Yoon, Hong-Seok Jang, Byung-Oak Choi; Cancer Res Treat. 2011;43(1):32-41. Published online March 31, 2011; DOI: https://doi.org/10.4143/crt.2011.43.1.32

Abstract PDF PubReader ePub

PURPOSE
To evaluate treatment outcomes and prognostic factors in non-small cell lung cancer (NSCLC) patients treated with concurrent chemoradiation.
MATERIALS AND METHODS
From January 2005 to June 2009, 51 patients were treated with concurrent chemoradiation for 3 different aims: locally advanced stage III, locally recurrent disease, and postoperative gross residual NSCLC. Median age was 63 years. Distribution of stages by the 6th edition of American Joint Committee on Cancer (AJCC) was as follows: IIIA (37.3%), IIIB (56.9%). Chemotherapy was administered every week concurrently with radiation using one of the following regimens: paclitaxel (60 mg/m2), docetaxel+cisplatin (20 mg/m2+20 mg/m2), cisplatin (30 mg/m2). Total radiation dose was 16-66.4 Gy (median, 59.4 Gy).
RESULTS
Median follow-up duration was 40.8 months. The overall response rate was 84.3% with 23 complete responses. The median survival duration for the overall patient group was 17.6 months. The 3-year survival rate was 17.8%. A total of 21 patients had recurrent disease at the following sites: loco-regional sites (23.6%), distant organs (27.5%). In the multivariate analysis of the overall patient group, a clinical tumor response (p=0.002) was the only significant prognostic factor for overall survival (OS). In the multivariate analysis of the definitive chemoradiation arm, the use of consolidation chemotherapy (p=0.022), biologically equivalent dose (BED)10 (p=0.007), and a clinical tumor response (p=0.030) were the significant prognostic factors for OS.The median survival duration of the locally recurrent group and the postoperative gross residual group were 26.4 and 23.9 months, respectively.
CONCLUSION
Our study demonstrated that clinical tumor response was significantly associated with OS in the overall patient group. Further investigations regarding the optimal radiation dose in the definitive chemoradiation and the optimal treatment scheme in locally recurrent NSCLC would be required.

Citations

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A scoping review on population-centered indicators for cancer care continuum
Vasuki Rajaguru, Jieun Jang, Jeoung A. Kwon, Jae Hyun Kim, Jaeyong Shin, Mison Chun
Frontiers in Public Health.2022;[Epub] CrossRef
Consolidation chemotherapy may improve survival for patients with locally advanced non-small-cell lung cancer receiving concurrent chemoradiotherapy - retrospective analysis of 203 cases
Lipin Liu, Nan Bi, Zhe Ji, Junling Li, Jingbo Wang, Xiaozhen Wang, Zhouguang Hui, Jima Lv, Jun Liang, Zongmei Zhou, Yan Wang, Weibo Yin, Luhua Wang
BMC Cancer.2015;[Epub] CrossRef
Treatment-related Lymphopenia in Patients With Stage III Non-Small-Cell Lung Cancer
Jian L. Campian, Xiaobu Ye, Malcolm Brock, Stuart A. Grossman
Cancer Investigation.2013; 31(3): 183. CrossRef
Does Pneumonectomy Have a Role in the Treatment of Stage IIIA Non-Small Cell Lung Cancer?
Asad A. Shah, Mathias Worni, Christopher R. Kelsey, Mark W. Onaitis, Thomas A. D'Amico, Mark F. Berry
The Annals of Thoracic Surgery.2013; 95(5): 1700. CrossRef
Thrombocytosis and immunohistochemical expression of connexin 43 at diagnosis predict survival in advanced non-small-cell lung cancer treated with cisplatin-based chemotherapy
Gangjun Du, Yingming Yang, Yaping Zhang, Ting Sun, Weijie Liu, Yingying Wang, Jiahuan Li, Houyun Zhang
Cancer Chemotherapy and Pharmacology.2013; 71(4): 893. CrossRef

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Gemcitabine and Carboplatin Combination Chemotherapy for Elderly Patients with Advanced Non-small Cell Lung Cancer: A Feasibility Study: Young Jin Yuh, Hyo Rak Lee, Sung Rok Kim; Cancer Res Treat. 2008;40(3):116-120. Published online September 30, 2008; DOI: https://doi.org/10.4143/crt.2008.40.3.116

Abstract PDF PubReader ePub

Purpose

Although platinum based chemotherapy is known to improve the survival duration for the patients with non-small cell lung cancer, the role of platinum for elderly patient is not yet clear. We administered gemcitabine and carboplatin combination therapy to elderly patients with NSCLC. The aim of this study was to evaluate the efficacy and toxicities of this regimen for elderly patients.

Materials and Methods

The eligibility criteria were as follows: pathologically confirmed NSCLC, an age ≥65 years, advanced disease with stage IIIB or IV and the patients were chemotherapy-naive. The treatment regimen was as follows; gemcitabine 1,000 mg/m² was administered on days 1 and 8 and carboplatin AUC=5 was administered on day 1. This regimen was repeated every 3 weeks. The efficacy was evaluated in terms of the response rate, the time to progression and the overall survival duration.

Results

From Dec 2001 to Feb 2005, a total of 20 patients were entered into this study. The median patient age was 68 years (range: 65~75). 19 patients were evaluable for their treatment response. A partial response was obtained in 8 patients (response rate: 42.1%, 95% CI: 19.4~64.8%). The median time to progression and the survival duration were 136 days and 453 days, respectively. Among a total of 65 cycles of treatment, grade 3 or 4 leukopenia and thrombocytopenia were observed in 7.7% and 13.9% of the cycles, respectively. Grade 3 or 4 vomiting was observed in 7.7% of the cycles. Grade 3 skin rash developed in 1.5% of the cycles. 1 patient died of septic shock after chemotherapy.

Conclusions

Gemcitabine and carboplatin combination chemotherapy was relatively safe and effective for treating elderly patients with NSCLC.

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Gefitinib-Integrated Regimen versus Chemotherapy Alone in Heavily Pretreated Patients with Epidermal Growth Factor Receptor–Mutated Lung Adenocarcinoma: A Case-Control Study
Nan-Jie Zhao, Zhao Sun, Yuzhou Wang, Xiaohong Ning, Ning Jia, Changting Meng, Yingyi Wang
Translational Oncology.2014; 7(4): 508. CrossRef
Can Serum be Used for Analyzing the EGFR Mutation Status in Patients with Advanced Non-small Cell Lung Cancer?
Seung Tae Kim, Hae-Yun Jung, Jae Sook Sung, Uk Hyun Jo, Tomoaki Tanaka, Koichi Hagiwara, Kyong Hwa Park, Sang Won Shin, Jun Suk Kim, Yeul Hong Kim
American Journal of Clinical Oncology.2013; 36(1): 57. CrossRef
Can mutations of EGFR and KRAS in serum be predictive and prognostic markers in patients with advanced non-small cell lung cancer (NSCLC)?
Seung Tae Kim, Jae Sook Sung, Uk Hyun Jo, Kyong Hwa Park, Sang Won Shin, Yeul Hong Kim
Medical Oncology.2013;[Epub] CrossRef
Efficacy and feasibility of gemcitabine and carboplatin as first-line chemotherapy in elderly patients with advanced non-small cell lung cancer
Kyu-Hyoung Lim, Hui-Young Lee, Seo-Young Song
Chinese Medical Journal.2013; 126(24): 4644. CrossRef
Randomized Phase II Study of Two Schedules of Carboplatin and Gemcitabine for Stage IIIB and IV Advanced Non-Small Cell Lung Cancer (JACCRO LC-01 Study)
Fumio Imamura, Makoto Nishio, Rintaro Noro, Masahiro Tsuboi, Norihiko Ikeda, Akira Inoue, Yoshinobu Ohsaki, Yukio Kimura, Kazumi Nishino, Junji Uchida, Takeshi Horai
Chemotherapy.2011; 57(4): 357. CrossRef
Carboplatin and Gemcitabine in First-Line Treatment of Elderly Patients with Advanced Non-Small Cell Lung Cancer: Data from a Retrospective Study
G. Genestreti, N. Giovannini, M. Frizziero, M. Maglie, S. Sanna, S. Cingarlini, A.M. Molino, S. Piciucchi, G.L. Cetto, A. Santo
Journal of Chemotherapy.2011; 23(4): 232. CrossRef
Comparison of gefitinib versus erlotinib in patients with nonsmall cell lung cancer who failed previous chemotherapy
Seung Tae Kim, Jeeyun Lee, Jeong‐hoon Kim, Young‐Woong Won, Jong‐Mu Sun, Jina Yun, Yeon Hee Park, Jin Seok Ahn, Keunchil Park, Myung‐Ju Ahn
Cancer.2010; 116(12): 3025. CrossRef
Treatment of Older Patients With Non–Small-Cell Lung Cancer: Walking the Therapeutic Tightrope
George R. Simon
Journal of Clinical Oncology.2010; 28(4): 523. CrossRef

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Cyclin D1 Overexpression, p16 Loss, and pRb Inactivation Play a Key Role in Pulmonary Carcinogenesis and have a Prognostic Implication for the Long-term Survival in Non-small Cell Lung Carcinoma Patients: Na-Hye Myong; Cancer Res Treat. 2008;40(2):45-52. Published online June 30, 2008; DOI: https://doi.org/10.4143/crt.2008.40.2.45

Abstract PDF PubReader ePub

Purpose

We investigated the immunoexpressions of cyclin D1, cyclin-dependent kinase inhibitor p16 and phosphorylated retinoblastoma (p-pRb) proteins in non-small cell lung carcinoma (NSCLC) to demonstrate their key roles in tumorigenesis, their relationship with the clinicopathologic factors, and their prognostic influences on the long-term survival.

Materials and Methods

115 surgically resected NSCLCs were immunohistochemically stained for the G₁/S cell cycle proteins, with using a tissue microarray. The correlation between their immunoexpressions and the clinicopathologic prognostic factors, their inter-relationships and their single or combined effects on the long-term survival (over 5 years) were statistically analyzed by SPSS15.0.

Results

Loss of p16 was found in 75% of the cases and cyclin D1 overexpression and phosphorylated pRb (p-pRb) were found in 64% and 46%, respectively. Cyclin D1 overexpression was correlated with the p16 loss and pRb inactivation by phosphorylation. The p16 loss was tightly associated with p-pRb. The Kaplan-Meier survival curves disclosed that the cyclin D1-positive group and the p16-negative group showed a rapid decline of survival at the point of about 5 years after surgery and thereafter. The combined actions of cyclin D1 overexpression, loss of p16 and pRb inactivation tended to have an adverse influence on the prolonged survival.

Conclusions

The observation that cyclin D1 overexpression, p16 loss and pRb inactivation were largely found in NSCLCs suggests that they play an important role in pulmonary carcinogenesis. Also, their inverse or positive correlations indicate that the G₁/S cell cycle proteins may act alternatively or synergistically on the mechanisms by which tumor cells escape the G₁ restriction point. Finally, their solitary or combined actions might have a long-term effect on the survival.

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Shimeng Zhao, Zhiguang Chen, Shuang Han, Hongmin Wu
Experimental and Therapeutic Medicine.2021;[Epub] CrossRef
Co-Occurrence of Differentiated Thyroid Cancer and Second Primary Malignancy: Correlation with Expression Profiles of Mismatch Repair Protein and Cell Cycle Regulators
Chih-Yi Liu, Ching-Shui Huang, Chi-Cheng Huang, Wei-Chi Ku, Hsing-Yu Shih, Chi-Jung Huang
Cancers.2021; 13(21): 5486. CrossRef
Ultrasound-Targeted Microbubble Destruction Mediated si-CyclinD1 Inhibits the Development of Hepatocellular Carcinoma via Suppression of PI3K/AKT Signaling Pathway

Wei Yan, Li Cheng, Dongmei Zhang
Cancer Management and Research.2020; Volume 12: 10829. CrossRef
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Sheetal Chauhan, Seema Sen, Anjana Sharma, Seema Kashyap, Radhika Tandon, Neelam Pushker, Murugesan Vanathi, Shyam S. Chauhan
Applied Immunohistochemistry & Molecular Morphology.2018; 26(6): e70. CrossRef
Bronchial-pulmonary adenocarcinoma subtyping relates with different molecular pathways
Vítor Sousa, Bruno Bastos, Maria Silva, Ana Maria Alarcão, Lina Carvalho
Revista Portuguesa de Pneumologia (English Edition).2015; 21(5): 259. CrossRef
Mechanisms of environmental chemicals that enable the cancer hallmark of evasion of growth suppression
Rita Nahta, Fahd Al-Mulla, Rabeah Al-Temaimi, Amedeo Amedei, Rafaela Andrade-Vieira, Sarah N. Bay, Dustin G. Brown, Gloria M. Calaf, Robert C. Castellino, Karine A. Cohen-Solal, Anna Maria Colacci, Nichola Cruickshanks, Paul Dent, Riccardo Di Fiore, Stefa
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Prognostic significance of WNT and hedgehog pathway activation markers in cancer of unknown primary
George Fotopoulos, Anna Gousia, Eleni Bareta, Epameinondas Koumpis, Sofia Chrisafi, Matthaios Bobos, Vassiliki Malamou‐Mitsi, George Fountzilas, Nicholas Pavlidis, George Pentheroudakis
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WITHDRAWN: Bronchial-pulmonary adenocarcinoma subtyping relates with different molecular pathways
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Yuan-Yuan Hu, Rong Zheng, Chong Guo, Yu-Ming Niu
Diagnostic Pathology.2014;[Epub] CrossRef
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Youssef Yakkioui, Jacobus J. van Overbeeke, Remco Santegoeds, Manon van Engeland, Yasin Temel
Biochimica et Biophysica Acta (BBA) - Reviews on Cancer.2014; 1846(2): 655. CrossRef
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