Improvement in Dysphagia Outcomes Following Clinical Target Volume Reduction in the De-ESCALaTE Study.

AIMS: The De-ESCALaTE study showed an overall survival advantage for the administration of synchronous cisplatin chemotherapy with radiotherapy in low-risk oropharyngeal cancer when compared with synchronous cetuximab. During the trial, a radiotherapy quality assurance protocol amendment permitted centres to swap from the original radiotherapy contouring protocol (incorporating the whole oropharynx into the high-dose clinical target volume (CTV); anatomical protocol) to a protocol that incorporated the gross tumour volume with a 10 mm margin into the CTV (volumetric protocol). The purpose of this study was to examine both toxicity and tumour control related to this protocol amendment. MATERIALS AND METHODS: Overall survival and recurrence at 2 years were used to compare tumour control in the two contouring cohorts. For toxicity, the cohorts were compared by both the number of severe (grades 3-5) and all grades acute and late toxicities. In addition, quality of life and swallowing were compared using EORTC-C30 and MD Anderson Dysphagia Inventory, respectively. RESULTS: Of 327 patients included in this study, 185 were contoured according to the anatomical protocol and 142 by the volumetric protocol. The two cohorts were well balanced, with the exception of significantly more patients in the anatomical cohort undergoing prophylactic feeding tube insertion (P < 0.001). With a minimum of 2 years of follow-up there was no significant difference in overall survival or recurrence between the two contouring protocols. Similarly, there was no significant difference in the rate of reported severe or all grades acute or late toxicity and no sustained significant difference in quality of life. However, there was a significant difference in favour of volumetric contouring in several domains of the MD Anderson Dysphagia Inventory questionnaire at 1 year, which persisted to 2 years in the dysphagia functional (P = 0.002), dysphagia physical (P = 0.009) and dysphagia overall function (P = 0.008) domains. CONCLUSION: In the context of the unplanned post-hoc analysis of a randomised trial, measurable improvement in long-term dysphagia has been shown following a reduction in the CTV. Further reductions in the CTV should be subject to similar scrutiny within the confines of a prospective study.

18F-FDG-PET in guided dose-painting with intensity modulated radiotherapy in oropharyngeal tumours: A phase I study (FiGaRO).

BACKGROUND AND PURPOSE: The FiGaRO trial assessed the feasibility and safety of using an FDG-PET-based dose-painting technique to deliver a radiotherapy (RT) boostto the FDG-avid primary tumour in patients with locally advanced high and intermediate risk oropharyngeal cancer. MATERIALS AND METHOD: Patients underwent a planning 18FDG-PET-CT scan, immobilised in the treatment position, after one cycle of induction chemotherapy. The volume of persistent FDG-avidity in the primary tumour was escalated to 71.5 Gy in30 fractions delivered using a simultaneous integrated boost Intensity Modulated RT (SIB-IMRT) technique. RT was delivered with concomitant Cisplatin following 2 cycles of induction chemotherapy. The primary outcome was the incidence of grade ≥ 3 late mucosal toxicity 12 months post-treatment, with an excess rate of >10% regarded as unacceptable. RESULTS: Twenty-nine patients were included and twenty-four were treated between 2014 and 2018, in two UK centres. Median follow-up was 36 months (range 4-56 months). Pre-defined planning target volume objectives and organ at risk dose constraints were met in all cases. There were no incidents of acute grade 4 toxicity. There were 4 cases of grade ≥ 3 mucosal toxicity at 12 months post-treatment (19.1%). There were no cases of persistent mucosal ulceration at 12 months. Overall survival at 3-years was 87.5%, 92.9% for intermediate and 70.0% for high risk patients. CONCLUSION: Late toxicity rates, although higher than anticipated, are comparable to contemporary published data for standard dose chemo-IMRT. Results suggest improved 3y survival rates for high risk patients. This approach merits further investigation. ClinicalTrials.gov Identifier: NCT02953197.

Experimental and computational studies of graphene oxide covalently functionalized by octylamine: electrochemical stability, hydrogen evolution, and corrosion inhibition of the AZ13 Mg alloy in 3.5% NaCl.

Recently, carbon allotropes were shown to play a key role in energy harvesting and as hydrophobic coatings on metal alloys. We have designed octylamine-functionalized graphene oxide materials for energy harvesting and as an anti-corrosion coating for metal alloy protection in a 3.5% NaCl medium. The material has been characterized by different techniques to confirm the structure and composition of the modified graphene oxide sheet: FTIR spectroscopy, XRD, Raman spectroscopy, FESEM and TEM. The electrochemical stability and corrosion inhibition efficiency were studied by electrochemical methods. The electrochemical stability increased with an increase in the applied voltage up to 500 mV, and the corrosion inhibition efficiency was shown to be 73%. The coating stability studies showed a long stability time in the corrosion medium.

Experimental and DFT studies of porous carbon covalently functionalized by polyaniline as a corrosion inhibition barrier on nickel-based alloys in acidic media.

In acidic medium, nickel alloys severely suffer from long term corrosion problems as a result of the breakdown of their passivating oxide. The present study considers polyaniline functionalized fish-scale graphitic carbon as an anticorrosion coating on the nickel alloy surface. The fish-scale porous carbon materials are characterized by XRD, ATR-FITR, UV, Raman, TGA, SS NMR, FESEM, and TEM methods. The surface of the alloy is covalently bound with a polyaniline long chain protonated polymer so that the polyaniline functionalized honeycomb fish-scale carbon structure can exchange electrons with the metal surface. The corrosion inhibition efficiency has been investigated in different acid media like sulfuric acid and hydrochloric acid by electrochemical methods. Polyaniline functionalized porous carbon showed in 1 M H2SO4 inhibition efficiency around 64% and in 1 M HCl inhibition efficiency was around 74%. The inhibition efficiency was higher in HCl because chloride ions were not able to penetrate the graphitic sheet. The novelty of this coating is in the fact that the polyaniline functionalized porous carbon has high conductivity and is electrochemically stable in acidic medium. It is able to donate electrons to the polarized metal surface.

Experimental and DFT studies on the ultrasonic energy-assisted extraction of the phytochemicals of Catharanthus roseus as green corrosion inhibitors for mild steel in NaCl medium.

Catharanthus roseus (Apocynaceae family) extract is rich in organic phytochemicals such as alkaloids, polyphenolic compounds, and flavonoids. It contains several functional entities such as fused heterocycles, and hydroxyl and carbonyl groups, which could be useful for corrosion inhibition of mild steel in NaCl environments. In the present work, ultrasonic energy was used to obtain the ethanolic extracts of root and stem which were then tested as corrosion inhibitors for mild steel in the presence of 3.5% NaCl. The corrosion inhibition process was studied by UV-visible spectroscopy, Fourier transform infrared spectroscopy, atomic force microscopy, weight loss, and electrochemical methods. After immersing in the corrosive medium, the microstructures of mild steel were investigated by scanning electron microscopy, X-ray diffraction, and ellipsometry. The extract of C. roseus showed excellent adsorption on mild steel surface as confirmed by DFT calculations. The results indicate that the extract of C. roseus acts as a mixed type corrosion inhibitor, where the stem extract is the most efficient inhibitor in 3.5% NaCl solution possibly due to the higher active area of stem phytochemicals.

Neodymium-decorated graphene oxide as a corrosion barrier layer on Ti6Al4V alloy in acidic medium.

Ti6Al4V alloy is light weight and is used in construction, oil industries and airbus, automobile, and bio implant materials. The native oxide layers of the alloy are not stable at high temperatures and strong mineral acid environments. The conventional epoxy-based layers are porous and the alloy finally fails in the harsh environment in the long term. Therefore, the carbon-based functional materials are being proposed as coating materials to overcome the alloy degradation. In the present contribution, we have used the neodymium-decorated graphene oxide as the corrosion inhibiting barrier for the Ti6Al4V alloy. As a novelty, we found that the few-layer graphene decorated with neodymium acts as a self-cleaning coating. The Nd-decorated graphene oxide were studied by XRD, TEM, FESEM, FTIR, UV, and Raman spectroscopy. The corrosion inhibition efficiency was studied by electrochemical methods.

Experimental and computational studies of a graphene oxide barrier layer covalently functionalized with amino acids on Mg AZ13 alloy in salt medium.

Magnesium alloys are promising materials for the biomedical and automobile industries. The Mg alloy's light-weight property leads to numerous industrial applications. However, the magnesium alloy oxide layers are not stable in salt environments. Organic inhibitors and epoxy coatings fail as long term barriers in such media. Recently, carbon based functionalized materials, graphene oxides, were shown to be promising materials for improving corrosion resistance in acid and salt environments. Our research considered graphene oxide covalently functionalized with the amino acid leucine to form anticorrosion coating materials. The functionalized materials were characterized by XRD, Raman, FESEM, HRTEM, FTIR, and AFM methods. The corrosion inhibition efficiency was monitored by electrochemical methods. The novelty of the functionalized graphene oxide materials is that they are water impermeable, and thus could enhance the anticorrosion resistance in salt environments.

Praseodymium-decorated graphene oxide as a corrosion inhibitor in acidic media for the magnesium AZ31 alloy.

In the present work, Pr-decorated graphene oxide was synthesized and tested as a corrosion barrier layer in acidic media for the magnesium AZ31 alloy. The morphology, composition and structure of Pr-decorated graphene oxide sheets were characterized via HRTEM, FESEM, Raman, XRD, DLS, UV and FTIR studies. The corrosion inhibition efficiency on the alloy surface was monitored via microstructural and electrochemical methods. The results indicate that Pr-decorated graphene oxide provides improved protection for the Mg AZ31 alloy compared to conventional epoxy coatings. The proposed mechanism arises from a combination of the barrier activities of the composite, GO + Pr, and the epoxy coating on the Mg alloy in acidic media.

Head and neck target delineation using a novel PET automatic segmentation algorithm.

PURPOSE: To evaluate the feasibility and impact of using a novel advanced PET auto-segmentation method in Head and Neck (H&N) radiotherapy treatment (RT) planning. METHODS: ATLAAS, Automatic decision Tree-based Learning Algorithm for Advanced Segmentation, previously developed and validated on pre-clinical data, was applied to 18F-FDG-PET/CT scans of 20 H&N patients undergoing Intensity Modulated Radiation Therapy. Primary Gross Tumour Volumes (GTVs) manually delineated on CT/MRI scans (GTVpCT/MRI), together with ATLAAS-generated contours (GTVpATLAAS) were used to derive the RT planning GTV (GTVpfinal). ATLAAS outlines were compared to CT/MRI and final GTVs qualitatively and quantitatively using a conformity metric. RESULTS: The ATLAAS contours were found to be reliable and useful. The volume of GTVpATLAAS was smaller than GTVpCT/MRI in 70% of the cases, with an average conformity index of 0.70. The information provided by ATLAAS was used to grow the GTVpCT/MRI in 10 cases (up to 10.6mL) and to shrink the GTVpCT/MRI in 7 cases (up to 12.3mL). ATLAAS provided complementary information to CT/MRI and GTVpATLAAS contributed to up to 33% of the final GTV volume across the patient cohort. CONCLUSIONS: ATLAAS can deliver operator independent PET segmentation to augment clinical outlining using CT and MRI and could have utility in future clinical studies.

A systematic review of organ motion and image-guided strategies in external beam radiotherapy for cervical cancer.

Advanced radiotherapy techniques, such as intensity-modulated radiotherapy (IMRT), may significantly benefit cervical cancer patients, in terms of reducing late toxicity and potentiating dose escalation. Given the steep dose gradients around the planning target volume (PTV) with IMRT planning, internal movement of organs during treatment may cause geographical miss of the target and unnecessary organs at risk (OAR) inclusion into high dose regions. It is therefore important to consider the extent and patterns of organ motion and to investigate potential image-guided radiotherapy (IGRT) solutions before implementing IMRT for cervical cancer. A systematic literature search was carried out using Medline, Embase, Cochrane Library, Web of Science, Cinahl and Pubmed. Database-appropriate search strategies were developed based upon terms for uterine neoplasms, IGRT, organ motion and target volume. In total, 448 studies were identified and screened to find 39 relevant studies, 12 of which were abstracts. These studies show that within the target volume for cervical cancer radiotherapy, uterine motion is greater than cervical. Uterine motion is predominantly influenced by bladder filling, cervical motion by rectal filling. Organ motion patterns are patient specific, with some having very little (5 mm) and others having much larger shifts (40 mm) of the target volume. Population-based clinical target volume (CTV)-PTV margins would be large (up to 4 cm around the uterus), resulting in unnecessary OAR inclusion within the PTV, reducing the benefits of IMRT. Potential solutions include anisotropic margins with increased margins in the anteroposterior and superoinferior directions, or greater PTV margins around the uterine fundus than the cervix. As pelvic organ motion seems to be patient specific, individualised PTV margins and adaptive IGRT strategies have also been recommended to ensure target volume coverage while increasing OAR sparing. Although these strategies are promising, they need significant validation before they can be adopted into clinical practice.

Ascariasis: challenges in the diagnosis of single worm disease.

One of the most common parasitic infections in humans is ascariasis. While most infectionsare asymptomatic, mild to moderate symptoms may occur due to migration of adult worms. The frequency of single worm infection seems to be increasing. Ascaris eggs are not found in the faeces of most cases infected with a single worm because it is an immature male or female. Diagnosis of such single worm infection is challenging.

Exploring the use and impact of adjuvant trastuzumab for HER2-positive breast cancer patients in a large UK cancer network. Do the results of international clinical trials translate into a similar benefit for patients in South East Wales?

BACKGROUND: Trastuzumab was approved in the United Kingdom for adjuvant treatment of human epidermal growth factor receptor 2 (HER2)+ breast cancer in 2006 at significant economic cost and with limited evidence in smaller T1N0 tumours. The South East Wales Cancer Network covers a population of 1,420,000 and maintains a database of treatments used. We examined this database to ensure the outcome of Trastuzumab use is as expected, especially in patients with T1N0 cancers. METHODS: Case notes of patients with HER2+ disease eligible for adjuvant Trastuzumab over 2005-2008 were reviewed. Disease-free survival (DFS) and overall survival (OS) were calculated with the Kaplan-Meier method using SPSS (version 16.0.01 for Windows, SPSS, Chicago, IL, USA). RESULTS: A total of 239 of 338 (70.7%) eligible HER2+ patients received treatment. At 3 years, the DFS of the treated group was 90.3% vs 73.3% and the OS was 98.5% vs 87.6%. In all, 47 of 92 stage I patients received Trastuzumab. Despite a trend towards worse prognostic factors in the treated group the DFS was 100% vs 84.1% and the OS was 100% vs 93.3%. CONCLUSION: Our results are comparable to those from landmark Trastuzumab trials. As evidence continues to emerge that smaller HER2+ cancers may behave aggressively our analysis of stage I tumours adds further support to the use of Trastuzumab in these patients.

Seroprevalence of Toxoplasma gondii in southern districts of Tamil Nadu using IgG-ELISA.

The present study was conducted to assess the seroprevalence of Toxoplasma gondii in and around Tirunelveli by in-house IgG assay using ELISA. Serum samples from 175 immunodeficient and 175 immunocompetent patients were collected at Tirunelveli district, Tamil Nadu from May 2006 to October 2007. They were subjected into in-house IgG assay using enzyme-linked immune sorbent assay (ELISA) in which tachyzoite soluble antigen derived from solubilised whole organisms was used. Out of 350 patients tested by IgG ELISA, 46 patients (13.14%) had antibodies for toxoplasmosis with mean OD value of 0.2 ± 0.073 and the OD value ranged from 0.144 to 0.444. Among the immunocompetent group of 175 patients, 19 patients (10.86%) had antibodies to toxoplasmosis whereas, in immunodeficient group of 175 patients, 27 patients (15.43%) had antibodies for toxoplasmosis. There was no statistical difference (P > 0.05) between the immunocompetent and immunodeficient group. The sensitivity and specificity of IgG ELISA in detecting toxoplasmosis was 90 and 100%, respectively. The overall seroprevalence of toxoplasmosis in and around Tirunelveli district of Tamil Nadu was 13.14% based on IgG ELISA. The study has proved ELISA to be a sensitive and specific procedure for the serodiagnosis of toxoplasmosis.

IgG--indirect fluorescent antibody technique to detect seroprevalence of Toxoplasma gondii in immunocompetent and immunodeficient patients in southern districts of Tamil Nadu.

PURPOSE: The purpose of the study was to determine the prevalence of Toxoplasma antibodies in selected immunocompetent and immunodeficient patients in and around Tirunelveli District of Tamil Nadu. MATERIALS AND METHODS: This study was carried out from May 2006 to October 2007 in 175 immunodeficient and 175 immunocompetent patients. Serum samples were subjected into in-house IgG assay using indirect fluorescent antibody test (IFAT). RESULTS: Out of 350 patients tested by IgG IFAT, 41 (11.71%) had antibodies for Toxoplasma gondii with a mean IFA titre of 43.42 ± 58.7 and the titre ranging from 1 : 16 to 1 : 256. Among the immunocompetent and immunodeficient groups, 19 patients (10.86%) and 22 patients (12.57%), respectively, had antibodies to T. gondii. Various risk factors associated within the study group was analysed and results were interpreted. CONCLUSIONS: The study has highlighted an overall seroprevalence of 11.71% with 12.57% in immunocompromised and 10.86% in immunocompetent patients respectively in a southern district, Tamil Nadu, which underlines the importance of screening of this parasite especially in the immunocompromised patients.