Locally-advanced non-small cell lung cancer: Shall immunotherapy be a new chance?

Locally advanced non-small cell lung cancer (NSCLC) represents approximately one third of presentations at diagnosis. Most patients are judged non-surgical due to disease extension, and chemo-radiotherapy still represents the standard therapeutic option, with unsatisfactory results in terms of overall survival (OS) despite advances in staging and radiation therapy planning and delivery. Immunotherapy, and in particular immune-checkpoint inhibitors targeting the PD-1/PD-L1 axis, gained wide popularity for NSCLC in light of the positive findings of several trials in metastatic disease. Stage III unresectable NSCLC is a remarkably interesting setting for the combined use of chemo-radiation and immunotherapy, also considering the multiple experimental evidences in favor of a synergistic effect between radiation and immune checkpoint inhibitors, with the potential of enhancing immuno-modulating effects and overcoming resistance. We here summarized the biological rationale and the initial clinical experiences testing for this combination, and we briefly discussed ongoing trials and future options in this field

Nutrition in patients with unilateral neglect

Objective: To evaluate the impact of neglect on patient nutrition and nursing skills to reduce malnutrition. To determine attitude of health care professionals towards nutritional needs in patients with neglect. Methods: The purpose of this narrative literature review was to explore empiric literature that surrounds the measures to be carried into the environment of the meal, diet and encourages patient independence with neglect. This literature review to include articles from all countries and national languages (English, Spanish and Italian) that pertain to this topic. Methods OVID Medline, CINAHL, Cochrane, Scopus, Google Scholar and Web of Science were used to identify articles. Twenty-five articles were included according to inclusion and exclusion criteria. Results: The review shows that damage to the right cerebral hemisphere leads to a higher frequency of dysphagia than lesions in the left cerebral hemisphere. The lack of awareness of the stimuli coming from one side of the space, caused in fact by the neglect, make the feeding of the patient difficult and lead to inhalation and aspiration pneumonia. Conclusions: Dysphagia contributes to more difficult rehabilitation: Patients with neglect have a high risk of developing malnutrition, reduced immune defenses, infections and aspiration pneumonia

Effect of glycerol on the physical and mechanical properties of thin gellan gum films for oral drug delivery

In this work, deacylated gellan gum and the plasticizer glycerol were used as primary components for the preparation of thin films intended for the oral delivery of therapeutic molecules. The samples were prepared by a solvent casting method and characterized for their thickness, tensile properties, swelling ability, mucoadhesion capacity and uniform drug distribution. The amount of glycerol was varied from 20% to 75% w/w in order to obtain films with tunable mechanical properties and high drug loading efficiency. The addition of glycerol was able to positively influence the mechanical characteristics of gellan gum thin film overcoming the brittleness caused by the rigid interconnection among the polymeric chains. Plasticized gellan gum films containing 50% w/w of glycerol showed optimal mechanical resistance and mucoadesion capacity, which were adversely affected by the inclusion of higher concentrations of glycerol. On the contrary, only high amounts of the plasticizer (⩾ 70% w/w) enabled a homogeneous distribution of the model drug fluconazole within the polymeric matrix. Overall these results indicate that gellan gum-based thin films can be potentially used for buccal drug delivery upon precise selection of the appropriate concentration of glycerol used as a plasticizer

No differences in radiological changes after 3D conformal vs VMAT-based stereotactic radiotherapy for early stage non-small cell lung cancer

OBJECTIVE: To compare patterns of acute and late radiological lung injury following either 3D conformal or image-guided volumetric modulated arc therapy stereotactic radiotherapy for Stage I non-small-cell lung cancer. METHODS: We included 148 patients from a prospective mono-institutional stereotactic body radiation therapy (SBRT) series (time interval 2004-2014), treated with prescription BED10 Gy (at 80%) in the range 100-120 Gy. The first 95 patients (2004-2010) were planned with 3D-CRT, with a stereotactic body frame. The second cohort (2010-2014) included 53 patients, planned with volumetric IMRT on a smaller planning target volume generated from a patient's specific internal target volume, with a frameless approach through cone-beam CT guidance. Acute and late radiological modifications were scored based on modified Kimura's and Koenig's classifications, respectively. RESULTS: Median follow-up time was 20.5 months. The incidence of acute radiological changes was superimposable between the groups: increased density was observed in 68.4 and 64.2% of patients for 3D-CRT and VMAT, respectively, and patchy ground glass opacity in 23.7 and 24.5%, respectively; diffuse ground glass opacity was 2.6 vs 9.4%, respectively, and patchy consolidation 2.6 vs 1.9%, respectively. Late changes occurred in approximately 60% of patients: modified conventional pattern was the most frequent modification (25 vs 32.6%, respectively); other patterns were less common (mass-like 19.6 vs 17.4%, and scar-like 13 vs 10.9%, respectively). CONCLUSION: Results of the present study indicate that the pattern of radiological lung changes following SBRT for peripheral early stage non-small-cell lung cancer is not influenced by the different techniques used for planning and delivery. Advances in knowledge: This comparative observational study shows that smaller margins, image guidance and most importantly dose distribution do not change the pattern of radiological injury after lung SBRT; the same scoring system can be used, and expected incidence is similar

Gellan gum-based nanocomposites films containing bio-reduced silver nanoparticles: Synthesis, characterisation and antifungal activity

The aim of this work was to develop and characterise nanocomposite thin films containing silver nanoparticles (AgNPs), as wound dressings and antifungal materials, using a green process for the nanoparticles’ synthesis and a single step procedure for the preparation of the nanocomposite films. To this end, polyphenol-rich extracts obtained from kiwi peels, an agri-food industrial by-product, were used as a reducing agent of silver nitrate salt. The AgNPs were let form within the film-forming solution, which was composed by low acyl gellan gum and a plasticising agent (glycerol or PEG 400 g/mol) and the corresponding nanocomposite films were deposited by the solvent casting technique. The plasticising agent affected the AgNPs distribution within the films, as observed by SEM and EDS analyses, and consequently their tensile behaviour. In specific, AgNPs act as stress intensifiers in the presence of glycerol, whereas they act as film reinforcement with PEG400. However, both glycerol-plasticised and PEG400-plasticised films exhibited similar antifungal efficacy against 16 clinical isolates of 5 different Candida spp (C. albicans, C. lusitaniae, C. haemulonii, C. krusei and C. glabrata). Globally, the present study provides a green and single-step procedure to develop nanocomposite films embedding AgNPs obtained by in situ reduction of silver ions with polyphenol-rich extracts

Design of a tunable nanocomposite double network hydrogel based on gellan gum for drug delivery applications

The design of an efficient drug delivery platform relies on the fabrication of a suitable polymeric network that can modulate the release of therapeutic molecules. In this study, we aimed to reach this goal by fabricating a novel nanocomposite double network (nDN) hydrogel, which contains the synthetic clay Laponite as the nanofiller necessary to influence the mechanical, physical and releasing properties of the designed carrier. Laponite concentration was varied from 0.5% up to 1.5% w/v to modulate the mechanical and swelling behavior of a hydrogel made of a methacrylate derivate of gellan gum (GG-MA), which served as the first brittle network of the nDN system. Additionally, polyethylene glycol dimethacrylate (PEG-DMA) was chosen as the second soft and elastic network. The inclusion of the clay at a concentration as low as 0.5% w/v positively influenced the single network (SN) hydrogel properties by increasing the stiffness and reducing the swelling ratio of the GG-MA hydrogels. The presence of Laponite® affected the amount of PEG-DMA diffused within the SN of GG-MA. The resulting stretchable and tough nDN system presented a higher swelling ratio in deionized water, and elasticity when compared to the DN hydrogels without any Laponite. Finally, the nDN system showed increased drug adsorption and displayed a better control in modulating the release kinetics of the model drug ofloxacin. Overall, these findings suggest the possible use of the designed nDN system as a novel drug delivery platform for the sustained release of therapeutic molecules

Solvent casting and UV photocuring for easy and safe fabrication of nanocomposite film dressings

The aim of this work was to optimize and characterize nanocomposite films based on gellan gum methacrylate (GG-MA) and silver nanoparticles (AgNPs) for application in the field of wound dressing. The films were produced using the solvent casting technique coupled with a photocuring process. The UV irradiation of GG-MA solutions containing glycerol as a plasticizer and different amounts of silver nitrate resulted in the concurrent crosslinking of the photocurable polymer and a reduction of Ag ions with consequent in situ generation of AgNPs. In the first part of the work, the composition of the films was optimized, varying the concentration of the different components, the GG-MA/glycerol and GG-MA/silver nitrate weight ratios as well as the volume of the film-forming mixture. Rheological analyses were performed on the starting solutions, whereas the obtained films were characterized for their mechanical properties. Colorimetric analyses and swelling studies were also performed in order to determine the AgNPs release and the water uptake capacity of the films. Finally, microbiological tests were carried out to evaluate the antimicrobial efficacy of the optimized films, in order to demonstrate their possible application as dressings for the treatment of infected hard-to-heal wounds, which is a demanding task for public healthcare

Induction Chemotherapy and Sequential Concomitant Chemo-radiation in Locally Advanced Head and Neck Cancers: How Induction-phase Intensity and Treatment Breaks May Impact on Clinical Outcomes

AIM: The purpose of the study was to assess outcomes of locally advanced head and neck (LAHNC) treated with induction chemotherapy (ICT) and subsequent concurrent chemo-radiation. PATIENTS AND METHODS: A total of 71 LAHNC patients were treated with 2-3 cycles of docetaxel, cisplatin and 5-fluorouracil as induction chemotherapy and subsequent concurrent chemoradiation with weekly cisplatin or carboplatin. Definitive radiotherapy was delivered with intensity-modulated radiation and a simultaneous integrated boost approach up to a total dose of 70 Gy in 35 fractions to the macroscopic primary and nodal disease. RESULTS: Actuarial 2-year OS, CSS, DFS, MFS, LC were 55.3% (95%CI=39.3-68.6), 58.6% (95%CI=41.9-72), 60.5% (95%CI=47.3-71.4), 87.3% (95%CI=76.2-93.5) and 74.7% (95%CI=61.5-83.9), respectively. On multivariate analysis undergoing to 3 vs. 2 cycles of TPF (HR=22.31; 95%CI=2.68-185.66; p=0.004) and radiotherapy treatment break >4 days (HR=1.28; 95%CI=1.06-1.55; p=0.01) negatively affected cancer-specific survival (CSS) with statistical significance. Achieving complete remission after ICT had a statistically significant impact on CSS (HR=0.9; 95%CI=0.01-0.54; p=0.009). Patients undergoing ICT with 3 cycles had more frequently treatment breaks compared to those submitted to 2 cycles (HR=1.36; 95%CI=1.06-1.73; p=0.01), and had statistically significant longer treatment break time (5.9+1.8 vs. 3+0.36; p=0.02). CONCLUSION: A shorter ICT phase may be a better option enhancing patients' tolerance during concurrent chemoradiation and affecting clinical outcomes