[Show abstract][Hide abstract] ABSTRACT: Recent advances in imaging, use of prognostic indices, and molecular profiling techniques have the potential to improve disease characterization and outcomes in lymphoma. International trials are under way to test image-based response-adapted treatment guided by early interim positron emission tomography (PET) -computed tomography (CT). Progress in imaging is influencing trial design and affecting clinical practice. In particular, a five-point scale to grade response using PET-CT, which can be adapted to suit requirements for early- and late-response assessment with good interobserver agreement, is becoming widely used both in practice- and response-adapted trials. A workshop held at the 11th International Conference on Malignant Lymphomas (ICML) in 2011 concluded that revision to current staging and response criteria was timely.
Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 08/2014;
[Show abstract][Hide abstract] ABSTRACT: The purpose of this work was to modernize recommendations for evaluation, staging, and response assessment of patients with Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL). A workshop was held at the 11th International Conference on Malignant Lymphoma in Lugano, Switzerland, in June 2011, that included leading hematologists, oncologists, radiation oncologists, pathologists, radiologists, and nuclear medicine physicians, representing major international lymphoma clinical trials groups and cancer centers. Clinical and imaging subcommittees presented their conclusions at a subsequent workshop at the 12th International Conference on Malignant Lymphoma, leading to revised criteria for staging and of the International Working Group Guidelines of 2007 for response. As a result, fluorodeoxyglucose (FDG) positron emission tomography (PET)-computed tomography (CT) was formally incorporated into standard staging for FDG-avid lymphomas. A modification of the Ann Arbor descriptive terminology will be used for anatomic distribution of disease extent, but the suffixes A or B for symptoms will only be included for HL. A bone marrow biopsy is no longer indicated for the routine staging of HL and most diffuse large B-cell lymphomas. However, regardless of stage, general practice is to treat patients based on limited (stages I and II, nonbulky) or advanced (stage III or IV) disease, with stage II bulky disease considered as limited or advanced disease based on histology and a number of prognostic factors. PET-CT will be used to assess response in FDG-avid histologies using the 5-point scale. The product of the perpendicular diameters of a single node can be used to identify progressive disease. Routine surveillance scans are discouraged. These recommendations should improve evaluation of patients with lymphoma and enhance the ability to compare outcomes of clinical trials.
Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 08/2014;
[Show abstract][Hide abstract] ABSTRACT: Quantitative size, shape, and texture features derived from computed tomographic (CT) images may be useful as predictive, prognostic, or response biomarkers in non-small cell lung cancer (NSCLC). However, to be useful, such features must be reproducible, non-redundant, and have a large dynamic range. We developed a set of quantitative three-dimensional (3D) features to describe segmented tumors and evaluated their reproducibility to select features with high potential to have prognostic utility. Thirty-two patients with NSCLC were subjected to unenhanced thoracic CT scans acquired within 15 min of each other under an approved protocol. Primary lung cancer lesions were segmented using semi-automatic 3D region growing algorithms. Following segmentation, 219 quantitative 3D features were extracted from each lesion, corresponding to size, shape, and texture, including features in transformed spaces (laws, wavelets). The most informative features were selected using the concordance correlation coefficient across test-retest, the biological range and a feature independence measure. There were 66 (30.14 %) features with concordance correlation coefficient ≥ 0.90 across test-retest and acceptable dynamic range. Of these, 42 features were non-redundant after grouping features with R (2) Bet ≥ 0.95. These reproducible features were found to be predictive of radiological prognosis. The area under the curve (AUC) was 91 % for a size-based feature and 92 % for the texture features (runlength, laws). We tested the ability of image features to predict a radiological prognostic score on an independent NSCLC (39 adenocarcinoma) samples, the AUC for texture features (runlength emphasis, energy) was 0.84 while the conventional size-based features (volume, longest diameter) was 0.80. Test-retest and correlation analyses have identified non-redundant CT image features with both high intra-patient reproducibility and inter-patient biological range. Thus making the case that quantitative image features are informative and prognostic biomarkers for NSCLC.
Journal of Digital Imaging 07/2014; · 1.10 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Quantitative biomarkers from medical images are becoming important tools for clinical diagnosis, staging, monitoring, treatment planning, and development of new therapies. While there is a rich history of the development of quantitative imaging biomarker (QIB) techniques, little attention has been paid to the validation and comparison of the computer algorithms that implement the QIB measurements. In this paper we provide a framework for QIB algorithm comparisons. We first review and compare various study designs, including designs with the true value (e.g. phantoms, digital reference images, and zero-change studies), designs with a reference standard (e.g. studies testing equivalence with a reference standard), and designs without a reference standard (e.g. agreement studies and studies of algorithm precision). The statistical methods for comparing QIB algorithms are then presented for various study types using both aggregate and disaggregate approaches. We propose a series of steps for establishing the performance of a QIB algorithm, identify limitations in the current statistical literature, and suggest future directions for research.
Statistical Methods in Medical Research 06/2014; · 2.36 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The cut-off values currently used to categorize tumor response to therapy are neither biologically based nor tailored for measurement reproducibility with contemporary imaging modalities. Sources and magnitudes of discordance in response assessment in metastatic colorectal cancer (mCRC) are unknown.
A subset of patients' CT images of chest, abdomen and pelvis were randomly chosen from a multi-center clinical trial evaluating IGF-1R targeted therapy in mCRC. Using Response Evaluation Criteria in Solid Tumors (RECIST), three radiologists selected target lesions and measured UNI (maximal diameter), BI (product of maximal diameter and maximal perpendicular diameter) and VOL (volume) on baseline and 6-week post-therapy scans in the following ways: (1) each radiologist independently selected and measured target lesions and (2) one radiologist's target lesions were blindly re-measured by the others. Variability in relative change of tumor measurements was analyzed using linear mixed effects models.
Three radiologists independently selected 138, 101 and 146 metastatic target lesions in the liver, lungs, lymph nodes and other organs (e.g., peritoneal cavity) in 29 patients. Of 198 target lesions total, 33% were selected by all three, 28% by two, and 39% by one radiologist. With independent selection, the variability in relative change of tumor measurements was 11% (UNI), 19% (BI) and 22% (VOL), respectively. When measuring the same lesions, the corresponding numbers were 8%, 14% and 12%.
The relatively low variability in change of mCRC measurements suggests that response criteria could be modified to allow more accurate and sensitive CT assessment of anti-cancer therapy efficacy.
Clinical Cancer Research 04/2014; · 7.84 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: In conjunction with biomarkers, imaging is an important component of the diagnostic work up and subsequent management of men with prostate cancer.
The relevant literature was retrieved from a search of MEDLINE with appropriate key words.
Osseous metastases develop in close to 90% of patients with metastatic prostate cancer, thus making bone scans (single photon, using Tc-99m labeled phosphonates) the mainstay of imaging in advanced prostate cancer. Bone scans are limited by their lack of specificity and an unclear relationship between bone scan changes and disease progression or response to therapy. In addition to Tc-99m bone scans, other technologies that accurately identify of sites of active disease would considerably aid castration resistant prostate cancer (CRPC) management. Accordingly, metabolic imaging, cell surface receptor targeting, and magnetic resonance imaging (MRI) are being studied for their role in evaluating metastatic disease. Due to the increasing availability of advanced imaging modalities, the optimal modality and appropriate clinical time point for its use remains unclear.
A number of imaging modalities are currently or imminently available for use in advanced prostate cancer. Future research will focus on the appropriate incorporation of these modalities in prostate cancer management.
The Canadian Journal of Urology 04/2014; 21(2 Supp 1):42-7. · 0.74 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: For patients with unresectable intrahepatic cholangiocarcinoma (ICC), treatment options are limited and survival is poor. This study summarizes the long-term outcome of two previously reported clinical trials using hepatic arterial infusion (HAI) with floxuridine and dexamethasone (with or without bevacizumab) in advanced ICC.
Prospectively collected clinicopathologic and survival data were retrospectively reviewed. Response was based on Response Evaluation Criteria in Solid Tumors (RECIST). Pre-HAI dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) images were reviewed, and tumor perfusion data correlated with outcome.
Forty-four patients were analyzed (floxuridine, 26; floxuridine/bevacizumab, 18). At a median follow-up of 29.3 months, 41 patients had died of disease. Partial response by RECIST was observed in 48 %, and 50 % had stable disease. Three patients underwent resection after response, and 82 % received additional HAI after removal from the trials. Median survival was similar in both trials (floxuridine 29.3 months vs. floxuridine/bevacizumab 28.5 months; p = 0.96). Ten (23 %) patients survived ≥3 years, including 5 (11 %) who survived ≥5 years. Tumor perfusion measured on pre-treatment DCE-MRI [area under the gadolinium concentration curve at 90 and 180 s (AUC90 and AUC180, respectively)] was significantly higher in ≥3-year survivors and was the only factor that distinguished this group from <3-year survivors (mean AUC90 22.6 vs. 15.9 mM s, p = 0.025, and mean AUC180 48.9 vs. 32.3 mM s, p = 0.003, respectively). Median hepatic progression-free survival was longer in ≥3-year survivors (12.9 vs. 9.3 months, respectively; p = 0.008).
HAI chemotherapy can result in prolonged survival in unresectable ICC. Pre-HAI DCE-MRI may predict treatment outcome.
Annals of Surgical Oncology 03/2014; · 4.12 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Lung cancer often coexists with acute and chronic lung diseases such as chronic obstructive pulmonary disease. Therefore, mediastinal lymph nodes may be false-positive on (18)F-FDG PET because of the inflammatory disease alone. Nevertheless, (18)F-FDG PET/CT is the primary imaging modality used for staging patients with lung cancer, including nodal status. The purpose of this study was to evaluate whether volumetric CT histogram analysis can improve the characterization of lymph nodes on PET/CT staging of patients with lung cancer.
Sixty histologically proven lymph nodes of 45 patients aged 43-76 y diagnosed with lung cancer were investigated. (18)F-FDG PET/CT, contrast-enhanced CT, and nonenhanced CT were performed before surgery or biopsy as part of the clinical staging procedure. Lymph nodes were analyzed on the basis of the (18)F-FDG standardized uptake value and volumetric CT histogram analysis. These findings were correlated to the gold standard of histopathology.
Histologic examination revealed 36 positive and 24 negative lymph nodes, which were also successfully analyzed by volumetric CT histogram. Median CT density was significantly higher for histologically positive lymph nodes (33.2 Hounsfield units [HU]; range, -29.8 to 59.1) than for histologically negative lymph nodes (10.1 HU; range, -21.0 to 87.4; P = 0.002). The incidence of malignancy was 88% above a cutoff value of 20 HU in the ten (18)F-FDG-equivocal lymph nodes; the incidence of benign findings was 100% in the interval between -20 and +20 HU. Visual- and density-based analysis on contrast-enhanced CT failed to differentiate affected from nonaffected lymph nodes.
Three-dimensional histogram analysis is a promising and potentially valuable imaging surrogate for N-stage stratification in patients with lung cancer with unclear glucose uptake during (18)F-FDG PET imaging. In cases of equivocal (18)F-FDG PET status, this technique might potentially bridge the diagnostic gap between noninvasive techniques and invasive lymph node sampling and could help improve the yield of core biopsies.
Journal of Nuclear Medicine 02/2014; · 5.77 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To explore the effects of computed tomography (CT) slice thickness and reconstruction algorithm on quantification of image features to characterize tumors using a chest phantom.
Twenty-two phantom lesions of known sizes (10 and 20 mm), shapes (spherical, elliptical, lobulated, and spiculated), and densities [-630, -10, and +100 Hounsfield Unit (HU)] were inserted into an anthropomorphic thorax phantom and scanned three times with relocations. The raw data were reconstructed using six imaging settings, i.e., a combination of three slice thicknesses of 1.25, 2.5, and 5 mm and two reconstruction kernels of lung and standard. Lesions were segmented and 14 image features representing lesion size, shape, and texture were calculated. Differences in the measured image features due to slice thickness and reconstruction algorithm were compared using linear regression method by adjusting three confounding variables (size, density, and shape).
All 14 features were significantly different between 1.25 and 5 mm slice images. The 1.25 and 2.5 mm slice thicknesses were better than 5 mm for volume, density mean, density SD gray-level co-occurrence matrix (GLCM) energy and homogeneity. As for the reconstruction algorithm, there was no significant difference in uni-dimension, volume, shape index 9, and compactness. Lung reconstruction was better for density mean, whereas standard reconstruction was better for density SD.
CT slice thickness and reconstruction algorithm can significantly affect the quantification of image features. Thinner (1.25 and 2.5 mm) and thicker (5 mm) slice images should not be used interchangeably. Sharper and smoother reconstructions significantly affect the density-based features.
[Show abstract][Hide abstract] ABSTRACT: LEARNING OBJECTIVES
1) To understand the role and value of quantitative volumes in oncology. 2) To understand the challenges associated with quantitative volume calculations in oncology.
Radiological Society of North America 2013 Scientific Assembly and Annual Meeting; 12/2013
[Show abstract][Hide abstract] ABSTRACT: PURPOSE
Radiogenomics promises the genetic assessment of cancer patients with non-invasive radiographic imaging studies. To date, little attention has been paid to the sensitivity of imaging features to repeat scans and acquisition parameters. This study explored the reproducibility of imaging features computed on repeat CT scans reconstructed at different parameters.
METHOD AND MATERIALS
This study included a retrospective dataset containing 32 lung cancer patients, each having two same-day repeat CT scans and reconstructed into 6 image series, i.e., a combination of 3 slice intervals (5, 2.5 and 1.25mm) and 2 reconstruction algorithms [Lung (L) and Standard (S)]. Three radiologists independently used an in-house algorithm to segment 32 tumors (≥ 1 cm; one per patient) in all image series. 261 imaging features describing tumor size, histogram, shape, edge and texture were computed from the final tumor volumes, based on the common volumes obtained by 2 out of the 3 radiologists. The concordance correlation coefficient (CCC) was used to measure the agreement between each feature computed from two repeat scans reconstructed at the 6 series, i.e., 1.25L (first scan) &1.25L (second scan), 1.25S&1.25S, 2.5L&2.5L, 2.5S&2.5S, 5L&5L and 5S&5S.
Out of the 261 features, CCC of 32 features were ≥ 0.95 and of 169 features were ≥ 0.75 for all 6 series. Size and histogram features were highly reproducible for all parameter settings; shape index and boundary gradient strength were the least reproducible. For 2.5S&2.5S re-scans, all run-length, GTDM and spatial correlation features had CCC≥0.95; surprisingly, many features showed inferior reproducibility with 1.25L&1.25L re-scans, possibly due to noise.
Imaging parameters and repeat scans affect the reproducibility of imaging features to various degrees. Generally, the reproducibility of size, histogram, GTDM, run-length, spatial correlation, Laws', Gabor, wavelet, LoG and GLCM features (except 1.25L&1.25L for several features) at all parameter combinations ranged from acceptable (CCC≥0.75) to excellent (CCC≥0.95). The correlation of these features to gene expression warrants further investigation.
Precautions should be taken with regard to CT imaging acquisition parameters when conducting radiogenomics studies.
Radiological Society of North America 2013 Scientific Assembly and Annual Meeting; 12/2013
[Show abstract][Hide abstract] ABSTRACT: Background:Pazopanib achieved the end point of clinical activity in pretreated patients with urothelial cancer in a single-group, phase 2 trial. The objective was to identify biological predictors of clinical benefit to pazopanib in these patients.Methods:EDTA blood samples were collected at baseline (T0) and after 4 weeks (T1) of treatment, together with radiological imaging in all 41 patients to analyse plasma circulating angiogenic factor levels by multiplex ELISA plates. Changes from T0 to T1 in marker levels were matched with response with the covariance analysis. Univariable and multivariable analyses evaluated the association with overall survival (OS), adjusted for prespecified clinical variables. Net reclassification improvement (NRI) tested the performance of the recognised Cox model.Results:Increasing IL8(T1) level associated with lower response probability at covariance analysis (P=0.010). Both IL8(T0) (P=0.019) and IL8(T1) (P=0.004) associated with OS and the prognostic model, including clinical variables and IL8(T1) best-predicted OS after backward selection. The NRI for this model was 39%.When analysed as a time-varying covariate, IL8(T1) level<80 pg ml(-1) portended significantly greater response (∼80%) and 6-month OS (∼60%) probability than level80.Conclusion:IL8-level changes during pazopanib allowed for a prognostic improvement and were associated with response probability.British Journal of Cancer advance online publication, 14 November 2013; doi:10.1038/bjc.2013.719 www.bjcancer.com.
British Journal of Cancer 11/2013; · 5.08 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To explore whether pre-reoperative dynamic contrast-enhanced (DCE)-MRI findings correlate with clinical outcome in patients who undergo surgical treatment for recurrent rectal carcinoma.
A retrospective study of DCE-MRI in patients with recurrent rectal cancer was performed after obtaining an IRB waiver. We queried our PACS from 1998 to 2012 for examinations performed for recurrent disease. Two radiologists in consensus outlined tumour regions of interest on perfusion images. We explored the correlation between K(trans), Kep, Ve, AUC90 and AUC180 with time to re-recurrence of tumour, overall survival and resection margin status. Univariate Cox PH models were used for survival, while univariate logistic regression was used for margin status.
Among 58 patients with pre-treatment DCE-MRI who underwent resection, 36 went directly to surgery and 18 had positive margins. K(trans) (0.55, P = 0.012) and Kep (0.93, P = 0.04) were inversely correlated with positive margins. No significant correlations were noted between K(trans), Kep, Ve, AUC90 and AUC180 and overall survival or time to re-recurrence of tumour.
K(trans) and Kep were significantly associated with clear resection margins; however overall survival and time to re-recurrence were not predicted. Such information might be helpful for treatment individualisation and deserves further investigation.
• Morphological MRI features are not sufficiently predictive of complete rectal tumour resection. • Survival and time to re-recurrence of tumour were not predicted by DCE-MRI. • But perfusion data from dynamic enhanced MRI may provide more helpful information. • Ktrans/Kep were shown to be significantly associated with clear resection margins. • Functional information from DCE-MRI might be helpful for treatment individualisation.
[Show abstract][Hide abstract] ABSTRACT: Aim: Radiopeptide therapy with beta emitter labeled (177)Lu/(90)Y- DOTA(0)-Phe(1)-Tyr(3)-octreotide (DOTATOC) and more recently also alpha emitting (213)Bi-DOTATOC are promising new treatments for neuroendocrine tumors. No early predictors for treatment response have been recognized and tumor-shrinkage after radiation therapy appears slowly. In some solid tumors a decline in tumor perfusion was found predictive of final treatment response but the gold standard multiphase computed tomography (CT) has a high radiation burden. Therefore we evaluated the ability of contrast-enhanced ultrasound (CEUS) to evaluate tumor perfusion as a response criteria. Materials and Methods: 14 patients with hepatic neuroendocrine tumor (NET) metastases were enrolled in the retrospective study. Eleven patients were treated with beta-emitting (177)Lu/(90)Y-DOTATOC, either intravenous (i.v.) (n = 5) or intra-arterial (i.a.) (n = 6) and three patients received alpha-emitting (213)Bi-DOTATOC (i.a.). CEUS and contrast-enhanced CT (CE-CT) were performed before and 3 months after treatment. Results: CE-CT and CEUS presented comparable results in the baseline study and in the assessment of perfusion changes due to the different treatment regimes. A therapy related decrease in tumor perfusion is an early predictor of longterm morphologic response. Conclusion: CEUS is available and radiation free technique which showed comparable results for perfusion and diameter of liver metastases compared to CE-CT. Intensity reduction in an arterial phase CEUS can be seen as a positive sign indicating long term tumor response to treatment. Therefore CEUS may be considered as an imaging modality for monitoring early treatment after focal alpha and beta targeted therapy.
[Show abstract][Hide abstract] ABSTRACT: BACKGROUND: Intraperitoneal chemotherapy is used to treat peritoneal surface-spreading malignancies. We sought to determine whether volume and surface area of the intraperitoneal chemotherapy compartments are associated with overall survival and posttreatment glomerular filtration rate (GFR) in malignant peritoneal mesothelioma (MPM) patients. METHODS: Thirty-eight MPM patients underwent X-ray computed tomography peritoneograms during outpatient intraperitoneal chemotherapy. We calculated volume and surface area of contrast-filled compartments by semiautomated computer algorithm. We tested whether these were associated with overall survival and posttreatment GFR. RESULTS: Decreased likelihood of mortality was associated with larger surface areas (p = 0.0201) and smaller contrast-filled compartment volumes (p = 0.0341), controlling for age, sex, histologic subtype, and presence of residual disease >0.5 cm postoperatively. Larger volumes were associated with higher posttreatment GFR, controlling for pretreatment GFR, body surface area, surface area, and the interaction between body surface area and volume (p = 0.0167). DISCUSSION: Computed tomography peritoneography is an appropriate modality to assess for maldistribution of intraperitoneal chemotherapy. In addition to identifying catheter failure and frank loculation, quantitative analysis of the contrast-filled compartment's surface area and volume may predict overall survival and cisplatin-induced nephrotoxicity. Prospective studies should be undertaken to confirm and extend these findings to other diseases, including advanced ovarian carcinoma.
Annals of Surgical Oncology 05/2013; · 4.12 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: PURPOSEIn clinical trials, traditional monitoring methods, paper documentation, and outdated collection systems lead to inaccuracies of study information and inefficiencies in the process. Integrated electronic systems offer an opportunity to collect data in real time. PATIENTS AND METHODS
We created a computer software system to collect 13 patient-reported symptomatic adverse events and patient-reported Karnofsky performance status, semi-automated RECIST measurements, and laboratory data, and we made this information available to investigators in real time at the point of care during a phase II lung cancer trial. We assessed data completeness within 48 hours of each visit. Clinician satisfaction was measured.ResultsForty-four patients were enrolled, for 721 total visits. At each visit, patient-reported outcomes (PROs) reflecting toxicity and disease-related symptoms were completed using a dedicated wireless laptop. All PROs were distributed in batch throughout the system within 24 hours of the visit, and abnormal laboratory data were available for review within a median of 6 hours from the time of sample collection. Manual attribution of laboratory toxicities took a median of 1 day from the time they were accessible online. Semi-automated RECIST measurements were available to clinicians online within a median of 2 days from the time of imaging. All clinicians and 88% of data managers felt there was greater accuracy using this system. CONCLUSION
Existing data management systems can be harnessed to enable real-time collection and review of clinical information during trials. This approach facilitates reporting of information closer to the time of events, and improves efficiency, and the ability to make earlier clinical decisions.
Journal of Clinical Oncology 04/2013; · 18.04 Impact Factor