Radiomics in the characterization of lipid-poor adrenal adenomas at unenhanced CT: time to look beyond usual density metrics.

OBJECTIVES: In this study, we developed a radiomic signature for the classification of benign lipid-poor adenomas, which may potentially help clinicians limit the number of unnecessary investigations in clinical practice. Indeterminate adrenal lesions of benign and malignant nature may exhibit different values of key radiomics features. METHODS: Patients who had available histopathology reports and a non-contrast-enhanced CT scan were included in the study. Radiomics feature extraction was done after the adrenal lesions were contoured. The primary feature selection and prediction performance scores were calculated using the least absolute shrinkage and selection operator (LASSO). To eliminate redundancy, the best-performing features were further examined using the Pearson correlation coefficient, and new predictive models were created. RESULTS: This investigation covered 50 lesions in 48 patients. After LASSO-based radiomics feature selection, the test dataset's 30 iterations of logistic regression models produced an average performance of 0.72. The model with the best performance, made up of 13 radiomics features, had an AUC of 0.99 in the training phase and 1.00 in the test phase. The number of features was lowered to 5 after performing Pearson's correlation to prevent overfitting. The final radiomic signature trained a number of machine learning classifiers, with an average AUC of 0.93. CONCLUSIONS: Including more radiomics features in the identification of adenomas may improve the accuracy of NECT and reduce the need for additional imaging procedures and clinical workup, according to this and other recent radiomics studies that have clear points of contact with current clinical practice. CLINICAL RELEVANCE STATEMENT: The study developed a radiomic signature using unenhanced CT scans for classifying lipid-poor adenomas, potentially reducing unnecessary investigations that scored a final accuracy of 93%. KEY POINTS: • Radiomics has potential for differentiating lipid-poor adenomas and avoiding unnecessary further investigations. • Quadratic mean, strength, maximum 3D diameter, volume density, and area density are promising predictors for adenomas. • Radiomics models reach high performance with average AUC of 0.95 in the training phase and 0.72 in the test phase.

Patient centered radiology: investigating 3 Tesla whole body MRI acceptance in cancer patients.

INTRODUCTION: Whole body magnetic resonance imaging (WB-MRI) is a promising emerging imaging technology for detecting bone and soft tissue pathology, especially in the onco-hematological field. This study aims to evaluate cancer patients' experience of WB-MRI performed on a 3T scanner compared to other diagnostic total body examinations. MATERIAL AND METHOD: In this prospective committee-approved study, patients completed a questionnaire in person (n = 134) after undergoing a WB-MRI scan to collect data on their physical and psychological reactions during the scan, the global satisfaction level, and preference for other types of MRI or computed tomography (CT), or positron emission tomography (PET/CT). Of all patients who had performed a CT or PET/CT the previous year, 61.9% had already undergone an MRI. The most common symptoms reported were: 38.1% perceived a localized increase in temperature and 34.4% numbness and tingling of the limbs. The scan time averaged 45 min and was well tolerated by most patients (112, 85.5%). Overall, WB-MRI was appreciated by the majority (121/134-90.3%) of patients who said they would probably undergo the procedure again. Patients preferred the WB-MRI in 68.7% of cases (92/134), followed by CT in 15.7% of cases (21/134) and by PET/CT in 7.4% (10/134), with 8.4% (11/134) of patients without any preference. The preference for imaging modalities was age-dependent (p = 0.011), while (p > 0.05) was independent of sex and a primary cancer site. CONCLUSION: These results demonstrate a high degree of WB-MRI acceptance from a patient's point of view.

Plasma tumor DNA is associated with increased risk of venous thromboembolism in metastatic castration-resistant cancer patients.

Cancer is a risk factor for venous thromboembolism (VTE). Plasma tumor DNA (ptDNA) is an independent predictor of outcome in metastatic castration-resistant prostate cancer (mCRPC). We aimed to investigate the association between ptDNA and VTE in mCRPC. This prospective biomarker study included 180 mCRPC patients treated with abiraterone and enzalutamide from April 2013 to December 2018. We excluded patients with a previous VTE history and/or ongoing anticoagulation therapy. Targeted next-generation sequencing was performed to determine ptDNA fraction from pretreatment plasma samples. VTE risk based on survival analysis was performed using cumulative incidence function and estimating sub-distributional hazard ratio (SHR). At a median follow-up of 58 months (range 0.5-111.0), we observed 21 patients who experienced VTE with a cumulative incidence at 12 months of 17.1% (95% confidence interval [CI] 10.3-23.9). Elevated ptDNA, visceral metastasis, prior chemotherapy and lactate dehydrogenase (LDH) were significantly associated with higher VTE incidence compared to patients with no thrombosis (12-month estimate, 18.6% vs 3.5%, P = .0003; 44.4% vs 14.8%, P = .015; 24.7% vs 4.5%, P = .006; and 30.0% vs 13.5%, P = .05, respectively). In the multivariate analysis including ptDNA level, visceral metastases, number of lesions and serum LDH, high ptDNA fraction was the only independent factor associated with the risk of thrombosis (HR 5.78, 95% CI 1.63-20.44, P = .006). These results first suggest that baseline ptDNA fraction in mCRPC patients treated with abiraterone or enzalutamide may be associated with increased VTE risk. These patients may be followed-up more closely for the VTE risk, and the need for a primary thromboprophylaxis should be taken into account in mCRPC with elevated ptDNA.

Dynamic contrast-enhanced ultrasonography (D-CEUS) for the early prediction of bevacizumab efficacy in patients with metastatic colorectal cancer.

OBJECTIVES: To investigate early changes in tumour perfusion parameters by dynamic contrast-enhanced ultrasonography (D-CEUS) and to identify any correlation with survival and tumour response in patients with metastatic colorectal cancer (CRC) treated with bevacizumab (B). METHODS: Thirty-seven patients randomized to either chemotherapy (C) plus B or C alone were considered for this study. D-CEUS was performed at baseline and after the first treatment cycle (day 15). Four D-CEUS perfusion parameters were considered: derived peak intensity (DPI), area under the curve (AUC), slope of wash-in (A) and time to peak intensity (TPI). RESULTS: In patients treated with C plus B, a ≥22.5 % reduction in DPI, ≥20 % increase in TPI and ≥10 % reduction in AUC were correlated with higher progression-free survival in the C+B arm (p = 0.048, 0.024 and 0.010, respectively) but not in the C arm. None of the evaluated parameter modifications had a correlation with tumour response or overall survival. CONCLUSIONS: D-CEUS could be useful for detecting and quantifying dynamic changes in tumour vascularity as early as 15 days after the start of B-based therapy. Although these changes may be predictive of progression-free survival, no correlation with response or overall survival was found. KEY POINTS: • D-CEUS showed early changes in liver metastasis perfusion in colorectal cancer. • A decrease in tumour perfusion was associated with longer progression-free survival. • The decrease in perfusion was not correlated with higher overall survival.

Long-term follow-up and role of FDG PET in advanced pancreatic neuroendocrine patients treated with 177Lu-D OTATATE.

PURPOSE: Lu-DOTATATE (Lu-PRRT) is a valid therapeutic option in differentiated pancreatic neuroendocrine tumors (P-NETs). FDG PET seems to be an important prognostic factor in P-NETs. We evaluated the efficacy of Lu-PRRT and the role of FDG PET in 60 patients with advanced P-NETs. METHODS: From March 2008 to June 2011, 60 consecutive patients with P-NETs were enrolled in the study. Follow-up lasted until March 2016. Eligible patients were treated with two different total cumulative activities (18.5 or 27.8 GBq in 5 cycles every 6-8 weeks), according to kidney and bone marrow parameters. RESULTS: Twenty-eight patients received a mean full activity (FA) of 25.9 GBq and 32 a mean reduced activity (RA) of 18.5 GBq. The disease control rate (DCR), defined as the sum of CR+PR+SD was 85.7 % in the FA group and 78.1 % in the RA group. Median progression-free survival (mPFS) was 53.4 months in the FA group and 21.7 months in the RA group (P = 0.353). Median overall survival (mOS) was not reached (nr) in FA patients and was 63.8 months in the RA group (P = 0.007). Fifty-five patients underwent an FDG PET scan before Lu-PRRT, 32 (58 %) showing an increased FDG uptake in tumor sites. mPFS was 21.1 months in FDG PET-positive patients and 68.7 months in the FDG PET-negative group (P < 0.0002), regardless of the total activity administered. CONCLUSION: Both FA and RA are active in patients undergoing Lu-PRRT. However, an FA of 27.8 GBq of Lu-PRRT prolongs PFS and OS compared to an RA of 18.5 GBq. Our results indicate that FDG PET is an independent prognostic factor in this patient setting.

Radiomics Analysis on [68Ga]Ga-PSMA-11 PET and MRI-ADC for the Prediction of Prostate Cancer ISUP Grades: Preliminary Results of the BIOPSTAGE Trial.

Prostate cancer (PCa) risk categorization based on clinical/PSA testing results in a substantial number of men being overdiagnosed with indolent, early-stage PCa. Clinically non-significant PCa is characterized as the presence of ISUP grade one, where PCa is found in no more than two prostate biopsy cores.MRI-ADC and [68Ga]Ga-PSMA-11 PET have been proposed as tools to predict ISUP grade one patients and consequently reduce overdiagnosis. In this study, Radiomics analysis is applied to MRI-ADC and [68Ga]Ga-PSMA-11 PET maps to quantify tumor characteristics and predict histology-proven ISUP grades. ICC was applied with a threshold of 0.6 to assess the features' stability with variations in contouring. Logistic regression predictive models based on imaging features were trained on 31 lesions to differentiate ISUP grade one patients from ISUP two+ patients. The best model based on [68Ga]Ga-PSMA-11 PET returned a prediction efficiency of 95% in the training phase and 100% in the test phase whereas the best model based on MRI-ADC had an efficiency of 100% in both phases. Employing both imaging modalities, prediction efficiency was 100% in the training phase and 93% in the test phase. Although our patient cohort was small, it was possible to assess that both imaging modalities add information to the prediction models and show promising results for further investigations.

The Primacy of High B-Value 3T-DWI Radiomics in the Prediction of Clinically Significant Prostate Cancer.

Predicting clinically significant prostate cancer (csPCa) is crucial in PCa management. 3T-magnetic resonance (MR) systems may have a novel role in quantitative imaging and early csPCa prediction, accordingly. In this study, we develop a radiomic model for predicting csPCa based solely on native b2000 diffusion weighted imaging (DWIb2000) and debate the effectiveness of apparent diffusion coefficient (ADC) in the same task. In total, 105 patients were retrospectively enrolled between January-November 2020, with confirmed csPCa or ncsPCa based on biopsy. DWIb2000 and ADC images acquired with a 3T-MRI were analyzed by computing 84 local first-order radiomic features (RFs). Two predictive models were built based on DWIb2000 and ADC, separately. Relevant RFs were selected through LASSO, a support vector machine (SVM) classifier was trained using repeated 3-fold cross validation (CV) and validated on a holdout set. The SVM models rely on a single couple of uncorrelated RFs (ρ < 0.15) selected through Wilcoxon rank-sum test (p ≤ 0.05) with Holm-Bonferroni correction. On the holdout set, while the ADC model yielded AUC = 0.76 (95% CI, 0.63-0.96), the DWIb2000 model reached AUC = 0.84 (95% CI, 0.63-0.90), with specificity = 75%, sensitivity = 90%, and informedness = 0.65. This study establishes the primary role of 3T-DWIb2000 in PCa quantitative analyses, whilst ADC can remain the leading sequence for detection.

Case Report: The Added Value of Liquid Biopsy in Advanced Colorectal Cancer From Clinical Case Experiences.

Liquid biopsy represents a valid strategy for tumor molecular characterization. It gives the opportunity to bypass tumor heterogeneity, to monitor tumor characteristics during the course of treatment, and to perform the analysis even when tumor tissue is not available or inadequate. In the clinical practice of metastatic colorectal cancer, tumor molecular characterization is crucial for patient management, as RAS and BRAF status could influence the treatment choice. Although for this type of cancer tumor tissue is usually available at diagnosis, liquid biopsy could give complementary information and could permit monitoring of the mutation status during the course of treatment. At present, there are no clinical indications for its use in clinical practice. However, we report four clinical cases for which liquid biopsy analysis gave integrative information with respect to tumor tissue characterization, which permits us to understand the unresponsiveness of patients to treatment, with potential implications in patient's management.

Radiotherapy and High-Dose Interleukin-2: Clinical and Immunological Results of a Proof of Principle Study in Metastatic Melanoma and Renal Cell Carcinoma.

High-dose interleukin-2 (HD IL-2) has curative potential in metastatic melanoma (MM) and renal cell carcinoma (RCC). Radiotherapy (RT) kills cancer cells and induces immunomodulatory effects. Prospective trials exploring clinical and immunological properties of combined RT/HD IL-2 are still needed. We designed a phase II, single-arm clinical trial for patients with MM and RCC. The treatment schedule consisted of 3 daily doses of 6-12 Gy of RT to 1-5 non-index metastatic fields, before IL-2 at the first and third treatment cycle. HD IL-2 was administered by continuous infusion for 72 hours and repeated every 3 weeks for up to 4 cycles, thereafter every 4 weeks for a maximum of 2 cycles. The primary endpoint was the immunological efficacy of the combined RT/HD IL-2 treatment (assessed by IFN-γ ELISPOT). Nineteen out of 22 patients were evaluable for immunological and clinical response. Partial response occurred in 3 (15.7%) patients and stable disease was observed in 7 (36.8%). The disease control rate was 52.6% after a median follow up of 39.2 months. According to Common Terminology Criteria for Adverse Events 4.0 (CTCAE 4.0), the majority of toxicities were grade 1-2. Immunological responses were frequent and detected in 16 (84.2%) patients. Increased levels of IL-8 and IL-10 in melanoma, circulating effector memory CD4+ and intratumoral CD8+ T cells in both tumor types were detected after therapy. Overall the treatment was well tolerated and immunologically active. Immunomonitoring and correlative data on tumor and peripheral blood cell subsets suggest that this combination treatment could be a promising strategy for patients progressing after standard treatments.

Neoadjuvant treatment (FOLFOX4 plus hypofractionated tomotherapy) for patients with locally advanced rectal cancer: a multicenter phase II trial.

AIMS: This study aims to evaluate the safety and efficacy of a new neoadjuvant regimen (FOLFOX4 plus hypofractionated tomotherapy) in patients with locally advanced rectal cancer. METHODS: Patients with stage II-III rectal cancer were treated with the pre-operative chemoradiotherapy regimen comprising FOLFOX4 (two cycles), TomoTherapy (25 Gy in five consecutive fractions, one fraction per day in 5 days on the clinical target volume at the isodose of 95% of the total dose), FOLFOX4 (two cycles), followed by surgery with total mesorectal excision and adjuvant chemotherapy with FOLFOX4 (eight cycles). The primary endpoint was pathological complete response (pCR). RESULTS: Fifty-two patients were enrolled and 50 patients were evaluable. A total of 46 (92%) patients completed chemoradiotherapy according to the study protocol and 49 patients underwent surgery. Overall, 12 patients achieved a pCR (24.5%, 95% CI 12.5-36.5). The most common grade 3 or more adverse events were neutropenia and alteration of the alvus. Adverse reactions due to radiotherapy, mainly grade 1-2 dermatitis, tenesmus, urinary dysfunction and pain, were tolerable and fully reversible. The most important surgical complications included infection, anastomotic leakage and fistula, all resolved with conservative treatment. CONCLUSION: FOLFOX and hypofractionated TomoTherapy is effective and safe in patients with locally advanced rectal cancer. Long-term efficacy needs to be further evaluated. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02000050 (registration date: 26 November 2013) https://clinicaltrials.gov/ct2/show/NCT02000050.

Erratum: Passardi, A. et al. Chemoradiotherapy (Gemox Plus Helical Tomotherapy) for Unresectable Locally Advanced Pancreatic Cancer: A Phase II Study. Cancers 2019, 11, 663.

The authors wish to make the following corrections to this paper [...].

Chemoradiotherapy (Gemox Plus Helical Tomotherapy) for Unresectable Locally Advanced Pancreatic Cancer: A Phase II Study.

The aim of the study was to evaluate the safety and efficacy of a new chemo-radiotherapy regimen for patients with locally advanced pancreatic cancer (LAPC). Patients were treated as follows: gemcitabine 1000 mg/m2 on day 1, and oxaliplatin 100 mg/m2 on day 2, every two weeks (GEMOX regimen) for 4 cycles, 15 days off, hypofractionated radiotherapy (35 Gy in 7 fractions in 9 consecutive days), 15 days off, 4 additional cycles of GEMOX, restaging. From April 2011 to August 2016, a total of 42 patients with non resectable LAPC were enrolled. Median age was 67 years (range 41-75). Radiotherapy was well tolerated and the most frequently encountered adverse events were mild to moderate nausea and vomiting, abdominal pain and fatigue. In total, 9 patients underwent surgical laparotomy (5 radical pancreatic resection 1 thermoablation and 3 explorative laparotomy), 1 patient became operable but refused surgery. The overall resectability rate was 25%, while the R0 resection rate was 12.5%. At a median follow-up of 50 months, the median progression-free survival and overall survival were 9.3 (95% CI 6.2-14.9) and 15.8 (95% CI 8.2-23.4) months, respectively. The results demonstrate the feasibility of a new chemo-radiotherapy regimen as a potential treatment for unresectable LAPC.

Three-dimensional contrast-enhanced ultrasonography of intraductal papillary mucinous neoplasms of the pancreas: a comparison with magnetic resonance imaging.

OBJECTIVES: The objective of this study was to prospectively compare the diagnostic accuracy of 3-dimensional contrast-enhanced ultrasonography (3D-CEUS) with that of magnetic resonance imaging (MRI) in the study of intraductal papillary mucinous neoplasms (IPMNs) of the pancreas. METHODS: Thirty consecutive patients with IPMN were studied. RESULTS: Three patients (10.0%) did not undergo diagnostic 3D-CEUS because of technical problems. Three dimensional CEUS identified 12 (44.4%) main-duct IPMNs versus no cases by MRI (P < 0.001). Intraductal papillary mucinous neoplasm localization showed poor agreement between 3D-CEUS and MRI (κ = 0.058), whereas good agreement was found in detecting the pancreatic calcifications (κ = 1.000). Significant differences between 3D-CEUS and MRI were found regarding the number of lesions detected (1.4 ± 0.8 vs 3.8 ± 3.6; P < 0.001), the detection of mucinous plugs (3.7% vs 50.0%; P < 0.001), chronic pancreatitis (7.4% vs 26.7%; P = 0.031), pancreatic atrophy (0% vs 50.0%; P < 0.001), thick septa (22.2% vs 53.3%; P = 0.004), and mural nodules (25.9% vs 3.3%; P = 0.016). Three dimensional CEUS showed similar results as compared with MRI in evaluating IPMNs smaller than 1 cm of diameter or greater than 2 cm. CONCLUSIONS: Even if MRI remains the criterion standard technique for the diagnosis of IPMNs, 3D-CEUS can be safely used to follow patients with IPMNs of less than 1 cm.