Kaposi's Sarcoma: Evaluation of Clinical Features, Treatment Outcomes, and Prognosis in a Single-Center Retrospective Case Series.

Kaposi's sarcoma (KS) is a rare angioproliferative tumor classified in four different clinical-epidemiological forms. The diagnosis is based on histopathological and immunohistochemical analyses. The treatment is heterogeneous and includes several local and systemic therapeutic strategies. Methods: This is a retrospective cohort study including 86 KS patients treated between 1993 and 2022 at the University Hospital of Padua (AOPD) and at the Veneto Institute of Oncology (IOV). The data were extracted from an electronic database. Survival curves were generated using the Kaplan-Meier method, and Cox regression models were employed to explore associations with overall and disease-free survival. The male sex (89.53%), classical variant (43.02%), and cutaneous involvement (77.9%) were predominant. More than 61.6% of patients received a single treatment. Surgery, antiretroviral therapy, and chemotherapy were the mostly adopted approaches. A persistent response was observed in approximately 65% of patients, with a 22% relapse rate (at least 2 years). The overall survival ranges from 90 to 70% at 2 to 10 years after the diagnosis. Iatrogenic KS demonstrated a higher mortality (52.9%). This study reflects our experience in the management of KS. Comorbidities are very frequent, and treatments are heterogeneous. A multidisciplinary approach involving multiple referral specialists is essential for the appropriate management of this disease during diagnosis, treatment, and follow-up.

Performance comparison of single-view digital breast tomosynthesis plus single-view digital mammography with two-view digital mammography.

OBJECTIVE: To determine the performance of combined single-view mediolateral oblique (MLO) digital breast tomosynthesis (DBT) plus single-view cranio-caudal (CC) mammography (MX) compared with that of standard two-view digital mammography. METHODS: A multi-reader multi-case (MRMC) receiver-operating characteristic (ROC) study was conducted, involving six breast radiologists. Two hundred fifty patients underwent bilateral MX and DBT imaging. MX and DBT images with the adjunct of the CC-MX view from 469 breasts were evaluated and rated independently by six readers. Differences in mean areas under the ROC curves (AUCs), mean sensitivity and mean specificity were analysed by analysis of variance (ANOVA) to assess clinical performance. RESULTS: The combined technique was found to be non-inferior to standard two-view mammography (MX((CC+MLO))) in mean AUC (difference: +0.021;95 % LCL = -0.011), but was not statistically significant for superiority (P = 0.197). The combined technique had equivalent sensitivity to standard mammography (76.2 % vs. 72.8 %, P = 0.269) and equivalent specificity (84.9 % vs. 83.0 %, P = 0.130). Specificity for benign lesions was significantly higher with the combination of techniques versus mammography (45.6 % vs. 36.8 %, P = 0.002). CONCLUSION: In this enriched study population, the combination of single-view MLO tomosynthesis plus single-view CC mammography was non-inferior to that of standard two-view digital mammography in terms of ROC curve area, sensitivity and specificity.

Combination of one-view digital breast tomosynthesis with one-view digital mammography versus standard two-view digital mammography: per lesion analysis.

OBJECTIVE: To evaluate the clinical value of combining one-view mammography (cranio-caudal, CC) with the complementary view tomosynthesis (mediolateral-oblique, MLO) in comparison to standard two-view mammography (MX) in terms of both lesion detection and characterization. METHODS: A free-response receiver operating characteristic (FROC) experiment was conducted independently by six breast radiologists, obtaining data from 463 breasts of 250 patients. Differences in mean lesion detection fraction (LDF) and mean lesion characterization fraction (LCF) were analysed by analysis of variance (ANOVA) to compare clinical performance of the combination of techniques to standard two-view digital mammography. RESULTS: The 463 cases (breasts) reviewed included 258 with one to three lesions each, and 205 with no lesions. The 258 cases with lesions included 77 cancers in 68 breasts and 271 benign lesions to give a total of 348 proven lesions. The combination, DBT(MLO)+MX(CC), was superior to MX (CC+MLO) in both lesion detection (LDF) and lesion characterization (LCF) overall and for benign lesions. DBT(MLO)+MX(CC) was non-inferior to two-view MX for malignant lesions. CONCLUSIONS: This study shows that readers' capabilities in detecting and characterizing breast lesions are improved by combining single-view digital breast tomosynthesis and single-view mammography compared to two-view digital mammography. KEY POINTS: • Digital breast tomosynthesis is becoming adopted as an adjunct to mammography (MX) • DBT (MLO) +MX (CC) is superior to MX (CC+MLO) in lesion detection (overall and benign lesions) • DBT (MLO) +MX (CC) is non-inferior to MX (CC+MLO) in cancer detection • DBT (MLO) +MX (CC) is superior to MX (CC+MLO) in lesion characterization (overall and benign lesions) • DBT (MLO) +MX (CC) is non-inferior to MX (CC+MLO) in characterization of malignant lesions.

Role of enhancement modifications in evaluating tumor response to immunotherapy in metastatic renal cell carcinoma.

INTRODUCTION: Evaluation of tumor response according only to dimensional criteria may underestimate treatment benefit in patients treated for metastatic renal cell carcinoma (RCC). In this study we evaluated the role of lesion enhancement modifications and Choi criteria in patients affected by renal cell carcinoma treated with immunotherapy. METHODS: We collected data of 60 consecutive patients (with a total of 154 measurable lesions) treated with immunotherapy (nivolumab or ipilimumab plus nivolumab) at a single Institution. We evaluated tumour response using both RECIST1.1 criteria and Choi criteria at the first radiological assessment; we subsequently associated response with progression free survival and overall survival. RESULTS: Choi criteria found a higher rate of objective response compared to RECIST criteria (38.3% vs 18.3%). An objective response according to both criteria was associated with longer progression free survival and overall survival. Response rate for Choi did not vary according to lesion site. CONCLUSION: Choi criteria seemed to be able to predict clinical benefit in a higher proportion of patients with renal cell carcinoma treated with immunotherapy than RECIST criteria. Partial response according to RECIST was confirmed as a predictor of longer progression-free survival and overall survival.

Artifact reduction in contrast-enhanced mammography.

OBJECTIVE: To evaluate the effectiveness of a new algorithm developed to reduce artifacts in dual-energy subtraction (DES) contrast-enhanced mammography (CEM) images while preserving contrast enhancement of possible lesions. METHODS: A retrospective multi-reader paired study was performed by using 134 CEM studies obtained from the first 134 women enrolled in a prospective clinical study aiming to compare the clinical performance of CEM to those of breast MRI in screening of women at increased risk of breast cancer. Four experienced readers compared independently the standard (STD) DES images with those obtained by reprocessing the raw images by a new algorithm (NEW), expected to reduce the DES artifact intensity. The intensity of three types of artifacts (breast-in-breast, ripple, and skinfold enhancement) and the intensity of possible contrast uptake were assessed visually and rated using a categorical ordinal scale. Proportions of images rated by the majority of readers as "Absent", "Weak", "Medium", "Strong" in each artifact intensity category were compared between the two algorithms. P-values lower than 0.05 were considered statistically significant. RESULTS: The NEW algorithm succeeded in eliminating 84.5% of breast-in-breast artifacts, 84.2% of ripple artifacts, and 56.9% of skinfold enhancement artifacts versus STD DES images, and reduced the artifact intensity in 12.1%, 13.0%, and 28.8% of the images, respectively. The visibility of lesion contrast uptake was the same with the STD and the NEW algorithms. CONCLUSION: The new dual-energy subtraction algorithm demonstrated to be effective in reducing/eliminating CEM-related artifacts while preserving lesion contrast enhancement.

Quantitative Breast Density in Contrast-Enhanced Mammography.

Contrast-enhanced mammography (CEM) demonstrates a potential role in personalized screening models, in particular for women at increased risk and women with dense breasts. In this study, volumetric breast density (VBD) measured in CEM images was compared with VBD obtained from digital mammography (DM) or tomosynthesis (DBT) images. A total of 150 women who underwent CEM between March 2019 and December 2020, having at least a DM/DBT study performed before/after CEM, were included. Low-energy CEM (LE-CEM) and DM/DBT images were processed with automatic software to obtain the VBD. VBDs from the paired datasets were compared by Wilcoxon tests. A multivariate regression model was applied to analyze the relationship between VBD differences and multiple independent variables certainly or potentially affecting VBD. Median VBD was comparable for LE-CEM and DM/DBT (12.73% vs. 12.39%), not evidencing any statistically significant difference (p = 0.5855). VBD differences between LE-CEM and DM were associated with significant differences of glandular volume, breast thickness, compression force and pressure, contact area, and nipple-to-posterior-edge distance, i.e., variables reflecting differences in breast positioning (coefficient of determination 0.6023; multiple correlation coefficient 0.7761). Volumetric breast density was obtained from low-energy contrast-enhanced spectral mammography and was not significantly different from volumetric breast density measured from standard mammograms.

Merkel Cell Carcinoma: Evaluation of the Clinico-Pathological Characteristics, Treatment Strategies and Prognostic Factors in a Monocentric Retrospective Series (n=143).

BACKGROUND: Merkel cell carcinoma (MCC) is a rare neuroendocrine tumor of the skin. The incidence of the disease has undergone a significant increase in recent years, which is caused by an increase in the average age of the population and in the use of immunosuppressive therapies. MCC is an aggressive pathology, which metastasizes early to the lymph nodes. These characteristics impose an accurate diagnostic analysis of the regional lymph node district with radiography, clinical examination and sentinel node biopsy. In recent years, there has been a breakthrough in the treatment of the advanced pathology thanks to the introduction of monoclonal antibodies acting on the PD-1/PD-L1 axis. This study aimed to describe the clinico-pathological characteristics, treatment strategies and prognostic factors of MCC. METHODS: A retrospective cohort study was conducted involving 143 consecutive patients who were diagnosed and/or treated for MCC. These patients were referred to the Veneto Institute of Oncology IOV-IRCCS and to the University Hospital of Padua (a third-level center) in the period between December 1991 and January 2020. In the majority of cases, diagnosis took place at the IOV. However, some patients were diagnosed elsewhere and subsequently referred to the IOV for a review of the diagnosis or to begin specific therapeutic regimens. RESULTS: 143 patients, with an average age of 71 years, were affected mainly with autoimmune and neoplastic comorbidities. Our analysis has shown that age, autoimmune comorbidities and the use of therapy with immunomodulating drugs (which include corticosteroids, statins and beta-blockers) are associated with a negative prognosis. In this sense, male sex is also a negative prognostic factor. CONCLUSIONS: Autoimmune and neoplastic comorbidities were frequent in the studied population. The use of drugs with immunomodulatory effects was also found to be a common feature of the population under examination. The use of this type of medication is considered a negative prognostic factor. The relevance of a multidisciplinary approach to the patient with MCC is confirmed, with the aim of assessing the risks and benefits related to the use of immunomodulating therapy in the individual patient.

Digital breast tomosynthesis versus digital mammography: a clinical performance study.

OBJECTIVE: To compare the clinical performance of digital breast tomosynthesis (DBT) with that of full-field digital mammography (FFDM) in a diagnostic population. METHODS: The study enrolled 200 consenting women who had at least one breast lesion discovered by mammography and/or ultrasound classified as doubtful or suspicious or probably malignant. They underwent tomosynthesis in one view [mediolateral oblique (MLO)] of both breasts at a dose comparable to that of standard screen-film mammography in two views [craniocaudal (CC) and MLO]. Images were rated by six breast radiologists using the BIRADS score. Ratings were compared with the truth established according to the standard of care and a multiple-reader multiple-case (MRMC) receiver-operating characteristic (ROC) analysis was performed. Clinical performance of DBT compared with that of FFDM was evaluated in terms of the difference between areas under ROC curves (AUCs) for BIRADS scores. RESULTS: Overall clinical performance with DBT and FFDM for malignant versus all other cases was not significantly different (AUCs 0.851 vs 0.836, p = 0.645). The lower limit of the 95% CI or the difference between DBT and FFDM AUCs was -4.9%. CONCLUSION: Clinical performance of tomosynthesis in one view at the same total dose as standard screen-film mammography is not inferior to digital mammography in two views.

A Therapeutic and Diagnostic Multidisciplinary Pathway for Merkel Cell Carcinoma Patients.

Merkel Cell Carcinoma (MCC) is a highly aggressive neuroendocrine neoplasm of the skin. Due to its rarity, the management of MCC is not standardized across centers. In this article, we present the experience of the Veneto region in the North-East of Italy, where a committee of skin cancer experts has proposed a clinical pathway for the diagnosis and treatment of MCC. Putting together the evidence available in the international literature, we outlined the best approach to the management of patients affected with this malignancy step- by- step for each possible clinical situation. Crucial in this pathway is the role of the multidisciplinary team to deal with the lack of robust information on each aspect of the management of this disease.

Immunotherapy and urothelial carcinoma: An overview and future prospectives.

BACKGROUND: Urothelial carcinoma (UC) is a common malignancy with a high mortality rate when metastatic. Traditionally, systemic therapy consisted in platinum-based regimens as first-line, with Taxanes or Vinflunine as further lines. Recently, checkpoint inhibitors (CPIs) immunotherapy has emerged as a new therapeutic option. METHODS: We searched in Medline, Pubmed and ClinicalTrial.gov databases for the relevant literature, reviewing the results of published trials and the design of ongoing studies involving CPIs in UC. RESULT: Strong evidence supports the use of CPIs after failure of Cisplatin-based chemotherapy, although no predictive parameter is available so far. Expression of Programmed-Death-1-Ligand has given conflicting results, and is currently indicated only for the selection of Cisplatin-ineligible patients who should receive CPIs. CONCLUSION: The therapeutic landscape of UC is rapidly changing due to the availability of CPIs. Neoadjuvant trials with CPIs and trials combining two CPIs are promising and will further expand the use of immunotherapy.

Trabectedin Drug Holiday and Rechallenge in Soft Tissue Sarcomas: Report of 4 Cases and Literature Review.

Soft tissue sarcomas are rare neoplasms, with a high mortality rate. Few drugs are available for the treatment of patients affected by metastatic sarcomas, who still have a 5-years survival rate lower than 20%. However, some of the more recent therapies can obtain long lasting responses in a portion of patients, such as Trabectedin. We analyzed four such cases treated at our Institute after progression to an anthracycline based regimen. In each case a therapeutic pause was proposed after at least 6 months of therapy with Trabectedin and in three out of four patients a re-challenge was proposed at progression, achieving again disease control or response. In two cases oligo-progressive sites were treated with localized therapies as stereotactic radiotherapy, delaying the systemic treatment re-start. In this article the reports of the patients involved are presented with a concise review of the relevant literature. Our findings support the favorable safety profile of Trabectedin and the feasibility of drug holidays, which should be at least discussed with the patient.

First-Line sunitinib in patients with renal cell carcinoma (RCC) in von Hippel-Lindau (VHL) disease: clinical outcome and patterns of radiological response.

UNLABELLED: von Hippel-Lindau (VHL) is a rare hereditary condition caused by germline alteration of VHL gene predisposing to renal carcinoma and multiple other tumors. Since acquired dysregulation of VHL-dependent pathways is often present in patients with sporadic RCC treated with the anti-angiogenic drug sunitinib, there is a strong rationale to use the same drug in VHL patients with progressive disease in the kidneys or other sites. Our primary objective was to evaluate the activity of sunitinib in terms of progression-free survival. SECONDARY OBJECTIVES: rate of radiological response, patterns of responses in different organs, treatment-related toxicities. We performed a retrospective analysis of sunitinib therapy in genetically-confirmed VHL patients treated at our Institution for multifocal or advanced RCC. From February 2007 to July 2012, 14 VHL patients started first-line sunitinib for recurrent or progressing RCC, mean age 48 years (27-71). Nine patients achieved a partial RECIST response (64.3%); responses were noted not only in renal and hepatic lesions but also in pancreatic nodules. Most lesions showed density reduction, while all CNS haemangioblastoma lesions remained stable. At a median follow-up of 37 months, six patients have progressed and three patients died, with a progression-free rate at 2 years of 71.4%. Sunitinib may therefore achieve a fairly good disease control in VHL patients. Radiological responses may be obtained not only in renal tumors but also in synchronous VHL-related lesions, especially pancreatic solid nodules whose exact nature (metastatic RCC or neuroendocrine tumor) cannot be ruled out without invasive biopsy.

Core needle biopsy of soft tissue tumors, CEUS vs US guided: a pilot study.

PURPOSE: The purpose of this study was to evaluate the usefulness of contrast-enhanced ultrasonography (CEUS) in the bioptic sampling of soft tissue tumors (STT) compared with unenhanced ultrasonography alone. METHODS: This is a prospective longitudinal study of 40 patients subjected to ultrasonography (US)-guided core needle biopsy (CNB) to characterize a suspected STT. Three series of bioptic samplings were carried out on each patient, respectively using unenhanced US alone and CEUS in both the areas of the tumor enhanced or not by the contrast medium. All bioptic samples underwent a histological evaluation and the results were analyzed by comparing the histology of the biopsy with the definitive diagnosis in 15 surgically excised samples. RESULTS: 27 (67.5 %) of the 40 patients completed the entire study procedure; in 19 cases (70.3 %) the three bioptic samplings gave unanimous results, also when compared to the surgical specimen; in seven cases (25.9 %) use of CEUS allowed to obtain additional or more accurate information about the mass in question, compared to simple US guidance without contrast; in one patient (3.7 %) sampling obtained using unenhanced ultrasonography guidance and in the areas enhanced by the contrast agent had precisely the same results of the surgical specimen. CONCLUSIONS: CEUS, due to its ability to evaluate microvascular areas, has proven to be a promising method in guiding bioptic sampling of soft tissue tumor, directing the needle to the most significant areas of the tumor. Given the small number of patients evaluated in our study, to achieve statistically significant results, it would be appropriate to obtain a larger sample size, since the very first results seem to be encouraging and to justify the increase of the population.

Melanoma m1: diagnosis and therapy.

This article reviews the epidemiology, pathogenesis, diagnosis, prognostic factors and treatment of metastatic melanoma, including the most recent developments in the specific field. It examines the sequential and non-linear models of development and progression of melanoma and the main molecular disorder involved in these processes. Clinical and diagnostic aspects have been divided according to clinical staging. Surgical resectability, the site and number of metastases, the number of involved organs, the duration of remission, serum lactate dehydrogenase levels and tumor doubling-time have the greatest prognostic value. Surgical treatment has been analyzed considering its rational function and examining all sites involved in metastasis. We also discuss the palliative role of radiotherapy in relation to various metastatic sites, chemotherapy and recently introduced targeted-therapy. The association of newer drugs and new biological therapies such as ipilimumab and verumafenib have improved the treatment landscape of stage IV melanoma.