The use of fentanyl buccal tablets for breakthrough pain by using doses proportional to opioid basal regimen in a home care setting.

Abstract The dose of rapid onset opioids to be given for breakthrough cancer pain (BTcP) is controversial. Dose proportional to the basal opioid regimen seem to be safe and effective in hospital units. However, data in other less protected settings, like home care, are lacking. The aim of this open-label study was to assess the efficacy and safety in a group of patients with BTcP followed at home, after giving a dose of fentanyl buccal tablets (FBT) proportional to the opioid basal regimen, skipping the steps for dose titration. Consecutive patients admitted to a home care program presenting BTcP episodes and receiving stable doses of opioids for background pain were selected. Data from four consecutive episodes of BTcP were collected. For each episode, patients were instructed to routinely collect changes in pain intensity and severe adverse effects when pain got severe (T0) and to reassess the same items 15 min after FBT, given as a rescue medication in doses proportional to the daily opioid doses used for background pain (T15). One hundred twenty episodes of BTcP were recorded in 30 patients. One hundred eight episodes were defined as successfully treated, while 12 episodes required a further administration of opioids. Pain intensity significantly decreased at T15 (p < 0.001). In 95.5 and 90.8 % of episodes treated, there was a reduction in pain intensity of more than 33 and 50 %, respectively. No relevant adverse effects were recorded, even in older patients. This study suggests that FBT given in doses proportional to the basal opioid regimen for the management of BTcP is very effective and safe in clinical practice in the home care setting

Opioid switching from and to tapentadol extended release in cancer patients: conversion ratio with other opioids

Objectives: The aim of this exploratory study was to assess the conversion ratios between tapentadol and other opioids in patients requiring an opioid switching. Methods: A prospective study was carried out in a convenience sample of consecutive patients admitted to an acute palliative care unit and a home care unit for a period of 1 year. Patients who were switched from/to tapentadol were selected. The initial ratio between tapentadol and other opioids, expressed as oral morphine equivalents was 1:3.3. The subsequent doses were flexible and were changed to fit the patients’ needs. Pain intensity and distress score were recorded until opioid doses were stable. In all, 37 patients were examined; 24 and 13 patients were switched from and to tapentadol, respectively. Results: The most frequent sequences were tapentadol–morphine (18 patients) in one direction, and morphine–tapentadol (8 patients) in the other direction. In the sequence tapentadol–morphine and morphine–tapentadol, the mean final tapentadol–morphine ratios were 3.9:1 (SD 2.3), and 1:4.5 (SD 3.2), respectively, which did not differ significantly from the initial established conversion ratio. A minority of patients were switched from/to tapentadol to/from other opioids. Globally, the initial ratio did not change after switching took place. Conclusion: Data suggest that a conversion ratio between tapentadol and other opioids, expressed in oral morphine equivalents could be 1:3.3 in both direction, particularly in patients who are switched in conditions of equianalgesia. The limited number of patients prevents a definitive conclusion to be drawn, and data should be interpreted with caution, given the exploratory nature of the study and the question of the low number of patients should be addressed in future studie

Tapentadol in cancer pain management: a prospective open-label study.

OBJECTIVES: The aim of this prospective, open-label study was to evaluate the efficacy and tolerability of tapentadol (TP) in the management of cancer pain. METHODS: A 4 weeks' prospective study was carried out in 50 opioid-naive cancer patients with moderate-severe pain. Each patient initially received twice-daily doses of slow-release TP 50 mg. Doses were then managed to maintain adequate relief or dose-limiting toxicity, on the basis of the clinical response. The following parameters were recorded at weekly intervals for 4 weeks: pain and opioid-related adverse effects, quality of life measured with the Spitzer score, TP escalation index percent (TPEI%) and TP escalation index in mg (TPEImg), calculated at the end of the study, pain mechanisms, and PainDETECT at baseline. RESULTS: Of 50 patients, 39 completed the entire study and 11 discontinued the treatment for different reasons. Pain intensity significantly decreased from baseline to all the week intervals (p < 0.0005), and adverse effects did not changed significantly, while quality of life improved. TP escalation indexes were low and no relationship was found with age, gender, and pain mechanisms. CONCLUSION: Tapentalol started in doses of 100 mg/day was well-tolerated and effective in opioid-naive patients with cancer pain, regardless of the pain mechanism. It can be considered as a flexible drug to be used in patients with moderate-severe pain. LIMITATIONS: This was an open-label study for exploratory purposes. Data should be confirmed in controlled studies with a larger number of patient

Relationship between background cancer pain, breakthrough pain, and analgesic treatment: a preliminary study for a better interpretation of epidemiological and clinical studies

Abstract Abstract Background: The different operational definitions of breakthrough cancer pain (BTcP) has generated unclear epidemiological data. Methods: A consecutive sample of patients was categorized on the basis of their background pain intensity, background analgesic treatment, and the presence of BTcP. Results: A total of 265 patients were surveyed; 117 patients had background pain and 91 patients presented peaks of pain intensity distinguishable from background pain. Of 117 patients with background pain, 49 patients were re-assessed after optimization of background analgesia (T1) within a mean of 8.2 days. Pain intensity significantly decreased in comparison with values recorded at admission (p\u2009<\u20090.0005); 75.5% of these patients had BTcP episodes, with a significant decrease in the number BTcP episodes in comparison with T0 (p\u2009<\u20090.0005). The mean BTcP intensity was significantly lower in comparison with T0 (p\u2009<\u20090.0005). Finally, the mean duration of untreated BTcP episodes decreased significantly in comparison with T0 (p\u2009=\u20090.016). After optimization of analgesic therapy, most patients with moderate or severe background pain receiving opioids for moderate pain, patients with moderate or severe pain receiving strong opioids, and patients with moderate or severe pain receiving no opioids moved to the group of patients with mild pain receiving strong opioids. The difference was significant (p\u2009=\u20090.022). Conclusion: Patients having good pain control after optimization of the analgesic regimen may have a decrease in number, intensity, and duration of BTcP, although the general prevalence of BTcP remains unchanged

The X-Gamma Imaging Spectrometer (XGIS) onboard THESEUS

A compact and modular X and gamma-ray imaging spectrometer (XGIS) has been designed as one of the instruments foreseen on-board the THESEUS mission proposed in response to the ESA M5 call. The experiment envisages the use of CsI scintillator bars read out at both ends by single-cell 25 mm 2 Silicon Drift Detectors. Events absorbed in the Silicon layer (lower energy X rays) and events absorbed in the scintillator crystal (higher energy X rays and Gamma-rays) are discriminated using the on-board electronics. A coded mask provides imaging capabilities at low energies, thus allowing a compact and sensitive instrument in a wide energy band (~2 keV up to ~20 MeV). The instrument design, expected performance and the characterization performed on a series of laboratory prototypes are discussed.Comment: To be published in the Proceedings of the THESEUS Workshop 2017 (http://www.isdc.unige.ch/theseus/workshop2017.html), Journal of the Italian Astronomical Society (Mem.SAIt), Editors L. Amati, E. Bozzo, M. Della Valle, D. Gotz, P. O'Brien. Details on the THESEUS mission concept can be found in the white paper Amati et al. 2017 (arXiv:171004638) and Stratta et al. 2017 (arXiv:1712.08153

Identification and Characterization of BRCA1 and BRCA2 Founder Mutations

A large number of cancer predisposing BRCA1/BRCA2 mutations have been reported, with a wide variety among populations. In some restricted groups, specific germline mutations in these tumor suppressor genes have been found with high predominance, due to a founder effect. We focused our review on the Italian founder mutations. The first Italian BRCA1 founder mutation, 5083del19, was found in Calabria: the presence of common allele in all carriers of this mutation (also in families with Calabrian origin living in other parts of Italy) confirmed its founder effect. The same BRCA1 mutation was identified in the Sicilian population, but only the haplotype analysis can reveal the common ancestor of these groups. Another BRCA1 founder mutation, 4843delC, was found in Sicily. Four distinct BRCA1 mutations are attributable to families original from Tuscany: 3348delAG, 3285delA, 1499insA and 5183delTGT; the latter has been shown to be a founder mutation from North-Eastern Italy. The first BRCA2 mutation was identified in Sardinia, 8765delAG, a mutation already described as a founder mutation in Jewish-Yemenite families and also in French-Canadian population but with independent origins of carriers in these three populations. BRCA2 3951del3 and BRCA1 917delTT have been described as founder mutations in Middle Sardinia and in South and Middle Sardinia, respectively. Studies regarding prevalence and penetrance of founder mutations can allow to quantify the degree of homogeneity within a population and can surely help the geneticist and oncologist to simplify their choices in the genetic testing on high-risk families, on the basis of their ethnical origin

Characterization of timing and spacial resolution of novel TI-LGAD structures before and after irradiation

The characterization of spacial and timing resolution of the novel Trench Isolated LGAD (TI-LGAD) technology is presented. This technology has been developed at FBK with the goal of achieving 4D pixels, where an accurate position resolution is combined in a single device with the precise timing determination for Minimum Ionizing Particles (MIPs). In the TI-LGAD technology, the pixelated LGAD pads are separated by physical trenches etched in the silicon. This technology can reduce the interpixel dead area, mitigating the fill factor problem. The TI-RD50 production studied in this work is the first one of pixelated TI-LGADs. The characterization was performed using a scanning TCT setup with an infrared laser and a $^90$Sr source setup

EGFR genomic alterations in cancer: prognostic and predictive values

none11: The role of EGFR in cancer development and progression has been recognized for long time in a variety of human malignancies including lung, head and neck, colon, breast, ovary and glioma. Recently its role as a target of antineoplastic agents has also been identified and a variety of EGFR-targeted drugs is already being used in a clinical setting and others are at present under investigation. Many data involving EGFR protein expression are now available for the choice of anti-EGFR monoclonal antibodies in colorectal cancer and with regard to EGFR gene mutations for the choice of tyrosine kinase inhibitors in lung cancer. Other EGFR-related molecular factors, including the EGFR gene copy number, are currently under investigation. This review summarizes both preclinical and clinical available data regarding EGFR genomic alterations as prognostic and predictive factors.openBronte, Giuseppe; Terrasi, Marianna; Rizzo, Sergio; Sivestris, Nicola; Ficorella, Corrado; Cajozzo, Massimo; Di Gaudio, Francesca; Gulotta, Gaspare; Siragusa, Sergio; Gebbia, Nicola; Russo, AntonioBronte, Giuseppe; Terrasi, Marianna; Rizzo, Sergio; Sivestris, Nicola; Ficorella, Corrado; Cajozzo, Massimo; Di Gaudio, Francesca; Gulotta, Gaspare; Siragusa, Sergio; Gebbia, Nicola; Russo, Antoni