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Ayeni A, Evbuomwan O, Vangu MDTW. The Role of [ 18F]FDG PET/CT in Monitoring of Therapy Response in Lung Cancer. Semin Nucl Med 2025; 55:175-189. [PMID: 40021362 DOI: 10.1053/j.semnuclmed.2025.02.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2025] [Accepted: 02/06/2025] [Indexed: 03/03/2025]
Abstract
Lung cancer remains a leading cause of cancer deaths worldwide, with an all stage 5-year relative survival rate of less than 30%. Multiple treatment strategies are available and continue to evolve, with therapy primarily tailored to the type and stage of the disease. Accurate monitoring of therapy response is crucial for optimizing treatment outcomes. PET/CT imaging with [18F]FDG has become the standard of care across various phases of lung cancer management due to its ability to assess metabolic activity. This review underscores the pivotal role of [18F]FDG PET/CT in evaluating therapy response in lung cancer, particularly in non-small cell lung cancer (NSCLC). It examines conventional response criteria and their adaptations in the era of immunotherapy, highlighting the value of integrating metabolic imaging with established criteria to improve treatment assessment and guide clinical decisions. The potential of non-[18F]FDG PET tracers targeting diverse biological pathways to provide deeper insights into tumor biology, therapy response and predictive outcomes is also explored. Additionally, the emerging role of radiomics in enhancing treatment efficacy assessment and improving patient management is briefly highlighted. Despite the challenges in the routine clinical application of various metabolic response criteria, [18F]FDG PET/CT remains a crucial tool in monitoring therapy response in lung cancer. Ongoing advancements in therapeutic strategies, radiopharmaceuticals, and imaging techniques continue to drive progress in lung cancer management, promising improved patient outcomes.
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Affiliation(s)
- Akinwale Ayeni
- Division of Nuclear Medicine, Department of Radiation Sciences, Faculty of Health Sciences, University of The Witwatersrand, Johannesburg, South Africa; Nuclear Medicine, Klerksdorp/Tshepong Hospital Complex, Klerksdorp, North West Province, South Africa; Division of Nuclear Medicine, Department of Radiation Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa.
| | - Osayande Evbuomwan
- Department of Nuclear Medicine, Faculty of Health Sciences, University of The Free State, Bloemfontein, South Africa
| | - Mboyo-Di-Tamba Willy Vangu
- Division of Nuclear Medicine, Department of Radiation Sciences, Faculty of Health Sciences, University of The Witwatersrand, Johannesburg, South Africa
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Bhoil A. Lesion Analysis in PERCIST 1.0: Clinical Ease versus Research Requisite-Where Does the Balance Exist? World J Nucl Med 2023; 22:100-107. [PMID: 37223629 PMCID: PMC10202569 DOI: 10.1055/s-0042-1750406] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/25/2023] Open
Abstract
Background Semiqualitative parameter SUVmax has been the most frequently used semiquantitative positron emission tomography (PET) parameter for response evaluation, but only metabolic activity of a single (most metabolic) lesion is predicted. Newer response parameters such as tumor lesion glycolysis (TLG) incorporating lesions' metabolic volume or whole-body metabolic tumor burden (MTBwb) are being explored for response evaluation. Evaluation and comparison of response with different semiquantitative PET parameters such as SUVmax and TLG in most metabolic lesion, multiple lesions (max of five), and MTBwb in advanced non-small cell lung cancer (NSCLC) patients were made. The different PET parameters were analyzed for response evaluation, overall survival (OS), and progression-free survival (PFS). Methods 18 F-FDG-PET/CT (18-fluorine-fluorodeoxyglucose positron emission tomography/computed tomography) imaging was performed in 23 patients (M = 14, F = 9, mean age = 57.6 years) with stage IIIB-IV advanced NSCLC before initiation of therapy with oral estimated glomerular filtration rate-tyrosine kinase inhibitor for early and late response evaluation. The quantitative PET parameters such as SUVmax and TLG were measured in single (most metabolic) lesion, multiple lesions, and MTBwb. The parameters SUVmax, TLG, and MTBwb were compared for early and late response evaluation and analyzed for OS and PFS Results No significant difference in change in response evaluation was seen in patients evaluated with most metabolic lesion, multiple lesions, or MTBwb. Difference in early (DC 22, NDC 1) and late (DC 20, NDC 3) response evaluation was seen that remained unchanged when lesions were measured in terms of number of lesions or the MTBwb. The early imaging was seen to be statistically significant to the OS compared with late imaging. Conclusions Single (most metabolic) lesion shows similar disease response and OS to multiple lesions and MTBwb. Response evaluation by late imaging offered no significant advantage compared with early imaging. Thus, early response evaluation with SUVmax parameter offers a good balance between clinical ease and research requisition.
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Affiliation(s)
- Amit Bhoil
- Department of Nuclear Medicine, Mahajan Imaging and Labs, New Delhi, India
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3
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Jiang Y, Zeng Q, Jiang Q, Peng X, Gao J, Wan H, Wang L, Gao Y, Zhou X, Lin D, Feng H, Liang S, Zhou H, Ding J, Ai J, Huang R. 18F-FDG PET as an imaging biomarker for the response to FGFR-targeted therapy of cancer cells via FGFR-initiated mTOR/HK2 axis. Am J Cancer Res 2022; 12:6395-6408. [PMID: 36168616 PMCID: PMC9475468 DOI: 10.7150/thno.74848] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2022] [Accepted: 08/16/2022] [Indexed: 11/05/2022] Open
Abstract
Rationale: The overall clinical response to FGFR inhibitor (FGFRi) is far from satisfactory in cancer patients stratified by FGFR aberration, the current biomarker in clinical practice. A novel biomarker to evaluate the therapeutic response to FGFRi in a non-invasive and dynamic manner is thus greatly desired. Methods: Six FGFR-aberrant cancer cell lines were used, including four FGFRi-sensitive ones (NCI-H1581, NCI-H716, RT112 and Hep3B) and two FGFRi-resistant ones (primary for NCI-H2444 and acquired for NCI-H1581/AR). Cell viability and tumor xenograft growth analyses were performed to evaluate FGFRi sensitivities, accompanied by corresponding 18F-fluorodeoxyglucose (18F-FDG) uptake assay. mTOR/PLCγ/MEK-ERK signaling blockade by specific inhibitors or siRNAs was applied to determine the regulation mechanism. Results: FGFR inhibition decreased the in vitro accumulation of 18F-FDG only in four FGFRi-sensitive cell lines, but in neither of FGFRi-resistant ones. We then demonstrated that FGFRi-induced transcriptional downregulation of hexokinase 2 (HK2), a key factor of glucose metabolism and FDG trapping, via mTOR pathway leading to this decrease. Moreover, 18F-FDG PET imaging successfully differentiated the FGFRi-sensitive tumor xenografts from primary or acquired resistant ones by the tumor 18F-FDG accumulation change upon FGFRi treatment. Of note, both 18F-FDG tumor accumulation and HK2 expression could respond the administration/withdrawal of FGFRi in NCI-H1581 xenografts correspondingly. Conclusion: The novel association between the molecular mechanism (FGFR/mTOR/HK2 axis) and radiological phenotype (18F-FDG PET uptake) of FGFR-targeted therapy was demonstrated in multiple preclinical models. The adoption of 18F-FDG PET biomarker-based imaging strategy to assess response/resistance to FGFR inhibition may benefit treatment selection for cancer patients.
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Affiliation(s)
- Yuchen Jiang
- School of Pharmacy, Nanchang University, Nanchang 330006, China.,Division of Antitumor Pharmacology, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China
| | - Qinghe Zeng
- Molecular Imaging Center, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China
| | - Qinghui Jiang
- Molecular Imaging Center, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.,University of Chinese Academy of Sciences, Beijing 100049, China
| | - Xia Peng
- Division of Antitumor Pharmacology, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China
| | - Jing Gao
- Analytical Research Center for Organic and Biological Molecules, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.,CAS Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China
| | - Haiyan Wan
- Division of Antitumor Pharmacology, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China
| | - Luting Wang
- Molecular Imaging Center, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China
| | - Yinglei Gao
- Division of Antitumor Pharmacology, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China
| | - Xiaoyu Zhou
- Molecular Imaging Center, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China
| | - Dongze Lin
- Division of Antitumor Pharmacology, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China
| | - Hanyi Feng
- School of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing 210023, China
| | - Sheng Liang
- Department of Nuclear Medicine, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200092, China
| | - Hu Zhou
- University of Chinese Academy of Sciences, Beijing 100049, China.,Analytical Research Center for Organic and Biological Molecules, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.,CAS Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China
| | - Jian Ding
- School of Pharmacy, Nanchang University, Nanchang 330006, China.,Division of Antitumor Pharmacology, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.,University of Chinese Academy of Sciences, Beijing 100049, China
| | - Jing Ai
- Division of Antitumor Pharmacology, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.,University of Chinese Academy of Sciences, Beijing 100049, China
| | - Ruimin Huang
- Molecular Imaging Center, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.,University of Chinese Academy of Sciences, Beijing 100049, China.,School of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing 210023, China
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Krarup MMK, Fischer BM, Christensen TN. New PET Tracers: Current Knowledge and Perspectives in Lung Cancer. Semin Nucl Med 2022; 52:781-796. [PMID: 35752465 DOI: 10.1053/j.semnuclmed.2022.05.002] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2022] [Accepted: 05/04/2022] [Indexed: 11/11/2022]
Abstract
PET/CT with the tracer 2-[18F]fluoro-2-deoxy-D-glucose ([18F]FDG) has improved diagnostic imaging in cancer and is routinely used for diagnosing, staging and treatment planning in lung cancer patients. However, pitfalls of [18F]FDG-PET/CT limit the use in specific settings. Additionally, lung cancer is still the leading cause of cancer associated death and has high risk of recurrence after curative treatment. These circumstances have led to the continuous search for more sensitive and specific PET tracers to optimize lung cancer diagnosis, staging, treatment planning and evaluation. The objective of this review is to present and discuss current knowledge and perspectives of new PET tracers for use in lung cancer. A literature search was performed on PubMed and clinicaltrials.gov, limited to the past decade, excluding case reports, preclinical studies and studies on established tracers such as [18F]FDG and DOTATE. The most relevant papers from the search were evaluated. Several tracers have been developed targeting specific tumor characteristics and hallmarks of cancer. A small number of tracers have been studied extensively and evaluated head-to-head with [18F]FDG-PET/CT, whereas others need further investigation and validation in larger clinical trials. At this moment, none of the tracers can replace [18F]FDG-PET/CT. However, they might serve as supplementary imaging methods to provide more knowledge about biological tumor characteristics and visualize intra- and inter-tumoral heterogeneity.
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Affiliation(s)
- Marie M K Krarup
- Department of Clinical Physiology and Nuclear Medicine, Rigshospitalet Copehagen University Hospital, Copenhagen, Denmark.
| | - Barbara M Fischer
- Department of Clinical Medicine, Faculty of Health, Univeristy of Copenhagen (UCPH), Copenhagen, Denmark; School of Biomedical Engineering and Imaging Sciences, King's College London, London, United Kingdom
| | - Tine N Christensen
- Department of Clinical Physiology and Nuclear Medicine, Rigshospitalet Copehagen University Hospital, Copenhagen, Denmark
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Jiang M, Zhang X, Chen Y, Chen P, Guo X, Ma L, Gao Q, Mei W, Zhang J, Zheng J. A Review of the Correlation Between Epidermal Growth Factor Receptor Mutation Status and 18F-FDG Metabolic Activity in Non-Small Cell Lung Cancer. Front Oncol 2022; 12:780186. [PMID: 35515138 PMCID: PMC9065410 DOI: 10.3389/fonc.2022.780186] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2021] [Accepted: 03/25/2022] [Indexed: 11/15/2022] Open
Abstract
PET/CT with 18F-2-fluoro-2-deoxyglucose (18F-FDG) has been proposed as a promising modality for diagnosing and monitoring treatment response and evaluating prognosis for patients with non-small cell lung cancer (NSCLC). The status of epidermal growth factor receptor (EGFR) mutation is a critical signal for the treatment strategies of patients with NSCLC. Higher response rates and prolonged progression-free survival could be obtained in patients with NSCLC harboring EGFR mutations treated with tyrosine kinase inhibitors (TKIs) when compared with traditional cytotoxic chemotherapy. However, patients with EGFR mutation treated with TKIs inevitably develop drug resistance, so predicting the duration of resistance is of great importance for selecting individual treatment strategies. Several semiquantitative metabolic parameters, e.g., maximum standard uptake value (SUVmax), metabolic tumor volume (MTV), and total lesion glycolysis (TLG), measured by PET/CT to reflect 18F-FDG metabolic activity, have been demonstrated to be powerful in predicting the status of EGFR mutation, monitoring treatment response of TKIs, and assessing the outcome of patients with NSCLC. In this review, we summarize the biological and clinical correlations between EGFR mutation status and 18F-FDG metabolic activity in NSCLC. The metabolic activity of 18F-FDG, as an extrinsic manifestation of NSCLC, could reflect the mutation status of intrinsic factor EGFR. Both of them play a critical role in guiding the implementation of treatment modalities and evaluating therapy efficacy and outcome for patients with NSCLC.
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Affiliation(s)
- Maoqing Jiang
- Department of PET/CT Center, Hwa Mei Hospital, University of Chinese Academy of Sciences, Ningbo, China
- Ningbo Institute of Life and Health Industry, University of Chinese Academy of Sciences, Ningbo, China
- Department of Nuclear Medicine, Hwa Mei Hospital, University of Chinese Academy of Sciences, Ningbo, China
| | - Xiaohui Zhang
- Department of PET/CT Center, Hwa Mei Hospital, University of Chinese Academy of Sciences, Ningbo, China
- Ningbo Institute of Life and Health Industry, University of Chinese Academy of Sciences, Ningbo, China
| | - Yan Chen
- Department of Physical Examination Center, Ningbo First Hospital, Ningbo, China
| | - Ping Chen
- Department of Nephrology, Hwa Mei Hospital, University of Chinese Academy of Sciences, Ningbo, China
| | - Xiuyu Guo
- Department of PET/CT Center, Hwa Mei Hospital, University of Chinese Academy of Sciences, Ningbo, China
- Ningbo Institute of Life and Health Industry, University of Chinese Academy of Sciences, Ningbo, China
| | - Lijuan Ma
- Department of PET/CT Center, Hwa Mei Hospital, University of Chinese Academy of Sciences, Ningbo, China
- Ningbo Institute of Life and Health Industry, University of Chinese Academy of Sciences, Ningbo, China
| | - Qiaoling Gao
- Department of PET/CT Center, Hwa Mei Hospital, University of Chinese Academy of Sciences, Ningbo, China
- Ningbo Institute of Life and Health Industry, University of Chinese Academy of Sciences, Ningbo, China
| | - Weiqi Mei
- Department of Nuclear Medicine, Hwa Mei Hospital, University of Chinese Academy of Sciences, Ningbo, China
| | - Jingfeng Zhang
- Department of Education, Hwa Mei Hospital, University of Chinese Academy of Sciences, Ningbo, China
| | - Jianjun Zheng
- Department of PET/CT Center, Hwa Mei Hospital, University of Chinese Academy of Sciences, Ningbo, China
- Ningbo Institute of Life and Health Industry, University of Chinese Academy of Sciences, Ningbo, China
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6
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18F-Fluorodeoxyglucose PET/CT for Early Prediction of Outcomes in Patients with Advanced Lung Adenocarcinomas and EGFR Mutations Treated with First-Line EGFR-TKIs. Cancers (Basel) 2022; 14:cancers14061507. [PMID: 35326662 PMCID: PMC8945925 DOI: 10.3390/cancers14061507] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2022] [Revised: 03/10/2022] [Accepted: 03/11/2022] [Indexed: 12/03/2022] Open
Abstract
Simple Summary Epithelial growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) are the first-line therapy for patients with advanced-stage lung adenocarcinoma with EGFR mutations. However, 17–31% of these patients do not respond to therapy, making early evaluation of treatment response crucial. This prospective study investigates the value of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) for timely prediction of response and survival of these patients. We evaluated 30 patients with stage IIIB/IV lung adenocarcinomas and EGFR mutations, receiving first-line EGFR-TKI therapy. 18F-FDG PET/CT was performed before and two weeks after initiation of treatment. Positron Emission Tomography Response Criteria in Solid Tumors served as an independent predictor of non-progressive disease; baseline and change of metabolic tumor volume represented independent predictors of progression-free survival and overall survival, respectively. Therefore, 18F-FDG PET/CT is an early predictor of outcomes and individual prognosis of patients with stage IIIB/IV lung adenocarcinomas and EGFR mutations receiving first-line EGFR-TKI therapy. Abstract This study aims to investigate the role of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) in early prediction of response and survival following epithelial growth factor receptor (EGFR)–tyrosine kinase inhibitor (TKI) therapy in patients with advanced lung adenocarcinomas and EGFR mutations. Thirty patients with stage IIIB/IV lung adenocarcinomas and EGFR mutations receiving first-line EGFR-TKIs were prospectively evaluated between November 2012 and May 2015. EGFR mutations were quantified by delta cycle threshold (dCt). 18F-FDG PET/CT was performed before and 2 weeks after treatment initiation. PET response was assessed based on PET Response Criteria in Solid Tumors (PERCIST). Baseline and percentage changes in the summed standardized uptake value, metabolic tumor volume (bsumMTV and ΔsumMTV, respectively), and total lesion glycolysis of ≤5 target lesions/patient were calculated. The association between parameters (clinical and PET) and non-progression disease after 3 months of treatment in CT based on the Response Evaluation Criteria in Solid Tumors Version 1.1 (nPD3mo), progression-free survival (PFS), and overall survival (OS) were tested. The median follow-up time was 19.6 months. The median PFS and OS were 12.0 and 25.3 months, respectively. The PERCIST criteria was an independent predictor of nPD3mo (p = 0.009), dCt (p = 0.014) and bsumMTV (p = 0.014) were independent predictors of PFS, and dCt (p = 0.014) and ΔsumMTV (p = 0.005) were independent predictors of OS. 18F-FDG PET/CT achieved early prediction of outcomes in patients with advanced lung adenocarcinomas and EGFR mutations receiving EGFR-TKIs.
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7
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FDG-PET/CT imaging for evaluating durable responses to immune check point inhibitors in patients with advanced cutaneous squamous cell carcinoma. Cancer Imaging 2021; 21:57. [PMID: 34645517 PMCID: PMC8515684 DOI: 10.1186/s40644-021-00426-2] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2021] [Accepted: 09/23/2021] [Indexed: 12/30/2022] Open
Abstract
Background The role of FDG-PET/CT imaging in assessing response to immunotherapy in advanced cutaneous squamous cell carcinoma (CSCC) is unknown. This study compared complete metabolic response (CMR) rates by FDG-PET and RECIST1.1 via CT or MRI in patients on cemiplimab for > 10 months. Methods This was a single-centre retrospective study of 15 patients treated with cemiplimab for advanced CSCC who had CT/MRI and FDG-PET/CT at > 10 months to assess metabolic treatment response. The median age was 73 years (range 55–84) and 93% were male. RECIST1.1 and PERCIST1.0 tumor responses were evaluated by blinded readers. Results Seventy-three percent (11/15) (95%CI 44.9, 92.2%) achieved a CMR on PET. Of these 11, on RECIST1.1 there was one complete response, 9 partial responses and one stable disease. Conclusions In patients on cemiplimab for > 10 months, there was discordance between CR rates on FDG-PET versus RECIST1.1. FDG-PET/CT may have utility for clarifying depth of response in patients treated with immunotherapy for CSCC.
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8
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Valerio L, Guidoccio F, Giani C, Tardelli E, Puccini G, Puleo L, Minaldi E, Boni G, Elisei R, Volterrani D. [18F]-FDG-PET/CT Correlates With the Response of Radiorefractory Thyroid Cancer to Lenvatinib and Patient Survival. J Clin Endocrinol Metab 2021; 106:2355-2366. [PMID: 33901285 DOI: 10.1210/clinem/dgab278] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/07/2021] [Indexed: 11/19/2022]
Abstract
CONTEXT 18F-fluoro-2-deoxy-D-glucose positron emission tomography-computed tomography ([18F]-FDG-PET/CT)-positive metastatic lesions in radioiodine-refractory differentiated thyroid cancer (RAI-R DTC) have a poor prognosis and lenvatinib represents the best therapy. OBJECTIVE We investigated the role of [18F]-FDG-PET/CT in the evaluation of metabolic response and prediction of the outcome of RAI-R DTC patients treated with lenvatinib. METHODS Patients (n = 33) with progressive metastatic RAI-R DTC who were treated with lenvatinib were investigated at baseline and during follow-up with biochemical (thyroglobulin and thyroglobulin antibodies), morphological (whole-body CT scan) and metabolic ([18F]-FDG-PET/CT) evaluation. RESULTS Nineteen (57.6%) patients showed the greatest metabolic response at the first [18F]-FDG-PET/CT scan, performed after 4 weeks of lenvatinib, while 5/33 (15.1%) patients had this response later. Moreover, 66.7% of patients had both a metabolic response at the first [18F]-FDG-PET/CT scan and a morphological response at the first CT scan. We observed a correlation between the metabolic response at [18F]-FDG-PET/CT scan performed after 4 weeks of treatment and the biochemical response at the same time in 60.6% of patients. The median overall survival (OS) was significantly longer in patients with either a metabolic response at last [18F]-FDG-PET/CT (40.00 vs 8.98 months) or a morphological response at last CT scan (37.22 vs 9.53 months) than in those without response. Moreover, the OS was longer in patients with a metabolic response at [18F]-FDG-PET/CT performed after 4 weeks of treatment (36.53 vs 11.28 months). CONCLUSIONS Our data show that [18F]-FDG-PET/CT can early predict the response to lenvatinib and correlates with the OS of RAI-R DTC patients treated with this drug.
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Affiliation(s)
- Laura Valerio
- University Hospital of Pisa, Department of Clinical and Experimental Medicine, Unit of Endocrinology, Pisa 56124, Italy
| | - Federica Guidoccio
- University Hospital of Pisa, Department of Diagnostic and Imaging, Unit of Nuclear Medicine, Pisa 56126, Italy
| | - Carlotta Giani
- University Hospital of Pisa, Department of Clinical and Experimental Medicine, Unit of Endocrinology, Pisa 56124, Italy
| | - Elisa Tardelli
- University Hospital of Pisa, Department of Diagnostic and Imaging, Unit of Nuclear Medicine, Pisa 56126, Italy
| | - Giulia Puccini
- University Hospital of Pisa, Department of Diagnostic and Imaging, Unit of Nuclear Medicine, Pisa 56126, Italy
| | - Luciana Puleo
- University Hospital of Pisa, Department of Clinical and Experimental Medicine, Unit of Endocrinology, Pisa 56124, Italy
| | - Elisa Minaldi
- University Hospital of Pisa, Department of Clinical and Experimental Medicine, Unit of Endocrinology, Pisa 56124, Italy
| | - Giuseppe Boni
- University Hospital of Pisa, Department of Diagnostic and Imaging, Unit of Nuclear Medicine, Pisa 56126, Italy
| | - Rossella Elisei
- University Hospital of Pisa, Department of Clinical and Experimental Medicine, Unit of Endocrinology, Pisa 56124, Italy
| | - Duccio Volterrani
- University Hospital of Pisa, Department of Diagnostic and Imaging, Unit of Nuclear Medicine, Pisa 56126, Italy
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Alwadani B, Dall'Angelo S, Fleming IN. Clinical value of 3'-deoxy-3'-[ 18F]fluorothymidine-positron emission tomography for diagnosis, staging and assessing therapy response in lung cancer. Insights Imaging 2021; 12:90. [PMID: 34213667 PMCID: PMC8253862 DOI: 10.1186/s13244-021-01026-1] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2021] [Accepted: 06/02/2021] [Indexed: 12/09/2022] Open
Abstract
Lung cancer has the highest mortality rate of any tumour type. The main driver of lung tumour growth and development is uncontrolled cellular proliferation. Poor patient outcomes are partly the result of the limited range of effective anti-cancer therapies available and partly due to the limited accuracy of biomarkers to report on cell proliferation rates in patients. Accordingly, accurate methods of diagnosing, staging and assessing response to therapy are crucial to improve patient outcomes. One effective way of assessing cell proliferation is to employ non-invasive evaluation using 3'-deoxy-3'-[18F]fluorothymidine ([18F]FLT) positron emission tomography [18F]FLT-PET. [18F]FLT, unlike the most commonly used PET tracer [18F]fluorodeoxyglucose ([18F]FDG), can specifically report on cell proliferation and does not accumulate in inflammatory cells. Therefore, this radiotracer could exhibit higher specificity in diagnosis and staging, along with more accurate monitoring of therapy response at early stages in the treatment cycle. This review summarises and evaluates published studies on the clinical use of [18F]FLT to diagnose, stage and assess response to therapy in lung cancer.
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Affiliation(s)
- Bandar Alwadani
- Diagnostic Radiology Department, College of Applied Medical Sciences, Jazan University, Al Maarefah Rd, POB 114, Jazan, 45142, Saudi Arabia.,Institute of Medical Sciences, University of Aberdeen, Aberdeen, AB25 2ZD, UK
| | - Sergio Dall'Angelo
- Institute of Medical Sciences, University of Aberdeen, Aberdeen, AB25 2ZD, UK
| | - Ian N Fleming
- Institute of Medical Sciences, University of Aberdeen, Aberdeen, AB25 2ZD, UK.
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10
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Butler E, Schwettmann B, Geboers S, Hao G, Kim J, Nham K, Sun X, Laetsch TW, Xu L, Williams NS, Skapek SX. Functional imaging of RAS pathway targeting in malignant peripheral nerve sheath tumor cells and xenografts. Pediatr Blood Cancer 2020; 67:e28639. [PMID: 32975370 DOI: 10.1002/pbc.28639] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/19/2020] [Revised: 07/21/2020] [Accepted: 07/22/2020] [Indexed: 11/10/2022]
Abstract
BACKGROUND Malignant peripheral nerve sheath tumor (MPNST) is an aggressive form of soft-tissue sarcoma (STS) in children. Despite intensive therapy, relatively few children with metastatic and unresectable disease survive beyond three years. RAS pathway activation is common in MPNST, suggesting MEK pathway inhibition as a targeted therapy, but the impact on clinical outcome has been small to date. PROCEDURE We conducted preclinical pharmacokinetic (PK) and pharmacodynamic studies of two MEK inhibitors, trametinib and selumetinib, in two MPNST models and analyzed tumors for intratumor drug levels. We then investigated 3'-deoxy-3'-[18 F]fluorothymidine (18 F-FLT) PET imaging followed by 18 F-FDG PET/CT imaging of MPNST xenografts coupled to short-term or longer-term treatment with selumetinib focusing on PET-based imaging as a biomarker of MEK inhibition. RESULTS Trametinib decreased pERK expression in MPNST xenografts but did not prolong survival or decrease Ki67 expression. In contrast, selumetinib prolonged survival of animals bearing MPNST xenografts, and this correlated with decreased pERK and Ki67 staining. PK studies revealed a significantly higher fraction of unbound selumetinib within a responsive MPNST xenograft model. Thymidine uptake, assessed by 18 F-FLT PET/CT, positively correlated with Ki67 expression in different xenograft models and in response to selumetinib. CONCLUSION The ability of MEK inhibitors to control MPNST growth cannot simply be predicted by serum drug levels or drug-induced changes in pERK expression. Tumor cell proliferation assessed by 18 F-FLT PET imaging might be useful as an early response marker to targeted therapies, including MEK inhibition, where a primary effect is cell-cycle arrest.
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Affiliation(s)
- Erin Butler
- Department of Pediatrics Division of Hematology/Oncology, University of Texas Southwestern Medical Center, Dallas, Texas
| | - Blake Schwettmann
- Department of Pediatrics Division of Hematology/Oncology, University of Texas Southwestern Medical Center, Dallas, Texas
| | - Sophie Geboers
- Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, Texas
| | - Guiyang Hao
- Department of Radiology, University of Texas Southwestern Medical Center, Dallas, Texas
| | - Jiwoong Kim
- Quantitative Biomedical Research Center, Department of Population and Data Sciences, University of Texas Southwestern Medical Center, Dallas, Texas
| | - Kien Nham
- Department of Radiology, University of Texas Southwestern Medical Center, Dallas, Texas
| | - Xiankai Sun
- Department of Radiology, University of Texas Southwestern Medical Center, Dallas, Texas.,The Advanced Imaging Research Center, University of Texas Southwestern Medical Center, Dallas, Texas
| | - Theodore W Laetsch
- Department of Pediatrics Division of Hematology/Oncology, University of Texas Southwestern Medical Center, Dallas, Texas.,The Harold C. Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, Texas
| | - Lin Xu
- Department of Pediatrics Division of Hematology/Oncology, University of Texas Southwestern Medical Center, Dallas, Texas.,Quantitative Biomedical Research Center, Department of Population and Data Sciences, University of Texas Southwestern Medical Center, Dallas, Texas.,The Harold C. Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, Texas
| | - Noelle S Williams
- Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, Texas
| | - Stephen X Skapek
- Department of Pediatrics Division of Hematology/Oncology, University of Texas Southwestern Medical Center, Dallas, Texas
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11
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Raggi D, Bandini M, Giannatempo P, Farè E, Marandino L, Colecchia M, Calareso G, Padovano B, Serafini G, Alessi A, Necchi A. Prognostic Role of Early Interim Fluorodeoxyglucose Positron Emission Tomography in Patients With Advanced Seminoma Undergoing Standard Treatment. Clin Genitourin Cancer 2020; 19:237-245.e2. [PMID: 32980271 DOI: 10.1016/j.clgc.2020.08.007] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2020] [Revised: 08/03/2020] [Accepted: 08/08/2020] [Indexed: 01/12/2023]
Abstract
BACKGROUND Patients with advanced seminoma have an exceedingly favorable prognosis. Studies aiming to reduce the total treatment burden and side effects in patients with well-defined disease and very good prognosis are warranted. PATIENTS AND METHODS In a prospective observational study, patients with advanced stage seminoma were treated with bleomycin, etoposide, and cisplatin (BEP) or EP according to guidelines. Fluorodeoxyglucose with positron emission tomography and computed tomography (FDG-PET/CT) examinations were performed at baseline, after 2 cycles (PET/CT2) in all patients, and after chemotherapy at the physician's discretion. Disease response to treatment assessed by PET/CT was qualitatively evaluated by 2 independent nuclear medicine physicians. Contrast-enhanced CT scans were also performed according to guidelines (at baseline, after treatment, during follow-up). The study's primary endpoint was to evaluate the association between PET/CT2 findings and relapse-free survival. RESULTS From January 2009 to January 2017, a total of 75 consecutive patients were enrolled, of whom 70 were included for analysis. The clinical disease stage was IIA-B and IIC-III in 40% and 60%, respectively. By local assessment, 46 PET/CT2 scans (65.7%) were reported as negative, and 46% of these patients had stage IIC-III disease. Five-year relapse-free survival of PET/CT2-positive patients was 75% (95% confidence interval, 60-95) compared to 97.8% (95% confidence interval, 93.7-100) of PET/CT2-negative patients (P = .002). In univariate analyses, PET/CT2 was significantly associated with relapse-free survival (P = .02). CONCLUSIONS No residual FDG uptake after 2 cycles of conventional chemotherapy is prognostic in advanced seminoma, but it may be useful to optimize the standard prognostic risk groups and may be tested within larger prospective clinical trials of chemotherapy deescalation.
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Affiliation(s)
- Daniele Raggi
- Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
| | - Marco Bandini
- Unit of Urology, Urological Research Institute (URI), IRCCS Ospedale San Raffaele, Vita-Salute San Raffaele University, Milan, Italy
| | - Patrizia Giannatempo
- Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
| | - Elena Farè
- Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
| | - Laura Marandino
- Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
| | - Maurizio Colecchia
- Department of Pathology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
| | - Giuseppina Calareso
- Department of Radiology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
| | - Barbara Padovano
- Department of Nuclear Medicine, PET Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
| | - Gianluca Serafini
- Department of Nuclear Medicine, PET Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
| | - Alessandra Alessi
- Department of Nuclear Medicine, PET Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
| | - Andrea Necchi
- Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
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12
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Konert T, Everitt S, La Fontaine MD, van de Kamer JB, MacManus MP, Vogel WV, Callahan J, Sonke JJ. Robust, independent and relevant prognostic 18F-fluorodeoxyglucose positron emission tomography radiomics features in non-small cell lung cancer: Are there any? PLoS One 2020; 15:e0228793. [PMID: 32097418 PMCID: PMC7041813 DOI: 10.1371/journal.pone.0228793] [Citation(s) in RCA: 20] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/03/2019] [Accepted: 01/22/2020] [Indexed: 12/14/2022] Open
Abstract
In locally advanced lung cancer, established baseline clinical variables show limited prognostic accuracy and 18F-fluorodeoxyglucose positron emission tomography (FDG PET) radiomics features may increase accuracy for optimal treatment selection. Their robustness and added value relative to current clinical factors are unknown. Hence, we identify robust and independent PET radiomics features that may have complementary value in predicting survival endpoints. A 4D PET dataset (n = 70) was used for assessing the repeatability (Bland-Altman analysis) and independence of PET radiomics features (Spearman rank: |ρ|<0.5). Two 3D PET datasets combined (n = 252) were used for training and validation of an elastic net regularized generalized logistic regression model (GLM) based on a selection of clinical and robust independent PET radiomics features (GLMall). The fitted model performance was externally validated (n = 40). The performance of GLMall (measured with area under the receiver operating characteristic curve, AUC) was highest in predicting 2-year overall survival (0.66±0.07). No significant improvement was observed for GLMall compared to a model containing only PET radiomics features or only clinical variables for any clinical endpoint. External validation of GLMall led to AUC values no higher than 0.55 for any clinical endpoint. In this study, robust independent FDG PET radiomics features did not have complementary value in predicting survival endpoints in lung cancer patients. Improving risk stratification and clinical decision making based on clinical variables and PET radiomics features has still been proven difficult in locally advanced lung cancer patients.
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Affiliation(s)
- Tom Konert
- Nuclear Medicine Department, Netherlands Cancer Institute, Amsterdam, The Netherlands
- Department of Radiation Oncology, Netherlands Cancer Institute, Amsterdam, The Netherlands
| | - Sarah Everitt
- Division of Radiation Oncology and Cancer Imaging, Peter MacCallum Cancer Centre, Melbourne, Australia
- Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, Australia
| | - Matthew D. La Fontaine
- Department of Radiation Oncology, Netherlands Cancer Institute, Amsterdam, The Netherlands
| | - Jeroen B. van de Kamer
- Department of Radiation Oncology, Netherlands Cancer Institute, Amsterdam, The Netherlands
| | - Michael P. MacManus
- Division of Radiation Oncology and Cancer Imaging, Peter MacCallum Cancer Centre, Melbourne, Australia
- Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, Australia
| | - Wouter V. Vogel
- Nuclear Medicine Department, Netherlands Cancer Institute, Amsterdam, The Netherlands
- Department of Radiation Oncology, Netherlands Cancer Institute, Amsterdam, The Netherlands
| | - Jason Callahan
- Division of Radiation Oncology and Cancer Imaging, Peter MacCallum Cancer Centre, Melbourne, Australia
| | - Jan-Jakob Sonke
- Department of Radiation Oncology, Netherlands Cancer Institute, Amsterdam, The Netherlands
- * E-mail:
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13
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Christensen TN, Langer SW, Villumsen KE, Johannesen HH, Löfgren J, Keller SH, Hansen AE, Kjaer A, Fischer BM. 18F-fluorothymidine (FLT)-PET and diffusion-weighted MRI for early response evaluation in patients with small cell lung cancer: a pilot study. Eur J Hybrid Imaging 2020; 4:2. [PMID: 34191195 PMCID: PMC8218141 DOI: 10.1186/s41824-019-0071-5] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/04/2019] [Accepted: 12/23/2019] [Indexed: 12/25/2022] Open
Abstract
Background Small cell lung cancer (SCLC) is an aggressive cancer often presenting in an advanced stage and prognosis is poor. Early response evaluation may have impact on the treatment strategy. Aim We evaluated 18F-fluorothymidine-(FLT)-PET/diffusion-weighted-(DW)-MRI early after treatment start to describe biological changes during therapy, the potential of early response evaluation, and the added value of FLT-PET/DW-MRI. Methods Patients with SCLC referred for standard chemotherapy were eligible. FLT-PET/DW-MRI of the chest and brain was acquired within 14 days after treatment start. FLT-PET/DW-MRI was compared with pretreatment FDG-PET/CT. Standardized uptake value (SUV), apparent diffusion coefficient (ADC), and functional tumor volumes were measured. FDG-SUVpeak, FLT-SUVpeak, and ADCmedian; spatial distribution of aggressive areas; and voxel-by-voxel analyses were evaluated to compare the biological information derived from the three functional imaging modalities. FDG-SUVpeak, FLT-SUVpeak, and ADCmedian were also analyzed for ability to predict final treatment response. Results Twelve patients with SCLC completed FLT-PET/MRI 1–9 days after treatment start. In nine patients, pretreatment FDG-PET/CT was available for comparison. A total of 16 T-sites and 12 N-sites were identified. No brain metastases were detected. FDG-SUVpeak was 2.0–22.7 in T-sites and 5.5–17.3 in N-sites. FLT-SUVpeak was 0.6–11.5 in T-sites and 1.2–2.4 in N-sites. ADCmedian was 0.76–1.74 × 10− 3 mm2/s in T-sites and 0.88–2.09 × 10−3 mm2/s in N-sites. FLT-SUVpeak correlated with FDG-SUVpeak, and voxel-by-voxel correlation was positive, though the hottest regions were dissimilarly distributed in FLT-PET compared to FDG-PET. FLT-SUVpeak was not correlated with ADCmedian, and voxel-by-voxel analyses and spatial distribution of aggressive areas varied with no systematic relation. LT-SUVpeak was significantly lower in responding lesions than non-responding lesions (mean FLT-SUVpeak in T-sites: 1.5 vs. 5.7; p = 0.007, mean FLT-SUVpeak in N-sites: 1.6 vs. 2.2; p = 0.013). Conclusions FLT-PET and DW-MRI performed early after treatment start may add biological information in patients with SCLC. Proliferation early after treatment start measured by FLT-PET is a promising predictor for final treatment response that warrants further investigation. Trial registration Clinicaltrials.gov, NCT02995902. Registered 11 December 2014 - Retrospectively registered.
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Affiliation(s)
- Tine Nøhr Christensen
- Department of Clinical Physiology, Nuclear Medicine & PET, Rigshospitalet, University of Copenhagen, Blegdamsvej 9, 2100, Copenhagen Ø, Denmark. .,Cluster for Molecular Imaging, University of Copenhagen, Copenhagen, Denmark.
| | - Seppo W Langer
- Department of Oncology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
| | - Katrine Engholm Villumsen
- Department of Clinical Physiology, Nuclear Medicine & PET, Rigshospitalet, University of Copenhagen, Blegdamsvej 9, 2100, Copenhagen Ø, Denmark
| | - Helle Hjorth Johannesen
- Department of Clinical Physiology, Nuclear Medicine & PET, Rigshospitalet, University of Copenhagen, Blegdamsvej 9, 2100, Copenhagen Ø, Denmark
| | - Johan Löfgren
- Department of Clinical Physiology, Nuclear Medicine & PET, Rigshospitalet, University of Copenhagen, Blegdamsvej 9, 2100, Copenhagen Ø, Denmark
| | - Sune Høgild Keller
- Department of Clinical Physiology, Nuclear Medicine & PET, Rigshospitalet, University of Copenhagen, Blegdamsvej 9, 2100, Copenhagen Ø, Denmark
| | - Adam Espe Hansen
- Department of Clinical Physiology, Nuclear Medicine & PET, Rigshospitalet, University of Copenhagen, Blegdamsvej 9, 2100, Copenhagen Ø, Denmark
| | - Andreas Kjaer
- Department of Clinical Physiology, Nuclear Medicine & PET, Rigshospitalet, University of Copenhagen, Blegdamsvej 9, 2100, Copenhagen Ø, Denmark.,Cluster for Molecular Imaging, University of Copenhagen, Copenhagen, Denmark
| | - Barbara Malene Fischer
- Department of Clinical Physiology, Nuclear Medicine & PET, Rigshospitalet, University of Copenhagen, Blegdamsvej 9, 2100, Copenhagen Ø, Denmark.,PET Centre, School of Biomedical Engineering and Imaging Science, Kings College London, London, UK
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14
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The need of a clinically oriented reporting of 18F-FDG PET/CT in non-small cell lung cancer (NSCLC). Clin Transl Imaging 2020. [DOI: 10.1007/s40336-019-00354-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
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15
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Werner RA, Bundschuh RA, Higuchi T, Javadi MS, Rowe SP, Zsótér N, Kroiss M, Fassnacht M, Buck AK, Kreissl MC, Lapa C. Volumetric and texture analysis of pretherapeutic 18F-FDG PET can predict overall survival in medullary thyroid cancer patients treated with Vandetanib. Endocrine 2019; 63:293-300. [PMID: 30206772 PMCID: PMC6394453 DOI: 10.1007/s12020-018-1749-3] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/18/2018] [Accepted: 09/04/2018] [Indexed: 12/14/2022]
Abstract
PURPOSE The metabolically most active lesion in 2-deoxy-2-(18F)fluoro-D-glucose (18F-FDG) PET/CT can predict progression-free survival (PFS) in patients with medullary thyroid carcinoma (MTC) starting treatment with the tyrosine kinase inhibitor (TKI) vandetanib. However, this metric failed in overall survival (OS) prediction. In the present proof of concept study, we aimed to explore the prognostic value of intratumoral textural features (TF) as well as volumetric parameters (total lesion glycolysis, TLG) derived by pre-therapeutic 18F-FDG PET. METHODS Eighteen patients with progressive MTC underwent baseline 18F-FDG PET/CT prior to and 3 months after vandetanib initiation. By manual segmentation of the tumor burden at baseline and follow-up PET, intratumoral TF and TLG were computed. The ability of TLG, imaging-based TF, and clinical parameters (including age, tumor marker doubling times, prior therapies and RET (rearranged during transfection) mutational status) for prediction of both PFS and OS were evaluated. RESULTS The TF Complexity and the volumetric parameter TLG obtained at baseline prior to TKI initiation successfully differentiated between low- and high-risk patients. Complexity allocated 10/18 patients to the high-risk group with an OS of 3.3 y (vs. low-risk group, OS = 5.3 y, 8/18, AUC = 0.78, P = 0.03). Baseline TLG designated 11/18 patients to the high-risk group (OS = 3.5 y vs. low-risk group, OS = 5 y, 7/18, AUC = 0.83, P = 0.005). The Hazard Ratio for cancer-related death was 6.1 for Complexity (TLG, 9.5). Among investigated clinical parameters, the age at initiation of TKI treatment reached significance for PFS prediction (P = 0.02, OS, n.s.). CONCLUSIONS The TF Complexity and the volumetric parameter TLG are both independent parameters for OS prediction.
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Affiliation(s)
- Rudolf A Werner
- Department of Nuclear Medicine, University Hospital Wuerzburg, Wuerzburg, Germany.
- The Russell H. Morgan Department of Radiology and Radiological Science, Division of Nuclear Medicine and Molecular Imaging, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
- Comprehensive Heart Failure Center, University Hospital Wuerzburg, Wuerzburg, Germany.
| | - Ralph A Bundschuh
- Department of Nuclear Medicine, University Medical Center Bonn, Bonn, Germany
| | - Takahiro Higuchi
- Department of Nuclear Medicine, University Hospital Wuerzburg, Wuerzburg, Germany
- Comprehensive Heart Failure Center, University Hospital Wuerzburg, Wuerzburg, Germany
- Department of Biomedical Imaging, National Cardiovascular and Cerebral Research Center, Suita, Japan
| | - Mehrbod S Javadi
- The Russell H. Morgan Department of Radiology and Radiological Science, Division of Nuclear Medicine and Molecular Imaging, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Steven P Rowe
- The Russell H. Morgan Department of Radiology and Radiological Science, Division of Nuclear Medicine and Molecular Imaging, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | | | - Matthias Kroiss
- Department of Internal Medicine I, Division of Endocrinology and Diabetes, University Hospital, University of Wuerzburg, Wuerzburg, Germany
- Comprehensive Cancer Center Mainfranken, University of Wuerzburg, Wuerzburg, Germany
- Würzburger Schilddrüsenzentrum, University Hospital Wuerzburg, Wuerzburg, Germany
| | - Martin Fassnacht
- Department of Internal Medicine I, Division of Endocrinology and Diabetes, University Hospital, University of Wuerzburg, Wuerzburg, Germany
- Comprehensive Cancer Center Mainfranken, University of Wuerzburg, Wuerzburg, Germany
- Würzburger Schilddrüsenzentrum, University Hospital Wuerzburg, Wuerzburg, Germany
| | - Andreas K Buck
- Department of Nuclear Medicine, University Hospital Wuerzburg, Wuerzburg, Germany
- Comprehensive Heart Failure Center, University Hospital Wuerzburg, Wuerzburg, Germany
| | - Michael C Kreissl
- Department of Nuclear Medicine, Hospital Augsburg, Augsburg, Germany
- Department of Radiology and Nuclear Medicine, University Hospital Magdeburg, Magdeburg, Germany
| | - Constantin Lapa
- Department of Nuclear Medicine, University Hospital Wuerzburg, Wuerzburg, Germany
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16
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Xie X, Chen H, Yang H, Lin H, Zhou S, Shen R, Lu C, Ling L, Lin W, Liao Z. Predictive value of positron emission tomography for the prognosis of molecularly targeted therapy in solid tumors. Onco Targets Ther 2018; 11:8885-8899. [PMID: 30573975 PMCID: PMC6290871 DOI: 10.2147/ott.s178076] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022] Open
Abstract
Objective This study aimed at comprehensively exploring the value applying positron emission tomography (PET) to predict the effect of molecularly targeted therapy in solid tumors. Materials and methods A systematic search was performed for potentially relevant studies from the time of inception to February 2017. The primary endpoints were progression-free survival (PFS), overall survival (OS), and time to progression (TTP). The results were analyzed by Review Manager version 5.3 (RevMan 5.3) statistical software. Subgroup analyses were implemented based on the type of molecularly targeted agents (monoclonal antibodies arm and small molecular targeted agents arm), mechanism (erlotinib/gefitinib arm and bevacizumab arm), radioactive tracers, type of tumor, and reevaluated PET timing. Results Twenty-six studies incorporating 865 individuals were eligible. Compared with PET nonresponse group, PET response group displayed a decrease in maximal standard uptake value (SUVmax), which was associated with a significantly prolonged PFS (HR =0.41, 95% CI [0.29, 0.59]; P<0.00001), OS (HR =0.52, 95% CI [0.40, 0.67]; P<0.00001), and TTP (HR =0.30, 95% CI [0.14, 0.66]; P=0.003). Similar results were obtained in the subgroup analyses of PFS in erlotinib/gefitinib arm and small molecular targeted agents arm; and OS in lung cancer arm, erlotinib/gefitinib arm, bevacizumab arm, small molecular targeted agents arm, monoclonal antibodies arm, 18F-fluorodeoxythymidine (18F-FLT) arm, 18F-fluorodeoxyglucose (18F-FDG) arm, and early PET timing arm. Conclusion Our study demonstrated that PET was a favorable approach to predict the prognosis of molecularly targeted therapy for solid tumors. PET assessment within 2 weeks could be useful to predict clinical outcome.
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Affiliation(s)
- Xianhe Xie
- Department of Chemotherapy, The First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, People's Republic of China,
| | - Huijuan Chen
- Department of Chemotherapy, The First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, People's Republic of China,
| | - Haitao Yang
- Department of Chemotherapy, The First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, People's Republic of China,
| | - Heng Lin
- Department of Oncology, Fuzhou Pulmonary Hospital, Fuzhou, Fujian, People's Republic of China
| | - Sijing Zhou
- Department of Chemotherapy, The First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, People's Republic of China,
| | - Ruifen Shen
- Department of Chemotherapy, The First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, People's Republic of China,
| | - Cuiping Lu
- Department of Medical Oncology, Longyan First Hospital Affiliated to Fujian Medical University, Longyan, Fujian, People's Republic of China
| | - Liting Ling
- Department of Chemotherapy, The First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, People's Republic of China,
| | - Wanzun Lin
- Department of Chemotherapy, The First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, People's Republic of China,
| | - Ziyuan Liao
- Department of Chemotherapy, The First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, People's Republic of China,
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17
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Li H, Yao Q, Xu F, Xu N, Sun W, Long S, Du J, Fan J, Wang J, Peng X. Lighting-Up Tumor for Assisting Resection via Spraying NIR Fluorescent Probe of γ-Glutamyltranspeptidas. Front Chem 2018; 6:485. [PMID: 30370267 PMCID: PMC6194167 DOI: 10.3389/fchem.2018.00485] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2018] [Accepted: 09/24/2018] [Indexed: 12/22/2022] Open
Abstract
For the precision resection, development of near-infrared (NIR) fluorescent probe based on specificity identification tumor-associated enzyme for lighting-up the tumor area, is urgent in the field of diagnosis and treatment. Overexpression of γ-glutamyltranspeptidase, one of the cell-membrane enzymes, known as a biomarker is concerned with the growth and progression of ovarian, liver, colon and breast cancer compared to normal tissue. In this work, a remarkable enzyme-activated NIR fluorescent probe NIR-SN-GGT was proposed and synthesized including two moieties: a NIR dicyanoisophorone core as signal reporter unit; γ-glutamyl group as the specificity identification site. In the presence of γ-GGT, probe NIR-SN-GGT was transformed into NIR-SN-NH2, the recovery of Intramolecular Charge Transfer (ICT), liberating the NIR fluorescence signal, which was firstly employed to distinguish tumor tissue and normal tissues via simple “spraying” manner, greatly promoting the possibility of precise excision. Furthermore, combined with magnetic resonance imaging by T2 weight mode, tumor transplanted BABL/c mice could be also lit up for first time by NIR fluorescence probe having a large stokes, which demonstrated that probe NIR-SN-GGT would be a useful tool for assisting surgeon to diagnose and remove tumor in clinical practice.
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Affiliation(s)
- Haidong Li
- State Key Laboratory of Fine Chemicals, Dalian University of Technology, Dalian, China
| | - Qichao Yao
- State Key Laboratory of Fine Chemicals, Dalian University of Technology, Dalian, China
| | - Feng Xu
- State Key Laboratory of Fine Chemicals, Dalian University of Technology, Dalian, China
| | - Ning Xu
- State Key Laboratory of Fine Chemicals, Dalian University of Technology, Dalian, China
| | - Wen Sun
- State Key Laboratory of Fine Chemicals, Dalian University of Technology, Dalian, China
| | - Saran Long
- State Key Laboratory of Fine Chemicals, Dalian University of Technology, Dalian, China
| | - Jianjun Du
- State Key Laboratory of Fine Chemicals, Dalian University of Technology, Dalian, China
| | - Jiangli Fan
- State Key Laboratory of Fine Chemicals, Dalian University of Technology, Dalian, China
| | - Jingyun Wang
- Department School of Life Science and Biotechnology, Dalian University of Technology, Dalian, China
| | - Xiaojun Peng
- State Key Laboratory of Fine Chemicals, Dalian University of Technology, Dalian, China
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18
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Konert T, van de Kamer JB, Sonke JJ, Vogel WV. The developing role of FDG PET imaging for prognostication and radiotherapy target volume delineation in non-small cell lung cancer. J Thorac Dis 2018; 10:S2508-S2521. [PMID: 30206495 DOI: 10.21037/jtd.2018.07.101] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
Advancements in functional imaging technology have allowed new possibilities in contouring of target volumes, monitoring therapy, and predicting treatment outcome in non-small cell lung cancer (NSCLC). Consequently, the role of 18F-fluorodeoxyglucose positron emission tomography (FDG PET) has expanded in the last decades from a stand-alone diagnostic tool to a versatile instrument integrated with computed tomography (CT), with a prominent role in lung cancer radiotherapy. This review outlines the most recent literature on developments in FDG PET imaging for prognostication and radiotherapy target volume delineation (TVD) in NSCLC. We also describe the challenges facing the clinical implementation of these developments and present new ideas for future research.
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Affiliation(s)
- Tom Konert
- Nuclear Medicine Department, Netherlands Cancer Institute, Amsterdam, The Netherlands.,Department of Radiation Oncology, Netherlands Cancer Institute, Amsterdam, The Netherlands
| | - Jeroen B van de Kamer
- Department of Radiation Oncology, Netherlands Cancer Institute, Amsterdam, The Netherlands
| | - Jan-Jakob Sonke
- Department of Radiation Oncology, Netherlands Cancer Institute, Amsterdam, The Netherlands
| | - Wouter V Vogel
- Nuclear Medicine Department, Netherlands Cancer Institute, Amsterdam, The Netherlands.,Department of Radiation Oncology, Netherlands Cancer Institute, Amsterdam, The Netherlands
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19
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Pierson C, Grinchak T, Sokolovic C, Holland B, Parent T, Bowling M, Arastu H, Walker P, Ju A. Response criteria in solid tumors (PERCIST/RECIST) and SUV max in early-stage non-small cell lung cancer patients treated with stereotactic body radiotherapy. Radiat Oncol 2018; 13:34. [PMID: 29486779 PMCID: PMC5830069 DOI: 10.1186/s13014-018-0980-7] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2017] [Accepted: 02/20/2018] [Indexed: 12/25/2022] Open
Abstract
Background The purpose of this study was to evaluate the prognostic impact of Positron Emission Tomography Response Criteria in Solid Tumors (PERCIST) and Response Evaluation Criteria in Solid Tumors (RECIST) and of pre- and post-treatment maximum Standard Uptake Value (SUVmax) in regards to survival and tumor control for patients treated for early-stage non-small cell lung cancer (ES-NSCLC) with stereotactic body radiotherapy (SBRT). Methods This is a retrospective review of patients with ES-NSCLC treated at our institution using SBRT. Lobar, locoregional, and distant failures were evaluated based on PERCIST/RECIST and clinical course. Univariate analysis of the Kaplan-Meier curves for overall survival (OS), progression free survival (PFS), lobar control (LC), locoregional control (LRC), and distant control (DC) was conducted using the log-rank test. Pre- and post-treatment SUVmax were evaluated using cutoffs of < 5 and ≥ 5, < 4 and ≥ 4, and < 3 and ≥ 3. ∆SUVmax was also evaluated at various cutoffs. Cox regression analysis was conducted to evaluate survival outcomes based on age, gender, pre-treatment gross tumor volume (GTV), longest tumor dimension on imaging, and Charlson Comorbidity Index (CCI). Results This study included 95 patients (53 female, 42 male), median age 75. Lung SBRT was delivered in 3–5 fractions to a total of 48–60 Gy, with a BEDα/β = 10Gy of at least 100 Gy. Median OS and PFS from the end of SBRT was 15.4 and 11.9 months, respectively. On univariate analysis, PERCIST/RECIST response correlated with PFS (p = 0.039), LC (p = 0.007), and LRC (p = 0.015) but not OS (p = 0.21) or DC (p = 0.94). Pre-treatment SUVmax and post-treatment SUVmax with cutoff values of < 5 and ≥ 5, < 4 and ≥ 4, and < 3 and ≥ 3 did not predict for OS, PFS, LC, LRC, or DC. ∆SUVmax did not predict for OS, PFS, LC, LRC, or DC. On multivariate analysis, pre-treatment GTV ≥ 30 cm3 was significantly associated with worse survival outcomes when accounting for other confounding variables. Conclusions PERCIST/RECIST response is associated with improved LC and PFS in patients treated for ES-NSCLC with SBRT. In contrast, pre- and post-treatment SUVmax is not predictive of disease control or survival.
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Affiliation(s)
- Cory Pierson
- Leo W. Jenkins Cancer Center, 600 Moye Boulevard, Greenville, NC, 27834, USA
| | - Taras Grinchak
- Leo W. Jenkins Cancer Center, 600 Moye Boulevard, Greenville, NC, 27834, USA
| | | | - Brandi Holland
- Leo W. Jenkins Cancer Center, 600 Moye Boulevard, Greenville, NC, 27834, USA
| | - Teresa Parent
- Leo W. Jenkins Cancer Center, 600 Moye Boulevard, Greenville, NC, 27834, USA
| | - Mark Bowling
- Department of Internal Medicine, 600 Moye Boulevard, Greenville, NC, 27834, USA
| | - Hyder Arastu
- Leo W. Jenkins Cancer Center, 600 Moye Boulevard, Greenville, NC, 27834, USA
| | - Paul Walker
- Department of Internal Medicine, 600 Moye Boulevard, Greenville, NC, 27834, USA
| | - Andrew Ju
- Leo W. Jenkins Cancer Center, 600 Moye Boulevard, Greenville, NC, 27834, USA.
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Dai D, Xu W, Wang Q, Li X, Zhu Y. [Current Status and Progress in Molecular Imaging of Non-small Cell Lung
Cancer for Molecular Targeted EGFR-TKI Treatment Sensitivity and
Treatment Tolerance Prediction]. ZHONGGUO FEI AI ZA ZHI = CHINESE JOURNAL OF LUNG CANCER 2017; 20:852-856. [PMID: 29277186 PMCID: PMC5973391 DOI: 10.3779/j.issn.1009-3419.2017.12.10] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
Abstract
肺癌80%以上为非小细胞肺癌（non-small cell lung cancer, NSCLC），表皮生长因子受体（epidermal growth factor receptor, EGFR）介导的信号通路与NSCLC发生发展密切相关。针对EGFR的小分子EGFR赖氨酸激酶抑制剂（EGFR-tyrosine kinase inhibitor, EGFR-TKI）被应用于NSCLC的临床治疗，正电子发射计算机断层显像（positron emission tomography/computed tomgraphy, PET/CT）能够无创地对NSCLC患者全身EGFR表达及突变状况进行连续动态监测。18F-FDG PET/CT显像对于EGFR活化突变、EGFR-TKI治疗疗效具有预测价值，并且能够在体直接观察到药物与全身肿瘤病灶EGFR靶向结合的具体情况，通过治疗前后的PET-CT显像，实现治疗前高敏人群筛选和治疗全过程的动态监测、治疗策略指导，对实现NSCLC的EGFR-TKI精准治疗至关重要。
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Affiliation(s)
- Dong Dai
- Department of Molecular Imaging and Nuclear Medicine, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin Key Laboratory of Cancer Prevention and Therapy, Tianjin 300060, China
| | - Wengui Xu
- Department of Molecular Imaging and Nuclear Medicine, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin Key Laboratory of Cancer Prevention and Therapy, Tianjin 300060, China
| | - Qi Wang
- Department of Molecular Imaging and Nuclear Medicine, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin Key Laboratory of Cancer Prevention and Therapy, Tianjin 300060, China
| | - Xiaofeng Li
- Department of Molecular Imaging and Nuclear Medicine, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin Key Laboratory of Cancer Prevention and Therapy, Tianjin 300060, China
| | - Yanjia Zhu
- Department of Molecular Imaging and Nuclear Medicine, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin Key Laboratory of Cancer Prevention and Therapy, Tianjin 300060, China
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Genomic Characterization of Lung Cancer and Its Impact on the Use and Timing of PET in Therapeutic Response Assessment. PET Clin 2017; 13:33-42. [PMID: 29157384 DOI: 10.1016/j.cpet.2017.08.004] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
Abstract
Significant advances in understanding the genomic landscape of non-small cell lung cancer (NSCLC) together with the coupling discovery of key oncogenic drivers and the development of effective targeted and immunotherapeutic agents have revolutionized the management of this malignancy. Although these therapies have resulted in improved outcomes for a subgroup of patients, their benefit may not necessarily be reflected by conventional response assessment criteria, because these therapeutic agents differ in their mechanism of action and response time compared with cytotoxic chemotherapy. Here the authors review available therapies in NSCLC and the utility of PET in therapeutic response assessment.
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Yabuuchi H, Kawanami S, Iwama E, Okamoto I, Kamitani T, Sagiyama K, Yamasaki Y, Honda H. Prediction of Therapeutic Effect of Chemotherapy for NSCLC Using Dual-Input Perfusion CT Analysis: Comparison among Bevacizumab Treatment, Two-Agent Platinum-based Therapy without Bevacizumab, and Other Non-Bevacizumab Treatment Groups. Radiology 2017; 286:685-695. [PMID: 29059037 DOI: 10.1148/radiol.2017162204] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
Abstract
Purpose To determine whether dual-input perfusion computed tomography (CT) can predict therapeutic response and prognosis in patients who underwent chemotherapy for non-small cell lung cancer (NSCLC). Materials and Methods The institutional review board approved this study and informed consent was obtained. Sixty-six patients with stage III or IV NSCLC (42 men, 24 women; mean age, 63.4 years) who underwent chemotherapy were enrolled. Patients were separated into three groups: those who received chemotherapy with bevacizumab (BV) (n = 20), those who received two-agent platinum-based therapy without BV (n = 25), and those who received other non-BV treatment (n = 21). Before treatment, pulmonary artery perfusion (PAP) and bronchial artery perfusion (BAP) of the tumors were calculated. Predictors of tumor reduction after two courses of chemotherapy and prognosis were identified by using univariate and multivariate analyses. Covariates included were age, sex, patient's performance status, baseline maximum diameter of the tumor, clinical stage, pretreatment PAP, and pretreatment BAP. For multivariate analyses, multiple linear regression analysis for tumor reduction rate and Cox proportional hazards model for prognosis were performed, respectively. Results Pretreatment BAP was independently correlated with tumor reduction rate after two courses of chemotherapy in the BV treatment group (P = .006). Pretreatment BAP was significantly associated with a highly cumulative risk of death (P = .006) and disease progression after chemotherapy (P = .015) in the BV treatment group. Pretreatment PAP and clinical parameters were not significant predictors of therapeutic effect or prognosis in three treatment groups. Conclusion Pretreatment BAP derived from dual-input perfusion CT seems to be a promising tool to help predict responses to chemotherapy with BV in patients with NSCLC. © RSNA, 2017.
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Affiliation(s)
- Hidetake Yabuuchi
- From the Department of Health Sciences (H.Y.), Department of Clinical Radiology (S.K., T.K., K.S., Y.Y., H.H.), and Research Institute for Diseases of the Chest (E.I., I.O.), Kyushu University Graduate School of Medical Sciences, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan
| | - Satoshi Kawanami
- From the Department of Health Sciences (H.Y.), Department of Clinical Radiology (S.K., T.K., K.S., Y.Y., H.H.), and Research Institute for Diseases of the Chest (E.I., I.O.), Kyushu University Graduate School of Medical Sciences, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan
| | - Eiji Iwama
- From the Department of Health Sciences (H.Y.), Department of Clinical Radiology (S.K., T.K., K.S., Y.Y., H.H.), and Research Institute for Diseases of the Chest (E.I., I.O.), Kyushu University Graduate School of Medical Sciences, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan
| | - Isamu Okamoto
- From the Department of Health Sciences (H.Y.), Department of Clinical Radiology (S.K., T.K., K.S., Y.Y., H.H.), and Research Institute for Diseases of the Chest (E.I., I.O.), Kyushu University Graduate School of Medical Sciences, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan
| | - Takeshi Kamitani
- From the Department of Health Sciences (H.Y.), Department of Clinical Radiology (S.K., T.K., K.S., Y.Y., H.H.), and Research Institute for Diseases of the Chest (E.I., I.O.), Kyushu University Graduate School of Medical Sciences, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan
| | - Koji Sagiyama
- From the Department of Health Sciences (H.Y.), Department of Clinical Radiology (S.K., T.K., K.S., Y.Y., H.H.), and Research Institute for Diseases of the Chest (E.I., I.O.), Kyushu University Graduate School of Medical Sciences, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan
| | - Yuzo Yamasaki
- From the Department of Health Sciences (H.Y.), Department of Clinical Radiology (S.K., T.K., K.S., Y.Y., H.H.), and Research Institute for Diseases of the Chest (E.I., I.O.), Kyushu University Graduate School of Medical Sciences, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan
| | - Hiroshi Honda
- From the Department of Health Sciences (H.Y.), Department of Clinical Radiology (S.K., T.K., K.S., Y.Y., H.H.), and Research Institute for Diseases of the Chest (E.I., I.O.), Kyushu University Graduate School of Medical Sciences, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan
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Fernandes RS, de Aguiar Ferreira C, Soares DCF, Maffione AM, Townsend DM, Rubello D, de Barros ALB. The role of radionuclide probes for monitoring anti-tumor drugs efficacy: A brief review. Biomed Pharmacother 2017; 95:469-476. [PMID: 28865367 DOI: 10.1016/j.biopha.2017.08.079] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2017] [Revised: 08/17/2017] [Accepted: 08/20/2017] [Indexed: 02/06/2023] Open
Abstract
Despite recent advances in the development of new therapeutic agents and diagnostic imaging modalities, cancer is still one of the main causes of death worldwide. A better understanding of the molecular signature of cancer has promoted the development of a new generation of anti-cancer drugs and diagnostic agents that specifically target molecular components such as genes, ligands, receptors and signaling pathways. However, intrinsic heterogeneity of tumors has hampered the overall success of target therapies even among patients with similar tumor types but unpredictable different responses to therapy. In this sense, post-treatment response monitoring becomes indispensable and nuclear medicine imaging modalities could provide the tools for an early indication of therapeutic efficacy. Herein, we briefly discuss the current role of PET and SPECT imaging in monitoring cancer therapy together with an update on the current radiolabeled probes that are currently investigated for tumor therapy response assessment.
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Affiliation(s)
- Renata Salgado Fernandes
- Laboratório de radioisótopos, Departamento de análises Clinicas, Universidade Federal de Minas Gerais (UFMG), Avenida Presidente Antônio Carlos, 6627, Belo Horizonte, Minas Gerais, Brazil
| | | | - Daniel Cristian Ferreira Soares
- Laboratório de Bioengenharia, Universidade Federal de Itajubá (UNIFEI), Rua Irmã Ivone Drumond, 200, Itabira, Minas Gerais, Brazil
| | - Anna Margherita Maffione
- Department of Nuclear Medicine, Radiology, Medical Physics and Clinical Pathology, Santa Maria della Misericordia Hospital, Rovigo, Italy
| | - Danyelle M Townsend
- Department of Drug Discovery and Pharmaceutical Sciences, Medical University of South Carolina, USA
| | - Domenico Rubello
- Department of Nuclear Medicine, Radiology, Medical Physics and Clinical Pathology, Santa Maria della Misericordia Hospital, Rovigo, Italy.
| | - André Luís Branco de Barros
- Laboratório de radioisótopos, Departamento de análises Clinicas, Universidade Federal de Minas Gerais (UFMG), Avenida Presidente Antônio Carlos, 6627, Belo Horizonte, Minas Gerais, Brazil.
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Korn RL, Von Hoff DD, Borad MJ, Renschler MF, McGovern D, Curtis Bay R, Ramanathan RK. 18F-FDG PET/CT response in a phase 1/2 trial of nab-paclitaxel plus gemcitabine for advanced pancreatic cancer. Cancer Imaging 2017; 17:23. [PMID: 28774338 PMCID: PMC5543580 DOI: 10.1186/s40644-017-0125-5] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2017] [Accepted: 07/06/2017] [Indexed: 12/18/2022] Open
Abstract
BACKGROUND Positron emission tomography (PET) is poised to become a useful imaging modality in staging and evaluating therapeutic responses in patients with metastatic pancreatic cancer (mPC). This analysis from a phase 1/2 study examined the utility of early PET imaging in patients with mPC treated with nab-paclitaxel plus gemcitabine. METHODS Tumors were measured by [18F]2-fluoro-2-deoxyglucose PET/computed tomography (CT) in patients who received nab-paclitaxel 100 (n = 13), 125 (n = 38), or 150 (n = 1) mg/m2 plus gemcitabine 1000 mg/m2 on days 1, 8, and 15 of a 28-day cycle. Lesion metabolic activity was evaluated at baseline and 6 and 12 weeks postbaseline. RESULTS Fifty-two patients had baseline and ≥1 follow-up PET scan. The median maximum standardized uptake values per pancreatic lesion in the nab-paclitaxel 100 mg/m2 and 125 mg/m2 cohorts were 5.1 and 6.5, respectively. Among patients who had a metabolic response by PET, those who received nab-paclitaxel 125 mg/m2 had a 4-month survival advantage over those who received 100 mg/m2. All patients in the nab-paclitaxel 125 mg/m2 cohort experienced an early complete metabolic response (CMR; 34%) or partial metabolic response (PMR; 66%). In the nab-paclitaxel 125 mg/m2 cohort, investigator-assessed objective response rates were 77% and 44% among patients with a CMR and PMR, respectively, with no correlation between PET and CT response (Spearman r s = 0.22; P = 0.193). Patients in the nab-paclitaxel 125 mg/m2 cohort with a CMR experienced a significantly longer overall survival vs those with a PMR (median, 23.0 vs 11.2 months; P = 0.011), and a significant correlation was found between best percentage change in tumor burden by PET and survival: for each 1% decrease in PET score, the risk of death decreased by 2%. CONCLUSIONS The majority of primary pancreatic tumors and their metastases were PET avid, and PET effectively measured changes in tumor metabolic activity at 6 and 12 weeks. These results support the antitumor activity of nab-paclitaxel 125 mg/m2 plus gemcitabine 1000 mg/m2 for treating mPC and the utility of PET for measuring treatment response. Treatment response by PET analysis may be considered when evaluating investigational agents in mPC. TRIAL REGISTRATION NCT00398086.
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Affiliation(s)
- Ronald L Korn
- Imaging Endpoints Core Lab, 9700 N 91st St, B-200, Scottsdale, AZ, 85258, USA.
| | - Daniel D Von Hoff
- Translational Genomics Research Institute and HonorHealth, 445 North Fifth St, Suite 600, Phoenix, AZ, 85004, USA
| | - Mitesh J Borad
- Mayo Clinic, 13400 E Shea Blvd, Scottsdale, AZ, 85259, USA
| | | | | | - R Curtis Bay
- Department of Interdisciplinary Health Sciences, A. T. Still University, 5850 E Still Circle, Mesa, AZ 85206, USA
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Everitt S, Ball D, Hicks RJ, Callahan J, Plumridge N, Trinh J, Herschtal A, Kron T, Mac Manus M. Prospective Study of Serial Imaging Comparing Fluorodeoxyglucose Positron Emission Tomography (PET) and Fluorothymidine PET During Radical Chemoradiation for Non-Small Cell Lung Cancer: Reduction of Detectable Proliferation Associated With Worse Survival. Int J Radiat Oncol Biol Phys 2017; 99:947-955. [PMID: 29063854 DOI: 10.1016/j.ijrobp.2017.07.035] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2017] [Revised: 07/19/2017] [Accepted: 07/24/2017] [Indexed: 12/25/2022]
Abstract
PURPOSE To investigate the associations between interim tumor responses on 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) and 18F-fluorothymidine (18F-FLT) PET and patient outcomes, especially progression-free survival (PFS) and overall survival (OS), in non-small cell lung cancer (NSCLC) patients. METHODS AND MATERIALS Patients with FDG-PET/computed tomography stage I-III NSCLC were prescribed concurrent chemotherapy and radiation therapy (60 Gy in 30 fractions). Scans were acquired at baseline (FDG-PET/computed tomography [FDGBL] for radiation therapy planning and FLT-PET [FLTBL]), week 2 (FDGwk2 and FLTwk2), and week 4 (FDGwk4 and FLTwk4) of chemoradiation therapy. Tumor responses were categorized as complete or partial responses or stable or progressive disease (SD, PD) using European Organization for Research and Treatment of Cancer criteria. Associations between response, OS, and PFS were analyzed with univariate Cox regressions and plotted using Kaplan-Meier curves. RESULTS Between 2009 and 2013, 60 patients were recruited. Thirty-seven (62%) were male, and the median age was 66 years (range, 31-86 years). Two-year OS and PFS were 0.51 and 0.26, respectively. Unexpectedly, SD on FLTwk2 compared with complete response/partial response was associated with longer OS (hazard ratio [95% confidence interval] 2.01 [0.87-4.65], P=.082) and PFS (2.01 [0.92-4.36], P=.061). Weeks 2 and 4 FDG PET/CT were not significantly associated with survival. Study scans provided additional information to FDGBL in 21 patients (35%). Distant metastases detected in 3 patients on FLTBL and in 2 patients on FDG/FLTwk2 changed treatment intent from curative to palliative. Locoregional progression during radiation therapy was observed in 5 (8%) patients, prompting larger radiation therapy fields. CONCLUSIONS Stable uptake of 18F-FLT at week 2 was paradoxically associated with longer OS and PFS. This suggests that suppression of tumor cell proliferation may protect against radiation-induced tumor cell killing. Baseline FLT, FLTwk2, and FDGwk2 detected rapid distant and locoregional progression in 10 patients (17%), prompting changes in management.
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Affiliation(s)
- Sarah Everitt
- Radiation Therapy Services, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia; Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, Australia; Department of Medical Imaging and Radiation Sciences, Faculty of Medicine, Nursing & Health Sciences, Monash University, Clayton, Victoria, Australia.
| | - David Ball
- Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, Australia; Division of Radiation Oncology, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia
| | - Rodney J Hicks
- Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, Australia; Centre for Cancer Imaging, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia
| | - Jason Callahan
- Department of Medical Imaging and Radiation Sciences, Faculty of Medicine, Nursing & Health Sciences, Monash University, Clayton, Victoria, Australia; Centre for Cancer Imaging, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia
| | - Nikki Plumridge
- Division of Radiation Oncology, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia
| | - Jenny Trinh
- Division of Radiation Oncology, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia
| | - Alan Herschtal
- Centre for Biostatistics and Clinical Trials, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia
| | - Tomas Kron
- Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, Australia; Department of Medical Imaging and Radiation Sciences, Faculty of Medicine, Nursing & Health Sciences, Monash University, Clayton, Victoria, Australia; Department of Physical Sciences, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia
| | - Michael Mac Manus
- Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, Australia; Division of Radiation Oncology, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia
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Goel R, Subramaniam RM, Wachsmann JW. PET/Computed Tomography Scanning and Precision Medicine: Esophageal Cancer. PET Clin 2017; 12:373-391. [PMID: 28867110 DOI: 10.1016/j.cpet.2017.05.001] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Esophageal cancer commonly has a poor prognosis, which requires an accurate diagnosis and early treatment to improve outcome. Other modalities for staging, such as endoscopic ultrasound imaging and computed tomography (CT) scans, have a role in diagnosis and staging. However, PET with fluorine-18 fluoro-2-deoxy-d-glucose/CT (FDG PET/CT) scanning allows for improved detection of distant metastatic disease and can help to prevent unnecessary interventions that would increase morbidity. FDG PET/CT scanning is valuable in the neoadjuvant chemotherapy assessment and predicting survival outcomes subsequent to surgery. FDG PET/CT scanning detects recurrent disease and metastases in follow-up.
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Affiliation(s)
- Reema Goel
- Department of Radiology, The University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390-8896, USA
| | - Rathan M Subramaniam
- Department of Radiology, The University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390-8896, USA; Department of Clinical Sciences, The University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390-8896, USA; Department of Biomedical Engineering, The University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390-8896, USA; Advanced Imaging Research Center, The University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390-8896, USA; Harold C. Simmons Comprehensive Cancer Center, The University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390-8896, USA
| | - Jason W Wachsmann
- Department of Radiology, The University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390-8896, USA.
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The Advantages and Challenges of Using FDG PET/CT for Response Assessment in Melanoma in the Era of Targeted Agents and Immunotherapy. Eur J Nucl Med Mol Imaging 2017; 44:67-77. [DOI: 10.1007/s00259-017-3691-7] [Citation(s) in RCA: 66] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2017] [Accepted: 03/23/2017] [Indexed: 12/15/2022]
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Ma J, Wu X, Li J, Wang Z, Wang Y. Prognostic value of early response assessment using (18F)FDG-PET in patients with advanced non-small cell lung cancer treated with tyrosine-kinase inhibitors. J Investig Med 2017; 65:935-941. [PMID: 28360035 DOI: 10.1136/jim-2017-000433] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/18/2017] [Indexed: 12/31/2022]
Abstract
The purpose of this meta-analysis was to determine the prognostic value of early response assessment using (18F)fluorodeoxyglucose (FDG)-positron emission thermography (PET) in patients with advanced non-small cell lung cancer (NSCLC) treated with tyrosine-kinase inhibitors (TKIs). MEDLINE, PubMed, Cochrane, EMBASE, and Google Scholar databases were searched until August 1, 2016 using the keywords non-small cell lung carcinoma, positron-emission tomography, fluorodeoxyglucose, prognosis, disease progression, survival, erlotinib, gefitinib, and afatinib. Inclusion criteria were studies of patients with stage III or IV NSCLC treated with a TKI and had response assessed by FDG-PET. Outcome measures were overall survival (OS) and progression-free survival (PFS). Of the 167 articles identified, 10 studies including 302 patients were included in the analysis. In 8 studies, patients were treated with erlotinib, and in 2 they were treated with gefitinib. The overall analysis revealed that early metabolic response was statistically associated with improved OS (HR=0.54; 95% CI 0.46 to 0.63; p<0.001), and with longer PFS (HR=0.23; 95% CI 0.17 to 0.33; p<0.001). Early response of patients with NSCLC treated with TKIs identified on FDG-PET is associated with improved OS and PFS.
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Affiliation(s)
- Jun Ma
- Department of Thoracic surgery, Heji Hospital Affiliated to Changzhi Medical College, Changzhi, China
| | - Xiaojing Wu
- Department of Respiratory Medicine, Heji Hospital Affiliated to Changzhi Medical College, Changzhi, China
| | - Jianghong Li
- Department of Thoracic surgery, Heji Hospital Affiliated to Changzhi Medical College, Changzhi, China
| | - Zhihua Wang
- Department of Thoracic surgery, Heji Hospital Affiliated to Changzhi Medical College, Changzhi, China
| | - Yi Wang
- Department of Thoracic surgery, Heji Hospital Affiliated to Changzhi Medical College, Changzhi, China
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Usmanij EA, Natroshvili T, Timmer-Bonte JN, Oyen WJ, van der Drift MA, Bussink J, Geus-Oei LFD. The Predictive Value of Early In-Treatment 18F-FDG PET/CT Response to Chemotherapy in Combination with Bevacizumab in Advanced Nonsquamous Non–Small Cell Lung Cancer. J Nucl Med 2017; 58:1243-1248. [DOI: 10.2967/jnumed.116.185314] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2016] [Accepted: 01/31/2017] [Indexed: 01/25/2023] Open
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Obrzut S, McCammack K, Badran KW, Balistreri A, Ou E, Nguyen BJ, Hoh CK, Rose SC. Prognostic value of post-Yttrium 90 radioembolization therapy 18F-fluorodeoxyglucose positron emission tomography in patients with liver tumors. Clin Imaging 2017; 42:43-49. [DOI: 10.1016/j.clinimag.2016.11.009] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2016] [Revised: 10/31/2016] [Accepted: 11/15/2016] [Indexed: 12/23/2022]
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Sheikhbahaei S, Mena E, Yanamadala A, Reddy S, Solnes LB, Wachsmann J, Subramaniam RM. The Value of FDG PET/CT in Treatment Response Assessment, Follow-Up, and Surveillance of Lung Cancer. AJR Am J Roentgenol 2017; 208:420-433. [PMID: 27726427 DOI: 10.2214/ajr.16.16532] [Citation(s) in RCA: 79] [Impact Index Per Article: 9.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
OBJECTIVE The purpose of this article is to summarize the evidence regarding the role of FDG PET/CT in treatment response assessment and surveillance of lung cancer and to provide suggested best practices. CONCLUSION FDG PET/CT is a valuable imaging tool for assessing treatment response for patients with lung cancer, though evidence for its comparative effectiveness with chest CT is still evolving. FDG PET/CT is most useful when there is clinical suspicion or other evidence for disease recurrence or metastases. The sequencing, cost analysis, and comparative effectiveness of FDG PET/CT and conventional imaging modalities in the follow-up setting need to be investigated.
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Affiliation(s)
- Sara Sheikhbahaei
- 1 Russell H. Morgan Department of Radiology and Radiological Sciences, Johns Hopkins University, Baltimore, MD
| | - Esther Mena
- 1 Russell H. Morgan Department of Radiology and Radiological Sciences, Johns Hopkins University, Baltimore, MD
| | - Anusha Yanamadala
- 1 Russell H. Morgan Department of Radiology and Radiological Sciences, Johns Hopkins University, Baltimore, MD
| | - Siddaling Reddy
- 1 Russell H. Morgan Department of Radiology and Radiological Sciences, Johns Hopkins University, Baltimore, MD
| | - Lilja B Solnes
- 1 Russell H. Morgan Department of Radiology and Radiological Sciences, Johns Hopkins University, Baltimore, MD
| | - Jason Wachsmann
- 2 Department of Radiology, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX 75390
| | - Rathan M Subramaniam
- 1 Russell H. Morgan Department of Radiology and Radiological Sciences, Johns Hopkins University, Baltimore, MD
- 2 Department of Radiology, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX 75390
- 3 Advanced Imaging Research Center, University of Texas Southwestern Medical Center, Dallas, TX
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Early Change in FDG-PET Signal and Plasma Cell-Free DNA Level Predicts Erlotinib Response in EGFR Wild-Type NSCLC Patients. Transl Oncol 2016; 9:505-511. [PMID: 27816687 PMCID: PMC5094375 DOI: 10.1016/j.tranon.2016.09.003] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2016] [Revised: 09/10/2016] [Accepted: 09/12/2016] [Indexed: 12/28/2022] Open
Abstract
INTRODUCTION: Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are a treatment option in the second- or third-line palliative setting in EGFR wild-type (wt) non–small cell lung cancer (NSCLC) patients. However, response rates are low, and only approximately 25% will achieve disease control. Early prediction of treatment resistance could accelerate discontinuation of ineffective treatment and reduce unnecessary toxicity. In this study, we evaluated early changes on 18F-fluoro-D-glucose (F-18-FDG) positron emission tomography/computed tomography (PET/CT) and in total plasma cell-free DNA (cfDNA) as markers of erlotinib response in EGFR-wt patients. METHODS: F-18-FDG-PET/CT scans and blood samples were obtained prior to erlotinib initiation and were repeated after 1 week (PET/CT) and 1 to 4 weeks (blood sample) of treatment. Level of cfDNA was measured by droplet digital polymerase chain reaction. Percentage change (%∆) in SULpeak and total lesion glycolysis (TLG) on FDG-PET/CT and in plasma cfDNA was correlated to radiological response, progression-free survival (PFS), and overall survival (OS). RESULTS: Fifty patients were prospectively enrolled. A significant correlation was found between CT response and %∆TLG (P = .003). All patients with early metabolic progression showed radiological progression. Increased %∆TLG and %∆cfDNA were significantly correlated with shorter PFS (P = .002 and P = .004, respectively) and OS (P = .009 and P = .009, respectively). Multivariate analysis indicated %∆cfDNA to be the strongest predictor of OS. CONCLUSION: Early increase in TLG on F-18-FDG-PET/CT correlates with radiological progression, and shorter PFS and OS. Early increase in cfDNA predicts shorter PFS and OS. Both assessments are promising tools for early detection of nonresponders and reduced OS in TKI-treated EGFR-wt NSCLC patients.
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Yankeelov TE, Mankoff DA, Schwartz LH, Lieberman FS, Buatti JM, Mountz JM, Erickson BJ, Fennessy FMM, Huang W, Kalpathy-Cramer J, Wahl RL, Linden HM, Kinahan PE, Zhao B, Hylton NM, Gillies RJ, Clarke L, Nordstrom R, Rubin DL. Quantitative Imaging in Cancer Clinical Trials. Clin Cancer Res 2016; 22:284-90. [PMID: 26773162 DOI: 10.1158/1078-0432.ccr-14-3336] [Citation(s) in RCA: 82] [Impact Index Per Article: 9.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
As anticancer therapies designed to target specific molecular pathways have been developed, it has become critical to develop methods to assess the response induced by such agents. Although traditional, anatomic CT, and MRI examinations are useful in many settings, increasing evidence suggests that these methods cannot answer the fundamental biologic and physiologic questions essential for assessment and, eventually, prediction of treatment response in the clinical trial setting, especially in the critical period soon after treatment is initiated. To optimally apply advances in quantitative imaging methods to trials of targeted cancer therapy, new infrastructure improvements are needed that incorporate these emerging techniques into the settings where they are most likely to have impact. In this review, we first elucidate the needs for therapeutic response assessment in the era of molecularly targeted therapy and describe how quantitative imaging can most effectively provide scientifically and clinically relevant data. We then describe the tools and methods required to apply quantitative imaging and provide concrete examples of work making these advances practically available for routine application in clinical trials. We conclude by proposing strategies to surmount barriers to wider incorporation of these quantitative imaging methods into clinical trials and, eventually, clinical practice. Our goal is to encourage and guide the oncology community to deploy standardized quantitative imaging techniques in clinical trials to further personalize care for cancer patients and to provide a more efficient path for the development of improved targeted therapies.
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Affiliation(s)
- Thomas E Yankeelov
- Institute of Imaging Science, Departments of Radiology and Radiological Sciences, Biomedical Engineering, Physics, and Cancer Biology, Vanderbilt University, Nashville, Tennessee.
| | - David A Mankoff
- Radiology/Nuclear Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania
| | | | - Frank S Lieberman
- Departments of Neurology, Neurosurgery and Medical Oncology, University of Pittsburgh, Pittsburgh, Pennsylvania
| | - John M Buatti
- Departments of Radiation Oncology, Otolaryngology, and Neurosurgery, University of Iowa, Iowa City, Iowa
| | - James M Mountz
- Division of Nuclear Medicine, Department of Radiology, University of Pittsburgh, Pittsburgh, Pennsylvania
| | | | - Fiona M M Fennessy
- Department of Radiology, Brigham and Women's Hospital, Boston, Massachusetts
| | - Wei Huang
- Advanced Imaging Research Center, Oregon Health and Science University, Portland, Oregon
| | - Jayashree Kalpathy-Cramer
- Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital/Harvard Medical School, Boston, Massachusetts
| | - Richard L Wahl
- Department of Radiology, Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Hannah M Linden
- Department of Medicine, University of Washington, Seattle, Washington
| | - Paul E Kinahan
- Department of Radiology, University of Washington, Seattle, Washington
| | - Binsheng Zhao
- Department of Radiology, Columbia University, New York, New York
| | - Nola M Hylton
- Department of Radiology, University of California, San Francisco, San Francisco, California
| | - Robert J Gillies
- Department of Radiology, H. Lee Moffitt Cancer Center and Research Institute, Tampa Bay, Florida
| | - Laurence Clarke
- Cancer Imaging Program, National Cancer Institute, Bethesda, Maryland
| | - Robert Nordstrom
- Cancer Imaging Program, National Cancer Institute, Bethesda, Maryland
| | - Daniel L Rubin
- Department of Radiology and Medicine, Stanford University, Palo Alto, California
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De Rosa V, Iommelli F, Monti M, Mainolfi CG, Fonti R, Del Vecchio S. Early 18F-FDG uptake as a reliable imaging biomarker of T790M-mediated resistance but not MET amplification in non-small cell lung cancer treated with EGFR tyrosine kinase inhibitors. EJNMMI Res 2016; 6:74. [PMID: 27726115 PMCID: PMC5056924 DOI: 10.1186/s13550-016-0229-0] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2016] [Accepted: 10/04/2016] [Indexed: 02/04/2023] Open
Abstract
BACKGROUND The two main mechanisms of resistance to EGFR tyrosine kinase inhibitors (TKIs) in non-small cell lung cancer (NSCLC) are the occurrence of T790M secondary mutation in the kinase domain of EGFR and MET amplification. The aim of the present study was to test whether early changes of 18F-fluorodeoxyglucose (18F-FDG) uptake in animal models bearing erlotinib-resistant NSCLC may have different imaging patterns of response to erlotinib depending on the molecular mechanisms underlying resistance. Animal tumor models were developed using NSCLC H1975 cells bearing the T790M mutation and H1993 cells with MET amplification. Nude mice bearing erlotinib-resistant H1975 and H1993 xenografts (four animals for each cell line and for each treatment) were subjected to 18F-FDG PET/CT scan before and immediately after treatment (50 mg/kg p.o. for 3 days) with erlotinib, WZ4002, crizotinib, or vehicle. A three-dimensional region of interest analysis was performed to determine the percent change of 18F-FDG uptake in response to treatment. At the end of the imaging studies, tumors were removed and analyzed for glycolytic and mitochondrial proteins as well as levels of cyclin D1. RESULTS Imaging studies with 18F-FDG PET/CT in H1975 tumor-bearing mice showed a reduction of 18F-FDG uptake of 25.87 % ± 8.93 % after treatment with WZ4002 whereas an increase of 18F-FDG uptake up to 23.51 % ± 9.72 % was observed after treatment with erlotinib or vehicle. Conversely, H1993 tumors showed a reduction of 18F-FDG uptake after treatment with both crizotinib (14.70 % ± 1.30 %) and erlotinib (18.40 % ± 9.19 %) and an increase of tracer uptake in vehicle-treated (56.65 % ± 5.65 %) animals. The in vivo reduction of 18F-FDG uptake was always associated with downregulation of HKII and p-PKM2 Tyr105 glycolytic proteins and upregulation of mitochondrial complexes (subunits I-IV) in excised tumors. CONCLUSIONS 18F-FDG uptake is a reliable imaging biomarker of T790M-mediated resistance and its reversal in NSCLC whereas it may not be accurate in the detection of MET-mediated resistance.
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Affiliation(s)
- Viviana De Rosa
- Institute of Biostructures and Bioimaging, National Research Council, Via T. De Amicis 95, 80145, Naples, Italy
| | - Francesca Iommelli
- Institute of Biostructures and Bioimaging, National Research Council, Via T. De Amicis 95, 80145, Naples, Italy
| | - Marcello Monti
- Department of Advanced Biomedical Sciences, University of Naples Federico II, Via Pansini 5, 80131, Naples, Italy
| | - Ciro Gabriele Mainolfi
- Department of Advanced Biomedical Sciences, University of Naples Federico II, Via Pansini 5, 80131, Naples, Italy
| | - Rosa Fonti
- Institute of Biostructures and Bioimaging, National Research Council, Via T. De Amicis 95, 80145, Naples, Italy
| | - Silvana Del Vecchio
- Department of Advanced Biomedical Sciences, University of Naples Federico II, Via Pansini 5, 80131, Naples, Italy.
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Schmitt RJ, Kreidler SM, Glueck DH, Amaria RN, Gonzalez R, Lewis K, Bagrosky BM, Kwak JJ, Koo PJ. Correlation between early 18F-FDG PET/CT response to BRAF and MEK inhibition and survival in patients with BRAF-mutant metastatic melanoma. Nucl Med Commun 2016; 37:122-8. [PMID: 26440571 DOI: 10.1097/mnm.0000000000000406] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
PURPOSE Metabolic response to treatment measured by fluorine-18 fluorodeoxyglucose ((18)F-FDG) PET has prognostic implications in many cancers. This study investigated the association between survival and early changes on (18)F-FDG PET/computed tomography (CT) for patients with BRAF-mutant melanoma receiving combined BRAF and MEK inhibition therapy. MATERIALS AND METHODS Overall, 24 patients with advanced BRAF-mutant melanoma were included. Patients were treated with a BRAF inhibitor (vemurafenib or dabrafenib) and a MEK inhibitor (cobimetinib or trametinib), and were imaged at baseline and shortly thereafter with (18)F-FDG PET/CT. Each scan yielded two values of maximum standardized uptake value (SUVmax): one for the most metabolically active focus and one for the least responsive focus. Short-term treatment response was assessed by evaluating the target lesions using the EROTC criteria. A Cox proportional hazards model was used to examine associations between overall survival (OS) and progression-free survival (PFS) and changes in SUVmax. RESULTS The mean time to follow-up (18)F-FDG PET/CT was 26 days. At follow-up, two patients achieved a complete response. For the most metabolically active focus, 22 patients showed a partial response. For the least responsive focus, 18 patients showed a partial response, two had stable disease, and two had progressive disease.A total of 16 patients were alive at the end of the study. For the most metabolically active tumor, no association was observed between changes in SUVmax and OS (P=0.73) or PFS (P=0.17). For the least responsive tumor, change in SUVmax was associated with PFS [hazard ratio (HR)=1.34, 95% confidence interval (CI): 1.06-1.71, P=0.01], but not OS (P=0.52). The ECOG score was associated with OS (HR=11.81, 95% CI: 1.42-97.60, P=0.02) and PFS (HR=24.72, 95% CI: 3.23-189.42, P=0.002). CONCLUSION Change in SUVmax for the least responsive tumor and baseline functional performance may be useful prognostic indicators for PFS in patients with BRAF-mutant melanoma.
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Affiliation(s)
- Ronald J Schmitt
- aDepartment of Radiology bDepartment of Medicine, Division of Medical Oncology, University of Colorado School of Medicine cDepartment of Biostatistics, Colorado School of Public Health, University of Colorado Denver, Aurora, Colorado dThe University of Texas MD Anderson Cancer Center, Houston, Texas, USA
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Nielsen CH, Jensen MM, Kristensen LK, Dahlman A, Fröhlich C, Jacobsen HJ, Poulsen TT, Lantto J, Horak ID, Kragh M, Kjaer A. In vivo imaging of therapy response to a novel pan-HER antibody mixture using FDG and FLT positron emission tomography. Oncotarget 2016; 6:37486-99. [PMID: 26460961 PMCID: PMC4741943 DOI: 10.18632/oncotarget.6060] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2015] [Accepted: 09/24/2015] [Indexed: 11/25/2022] Open
Abstract
Purpose Overexpression of the human epidermal growth factor receptor (HER) family and their ligands plays an important role in many cancers. Targeting multiple members of the HER family simultaneously may increase the therapeutic efficacy. Here, we report the ability to image the therapeutic response obtained by targeting HER family members individually or simultaneously using the novel monoclonal antibody (mAb) mixture Pan-HER. Experimental design and results Mice with subcutaneous BxPC-3 pancreatic adenocarcinomas were divided into five groups receiving vehicle or mAb mixtures directed against either EGFR (HER1), HER2, HER3 or all three receptors combined by Pan-HER. Small animal positron emission tomography/computed tomography (PET/CT) with 2′-deoxy-2′-[18F]fluoro-D-glucose (FDG) and 3′-deoxy-3′-[18F]fluorothymidine (FLT) was performed at baseline and at day 1 or 2 after initiation of therapy. Changes in tumor uptake of tracers were quantified and compared to reduction in tumor size. Imaging results were further validated by immunohistochemistry and qPCR. Mean FDG and FLT uptake in the Pan-HER treated group decreased by 19±4.3% and 24±3.1%, respectively. The early change in FDG and FLT uptake correlated with tumor growth at day 23 relative to day 0. Ex vivo molecular analyses of markers associated with the mechanisms of FDG and FLT uptake confirmed the in vivo imaging results. Conclusions Taken together, the study supports the use of FDG and FLT as imaging biomarkers of early response to Pan-HER therapy. FDG and FLT PET/CT imaging should be considered as imaging biomarkers in clinical evaluation of the Pan-HER mAb mixture.
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Affiliation(s)
- Carsten H Nielsen
- Minerva Imaging ApS, Copenhagen, Denmark.,Department of Clinical Physiology, Nuclear Medicine and PET and Cluster for Molecular Imaging, Rigshospitalet and University of Copenhagen, Copenhagen, Denmark
| | - Mette M Jensen
- Minerva Imaging ApS, Copenhagen, Denmark.,Department of Clinical Physiology, Nuclear Medicine and PET and Cluster for Molecular Imaging, Rigshospitalet and University of Copenhagen, Copenhagen, Denmark
| | - Lotte K Kristensen
- Minerva Imaging ApS, Copenhagen, Denmark.,Department of Clinical Physiology, Nuclear Medicine and PET and Cluster for Molecular Imaging, Rigshospitalet and University of Copenhagen, Copenhagen, Denmark
| | | | | | | | | | | | | | | | - Andreas Kjaer
- Minerva Imaging ApS, Copenhagen, Denmark.,Department of Clinical Physiology, Nuclear Medicine and PET and Cluster for Molecular Imaging, Rigshospitalet and University of Copenhagen, Copenhagen, Denmark
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Mena E, Yanamadala A, Cheng G, Subramaniam RM. The Current and Evolving Role of PET in Personalized Management of Lung Cancer. PET Clin 2016; 11:243-59. [DOI: 10.1016/j.cpet.2016.02.010] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/17/2023]
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Hureaux J, Couturier O, Lacœuille F, Bouchet F, Chouaïd C, Saulnier P, Urban T. [Can positron emission tomography assessment of response to treatment help to individualize use of erlotinib in non-small cell lung cancer?]. Rev Mal Respir 2016; 33:817-823. [PMID: 27257103 DOI: 10.1016/j.rmr.2016.03.009] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2016] [Accepted: 03/08/2016] [Indexed: 11/30/2022]
Abstract
Erlotinib can be prescribed in the treatment of locally advanced or metastatic non-small lung cancer cell (NSCLC) after failure of at least one prior chemotherapy regimen on the basis of the BR-21 study. Several publications have recently questioned these results. The metabolic imaging of solid tumours by positron emission tomography is a research field that could help customize the treatment of NSCLC and so complement the treatment approaches allowed by genetic analyses. This strategy is part of an innovative "early metabolic look" approach. The primary objective of this study is to determine if metabolic progression observed between the 7th and 14th day after initiation of treatment with erlotinib by 3'-Deoxy-3'-[18F]-Fluorothymidine PET in patients with EGFR naive NSCLC is predictive for morphological progression after 6 to 8 weeks of treatment. A health economic analysis will be conducted. This study is particularly innovative because it begins the exploration of the era of metabolic evaluation of therapeutic response in NSCLC.
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Affiliation(s)
- J Hureaux
- Département de pneumologie, allergologie et oncologie, LUNAM université, centre hospitalier universitaire, 4, rue Larrey, 49933 Angers cedex 9, France.
| | - O Couturier
- Service de médecine nucléaire, LUNAM université, centre hospitalier universitaire, 4, rue Larrey, 49933 Angers cedex 9, France
| | - F Lacœuille
- Service de médecine nucléaire, LUNAM université, centre hospitalier universitaire, 4, rue Larrey, 49933 Angers cedex 9, France
| | - F Bouchet
- Service de médecine nucléaire, LUNAM université, centre hospitalier universitaire, 4, rue Larrey, 49933 Angers cedex 9, France
| | - C Chouaïd
- Service de pneumologie, centre interhospitalier de Créteil, 94000 Créteil, France
| | - P Saulnier
- DRCI - cellule de méthodologie et de biostatistiques, centre hospitalier universitaire, 4, rue Larrey, 49933 Angers cedex 9, France
| | - T Urban
- Département de pneumologie, allergologie et oncologie, LUNAM université, centre hospitalier universitaire, 4, rue Larrey, 49933 Angers cedex 9, France
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Ho KC, Fang YHD, Chung HW, Liu YC, Chang JWC, Hou MM, Yang CT, Cheng NM, Su TP, Yen TC. TLG-S criteria are superior to both EORTC and PERCIST for predicting outcomes in patients with metastatic lung adenocarcinoma treated with erlotinib. Eur J Nucl Med Mol Imaging 2016; 43:2155-2165. [PMID: 27260520 DOI: 10.1007/s00259-016-3433-2] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2016] [Accepted: 05/26/2016] [Indexed: 12/15/2022]
Abstract
PURPOSE In this retrospective review of prospectively collected data, we sought to investigate whether early FDG-PET assessment of treatment response based on total lesion glycolysis measured using a systemic approach (TLG-S) would be superior to either local assessment with EORTC (European Organization for Research and Treatment of Cancer) criteria or single-lesion assessment with PERCIST (PET Response Criteria in Solid Tumors) for predicting clinical outcomes in patients with metastatic lung adenocarcinoma treated with erlotinib. We also examined the effect of bone flares on tumor response evaluation by single-lesion assessment with PERCIST in patients with metastatic bone lesions. METHODS We performed a retrospective review of prospectively collected data from 23 patients with metastatic lung adenocarcinoma treated with erlotinib. All participants underwent FDG-PET imaging at baseline and on days 14 and 56 after completion of erlotinib treatment. In addition, diagnostic CT scans were performed at baseline and on day 56. FDG-PET response was assessed with TLG-S, EORTC, and PERCIST criteria. Response assessment based on RECIST 1.1 (Response Evaluation Criteria in Solid Tumors) from diagnostic CT imaging was used as the reference standard. Two-year progression-free survival (PFS) and overall survival (OS) served as the main outcome measures. RESULTS We identified 13 patients with bone metastases. Of these, four (31 %) with persistent bone uptake due to bone flares on day 14 were erroneously classified as non-responders according to the PERCIST criteria, but they were correctly classified as responders according to both the EORTC and TLG-S criteria. Patients who were classified as responders on day 14 based on TLG-S criteria had higher rates of 2-year PFS (26.7 % vs. 0 %, P = 0.007) and OS (40.0 % vs. 7.7 %, P = 0.018). Similar rates were observed in patients who showed a response on day 56 based on CT imaging according to the RECIST criteria. Patients classified as responders on day 14 according to the EORTC criteria on FDG-PET imaging had better rates of 2-year OS than did non-responders (36.4 % vs. 8.3 %, P = 0.015). CONCLUSIONS TLG-S criteria may be of greater help in predicting survival outcomes than other forms of assessment. Bone flares, which can interfere with the interpretation of treatment response based on PERCIST criteria, are not uncommon in patients with metastatic lung adenocarcinoma treated with erlotinib.
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Affiliation(s)
- Kung-Chu Ho
- Graduate Institute of Biomedical Electronics and Bioinformatics, National Taiwan University, Taipei, Taiwan.,Department of Nuclear Medicine and Center for Advanced Molecular Imaging and Translation, Chang Gung Memorial Hospital and Chang Gung University, 5 Fu-Shin Street, Kueishan, Taoyuan, 333, Taiwan
| | - Yu-Hua Dean Fang
- Department of Biomedical Engineering, National Cheng Kung University, Tainan, Taiwan
| | - Hsiao-Wen Chung
- Graduate Institute of Biomedical Electronics and Bioinformatics, National Taiwan University, Taipei, Taiwan
| | - Yuan-Chang Liu
- Department of Medical Imaging and Intervention, Chang Gung Memorial Hospital and Chang Gung University, Taoyuan, Taiwan
| | - John Wen-Cheng Chang
- Division of Hematology-Oncology, Department of Internal Medicine, Chang Gung Memorial Hospital and Chang Gung University, Taoyuan, Taiwan
| | - Ming-Mo Hou
- Division of Hematology-Oncology, Department of Internal Medicine, Chang Gung Memorial Hospital and Chang Gung University, Taoyuan, Taiwan
| | - Cheng-Ta Yang
- Department of Thoracic Medicine, Chang Gung Memorial Hospital and Chang Gung University, Taoyuan, Taiwan
| | - Nai-Ming Cheng
- Department of Nuclear Medicine and Center for Advanced Molecular Imaging and Translation, Chang Gung Memorial Hospital and Chang Gung University, 5 Fu-Shin Street, Kueishan, Taoyuan, 333, Taiwan
| | - Tzu-Pei Su
- Department of Nuclear Medicine, Chang Gung Memorial Hospital, Keelung, Taiwan
| | - Tzu-Chen Yen
- Department of Nuclear Medicine and Center for Advanced Molecular Imaging and Translation, Chang Gung Memorial Hospital and Chang Gung University, 5 Fu-Shin Street, Kueishan, Taoyuan, 333, Taiwan.
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40
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Weller A, O'Brien MER, Ahmed M, Popat S, Bhosle J, McDonald F, Yap TA, Du Y, Vlahos I, deSouza NM. Mechanism and non-mechanism based imaging biomarkers for assessing biological response to treatment in non-small cell lung cancer. Eur J Cancer 2016; 59:65-78. [PMID: 27016624 DOI: 10.1016/j.ejca.2016.02.017] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2016] [Accepted: 02/18/2016] [Indexed: 12/18/2022]
Abstract
Therapeutic options in locally advanced non-small cell lung cancer (NSCLC) have expanded in the past decade to include a palate of targeted interventions such as high dose targeted thermal ablations, radiotherapy and growing platform of antibody and small molecule therapies and immunotherapies. Although these therapies have varied mechanisms of action, they often induce changes in tumour architecture and microenvironment such that response is not always accompanied by early reduction in tumour mass, and evaluation by criteria other than size is needed to report more effectively on response. Functional imaging techniques, which probe the tumour and its microenvironment through novel positron emission tomography and magnetic resonance imaging techniques, offer more detailed insights into and quantitation of tumour response than is available on anatomical imaging alone. Use of these biomarkers, or other rational combinations as readouts of pathological response in NSCLC have potential to provide more accurate predictors of treatment outcomes. In this article, the robustness of the more commonly available positron emission tomography and magnetic resonance imaging biomarker indices is examined and the evidence for their application in NSCLC is reviewed.
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Affiliation(s)
- A Weller
- CRUK Cancer Imaging Centre, Institute of Cancer Research and Royal Marsden NHS Foundation Trust, UK.
| | - M E R O'Brien
- Department of Medicine, Royal Marsden NHS Foundation Trust, Downs Road, Surrey, SM2 5PT, UK
| | - M Ahmed
- Department of Radiotherapy, Royal Marsden NHS Foundation Trust, Downs Road, Surrey, SM2 5PT, UK
| | - S Popat
- Department of Medicine, Royal Marsden NHS Foundation Trust, Downs Road, Surrey, SM2 5PT, UK
| | - J Bhosle
- Department of Medicine, Royal Marsden NHS Foundation Trust, Downs Road, Surrey, SM2 5PT, UK
| | - F McDonald
- Department of Radiotherapy, Royal Marsden NHS Foundation Trust, Downs Road, Surrey, SM2 5PT, UK
| | - T A Yap
- Department of Medicine, Royal Marsden NHS Foundation Trust, Downs Road, Surrey, SM2 5PT, UK
| | - Y Du
- Department of Nuclear Medicine, Royal Marsden NHS Foundation Trust, Downs Road, Surrey, SM2 5PT, UK
| | - I Vlahos
- Radiology Department, St George's Hospital NHS Trust, London, SW17 0QT, UK
| | - N M deSouza
- CRUK Cancer Imaging Centre, Institute of Cancer Research and Royal Marsden NHS Foundation Trust, UK
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Cho A, Hur J, Moon YW, Hong SR, Suh YJ, Kim YJ, Im DJ, Hong YJ, Lee HJ, Kim YJ, Shim HS, Lee JS, Kim JH, Choi BW. Correlation between EGFR gene mutation, cytologic tumor markers, 18F-FDG uptake in non-small cell lung cancer. BMC Cancer 2016; 16:224. [PMID: 26979333 PMCID: PMC4793740 DOI: 10.1186/s12885-016-2251-z] [Citation(s) in RCA: 50] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2015] [Accepted: 03/07/2016] [Indexed: 11/10/2022] Open
Abstract
Background EGFR mutation-induced cell proliferation causes changes in tumor biology and tumor metabolism, which may reflect tumor marker concentration and 18F-FDG uptake on PET/CT. Direct aspirates of primary lung tumors contain different concentrations of tumor markers than serum tumor markers, and may correlate better with EGFR mutation than serum tumor markers. The purpose of this study is to investigate an association between cytologic tumor markers and FDG uptake with EGFR mutation status in non-small cell lung cancer (NSCLC). Methods We prospectively collected tumor aspirates of 61 patients who underwent EGFR mutation analysis. Serum and cytologic CYFRA 21-1, CEA, and SCCA levels were measured and correlated with EGFR gene mutations. FDG PET/CT was performed on 58 patients for NSCLC staging, and SUV was correlated with EGFR mutation status. Results Thirty (50 %) patients had EGFR mutation and 57 patients had adenocarcinoma subtype. Univariate analysis showed that female gender, never smoker, high levels of cytologic CYFRA 21-1 (c-CYFRA) and lower maximum standard uptake value (SUVmax) were correlated with EGFR mutations. ROC generated cut-off values of 20.8 ng/ml for c-CYFRA and SUVmax of 9.6 showed highest sensitivity for EGFR mutation detection. Multivariate analysis revealed that female gender [hazard ratio (HR): 18.15, p = 0.025], higher levels of c-CYFRA (HR: 7.58, and lower SUVmax (HR: 0.08, p = 0.005) were predictive of harboring EGFR mutation. Conclusions The cytologic tumor marker c-CYFRA was positively associated with EGFR mutations in NSCLC. EGFR mutation-positive NSCLCs have relatively lower glycolysis compared with NSCLCs without EGFR mutation.
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Affiliation(s)
- Arthur Cho
- Department of Nuclear Medicine, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea.,Department of Radiology, Severance Hospital, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul, 120-752, Korea
| | - Jin Hur
- Department of Radiology and Research Institute of Radiological Science, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea.
| | - Yong Wha Moon
- Yonsei Cancer Center, Division of Medical Oncology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea.,Medical Oncology, Department of Internal Medicine, CHA Bundang Medical Center, CHA University, Seongnam, Korea
| | - Sae Rom Hong
- Department of Radiology and Research Institute of Radiological Science, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Young Joo Suh
- Department of Radiology and Research Institute of Radiological Science, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Yun Jung Kim
- Department of Radiology and Research Institute of Radiological Science, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Dong Jin Im
- Department of Radiology and Research Institute of Radiological Science, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Yoo Jin Hong
- Department of Radiology and Research Institute of Radiological Science, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Hye-Jeong Lee
- Department of Radiology and Research Institute of Radiological Science, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Young Jin Kim
- Department of Radiology and Research Institute of Radiological Science, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Hyo Sup Shim
- Department of Pathology, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Jae Seok Lee
- Department of Pathology, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea.,Department of Pathology, Dongguk University Ilsan Hospital, Dongguk University College of Medicine, Goyang, Korea
| | - Joo-Hang Kim
- Yonsei Cancer Center, Division of Medical Oncology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea.,Medical Oncology, Department of Internal Medicine, CHA Bundang Medical Center, CHA University, Seongnam, Korea
| | - Byoung Wook Choi
- Department of Radiology and Research Institute of Radiological Science, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
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Abstract
OBJECTIVES To discuss the recent scientific advances that influence current oncology care and explore the implications of these advances for the future of oncology nursing. DATA SOURCES Current nursing, medical and basic science literature; Clinicaltrials.gov. CONCLUSION The future of oncology care will be influenced by an aging population and increasing number of patients diagnosed with cancer. The advancements in molecular sequencing will lead to more clinical trials, targeted therapies, and treatment decisions based on the genetic makeup of both the patient and the tumor. Nurses must stay current with an ever changing array of targeted therapies and developing science. Nurses will influence cancer care quality, value, cost, and patient satisfaction. IMPLICATIONS FOR NURSING PRACTICE It is critical for oncology nurses and nursing organizations to engage with all oncology care stakeholders in identifying the future needs of oncology patients and the environment in which care will be delivered. Nurses themselves must identify the roles that will be needed to ensure a workforce that is adequate in number and well trained to meet the future challenges of care delivery.
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A systematic review on [(18)F]FLT-PET uptake as a measure of treatment response in cancer patients. Eur J Cancer 2016; 55:81-97. [PMID: 26820682 DOI: 10.1016/j.ejca.2015.11.018] [Citation(s) in RCA: 80] [Impact Index Per Article: 8.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2015] [Accepted: 11/15/2015] [Indexed: 12/19/2022]
Abstract
Imaging biomarkers have a potential to depict the hallmarks of cancers that characterise cancer cells as compared to normal cells. One pertinent example is 3'-deoxy-3'-(18)F-fluorothymidine positron emission tomography ([(18)F]FLT-PET), which allows non-invasive in vivo assessment of tumour proliferation. Most importantly, [(18)F]FLT does not seem to be accumulating in inflammatory processes, as seen in [(18)F]-fludeoxyglucose, the most commonly used PET tracer for assessment of cell metabolism. [(18)F]FLT could therefore provide additional information about the tumour biology before, during and after treatment. This systematic review focuses on the use of [(18)F]FLT-PET tumour uptake values as a measure of tumour response to therapeutic interventions. The clinical studies which evaluated the role of [(18)F]FLT-PET as a measure of tumour response to treatment are summarised and the evidence linking [(18)F]FLT-PET tumour uptake values with clinical outcome is evaluated.
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Fledelius J, Khalil AA, Hjorthaug K, Frøkiaer J. Using positron emission tomography (PET) response criteria in solid tumours (PERCIST) 1.0 for evaluation of 2′-deoxy-2′-[18F] fluoro-D-glucose-PET/CT scans to predict survival early during treatment of locally advanced non-small cell lung cancer (NSCLC). J Med Imaging Radiat Oncol 2015; 60:231-8. [DOI: 10.1111/1754-9485.12427] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2015] [Accepted: 11/18/2015] [Indexed: 11/28/2022]
Affiliation(s)
- Joan Fledelius
- Department of Nuclear Medicine; Herning Regional Hospital; Herning Denmark
| | | | - Karin Hjorthaug
- Department of Nuclear Medicine and PET Centre; Aarhus University Hospital; Aarhus Denmark
| | - Jørgen Frøkiaer
- Department of Nuclear Medicine and PET Centre; Aarhus University Hospital; Aarhus Denmark
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Early metabolic change in 18F-FDG-PET by measuring the single largest lesion predicts chemotherapeutic effects and patients’ survival: PEACH study. Cancer Chemother Pharmacol 2015; 77:121-6. [DOI: 10.1007/s00280-015-2935-0] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2015] [Accepted: 11/29/2015] [Indexed: 01/30/2023]
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Dynamic volume perfusion computed tomography parameters versus RECIST for the prediction of outcome in lung cancer patients treated with conventional chemotherapy. J Thorac Oncol 2015; 10:164-71. [PMID: 25247342 DOI: 10.1097/jto.0000000000000376] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
Abstract
INTRODUCTION To compare dynamic volume perfusion computed tomography (dVPCT) parameters with Response Evaluation Criteria in Solid Tumors (RECIST 1.1) for prediction of therapy response and overall survival (OS) in non-small-cell lung cancer (NSCLC) and small-cell lung cancer (SCLC) patients treated with conventional chemotherapy. METHODS A total of 173 lung cancer patients (131 men; 61 ± 10 years) undergoing dVPCT before (T1) and after chemotherapy (T2) and follow-up were prospectively included. dVPCT-derived blood flow, blood volume, mean transit time, and permeability (PERM) were assessed, compared between NSCLC and SCLC and patients' response to therapy was determined according to RECIST 1.1. RESULTS One hundred of one hundred and seventy-three patients underwent dVPCT at T1 and T2 within a median of 44 (range, 31-108) days. dVPCT values were differing in NSCLC and SCLC, but were not significantly differing between patients with partial response, stable, or progressive disease. Eighty-five patients (NSCLC = 72 and SCLC = 13) with a follow-up for greater than or equal to 6 months were analyzed for OS. Fifty-six of eighty-five patients died during follow-up. Receiver operating characteristic analysis determined T1/T2 with highest predictive values regarding OS for blood flow, blood volume, mean transit time, and permeability (area under the curve: 0.53, 0.61, 0.54, and 0.53, respectively, all p > 0.05). Kaplan-Meier statistics revealed OS of patient groups assigned according to dVPCT T1/T2 cutoff values was not differing for neither dVPCT parameter, whereas RECIST groups significantly differed in OS (p = 0.02). Cox proportional hazards regression determined progressive disease status to independently predict OS (p = 0.004), while none of the dVPCT parameters did so. CONCLUSIONS dVPCT values, differ between NSCLC and SCLC, are not related to RECIST 1.1 classification and do not improve OS prediction in lung cancer patients treated with conventional chemotherapy.
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Necchi A, Nicolai N, Alessi A, Miceli R, Giannatempo P, Raggi D, Tana S, Serafini G, Padovano B, Mariani L, Crippa F, Salvioni R. Interim (18)F-Fluorodeoxyglucose Positron Emission Tomography for Early Metabolic Assessment of Response to Cisplatin, Etoposide, and Bleomycin Chemotherapy for Metastatic Seminoma: Clinical Value and Future Directions. Clin Genitourin Cancer 2015; 14:249-54. [PMID: 26433626 DOI: 10.1016/j.clgc.2015.08.010] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2015] [Revised: 08/19/2015] [Accepted: 08/24/2015] [Indexed: 11/26/2022]
Abstract
BACKGROUND In patients with metastatic seminoma, designing a risk-adapted strategy that may help personalize the burden of treatment and follow-up is required. PATIENTS AND METHODS Patients who were administered cisplatin, etoposide, and bleomycin (PEB) were staged at baseline with computed tomography (CT), positron emission tomography (PET), and serum tumor markers. Restaging was then performed with PET after 2 cycles of PEB (PET2) and with CT after 3 to 4 cycles of treatment. The 20% cutoff of maximal standardized uptake value (SUVmax) changes and Response Evaluation Criteria in Solid Tumors (RECIST, version 1.1) criteria were applied to define the response. The Wilcoxon rank sum test was used to analyze the association between metabolic response and the shrinkage of target lesions. RESULTS Between February 2009 and November 2013, 37 patients were enrolled. After 2 cycles of PEB, 27 patients (72.9%; 95% confidence interval [CI], 55.8-86.2) had a metabolic complete response (CR) and 10 patients had a partial response (PR; 27%; 95% CI, 13.8-44.1). A significant association was found between PET2 response and baseline (P = .003), final diameter (P < .001), and percentage of tumor shrinkage (P = .014) of target lesions. After 18 months' (interquartile range [IQR], 13-23) median follow-up, 2 patients with PET2 PR had relapsed disease; none of those with a CR had relapsed disease. CONCLUSIONS A significant association was found between early metabolic response and tumor shrinkage in patients with advanced seminoma. Patients achieving a PET2 CR could be predicted not to need additional treatment after PEB, and simplifying their follow-up should be an end point. PET2 might also identify difficult to treat cases at an early stage.
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Affiliation(s)
- Andrea Necchi
- Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
| | - Nicola Nicolai
- Department of Surgery-Urology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
| | - Alessandra Alessi
- Nuclear Medicine and PET Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
| | - Rosalba Miceli
- Clinical Epidemiology and Trials Organization Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
| | - Patrizia Giannatempo
- Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
| | - Daniele Raggi
- Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
| | - Silvia Tana
- Department of Radiotherapy, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
| | - Gianluca Serafini
- Nuclear Medicine and PET Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
| | - Barbara Padovano
- Nuclear Medicine and PET Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
| | - Luigi Mariani
- Clinical Epidemiology and Trials Organization Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
| | - Flavio Crippa
- Nuclear Medicine and PET Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
| | - Roberto Salvioni
- Department of Surgery-Urology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
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Cook GJR, O'Brien ME, Siddique M, Chicklore S, Loi HY, Sharma B, Punwani R, Bassett P, Goh V, Chua S. Non-Small Cell Lung Cancer Treated with Erlotinib: Heterogeneity of (18)F-FDG Uptake at PET-Association with Treatment Response and Prognosis. Radiology 2015; 276:883-93. [PMID: 25897473 DOI: 10.1148/radiol.2015141309] [Citation(s) in RCA: 129] [Impact Index Per Article: 12.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
PURPOSE To determine if first-order and high-order textural features on fluorine 18 ((18)F) fluorodeoxyglucose (FDG) positron emission tomography (PET) images of non-small cell lung cancer (NSCLC) (a) at baseline, (b) at 6 weeks, or (c) the percentage change between baseline and 6 weeks can predict response or survival in patients treated with erlotinib. MATERIALS AND METHODS Institutional review board approval was obtained for post hoc analysis of data from a prospective single-center study for which informed consent was obtained. The study included 47 patients with NSCLC who underwent (18)F-FDG PET/computed tomography (CT) at baseline (n = 47) and 6 weeks (n = 40) after commencing treatment with erlotinib. First-order and high-order primary tumor texture features reflecting image heterogeneity, standardized uptake values, metabolic tumor volume, and total lesion glycolysis were measured for all (18)F-FDG PET studies. Response to erlotinib was assessed by using the Response Evaluation Criteria in Solid Tumors (RECIST) on CT images obtained at 12 weeks (n = 32). Associations between PET parameters, overall survival (OS), and RECIST-based treatment response were tested by Cox and logistic regression analyses, respectively. RESULTS Median OS was 14.1 months. According to CT RECIST at 12 weeks, there were 21 nonresponders and 11 responders. Response to erlotinib was associated with reduced heterogeneity (first-order standard deviation, P = .01; entropy, P = .001; uniformity, P = .001). At multivariable analysis, high-order contrast at 6 weeks (P = .002) and percentage change in first-order entropy (P = .03) were independently associated with survival. Percentage change in first-order entropy was also independently associated with treatment response (P = .01). CONCLUSION Response to erlotinib is associated with reduced heterogeneity at (18)F-FDG PET. Changes in first-order entropy are independently associated with OS and treatment response.
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Affiliation(s)
- Gary J R Cook
- From the Division of Imaging Sciences and Biomedical Engineering, King's College London, St Thomas' Hospital, London SE1 7EH, England (G.J.R.C., M.S., S.C., V.G.); the Lung Unit (M.E.O., R.P.) and Department of Nuclear Medicine and PET (H.Y.L., B.S., S.C.), the Royal Marsden National Health Service (NHS) Foundation Trust, Sutton, England; and Statsconsultancy, Amersham, Buckinghamshire, England (P.B.)
| | - Mary E O'Brien
- From the Division of Imaging Sciences and Biomedical Engineering, King's College London, St Thomas' Hospital, London SE1 7EH, England (G.J.R.C., M.S., S.C., V.G.); the Lung Unit (M.E.O., R.P.) and Department of Nuclear Medicine and PET (H.Y.L., B.S., S.C.), the Royal Marsden National Health Service (NHS) Foundation Trust, Sutton, England; and Statsconsultancy, Amersham, Buckinghamshire, England (P.B.)
| | - Muhammad Siddique
- From the Division of Imaging Sciences and Biomedical Engineering, King's College London, St Thomas' Hospital, London SE1 7EH, England (G.J.R.C., M.S., S.C., V.G.); the Lung Unit (M.E.O., R.P.) and Department of Nuclear Medicine and PET (H.Y.L., B.S., S.C.), the Royal Marsden National Health Service (NHS) Foundation Trust, Sutton, England; and Statsconsultancy, Amersham, Buckinghamshire, England (P.B.)
| | - Sugama Chicklore
- From the Division of Imaging Sciences and Biomedical Engineering, King's College London, St Thomas' Hospital, London SE1 7EH, England (G.J.R.C., M.S., S.C., V.G.); the Lung Unit (M.E.O., R.P.) and Department of Nuclear Medicine and PET (H.Y.L., B.S., S.C.), the Royal Marsden National Health Service (NHS) Foundation Trust, Sutton, England; and Statsconsultancy, Amersham, Buckinghamshire, England (P.B.)
| | - Hoi Y Loi
- From the Division of Imaging Sciences and Biomedical Engineering, King's College London, St Thomas' Hospital, London SE1 7EH, England (G.J.R.C., M.S., S.C., V.G.); the Lung Unit (M.E.O., R.P.) and Department of Nuclear Medicine and PET (H.Y.L., B.S., S.C.), the Royal Marsden National Health Service (NHS) Foundation Trust, Sutton, England; and Statsconsultancy, Amersham, Buckinghamshire, England (P.B.)
| | - Bhupinder Sharma
- From the Division of Imaging Sciences and Biomedical Engineering, King's College London, St Thomas' Hospital, London SE1 7EH, England (G.J.R.C., M.S., S.C., V.G.); the Lung Unit (M.E.O., R.P.) and Department of Nuclear Medicine and PET (H.Y.L., B.S., S.C.), the Royal Marsden National Health Service (NHS) Foundation Trust, Sutton, England; and Statsconsultancy, Amersham, Buckinghamshire, England (P.B.)
| | - Ravi Punwani
- From the Division of Imaging Sciences and Biomedical Engineering, King's College London, St Thomas' Hospital, London SE1 7EH, England (G.J.R.C., M.S., S.C., V.G.); the Lung Unit (M.E.O., R.P.) and Department of Nuclear Medicine and PET (H.Y.L., B.S., S.C.), the Royal Marsden National Health Service (NHS) Foundation Trust, Sutton, England; and Statsconsultancy, Amersham, Buckinghamshire, England (P.B.)
| | - Paul Bassett
- From the Division of Imaging Sciences and Biomedical Engineering, King's College London, St Thomas' Hospital, London SE1 7EH, England (G.J.R.C., M.S., S.C., V.G.); the Lung Unit (M.E.O., R.P.) and Department of Nuclear Medicine and PET (H.Y.L., B.S., S.C.), the Royal Marsden National Health Service (NHS) Foundation Trust, Sutton, England; and Statsconsultancy, Amersham, Buckinghamshire, England (P.B.)
| | - Vicky Goh
- From the Division of Imaging Sciences and Biomedical Engineering, King's College London, St Thomas' Hospital, London SE1 7EH, England (G.J.R.C., M.S., S.C., V.G.); the Lung Unit (M.E.O., R.P.) and Department of Nuclear Medicine and PET (H.Y.L., B.S., S.C.), the Royal Marsden National Health Service (NHS) Foundation Trust, Sutton, England; and Statsconsultancy, Amersham, Buckinghamshire, England (P.B.)
| | - Sue Chua
- From the Division of Imaging Sciences and Biomedical Engineering, King's College London, St Thomas' Hospital, London SE1 7EH, England (G.J.R.C., M.S., S.C., V.G.); the Lung Unit (M.E.O., R.P.) and Department of Nuclear Medicine and PET (H.Y.L., B.S., S.C.), the Royal Marsden National Health Service (NHS) Foundation Trust, Sutton, England; and Statsconsultancy, Amersham, Buckinghamshire, England (P.B.)
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De Rosa V, Iommelli F, Monti M, Fonti R, Votta G, Stoppelli MP, Del Vecchio S. Reversal of Warburg Effect and Reactivation of Oxidative Phosphorylation by Differential Inhibition of EGFR Signaling Pathways in Non-Small Cell Lung Cancer. Clin Cancer Res 2015. [PMID: 26216352 DOI: 10.1158/1078-0432.ccr-15-0375] [Citation(s) in RCA: 117] [Impact Index Per Article: 11.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
PURPOSE One of the hallmarks of cancer cells is the excessive conversion of glucose to lactate under normoxic conditions, also known as the Warburg effect. Here, we tested whether the targeted inhibition of EGFR may revert this effect and reactivate mitochondrial oxidative phosphorylation in non-small cell lung cancer (NSCLC). EXPERIMENTAL DESIGN Sensitive (HCC827) and resistant (H1975 and H1993) NSCLC cells were treated with a panel of EGFR or MET inhibitors, and then tested for changes of EGFR signaling, glycolytic cascade, and mitochondrial function. Silencing of key glycolytic enzymes was then performed with targeted siRNAs. Furthermore, tumor-bearing nude mice treated with EGFR inhibitors were evaluated with (18)F-FDG PET/CT and tumors were analyzed for glycolytic and mitochondrial proteins. RESULTS Effective inhibition of EGFR signaling in NSCLC cells induced a dramatic reduction of hexokinase II (HKII) and phospho-pyruvate kinase M2 (p-PKM2, Tyr105) levels as well as an upregulation of mitochondrial complexes subunits (OXPHOS). Accordingly, a decreased lactate secretion and increased intracellular ATP levels were also observed in response to EGFR inhibitors. Downregulation of HKII and PKM2 by targeted siRNA transfection did not cause upregulation of OXPHOS but enhanced the effects of EGFR TKIs. Conversely, selective inhibition of AKT and ERK1/2 caused OXPHOS upregulation and glycolysis inhibition, respectively. Similar findings were obtained in tumors from animals treated with appropriate EGFR inhibitors. CONCLUSIONS Our findings indicate that EGFR inhibitors may reactivate oxidative phosphorylation of cancer cells and provide a mechanistic clue for the rational combination of agents targeting EGFR-dependent proliferation and glucose metabolism in cancer therapy.
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Affiliation(s)
- Viviana De Rosa
- Institute of Biostructures and Bioimages, National Research Council, Naples, Italy
| | - Francesca Iommelli
- Institute of Biostructures and Bioimages, National Research Council, Naples, Italy
| | - Marcello Monti
- Department of Advanced Biomedical Sciences, University of Naples Federico II, Naples, Italy
| | - Rosa Fonti
- Institute of Biostructures and Bioimages, National Research Council, Naples, Italy
| | - Giuseppina Votta
- Institute of Genetics and Biophysics, National Research Council, Naples, Italy
| | | | - Silvana Del Vecchio
- Institute of Biostructures and Bioimages, National Research Council, Naples, Italy. Department of Advanced Biomedical Sciences, University of Naples Federico II, Naples, Italy.
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Prognostic Value Comparison Between 18F-FLT PET/CT and 18F-FDG PET/CT Volume-Based Metabolic Parameters in Patients with Head and Neck Cancer. Clin Nucl Med 2015; 40:464-8. [DOI: 10.1097/rlu.0000000000000652] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/01/2023]
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