Imatinib and everolimus in patients with progressing advanced chordoma: A phase 2 clinical study.

BACKGROUND: We present the results of an academic phase 2 study on imatinib plus everolimus in patients who have progressive advanced chordoma. METHODS: In January 2011, 43 adult chordoma patients were enrolled in the study and received imatinib 400 mg/day and everolimus 2.5 mg/day until progression or limiting toxicity. Eligible patients had progressed in the 6 months before study entry. PDGFRB, S6, and 4EBP1 expression and phosphorylation were evaluated by way of immunohistochemistry and/or western blotting. The primary endpoint was the overall response rate (ORR) according to Choi criteria. Secondary endpoints were RECIST 1.1 response, progression-free survival (PFS), overall survival (OS), correlation between S6/4EBP1 phosphorylation and response. RESULTS: Thirteen of 43 patients were pretreated with imatinib. Among 40 of the 43 patients who were evaluable by Choi criteria, the best responses were 9 with partial response (ORR, 20.9%), 24 with stable disease (SD) (ORR, 55.8%), and 7 with progressive disease (ORR, 16.3%). Forty-two patients were evaluable by RECIST criteria, with 1 partial response (ORR, 2.3%), 37 stable disease (ORR, 86%), and 4 progressive disease (ORR, 9.3%). The median PFS according to Choi criteria was 11.5 months (range, 4.6-17.6 months), and 58.8% and 48.1% of patients were progression-free at 9 and 12 months, respectively. The median PFS by RECIST criteria was 14 months; the median OS was 47.1 months. When assessable, S6/4EBP1 was phosphorylated in a high and moderate/low proportion of tumor cells in responsive and nonresponsive patients, respectively. Toxicity caused a temporary and definitive treatment discontinuation in 60.5% and 30.2% of patients, respectively. CONCLUSIONS: Imatinib plus everolimus showed a limited activity in progressing advanced chordoma. Interestingly, the amount of tumor cells activated for mammalian target of rapamycin effectors correlated with the response. Toxicity was not negligible.

Magnetic resonance imaging patterns of tumor response to chemotherapy in desmoid-type fibromatosis.

BACKGROUND: We aimed to investigate changes in volume and MRI T2-weighted intensity in desmoid-type fibromatosis (DF) receiving methotrexate plus vinca-alkaloids (MTX-VA) at Istituto Nazionale dei Tumori, Milan. METHODS: All cases of sporadic DF treated with MTX-VA from 1999 to 2019 were reviewed. MRIs at baseline, 6 and 12 months of chemotherapy and at treatment withdrawal were retrospectively reviewed, contouring the tumor lesion and measuring diameters, volume, and mean T2-signal intensity (normalized to muscle) changes. These parameters were also evaluated according to clinical variables. RESULTS: Thirty-two DF patients were identified. Best RECIST response was: 25% partial response, 69% stable disease, 6% progression. A ≥65% tumor volume reduction was observed in 38%, <65% reduction in 53%, an increase in 9%. 22% had RECIST stable disease with a ≥65% tumor volume reduction. T2-signal intensity decreased by ≥50% in 47%, <50% in 41% and increased in 12%. In patients with symptomatic improvement while on therapy and in patients maintaining symptomatic improvement during follow-up, median T2-signal intensity showed a reduction along the time points (3.0, 1.9, 1.2, 1.1; 2.9, 2.0, 1.2, 1.2, respectively); in patients without symptomatic improvement and in those clinically progressing during follow-up, a reduction was not observed. High T2-signal intensity at baseline was observed in patients showing RECIST progression during follow-up. CONCLUSIONS: In this series, RECIST detected a lower proportion of responses as compared to volumetric and T2-signal changes. T2-signal reduction seemed to better reflect symptomatic improvement. High T2-signal intensity at baseline was related to a higher proportion of further progression.

Eavesdropping on dolphins: Investigating the habits of bottlenose dolphins (Tursiops truncatus) through fixed acoustic stations.

This study investigates the bottlenose dolphin (Tursiops truncatus, Montagu 1821) habitat use in the Portofino marine protected area (NW Italy) and adjacent waters, a core area for the dolphins and a highly touristic area in the Mediterranean Sea. A permanent automated real-time passive acoustic monitoring system, able to detect and track dolphins continuously, was tested in the area within the activities of the Life+ Nature project ARION. The habits of bottlenose dolphins was investigated considering the resident rate inside the area, which quantifies the amount of time dolphins spent in these waters, by means of random forest regression. The dependency of dolphin resident rate was analyzed in relation to four explanatory variables: sea surface temperature, season, time of day, and proximity to the coast. Dolphins spent more time in the area during spring and when sea surface temperature ranged between 15-16°C. Summer resulted the season with lower dolphin residency with significant difference between working day and weekend, in the last the lowest residency was recorded. Main findings provide important information to properly manage the area in order to protect bottlenose dolphins.

Long-term Efficacy of Methotrexate Plus Vinblastine/Vinorelbine in a Large Series of Patients Affected by Desmoid-Type Fibromatosis.

PURPOSE: Today, surgery and radiation therapy have a limited role in desmoid-type fibromatosis. Different systemic treatments were shown to be effective. Herein, we report on our institutional experience with low-dose methotrexate (MTX) + vinca alkaloids in this disease over the last 25 years. METHODS: We retrospectively reviewed data from all adult patients with sporadic desmoid-type fibromatosis treated with MTX and vinca alkaloids at our institution between 1989 and 2014. RESULTS: We identified 75 patients treated with MTX + vinblastine (40%), MTX + vinorelbine (57%), and vinorelbine alone (3%). All patients had progressive disease before chemotherapy; 72%, 10%, and 48% of patients had received previous surgery, radiation therapy, and/or systemic treatments, respectively. Chemotherapy was administered for a median duration of 14 months and a median number of 37.5 cycles. Eight patients interrupted chemotherapy because of toxicity. According to RECIST (Response Evaluation Criteria in Solid Tumors) complete response, partial response, stable disease, and progressive disease were observed in 1%, 47%, 51%, and 1% of patients, respectively. Symptomatic relief was obtained in 80% of symptomatic cases. The median progression-free survival (PFS) was 75 months; it was 136 months in responding patients. Upon progression, after chemotherapy withdrawal, MTX plus vinblastine/vinorelbine was offered to 11 patients with partial response, stable disease, and progressive disease in 4, 6, and 1 cases, resulting in a median PFS of 53 months. CONCLUSIONS: In this series, chemotherapy with MTX and vinca alkaloids is confirmed to be active and effective, with a remarkable PFS, higher in responding patients, and limited toxicity. Even progression can be successfully rechallenged.

Eleven-year management of prostate cancer patients on active surveillance: what have we learned?

PURPOSE: To evaluate the outcomes of active surveillance (AS) on patients with low-risk prostate cancer (PCa) and to identify predictors of disease reclassification. METHODS: In 2005, we defined an institutional AS protocol (Sorveglianza Attiva Istituto Nazionale Tumori [SAINT]), and we joined the Prostate Cancer Research International: Active Surveillance (PRIAS) study in 2007. Eligibility criteria included clinical stage ≤T2a, initial prostate-specific antigen (PSA) <10 ng/mL, and Gleason Pattern Score (GPS) ≤3 + 3 (both protocols); ≤25% positive cores with a maximum core length containing cancer ≤50% (SAINT); and ≤2 positive cores and PSA density <0.2 ng/mL/cm3 (PRIAS). Switching to active treatment was advised for a worsening of GPS, increased positive cores, or PSA doubling time <3 years. Active treatment-free survival (ATFS) was assessed using the Kaplan-Meier method. Factors associated with ATFS were evaluated with a multivariate Cox proportional hazards model. RESULTS: A total of 818 patients were included: 200 in SAINT, 530 in PRIAS, and 88 in personalized AS monitoring. Active treatment-free survival was 50% after a median follow-up of 60 months. A total of 404/818 patients (49.4%) discontinued AS: 274 for biopsy-related reclassification, 121/404 (30%) for off-protocol reasons, 9/404 (2.2%) because of anxiety. Biopsy reclassification was associated with PSA density (hazard ratio [HR] 1.8), maximum percentage of core involvement (HR 1.5), positive cores at diagnostic biopsy (HR 1.6), older age (HR 1.5), and prostate volume (HR 0.6) (all p<0.01). Patients from SAINT were significantly more likely to discontinue AS than were the patients from PRIAS (HR 1.65, p<0.0001). CONCLUSIONS: Five years after diagnosis, 50% of patients with early PCa were spared from active treatment. Wide inclusion criteria are associated with lower ATFS. However, at preliminary analysis, this does not seem to affect the probability of unfavorable pathology.

A Permanent Automated Real-Time Passive Acoustic Monitoring System for Bottlenose Dolphin Conservation in the Mediterranean Sea.

Within the framework of the EU Life+ project named LIFE09 NAT/IT/000190 ARION, a permanent automated real-time passive acoustic monitoring system for the improvement of the conservation status of the transient and resident population of bottlenose dolphin (Tursiops truncatus) has been implemented and installed in the Portofino Marine Protected Area (MPA), Ligurian Sea. The system is able to detect the simultaneous presence of dolphins and boats in the area and to give their position in real time. This information is used to prevent collisions by diffusing warning messages to all the categories involved (tourists, professional fishermen and so on). The system consists of two gps-synchronized acoustic units, based on a particular type of marine buoy (elastic beacon), deployed about 1 km off the Portofino headland. Each one is equipped with a four-hydrophone array and an onboard acquisition system which can record the typical social communication whistles emitted by the dolphins and the sound emitted by boat engines. Signals are pre-filtered, digitized and then broadcast to the ground station via wi-fi. The raw data are elaborated to get the direction of the acoustic target to each unit, and hence the position of dolphins and boats in real time by triangulation.

Rectal villous tumours: MR features and correlation with TRUS in the preoperative evaluation.

AIM: The aim of this study was to assess the clinical relevance of MR and transrectal ultrasonography (TRUS) imaging of rectal villous tumours to elucidate the correlation between imaging results and specific histopathological tumour features, such as tumour size (T) and lymph node involvement (N), in order to establish the better technique for the pre-surgical patient evaluation. PATIENTS AND METHODS: 23 cases of villous tumours of the rectum were studied with phased-array MR and TRUS. All patients underwent either surgical or endoscopic treatment. Final diagnosis was based on histopathological results. In particular, the following features were characterized by the imaging techniques mentioned above: lesion site, distance between lesion and ano-rectal junction, size, morphology and contrast enhancement of lesions, fluid layer around the lesion, alterations of the deep layers of the rectal wall, sphincter infiltration, presence or absence of mesorectal, iliac and obturatory lymphnode involvement. RESULTS: Histology established muscular involvement in 7 cases (T2), perirectal fat infiltration in 1 case (T3); in the remaining 15 cases, staging was Tis-T1. In 17/23 cases (73.9%) the lesions were correctly staged with both imaging techniques, whereas in 5/23 cases (21.7%) the lesions were overstaged. No cases were understaged. TRUS concorded with histological exams in 17/23 cases (73.9%). 5/23 cases (21.7%) were overstaged and 1/23 (4%) was understaged. MR and TRUS were in accordance in 20/23 cases (86.9%). DISCUSSION: Considering the frequent degeneration of villous tumours, correct preoperative identification and precise evaluation of these lesions, such as the detection of rectal wall invasion, is essential in deciding optimal treatment strategy. MRI and TRUS allow the identification of specific features of villous tumours and of malignant degeneration, allowing for a correct local disease staging.

Gray-scale and color Doppler findings in bilateral internal jugular vein thrombosis caused by anaplastic carcinoma of the thyroid.

Bilateral internal jugular vein thrombosis is a rare complication of thyroid cancer. The most common manifestation of this condition is superior vena cava syndrome. We report the sonographic findings in a case of bilateral internal jugular vein thrombosis with mild symptoms. There was evidence of direct infiltration of anaplastic thyroid carcinoma into the left internal jugular vein. Sonographic and CT examinations also demonstrated multiple dilated collateral veins.

Preoperative locoregional staging of rectal carcinoma: comparison of MR, TRUS and Multislice CT. Personal experience.

PURPOSE: The aim of this study was to measure the sensitivity and clinical indications of Magnetic Resonance (MR) as compared to Transrectal Ultrasonography (TRUS) and spiral Computed Tomography (CT) in the preoperative staging and evaluation of rectal carcinoma. MATERIALS AND METHODS: Twenty patients with histologically proven rectal carcinoma were examined with phased-array coil MRI. We used T1 and T2, spin-echo, turbo-spin-echo, flash2D sequences with and without fat suppression; FOV 180-280; 4-6 mm slice thickness; i.v. Gadolinium. The MR images were compared with TRUS, spiral CT and with the final histological diagnosis. RESULTS: MR showed a 92.3% sensitivity for rectal wall infiltration vs. 100% of TRUS and 75% of CT. The sensitivity for lymph node metastases was 76.4% vs. 72.2% for TRUS and 88% for CT. CONCLUSIONS: Locoregional staging of rectal cancer by MRI shows a high sensitivity and is also feasible in stenosing or proximal rectal lesions. TRUS, despite its limitations, is still the most sensitive method for the evaluation of wall infiltration. CT was less sensitive than the other two METHODS: The sensitivity of MR and CT for lymph node metastases is comparable, but the former is more specific.