Cancer Research and Treatment

Original Articles

Lung and Thoracic cancer

Histologic Changes in Non–Small Cell Lung Cancer under Various Treatments: A Comparison of Histology and Mutation Status in Serial Samples: Chang Gok Woo, Seung-Myoung Son, Ho-Chang Lee, Hye Sook Han, Ki Hyeong Lee, Dohun Kim, Eung-Gook Kim, Ok-Jun Lee; Cancer Res Treat. 2022;54(3):737-743. Published online September 24, 2021; DOI: https://doi.org/10.4143/crt.2021.773

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Purpose
Histologic change is a resistant mechanism in lung cancer. The most common histological change is the switch from adenocarcinoma (AdenoCa) to small cell carcinoma (SCC) against to tyrosine kinase inhibitors (TKI). However, it is not clear whether other treatment modalities are involved in the histologic changes.
Materials and Methods
We investigated histological changes in eight cases, after various treatments, and compared the molecular profiles between primary tumors and changed tumors using exome sequencing where tissue was available.
Results
Three cases of AdenoCa that were changed into SCC retained the initial mutations after TKI and/or surgical treatment. After treatment with TKI and immunotherapy, an EGFR (epidermal growth factor receptor)-mutant AdenoCa changed to squamous cell carcinoma (SqCa). SqCa in a patient treated with surgery was changed into combined AdenoCa and SqCa. These two cases showed the same genetic variations between the two distinct non–small cell carcinomas (NSCC). Three patients experienced two histologic changes, which the changed tumors returned to its original subtype or changed to a combined tumor after treatments. Four cases showed combined histology in the first or second change.
Conclusion
The histology of NSCC can be changed to a single pattern or combined subtypes after various treatment modalities, and the phenotypic changes seem not fixed. Therefore, additional morphologic changes may occur regardless of their genetic status and types of treatments. To refine the new treatment strategy, consecutive repeated biopsies in progressive disease or recurrent tumor are necessary.

Citations

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Using ex vivo bioengineered lungs to model pathologies and screening therapeutics: A proof‐of‐concept study
Mohammadali Ahmadipour, Jorge Castilo Prado, Benyamin Hakak‐Zargar, Malik Quasir Mahmood, Ian M. Rogers
Biotechnology and Bioengineering.2024; 121(10): 3020. CrossRef
Noninvasive Lung Cancer Subtype Classification Using Tumor-Derived Signatures and cfDNA Methylome
Shuo Li, Wenyuan Li, Bin Liu, Kostyantyn Krysan, Steven M. Dubinett
Cancer Research Communications.2024; 4(7): 1738. CrossRef
Hepatoid Adenocarcinoma of the Lung: A Review of the Most Updated Literature and a Presentation of Three Cases
Alessandro Bonis, Andrea Dell’Amore, Vincenzo Verzeletti, Luca Melan, Giovanni Zambello, Chiara Nardocci, Giovanni Maria Comacchio, Federica Pezzuto, Fiorella Calabrese, Federico Rea
Journal of Clinical Medicine.2023; 12(4): 1411. CrossRef
Gene‐level dissection of chromosome 3q locus amplification in squamous cell carcinoma of the lung using the nCounter assay
Taesung Jeon, Uk Jeen Oh, Jaeyoung Min, Chungyeul Kim
Thoracic Cancer.2023; 14(26): 2635. CrossRef
Clinical Outcome of Stereotactic Body Radiotherapy in Patients with Early-Stage Lung Cancer with Ground-Glass Opacity Predominant Lesions: A Single Institution Experience
Jeong Yun Jang, Su Ssan Kim, Si Yeol Song, Young Seob Shin, Sei Won Lee, Wonjun Ji, Chang-Min Choi, Eun Kyung Choi
Cancer Research and Treatment.2023; 55(4): 1181. CrossRef
Challenges and Opportunities for Immunoprofiling Using a Spatial High-Plex Technology: The NanoString GeoMx® Digital Spatial Profiler
Sharia Hernandez, Rossana Lazcano, Alejandra Serrano, Steven Powell, Larissa Kostousov, Jay Mehta, Khaja Khan, Wei Lu, Luisa M. Solis
Frontiers in Oncology.2022;[Epub] CrossRef

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EGFR Mutation Status in Lung Adenocarcinoma-Associated Malignant Pleural Effusion and Efficacy of EGFR Tyrosine Kinase Inhibitors: Jiyoul Yang, Ok-Jun Lee, Seung-Myoung Son, Chang Gok Woo, Yusook Jeong, Yaewon Yang, Jihyun Kwon, Ki Hyeong Lee, Hye Sook Han; Cancer Res Treat. 2018;50(3):908-916. Published online September 19, 2017; DOI: https://doi.org/10.4143/crt.2017.378

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Purpose
Malignant pleural effusions (MPEs) are often observed in lung cancer, particularly adenocarcinoma. The aim of this study was to investigate epidermal growth factor receptor (EGFR) mutation status in lung adenocarcinoma-associated MPEs (LA-MPEs) and its correlation with efficacy of EGFR tyrosine kinase inhibitor (TKI) therapy.
Materials and Methods
Samples comprised 40 cell blocks of pathologically-confirmed LA-MPEs collected before the start of EGFR TKI therapy. EGFR mutation status was re-evaluated by peptide nucleic acid clamping and the clinical outcomes of EGFR TKI‒treated patients were analyzed retrospectively.
Results
EGFR mutations were detected in 72.5% of LA-MPE cell blocks (29/40). The median progression-free survival for patients with EGFR mutations in LA-MPEs was better than that for patients with wild-type EGFR (7.33 months vs. 2.07 months; hazard ratio, 0.486; 95% confidence interval, 0.206 to 1.144; p=0.032). The objective response rate (ORR) of 26 patients with EGFR mutations in LA-MPEs among the 36 patients with measurable lesions was 80.8%, while the ORR of the 10 patients with wild-type EGFR in LA-MPEs was 10% (p < 0.001). Among the 26 patients with EGFR mutations in LA-MPEs, the ORR of target lesions and LA-MPEs were 88.5% and 61.5%, respectively (p=0.026).
Conclusion
EGFR mutation status in cell blocks of LA-MPEs confirmed by pathologic diagnosis is highly predictive of EGFR TKI efficacy. For patients with EGFR mutations in LA-MPEs, the response to EGFR TKIs seems to be worse for pleural effusions than for solid tumors.

Citations

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Cancer‐associated fibroblast‐derived colony‐stimulating factor 2 confers acquired osimertinib resistance in lung adenocarcinoma via promoting ribosome biosynthesis
Yutang Huang, Xiaoqing Wang, Chunjie Wen, Jingchan Wang, Honghao Zhou, Lanxiang Wu
MedComm.2024;[Epub] CrossRef
Effect of chemotherapy, immunotherapy, and targeted therapies on removal of indwelling pleural catheters in non-small cell lung cancer patients with malignant pleural effusions
Melissa Wang, Kaitlin Sparrow, Chrystal Chan, Ashley Gillson, Daniel Stollery, Pen Li
Respiratory Medicine.2023; 206: 107093. CrossRef
Malignant pleural effusion diagnosis and therapy
Liangliang Yang, Yue Wang
Open Life Sciences.2023;[Epub] CrossRef
Failure pattern and radiotherapy exploration in malignant pleural effusion non-small cell lung cancer treated with targeted therapy
Qingsong Li, Cheng Hu, Shengfa Su, Zhu Ma, Yichao Geng, Yinxiang Hu, Huiqin Li, Bing Lu
Frontiers in Oncology.2023;[Epub] CrossRef
Impact of thoracic tumor radiotherapy on survival in non‐small‐cell lung cancer with malignant pleural effusion treated with targeted therapy: Propensity score matching study
Qingsong Li, Cheng Hu, Shengfa Su, Zhu Ma, Yichao Geng, Yinxiang Hu, Haijie Jin, Huiqin Li, Bing Lu
Cancer Medicine.2023; 12(14): 14949. CrossRef
EGFR Mutation is a Prognostic Factor in Lung Cancer Patients with Pleural Dissemination Detected During or After Surgery
Toshiya Fujiwara, Kazuhiko Shien, Motoki Matsuura, Junichi Soh, Hiromasa Yamamoto, Soshi Takao, Yuho Maki, Tsuyoshi Ueno, Ryujiro Sugimoto, Ken Suzawa, Mikio Okazaki, Hiroyuki Tao, Makio Hayama, Masafumi Kataoka, Yoshifumi Sano, Hidetoshi Inokawa, Motohir
Annals of Surgical Oncology.2023; 30(11): 6697. CrossRef
Efficacy of hyperthermic intrathoracic chemotherapy for initially diagnosed lung cancer with symptomatic malignant pleural effusion
Zihui Li, Jie Deng, Fei Yan, Li Liu, Yanling Ma, Jianhai Sun
Scientific Reports.2023;[Epub] CrossRef
Establishment of prognostic nomograms for predicting the progression free survival of EGFR‐sensitizing mutation, advanced lung cancer patients treated with EGFR‐TKIs
Xinyang Du, Hua Bai, Zhijie Wang, Jianchun Daun, Zheng Liu, Jiachen Xu, Geyun Chang, Yixiang Zhu, Jie Wang
Thoracic Cancer.2022; 13(9): 1289. CrossRef
Clinical features and prognosis according to genomic mutations in primary and metastatic lesions of non‐small‐cell lung cancer
Wei Zhang, Wenjuan Han, Bo Yu, Xin Zhao, Gaojun Lu, Wendy Wu, Yi Zhang
Thoracic Cancer.2022; 13(11): 1642. CrossRef
Management of Malignant Pleural Effusion: Where Are We Now?
Julien Guinde, Hervé Dutau, Philippe Astoul
Seminars in Respiratory and Critical Care Medicine.2022; 43(04): 559. CrossRef
Non-Small Cell Lung Cancer with Malignant Pleural Effusion May Require Primary Tumor Radiotherapy in Addition to Drug Treatment
Qingsong Li, Cheng Hu, Shengfa Su, Zhu Ma, Yichao Geng, Yinxiang Hu, Huiqin Li, Bing Lu
Cancer Management and Research.2022; Volume 14: 3347. CrossRef
The impact of smoking status on the progression‐free survival of non‐small cell lung cancer patients receiving molecularly target therapy or immunotherapy versus chemotherapy: A meta‐analysis
Xinyi Li, Cong Huang, Xiaohui Xie, Ziyang Wu, Xia Tian, Yibo Wu, Xin Du, Luwen Shi
Journal of Clinical Pharmacy and Therapeutics.2021; 46(2): 256. CrossRef
Risk Factors for and Time to Recurrence of Symptomatic Malignant Pleural Effusion in Patients With Metastatic Non-Small Cell Lung Cancer with EGFR or ALK Mutations
Audra J. Schwalk, David E. Ost, Sahara N. Saltijeral, Henriette De La Garza, Roberto F. Casal, Carlos A. Jimenez, Georgie A. Eapen, Jeff Lewis, Waree Rinsurongkawong, Vadeerat Rinsurongkawong, Jack Lee, Yasir Elamin, Jianjun Zhang, Jack A. Roth, Stephen S
Chest.2021; 159(3): 1256. CrossRef
Advances in pleural infection and malignancy
Eihab O. Bedawi, Julien Guinde, Najiib M. Rahman, Philippe Astoul
European Respiratory Review.2021; 30(159): 200002. CrossRef
Diving into the Pleural Fluid: Liquid Biopsy for Metastatic Malignant Pleural Effusions
Maria Alba Sorolla, Anabel Sorolla, Eva Parisi, Antonieta Salud, José M. Porcel
Cancers.2021; 13(11): 2798. CrossRef
Clinical Characteristics and Therapeutic Outcomes of Metastatic Peritoneal Carcinomatosis in Non-Small-Cell Lung Cancer
Tetsuo Tani, Ichiro Nakachi, Shinnosuke Ikemura, Shigenari Nukaga, Keiko Ohgino, Aoi Kuroda, Hideki Terai, Keita Masuzawa, Taro Shinozaki, Kota Ishioka, Yohei Funatsu, Hidefumi Koh, Koichi Fukunaga, Kenzo Soejima
Cancer Management and Research.2021; Volume 13: 7497. CrossRef
LENT Score: Predicting the Survival of Malignant Pleural Effusion – A Prospective Study of Three Years
Sara Raimundo, Ana Isabel Loureiro, Fortunato Vieira, Ana Fernandes
Archivos de Bronconeumología.2020; 56(7): 465. CrossRef
Current applications of molecular testing on body cavity fluids
Daniel Pinto, Fernando Schmitt
Diagnostic Cytopathology.2020; 48(9): 840. CrossRef
Gene Alterations in Paired Supernatants and Precipitates from Malignant Pleural Effusions of Non-Squamous Non-Small Cell Lung Cancer
Jianqiang Li, Xingliang Li, Wenxian Wang, Yang Shao, Yiping Zhang, Zhengbo Song
Translational Oncology.2020; 13(8): 100784. CrossRef
Progression of malignant pleural effusion during the early stage of gefitinib treatment in advanced EGFR-mutant lung adenocarcinoma involving complex driver gene mutations
Ning Liu, Min Yu, Tao Yin, Yong Jiang, Xuelian Liao, Jie Tang, Yanying Li, Diyuan Qin, Dan Li, Yongsheng Wang
Signal Transduction and Targeted Therapy.2020;[Epub] CrossRef
LENT Score: Predicting the Survival of Malignant Pleural Effusion – A Prospective Study of Three Years
Sara Raimundo, Ana Isabel Loureiro, Fortunato Vieira, Ana Fernandes
Archivos de Bronconeumología (English Edition).2020; 56(7): 465. CrossRef
Recent Developments in the Management of Malignant Pleural Effusions: a Narrative Review
Clifford E. Coile, Jessie G. Harvey, Michal Senitko
Current Pulmonology Reports.2020; 9(4): 164. CrossRef
Detecting EGFR mutations and ALK/ROS1 rearrangements in non‐small cell lung cancer using malignant pleural effusion samples
Yi Yao, Min Peng, Qinglin Shen, Qinyong Hu, Hongyun Gong, Qingqing Li, Zhongliang Zheng, Bin Xu, Yingge Li, Yi Dong
Thoracic Cancer.2019; 10(2): 193. CrossRef
Making cold malignant pleural effusions hot: driving novel immunotherapies
Pranav Murthy, Chigozirim N. Ekeke, Kira L. Russell, Samuel C. Butler, Yue Wang, James D. Luketich, Adam C. Soloff, Rajeev Dhupar, Michael T. Lotze
OncoImmunology.2019; 8(4): e1554969. CrossRef
Novel insights into the systemic treatment of lung cancer malignant pleural effusion
Claire Tissot, Pierre Gay, Clément Brun, Marios E. Froudarakis
The Clinical Respiratory Journal.2019; 13(3): 131. CrossRef
Proceedings of the American Society of Cytopathology companion session at the 2019 United States and Canadian Academy of Pathology Annual meeting, part 2: effusion cytology with focus on theranostics and diagnosis of malignant mesothelioma
Momin T. Siddiqui, Fernando Schmitt, Andrew Churg
Journal of the American Society of Cytopathology.2019; 8(6): 352. CrossRef

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Diagnostic Value of Circulating Extracellular miR-134, miR-185, and miR-22 Levels in Lung Adenocarcinoma-Associated Malignant Pleural Effusion: Yoon Mi Shin, Jieun Yun, Ok-Jun Lee, Hye-Suk Han, Sung-Nam Lim, Jin Young An, Ki Hyeong Lee, Ki Man Lee, Kang Hyeon Choe; Cancer Res Treat. 2014;46(2):178-185. Published online April 15, 2014; DOI: https://doi.org/10.4143/crt.2014.46.2.178

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Purpose

The accurate and timely diagnosis of malignant pleural effusion (MPE) in lung cancer patients is important because MPE has a poor prognosis and is classified as stage IV disease. Molecular biomarkers for pleural effusion, such as circulating extracellular microRNAs (miRNAs) isolated from pleural fluid, may help in the diagnosis of MPE. The present study examined whether miRNAs that are deregulated in lung cancer (miR-134, miR-185, and miR-22) can serve as diagnostic markers for lung adenocarcinoma-associated MPE (LA-MPE).

Materials and Methods

Real-time reverse transcription quantitative polymerase chain reaction was used to measure the expression of the three miRNAs in samples from 87 patients with pleural effusion comprising 45 LA-MPEs and 42 benign pleural effusions (BPEs). The area under the receiver operating characteristic curve (AUC) was then used to evaluate the diagnostic performance of each of the three miRNAs and compare it with that of the common tumor marker, carcinoembryonic antigen (CEA).

Results

The expression of all three miRNAs was significantly lower in LA-MPE than in BPE (p <0.001). The AUCs for miR-134, miR-185, miR-22, and CEA were 0.721, 0.882, 0.832, and 0.898, respectively. Combining CEA with the three miRNAs increased the diagnostic performance, yielding an AUC of 0.942 (95% confidence interval, 0.864 to 0.982), with a sensitivity of 91.9% and a specificity of 92.5%.

Conclusion

The present study suggests that the expression levels of circulating extracellular miR-134, miR-185, and miR-22 in patients with pleural effusion may have diagnostic value when differentiating between LA-MPE and BPE.

Citations

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Key methodological challenges in detecting circulating miRNAs in different biofluids
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International Journal of Molecular Sciences.2023; 24(17): 13302. CrossRef
High Diagnostic and Prognostic Value of miRNAs Compared with the Carcinoembryonic Antigen As A Traditional Tumor Marker
Neda Yaghoubi , Farnaz Zahedi Avval , Majid Khazaei, Amirhossein Sahebkar , Seyed Hamid Aghaee-Bakhtiari
Anti-Cancer Agents in Medicinal Chemistry.2022; 22(2): 206. CrossRef
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Wen Zhao, Xi-Shan Cao, Yu-Ling Han, Xu-Hui Wen, Wen-Qi Zheng, Zhi-De Hu
Clinical Chemistry and Laboratory Medicine (CCLM).2022; 60(10): 1518. CrossRef
Construction and analysis of expression profile of exosomal lncRNAs in pleural effusion in lung adenocarcinoma
Xiaolu Huang, Huixin Zhou, Xiang Yang, Wenjing Shi, Lijuan Hu, Junjun Wang, Fan Zhang, Fanggui Shao, Meijuan Zhang, Feng Jiang, Yumin Wang
Journal of Clinical Laboratory Analysis.2022;[Epub] CrossRef
Molecular testing on serous effusions
Ben Davidson
Diagnostic Cytopathology.2021; 49(5): 640. CrossRef
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Four plasma miRNAs act as biomarkers for diagnosis and prognosis of non‑small cell lung cancer
He-Guo Jiang, Chun-Hua Dai, Ya-Ping Xu, Qian Jiang, Xian-Bin Xia, Yang Shu, Jian Li
Oncology Letters.2021;[Epub] CrossRef
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Cytojournal.2021; 18: 35. CrossRef
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Kimberly A. Birnie, Cecilia M. Prêle, Arthur W. (Bill) Musk, Nicholas de Klerk, Y. C. Gary Lee, Deirdre Fitzgerald, Richard J. N. Allcock, Philip J. Thompson, Jenette Creaney, Bahareh Badrian, Steven E. Mutsaers
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Case Reports

Multiple Cardiac Metastases from a Nonfunctioning Pancreatic Neuroendocrine Tumor: Yong Hyeok Choi, Hye-Suk Han, Sung-Nam Lim, Sang Yeub Lee, Ji Hae Koo, Ok-Jun Lee, Ki Hyeong Lee, Seung Taik Kim; Cancer Res Treat. 2013;45(2):150-154. Published online June 30, 2013; DOI: https://doi.org/10.4143/crt.2013.45.2.150

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Pancreatic neuroendocrine tumors (pNETs) are rare neoplasms, which most commonly metastasize to the liver. However, intrathoracic metastases from pNETs are encountered infrequently. This report describes a case of nonfunctioning pNET with multiple cardiac metastases. A 56-year-old male presented with a palpable abdominal mass that showed progressive enlargement. Findings on computed tomography (CT) of the abdomen revealed two relatively well-marginated inhomogeneous low-attenuation masses, one in the head of the pancreas and the other in the tail. Multiple enhancing masses in the left pericardium with myocardial involvement were observed on chest CT and transthoracic echocardiography. Needle biopsies were performed on the mass in the tail of the pancreas and the left ventricular apical pericardium; histologic examination by hematoxylin and eosin morphology and immunohistochemical staining showed pNET in both. This is the first report of pNET with multiple cardiac metastases to previously undescribed metastatic sites.

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Shengming Deng, Bin Zhang, Jihui Li, Shibiao Sang, Wei Zhang
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Poorly Differentiated Neuroendocrine Carcinoma in a Perigastric Lymph Node from an Unknown Primary Site: Hee Seung Lee, Hye-Suk Han, Sung-Nam Lim, Hyun-Jung Jeon, Ho-chang Lee, Ok-Jun Lee, Hyo Young Yun, Ki Hyeong Lee, Seung Taik Kim; Cancer Res Treat. 2012;44(4):271-274. Published online December 31, 2012; DOI: https://doi.org/10.4143/crt.2012.44.4.271

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Neuroendocrine carcinomas from an unknown primary site are uncommon. The authors report on a case of neuroendocrine carcinoma in a perigastric lymph node (LN) with no primary site. A 52-year-old male patient with early gastric adenocarcinoma underwent treatment by endoscopic submucosal dissection, and, six months later, findings on a computed tomographic scan of the abdomen revealed a LN enlargement measuring 2.0 cm in the perigastric region. The patient underwent subtotal gastrectomy and regional LN dissection under a suggestive preoperative diagnosis of gastric adenocarcinoma with LN metastasis. However, microscopically, no residual tumor was found in the stomach, and the perigastric LN showed poorly differentiated neuroendocrine carcinoma (PDNEC). After an extensive workup, no primary site was identified. The patient also received four cycles of etoposide and cisplatin. Despite its extremely rare incidence, this case suggests that PDNEC of an unknown primary site is limited to a single site, and that resection should be considered in combination with chemotherapy.

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HONG-FANG YING, YANG-YANG BAO, SHUI-HONG ZHOU, LIANG CHAI, KUI ZHAO, TING-TING WU
Oncology Letters.2014; 8(3): 1065. CrossRef

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Metastatic Renal Cell Carcinoma in a Supraclavicular Lymph Node with No Known Primary: A Case Report: Young-Rak Choi, Hye-Suk Han, Ok-Jun Lee, Sung-Nam Lim, Mi-Jin Kim, Myeong-Ho Yeon, Hyun-Jung Jeon, Ki Hyeong Lee, Seung Taik Kim; Cancer Res Treat. 2012;44(3):215-218. Published online September 30, 2012; DOI: https://doi.org/10.4143/crt.2012.44.3.215

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Although metastasis is relatively frequent in cases of renal cell carcinoma (RCC), metastasis in the cervical or supraclavicular lymph node (LN) is relatively rare. Moreover, cases of metastatic RCC with a non-identifiable kidney mass are extremely rare. Here, the authors report a case of metastatic RCC in a supraclavicular LN without a primary kidney lesion. A 69-year-old man presented with a progressively enlarging right supraclavicular mass. Incisional biopsy of the affected supraclavicular LN was performed, and histological examination revealed metastatic RCC. However, no tumor was found in either kidney, despite various examinations. The patient was treated with radiotherapy followed by sunitinib. After three months on sunitinib, a follow-up computed tomography scan revealed that the supraclavicular LN had markedly decreased, and after 20 months, the disease had not progressed. This case suggests that, even when there is no primary kidney lesion, clinicians must consider the possibility of metastatic RCC when evaluating patients with clear cell carcinoma with an unknown primary site.

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