MRI-based radiomics signature for localized prostate cancer: a new clinical tool for cancer aggressiveness prediction? Sub-study of prospective phase II trial on ultra-hypofractionated radiotherapy (AIRC IG-13218).

OBJECTIVES: Radiomic involves testing the associations of a large number of quantitative imaging features with clinical characteristics. Our aim was to extract a radiomic signature from axial T2-weighted (T2-W) magnetic resonance imaging (MRI) of the whole prostate able to predict oncological and radiological scores in prostate cancer (PCa). METHODS: This study included 65 patients with localized PCa treated with radiotherapy (RT) between 2014 and 2018. For each patient, the T2-W MRI images were normalized with the histogram intensity scale standardization method. Features were extracted with the IBEX software. The association of each radiomic feature with risk class, T-stage, Gleason score (GS), extracapsular extension (ECE) score, and Prostate Imaging Reporting and Data System (PI-RADS v2) score was assessed by univariate and multivariate analysis. RESULTS: Forty-nine out of 65 patients were eligible. Among the 1702 features extracted, 3 to 6 features with the highest predictive power were selected for each outcome. This analysis showed that texture features were the most predictive for GS, PI-RADS v2 score, and risk class; intensity features were highly associated with T-stage, ECE score, and risk class, with areas under the receiver operating characteristic curve (ROC AUC) ranging from 0.74 to 0.94. CONCLUSIONS: MRI-based radiomics is a promising tool for prediction of PCa characteristics. Although a significant association was found between the selected features and all the mentioned clinical/radiological scores, further validations on larger cohorts are needed before these findings can be applied in the clinical practice. KEY POINTS: • A radiomic model was used to classify PCa aggressiveness. • Radiomic analysis was performed on T2-W magnetic resonance images of the whole prostate gland. • The most predictive features belong to the texture (57%) and intensity (43%) domains.

Inter-observer agreement on the morphology of screening-detected lung cancer: beyond pulmonary nodules and masses.

OBJECTIVES: Pulmonary nodules and masses are the typical presentations of lung cancer. However, a spectrum of focal opacities cannot be defined as either "pulmonary nodule" or "mass," despite representing cancer. We aimed to assess the morphology of screening-detected lung cancers at low-dose computed tomography LDTC and to evaluate inter-observer agreement in their classification. METHODS: Four radiologists with different experiences in thoracic imaging retrospectively reviewed 273 screening-detected lung cancers. Readers were asked to assess if morphology at the time of diagnosis was consistent with the Fleischner Society definition of pulmonary "nodule" or "mass." Cancers not consistent were defined as "non-nodular/non-mass" (NN/NM) and sub-classified as follows: associated with cystic airspaces, stripe-like, scar-like, endobronchial, or not otherwise defined (NOD). Inter-observer agreement was evaluated using Cohen's K statistic among pairs of readers and modified Fleiss' kappa statistic for overall agreement. RESULTS: Two hundred forty-one of the 273 (88%) lesions were defined as pulmonary nodule or mass by complete agreement, while 20/273 (7.3%) were defined as NN/NM. Six (2.2%) of 273 were sub-classified as lesions associated with cystic airspace, six (2.2%) as scar-like, five (1.8%) as endobronchial, and one (0.7%) as NOD by complete agreement. The concordance in defining morphology was excellent (261/273; 96%, 95%CI 92-98%; k 0.85, 95%CI 0.75-0.92) and also in the sub-classification (18/20; 90%, 95%CI 68-99%, k 0.93, 95%CI 0.86-1.00). There was incomplete agreement regarding lesion morphology in 4.4% (12/273) of cases. CONCLUSIONS: A non-negligible percentage of screening-detected lung cancers has a NN/NM appearance at LDCT. The concordance in defining lesion morphology was excellent. The awareness of various presentations can avoid missed or delayed diagnosis. KEY POINTS: • A non-negligible percentage of screening-detected lung cancers have neither nodular nor mass appearance at low-dose CT. • The awareness of various LDCT presentations of lung cancer can avoid missed or delayed diagnosis. • Optimal protocol management in CT screening should take into consideration lung nodules as well as various other focal abnormalities.

Low PI-RADS assessment category excludes extraprostatic extension (≥pT3a) of prostate cancer: a histology-validated study including 301 operated patients.

OBJECTIVES: To evaluate whether low PI-RADS v2 assessment categories are effective at excluding extraprostatic extension (EPE) of prostate cancer (≥pT3a PCa). METHODS: The local institutional ethics committee approved this retrospective analysis of 301 consecutive PCa patients. Patients were classified as low- or intermediate/high-risk based on clinical parameters and underwent pre-surgical multiparametric magnetic resonance imaging. A PI-RADS v2 assessment category and ESUR EPE score were assigned for each lesion by two readers working in consensus. Histopathologic analysis of the whole-mount radical prostatectomy specimen was the reference standard. Univariate and multivariate analyses were performed to evaluate the association of PI-RADS v2 assessment category with final histology ≥pT3a PCa. RESULTS: For a PI-RADS v2 assessment category threshold of 3, the overall performance for ruling out (sensitivity, negative predictive value, negative likelihood ratio) ≥pT3a PCa was 99%/98%/0.04 and was similar in both the low-risk (96%/97%/0.12; N = 137) and the intermediate/high-risk groups (100%/100%/0.0; N = 164). In univariate analysis, all clinical and tumor characteristics except age were significantly associated with ≥pT3a PCa. In multivariate analysis, PI-RADS v2 assessment categories ≤ 3 had a protective effect relative to categories 4 and 5. The inclusion of ESUR EPE score improved the AUC of ≥pT3a PCa prediction (from 0.73 to 0.86, p = 0.04 in the overall cohort). The impact of PI-RADS v2 assessment category is reflected in a nomogram derived on the basis of our cohort. CONCLUSIONS: In our cohort, low PI-RADS v2 assessment categories of 3 or less confidently ruled out the presence of ≥pT3a PCa irrespective of clinical risk group. KEY POINTS: • Our analysis of 301 mp-MRI and RARP specimens showed that the addition of PI-RADS v2 assessment categories to clinical parameters improves the exclusion of ≥pT3a (extraprostatic) prostate cancer. • PI-RADS v2 assessment categories of 1 to 3 are useful for excluding ≥pT3a prostate cancer with a NPV of 98%; such patients can be considered as candidates for less invasive approaches. • The ability to exclude ≥pT3a prostate cancer may improve confidence in choosing nerve-sparing surgery or in avoiding pelvic nodal dissections, and similarly for patients undergoing radiotherapy, in adopting short-course adjuvant hormonal therapy or foregoing prophylactic nodal irradiation.

Do DWI and quantitative DCE perfusion MR have a prognostic value in high-grade serous ovarian cancer?

PURPOSE: To evaluate whether perfusion and diffusion parameters from staging MR in ovarian cancer (OC) patients may predict the presence of residual tumor at surgery and the progression-free survival (PFS) in 12 months. MATERIALS AND METHODS: Patients who are from a single institution, candidate for OC to cytoreductive surgery and undergoing MR for staging purposes were included in this study. Inclusion criteria were: preoperative MR including diffusion-weighted imaging (DWI) and perfusion dynamic contrast-enhanced (DCE) sequence; cytoreductive surgery performed within a month from MR; and minimum follow-up of 12 months. Patients' characteristics including the presence of residual tumor at surgery (R0 or R1) and relapse within 12 months from surgery were recorded. DWI parameters included apparent diffusion coefficient (ADC) of the largest ovarian mass (O-ADC) and normalized ovarian ADC as a ratio between ovarian ADC and muscle ADC (M-ADC). DCE quantitative parameters included were descriptors of tumor vascular properties such as forward and backward transfer constants, plasma volume and volume of extracellular space. Statistical analysis was performed, and p values < 0.05 were considered significant. RESULTS: Forty-nine patients were included. M-ADC showed a slightly significant association with the presence of residual tumor at surgery. None of the other functional parameters showed either difference between R0 and R1 patients or association with PFS in the first 12 months. CONCLUSIONS: This preliminary study demonstrated a slightly significant association between normalized ovarian ADC and the presence of residual tumor at surgery. The other perfusion and diffusion parameters were not significant for the endpoints of this study.

Whole-body magnetic resonance imaging (WB-MRI) in oncology: recommendations and key uses.

The past decade has witnessed a growing role and increasing use of whole-body magnetic resonance imaging (WB-MRI). Driving these successes are developments in both hardware and software that have reduced overall examination times and significantly improved MR imaging quality. In addition, radiologists and clinicians have continued to find promising new applications of this innovative imaging technique that brings together morphologic and functional characterization of tissues. In oncology, the role of WB-MRI has expanded to the point of being recommended in international guidelines for the assessment of several cancer histotypes (multiple myeloma, melanoma, prostate cancer) and cancer-prone syndromes (Li-Fraumeni and hereditary paraganglioma-pheochromocytoma syndromes). The literature shows growing use of WB-MRI for the staging and follow-up of other cancer histotypes and cancer-related syndromes (including breast cancer, lymphoma, neurofibromatosis, and von Hippel-Lindau syndromes). The main aim of this review is to examine the current scientific evidence for the use of WB-MRI in oncology.

Iodixanol versus iopromide in cancer patients: Evidence from a randomized clinical trial.

To assess the safety profile of iso-osmolar contrast medium (CM) versus low osmolar CM in cancer patients with an estimated glomerular filtration rate (eGFR) >60 ml/min. In this multicenter, blind trial of patients seeking a chest-abdomen-pelvis contrast enhanced computed tomography (CT) with iodated CM, participants were centrally randomized to iodixanol or iopromide. Contrast induced nephropathy (CIN) at 24 and/or 72 hr were our primary outcomes. We further considered irreversible CIN, average eGFR percentage variation (%Δ), and adverse events (AEs). Overall, 607 patients were enrolled. Among them, 497 eligible patients were randomized to iodixanol (N: 247) or iopromide (N: 250). No differences emerged by descriptive characteristics. Seven and 3 CIN at 24 hr (p = 0.34) and 8 and 2 CIN at 72 hr (p = 0.11) occurred in the iopromide and iodixanol group, respectively. Within the subgroup of individual patients who developed CIN (N: 17), the event rate was higher in the iopromide arm (p = 0.045). No cases of permanent CIN or significant differences in terms of AEs or GFR %Δ were observed. Our results suggest a more favorable safety profile of iodixanol versus iopromide. Adequately sized trials with similar design are warranted to confirm our findings and clarify the underlying biological mechanisms.

Metastatic and non-metastatic lymph nodes: quantification and different distribution of iodine uptake assessed by dual-energy CT.

OBJECTIVES: To evaluate quantification of iodine uptake in metastatic and non-metastatic lymph nodes (LNs) by dual-energy CT (DECT) and to assess if the distribution of iodine within LNs at DECT correlates with the pathological structure. METHODS: Ninety LNs from 37 patients (23 with lung and 14 with gynaecological malignancies) were retrospectively selected. Information of LNs sent for statistical analysis included Hounsfield units (HU) at different energy levels; decomposition material densities fat-iodine, iodine-fat, iodine-water, water-iodine. Statistical analysis included evaluation of interobserver variability, material decomposition densities and spatial HU distribution within LNs. RESULTS: Interobserver agreement was excellent. There was a significant difference in iodine-fat and iodine-water decompositions comparing metastatic and non-metastatic LNs (p < 0.001); fat-iodine and water-iodine did not show significant differences. HU distribution showed a significant gradient from centre to periphery within non-metastatic LNs that was significant up to 20-30% from the centre, whereas metastatic LNs showed a more homogeneous distribution of HU, with no significant gradient. CONCLUSIONS: DECT demonstrated a lower iodine uptake in metastatic compared to non-metastatic LNs. Moreover, the internal iodine distribution showed an evident gradient of iodine distribution from centre to periphery in non-metastatic LNs, and a more homogeneous distribution within metastatic LNs, which corresponded to the pathological structure. KEY POINTS: • This study demonstrated a lower iodine uptake in metastatic than non-metastatic LNs. • Internal distribution of HU was different between metastatic and non-metastatic lymph nodes. • The intranodal iodine distribution disclosed a remarkable correlation with the histological LN structure.

Radiomics of high-grade serous ovarian cancer: association between quantitative CT features, residual tumour and disease progression within 12 months.

OBJECTIVES: To determine if radiomic features, alone or combined with clinical data, are associated with residual tumour (RT) at surgery, and predict the risk of disease progression within 12 months (PD12) in ovarian cancer (OC) patients. METHODS: This retrospective study enrolled 101 patients according to the following inclusion parameters: cytoreductive surgery performed at our institution (9 May 2007-23 February 2016), assessment of BRCA mutational status, preoperative CT available. Radiomic features of the ovarian masses were extracted from 3D structures drawn on CT images. A phantom experiment was performed to assess the reproducibility of radiomic features. The final radiomic features included in the analysis (n = 516) were grouped into clusters using a hierarchical clustering procedure. The association of each cluster's representative radiomic feature with RT and PD12 was assessed by chi-square test. Multivariate analysis was performed using logistic regression models. P values < 0.05 were considered significant. RESULTS: Patients with values of F2-Shape/Compactness1 below the median, of F1- GrayLevelCooccurenceMatrix25/0-1InformationMeasureCorr2 below the median and of F1-GrayLevelCooccurenceMatrix25/-333-1InverseVariance above the median showed higher risk of RT (36%, 36% and 35%, respectively, as opposed to 18%, 18% and 18%). Patients with values of F4-GrayLevelRunLengthMatrix25/-333RunPercentage above the median, of F2 shape/Max3DDiameter below the median and F1-GrayLevelCooccurenceMatrix25/45-1InverseVariance above the median showed higher risk of PD12 (22%, 24% and 23%, respectively, as opposed to 6%, 5% and 6%). At multivariate analysis F2-Shape/Max3DDiameter remained significant (odds ratio (95% CI) = 11.86 (1.41-99.88)). To predict PD12, a clinical radiomics model performed better than a base clinical model. CONCLUSION: This study demonstrated significant associations between radiomic features and prognostic factors such as RT and PD12. KEY POINTS: • No residual tumour (RT) at surgery is the most important prognostic factor in OC. • Radiomic features related to mass size, randomness and homogeneity were associated with RT. • Progression of disease within 12 months (PD12) indicates worse prognosis in OC. • A model including clinical and radiomic features performed better than only-clinical model to predict PD12.

Evaluation of deep myometrial invasion in endometrial cancer patients: is dual-energy CT an option?

OBJECTIVES: Assessment of deep (>50%) myometrial invasion by dual-energy CT (DECT) and Trans-Vaginal US (TVUS) in patients with endometrial cancer. METHODS: We retrospectively enrolled patients with endometrial cancer who underwent DECT and TVUS for pre-surgical staging. Three sets of images were evaluated: 70 keV (routine CT images), 50 keV, and iodine-water reconstructions. The gold standard was pathology after surgery. The agreement between the different imaging modalities and the gold standard was estimated. Sensitivity, specificity and accuracy for each imaging modality were evaluated with 95% confidence intervals (CI). RESULTS: Thirty-nine patients were included. Median time from CT and TVUS to surgery was 23 and 18 days, respectively. The best agreement between evaluation of myometrial infiltration and the gold standard was 0.88 (0.72, 1.00) for the 50 keV images; the worst agreement was 0.43 (0.00, 0.88) for the 70 keV images. CT iodine reconstructions and US agreement were comparable. Specificity, sensitivity and accuracy were 0.91, 1.00, 0.94; 0.57, 0.86, 0.71; 0.82, 1.00, 0.87; 0.91, 0.77, 0.86 for 50 keV, 70 keV, iodine reconstructions and ultrasound, respectively. CONCLUSIONS: DECT is a promising tool for assessment of myometrial invasion in endometrial cancer patients, with a special focus on 50 keV images.

Diagnostic accuracy of surface coil MRI in assessing cartilaginous invasion in laryngeal tumours: Do we need contrast-agent administration?

OBJECTIVES: To assess the diagnostic accuracy of MRI performed using surface coils, with and without contrast medium, in predicting thyroid and cricoid cartilage infiltration in laryngeal tumours, and to investigate whether the radiologist's experience influences diagnostic accuracy. METHODS: We retrospectively enrolled patients with biopsy-proven laryngeal cancer who had undergone preoperative staging MRI and open surgery. Two radiologists with different experience (senior vs. junior) reviewed the MR images without (session A1) and with contrast medium (session A2) separately. We calculated the accuracy of MRI with and without contrast medium in detecting infiltration of the thyroid and cricoid cartilages. Interobserver agreement was calculated by Cohen's Kappa (k). RESULTS: Forty-two patients were enrolled, for a total of 62 cartilages. In session A1 the senior and junior radiologists showed an accuracy of 85% and 71%, respectively, with k = 0.53 (0.33-0.72). In session A2 the senior and junior radiologists showed an accuracy of 84% and 77%, respectively, with k = 0.68 (0.49-0.86). CONCLUSIONS: Staging of laryngeal tumours with surface coil MRI showed good diagnostic accuracy in assessing cartilaginous infiltration. We observed similar values of diagnostic accuracy for the analysis performed with and without contrast medium for the senior radiologist. KEY POINTS: • Surface coil MRI demonstrated good accuracy in assessing laryngeal cartilage invasion. • The radiologist's experience can influence the diagnostic accuracy. • Gadolinium administration may increase interobserver concordance.

Signal intensity change on unenhanced T1-weighted images in dentate nucleus and globus pallidus after multiple administrations of gadoxetate disodium: an intraindividual comparative study.

PURPOSE: To investigate whether there is an increased signal intensity (SI) of dentate nucleus (DN) and globus pallidus (GP) on unenhanced T1-weighted magnetic resonance imaging (MRI), in patients who had undergone multiple administrations of gadoxetate disodium. MATERIALS AND METHODS: We retrospectevely included stage III melanoma patients, who had been previously enrolled in a trial of adjuvant therapy and who had undergone whole-body contrast-enhanced MRIs with gadoxetate disodium every three months for their follow-up. The SI ratios of DN-to-pons and GP-to-thalamus on unenhanced T1-weighted images were calculated. The difference in SI ratios between the first and the last MRI examinations was assessed and a linear mixed model was performed to detect how SI ratios varied with the number of administrations. RESULTS: Eighteen patients were included in our study. The number of gadoxetate disodium administrations ranged from 2 to 18. Paired t-test did not show any significant difference in DN-to-pons (p=0.21) and GP-to-thalamus (p=0.09) SI ratios by the end of the study. DN-to-pons SI ratio and GP-to-thalamus SI ratio did not significantly increase with increasing the number of administrations (p=0.14 and p=0.06, respectively). CONCLUSION: Multiple administrations of gadoxetate disodium are not associated with increased SI in DN and GP in the brain. KEY POINTS: • Gadolinium may deposit in the human brain after multiple GBCA administrations. • Gadolinium deposition is associated with increased T1W signal intensity • Increase in signal intensity is most apparent within the DN and GP • Multiple administrations of gadoxetate disodium do not increase T1W signal.

Optimization and Standardization of Circulating MicroRNA Detection for Clinical Application: The miR-Test Case.

BACKGROUND: The identification of circulating microRNAs (miRNAs) in the blood has been recently exploited for the development of minimally invasive tests for the early detection of cancer. Nevertheless, the clinical transferability of such tests is uncertain due to still-insufficient standardization and optimization of methods to detect circulating miRNAs in the clinical setting. METHODS: We performed a series of tests to optimize the quantification of serum miRNAs that compose the miR-Test, a signature for lung cancer early detection, and systematically analyzed variables that could affect the performance of the test. We took advantage of a large-scale (>1000 samples) validation study of the miR-Test that we recently published, to evaluate, in clinical samples, the effects of analytical and preanalytical variables on the quantification of circulating miRNAs and the clinical output of the signature (risk score). RESULTS: We developed a streamlined and standardized pipeline for the processing of clinical serum samples that allows the isolation and analysis of circulating miRNAs by quantitative reverse-transcription PCR, with a throughput compatible with screening trials. The major source of analytical variation came from RNA isolation from serum, which could be corrected by use of external (spike-in) or endogenous miRNAs as a reference for normalization. We also introduced standard operating procedures and QC steps to check for unspecific fluctuations that arise from the lack of standardized criteria in the collection or handling of the samples (preanalytical factors). CONCLUSIONS: We propose our methodology as a reference for the development of clinical-grade blood tests on the basis of miRNA detection.

CT Radiogenomic Characterization of EGFR, K-RAS, and ALK Mutations in Non-Small Cell Lung Cancer.

OBJECTIVES: To assess the association between CT features and EGFR, ALK, KRAS mutations in non-small cell lung cancer. METHODS: Patients undergoing chest CT and testing for the above gene mutations were included. Qualitative evaluation of CTs included: lobe; lesion diameter; shape; margins; ground-glass opacity; density; cavitation; air bronchogram; pleural thickening; intratumoral necrosis; nodules in tumour lobe; nodules in non-tumour lobes; pleural retraction; location; calcifications; emphysema; fibrosis; pleural contact; pleural effusion. Statistical analysis was performed to assess association of features with each gene mutation. ROC curves for gene mutations were drawn; the corresponding area under the curve was calculated. P-values <0.05 were considered significant. RESULTS: Of 285 patients, 60/280 (21.43 %) were positive for EGFR mutation; 31/270 (11.48 %) for ALK rearrangement; 64/240 (26.67 %) for KRAS mutation. EGFR mutation was associated with air bronchogram, pleural retraction, females, non-smokers, small lesion size, and absence of fibrosis. ALK rearrangements were associated with age and pleural effusion. KRAS mutation was associated with round shape, nodules in non-tumour lobes, and smoking. CONCLUSIONS: This study disclosed associations between CT features and alterations of EGFR (air bronchogram, pleural retraction, small lesion size, absence of fibrosis), ALK (pleural effusion) and KRAS (round lesion shape, nodules in non-tumour lobes). KEY POINTS: Air bronchogram, pleural retraction, small size relate to EGFR mutation in NSCLC. Pleural effusion and younger age relate to ALK mutation. Round lesion shape, nodules in non-tumour lobes relate to KRAS mutation.

Combining standardized uptake value of FDG-PET and apparent diffusion coefficient of DW-MRI improves risk stratification in head and neck squamous cell carcinoma.

OBJECTIVES: To assess the independent prognostic value of standardized uptake value (SUV) and apparent diffusion coefficient (ADC), separately and combined, in order to evaluate if the combination of these two variables allows further prognostic stratification of patients with head and neck squamous cell carcinomas (HNSCC). METHODS: Pretreatment SUV and ADC were calculated in 57 patients with HNSCC. Mean follow-up was 21.3 months. Semiquantitative analysis of primary tumours was performed using SUVmaxT/B, ADCmean, ADCmin and ADCmax. The prognostic value of SUVmaxT/B, ADCmean, ADCmin and ADCmax in predicting disease-free survival (DFS) was evaluated with log-rank test and Cox regression models. RESULTS: Patients with SUVmaxT/B ≥5.75 had an overall worse prognosis (p = 0.003). After adjusting for lymph node status and diameter, SUVmaxT/B and ADCmin were both significant predictors of DFS with hazard ratio (HR) = 10.37 (95 % CI 1.22-87.95) and 3.26 (95 % CI 1.20-8.85) for SUVmaxT/B ≥5.75 and ADCmin ≥0.58 × 10-3 mm2/s, respectively. When the analysis was restricted to subjects with SUVmaxT/B ≥5.75, high ADCmin significantly predicted a worse prognosis, with adjusted HR = 3.11 (95 % CI 1.13-8.55). CONCLUSIONS: The combination of SUVmaxT/B and ADCmin improves the prognostic role of the two separate parameters; patients with high SUVmaxT/B and high ADCmin are associated with a poor prognosis. KEY POINTS: • High SUV maxT/B is a poor prognostic factor in HNSCC • High ADC min is a poor prognostic factor in HNSCC • In patients with high SUV maxT/B , high ADC min identified those with worse prognosis.

Dietary inflammatory index and risk of lung cancer and other respiratory conditions among heavy smokers in the COSMOS screening study.

PURPOSE: To test whether the inflammatory potential of diet, as measured using the dietary inflammatory index (DII), is associated with risk of lung cancer or other respiratory conditions and to compare results obtained with those based on the aMED score, an established dietary index that measures adherence to the traditional Mediterranean diet. METHODS: In 4336 heavy smokers enrolled in a prospective, non-randomized lung cancer screening program, we measured participants' diets at baseline using a self-administered food frequency questionnaire from which dietary scores were calculated. Cox proportional hazards and logistic regression models were used to assess association between the dietary indices and lung cancer diagnosed during annual screening, and other respiratory outcomes that were recorded at baseline, respectively. RESULTS: In multivariable analysis, adjusted for baseline lung cancer risk (estimated from age, sex, smoking history, and asbestos exposure) and total energy, both DII and aMED scores were associated with dyspnoea (p trend = 0.046 and 0.02, respectively) and radiological evidence of emphysema (p trend = 0.0002 and 0.02). After mutual adjustment of the two dietary scores, only the association between DII and radiological evidence of emphysema (Q4 vs. Q1, OR 1.30, 95 % CI 1.01-1.67, p trend = 0.012) remained statistically significant. At univariate analysis, both DII and aMED were associated with lung cancer risk, but in fully adjusted multivariate analysis, only the association with aMED remained statistically significant (p trend = 0.04). CONCLUSIONS: Among heavy smokers, a pro-inflammatory diet, as indicated by increasing DII score, is associated with dyspnoea and radiological evidence of emphysema. A traditional Mediterranean diet, which is associated with a lower DII, may lower lung cancer risk.

Squamous cell carcinoma of the oral cavity and oropharynx: what does the apparent diffusion coefficient tell us about its histology?

Background Diffusion-weighted imaging obtained with magnetic resonance (DW-MRI) is a non-invasive imaging tool potentially able to provide information about microstructural tumor characteristics. Purpose To prospectively analyze the correlation between the apparent diffusion coefficient (ADC) and clinical-histologic characteristics of squamous cell carcinoma (SCCA) of the oral cavity and oropharynx. Material and Methods Sixty-seven patients with untreated, histologically proven SCCA of the oral cavity and oropharynx underwent conventional and diffusion-weighted (b-values 0, 50, 250, 500, and 900 s/mm2) MRI. Tumor ADC was calculated from regions of interest drawn manually on the highest b-value images using ImageJ (ImageJ, NIH) and fsl (fsl 4, University of Oxford) image processing packages. ADC was calculated in two ways: standard ADC using all b-values; and ADCHigh using only b-values ≥ 250 s/mm2. We assessed the correlations between both ADC and ADCHigh and the clinical-histological characteristics of SCCA. Results Fifty-two patients (36 men, 16 women; mean age, 55 ± 13 years) were suitable for ADC calculation. Mean ADC was 1136.0 ± 108.5 × 10-6 mm2/s. Mean tumor ADCHigh was 991.2 ± 152.1 × 10-6 mm2/s. Mean tumor size was 32.3 ± 13.4 mm (range, 14.0-69.0 mm). We observed no correlation of either ADC or ADCHigh values with any of the clinical-histological tumor characteristics. Undifferentiated tumors (G3) showed lower apparent diffusion coefficient values compared to differentiated ones (G1-G2), without reaching statistical significance. Conclusion We did not observe any statistically significant correlation between ADC values and clinical-histological characteristics of SCCA of the oral cavity and oropharynx.

Evaluation of diffusion-weighted imaging (DWI) and MR spectroscopy (MRS) as early response biomarkers in cervical cancer patients.

PURPOSE: To prospectively assess whether choline levels and Apparent Diffusion Coefficient (ADC) values within cervical cancers before, during, and after non-surgical therapy are predictive of tumour response. PATIENTS AND METHODS: Patients undergoing MR examination for staging of cervical cancer, candidate for non-surgical therapy, were prospectively enrolled. According to the status at the end of therapies, patients were divided into responders and non-responders. The final outcome after a 5-year follow-up was classified as No Evidence of Disease (NED) or Progression of Disease (PD). Baseline values of mean ADC and Cho/H2O were compared between responders and non-responders, as well as between patients with NED and PD. The percent variation of ADC and Cho/H2O values over time was compared. P values <0.05 were considered significant. RESULTS: 16 patients were included. There was no significant difference at baseline between responders (n = 12) and non-responders (n = 4), nor between NED (n = 11) PD patients (n = 5), in ADC values and Cho/H2O ratio. There was no significant difference in percent variation of ADC values and of Cho/H2O, comparing responders and non-responders. There was a significant increase in absolute values of ADC from the initial to mid-therapy MRI (p = 0.0001), while Cho/H2O was stable (p value: 0.61). In the four non-responders, the ADC increase was not significant (p value: 0.25), while it was significant in the 11 responders (p value: 0.001). Values of spectroscopy were stable in both responders and non-responders. CONCLUSIONS: High increases of ADC values from baseline to mid-therapy MR reflect response to therapies. There were no significant variations in choline/water ratios over time.

Robot-assisted radical prostatectomy: Multiparametric MR imaging-directed intraoperative frozen-section analysis to reduce the rate of positive surgical margins.

PURPOSE: To investigate whether use of multiparametric magnetic resonance (MR) imaging-directed intraoperative frozen-section (IFS) analysis during nerve-sparing robot-assisted radical prostatectomy reduces the rate of positive surgical margins. MATERIALS AND METHODS: This retrospective analysis of prospectively acquired data was approved by an institutional ethics committee, and the requirement for informed consent was waived. Data were reviewed for 134 patients who underwent preoperative multiparametric MR imaging (T2 weighted, diffusion weighted, and dynamic contrast-material enhanced) and nerve-sparing robot-assisted radical prostatectomy, during which IFS analysis was used, and secondary resections were performed when IFS results were positive for cancer. Control patients (n = 134) matched for age, prostate-specific antigen level, and stage were selected from a pool of 322 patients who underwent nerve-sparing robot-assisted radical prostatectomy without multiparametric MR imaging and IFS analysis. Rates of positive surgical margins were compared by means of the McNemar test, and a multivariate conditional logistic regression model was used to estimate the odds ratio of positive surgical margins for patients who underwent MR imaging and IFS analysis compared with control subjects. RESULTS: Eighteen patients who underwent MR imaging and IFS analysis underwent secondary resections, and 13 of these patients were found to have negative surgical margins at final pathologic examination. Positive surgical margins were found less frequently in the patients who underwent MR imaging and IFS analysis than in control patients (7.5% vs 18.7%, P = .01). When the differences in risk factors are taken into account, patients who underwent MR imaging and IFS had one-seventh the risk of having positive surgical margins relative to control patients (adjusted odds ratio: 0.15; 95% confidence interval: 0.04, 0.61). CONCLUSION: The significantly lower rate of positive surgical margins compared with that in control patients provides preliminary evidence of the positive clinical effect of multiparametric MR imaging-directed IFS analysis for patients who undergo prostatectomy.

Positron emission tomography in the diagnostic work-up of screening-detected lung nodules.

Low-dose computed tomography (CT) screening for lung cancer can reduce lung cancer mortality, but overdiagnosis, false positives and invasive procedures for benign nodules are worrying. We evaluated the utility of positron emission tomography (PET)-CT in characterising indeterminate screening-detected lung nodules. 383 nodules, examined by PET-CT over the first 6 years of the COSMOS (Continuous Observation of Smoking Subjects) study to diagnose primary lung cancer, were reviewed and compared with pathological findings (surgically-treated patients) or follow-up (negative CT for ⩾2 years, considered negative); 196 nodules were malignant. The sensitivity, specificity and accuracy of PET-CT for differentially diagnosing malignant nodules were, respectively, 64%, 89% and 76% overall, and 82%, 92% and 88% for baseline-detected nodules. Performance was lower for nodules found at repeat annual scans, with sensitivity ranging from 22% for nonsolid to 79% for solid nodules (p=0.0001). Sensitivity (87%) and specificity (73%) were high for nodules ⩾15 mm, better (sensitivity 98%) for solid nodules ⩾15 mm. PET-CT was highly sensitive for the differential diagnosis of indeterminate nodules detected at baseline, nodules ⩾15 mm and solid nodules. Sensitivity was low for sub-solid nodules and nodules discovered after baseline for which other methods, e.g. volume doubling time, should be used.

Correlation between CT perfusion and clinico-pathological features in prostate cancer: a prospective study.

BACKGROUND: The aim of the study was to assess the correlation between computed tomography perfusion (PCT) parameters and PSA levels, Gleason score, and pTNM stage in patients with prostate cancer (PCa). MATERIAL/METHODS: One hundred twenty-five patients with localized PCa were prospectively enrolled in the study. All patients were diagnosed due to suspicious prostate findings and elevated PSA serum levels and underwent PCT followed by core biopsy and radical prostatectomy. Blood flow (BF), blood volume (BV), mean transit time (MTT), and permeability-surface (PS) area product were computed in the suspected PCa area and normal prostatic tissue. Core biopsy followed by prostatectomy was performed 2-4 weeks after PCT. Correlation between PCT findings and PSA levels, Gleason score, and pTNM stage were analyzed. RESULTS: The mean age of patients was 64 years. All patients had elevated PSA levels (mean value 6.2 ng/ml). Nineteen patients (15.9%) were at low risk of recurrence, 91 (76.5%) were at moderate risk, and 9 (7.6%) were at high risk according to National Comprehensive Cancer Network criteria. PCa was visible on PCT as focal peripheral CT enhancement in 119 out of 125 patients (sensitivity 95.2%). Significant correlations between BV, BF, and PS values and PSA level were found (p<0.05), as well as a trend for difference between BV, BF, and PS in poorly and moderately differentiated tumors (according to Gleason score) in comparison with highly differentiated PCa (p<0.08). The analysis also revealed a correlation between mean perfusion values and BV, MTT, PS, and pTNM cancer stage (p<0.04). CONCLUSIONS: Our study suggests that in low- and intermediate- risk patients, PCT parameters correlate with PSA values, Gleason score, and pTNM stage and can be useful for initial tumor staging.