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Gandhi Z, Gurram P, Amgai B, Lekkala SP, Lokhandwala A, Manne S, Mohammed A, Koshiya H, Dewaswala N, Desai R, Bhopalwala H, Ganti S, Surani S. Artificial Intelligence and Lung Cancer: Impact on Improving Patient Outcomes. Cancers (Basel) 2023; 15:5236. [PMID: 37958411 PMCID: PMC10650618 DOI: 10.3390/cancers15215236] [Citation(s) in RCA: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2023] [Revised: 10/23/2023] [Accepted: 10/24/2023] [Indexed: 11/15/2023] Open
Abstract
Lung cancer remains one of the leading causes of cancer-related deaths worldwide, emphasizing the need for improved diagnostic and treatment approaches. In recent years, the emergence of artificial intelligence (AI) has sparked considerable interest in its potential role in lung cancer. This review aims to provide an overview of the current state of AI applications in lung cancer screening, diagnosis, and treatment. AI algorithms like machine learning, deep learning, and radiomics have shown remarkable capabilities in the detection and characterization of lung nodules, thereby aiding in accurate lung cancer screening and diagnosis. These systems can analyze various imaging modalities, such as low-dose CT scans, PET-CT imaging, and even chest radiographs, accurately identifying suspicious nodules and facilitating timely intervention. AI models have exhibited promise in utilizing biomarkers and tumor markers as supplementary screening tools, effectively enhancing the specificity and accuracy of early detection. These models can accurately distinguish between benign and malignant lung nodules, assisting radiologists in making more accurate and informed diagnostic decisions. Additionally, AI algorithms hold the potential to integrate multiple imaging modalities and clinical data, providing a more comprehensive diagnostic assessment. By utilizing high-quality data, including patient demographics, clinical history, and genetic profiles, AI models can predict treatment responses and guide the selection of optimal therapies. Notably, these models have shown considerable success in predicting the likelihood of response and recurrence following targeted therapies and optimizing radiation therapy for lung cancer patients. Implementing these AI tools in clinical practice can aid in the early diagnosis and timely management of lung cancer and potentially improve outcomes, including the mortality and morbidity of the patients.
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Affiliation(s)
- Zainab Gandhi
- Department of Internal Medicine, Geisinger Wyoming Valley Medical Center, Wilkes Barre, PA 18711, USA
| | - Priyatham Gurram
- Department of Medicine, Mamata Medical College, Khammam 507002, India; (P.G.); (S.P.L.); (S.M.)
| | - Birendra Amgai
- Department of Internal Medicine, Geisinger Community Medical Center, Scranton, PA 18510, USA;
| | - Sai Prasanna Lekkala
- Department of Medicine, Mamata Medical College, Khammam 507002, India; (P.G.); (S.P.L.); (S.M.)
| | - Alifya Lokhandwala
- Department of Medicine, Jawaharlal Nehru Medical College, Wardha 442001, India;
| | - Suvidha Manne
- Department of Medicine, Mamata Medical College, Khammam 507002, India; (P.G.); (S.P.L.); (S.M.)
| | - Adil Mohammed
- Department of Internal Medicine, Central Michigan University College of Medicine, Saginaw, MI 48602, USA;
| | - Hiren Koshiya
- Department of Internal Medicine, Prime West Consortium, Inglewood, CA 92395, USA;
| | - Nakeya Dewaswala
- Department of Cardiology, University of Kentucky, Lexington, KY 40536, USA;
| | - Rupak Desai
- Independent Researcher, Atlanta, GA 30079, USA;
| | - Huzaifa Bhopalwala
- Department of Internal Medicine, Appalachian Regional Hospital, Hazard, KY 41701, USA; (H.B.); (S.G.)
| | - Shyam Ganti
- Department of Internal Medicine, Appalachian Regional Hospital, Hazard, KY 41701, USA; (H.B.); (S.G.)
| | - Salim Surani
- Departmet of Pulmonary, Critical Care Medicine, Texas A&M University, College Station, TX 77845, USA;
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Okasha HH, El-Meligui A, Pawlak KM, Żorniak M, Atalla H, Abou-Elmagd A, Abou-Elenen S, El-Husseiny R, Alzamzamy A. Practical approach to linear EUS examination of the mediastinum. Endosc Ultrasound 2021; 10:406-413. [PMID: 34854401 PMCID: PMC8785678 DOI: 10.4103/eus-d-21-00019] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/08/2021] [Accepted: 07/13/2021] [Indexed: 11/16/2022] Open
Abstract
EUS has become a substantial diagnostic and therapeutic modality for many anatomical regions. The extent of endosonographic assessment is wide, and among others, allows for the evaluation of the mediastinal anatomy and related pathologies such as mediastinal lymphadenopathy and staging of central malignant lung lesions. Moreover, EUS assessment has proved more accurate in detecting small lesions missed by standard imaging examinations such as computed tomography or magnetic resonance. Endosonographically, various mediastinal anatomical landmarks and stations can be visualized by transesophageal scanning, thus providing arranged systematic examination of the mediastinum. In addition, the correct position during the examination is crucial for EUS-guided procedures such as tissue sampling and drainage of mediastinal abscesses. The evolution of EUS-guided diagnostic and interventional procedures has contributed to the increasing importance of understanding the mediastinal anatomy during the EUS examination.
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Affiliation(s)
- Hussein Hassan Okasha
- Department of Internal Medicine, Division of Gastroenterology, Kasr Al-Aini School of Medicine, Cairo University, Cairo, Egypt
| | - Ahmed El-Meligui
- Department of Internal Medicine, Division of Gastroenterology, Kasr Al-Aini School of Medicine, Cairo University, Cairo, Egypt
| | - Katarzyna M. Pawlak
- Department of Internal Medicine, Cardiology, Gastroenterology and Endocrinology, Hospital of the Ministry of Interior and Administration, Szczecin, Poland
| | - Michał Żorniak
- Department of Medicine II, LMU Klinikum, Ludwig-Maximilians-University, Munich, Germany
- Department of Gastroenterology, Hepatology and Oncology, Medical Center for Postgraduate Education, Warsaw, Poland
| | - Hassan Atalla
- Department of Internal Medicine, Hepatology and Gastroenterology Unit, Faculty of Medicine, Mansoura University, Mansoura, Egypt
| | - Amr Abou-Elmagd
- Department of Internal Medicine, Armed Forces College of Medicine, Cairo, Egypt
| | - Sameh Abou-Elenen
- Department of Gastroenterology and Hepatology, Military Medical Academy, Cairo, Egypt
| | - Ramy El-Husseiny
- National Hepatology and Tropical Medicine Research Institute, Cairo, Egypt
| | - Ahmed Alzamzamy
- Department of Gastroenterology and Hepatology, Military Medical Academy, Cairo, Egypt
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Zhao K, Wang C, Shi F, Huang Y, Ma L, Li M, Song Y. Combined prognostic value of the SUVmax derived from FDG-PET and the lymphocyte-monocyte ratio in patients with stage IIIB-IV non-small cell lung cancer receiving chemotherapy. BMC Cancer 2021; 21:66. [PMID: 33446134 PMCID: PMC7809816 DOI: 10.1186/s12885-021-07784-x] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2020] [Accepted: 01/02/2021] [Indexed: 11/16/2022] Open
Abstract
Background We evaluated the prognostic potential of tumor 18F-fluorodeoxyglucose (FDG) uptake derived from positron emission tomography (PET) and known inflammatory hematological markers, both individually and in combination, for chemosensitivity and survival in patients with stage IIIB-IV non-small cell lung cancer (NSCLC) receiving first-line chemotherapy. Methods A total of 149 patients with stage IIIB and IV NSCLC (based on TNM 7th edition) were retrospectively reviewed. Maximum standardized uptake value (SUVmax) were used to quantitatively assess FDG uptake. The lymphocyte-monocyte ratio (LMR), neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) were selected as hematological markers. Receiver operating characteristic (ROC) curves were constructed for the determination of optimal cut-off values to predict chemotherapeutic response. Results Patients with SUVmax > 11.6 or LMR ≤3.73 exhibited a significantly lower objective response rate (ORR) to chemotherapy (p < 0.001 and p < 0.001). Through multivariable logistic regression analysis, both the SUVmax and LMR were identified as independent predictive factors for chemotherapeutic response (p = 0.001 and p < 0.001). Furthermore, a multivariable Cox proportional hazard model identified a high SUVmax (> 11.6) and low LMR (≤3.73) as independent predictors of poor PFS (p < 0.001 and p = 0.025) and OS (p < 0.001 and p = 0.032). A novel score system was constructed based on the SUVmax and LMR (SUV_LMR score), and patients were stratified into three subgroups. The patients with a score of 0 had a significantly higher ORR (88.9%) than did those with a score of 1 (59.6%) and score of 2 (25.0%) (p < 0.001). Moreover, multivariable Cox analysis further identified the SUV_LMR score as an independent prognostic factor for PFS (p < 0.001) and OS (p < 0.001). Conclusions Pre-treatment SUVmax and LMR were not only predictive factors for chemotherapeutic response but also independent prognostic factors of survival in stage IIIB-IV NSCLC. Moreover, the SUV_LMR score, which is based on primary tumor metabolic activity and the systemic inflammatory response, might provide a promising tool to predict chemosensitivity, recurrence and survival of advanced NSCLC.
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Affiliation(s)
- Kewei Zhao
- Department of Radiation Oncology, Yantai Yuhuangding Hospital, 20 Yudong Road, Yantai, 264000, Shandong, People's Republic of China
| | - Chunsheng Wang
- Department of Radiation Oncology, Yantai Yuhuangding Hospital, 20 Yudong Road, Yantai, 264000, Shandong, People's Republic of China
| | - Fang Shi
- Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong University, 440 Jiyan Road, Jinan, 250117, Shandong, People's Republic of China
| | - Yong Huang
- Department of Nuclear Medicine, Shandong Cancer Hospital and Institute, Shandong University, 440 Jiyan Road, Jinan, 250117, Shandong, People's Republic of China
| | - Li Ma
- Department of Nuclear Medicine, Shandong Cancer Hospital and Institute, Shandong University, 440 Jiyan Road, Jinan, 250117, Shandong, People's Republic of China
| | - Minghuan Li
- Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong University, 440 Jiyan Road, Jinan, 250117, Shandong, People's Republic of China
| | - Yipeng Song
- Department of Radiation Oncology, Yantai Yuhuangding Hospital, 20 Yudong Road, Yantai, 264000, Shandong, People's Republic of China.
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Yu H, Xu L, Liu Z, Guo B, Han Z, Xin H. Circ_MDM2_000139, Circ_ATF2_001418, Circ_CDC25C_002079, and Circ_BIRC6_001271 Are Involved in the Functions of XAV939 in Non-Small Cell Lung Cancer. Can Respir J 2019; 2019:9107806. [PMID: 31885751 PMCID: PMC6900950 DOI: 10.1155/2019/9107806] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2019] [Revised: 09/29/2019] [Accepted: 10/05/2019] [Indexed: 01/26/2023] Open
Abstract
Background The small molecule inhibitor XAV939 could inhibit the proliferation and promote the apoptosis of non-small cell lung cancer (NSCLC) cells. This study was conducted to identify the key circular RNAs (circRNAs) and microRNAs (miRNAs) in XAV939-treated NSCLC cells. Methods After grouping, the NCL-H1299 cells in the treatment group were treated by 10 μM XAV939 for 12 h. RNA-sequencing was performed, and then the differentially expressed circRNAs (DE-circRNAs) were analyzed by the edgeR package. Using the clusterprofiler package, enrichment analysis for the hosting genes of the DE-circRNAs was performed. Using Cytoscape software, the miRNA-circRNA regulatory network was built for the disease-associated miRNAs and the DE-circRNAs. The DE-circRNAs that could translate into proteins were predicted using circBank database and IRESfinder tool. Finally, the transcription factor (TF)-circRNA regulatory network was built by Cytoscape software. In addition, A549 and HCC-827 cell treatment with XAV939 were used to verify the relative expression levels of key DE-circRNAs. Results There were 106 DE-circRNAs (including 61 upregulated circRNAs and 45 downregulated circRNAs) between treatment and control groups. Enrichment analysis for the hosting genes of the DE-circRNAs showed that ATF2 was enriched in the TNF signaling pathway. Disease association analysis indicated that 8 circRNAs (including circ_MDM2_000139, circ_ATF2_001418, circ_CDC25C_002079, and circ_BIRC6_001271) were correlated with NSCLC. In the miRNA-circRNA regulatory network, let-7 family members⟶circ_MDM2_000139, miR-16-5p/miR-134-5p⟶circ_ATF2_001418, miR-133b⟶circ_BIRC6_001271, and miR-221-3p/miR-222-3p⟶circ_CDC25C_002079 regulatory pairs were involved. A total of 47 DE-circRNAs could translate into proteins. Additionally, circ_MDM2_000139 was targeted by the TF POLR2A. The verification test showed that the relative expression levels of circ_MDM2_000139, circ_CDC25C_002079, circ_ATF2_001418, and circ_DICER1_000834 in A549 and HCC-827 cell treatment with XAV939 were downregulated comparing with the control. Conclusions Let-7 family members and POLR2A targeting circ_MDM2_000139, miR-16-5p/miR-134-5p targeting circ_ATF2_001418, miR-133b targeting circ_BIRC6_001271, and miR-221-3p/miR-222-3p targeting circ_CDC25C_002079 might be related to the mechanism in the treatment of NSCLC by XAV939.
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Affiliation(s)
- Haixiang Yu
- Department of Thoracic Surgery, China-Japan Union Hospital of Jilin University, Changchun, Jilin Province 130033, China
| | - Lei Xu
- Department of Thoracic Surgery, China-Japan Union Hospital of Jilin University, Changchun, Jilin Province 130033, China
| | - Zhengjia Liu
- Department of Thoracic Surgery, China-Japan Union Hospital of Jilin University, Changchun, Jilin Province 130033, China
| | - Bo Guo
- Department of Thoracic Surgery, China-Japan Union Hospital of Jilin University, Changchun, Jilin Province 130033, China
| | - Zhifeng Han
- Department of Thoracic Surgery, China-Japan Union Hospital of Jilin University, Changchun, Jilin Province 130033, China
| | - Hua Xin
- Department of Thoracic Surgery, China-Japan Union Hospital of Jilin University, Changchun, Jilin Province 130033, China
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Cho WCS, Tan KT, Ma VWS, Li JYC, Ngan RKC, Cheuk W, Yip TTC, Yang YT, Chen SJ. Targeted next-generation sequencing reveals recurrence-associated genomic alterations in early-stage non-small cell lung cancer. Oncotarget 2018; 9:36344-36357. [PMID: 30555633 PMCID: PMC6284742 DOI: 10.18632/oncotarget.26349] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2018] [Accepted: 11/01/2018] [Indexed: 12/14/2022] Open
Abstract
Purpose The identification of genomic alterations related to recurrence in early-stage non-small cell lung cancer (NSCLC) patients may help better stratify high-risk individuals and guide treatment strategies. This study aimed to identify the molecular biomarkers of recurrence in early-stage NSCLC. Results Of the 42 tumors evaluable for genomic alterations, TP53 and EGFR were the most frequent alterations with population frequency 52.4% and 50.0%, respectively. Fusion genes were detected in four patients, which had lower mutational burden and relatively better genomic stability. EGFR mutation and fusion gene were mutually exclusive in this study. CDKN2A, FAS, SUFU and SMARCA4 genomic alterations were only observed in the relapsed patients. Increased copy number alteration index was observed in early relapsed patients. Among these genomic alterations, early-stage NSCLCs harboring CDKN2A, FAS, SUFU and SMARCA4 genomic alterations were found to be significantly associated with recurrence. Some of these new findings were validated using The Cancer Genome Atlas (TCGA) dataset. Conclusions The genomic alterations of CDKN2A, FAS, SUFU and SMARCA4 in early-stage NSCLC are found to be associated with recurrence, but confirmation in a larger independent cohort is required to define the clinical impact. Materials and Methods Paired primary tumor and normal lung tissue samples were collected for targeted next-generation sequencing analysis. A panel targets exons for 440 genes was used to assess the mutational and copy number status of selected genes in three clinically relevant groups of stage I/II NSCLC patients: 1) Early relapse; 2) Late relapse; and 3) No relapse.
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Affiliation(s)
- William C S Cho
- Department of Clinical Oncology, Queen Elizabeth Hospital, Kowloon, Hong Kong
| | | | - Victor W S Ma
- Department of Clinical Oncology, Queen Elizabeth Hospital, Kowloon, Hong Kong
| | - Jacky Y C Li
- Department of Clinical Oncology, Queen Elizabeth Hospital, Kowloon, Hong Kong
| | - Roger K C Ngan
- Department of Clinical Oncology, The University of Hong Kong, Gleneagles Hong Kong Hospital, Wong Chuk Hang, Hong Kong
| | - Wah Cheuk
- Department of Pathology, Queen Elizabeth Hospital, Kowloon, Hong Kong
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Saito S, Espinoza-Mercado F, Liu H, Sata N, Cui X, Soukiasian HJ. Current status of research and treatment for non-small cell lung cancer in never-smoking females. Cancer Biol Ther 2017; 18:359-368. [PMID: 28494184 DOI: 10.1080/15384047.2017.1323580] [Citation(s) in RCA: 53] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
Lung cancer is the leading cause of cancer-related deaths worldwide with over 1 million deaths each year. The overall prognosis of lung cancer patients remains unsatisfactory, with a 5-year overall survival rate of less than 15%. Although most lung cancers are a result of smoking, approximately 25% of lung cancer cases worldwide are not attributable to tobacco use. Notably, more than half of the lung cancer cases in women occur in non-smokers. Among non-small-cell lung cancer (NSCLC) cases, cigarette-smokers have a greater association with squamous cell carcinoma than adenocarcinoma, which is more common in non-smokers. These findings imply that specific molecular and pathological features may associate with lung adenocarcinoma arising in non-smoker female patients. Over the past decade, whole genome sequencing and other '-omics' technologies led to the discovery of pathogenic mutations that drive tumor cell formation. These technological developments may enable tailored patient treatments throughout the course of their disease, potentially leading to improved patient outcomes. Some clinical and laboratory studies have shown success outcomes using epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors (TKI) in patients with EGFR mutations and ALK rearrangements, respectively. In fact, these 2 mutations are predominantly present in female non-smokers with adenocarcinoma. Immunotherapy has also recently emerged as a major therapeutic modality in NSCLC. In this review, we summarize the current understanding of NSCLC biology and new therapeutic molecular targets, focusing on the pathogenesis of non-smoker female NSCLC patients.
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Affiliation(s)
- Shin Saito
- a Department of Surgery , Jichi Medical University , Yakushiji, Shimotsuke-City , Tochigi , Japan
| | - Fernando Espinoza-Mercado
- b Department of Surgery, Division of Thoracic Surgery , Cedars-Sinai Medical Center , Los Angeles , CA , USA
| | - Hui Liu
- c College of Medical Laboratory Techniques, Tianjin Medical University , Tianjin , China
| | - Naohiro Sata
- a Department of Surgery , Jichi Medical University , Yakushiji, Shimotsuke-City , Tochigi , Japan
| | - Xiaojiang Cui
- d Department of Surgery , Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center , Los Angeles , CA , USA
| | - Harmik J Soukiasian
- b Department of Surgery, Division of Thoracic Surgery , Cedars-Sinai Medical Center , Los Angeles , CA , USA
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Tang H, Wang S, Xiao G, Schiller J, Papadimitrakopoulou V, Minna J, Wistuba II, Xie Y. Comprehensive evaluation of published gene expression prognostic signatures for biomarker-based lung cancer clinical studies. Ann Oncol 2017; 28:733-740. [PMID: 28200038 DOI: 10.1093/annonc/mdw683] [Citation(s) in RCA: 61] [Impact Index Per Article: 7.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2006] [Accepted: 12/08/2016] [Indexed: 02/05/2023] Open
Abstract
Background A more accurate prognosis for non-small-cell lung cancer (NSCLC) patients could aid in the identification of patients at high risk for recurrence. Many NSCLC mRNA expression signatures claiming to be prognostic have been reported in the literature. The goal of this study was to identify the most promising mRNA prognostic signatures in NSCLC for further prospective clinical validation. Experimental design We carried out a systematic review and meta-analysis of published mRNA prognostic signatures for resected NSCLC. The prognostic performance of each signature was evaluated via a meta-analysis of 1927 early stage NSCLC patients collected from 15 studies using three evaluation metrics (hazard ratios, concordance scores, and time-dependent receiver-operating characteristic curves). The performance of each signature was then evaluated against 100 random signatures. The prognostic power independent of clinical risk factors was assessed by multivariate Cox models. Results Through a literature search, we identified 42 lung cancer prognostic signatures derived from genome-wide expression profiling analysis. Based on meta-analysis, 25 signatures were prognostic for survival after adjusting for clinical risk factors and 18 signatures carried out significantly better than random signatures. When analyzing histology types separately, 17 signatures and 8 signatures are prognostic for adenocarcinoma and squamous cell lung cancer, respectively. Despite little overlap among published gene signatures, the top-performing signatures are highly concordant in predicted patient outcomes. Conclusions Based on this large-scale meta-analysis, we identified a set of mRNA expression prognostic signatures appropriate for further validation in prospective clinical studies.
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Affiliation(s)
- H Tang
- Department of Breast Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong, People's Republic of China
| | - S Wang
- Department of Medical Oncology, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, Guangdong, P.R. China
| | - G Xiao
- Department of Thoracic Surgery and Oncology, the Second Department of Thoracic Surgery, Cancer Center, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi Province, China
| | - J Schiller
- Inova Schar Cancer Institute, Falls Church, VA, USA
| | - V Papadimitrakopoulou
- Department of Thoracic/Head & Neck Medical Oncology, The University of Texas, MD Anderson Cancer Center, 1515 Holcombe Blvd. Unit 0085, Houston, TX, USA
| | - J Minna
- Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, USA.,Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, USA.,Hamon Center for Therapeutic Oncology, University of Texas Southwestern Medical Center, Dallas, USA
| | - I I Wistuba
- Department of Thoracic/Head & Neck Medical Oncology, The University of Texas, MD Anderson Cancer Center, 1515 Holcombe Blvd. Unit 0085, Houston, TX, USA.,Department of Translational Molecular Pathology, MD Anderson Cancer Center, University of Texas, Houston, USA
| | - Y Xie
- Department of Oncology, First Affiliated Hospital, Soochow University, Suzhou, China.,Departments of Head and Neck and Mammary Gland Oncology and Medical Oncology, Cancer Center and State Key Laboratory of Biotherapy, Laboratory of Molecular Diagnosis of Cancer, West China Hospital, Sichuan University, Chengdu, Sichuan, China
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Shen L, Yang M, Lin Q, Zhang Z, Zhu B, Miao C. COL11A1 is overexpressed in recurrent non-small cell lung cancer and promotes cell proliferation, migration, invasion and drug resistance. Oncol Rep 2016; 36:877-85. [PMID: 27373316 DOI: 10.3892/or.2016.4869] [Citation(s) in RCA: 71] [Impact Index Per Article: 7.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2015] [Accepted: 12/07/2015] [Indexed: 11/05/2022] Open
Abstract
Collagen type XI α1 (COL11A1), a minor fibrillar collagen, has been demonstrated to be involved in cell proliferation, migration and the tumorigenesis of many human malignancies. Previous studies have shown that COL11A1 may be a valuable diagnostic marker for non-small cell lung carcinoma (NSCLC). However, its biological function in NSCLC progression remains largely unclear. In the present study, we investigated the expression levels of COL11A1 in different human NSCLC samples, and found that COL11A1 was overexpressed in NSCLC with lymph node metastasis and in recurrent NSCLC tissues. We also revealed that COL11A1 promoted the cell proliferation, migration and invasion of NSCLC cell lines in vitro. Furthermore, our results highlighted the importance of COL11A1 in chemoresistance to cisplatin. Mechanistically, we found that the effects of the overexpression of COL11A1 in NSCLC cells were mediated by Smad signaling. Collectively, our findings suggest that COL11A1 may sever as a biomarker for metastatic NSCLC, and can be used to predict recurrence after surgical resection. Therapeutic approaches targeting COL11A1 may facilitate the optimization of cisplatin treatment of NSCLC by overcoming chemoresistance.
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Affiliation(s)
- Lihua Shen
- Department of Anaesthesia, Critical Care and Pain Medicine, Fudan University Shanghai Cancer Center, Shanghai 200032, P.R. China
| | - Min Yang
- Department of Respiratory Diseases, Tianjin First Center Hospital, Tianjin 300192, P.R. China
| | - Qionghua Lin
- Department of Anaesthesia, Critical Care and Pain Medicine, Fudan University Shanghai Cancer Center, Shanghai 200032, P.R. China
| | - Zhongwei Zhang
- Department of Anaesthesia, Critical Care and Pain Medicine, Fudan University Shanghai Cancer Center, Shanghai 200032, P.R. China
| | - Biao Zhu
- Department of Anaesthesia, Critical Care and Pain Medicine, Fudan University Shanghai Cancer Center, Shanghai 200032, P.R. China
| | - Changhong Miao
- Department of Anaesthesia, Critical Care and Pain Medicine, Fudan University Shanghai Cancer Center, Shanghai 200032, P.R. China
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Jacobsen B, Kriegbaum MC, Santoni-Rugiu E, Ploug M. C4.4A as a biomarker in pulmonary adenocarcinoma and squamous cell carcinoma. World J Clin Oncol 2014; 5:621-632. [PMID: 25302166 PMCID: PMC4129527 DOI: 10.5306/wjco.v5.i4.621] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/04/2014] [Revised: 03/10/2014] [Accepted: 06/16/2014] [Indexed: 02/06/2023] Open
Abstract
The high prevalence and mortality of lung cancer, together with a poor 5-year survival of only approximately 15%, emphasize the need for prognostic and predictive factors to improve patient treatment. C4.4A, a member of the Ly6/uPAR family of membrane proteins, qualifies as such a potential informative biomarker in non-small cell lung cancer. Under normal physiological conditions, it is primarily expressed in suprabasal layers of stratified squamous epithelia. Consequently, it is absent from healthy bronchial and alveolar tissue, but nevertheless appears at early stages in the progression to invasive carcinomas of the lung, i.e., in bronchial hyperplasia/metaplasia and atypical adenomatous hyperplasia. In the stages leading to pulmonary squamous cell carcinoma, expression is sustained in dysplasia, carcinoma in situ and invasive carcinomas, and this pertains to the normal presence of C4.4A in squamous epithelium. In pulmonary adenocarcinomas, a fraction of cases is positive for C4.4A, which is surprising, given the origin of these carcinomas from mucin-producing and not squamous epithelium. Interestingly, this correlates with a highly compromised patient survival and a predominant solid tumor growth pattern. Circumstantial evidence suggests an inverse relationship between C4.4A and the tumor suppressor LKB1. This might provide a link to the prognostic impact of C4.4A in patients with adenocarcinomas of the lung and could potentially be exploited for predicting the efficacy of treatment targeting components of the LKB1 pathway.
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El-Sherief AH, Lau CT, Wu CC, Drake RL, Abbott GF, Rice TW. International association for the study of lung cancer (IASLC) lymph node map: radiologic review with CT illustration. Radiographics 2014; 34:1680-91. [PMID: 25310423 DOI: 10.1148/rg.346130097] [Citation(s) in RCA: 84] [Impact Index Per Article: 7.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/11/2023]
Abstract
Accurate clinical or pretreatment stage classification of lung cancer leads to optimal treatment outcomes and improved prognostication. Such classification requires an accurate assessment of the clinical extent of regional lymph node metastasis. Consistent and reproducible regional lymph node designations facilitate reliable assessment of the clinical extent of regional lymph node metastasis. Regional lymph node maps, such as the Naruke lymph node map and the Mountain-Dresler modification of the American Thoracic Society lymph node map, were proposed for this purpose in the past. The most recent regional lymph node map to be published is the International Association for the Study of Lung Cancer (IASLC) lymph node map. The IASLC lymph node map supersedes all previous maps and should be used in tandem with the current seventh edition of the tumor, node, metastasis stage classification for lung cancer.
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Affiliation(s)
- Ahmed H El-Sherief
- From the Divisions of Thoracic Imaging (A.H.E., C.T.L.) and Thoracic and Cardiovascular Surgery (T.W.R.), Cleveland Clinic, 9500 Euclid Ave, Desk Hb6, Cleveland, OH 44195; Division of Thoracic Imaging and Intervention, Massachusetts General Hospital, Boston, Mass (C.C.W., G.F.A.); and Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, Ohio (R.L.D.)
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Ly6/uPAR-related protein C4.4A as a marker of solid growth pattern and poor prognosis in lung adenocarcinoma. J Thorac Oncol 2013; 8:152-60. [PMID: 23287851 DOI: 10.1097/jto.0b013e318279d503] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
INTRODUCTION We have recently shown that the protein C4.4A is induced in early precursor lesions of pulmonary adenocarcinomas and squamous cell carcinomas. In the present study, we aimed at analyzing the impact of C4.4A on the survival of non-small cell lung cancer patients and determining whether its unexpected expression in adenocarcinomas could be attributed to a specific growth type (lepidic, acinar, papillary, micropapillary, solid). METHODS Sections from the center and periphery of the primary tumor, as well as N2-positive lymph node metastases, were stained by immunohistochemistry for C4.4A and scored semi-quantitatively for intensity and frequency of positive tumor cells. RESULTS C4.4A score (intensity × frequency) in the tumor center was a highly significant prognostic factor in adenocarcinomas (n = 88), both in univariate (p = 0.004; hazard ratio [95% confidence interval] = 1.44 [1.12-1.85]) and multivariate statistical analysis (p = 0.0005; hazard ratio = 1.65 [1.24-2.19]), demonstrating decreasing survival with increasing score. In contrast, C4.4A did not provide prognostic information in squamous cell carcinomas (n = 104). Pathological stage was significant in both groups. In the adenocarcinomas, C4.4A expression was clearly associated with, but a stronger prognostic factor than, solid growth. CONCLUSIONS The present results substantiate the potential value of C4.4A as a prognostic marker in pulmonary adenocarcinomas seen earlier in a smaller, independent patient cohort. Importantly, we also show that C4.4A is a surrogate marker for adenocarcinoma solid growth. Recent data suggest that C4.4A is negatively regulated by the tumor suppressor liver kinase B1, which is inactivated in some adenocarcinomas, providing a possible link to the impact of C4.4A on the survival of these patients.
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Cerci JJ, Takagaki TY, Trindade E, Morgado R, Morabito F, Musolino RS, Soares Junior J, Meneghetti JC. A tomografia por emissão de pósitrons com 2-[18F]-fluoro-2-desoxi-D-glicose é custo-efetiva em pacientes com câncer de pulmão não pequenas células no Brasil. Radiol Bras 2012. [DOI: 10.1590/s0100-39842012000400004] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022] Open
Abstract
OBJETIVO: Comparar a acurácia e a custo-efetividade do estadiamento metabólico (EM) com o FDG-PET em relação ao estadiamento convencional (EC) no estadiamento inicial de pacientes com câncer de pulmão não pequenas células (CPNPC). MATERIAIS E MÉTODOS: Noventa e cinco pacientes com diagnóstico inicial de CPNPC foram estadiados antes do início do tratamento. Os resultados do EC e EM foram comparados quanto a definição do tratamento e incidência de toracotomia fútil em cada estratégia. RESULTADOS: O EM com FDG-PET classificou 48,4% dos pacientes como estádio mais avançado e 5,3% como menos avançado. O resultado do EM modificaria o tratamento em 41% dos pacientes. A toracotomia foi considerada fútil em 47% dos pacientes com EC e em 19% dos casos com EM. O custo das toracotomias fúteis em oito pacientes no EM foi de R$ 79.720, enquanto em 31 pacientes no EC seria de R$ 308.915. Apenas esta economia seria mais que suficiente para cobrir os custos de todos os exames de FDG-PET nos 95 pacientes (R$ 126.350) ou de FDG-PET/CT (R$ 193.515). CONCLUSÃO: O EM com FDG-PET tem maior acurácia que o EC em pacientes com CPNPC. A FDG-PET e FDG-PET/CT são custo-efetivas e sua utilização se justifica economicamente na saúde pública no Brasil.
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Kadara H, Behrens C, Yuan P, Solis L, Liu D, Gu X, Minna JD, Lee JJ, Kim E, Hong WK, Wistuba II, Lotan R. A five-gene and corresponding protein signature for stage-I lung adenocarcinoma prognosis. Clin Cancer Res 2011; 17:1490-501. [PMID: 21163870 PMCID: PMC3079395 DOI: 10.1158/1078-0432.ccr-10-2703] [Citation(s) in RCA: 58] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/23/2023]
Abstract
PURPOSE Identification of effective markers for outcome is expected to improve the clinical management of non-small cell lung cancer (NSCLC). Here, we assessed in NSCLC the prognostic efficacy of genes, which we had previously found to be differentially expressed in an in vitro model of human lung carcinogenesis. EXPERIMENTAL DESIGN Prediction algorithms and risk-score models were applied to the expression of the genes in publicly available NSCLC expression data sets. The prognostic capacity of the immunohistochemical expression of proteins encoded by these genes was also tested using formalin-fixed paraffin-embedded (FFPE) tissue specimens from 156 lung adenocarcinomas and 79 squamous cell carcinomas (SCCs). RESULTS The survival of all-stages (P < 0.001, HR = 2.0) or stage-I (P < 0.001, HR = 2.84) adenocarcinoma patients that expressed the five-gene in vitro lung carcinogenesis model (FILM) signature was significantly poorer than that of patients who did not. No survival differences were observed between SCCs predicted to express or lack FILM signature. Moreover, all stages (P < 0.001, HR = 1.95) or stage-I (P = 0.001, HR = 2.6) adenocarcinoma patients predicted to be at high risk by FILM transcript exhibited significantly worse survival than patients at low risk. Furthermore, the corresponding protein signature was associated with poor survival (all stages, P < 0.001, HR = 3.6; stage-I, P < 0.001, HR = 3.5; stage-IB, P < 0.001, HR = 4.6) and mortality risk (all stages, P = 0.001, HR = 4.0; stage-I, P = 0.01, HR = 3.4; stage-IB, P < 0.001, HR = 7.2) in lung adenocarcinoma patients. CONCLUSIONS Our findings highlight a gene and corresponding protein signature with effective capacity for identification of stage-I lung adenocarcinoma patients with poor prognosis that are likely to benefit from adjuvant therapy.
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Affiliation(s)
- Humam Kadara
- Department of Thoracic/Head and Neck Medical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston TX
| | - Carmen Behrens
- Department of Thoracic/Head and Neck Medical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston TX
| | - Ping Yuan
- Department of Pathology, The University of Texas M.D. Anderson Cancer Center, Houston TX
| | - Luisa Solis
- Department of Pathology, The University of Texas M.D. Anderson Cancer Center, Houston TX
| | - Diane Liu
- Department of Biostatistics, The University of Texas M.D. Anderson Cancer Center, Houston TX
| | - Xuemin Gu
- Department of Biostatistics, The University of Texas M.D. Anderson Cancer Center, Houston TX
| | - John D. Minna
- Hamon Center for Therapeutic Oncology the University of Texas Southwestern, Dallas, TX
| | - J. Jack Lee
- Department of Biostatistics, The University of Texas M.D. Anderson Cancer Center, Houston TX
| | - Edward Kim
- Department of Thoracic/Head and Neck Medical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston TX
| | - Waun-Ki Hong
- Department of Thoracic/Head and Neck Medical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston TX
| | - Ignacio I. Wistuba
- Department of Thoracic/Head and Neck Medical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston TX
- Department of Pathology, The University of Texas M.D. Anderson Cancer Center, Houston TX
| | - Reuben Lotan
- Department of Thoracic/Head and Neck Medical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston TX
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What should physicians look for in evaluating prognostic gene-expression signatures? Nat Rev Clin Oncol 2010; 7:327-34. [PMID: 20421890 DOI: 10.1038/nrclinonc.2010.60] [Citation(s) in RCA: 76] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
Most cancer treatments benefit only a minority of patients. This has led to a widespread interest in the identification of gene-expression-based prognostic signatures. Well-developed and validated genomic signatures can lead to personalized treatment decisions resulting in improved patient management. However, the pace of acceptance of these signatures in clinical practice has been slow. This is because many of the signatures have been developed without clear focus on the intended clinical use, and proper independent validation studies establishing their medical utility have rarely been performed. The practicing physician and the patient are thus left in doubt about the reliability and medical utility of the signatures. We aim to provide guidance to physicians in critically evaluating published studies on prognostic gene-expression signatures so that they are better equipped to decide which signatures, if any, have sufficient merit for use, in conjunction with other factors in helping their patients to make good treatment decisions. A discussion of the lessons to be learned from the successful development of the Oncotype DX genetic test for breast cancer is presented and contrasted with a review of the current status of prognostic gene-expression signatures in non-small-cell lung cancer.
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Subramanian J, Simon R. Gene expression-based prognostic signatures in lung cancer: ready for clinical use? J Natl Cancer Inst 2010; 102:464-74. [PMID: 20233996 DOI: 10.1093/jnci/djq025] [Citation(s) in RCA: 266] [Impact Index Per Article: 17.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
A substantial number of studies have reported the development of gene expression-based prognostic signatures for lung cancer. The ultimate aim of such studies should be the development of well-validated clinically useful prognostic signatures that improve therapeutic decision making beyond current practice standards. We critically reviewed published studies reporting the development of gene expression-based prognostic signatures for non-small cell lung cancer to assess the progress made toward this objective. Studies published between January 1, 2002, and February 28, 2009, were identified through a PubMed search. Following hand-screening of abstracts of the identified articles, 16 were selected as relevant. Those publications were evaluated in detail for appropriateness of the study design, statistical validation of the prognostic signature on independent datasets, presentation of results in an unbiased manner, and demonstration of medical utility for the new signature beyond that obtained using existing treatment guidelines. Based on this review, we found little evidence that any of the reported gene expression signatures are ready for clinical application. We also found serious problems in the design and analysis of many of the studies. We suggest a set of guidelines to aid the design, analysis, and evaluation of prognostic signature studies. These guidelines emphasize the importance of focused study planning to address specific medically important questions and the use of unbiased analysis methods to evaluate whether the resulting signatures provide evidence of medical utility beyond standard of care-based prognostic factors.
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Affiliation(s)
- Jyothi Subramanian
- Biometric Research Branch, Department of Cancer Treatment and Diagnosis, National Cancer Institute, 9000 Rockville Pike, Bethesda, MD 20892-7434, USA
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Godoy MCB, Naidich DP. Subsolid Pulmonary Nodules and the Spectrum of Peripheral Adenocarcinomas of the Lung: Recommended Interim Guidelines for Assessment and Management. Radiology 2009; 253:606-22. [PMID: 19952025 DOI: 10.1148/radiol.2533090179] [Citation(s) in RCA: 229] [Impact Index Per Article: 14.3] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Affiliation(s)
- Myrna C B Godoy
- Department of Radiology, New York University-Langone Medical Center, 560 First Ave, IRM 236, New York, NY 10016, USA
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Efficacy of endobronchial ultrasound-guided transbronchial needle aspiration of hilar lymph nodes for diagnosing and staging cancer. J Thorac Oncol 2009; 4:947-50. [PMID: 19590457 DOI: 10.1097/jto.0b013e3181add88d] [Citation(s) in RCA: 64] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
INTRODUCTION Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is used mostly in patients with non-small cell lung cancer (NSCLC) to sample mediastinal lymph nodes that are visible on computed tomography (CT). We sought to determine the efficacy of EBUS-TBNA in sampling enlarged hilar lymph nodes in this patient population. METHODS From January 2004 to May 2007, patients with suspected NSCLC and CT or positron emission tomography (PET) imaging demonstrating enlarged (>1 cm) or PET-positive hilar lymph nodes underwent EBUS-TBNA. Patients with enlarged central mediastinal nodes were excluded. Identifiable lymph nodes at locations 10R, 10L, 11R, and 11L were aspirated. All patients underwent subsequent surgical staging or clinical follow-up as indicated. Diagnoses based on aspirates were compared with those based on surgical or clinical results. RESULTS Of 213 patients evaluated (mean age, 56 years; 138 men), 188 (mean age, 56.3 years; 120 men) were diagnosed with NSCLC and were analyzed. In these patients, 229 lymph nodes, ranging 8 to 20 mm, were detected, and all were sampled. Of the 188 patients, 25 had a single enlarged node in a contralateral hilar position (N3), 40 had multiple enlarged ipsilateral nodes in the N1 position, and 123 had an ipsilateral single enlarged node in the N1 position. Overall, diagnostic sensitivity of EBUS-TBNA was 91%, specificity was 100%, and the positive predictive value was 92.4%. In the 25 patients with contralateral hilar nodes, sensitivity was 66%, specificity was 100%, and the positive predictive value was 96%. CONCLUSIONS No complications occurred. In experienced hands, EBUS-TBNA of enlarged hilar lymph visible on CT or hilar nodes that are PET scan-positive can provide diagnostic results similar to those for central mediastinal nodes.
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Song JW, Oh YM, Shim TS, Kim WS, Ryu JS, Choi CM. Efficacy comparison between 18F-FDG PET/CT and bone scintigraphy in detecting bony metastases of non-small-cell lung cancer. Lung Cancer 2009; 65:333-8. [DOI: 10.1016/j.lungcan.2008.12.004] [Citation(s) in RCA: 47] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2008] [Revised: 11/20/2008] [Accepted: 12/01/2008] [Indexed: 11/26/2022]
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Fischer B, Lassen U, Mortensen J, Larsen S, Loft A, Bertelsen A, Ravn J, Clementsen P, Høgholm A, Larsen K, Rasmussen T, Keiding S, Dirksen A, Gerke O, Skov B, Steffensen I, Hansen H, Vilmann P, Jacobsen G, Backer V, Maltbaek N, Pedersen J, Madsen H, Nielsen H, Højgaard L. Preoperative staging of lung cancer with combined PET-CT. N Engl J Med 2009; 361:32-9. [PMID: 19571281 DOI: 10.1056/nejmoa0900043] [Citation(s) in RCA: 409] [Impact Index Per Article: 25.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/03/2023]
Abstract
BACKGROUND Fast and accurate staging is essential for choosing treatment for non-small-cell lung cancer (NSCLC). The purpose of this randomized study was to evaluate the clinical effect of combined positron-emission tomography and computed tomography (PET-CT) on preoperative staging of NSCLC. METHODS We randomly assigned patients who were referred for preoperative staging of NSCLC to either conventional staging plus PET-CT or conventional staging alone. Patients were followed until death or for at least 12 months. The primary end point was the number of futile thoracotomies, defined as any one of the following: a thoracotomy with the finding of pathologically confirmed mediastinal lymph-node involvement (stage IIIA [N2]), stage IIIB or stage IV disease, or a benign lung lesion; an exploratory thoracotomy; or a thoracotomy in a patient who had recurrent disease or death from any cause within 1 year after randomization. RESULTS From January 2002 through February 2007, we randomly assigned 98 patients to the PET-CT group and 91 to the conventional-staging group. Mediastinoscopy was performed in 94% of the patients. After PET-CT, 38 patients were classified as having inoperable NSCLC, and after conventional staging, 18 patients were classified thus. Sixty patients in the PET-CT group and 73 in the conventional-staging group underwent thoracotomy (P=0.004). Among these thoracotomies, 21 in the PET-CT group and 38 in the conventional-staging group were futile (P=0.05). The number of justified thoracotomies and survival were similar in the two groups. CONCLUSIONS The use of PET-CT for preoperative staging of NSCLC reduced both the total number of thoracotomies and the number of futile thoracotomies but did not affect overall mortality. (ClinicalTrials.gov number, NCT00867412.)
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Affiliation(s)
- Barbara Fischer
- Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.
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