Regorafenib monotherapy as second-line treatment of patients with RAS-mutant advanced colorectal cancer (STREAM): an academic, multicenter, single-arm, two-stage, phase II study.

BACKGROUND: Maintaining angiogenesis inhibition and switching the chemotherapy backbone represent the current second-line therapy in patients with RAS-mutant metastatic colorectal cancer (mCRC). Regorafenib, an oral multikinase inhibitor, prolonged overall survival (OS) in the chemorefractory setting. MATERIALS AND METHODS: STREAM was an academic, multicenter, single-arm phase II trial, evaluating the activity of regorafenib in RAS-mutant mCRC, in terms of the rate of patients who were progression-free after 6 months from study entry (6mo-PF). Patients were pretreated with fluoropyrimidine, oxaliplatin, and bevacizumab. According to Simon's two-stage design, ≥18 patients 6mo-PF were needed in the overall population (N = 46). Secondary endpoints were safety, objective response rate (ORR), progression-free survival (PFS), and OS. Early metabolic response by [18F]2-fluoro-2-deoxy-D-glucose-positron emission tomography/computed tomography ([18F]-FDG PET/CT) scan was an exploratory endpoint. EudraCT Number: 2015-001105-13. RESULTS: The number of patients 6mo-PF was 8/22 at the first stage and 14/46 in the overall population. The ORR was 10.9%, disease control rate was 54.6%, median (m)PFS was 3.6 months [95% confidence interval (CI) 1.9-6.7 months], mOS was 18.9 months (95% CI 10.3-35.3 months), and mPFS2 (from study entry to subsequent-line progression) was 13.3 months (95% CI 8.4-19.7 months). Long benefiter patients (>6mo-PF) significantly more often had a single metastatic site and lung-limited disease. No unexpected toxicity was reported. Grade ≥3 events occurred in 39.1% of patients, with hand-foot syndrome (13%), fatigue, and hyperbilirubinemia (6.5%) occurring mostly. Baseline metabolic assessment was associated with OS in the multivariate analysis, while early metabolic response was not associated with clinical outcomes. CONCLUSIONS: The study did not meet its primary endpoint. However, regorafenib was well tolerated and did not preclude subsequent treatments. Patients with good prognostic features (single metastatic site and lung-limited disease) reported clinical benefit with regorafenib. The exploratory metabolic analysis suggests that baseline [18F]-FDG PET/CT might be useful to select patients with a favorable outcome. A chemotherapy-free interval with regorafenib was associated with durable disease control in a selected group of patients with favorable clinical characteristics.

Radiological assessment of peritoneal carcinomatosis: a primer for resident.

The imaging has critical responsibility in the assessment of peritoneal lesions along with estimating the overall extent. Valuing disease burden is crucial for selection of combining cytoreductive surgery (CRS) and intraperitoneal hyperthermic chemotherapy (HIPEC) treatment. An approach that combines the strength of several imaging tools and increases diagnostic accuracy, should be chosen, even if the preferred imaging tool in patients with suspected Peritoneal Carcinomatosis (PC) is CT. The outcomes of PC are mainly correlated to tumor spread, localization, and lesion size. Accurate assessment of these features is critical for prognosis and treatment planning. These data can be evaluated by Peritoneal Cancer Index (PCI), a quantitative index suggested by Harman and Sugarbaker. Additionally, precise predictive biomarkers should be established to predict PC in patients at risk. The radiomics analysis could predict PC throughout the evaluation of cancers heterogeneity.

Diagnostic performance of LI-RADS in adult patients with rare hepatic tumors.

OBJECTIVE: The rare hepatic tumor can have a wide spectrum of radiologic features, representing a diagnostic challenge. Our purpose is to report the experience of a National Cancer Center, emphasizing the radiological features encountered and assessing the LR-M categories in the diagnostic performances for these lesions. PATIENTS AND METHODS: We assessed 113 patients who underwent surgical resection or biopsy for rare liver lesions from May 2010 to December 2020. For these patients a computerized search of radiological records was performed to identify which had been studied with MRI and CT. For each lesion, the radiologists recorded the attenuation on CT studies and signal intensity (SI) in T1 weighted (W), in T2-W, DWI and in the related map of the apparent diffusion coefficient (ADC). We assessed the presence and the type of contrast enhancement (CE) during contrast study on CT and MRI and the enhancement was categorized according to LI-RADS 2018. We also assessed the presence of other features in LR-M categories (ancillary LR-M features) in order to classify different subgroups. The lesions were classified according to LR categories, and the gold standard was histological analysis. RESULTS: The final study population included 95 patients (46 females and 49 males), with a mean age of 51 years (range 38-83 years). 83 patients had solid lesions, 12 patients had cystic lesions (simple or complex). According to histological analysis, we categorized 79 patients with malignant lesions and 16 patients with benign lesions. According to radiological features we assessed as malignant 82 patients (79 true malignant and 3 false malignant), as benign 13 patients (all true benign). Therefore, sensitivity, specificity, positive predictive value, negative predictive value and accuracy of radiological features to identify benign and malignant lesions were 100.0%, 81.3%, 96.3%, 100.0% and 96.8%, respectively. We found no significant difference in signal and contrast enhancement appearance among all LR-M categories (p-value =0.34 at Chi square test). However, among LR-M categories the presence of satellite nodules was a feature typical of cHCC-CC (p-value < 0.05 at Chi square test). The presence of intra lesion necrosis and haemorrhage was suggestive of sarcoma (p-value < 0.05 at Chi square test). CONCLUSIONS: High diagnostic accuracy was obtained by LI-RADS classification between malignant and benign lesion. The presence of ancillary features could help the radiologist towards a correct diagnosis.

Pancreatic cancer detection and characterization: state of the art and radiomics.

Pancreatic ductal adenocarcinoma (PDAC) represents a challenge for a multidisciplinary oncology team. Diagnosis of PDAC remains challenging due to overlapping imaging features with benign lesions, notwithstanding great advances with computed tomography (CT) and magnetic resonance imaging (MRI). The term "Radiomics" has recently been introduced to define a mathematical process to extract countless quantitative features from medical images (including each diagnostic technique) with high throughput computing for diagnosis and prediction. This article is an updated overview of the imaging techniques to be employed during detection and characterization of pancreatic cancer diagnostic workup. Particularly, the limitations and advantages of the different imaging techniques are discussed, with a particular focus on functional imaging. This overview is the result of a self-study without protocol and registration number. Articles published in the English language from January 2000 to January 2021 were included. We analyzed 15 papers on radiomics. The possibility of functional imaging, such as CT, MRI, and radiomics has revolutionized pancreatic imaging, improving the detection and characterization of the lesions and allowing a prognosis related to radiological features, favoring the process of personalized medicine.

Metastatic endo and perineural involvement of the ulnar nerve from malignant melanoma: ultrasound (US) and magnetic resonance imaging (MRI) findings.

Malignant melanoma metastases occur in about 15% of patients. The most common localizations are lymph nodes, lungs, pancreas, bones. The central nervous system and the perineural region are rarely affected. In case of distant metastases, the survival rate is lower (about 25%). Involvement of peripheral nerve metastases from melanoma is reported in the literature just in one case. We report the ultrasound (US) integrated with Color-Doppler Ultrasound (CDU), elastosonography, and magnetic resonance imaging (MRI) findings of a rare case of metastatic endo- and perineural involvement of the ulnar nerve from cutaneous melanoma. Our purpose is to increase the clinicians' and radiologists' awareness on the possibility of metastatic spread to the peripheral nervous system and improve the differential diagnosis with other peripheral nerve sheath tumors.

Electroporation-based treatments in minimally invasive percutaneous, laparoscopy and endoscopy procedures for treatment of deep-seated tumors.

Electroporation (EP) techniques, used alone (Irreversible Electroporation, IRE) or in combination with anti-cancer drugs (Electrochemotherapy, ECT), have been shown to be effective in the treatment of several types of cancers. The efficacy of ECT and IRE is well demonstrated for the treatment of non-superficial tumor metastases, and it depends on the applied electrical parameters. Particularly, ECT is an effective local therapy that uses electroporation to enhance the cytotoxic effect of bleomycin or cisplatin injected intravenously or intratumorally. Pre-clinical investigations to test alternative anti-cancer drugs, explore new combinations of treatment modalities, and evaluate different sets of pulse protocols for effective tissue electroporation, are ongoing. Further ECT developments include the treatment of deep-seated tumors with percutaneous, laparoscopy, and endoscopy approaches, with the aim of establishing a less invasive approach. ECT is highly effective in the treatment of tumors of any histology, in minimizing the damage of critical normal tissue or organs, and in reducing pain and muscular contractions. This work describes the new technological advances in the field of ECT treatment for deep-seated tumors.

Home mobile radiography service in the COVID-19 era.

Demographic changes in the Western world linked to the increase in the elderly population, life expectancy and above all cancer patients and chronically ill patients, often entrusted to home care or in healthcare residences, highlight an exponential increase in requests for diagnostic tests at home. Conventional radiographic examinations, such as thoracic, musculoskeletal and abdominal images are the most requested and are important first level diagnostic tests. To date and, in particular, in times of COVID-19 emergency, these patients need to be transferred to the hospital to perform radiological examinations which involve an increase in costs for the health system and an increased risk for the health of these patients, already often debilitated and immunocompromised. This article discussed the benefits of taking conventional chest x-rays directly at the patient's home.

Electrochemotherapy of cholangiocellular carcinoma at hepatic hilum: a case report.

OBJECTIVE: Cholangiocarcinoma (CCA) is the second most common primary hepatic malignancy after hepatocellular carcinoma. The current standard palliative treatment, chemotherapy regimen with gemcitabine and cisplatin, prolongs overall survival only of a few months. Established locoregional therapies are not a curative option or an alternative to surgery in the treatment of CCA. We report a case of a patient affected by a cholangiocellular carcinoma at hepatic hilum treated by Electrochemotherapy (ECT) at our oncologic center. CASE PRESENTATION: A 71 years old male affected by a CCA at hepatic hilum was treated with ECT according to ESOPE guidelines. No complications occurred during ECT procedure. The patient was discharged after 10 days. The functional MR evaluation at 2 and at 4 months post-treatment showed a significant response without significant post-treatment adverse events. The Computed tomography (CT) assessment after 18 months did not show progression of disease. CONCLUSIONS: ECT is safe and its use could be suggested as a palliative treatment of advanced neoplastic lesions in which radical surgical treatment is not possible.

Liver radiologic findings of chemotherapy-induced toxicity in liver colorectal metastases patients.

There are a number of chemotherapy-effects that should be assessed with liver imaging since they have an influence on surgical morbidity. Chemotherapy-related complications, steatosis, chemotherapy-associated steatohepatitis (CASH), and SOS might impair the hepatic parenchyma, thus reducing the functionality and influencing the outcome following resection. The main role of a radiologist is to provide an accurate diagnosis of the lesion. With constant advances in medicine, a radiologist's role should extend beyond just reporting the data of tumor, providing additional information that may greatly improve patient care. Radiologists should assess both chemotherapy effects on the hepatic metastasis itself, as well as chemo-induced focal and diffuse modifications of non-tumor hepatic parenchyma, since it is important to avoid impaired hepatic function after hepatic resection.

Trabectedin in Ovarian Cancer: is it now a Standard of Care?

In patients with recurrent ovarian cancer, the choice of second-line therapy is complex. Several factors have to be considered, such as platinum-free interval (PFI), residual toxicity from the previous treatments, BRCA1/2 gene mutation status. Trebectedin is a minor groove DNA binder derived from a marine organism that has shown efficacy in different settings in ovarian cancer therapy. It has been approved in the treatment of partially platinum sensitive (PPS) (PFI between 6 and 12 months) relapsed ovarian cancer according to the statistically significant progression-free survival (7.3 versus 5.8 months) and overall survival (22.2 versus 18.9 months) benefit compared with single-agent pegylated liposomal doxorubicin (PLD) in the OVA 301 phase III trial. This drug has been shown to prolong the time to first subsequent treatment and improve the efficacy of further platinum-based chemotherapy. The role of trabectedin/PLD followed by platinum combination compared with the reverse sequence in PPS is actually in evaluation in the INOVATYON phase III study, which will clarify the best sequence to be adopted in this setting. Trabectedin has been shown to be active in patient carriers of BRCA mutations, probably for its mechanism of action directly affecting DNA and it is actually tested as a single agent in some phase III trials in BRCA mutated and BRCAness ovarian cancer patients. Trabectedin is also active on the immune system. There is, therefore, the rational for new trials of a combination with immune checkpoint inhibitors.

Superficial temporal artery pseudoaneurysm: what is the role of ultrasound?

PURPOSE: The superficial temporal artery (STA) is one of the terminal branches of the external carotid artery; STA pseudoaneurysms are uncommon vascular lesion, generally subsequent to blunt or penetrating trauma that could represent a trick for radiologist, especially when the only anamnestic information is "palpable superficial swelling". In this article, we describe our ultrasonographic experience about STA pseudoaneurysm reporting several cases with different etiopatogenesis. METHODS: Between January 2004 and March 2015 six patients (4F and 2M; aged 15-55 years, mean 36 year) presented at our department with superficial palpable swelling in temporal region (four with trauma history, two with iatrogenic cause) underwent to ultrasonographic study to assess the presence of STA pseudoaneurysm. Ultrasonographic findings suggestive of pseudoaneurysm was a well-defined, pulsatile, anechoic mass in B-mode, a swirling or disorganized pattern of blood flow in the lesion with demonstration of direct communication between arterial lumen and pseudoaneurysm at colour-Doppler and a typical to-and-fro waveform on pseudoaneurysm neck at pulsed-Doppler. RESULTS: B-mode proves the presence of anechoic mass in five on six patients. Colour-Doppler demonstrates the presence of flow inside the lesion in five patients and a direct communication in all patients. To-and-fro typical waveform has been demonstrated in five patients. Ultrasound made diagnosis in all patients with a sensibility and specificity of 100 %. CONCLUSION: US is the imaging modality of choice, since it can provide detailed information about vascular anatomy without incurring the risks of invasive methods like angiography or radiation.

Sclerosing hemangioma of the lung mimicking pulmonary metastasis.

Sclerosing hemangioma (SH) of the lung is a rare, benign neoplasm, initially thought to be of vascular origin, but immunohistochemical results suggest an origin from primitive respiratory epithelium. We report a case of SH initially misdiagnosed as malignant due to the strong FDG-PET uptake.

Contrast-enhanced ultrasound in the characterization of complex cystic focal liver lesions.

Complex cystic focal liver lesions (FLLs) found at non-contrast ultrasound (US) may turn out to be malignant. In this prospective, monocentric study we investigated the value of contrast-enhanced US (CEUS) in the differential diagnosis of complex cystic FLLs. In the past 3 years, all patients with complex cystic FLLs unclassifiable at US underwent CEUS with low-transmit insonation power. We evaluated 36 consecutive patients with 61 FLLs (1-6/patient, mean = 2). The diameter of the lesions ranged from 1.1 to 7.9 cm (mean = 3.9 cm). Sixteen patients had an extrahepatic malignancy. There were 42 malignant lesions and 19 benign lesions. No lesion had a certain diagnosis at conventional US, whereas 16 FLLs were classified as probable (benign or malignant) and 45 as uncertain. CEUS correctly categorized 95% of the malignant cases. CEUS was not able to differentiate the biliary cystadenoma from its malignant counterpart and misdiagnosed two abscesses. Complete non-enhancement throughout three phases or sustained enhancement in the portal/late phase was exhibited in most benign complex cystic FLLs, except for 1 (of the 3) cystadenomas and in 2 (of the 4) abscesses. On the other hand, all malignant lesions presented a contrast washout with a hypo-enhancing appearance. CEUS may provide added diagnostic value in all complex cystic FLLs found uncertain at conventional US, potentially avoiding the use of more invasive and expensive imaging modalities.

Intravesical chemo-immunotherapy in non muscle invasive bladder cancer.

Non-Muscle-Invasive-Bladder-Cancer represents 75-85% of the new bladder cancer cases per year. Trans-uretral vesical resection is the milestone for diagnosis and therapy. After primary treatment, recurrence is frequent depending on the presence of several established risk factors: multiplicity, T dimension, prior recurrence. In some patients disease progress to an advanced stage. Adjuvant chemo-immunotherapy has been widely used depending on the risk category assigned on the basis of the risk factors for recurrence. In low risk categories a one shot treatment with chemotherapy is considered the standard treatment without any maintenance therapy. In intermediate risk patients, adjuvant induction therapy and maintenance chemotherapy or immunotherapy for at least one year is recommended. In high risk patients adjuvant induction and maintenance immunotherapy until 3 years is considered the best strategy. In this review data on the different drugs used in this setting will be discussed.

Source and clinical motivation of orders for contrast-enhanced sonography (CEUS) of the liver: A prospective single-center survey.

Contrast-enhanced sonography (CEUS) has become a routine part of diagnostic imaging of the liver. Its possibilities, limitations, and indications have been defined in adequately large clinical series and in guidelines and recommendations. We prospectively evaluated physicians' orders for hepatic CEUS received in the radiology department of a large oncology center in Naples, Italy from May 2009 to April 2010. Radiologists performing the CEUS examinations filled out a form that included patient demography, source and type of patient referral, and clinical indications for the examination. During the study period, 564 patients aged 17-86 years (mean, 58 years) were referred to our department for CEUS liver studies (total: 644; 491 outpatient studies, 153 inpatient studies). This included 4 examinations that were ordered by the patient's physician but not performed by our staff. The majority of the CEUS examinations (n = 583; 90.5%) were regularly scheduled procedures ordered by clinical specialists from our center (77.3%) or other centers (11.8%); by general practitioners (on their own initiative) (0.8%); or by other figures (0.6%). The remaining 61 examinations (9.5%) were unscheduled procedures done on the initiative of a radiologist following conventional sonography (US). Fewer than half (47.8%) of the examinations were requested as first-line assessments. The others were ordered to clarify inconclusive findings generated by conventional US (30%) or by a more sophisticated imaging study (CT, MRI, PET) (16.1%) or to resolve discrepancies between CT, MRI, and/or PET findings (6%). CEUS is a relatively noninvasive, low-cost imaging study that is simple to perform and requires no particular patient preparation. This may explain its increasing use to clarify doubts raised by conventional US and other more sophisticated imaging studies.

Contrast-enhanced sonography of the kidney.

Contrast-enhanced sonography (CEUS) is a recently introduced, promising technique in the evaluation of the kidney. CEUS allows real-time assessment of normal and abnormal renal perfusions. As a consequence of the macrocirculation analysis allowed by Doppler techniques, it is possible to obtain real-time information about microcirculation. US contrast media are not nephrotoxic and can be employed safely, even in subjects with impaired renal function. There are several clinical scenarios where CEUS may play the role of a low-cost, scarcely invasive tool, including renal tumors (with special reference to small, indeterminate masses, i.e., differentiation between carcinoma and angiomyolipoma), renal atypical cystic masses (i.e., differentiation of malignant from benign cysts and follow-up of cystic lesions managed conservatively), renal infarction, renal infections, and renal injuries. In addition, CEUS can be useful in the assessment of renal pseudotumors (including any case with possible renal mass on conventional US imaging) and has been employed in radiofrequency ablation guidance. This pictorial review illustrates the CEUS findings recognizable in a wide spectrum of renal disorders and discusses the strengths and limitations of renal imaging with CEUS.