Activity of sirolimus in patients with progressive epithelioid hemangioendothelioma: A case-series analysis within the Italian Rare Cancer Network.

BACKGROUND: The objective of this study was to report on a retrospective series of patients with epithelioid hemangioendothelioma (EHE) who received treatment with sirolimus within the Italian Rare Cancer Network. METHODS: From January 2005, 38 adult patients with advanced EHE received continuous-dosing sirolimus, 5 mg daily, until they developed either toxicity or disease progression. Disease progression in the 6 months before the start of treatment was required. Each pathologic diagnosis was reviewed. The daily dose of sirolimus was adjusted based on plasma levels. Response was retrospectively assessed by local investigators using Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST). Survival was estimated using the Kaplan-Meier method. RESULTS: All 38 patients (WW Domain Containing Transcription Regulator 1 [WWTR1]-positive, n = 37; transcription factor E3 [TFE3]-positive, n = 1) had disease progression before starting sirolimus (at baseline, 13 of 38 patients had the presence of serosal effusions and systemic symptoms). Thirty-seven patients were evaluable for response (there was 1 early interruption). The best RECIST responses were a partial response in 4 patients (10.8%), stable disease in 28 patients (75.7%), and disease progression in 5 patients (13.5%). At a 41.5-month median follow-up (interquartile range [IQR], 23.9-56.8 months), the median PFS was 13 months (95% CI, 3.7 months to not estimated [NE]), and the median OS was 18.8 months (95% CI, 10.6 months to NE). In patients who had serosal effusions at baseline, the median PFS was 4.8 months (IQR, 3.5-11.7 months), and the median OS was 10.6 months (IQR, 5.1-13.0 months), compared with 47.8 months (IQR, 11.4 months to NE) and 47.8 months (IQR, 15.7 months to NE), respectively, in patients without serosal effusions. Overall, sirolimus was fairly well tolerated, with 10 patients reporting irregular menstruation/ovary disfunction. CONCLUSIONS: The current results confirm that sirolimus is active in EHE, leading to prolonged stabilization in most patients who present without serosal effusions. Serosal effusions are confirmed as an unfavorable prognostic sign associated with short survival, and sirolimus displays limited activity in this subgroup.

Assessment of Stability and Discrimination Capacity of Radiomic Features on Apparent Diffusion Coefficient Images.

The objectives of the study are to develop a new way to assess stability and discrimination capacity of radiomic features without the need of test-retest or multiple delineations and to use information obtained to perform a preliminary feature selection. Apparent diffusion coefficient (ADC) maps were computed from diffusion-weighted magnetic resonance images (DW-MRI) of two groups of patients: 18 with soft tissue sarcomas (STS) and 18 with oropharyngeal cancers (OPC). Sixty-nine radiomic features were computed, using three different histogram discretizations (16, 32, and 64 bins). Geometrical transformations (translations) of increasing entity were applied to the regions of interest (ROIs), and the intra-class correlation coefficient (ICC) was used to compare the features computed on the original and modified ROIs. The distribution of ICC values for minimal and maximal entity translations (ICC10 and ICC100, respectively) was used to adjust thresholds of ICC (ICCmin and ICCmax) used to discriminate between good, unstable (ICC10 < ICCmin), and non-discriminative features (ICC100 > ICCmax). Fifty-four and 59 radiomic features passed the stability-based selection for all the three histogram discretizations for the OPC and STS datasets, respectively. The excluded features were similar across the different histogram discretizations (Jaccard's index 0.77 ± 0.13 and 0.9 ± 0.1 for OPC and STS, respectively) but different between datasets (Jaccard's index 0.19 ± 0.02). The results suggest that the observed radiomic features are mainly stable and discriminative, but the stability depends on the region of the body under observation. The method provides a way to assess stability without the need of test-retest or multiple delineations.

Different pixel pitch and maximum luminance of medical grade displays may result in different evaluations of digital radiography images.

AIM: To evaluate the effects of display pixel pitch and maximum luminance on intra- and inter-observer reproducibility and observer performance when evaluating chest lesions and bone fractures. MATERIALS AND METHODS: This was a multi-institutional study for a retrospective interpretation of selected digital radiography images. Overall, 82 images were selected by senior radiologists, including 50 cases of chest lesions and 32 cases of bone fractures. These images were displayed at two pixel pitches (0.212 and 0.165 mm size pixels) and two maximum luminance values (250 and 500 cd/m2) and reviewed twice by senior and junior radiologists. All the observers had to indicate the likelihood of the presence of the lesions and to rate the relative confidence of their assessment. Cohen Kappa statistic was computed to estimate the reproducibility in correctly identifying lesions; for multi-reader-multi-case (MRMC) analysis, weighted Jackknife Alternative Free-response Receiver Operating Characteristic (wJAFROC) statistical tools was applied. RESULTS: The intra-radiologist and inter-observer reproducibility values were the highest for the 0.165 mm size pixel at 500 cd/m2 display, for both chest lesions and bone fractures evaluations. As regards chest lesions, observer performances were significantly greater with 0.165 mm size pixel display at 500 cd/m2 than with lower maximum luminance and/or larger pixel pitch displays. Concerning bone fractures, the performance obtained with 0.212 mm size pixel display at 250 cd/m2 was statistically lower than that obtained with 0.165 mm sixe pixel display at 500 cd/m2. CONCLUSION: Our results indicate that an increased maximum luminance level and a decreased pixel pitch of medical-grade display improve the accuracy of detecting both chest lesions and bone fractures.

Transarterial chemoembolization using 40 µm drug eluting beads for hepatocellular carcinoma.

AIM: To assess the safety and efficacy of transarterial chemoembolization (TACE) of hepatocellular carcinoma (HCC) using a new generation of 40 µm drug eluting beads in patients not eligible for curative treatment. METHODS: Drug eluting bead TACE (DEB-TACE) using a new generation of microspheres (embozene tandem, 40 µm) preloaded with 100 mg of doxorubicin was performed on 48 early or intermediate HCC patients with compensated cirrhosis. Response to therapy was assessed with Response Evaluation Criteria in Solid Tumors (RECIST) and modified RECIST (mRECIST) guidelines applied to computed tomography or magnetic resonance imaging. Eleven out of the 48 treated patients treated progressed on to receive liver orthotopic transplantation (OLT). This allowed for histological analysis on the treated explanted nodules. RESULTS: DEB-TACE with 40 µm showed a good safety profile without major complications or 30-d mortality. The objective response rate of treated tumors was 72.6% and 26.7% according to mRECIST and RECIST respectively. Histological examination in 11 patients assigned to OLT showed a necrosis degree > 90% in 78.6% of cases. The overall time to progression was 13 mo (11-21). CONCLUSION: DEB-TACE with 40 µm particles is an effective treatment for the treatment of HCC in early-intermediate patients (Barcelona Clinic Liver Cancer stage A/B) with a good safety profile and good results in term of objective response rate and necrosis.

Response to isolated limb perfusion and chemotherapy with epirubicin plus ifosfamide in a metastatic malignant ossifying fibromyxoid tumor.

BACKGROUND: Ossifying fibromyxoid tumor (OFMT) is a rare soft tissue neoplasm of uncertain lineage and intermediate biological potential. It is more common in middle-aged men, usually arising from the deep tissues of the extremities. It is now established that it is a translocation related tumor, most often marked by translocation of PHF1 gene. Surgery is the mainstay of treatment and proves usually curative, although, in rarer cases the disease shows malignant features and tendency to recur both locally and at distant sites. In such cases, no standard treatment exists. CASE PRESENTATION: We report on a case of malignant advanced OFMT of the hand with lung metastases responding to isolated limb perfusion with human recombinant tumor necrosis factor and melphalan and chemotherapy with epirubicin and ifosfamide. CONCLUSIONS: To our knowledge, this is the first report of activity of soft tissue sarcoma-oriented chemotherapy in advanced OFMT.