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Computer-aided design/computer-assisted manufacture (CAD/CAM) guides for surgery are becoming a widespread tool in implant dentistry. This study sought to evaluate the accuracy and precision of a new guided surgery system. Twenty-five patients were treated in eight centers, and a total of 117 implants were placed using CAD/CAM surgical guides supported by bone, mucosa, and/or teeth. A postoperative computed tomographic (CT) scan of each patient was taken and superimposed on a preoperative CT scan to evaluate any discrepancies between the planned and actual implant positions (apex and platform positions), as well as the implant tilt. Implant placement using bone- and mucosa-supported guides was found to be more precise compared to using guides supported by teeth or a combination of teeth and mucosa. However, the differences were not statistically significant. The accuracy of the guided surgery system is in line with the data found in the literature. Considering the mean positioning discrepancies between the planned and actual implant outcomes, clinicians are advised to maintain a safe distance between implants and anatomical structures of at least 2 mm. In immediate loading cases, relining a provisional prosthesis to compensate for any discrepancies between the virtual and clinical implant positions is recommended. [ABSTRACT FROM AUTHOR]

Background Management of melanoma during pregnancy can be extremely challenging. The reported incidence of melanoma in pregnancy ranges from 2.8 to 5.0 per 100 000 pregnancies. There are no guidelines for the management of melanoma during pregnancy. Methods The survey was designed to investigate the opinions of melanoma physicians on decision making in relation to pregnancy and melanoma. A clinical scenario-based survey on management of pregnancy in melanoma was distributed all over Europe via the membership of the EORTC and other European melanoma societies. Results A total of 290 questionnaires were returned with a larger participation from southern Europe. A large heterogeneity was found for the answers given in the different clinical scenarios with 50% of the answers showing discordance, especially regarding sentinel lymph node biopsy during pregnancy. Discordant answers were also found for the counselling of women about a potential delay in getting pregnant after a high-risk melanoma (35% for a 2 year wait minimum vs. 57% no waiting needed), while for thin melanomas, as expected, there was more concordance with 70% of the physicians recommending no delay. Fifteen per cent of physicians recommended an abortion in stage II melanoma during the third month of pregnancy. Twenty per cent of the responders advised against hormonal replacement therapy in melanoma patients. Conclusions The management of melanoma during pregnancy varies widely in Europe. At present, there is a lack of consensus in Europe, which may lead to very important decisions in women with melanoma, and guidelines are needed. [ABSTRACT FROM AUTHOR]

The article offers the author's insights on the future of personalised medicine in the European Union (EU). He mentions that during the European Health Forum Gastein in October 2010, personalized medicine was presented as a new paradigm for healthcare. He notes that genomics will not only have the possibility of epidemiological research, but also for individual prediction and prevention of health risks as well as for personalized treatment and care.

Dermatofibrosarcoma protuberans (DFSP) is a skin fibroblastic tumour that is locally aggressive, with a tendency for local recurrence, but rarely metastasizes. A unique collaboration of multi-disciplinary experts from the European Dermatology Forum (EDF), the European Association of Dermato-Oncology (EADO) and the European Organization of Research and Treatment of Cancer (EORTC) was formed to make recommendations on DFSP diagnosis and treatment, based on systematic literature reviews and the experts’ experience. Diagnosis is suspected clinically and confirmed by pathology. Analysis by fluorescence in situ hybridisation (FISH) or multiplex reverse transcriptase-polymerase chain reaction (RT-PCR) to detect specific chromosomal translocations and fusion gene transcripts is useful to confirm a difficult DFSP diagnosis. Treatment is mainly surgical, with the aim to achieve complete resection of the tumour. In order to reduce the recurrence rate, the treatment of choice of DFSP seems to be Mohs’ micrographic surgery (MMS) and related variants. In hospitals where only standard histopathological procedures are available, standard excision with lateral safety margin of 3 cm is advisable. Imatinib (Glivec®) is approved in Europe for the treatment of inoperable primary tumours, locally inoperable recurrent disease, and metastatic DFSP. Imatinib has also been given to patients with extensive, difficult-to-operate tumours for preoperative reduction of tumour size, but the usefulness of this attitude should be confirmed by clinical trials. Therapeutic decisions for patients with fibrosarcomatous DFSP should be primarily made by an interdisciplinary oncology team (‘tumour board’). [ABSTRACT FROM AUTHOR]

Cutaneous squamous cell carcinoma (cSCC) is one of the most common cancers in Caucasian populations, accounting for 20% of all cutaneous malignancies. A unique collaboration of multi-disciplinary experts from the European Dermatology Forum (EDF), the European Association of Dermato-Oncology (EADO) and the European Organization of Research and Treatment of Cancer (EORTC) was formed to make recommendations on cSCC diagnosis and management, based on a critical review of the literature, existing guidelines and the expert’s experience. The diagnosis of cSCC is primarily based on clinical features. A biopsy or excision and histologic confirmation should be performed in all clinically suspicious lesions in order to facilitate the prognostic classification and correct management of cSCC. The first line treatment of cutaneous SCC is complete surgical excision with histopathological control of excision margins. The EDF–EADO–EORTC consensus group recommends a standardised minimal margin of 5 mm even for low-risk tumours. For tumours, with histological thickness of >6 mm or in tumours with high risk pathological features, e.g. high histological grade, subcutaneous invasion, perineural invasion, recurrent tumours and/or tumours at high risk locations an extended margin of 10 mm is recommended. As lymph node involvement by cSCC increases the risk of recurrence and mortality, a lymph node ultrasound is highly recommended, particularly in tumours with high-risk characteristics. In the case of clinical suspicion or positive findings upon imaging, a histologic confirmation should be sought either by fine needle aspiration or by open lymph node biopsy. In large infiltrating tumours with signs of involvement of underlying structures, additional imaging tests, such as CT or MRI imaging may be required to accurately assess the extent of the tumour and the presence of metastatic spread. Current staging systems for cSCC are not optimal, as they have been developed for head and neck tumours and lack extensive validation or adequate prognostic discrimination in certain stages with heterogeneous outcome measures. Sentinel lymph node biopsy has been used in patients with cSCC, but there is no conclusive evidence of its prognostic or therapeutic value. In the case of lymph node involvement by cSCC, the preferred treatment is a regional lymph node dissection. Radiation therapy represents a fair alternative to surgery in the non-surgical treatment of small cSCCs in low risk areas. It generally should be discussed either as a primary treatment for inoperable cSCC or in the adjuvant setting. Stage IV cSCC can be responsive to various chemotherapeutic agents; however, there is no standard regimen. EGFR inhibitors such as cetuximab or erlotinib, should be discussed as second line treatments after mono- or polychemotherapy failure and disease progression or within the framework of clinical trials. There is no standardised follow-up schedule for patients with cSCC. A close follow-up plan is recommended based on risk assessment of locoregional recurrences, metastatic spread or development of new lesions. [ABSTRACT FROM AUTHOR]

Purpose The purpose of this study was to set up a prognostic model for the identification of survival predictors specific for melanoma patients treated with ipilimumab. Experimental design The following prospectively collected data were utilised: patient and primary tumour characteristics, relapse-free-interval, site and number of metastases, previous therapies and level of serum biomarkers (lactic dehydrogenase (LDH), C-reactive protein, β2-microglobulin, vascular endothelial growth factor (VEGF), IL2, IL6, S-100, alkaline phosphatase (ALP), transaminases, leucocyte count, lymphocytes subpopulations). A multivariate prognostic model was developed using the Cox regression model fitted to the data of 113 consecutive metastatic patients treated with ipilimumab (3 mg/kg, q3w) at Veneto Institute of Oncology (IOV). External validation was obtained using the data of 69 and 34 patients treated at European Oncology Institute (IEO) and University of Torino (UT), respectively. Results Median survival was 8.3, 4.9 and 7.1 months from first ipilimumab administration at IOV, IEO and UT, respectively. Both higher baseline levels of LDH (Hazard Ratio [HR] v = 1.36, 95% Confidence Interval [CI] 1.16–1.58, P < .001) and neutrophils (HR = 1.76, 95% CI 1.41–2.10, P < .001) were associated with worse prognosis. Model performance was satisfactory both upon internal validation (Dxy = 0.42) and external validation (Dxy = 0.40). Serum LDH and neutrophil count discriminated patients who lived more (low neutrophils and low LDH) or less (high LDH or neutrophils) than 24 months. Conclusion Serum LDH and neutrophil count were significant independent prognostic factors. This externally validated prognostic nomogram, could help clinicians to identify the patients who would benefit most from ipilimumab and consequently to improve resource allocation. These easily available biomarkers deserve further validation. [ABSTRACT FROM AUTHOR]

Abstract: Background: MELanoma treatment patterns and Outcomes among patients with unresectable stage III or stage IV Disease: a retrospective longitudinal surveY (MELODY), the first multicountry, observational survey in patients with advanced melanoma, aimed to quantify the impact of existing treatment strategies by capturing information on treatment patterns and clinical outcomes. Patients and methods: Patients attending a participating site between 1st July 2005 and 30th June 2006 with ⩾2months follow-up were eligible. Data were retrieved retrospectively from advanced melanoma diagnosis until 1st May 2008. Treatment data were collected by line of therapy and response and progression-free survival data by line of systemic treatment. Overall survival (OS) was evaluated for all treated patients. Results: Among all patients screened, 776 were eligible for this analysis. Median OS from the date of advanced disease diagnosis was 16.4months. After excluding patients diagnosed prior to 1st July 2005 to account for any bias resulting from patient selection, the 12-month survival rate and median OS from the start date of second-line treatment was 28.8% and 6.8months, respectively. Survival was lower in patients with brain metastases, elevated lactate dehydrogenase levels and more advanced disease. Rates of complete/partial tumour response were 15% and 7% in patients treated with first- and second-line systemic therapy, respectively. Conclusions: Despite receiving first- and second-line treatment, most patients with advanced melanoma have short survival times and poor prognoses, reinforcing the need for new treatments. [Copyright &y& Elsevier]

Background: In light of the evolving landscape of adjuvant therapy in melanoma and the recently confirmed absent survival benefit of completion lymph node dissection (CLND), it becomes important to explore possible consequences of omitting CLND, and whether it is possible to adequately stratify positive sentinel node (SN) patients solely based on information retrieved from the melanoma up to the sentinel lymph node biopsy (SLNB)., Methods: A retrospective cohort from nine European Organization for Research and Treatment of Cancer Melanoma Group centres was used. Patients were staged based on SLNB and CLND result according to the American Joint Committee on Cancer (AJCC) criteria and stratified by ulceration and SN tumour burden. These were incorporated in Cox regression models. Predictive ability was assessed using Harrell's concordance index (c-index) and the Akaike information criterion (AIC)., Results: In total, 1015 patients were eligible. CLND led to upstaging in N-category in 19% and in AJCC stage in 5-6%. The model incorporating only ulceration and SN tumour burden performed equally well as the model incorporating substages after CLND. The model incorporating substages based on SLNB had the lowest predictive ability. Stratifying by ulceration and SN tumour burden resulted in four positive SN groups from which low-, intermediate- and high-risk prognostic classes could be derived., Conclusions: Adequate stratification of positive SN patients was possible based on ulceration and SN tumour burden category. The identification of low-, intermediate- and high-risk patients could guide adjuvant therapy in clinical practice. Omitting CLND seems to have little consequences., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Merkel cell carcinoma (MCC) is a rare tumour of the skin of neuro-endocrine origin probably developing from neuronal mechanoreceptors. A collaborative group of multidisciplinary experts form the European Dermatology Forum (EDF), The European Association of Dermato-Oncology (EADO) and the European Organization of Research and Treatment of Cancer (EORTC) was formed to make recommendations on MCC diagnosis and management, based on a critical review of the literature, existing guidelines and expert's experience. Clinical features of the cutaneous/subcutaneous nodules hardly contribute to the diagnosis of MCC. The diagnosis is made by histopathology, and an incisional or excisional biopsy is mandatory. Immunohistochemical staining contributes to clarification of the diagnosis. Initial work-up comprises ultrasound of the loco-regional lymph nodes and total body scanning examinations. The primary tumour should be excised with 1-2cm margins. In patients without clinical evidence of regional lymph node involvement, sentinel node biopsy is recommended, if possible, and will be taken into account in a new version of the AJCC classification. In patients with regional lymph node involvement radical lymphadenectomy is recommended. Adjuvant radiotherapy might be considered in patients with multiple affected lymph nodes of extracapsular extension. In unresectable metastatic MCC mono- or poly-chemotherapy achieve high remission rates. However, responses are usually short lived. Treatment within clinical trials is regarded as a standard of care in disseminated MCC., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Background: In recent decades, melanoma incidence has been increasing in European countries; in 2006, there were approximately 60,000 cases leading to 13,000 deaths. Within Europe there is some geographical variation in the incidence of melanoma, with the highest rates reported in Scandinavia (15 cases per 100,000 inhabitants per year) and the lowest in the Mediterranean countries (5 to 7 cases per 100,000 inhabitants per year)., Methods: The present article is based on the information collected in the MELODY study (MELanoma treatment patterns and Outcomes among patients with unresectable stage III or stage IV Disease: a retrospective longitudinal survey).In that study, the medical charts of patients were reviewed to document current treatment patterns and to analyse information on patients, disease characteristics and healthcare resource utilization related to the treatment of advanced melanoma regarding patients who presented with a diagnosis of malignant melanoma (stage I to IV) at participating sites between 01 July, 2005 and 30 June, 2006., Results: Summarizing, though the length of the follow-up period varies among sample patients, an amount of the yearly cost per patient can be estimated, dividing the average per patient total cost (€ 5.040) by the average follow-up duration (17.5 months) and reporting to one year; on these grounds, unresectable stage III or stage IV melanoma in Italy would cost € 3,456 per patient per year.

Objective: To describe patterns of healthcare resource utilisation and associated costs for patients with advanced melanoma in the United Kingdom (UK), Italy, and France., Methods: For patients receiving systemic treatment, or supportive care, data describing hospitalisations, hospice care, and outpatient visits were retrieved retrospectively from advanced disease diagnosis as part of a multicountry observational study. Costs were estimated by multiplying utilisation level by unit cost. In an exploratory analysis, costs were compared between individuals who died within one year of initiating first-line treatment (short-term survivors) and those with ≥ 1 year follow-up (long-term survivors)., Results: Hospitalisation costs were highest in France (€6262 per-person compared with €3225 in the UK and €2486 in Italy), reflecting higher rates of hospitalisation. In contrast, outpatient costs were highest in the UK (€782 per-person, compared with €115 in France and €72 in Italy), reflecting the highest rate and frequency of outpatient visits and the highest cost per visit. Hospitalisation rates were consistently higher during supportive care compared with systemic therapy. Roughly one-third of patients entered clinical trials and were not included in the analysis. In exploratory analysis, total costs were generally higher for long-term survivors, but monthly per-patient costs were generally lower for long-term survivors, consistent with a hypothesis that resource utilisation and costs do not necessarily increase proportionally with extended survival., Conclusion: Total costs associated with resource utilisation for advanced melanoma patients varied across countries. Overall cost differences were due to differences in frequency and intensity of utilisation patterns and variation in unit costs of health resources., (Copyright © 2012. Published by Elsevier Ltd.)