French guidelines for the management of oral lichen planus (excluding pharmacological therapy).

INTRODUCTION: Oral lichen is a chronic inflammatory disease for which diagnostic management and follow-up are heterogeneous given the absence of specific guidelines in France. Our objective was to develop French multidisciplinary guidelines for the management of oral lichen. MATERIALS AND METHODS: Working groups from the Groupe d'Etude de la Muqueuse Buccale (GEMUB) formulated a list of research questions and the corresponding recommendations according to the "formal consensus" method for developing practice guidelines. These recommendations were submitted to a group of experts and the degree of agreement for each recommendation was assessed by a scoring group. RESULTS: Twenty-two research questions, divided into 3 themes (nosological classification and initial assessment, induced oral lichenoid lesions, and follow-up) resulted in 22 recommendations. Initial biopsy for histology is recommended in the absence of reticulated lesions. Biopsy for direct immunofluorescence is recommended for ulcerated, erosive, bullous types and for diffuse erythematous gingivitis. Management should include a periodontal and dental check-up, and investigation for extra-oral lesions. Hepatitis C testing is recommended only if risk factors are present. Definitions, triggering factors and the management of "induced oral lichenoid lesions" were clarified. Oral lichen must be monitored by a practitioner familiar with the disease at least once a year, using objective tools. CONCLUSION: This formalised consensus of multidisciplinary experts provides clinical practice guidelines on the management and monitoring of oral lichen.

[Proliferative verrucous leukoplakia: Three cases and literature review]. / Leucoplasie verruqueuse proliférative : trois observations et revue de la littérature.

BACKGROUND: The aim of this study was to collect epidemiological, aetiopathogenic, clinical, histological and therapeutic data concerning proliferative verrucous leucoplakia (PVL) and to report three new cases. PATIENTS AND METHODS: A literature review performed using the Medline database enabled us to collate 39 studies involving 607 cases. Three new cases were added. RESULTS: PVL is a rare disease characterized by extensive and multifocal oral leucoplakic lesions. Its histological pattern depends on the stage of the disease: hyperkeratosis, verrucous hyperplasia, verrucous carcinoma and squamous cell carcinoma. The aetiopathogenesis of PVL is poorly understood and there is no clear consensus concerning therapy. Malignant transformation occurs in over 50 % of cases. DISCUSSION: Diagnosis of PVL is difficult because of the presenting signs, which can be mistaken for those of other diseases. Management may be complicated and long-term follow-up is essential.

Adjustable Velcro Compression Devices are More Effective than Inelastic Bandages in Reducing Venous Edema in the Initial Treatment Phase: A Randomized Controlled Trial.

OBJECTIVE/BACKGROUND: The objective of this study was to compare the efficacy and comfort of inelastic bandages (IBs) and adjustable Velcro compression devices (AVCDs) in reducing venous leg edema in the initial treatment phase. METHODS: Forty legs from 36 patients with untreated venous edema (C3EpsAsdPr) were randomized to two groups. Patients in the first group received IBs (n = 20) and those in the second AVCDs (n = 20). Both compression devices were left on the leg day and night, and were renewed after 1 day. Patients in the AVCD group were asked to re-adjust the device as needed when it felt loose. Leg volume was calculated using the truncated cone formula at baseline (T0), after 1 day (T1) and after 7 days (T7). The interface pressure of the two compression devices was measured by an air filled probe, and the static stiffness index calculated after applying compression at T0 and T1, and just before removal of compression on T1 and T7. Patient comfort with regard to the two compression systems was assessed by grading signs and symptoms using a visual analog scale. RESULTS: At T1, the median percent volume reduction was 13% for the IB group versus 19% for the AVCD group; at T7 it was 19% versus 26%, respectively (p < .001). The pressure of the IBs was significantly higher compared with the AVCDs at T0 (63 vs. 43 mmHg) but dropped by > 50% over time, while it remained unchanged with AVCDs owing to the periodic readjustment by the patient. Comfort was reported to be similar with the two compression devices. CONCLUSION: Re-adjustable AVCDs with a resting pressure of around 40 mmHg are more effective in reducing chronic venous edema than IBs with a resting pressure of around 60 mmHg. AVCDs are effective and well tolerated, not only during maintenance therapy, but also in the initial decongestive treatment phase of patients with venous leg edema.

REBECA: a phase I study of bevacizumab and whole-brain radiation therapy for the treatment of brain metastasis from solid tumours.

BACKGROUND: Brain metastases (BMs) are associated with a poor prognosis. Standard treatment comprises whole-brain radiation therapy (WBRT). As neo-angiogenesis is crucial in BM growth, combining angiogenesis inhibitors such as bevacizumab with radiotherapy is of interest. We aimed to identify the optimal regimen of bevacizumab combined with WBRT for BM for phase II evaluation and provide preliminary efficacy data. PATIENTS AND METHODS: In this multicentre single-arm phase I study with a 3 + 3 dose-escalation design, patients with unresectable BM from solid tumours received three cycles of bevacizumab at escalating doses [5, 10 and 15 mg/kg every 2 weeks at dose levels (DL) 0, 1 and 2, respectively] and WBRT (30 Gy/15 fractions/3 weeks) administered from day 15. DL3 consisted of bevacizumab 15 mg/kg with WBRT from day 15 in 30 Gy/10 fractions/2 weeks. Safety was evaluated using NCI-CTCAE version 3. BM response (RECIST 1.1) was assessed by magnetic resonance imaging at 6 weeks and 3 months after WBRT. RESULTS: Nineteen patients were treated, of whom 13 had breast cancer. There were no DLTs. Grade 1-2 in-field and out-field toxicities occurred for five and nine patients across all DLs, respectively, including three and six patients (including one patient with both, so eight patients overall) of nine patients in DL3. One patient experienced BM progression during treatment (DL0). At the 3-month post-treatment assessment, 10 patients showed a BM response: one of three treated at DL0, one of three at DL1, two of three at DL2 and six of seven at DL3, including one complete response. BM progression occurred in five patients, resulting in two deaths. The remaining patient died from extracranial disease progression. CONCLUSION: Bevacizumab combined with WBRT appears to be a tolerable treatment of BM. DL3 warrants further efficacy evaluation based on the favourable safety/efficacy balance. ClinicalTrials.gov Identifier: NCT01332929.

Concurrent administration of trastuzumab with locoregional breast radiotherapy: long-term results of a prospective study.

This single-center prospective study aims to assess the outcomes and the toxicities related to the concurrent administration of trastuzumab (T) with adjuvant locoregional radiotherapy (RT) in localized breast cancer. Data of 308 patients were analyzed. T was delivered every 3 weeks (loading dose of 8 mg/kg, then 6 mg/kg) for 1 year. Left ventricular ejection fraction (LVEF), measured by echocardiography or myocardial scintigraphy, was considered as impaired when below 55%. Toxicities were assessed according to the Common Terminology Criteria for Adverse Events version 3.0. Univariate and multivariate analyses were carried out using the Cox model. Median follow-up was 50.2 months (13.0-126.0). Median age at diagnosis was 52 years (25-83). Internal mammary node (IMN) RT was performed in 227 patients (73.7%). After completion of RT, 26 patients (8.4%) presented an impaired LVEF: 17 (5.5%) of grade 1, 7 (2.3%) of grade 2, and 2 (0.6%) of grade 3. At 48 months, locoregional control rate was 95% [95% CI 92; 98], and overall survival rate was 98% [95% CI 96; 100]. In univariate analysis, neither the treated breast side (p = 0.655) nor IMN RT (p = 0.213) exposed patients to LVEF alteration. In multivariate analysis, clinical lymph node involvement was associated with an increased risk of locoregional and distant recurrence (p = 0.016 and p = 0.007, respectively). In this prospective study, the toxicities of concurrent T with locoregional breast RT were acceptable and the outcomes favorable. Longer follow-up is warranted to confirm these results.

Oral giant cell tumor or giant cell granuloma: How to know?

Introduction: The distinction between giant cell tumors and giant cell granulomas is challenging, as both entities have overlapping diagnostic criteria, especially in oral locations. The two entities have similar clinical and radiological presentations, but they differ in their prognoses. Objective: The main objective of this study was to list the clinical, radiological, histological, and prognostic features of maxillomandibular giant cell tumors and giant cell granulomas cases n order to assess their value as a diagnostic referral factor that may allow the distinction between maxillo-mandibular giant cell granuloma and giant cell tumor. Study design: Data of maxillomandibular giant cell granulomas and giant cell tumors were assessed through a scoping review and a pre-existing systematic review of literature. We have also realized a bicentric retrospective study. Results: Various criteria facilitate the differential diagnosis like age, size, locularity and presence of necrosis zone but not the gender. The most discriminating factors was symptomatology (reported in 72% of GCTs while only 15% of GCGs) and the distribution pattern of giant cells in the stroma (homogeneously dispersed in 80% of GCTs versus grouped in clusters in 86.7% of GCGs). Recurrences were most described for giant cell tumors than giant cell granulomas. Malignant transformation and pulmonary metastasis were exclusively reported for giant cell tumors. Conclusion: As clinical and radiological elements are not sufficient to distinguish between these two entities, immunohistochemistry and molecular genetics can be represent diagnostic biomarkers to distinguish giant cell granulomas and giant cell tumors in oral cavity. We have attempted to define the main criteria for the differentiation of giant cell tumor and giant cell granuloma and propose a decision tree for the management of single maxillomandibular giant cell lesions.

[The morbidity and mortality review meetings in radiotherapy departments: Procedure, implementation and prospects of the "Proust" French national project]. / Revue de morbidité et mortalité en radiothérapie : procédure, implémentation et perspectives du projet national français « Proust ¼.

Radiation-induced acute and late toxicity depends on several parameters. The type, severity and duration of morbidity are mainly related to irradiated volume, total dose and its fractionation and the intrinsic radiosensitivity of the patients. The follow-up of these toxicities is essential. However, unlike many specialties, morbidity and mortality reviews procedures are not developed as part of quality governance programs in radiation therapy departments for the monitoring of toxicity which sometimes hinder the patients' quality of life. One French survey published within the framework of the project entitled Prospective Registration of Morbidity and Mortality, Individual Radiosensitivity and Radiation Technique (Proust), conclude that there was a lack of knowledge of morbidity and mortality reviews and considerable confusion between these reviews and other quality processes without perspective for the local morbidity and mortality reviews development in a large number of the participated centers. In this article, we will discuss the procedure of the "ideal morbidity and mortality reviews" and its implementation through a monocentric experience started in 2015. Thus, the Proust project is a unique opportunity to implement and standardize a national morbidity and mortality reviews implementation in radiation therapy departments by involving the French regions.

Duplex ultrasound and magnetic resonance imaging of the supra-aortic arches in patients with non recurrent inferior laryngeal nerve: a comparative study.

BACKGROUND: Non-recurrent inferior laryngeal nerve (NRILN) is usually discovered during thyroid surgery. It is often associated with vascular abnormalities that can be detected with magnetic resonance imaging (MRI) or duplex ultrasound scan. The aim of this study was to compare the diagnostic sensitivity of ultrasonography with MRI to identify the vascular abnormalities associated to NRILN. PATIENTS AND METHODS: We revised 2713 total thyroidectomies to select patients with NRILN. The NRILN was identified in 17 patients (0,6%). A postoperative ultrasonic duplex scanning and a MRI was performed in 15 cases as 2 patients refused to submit to the exams. RESULTS: At MRI an unique origin of common carotid trunk and a concomitant aberrant retroesophageal subclavian right artery was showed in 11 patients. In 2 cases vascular abnormality consisted in separated origin of supra-aortic arteries. At duplex ultrasound scan only in 2 patients was impossible to identify vascular abnormalities detected at MRI. Tthe diagnostic sensitivity of duplex ultrasound was 84,6%. CONCLUSIONS: Preoperative duplex ultrasound is a non invasive method with high diagnostic sensitivity that can easily complete the preoperative thyroid ultrasonography.

Breast-conserving surgery with or without radiotherapy vs mastectomy for ductal carcinoma in situ: French Survey experience.

From March 2003 to April 2004, 77 physicians throughout France prospectively recruited 1289 ductal carcinoma in situ (DCIS) patients and collected data on diagnosis, patient and tumour characteristics, and treatments. Median age was 56 years (range, 30-84). Ductal carcinoma in situ was diagnosed by mammography in 87.6% of patients. Mastectomy, conservative surgery alone (CS) and CS with radiotherapy (CS+RT) were performed in 30.5, 7.8 and 61.7% of patients, respectively. Thus, 89% of patients treated by CS received adjuvant RT. Sentinel node biopsy (SNB) and axillary dissection (AD) were performed in 21.3 and 10.4% of patients, respectively. Hormone therapy was administered to 13.4% of the patients (80% tamoxifen). Median tumour size was 14.5 mm (6, 11 and 35 mm for CS, CS+RT and mastectomy, respectively, P<0.0001). Nuclear grade was high in 21% of patients, intermediate in 38.5% and low in 40.5%. Excision was considered complete in 92% (CS) and 88.3% (CS+RT) of patients. Oestrogen receptors were positive in 69.8% of assessed cases (31%). Treatment modalities varied widely according to region: mastectomy rate, 20-37%; adjuvant RT, 84-96%; hormone treatment, 6-34%. Our survey on current DCIS management in France has highlighted correlations between pathological features (tumour size, margin and grade) and treatment options, with several similar variations to those observed in recent UK and US studies.

[Hypofractionated breast radiotherapy in 13 fractions, perfect tolerance or delayed early reaction? Prospective study of Curie Institute]. / La radiothérapie mammaire hypofractionnée en 13 séances, parfaite tolérance ou réaction cutanée décalée ? Etude prospective de l'institut Curie.

PURPOSE: To assess the skin toxicity of this scheme and the time to its appearance. PATIENTS AND METHODS: Eighty-one prospectively recorded patients (pts), treated in Radiotherapy Department for Breast Cancer (BC) with radiotherapy (RT) to the whole breast at the dose of 42.9Gy per 13 fractions (F) per 5 weeks have been studied. Skin reactions were monitored weekly using the National Cancer Institute-Common Toxicity Criteria scoring system, version 3. All risk factors as tobacco smoking, diabetes, obesity were also recorded. RESULTS: All 81 pts, aged from 40 to 83 years (median: 70 years) received whole breast RT 42.9Gy per 13 F without lymph node irradiation after breast conserving surgery. There were no pts with concurrent chemo- and/or hormonal therapy. Seventeen patients (21%) have been treated using decubitus dorsal (DD) technique and 64 (79%) using the previously described isocentric decubitus lateral (IDL) technique. During the RT, only 34 pts (42%) experienced grade I skin reactions and 47 pts (58%) were without. At the last day of the breast irradiation, there were 66 (81%) grade I (N=59) and II (N=7) skin reactions and 15 pts (19%) without. The early skin tolerance of this scheme was considered to be excellent. But in the 2 weeks after the RT, 20 pts (25%) asked for new clinics with their radiation oncologist as a matter of urgency due to worsening of their skin condition. All of them have been seen by their physician and/or the nurse. Of them, nine presented grade I and 11 presented grade II skin reactions, with necessity of special skin care. The analysis of these results was realized and delayed clinics were organized for all pts treated with this scheme 10-14 days after the end of the radiation treatment. CONCLUSIONS: The breast RT 42.9Gy/13 F have been previously described as an efficacious and well tolerated scheme. This prospective homogeneous group of patients showed that delayed early skin reactions could appear in some cases. Therefore complementary clinics are needed to detect and treat these reactions.

[Adjuvant irradiation in breast cancer patients with ATM gene heterozygous mutations: special focus on clinical efficacy/toxicity]. / Toxicité et efficacité de la radiothérapie adjuvante chez les patientes traitées pour un cancer du sein et porteuses d'une mutation hétérozygote du gène de l'ataxie-télangiectasie.

Dysfunction of the ataxia telangiectasia mutated (ATM) gene has been related to defective cell cycle control and genomic instability due to the impaired repair of DNA double strand breaks. Although increased radiosensitivity in ATM heterozygous patients has been suggested in preclinical data, clinical implication of ATM variant remains debated. Despite frequent in vitro hypersensitivity in patients with severe radiation-induced delayed toxicity, heterozygoty for ATM gene does not represent the major cause of unexpected complications after radiation therapy. This might be partially due to potential coexistence of alterations in additional genes that would play a role in development of late radiation-induced adverse response. Although several data suggest that some ATM polymorphisms would increase grade 3 subcutaneous fibrosis at lower doses compared with patients who did not possess these genetic alterations, the relationship between the presence of ATM mutations or sequence variants and radiation-induced toxicity remains controversial in part because of their biological and functional significance. Considering the lack of prospective data, patients with ATM mutation should be considered as candidates for both dose volume and dose reduction clinical trials.

[Definition of nodal volumes in breast cancer treatment and segmentation guidelines]. / Définition des volumes ganglionnaires dans le cadre du traitement d'un cancer du sein et règles de contourage.

PURPOSE: To assist in the determination of breast and nodal volumes in the setting of radiotherapy for breast cancer and establish segmentation guidelines. Materials and methods. Contrast metarial enhanced CT examinations were obtained in the treatment position in 25 patients to clearly define the target volumes. The clinical target volume (CTV) including the breast, internal mammary nodes, supraclavicular and subclavicular regions and axxilary region were segmented along with the brachial plexus and interpectoral nodes. The following critical organs were also segmented: heart, lungs, contralateral breast, thyroid, esophagus and humeral head. RESULTS: A correlation between clinical and imaging findings and meeting between radiation oncologists and breast specialists resulted in a better definition of irradiation volumes for breast and nodes with establishement of segmentation guidelines and creation of an anatomical atlas. CONCLUSION: A practical approach, based on anatomical criteria, is proposed to assist in the segmentation of breast and node volumes in the setting of breast cancer treatment along with a definition of irradiation volumes.

Angina bullosa haemorrhagica: a systematic review and proposal for diagnostic criteria.

The aim of this study was to perform a critical review of published data on the epidemiological, aetiological, clinical, histological, biological, and therapeutic characteristics of patients with angina bullosa haemorrhagica (ABH). A literature search was conducted in the PubMed, Science Direct, Web of Science, and Cochrane Library databases. All publications fulfilling the selection criteria were included in the eligibility assessment according to the PRISMA statement. The full texts of 54 retrieved articles were screened. Forty articles published between 1985 and 2016 describing 225 cases of ABH were finally selected. The mean age of the patients was 55.4 years; the male to female ratio was 0.7. The predominant localization was the palate (66%). A third of patients had no medical history. When specified, a triggering event or promoting factor was frequently found (82%). Biological tests were normal. A biopsy was performed on 35% of the patients. Treatment was symptomatic with a favourable outcome. Recurrences were frequent (62%). In conclusion, ABH is poorly documented and only by studies of low-level evidence. This review did not allow any aetiopathogenic association to be made with a general pathology or treatment. On the basis of this systematic review of the literature, diagnostic criteria aiming to improve the care of patients presenting with ABH are proposed.

[Meta-analyses of the effects of radiotherapy in breast cancer: the ultimate evidence?]. / Méta-analyses des effets de la radiothérapie dans le cancer du sein: la preuve absolue?

Several meta-analyses of the effects of radiotherapy in breast cancer were published. Methodological quality varied largely in these studies, from simply gathering data from published studies or even published abstracts, to more rigorous studies gathering individual data from each patient having participated in the trials analysed. A model of the latter is represented by the successive meta-analyses from the Early Breast Cancer Trialists' Cooperative Group (EBCTCG). These studies have had a strong impact on the clinical practice of radiotherapy in breast cancer, by demonstrating its long-term potential toxic effects, but also its ability to decrease the long-term breast-cancer mortality, regardless of the effects of other breast-cancer treatments. Therefore, it has contributed to the continuous improvement in the techniques of radiotherapy, as well as to its use in the multidisciplinary management of breast-cancer patients.