Cancer Research and Treatment

Original Articles

Breast cancer

A Phase II Trial of S-1 and Oxaliplatin in Patients with Metastatic Breast Cancer Previously Treated with Anthracycline and Taxane (KCSG-BR07-03): Dae-Won Lee, Bhumsuk Keam, Keun Seok Lee, Jin-Hee Ahn, Joohyuk Sohn, Jin Seok Ahn, Moon Hee Lee, Jee Hyun Kim, Kyung Eun Lee, Hyo Jung Kim, Si-Young Kim, Yeon Hee Park, Chan-Young Ock, Kyung-Hun Lee, Sae-Won Han, Sung-Bae Kim, Young Hyuck Im, Hyun Cheol Chung, Do-Youn Oh, Seock-Ah Im; Cancer Res Treat. 2023;55(2):523-530. Published online November 8, 2022; DOI: https://doi.org/10.4143/crt.2022.1360

Purpose
This single-arm phase II trial investigate the efficacy and safety of S-1 plus oxaliplatin (SOX) in patients with metastatic breast cancer.
Materials and Methods
Patients with metastatic breast cancer previously treated with anthracyclines and taxanes were enrolled. Patients received S-1 (40-60 mg depending on patient’s body surface area, twice a day, day 1-14) and oxaliplatin (130 mg/m2, day 1) in 3 weeks cycle until disease progression or unacceptable toxicity. The primary endpoint was objective response rate (ORR) according to Response Evaluation Criteria in Solid Tumor 1.1. Secondary endpoints included time-to-progression (TTP), duration-of-response (DoR), overall survival (OS), and adverse events.
Results
A total of 87 patients were enrolled from 11 institutions in Korea. Hormone receptor was positive in 54 (62.1%) patients and six (6.9%) had human epidermal growth factor receptor 2–positive disease. Forty-eight patients (85.1%) had visceral metastasis and 74 (55.2%) had more than three sites of metastases. The ORR of SOX regimen was 38.5% (95% confidence interval [CI], 26.9 to 50.0) with a median TTP of 6.0 months (95% CI, 5.1 to 6.9). Median DoR and OS were 10.3 months (95% CI, 5.5 to 15.1) and 19.4 (95% CI, not estimated) months, respectively. Grade 3 or 4 neutropenia was reported in 28 patients (32.1%) and thrombocytopenia was observed in 23 patients (26.6%).
Conclusion
This phase II study showed that SOX regimen is a reasonable option in metastatic breast cancer previously treated with anthracyclines and taxanes.

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Unraveling the immune landscape and therapeutic biomarker PMEPA1 for oxaliplatin resistance in colorectal cancer: A comprehensive approach
Zhengguang Zhang, Tianming Lu, Zhe Zhang, Zixian Liu, Ruoning Qian, Ruogu Qi, Fuqiong Zhou, Min Li
Biochemical Pharmacology.2024; 222: 116117. CrossRef
Efficacy and safety of utidelone plus capecitabine in advanced first-line therapy for metastatic breast cancer: A multicenter real-world study
Pingping Bi, Xi Wang, Rui Liu, Xiuqin Li, Shanrong Wei, Jiawen Zhao, Xin Tan, Fan Zhang, Qing Mao, Ying Zhang, Baoyan Tang, Xueqiong Xun, Rong Guo, Kai Zheng, Shaoqiang Zhou, Shicong Tang
Surgery Open Science.2023; 16: 171. CrossRef

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A Retrospective Analysis for Patients with HER2-Positive Gastric Cancer Who Were Treated with Trastuzumab-Based Chemotherapy: In the Perspectives of Ethnicity and Histology: Jun Ho Yi, Jung Hun Kang, In Gyu Hwang, Hee Kyung Ahn, Hyun Jin Baek, Soon Il Lee, Do Hyoung Lim, Young-Woong Won, Jun Ho Ji, Hyo Song Kim, Sun Young Rha, Sung Yong Oh, Kyung Eun Lee, Taekyu Lim, Chi Hoon Maeng, Moon Jin Kim, Seung Tae Kim, Jeeyun Lee, Joon Oh Park, Young Suk Park, Ho Yeong Lim, Won Ki Kang, Se Hoon Park; Cancer Res Treat. 2016;48(2):553-560. Published online August 10, 2015; DOI: https://doi.org/10.4143/crt.2015.155

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Purpose
While the Trastuzumab for Gastric Cancer (ToGA) trial demonstrated the efficacy and safety of trastuzumab-based chemotherapy in HER2-positive metastatic gastric cancer, the overall survival (OS) benefit was not found in Asian and diffuse-type cancer patients. The aim of the study is to investigate predictive markers for trastuzumab-based chemotherapy.
Materials and Methods
Data of patients with HER2-positive gastric cancer treated with trastuzumab-based chemotherapy were analyzed retrospectively.
Results
A total of 168 Asian patients were included. The median age was 60 years (range, 27 to 85 years) and the male:female ratio was 118 (70.2%):50 (29.8%). Fourteen (8.3%), 63 (37.5%), 75 (44.6%), and 11 (6.5%) patients had well, moderately, poorly-differentiated tubular adenocarcinoma and signet ring cell carcinoma, respectively. With 14 complete responses and 73 partial responses, the response rate was 50.6%. The median progression-free survival (PFS) was 10.2 months (95% confidence interval [CI], 8.7 to 11.7), and the median OS was 18.5 months (95% CI, 16.4 to 50.6). Next, we investigated the effect of poorly-differentiated histology (PDH, poorly-differentiated tubular adenocarcinoma+signet ring cell carcinoma) on clinical outcomes. The median PFS (8.9 months vs. 11.5 months, p=0.16) was slightly inferior in PDH patients, and the median OS was significantly shorter in PDH patients (14.6 months vs. 19.0 months, p=0.025).
Conclusion
While subset analysis of the ToGA trial demonstrated that trastuzumab-based chemotherapy may not be beneficial for Asians and patients with PDH, our data may suggest that even in Asian patients and patients with PDH, trastuzumab-based chemotherapy could be associated with improved clinical outcomes in patients with HER2-positive gastric cancer.

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Timing to Surgery and Lymph Node Upstaging in Gastric Cancer: An NCDB Analysis
Maria Cristina Riascos, Jacques A. Greenberg, Federico Palacardo, Rodrigo Edelmuth, V. Colby Lewis, Anjile An, Haythem Najah, Hala Al Asadi, Parima Safe, Brendan M. Finnerty, Paul J. Christos, Thomas J. Fahey, Rasa Zarnegar
Annals of Surgical Oncology.2024; 31(3): 1714. CrossRef
Deviating HER2 test results in gastric cancer: analysis from the prospective multicenter VARIANZ study
Katharina Kolbe, Ivonne Haffner, Katrin Schierle, Dieter Maier, Birgitta Geier, Birgit Luber, Hendrik Bläker, Christian Wittekind, Florian Lordick
Journal of Cancer Research and Clinical Oncology.2023; 149(3): 1319. CrossRef
Trastuzumab Combined With Ramucirumab and Paclitaxel in Patients With Previously Treated Human Epidermal Growth Factor Receptor 2–Positive Advanced Gastric or Gastroesophageal Junction Cancer
Chang Gon Kim, Minkyu Jung, Hyo Song Kim, Choong-kun Lee, Hei-Cheul Jeung, Dong-Hoe Koo, Woo Kyun Bae, Dae Young Zang, Bum Jun Kim, Hyunki Kim, Un-Jung Yun, Jingmin Che, Sejung Park, Tae Soo Kim, Woo Sun Kwon, Juin Park, Sang Woo Cho, Chung Mo Nam, Hyun C
Journal of Clinical Oncology.2023; 41(27): 4394. CrossRef
Novel HER2-targeted therapy to overcome trastuzumab resistance in HER2-amplified gastric cancer
Juin Park, Sun Kyoung Kang, Woo Sun Kwon, Inhye Jeong, Tae Soo Kim, Seo Young Yu, Sang Woo Cho, Hyun Cheol Chung, Sun Young Rha
Scientific Reports.2023;[Epub] CrossRef
Do proton pump inhibitors affect the effectiveness of chemotherapy in colorectal cancer patients? A systematic review with meta-analysis
Wan-Ying Lin, Shih-Syuan Wang, Yi-No Kang, Andrea S. Porpiglia, Yu Chang, Chin-Hsuan Huang, Ronak Bhimani, Eahab Abdul-Lattif, Muneeba Azmat, Tsu-Hsien Wang, Yu-Shiuan Lin, Yu-Cheng Chang, Kuan-Yu Chi
Frontiers in Pharmacology.2022;[Epub] CrossRef
Effectiveness of Trastuzumab in Routine Clinical Practice: A Population-based Study of Patients with HER-2-positive Oesophageal, Gastroesophageal and Gastric Cancer
S.J. Merchant, W. Kong, B. Gyawali, T. Hanna, W. Chung, S. Nanji, S.V. Patel, C.M. Booth
Clinical Oncology.2021; 33(3): 202. CrossRef
Trastuzumab-based palliative chemotherapy for HER2-positive gastric cancer: a single-center real-world data
Tae-Hwan Kim, Hun Do Cho, Yong Won Choi, Hyun Woo Lee, Seok Yun Kang, Geum Sook Jeong, Jin-Hyuk Choi, Mi Sun Ahn, Seung-Soo Sheen
BMC Cancer.2021;[Epub] CrossRef
HER2 Expression, Test Deviations, and Their Impact on Survival in Metastatic Gastric Cancer: Results From the Prospective Multicenter VARIANZ Study
Ivonne Haffner, Katrin Schierle, Elba Raimúndez, Birgitta Geier, Dieter Maier, Jan Hasenauer, Birgit Luber, Axel Walch, Katharina Kolbe, Jorge Riera Knorrenschild, Albrecht Kretzschmar, Beate Rau, Ludwig Fischer von Weikersthal, Miriam Ahlborn, Gabriele S
Journal of Clinical Oncology.2021; 39(13): 1468. CrossRef
Current therapeutic options for gastric adenocarcinoma
C.R. Akshatha, Smitha Bhat, R. Sindhu, Dharini Shashank, Sarana Rose Sommano, Wanaporn Tapingkae, Ratchadawan Cheewangkoon, Shashanka K. Prasad
Saudi Journal of Biological Sciences.2021; 28(9): 5371. CrossRef
Efficacy of Trastuzumab and Potential Risk Factors on Survival in Patients with HER2-Positive Metastatic Gastric Cancer
Atakan Topcu, Muhammed Mustafa Atci, Saban Secmeler, Mehmet Besiroglu, Murat Ayhan, Metin Ozkan, Oktay Bozkurt, Zuhat Urakci, Seval Ay, Caglayan Geredeli, Ayse Irem Yasin, Haci Mehmet Turk
Future Oncology.2021; 17(31): 4157. CrossRef
Reliability of Conclusions from Early Analyses of Real-World Data for Newly Approved Drugs in Advanced Gastric Cancer in the United States

Lisa M Hess, Michael Grabner, Liya Wang, Astra M Liepa, Xiaohong Ivy Li, Zhanglin Lin Cui, Lee Bowman, William R Schelman
Pragmatic and Observational Research.2020; Volume 11: 27. CrossRef
Targeting HER2-positive gastric cancer with a novel 18F-labeled ZHER2:342 probe
Yunyun Pan, Zhengyang Yang, Yuping Xu, Zhicheng Bai, Donghui Pan, Runlin Yang, Lizhen Wang, Wenxian Guan, Min Yang
RSC Advances.2019; 9(19): 10990. CrossRef
Clinical significance of overexpression of NRG1 and its receptors, HER3 and HER4, in gastric cancer patients
Sumi Yun, Jiwon Koh, Soo Kyung Nam, Jung Ok Park, Sung Mi Lee, Kyoungyul Lee, Kyu Sang Lee, Sang-Hoon Ahn, Do Joong Park, Hyung-Ho Kim, Gheeyoung Choe, Woo Ho Kim, Hye Seung Lee
Gastric Cancer.2018; 21(2): 225. CrossRef
Correlation of trastuzumab-based treatment with clinical characteristics and prognosis in HER2-positive gastric and gastroesophageal junction cancer: A retrospective single center analysis
A. Ilhan-Mutlu, H. Taghizadeh, A. Beer, W. Dolak, A. Ba-Ssalamah, S. F. Schoppmann, M. Hejna, P. Birner, M. Preusser
Cancer Biology & Therapy.2018; 19(3): 169. CrossRef
Docetaxel, oxaliplatin, 5FU, and trastuzumab as first-line therapy in patients with human epidermal receptor 2-positive advanced gastric or gastroesophageal junction cancer
Giandomenico Roviello, Roberto Petrioli, Valerio Nardone, Pietro Rosellini, Andrea Giovanni Multari, Raffaele Conca, Michele Aieta
Medicine.2018; 97(20): e10745. CrossRef

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Case Report

Cancer of Unknown Primary Finally Revealed to Be a Metastatic Prostate Cancer: A Case Report: Jung Yeon Cho, Eun Jin Shim, In Seon Kim, Eun Mi Nam, Moon Young Choi, Kyung Eun Lee, Yeung Chul Mun, Chu Myoung Seoung, Soon Nam Lee, Dong Eun Song, Woon Sup Han; Cancer Res Treat. 2009;41(1):45-49. Published online March 31, 2009; DOI: https://doi.org/10.4143/crt.2009.41.1.45

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The vast majority of patients with metastatic prostate cancer present with bone metastases and high prostate specific antigen (PSA) level. Rarely, prostate cancer can develop in patients with normal PSA level. Here, we report a patient who presented with a periureteral tumor of unknown primary site that was confirmed as prostate adenocarcinoma after three years with using specific immunohistochemical examination. A 64-year old man was admitted to our hospital with left flank pain associated with masses on the left pelvic cavity with left hydronephrosis. All tumor markers including CEA, CA19-9, and PSA were within the normal range. After an exploratory mass excision and left nephrectomy, the pelvic mass was diagnosed as poorly differentiated carcinoma without specific positive immunohistochemical markers. At that time, we treated him as having a cancer of unknown primary site. After approximately three years later, he revisited the hospital with a complaint of right shoulder pain. A right scapular mass was newly detected with a high serum PSA level (101.7 ng/ml). Tissues from the scapular mass and prostate revealed prostate cancer with positive immunoreactivity for P504S, a new prostate cancer-specific gene. The histological findings were the same as the previous pelvic mass; however, positive staining for PSA was observed only in the prostate mass. This case demonstrates a patient with prostate cancer and negative serological test and tissue staining that turned out to be positive during progression. We suggest the usefulness of newly developed immunohistochemical markers such as P504S to determine the specific primary site of metastatic poorly differentiated adenocarcinoma in men.

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A Unique Case of Prostate Carcinoma Presenting as Retroperitoneal Lymphadenopathy With Normal Levels of Prostate-Specific Antigen and a Prostate of Normal Size: A Case Report
Swapnil Patil, Mayank Mundada, Pradnya M Diggikar, Raju Hansini Reddy, Sree Vidya Yekkaluru
Cureus.2024;[Epub] CrossRef
Prostate cancer metastasis to the distal phalanx of the left hallux: The first confirmed case and literature review
Xinbing Sui, Yan Hu, Cheng Zhang, Hongming Pan, Da Li
Oncology Letters.2016; 12(2): 1074. CrossRef
Metastasis of prostate carcinoma in the mandible manifesting as numb chin syndrome
Secil Aksoy, Kaan Orhan, Sebnem Kursun, Mehmet Eray Kolsuz, Berkan Celikten
World Journal of Surgical Oncology.2014;[Epub] CrossRef

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Original Article

The Prognostic Significance of the Overexpression of HER-2/ neu in Korean Gastric Carcinomas and the In Vitro Effects of Anti-HER-2/neu Antibody on Cell Growth in the Gastric Carcinoma Cell Lines: Seock Ah Im, Kyung Eun Lee, Eunmi Nam, Seung Hyun Nam, Do Yeun Kim, Chu Myong Seong, Hae Young Park, Woon Sup Han, Ju Young Seoh, Soon Nam Lee; Cancer Res Treat. 2003;35(2):109-116. Published online April 30, 2003; DOI: https://doi.org/10.4143/crt.2003.35.2.109

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PURPOSE
The HER2 gene encodes a 185-kd transmembrane glycoprotein receptor (p185(HER2)) that has partial homology with the epidermal growth factor receptor (EGFR) and shares intrinsic tyrosine kinase activity. The HER2 gene has been found to be amplified in various human cancers and to be associated with poor prognosis. The authors investigated the correlation between clinicopathologic factors and the overexpression of the p185(HER2) in Korean gastric adenocarcinoma patients, and determined whether the antiproliferative effects of anti- p185(HER2) antibody can also be observed on gastric cancer cell lines that overexpress this growth factor receptor. MATERIALS AND METHODS: We evaluated the relationship between p185(HER2) overexpression and clinicopathological features in 94 (M: F=52: 42) gastric adenocarcinoma patients (median age 59 years). Protein expression was analysed by immunohistochemical staining in paraffin embedded tissues with monoclonal antibody for p185(HER2). To explore the role of humanized anti-p185(HER2) monoclonal antibody trastuzumab (Herceptin ) in vitro, the growth curve of Korean gastric cancer cells that overexpress the p185(HER2) protein was studied and a cell cycle analysis was performed. RESULTS: p185(HER2) overexpression correlates positively with lymph node metastasis (p=0.002), distant metastasis (p=0.01), AJCC classification (p=0.01), higher relapse rate p=0.001), and a tendential association with the pT stage (p=0.054). p185(HER2) overexpression was found to be more frequent in advanced gastric cancer than early gastric cancer (54.1% vs 24.2%, p=0.008). Patients with overexpression of p185(HER2) were found to have significantly lower relapse-free (p=0.003) and overall survival (p= 0.0004) than patients without overexpression. Among several Korean gastric cancer cell lines, SNU-1, SNU-5, and SNU-620 overexpress p185(HER2). Trastuzumab inhibited the proliferation of p185(HER2) overexpressed Korean gastric cancer cell line by 21% with down-regulation of p185(HER2) protein expression. DNA fluorescence flow cytometry of propidium iodide-stained nuclei showed a reduction in the fraction of the S phase following treatment with trastuzumab. CONCLUSIONS: Taken together, our observations suggest the potential prognostic significance of p185(HER2) overexpression in Korean gastric adenocarcinoma patients and point to the need for further research on this mechanism. This suggests the possible use of p185(HER2) as a therapeutic target in gastric cancer.

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A case of pathological complete regression in combined modality treatment of resectable Her2/neu-positive gastric cancer
A. V. Avgustinovich, S. G. Afanasyev, L. V. Spirina, E. V. Kaygorodova, R. V. Ermolenko, E. N. Samtsov, I. G. Frolova, O. V. Cheremisina
Siberian journal of oncology.2024; 23(1): 170. CrossRef
The Chinese Society of Clinical Oncology (CSCO): clinical guidelines for the diagnosis and treatment of gastric cancer
Feng‐Hua Wang, Lin Shen, Jin Li, Zhi‐Wei Zhou, Han Liang, Xiao‐Tian Zhang, Lei Tang, Yan Xin, Jing Jin, Yu‐Jing Zhang, Xiang‐Lin Yuan, Tian‐Shu Liu, Guo‐Xin Li, Qi Wu, Hui‐Mian Xu, Jia‐Fu Ji, Yuan‐Fang Li, Xin Wang, Shan Yu, Hao Liu, Wen‐Long Guan, Rui‐Hu
Cancer Communications.2019; 39(1): 1. CrossRef
The neutrophil-to-lymphocyte ratio prechemotherapy and postchemotherapy as a prognostic marker in metastatic gastric cancer
Hyunho Kim, Sang Mi Ro, Ji Hyun Yang, Joon Won Jeong, Ji Eun Lee, Sang Young Roh, In-Ho Kim
The Korean Journal of Internal Medicine.2018; 33(5): 990. CrossRef
Potential Prognostic Significance of p185HER2 Overexpression with Loss of PTEN Expression in Gastric Carcinomas
Seock-Ah lm, Kyung Eun Lee, Eunmi Nam, Do Yeun Kim, Joo-Ho Lee, Ho-Seong Han, Ju-Young Seoh, Hae-Young Park, Min-Sun Cho, Woon Sup Han, Soon Nam Lee
Tumori Journal.2005; 91(6): 513. CrossRef

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Case Report

A Case of Primary Gastric Choriocarcinoma Presenting with Amenorrhea: Seung Hyun Nam, Seock Ah Im, Ki Sun Bae, In Sook Kang, Jung Mi Kwon, Kyung Eun Lee, Hye Sung Moon, Sun Hee Sung, Woon Sup Han, Chu Myong Seong, Soon Nam Lee; Cancer Res Treat. 2002;34(6):457-460. Published online December 31, 2002; DOI: https://doi.org/10.4143/crt.2002.34.6.457

Abstract PDF

Primary gastric choriocarcinomas are very rare, and their prognosis is extremely poor. A 37-year-old woman presented with amenorrhea, vaginal spotting and severe nausea, which mimicked a pregnancy and gestational trophoblastic disease. The serum level of the beta-subunit of human chorionic gonadotrophin (beta-hCG) was significantly increased. An endoscopic biopsy of the stomach mass showed the features of a choriocarcinoma, with marked anaplasia and necrosis. Immunohistochemical staining for beta-hCG showed positive results in the choriocarcinoma. Chemotherapy for the choriocarcinoma was administered, but she died 8 months following diagnosis.

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Primary Gastric Choriocarcinoma: Two Case Reports and Review of the Literatures
Jung Ho Yoon, Min Soo Kim, Eun Hee Kook, Se Han Ahn, Se Young Jeong, Min Sung Han, Jung Kwon Huh, Hye Jin Kang, Im Il Na, Soo Youn Cho, Sang Bum Kim, Baek Yeol Ryoo, Sung Hyun Yang
Cancer Research and Treatment.2008; 40(3): 145. CrossRef

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Original Article

Clinical Features and Prognosis of Lung Cancer with Brain Metastasis: Kyung Eun Lee, Eun Mi Nam, He Jin Lee, Seung Hyun Nam, Do Yeun Kim, Seock Ah Im, Chu Myung Seong, Soon Nam Lee, Kyung Ja Lee; Cancer Res Treat. 2001;33(3):250-255. Published online June 30, 2001; DOI: https://doi.org/10.4143/crt.2001.33.3.250

Abstract PDF

PURPOSE
Brain metastasis is estimated to occur in 20~40% of solid tumor patients and the most common primary tumor is lung cancer. Even though the prognosis of brain metastasis is grave and the 1-year survival rate is only 15%, symptom palliations are made with whole brain radiation therapy. We retrospectively evaluated the clinical features and prognostic factors of lung cancer with brain metastasis.
MATERIALS AND METHODS
From January 1987 to October 1999, 50 lung cancer patients with brain metastasis underwent whole brain radiation therapy. We reviewed the improvement in neurologic symptoms and survival according to the following parameters; performance status, histological type, presence of brain metastasis at the initial diagnosis of lung cancer, presence of extracranial metastasis, multiplicity of brain lesion, presence of primary lung symptom and treatment modalities.
RESULTS
The most frequent symptom with brain metastasis was a headache (50%). Palliation of the headache and other symptoms was achieved in 81% of the patients. Median overall survival after brain metastasis was 21 weeks and the 1 year survival rate was 15%. Patients without extracranial metastasis had a longer median survival than those with, 38 weeks versus 15 weeks, respectively (p=0.01).
CONCLUSION
In lung cancer with brain metastasis, neurologic symptoms can be palliated with whole brain radiation therapy, and in this study among such patients, absence of extracranial metastasis can be a good prognostic factor.

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Combination of EGFR-Directed Tyrosine Kinase Inhibitors (EGFR-TKI) with Radiotherapy in Brain Metastases from Non-Small Cell Lung Cancer: A 2010–2019 Retrospective Cohort Study
Vineeth Tatineni, Patrick J. O’Shea, Shreya Saxena, Atulya A. Khosla, Ahmad Ozair, Rupesh R. Kotecha, Xuefei Jia, Yasmeen Rauf, Erin S. Murphy, Samuel T. Chao, John H. Suh, David M. Peereboom, Manmeet S. Ahluwalia
Cancers.2023; 15(11): 3015. CrossRef

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