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Evidence-based medicine and clinical fluorodeoxyglucose PET/MRI in oncology. - Cancer imaging : the official publication of the International Cancer Imaging Society
Positron Emission Tomography/Magnetic Resonance Imaging (PET/MRI) is a hybrid of two technologies each with its own evidence for clinical effectiveness. This article amalgamates evidence for clinical effectiveness of fluorodeoxyglucose (FDG) PET/CT and MRI as separate modalities with current evidence for hybrid PET/MRI and considers whether such an approach might provide a stronger case for the clinical use of PET/MRI at an earlier stage.Because links between diagnostic accuracy and health outcomes have already been established for FDG-PET/CT in the investigation of suspected residual or recurrent malignancies, evidence showing improved diagnostic performance and therapeutic impact from the use of PET/MRI as an alternative would imply clinical effectiveness of this modality for this application. A meta-analysis of studies comparing FDG-PET/CT to MRI in patients with suspected residual disease or recurrence of tumours indicates complementary roles for these modalities. PET demonstrates greater sensitivity for recurrence within lymph nodes whereas MRI is more effective that PET/CT in the detection of skeletal and hepatic recurrence. A review of studies assessing therapeutic impact of PET/MRI suggests a greater likelihood for change in clinical management when PET/MRI is used for assessment of suspected residual or recurrent disease rather than tumour staging.Supplementing the evidence-base for FDG-PET/MRI with studies that compare the components of this hybrid technology deployed separately indicates that FDG-PET/MRI is likely to be clinical effective for the investigation of patients with a range of suspected residual or recurrent cancers. This indication should therefore be prioritised for further health technology assessment.
Gallium-68 PSMA uptake in adrenal adenoma. - Journal of medical imaging and radiation oncology
Gallium-68 (Ga-68) labelled prostate-specific membrane antigen (PSMA) imaging by positron emission tomography (PET) has emerged as a promising tool for staging of prostate cancer and restaging of disease in recurrence or biochemical failure after definitive treatment of prostate cancer. Ga-68 PSMA PET produces high target-to-background images of prostate cancer and its metastases which are reflective of the significant overexpression of PSMA in these cells and greatly facilitates tumour detection. However, relatively little is known about the PSMA expression of benign neoplasms and non-prostate epithelial malignancies. This is a case report of PSMA uptake in an adrenal adenoma incidentally discovered on PET performed for restaging of biochemically suspected prostate cancer recurrence. With the increasing use of PSMA PET in the management of prostate cancer - and the not infrequent occurrence of adrenal adenomas - the appearance of low- to moderate-grade PSMA uptake in adrenal adenomas should be one with which reporting clinicians are familiar.Â© 2015 The Royal Australian and New Zealand College of Radiologists.
Old tracer for a new purpose: potential role for 99mTc-2-Methoxyisobutylisonitrile (99mTc-MIBI) in renal transplant care. - Nuclear medicine communications
Calcineurin inhibitors are substrates for P-glycoprotein (P-gp), the expression of which is associated with ABCB1 C3435T polymorphism. Individual P-gp response to calcineurin inhibitor may be linked to nephrotoxicity or rejection. Tc-2-Methoxyisobutylisonitrile (Tc-MIBI) is also a P-gp substrate. The aim of this study, therefore, was to determine Tc-MIBI organ kinetics and compare them with ABCB1 genotype with a view to replacing Tc-mercaptoacetyltriglycine (Tc-MAG3) with Tc-MIBI in renal transplant care.Thirty prospective donors (13 male) were imaged for 20 min after administration of Tc-MIBI (400 MBq) intravenously. Posterior images of the abdomen were acquired at 30 and 120 min. Organ 30 min/peak count rate ratios and exponential two-point (30-120 min) rate constants (k, min) were calculated. Nineteen donors were genotyped for C3435T (exon 26), G2677T (exon 21), C1236T (exon 12), and G1199A (exon 11) ABCB1 polymorphisms using a PCR-based technique.Tc-MIBI and Tc-MAG3 gave similar perfusion images. Although their patterns of renal elimination were different, differential renal function was not significantly different. There was a negative trend between the hepatic 30 min/peak ratio and C3435T genotype (CC: 0.8374 Â± 0.0502; TC: 0.6806 Â± 0.1300; TT: 0.6919 Â± 0.1506; P=0.083). Renal k showed a negative trend with C3435T (CC: 0.0021 Â± 0.0020; TC: 0.0037 Â± 0.0013; TT: 0.0040 Â± 0.0012 min; P=0.087) but with no other genotypes. There were no significant sex-related differences in Tc-MIBI kinetics.Tc-MIBI can replace Tc-MAG3 for pretransplant workup. The ABCB1 C3435T polymorphism may influence Tc-MIBI kinetics and thus have a role in renal transplant care. Further prospective trials are required to establish the full potential of Tc-MIBI in renal transplant management.
Noninvasive image texture analysis differentiates K-ras mutation from pan-wildtype NSCLC and is prognostic. - PloS one
Non-invasive characterization of a tumor's molecular features could enhance treatment management. Quantitative computed tomography (CT) based texture analysis (QTA) has been used to derive tumor heterogeneity information, and the appearance of the tumors has been shown to relate to patient outcome in non-small cell lung cancer (NSCLC) and other cancers. In this study, we examined the potential of tumoral QTA to differentiate K-ras mutant from pan-wildtype tumors and its prognostic potential using baseline pre-treatment non-contrast CT imaging in NSCLC.Tumor DNA from patients with early-stage NSCLC was analyzed on the LungCarta Panel. Cases with a K-ras mutation or pan-wildtype for 26 oncogenes and tumor suppressor genes were selected for QTA. QTA was applied to regions of interest in the primary tumor. Non-parametric Mann Whitney test assessed the ability of the QTA, clinical and patient characteristics to differentiate between K-ras mutation from pan-wildtype. A recursive decision tree was developed to determine whether the differentiation of K-ras mutant from pan-wildtype tumors could be improved by sequential application of QTA parameters. Kaplan-Meier survival analysis assessed the ability of these markers to predict survival.QTA was applied to 48 cases identified, 27 had a K-ras mutation and 21 cases were pan-wildtype. Positive skewness and lower kurtosis were significantly associated with the presence of a K-ras mutation. A five node decision tree had sensitivity, specificity, and accuracy values (95% CI) of 96.3% (78.1-100), 81.0% (50.5-97.4), and 89.6% (72.9-97.0); respectively. Kurtosis was a significant predictor of OS and DFS, with a lower kurtosis value linked with poorer survival.Lower kurtosis and positive skewness are significantly associated with K-ras mutations. A QTA feature such as kurtosis is prognostic for OS and DFS. Non-invasive QTA can differentiate the presence of K-ras mutation from pan-wildtype NSCLC and is associated with patient survival.
Multifunctional imaging signature for V-KI-RAS2 Kirsten rat sarcoma viral oncogene homolog (KRAS) mutations in colorectal cancer. - Journal of nuclear medicine : official publication, Society of Nuclear Medicine
This study explores the potential for multifunctional imaging to provide a signature for V-KI-RAS2 Kirsten rat sarcoma viral oncogene homolog (KRAS) gene mutations in colorectal cancer.This prospective study approved by the institutional review board comprised 33 patients undergoing PET/CT before surgery for proven primary colorectal cancer. Tumor tissue was examined histologically for presence of the KRAS mutations and for expression of hypoxia-inducible factor-1 (HIF-1) and minichromosome maintenance protein 2 (mcm2). The following imaging parameters were derived for each tumor: (18)F-FDG uptake ((18)F-FDG maximum standardized uptake value [SUVmax]), CT texture (expressed as mean of positive pixels [MPP]), and blood flow measured by dynamic contrast-enhanced CT. A recursive decision tree was developed in which the imaging investigations were applied sequentially to identify tumors with KRAS mutations. Monte Carlo analysis provided mean values and 95% confidence intervals for sensitivity, specificity, and accuracy.The final decision tree comprised 4 decision nodes and 5 terminal nodes, 2 of which identified KRAS mutants. The true-positive rate, false-positive rate, and accuracy (95% confidence intervals) of the decision tree were 82.4% (63.9%-93.9%), 0% (0%-10.4%), and 90.1% (79.2%-96.0%), respectively. KRAS mutants with high (18)F-FDG SUVmax and low MPP showed greater frequency of HIF-1 expression (P = 0.032). KRAS mutants with low (18)F-FDG SUV(max), high MPP, and high blood flow expressed mcm2 (P = 0.036).Multifunctional imaging with PET/CT and recursive decision-tree analysis to combine measurements of tumor (18)F-FDG uptake, CT texture, and perfusion has the potential to identify imaging signatures for colorectal cancers with KRAS mutations exhibiting hypoxic or proliferative phenotypes.
CT texture analysis using the filtration-histogram method: what do the measurements mean? - Cancer imaging : the official publication of the International Cancer Imaging Society
Analysis of texture within tumours on computed tomography (CT) is emerging as a potentially useful tool in assessing prognosis and treatment response for patients with cancer. This article illustrates the image and histological features that correlate with CT texture parameters obtained from tumours using the filtration-histogram approach, which comprises image filtration to highlight image features of a specified size followed by histogram analysis for quantification. Computer modelling can be used to generate texture parameters for a range of simple hypothetical images with specified image features. The model results are useful in explaining relationships between image features and texture parameters. The main image features that can be related to texture parameters are the number of objects highlighted by the filter, the brightness and/or contrast of highlighted objects relative to background attenuation, and the variability of brightness/contrast of highlighted objects. These relationships are also demonstrable by texture analysis of clinical CT images. The results of computer modelling may facilitate the interpretation of the reported associations between CT texture and histopathology in human tumours. The histogram parameters derived during the filtration-histogram method of CT texture analysis have specific relationships with a range of image features. Knowledge of these relationships can assist the understanding of results obtained from clinical CT texture analysis studies in oncology.
Predicting tumour response. - Cancer imaging : the official publication of the International Cancer Imaging Society
Response prediction is an important emerging concept in oncologic imaging, with tailored, individualized treatment regimens increasingly becoming the standard of care. This review aims to define tumour response and illustrate the ways in which imaging techniques can demonstrate tumour biological characteristics that provide information on the likely benefit to be received by treatment. Two imaging approaches are described: identification of therapeutic targets and depiction of the treatment-resistant phenotype. The former approach is exemplified by the use of radionuclide imaging to confirm target expression before radionuclide therapy but with angiogenesis imaging and imaging correlates for genetic response predictors also demonstrating potential utility. Techniques to assess the treatment-resistant phenotype include demonstration of hypoperfusion with dynamic contrast-enhanced computed tomography and magnetic resonance imaging (MRI), depiction of necrosis with diffusion-weighted MRI, imaging of hypoxia and tumour adaption to hypoxia, and 99mTc-MIBI imaging of P-glycoprotein mediated drug resistance. To date, introduction of these techniques into clinical practice has often been constrained by inadequate cross-validation of predictive criteria and lack of verification against appropriate response end points such as survival. With further refinement, imaging predictors of response could play an important role in oncology, contributing to individualization of therapy based on the specific tumour phenotype. This ability to predict tumour response will have implications for improving efficacy of treatment, cost-effectiveness and omission of futile therapy.
Incorporating prognostic imaging biomarkers into clinical practice. - Cancer imaging : the official publication of the International Cancer Imaging Society
A prognostic imaging biomarker can be defined as an imaging characteristic that is objectively measurable and provides information on the likely outcome of the cancer disease in an untreated individual and should be distinguished from predictive imaging biomarkers and imaging markers of response. A range of tumour characteristics of potential prognostic value can be measured using a variety imaging modalities. However, none has currently been adopted into routine clinical practice. This article considers key examples of emerging prognostic imaging biomarkers and proposes an evaluation framework that aims to demonstrate clinical efficacy and so support their introduction into the clinical arena. With appropriate validation within an established evaluation framework, prognostic imaging biomarkers have the potential to contribute to individualized cancer care, in some cases reducing the financial burden of expensive cancer treatments by facilitating their more rational use.
Combined (99m)Tc-methoxyisobutylisonitrile scintigraphy and fine-needle aspiration cytology offers an accurate and potentially cost-effective investigative strategy for the assessment of solitary or dominant thyroid nodules. - European journal of nuclear medicine and molecular imaging
Fine-needle aspiration (FNA) has revolutionised the care of patients with thyroid nodules and is the initial investigation of choice. However, as a result of nondiagnostic (Thy1) and nonneoplastic (Thy2) specimens, it remains an imperfect sole solution with a range of sensitivities and a high inadequate ratio. Therefore the British Thyroid Association (BTA) guidelines recommend a second FNA immediately for Thy1 specimens and 3-6 months later for Thy2 specimens. Patients must be followed up to exclude malignancy. In this study we assessed the performance of MIBI scintigraphy for diagnosing thyroid malignancy and the cost-effectiveness of a combined FNA/MIBI investigative strategy for the management of thyroid nodules.The diagnostic performance of MIBI scintigraphy was calculated from a retrospective review of local data combined with a meta-analysis of the published literature. Decision tree analysis was used to calculate the cost-effectiveness of a combined FNA/MIBI investigative strategy compared to the BTA guidelines.From 712 patients, the sensitivity, specificity, PPV and NPV of MIBI scintigraphy for the diagnosis of malignancy were 96 %, 46 %, 34 % and 97 %, respectively. MIBI-based strategies were more accurate and associated with lower cost per patient (Â£1,855/
2,125 vs. Â£2,445/ 2,801) and lower cost per cancer diagnosed (Â£1,902/ 2,179 vs. Â£2,469/ 2,828) with negligible change in life expectancy.Due to its high NPV, MIBI scintigraphy can usefully exclude malignancy for Thy1 and Thy2 lesions. Its low specificity means MIBI scintigraphy cannot be recommended as a first-line investigation, but as a second-line investigation MIBI scintigraphy may lead to a lower rate of unnecessary thyroidectomies. Combined FNA/MIBI strategies are potentially cost-effective in the management of solitary or dominant thyroid nodules.
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