MR fingerprinting allows rapid simultaneous quantification of T1 and T2 relaxation times. This study assessed the utility of MR fingerprinting in differentiating common types of adult intra-axial ...brain tumors.
MR fingerprinting acquisition was performed in 31 patients with untreated intra-axial brain tumors: 17 glioblastomas, 6 World Health Organization grade II lower grade gliomas, and 8 metastases. T1, T2 of the solid tumor, immediate peritumoral white matter, and contralateral white matter were summarized within each ROI. Statistical comparisons on mean, SD, skewness, and kurtosis were performed by using the univariate Wilcoxon rank sum test across various tumor types. Bonferroni correction was used to correct for multiple-comparison testing. Multivariable logistic regression analysis was performed for discrimination between glioblastomas and metastases, and area under the receiver operator curve was calculated.
Mean T2 values could differentiate solid tumor regions of lower grade gliomas from metastases (mean, 172 ± 53 ms, and 105 ± 27 ms, respectively;
= .004, significant after Bonferroni correction). The mean T1 of peritumoral white matter surrounding lower grade gliomas differed from peritumoral white matter around glioblastomas (mean, 1066 ± 218 ms, and 1578 ± 331 ms, respectively;
= .004, significant after Bonferroni correction). Logistic regression analysis revealed that the mean T2 of solid tumor offered the best separation between glioblastomas and metastases with an area under the curve of 0.86 (95% CI, 0.69-1.00;
< .0001).
MR fingerprinting allows rapid simultaneous T1 and T2 measurement in brain tumors and surrounding tissues. MR fingerprinting-based relaxometry can identify quantitative differences between solid tumor regions of lower grade gliomas and metastases and between peritumoral regions of glioblastomas and lower grade gliomas.
Abstract The majority of aggressive lymphomas is characterized by an up regulated glycolytic activity, which enables the visualization by F-18 FDG-PET/CT. One-stop hybrid FDG-PET/CT combines the ...functional and morphologic information, outperforming both, CT and FDG-PET as separate imaging modalities. This has resulted in several recommendations using FDG-PET/CT for staging, restaging, monitoring during therapy, and assessment of treatment response as well as identification of malignant transformation. FDG-PET/CT may obviate the need for a bone marrow biopsy in patients with Hodgkin's lymphoma and diffuse large B cell lymphoma. FDG-PET/CT response assessment is recommended for FDG-avid lymphomas, whereas CT-based response evaluation remains important in lymphomas with low or variable FDG avidity. The treatment induced change in metabolic activity allows for assessment of response after completion of therapy as well as prediction of outcome early during therapy. The five-point scale Deauville Criteria allows the assessment of treatment response based on visual FDG-PET analysis. Although the use of FDG-PET/CT for prediction of therapeutic response is promising it should only be conducted in the context of clinical trials. Surveillance FDG-PET/CT after complete remission is discouraged due to the relative high number of false-positive findings, which in turn may result in further unnecessary investigations. Future directions include the use of new PET tracers such as F-18 fluorothymidine (FLT), a surrogate biomarker of cellular proliferation and Ga-68 CXCR4, a chemokine receptor imaging biomarker as well as innovative digital PET/CT and PET/MRI techniques.
BACKGROUND: Current MR imaging allows primarily qualitative distinctions between the signal intensities of various T1 or T2 weighted imaging paradigms. Magnetic Resonance Fingerprinting (MRF) ...represents a novel framework for simultaneous, and precise quantitation of multiple MR tissue properties. Here we assess the capability of MRF based T1 and T2 relaxometry to evaluate different types of intra-axial brain tumors. MATERIALS AND METHODS: 20 patients including 10 glioblastoma multiforme (GBM), 5 oligodendrogliomas (OG) and 5 metastases (METS) were scanned using a MRF protocol. Imaging was acquired through representative areas of brain and quantitative T1 and T2 maps were generated. T1 and T2 quantification of solid tumor component, immediate perilesional white matter (PWM) within 1 cm of enhancing margin, and contralateral white matter (CWM) was performed using ROI analysis. Student's t-test was used for statistical analysis. RESULTS: Solid tumor T1, T2 were distinct from T1, T2 of CWM (n = 20, p < 0.001). There were differences between T1, T2 of PWM of GBMs and METS as compared to their CWM (n = 15, p < 0.001, p < 0.001). Also, there were differences between the T1, T2 of both the solid and PWM regions of GBMs and METS (p < 0.01; p < 0.05 respectively). T2 relaxometry revealed difference between GBMs and OGs (p < 0.02). CONCLUSIONS: MRF can simultaneously measure T1, T2 values of brain tumors and surrounding tissues distinguishing various tumor types and their associated PWM changes from CWM with high statistical significance. Preliminary data supports using MRF to identify regions of infiltrative edema in GBM, and differentiation of tumor types and grades. Statement of Clinical Relevance: Our preliminary data suggests MRF may have a role in non-invasively distinguishing various types intracranial masses, delineate tumor margins, and possibly characterize therapeutic response.
Recent studies suggest that tumor-infiltrating lymphocytes (TILs) are associated with disease-free (DFS) and overall survival (OS) in operable triple-negative breast cancer (TNBC). We seek to ...validate the prognostic impact of TILs in primary TNBCs in two adjuvant phase III trials conducted by the Eastern Cooperative Oncology Group (ECOG).
Full-face hematoxylin and eosin–stained sections of 506 tumors from ECOG trials E2197 and E1199 were evaluated for density of TILs in intraepithelial (iTILs) and stromal compartments (sTILs). Patient cases of TNBC from E2197 and E1199 were randomly selected based on availability of sections. For the primary end point of DFS, association with TIL scores was determined by fitting proportional hazards models stratified on study. Secondary end points were OS and distant recurrence–free interval (DRFI). Reporting recommendations for tumor marker prognostic studies criteria were followed, and all analyses were prespecified.
The majority of 481 evaluable cancers had TILs (sTILs, 80%; iTILs, 15%). With a median follow-up of 10.6 years, higher sTIL scores were associated with better prognosis; for every 10% increase in sTILs, a 14% reduction of risk of recurrence or death (P = .02), 18% reduction of risk of distant recurrence (P = .04), and 19% reduction of risk of death (P = .01) were observed. Multivariable analysis confirmed sTILs to be an independent prognostic marker of DFS, DRFI, and OS.
In two national randomized clinical trials using contemporary adjuvant chemotherapy, we confirm that stromal lymphocytic infiltration constitutes a robust prognostic factor in TNBCs. Studies assessing outcomes and therapeutic efficacies should consider stratification for this parameter.
This randomized trial assessed whether urate-lowering treatment with allopurinol could attenuate eGFR decline in at-risk patients with stage 3 or 4 chronic kidney disease. Allopurinol did not slow ...the decline in eGFR as compared with placebo.
In patients with ischemic stroke and a proximal cerebral arterial occlusion and salvageable tissue on imaging, alteplase followed by thrombectomy with a stent retriever was more effective than ...alteplase alone in improving reperfusion, neurologic recovery, and functional outcome.
The results of the Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands (MR CLEAN) trial,
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which showed reduced disability among patients with ischemic stroke who were treated with endovascular thrombectomy in addition to standard care, represent an advance in stroke care. The MR CLEAN study followed several trials that had neutral findings with respect to the use of endovascular thrombectomy.
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In the largest of these trials, the Interventional Management of Stroke 3 (IMS-3) study, investigators compared the administration of 0.9 mg of alteplase per kilogram of body weight to a bridging strategy of . . .
To determine the 12-year risk of developing an ipsilateral breast event (IBE) for women with ductal carcinoma in situ (DCIS) of the breast treated with surgical excision (lumpectomy) without ...radiation.
A prospective clinical trial was performed for women with DCIS who were selected for low-risk clinical and pathologic characteristics. Patients were enrolled onto one of two study cohorts (not randomly assigned): cohort 1: low- or intermediate-grade DCIS, tumor size 2.5 cm or smaller (n = 561); or cohort 2: high-grade DCIS, tumor size 1 cm or smaller (n = 104). Protocol specifications included excision of the DCIS tumor with a minimum negative margin width of at least 3 mm. Tamoxifen (not randomly assigned) was given to 30% of the patients. An IBE was defined as local recurrence of DCIS or invasive carcinoma in the treated breast. Median follow-up time was 12.3 years.
There were 99 IBEs, of which 51 (52%) were invasive. The IBE and invasive IBE rates increased over time in both cohorts. The 12-year rates of developing an IBE were 14.4% for cohort 1 and 24.6% for cohort 2 (P = .003). The 12-year rates of developing an invasive IBE were 7.5% and 13.4%, respectively (P = .08). On multivariable analysis, study cohort and tumor size were both significantly associated with developing an IBE (P = .009 and P = .03, respectively).
For patients with DCIS selected for favorable clinical and pathologic characteristics and treated with excision without radiation, the risks of developing an IBE and an invasive IBE increased through 12 years of follow-up, without plateau. These data help inform the treatment decision-making process for patients and their physicians.
The extent of tumor-infiltrating lymphocytes (TILs), along with immunomodulatory ligands, tumor-mutational burden and other biomarkers, has been demonstrated to be a marker of response to ...immune-checkpoint therapy in several cancers. Pathologists have therefore started to devise standardized visual approaches to quantify TILs for therapy prediction. However, despite successful standardization efforts visual TIL estimation is slow, with limited precision and lacks the ability to evaluate more complex properties such as TIL distribution patterns. Therefore, computational image analysis approaches are needed to provide standardized and efficient TIL quantification. Here, we discuss different automated TIL scoring approaches ranging from classical image segmentation, where cell boundaries are identified and the resulting objects classified according to shape properties, to machine learning-based approaches that directly classify cells without segmentation but rely on large amounts of training data. In contrast to conventional machine learning (ML) approaches that are often criticized for their "black-box" characteristics, we also discuss explainable machine learning. Such approaches render ML results interpretable and explain the computational decision-making process through high-resolution heatmaps that highlight TILs and cancer cells and therefore allow for quantification and plausibility checks in biomedical research and diagnostics.
For women with ductal carcinoma in situ (DCIS) of the breast, the risk of developing an ipsilateral breast event (IBE; defined as local recurrence of DCIS or invasive carcinoma) after surgical ...excision without radiation is not well defined by clinical and pathologic characteristics.
The Oncotype DX breast cancer assay was performed for patients with DCIS treated with surgical excision without radiation in the Eastern Cooperative Oncology Group (ECOG) E5194 study. The association of the prospectively defined DCIS Score (calculated from seven cancer-related genes and five reference genes) with the risk of developing an IBE was analyzed using Cox regression. All statistical tests were two-sided.
There were 327 patients with adequate tissue for analysis. The continuous DCIS Score was statistically significantly associated with the risk of developing an IBE (hazard ratio HR = 2.31, 95% confidence interval CI = 1.15 to 4.49; P = .02) when adjusted for tamoxifen use (prespecified primary analysis) and with invasive IBE (unadjusted HR = 3.68, 95% CI = 1.34 to 9.62; P = .01). For the prespecified DCIS risk groups of low, intermediate, and high, the 10-year risks of developing an IBE were 10.6%, 26.7%, and 25.9%, respectively, and for an invasive IBE, 3.7%, 12.3%, and 19.2%, respectively (both log rank P ≤ .006). In multivariable analyses, factors associated with IBE risk were DCIS Score, tumor size, and menopausal status (all P ≤ .02).
The DCIS Score quantifies IBE risk and invasive IBE risk, complements traditional clinical and pathologic factors, and provides a new clinical tool to improve selecting individualized treatment for women with DCIS who meet the ECOG E5194 criteria.
When a genetic test was used to assess prognosis, women with midrange scores were found to have similar outcomes after adjuvant treatment with either endocrine therapy alone or chemotherapy plus ...endocrine therapy.