Management of radiation dermatitis in patients receiving cetuximab and radiotherapy for locally advanced squamous cell carcinoma of the head and neck: proposals for a revised grading system and consensus management guidelines

Background: Radiation dermatitis developing in patients receiving cetuximab concomitantly with radiotherapy for locally advanced squamous cell carcinoma of the head and neck (LA SCCHN) is now recognized to have different pathophysiological and clinical characteristics to the radiation dermatitis associated with radiotherapy or concomitant chemotherapy and radiotherapy. Current grading tools were not designed to grade this type of radiation dermatitis; their use may lead to misclassification of reactions and inappropriate management strategies, potentially compromising cancer treatment. Patients and methods: An advisory board of seven leading European specialists (three medical oncologists, three radiation oncologists and a dermatologist) with extensive experience of the use of cetuximab plus radiotherapy produced consensus guidelines for the grading and management of radiation dermatitis in patients receiving cetuximab plus radiotherapy. Results: Modifications to the current, commonly used National Cancer Institute—Common Terminology Criteria for Adverse Events version 4.3 for grading radiation dermatitis were proposed. Updated management guidelines, building on previously published guidelines from 2008, were also proposed. Conclusions: The proposed revisions to the grading system and updated management guidelines described here represent important developments toward the more appropriate grading and effective management of radiation dermatitis in patients receiving cetuximab plus radiotherapy for LA SCCH

Gastric normal adjacent mucosa versus healthy and cancer tissues: Distinctive transcriptomic profiles and biological features

Gastric cancer (GC) is a leading cause of cancer-related deaths in the world. Molecular heterogeneity is a major determinant for the clinical outcomes and an exhaustive tumor classification is currently missing. Histologically normal tissue adjacent to the tumor (NAT) is commonly used as a control in cancer studies, nevertheless a recently published paper described the unique characteristics of the NAT in several tumor types. Little is known about the global gene expression profile of gastric NAT (gNAT) which could be an effective tool for a more realistic definition of GC molecular signature. Here, we integrated data of 512 samples from the Genotype- Tissue Expression project (GETx) and The Cancer Genome Atlas (TCGA) to analyze the transcriptome of healthy gastric tissues, gNAT, and GC samples. We validated TCGA-GETx data mining through inHouse gNAT and GC expression dataset. Differential gene expression together with pathway enrichment analyses, indeed, led to different results when using the gNAT or the healthy tissue as control. Based on our analyses, gNAT showed a peculiar gene signature and biological features, like the estrogen receptor pathways activation, suggesting a molecular behavior partially different from both healthy and GC tissues. Therefore, using gNAT as healthy control tissue in the characterization of tumor associated biological processes and pathways could lead to suboptimal results

Current state of interventional radiotherapy (brachytherapy) education in Italy: Results of the INTERACTS survey

Purpose: Increased complexity of interventional radiotherapy (brachytherapy - BT) treatment planning and quality control procedures has led to the need of a specific training. However, the details of the features of BT learning objectives and their distribution in the training paths of the Italian Radiation Oncology Schools are not known. This paper aims to provide the actual 'state-of-the-art' of BT education in Italy and to stimulate the debate on this issue.Material and methods: All the Italian radiation oncology schools' directors (SD) were involved in a web survey, which included questions on the teaching of BT, considering also the 2011 ESTRO core curriculum criteria. The survey preliminary results were discussed at the 8th Rome INTER-MEETING (INTERventional Radiotherapy Multidisciplinary Meeting), June 24th, 2017. The present paper describes the final results of the survey and possible future teaching strategies resulting from the discussion.Results: A total of 23 SDs answered the survey. The results evidenced a wide heterogeneity in the learning activities available to trainees in BT across the country. While theoretical knowledge is adequately and homogeneously transmitted to trainees, the types of practice to which they are exposed varies significantly among different schools.Conclusions: This survey proves the need for an improvement of practical BT education in Italy and the advisability of a national BT education programme networking schools of different Universities. Beside the organization of national/international courses for BT practical teaching, Universities may also establish post-specialization courses ('second level' Masters) to allow professionals (already certified in radiation oncology) to acquire more advanced BT knowledge

Development of DYNAMIX Policy Mixes - Deliverable 4.2, revised version, of the DYNAMIX project

This report documents the development of the initial dynamic policy mixes that were developed for assessment in the DYNAMIX project. The policy mixes were designed within three different policy areas: overarching policy, land-use and food, and metals and other materials. The policy areas were selected to address absolute decoupling in general and, specifically, the DYNAMIX targets related to the use of virgin metals, the use of arable land and freshwater, the input of the nutrients nitrogen and phosphorus, and emissions of greenhouse gases. Each policy mix was developed within a separate author team, using a common methodological framework that utilize previous findings in the project. Specific drivers and barriers for resource use and resource efficiency are discussed in each policy area. Specific policy objectives and targets are also discussed before the actual policy mix is presented. Each policy mix includes a set of key instruments, which can be embedded in a wider set of supporting and complementary policy instruments. All key instruments are described in the report through responses to a set of predefined questions. The overarching mix includes a broad variety of key instruments. The land-use policy mix emphasizes five instruments to improve food production through, for example, revisions of already existing policy documents. It also includes three instruments to influence the food consumption and food waste. The policy mix on metals and other materials primarily aims at reducing the use of virgin metals through increased recycling, increased material efficiency and environmentally justified material substitution. To avoid simply shifting of burdens, it includes several instruments of an overarching character

Is there a role for postoperative radiotherapy following open partial laryngectomy when prognostic factors on the pathological specimen are unfavourable? A survey of head and neck surgical/radiation oncologists

Our aim was to survey the opinions of Italian radiation and ENT oncologists regarding the role of postoperative radiotherapy (PRT) and the appropriate dose to be given to patients with remnant larynx (RL) after open partial laryngectomy (OPL). The radio-oncologists (RO s) of the Italian Radiation-Oncologist Association (AIRO) and the ENTs of the Head-Neck Oncology Society (AIOCC-IHNS) were contacted through a SurveyMonkey online interface questionnaire. There were 148 usable responses. The majority of RO s recommended PRT in the case of positive/close margins (R(+)/Rclose) or in the case of initial involvement of thyroid cartilage (pT3tci). In the same cases, ENTs prefer a "watch and wait" policy (w&w). Both disciplines recommended w&w in the case of negative margins (R(-)). Finally, the majority of RO s recommended irradiating RL with 62-66 Gy in R(+), with 56-66 Gy (61.4%) in Rclose and with 56-60 Gy (34%) in pT3tci. In Conclusion, OPL raises new considerations about PRT

Does a 6-point scale approach to post-treatment 18F-FDG PET-CT allow to improve response assessment in head and neck squamous cell carcinoma? A multicenter study

Abstract Purpose Response assessment to definitive non-surgical treatment for head and neck squamous cell carcinoma (HNSCC) is centered on the role of 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET-CT) 12 weeks after treatment. The 5-point Hopkins score is the only qualitative system available for standardized reporting, albeit limited by suboptimal positive predictive value (PPV). The aim of our study was to explore the feasibility and assess the diagnostic accuracy of an experimental 6-point scale ("Cuneo score"). Methods We performed a retrospective, multicenter study on HNSCC patients who received a curatively-intended, radiation-based treatment. A centralized, independent qualitative evaluation of post-treatment FDG-PET/CT scans was undertaken by 3 experienced nuclear medicine physicians who were blinded to patients' information, clinical data, and all other imaging examinations. Response to treatment was evaluated according to Hopkins, Cuneo, and Deauville criteria. The primary endpoint of the study was to evaluate the PPV of Cuneo score in assessing locoregional control (LRC). We also correlated semi-quantitative metabolic factors as included in PERCIST and EORTC criteria with disease outcome. Results Out of a total sample of 350 patients from 11 centers, 119 subjects (oropharynx, 57.1%; HPV negative, 73.1%) had baseline and post-treatment FDG-PET/CT scans fully compliant with EANM 1.0 guidelines and were therefore included in our analysis. At a median follow-up of 42 months (range 5-98), the median locoregional control was 35 months (95% CI, 32-43), with a 74.5% 3-year rate. Cuneo score had the highest diagnostic accuracy (76.5%), with a positive predictive value for primary tumor (Tref), nodal disease (Nref), and composite TNref of 42.9%, 100%, and 50%, respectively. A Cuneo score of 5-6 (indicative of residual disease) was associated with poor overall survival at multivariate analysis (HR 6.0; 95% CI, 1.88-19.18; p = 0.002). In addition, nodal progressive disease according to PERCIST criteria was associated with worse LRC (OR for LR failure, 5.65; 95% CI, 1.26-25.46; p = 0.024) and overall survival (OR for death, 4.81; 1.07-21.53; p = 0.04). Conclusions In the frame of a strictly blinded methodology for response assessment, the feasibility of Cuneo score was preliminarily validated. Prospective investigations are warranted to further evaluate its reproducibility and diagnostic accuracy