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25 "Jong-Mu Sun"
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Original Articles
Clinical Relevance of Starting Alectinib at a Reduced Dose in Patients with ALK-Positive Non-Small Cell Lung Cancer
Junkyu Kim, Min-Ji Kim, Jinyong Kim, Sehhoon Park, Hyun Ae Jung, Se-Hoon Lee, Jin Seok Ahn, Myung-Ju Ahn, Jong-Mu Sun
Received December 14, 2024  Accepted April 22, 2025  Published online April 24, 2025  
DOI: https://doi.org/10.4143/crt.2024.1209    [Accepted]
AbstractAbstract PDF
Purpose
Alectinib has been approved for Anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC) at 300mg twice daily in Japan, lower than global standard of 600mg twice daily. This study evaluated the clinical relevance of the reduced dose by comparing outcomes between the two doses.
Materials and Methods
This study included patients with advanced ALK-positive NSCLC who received alectinib at Samsung Medical Center, Korea. The progression-free survival (PFS), overall survival, cumulative incidence of central nervous system (CNS) progression, and safety profiles were retrospectively reviewed and compared.
Results
Among 306 patients, 32 and 274 received alectinib at either 300 or 600 mg twice daily, respectively. The 300 mg group showed a slight but not significant advantage in PFS (HR 0.82, 95% CI, 0.44-1.51; p=0.51) and overall survival (HR 0.51, 95% CI, 0.20-1.21; p=0.13). Superior outcome with 300mg was remarkable in patients with lower body weight (≤60 kg), but diminished in patients with higher body weights. Patients with baseline brain metastasis in the 300mg group exhibited a slight increase in incidence of CNS failure (HR 1.76, 95% CI, 0.53-5.8; p=0.36). Although the safety profiles were mostly mild, adverse events were more frequent in the 600mg group, 50% of which requiring dose reduction.
Conclusion
Alectinib at 300 mg twice daily seems an acceptable dose in East Asians with ALK-positive NSCLC. Notably, our data favor 300 mg twice daily in patients with lower body weight and no baseline brain metastasis, considering the more tolerable safety profiles and the potential to reduce medical costs.
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Gastrointestinal cancer
Salvage Radiotherapy for Loco-regional Recurrence of Esophageal Cancer Following Surgery
Won Kyung Cho, Jae Myoung Noh, Dongryul Oh, Yong Chan Ahn, Jong-Mu Sun, Hong Kwan Kim, Young Mog Shim
Cancer Res Treat. 2025;57(1):165-173.   Published online July 26, 2024
DOI: https://doi.org/10.4143/crt.2024.191
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
There is few evidence regarding the optimal salvage treatment options for loco-reginal recurrence of esophageal cancer. This study aimed to evaluate the clinical outcomes of salvage radiotherapy (RT) in patients with loco-regional recurrence (LRR) after surgery for esophageal cancer.
Materials and Methods
We retrospectively reviewed 147 esophageal cancer patients who received salvage RT for loco-regional recurrence between 1996 and December 2019. A total dose of 60 Gy in 20 fractions was used for RT alone and 60-70 Gy in 30-35 fractions for concurrent chemoradiotherapy (CCRT).
Results
The patients’ median age was 65 years (range, 41 to 86 years). The median disease-free interval was 13.5 months (1.0 to 97.4 months). After a median 18.8 months follow-up, the 2-year overall survival (OS) and progression-free survival (PFS) rates were 38.1% and 25.9%, respectively. The median OS and PFS were 18.8 and 8.4 months, respectively. The CCRT could not improve OS compared to RT (p=0.336), but there was a trend of better PFS in the CCRT group. Regarding toxicities, the rate of grade 3 or higher toxicity was 10.9% occurring in 16 patients, and it was higher in patients who received CCRT than in the RT alone group (19.6% vs. 6.3%, p=0.023).
Conclusion
Salvage RT alone as well as CCRT could be effective in patients with locoregionally recurrent esophageal cancer.

Citations

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  • Salvage Chemoradiotherapy for Loco-Regional Recurrence of Esophageal Squamous Cell Carcinoma After Esophagectomy
    Atsuto Katano, Tomoki Kiritoshi, Subaru Sawayanagi, Hideomi Yamashita
    Journal of Clinical Medicine.2025; 14(5): 1540.     CrossRef
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  • 90 Download
  • 1 Web of Science
  • 1 Crossref
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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
AbstractAbstract PDFSupplementary MaterialPubReaderePub
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-67D7/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.

Citations

Citations to this article as recorded by  
  • Adjuvant immunotherapy improves survival in completely resected stage IB–III NSCLC: a systematic review and meta-analysis
    Hong Huang, Pengchen Bao, Hongyu Jin, Wenyang Li, Hui Shen, Zhen Qin, Ying Pan, Xinming Su, Delei Kong
    Frontiers in Oncology.2025;[Epub]     CrossRef
  • 3,155 View
  • 156 Download
  • 1 Web of Science
  • 1 Crossref
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Gastrointestinal cancer
Neoadjuvant Nivolumab Therapy for Esophageal Squamous Cell Carcinoma: A Single-Arm, Phase II Study
Sehhoon Park, Yurimi Lee, Jiyun Lee, Yang Won Min, Hong Kwan Kim, Joon Young Choi, Hyun Ae Jung, Yong Soo Choi, Yoon-La Choi, Young Mog Shim, Jong-Mu Sun
Cancer Res Treat. 2024;56(2):567-579.   Published online October 16, 2023
DOI: https://doi.org/10.4143/crt.2023.897
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
Programmed death-1/programmed death-ligand 1 (PD-L1) inhibitors have shown efficacy in metastatic esophageal squamous cell carcinoma (ESCC) therapy. However, data is still limited regarding neoadjuvant immunotherapy for operable ESCC.
Materials and Methods
Patients with clinical stage T2 or T3 and N0 ESCC received three cycles of nivolumab therapy every two weeks before surgical resection. The primary endpoint is major pathologic responses (MPR) rate (≤ 10% of residual viable tumor [RVT]).
Results
Total 20 patients completed the planned nivolumab therapy. Among them, 17 patients underwent surgery as protocol, showing MPR in two patients (MPR rate, 11.8%), including one pathologic complete response, on conventional pathologic response evaluation. Pathologic response was re-evaluated using the immune-related pathologic response criteria based on immune-related RVT (irRVT). Three patients were classified as immunologic major pathologic response (iMPR; ≤ 10% irRVT, iMPR rate: 17.6%), five as pathologic partial response (> 10% and < 90% irRVT), and nine as pathologic nonresponse (≥ 90% irRVT). The combined positive score (CPS) for PD-L1 in the baseline samples was predictable for iMPR, with the probability as 37.5% in CPS ≥ 10 (3/8) and 0% in CPS < 10 (0/9).
Conclusion
Although the efficacy of neoadjuvant nivolumab therapy was modest in unselected ESCC patients, further researches on neoadjuvant immunotherapy are necessary in patients with PD-L1 expressed ESCC.
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Lung and Thoracic cancer
First-Line Alectinib vs. Brigatinib in Advanced Non–Small Cell Lung Cancer with ALK Rearrangement: Real-World Data
Youngkyung Jeon, Sehhoon Park, Hyun Ae Jung, Jong-Mu Sun, Se-Hoon Lee, Jin Seok Ahn, Myung-Ju Ahn
Cancer Res Treat. 2024;56(1):61-69.   Published online July 14, 2023
DOI: https://doi.org/10.4143/crt.2023.461
AbstractAbstract PDFPubReaderePub
Purpose
Alectinib and brigatinib are second-generation anaplastic lymphoma receptor tyrosine kinases (ALKs) that are widely used as first-line therapy for treating ALK-positive advanced non–small cell lung cancer (NSCLC). Given the lack of a head-to-head comparison of these drugs as first-line therapies, this retrospective observational study aimed to compare the real-world efficacy and safety of alectinib and brigatinib.
Materials and Methods
Patients who received alectinib or brigatinib as the first-line treatment for ALK-positive advanced NSCLC were evaluated for clinical outcomes of objective response rate (ORR), intracranial ORR, time to next treatment (TTNT), progression-free survival (PFS), overall survival (OS), and safety profiles.
Results
Of 208 patients who received either alectinib or brigatinib as a first-line treatment, 176 received alectinib and 32 received brigatinib. At the data cutoff point, the median follow-up duration was 16.5 months (95% confidence interval [CI], 14.7 to 18.3) in the brigatinib group and 27.5 months (95% CI, 24.6 to 30.4) in the alectinib group. The ORR was 92.5% with alectinib and 93.8% for brigatinib. The intracranial ORR rates were 92.7% (38/41) and 100% (10/10), respectively. The rate of PFS at 12 months was comparable between the alectinib group and the brigatinib groups (84.4% vs. 84.1%, p=0.64), and the median TTNT, PFS, and OS were not reached in either group. Treatment-related adverse events were usually mild, and treatment discontinuation due to adverse events was rare (alectinib 4.5% vs. brigatinib 6.25%).
Conclusion
Alectinib and brigatinib had similar clinical benefits when used as the first-line treatment of NSCLC patients with ALK rearrangement in the real world.

Citations

Citations to this article as recorded by  
  • Efficacy and safety of brigatinib in patients with ALK TKI-naive advanced ALK+ NSCLC: Integrated analysis of the ALTA-1L and J-ALTA trials
    D. Ross Camidge, Shunichi Sugawara, Masashi Kondo, Hye Ryun Kim, Myung-Ju Ahn, James C.H. Yang, Ji-Youn Han, Maximilian J. Hochmair, Ki Hyeong Lee, Angelo Delmonte, Kentarou Kudou, Takayuki Asato, Bradley Hupf, Florin Vranceanu, Robert J. Fram, Yuichiro O
    Lung Cancer.2025; 201: 108424.     CrossRef
  • Effectiveness of First-Line Treatment with Anaplastic Lymphoma Kinase and ROS1 Protoncogene Inhibitors in Non-Small Cell Lung Cancer Patients—Real-World Evidence of Two Polish Cancer Centers
    Michał Gil, Kinga Winiarczyk, Paweł Krawczyk, Kamila Wojas-Krawczyk, Aleksandra Łomża-Łaba, Adrian Obara, Łukasz Gajek, Katarzyna Reszka, Andrzej Tysarowski, Jarosław Buczkowski, Izabela Chmielewska, Tomasz Jankowski, Magdalena Szuba-Gil, Maciej Strzemski
    Cancers.2025; 17(7): 1253.     CrossRef
  • Oncogenic Fusions in NSCLC: From Mechanisms to Clinical Applications
    Nyein Wint Yee Theik, Suset Almuinas De Armas, Daniel Rosas, Amy Kiamos, Nyein Nyein Thaw Dar, Ahmed Shoreibah, Atif Hussein, Luis E. Raez
    International Journal of Molecular Sciences.2025; 26(8): 3802.     CrossRef
  • Bridging the Gap between Trial Adverse Events and Real-World Data
    Sang Hyuk Kim, Hyun Lee, Dong Won Park
    Cancer Research and Treatment.2024; 56(3): 972.     CrossRef
  • Real‐world evidence of brigatinib as second‐line treatment after crizotinib for ALK+ non‐small cell lung cancer using South Korean claims data (K‐AREAL)
    Jeong Eun Lee, Jin Hyun Nam, Sun Hong Kwon, Bo Kyung Kim, Seung Min Ha
    Cancer Medicine.2024;[Epub]     CrossRef
  • Cost‐Effectiveness Analysis of Adjuvant Alectinib versus Platinum‐Based Chemotherapy in Resected ALK‐Positive Non‐Small‐Cell Lung Cancer in the Chinese Health Care System
    Qiran Wei, Yifang Liang, Jiahui Mao, Xin Guan
    Cancer Medicine.2024;[Epub]     CrossRef
  • 6,053 View
  • 609 Download
  • 7 Web of Science
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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
AbstractAbstract PDFPubReaderePub
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

Citations to this article as recorded by  
  • 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
  • 3,711 View
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  • 5 Web of Science
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The Role of Brain Radiotherapy before First-Line Afatinib Therapy, Compared to Gefitinib or Erlotinib, in Patients with EGFR-Mutant Non–Small Cell Lung Cancer
Hyun Ae Jung, Sehhoon Park, Se-Hoon Lee, Jin Seok Ahn, Myung-Ju Ahn, Jong-Mu Sun
Cancer Res Treat. 2023;55(2):479-487.   Published online December 27, 2022
DOI: https://doi.org/10.4143/crt.2022.1344
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
Brain metastasis is common in patients with epidermal growth factor receptor (EGFR)–mutant non–small cell lung cancer (NSCLC) at initial presentation. A previous study showed that brain radiotherapy (RT) before first-generation (first-G) EGFR–tyrosine kinase inhibitor (TKI) therapy is associated with longer overall survival than TKI therapy alone. However, there is no data regarding the role of additional brain RT before afatinib therapy.
Materials and Methods
Between October 2014 and June 2019, EGFR-mutant NSCLC patients with brain metastases who started first-G EGFR-TKIs (gefitinib or erlotinib) or afatinib as first-line therapy were retrospectively analyzed. This study compared overall survival and intracranial progression-free survival (PFS) between patients who received EGFR-TKIs alone and EGFR-TKIs with brain RT and either a first-G EGFR-TKI or afatinib, respectively.
Results
The median follow-up duration was 29.6 months (range, 1.5 to 116.9 months). In the first-G EGFR-TKI group (n=155), 94 patients (60.6%) received the first-G EGFR-TKI alone and 61 patients (39.4%) received brain RT prior to their first-G EGFR-TKI. In the afatinib group (n=204), 126 patients (61.8%) received afatinib alone and 78 patients (38.2%) received brain RT prior to afatinib. There was no difference in overall survival rates between the groups with RT (35.6 months: 95% confidence interval [CI], 27.9 to 43.3) and without RT (31.4 months: 95% CI, 23.9 to 38.9) in the afatinib group (p=0.58), but there was a significant difference in overall survival in the first-G EGFR-TKI group in a manner favoring additional brain RT (41.1 months: 95% CI, 30.5 to 51.7 vs. 25.8 months: 95% CI, 20.1 to 31.5; p=0.02). Meanwhile, median intracranial PFS was not different between patients who received EGFR-TKI therapy alone vs. EGFR-TKI therapy with brain RT in both the first-G EGFR-TKI (p=0.39) and afatinib (p=0.24) groups.
Conclusion
Afatinib therapy alone showed comparable survival outcomes to those of afatinib with brain RT. The current study suggests that brain RT could be an optional, not mandatory, treatment modality when afatinib therapy is considered in patients with EGFR-mutant NSCLC.

Citations

Citations to this article as recorded by  
  • Integrated single cell and bulk RNA sequencing analyses reveal the impact of tryptophan metabolism on prognosis and immunotherapy in colon cancer
    Yanyan Hu, Ximo Xu, Hao Zhong, Chengshen Ding, Sen zhang, Wei Qin, Enkui Zhang, Duohuo Shu, Mengqin Yu, Naijipu Abuduaini, Xiao Yang, Bo Feng, Jianwen Li
    Scientific Reports.2025;[Epub]     CrossRef
  • Radiation Recall Pneumonitis: The Open Challenge in Differential Diagnosis of Pneumonia Induced by Oncological Treatments
    Francesca Grassi, Vincenza Granata, Roberta Fusco, Federica De Muzio, Carmen Cutolo, Michela Gabelloni, Alessandra Borgheresi, Ginevra Danti, Carmine Picone, Andrea Giovagnoni, Vittorio Miele, Nicoletta Gandolfo, Antonio Barile, Valerio Nardone, Roberta G
    Journal of Clinical Medicine.2023; 12(4): 1442.     CrossRef
  • Dacomitinib in EGFR-mutant non-small-cell lung cancer with brain metastasis: a single-arm, phase II study
    H.A. Jung, S. Park, S.-H. Lee, J.S. Ahn, M.-J. Ahn, J.-M. Sun
    ESMO Open.2023; 8(6): 102068.     CrossRef
  • Recent advances progress of targeted drugs combined with radiotherapy for advanced non-small cell lung cancer: a review
    Jiamin Xu, Zhongming Wang
    Frontiers in Oncology.2023;[Epub]     CrossRef
  • 4,605 View
  • 157 Download
  • 5 Web of Science
  • 4 Crossref
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EGFR Mutation–Positive Unresectable Stage III Non-Squamous Lung Cancer Is Associated with a High Incidence of Brain Metastasis
Hongsik Kim, Sehhoon Park, Hyun Ae Jung, Jong-Mu Sun, Se-Hoon Lee, Jin Seok Ahn, Myung-Ju Ahn
Cancer Res Treat. 2023;55(2):498-505.   Published online October 4, 2022
DOI: https://doi.org/10.4143/crt.2022.388
AbstractAbstract PDFPubReaderePub
Purpose
The impact of epidermal growth factor receptor (EGFR) mutation in locally advanced non–small cell lung cancer (NSCLC) remains controversial. This study was conducted to investigate the clinical outcomes and recurrence patterns after definitive chemoradiotherapy (CRT) in patients with unresectable stage III non-squamous-cell lung cancer according to EGFR mutation status.
Materials and Methods
We retrospectively reviewed 604 patients with pathologically confirmed stage III NSCLC who were treated with definitive CRT and were examined for EGFR mutation at Samsung Medical Center, Korea, from January 2013 to December 2018. Among them, we identified 236 patients with stage III non-squamous-cell lung cancer who were treated with definitive CRT and were examined for EGFR mutation status. We analyzed the frequency of EGFR mutation, progression-free survival (PFS), overall survival (OS), objective response rate (ORR), and recurrence pattern.
Results
Among 236 patients, EGFR mutation was detected in 71 patients (30.1%) and the median follow-up duration was 41.7 months. There were no significant differences in PFS (9.9 vs. 10.9 months, p=0.236), and ORR to CRT (93.0% vs. 90.3%, p=0.623) according to EGFR mutation status. However, the EGFR mutant group showed significantly higher recurrence (88.7% vs. 75.2%, p=0.022), distant metastasis (76.1% vs. 61.2%, p=0.036) rates, especially brain (38.0% vs. 12.7%, p < 0.001), and better median OS (59.2 vs. 41.3 months, p=0.037) compared with patients without EGFR mutation.
Conclusion
Patients with EGFR mutation–positive unresectable stage III non-squamous lung cancer exhibited higher recurrence and distant metastasis rates, especially brain metastasis.

Citations

Citations to this article as recorded by  
  • TFAP2A facilitates the metastasis and radioresistance of esophageal cancer by promoting EGFR transcription
    Jinjin Yuan, Junqi Liu, Ruitai Fai, Zongwen Liu
    Naunyn-Schmiedeberg's Archives of Pharmacology.2025;[Epub]     CrossRef
  • Cost-Effectiveness of Adjuvant Osimertinib With and Without Chemotherapy for Surgically Resected NSCLC
    Angelos Vasilopoulos, Alexander Pohlman, Ayham Odeh, K. Robert Shen, Julia M. Coughlin, Zaid M. Abdelsattar
    JTO Clinical and Research Reports.2025; 6(6): 100833.     CrossRef
  • Prognostic Factors in Postoperative Brain Metastases Derive From Non-small Cell Lung Cancer: A Retrospective Analysis
    Haibin Chen, Liang Sun, Zhi Yang, Yuanyuan Qu, Nanyang Tong, Caixing Sun, Liang Xia
    Clinical Medicine Insights: Oncology.2024;[Epub]     CrossRef
  • Brain metastasis screening in the molecular age
    Joanna K Tabor, Amanda Onoichenco, Vinayak Narayan, A Gabriella Wernicke, Randy S D’Amico, Morana Vojnic
    Neuro-Oncology Advances.2023;[Epub]     CrossRef
  • 5,501 View
  • 247 Download
  • 6 Web of Science
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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
AbstractAbstract PDFPubReaderePub
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

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  • Surgery for Stage IV Disease—Is It Prime Time Yet?
    Marianna V. Papageorge, Mara B. Antonoff
    Surgical Oncology Clinics of North America.2025;[Epub]     CrossRef
  • Analysis of prognostic factors and risk prediction in brain metastases: a SEER population-based study
    Qiang Ji, Zixuan Yang, Xun Kang, Lili Zhou, Feng Chen, Wenbin Li
    Frontiers in Oncology.2025;[Epub]     CrossRef
  • ‘Perspectives of pulmonologists and thoracic surgeons on Oligometastatic disease: curability, treatment approaches, and disease trajectory’
    Damla Azaklı, Inanc Yazici, Aysegul Erinc, Celal Satici
    Future Oncology.2025; : 1.     CrossRef
  • 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
  • 6,611 View
  • 158 Download
  • 4 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
AbstractAbstract PDFPubReaderePub
The non-small cell lung cancer with activating epidermal growth factor receptor (EGFR) mutation eventually acquires resistant to either first or second-generation EGFR tyrosine kinase inhibitor (TKI). As the following option, targeting EGFR T790M with third-generation EGFR TKI is now established as a standard treatment option. In this study, we are reporting the first case of resistance mechanism to the novel third-generation EGFR TKI, lazertinib, which showed promising clinical efficacy in phase 1-2 study. The patients showed resistance to the treatment by acquiring the additional EGFR C797S mutation in cis which is also confirmed from the patient-derived cell lines.

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

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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
AbstractAbstract PDFPubReaderePub
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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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
AbstractAbstract PDFPubReaderePub
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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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
AbstractAbstract PDFSupplementary MaterialPubReaderePub
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
AbstractAbstract PDFPubReaderePub
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
AbstractAbstract PDFSupplementary MaterialPubReaderePub
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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Close layer
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
AbstractAbstract PDFSupplementary MaterialPubReaderePub
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
Retrospective Molecular Epidemiology Study of PD-L1 Expression in Patients with EGFR-Mutant Non-small Cell Lung Cancer
Jong Ho Cho, Wei Zhou, Yoon-La Choi, Jong-Mu Sun, Hyejoo Choi, Tae-Eun Kim, Marisa Dolled-Filhart, Kenneth Emancipator, Mary Anne Rutkowski, Jhingook Kim
Cancer Res Treat. 2018;50(1):95-102.   Published online March 17, 2017
DOI: https://doi.org/10.4143/crt.2016.591
AbstractAbstract PDFPubReaderePub
Purpose
Data are limited on programmed death ligand 1 (PD-L1) expression in epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC).
Materials and Methods
We retrospectively evaluated the relationship between PD-L1 expression and recurrence-free survival (RFS) and overall survival in 319 patients with EGFR-mutant NSCLC who were treated at Samsung Medical Center from 2006 to 2014. Membranous PD-L1 expression on tumor cells was measured using the PD-L1 IHC 22C3 pharmDx antibody and reported as tumor proportion score (TPS). Kaplan-Meier methods, log-rank test, and Cox proportional hazards models were used for survival analysis.
Results
All patients had ≥ 1 EGFR mutation—54% in exon 19 and 39% in exon 21. Overall, 51% of patients had PD-L1–positive tumors. The prevalence of PD-L1 positivity was higher among patients with stages II-IV versus stage I disease (64% vs. 44%) and among patients with other EGFR mutations (75%) than with L858R mutation (39%) or exon 19 deletion (52%). PD-L1 positivity was associated with shorter RFS, with an adjusted hazard ratio of 1.52 (95% confidence interval [CI], 0.81 to 2.84; median, 18 months) for the PD-L1 TPS ≥ 50% group, 1.51 (95% CI, 1.02 to 2.21; median, 31 months) for the PD-L1 TPS 1%-49% group, and 1.51 (95% CI, 1.05 to 2.18) for the combined PD-L1–positive groups (TPS ≥ 1%) compared with the PD-L1–negative group (median, 35 months).
Conclusion
PD-L1 expression is associated with disease stage and type of EGFR mutation. PD-L1 positivity might be associated with worse RFS among patients with surgically treated EGFR-mutant NSCLC.

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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
AbstractAbstract PDFPubReaderePub
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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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
AbstractAbstract PDFPubReaderePub
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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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
AbstractAbstract PDFSupplementary MaterialPubReaderePub
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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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
AbstractAbstract PDFPubReaderePub
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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    Feng Yang-Chun, Cheng Zhen-Zhen, Huang Yan-Chun, Ma Xiu-Min
    Medicine.2017; 96(25): e7270.     CrossRef
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    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
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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
AbstractAbstract PDFPubReaderePub
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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    Junghee Lee, Yun Soo Hong, Jin Lee, Genehee Lee, Danbee Kang, Jiyoun Park, Yeong Jeong Jeon, Seong Yong Park, Jong Ho Cho, Yong Soo Choi, Jhingook Kim, Young Mog Shim, Eliseo Guallar, Juhee Cho, Hong Kwan Kim
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    Choi Eunsook, Park Sunhee
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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
AbstractAbstract PDFPubReaderePub
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.

Citations

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    Larry E Nyanti, Andy Sing Ong Tang, Adam Malik b Ismail, Lee Ping Chew, Tze Shin Leong
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Original Article
Predictive Value of the ERCC1 Expression for Treatment Response and Survival in Advanced Gastric Cancer Patients Receiving Cisplatin-based First-line Chemotherapy
Jina Yun, Kyoung-Mee Kim, Seung Tae Kim, Jung-Hoon Kim, Jung A Kim, Jee Hyun Kong, Soo Hyeon Lee, Young-Woong Won, Jong-Mu Sun, Jeeyun Lee, Se Hoon Park, Joon Oh Park, Young Suk Park, Ho Yeong Lim, Won Ki Kang
Cancer Res Treat. 2010;42(2):101-106.   Published online June 30, 2010
DOI: https://doi.org/10.4143/crt.2010.42.2.101
AbstractAbstract PDFPubReaderePub
Purpose

The aim of this study was to determine whether the ERCC1 expression is effective to predict the clinical outcomes of patients with advanced gastric cancer (AGC) and who were treated with cisplatin-based first-line chemotherapy.

Materials and Methods

A total of 89 measurable AGC patients received cisplatin and capecitabine, with or without epirubicin, as a part of a randomized phase II study. Patients were included for the current molecular analysis if they had received two or more cycles of chemotherapy, their objective tumor responses were measured and if their paraffin-embedded tumor samples were available. The ERCC1 expression was examined by performing immunohistochemical (IHC) staining, and the patients were divided into two groups (positive or negative) according to the presence of IHC staining of the tumor cell nuclei.

Results

Of the 32 eligible patients, 21 patients (66%) had tumor with a positive expression of ERCC1 and the remaining 11 patients had tumor with a negative ERCC1-expression. The ERCC1-negative patients achieved a higher response rate than that of the ERCC1-positive patients (44% vs. 28%, respectively), although the difference was not statistically significant (p=0.42). The median survival time for the all patients was 14.6 months (95% CI: 13.6 to 15.6 months). The one-year survival rate was similar for the ERCC1-negative patients (61%) and the ERCC1-positive patients (70%).

Conclusion

In the current study, the tumor ERCC1 expression by IHC staining could not predict the clinical response or survival of AGC patients who were treated with cisplatin-based first-line chemotherapy. The ERCC1 protein expression does not appear to be a useful tool for the selection of tailored chemotherapy for these patients.

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    Eduardo Henrique Cunha Neves Filho, Rosane Oliveira de Sant'Ana, Luiz Vianney Saldanha Cidrão Nunes, Adriana Pinheiro Bezerra Pires, Maria do Perpétuo Socorro Saldanha da Cunha
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    Anqi Yao, You Wang, Xiaohong Peng, Rong Ye, Qiaoli Wang, Yuexiao Qi, Fuxiang Zhou
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    Joshua D. Lawson, Jason K. Sicklick, Paul T. Fanta
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