Cancer Research and Treatment

Original Articles

General

The Survival and Financial Benefit of Investigator-Initiated Trials Conducted by Korean Cancer Study Group: Bum Jun Kim, Chi Hoon Maeng, Bhumsuk Keam, Young-Hyuck Im, Jungsil Ro, Kyung Hae Jung, Seock-Ah Im, Tae Won Kim, Jae Lyun Lee, Dae Seog Heo, Sang-We Kim, Keunchil Park, Myung-Ju Ahn, Byoung Chul Cho, Hoon-Kyo Kim, Yoon-Koo Kang, Jae Yong Cho, Hwan Jung Yun, Byung-Ho Nam, Dae Young Zang; Cancer Res Treat. 2025;57(1):39-46. Published online July 10, 2024; DOI: https://doi.org/10.4143/crt.2024.421

Abstract PDF PubReader ePub: Purpose
The Korean Cancer Study Group (KCSG) is a nationwide cancer clinical trial group dedicated to advancing investigator-initiated trials (IITs) by conducting and supporting clinical trials. This study aims to review IITs conducted by KCSG and quantitatively evaluate the survival and financial benefits of IITs for patients.
Materials and Methods
We reviewed IITs conducted by KCSG from 1998 to 2023, analyzing progression-free survival (PFS) and overall survival (OS) gains for participants. PFS and OS benefits were calculated as the difference in median survival times between the intervention and control groups, multiplied by the number of patients in the intervention group. Financial benefits were assessed based on the cost of investigational products provided.
Results
From 1998 to 2023, KCSG conducted 310 IITs, with 133 completed and published. Of these, 21 were included in the survival analysis. The analysis revealed that 1,951 patients in the intervention groups gained a total of 2,558.4 months (213.2 years) of PFS and 2,501.6 months (208.5 years) of OS, with median gains of 1.31 months in PFS and 1.58 months in OS per patient. When analyzing only statistically significant results, PFS and OS gain per patients was 1.69 months and 3.02 months, respectively. Investigational drug cost analysis from six available IITs indicated that investigational products provided to 252 patients were valued at 10,400,077,294 won (approximately 8,046,481 US dollars), averaging about 41,270,148 won (approximately 31,930 US dollars) per patient.
Conclusion
Our findings, based on analysis of published research, suggest that IITs conducted by KCSG led to survival benefits for participants and, in some studies, may have provided financial benefits by providing investment drugs.

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Lung and Thoracic cancer

Adjuvant Pembrolizumab in Patients with Stage IIIA/N2 Non–Small Cell Lung Cancer Completely Resected after Neoadjuvant Concurrent Chemoradiation: A Prospective, Open-Label, Single-Arm, Phase 2 Trial: Junghoon Shin, Sehhoon Park, Kyung Hwan Kim, Eui-Cheol Shin, Hyun Ae Jung, Jong Ho Cho, Jong-Mu Sun, Se-Hoon Lee, Yong Soo Choi, Jin Seok Ahn, Jhingook Kim, Keunchil Park, Young Mog Shim, Hong Kwan Kim, Jae Myoung Noh, Yong Chan Ahn, Hongryull Pyo, Myung-Ju Ahn; Cancer Res Treat. 2024;56(4):1084-1095. Published online April 30, 2024; DOI: https://doi.org/10.4143/crt.2024.084

Abstract PDF Supplementary Material PubReader ePub: Purpose
Optimal treatment for stage IIIA/N2 non–small cell lung cancer (NSCLC) is controversial. We aimed to assess the efficacy and safety of adjuvant pembrolizumab for stage IIIA/N2 NSCLC completely resected after neoadjuvant concurrent chemoradiation therapy (CCRT).
Materials and Methods
In this open-label, single-center, single-arm phase 2 trial, patients with stage IIIA/N2 NSCLC received adjuvant pembrolizumab for up to 2 years after complete resection following neoadjuvant CCRT. The primary endpoint was disease-free survival (DFS). Secondary endpoints included overall survival (OS) and safety. As an exploratory biomarker analysis, we evaluated the proliferative response of blood CD39⁺PD-1⁺CD8⁺ T cells using fold changes in the percentage of proliferating Ki-67⁺ cells from days 1 to 7 of cycle 1 (Ki-67_D7/D1).
Results
Between October 2017 and October 2018, 37 patients were enrolled. Twelve (32%) and three (8%) patients harbored EGFR and ALK alterations, respectively. Of 34 patients with programmed cell death ligand 1 assessment, 21 (62%), nine (26%), and four (12%) had a tumor proportion score of < 1%, 1%-50%, and ≥ 50%, respectively. The median follow-up was 71 months. The median DFS was 22.4 months in the overall population, with a 5-year DFS rate of 29%. The OS rate was 86% at 2 years and 76% at 5 years. Patients with tumor recurrence within 6 months had a significantly lower Ki-67D7/D1 among CD39⁺PD-1⁺CD8⁺ T cells than those without (p=0.036). No new safety signals were identified.
Conclusion
Adjuvant pembrolizumab may offer durable disease control in a subset of stage IIIA/N2 NSCLC patients after neoadjuvant CCRT and surgery.

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Expanded Access Program Pralsetinib in Advanced Non–Small Cell Lung Cancer with Rearranged during Transfection (RET) Gene Rearrangement: Youngkyung Jeon, Hyun Ae Jung, Sehhoon Park, Jong-Mu Sun, Jin Seok Ahn, Myung-Ju Ahn, Keunchil Park, Se-Hoon Lee; Cancer Res Treat. 2023;55(4):1144-1151. Published online May 22, 2023; DOI: https://doi.org/10.4143/crt.2023.403

Abstract PDF PubReader ePub

Purpose
Rearranged during transfection (RET) gene rearrangement is a well-known driver event in non–small cell lung cancer (NSCLC). Pralsetinib is a selective inhibitor of RET kinase and has shown efficacy in oncogenic RET-altered tumors. This study evaluated the efficacy and safety of expanded access program (EAP) use of pralsetinib in pretreated, advanced NSCLC patients with RET rearrangement.
Materials and Methods
Patients who received pralsetinib as part of the EAP at Samsung Medical Center were evaluated through a retrospective chart review. The primary endpoint was overall response rate (ORR) per the Response Evaluation Criteria in Solid Tumors (RECIST) ver. 1.1 guidelines. Secondary endpoints were duration of response, progression-free survival (PFS), overall survival (OS), and safety profiles.
Results
Between April 2020 and September 2021, 23 of 27 patients were enrolled in the EAP study. Two patients who were not analyzed due to brain metastasis and two patients whose expected survival was within 1 month were excluded from the analysis. After a median follow-up period of 15.6 months (95% confidence interval [CI], 10.0 to 21.2), ORR was 56.5%, the median PFS was 12.1 months (95% CI, 3.3 to 20.9), and the 12-month OS rate was 69.6%. The most frequent treatment-related adverse events (TRAEs) were edema (43.5%) and pneumonitis (39.1%). A total of 8.7% of patients experienced extra-pulmonary tuberculosis. TRAEs with a common grade of three or worse were neutropenia (43.5%) and anemia (34.8%). Dose reduction was required in nine patients (39.1%).
Conclusion
Pralsetinib presents a clinical benefit when used in patients with RET-rearranged NSCLC, consistent with a pivotal study.

Citations

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Real-World Outcomes of Pralsetinib in RET Fusion-Positive NSCLC
Francesca Lucibello, Valérie Gounant, Mihaela Aldea, Michaël Duruisseaux, Maurice Perol, Christos Chouaid, Jaafar Bennouna, Vincent Fallet, Aldo Renault, Florian Guisier, Etienne Giroux-Leprieur, Marie Wislez, Anne-Claire Toffart, Julien Mazieres, Clémenc
JTO Clinical and Research Reports.2025; 6(1): 100743. CrossRef
Clinical evidence and adverse event management update of patients with RET- rearranged advanced non-small-cell lung cancer (NSCLC) treated with pralsetinib
Giuseppe Lo Russo, Paolo Bironzo, Chiara Bennati, Laura Bonanno, Annamaria Catino, Giulio Metro, Iacopo Petrini, Marco Russano, Antonio Passaro
Critical Reviews in Oncology/Hematology.2024; 194: 104243. CrossRef
RET Fusion Testing in Patients With NSCLC: The RETING Study
Esther Conde, Susana Hernandez, Jose Luis Rodriguez Carrillo, Rebeca Martinez, Marta Alonso, Daniel Curto, Beatriz Jimenez, Alejandra Caminoa, Amparo Benito, Pilar Garrido, Sergi Clave, Edurne Arriola, Isabel Esteban-Rodriguez, Javier De Castro, Irene San
JTO Clinical and Research Reports.2024; 5(4): 100653. CrossRef
Efficacy and safety of pralsetinib in patients with RET fusion positive non–small cell lung cancer: An observational real world study
Dehua Liao, Minghui Long, Jiwen Zhang, Xingyu Wei, Fei Li, Ting Yan, Desong Yang
Lung Cancer.2024; 196: 107936. CrossRef

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Head and Neck cancer

Phase II Trial of Combined Durvalumab Plus Tremelimumab with Proton Therapy for Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma: Hana Kim, Sehhoon Park, Hyun Ae Jung, Se-Hoon Lee, Keunchil Park, Yong Chan Ahn, Dongryul Oh, Myung-Ju Ahn; Cancer Res Treat. 2023;55(4):1104-1112. Published online May 17, 2023; DOI: https://doi.org/10.4143/crt.2023.502

Abstract PDF Supplementary Material PubReader ePub

Purpose
This phase II study investigated whether durvalumab/tremelimumab with proton therapy improves the objective response rate (ORR), overall survival (OS), and progression-free survival (PFS) in heavily treated recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) patients.
Materials and Methods
Patients who previously received more than one chemotherapy, including at least one platinum-based regimen, and who had at least two measurable lesions were enrolled. Patients received 1,500 mg durvalumab intravenously combined with 75 mg tremelimumab intravenously every 4 weeks for four cycles followed by 1,500 mg durvalumab every 4 weeks. After one cycle of the durvalumab/tremelimumab treatment, proton therapy was given with a total dose of 25 Gy in 5 Gy daily fractions to one of the measurable lesions. We also assessed the ORR in the target lesion outside the radiation field to evaluate the abscopal effect.
Results
Thirty-one patients were enrolled between March 2018 and July 2020. With 8.6 months of follow-up, the ORR was 22.6% (7/31), including one complete response and six partial responses. The median OS was 8.4 months (95% confidence interval [CI], 2.5 to 14.3) and the median PFS was 2.4 months (95% CI, 0.6 to 4.2). Among the 23 evaluable patients who completed proton therapy, the ORR was 30.4% (7/23). The median OS was 11.1 months (95% CI, 6.5 to 15.8), and the median PFS was 3.7 months (95% CI, 1.6 to 5.7). Grade 3 or higher adverse events were observed in six patients (19.4%) as follows: anemia (n=1), constipation (n=1), electrolyte imbalances (n=2), hyperglycemia (n=1), and pneumonia (n=1).
Conclusion
The combination of durvalumab/tremelimuab with proton therapy was tolerated well and had encouraging anti-tumor efficacy in non-irradiated tumor lesions of heavily treated HNSCC patients.

Citations

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Abscopal effect in maxillary sinus cancer: Insights from two case reports and a literature review
Akihiro Sakai, Koji Ebisumoto, Hiroaki Iijima, Mayu Yamauchi, Daisuke Maki, Tsuyoshi Fukuzawa, Kenji Okami
Cancer Reports.2024;[Epub] CrossRef
Solid tumours showing oligoprogression to immune checkpoint inhibitors have the potential for abscopal effects
Makoto Ito, Souichiro Abe, Sou Adachi, Yukihiko Oshima, Arisa Takeuchi, Wataru Ohashi, Takashi Iwata, Tetsuya Ogawa, Akiko Ota, Yasuaki Kubota, Takahito Okuda, Kojiro Suzuki
Japanese Journal of Radiology.2024; 42(4): 424. CrossRef
Durvalumab with or without tremelimumab for patients with recurrent or metastatic squamous cell carcinoma of the head and neck: a systematic review and meta-analysis
Xiao Han, Haidong Zhang, Kai Sun, Jing Li, Wanjuan Wu, Kai Liu, Zhenkun Yu
Frontiers in Immunology.2024;[Epub] CrossRef
Kaplan lecture 2023: lymphopenia in particle therapy
Marco Durante
International Journal of Radiation Biology.2024; 100(5): 669. CrossRef
Clinical application of high‐LET radiotherapy combined with immunotherapy in malignant tumors
Kexin Meng, Haijun Lu
Precision Radiation Oncology.2024; 8(1): 42. CrossRef
Research progress of immunotherapy for advanced head and neck cancer
Anchi Sun, Zhiwei Xing, Rongrong Lv, Pengyuan Niu, Bao Zhao, Shiyin Ma, Hui Li
Medical Oncology.2024;[Epub] CrossRef
A review and bibliometric analysis of global research on proton radiotherapy
Ge Song, Zhi Zheng, Yingming Zhu, Yaoting Wang, Song Xue
Medicine.2024; 103(19): e38089. CrossRef
Cutaneous Squamous Cell Carcinoma: An Updated Review
Rina Jiang, Mike Fritz, Syril Keena T. Que
Cancers.2024; 16(10): 1800. CrossRef
Radiotherapy and immunology
Liangliang Wang, Connor Lynch, Sean P. Pitroda, András Piffkó, Kaiting Yang, Amy K. Huser, Hua Laura Liang, Ralph R. Weichselbaum
Journal of Experimental Medicine.2024;[Epub] CrossRef
The Evolving Paradigm of Immunotherapy in Head-and-neck Squamous Cell Cancers
Riccardo Gili, Paolo Bossi
Journal of Head & Neck Physicians and Surgeons.2024; 12(1): 13. CrossRef
Neoadjuvant Immunotherapy in Head and Neck Cancers: A Paradigm Shift in Treatment Approach
Alessia Zotta, Maria Luisa Marciano, Francesco Sabbatino, Alessandro Ottaiano, Marco Cascella, Monica Pontone, Massimo Montano, Ester Calogero, Francesco Longo, Morena Fasano, Teresa Troiani, Fortunato Ciardiello, Fabiana Raffaella Rampetta, Giovanni Salz
Biomedicines.2024; 12(10): 2337. CrossRef
Emerging Radiotherapy Technologies for Head and Neck Squamous Cell Carcinoma: Challenges and Opportunities in the Era of Immunotherapy
Carmen Kut, Harry Quon, Xuguang Scott Chen
Cancers.2024; 16(24): 4150. CrossRef

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Lung and Thoracic cancer

Efficacy and Safety of Ceritinib 450 mg/day with Food and 750 mg/day in Fasted State in Treatment-Naïve Patients with ALK+ Non–Small Cell Lung Cancer: Results from the ASCEND-8 Asian Subgroup Analysis: Byoung Chul Cho, Dong-Wan Kim, Ullas Batra, Keunchil Park, Sang-We Kim, Cheng-Ta Yang, Pei-Jye Voon, Virote Sriuranpong, K. Govind Babu, Khalid Amin, Yingbo Wang, Paramita Sen, Khemaies Slimane, Sarayut Geater; Cancer Res Treat. 2023;55(1):83-93. Published online March 25, 2022; DOI: https://doi.org/10.4143/crt.2021.1571

Abstract PDF Supplementary Material PubReader ePub

Purpose
Previous report from the ASCEND-8 trial showed consistent efficacy with less gastrointestinal (GI) toxicity in patients with anaplastic lymphoma kinase-rearranged (ALK+) advanced/metastatic non–small cell lung cancer (NSCLC) treated with ceritinib 450-mg with food compared with 750-mg fasted. In this subgroup analysis, we report outcomes in Asian patients of the ASCEND-8 trial.
Materials and Methods
Key efficacy endpoints were blinded independent review committee (BIRC)–assessed overall response rate (ORR) and duration of response (DOR) evaluated per Response Evaluation Criteria in Solid Tumors v1.1. Other efficacy endpoints were investigator-assessed ORR and DOR; BIRC- and investigator-assessed progression-free survival (PFS) and disease control rate; overall survival (OS). Safety was evaluated by frequency and severity of adverse events.
Results
At final data cutoff (6 March 2020), 198 treatment-naïve patients were included in efficacy analysis, of which 74 (37%) comprised the Asian subset; 450-mg fed (n=29), 600-mg fed (n=19), and 750-mg fasted (n=26). Baseline characteristics were mostly comparable across study arms. At baseline, more patients in 450-mg fed arm (44.8%) had brain metastases than in 750-mg fasted arm (26.9%). Per BIRC, patients in the 450-mg fed arm had a numerically higher ORR, 24-month DOR rate and 24-month PFS rate than the 750-mg fasted arm. The 36-month OS rate was 93.1% in 450-mg fed arm and 70.9% in 750-mg fasted arm. Any-grade GI toxicity occurred in 82.8% and 96.2% of patients in the 450-mg fed and 750-mg fasted arms, respectively.
Conclusion
Asian patients with ALK+ advanced/metastatic NSCLC treated with ceritinib 450-mg fed showed numerically higher efficacy and lower GI toxicity than 750-mg fasted patients.

Citations

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Economic Evaluation of Targeted Therapies for Anaplastic Lymphoma Kinase– and ROS1 Fusion–Positive Non–Small Cell Lung Cancer in India
Dharna Gupta, Nidhi Gupta, Navneet Singh, Shankar Prinja
JCO Global Oncology.2024;[Epub] CrossRef
Uniqueness of lung cancer in Southeast Asia
Vanita Noronha, Atul Budukh, Pankaj Chaturvedi, Srikanth Anne, Anshu Punjabi, Maheema Bhaskar, Tarini P. Sahoo, Nandini Menon, Minit Shah, Ullas Batra, Shrinidhi Nathany, Rajiv Kumar, Omshree Shetty, Trupti Pai Ghodke, Abhishek Mahajan, Nivedita Chakrabar
The Lancet Regional Health - Southeast Asia.2024; 27: 100430. CrossRef
Small intestinal metastasis in a lung adenocarcinoma patient with concurrent EML4-ALK V3 and TP53 mutations after distinct responses to tyrosine kinase inhibitors: A case report
Lingling Zhu, Yingchun Zhao, Yongqian Zhang, Zhai Liu, Wenhua Ma, Ying Guo, Qian Wang, Yan Guo, Hengxu Lv, Min Zhao
Heliyon.2024; 10(19): e38839. CrossRef

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Long-term Survival in Non–Small Cell Lung Cancer Patients with Metachronous Brain-Only Oligorecurrence Who Underwent Definitive Treatment: Hongsik Kim, Sehhoon Park, Hyun Ae Jung, Jong-Mu Sun, Se-Hoon Lee, Jin Seok Ahn, Keunchil Park, Myung-Ju Ahn; Cancer Res Treat. 2022;54(1):150-156. Published online May 6, 2021; DOI: https://doi.org/10.4143/crt.2021.306

Abstract PDF PubReader ePub

Purpose
Metachronous brain-only oligorecurrence in patients with non–small cell lung cancer (NSCLC) is a rare event with favorable prognosis, but the clinical outcome has not been fully determined. We retrospectively analyzed clinical outcomes and prognostic factors in metachronous brain-only oligorecurrence in patients with NSCLC who underwent definitive treatment.
Materials and Methods
We reviewed 4,437 NSCLC patients without oncogenic driver mutations who underwent definitive treatment between 2008 and 2018. Among them, we identified 327 patients who developed 1 to 5 brain metastases with or without systemic metastasis. Of the 327 patients, 71 had metachronous brain-only oligorecurrence without extracranial progression and were treated with local therapy to the brain. Overall survival (OS), progression-free survival (PFS), and prognostic factors affecting OS were analyzed.
Results
The median OS was 38.9 months (95% confidence interval [CI], 21.8 to 56.1 months) in 71 patients. The 2-year OS rate was 67.8% and the 5-year OS rate was 33.1%. The median PFS was 25.5 months (95% CI, 12.2 to 14.4 months). The longest surviving patient had a survival period of 115 months. Through multivariate analysis, Eastern Cooperative Oncology Group ≥ 1 (hazard ratio, 5.33; p=0.005) was associated with poor survival. There was no significant difference in OS between patients with local therapy and those with local plus systemic therapy (18.5 months vs. 34.7 months, p=0.815).
Conclusion
Metachronous brain-only oligorecurrence NSCLC patients who underwent definitive treatment experienced long-term survival with local therapy, highlighting the unique patient population. The role of systemic chemotherapy in this patient population requires further investigation.

Citations

Citations to this article as recorded by

Brain Metastasis of Non-small Cell Lung Cancer After Disease-Free Survival of 5 years: Case Series and Comprehensive Literature Review
Takahiro Suzuki, Shoichi Deguchi, Keigo Matsushima, Shinya Katsumata, Hideaki Kojima, Maeda Koki, Hayato Konno, Mitsuhiro Isaka, Takuma Oishi, Yasuhisa Ohde, Takashi Sugino, Koichi Mitsuya, Nakamasa Hayashi
World Neurosurgery.2024; 186: e353. CrossRef
Complex situations in lung cancer: multifocal disease, oligoprogression and oligorecurrence
Raphael Werner, Nina Steinmann, Herbert Decaluwe, Hiroshi Date, Dirk De Ruysscher, Isabelle Opitz
European Respiratory Review.2024; 33(172): 230200. CrossRef

6,317 View
157 Download
2 Web of Science
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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.

Citations

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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

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.

Citations

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Targeting the Tumor Microenvironment in EGFR-Mutant Lung Cancer: Opportunities and Challenges
Jeong Uk Lim, Junyang Jung, Yeon Wook Kim, Chi Young Kim, Sang Hoon Lee, Dong Won Park, Sue In Choi, Wonjun Ji, Chang Dong Yeo, Seung Hyeun Lee
Biomedicines.2025; 13(2): 470. CrossRef
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,
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Salvage Concurrent Chemo-radiation Therapy for Loco-regional Recurrence Following Curative Surgery of Non-small Cell Lung Cancer: Kyung Hwa Lee, Yong Chan Ahn, Hongryull Pyo, Jae Myoung Noh, Seung Gyu Park, Tae Gyu Kim, Eonju Lee, Heerim Nam, Hyebin Lee, Jong-Mu Sun, Jin Seok Ahn, Myung-Ju Ahn, Keunchil Park; Cancer Res Treat. 2019;51(2):769-776. Published online September 11, 2018; DOI: https://doi.org/10.4143/crt.2018.366

Abstract PDF PubReader ePub

Purpose
This study is to report clinical outcomes of salvage concurrent chemo-radiation therapy (CCRT) in treating patients with loco-regional recurrence (LRR) following initial complete resection of non-small cell lung cancer.
Materials and Methods
Between February 2004 and December 2016, 127 patients underwent salvage CCRT for LRR. The median radiation therapy (RT) dose was 66 Gy and clinical target volume was to cover recurrent lesion with margin without elective inclusion of regional lymphatics. Majority of patients (94.5%) received weekly platinum-based doublet chemotherapy during RT course.
Results
The median follow-up time from the start of CCRT was 25 months. The median survival duration was 49 months, and overall survival (OS) rates at 2 and 5 years were 72.9% and 43.9%. The 2- and 5-year rates of in-field failure-free survival, distant metastasis free survival, and progression free survival were 82.4% and 73.8%, 50.4% and 39.9%, and 34.6% and 22.3%, respectively. Grade ≥ 3 radiation-related esophagitis and pneumonitis occurred in 14 (11.0%) and six patients (4.7%), respectively. On both univariate and multivariate analysis, higher biologically equivalent dose (BED10) (≥ 79.2 Gy10 vs. < 79.2 Gy10; hazard ratio [HR], 0.431), smaller CTV (≤ 80 cm3 vs. > 80 cm3; HR, 0.403), and longer disease-free interval (> 1 year vs. ≤ 1 year; HR, 0.489) were significantly favorable factors for OS.
Conclusion
The current study has demonstrated that high dose salvage CCRT focused to the involved lesion only was highly effective and safe. In particular, higher BED₁₀, smaller CTV, and longer disease-free interval were favorable factors for improved survival.

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Yoichi Ohtaki, Toshiteru Nagashima, Naoko Okano, Nobuteru Kubo, Takeru Ohtaka, Noriaki Sunaga, Reiko Sakurai, Yosuke Miura, Seshiru Nakazawa, Natsuko Kawatani, Tomohiro Yazawa, Ryohei Yoshikawa, Eiji Narusawa, Ken Shirabe
Thoracic Cancer.2024; 15(11): 859. CrossRef
Durvalumab after chemoradiotherapy for locoregional recurrence of completely resected non–small‐cell lung cancer (NEJ056)
Megumi Furuta, Hidehito Horinouchi, Isao Yokota, Teppei Yamaguchi, Shoichi Itoh, Takafumi Fukui, Akira Iwashima, Jun Sugisaka, Yu Miura, Hisashi Tanaka, Taichi Miyawaki, Hiroshi Yokouchi, Keita Miura, Ryota Saito, Go Saito, Tatsuhiko Kamoshida, Yusuke Uch
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Hongsheng Deng, Juan Zhou, Hualin Chen, Xiuyu Cai, Ran Zhong, Feng Li, Bo Cheng, Caichen Li, Qingzhu Jia, Caicun Zhou, René Horsleben Petersen, Gaetano Rocco, Alex Brunelli, Calvin S.H. Ng, Thomas A. D’Amico, Chunxia Su, Jianxing He, Wenhua Liang, Bo Zhu
International Journal of Surgery.2023;[Epub] CrossRef
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Kathleen Bowes, Nick Jovanoski, Audrey E. Brown, Danilo Di Maio, Rossella Belleli, Shkun Chadda, Seye Abogunrin
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Hyunju Shin, Jae Myoung Noh, Hongryull Pyo, Yong Chan Ahn, Dongryul Oh
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Lung Cancer.2021; 156: 82. CrossRef
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Yoon Young Jo, Su Ssan Kim, Si Yeol Song, Eun Kyung Choi
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Cole Friedes, Nicholas Mai, Wei Fu, Chen Hu, Peijin Han, Kristen A. Marrone, K. Ranh Voong, Russell K. Hales
Lung Cancer.2020; 145: 119. CrossRef

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A Randomized, Open-Label, Phase II Study Comparing Pemetrexed Plus Cisplatin Followed by Maintenance Pemetrexed versus Pemetrexed Alone in Patients with Epidermal Growth Factor Receptor (EGFR)-Mutant Non-small Cell Lung Cancer after Failure of First-Line EGFR Tyrosine Kinase Inhibitor: KCSG-LU12-13: Kwai Han Yoo, Su Jin Lee, Jinhyun Cho, Ki Hyeong Lee, Keon Uk Park, Ki Hwan Kim, Eun Kyung Cho, Yoon Hee Choi, Hye Ryun Kim, Hoon-Gu Kim, Heui June Ahn, Ha Yeon Lee, Hwan Jung Yun, Jin-Hyoung Kang, Jaeheon Jeong, Moon Young Choi, Sin-Ho Jung, Jong-Mu Sun, Se-Hoon Lee, Jin Seok Ahn, Keunchil Park, Myung-Ju Ahn; Cancer Res Treat. 2019;51(2):718-726. Published online September 3, 2018; DOI: https://doi.org/10.4143/crt.2018.324

Abstract PDF PubReader ePub

Purpose
The optimal cytotoxic regimens have not been established for patients with non-small cell lung cancer (NSCLC) who develop disease progression on first-line epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI).
Materials and Methods
We conducted a multi-center randomized phase II trial to compare the clinical outcomes between pemetrexed plus cisplatin combination therapy followed by maintenance pemetrexed (PC) and pemetrexed monotherapy (P) after failure of first-line EGFR-TKI. The primary objective was progression-free survival (PFS), and secondary objectives included overall response rate (ORR), overall survival (OS), health-related quality of life (HRQOL), and safety and toxicity profiles.
Results
A total of 96 patientswere randomized, and 91 patientswere treated at 14 centers in Korea. The ORR was 34.8% (16/46) for the PC arm and 17.8% (8/45) for the P arm (p=0.066). With 23.4 months of follow-up, the median PFS was 5.4 months in the PC arm and 6.4 months in the P arm (p=0.114). The median OS was 17.9 months and 15.7 months in PC and P arms, respectively (p=0.787). Adverse events ≥ grade 3 were reported in 12 patients (26.1%) in the PC arm and nine patients (20.0%) in the P arm (p=0.491). The overall time trends of HRQOL were not significantly different between the two arms.
Conclusion
The outcomes of pemetrexed therapy in NSCLC patients with disease progression after firstline EGFR-TKI might not be improved by adding cisplatin.

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The Survival and Financial Benefit of Investigator-Initiated Trials Conducted by Korean Cancer Study Group
Bum Jun Kim, Chi Hoon Maeng, Bhumsuk Keam, Young-Hyuck Im, Jungsil Ro, Kyung Hae Jung, Seock-Ah Im, Tae Won Kim, Jae Lyun Lee, Dae Seog Heo, Sang-We Kim, Keunchil Park, Myung-Ju Ahn, Byoung Chul Cho, Hoon-Kyo Kim, Yoon-Koo Kang, Jae Yong Cho, Hwan Jung Yu
Cancer Research and Treatment.2025; 57(1): 39. CrossRef
A randomised non-comparative phase II study of atezolizumab, bevacizumab and chemotherapy in EGFR-mutant NSCLC with acquired resistance – The ETOP 15-19 ABC-lung trial
R.A. Soo, K. Vervita, M. Früh, B.C. Cho, M. Majem, D. Rodriguez Abreu, K. Ribi, A. Callejo, T. Moran, M. Domine Gomez, M. Provencio, A. Addeo, J.Y. Han, A.L. Ortega Granados, M. Reck, A. Blasco, R. Garcia Campelo, M.A. Sala González, C. Britschgi, H. Rosc
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Osimertinib with Chemotherapy in EGFR -Mutated NSCLC

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Real-world outcomes on platinum-containing chemotherapy for EGFR-mutated advanced nonsquamous NSCLC with prior exposure to EGFR tyrosine kinase inhibitors
Balazs Halmos, Pragya Rai, Jae Min, Xiaohan Hu, Diana Chirovsky, Mark Shamoun, Bin Zhao
Frontiers in Oncology.2024;[Epub] CrossRef
Clinical efficacy and safety of pemetrexed with or without either Bevacizumab or Pembrolizumab in patients with metastatic nonsquamous non–small cell carcinoma
Wang Chun Kwok, Tan Fong Cheong, Ka Yan Chiang, James Chung Man Ho, David Chi Leung Lam, Mary Sau Man Ip, Terence Chi Chun Tam
Asia-Pacific Journal of Clinical Oncology.2023; 19(1): 87. CrossRef
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Cheng-Yu Chang, Chung-Yu Chen, Shih-Chieh Chang, Ching-Yi Chen, Yi-Chun Lai, Chun-Fu Chang, Yu-Feng Wei
Frontiers in Oncology.2023;[Epub] CrossRef
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Joseph N. Samuel, Christopher M. Booth, Elizabeth Eisenhauer, Michael Brundage, Scott R. Berry, Bishal Gyawali
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Ruizhu Sun, Zhansheng Hou, Yankui Zhang, Bo Jiang
Oncology Letters.2022;[Epub] CrossRef
Haematological toxicity of pemetrexed in patients with metastatic non-squamous non-small cell carcinoma of lung with third-space fluid
Wang Chun Kwok, Tan Fong Cheong, Ka Yan Chiang, James Chung Man Ho, David Chi Leung Lam, Mary Sau Man Ip, Terence Chi Chun Tam
Lung Cancer.2021; 152: 15. CrossRef
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Rashmi Rana, Vaishnavi Rathi, Kirti Chauhan, Kriti Jain, Satnam Singh Chhabra, Rajesh Acharya, Samir Kumar Kalra, Anshul Gupta, Sunila Jain, Nirmal Kumar Ganguly, Dharmendra Kumar Yadav, Timir Tripathi
PLOS ONE.2021; 16(9): e0255133. CrossRef
Risk factors of nephrotoxicity of maintenance pemetrexed in patients with metastatic non-squamous non-small cell carcinoma of lung
Wang Chun Kwok, Ka Yan Chiang, James Chung Man Ho, David Chi Leung Lam, Mary Sau Man Ip, Terence Chi Chun Tam
Lung Cancer.2021; 162: 169. 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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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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Efficacy and Safety of Afatinib for EGFR-mutant Non-small Cell Lung Cancer, Compared with Gefitinib or Erlotinib: Youjin Kim, Se-Hoon Lee, Jin Seok Ahn, Myung-Ju Ahn, Keunchil Park, Jong-Mu Sun; Cancer Res Treat. 2019;51(2):502-509. Published online June 13, 2018; DOI: https://doi.org/10.4143/crt.2018.117

Abstract PDF Supplementary Material PubReader ePub

Purpose
We tried to evaluate whether there are any specific features in treatment outcomes of firstline afatinib in patients with epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC), compared with gefitinib or erlotinib.
Materials and Methods
We analyzed patients treated with first-line afatinib, gefitinib, or erlotinib for advanced EGFR-mutant NSCLC at Samsung Medical Center between 2014 and 2016.
Results
In total, 467 patients received first-line afatinib (n=165), gefitinib (n=230), or erlotinib (n=72). Afatinib was used more often in patients with tumors harboring deletion in exon 19 (Del19), whereas the gefitinib group had more elderly, females, and never smokers. The median progression-free survival (PFS) time for afatinib, gefitinib, and erlotinib was 19.1 months, 13.7 months, and 14.0 months, respectively (p=0.001). The superior PFS of afatinib was more remarkable in subgroups of Del19 or uncommon EGFR mutations. Overall toxicity profiles of the three drugs were comparable, though more grade 3 or 4 toxicities were detected in afatinib (7.3%) compared with gefitinib (2.6%) or erlotinib (1.8%). The common grade 3 or 4 toxicities of afatinib included diarrhea (3.0%), paronychia (2.4%), and skin rash (1.8%). Dose modification was more frequently required in patients treated with afatinib (112/165, 68%), compared with gefitinib (5/230, 2%) and erlotinib (4/72, 6%). Interestingly, however, dose reduction in the afatinib group did not impair its efficacy in terms of PFS (dose reduction vs. no reduction group, 23.5 months vs. 12.4 months).
Conclusion
First-line afatinib showed satisfactory efficacy data and manageable toxicity profiles.

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Case Report

Rare Mechanism of Acquired Resistance to Osimertinib in Korean Patients with EGFR-mutated Non-small Cell Lung Cancer: Jiyun Lee, Joon Ho Shim, Woong-Yang Park, Hee Kyung Kim, Jong-Mu Sun, Se-Hoon Lee, Jin Seok Ahn, Keunchil Park, Myung-Ju Ahn; Cancer Res Treat. 2019;51(1):408-412. Published online May 23, 2018; DOI: https://doi.org/10.4143/crt.2018.138

Abstract PDF Supplementary Material PubReader ePub

Epidermal growth factor receptor (EGFR)‒tyrosine kinase inhibitors (TKIs) are effective clinical therapeutics for EGFR-mutant non-small cell lung cancer (NSCLC). Osimertinib, a thirdgeneration EGFR TKI, has proven effective against T790M mutations. However, the vast majority of patients acquire resistance following successful treatment. A 59-year-old female patient with metastatic NSCLC developed resistance after 43 weeks of osimertinib. CancerSCAN of the metastatic liver lesion revealed a EGFR C797G mutation at an allele frequency of 72%, a preexisting T790M mutation (73%) in cis and an exon 19 deletion (87%). Another 53-year-old female patient developed systemic progression after 10 months of osimertinib. CancerSCAN of the lung biopsy identified an EGFR L718Q mutation at an allele frequency of 7%, concomitant PIK3CA E545K (12.90%) and preexisting EGFR L858R (38%), but loss of the T790M mutation. The heterogeneity of osimertinib resistance mechanisms warrants further investigation into novel or combination agents to overcome the rare acquired resistances.

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Original Articles

Landscape of Actionable Genetic Alterations Profiled from 1,071 Tumor Samples in Korean Cancer Patients: Se-Hoon Lee, Boram Lee, Joon Ho Shim, Kwang Woo Lee, Jae Won Yun, Sook-Young Kim, Tae-You Kim, Yeul Hong Kim, Young Hyeh Ko, Hyun Cheol Chung, Chang Sik Yu, Jeeyun Lee, Sun Young Rha, Tae Won Kim, Kyung Hae Jung, Seock-Ah Im, Hyeong-Gon Moon, Sukki Cho, Jin Hyoung Kang, Jihun Kim, Sang Kyum Kim, Han Suk Ryu, Sang Yun Ha, Jong Il Kim, Yeun-Jun Chung, Cheolmin Kim, Hyung-Lae Kim, Woong-Yang Park, Dong-Young Noh, Keunchil Park; Cancer Res Treat. 2019;51(1):211-222. Published online April 23, 2018; DOI: https://doi.org/10.4143/crt.2018.132

Abstract PDF Supplementary Material PubReader ePub

Purpose
With the emergence of next-generation sequencing (NGS) technology, profiling a wide range of genomic alterations has become a possibility resulting in improved implementation of targeted cancer therapy. In Asian populations, the prevalence and spectrum of clinically actionable genetic alterations has not yet been determined because of a lack of studies examining high-throughput cancer genomic data.
Materials and Methods
To address this issue, 1,071 tumor samples were collected from five major cancer institutes in Korea and analyzed using targeted NGS at a centralized laboratory. Samples were either fresh frozen or formalin-fixed, paraffin embedded (FFPE) and the quality and yield of extracted genomic DNA was assessed. In order to estimate the effect of sample condition on the quality of sequencing results, tissue preparation method, specimen type (resected or biopsied) and tissue storage time were compared.
Results
We detected 7,360 non-synonymous point mutations, 1,164 small insertions and deletions, 3,173 copy number alterations, and 462 structural variants. Fifty-four percent of tumors had one or more clinically relevant genetic mutation. The distribution of actionable variants was variable among different genes. Fresh frozen tissues, surgically resected specimens, and recently obtained specimens generated superior sequencing results over FFPE tissues, biopsied specimens, and tissues with long storage duration.
Conclusion
In order to overcome, challenges involved in bringing NGS testing into routine clinical use, a centralized laboratory model was designed that could improve the NGS workflows, provide appropriate turnaround times and control costs with goal of enabling precision medicine.

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Randomized Phase III Trial of Irinotecan Plus Cisplatin versus Etoposide Plus Cisplatin in Chemotherapy-Naïve Korean Patients with Extensive-Disease Small Cell Lung Cancer: Dong-Wan Kim, Hoon-Gu Kim, Joo-Hang Kim, Keunchil Park, Hoon-Kyo Kim, Joung Soon Jang, Bong-Seog Kim, Jin-Hyoung Kang, Kyung Hee Lee, Sang-We Kim, Hun Mo Ryoo, Jin-Soo Kim, Ki Hyeong Lee, Jung Hye Kwon, Jin-Hyuk Choi, Sang Won Shin, Seokyung Hahn, Dae Seog Heo; Cancer Res Treat. 2019;51(1):119-127. Published online March 12, 2018; DOI: https://doi.org/10.4143/crt.2018.019

Abstract PDF Supplementary Material PubReader ePub

Purpose
This randomized phase III study was designed to compare the efficacy and safety of irinote-can plus cisplatin (IP) over etoposide plus cisplatin (EP) in Korean patients with extensive-disease small-cell lung cancer (SCLC).
Materials and Methods
Patients were randomly assigned to receive IP, composed of irinotecan 65 mg/m² intravenously on days 1 and 8+cisplatin 70 mg/m² intravenously on day 1 every 3 weeks, or EP, composed of etoposide 100 mg/m² intravenously on days 1, 2, 3+cisplatin 70 mg/m² intravenously on day 1, every 3 weeks for a maximum of six cycles, until disease progression, or until unacceptable toxicity occurred. The primary endpoint was overall survival.
Results
A total of 362 patients were randomized to IP (n=173) and EP (n=189) arms. There were no significant differences between IP and EP arms for the median overall survival (10.9 months vs. 10.3 months, p=0.120) and the median progression-free survival (6.5 months vs. 5.8 months, p=0.115). However, there was a significant difference in response rate (62.4% vs. 48.2%, p=0.006). The pre-planned subgroup analyses showed that IP was associated with longer overall survival in male (11.3 months vs. 10.1 months, p=0.036), < 65 years old (12.7 months vs. 11.3 months, p=0.024), and Eastern Cooperative Oncology Group performance status 0/1 (12.4 months vs. 10.9 months, p=0.040) patient groups. The severity of treatment-related adverse events such as grade 3/4 anemia, nausea and diarrhea was more frequent in patients treated with IP.
Conclusion
The IP chemotherapy did not significantly improve the survival compared with EP chemotherapy in Korean patients with extensive-disease SCLC.

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Ichiro Sekine, Kan Kishibe, Miki Takahara, Hiroaki Katada, Tatsuya Hayashi, Yasuaki Harabuchi
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Ellen Cusano, Chelsea Wong, Eddy Taguedong, Marcus Vaska, Tasnima Abedin, Nancy Nixon, Safiya Karim, Patricia Tang, Daniel Y. C. Heng, Doreen Ezeife
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Gyeong‐Won Lee, Se‐Il Go, Dong‐Wan Kim, Hoon‐Gu Kim, Joo‐Hang Kim, Ho Jung An, Joung Soon Jang, Bong‐Seog Kim, Seokyung Hahn, Dae Seog Heo
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IRS2 Amplification as a Predictive Biomarker in Response to Ceritinib in Small Cell Lung Cancer
Mi-Sook Lee, Kyungsoo Jung, Ji-Young Song, Min-Jung Sung, Sung-Bin Ahn, Boram Lee, Doo-Yi Oh, Yoon-La Choi
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Etoposide and cisplatin versus irinotecan and cisplatin as the first‐line therapy for patients with advanced, poorly differentiated gastroenteropancreatic neuroendocrine carcinoma: A randomized phase 2 study
Panpan Zhang, Jie Li, Jian Li, Xiaotian Zhang, Jun Zhou, Xicheng Wang, Zhi Peng, Lin Shen, Ming Lu
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Systematic review of first-line chemotherapy for chemo-naïve extensive-stage small-cell lung cancer: network meta-analysis
Hao Chen, Nobuyuki Horita, Kentaro Ito, Hideyuki Nagakura, Yu Hara, Nobuaki Kobayash, Masaki Yamamoto, Makoto Kudo, Takeshi Kaneko
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A Retrospective Cohort Study on Pretreated Neutrophil-to-Lymphocyte Ratio and Prognosis of Small Cell Lung Cancer: Evidence of Effect Modification by Chemotherapy Regimen

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Comparison of First-Line Treatments for Patients With Extensive-Stage Small Cell Lung Cancer
Ting Zhou, Zhonghan Zhang, Fan Luo, Yuanyuan Zhao, Xue Hou, Tingting Liu, Kai Wang, Hongyun Zhao, Yan Huang, Li Zhang
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Thérapie ciblée et immunothérapie du cancer bronchique à petites cellules
J.-L. Pujol, C. Goze, C. Pujol, B. Roch
Revue des Maladies Respiratoires Actualités.2019; 11(3): 315. CrossRef
Irinotecan-platinum combination therapy for previously untreated extensive-stage small cell lung cancer patients: a meta-analysis
Fei Xu, Xiaoli Ren, Yuan Chen, Qianxia Li, Ruichao Li, Yu Chen, Shu Xia
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Traitement médical du cancer bronchique à petites cellules : peut-on sortir de l’aire du cisplatine–étoposide ?
Jean-Louis Pujol, Benoît Roch, Camille N. Pujol, Catherine Goze
Bulletin du Cancer.2018;[Epub] CrossRef

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Efficacy and Safety of First-Line Necitumumab Plus Gemcitabine and Cisplatin Versus Gemcitabine and Cisplatin in East Asian Patients with Stage IV Squamous Non-small Cell Lung Cancer: A Subgroup Analysis of the Phase 3, Open-Label, Randomized SQUIRE Study: Keunchil Park, Eun Kyung Cho, Maximino Bello, Myung-Ju Ahn, Sumitra Thongprasert, Eun-Kee Song, Victoria Soldatenkova, Henrik Depenbrock, Tarun Puri, Mauro Orlando; Cancer Res Treat. 2017;49(4):937-946. Published online January 6, 2017; DOI: https://doi.org/10.4143/crt.2016.423

Abstract PDF PubReader ePub

Purpose
The phase 3 randomized SQUIRE study revealed significantly longer overall survival (OS) and progression-free survival (PFS) for necitumumab plus gemcitabine and cisplatin (neci+GC) than for gemcitabine and cisplatin alone (GC) in 1,093 patients with previously untreated advanced squamous non-small cell lung cancer (NSCLC). This post hoc subgroup analysis assessed the efficacy and safety of neci+GC among East Asian (EA) patients enrolled in the study.
Materials and Methods
All patients received up to six 3-week cycles of gemcitabine (days 1 and 8, 1,250 mg/m²) and cisplatin (day 1, 75 mg/m²). Patients in the neci+GC arm also received necitumumab (days 1 and 8, 800 mg) until disease progression or unacceptable toxicity. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated from stratified Cox proportional hazards models.
Results
In EA patients, there were improvements for neci+GC (n=43) versus GC (n=41) in OS (HR, 0.805; 95% CI, 0.484 to 1.341) and PFS (HR, 0.720; 95% CI, 0.439 to 1.180), consistent with the results for non-EA patients observed in the present study. The overall safety data were consistent between EA and non-EA patients. A numerically higher proportion of patients experienced serious adverse events (AEs), grade ≥ 3 AEs, and AEs with an outcome of death for neci+GC versus GC in EA patients and EA patients versus non-EA patients for neci+GC.
Conclusion
Although limited by the small sample size and post hoc nature of the analysis, these findings are consistent with those of the overall study and suggest that neci+GC offers a survival advantage and favorable benefit/risk for EA patients with advanced squamous NSCLC.

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Phytochemicals intended for anticancer effects at preclinical levels to clinical practice: Assessment of formulations at nanoscale for non-small cell lung cancer (NSCLC) therapy
The Hong Phong Nguyen, V. Bharath Kumar, Vinoth Kumar Ponnusamy, Thi Thu Thao Mai, Phuong Tran Nhat, Kathirvel Brindhadevi, Arivalagan Pugazhendhi
Process Biochemistry.2021; 104: 55. CrossRef
Effects of adding necitumumab to first-line chemotherapy in patients with stage IV non-small-cell lung cancer: Meta-analysis
Irena Ilic, Sandra Sipetic, Jovan Grujicic, Milena Ilic
Journal of Oncology Pharmacy Practice.2020; 26(6): 1331. CrossRef
Recent progress in systemic treatment for lung cancer
Jeffrey W. Clark, Dan L. Longo
Current Opinion in Pulmonary Medicine.2018; 24(4): 355. CrossRef
Necitumumab in the treatment of non-small-cell lung cancer: clinical controversies
Vincenzo di Noia, Ettore D’Argento, Sara Pilotto, Giulia Grizzi, Mario Caccese, Roberto Iacovelli, Giampaolo Tortora, Emilio Bria
Expert Opinion on Biological Therapy.2018; 18(9): 937. CrossRef
SELECT-3: a phase I study of selumetinib in combination with platinum-doublet chemotherapy for advanced NSCLC in the first-line setting
Alastair Greystoke, Nicola Steele, Hendrik-Tobias Arkenau, Fiona Blackhall, Noor Md Haris, Colin R Lindsay, Raffaele Califano, Mark Voskoboynik, Yvonne Summers, Karen So, Dana Ghiorghiu, Angela W Dymond, Stuart Hossack, Ruth Plummer, Emma Dean
British Journal of Cancer.2017; 117(7): 938. CrossRef

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Genetic Alterations and Their Clinical Implications in High-Recurrence Risk Papillary Thyroid Cancer: Min-Young Lee, Bo Mi Ku, Hae Su Kim, Ji Yun Lee, Sung Hee Lim, Jong-Mu Sun, Se-Hoon Lee, Keunchil Park, Young Lyun Oh, Mineui Hong, Han-Sin Jeong, Young-Ik Son, Chung-Hwan Baek, Myung-Ju Ahn; Cancer Res Treat. 2017;49(4):906-914. Published online December 26, 2016; DOI: https://doi.org/10.4143/crt.2016.424

Abstract PDF PubReader ePub

Purpose
Papillary thyroid carcinomas (PTCs) frequently involve genetic alterations. The objective of this study was to investigate genetic alterations and further explore the relationships between these genetic alterations and clinicopathological characteristics in a high-recurrence risk (node positive, N1) PTC group.
Materials and Methods
Tumor tissue blocks were obtained from 240 surgically resected patients with histologically confirmed stage III/IV (pT3/4 or N1) PTCs. We screened gene fusions using NanoString’s nCountertechnology and mutational analysiswas performed by directDNA sequencing.Data describing the clinicopathological characteristics and clinical courses were retrospectively collected.
Results
Of the 240 PTC patients, 207 (86.3%) had at least one genetic alteration, including BRAF mutation in 190 patients (79.2%), PIK3CA mutation in 25 patients (10.4%), NTRK1/3 fusion in six patients (2.5%), and RET fusion in 24 patients (10.0%). Concomitant presence of more than two genetic alterations was seen in 36 patients (15%). PTCs harboring BRAF mutation were associated with RET wild-type expression (p=0.001). RET fusion genes have been found to occur with significantly higher frequency in N1b stage patients (p=0.003) or groups of patients aged 45 years or older (p=0.031); however, no significant correlation was found between other genetic alterations. There was no trend toward favorable recurrence-free survival or overall survival among patients lacking genetic alterations.
Conclusion
In the selected high-recurrence risk PTC group, most patients had more than one genetic alteration. However, these known alterations could not entirely account for clinicopathological features of high-recurrence risk PTC.

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Zhipeng Hu, Rong Xue, Zhixi Liu, Liang Liu, Zheli Gong
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BRAF V600E mutation co-existing with oncogenic mutations is associated with aggressive clinicopathologic features and poor prognosis in papillary thyroid carcinoma
Nobuyuki Bandoh, Takashi Goto, Yasutaka Kato, Akinobu Kubota, Shota Sakaue, Ryuhei Takeda, Shuto Hayashi, Misaki Hayashi, Shogo Baba, Tomomi Yamaguchi-Isochi, Hiroshi Nishihara, Hajime Kamada
Asian Journal of Surgery.2024; 47(1): 413. CrossRef
FHL1: A novel diagnostic marker for papillary thyroid carcinoma
Yeting Zeng, Dehua Zeng, Xingfeng Qi, Hanxi Wang, Xuzhou Wang, Xiaodong Dai, Lijuan Qu
Pathology International.2024; 74(9): 520. CrossRef
Rearranged During Transfection Rearrangement Detection by Fluorescence In Situ Hybridization Compared With Other Techniques in NSCLC
Anne Mc Leer, Julie Mondet, Nelly Magnat, Mailys Mersch, Diane Giovannini, Camille Emprou, Anne-Claire Toffart, Nathalie Sturm, Sylvie Lantuéjoul, David Benito
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Essential news for clinical practice—thyroid cancer
Barbara Kiesewetter, Ladislaia Wolff, Markus Raderer
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A new paradigm for epidermal growth factor receptor expression exists in PTC and NIFTP regulated by microRNAs
Abeer Al-Abdallah, Iman Jahanbani, Rola H. Ali, Nabeel Al-Brahim, Jeena Prasanth, Bashayer Al-Shammary, Maie Al-Bader
Frontiers in Oncology.2023;[Epub] CrossRef
NanoString in the screening of genetic abnormalities associated with thyroid cancer
Elisabetta Macerola, Anello Marcello Poma, Fulvio Basolo
Seminars in Cancer Biology.2022; 79: 132. CrossRef
The budget impact of adding pralsetinib to a US health plan formulary for treatment of non-small cell lung cancer and thyroid cancer with RET alterations
Steve Duff, Francesca Bargiacchi, Chelsea Norregaard, Melanie Brener, Erin Sullivan
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Alice W. Lee, Roy A. Mendoza, Shehla Aman, Robert Hsu, Lihua Liu
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Analytical Accuracy of RET Fusion Detection by Break-Apart Fluorescence In Situ Hybridization
Jessica A. Baker, Anthony N. Sireci, Narasimha Marella, Holly Kay Cannon, Tyler J. Marquart, Timothy R. Holzer, Leslie O'Neill Reising, Joel D. Cook, Sameera R. Wijayawardana, Juraj Bodo, Eric D. Hsi, Andrew E. Schade, Gerard J. Oakley
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Intratumoral Genetic Heterogeneity in Papillary Thyroid Cancer: Occurrence and Clinical Significance
Laura Fugazzola, Marina Muzza, Gabriele Pogliaghi, Mario Vitale
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The stress-activated protein kinase pathway and the expression of stanniocalcin-1 are regulated by miR-146b-5p in papillary thyroid carcinogenesis
Abeer Al-Abdallah, Iman Jahanbani, Heba Mehdawi, Rola H Ali, Nabeel Al-Brahim, Olusegun Mojiminiyi
Cancer Biology & Therapy.2020; 21(5): 412. CrossRef
Risk Stratification Using a Novel Genetic Classifier IncludingPLEKHS1Promoter Mutations for Differentiated Thyroid Cancer with Distant Metastasis
Chan Kwon Jung, Seung-Hyun Jung, Sora Jeon, Young Mun Jeong, Yourha Kim, Sohee Lee, Ja-Seong Bae, Yeun-Jun Chung
Thyroid.2020; 30(11): 1589. CrossRef
Prediction of cervical lymph node metastasis with contrast-enhanced ultrasound and association between presence of BRAFV600E and extrathyroidal extension in papillary thyroid carcinoma
Jia Zhan, Long-hui Zhang, Qing Yu, Chao-lun Li, Yue Chen, Wen-Ping Wang, Hong Ding
Therapeutic Advances in Medical Oncology.2020;[Epub] CrossRef
Clinical significance of eukaryotic translation initiation factor 5A2 in papillary thyroid cancer
Hongmei Zhang, Kejun Zhang, Liang Ning, Dong Chen, Fengyun Hao, Peng Li
Bioengineered.2020; 11(1): 1325. CrossRef
High Preponderance of BRAF V600E Mutation in Papillary Thyroid Carcinoma Among Filipinos: A Clinicopathologic Study
Gerard Anthony M. Espiritu, Joemari T. Malana, Arlie Jean Grace V. Dumasis, Daphne C. Ang
Journal of Global Oncology.2019; (5): 1. CrossRef
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Ali Alqahtani, Hazem S. K. Ayesh, Hafez Halawani
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Targeted next‑generation sequencing of cancer‑related genes in thyroid carcinoma: A single institution's experience
Nobuyuki Bandoh, Toshiaki Akahane, Takashi Goto, Michihisa Kono, Haruyuki Ichikawa, Takahiro Sawada, Tomomi Yamaguchi, Hiroshi Nakano, Yumiko Kawase, Yasutaka Kato, Hajime Kamada, Yasuaki Harabuchi, Kazuo Shimizu, Hiroshi Nishihara
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Niclosamide induces apoptosis through mitochondrial intrinsic pathway and inhibits migration and invasion in human thyroid cancer in vitro
Kai Yu, Tingting Wang, Yujue Li, Chun Wang, Xia Wang, Mei Zhang, Yongmei Xie, Shuangqing Li, Zhenmei An, Tinghong Ye
Biomedicine & Pharmacotherapy.2017; 92: 403. CrossRef

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Role of Adjuvant Thoracic Radiation Therapy and Full Dose Chemotherapy in pN2 Non-small Cell Lung Cancer: Elucidation Based on Single Institute Experience: Hyojung Park, Dongryul Oh, Yong Chan Ahn, Hongryull Pyo, Jae Myung Noh, Jong-Mu Sun, Jin Seok Ahn, Myung-Ju Ahn, Keunchil Park, Hong Kwan Kim, Yong Soo Choi, Jhingook Kim, Jae Ill Zo, Young Mog Shim; Cancer Res Treat. 2017;49(4):880-889. Published online December 12, 2016; DOI: https://doi.org/10.4143/crt.2016.442

Abstract PDF PubReader ePub

Purpose
The optimal adjuvant therapy modality for treating pN2 non-small cell lung cancer patients has not yet been established. In this study, the authors investigated clinical outcomes following three different adjuvant therapy modalities.
Materials and Methods
From January 2006 to December 2012, 240 patients with cN0/1 disease were found to have pN2 disease following curative resection and received one of three adjuvant therapy modalities:thoracic radiation therapy (TRT) and concurrent chemotherapy (CTx) (CCRT) (group I), CCRT plus consolidation CTx (group II), and CTx alone (group III). TRT was delivered to 155 patients (groups I/II), and full dose CTxwas delivered to 172 patients either as a consolidative or a sole modality (group II/III).
Results
During 30 months of median follow-up, 44 patients died and 141 developed recurrence. The 5-year overall survival (OS), locoregional control (LRC), distant metastasis-free survival (DMFS), and disease-free survival (DFS) rates of all patients were 76.2%, 80.7%, 36.4%, and 29.6%, respectively. There was no difference in OS among groups. TRT (groups I/II) significantly improved LRC, full dose CTx (groups II/III) did DMFS, and CCRT plus consolidation CTx (group II) did DFS, respectively.
Conclusion
The current study could support that TRT could improve LRC and full dose CTx could improve DMFS and that CCRT plus consolidation CTx could improve DFS.

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The effect of adjuvant chemoradiotherapy on survival after R0 resection for stage III-N2 nonsmall cell lung cancer: A meta-analysis
Dailong Li, Wanqiang Li, Yaqi Pang, Lu Xu, Xinhua Xu
Medicine.2022; 101(28): e29580. CrossRef
The efficacy of postoperative radiotherapy for patients with non-small cell lung cancer
Zexu Wang, Baixia Yang, Ping Zhan, Li Wang, Bing Wan
Journal of Cancer Research and Therapeutics.2022; 18(7): 1910. CrossRef

44,378 View
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A Randomized Phase II Study of Leucovorin/5-Fluorouracil with or without Oxaliplatin (LV5FU2 vs. FOLFOX) for Curatively-Resected, Node-Positive Esophageal Squamous Cell Carcinoma: Sung Hee Lim, Young Mog Shim, Se Hoon Park, Hong Kwan Kim, Young Soo Choi, Myung-Ju Ahn, Keunchil Park, Jae Ill Zo, Jong-Mu Sun; Cancer Res Treat. 2017;49(3):816-823. Published online November 9, 2016; DOI: https://doi.org/10.4143/crt.2016.417

Abstract PDF Supplementary Material PubReader ePub

Purpose
The optimal perioperative treatment for resectable esophageal squamous cell carcinoma (ESCC) remains controversial. We evaluated the efficacy and safety of leucovorin and 5-fluorouracil (LV5FU2) and LV5FU2 plus oxaliplatin (FOLFOX) combination chemotherapies administered adjuvantly for curatively-resected, node-positive ESCC.
Materials and Methods
Patients with pathologically node-positive esophageal cancer after curative R0 resection were enrolled and randomly assigned to receive LV5FU2 or FOLFOX biweekly for up to eight cycles. The primary endpoint was disease-free survival (DFS).
Results
Between 2011 and 2015, 62 patients were randomized into the two treatment groups (32 in the LV5FU2 arm and 30 in the FOLFOX arm). The median age was 60 years and both groups had similar pathologic characteristics in tumor, nodal status, and location. Treatment completion rates were similarly high in both groups. The DFS rate at 12 months was 67% in the LV5FU2 group and 63% in the FOLFOX group with a hazard ratio of 1.3 (95% confidence interval [CI], 0.66 to 2.62). After a median follow-up period of 27 months, the median DFS was 29.6 months (95% CI, 4.9 to 54.2) in the LV5FU2 arm and 16.8 months (95% CI, 7.5 to 26.1) in the FOLFOX arm (p=0.428), respectively, while the median overall survival was not reached in either arm. Grade 3 or 4 neutropenia was more frequent in patients in the FOLFOX arm than the LV5FU2 arm (20.0% vs. 3.1%).
Conclusion
The addition of oxaliplatin (FOLFOX) did not lead to better efficacy compared to LV5FU2 chemotherapy in an adjuvant setting in node-positive ESCC patients.

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Adjuvant chemotherapy in node‐positive patients after esophagectomy for esophageal squamous cell carcinoma
Yeong Jeong Jeon, Jong Ho Cho, Yong Soo Choi, Young Mog Shim, Jong‐Mu Sun, Hong Kwan Kim
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Disease-free survival as a surrogate endpoint for overall survival in adults with resectable esophageal or gastroesophageal junction cancer: A correlation meta-analysis
Jaffer A. Ajani, Lisa Leung, Prianka Singh, Murat Kurt, Inkyu Kim, Mir-Masoud Pourrahmat, Steve Kanters
European Journal of Cancer.2022; 170: 119. CrossRef
Substrate-controlled selective acylation of quinazolinones: Access to 2-benzamido-N-formylbenzamides and 3-benzoylquinazolinones
Xianglin Yu, Peng Chen, Ling Jiang, Jun Lin, Yi Jin
Tetrahedron Letters.2022; 103: 153988. CrossRef
Catalyst-free highly regioselective hydrated ring-opening and formylation of quinazolinones
Xianglin Yu, Zhiliang Tang, Kun He, Weina Li, Jun Lin, Yi Jin
Organic & Biomolecular Chemistry.2022; 20(33): 6654. CrossRef
Clinical Trends in Management of Locally Advanced ESCC: Real-World Evidence from a Large Single-Center Cohort Study
Yeong Jeong Jeon, Junsang Yoo, Jong Ho Cho, Young Mog Shim
Cancers.2022; 14(19): 4953. CrossRef
Cardiotoxic effects induced by the use of antimetabolites in the chemotherapy of oncological diseases
Alina A. Aliab'eva, Galina S. Mal
CardioSomatics.2021; 12(3): 177. CrossRef
Antibiotics Improve the Treatment Efficacy of Oxaliplatin-Based but Not Irinotecan-Based Therapy in Advanced Colorectal Cancer Patients
Hiroo Imai, Ken Saijo, Keigo Komine, Yuya Yoshida, Keiju Sasaki, Asako Suzuki, Kota Ouchi, Masahiro Takahashi, Shin Takahashi, Hidekazu Shirota, Masanobu Takahashi, Chikashi Ishioka
Journal of Oncology.2020; 2020: 1. CrossRef
Adjuvant Therapy for Esophageal Squamous Cell Carcinoma
Jong-Mu Sun
The Korean Journal of Thoracic and Cardiovascular Surgery.2020; 53(4): 168. CrossRef
Copper-Catalyzed N-Formylation of Amines through Tandem Amination/Hydrolysis/Decarboxylation Reaction of Ethyl Bromodifluoroacetate
Xiao-Fang Li, Xing-Guo Zhang, Fan Chen, Xiao-Hong Zhang
The Journal of Organic Chemistry.2018; 83(20): 12815. CrossRef
Palliative chemotherapy and targeted therapies for esophageal and gastroesophageal junction cancer
Vincent T Janmaat, Ewout W Steyerberg, Ate van der Gaast, Ron HJ Mathijssen, Marco J Bruno, Maikel P Peppelenbosch, Ernst J Kuipers, Manon CW Spaander
Cochrane Database of Systematic Reviews.2017;[Epub] CrossRef

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East Asian Subgroup Analysis of a Randomized, Double-Blind, Phase 3 Study of Docetaxel and Ramucirumab Versus Docetaxel and Placebo in the Treatment of Stage IV Non-small Cell Lung Cancer Following Disease Progression after One Prior Platinum-Based Therapy (REVEL): Keunchil Park, Joo-Hang Kim, Eun Kyung Cho, Jin-Hyoung Kang, Jin-Yuan Shih, Annamaria Hayden Zimmermann, Pablo Lee, Ekaterine Alexandris, Tarun Puri, Mauro Orlando; Cancer Res Treat. 2016;48(4):1177-1186. Published online February 22, 2016; DOI: https://doi.org/10.4143/crt.2015.401

Abstract PDF PubReader ePub

Purpose
REVEL demonstrated improved overall survival (OS), progression-free survival (PFS), and objective response rate (ORR) with docetaxel+ramucirumab versus docetaxel+placebo in 1,253 intent-to-treat (ITT) stage IV non-small cell lung cancer patients with disease progression following platinum-based chemotherapy. Results from the East Asian subgroup analysis are reported.
Materials and Methods
Subgroup analyses were performed in the East Asian ITT population (n=89). Kaplan-Meier analysis and Cox proportional hazards regression were performed for OS and PFS, and the Cochran-Mantel-Haenszel test was performed for response rate.
Results
In docetaxel+ramucirumab (n=43) versus docetaxel+placebo (n=46), median OS was 15.44 months versus 10.17 months (hazard ratio [HR], 0.762; 95% confidence interval [CI], 0.444 to 1.307), median PFS was 4.88 months versus 2.79 months (HR, 0.658; 95% CI, 0.408 to 1.060), and ORR was 25.6% (95% CI, 13.5 to 41.2) versus 8.7% (95% CI, 2.4 to 20.8). Due to increased incidence of neutropenia and febrile neutropenia in East Asian patients, starting dose of docetaxel was reduced for newly enrolled East Asian patients (75 to 60 mg/m2, n=24). In docetaxel+ramucirumab versus docetaxel+placebo, incidence of neutropenia was 84.4% versus 72.7% (75 mg/m2) and 54.5% versus 38.5% (60 mg/m2). Incidence of febrile neutropenia was 43.8% versus 12.1% (75 mg/m2) and 0% versus 7.7% (60 mg/m2).
Conclusion

Results
of this subgroup analysis showed a trend favoring ramucirumab+docetaxel for median OS, PFS, and improved ORR in East Asian patients, consistent with ITT population results. Reduction of starting dose of docetaxel in East Asian patients was associated with improved safety.

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memo - Magazine of European Medical Oncology.2016; 9(4): 191. CrossRef

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Erratum

ERRATUM: Role of Chemotherapy in Stage II Nasopharyngeal Carcinoma Treated with Curative Radiotherapy: Min Kyu Kang, Dongryul Oh, Kwan Ho Cho, Sung Ho Moon, Hong-Gyun Wu, Dae-Seog Heo, Yong Chan Ahn, Keunchil Park, Hyo Jung Park, Jun Su Park, Ki Chang Keum, Jihye Cha, Jun Won Kim, Yeon-Sil Kim, Jin Hyoung Kang, Young-Taek Oh, Ji-Yoon Kim, Sung Hwan Kim, Jin-Hee Kim, Chang Geol Lee; Cancer Res Treat. 2016;48(1):425-425. Published online January 10, 2016; DOI: https://doi.org/10.4143/crt.2014.141.2; Corrects: Cancer Res Treat 2015;47(4):871

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Special Article

Tolerability and Outcomes of First-Line Pemetrexed-Cisplatin Followed by Gefitinib Maintenance Therapy Versus Gefitinib Monotherapy in Korean Patients with Advanced Nonsquamous Non-small Cell Lung Cancer: A Post Hoc Descriptive Subgroup Analysis of a Randomized, Phase 3 Trial: Jin Hyoung Kang, Myung-Ju Ahn, Dong-Wan Kim, Eun Kyung Cho, Joo-Hang Kim, Sang Won Shin, Xin Wang, Jong Seok Kim, Mauro Orlando, Keunchil Park; Cancer Res Treat. 2016;48(2):458-464. Published online October 14, 2015; DOI: https://doi.org/10.4143/crt.2015.135

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Purpose
We recently reported on a randomized, open-label, phase 3 trial comparing pemetrexed-cisplatin chemotherapy followed by gefitinib maintenance therapy (PC/G) with gefitinib monotherapy in patients with non-small cell lung cancer (NSCLC). Here, we report on a post hoc subgroup analysis of that study assessing the demographics and disposition of the Korean patient subgroup, and comparing the tolerability of PC/G and gefitinib monotherapy and the tumor response with respect to epidermal growth factor receptor (EGFR) status.
Materials and Methods
Patients, who were ≥ 18 years, chemonaïve, Korean, light ex-smokers/never-smokers with advanced NSCLC, were randomly assigned (1:1) to PC/G or gefitinib monotherapy. Treatment-emergent adverse events (TEAEs) were graded, and tumor response was measured as change in lesion sum from baseline at best response. The study was registered with ClinicalTrials. gov, NCT01017874.
Results
Overall, 111 Korean patients were treated (PC/G, 51; gefitinib, 60). Between-arm characteristics were balanced and similar to those of the overall population. Treatment discontinuations due to adverse events were low (PC/G: 1, 2.0%; gefitinib: 7, 11.7%). Overall, 92 patients (82.9%) reported ≥ 1 TEAE (PC/G, 44; gefitinib, 48); few patients (PC/G, 16; gefitinib, 7) reported severe TEAEs; the most frequent was neutropenia (PC/G arm) and elevated alanine aminotransferase (gefitinib arm). The lesion sum was decreased by PC/G treatment in most patients, regardless of EGFRmutation status, while gefitinib monotherapy reduced the lesion sum in EGFR-positive patients but had no effect in EGFR-negative patients.
Conclusion
Our results confirm that both PC/G and gefitinib were well tolerated in Korean patients, regardless of EGFR status; however, patients with EGFR wild-type NSCLC may not benefit from gefitinib monotherapy.

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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

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Original Articles

Association between PD-L1 and HPV Status and the Prognostic Value of PD-L1 in Oropharyngeal Squamous Cell Carcinoma: Hae Su Kim, Ji Yun Lee, Sung Hee Lim, Keunchil Park, Jong-Mu Sun, Young Hyeh Ko, Chung-Hwan Baek, Young-ik Son, Han Sin Jeong, Yong Chan Ahn, Min-Young Lee, Mineui Hong, Myung-Ju Ahn; Cancer Res Treat. 2016;48(2):527-536. Published online September 15, 2015; DOI: https://doi.org/10.4143/crt.2015.249

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Purpose
Oropharyngeal squamous cell carcinoma (OSCC) has been recognized as an immunosuppressive disease. Various mechanisms have been proposed for immune escape, including dysregulation of immune checkpoints such as the PD-1:PD-L1 pathway. We investigated the expression of programmed cell death-ligand 1 (PD-L1) in HPV-negative and HPV-positive OSCC to determine its prevalence and prognostic relevance.
Materials and Methods
Using immunohistochemistry, 133 cases of OSCC were evaluated for expression of PD-L1. Formalin-fixed paraffin-embedded tumor samples were stained with monoclonal antibody (clone 5H1) to PD-L1. PD-L1 positivity was defined as membrane staining in ≥20% of tumor cells. Correlations between PD-L1 expression and HPV status and survival parameters were analyzed.
Results
Of the 133 patients, 68% showed PD-L1 expression, and 67% of patients were positive for p16 expression by immunohistochemistry. No significant difference in PD-L1 expression was observed between HPV(-) and HPV(+) tumors (61% vs. 71%, p=0.274). No significant difference in age, gender, smoking history, location of tumor origin, or stage was observed according to PD-L1 status. With a median follow-up period of 44 months, older age (≥65) (p=0.017) and T3-4 stage (p<0.001) were associated with poor overall survival (OS), whereas PD-L1 expression did not affect OS in univariate and multivariate analysis.
Conclusion
PD-L1 expression was observed in the majority of OSCC patients regardless of HPV status. Further large prospective studies are required to determine the role of PD-L1 expression as a prognostic or predictive biomarker, and clinical studies of immune checkpoint inhibitors in OCSS are warranted regardless of HPV status.

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Nabil F. Saba, Zhuo Gerogia Chen, Missak Haigentz, Paolo Bossi, Alessandra Rinaldo, Juan P. Rodrigo, Antti A. Mäkitie, Robert P. Takes, Primoz Strojan, Jan B. Vermorken, Alfio Ferlito
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PD-L1 Expression in Tumor Cells Is an Independent Unfavorable Prognostic Factor in Oral Squamous Cell Carcinoma
Juan C. de Vicente, Tania Rodríguez-Santamarta, Juan P. Rodrigo, Verónica Blanco-Lorenzo, Eva Allonca, Juana M. García-Pedrero
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Beyond the Percentages of PD-L1-Positive Tumor Cells: Induced Versus Constitutive PD-L1 Expression in Primary and Metastatic Head and Neck Squamous Cell Carcinoma
Theresa Scognamiglio, Yao-Tseng Chen
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The Current State of Biological and Clinical Implications of Human Papillomavirus-Related Oropharyngeal Cancer
Shao Hui Huang, Brian O'Sullivan, John Waldron
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Implications of the tumor immune microenvironment for staging and therapeutics
Janis M Taube, Jérôme Galon, Lynette M Sholl, Scott J Rodig, Tricia R Cottrell, Nicolas A Giraldo, Alexander S Baras, Sanjay S Patel, Robert A Anders, David L Rimm, Ashley Cimino-Mathews
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Head and neck squamous cell carcinoma: Genomics and emerging biomarkers for immunomodulatory cancer treatments
Benjamin Solomon, Richard J. Young, Danny Rischin
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Immuno-oncology in head and neck squamous cell cancers: News from clinical trials, emerging predictive factors and unmet needs
Stefano Cavalieri, Licia Rivoltini, Cristiana Bergamini, Laura D. Locati, Lisa Licitra, Paolo Bossi
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Clinical implication of programmed cell death-1 ligand-1 expression in tonsillar squamous cell carcinoma in association with intratumoral heterogeneity, human papillomavirus, and epithelial-to-mesenchymal transition
Mi Jung Kwon, Young-Soo Rho, Eun Sook Nam, Seong Jin Cho, Hye-Rim Park, Soo Kee Min, Jinwon Seo, Ji-Young Choe, Eun Soo Kim, Bumjung Park, Mineui Hong, Kyueng-Whan Min
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The Role of the Programmed Death Receptor-1/Programmed Death Ligand-1: Immunologic Checkpoint in Human Papillomavirus–Associated Head and Neck Squamous Cell Carcinoma
Christine Kunkle, Flavia G Rosado
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Genomic Landscapes of EBV-Associated Nasopharyngeal Carcinoma vs. HPV-Associated Head and Neck Cancer
Hoi-Lam Ngan, Lan Wang, Kwok-Wai Lo, Vivian Wai Yan Lui
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PD‐1 and PD‐L1 expression in HNSCC primary cancer and related lymph node metastasis – impact on clinical outcome
Sven Schneider, Lorenz Kadletz, Robert Wiebringhaus, Lukas Kenner, Edgar Selzer, Thorsten Füreder, Orsolya Rajky, Anna S Berghoff, Matthias Preusser, Gregor Heiduschka
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The prognostic role of PD-L1 expression for survival in head and neck squamous cell carcinoma: A systematic review and meta-analysis
Wei-fa Yang, May C.M. Wong, Peter J. Thomson, Kar-Yan Li, Yu-xiong Su
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Prognostic value of PD -L1 expression in patients with primary solid tumors
Xiao Xiang, Peng-Cheng Yu, Di Long, Xiao-Li Liao, Sen Zhang, Xue-Mei You, Jian-Hong Zhong, Le-Qun Li
Oncotarget.2018; 9(4): 5058. CrossRef
Drug-Sensitivity Screening and Genomic Characterization of 45 HPV-Negative Head and Neck Carcinoma Cell Lines for Novel Biomarkers of Drug Efficacy
Tatiana Lepikhova, Piia-Riitta Karhemo, Riku Louhimo, Bhagwan Yadav, Astrid Murumägi, Evgeny Kulesskiy, Mikko Kivento, Harri Sihto, Reidar Grénman, Stina M. Syrjänen, Olli Kallioniemi, Tero Aittokallio, Krister Wennerberg, Heikki Joensuu, Outi Monni
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Immune check point inhibitors for head and neck cancer
Naomi Kiyota
Toukeibu Gan.2018; 44(4): 336. CrossRef
Immune check point inhibitors for head and neck cancer and its proper management on utilizing head and neck cancer collaborative program
Naomi Kiyota
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Is There Evidence for the Presence and Relevance of the PD-1/PD-L1 Pathway in Oral Squamous Cell Carcinoma? Hints From an Immunohistochemical Study
Matthias Troeltzsch, Timothy Woodlock, Alix Pianka, Sven Otto, Markus Troeltzsch, Michael Ehrenfeld, Thomas Knösel
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Sophie Outh-Gauer, Christophe Le Tourneau, Chloé Broudin, Florian Scotte, Hélène Roussel, Stéphane Hans, Marion Mandavit, Eric Tartour, Cécile Badoual
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Overview of Sinonasal and Ventral Skull Base Malignancy Management
Peter F. Svider, Michael Setzen, Soly Baredes, James K. Liu, Jean Anderson Eloy
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PD-L1 expression and CD8+ infiltration shows heterogeneity in Juvenile Recurrent Respiratory Papillomatosis
Tingyu Liu, Max Greenberg, Carissa Wentland, Brandon Sepe, Sarah Bowe, Gillian Diercks, Tiffany Huynh, Mari Mino-Kenudson, Richard Schlegel, David Kodack, Cyril Benes, Jeffrey Engelman, Christopher Hartnick
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Programmed cell death ligand 1 as a biomarker in head and neck cancer
Sara I. Pai, William C. Faquin
Cancer Cytopathology.2017; 125(7): 529. CrossRef
Turning the tide: Clinical utility of PD-L1 expression in squamous cell carcinoma of the head and neck
Astrid De Meulenaere, Tijl Vermassen, Sandrine Aspeslagh, Wouter Huvenne, Jo Van Dorpe, Liesbeth Ferdinande, Sylvie Rottey
Oral Oncology.2017; 70: 34. CrossRef
Time to change perspectives on HPV in oropharyngeal cancer. A systematic review of HPV prevalence per oropharyngeal sub-site the last 3 years
Linnea Haeggblom, Torbjörn Ramqvist, Massimo Tommasino, Tina Dalianis, Anders Näsman
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The PD-1/PD-L1 axis and human papilloma virus in patients with head and neck cancer after adjuvant chemoradiotherapy: A multicentre study of the German Cancer Consortium Radiation Oncology Group (DKTK-ROG)
Panagiotis Balermpas, Franz Rödel, Mechthild Krause, Annett Linge, Fabian Lohaus, Michael Baumann, Inge Tinhofer, Volker Budach, Ali Sak, Martin Stuschke, Eleni Gkika, Anca-Ligia Grosu, Amir Abdollahi, Jürgen Debus, Stefan Stangl, Ute Ganswindt, Claus Bel
International Journal of Cancer.2017; 141(3): 594. CrossRef
Prognostic value of programmed cell death ligand 1 expression in patients with head and neck cancer: A systematic review and meta-analysis
Ji Li, Ping Wang, Youliang Xu, Jung Weon Lee
PLOS ONE.2017; 12(6): e0179536. CrossRef
Association between PD-L1 and HPV status and the prognostic value for HPV treatment in premalignant cervical lesion patients
Feng Yang-Chun, Cheng Zhen-Zhen, Huang Yan-Chun, Ma Xiu-Min
Medicine.2017; 96(25): e7270. CrossRef
Expressions of programmed death (PD)‐1 and PD‐1 ligand (PD‐L1) in cervical intraepithelial neoplasia and cervical squamous cell carcinomas are of prognostic value and associated with human papillomavirus status
Wen Yang, Yan‐Ping Lu, Yi‐Zhou Yang, Jia‐Rui Kang, Yi‐Duo Jin, Hong‐Wei Wang
Journal of Obstetrics and Gynaecology Research.2017; 43(10): 1602. CrossRef
Safety and Antitumor Activity of Pembrolizumab in Patients With Programmed Death-Ligand 1–Positive Nasopharyngeal Carcinoma: Results of the KEYNOTE-028 Study
Chiun Hsu, Se-Hoon Lee, Samuel Ejadi, Caroline Even, Roger B. Cohen, Christophe Le Tourneau, Janice M. Mehnert, Alain Algazi, Emilie M.J. van Brummelen, Sanatan Saraf, Pradeep Thanigaimani, Jonathan D. Cheng, Aaron R. Hansen
Journal of Clinical Oncology.2017; 35(36): 4050. CrossRef
Human papillomavirus-related oropharyngeal cancer
M. Taberna, M. Mena, M.A. Pavón, L. Alemany, M.L. Gillison, R. Mesía
Annals of Oncology.2017; 28(10): 2386. CrossRef
Circulating tumour cell PD-L1 test for head and neck cancers
Arutha Kulasinghe, Liz Kenny, Chamindie Punyadeera
Oral Oncology.2017; 75: 6. CrossRef
Tumor PD-L1 status and CD8+ tumor-infiltrating T cells: markers of improved prognosis in oropharyngeal cancer
Astrid De Meulenaere, Tijl Vermassen, Sandrine Aspeslagh, Philippe Deron, Fréderic Duprez, Debby Laukens, Jo Van Dorpe, Liesbeth Ferdinande, Sylvie Rottey
Oncotarget.2017; 8(46): 80443. CrossRef
Characterization of tumor-associated T-lymphocyte subsets and immune checkpoint molecules in head and neck squamous cell carcinoma
Axel Lechner, Hans Schlößer, Sacha I. Rothschild, Martin Thelen, Sabrina Reuter, Peter Zentis, Alexander Shimabukuro-Vornhagen, Sebastian Theurich, Kerstin Wennhold, Maria Garcia-Marquez, Lars Tharun, Alexander Quaas, Astrid Schauss, Jörg Isensee, Tim Huc
Oncotarget.2017; 8(27): 44418. CrossRef
Tumoral PD-L1 expression defines a subgroup of poor-prognosis vulvar carcinomas with non-viral etiology
Thomas Hecking, Thore Thiesler, Cynthia Schiller, Jean-Marc Lunkenheimer, Tiyasha H. Ayub, Andrea Rohr, Mateja Condic, Mignon-Denise Keyver-Paik, Rolf Fimmers, Jutta Kirfel, Walther Kuhn, Glen Kristiansen, Kirsten Kübler
Oncotarget.2017; 8(54): 92890. CrossRef
Evaluation of PD-L1 Expression in Tumor Tissue of Patients with Lung Carcinoma and Correlation with Clinical and Demographic Data
Gustavo Dix Junqueira Pinto, Luciano de Souza Viana, Cristovam Scapulatempo Neto, Sérgio Vicente Serrano
Journal of Immunology Research.2016; 2016: 1. CrossRef
Development of a programmed cell death ligand-1 immunohistochemical assay validated for analysis of non-small cell lung cancer and head and neck squamous cell carcinoma
Marlon C. Rebelatto, Anita Midha, Amita Mistry, Constantine Sabalos, Nicole Schechter, Xia Li, Xiaoping Jin, Keith E. Steele, Paul B. Robbins, John A. Blake-Haskins, Jill Walker
Diagnostic Pathology.2016;[Epub] CrossRef
Current clinical immunotherapeutic approaches for head and neck cancer
Carolina Soto Chervin, Bruce Brockstein
F1000Research.2016; 5: 803. CrossRef
PD-L1 expression in tonsillar cancer is associated with human papillomavirus positivity and improved survival: implications for anti-PD1 clinical trials
Angela M Hong, Ricardo E Vilain, Sarah Romanes, Jean Yang, Elizabeth Smith, Deanna Jones, Richard A Scolyer, C Soon Lee, Mei Zhang, Barbara Rose
Oncotarget.2016; 7(47): 77010. CrossRef

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Role of Chemotherapy in Stage II Nasopharyngeal Carcinoma Treated with Curative Radiotherapy: Min Kyu Kang, Dongryul Oh, Kwan Ho Cho, Sung Ho Moon, Hong-Gyun Wu, Dae-Seog Heo, Yong Chan Ahn, Keunchil Park, Hyo Jung Park, Jun Su Park, Ki Chang Keum, Jihye Cha, Jun Won Kim, Yeon-Sil Kim, Jin Hyoung Kang, Young-Taek Oh, Ji-Yoon Kim, Sung Hwan Kim, Jin-Hee Kim, Chang Geol Lee; Cancer Res Treat. 2015;47(4):871-878. Published online February 13, 2015; DOI: https://doi.org/10.4143/crt.2014.141; Correction in: Cancer Res Treat 2016;48(1):425

Abstract PDF PubReader ePub

Purpose
To define the role of neoadjuvant and concurrent chemotherapy in stage II nasopharyngeal carcinoma, we compared the treatment outcomes of patients treated with curative radiotherapy with or without chemotherapy. Materials and Methods From 2004 to 2011, 138 patients with American Joint Committee on Cancer (AJCC) 2002 stage II nasopharyngeal carcinoma were treated with curative radiotherapy in 12 hospitals in South Korea. Treatment methods included radiotherapy alone in 34 patients, neoadjuvant chemotherapy followed by radiotherapy alone in seven, concurrent chemoradiotherapy in 80, and neoadjuvant chemotherapy followed by concurrent chemoradiotherapy in 17. Adjuvant chemotherapy was used in 42 patients. Total radiation dose ranged from 64 Gy to 74.2 Gy (median, 70 Gy).
Results
Median follow-up was 48 months (range, 7 to 97 months) for all patients. At the last followup, 13 patients had died and 32 had experienced treatment failure; locoregional failure occurred in 14, distant failure in 16, and both in two. Five-year locoregional relapse-free survival, distant metastasis-free survival, progression-free survival, and overall survival were 86.2%, 85.5%, 74.4%, and 88.2%, respectively. Multivariate analyses showed that the significant prognostic factors were concurrent chemotherapy and N stage for locoregional relapse-free survival, concurrent chemotherapy for progression-free survival, and age and N stage for overall survival. Neither neoadjuvant nor concurrent chemotherapy improved distant metastasis-free survival. Conclusion Concurrent chemotherapy significantly improved 5-year locoregional relapse-free survival and progression-free survival in stage II nasopharyngeal carcinoma. However, neoadjuvant chemotherapy failed to improve either.

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Concurrent chemoradiotherapy versus radiotherapy alone in older patients with stage II nasopharyngeal carcinoma after intensity-modulated radiotherapy: A propensity score-matched cohort study
Fang Wang, Lu Zhou, Li-Jun Zhang, Chang-Bin Xie, Zhi-Wei Liao, Xiao-Dan Lin, Yue-Feng Wen
Radiotherapy and Oncology.2024; 191: 110081. CrossRef
A Systematic Review and Meta-Analysis of Studies Comparing Concurrent Chemoradiotherapy With Radiotherapy Alone in the Treatment of Stage II Nasopharyngeal Carcinoma
Yao-Can Xu, Kai-Hua Chen, Zhong-Guo Liang, Xiao-Dong Zhu
Frontiers in Oncology.2022;[Epub] CrossRef
MRI-identified multidimensional nodal features predict survival and concurrent chemotherapy benefit for stage II nasopharyngeal carcinoma
Yang Liu, Jianghu Zhang, Jingbo Wang, Runye Wu, Xiaodong Huang, Kai Wang, Yuan Qu, Xuesong Chen, Yexiong Li, Ye Zhang, Junlin Yi
Radiology and Oncology.2022; 56(4): 479. CrossRef
The efficacy of chemotherapy in survival of stage II nasopharyngeal carcinoma
Xin-Bin Pan, Ling Li, Song Qu, Long Chen, Shi-Xiong Liang, Xiao-Dong Zhu
Oral Oncology.2020; 101: 104520. CrossRef
Survival of stage II nasopharyngeal carcinoma patients with or without concurrent chemotherapy: A propensity score matching study
Di‐Han Liu, Xiao‐Yu Zhou, You‐Guang Pan, Si Chen, Zheng‐Hao Ye, Gang‐Dong Chen
Cancer Medicine.2020; 9(4): 1287. CrossRef
Concurrent Chemoradiotherapy With or Without Induction Chemotherapy for Patients with Stage II Nasopharyngeal Carcinoma: An Update
Ting Jin, Qun Zhang, Dong-Hua Luo, Feng Jiang, Qi-Feng Jin, Yuan-Yuan Chen, Xiao-Zhong Chen, Wei-Min Mao
Translational Oncology.2020; 13(1): 25. CrossRef
Predictive factors of chemotherapy use in stage II nasopharyngeal carcinoma
Xin-Bin Pan, Shi-Ting Huang, Kai-Hua Chen, Yan-Ming Jiang, Xiao-Dong Zhu
Medicine.2019; 98(7): e14512. CrossRef
The role of chemotherapy in the treatment of stage II nasopharyngeal carcinoma: Retrospective analysis of the national cancer database
Zaheer Ahmed, Lara Kujtan, Kevin Kennedy, Valerie Wood, David Schomas, Janakiraman Subramanian
Cancer Medicine.2019; 8(4): 1500. CrossRef
Patterns of Failure and Survival Trends in 3,808 Patients with Stage II Nasopharyngeal Carcinoma Diagnosed from 1990 to 2012: A Large-Scale Retrospective Cohort Study
Xue-Song Sun, Di-Han Liu, Sai-Lan Liu, Qiu-Yan Chen, Shan-Shan Guo, Yue-Feng Wen, Li-Ting Liu, Hao-Jun Xie, Qing-Nan Tang, Yu-Jing Liang, Xiao-Yun Li, Jin-Jie Yan, Ming-Huang Hong, Jun Ma, Lin-Quan Tang, Hai-Qiang Mai
Cancer Research and Treatment.2019; 51(4): 1449. CrossRef
Combined chemoradiation vs radiation therapy alone in stage-II nasopharyngeal carcinoma: A meta-analysis of the published literature
Sufang Wang, Shan Li, Liangfang Shen
Current Problems in Cancer.2018; 42(3): 302. CrossRef
The efficacy of induction chemotherapy in the treatment of stage II nasopharyngeal carcinoma in intensity modulated radiotherapy era
Pei-Jing Li, Hao-Yuan Mo, Dong-Hua Luo, Wei-Han Hu, Ting Jin
Oral Oncology.2018; 85: 95. CrossRef
Concurrent chemoradiotherapy degrades the quality of life of patients with stage II nasopharyngeal carcinoma as compared to radiotherapy
Xin-Bin Pan, Shi-Ting Huang, Kai-Hua Chen, Yan-Ming Jiang, Jia-Lin Ma, Song Qu, Ling Li, Long Chen, Xiao-Dong Zhu
Oncotarget.2017; 8(8): 14029. CrossRef
Chemotherapy use and survival in stage II nasopharyngeal carcinoma
Xin-Bin Pan, Shi-Ting Huang, Kai-Hua Chen, Xiao-Dong Zhu
Oncotarget.2017; 8(60): 102573. CrossRef
Long-term survival of nasopharyngeal carcinoma patients with Stage II in intensity-modulated radiation therapy era
Qiaojuan Guo, Tianzhu Lu, Shaojun Lin, Jingfeng Zong, Zhuhong Chen, Xiaofei Cui, Yu Zhang, Jianji Pan
Japanese Journal of Clinical Oncology.2016; 46(3): 241. CrossRef
Comparison of the efficacy between concurrent chemoradiotherapy with or without adjuvant chemotherapy and intensity-modulated radiotherapy alone for stage II nasopharyngeal carcinoma
Kai-Hua Chen, Xiao-Dong Zhu, Ling Li, Song Qu, Zhen-Qiang Liang, Xia Liang, Xin-Bin Pan, Zhong-Guo Liang, Yan-Ming Jiang
Oncotarget.2016; 7(42): 69041. CrossRef
Propensity score matching analysis of cisplatin-based concurrent chemotherapy in low risk nasopharyngeal carcinoma in the intensity-modulated radiotherapy era
Lu-Ning Zhang, Yuan-Hong Gao, Xiao-Wen Lan, Jie Tang, Zhen Su, Jun Ma, Wuguo Deng, Pu-Yun OuYang, Fang-Yun Xie
Oncotarget.2015; 6(41): 44019. CrossRef

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Definitive Bimodality Concurrent Chemoradiotherapy in Patients with Inoperable N2-positive Stage IIIA Non-small Cell Lung Cancer: Jae Myoung Noh, Yong Chan Ahn, Hyebin Lee, Hongryull Pyo, BoKyong Kim, Dongryul Oh, Hyojung Park, Eonju Lee, Keunchil Park, Jin Seok Ahn, Myung-Ju Ahn, Jong-Mu Sun; Cancer Res Treat. 2015;47(4):645-652. Published online February 12, 2015; DOI: https://doi.org/10.4143/crt.2014.144

Abstract PDF PubReader ePub

Purpose
This study was conducted to evaluate the treatment outcomes following definitive bimodality concurrent chemoradiotherapy (CCRT) in patients with inoperable N2-positive stage IIIA (N2- IIIA) non-small cell lung cancer (NSCLC). Materials and Methods From May 1997 to December 2012, 65 out of 633 patients with N2-IIIA NSCLC received bimodality therapy. The treatment modality was selected during/after neoadjuvant CCRT in 21 patients or primarily at diagnosis in 44 through a multidisciplinary consensus meeting. The median age was 65 years (range, 36 to 76 years). Sixty patients (92.3%) had clinically evident N2 disease, while 22 (33.8%) had multi-station N2 involvement. The median radiation therapy dose was 66 Gy in 33 fractions, while the dose was elevated to 72 Gy in 13 patients who had a treatment break due to delayed decision regarding resectability. The most frequent chemotherapy regimen was weekly paclitaxel or docetaxel plus cisplatin or carboplatin (54, 83.1%).
Results
During the median follow-up of 18.8 months (range, 1.6 to 173.1 months), 34 patients (52.3%) experienced disease progression, with distant metastasis being the most common first treatment failure pattern (23, 34.8%). The median and 2-year rates of progression-free survival were 18.8 months and 45.9%, respectively. The median and 2-year rates of overall survival were 28.6 months and 50.1%, respectively. Conclusion Definitive bimodality therapy in patients with N2-IIIA NSCLC demonstrated favorable outcomes, while trimodality therapy could be considered for candidates for less than pneumonectomy.

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Toxicity of Proton Therapy versus Photon Therapy on Salvage Re-Irradiation for Non-Small Cell Lung Cancer
Kyungmi Yang, Yang-Gun Suh, Hyunju Shin, Hongryull Pyo, Sung Ho Moon, Yong Chan Ahn, Dongryul Oh, Eunah Chung, Kwanghyun Jo, Jae Myoung Noh
Life.2022; 12(2): 292. CrossRef
Salvage proton beam therapy for locoregional recurrence of non-small cell lung cancer
Hyunju Shin, Jae Myoung Noh, Hongryull Pyo, Yong Chan Ahn, Dongryul Oh
Radiation Oncology Journal.2021; 39(1): 24. CrossRef
Experiences of patients with lung cancer receiving concurrent chemo-radiotherapy
Choi Eunsook, Park Sunhee
Clinical Journal of Nursing Care and Practice.2021; 5(1): 015. CrossRef
Prognostic significance of tumor poliovirus receptor and CTLA4 expression in patients with surgically resected non-small-cell lung cancer
Hui You, Yi-Zhong Zhang, Huan-Ling Lai, Dan Li, Yu-Quan Liu, Run-Ze Li, Imran Khan, Wendy Wen-Lun Hsiao, Fu-Gang Duan, Xing-Xing Fan, Xiao-Jun Yao, Ya-Bing Cao, Qi-Biao Wu, Elaine Lai-Han Leung, Mei-Fang Wang
Journal of Cancer Research and Clinical Oncology.2020; 146(6): 1441. CrossRef
Erlotinib as Neoadjuvant Therapy in Stage IIIA (N2) EGFR Mutation-Positive Non-Small Cell Lung Cancer: A Prospective, Single-Arm, Phase II Study
Liwen Xiong, Rong Li, Jiayuan Sun, Yuqing Lou, Weiyan Zhang, Hao Bai, Huiming Wang, Jie Shen, Bo Jing, Chunlei Shi, Hua Zhong, Aiqin Gu, Liyan Jiang, Jianxing Shi, Wentao Fang, Heng Zhao, Jie Zhang, Junyuan Wang, Junyi Ye, Baohui Han
The Oncologist.2019; 24(2): 157. CrossRef
Recurrence dynamics after trimodality therapy (Neoadjuvant concurrent chemoradiotherapy and surgery) in patients with stage IIIA (N2) lung cancer
Junghee Lee, Hong Kwan Kim, Byung Jo Park, Jong Ho Cho, Yong Soo Choi, Jae Ill Zo, Young Mog Shim, Hongryull Pyo, Yong Chan Ahn, Jin Seok Ahn, Myung-Ju Ahn, Keunchil Park, Jhingook Kim
Lung Cancer.2018; 115: 89. CrossRef

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Case Report

Tumor Lysis Syndrome in a Solid Tumor: A Case Report of a Patient with Invasive Thymoma: Ji Yun Lee, Sung Hee Lim, Ji Young Lee, Ji Hoon Kim, Ki Hong Choi, Keunchil Park, Jong-Mu Sun, Jin Seok Ahn, Myung-Ju Ahn; Cancer Res Treat. 2013;45(4):343-348. Published online December 31, 2013; DOI: https://doi.org/10.4143/crt.2013.45.4.343

Abstract PDF PubReader ePub

Tumor lysis syndrome (TLS) has rarely been observed in solid tumors. We report on a case of a patient with advanced invasive thymoma who developed tumor lysis syndrome after chemotherapy. The potential complications of TLS should be considered in treatment of extensive thymoma.

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Spontaneous tumour lysis syndrome as a rare presentation of thymoma with peripheral blood lymphocytosis
Larry E Nyanti, Andy Sing Ong Tang, Adam Malik b Ismail, Lee Ping Chew, Tze Shin Leong
Proceedings of Singapore Healthcare.2022;[Epub] CrossRef
Tumor Lysis Syndrome in Patients With Solid Tumors: A Systematic Review of Reported Cases
Riyadh M Alqurashi , Husam H Tamim, Ziyad D Alsubhi, Alyazid A Alzahrani, Emad Tashkandi
Cureus.2022;[Epub] CrossRef
Spontaneous tumour lysis syndrome in cervical cancer
Yu Kyung Kim, Ji Yeon Ham, Won-Kil Lee, Kyung Eun Song
Journal of Obstetrics and Gynaecology.2017; 37(5): 679. CrossRef
Ifosfamide/mesna/paclitaxel

Reactions Weekly.2015; 1547(1): 151. CrossRef
Tumor Lysis Syndrome in Solid Tumors: An up to Date Review of the Literature
Aibek E. Mirrakhimov, Alaa M. Ali, Maliha Khan, Aram Barbaryan
Rare Tumors.2014; 6(2): 68. CrossRef

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4 Web of Science
5 Crossref

Original Article

Modest Anti-Cancer Activity of a Bile Acid Acylated Heparin Derivative in a PC14PE6 Induced Orthotopic Lung Cancer Model: Zheng Yun Cui, Min Jae Park, Jeeyun Lee, Jin Seok Ahn, Myung Ju Ahn, Soo Won Seo, Jin Woo Park, Youngro Byun, Keunchil Park; Cancer Res Treat. 2009;41(2):80-86. Published online June 30, 2009; DOI: https://doi.org/10.4143/crt.2009.41.2.80

Abstract PDF PubReader ePub

Purpose

A novel chemically modified heparin derivative, heparin-deoxycholic acid nano-particles, has lower anticoagulant activity, and was recently reported to have significant anti-tumor effects on squamous head and neck cancer cells. Therefore, the aim of this study was to evaluate the anti-tumor effects of heparin-deoxycholic acid nano-particles in a human lung adenocarcinoma cell line.

Materials and Methods

An orthotopic lung cancer model in 16 mice was developed using intra-thoracic injections of 0.5×10⁶ PC14PE6 cells. Ten days after inoculation, the mice were divided into two groups. PBS and Heparin-DOCA particles were injected once a day every 3 days in the tail vein, for a total of 5 injections. The body weight and survival of each mouse were monitored and the tumor size in the lung was measured by SPECT-CT before and after heparin-DOCA nano-particle treatment.

Results

IThe HD particles had no significant cytotoxicity when the PC9 cells were treated in vitro. There was no statistical difference in tumor size, body weight and survival between the HD treated and control groups in vivo. Furthermore, there was no difference in the amount of CD31 between tumor tissues in the two study groups.

Conclusion

HD synthesized with unfractionated heparin had no apparent inhibitory effects on tumor growth in a PC14PE6 cell induced orthotopic lung cancer mouse model. The HD particles did not significantly inhibit tumor-induced angiogenesis at the tumor sites.

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Improvement of orthotopic lung cancer mouse model via thoracotomy and orotracheal intubation enabling in vivo imaging studies
Geun Ho Im, Moon-Sun Jang, Julius Juhyun Chung, Kyoung-Nam Kim, Jae-Hun Kim, Sun I Kim, Jung Hee Lee
Laboratory Animals.2014; 48(2): 124. CrossRef
The antiangiogenic properties of sulfated β-cyclodextrins in anticancer formulations incorporating 5-fluorouracil
Clare A. Watson, Kara L. Vine, Julie M. Locke, Anna Bezos, Christopher R. Parish, Marie Ranson
Anti-Cancer Drugs.2013; 24(7): 704. CrossRef

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2 Crossref

Case Report

Orbital Infiltration as the First Site of Relapse of Primary Testicular T-cell Lymphoma: Hyun Jung Jun, Won Seog Kim, Ji Hyun Yang, Seong Yoon Yi, Young H. Ko, Jeeyun Lee, Chul Won Jung, Se Woong Kang, Keunchil Park; Cancer Res Treat. 2007;39(1):40-43. Published online March 31, 2007; DOI: https://doi.org/10.4143/crt.2007.39.1.40

Abstract PDF PubReader ePub

A 43-year-old male presented with a painless left testicular mass. The pathologic diagnosis of the radical orchiectomy specimen was peripheral T-cell lymphoma, unspecified (PTCL-u). According to the Ann Arbor staging system, his initial stage was III because of the right nasopharyngeal involvement. After first-line chemotherapy with four courses of the CHOP regimen and this was followed by involved-field radiotherapy, he achieved complete remission. Two months later, disease recurred to the left ciliary body of the left eye without evidence of involvement at other sites. Although the patient received intensive chemotherapy with autologous hematopoietic stem cell transplantation, he ultimately died of leptomeningeal seeding. Because both the central nervous system (CNS) and the orbit are sanctuary sites for chemotherapy, orbital infiltration of lymphoma should prompt physicians to evaluate involvement of the CNS and to consider performing prophylactic intrathecal chemotherapy as a treatment option.

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Relapse of Ocular Lymphoma following Primary Testicular Diffuse Large B-cell Lymphoma
Hye Ji Kwon, Joo Yong Lee
Journal of Retina.2023; 8(1): 58. CrossRef
Chronic lymphocytic leukemia and concurrent seminoma in the same testis
Kosuke Miyai, Fumihisa Kumazawa, Kimiya Sato, Hitoshi Tsuda
Journal of Pathology and Translational Medicine.2022; 56(1): 48. CrossRef
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Original Article

Mouse Orthotopic Lung Cancer Model Induced by PC14PE6: Zheng Yun Cui, Jin Seok Ahn, Jee Yun Lee, Won Seog Kim, Ho Yeong Lim, Hyun Jung Jeon, Soo Won Suh, Jin Hoon Kim, Won Ho Kong, Ji Min Kang, Do Hyun Nam, Keunchil Park; Cancer Res Treat. 2006;38(4):234-239. Published online December 31, 2006; DOI: https://doi.org/10.4143/crt.2006.38.4.234

Abstract PDF PubReader ePub

Purpose

This study was undertaken to investigate in detail the xenograft mouse orthotopic lung cancer model induced by PC14PE6 adenocarcinoma cells.

Materials and Methods

Three cell doses (0.5×10⁶; 1×10⁶; 2×10⁶) of PC14PE6 cells were injected into the lungs of male BALB/c nude mice by the intrathoracic injection method. The lung and other organs, including brain, liver, spleen, kidney, muscle, adrenal gland, and lymph node on knee, were removed and stained with H/E to detect the presence of tumor cells.

Results

The reliable tumorigenicity time in the PC14PE6 adenocarcinoma cell-inoculated BALB/c nude mouse was 10 days after intrathoracic injection. The average life span of the three groups after inoculation was 14 days in the 2×10⁶ cells inoculum group; 25 days in the 1×10⁶ cells inoculum group; and 32 days in the 0.5×10⁶ cells inoculum group. The PC14PE6 adenocarcinoma cells induced orthotopic lung cancer limited within the thorax.

Conclusions

This orthotopic lung cancer model is an efficient cancer model with easy inoculation methods, rapid and high tumorigenicity, and simple monitoring methods for metastasis.

Citations

Citations to this article as recorded by

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