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Background: Information about the adherence to scientific societies guidelines in the ‘real-world’ therapeutic management of oncological patients are lacking. This multicenter, prospective survey was aimed to improve the knowledge relative to 2017-2018 recommendations of the Italian Association of Medical Oncology (AIOM). Patients and methods: Treatment-naive adult patients with pancreatic adenocarcinoma were enrolled. Group A received adjuvant therapy, group B received primary chemotherapy, and group C had metastatic disease. The results on patients accrued until 31 October 2019 with a mature follow-up were presented. Results: Since July 2017, 833 eligible patients of 923 (90%) were enrolled in 44 Italian centers. The median age was 69 years (range 36-89 years; 24% >75 years); 48% were female; 93% had Eastern Cooperative Oncology Group (ECOG) performance status (PS) score of 0 or 1; group A: 16%, group B: 30%; group C: 54%; 72% Nord, 13% Center, 15% South. In group A, guidelines adherence was 68% [95% confidence interval (CI) 59% to 76%]; 53% of patients received gemcitabine and 15% gemcitabine þ capecitabine; median CA19.9 was 29 (range 0-7300; not reported 15%); median survival was 36.4 months (95% CI 27.5-47.3 months). In group B, guidelines adherence was 96% (95% CI 92% to 98%); 55% of patients received nab-paclitaxel þ gemcitabine, 27% FOLFIRINOX, 12% gemcitabine, and 3% clinical trial; median CA19.9 was 337 (range 0-20220; not reported 9%); median survival was 18.1 months (95% CI 15.6-19.9 months). In group C, guidelines adherence was 96% (95% CI 94% to 98%); 71% of patients received nabpaclitaxel þ gemcitabine, 16% gemcitabine, 8% FOLFIRINOX, and 4% clinical trial; liver and lung metastases were reported in 76% and 23% of patients, respectively; median CA19.9 value was 760 (range 0-1374500; not reported 9%); median survival was 10.0 months (95% CI 9.1-11.1 months). Conclusions: The GARIBALDI survey shows a very high rate of adherence to guidelines and survival outcome in line with the literature. CA19.9 testing should be enhanced; nutritional and psychological counseling represent an unmet need. Enrollment to assess adherence to updated AIOM guidelines is ongoing.

This research is focused on the screw-structure interaction under dynamic impulses aimed to the contact analysis of gap propagation at dental implant-abutment interface under dynamic loading. The purpose is to investigate the fracture mechanism that occurs during the screw penetration in a support and during the support vibration. Numerical Finite Element (FEM) analyses are calibrated through experimental laboratory measurements on support materials and screws typologies. Uncertainty due to the laboratory error propagation is investigated using Polynomial Chaos Expansion (PCE) of experimental measurements. The research is planned through the following steps: FEM calibration trough laboratory experiments on materials; laboratory experiments and material mechanics identification; uncertainty error propagation analysis through PCE expansion; fragility curves for numerical model calibration; FEM models calibration trough laboratory measurements on cycling loads. Therefore, the main purpose of the research activity, of which this article constitutes a preliminary and an explorative step, is to study a methodology that minimizes the local damage of the dental material due to the generation of micro-cracks following the implantation actions. Accordingly, in this paper, preliminary results are reported.

Gastric cancer is one of the most common malignancy worldwide with a prognosis less than 1 year in unresectable or metastatic disease. HER2 expression is the main biomarker to lead the addition of trastuzumab to first line systemic chemotherapy improving the overall survival in advanced HER2-positivegastric adenocarcinoma. The inevitable development of resistance to trastuzumab remains a great problem inasmuch several treatment strategies that have proven effective in breast cancer failed to show clinical benefit in advanced gastric cancer. In this review, we summarize the available data on the mechanisms underlying primary and secondary resistance toHER2-targeted therapy and current challenges in the treatment of HER2-positive advanced gastric cancer refractory to trastuzumab. Further, we describe the prognostic value of new non-invasive screening techniques, the current development of novel agents such us HER2 antibody-drug conjugates and bispecific antibodies, and the strategies with antitumor activity on going.

Fractal analysis is a mathematical method used to describe the internal architecture of complex structures, such as the bone tissue. The aim of this study was to determine whether fractal dimension (FD) is able to distinguish between different bone densities (BD), assessed histomorphometrically, and whether there is a linear dependence between the FD and BD in order to support the use of FD as a supplementary non-invasive method for BD measurement. Microscopic photographs of bone specimens stained with acid fuchsin and toluidine blue obtained during block biopsies from nine segments of bovine ribs were used. A total of 42 regions of interest (ROI) were cut off from the original photo, converted into a bitmap and binarized. The evaluation of FD was carried out using the box counting method. Comparison of FD values in the four different densities bone sites (D1-D4) was made by means of Kruskal-Wallis test followed by Dunn's multiple comparison test. The linear dependence between the two variables (FD and BD) was investigated calculating the Pearson's r test correlation coefficient, which was considered significant when P < .05. The more the bone was compact, the higher were FD values. A strong positive correlation between BD evaluated by histomorphometry and FD (R : 0:9651), p-value < .00001 was found. The increase in the values of the FD strongly correlated with the increase of the percentage of the bone trabeculae observed in the histological slides. This pilot study demonstrates that FD might be able to distinguish different densities in bone sites and that there is a linear correlation between BD and FD on histological samples. Future studies will be addressed at evaluating whether this data can be confirmed on a larger samples size and on radiographic images. This will be useful for the early and non-invasive detection of structural changes in the trabecular bone pattern during healing, inflammatory processes and pathologies associated to bone breakdown.

Background: Previous studies on oxaliplatin and fluoropyrimidines as adjuvant therapy in older patients with stage III colon cancer (CC) produced conflicting results. Patients and methods: We assessed the impact of age on time to tumour recurrence (TTR), disease-free survival (DFS), cancer-specific survival (CSS), and overall survival (OS) in 2360 patients with stage III CC (1667 aged

Fractal dimension (FD) calculated on oral radiographs has been proposed as a useful tool to screen for osteoporosis. This systematic review and meta-analysis firstly aimed at assessing the reliability of FD measures in distinguishing osteoporotic patients (OP) from healthy controls (HC), and secondly, to identify a standardized procedure of FD calculation in dental radiographs for the possible use as a surrogate measure of osteoporosis. A comprehensive search was conducted up to September 2020 using PubMed, Web of Science, and SCOPUS databases. The Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) statement was followed. Meta-analysis was performed on FD values calculated for HC and OP. Overall, 293 articles were identified. After a three steps screening, 19 studies were included in the qualitative appraisal and 12 were considered for meta-analysis. The methodological quality of the retrieved studies was generally low. Most of the studies included used White and Rudolph and box counting to process the images and to calculate FD, respectively. Overall, 51% of the studies found a meaningful difference between HC and OP groups. Meta-analyses showed that to date, FD measures on dental radiographs are not able to distinguish the OP from HC group significantly. From the current evidence, the use of FD for the identification of OP is not reliable, and no clear conclusion can be drawn due to the heterogeneity of studies. The present review revealed the need for further studies and provided the fundamentals to design them in order to find a standardized procedure for FD calculation (regions for FD assessment; images processing technique; methods for FD measurement). More effort should be made to identify osteoporosis using dental images which are cheap and routinely taken during periodic dental examinations. Supplementary Information The online version contains supplementary material available at 10.1007/s00198-021-05852-3.

BACKGROUND The phase III TRIBE and TRIBE2 studies randomized metastatic colorectal cancer patients to first-line FOLFOXIRI/bevacizumab or a doublet (FOLFIRI or FOLFOX)/bevacizumab. The studies demonstrated a significant benefit from the triplet at the price of an increased incidence of chemotherapy-related adverse events (AEs). In both trials, males and females aged between 18 and 70 years with ECOG PS ≤2 and between 71 and 75 years with ECOG PS = 0 were eligible. We investigated the effect of FOLFOXIRI/bevacizumab versus doublets/bevacizumab according to age and gender. PATIENTS AND METHODS Subgroup analyses according to age (

Mechanisms of acquired resistance to trastuzumab-based treatment in gastric cancer are largely unknown. In this study, we analyzed 22 pairs of tumor samples taken at baseline and post-progression in patients receiving chemotherapy and trastuzumab for advanced HER2-positive [immunohistochemistry (IHC) 3+ or 2+ with in-situ hybridization (ISH) amplification] gastric or gastroesophageal cancers. Strict clinical criteria for defining acquired trastuzumab resistance were adopted. Loss of HER2 positivity and loss of HER2 over-expression were defined as post-trastuzumab IHC score

Background Obesity is associated with an increased risk of development and recurrence of colorectal cancer. The role of obesity in mCRC patients (pts) is still unclear, especially in those treated with triplet plus bevacizumab (bev). The aim of our study was to evaluate the prognostic and predictive role of BMI in mCRC pts treated with FOLFOXIRI plus bev or FOLFIRI/FOLFOX plus bev in the TRIBE and TRIBE-2 trial. Methods 1160 pts enrolled in TRIBE and TRIBE-2 trials were included. Baseline height and weight were used to assign patients to one of the following BMI categories: underweight (group A = BMI 30 kg/m2; 156 pts). Results In our population, no differences in terms of PFS (p = 0.38) or OS (p = 0.93) resulted between three groups. No interaction effect between treatment arm and BMI was evident in terms of PFS (HR: 0.70 [95%CI: 0.40-1.22]; HR: 0.78 [95%CI: 0.68-0.89]; HR: 0.66 [95%CI: 0.48-0.91]; p for interaction= 0.61, in group A,B,C respectively) or OS (Group A HR: 0.62 [95%CI: 0.31-1.25]; Group B HR: 0.84 [95%CI: 0.72-0.98];Group C HR: 0.67 [95%CI: 0.46-0.99] p for interaction= 0.44). No statistically significant difference in terms of dose reductions due to toxicities were required according to BMI in overall population (p = 0.48) and in pts treated with FOLFOXIRI plus bev (p = 0.57). Conclusions BMI was not prognostic either for PFS or for OS in our population. Our analyses showed that the advantage of FOLFOXIRI plus bev versus FOLFIRI/FOLFOX plus bev was independent from BMI. Legal entity responsible for the study Daniele Santini. Funding Has not received any funding. Disclosure A. Falcone: Advisory / Consultancy, advisory board and Institutional funding to research: Amgen; Advisory / Consultancy, advisory board and Institutional funding to research: Roche; Advisory / Consultancy, advisory board and Institutional funding to research: Bayer; Advisory / Consultancy, advisory board and Institutional funding to research: Merck; Advisory / Consultancy, advisory board and Institutional funding to research: Servier; Advisory / Consultancy, advisory board and Institutional funding to research: Lilly. All other authors have declared no conflicts of interest.

ABSTRACT Aim: To explore the prognostic value of extended mutational profiling for metastatic colorectal cancer (mCRC). Materials & methods: We retrospectively reviewed survival results of 194 mCRC patients that were assigned to four molecular subgroups: BRAF mutated; KRAS mutated codons 12-13 only; any of KRAS codons 61-146, PIK3CA or NRAS mutations and all wild-type. Point mutations were investigated by pyrosequencing. Results: BRAF (5.2%) and KRAS 12-13 (31.9%) mutations were associated with poorer survival (HR 2.8 and 1.76, respectively). Presenting with right-sided colon cancer, not resected primary tumor, WBC >10 × 109/l, receiving less chemotherapy or no bevacizumab were all associated with inferior outcome. The all-wild-type subgroup (39.2%) reported the longest survival. Conclusion: Extended mutational profile combined with clinical factors may impact on survival in mCRC.

This phase II, open-label, randomised study evaluated whether patients with metastatic pancreatic cancer receiving erlotinib/gemcitabine derived survival benefits from increasing the erlotinib dose., SCOPUS: ar.j, info:eu-repo/semantics/published

Summary Background Vascular endothelial growth factor (VEGF) and VEGF receptor-2 (VEGFR-2)-mediated signalling and angiogenesis can contribute to the pathogenesis and progression of gastric cancer. We aimed to assess whether ramucirumab, a monoclonal antibody VEGFR-2 antagonist, prolonged survival in patients with advanced gastric cancer. Methods We did an international, randomised, double-blind, placebo-controlled, phase 3 trial between Oct 6, 2009, and Jan 26, 2012, at 119 centres in 29 countries in North America, Central and South America, Europe, Asia, Australia, and Africa. Patients aged 24–87 years with advanced gastric or gastro-oesophageal junction adenocarcinoma and disease progression after first-line platinum-containing or fluoropyrimidine-containing chemotherapy were randomly assigned (2:1), via a central interactive voice-response system, to receive best supportive care plus either ramucirumab 8 mg/kg or placebo, intravenously once every 2 weeks. The study sponsor, participants, and investigators were masked to treatment assignment. The primary endpoint was overall survival. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00917384. Findings 355 patients were assigned to receive ramucirumab (n=238) or placebo (n=117). Median overall survival was 5·2 months (IQR 2·3–9·9) in patients in the ramucirumab group and 3·8 months (1·7–7·1) in those in the placebo group (hazard ratio [HR] 0·776, 95% CI 0·603–0·998; p=0·047). The survival benefit with ramucirumab remained unchanged after multivariable adjustment for other prognostic factors (multivariable HR 0·774, 0·605–0·991; p=0·042). Rates of hypertension were higher in the ramucirumab group than in the placebo group (38 [16%] vs nine [8%]), whereas rates of other adverse events were mostly similar between groups (223 [94%] vs 101 [88%]). Five (2%) deaths in the ramucirumab group and two (2%) in the placebo group were considered to be related to study drug. Interpretation Ramucirumab is the first biological treatment given as a single drug that has survival benefits in patients with advanced gastric or gastro-oesophageal junction adenocarcinoma progressing after first-line chemotherapy. Our findings validate VEGFR-2 signalling as an important therapeutic target in advanced gastric cancer. Funding ImClone Systems.

Background FOLFOXIRI + bev is regarded as a valuable option in the first-line tx of mCRC pts. A possible concern for the adoption is the feasibility and efficacy of tx after progression, and especially the reintroduction of the same agents used upfront. The aim of the study was to evaluate the efficacy of tx after progression among pts treated with first-line FOLFOXIRI + bev in the phase III TRIBE (NCT00719797) and TRIBE2 (NCT02339116) studies. The impact of the oxaliplatin and irinotecan free interval (OIFI), defined as the time from the last administration of oxaliplatin and irinotecan to disease progression, on the efficacy of tx after progression was also investigated. Methods Data about tx received after progression including 2ndPFS (i.e. the time from 2nd line tx start to disease progression or death) were collected. The efficacy of tx after progression according to the duration of the OIFI was explored. A cut-off value of 4 months was adopted. Results Out of 586 pts treated with upfront FOLFOXIRI + bev, 520 progressed. Among 409 (79%) pts who received a tx after progression, 168 (41%) received FOLFOXIRI ± bev (Group A) and 241 (59%) received other tx (Group B), including FOLFOX or FOLFIRI ± bev or other agents not used in first line in 124 and 117 cases, respectively. Anti-EGFR moAbs were administered in 68 cases. Pts in Group A experienced significantly longer 2nd PFS than pts in Group B (median 2nd PFS: 6.1 vs 4.2, HR 0.76, 95%CI 0.62-0.94; p = 0.012). Pts with an OIFI ≥ 4 mos (n = 279) had longer 2nd PFS than those with an OIFI Conclusions Tx after progression to first-line FOLFOXIRI + bev were feasible. Pts with longer OIFI showed better 2nd PFS and seemed to derive more benefit from the reintroduction of the triplet. Clinical trial identification TRIBE NCT00719797 TRIBE2 NCT02339116. Legal entity responsible for the study G.O.N.O.: Gruppo Oncologico Nord Ovest. Funding Has not received any funding. Disclosure S. Lonardi: Advisory / Consultancy, Research grant / Funding (institution): Amgen; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): Merck Serono; Advisory / Consultancy, Speaker Bureau / Expert testimony: Lilly; Speaker Bureau / Expert testimony: Roche; Speaker Bureau / Expert testimony: Bristol-Myers Squibb; Speaker Bureau / Expert testimony: Servier. D. Santini: Advisory / Consultancy: Amgen; Advisory / Consultancy: Novartis; Advisory / Consultancy: Roche; Advisory / Consultancy: MSD; Advisory / Consultancy: Eisai; Advisory / Consultancy: Sanofi; Advisory / Consultancy: Ipsen; Advisory / Consultancy: Janssen; Advisory / Consultancy: Merck. A. Falcone: Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Amgen; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Bayer; Advisory / Consultancy: Bristol-Myers Squibb; Honoraria (institution), Advisory / Consultancy: Lilly; Honoraria (institution), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Merck; Honoraria (institution), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Roche; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Servier. C. Cremolini: Advisory / Consultancy, Travel / Accommodation / Expenses: Roche; Advisory / Consultancy, Travel / Accommodation / Expenses: Bayer; Advisory / Consultancy: Amgen; Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Servier. All other authors have declared no conflicts of interest.

Background Advances in therapy, surgery and loco-regional procedures improved survival of patients (pts) with metastatic colorectal cancer (mCRC). Interruptions, defined Drug Holidays (DH), could reduce toxicity in pts with stable disease. We evaluated the association between DH and overall survival (OS). Methods 754 consecutive pts treated for mCRC, at University Hospital of Udine and IRCCS CRO of Aviano from 1/1/2005 to 15/03/2017, were included. DH was defined as 56 or more consecutive days of interruption, during first line. The association of DH to OS was evaluated through uni- and multivariate Cox regression analyses. OS was estimated with Kaplan-Meier curves. Results Overall, 459 (60.9%) pts received continuous treatment while 255 (33.8%) a DH (5.3% missing data). After median follow-up of 68.6 months, median OS was 23.15 months. By univariate analysis, KRAS (HR 1.39; 95%CI 1.17-1.66; p 1 metastatic sites (HR 1.61;95%CI 1.36-1.91; p Conclusions DH was independently associated with better prognosis. Probably, DH is a proxy of better prognosis that clinicians intercept. Therefore, in accurately selected pts, DH can be safely offered. Legal entity responsible for the study Dipartimento di Oncologia, Azienda Sanitaria Universitaria Integrata di Udine. Funding Has not received any funding. Disclosure F. Puglisi: Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution), Travel / Accommodation / Expenses: Hoffmann-La Roche; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution), Travel / Accommodation / Expenses: AstraZeneca; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Amgen; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Celgene; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Eisai; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Eli Lilly; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Ipsen; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Novartis; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Pierre-Fabre; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Pfizer; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Takeda; Advisory / Consultancy: Merck Sharp & Dohme. All other authors have declared no conflicts of interest.

Background Regorafenib and TAS-102 have recently demonstrated statistically significant survival gains in patients with refractory metastatic colorectal cancer (mCRC). Life expectancy ≥12 weeks was an inclusion criterion in registrative trials, and the identification of proper clinical selection tools for the daily use of these drugs in heavily pre-treated patients is needed to improve the cost-benefit ratio. We aimed at building a nomogram able to predict death probability within 12 weeks from the date of assessment of refractory mCRC. Patients and methods Four hundred eleven refractory mCRC patients with ECOG performance status (PS) ≤2 receiving regorafenib, TAS-102 or other treatments were used as developing set. Putative prognostic variables were selected using a random forest model and included in a binary logistic model from which the nomogram was developed. The nomogram was externally validated and its performance was evaluated by examining calibration (how close predictions were to the actual outcome) and discriminative ability (Harrell C index) both on developing (internal validation) and validating (external validation) sets. Results Four variables were selected and included in the nomogram: PS (P

As a result of the growing cancer incidence and the increasing trend towards chemotherapy treatment, a higher number of cancer outpatients ask for unplanned visits. This study aimed to describe the nature and magnitude of this phenomenon and to identify risk factors for repeated unplanned presentations and hospital admission. Unplanned consultations (2,811) of 1,431 cancer patients who accessed our acute oncology clinic over a 2-year period were reviewed. Demographics, clinical variables and reason(s) for presentation were all recorded. Recurrent event survival analysis was used to evaluate the relation of potential predictors to the two outcome events repeated presentations and hospitalization. A stratified Cox proportional hazard model was used. Of 1,431 patients, 625 (43 %) received chemotherapy during the 90 days before the unplanned visit. Pain (27.7 %), fatigue (17.6 %), dyspnoea (13.8 %), fever (11.5 %) and gastrointestinal problems (31 %) were reported frequently. The time interval since the last chemotherapy was significantly related to the rate of repeated presentation. Two hundred and nine patients (7 %) were hospitalized after an unplanned presentation. Number of symptoms and selected toxicities, along with distance from the hospital, were all predictors for hospitalization. The management of unscheduled presentations of cancer outpatients is becoming crucial to avoid inappropriate selection for hospital admission and interferences with the ordinary work plan, improving quality of oncology services.

PURPOSE The aim of this study was to assess the fractal dimension (Df) of disks with 3 different surface topographies. MATERIALS AND METHODS Thirty disk-shaped samples (10 × 2 mm) with 3 different surface topographies (Dental Tech, Misinto, Italy) were analyzed by scanning electron microscopy: group A, machined surface; group B, titanium plasma-spray surface; group C, acid-etched and sandblasted surface (Blasted Wrinkled Surface). RESULTS The amplitude roughness parameter (Sa) of the machined surfaces was 0.6 μm, while the developed surface area ratio (Sdr) was 14%; for the titanium plasma-spray surfaces, the values were, respectively, 5.3 μm and 97%, and for the Blasted Wrinkled Surfaces, 1.5 μm and 63%. Images at 1.000, 20.000, and 50.000 magnifications were processed for quantitative analysis of Df using the box-counting method. At 1.000×, Df for group A, B, and C was 1.86, 1.80, and 1.81, respectively; at 20.000×, Df for group A, B, and C was 1.85, 1.71, 1.58, respectively; and at 50.000×, Df was 1.83, 1.61, and 1.51 for A, B, and C groups. Statistically significant differences were found for Df values. CONCLUSIONS Df provides not only an index of roughness size values but also a measure of roughness spatial organization; therefore, it could be a promising method to differentiate between rough surfaces capable of supporting osseointegration.