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Neuroendocrine neoplasms represent a heterogeneous group of rare tumors, more frequently arising from gastroenteropancreatic tract and lungs. At the time of diagnosis, 20% of cases are metastatic, and 10% of cases are considered as cancer of unknown primary origin. Several immunohistochemical markers are routinely used to confirm the neuroendocrine differentiation, first among all Synaptophysin and Chromogranin-A; on the other hand, different immunohistochemical markers are used to establish primary anatomical site, as TTF1, CDX2, Islet-1 and Calcitonin, but no marker is available in order to distinguish among different sites of the digestive tract. DOG1 (discovered on GIST-1) is a gene normally expressed in interstitial cells of Cajal and, in routine practice, DOG1 immunostaining is used in diagnosis of GIST (gastrointestinal stromal tumor). DOG1 expression has been described in several neoplasms other than GIST, both in mesenchymal and epithelial neoplasms. In the present study, DOG1 immunostaining has been performed in a large cohort of neuroendocrine neoplasms, including neuroendocrine tumors and neuroendocrine carcinomas, in order to evaluate frequency, intensity and pattern of expression in different anatomical site and in different tumor grade. DOG1 expression was detected in a large percentage of neuroendocrine tumors, with statistically significant association between DOG1 expression and gastrointestinal tract neuroendocrine tumors. As a consequence, DOG1 could be included in marker panel for the identification of primary site in neuroendocrine metastases of unknown primary origin; moreover, these results recommend careful evaluation of DOG1 expression in gastrointestinal neoplasms, in particular in differential diagnosis between epithelioid GIST and neuroendocrine tumors., Competing Interests: Declaration of Competing Interest We have no conflict of interests., (Copyright © 2023 Elsevier GmbH. All rights reserved.)

Purpose: This systematic review and meta-analysis aimed to evaluate the efficacy of barrier films and dressings in preventing acute radiation dermatitis (RD)., Methods: OVID Medline, Embase, and Cochrane databases were searched from 1946 to September 2020 to identify randomized controlled trials on the use of barrier films or dressings to prevent RD. For comparable outcomes between studies, pooled effect sizes and 95% confidence intervals (CI) were calculated using the random effects analysis in RevMan 5.4., Results: Fourteen and 11 studies were included in the qualitative and quantitative analyses, respectively. Five types of barrier films used for RD were identified: Hydrofilm, StrataXRT®, Mepitel® Film, 3 M™ Cavilon™ No-Sting Barrier Film, and silver leaf nylon dressing. Hydrofilm and Mepitel Film significantly reduced the development of RD grade ≥ 2 in breast and head and neck cancer patients (RR 0.32, 95%CI 0.19, 0.56, p < 0.0001; RR 0.21, 95%CI 0.05, 0.89, p = 0.03, resp.). Moreover, Hydrofilm had a beneficial effect on patient-reported outcomes (PROs) (SMD -0.75, 95%CI -1.2, -0.29, p = 0.001). The meta-analyses on the other barrier films did not show any significant effect., Conclusion: This review and meta-analysis demonstrated that Hydrofilm and Mepitel Film could effectively reduce RD severity and improve PROs. The evidence is generally weak for all the studies on barrier films and dressings due to a limited study number, high risk of bias, small sample sizes, and minimal comparable outcome measures. It's potential has been proven, but future research in this field is recommended to confirm the efficacy of these products and assess real-world feasibility., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Oligoprogression (OPD) is defined as a condition where limited progression (1-3 metastases) is observed in patients undergoing systemic cancer treatment. In this study we investigated the impact of stereotactic body radiotherapy (SBRT) in patients with OPD from metastatic lung cancer., Material and Methods: Data from a cohort of consecutive patients with SBRT treated between June 2015 and August 2021 were collected. All extracranial metastatic sites of OPD from lung cancer were included. Dose regimens consisted of mainly 24 in 2 fractions, 30-51 Gy in 3 fractions, 30-55 Gy in 5 fractions, 52.5 Gy in 7 fractions and 44-56 Gy in 8 fractions. Kaplan-Meier method was used to calculate Overall Survival (OS), Local Control (LC), and Disease-Free Survival (DFS) from the start date of SBRT to the event., Results: Sixty-three patients, 34 female and 29 males were included. Median age was 75 years (range 25-83). All patients received concurrent systemic treatment before the start of the SBRT: 19 chemotherapy (CT), 26 CT plus immunotherapy (IT) or Tyrosin kinase inhibitors (TKI) and 18 IT/TKI. SBRT was delivered to the lung ( n  = 29), mediastinal node ( n  = 9), bone ( n  = 7), adrenal gland ( n  = 19), other visceral metastases (1) and other node metastases ( n  = 4). After a median follow-up of 17 months, median OS was 23 months. LC was 93% at 1 year and 87% at 2 years. DFS was 7 months. According to our results, there was no statistically significant correlation between prognostic factors and OS after SBRT in OPD patients., Conclusions: Median DFS was 7 months, translating into the continuation of effective systemic treatment as other metastases grow slowly. In patients with oligoprogression disease, SBRT is a valid and efficient treatment that may enable postponing the switch of systemic line.

Trabectedin is used for the treatment of advanced soft tissue sarcomas (STSs). In this study, we evaluated if trabectedin could enhance the efficacy of irradiation (IR) by increasing the intrinsic cell radiosensitivity and modulating tumor micro-environment in fibrosarcoma (HS 93.T), leiomyosarcoma (HS5.T), liposarcoma (SW872), and rhabdomyosarcoma (RD) cell lines. A significant reduction in cell surviving fraction (SF) following trabectedin + IR compared to IR alone was observed in liposarcoma and leiomyosarcoma (enhancement ratio at 50%, ER50: 1.45 and 2.35, respectively), whereas an additive effect was shown in rhabdomyosarcoma and fibrosarcoma. Invasive cells' fraction significantly decreased following trabectedin ± IR compared to IR alone. Differences in cell cycle distribution were observed in leiomyosarcoma and rhabdomyosarcoma treated with trabectedin + IR. In all STS lines, trabectedin + IR resulted in a significantly higher number of γ-H2AX (histone H2AX) foci 30 min compared to the control, trabectedin, or IR alone. Expression of ATM, RAD50, Ang-2, VEGF, and PD-L1 was not significantly altered following trabectedin + IR. In conclusion, trabectedin radiosensitizes STS cells by affecting SF (particularly in leiomyosarcoma and liposarcoma), invasiveness, cell cycle distribution, and γ-H2AX foci formation. Conversely, no synergistic effect was observed on DNA damage repair, neoangiogenesis, and immune system.

Purpose: To explore the benefit yielded by radiotherapy (RT), we report a series of metastatic renal cell carcinoma (RCC) patients treated with concomitant RT plus Nivolumab., Methods/patients: Patients undergoing Nivolumab treatment plus concomitant RT (ablative or palliative) were included. RT was defined Ablative if >5 Gy/fraction were delivered., Results: Ablative RT intent was the only independent predictor of both progression free and overall survival (HR 3.51, 95% CI 1.6-7.5, p = 0.0012 and HR 2.8, 95% CI 0.99-8.07, p = 0.05, respectively)., Conclusion: Ablative RT may improve oncologic outcomes in selected patients with metastatic RCC treated with Nivolumab as compared to palliative RT., (© 2022. The Author(s).)

Background: ARTO trial was designed to evaluate the difference in terms of outcomes between patients affected by oligo metastatic castrate resistant prostate cancer (mCRPC) treated with Abiraterone acetate and randomized to receive or not SBRT on all sites of disease. Here, we present a preliminary analysis conducted on patients enrolled at promoting institution., Objective: To present a preliminary overview about population features, clinical outcomes, adverse events, quality of life and explorative translational research., Design, Setting, and Participants: ARTO (NCT03449719) is a phase II trial including patients affected by oligo mCRPC, randomized to receive standard of care (GnRH agonist or antagonist plus abiraterone acetate 1000 mg and oral prednisone 10 mg daily) with or without SBRT on all metastatic sites of disease. All subjects have < 3 bone or nodal metastases. All patients are treated in I line mCRPC setting, no previous lines of treatment for mCRPC are allowed., Outcome Measurements and Statistical Analysis: Data about a mono-centric cohort of 42 patients enrolled are presented in the current analysis, with focus on baseline population features, PSA drop at 3 months, biochemical response, and quality of life outcomes. Descriptive statistics regarding translational research are also presented., Results and Limitation: Significant difference in terms of PSA drop at three months was not detected (p = 0.68). Biochemical response (PSA reduction > 50%) was reported in 73.7 versus 76.5% of patients in control vs SBRT arm, respectively (p = 0.84). All patients are alive. Progression occurred in 1 versus 0 patients in the control versus SBRT arm, respectively. After 3 months, an average decrease of 13 points in terms of Global Health Score was reported for the overall population. However, complete recovery was noticed at 6 months. Circulating tumor cells detection rate was 40%., Conclusions: SBRT + Abiraterone treatment was safe and well tolerated, non-significant trend in terms of PSA drop and biochemical response at 3 months was detected in SBRT arm. Interestingly, CTCs detection in this selected cohort of oligo-mCRPC was lower if compared to historical data of unselected mCRPC patients., (© 2022. The Author(s).)

Background: tumor recurrence after NSCLC surgical resection is the most common cause of treatment failure that sharply reduces the patient's life expectancy. The optimal treatment strategy for loco-regional recurrences developing after surgical resection in patients with non-small-cell lung cancer (NSCLC) is not established yet. This report aims to describe the pattern of relapse, PFS, and OS in patients treated with radio-chemotherapy and durvalumab for loco-regional relapse after surgery., Methods:  We conducted a multicenter, retrospective study including subjects who underwent surgical resection for NSCLC and were treated with Pacific protocol after loco-regional relapse., Results: Twenty-four patients met the inclusion criteria. At the time of diagnosis mean age was 65 years (range 47-78), the majority being male (58.3%). The 12-month progression-free survival rate was 68.7%, the 18-month progression-free survival rate was 45.8%, and the 24-month progression-free survival rate was 34.3%. There were three deaths: the 12-month survival rate was 91%, and the 18-month survival rate was 82.8%., Conclusions: In this article, we propose a treatment strategy that might prolong post recurrence survival in patients with good performance status experiencing loco-regional relapse after surgery., (© 2022. The Author(s).)

Circulating tumor cells detection and ARV7 expression are associated with worse clinical outcomes in metastatic Castration-Resistant Prostate Cancer (mCRPC) undergoing Androgen Receptor Targeted Agents. ARFL, PSMA and PSA may help to refine prognostic models. In our institution, a prospective observational trial testing CTC detection in mCPRC undergoing I line ARTA therapy terminated the planned enrollment in 2020. Here, we present a pre-planned interim analysis with 18 months of median follow-up. RT-qPCR was used to determine the CTC expression of PSA, PSMA, AR and ARV7 before starting ARTA. PSA-drop, Progression-Free and Overall Survival (PFS and OS) and their correlation with CTC detection were reported. Forty-four patients were included. CTC were detected in 43.2% of patients, of whom 8.94% expressed PSA, 15.78% showed ARV7, 63.15% and 73.68% displayed ARFL and PSMA, respectively. Biochemical response was significantly improved in CTC + vs CTC- patients, with median PSA-drop of 18.5 vs 2.5 ng/ml (p = 0.03). After a median follow-up of 18 months, 50% of patients progressed. PFS was significantly longer in CTC- patients (NR vs 16 months). Eight (18.2%) patients died, a non-significant trend in terms of OS was detected in favor of CTC- patients (NR vs 29 months, p = 0.05). AR, PSA and PSMA expression in CTC + had no significant impact on PSA-drop, PFS or OS. PRIMERA-trial confirmed the CTC detection predictive importance in mCRPC patients., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: To summarize the principal studies investigating the role of postoperative radiation therapy (PORT) for non-small cell lung cancer (NSCLC) and to discuss the recent major breakthroughs deriving from the Lung ART trial, in order to provide a real-world scenario of the management of resected NSCLC patients., Background: Surgery followed by platinum-based chemotherapy remains the mainstay of adjuvant treatments for completely resected stage II and IIIA NSCLC. Less consistent is the employment of PORT, as no significant benefit was clearly identified from the previous published meta-analysis. Furthermore, the recent results of Lung ART trial questioned for the first time the efficacy of PORT for pathological N2 (pN2) NSCLC patients. Hence, the need to define if PORT still has a role for resected NSCLC and which subgroup of patients could benefit most from this treatment., Methods: A literature search of PubMed was performed to identify publications, including prospective and retrospective clinical studies, meta-analysis and systematic review of PORT for NSCLC. No limit concerning years of publication or publication status were applied. Only papers using the English language were selected. The ESMO 2020 and ESMO 2021 online resources were used to analyze the Lung ART trial results. The authors provide a narrative summary of the findings and implications of these studies and how they improve the clinical practice., Conclusions: PORT was considered the standard of care for patients with completely resected pN2 NSCLC based on the results of an old meta-analysis that did not demonstrate a detrimental effect. The more recent randomized phase III Lung ART trial concluded that PORT could not anymore be recommended for pN2 NSCLC as a significant benefit in terms of 3 years disease-free survival (DFS) was not reached and an increased rate of radiotherapy related toxicity was observed. Retrospective studies suggest a possible role of PORT for incompletely resected NSCLC patients and those with an extranodal extension (ENE), but this issue needs to be reinforced from randomized prospective trials. The extensive publication of Lung ART trial is largely awaited to define if there is a role of PORT for resected NSCLC patients., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://med.amegroups.com/article/view/10.21037/med-21-31/coif). The series “Changes in management of mediastinal tumours following the surge of COVID-19 pandemic” was commissioned by the editorial office without any funding or sponsorship. The authors have no other conflicts of interest to declare., (2022 Mediastinum. All rights reserved.)

Background and Purpose: COVID-19 constitutes a worldwide threat, prompting Italian Government to implement specific measures on March 8, 2020, to protect patients and health workers from disease transmission. The impact of preventive measures on daily activity of a radiotherapy facility may hamper the ability to fulfill normal workload burden. Thus, we assessed the number of delivered treatments in a specific observation period after the adoption of preventive measures (since March 11 to April 24, 2020) and compared it with the corresponding period of the year 2019., Materials and Methods: Overall number of delivered fractions was related to actual time of platform daily activity and reported as a ratio between number of delivered fractions and activity hours (Fr/Hrs). Fr/Hrs were calculated and compared for two different periods of time, March 11-April 24, 2019 (Fr/Hrs1), and March 11-April 24, 2020 (Fr/Hrs2)., Results: Fr/Hrs1 and Fr/Hrs2 were 2.66 and 2.54 for year 2019 and 2020, respectively, for a Fr/Hrs ratio of 1.07 (95% CI 1.03-1.12, p = 0.0005). Fr/Hrs1 was significantly higher than Fr/Hrs2 for Sli R and Precise R , with Fr/Hrs ratio of 1.92 (95% CI 1.66-2.23, p < 0.0001) and 1.11 (95% CI 1.03-1.2, p = 0.003), respectively. No significant difference was reported for Synergy R and Cyberknife R with Fr/Hrs ratio of 0.99 (95% CI 0.91-1.08, p = 0.8) and 0.9 (95% CI 0.77-1.06, p = 0.2), respectively. Fr/Hrs1 was significantly lower than Fr/Hrs2 for Tomotherapy R , with Fr/Hrs ratio of 0.88 (95% CI 0.8-0.96, p = 0.007)., Conclusion: Preventive measures did not influence workload burden performed. Automation in treatment delivery seems to compensate effectively for health workers number reduction.

Background: The cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) represent the standard treatment for hormone receptor-positive, human epidermal growth factor receptor 2-negative metastatic breast cancer. Data about the balance between efficacy and toxicity of combined palliative radiotherapy (RT) and CDK4/6 inhibition are lacking., Patients and Methods: We undertook a review of 46 patients with metastatic breast cancer on systemic treatment with CDK4/6i who underwent 62 metastases-directed RT. Clinical, laboratory, and RT treatment planning data were collected. Statistical analyses included Student t test, paired sample t test, and logistic regression modeling., Results: Thirty patients (65.2%) received palbociclib, 15 (32.6%) received ribociclib, and one patient received abemaciclib (2.2%). Median total prescribed RT dose was 20 Gy (range, 8-63 Gy). Sites of RT were bone (n = 50; 80.7%), visceral (n = 7; 11.3%), or brain metastases (n = 3; 4.8%), as well as primary tumor of the breast (n = 2; 3.2%). Overall, the rates of grade 3 or higher adverse events (AEs) were 6.5%, 4.3%, 15.2%, and 23.9% before the start of RT, during RT, 2 and 6 weeks after RT completion, respectively. We found no correlation between dose distribution to organs at risk and the development of AEs. The local control rates for the entire cohort were 98% at 6 months and 90% at 12 months. Overall, pain relief (complete or partial) was experienced by 80% (24/30) of patients who initially reported pain at the treated metastatic site., Conclusion: We observed a modest increase in the rates of grade 3 or higher AEs after combined RT and CDK4/6i, with maintained efficacy of concomitant RT., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Alzheimer's disease (AD) is one of the most disabling diseases to affect large numbers of elderly people worldwide. Because of the characteristics of this disease, patients with AD require daily assistance from service providers both in nursing homes and at home. Domiciliary assistance has been demonstrated to be cost effective and efficient in the first phase of the disease, helping to slow down the course of the illness, improve the quality of life and care, and extend independence for patients and caregivers. In this context, the aim of this work is to demonstrate the technical effectiveness and acceptability of an innovative domiciliary smart sensor system for providing domiciliary assistance to patients with AD which has been developed with an Ambient Assisted Living (AAL) approach., Methods: The design, development, testing, and evaluation of the innovative technological solution were performed by a multidisciplinary team. In all, 15 sociomedical operators and 14 patients with AD were directly involved in defining the end-users' needs and requirements, identifying design principles with acceptability and usability features and evaluating the technological solutions before and after the real experimentation., Results: A modular technological system was produced to help caregivers continuously monitor the health status, safety, and daily activities of patients with AD. During the experimentation, the acceptability, utility, usability, and efficacy of this system were evaluated as quite positive., Conclusion: The experience described in this article demonstrated that AAL technologies are feasible and effective nowadays and can be actively used in assisting patients with AD in their homes. The extensive involvement of caregivers in the experimentation allowed to assess that there is, through the use of the technological system, a proven improvement in care performance and efficiency of care provision by both formal and informal caregivers and consequently an increase in the quality of life of patients, their relatives, and their caregivers., (© The Author(s) 2014.)

Nowadays, the increasing old population 65+ as well as the pace imposed by work activities lead to a high number of people that have particular injuries for limbs. In addition to persistent or temporary disabilities related to accidental injuries we must take into account that part of the population suffers from motor deficits of the hands due to stroke or diseases of various clinical nature. The most recurrent technological solutions to measure the rehabilitation or skill motor performance of the hand are glove-based devices, able to faithfully capture the movements of the hand and fingers. This paper presents a system for hand motion analysis based on 9-axis complete inertial modules and dedicated microcontroller which are fixed on fingers and forearm. The technological solution presented is able to track the patients' hand motions in real-time and then to send data through wireless communication reducing the clutter and the disadvantages of a glove equipped with sensors through a different technological structure. The device proposed has been tested in the study of Parkinson's disease.

The ageing of population is a social phenomenon that most of worldwide countries are facing. They are, and will be even more in the future, indeed trying to find solutions for improving quality of life of their elderly citizens. The project RITA wants to demonstrate that an update of the current socio-medical services with an Ambient Assisted Living (AAL) approach could improve the service efficiency and the quality of life of both elderly and caregiver. This paper presents the preliminary results obtained in RITA.

This paper aims to show the effectiveness of a (inter / multi)disciplinary team, based on the technology developers, elderly care organizations, and designers, in developing the ASTRO robotic system for domiciliary assistance to elderly people. The main issues presented in this work concern the improvement of robot's behavior by means of a smart sensor network able to share information with the robot for localization and navigation, and the design of the robot's appearance and functionalities by means of a substantial analysis of users' requirements and attitude to robotic technology to improve acceptability and usability.

Magnesium (Mg(++)) therapy has been shown to be neuroprotective and to facilitate recovery of motor and sensorimotor function in a variety of animal models of traumatic brain injury. However, few studies have investigated the efficacy of Mg(++) therapy on cognitive impairments following injury. The present study evaluated the ability of magnesium chloride (MgCl(2)) to facilitate recovery of function following bilateral anterior medial cortex lesions (bAMC). Rats received electrolytic bAMC lesions or sham surgery and were then treated with 1 mmol/kg, i.p. MgCl(2), 2 mmol/kg, i.p. MgCl(2), or 1.0 ml/kg, i.p. 0.9% saline. Drug treatment was administered 15 min following injury with subsequent injections administered at 24 and 72 h. Rats were tested on a battery of behavioral tests that measured both cognitive (reference and working memory in the Morris Water Maze (MWM) and spatial delayed matching-to-sample (DMTS)) and sensorimotor performance (bilateral tactile adhesive removal). The results indicated that bAMC lesions produced significant cognitive impairments in reference memory and working memory in the MWM, DMTS and sensorimotor impairments compared to shams. Mg(++) therapy exhibited a dose-dependent effect in facilitating recovery of function. Administration of 2mmol of MgCl(2) significantly improved performance on the bilateral adhesive tactile removal test, DMTS and working memory tests. The 1 mmol dose of MgCl(2) reduced the initial deficit on the tactile adhesive removal test and reduced the working memory impairment on the second day of testing. These results suggest Mg(++) therapy improves cognitive performance following injury in a dose-dependent manner.