Prediction of 177Lu-DOTATATE PRRT Outcome Using Multimodality Imaging in Patients with Gastroenteropancreatic Neuroendocrine Tumors: Results from a Prospective Phase II LUMEN Study.

Our objective was to predict the outcome of peptide receptor radionuclide therapy (PRRT) using multimodality imaging and tumor dosimetry on gastroenteropancreatic neuroendocrine tumor (GEP-NET) lesions and patients. Methods: This prospective study included patients with progressive GEP-NETs. Treatment consisted of 4 cycles of 7.4 GBq of 177Lu-DOTATATE. Imaging parameters were measured on 68Ga-DOTATATE PET/CT (SUVmax/mean, somatostatin receptor [SSTR] tumor volume [TV], total lesion SSTR expression, and tumor-to-blood and tumor-to-spleen ratios), 18F-FDG PET/CT (SUVmax/mean, metabolically active TV, and total lesion glycolysis), and diffusion-weighted MRI (apparent diffusion coefficient) in a maximum of 5 target lesions per patient at approximately 10 wk after each injection. Tumor dosimetry was performed using SPECT/CT at 3 time points for every cycle. Baseline imaging parameters, their relative changes after PRRT cycle 1 (C1), and the tumor-absorbed dose at C1 were correlated with lesion morphologic outcome. The average values of the imaging parameters and the minimal, maximal, and mean C1 tumor-absorbed dose in each patient were tested for association with progression-free survival (PFS) and best objective response (RECIST 1.1). Results: In the 37 patients, the median PFS was 28 mo. Eleven of the 37 (30%) achieved a partial response (RECIST 1.1). After a median follow-up of 57 mo, the median time to lesion progression had not been reached in 84 morphologically evaluable lesions, with only 12 (14%) progressing (size increase ≥ 20% from baseline). Patients receiving a minimal C1 dose of 35 Gy in all target lesions exhibited a significantly longer PFS (48.1 vs. 26.2 mo; hazard ratio, 0.37; 95% CI, 0.17-0.82; P = 0.02). Volumetric 68Ga-DOTATATE PET parameters correlated with lesion and patient outcome: patients with an SSTR TV decrease of more than 10% after C1 had a longer PFS (51.3 vs. 22.8 mo; hazard ratio, 0.35; 95% CI, 0.16-0.75; P = 0.003). There was no statistical evidence of an association between other dosimetric or imaging parameters and the lesion or patient outcome. Conclusion: Minimal tumor-absorbed dose at C1 is predictive of outcome in patients with GEP-NETs treated with PRRT, providing a basis for personalized dosimetry-guided treatment strategies. An SSTR TV decrease after C1 could be used for early therapy response assessment as a predictor of PRRT outcome.

Effectiveness of Carbon Localization for Invasive Breast Cancer: An Institutional Experience.

Introduction: The final oncological and aesthetic results of breast-conserving surgery (BCS) are influenced by the precise localization of breast cancer (BC) tumors and by the quality of the intraoperative margin assessment technique. This study aimed to assess the effectiveness of the carbon localization (CL) technique by determining the success rate of BC identification and the proportion of adequate complete resection of BC lesions. Methods: We conducted a cross-sectional retrospective study of patients treated with primary BCS for invasive BC who underwent CL of their BC lesion at the Jules Bordet Institute between January 2015 and December 2017. Descriptive statistics with categorical and continuous variables were used. The success rate of tumor identification and the rate of adequate excision were calculated using the test of percentages for independent dichotomous data. Results: This study included 542 patients with 564 nonpalpable BC lesions. The median pathological tumor size was 12 mm. Of these, 460 were invasive ductal carcinomas. Most of the tumors were of the luminal subtype. CL was performed using ultrasound guidance in 98.5% of cases. The median delay between CL and surgery was 5 days, with 46% of the patients having CL one day before surgery. The lumpectomy weighed 38 g on average, with a median diameter of the surgical sample at 6 cm and a median volume of 44 cm3 (6-369). One-stage complete resection was successfully performed in 93.4% of cases. In 36% of cases, an intraoperative re-excision was performed, based on intraoperative macroscopic pathological margin evaluation. The tumor was identified in 98.9% of cases in the breast surgical specimen. Conclusion: This study demonstrated high success rates for BC tumor identification (99%) and one-stage complete resection (93.4%) after BCS and CL. These results show that CL is an effective, simple, and inexpensive localization technique for successful excision of BC lesions during BCS.

Rectal cancer response to neoadjuvant chemoradiotherapy evaluated with MRI: Development and validation of a classification algorithm.

OBJECTIVE: The aim of this study was to develop and validate a decision support model using data mining algorithms, based on morphologic features derived from MRI images, to discriminate between complete responders (CR) and non-complete responders (NCR) patients after neoadjuvant chemoradiotherapy (CRT), in a population of patients with locally advanced rectal cancer (LARC). METHODS: Two populations were retrospectively enrolled: group A (65 patients) was used to train a data mining decision tree algorithm whereas group B (30 patients) was used to validate it. All patients underwent surgery; according to the histology evaluation, patients were divided in CR and NCR. Staging and restaging MRI examinations were retrospectively analysed and seven parameters were considered for data mining classification. Five different classification methods were tested and evaluated in terms of sensitivity, specificity, accuracy and AUC in order to identify the classification model able to achieve the best performance. The best classification algorithm was subsequently applied to group B for validation: sensitivity, specificity, positive and negative predictive value, accuracy and ROC curve were calculated. Inter and intra-reader agreement were calculated. RESULTS: Four features were selected for the development of the classification algorithm: MRI tumor regression grade (MR-TRG), staging volume (SV), tumor volume reduction rate (TVRR) and signal intensity reduction rate (SIRR). The decision tree J48 showed the highest efficiency: when applied to group B, all the CR and 18/21 NCR were correctly classified (sensitivity 85.71%, specificity 100%, PPV 100%, NPV 94.2%, accuracy 95.7%, AUC 0.833). Both inter- and intra-reader evaluation showed good agreement (κ > 0.6). CONCLUSIONS: The proposed decision support model may help in distinguishing between CR and NCR patients with LARC after CRT.

Early Response to Chemotherapy in Malignant Pleural Mesothelioma Evaluated Using Diffusion-Weighted Magnetic Resonance Imaging: Initial Observations.

INTRODUCTION: We compared the magnetic resonance imaging total tumor volume (TTV) and median apparent diffusion coefficient (ADC) of malignant pleural mesothelioma (MPM) before and at 4 weeks after chemotherapy, to evaluate whether these are potential early markers of treatment response. METHODS: Diffusion-weighted magnetic resonance imaging was performed in 23 patients with MPM before and after 4 weeks of chemotherapy. The TTV was measured by semiautomatic segmentation (GrowCut) and transferred onto ADC maps to record the median ADC. Test-retest repeatability of TTV and ADC was evaluated in eight patients. TTV and median ADC changes were compared between responders and nonresponders, defined using modified Response Evaluation Criteria In Solid Tumors on computed tomography (CT) at 12 weeks after treatment. TTV and median ADC were also correlated with CT size measurement and disease survival. RESULTS: The test-retest 95% limits of agreement for TTV were -13.9% to 16.2% and for median ADC -1.2% to 3.3%. A significant increase in median ADC in responders was observed at 4 weeks after treatment (p = 0.02). Correlation was found between CT tumor size change at 12 weeks and median ADC changes at 4 weeks post-treatment (r = -0.560, p = 0.006). An increase in median ADC greater than 5.1% at 4 weeks has 100% sensitivity and 90% specificity for responders (area under the curve = 0.933, p < 0.001). There was also moderate correlation between median tumor ADC at baseline and overall survival (r = 0.45, p = 0.03). CONCLUSIONS: Diffusion-weighted magnetic resonance imaging measurements of TTV and median ADC in MPM have good measurement repeatability. Increase in ADC at 4 weeks post-treatment has the potential to be an early response biomarker.

DCE-MRI is more sensitive than IVIM-DWI for assessing anti-angiogenic treatment-induced changes in colorectal liver metastases.

BACKGROUND: Diffusion weighted imaging (DWI) with intravoxel incoherent motion (IVIM) modelling can inform on tissue perfusion without exogenous contrast administration. Dynamic-contrast-enhanced (DCE) MRI can also characterise tissue perfusion, but requires a bolus injection of a Gadolinium-based contrast agent. This study compares the use of DCE-MRI and IVIM-DWI methods in assessing response to anti-angiogenic treatment in patients with colorectal liver metastases in a cohort with confirmed treatment response. METHODS: This prospective imaging study enrolled 25 participants with colorectal liver metastases to receive Regorafenib treatment. A target metastasis > 2 cm in each patient was imaged before and at 15 days after treatment on a 1.5T MR scanner using slice-matched IVIM-DWI and DCE-MRI protocols. MRI data were motion-corrected and tumour volumes of interest drawn on b=900 s/mm2 diffusion-weighted images were transferred to DCE-MRI data for further analysis. The median value of four IVIM-DWI parameters [diffusion coefficient D (10-3 mm2/s), perfusion fraction f (ml/ml), pseudodiffusion coefficient D* (10-3 mm2/s), and their product fD* (mm2/s)] and three DCE-MRI parameters [volume transfer constant Ktrans (min-1), enhancement fraction EF (%), and their product KEF (min-1)] were recorded at each visit, before and after treatment. Changes in pre- and post-treatment measurements of all MR parameters were assessed using Wilcoxon signed-rank tests (P<0.05 was considered significant). DCE-MRI and IVIM-DWI parameter correlations were evaluated with Spearman rank tests. Functional MR parameters were also compared against Response Evaluation Criteria In Solid Tumours v.1.1 (RECIST) evaluations. RESULTS: Significant treatment-induced reductions of DCE-MRI parameters across the cohort were observed for EF (91.2 to 50.8%, P<0.001), KEF (0.095 to 0.045 min-1, P<0.001) and Ktrans (0.109 to 0.078 min-1, P=0.002). For IVIM-DWI, only D (a non-perfusion parameter) increased significantly post treatment (0.83 to 0.97 × 10-3 mm2/s, P<0.001), while perfusion-related parameters showed no change. No strong correlations were found between DCE-MRI and IVIM-DWI parameters. A moderate correlation was found, after treatment, between Ktrans and D* (r=0.60; P=0.002) and fD* (r=0.67; P<0.001). When compared to RECIST v.1.1 evaluations, KEF and D correctly identified most clinical responders, whilst non-responders were incorrectly identified. CONCLUSION: IVIM-DWI perfusion-related parameters showed limited sensitivity to the anti-angiogenic effects of Regorafenib treatment in colorectal liver metastases and showed low correlation with DCE-MRI parameters, despite profound and significant post-treatment reductions in DCE-MRI measurements. TRIAL REGISTRATION: NCT03010722 clinicaltrials.gov; registration date 6th January 2015.

Preoperative measurement of the hiatal surface with MDCT: impact on surgical planning.

OBJECTIVE: To evaluate the accuracy and reproducibility of hiatal surface area (HSA) measurement on dedicated multidetector computed tomography (MDCT) acquisition, in patients, previously subjected to laparoscopic sleeve gastrectomy (LSG), and affected by gastroesophageal reflux disease (GERD). Intraoperative HSA measurement was considered the reference standard. METHODS: Fifty-two candidates for laparoscopic hiatal hernia repair were prospectively included in the study. MDCT images were acquired during swallowing of oral iodinated contrast media and during strain. Measurements were performed by nine readers divided into three groups according to their experience. Results were compared with intraoperative measurements by means of Spearman correlation coefficient. Reproducibility was evaluated with intra- and interreader agreement by means of weighted Cohen's kappa and intraclass correlation coefficient (ICC). RESULTS: Significant differences between MDCT and intraoperative HSA measurements were observed for swallowing imaging for less experienced readers (p = 0.037, 0.025, 0.028 and 0.019). No other statistically significant differences were observed (p > 0.05). The correlation between HSA measured intraoperatively and on MDCT was higher for strain imaging compared to swallowing (r = 0.94-0.92 vs 0.94-0.89). The overall reproducibility of MDCT HSA measurement was excellent (ICC of 0.95; 95% CI 0,8993 to 0,9840) independently of reader's experience CONCLUSION: HSA can be accurately measured on MDCT images. This method is reproducible and minimally influenced by reader experience. The preoperative measurement of HSA has potential advantages for surgeons in terms of correct approach to hiatal defects in obese patient.

Balloon-occluded chemoembolization for hepatocellular carcinoma: a prospective study of safety, feasibility and outcomes.

AIM: Evaluation of safety and efficacy of selective balloon-occluded transarterial chemoembolization using polyethylene glycol embolizing microspheres in patients with hepatocellular carcinoma. MATERIALS & METHODS: Twenty-four consecutive patients were included in this monocentric prospective trial. Adverse events were evaluated at 24 h and 1 month. Imaging response according to modified response evaluation criteria in solid tumors was assessed at 1, 3 and 6 months. RESULTS: The median time of follow-up was of 22.8 months (interquartile range (IQR) 17.38-26.22). Clinical grade 1/2 toxicities (0% >grade 2) were reported in 25.7% of patients, with abdominal pain being the most frequent complication (17.1%). No 30-days mortalities or liver decompensation were observed. The 1-month follow-up MRI showed an overall response rate of 74.3%. CONCLUSION: Balloon-occluded transarterial chemoembolization was shown to be safe and effective.

Radiological and histological findings of an asymptomatic ever-increasing neoplasm: The small bowel neuroendocrine tumor (NET).

The small bowel neuroendocrine tumor is a rare but ever-increasing tumor, most of the time asymptomatic and found incidentally. An early diagnosis can consistently change the prognosis.

MRI Tumor Regression Grade and Circulating Tumor DNA as Complementary Tools to Assess Response and Guide Therapy Adaptation in Rectal Cancer.

PURPOSE: Response to preoperative chemo-radiotherapy (CRT) varies. We assessed whether circulating tumor DNA (ctDNA) might be an early indicator of tumor response or progression to guide therapy adaptation in rectal cancer. EXPERIMENTAL DESIGN: A total of 243 serial plasma samples were analyzed from 47 patients with localized rectal cancer undergoing CRT. Up to three somatic variants were tracked in plasma using droplet digital PCR. RECIST and MRI tumor regression grade (mrTRG) evaluated response. Survival analyses applied Kaplan-Meier method and Cox regression. RESULTS: ctDNA detection rates were: 74% (n = 35/47) pretreatment, 21% (n = 10/47) mid CRT, 21% (n = 10/47) after completing CRT, and 13% (n = 3/23) after surgery. ctDNA status after CRT was associated with primary tumor response by mrTRG (P = 0.03). With a median follow-up of 26.4 months, metastases-free survival was shorter in patients with detectable ctDNA after completing CRT [HR 7.1; 95% confidence interval (CI), 2.4-21.5; P < 0.001], persistently detectable ctDNA pre and mid CRT (HR 3.8; 95% CI, 1.2-11.7; P = 0.02), and pre, mid, and after CRT (HR 11.5; 95% CI, 3.3-40.4; P < 0.001) compared with patients with undetectable or nonpersistent ctDNA. In patients with detectable ctDNA, a fractional abundance threshold of ≥0.07% mid CRT or ≥0.13% after completing CRT predicted for metastases with 100% sensitivity and 83.3% specificity for mid CRT and 66.7% for CRT completion. All 3 patients with detectable ctDNA post-surgery relapsed compared with none of the 20 patients with undetectable ctDNA (P = 0.001). CONCLUSIONS: ctDNA identified patients at risk of developing metastases during the neoadjuvant period and post-surgery, and could be used to tailor treatment.

Dynamic MR of the pelvic floor: Influence of alternative methods to draw the pubococcygeal line (PCL) on the grading of pelvic floor descent.

OBJECTIVE: To evaluate the impact of the pubococcygeal line (PCL) position on hiatal descent grading, comparing the method recommended by the official guidelines with the other two most common methods reported in literature. METHODS: Female patients prospectively included performed dynamic-MR (1,5 T) in supine position. Rectum and vagina were filled with ultrasound gel. MR protocol included TSE T2 weighted sequences on axial/sagittal/coronal planes and steady-state sequences (FIESTA) on midsagittal plane during three phases (rest, strain and defecation). On each phase, the posterior point of PCL was traced in the region recommended by the official guidelines (last coccygeal joint or PCLcc) and in the other two regions: coccyx's tip (PCLtip) and sacrococcygeal joint (PCLsc). The resulting grades of pelvic floor descent (according to HMO-System) were compared. Inter-reader and intra-reader agreement were evaluated. RESULTS: The final population consisted of 60 patients (56yy±10). No significant differences in grading were observed using PCLtip and PCLcc in all phases (p = 0.3016/0.0719/0.0719 during rest/strain/defecation). Using PCLsc, the grading was significantly overestimated compared to PCLcc in all phases (p = 0.0041/0.0001/0.0001 during rest/strain/defecation). Inter-reader and intra-reader agreement were significantly higher using PCLtip (p < 0.05). CONCLUSIONS: PCLtip is a reliable and highly reproducible option to the official PCLcc to correctly grade the pelvic floor descent and could be used when the PCLcc is not clearly visible. The use of PCLsc overestimates the grading compared to the official PCLcc and should not be used to avoid wrong patients' management.

Pseudoprogression on treatment with immune-checkpoint inhibitors in patients with gastrointestinal malignancies: Case series and short literature review.

Gastrointestinal cancers are very common cancers with colorectal being the fourth most common type, gastric the sixth, and esophageal the tenth. Although recent advances have been made in management including incorporation of antiangiogenic, anti-EGFR, and anti-HER2 directed therapies, overall their prognosis remains poor. Anti-PD-1 therapy with nivolumab and pembrolizumab are licensed for advanced chemorefractory gastroesophageal cancer and many other checkpoint inhibitor therapies are being assessed alone and in combination in these diseases. One of the challenges posed in assessing response to immunotherapy treatment is the phenomenon of pseudoprogression. This phenomenon, which is well described in patients with malignant melanoma is most frequently described as a size increase of contrast enhancing lesions or appearance of new lesions that stabilize or reduce in size with time. Most other solid tumors have a low incidence of pseudoprogression although cases have been reported for lung, head, and neck cancer and a range of gliomas. Herein we present 6 cases of patients with gastrointestinal cancers who were treated with anti-PD1 (programmed cell death) and anti-PD-L1 (programmed cell death ligand-1) antibodies, and experience pseudoprogression.

Liver metastasis from adenoid cystic carcinoma: imaging and histologic features.

Adenoid cystic carcinoma is a rare tumour. The reported incidence of isolated metastases to the liver is rare but possible and it seems to be more likely in case of perineural invasion.

Bifocal hepatocellular carcinoma: Magnetic resonance imaging features after transarterial embolization.

The aim of this article is to show the typical appearance of a bifocal hepatocellular carcinoma on contrast enhanced magnetic resonance imaging before and after locoregional treatment consisting of transarterial embolization (TAE).

MDCT of the liver in obese patients: evaluation of a different method to optimize iodine dose.

PURPOSE: To prospectively compare two different approaches for estimating the amount of intravenous contrast media (CM) needed for multiphasic MDCT of the liver in obese patients. MATERIALS AND METHODS: This single-center, HIPAA-compliant prospective study was approved by our Institutional Review Board. Ninety-six patients (55 men, 41 women), with a total of 42 hypovascular liver lesions, underwent MDCT of the liver. The amount of contrast medium injected was computed according to the patient's lean body weight which was estimated using either a bioimpedance device (Group A) or the James formula (Group B). The following variables were compared between the two groups: the amount of contrast medium injected (in grams of Iodine, gI), the contrast enhancement index (CEI) and the lesion-to-liver contrast-to-noise ratio. RESULTS: Protocols A and B yielded significant differences in the amount of CM injected (mean values 41.9 ± 4.41 gI in Group A vs. 35.9 ± 5.75 gI in Group B; P = 0.021). The mean CEI value and lesion-to-liver contrast-to-noise ratio measured on the portal phase were significantly higher with protocol A than with protocol B (P < 0.05). CONCLUSIONS: Our study shows that the adoption of a bioimpedance device in obese patients improves liver parenchymal enhancement and lesion conspicuity.

Magnetic resonance tumor regression grade (MR-TRG) to assess pathological complete response following neoadjuvant radiochemotherapy in locally advanced rectal cancer.

This study aims to evaluate the feasibility of a magnetic resonance (MR) automatic method for quantitative assessment of the percentage of fibrosis developed within locally advanced rectal cancers (LARC) after neoadjuvant radiochemotherapy (RCT). A total of 65 patients were enrolled in the study and MR studies were performed on 3.0 Tesla scanner; patients were followed-up for 30 months. The percentage of fibrosis was quantified on T2-weighted images, using automatic K-Means clustering algorithm. According to the percentage of fibrosis, an optimal cut-off point for separating patients into favorable and unfavorable pathologic response groups was identified by ROC analysis and tumor regression grade (MR-TRG) classes were determined and compared to histopathologic TRG. An optimal cut-off point of 81% of fibrosis was identified to differentiate between favorable and unfavorable pathologic response groups resulting in a sensitivity of 78.26% and a specificity of 97.62% for the identification of complete responders (CRs). Interobserver agreement was good (0.85). The agreement between P-TRG and MR-TRG was excellent (0.923). Significant differences in terms of overall survival (OS) and disease free survival (DFS) were found between favorable and unfavorable pathologic response groups. The automatic quantification of fibrosis determined by MR is feasible and reproducible.

Metabolic syndrome and polycystic ovary syndrome: an intriguing overlapping.

Metabolic syndrome is an increasing pathology in adults and in children, due to a parallel rise of obesity. Sedentary lifestyle, food habits, cultural influences and also a genetic predisposition can cause dyslipidemia, hypertension, abdominal obesity and insulin resistance which are the two main features of metabolic syndrome. Polycystic ovary syndrome (PCOS) is a condition directly associated with obesity, insulin resistance (HOMA index) and metabolic syndrome, and it is very interesting for its relationship and overlap with the metabolic syndrome. The relationship between the two syndromes is mutual: PCOS women have a higher prevalence of metabolic syndrome and also women with metabolic syndrome commonly present the reproductive/endocrine trait of PCOS. Prevention and treatment of metabolic syndrome and PCOS are similar for various aspects. It is necessary to treat excess adiposity and insulin resistance, with the overall goals of preventing cardiovascular disease and type 2 diabetes and improving reproductive failure in young women with PCOS. First of all, lifestyle changes, then pharmacological therapy, bariatric surgery and laparoscopic ovarian surgery represent the pillars for PCOS treatment.