Fat Fraction Extracted from Whole-Body Magnetic Resonance (WB-MR) in Bone Metastatic Prostate Cancer: Intra- and Inter-Reader Agreement of Single-Slice and Volumetric Measurements.

BACKGROUND: This study evaluates the repeatability and reproducibility of fat-fraction percentage (FF%) in whole-body magnetic resonance imaging (WB-MRI) of prostate cancer patients with bone metastatic hormone naive disease. METHODS: Patients were selected from the database of a prospective phase-II trial. The treatment response was assessed using the METastasis Reporting and Data System for Prostate (MET-RADS-P). Two operators identified a Small Active Lesion (SAL, <10 mm) and a Large Active Lesion (LAL, ≥10 mm) per patient, performing manual segmentation of lesion volume and the largest cross-sectional area. Measurements were repeated by one operator after two weeks. Intra- and inter-reader agreements were assessed via Interclass Correlation Coefficient (ICC) on first-order radiomics features. RESULTS: Intra-reader ICC showed high repeatability for both SAL and LAL in a single slice (SS) and volumetric (VS) measurements with values ranging from 0.897 to 0.971. Inter-reader ICC ranged from 0.641 to 0.883, indicating moderate to good reproducibility. Spearman's rho analysis confirmed a strong correlation between SS and VS measurements for SAL (0.817) and a moderate correlation for LAL (0.649). Both intra- and inter-rater agreement exceeded 0.75 for multiple first-order features across lesion sizes. CONCLUSION: This study suggests that FF% measurements are reproducible, particularly for larger lesions in both SS and VS assessments.

Magnetic resonance neurography and diffusion tensor imaging of the sciatic nerve in hereditary transthyretin amyloidosis polyneuropathy.

The therapeutic advance in hereditary transthyretin amyloidosis (ATTRv amyloidosis) requires quantitative biomarkers of nerve involvement in order to foster early diagnosis and monitor therapy response. We aimed at quantitatively assessing Magnetic Resonance Neurography (MRN) and Diffusion Tensor Imaging (DTI) properties of the sciatic nerve in subjects with ATTRv-amyloidosis-polyneuropathy (ATTRv-PN) and pre-symptomatic carriers (ATTRv-C). Twenty subjects with pathogenic variants of the TTR gene (mean age 62.20 ± 12.04 years), 13 ATTRv-PN, and 7 ATTRv-C were evaluated and compared with 20 healthy subjects (mean age 60.1 ± 8.27 years). MRN and DTI sequences were performed at the right thigh from the gluteal region to the popliteal fossa. Cross-sectional-area (CSA), normalized signal intensity (NSI), and DTI metrics, including fractional anisotropy (FA), mean (MD), axial (AD), and radial diffusivity (RD) of the right sciatic nerve were measured. Increased CSA, NSI, RD, and reduced FA of sciatic nerve differentiated ATTRv-PN from ATTRv-C and healthy subjects at all levels (p < 0.01). NSI differentiated ATTRv-C from controls at all levels (p < 0.05), RD at proximal and mid-thigh (1.04 ± 0.1 vs 0.86 ± 0.11 p < 0.01), FA at mid-thigh (0.51 ± 0.02 vs 0.58 ± 0.04 p < 0.01). According to receiver operating characteristic (ROC) curve analysis, cutoff values differentiating ATTRv-C from controls (and therefore identifying subclinical sciatic involvement) were defined for FA, RD, and NSI. Significant correlations between MRI measures, clinical involvement and neurophysiology were found. In conclusion, the combination of quantitative MRN and DTI of the sciatic nerve can reliably differentiate ATTRv-PN, ATTRv-C, and healthy controls. More important, MRN and DTI were able to non-invasively identify early subclinical microstructural changes in pre-symptomatic carriers, thus representing a potential tool for early diagnosis and disease monitoring.

Onset of Chiari type 1 malformation: insights from a small series of intrauterine MR imaging cases.

PURPOSE: Morphometric studies on idiopathic Chiari malformation type 1 (CM1) pathogenesis have been mainly based on post-natal neuroimaging. Prenatal clues related to CM1 development are lacking. We present pre- and post-natal imaging time course in idiopathic CM1 and assess fetal skull and brain biometry to establish if clues about CM1 development are present at fetal age. METHODS: Multicenter databases were screened to retrieve intrauterine magnetic resonance (iuMR) of children presenting CM1 features at post-natal scan. Syndromes interfering with skull-brain growth were excluded. Twenty-two morphometric parameters were measured at fetal (average 24.4 weeks; range 21 to 32) and post-natal (average 15.4 months; range 1 to 45) age; matched controls were included. RESULTS: Among 7000 iuMR cases, post-natal scans were available for 925, with postnatal CM1 features reported in seven. None of the fetuses presented CM1 features. Tonsillar descent was clear at a later post-natal scan in all seven cases. Six fetal parameters resulted to be statistically different between CM1 and controls: basal angle (p = 0.006), clivo-supraoccipital angle (p = 0.044), clivus' length (p = 0.043), posterior cranial fossa (PCF) width (p = 0.009), PCF height (p = 0.045), and PCFw/BPDb (p = 0.013). Postnatally, only the clivus' length was significant between CM1 cases and controls. CONCLUSION: Pre- and post-natal CM1 cases did not share striking common features, making qualitative prenatal assessment not predictive; however, our preliminary results support the view that some of the pathogenetic basis of CM1 may be embedded to some extent already in intrauterine life.

Women's perceptions and attitudes to the use of AI in breast cancer screening: a survey in a cancer referral centre.

OBJECTIVE: Although breast cancer screening can benefit from Artificial Intelligence (AI), it is still unknown whether, to which extent or under which conditions, the use of AI is going to be accepted by the general population. The aim of our study is to evaluate what the females who are eligible for breast cancer screening know about AI and how they perceive such innovation. METHODS: We used a prospective survey consisting of a 11-multiple-choice questionnaire evaluating statistical associations with Chi-Square-test or Fisher-exact-test. Multinomial-logistic-regression was performed on items with more than two response categories. Odds ratio (OR) with 95% CI were computed to estimate the probability of a specific response according to patient's characteristics. RESULTS: In the 800 analysed questionnaires, 51% of respondents confirmed to have knowledge of AI. Of these, 88% expressed a positive opinion about its use in medicine. Non-Italian respondents were associated with the belief of having a deep awareness about AI more often than Italian respondents (OR = 1.91;95% CI[1.10-3.33]). Higher education level was associated with better opinions on the use of AI in medicine (OR = 4.69;95% CI[1.36-16.12]). According to 94% of respondents, the radiologists should always produce their own report on mammograms, whilst 77% agreed that AI should be used as a second reader. Most respondents (52%) considered that both the software developer and the radiologist should be held accountable for AI errors. CONCLUSIONS: Most of the females undergoing screening in our Institute approve the introduction of AI, although only as a support to radiologist, and not in substitution thereof. Yet, accountability in case of AI errors is still unsolved. advances in knowledge:This survey may be considered as a pilot-study for the development of large-scale studies to understand females's demands and concerns about AI applications in breast cancer screening.

Prediction of the Pathological Response to Neoadjuvant Chemotherapy in Breast Cancer Patients With MRI-Radiomics: A Systematic Review and Meta-analysis.

We performed a systematic review and a meta-analysis of studies using MRI-radiomics for predicting the pathological complete response in breast cancer patients undergoing neoadjuvant therapy , and we evaluated their methodological quality using the radiomics-quality-score (RQS). Random effects meta-analysis was performed pooling area under the receiver operating characteristics curves. Publication-bias was assessed using the Egger's test and visually inspecting the funnel plot. Forty-three studies were included in the qualitative review and 34 in the meta-analysis. Summary area under the receiver operating characteristics curve was 0,78 (95%CI:0,74-0,81). Heterogeneity according to the I2 statistic was substantial (71%) and there was no evidence of publication bias (P-value = 0,2). The average RQS was 12,7 (range:-1-26), with an intra-class correlation coefficient of 0.93 (95%CI:0.61-0.97). Year of publication, field intensity and synthetic RQS score do not appear to be moderators of the effect (P-value = 0.36, P-value = 0.28 and P-value = 0.92, respectively). MRI-radiomics may predict response to neoadjuvant therapy in breast cancer patients but the heterogeneity of the current studies is still substantial.

Value of [18F]FDG PET-CT in the follow-up of surgically treated oral tongue squamous cell carcinoma: single centre cohort analysis on 87 patients.

BACKGROUND: To evaluate the diagnostic performance of [¹8F]fluorodeoxyglucose positron emission tomography/computed tomography ([¹8F]FDG-PET/CT) scan in detecting local recurrences in patients with surgically treated oral tongue squamous cell cancer (OTSCC). MATERIAL AND METHODS: Eighty-seven patients who had undergone surgery for OTSCC were monitored clinically and [¹8F]FDGPET/CT and magnetic resonance (MR). PET uptakes were classified as functional (Type A), suspicious (Type B), or highly suggestive of local recurrence (Type C). A multidisciplinary team (MDT) evaluated case-by-case the surveillance strategy based on PET uptake. RESULTS: Fifty-nine patients presented FDG-PET uptake during follow-up: this report was significantly more frequent in patients who received flap reconstruction than in those without (73% vs 50%; p = 0.05). In 13 patients with Type A (n = 1), Type B (n = 9), and Type C (n = 3) uptakes an additional MR was considered preferable and discovered recurrence in 12.PET-CT had 9 true positives, 17 false positives, 71 true negatives, and no false-negative, resulting in sensitivity, specificity, positive (PPV) and negative predictive values (NPV) of 100%, 80.7%, 34.6%, and 100%. CONCLUSIONS: The present results demonstrated a change in diagnostic strategy, as decided by the MDT, in about one-fifth of patients. The results should prompt in designing a rational surveillance schedule in surgically treated OTSCC.

Comparison of Sensitivity and Specificity of Biparametric versus Multiparametric Prostate MRI in the Detection of Prostate Cancer in 431 Men with Elevated Prostate-Specific Antigen Levels.

(1) Background: the study of dynamic contrast enhancement (DCE) has a limited role in the detection of prostate cancer (PCa), and there is a growing interest in performing unenhanced biparametric prostate-MRI (bpMRI) instead of the conventional multiparametric-MRI (mpMRI). In this study, we aimed to retrospectively compare the performance of the mpMRI, which includes DCE study, and the unenhanced bpMRI, composed of only T2-weighted imaging and diffusion-weighted imaging (DWI), in PCa detection in men with elevated prostate-specific-antigen (PSA) levels. (2) Methods: a 1.5 T MRI, with an endorectal-coil, was performed on 431 men (aged 61.5 ± 8.3 years) with a PSA ≥4.0 ng/mL. The bpMRI and mpMRI tests were independently assessed in separate sessions by two readers with 5 (R1) and 3 (R2) years of experience. The histopathology or ≥2 years follow-up served as a reference standard. The sensitivity and specificity were calculated with their 95% CI, and McNemar's and Cohen's κ statistics were used. (3) Results: in 195/431 (45%) of histopathologically proven PCa cases, 62/195 (32%) were high-grade PCa (GS ≥ 7b) and 133/195 (68%) were low-grade PCa (GS ≤ 7a). The PCa could be excluded by histopathology in 58/431 (14%) and by follow-up in 178/431 (41%) of patients. For bpMRI, the sensitivity was 164/195 (84%, 95% CI: 79-89%) for R1 and 156/195 (80%, 95% CI: 74-86%) for R2; while specificity was 182/236 (77%, 95% CI: 72-82%) for R1 and 175/236 (74%, 95% CI: 68-80%) for R2. For mpMRI, sensitivity was 168/195 (86%, 95% CI: 81-91%) for R1 and 160/195 (82%, 95% CI: 77-87%) for R2; while specificity was 184/236 (78%, 95% CI: 73-83%) for R1 and 177/236 (75%, 95% CI: 69-81%) for R2. Interobserver agreement was substantial for both bpMRI (κ = 0.802) and mpMRI (κ = 0.787). (4) Conclusions: the diagnostic performance of bpMRI and mpMRI were similar, and no high-grade PCa was missed with bpMRI.

Recent Radiomics Advancements in Breast Cancer: Lessons and Pitfalls for the Next Future.

Radiomics is an emerging translational field of medicine based on the extraction of high-dimensional data from radiological images, with the purpose to reach reliable models to be applied into clinical practice for the purposes of diagnosis, prognosis and evaluation of disease response to treatment. We aim to provide the basic information on radiomics to radiologists and clinicians who are focused on breast cancer care, encouraging cooperation with scientists to mine data for a better application in clinical practice. We investigate the workflow and clinical application of radiomics in breast cancer care, as well as the outlook and challenges based on recent studies. Currently, radiomics has the potential ability to distinguish between benign and malignant breast lesions, to predict breast cancer's molecular subtypes, the response to neoadjuvant chemotherapy and the lymph node metastases. Even though radiomics has been used in tumor diagnosis and prognosis, it is still in the research phase and some challenges need to be faced to obtain a clinical translation. In this review, we discuss the current limitations and promises of radiomics for improvement in further research.

Inter-Reader Agreement of Diffusion-Weighted Magnetic Resonance Imaging for Breast Cancer Detection: A Multi-Reader Retrospective Study.

PURPOSE: In order to evaluate the use of un-enhanced magnetic resonance imaging (MRI) for detecting breast cancer, we evaluated the accuracy and the agreement of diffusion-weighted imaging (DWI) through the inter-reader reproducibility between expert and non-expert readers. MATERIAL AND METHODS: Consecutive breast MRI performed in a single centre were retrospectively evaluated by four radiologists with different levels of experience. The per-breast standard of reference was the histological diagnosis from needle biopsy or surgical excision, or at least one-year negative follow-up on imaging. The agreement across readers (by inter-reader reproducibility) was examined for each breast examined using Cohen's and Fleiss' kappa (κ) statistics. The Wald test was used to test the difference in inter-reader agreement between expert and non-expert readers. RESULTS: Of 1131 examinations, according to our inclusion and exclusion criteria, 382 women were included (49.5 ± 12 years old), 40 of them with unilateral mastectomy, totaling 724 breasts. Overall inter-reader reproducibility was substantial (κ = 0.74) for expert readers and poor (κ = 0.37) for non- expert readers. Pairwise agreement between expert readers and non-expert readers was moderate (κ = 0.60) and showed a statistically superior agreement of the expert readers over the non-expert readers (p = 0.003). CONCLUSIONS: DWI showed substantial inter-reader reproducibility among expert-level readers. Pairwise comparison showed superior agreement of the expert readers over the non-expert readers, with the expert readers having higher inter-reader reproducibility than the non-expert readers. These findings open new perspectives for prospective studies investigating the actual role of DWI as a stand-alone method for un-enhanced breast MRI.

Quantitative Whole-Body Diffusion-weighted MRI after One Treatment Cycle for Aggressive Non-Hodgkin Lymphoma Is an Independent Prognostic Factor of Outcome.

Purpose: To evaluate the prognostic utility of apparent diffusion coefficient (ADC) changes at whole-body diffusion-weighted (WB-DW) MRI after one treatment cycle for aggressive non-Hodgkin lymphoma (NHL) compared with response assessment at interim and end-of-treatment fluorine 18 (18F) fluorodeoxyglucose (FDG) PET/CT. Materials and Methods: This was a secondary analysis of a prospective study (ClinicalTrials.gov identifier: NCT01231269) in which participants with aggressive NHL were recruited between March 2011 and April 2015 and underwent WB-DW MRI before and after one cycle of immunochemotherapy. Volunteers were recruited for test-retest WB-DW MRI (ClinicalTrials.gov identifier: NCT01231282) to assess ADC measurement repeatability. Response assessment was based on ADC change after one treatment cycle at WB-DW MRI and Deauville criteria at 18F-FDG PET/CT. To evaluate prognostic factors of disease-free survival (DFS), Kaplan-Meier survival analysis and univariable and multivariable Cox regression were performed; intraclass correlation coefficient (ICC) and mean difference with limits of agreement were calculated to determine inter- and intraobserver repeatability of ADC measurements. Results: Forty-five patients (mean age, 58 years ± 17 [standard deviation]; 31 men) and nine volunteers (mean age, 22 years ± 3; seven men) were enrolled. Median DFS was 48 months (range, 2-48 months). Outcome prediction accuracy was 86.7% (39 of 45), 71.4% (30 of 42), and 73.8% (31 of 42) for WB-DW MRI and interim and end-of-treatment 18F-FDG PET/CT, respectively. WB-DW MRI (hazard ratio [HR], 17.8; P < .001) and interim (HR, 5; P = .008) and end-of-treatment (HR, 4.3; P = .017) 18F-FDG PET/CT were prognostic of DFS. After multivariable analysis, WB-DW MRI remained an independent predictor of outcome (HR, 26.8; P = .002). Intra- and interobserver agreement for ADC measurements were excellent (ICC = 0.85-0.99). Conclusion: Quantitative WB-DW MRI after only one cycle of immunochemotherapy predicts DFS in aggressive NHL and is noninferior to routinely performed interim and end-of-treatment 18F-FDG PET/CT.Keywords: MR-Diffusion Weighted Imaging, Lymphoma, Oncology, Tumor Response, Whole-Body ImagingSupplemental material is available for this article.© RSNA, 2021.

CT texture analysis for prediction of EGFR mutational status and ALK rearrangement in patients with non-small cell lung cancer.

PURPOSE: To develop a CT texture-based model able to predict epidermal growth factor receptor (EGFR)-mutated, anaplastic lymphoma kinase (ALK)-rearranged lung adenocarcinomas and distinguish them from wild-type tumors on pre-treatment CT scans. MATERIALS AND METHODS: Texture analysis was performed using proprietary software TexRAD (TexRAD Ltd, Cambridge, UK) on pre-treatment contrast-enhanced CT scans of 84 patients with metastatic primary lung adenocarcinoma. Textural features were quantified using the filtration-histogram approach with different spatial scale filters on a single 5-mm-thick central slice considered representative of the whole tumor. In order to deal with class imbalance regarding mutational status percentages in our population, the dataset was optimized using the synthetic minority over-sampling technique (SMOTE) and correlations with textural features were investigated using a generalized boosted regression model (GBM) with a nested cross-validation approach (performance averaged over 1000 resampling episodes). RESULTS: ALK rearrangements, EGFR mutations and wild-type tumors were observed in 19, 28 and 37 patients, respectively, in the original dataset. The balanced dataset was composed of 171 observations. Among the 29 original texture variables, 17 were employed for model building. Skewness on unfiltered images and on fine texture was the most important features. EGFR-mutated tumors showed the highest skewness while ALK-rearranged tumors had the lowest values with wild-type tumors showing intermediate values. The average accuracy of the model calculated on the independent nested validation set was 81.76% (95% CI 81.45-82.06). CONCLUSION: Texture analysis, in particular skewness values, could be promising for noninvasive characterization of lung adenocarcinoma with respect to EGFR and ALK mutations.

Which role for chest x-ray score in predicting the outcome in COVID-19 pneumonia?

OBJECTIVE: We aim to demonstrate that a chest X-ray (CXR) scoring system for COVID-19 patients correlates with patient outcome and has a prognostic value. METHODS: This retrospective study included CXRs of COVID-19 patients that reported the Brixia score, a semi-quantitative scoring system rating lung involvement from 0 to 18. The highest (H) and lowest (L) values were registered along with scores on admission (A) and end of hospitalization (E). The Brixia score was correlated with the outcome (death or discharge). RESULTS: A total of 953 patients met inclusion criteria. In total, 677/953 were discharged and 276/953 died during hospitalization. A total of 524/953 had one CXR and 429/953 had more than one CXR. H-score was significantly higher in deceased (median, 12; IQR 9-14) compared to that in discharged patients (median, 8; IQR 5-11) (p < 0.0001). In 429/953 patients with multiple CXR, A-score, L-score, and E-score were higher in deceased than in discharged patients (A-score 9 vs 8; p = 0.039; L-score 7 vs 5; p < 0.0003; E-score 12 vs 7; p < 0.0001). In the entire cohort, logistic regression showed a significant predictive value for age (p < 0.0001, OR 1.13), H-score (p < 0.0001, OR 1.25), and gender (p = 0.01, male OR 1.67). AUC was 0.863. In patients with ≥ 2 CXR, A-, L-, and E-scores correlated significantly with the outcome. Cox proportional hazards regression indicated age (p < 0.0001, HR 4.17), H-score (< 9, HR 0.36, p = 0.0012), and worsening of H-score vs A score > 3 (HR 1.57, p = 0.0227) as associated with worse outcome. CONCLUSIONS: The Brixia score correlates strongly with disease severity and outcome; it may support the clinical decision-making, particularly in patients with moderate-to-severe signs and symptoms. The Brixia score should be incorporated in a prognostic model, which would be desirable, particularly in resource-constraint scenarios. KEY POINTS: • To demonstrate the importance of the Brixia score in assessing and monitoring COVID-19 lung involvement. • The Brixia score strongly correlates with patient outcome and can be easily implemented in the routine reporting of CXR.

Diagnostic accuracy of contrast-enhanced spectral mammography for breast lesions: A systematic review and meta-analysis.

Breast cancer diagnosis and staging is based on mammography, ultrasound, and magnetic resonance imaging (MRI). Contrast enhanced spectral mammography (CESM) has gained momentum as an innovative and clinically useful method for breast assessment. CESM is based on abnormal enhancement of neoplastic tissue compared to surrounding breast tissue. We performed a systematic review of prospective trial to evaluate its diagnostic performance, following standard PRISMA-DTA. We used a bivariate random-effects regression approach to obtain summary estimates of both sensitivity and specificity of CESM. 8 studies published between 2003 and 2019 were included in the meta-analysis for a total of 945 lesions. The summary area under the curve obtained from all the study was 89% [95% CI 86%-91%], with a sensitivity of 85% [95% CI 73%-93%], and a specificity of 77% [95% CI 60%-88%]. With a pre-test probability of malignancy of 57% a positive finding at CESM gives a post-test probability of 83% while a negative finding a post-test probability of 20%. CESM shows a suboptimal sensitivity and specificity in the diagnosis of breast cancer in a selected population, and at present time, it could be considered only as a possible alternative test for breast lesions assessment when mammography and ultrasound are not conclusive or MRI is contraindicated or not available.

Prognostic and predictive value of histogram analysis in patients with non-small cell lung cancer refractory to platinum treated by nivolumab: A multicentre retrospective study.

PURPOSE: The aim of this study was to assess computed-tomography histogram analysis (CTHA) as prognostic and predictive factor in platinum-refractory non-small cell lung carcinoma (NSCLC) treated with immune checkpoint inhibitor Nivolumab. METHOD: One hundred and four patients were enrolled from 3 different centers. CT was performed using similar parameters among different scanners. CTHA was performed with the proprietary software TexRAD, which extracts histogram features at different spatial scale (spatial scale filters, SSF) producing 30 CTHA features per patients. Cross-validated Least Absolute Shrinkage and Selection Operator LASSO was used to select those features which were related to overall and progression-free survival (OS and PFS, respectively). High- and low-risk subgroups were identified using the best cutoff. RESULTS: Median follow-up was 13.8 weeks. Median OS and PFS were 7.3 and 3 months, respectively. LASSO selected kurtosis obtained by SSF = 4 mm as the single feature related to OS, leading to an hazard ratio (HR) of 0.476 (95%CI 0.29-0.77). PFS was related with kurtosis SSF = 6 mm, with HR of 0.556 (95%CI 0.36-0.86). CONCLUSION: Despite its limitations, this study is the first which suggests that CTHA could play a role in stratifying prognosis and treatment response in patients with NSCLC treated with Nivolumab.

Texture features of colorectal liver metastases on pretreatment contrast-enhanced CT may predict response and prognosis in patients treated with bevacizumab-containing chemotherapy: a pilot study including comparison with standard chemotherapy.

PURPOSE: Bevacizumab added to chemotherapy can improve survival in patients with metastatic colorectal cancer, but no predictive factors of efficacy are available in clinical practice. The aim of this study is to assess the predictive and prognostic value of texture analysis on pretreatment contrast-enhanced CT in patients affected by colorectal liver metastases. MATERIALS AND METHODS: Forty-three patients with colorectal liver metastases were retrospectively included in the study: 23 treated with bevacizumab-containing chemotherapy (group A), and 20 with standard chemotherapy (group B). Target liver lesions were analyzed by texture analysis of pretreatment contrast-enhanced CT. Texture analysis produced the parameter uniformity, describing lesion heterogeneity. Radiological response was classified after 3 months according to RECIST-1.1. Overall survival (OS) and progression-free survival (PFS) were considered to be outcome indicators. Multivariable logistic regression and survival analysis were performed. RESULTS: Uniformity was lower in responders than in nonresponders (p < 0.001) in group A but not in group B. Lesion CT density was lower in nonresponders in both groups (p = 0.03 and 0.02, respectively). In group A, uniformity was independently correlated with radiological response (odds ratio = 20, p = 0.01), OS and PFS (relative risks 6.94 and 5.05, respectively; p = 0.005 and p = 0.004, respectively). In group B, no variables were correlated with radiological response, OS or PFS. CONCLUSION: Texture analysis on contrast-enhanced CT stratified response probability and prognosis in patients with colorectal liver metastases treated with bevacizumab-containing therapy. This result was specific for the bevacizumab group.

Second line treatment of recurrent glioblastoma with sunitinib: results of a phase II study and systematic review of literature.

INTRODUCTION: Second line treatment of recurrent or progressive glioblastoma multiforme (GBM) is not standardized. Anti-angiogenic strategies with tyrosine-kinase inhibitors have been tested with conflicting results. We tested the association of sunitinib plus irinotecan (CPT-11) in a phase II trial in terms of response rate (RR) and 6-months progression-free survival (6-PFS). We also reviewed the clinical evidence from all the trials with sunitinib in this setting published to date and summarized it in a meta-analysis. EVIDENCE ACQUISITION: Patients with GBM recurrent or progressive after surgery and standard chemo-radiotherapy were treated with sunitinib 37.5 mg/day for 14 days + CPT-11 125 mg/sqm every 14 days in a Simon's two-stage phase II study. A summary data meta-analysis was performed to establish the 6-PFS in patients with ascertained histological diagnosis of GBM treated with sunitinib. EVIDENCE SYNTHESIS: Six patients were enrolled in the stage I of the trial and only one had a stable disease. The overall response rate was 17% and 6-PFS was not reached. Therefore, the trial was stopped early for insufficient activity. All toxicities were grade 1-2. Systematic review of the literature identified 9 studies (including the present one) for a total of 221 patients. Pooled 6-PFS was 15.1% (95% CI: 9.0-24.4). Subgroup analysis by different schedule revealed a 6-PFS of 17.5% (95% CI: 10.3-28.1) in the weekly setting which was consistent across all the studies (I2=0%, P=0.66) and a pooled 6-PFS of 12.7% (95% CI: 4.9-29.1) in the daily setting with a substantial amount of heterogeneity (I2=65%, P=0.01). CONCLUSIONS: Results of this trial and those of the systematic review indicate that, compared to conventional chemotherapy or bevacizumab, sunitinib has insufficient activity in the setting of recurrent GBM. Better patient's molecular stratification for second-line treatment in GBM is warranted.

CT texture analysis as predictive factor in metastatic lung adenocarcinoma treated with tyrosine kinase inhibitors (TKIs).

PURPOSE: To assess the predictive and prognostic value of pre-treatment CT texture features in lung adenocarcinoma treated with tyrosine kinase inhibitors (TKI). MATERIALS AND METHODS: Texture analysis was performed using commercially available software (TexRAD Ltd, Cambridge, UK) on pre-treatment contrast-enhanced CT studies from 50 patients with metastatic lung adenocarcinoma treated by TKI. Texture features were quantified on a 5-mm-thick central slice of the primary tumor and were correlated with progression-free and overall survival (PFS and OS) using an internally cross-validated machine learning approach then validated on a bootstrapped sample. RESULTS: Median PFS and OS were 10.5 and 20.7 months, respectively. A noninvasive signature based on five texture parameters predicted 6-month progression with Area Under the Curve (AUC) of 0.8 (95% CI) and 1-year progression with AUC of 0.76. A high-risk group had hazard ratios for progression of 4.63 and 5.78 when divided by median and best cut-off points, respectively. Texture signature did not correlate with OS. Available clinical variables did not correlate with PFS or with OS. CONCLUSION: Texture features seem to be associated with PFS in lung adenocarcinoma treated with TKI.