Clinical, Pathological and Prognostic Features of Rare BRAF Mutations in Metastatic Colorectal Cancer (mCRC): A Bi-Institutional Retrospective Analysis (REBUS Study)

Simple SummarySomatic BRAF mutations occur in approximately 10% of metastatic colorectal cancers (mCRCs) and, according to the involved codon, are classified as V600E and in non-V600, accounting for 80% and 20%, respectively. Being the most frequent mutation, the BRAF V600E mutation has been extensively investigated and up to now its clinical, pathological and molecular phenotype and its prognostic impact have been clearly described. On the contrary, evidence concerning BRAF non-V600 is weaker. We retrospectively evaluated 537 mCRC patients treated at two Italian Institutions. This study corroborates and strengthens available evidence concerning phenotype and prognostic performance of BRAF non-V600 compared to BRAF V600E and BRAF wild-type mCRCs. This deeper insight on rare BRAF non-V600 mutated mCRC is a primary issue in the precision oncology era, since the wider application of NGS is expected to increase the identification of those aberrations.Recently, retrospective analysis began to shed light on metastatic colorectal cancers (mCRCs) harboring rare BRAF non-V600 mutations, documenting a distinct phenotype and a favorable prognosis. This study aimed to confirm features and prognosis of rare BRAF non-V600 mCRCs compared to BRAF V600E and BRAF wild-type mCRCs treated at two Italian Institutions. Overall, 537 cases were retrospectively evaluated: 221 RAS/BRAF wild-type, 261 RAS mutated, 46 BRAF V600E and 9 BRAF non-V600. Compared to BRAF V600E mCRC, BRAF non-V600 mCRC were more frequently left-sided, had a lower tumor burden and displayed a lower grade and an MMR proficient/MSS status. In addition, non-V600 mCRC patients underwent more frequently to resection of metastases with radical intent. Median overall survival (mOS) was significantly longer in the non-V600 compared to the V600E group. At multivariate analysis, only age < 65 years and ECOG PS 0 were identified as independent predictors of better OS. BRAF V600E mCRCs showed a statistically significant worse mOS when compared to BRAF wild-type mCRCs, whereas no significant difference was observed between BRAF non-V600 and BRAF wild-type mCRCs. Our study corroborates available evidence concerning incidence, clinicopathologic characteristics and prognosis of BRAF-mutated mCRCs

The archaeological evidence of sea level change in the Mediterranean: guidelines and reappraisals

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The Bay of Savudrija: Harbour and the Coastal Landscape in the Roman Age

U uvali Savudrija, u svibnju 2011. g., započela su istraživanja antičke lučke arhitekture čiji je cilj rekonstrukcija antičkog krajolika i pokušaj evaluacije obalne linije u rimsko vrijeme na području Savudrije. istraživanja su pokrenuta u sklopu istraživačkog projekta Storie del mare, u suradnji triju supotpisnika – nositelja projekta Dipartimento di Storia e Culture dall’Antichità al Mondo Contemporaneo (DiSCAM), pri Sveučilištu u Trstu (Italija), Arheološkog muzeja Istre iz Pule i Muzeja grada Umaga – Museo civico di Umago (Hrvatska).As a part of the main Project Storie dal mare which has been carried by Department of Humanistic Studies, University of Trieste and in collaboration between Archeological Museum of Istria in Pula and Umag Municipal Museum in Croatia the research has been conducted in the Bay of Savudrija. The main aim of this project was the reconstruction of the ancient landscape and the evaluation of the shoreline during Roman Age. The goal of archaeological campaign in 2011 was to make a complete documentation of southern breakwater and pier (using the multibeam technique and total station) and to try to make topography of all roman architectural structures, visible along the coast. The ancient port basin in the bay of Savudrija includes a complex consisting of different structures, some of which are visible along the bay. The basin was triangular in shape, and was closed by two symmetrically placed breakwaters. The other archaeological structures as pier and walls on the coast extend themselves along the southern line of the bay. The area containing the Roman structures belonged to a section of the first lowest terrace of a Roman structure which during Roman Age should be extended towards the sea. A preliminary analysis of the archaeological materials excavated in the bay indicates that the area was used since the beginnings of the Empire until the Late Roman period, that is from the 1st to the 6th century

The Bay of Savudrija: Harbour and the Coastal Landscape in the Roman Age

U uvali Savudrija, u svibnju 2011. g., započela su istraživanja antičke lučke arhitekture čiji je cilj rekonstrukcija antičkog krajolika i pokušaj evaluacije obalne linije u rimsko vrijeme na području Savudrije. istraživanja su pokrenuta u sklopu istraživačkog projekta Storie del mare, u suradnji triju supotpisnika – nositelja projekta Dipartimento di Storia e Culture dall’Antichità al Mondo Contemporaneo (DiSCAM), pri Sveučilištu u Trstu (Italija), Arheološkog muzeja Istre iz Pule i Muzeja grada Umaga – Museo civico di Umago (Hrvatska).As a part of the main Project Storie dal mare which has been carried by Department of Humanistic Studies, University of Trieste and in collaboration between Archeological Museum of Istria in Pula and Umag Municipal Museum in Croatia the research has been conducted in the Bay of Savudrija. The main aim of this project was the reconstruction of the ancient landscape and the evaluation of the shoreline during Roman Age. The goal of archaeological campaign in 2011 was to make a complete documentation of southern breakwater and pier (using the multibeam technique and total station) and to try to make topography of all roman architectural structures, visible along the coast. The ancient port basin in the bay of Savudrija includes a complex consisting of different structures, some of which are visible along the bay. The basin was triangular in shape, and was closed by two symmetrically placed breakwaters. The other archaeological structures as pier and walls on the coast extend themselves along the southern line of the bay. The area containing the Roman structures belonged to a section of the first lowest terrace of a Roman structure which during Roman Age should be extended towards the sea. A preliminary analysis of the archaeological materials excavated in the bay indicates that the area was used since the beginnings of the Empire until the Late Roman period, that is from the 1st to the 6th century

A Feasibility Study Investigating an Exercise Program in Metastatic Cancer Based on the Patient-Preferred Delivery Mode

Background: Feasibility of exercise in patients with metastatic cancer is still a challenge. This study aimed to determine the feasibility and preliminary efficacy of an exercise intervention based on a patient-preferred delivery mode in patients affected by metastatic cancer. Materials and methods: Forty-four patients with a confirmed diagnosis of metastatic cancer were recruited in a 3-month exercise program. Whereas the exercise program consisted of aerobic and resistance activities performed twice a week, the participants may choose the mode of delivery: home based, personal training, or group based. The primary endpoint was the feasibility, defined by recruitment rate, attendance, adherence, dropout rate, tolerability (comparing the session RPE with the target RPE), and safety (using the Common Terminology Criteria for Adverse Events, version 5.0). Secondary endpoints included cardiorespiratory fitness (six minutes walking test), muscle strength (handgrip strength test and isometric leg press test), flexibility (the back scratch and chair sit and reach tests), anthropometric parameters (body mass index and waist-hip ratio), quality of life (EORTC QLQ C-30 questionnaire), and amount of physical exercise (Godin's Shepard Leisure Time Exercise Questionnaire). Descriptive statistics, Student t test, and Wilcoxon signed rank test were used to analyze data. Results: The study recruitment rate was 81%. Out of 44 recruited patients, 28 chose the personal training program, 16 chose the home-based program, and none chose the group-based program. Nine dropouts occurred (20%), 6 in the personal training program, and 3 in the home-based intervention. The median attendance rate was 92%, adherence was 88%, tolerability was 100%, and 9 nonsevere adverse events were registered during the exercise sessions. An increase in cardiorespiratory fitness (P < .001) and flexibility (P = .011 for chair sit and reach; P = .040 for back scratch) was observed at the end of the intervention, while no changes in anthropometric values and muscle strength were detected. Different quality-of-life domains were improved following the intervention, including physical (P = .002), emotional (P < .001), and role functioning (P = .018), fatigue (P = .030), and appetite loss (P = .005). Conclusion: A 3-month exercise program based on a patient-preferred delivery mode is feasible in patients with metastatic cancer and may improve physical function and quality of life. Trial registration: NCT04226508

Atmospheric neutrino induced muons in the MACRO detector

A measurement of the flux of neutrino-induced muons using the MACRO detector is presented. Different event topologies, corresponding to different neutrino parent energies can be detected. The upward throughgoing muon sample is the larger event sample. The observed upward-throughgoing muons are 26% fewer than expected and the zenith angle distribution does not fit with the expected one. Assuming neutrino oscillations, both measurements suggest maximum mixing and Dm2 of a few times 10-3 eV2. The other samples are due to the internally produced events and to upward-going stopping muons. These data show a regular deficit of observed events in each angular bin, as expected assuming neutrino oscillations with maximum mixing, in agreement with the analysis of the upward-throughgoing muon sample.Comment: 7 pages 6 figures to appear in the proceedings of XVIII International Conference on Neutrino Physics and Astrophysics (Neutrino'98), Takayama, Japan 4-9 June, 199