Feasibility and Activity of Megestrol Acetate in Addition to Etoposide, Doxorubicin, Cisplatin, and Mitotane as First-Line Therapy in Patients with Metastatic/Unresectable Adrenocortical Carcinoma with Low Performance Status.

(1) Background: The standard first-line therapy for advanced adrenocortical carcinoma (ACC) is represented by EDP-M (etoposide, doxorubicin, cisplatin + mitotane). Progestins have shown cytotoxic activity both in vitro and in vivo on ACC; better EDP-M tolerability and efficacy have been hypnotized due to the association with progestins. (2) Methods: The feasibility and tolerability of EDP-M combined with oral megestrol acetate (EDP-MM) were tested in 24 patients (pts) affected by metastatic ACC with a low performance status (PS); the case group was compared with a 48 pts control group according to the propensity score. The secondary objectives were clinical benefit rate (CBR), progression-free survival (PFS), and overall survival (OS). (3) Results: Thirteen pts (54.2%) in the EDP-MM population experienced progestin-related toxicities; in particular, five pts experienced vaginal bleeding (20.8%); four pts experienced weight gain (16.7%); and thromboembolic events, worsening of hypertension, skin rashes, and hyperglycemia were registered in one patient each (4.2%). This led to the discontinuation of megestrol acetate in four pts (16.7%). EDP-M-related toxicities were similar in both groups. No differences in PFS and OS curves were observed; the CBR was 75.0% and 60.4%, respectively. (4) Conclusions: The association of EDP-M + megestrol acetate in ACC pts with a low PS is feasible and well tolerated; its efficacy appeared to be non-inferior to EDP-M administered to pts with a good PS.

Different Lung Parenchyma Quantification Using Dissimilar Segmentation Software: A Multi-Center Study for COVID-19 Patients.

BACKGROUND: Chest Computed Tomography (CT) imaging has played a central role in the diagnosis of interstitial pneumonia in patients affected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and can be used to obtain the extent of lung involvement in COVID-19 pneumonia patients either qualitatively, via visual inspection, or quantitatively, via AI-based software. This study aims to compare the qualitative/quantitative pathological lung extension data on COVID-19 patients. Secondly, the quantitative data obtained were compared to verify their concordance since they were derived from three different lung segmentation software. METHODS: This double-center study includes a total of 120 COVID-19 patients (60 from each center) with positive reverse-transcription polymerase chain reaction (RT-PCR) who underwent a chest CT scan from November 2020 to February 2021. CT scans were analyzed retrospectively and independently in each center. Specifically, CT images were examined manually by two different and experienced radiologists for each center, providing the qualitative extent score of lung involvement, whereas the quantitative analysis was performed by one trained radiographer for each center using three different software: 3DSlicer, CT Lung Density Analysis, and CT Pulmo 3D. RESULTS: The agreement between radiologists for visual estimation of pneumonia at CT can be defined as good (ICC 0.79, 95% CI 0.73-0.84). The statistical tests show that 3DSlicer overestimates the measures assessed; however, ICC index returns a value of 0.92 (CI 0.90-0.94), indicating excellent reliability within the three software employed. ICC was also performed between each single software and the median of the visual score provided by the radiologists. This statistical analysis underlines that the best agreement is between 3D Slicer "LungCTAnalyzer" and the median of the visual score (0.75 with a CI 0.67-82 and with a median value of 22% of disease extension for the software and 25% for the visual values). CONCLUSIONS: This study provides for the first time a direct comparison between the actual gold standard, which is represented by the qualitative information described by radiologists, and novel quantitative AI-based techniques, here represented by three different commonly used lung segmentation software, underlying the importance of these specific values that in the future could be implemented as consistent prognostic and clinical course parameters.

Clinical Prognostic Factors in Patients With Metastatic Adrenocortical Carcinoma Treated With Second Line Gemcitabine Plus Capecitabine Chemotherapy.

Gemcitabine plus Capecitabine (Gem/Cape) is a frequently adopted second line chemotherapy for metastatic adrenocortical carcinoma (ACC), but only a minority of patients is destined to obtain a clinical benefit. The identification of baseline predictive factors of efficacy is relevant. We retrospectively analyzed clinical data from 50 consecutive patients with metastatic progressing ACC treated between 2011 and 2019. Patients received intravenous Gemcitabine and oral Capecitabine on a metronomic schedule. Previous mitotane therapy was maintained. Clinical benefit (partial response + stable disease) at 4 months was 30%, median progression-free survival (PFS) and disease-specific survival (DSS) from Gem/Cape start were 3 and 8 months, respectively. Among clinical variables evaluated before the start of Gem/Cape, presence of ECOG performance status ≥1 [HR 6.93 95% confidence interval (CI) 0.03-0.54, p.004] and neutrophil-to-lymphocyte ratio (NLR) ≥5 [HR 3.88, 95% (CI) 0.81-0.90, p.003] were independent indicators of poor PFS at multivariate analysis. Conversely, surgery of primary tumor, the presence of lung or lymph-node metastases, blood mitotane level, anemia, and the Advanced Lung cancer Inflammation index (ALI) failed to be independently associated. This study confirms that the Gem/Cape schedule is modestly active in heavily pretreated ACC patients (28% received at least two previous chemotherapy lines). NLR and performance status (PS) are easily available clinical parameters that are helpful to identify patients not likely to derive significant advantage from Gem/Cape chemotherapy.

MRI for Rectal Cancer Primary Staging and Restaging After Neoadjuvant Chemoradiation Therapy: How to Do It During Daily Clinical Practice.

PURPOSE: To provide a practical overview regarding the state-of-the-art of the magnetic resonance imaging (MRI) protocol for rectal cancer imaging and interpretation during primary staging and restaging after neoadjuvant chemoradiation therapy (CRT), pointing out technical skills and findings that radiologists should consider for their reports during everyday clinical activity. METHOD: Both 1.5T and 3.0T scanners can be used for rectal cancer evaluation, using pelvic phased array external coils. The standard MR protocol includes T2-weighted imaging of the pelvis, high-resolution T2-weighted sequences focused on the tumor and diffusion-weighted imaging (DWI). The mnemonic DISTANCE is helpful for the interpretation of MR images: DIS, for distance from the inferior part of the tumor to the anorectal-junction; T, for T staging; A, for anal sphincter complex status; N, for nodal staging; C, for circumferential resection margin status; and E, for extramural venous invasion. RESULTS: Primary staging with MRI is a cornerstone in the preoperative workup of patients with rectal cancer, because it provides clue information for decisions on the administration of CRT and surgical treatment. Restaging after CRT is crucial for treatment planning, and findings on post-CRT MRI correlate with the patient's prognosis and survival. It may be useful to remember the mnemonic word "DISTANCE" to check and describe all the relevant MRI findings necessary for an accurate radiological definition of tumor stage and response to CRT. CONCLUSIONS: "DISTANCE" assessment for rectal cancer staging and treatment response estimation after CRT may be helpful as a checklist for a structured reporting.

Adrenocortical Carcinoma and CT Assessment of Therapy Response: The Value of Combining Multiple Criteria.

We evaluated tumor response at Computed Tomography (CT) according to three radiologic criteria: RECIST 1.1, CHOI and tumor volume in 34 patients with metastatic adrenocortical carcinoma (ACC) submitted to standard chemotherapy. These three criteria agreed in defining partial response, stable or progressive disease in 24 patients (70.5%). Partial response (PR) was observed in 29.4%, 29.4% and 41.2% of patients according to RECIST 1.1, CHOI and tumor volume, respectively. It was associated with a favorable prognosis, regardless of the criterion adopted. The concordance of all the 3 criteria in defining the disease response identified 8 patients (23.5%) which displayed a very good prognosis: median progression free survival (PFS) and overall survival (OS) 14.9 and 37.7 months, respectively. Seven patients (20.6%) with PR assessed by one or two criteria, however, still had a better prognosis than non-responding patients, both in terms of PFS: median 12.3 versus 9.9 months and OS: 21 versus 12.2, respectively. In conclusions, the CT assessment of disease response of ACC patients to chemotherapy with 3 different criteria is feasible and allows the identification of a patient subset with a more favorable outcome. PR with at least one criterion can be useful to early identify patients that deserve continuing the therapy.

Dynamic contrast-enhanced MRI in oncology: how we do it.

Magnetic resonance imaging (MRI) is particularly attractive for clinical application in perfusion imaging thanks to the absence of ionizing radiation and limited volumes of contrast agent (CA) necessary. Dynamic contrast-enhanced MRI (DCE-MRI) involves sequentially acquiring T1-weighted images through an organ of interest during the passage of a bolus administration of CA. It is a particularly flexible approach to perfusion imaging as the signal intensity time course allows not only rapid qualitative assessment, but also quantitative measures of intrinsic perfusion and permeability parameters. We examine aspects of the T1-weighted image series acquisition, CA administration, post-processing that constitute a DCE-MRI study in clinical practice, before considering some heuristics that may aid in interpreting the resulting contrast enhancement time series. While qualitative DCE-MRI has a well-established role in the diagnostic assessment of a range of tumours, and a central role in MR mammography, clinical use of quantitative DCE-MRI remains limited outside of clinical trials. The recent publication of proposals for standardized acquisition and analysis protocols for DCE-MRI by the Quantitative Imaging Biomarker Alliance may be an opportunity to consolidate and advance clinical practice.

Efficacy of the EDP-M Scheme Plus Adjunctive Surgery in the Management of Patients with Advanced Adrenocortical Carcinoma: The Brescia Experience.

Etoposide, doxorubicin and cisplatin plus oral mitotane (EDP-M) comprise the reference regimen in the management of patients with adrenocortical carcinoma (ACC). In this paper, we described the outcome of 58 patients with advanced/metastatic ACC consecutively treated with EDP-M in a reference center for this rare disease in Italy. In this series, EDP-M obtained a partial response in 50% of patients; median progression free survival (PFS) and overall survival were 10.1 months (95% Confidence Interval [CI 95%] 8.1-12.8) and 18.7 months (95% CI: 14.6-22.8), respectively. EDP-M was not interrupted in five patients showing disease progression after two cycles without the appearance of new lesions and mitotane levels below the therapeutic range. In two of them, the disease remained stable at further imaging evaluations and the other three obtained a partial response. Twenty-six responding patients underwent surgery of residual disease and 13 of them became disease free. Surgery identified a pathological complete response (pCR) in four patients (7%) and Ki67 expression in post-chemotherapy tumor specimens, inferior to 15% (median value), was associated with better PFS and survival. In the present study, the EDP-M regimen is confirmed to have a limited efficacy. Early disease progression does not mean treatment inefficacy. Surgery of residual disease in partially responding patients allows for the detection of pCR in few of them and this condition is predictive of long-term survival. Ki67 expression of post-chemotherapy residual disease could be an additional prognostic factor that deserves to be studied further.

Evaluation of incidence of acute transient dyspnea and related artifacts after administration of gadoxetate disodium: a prospective observational study.

AIMS: To evaluate motion artifacts, breath-hold failure, acute transient dyspnea, and clinical parameters during hepatic arterial phase of gadoxetate disodium-enhanced magnetic resonance (MR) imaging. METHODS: This was an institutional review board-approved observational prospective study (written informed consent acquired) performed in 250 consecutive patients, who underwent liver MR with a multiarterial phase technique. Oxygen saturation (SatO2) and heart rate (HR) were monitored, while patients reported subjective symptoms. Breath-holds were assessed using prospective acquisition correction technique (PACE) monitors. Three readers independently analyzed all images to establish the presence of motion artifacts. Nonparametric statistical testing and Fleiss' kappa were used. RESULTS: No statistical differences in SatO2 and HR values were observed during the entire length of MR examination. The PACE graphs showed an altered breath-hold in 16/250 patients (6.4%), however only 6 patients self-reported symptoms during the procedure, and among these 6 subjects, only 2 suffered from acute transient dyspnea (0.8%). Motion-related artifacts increased mostly in the third arterial phase of gadoxetate disodium acquisition (p < 0.0001): The artifacts incidence was 2.9% in the first phase; 4.0% in the second; and 19.5% in the third. This increase was mainly due to patients' inability to hold their breath for the entire duration of the examination. However, at least one gadoxetate disodium arterial phase without motion artifacts and adequate for acquisition timing, was acquired in all MR examinations. CONCLUSION: The incidence of breath-hold failure and acute transient dyspnea after gadoxetate disodium administration increased during the third arterial phase only. Our protocol allowed the acquisition of at least one arterial phase not compromised by motion artifacts and adequate for acquisition timing, in all patients.

Primary benign liver lesions.

Benign focal liver lesions can origin from all kind of liver cells: hepatocytes, mesenchymal and cholangiocellular line. Their features at imaging may sometimes pose difficulties in differential diagnosis with malignant primary and secondary lesions. In particular, the use of MDCT and MRI with extracellular and hepatobiliary Contrast Agents may non invasively help in correct interpretation and definition of hepatocellular or mesenchymal and inflammatory nature, allowing to choose the best treatment option. The peculiarities of main benign liver lesions at US, CT and MRI are described, with special attention to differential diagnosis and diagnostic clues.

Peritoneal hydatidosis.

Secondary peritoneal hydatidosis is caused by spontaneous or iatrogenic rupture of hepatic echinococcal cysts. We describe the case of a 65-year-old Tunisian male patient with previous history of liver hydatidosis who presented to our attention with subocclusive status. Imaging revealed a retrovesical hydatid cyst, adherent to the sigmoid colon. The treatment of choice was surgical removal of the cyst and the sigmoid colon. The patient is now being closely followed up.

Inflammatory chronic disease of the colon: how to image.

Inflammatory bowel disease, including Crohn's disease and UC, is a chronic disorder of the gastrointestinal tract. The inflammatory process in UC is confined to the mucosa and submucosa and it involves only the colon. In contrast, in Crohn's disease the inflammation process extends through the bowel wall layers and it can involve any part of gastrointestinal tract. Moreover, inflammatory bowel disease of the colon may be associated with complications, such as toxic megacolon, fulminant colitis, acute bleeding, fistulas and abscesses. Radiographic imaging studies are useful for the diagnosis of inflammatory bowel disease, and may be used to assess the extent and severity of disease, rule out complications, and monitor the response to therapy. The double-contrast barium study is a valuable technique for diagnosing inflammatory bowel disease colonic alterations, even in patients with early mucosal abnormalities. The earliest finding of UC is characterized by a fine granular appeareance of the colonic mucosa, usually involving the rectosigmoid junction. In chronic UC double-contrast enema may reveal marked colonic shortening with tubular narrowing of the bowel and loss of haustration. The earliest radiographics findings of Crohn's disease are represented by aphthous ulcers. As disease progresses, aphthous ulcers may enlarge and coalesce to form stellate or linear areas of ulceration. In advanced Crohn's disease, transmural ulceration may lead to the development of fissures, sinus tracts, fistulas, and abscesses. Cross sectional studies such as computed tomography, magnetic resonance imaging and sometimes ultrasound, are useful alternative tools not only in the assessment of bowel wall abnormalities, but also for the assessment of extraluminal alterations in patients with advanced disease.

Cirrhosis: CT and MR imaging evaluation.

In this article, we present the CT and MR imaging characteristics of the cirrhotic liver. We describe the altered liver morphology in different forms of viral, alcoholic and autoimmune end-stage liver disease. We present the spectrum of imaging findings in portal hypertension, such as splenomegaly, ascites and varices. We describe the patchy and lacelike patterns of fibrosis, along with the focal confluent form. The process of hepatocarcinogenesis is detailed, from regenerative to dysplastic nodules to overt hepatocellular carcinoma. Different types of non-neoplastic focal liver lesions occurring in the cirrhotic liver are discussed, including arterially enhancing nodules, hemangiomas and peribiliary cysts. We show different conditions causing liver morphology changes that can mimic cirrhosis, such as congenital hepatic fibrosis, "pseudo-cirrhosis" due to breast metastases treated with chemotherapy, Budd-Chiari syndrome, sarcoidosis and cavernous transformation of the portal vein.

Preoperative T and N staging of colorectal cancer: accuracy of contrast-enhanced multi-detector row CT colonography--initial experience.

PURPOSE: To evaluate the accuracy of contrast material-enhanced multi-detector row computed tomographic (CT) colonography for preoperative staging of colorectal cancer. MATERIALS AND METHODS: Forty-one patients with colorectal carcinoma underwent preoperative contrast-enhanced multi-detector row CT colonography. Images were obtained in the arterial (start delay of 35 seconds) and portal venous (start delay of 70 seconds) phases. The arterial phase was focused on the suspected region of neoplasm, whereas the venous phase included the whole abdomen and pelvis. Two radiologists independently evaluated the depth of tumor invasion into the colorectal wall (T) and regional lymph node involvement (N) on transverse CT images alone and in combination with multiplanar reformations (MPRs). Disagreements were resolved by means of consensus. CT findings were compared with pathologic results, which served as the reference standard. Sensitivity, specificity, accuracy, positive predictive value, and negative predictive value were assessed. Differences in accuracy for T and N staging were assessed by using the McNemar test. RESULTS: In T staging, overall accuracy was 73% when transverse images were evaluated alone and 83% when they were evaluated in combination with MPRs. This difference was not significant. N staging was associated with an overall accuracy of 59% with transverse images alone and 80% with combined transverse and MPR images (P <.01). CONCLUSION: Contrast-enhanced multi-detector row CT colonography is an accurate technique for preoperative local staging of colorectal tumors.

Clinical impact of MR cholangiopancreatography in patients with biliary disease.

PURPOSE: To evaluate the role of MR Cholangiopan-creatography (MRCP) as a first imaging modality in patients with suspected biliary tree pathology and indications to endoscopic retrograde cholangiopancreatography (ERCP). MATERIAL AND METHODS: Eighty-eight patients, with clinical signs of biliary tree pathology underwent MRCP, performed with a 1.5 T unit and a phased-array coil. Surgery, intraoperative cholangiography, percutaneous transhepatic cholangiography (PTC) or ERCP were regarded as the gold standard in patients with obstruction; the remaining patients underwent follow-up MRCP examinations at 6-9 months. The MR examination was performed with baseline T1w 2D FLASH and T2w TSE sequences, followed by the MRCP study (single-slab breath-hold RARE and multislice breath-hold HASTE sequences). The MR images were independently evaluated by two radiologists. RESULTS: MRCP showed normal findings in 20 patients; 68 patients had biliary duct dilatation. In 11 out of 68 patients MRCP did not identify any obstruction (9/11 were true negative cases). A diagnosis of benign obstruction was expressed in 36/59 patients (4 chronic pancreatitis, 29 choledocolithiasis, 4 inflammatory obstruction, 2 primary sclerosing cholangitis), with 1 false positive and 5 false negatives (sensitivity, specificity and diagnostic accuracy of 86%, 95% and 90%, respectively). MRCP identified 23 neoplastic stenoses (20/23 were true positives): the sensitivity, specificity and diagnostic accuracy values were 100%, 87% and 95%, respectively. MRCP correctly identified the level of obstruction in 100% of cases. CONCLUSIONS: MRCP may be considered as a first-step imaging method in patients with clinical signs of biliary disease. The workload of ERCP in the diagnostic stage could therefore be reduced and its use be reserved for therapeutic indications.