End-to-end test for lung SBRT: An Italian multicentric pilot experience.

PURPOSE: Set up a lung SBRT end-to-end (e2e) test and perform a multicentre validation. MATERIAL AND METHODS: A group of medical physicists from four hospitals and the Italian Institute of Ionizing Radiation Metrology designed the present e2e test. One sub-group set up the test, while another tested its feasibility and ease of use. A satisfaction questionnaire was used to collect user feedback. Each participating centre (PC) received the ADAM breathing phantom, a microDiamond detector and radiochromic films. Following the e2e protocol, each PC performed its standard internal procedure for simulating, planning, and irradiating the phantom. Each PC uploaded its planning and treatment delivery data in a shared Google Drive. A single centre analyzed all the data. RESULTS: The e2e test was successfully performed by all PCs. Participants' comments indicated that ADAM was well suited to the purpose and the protocol well described. All PCs performed the test in static and dynamic modes. The ratio between measured and planned point dose obtained by PC1, PC2, PC3, PC4 was: 0.99, 0.96, 1.01 and 1.01 (static track) and 0.99, 1.02, 1.01 and 0.94 (dynamic track). The gamma passing rates (3 % global, 3 mm) between planned and measured dose maps were 98.5 %, 94.0 %, 99.1 % and 94.0 % (static track) and 99.5 %, 96.5 %, 86.0 % and 94.5 % (dynamic track) for PC1, PC2, PC3 and PC4, respectively. CONCLUSIONS: An e2e test for lung SBRT has been proposed and tested in a multicentre framework. The results and user feedback prove the validity of the proposed e2e test.

A semi-automatic planning technique for whole breast irradiation with tangential IMRT fields.

PURPOSE: To implement a semi-automatic planning technique for whole breast irradiation with two tangential IMRT fields and to test the produced dose distribution against clinical 3DCRT plans, for introducing the technique in clinical practice. METHODS: The Auto-Planning module of the Pinnacle3 (Philips) treatment planning system was used for generating a Treatment Technique on left-sided breast cancer patients treated in free breathing or in deep inspiration breath hold (DIBH) and to right-sided breast cancer patients. The technique was evaluated against 3DCRT clinical plans in terms of dosimetric plan parameters. Plan robustness toward patient displacements was assessed on a subset of patients by inducing shifts to the isocenter. RESULTS: A statistically significant improvement in target coverage and dose homogeneity was observed for autoIMRT. No statistically significant differences were observed for ipsilateral organs, except for the ipsilateral lung in left DIBH, where slightly lower Dmean and V18% are registered for autoIMRT. Slightly higher Dmean doses (although far below the constraints) to contralateral organs were observed for autoIMRT plans. AutoIMRT plans were shown to be as robust as 3DCRT plans toward isocenter shifts, with a maximum decrease in CTV coverage of -2.2% and -2.1% for autoIMRT and 3DCRT, respectively. Average planning times were 40 min for 3DCRT and 6 min for IMRT plans. CONCLUSIONS: The developed autoIMRT technique was proven to be advantageous for target coverage and homogeneity and sufficiently robust towards isocenter displacements. The use of automated planning consistently reduces the planning workload with improvements in plan quality.

Comparison of volumetric modulated arc therapy and intensity-modulated radiotherapy for left-sided whole-breast irradiation using automated planning.

BACKGROUND: Published treatment technique comparisons for postoperative left-sided whole breast irradiation (WBI) with deep-inspiration breath-hold (DIBH) are scarce, small, and inconclusive. In this study, fully automated multi-criterial plan optimization, generating a single high-quality, Pareto-optimal plan per patient and treatment technique, was used to compare for a large patient cohort 1) intensity modulated radiotherapy (IMRT) with two tangential fields and 2) volumetric modulated arc therapy (VMAT) with two small tangential subarcs. MATERIALS AND METHODS: Forty-eight randomly selected patients recently treated with DIBH and 16â€¯× 2.66 Gy were included. The optimizer was configured for the clinical planning protocol. Comparisons between IMRT and VMAT included dosimetric plan parameters, estimated excess relative risks (ERR) for toxicities, delivery times, MUs, and deliverability accuracy at a linac. RESULTS: The automatically generated IMRT and VMAT plans applied in this study were similar or higher in quality than the manually generated clinical plans. For equal PTVin V95% (98.4 ± 0.9%), VMAT had significant advantages compared to IMRT regarding breast dose homogeneity and doses in heart and ipsilateral lung, at the cost of some minor deteriorations for contralateral breast (few cases with larger deteriorations) and lung. Conformality improved from 1.38 to 1.18 (p < 0.001). With VMAT, ERR for major coronary events and ipsilateral lung tumors were reduced by 3% (range: -1-12%) and 16% (range: -3-38%), respectively. MUs and delivery times were higher for VMAT. There were no statistical differences in γ passing rates. CONCLUSION: For WBI in conservative therapy of left-sided breast patients treated with DIBH, VMAT with two tangential subarcs was generally dosimetrically superior to IMRT with two tangential static fields. Results need confirmation by robustness analyses.

Automatic VMAT technique to treat glioblastoma: A two years' experience.

PURPOSE: The present work aims to guide the physicist in order to start automated planning for the VMAT treatment of glioblastoma multiforme (GBM) by giving a recipe that was set up and tested during a long-term (two years) evaluation. METHODS: An automatic technique in AutoPlanning module of the Pinnacle3 (Philips Medical Systems, Fitchburg, WI) treatment planning system was created and validated by comparing dose distributions of automatic plans (APs) and manual plans (MPs) and by performing a blind AP-MP comparison on a cohort of 20 patients. Automatic technique was then applied to 145 patients and failures were recorded i.e. the number of times for which dose distributions produced by the automatic module were not suitable for treatment. RESULTS: Each of the 20 APs considered in the validation step was clinically acceptable and proved to be better (15 cases) or equal (5 cases) respect to MPs. A statistically significant improvement in brain stem, optic pathways, cochleae, pituitary gland and scalp sparing was observed for APs, while no statistically significant differences were recorded in target coverage or plan parameters. For only 5 cases out of the 145 plans the operator intervention was needed in order to obtain a clinical acceptable plan, while for the remaining 140 plans the automatic created solution was suitable. CONCLUSIONS: A straightforward automatic procedure has been created and tested in our clinic. The AutoPlanning technique proposed represents a reliable tool to improve treatment planning efficiency and the recipe, here presented, could be simply imported to every radiotherapy center.

Use of brodalumab for the treatment of chronic plaque psoriasis: a one-year real-life study in the Lazio region, Italy.

Background: Information is limited from real-life studies evaluating the efficacy and safety of brodalumab.Research design and methods: In this real-life study, we retrospectively examined a database of 90 patients with moderate-to-severe psoriasis treated with brodalumab (210 mg, s.c.) and followed for 1 year. Disease severity and treatment response were assessed by the Psoriasis Area and Severity Index (PASI) at baseline and after 4, 12, 24, 36, and 48 weeks. Predictors of a PASI response were evaluated by logistic regression.Results: After 48 weeks, 92.2% of patients (mean age 50.2 ± 15 years) treated with brodalumab achieved a PASI score of <3. PASI score decreased from 17.4 ± 10.3 at baseline to 1.7 ± 3.9 and 1.4 ± 3.7 at 12 and 24 weeks, and PASI 75, 90, and 100 response was achieved in 87.3%, 81.8%, and 72.7% of patients, respectively, at 48 weeks.Univariate regression revealed that previous exposure to anti-IL17A treatment was associated with poorer PASI response between 36 and 48 weeks. In difficult-to-treat cases previously having failed with other biologics, brodalumab significantly improved outcome, leading to complete remission.Conclusion: Brodalumab was observed to be effective and safe in patients with moderate-to-severe chronic psoriasis in a real-world setting.

In phantom evaluation of targeting accuracy in MRI-based brain radiosurgery.

PURPOSE: To determine the targeting accuracy of brain radiosurgery when planning procedures employing different MRI and MRI + CT combinations are adopted. MATERIALS AND METHOD: A new phantom, the BrainTool, has been designed and realized to test image co-registration and targeting accuracy in a realistic anatomical situation. The phantom was created with a 3D printer and materials that mimic realistic brain MRI and CT contrast using a model extracted from a synthetic MRI study of a human brain. Eight markers distributed within the BrainTool provide for assessment of the accuracy of image registrations while two cavities that host an ionization chamber are used to perform targeting accuracy measurements with an iterative cross-scan method. Two procedures employing 1.5 T MRI-only or a combination of MRI (taken with 1.5 T or 3 T scanners) and CT to carry out Gamma Knife treatments were investigated. As distortions can impact targeting accuracy, MR images were preliminary evaluated to assess image deformation extent using GammaTool phantom. RESULTS: MR images taken with both scanners showed average and maximum distortion of 0.3 mm and 1 mm respectively. The marker distances in co-registered images resulted below 0.5 mm for both MRI scans. The targeting mismatches obtained were 0.8 mm, 1.0 mm and 1.2 mm for MRI-only and MRI + CT (1,5T and 3 T), respectively. CONCLUSIONS: Procedures using a combination of MR and CT images provide targeting accuracies comparable to those of MRI-only procedures. The BrainTool proved to be a suitable tool for carrying out co-registration and targeting accuracy of Gamma Knife brain radiosurgery treatments.

Sex- and gender-associated clinical and psychosocial characteristics of patients with psoriasis.

BACKGROUND: Sex and gender may affect disease prevalence, adverse effects and response to therapy. AIM: To analyse sex and gender differences in outpatients with psoriasis. METHODS: A cross-sectional study was conducted at IDI-IRCCS, Rome, over a 3-year period. In total, 3023 patients with psoriasis were enrolled. Anthropometric and demographic characteristics were recorded, and a dermatologist evaluated the clinical severity of disease. Quality of life (QoL) questionnaires were collected. Univariate and multivariate analyses were performed to examine factors associated with sex. RESULTS: We found sex- and gender-associated differences in clinical characteristics, disease severity, psychological distress and quality of life. Male sex was associated with body mass index, smoking, alcohol consumption, Psoriasis Area Severity Index ≥ 10 and age at onset ≥ 20 years. Female sex was associated with family history of diabetes, joint involvement, clinical type other than diffuse plaque psoriasis, higher psychological distress and a greater effect on QoL. CONCLUSION: Our study identified sex and gender differences of potential clinical relevance in psoriasis.

TomoTherapy treatments of multiple brain lesions: an in-phantom accuracy evaluation.

Aim of the present study was to evaluate the accuracy which can be obtained with helical TomoTherapy® (HT, Accuray) systems in the case of multiple intracranial targets treatments. Set-up accuracy was measured, for different registration options and MegaVoltage CT (MVCT) slice thickness, by applying known misalignments to an ad-hoc developed phantom. End-to-end (E2E) tests were performed to assess the delivery accuracy in phantoms containing multiple targets by using radiochromic films: measured dose distribution centroids were compared with physical and calculated target positions on axial and coronal planes. A Gamma index analysis was carried out on planned and measured planar dose maps. The bone and tissue algorithm with the fine MVCT reconstruction grid gave the best results among the automatic options. The most accurate registration modality resulted to be the manual one with a sub-voxel accuracy shifts and a capability in the detection of rotations within 0.3°. For the E2E along the coronal plane (six targets), a mean deviation between measured dose distribution centroids and physical barycenters of 0.6 mm (range 0.1 mm-1.3 mm) was observed. Along the axial plane (five targets), a mean deviation of 1.2 mm (range 0.7 mm-2.1 mm) was found for the centroids shifts. Gamma index (5%, 1 mm, local) passing rates higher than 87.5% between planned and delivered dose distributions were measured. These results demonstrate that multiple brain lesion HT treatments are feasible with an accuracy at least comparable to frameless linac-based delivery, when a set-up capable to assure angular corrections and a reliable patient immobilization is employed.

The use of double lasso, fully covered self-expandable metal stents with new "anchoring flap" system in the treatment of benign biliary diseases.

BACKGROUND: Many benign biliary diseases (BBD) can be treated with fully covered, self-expandable metal stents (FCSEMS) but stent migration occurs in up to 35.7 %. The aim of this study was to prospectively assess the rate of, safety and effectiveness and stent migration of a new biliary FCSEMS with an anti-migration flap (FCSEMS-AF) in patients with BBD. PATIENTS AND METHODS: This was a prospective study from four Italian referral endoscopy centers of 32 consecutive patients (10 females and 22 males; mean age: 60.1 ± 14.8 years; range: 32-84 years) with BBD who were offered endoscopic placement of a FCSEMS-AF as first-line therapy. RESULTS: Were 24 strictures and 8 leaks. Stent placement was technically successful in 32/32 patients (100 %). Immediate clinical improvement was seen in all 32 patients (100 %). One late stent migration occurred (3.3 %). FCSEMS-AF were removed from 30 of the 32 patients (93.7 %) at a mean (± SD) of 124.4 ± 84.2 days (range: 10-386 days) after placement. All patients remained clinically and biochemically well at 1- and 3-month follow-up. One patient (3.3 %) with a post-laparoscopic cholecystectomy stricture developed distal stent migration at 125 days. CONCLUSION: This new FCSEMS with anti-migration flap seems to be a safe and effective first-line treatment option for patients with BBD.

Efficacy and acceptability of sodium picosulphate/magnesium citrate vs low-volume polyethylene glycol plus ascorbic acid for colon cleansing: a randomized controlled trial.

AIM: The study compared the efficacy, safety and tolerability of a low-volume picosulphate/magnesium citrate preparation with that of polyethylene glycol plus ascorbic acid (PEG + ASC) in a randomized clinical trial (RCT). METHOD: A multicentre randomized, single-blinded study was designed. Adult outpatients undergoing colonoscopy received either picosulphate/magnesium citrate (Group 1) or PEG + ASC (Group 2). Bowel cleansing was assessed using the Boston Bowel Preparation Scale (BBPS) and rated as adequate if ≥ 2 in each segment. Patient acceptance, satisfaction and related symptoms were recorded. RESULTS: Two-hundred and eighty-five patients were included. Preparation was adequate in 75.7% of patients in Group 1 and in 76.5% of patients in Group 2. The mean BBPS scores for the entire colon and for the right colon were comparable between groups. In addition, 97.1% patients in Group 1 and 84.8% in Group 2 reported no or mild discomfort (P < 0.0003) and 97.8% and 83.4% expressed their willingness to repeat the preparation (P < 0.0001). Palatability was better in Group 1, whereas related symptoms occurred more frequently in Group 2. Regardless of which preparation was used, the split regimen was associated with better cleansing compared with the same-day method (OR = 3.39; 95% CI: 1.1-10.4; P = 0.03). Other predictors of poor cleansing were comorbidity, discomfort during preparation and incomplete (< 75%) preparation. CONCLUSION: Both picosulphate/magnesium citrate and PEG + ASC are effective for bowel preparation. Tolerability and palatability are better for picosulphate/magnesium citrate. A split schedule is associated with higher cleansing quality also for low-volume regimens.

Anti-apoptotic effects of suppressor of cytokine signaling 3 and 1 in psoriasis.

Because of their genetically determined capacity to respond to pro-inflammatory stimuli, keratinocytes have a crucial role in the pathogenesis of psoriasis. Upon IFN-γ and TNF-α exposure, psoriatic keratinocytes express exaggerated levels of inflammatory mediators, and show aberrant hyperproliferation and terminal differentiation. The thickening of psoriasic skin also results from a peculiar resistance of keratinocytes to cytokine-induced apoptosis. In this study, we investigated on the molecular mechanisms concurring to the resistance of psoriatic keratinocytes to cell death, focusing on the role having suppressor of cytokine signaling (SOCS)1 and SOCS3, two molecules abundantly expressed in IFN-γ/TNF-α-activated psoriatic keratinocytes, in sustaining anti-apoptotic pathways. We found that SOCS1 and SOCS3 suppress cytokine-induced apoptosis by sustaining the activation of the PI3K/AKT pathway in keratinocytes. The latter determines the activation of the anti-apoptotic NF-κB cascade and, in parallel, the inhibition of the pro-apoptotic BAD function in keratinocytes. For the first time, we report that phosphorylated AKT and phosphorylated BAD are strongly expressed in lesional psoriatic skin, compared with healthy or not lesional skin, and they strictly correlate to the high expression of SOCS1 and SOCS3 molecules in the psoriatic epidermis. Finally, the depletion of SOCS1 and SOCS3, as well as the chemical inactivation of PI3K activity in psoriatic keratinocytes, definitively unveils the role of PI3K/AKT cascade on the resistance of diseased keratinocytes to apoptosis.

Modulation of Toll-like receptors in psoriatic patients during therapy with adalimumab.

Toll-like receptors (TLRs) are a key part of the innate immune system that detect pathogen-associated molecular patterns (PAMPs) of microorganisms and their stimulation results in the activation of signaling pathways leading to the modulation of inflammatory and immune responses. Since psoriasis is a complex, inflammatory and immune skin disease, characterized by an abnormal immune response and increased proliferation of keratinocytes, with an increased production of proinflammatory cytokines, TLRs could play an important role in the pathogenesis of the disease. We propose to assess the modulation of TLR expression on psoriatic skin of patients treated with Adalimumab and systemic conventional therapies. We therefore recruited fifteen patients: ten were treated with adalimumab and five with systemic conventional therapies; their clinical conditions were analyzed by PASI index and skin biopsies were evaluated for TLR1 and TLR2 expression by immunohistochemistry assays. Our data suggest adalimumab is not only able to improve the clinical condition of psoriatic patients, but also to modulate TLR1 and TLR2 expression involved in psoriasis, as in healthy skin. Adalimumab is a most promising biological drug able to orchestrate immune and inflammatory responses in psoriatic lesions, recovering TLR expression on basal keratinocytes and improving clinical conditions of psoriatic patients, with no evident side effects.

Systematic review: gastro-oesophageal reflux disease and dental lesions.

BACKGROUND: Dental erosion (DE), which is the irreversible loss of tooth substance that does not involve bacteria ranging from a minimal loss of surface enamel to the partial or complete exposure of dentine by a chemical process, is acknowledged as an established extra-oesophageal manifestation of gastro-oesophageal reflux disease (GERD). However, the real impact of GERD in the genesis of this lesion remains unclear. AIM: To review the existing literature to assess the relationship between DE and GERD. METHODS: Studies that assessed the prevalence of DE in individuals with GERD or vice versa were identified in Medline and the Cochrane Controlled Trials Register via a systematic research strategy. RESULTS: Seventeen studies met the selection criteria. Studies, however, differed greatly as far as design, population methods of diagnosing GERD, duration of follow-up and, consequently, findings. The median prevalence of DE in GERD patients was 24%, with a large range (5-47.5%), and the median prevalence of GERD in DE adults patients was 32.5% (range: 21-83%) and in paediatric population 17% (range: 14-87%). Children with GERD are found by a majority of studies at increased risk of developing DEs in comparison with healthy subjects, as are intellectually disabled people. CONCLUSIONS: This systematic review shows that there is a strong association between GERD and DE. The severity of DEs seems to be correlated with the presence of GERD symptoms, and also, at least in adults, with the severity of proximal oesophageal or oral exposure to an acidic pH. The inspection of the oral cavity in search for DEs should become a routine manoeuvre in patients with GERD.

Assessment of gastro-oesophageal reflux symptoms in Italian physicians -- a survey by Reflux Disease Questionnaire.

BACKGROUND: The prevalence of gastro-oesophageal reflux disease symptoms in physicians, as compared to that of the general population, is not known. METHODS: We submitted a validated Italian version of a simple questionnaire (Reflux Disease Questionnaire) to 490 physicians and 430 controls to assess: (i) the presence, frequency and severity of gastro-oesophageal reflux disease symptoms in the two populations; (ii) how the self-assessment of troublesome gastro-oesophageal reflux disease symptoms by physicians correlate with a pathological Reflux Disease Questionnaire, judged on the basis of a total Reflux Disease Questionnaire score >or=8. RESULTS: A valid and complete questionnaire was obtained in 456/490 (93.1%) physicians and 367/430 (85.3%) controls. Between the two groups there were no differences in terms of total Reflux Disease Questionnaire score or individual items, with the only exception of "severity of burning feeling behind breastbone" which was significantly higher in the physician group. An excellent correlation was found between the self-assessment by physician and the total Reflux Disease Questionnaire score. CONCLUSIONS: The prevalence of gastro-oesophageal reflux disease symptoms among Italian doctors is not different from that reported by a matched control group, and that their ability in self-assessing a troublesome gastro-oesophageal reflux disease is optimal.

Fixation of a covered self-expandable metal stent by means of a polypectomy snare: an easy method to prevent stent migration.

Management of oesophageal leaks is controversial. Covered self-expandable-metallic stents have been used for several conditions, but migration of the stents is frequent. We report the case of a patient with post-surgery oesophageal fistula in which, to prevent dislocation, a covered self-expandable-metallic stent was fixed externally using a polypectomy snare.