References for this review were identified by searches of PubMed using the radiological search terms “MRI”, “magnetic resonance”, “diffusion-weighted MRI”, “DWI”, “dynamic”, “contrast-enhanced”, “DCE-MRI”, “spectroscopy”, “MRS”, “positron emission tomography”, “PET”, and “FDG-PET”, and the oncological search terms “cancer”, “response”, “predict”, and “biomarker”. Only papers published between January, 1987, and August, 2009, were included. Additional articles were identified from the
ReviewUse of new imaging techniques to predict tumour response to therapy
Introduction
The ability to rapidly and accurately predict the response of a tumour to therapy would have immense value in clinical practice. Persisting with ineffective treatment is associated with increased toxic effects and morbidity, accelerated tumour growth, a delay in commencing alternative, potentially effective treatment, and unnecessary expense. Additionally, because of tumour heterogeneity, all cancers of a particular type rarely respond to the recommended therapy,1 emphasising the urgent need for a reliable, accurate, and early predictor of tumour response, which would enable the development of individualised regimens.
Imaging has a fundamental role in oncology, especially in the assessment of tumour response to therapy. By using tumour shrinkage as a standard endpoint of response, current conventional imaging follow-up is based on morphological criteria, with changes in tumour dimension determining response or progression. Unfortunately, this traditional method of quantifying tumour response is hampered by various limitations of using size change as a response variable. For example, observer variation can lead to inaccuracy, and infiltrative, irregular lesions can be difficult or almost impossible to measure. Crucially, changes in gross tumour size are notably delayed and substantially lag behind the biological and molecular changes that are known to occur early in responders.2, 3
New functional and metabolic imaging techniques that have the ability to integrate pathological, physiological, and morphological changes, offer substantial potential as early predictors of therapy response (figure 1). These include diffusion-weighted MRI (DW-MRI), which assesses water motion and tumour cellularity, dynamic contrast-enhanced MRI (DCE-MRI), which assesses the biodistribution of contrast within tumours, magnetic resonance spectroscopy (MRS), which analyses the relative amount of chemical components within biological tissues, and 18-fluorodeoxyglucose-PET ([18F]FDG-PET), which provides an indication of the metabolic and proliferative activity within tumours. Recent advances in the development of these functional techniques have provided an ability to detect microscopic changes in tumour microenvironment and tissue cytoarchitecture, allowing earlier assessment of therapy response by observing alterations in perfusion, oxygenation, and metabolism.
The concept of an imaging biomarker is especially attractive, because it can allow for customised treatment regimens according to the predicted response, and aid the development of improved clinical trials of new therapeutic agents by providing an accurate response indicator. Another appealing factor is the ability of several of these imaging modalities to capture and quantify regional tumour heterogeneity and the changes that occur after treatment. This review aims to highlight the use of these emerging techniques in oncology, with emphasis on the current understanding of their clinical usefulness as predictors or early biomarkers of response.
Section snippets
Diffusion-weighted MRI
DW-MRI is sensitive to the microscopic motion of water molecules, and allows for non-invasive characterisation of biological tissues on the basis of their water-diffusion properties.4, 5 By exploiting information about tissue cellularity and the integrity of cellular membranes, DW-MRI can be used to characterise highly cellular and acellular regions of tumours, distinguish cystic from solid regions, and monitor change in cellularity within the tumour over time, which is reflective of response
Dynamic contrast-enhanced MRI
DCE-MRI has the ability to non-invasively characterise tissue vasculature, including the antiangiogenic response of tumour tissue during therapeutic intervention. By providing additional insight into tumour perfusion and capillary permeability, this technique allows assessment of treatment response more readily than indirect and delayed assessments of tumour size.
Magnetic resonance spectroscopy
MRS is an application of MRI that is able to provide chemical information about tissue metabolites. Whereas conventional MRI offers an illustration of gross anatomy, by detecting the nuclear magnetic resonance spectra of water in tissues, MRS alternatively detects the resonance spectra of chemical compounds except water, allowing for a true representation of the chemical and molecular composition of tissues. Although initially developed for neurological applications, the scope of MRS has been
FDG-PET
PET has the ability to assess tissue metabolism by using radiolabelled molecules to image biological processes in vivo, with most PET imaging studies using [18F]FDG, a glucose analogue. [18F]FDG-PET has been shown to be of value in the differentiation of benign and malignant tissue, preoperative staging, detecting recurrent disease, and, more recently, in the identification of early tumour response to therapy.
Conclusion
Current conventional structural imaging, done at a single timepoint, does not adequately provide information on the likelihood of tumour response to therapeutic intervention, because details on the molecular, physiological, and biological characteristics are not available. This is exemplified by the Response Evaluation Criteria in Solid Tumours (RECIST) criteria for assessing tumour response, which is based only on unidimensional size measurement of a lesion and does not take into account
Search strategy and selection criteria
References (88)
- et al.
Diffusion changes precede size reduction in neoadjuvant treatment of breast cancer
Magn Reson Imaging
(2006) Functional MRI for anticancer therapy assessment
Eur J Cancer
(2002)- et al.
Early increases in breast tumor xenograft water mobility in response to paclitaxel therapy detected by non-invasive diffusion magnetic resonance imaging
Neoplasia
(1999) - et al.
Pretreatment prediction of brain tumors' response to radiation therapy using high b-value diffusion-weighted MRI
Neoplasia
(2004) - et al.
Diffusion MRI for prediction of response of rectal cancer to chemoradiation
Lancet
(2002) - et al.
Tumor microcirculation and diffusion predict therapy outcome for primary rectal carcinoma
Int J Radiat Oncol Biol Phys
(2003) - et al.
Changes in water mobility measured by diffusion MRI predict response of metastatic breast cancer to chemotherapy
Neoplasia
(2004) - et al.
A feasibility study evaluating the functional diffusion map as a predictive imaging biomarker for detection of treatment response in a patient with metastatic prostate cancer to the bone
Neoplasia
(2007) - et al.
The role of functional MR imaging in the assessment of tumor response after chemoembolization in patients with hepatocellular carcinoma
J Vasc Interv Radiol
(2006) - et al.
Diffusion-weighted magnetic resonance imaging allows noninvasive in vivo monitoring of the effects of combretastatin a-4 phosphate after repeated administration
Neoplasia
(2005)
Diffusion-weighted magnetic resonance imaging for monitoring diffusion changes in rectal carcinoma during combined, preoperative chemoradiation: preliminary results of a prospective study
Eur J Radiol
Diffusion-weighted magnetic resonance imaging in the early detection of response to chemoradiation in cervical cancer
Gynecol Oncol
Dynamic enhanced MRI predicts chemosensitivity in breast cancer patients
Eur J Radiol
Dynamic contrast-enhanced magnetic resonance imaging in radiotherapeutic efficacy in the head and neck tumors
Am J Otolaryngol
Tumor perfusion studies using fast magnetic resonance imaging technique in advanced cervical cancer: a new noninvasive predictive assay
Int J Radiat Oncol Biol Phys
Prediction of radiotherapy outcome using dynamic contrast enhanced MRI of carcinoma of the cervix
Int J Radiat Oncol Biol Phys
Prediction of treatment response of head and neck cancers with P-31 MR spectroscopy from pretreatment relative phosphomonoester levels
Acad Radiol
Predicting treatment response in non-Hodgkin's lymphoma from the pretreatment tumor content of phosphoethanolamine plus phosphocholine
Acad Radiol
Measurement of clinical and subclinical tumour response using [18F]-fluorodeoxyglucose and positron emission tomography: review and 1999 EORTC recommendations. European Organization for Research and Treatment of Cancer (EORTC) PET Study Group
Eur J Cancer
18F-FDG uptake as a biologic factor predicting outcome in patients with resected non-small-cell lung cancer
Chin Med J (Engl)
Preoperative 18[F]-fluorodeoxyglucose positron emission tomography standardized uptake values predict survival after oesophageal adenocarcinoma resection
Ann Thorac Surg
Value of complete metabolic response by (18)F-fluorodeoxyglucose-positron emission tomography in oesophageal cancer for prediction of pathologic response and survival after preoperative chemoradiotherapy
Eur J Cancer
F-18 fluorodeoxyglucose uptake in primary cervical cancer as an indicator of prognosis after radiation therapy
Gynecol Oncol
Baseline MRI delivery characteristics predict change in invasive ductal breast carcinoma PET metabolism as a result of primary chemotherapy administration
Ann Oncol
The cellular basis of tumor progression
Int Rev Cytol
Diffusion magnetic resonance imaging: an early surrogate marker of therapeutic efficacy in brain tumors
J Natl Cancer Inst
Diffusion magnetic resonance imaging: a biomarker for treatment response in oncology
J Clin Oncol
Monitoring early response of experimental brain tumors to therapy using diffusion magnetic resonance imaging
Clin Cancer Res
Early detection of response to radiation therapy in patients with brain malignancies using conventional and high b-value diffusion-weighted magnetic resonance imaging
J Clin Oncol
Functional diffusion map: a noninvasive MRI biomarker for early stratification of clinical brain tumor response
Proc Natl Acad Sci USA
Evaluation of the functional diffusion map as an early biomarker of time-to-progression and overall survival in high-grade glioma
Proc Natl Acad Sci USA
Diffusion changes in a tumor and peritumoral tissue after stereotactic irradiation for brain tumors: possible prediction of treatment response
J Comput Assist Tomogr
[Diffusion-weighted MRI—a new parameter for advanced rectal carcinoma?]
Rofo
Preliminary results on the influence of chemoradiation on apparent diffusion coefficients of primary rectal carcinoma measured by magnetic resonance imaging
Strahlenther Onkol
Evaluation of tumour necrosis during chemotherapy with diffusion-weighted MR imaging: preliminary results in osteosarcomas
Pediatr Radiol
Usefulness of diffusion-weighted MRI with echo-planar technique in the evaluation of cellularity in gliomas
J Magn Reson Imaging
Monitoring therapeutic responses of primary bone tumors by diffusion-weighted image: initial results
Eur Radiol
Magnetic resonance imaging and spectroscopy: application to experimental neuro-oncology
Q Magn Reson Biol Med
Combined effect of tumor necrosis factor-related apoptosis-inducing ligand and ionizing radiation in breast cancer therapy
Proc Natl Acad Sci USA
MRI-diffusion imaging of neuroblastomas: first results and correlation to histology
Eur Radiol
In vivo measurement of the apparent diffusion coefficient in normal and malignant prostatic tissue using thin-slice echo-planar imaging
Radiol Med (Torino)
Measurement of the blood-brain barrier permeability and leakage space using dynamic MR imaging. 1. Fundamental concepts
Magn Reson Med
Role of dynamic contrast enhanced MRI in monitoring early response of locally advanced breast cancer to neoadjuvant chemotherapy
Breast Cancer Res Treat
Non-invasive methods of assessing angiogenesis and their value in predicting response to treatment in colorectal cancer
Br J Surg
Cited by (149)
Integration of functional imaging in brachytherapy
2022, Cancer/RadiotherapiePrognostic and therapeutic evaluation of nasopharyngeal carcinoma by dynamic contrast-enhanced (DCE), diffusion-weighted (DW) magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS)
2021, Magnetic Resonance ImagingCitation Excerpt :The recent breakthrough in functional magnetic resonance imaging (fMRI) assessment facilitates close monitoring of tumour physiological changes [6,7]. In addition to acquiring morphological changes, functional MRI monitors therapeutic response and detects persistent tumour by measuring physiological changes in tumour microenvironment [6,8]. Among different functional MRI assessments, dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), diffusion-weighted magnetic resonance imaging (DW-MRI), and magnetic resonance spectroscopy (MRS) are most often described.
Menstruation: science and society
2020, American Journal of Obstetrics and GynecologyFunctional nanostructures for drug resistance breast cancer theranostics
2020, Nanomedicines for Breast Cancer Theranostics