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Bashir U, Weeks A, Goda JS, Siddique M, Goh V, Cook GJ. Measurement of 18F-FDG PET tumor heterogeneity improves early assessment of response to bevacizumab compared with the standard size and uptake metrics in a colorectal cancer model. Nucl Med Commun 2019; 40:611-617. [PMID: 30893213 PMCID: PMC6553522 DOI: 10.1097/mnm.0000000000000992] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2018] [Accepted: 01/24/2019] [Indexed: 12/24/2022]
Abstract
PURPOSE Treatment of metastatic colorectal cancer frequently includes antiangiogenic agents such as bevacizumab. Size measurements are inadequate to assess treatment response to these agents, and newer response assessment criteria are needed. We aimed to evaluate F-FDG PET-derived texture parameters in a preclinical colorectal cancer model as alternative metrics of response to treatment with bevacizumab. MATERIALS AND METHODS Fourteen CD1 athymic mice injected in the flank with 5×106 LS174T cells (human colorectal carcinoma) were either untreated controls (n=7) or bevacizumab treated (n=7). After 2 weeks, mice underwent F-FDG PET/CT. Calliper-measured tumor growth (Δvol) and final tumor volume (Volcal), F-FDG PET metabolically active volume (Volmet), mean metabolism (Metmean), and maximum metabolism (Metmax) were measured. Twenty-four texture features were compared between treated and untreated mice. Immunohistochemical mean tumor vascular density was estimated by anti-CD-34 staining after tumor resection. RESULTS Treated mice had significantly lower tumor vascular density (P=0.032), confirming the antiangiogenic therapeutic effect of bevacizumab. None of the conventional measures were different between the two groups: Δvol (P=0.9), Volcal (P=0.7), Volmet (P=0.28), Metmax (P=0.7), or Metmean (P=0.32). One texture parameter, GLSZM-SZV (visually indicating that the F-FDG PET images of treated mice comprise uniformly sized clusters of different activity) had significantly different means between the two groups of mice (P=0.001). CONCLUSION F-FDG PET derived texture parameters, particularly GLSZM-SZV, may be valid biomarkers of tumor response to treatment with bevacizumab, before change in volume.
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Affiliation(s)
- Usman Bashir
- Department of Radiology, Barts and London NHS Trust
| | - Amanda Weeks
- Department of Cancer Imaging, School of Biomedical Engineering and Imaging Sciences
| | - Jayant S. Goda
- Department of Cancer Imaging, School of Biomedical Engineering and Imaging Sciences
| | - Muhammad Siddique
- Department of Cancer Imaging, School of Biomedical Engineering and Imaging Sciences
| | - Vicky Goh
- Department of Radiology, Barts and London NHS Trust
- Department of Radiology, Guy’s Hospital, London, UK
| | - Gary J. Cook
- Department of Radiology, Barts and London NHS Trust
- PET Imaging Centre and the Division of Imaging Sciences and Biomedical Engineering, King’s College London
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Li W, Quan YY, Li Y, Lu L, Cui M. Monitoring of tumor vascular normalization: the key points from basic research to clinical application. Cancer Manag Res 2018; 10:4163-4172. [PMID: 30323672 PMCID: PMC6175544 DOI: 10.2147/cmar.s174712] [Citation(s) in RCA: 36] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
Tumor vascular normalization alleviates hypoxia in the tumor microenvironment, reduces the degree of malignancy, and increases the efficacy of traditional therapy. However, the time window for vascular normalization is narrow; therefore, how to determine the initial and final points of the time window accurately is a key factor in combination therapy. At present, the gold standard for detecting the normalization of tumor blood vessels is histological staining, including tumor perfusion, microvessel density (MVD), vascular morphology, and permeability. However, this detection method is almost unrepeatable in the same individual and does not dynamically monitor the trend of the time window; therefore, finding a relatively simple and specific monitoring index has important clinical significance. Imaging has long been used to assess changes in tumor blood vessels and tumor changes caused by the oxygen environment in clinical practice; some preclinical and clinical research studies demonstrate the feasibility to assess vascular changes, and some new methods were in preclinical research. In this review, we update the most recent insights of evaluating tumor vascular normalization.
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Affiliation(s)
- Wei Li
- Department of General Surgery, Zhuhai People's Hospital, Jinan University, Zhuhai, Guangdong, People's Republic of China,
| | - Ying-Yao Quan
- Department of Precision Medical Center, Zhuhai People's Hospital, Jinan University, Zhuhai, Guangdong, People's Republic of China
| | - Yong Li
- Department of Intervention, Zhuhai People's Hospital, Jinan University, Zhuhai, Guangdong, People's Republic of China,
| | - Ligong Lu
- Department of Intervention, Zhuhai People's Hospital, Jinan University, Zhuhai, Guangdong, People's Republic of China,
| | - Min Cui
- Department of General Surgery, Zhuhai People's Hospital, Jinan University, Zhuhai, Guangdong, People's Republic of China,
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Heijmen L, Ter Voert EGW, Punt CJA, Heerschap A, Oyen WJG, Bussink J, Sweep CGJ, Laverman P, Span PN, de Geus-Oei LF, Boerman OC, van Laarhoven HWM. Monitoring hypoxia and vasculature during bevacizumab treatment in a murine colorectal cancer model. CONTRAST MEDIA & MOLECULAR IMAGING 2015; 9:237-45. [PMID: 24700751 DOI: 10.1002/cmmi.1564] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/13/2012] [Revised: 07/24/2013] [Accepted: 08/01/2013] [Indexed: 01/17/2023]
Abstract
The purpose of this study was to assess the effect of bevacizumab on vasculature and hypoxia in a colorectal tumor model. Nude mice with subcutaneous LS174T tumors were treated with bevacizumab or saline. To assess tumor properties, separate groups of mice were imaged using (18) F-Fluoromisonidazole (FMISO) and (18) F-Fluorodeoxyglucose (FDG) positron emission tomography or magnetic resonance imaging before and 2, 6 and 10 days after the start of treatment. Tumors were harvested after imaging to determine hypoxia and vascular density immunohistochemically. The T2 * time increased significantly less in the bevacizumab group. FMISO uptake increased more over time in the control group. Vessel density significantly decreased in the bevacizumab-treated group. The Carbonic anhydrase 9 (CAIX) and glucose uptake transporter 1 (GLUT1) fractions were higher in bevacizumab-treated tumors. However, the hypoxic fraction showed no significant difference. Bevacizumab led to shorter T2 * times and higher GLUT1 and CAIX expression, suggesting an increase in hypoxia and a higher glycolytic rate. This could be a mechanism of resistance to bevacizumab. The increase in hypoxia, however, could not be demonstrated by pimonidazole/FMISO, possibly because distribution of these tracers is hampered by bevacizumab-induced effects on vascular permeability and perfusion.
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Affiliation(s)
- L Heijmen
- Department of Medical Oncology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
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De Robertis R, Tinazzi Martini P, Demozzi E, Puntel G, Ortolani S, Cingarlini S, Ruzzenente A, Guglielmi A, Tortora G, Bassi C, Pederzoli P, D’Onofrio M. Prognostication and response assessment in liver and pancreatic tumors: The new imaging. World J Gastroenterol 2015; 21:6794-6808. [PMID: 26078555 PMCID: PMC4462719 DOI: 10.3748/wjg.v21.i22.6794] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/28/2015] [Revised: 03/25/2015] [Accepted: 05/04/2015] [Indexed: 02/06/2023] Open
Abstract
Diffusion-weighted imaging (DWI), dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and perfusion computed tomography (CT) are technical improvements of morphologic imaging that can evaluate functional properties of hepato-bilio-pancreatic tumors during conventional MRI or CT examinations. Nevertheless, the term “functional imaging” is commonly used to describe molecular imaging techniques, as positron emission tomography (PET) CT/MRI, which still represent the most widely used methods for the evaluation of functional properties of solid neoplasms; unlike PET or single photon emission computed tomography, functional imaging techniques applied to conventional MRI/CT examinations do not require the administration of radiolabeled drugs or specific equipments. Moreover, DWI and DCE-MRI can be performed during the same session, thus providing a comprehensive “one-step” morphological and functional evaluation of hepato-bilio-pancreatic tumors. Literature data reveal that functional imaging techniques could be proposed for the evaluation of these tumors before treatment, given that they may improve staging and predict prognosis or clinical outcome. Microscopic changes within neoplastic tissues induced by treatments can be detected and quantified with functional imaging, therefore these techniques could be used also for post-treatment assessment, even at an early stage. The aim of this editorial is to describe possible applications of new functional imaging techniques apart from molecular imaging to hepatic and pancreatic tumors through a review of up-to-date literature data, with a particular emphasis on pathological correlations, prognostic stratification and post-treatment monitoring.
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Correlation of perfusion MRI and 18F-FDG PET imaging biomarkers for monitoring regorafenib therapy in experimental colon carcinomas with immunohistochemical validation. PLoS One 2015; 10:e0115543. [PMID: 25668193 PMCID: PMC4323201 DOI: 10.1371/journal.pone.0115543] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2014] [Accepted: 11/25/2014] [Indexed: 12/15/2022] Open
Abstract
Objectives To investigate a multimodal, multiparametric perfusion MRI / 18F-fluoro-deoxyglucose-(18F-FDG)-PET imaging protocol for monitoring regorafenib therapy effects on experimental colorectal adenocarcinomas in rats with immunohistochemical validation. Materials and Methods Human colorectal adenocarcinoma xenografts (HT-29) were implanted subcutaneously in n = 17 (n = 10 therapy group; n = 7 control group) female athymic nude rats (Hsd:RH-Foxn1rnu). Animals were imaged at baseline and after a one-week daily treatment protocol with regorafenib (10 mg/kg bodyweight) using a multimodal, multiparametric perfusion MRI/18F-FDG-PET imaging protocol. In perfusion MRI, quantitative parameters of plasma flow (PF, mL/100 mL/min), plasma volume (PV, %) and endothelial permeability-surface area product (PS, mL/100 mL/min) were calculated. In 18F-FDG-PET, tumor-to-background-ratio (TTB) was calculated. Perfusion MRI parameters were correlated with TTB and immunohistochemical assessments of tumor microvascular density (CD-31) and cell proliferation (Ki-67). Results Regorafenib significantly (p<0.01) suppressed PF (81.1±7.5 to 50.6±16.0 mL/100mL/min), PV (12.1±3.6 to 7.5±1.6%) and PS (13.6±3.2 to 7.9±2.3 mL/100mL/min) as well as TTB (3.4±0.6 to 1.9±1.1) between baseline and day 7. Immunohistochemistry revealed significantly (p<0.03) lower tumor microvascular density (CD-31, 7.0±2.4 vs. 16.1±5.9) and tumor cell proliferation (Ki-67, 434.0 ± 62.9 vs. 663.0 ± 98.3) in the therapy group. Perfusion MRI parameters ΔPF, ΔPV and ΔPS showed strong and significant (r = 0.67-0.78; p<0.01) correlations to the PET parameter ΔTTB and significant correlations (r = 0.57-0.67; p<0.03) to immunohistochemical Ki-67 as well as to CD-31-stainings (r = 0.49-0.55; p<0.05). Conclusions A multimodal, multiparametric perfusion MRI/PET imaging protocol allowed for non-invasive monitoring of regorafenib therapy effects on experimental colorectal adenocarcinomas in vivo with significant correlations between perfusion MRI parameters and 18F-FDG-PET validated by immunohistochemistry.
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Versleijen-Jonkers YMH, Vlenterie M, van de Luijtgaarden ACM, van der Graaf WTA. Anti-angiogenic therapy, a new player in the field of sarcoma treatment. Crit Rev Oncol Hematol 2014; 91:172-85. [PMID: 24613529 DOI: 10.1016/j.critrevonc.2014.02.001] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2013] [Revised: 12/19/2013] [Accepted: 02/05/2014] [Indexed: 01/12/2023] Open
Abstract
Sarcomas encompass a heterogeneous family of mesenchymal malignancies. In metastatic disease improvement in outcome has been limited and there is a clear need for the development of new therapies. One potential target is angiogenesis, already an accepted target for treatment of more prevalent cancers. Multiple (pre)clinical studies focused on the role of angiogenesis and anti-angiogenic treatment in sarcomas. However, getting significant results is complicated due to the relatively small number of patients and the broad range of sarcoma subtypes. Recently, pazopanib has been approved for the treatment of advanced soft tissue sarcoma patients, which is an important step forward and paves the way for the introduction of anti-angiogenic treatment in sarcomas. However, more studies are needed to understand the biological mechanisms by which patients respond to angiogenic inhibitors and to detect markers of response. This review covers the knowledge that has been gained on the role of angiogenesis and anti-angiogenic therapy in sarcomas.
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Affiliation(s)
- Yvonne M H Versleijen-Jonkers
- Department of Medical Oncology, Radboud University Medical Center, Internal Postal Code 452, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands.
| | - Myrella Vlenterie
- Department of Medical Oncology, Radboud University Medical Center, Internal Postal Code 452, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands.
| | - Addy C M van de Luijtgaarden
- Department of Medical Oncology, Radboud University Medical Center, Internal Postal Code 452, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands.
| | - Winette T A van der Graaf
- Department of Medical Oncology, Radboud University Medical Center, Internal Postal Code 452, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands.
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Rødal J, Rusten E, Søvik Å, Skogmo HK, Malinen E. Functional imaging to monitor vascular and metabolic response in canine head and neck tumors during fractionated radiotherapy. Acta Oncol 2013; 52:1293-9. [PMID: 23879646 DOI: 10.3109/0284186x.2013.812800] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
Abstract
Radiotherapy causes alterations in tumor biology, and non-invasive early assessment of such alterations may become useful for identifying treatment resistant disease. The purpose of the current work is to assess changes in vascular and metabolic features derived from functional imaging of canine head and neck tumors during fractionated radiotherapy. Material and methods. Three dogs with spontaneous head and neck tumors received intensity-modulated radiotherapy (IMRT). Contrast-enhanced cone beam computed tomography (CE-CBCT) at the treatment unit was performed at five treatment fractions. Dynamic (18)FDG-PET (D-PET) was performed prior to the start of radiotherapy, at mid-treatment and at 3-12 weeks after the completion of treatment. Tumor contrast enhancement in the CE-CBCT images was used as a surrogate for tumor vasculature. Vascular and metabolic tumor parameters were further obtained from the D-PET images. Changes in these tumor parameters were assessed, with emphasis on intra-tumoral distributions. Results. For all three patients, metabolic imaging parameters obtained from D-PET decreased from the pre- to the inter-therapy session. Correspondingly, for two of three patients, vascular imaging parameters obtained from both CE-CBCT and D-PET increased. Only one of the tumors showed a clear metabolic response after therapy. No systematic changes in the intra-tumor heterogeneity in the imaging parameters were found. Conclusion. Changes in vascular and metabolic parameters could be detected by the current functional imaging methods. Vascular tumor features from CE-CBCT and D-PET corresponded well. CE-CBCT is a potential method for easy response assessment when the patient is at the treatment unit.
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Affiliation(s)
- Jan Rødal
- Department of Medical Physics, Oslo University Hospital , Oslo , Norway
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The future of NMR metabolomics in cancer therapy: towards personalizing treatment and developing targeted drugs? Metabolites 2013; 3:373-96. [PMID: 24957997 PMCID: PMC3901278 DOI: 10.3390/metabo3020373] [Citation(s) in RCA: 35] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2013] [Revised: 05/07/2013] [Accepted: 05/10/2013] [Indexed: 12/20/2022] Open
Abstract
There has been a recent shift in how cancers are defined, where tumors are no longer simply classified by their tissue origin, but also by their molecular characteristics. Furthermore, personalized medicine has become a popular term and it could start to play an important role in future medical care. However, today, a "one size fits all" approach is still the most common form of cancer treatment. In this mini-review paper, we report on the role of nuclear magnetic resonance (NMR) metabolomics in drug development and in personalized medicine. NMR spectroscopy has successfully been used to evaluate current and potential therapies, both single-agents and combination therapies, to analyze toxicology, optimal dose, resistance, sensitivity, and biological mechanisms. It can also provide biological insight on tumor subtypes and their different responses to drugs, and indicate which patients are most likely to experience off-target effects and predict characteristics for treatment efficacy. Identifying pre-treatment metabolic profiles that correlate to these events could significantly improve how we view and treat tumors. We also briefly discuss several targeted cancer drugs that have been studied by metabolomics. We conclude that NMR technology provides a key platform in metabolomics that is well-positioned to play a crucial role in realizing the ultimate goal of better tailored cancer medicine.
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Heskamp S, Boerman OC, Molkenboer-Kuenen JDM, Oyen WJG, van der Graaf WTA, van Laarhoven HWM. Bevacizumab reduces tumor targeting of antiepidermal growth factor and anti-insulin-like growth factor 1 receptor antibodies. Int J Cancer 2013; 133:307-14. [PMID: 23335047 DOI: 10.1002/ijc.28046] [Citation(s) in RCA: 46] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2012] [Accepted: 12/28/2012] [Indexed: 12/31/2022]
Abstract
Bevacizumab (antivascular endothelial growth factor [anti-VEGF]) and cetuximab (antiepidermal growth factor receptor [anti-EGFR]) are approved antibodies for treatment of cancer. However, in advanced colorectal cancer, the combination fails to improve survival. As the reason for the lack of activity is unknown, our study aims to determine the effect of bevacizumab on targeting of anti-EGFR and insulin-like growth factor 1 receptor (IGF-1R) antibodies in tumors with single-photon emission computed tomography (SPECT)/CT imaging. Mice with subcutaneous EGFR and IGF-1R-expressing SUM149 xenografts received a single dose of bevacizumab (10 mg/kg) or saline. After 4 days, mice were injected with radiolabeled cetuximab or R1507, an anti-IGF-1R antibody. A control group received a radiolabeled irrelevant IgG (hLL2). Three days later, SPECT/CT images were acquired and mice were dissected to determine the concentration of antibodies in the tissues. Tumors were analyzed immunohistochemically to determine vascular density (CD34), VEGF, EGFR and IGF-1R expression. SPECT/CT imaging revealed that bevacizumab treatment significantly reduced tumor targeting of radiolabeled cetuximab by 40% from 33.1 ± 1.1 %ID/g to 19.8 ± 5.7 %ID/g (p = 0.009) for untreated and bevacizumab-treated tumors, respectively. A similar effect was found for (111) In-R1507: tumor targeting of R1507 decreased by 35%. No significant differences in tumor uptake were observed in mice that received an irrelevant IgG. Uptake in normal organs was not altered by bevacizumab. Immunohistochemical analysis showed that vascular density decreased with 43%, whereas EGFR and IGF-1R expression was unaltered. In conclusion, bevacizumab treatment significantly reduces tumor targeting of anti-EGFR and anti-IGF-1R antibodies. This emphasizes the importance of timing and sequencing of bevacizumab in combination with other antibodies.
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Affiliation(s)
- Sandra Heskamp
- Department of Medical Oncology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
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Assessing the in vivo efficacy of biologic antiangiogenic therapies. Cancer Chemother Pharmacol 2012; 71:1-12. [PMID: 23053262 DOI: 10.1007/s00280-012-1978-8] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2012] [Accepted: 09/13/2012] [Indexed: 12/13/2022]
Abstract
PURPOSE To review key clinical issues underlying the assessment of in vivo efficacy when using antiangiogenic therapies for cancer treatment. METHODS Literature relevant to use of antiangiogenic therapies in cancer was reviewed, with particular emphasis on the assessment of in vivo efficacy of these agents, as well as additional angiogenic factors that could play a role in escape from angiogenesis inhibition. RESULTS In order to grow and metastasize, tumors need to continually acquire new blood supplies; therefore, therapeutic inhibition of angiogenesis has become a component of anticancer treatment for many tumor types. Bevacizumab, a humanized monoclonal antibody directed at vascular endothelial growth factor A (VEGF-A), has shown activity in combination with chemotherapy in metastatic colorectal cancer. Nevertheless, the use of antiangiogenic therapies remains suboptimal; specifically, optimal dose, duration of therapy, and combination of agents remain unknown. Also, at present, it is not possible to determine which patients are most likely to respond to a given form of antiangiogenic therapy. There has been increased recognition of alternative pathways possibly associated with disease progression in patients undergoing antiangiogenic therapy targeted at VEGF-A. Multiligand-targeted antiangiogenic therapies, such as ziv-aflibercept (formerly known as aflibercept, VEGF Trap), are currently undergoing clinical evaluation. Ziv-aflibercept forms monomeric complexes with VEGF-A, VEGF-B, and PlGF, which have a long half-life, allowing optimization of ziv-aflibercept doses and angiogenic blockage. CONCLUSIONS Although antiangiogenic therapies have increased treatment options for cancer patients, their use is limited by a lack of established and standardized methodology to evaluate their efficacy in vivo. Circulating endothelial cells, hypertension, and several molecular and imaging-based markers have potential for use as biomarkers in these patients and may better define appropriate patient populations.
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Heijmen L, Verstappen MCHM, Ter Voert EEGW, Punt CJA, Oyen WJG, de Geus-Oei LF, Hermans JJ, Heerschap A, van Laarhoven HWM. Tumour response prediction by diffusion-weighted MR imaging: ready for clinical use? Crit Rev Oncol Hematol 2012; 83:194-207. [PMID: 22269446 DOI: 10.1016/j.critrevonc.2011.12.008] [Citation(s) in RCA: 52] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/02/2011] [Revised: 12/06/2011] [Accepted: 12/28/2011] [Indexed: 12/16/2022] Open
Abstract
BACKGROUND The efficacy of anticancer therapy is usually evaluated by anatomical imaging. However, this method may be suboptimal for the evaluation of novel treatment modalities, such as targeted therapy. Theoretically, functional assessment of tumour response by diffusion weighted imaging (DWI) is an attractive tool for this purpose and may allow an early prediction of response. The optimal use of this method has still to be determined. METHOD We reviewed the published literature on clinical DWI in the prediction of response to anticancer therapy, especially targeted therapy. Studies investigating the role of DWI in patients with cancer either for response prediction and/or response monitoring were selected for this analysis. RESULTS We identified 24 studies that met our criteria. Most studies showed a significant correlation between (changes in) apparent diffusion coefficient (ADC) values and treatment response. However, in different tumours and studies, both high and low pretreatment ADC were found to be associated with response rate. In the course of treatment, an increase in ADC was associated with response in most cases. CONCLUSION The potential of DWI for (early) response monitoring of anticancer therapies has been demonstrated. However, validation is hampered by the lack of reproducibility and standardisation. We recommend that these issues should be properly addressed prior to further testing the clinical use of DWI in the assessment of treatments.
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Affiliation(s)
- Linda Heijmen
- Department of Medical Oncology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
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