[Proposal for the delineation of postoperative primary clinical target volumes in maxillary sinus and nasal cavity cancers]. / Proposition de délinéation des volumes cibles anatomocliniques postopératoires de la tumeur primitive des cancers du sinus maxillaire et des cavités nasales.

In this article, we propose a consensus delineation of postoperative clinical target volumes for the primary tumour in maxillary sinus and nasal cavity cancers. These guidelines are developed based on radioanatomy and the natural history of those cancers. They require the fusion of the planning CT with preoperative imaging for accurate positioning of the initial GTV and the combined use of the geometric and anatomical concepts for the delineation of clinical target volume for the primary tumour. This article does not discuss the indications of external radiotherapy (nor concurrent systemic treatment) but focuses on target volumes when there is an indication for radiotherapy.

Validation and optimization of the French Generic Adherence for Chronic Diseases Profile (GACID-P) using classical test and item response theory.

BACKGROUND: The Generic Adherence for Chronic Diseases Profile is a French generic scale (GACID-P) developed to measure adherence in several disease areas such as cardiology, rheumatology, diabetes, cancer and infectiology. METHOD: We aimed to study the measurement invariance of the Generic Adherence for Chronic Diseases Profile by an item response model, optimize the new instrument version from item response model and qualitative content analyses results, and validate the instrument. The metric properties of the optimized version were studied according to classical test theory and item response model analysis. RESULTS: A sample of 397 patients consulting at two French hospitals (in diabetes, cardiology, rheumatology, cancerology and infectiology) and in four private practices was recruited; 314 (79%) patients also completed the questionnaire 15 days later. Factor analyses revealed four dimensions: "Forgetting to take medication", "Intention to comply with treatment", "Limitation of risk-related consumer habits" and "Healthy lifestyle". The item response model and content analyses optimized these four dimensions, regrouping 32 items in four dimensions of 25 items, including one item conditioned on tobacco use. The psychometric properties and scale calibration were satisfactory. One score per dimension was calculated as the sum of the items for the dimensions "Forgetting to take medication" and "Intention to comply with treatment" and as a weighted score according to the item response model analysis for the two other dimensions because of differential item functioning found for two items. CONCLUSION: Four adherence profile scores were obtained. The instrument validity was documented by a theoretical approach and content analysis. The Generic Adherence for Chronic Diseases Profile is now available for research targeting adherence in a broad perspective.

[Dosimetric and toxicity comparison of IMRT and 3D-CRT of non-small cell lung cancer]. / Comparaison dosimétrique et de la toxicité de la radiothérapie conformationnelle avec modulation d'intensité et de la radiothérapie conformationnelle tridimensionnelle des carcinomes bronchiques non à petites cellules.

PURPOSE: Although three-dimensional conformal radiotherapy (3D-CRT) remains the gold standard as a curative treatment for NSCLC when surgery is not possible, intensity modulated radiotherapy (IMRT) is increasingly used routinely. The purpose of this study was to assess the clinical (immediate toxicities) and dosimetric impact of IMRT compared to 3D-CRT in the treatment of locally advanced (stages IIIA to IIIC) non-small cell lung cancer (NSCLC) treated with concomitant radiochemotherapy, while IMRT in lung cancer was implemented in the radiotherapy department of the Jean-Perrin Center. PATIENTS AND METHODS: Between March 2015 and October 2019, 64 patients treated with concomitant radiochemotherapy were retrospectively included. Thirty-two received 3D-CRT and 32 IMRT. The radiotherapy prescription was 66Gy in 33 fractions of 2Gy. RESULTS: IMRT has improved coverage of target volumes (V95 increased by 14.81% in IMRT; P<0.001) without increasing doses to OARs and reducing dysphagia (RR=0.67; P=0.027). Low doses to the lung were not significantly increased in IMRT (pulmonary V5 increased by 7.46% in IMRT). CONCLUSION: Intensity modulated radiotherapy, compared with the standard RC3D technique, improve the coverage of target volumes without increasing the dose to the OARs. It also improves the immediate tolerance of the treatment by reducing the number of dysphagia.

[Predictive factors for mandibular osteoradionecrosis after irradiation of head and neck cancers]. / Facteurs prédictifs de l'ostéoradionécrose mandibulaire après irradiation des cancers des voies aérodigestives supérieures.

The identification of the different risk factors for mandibular osteoradionecrosis (ORN) must be done before and after the management of patients with head and neck cancer. Various clinical criteria for this severe radiation-induced complication are related to the patient (intrinsic radiosensitivity, malnutrition associated with thin weight loss, active smoking intoxication, microcapillary involvement, precarious oral status, hyposalivation) and/or related to the disease (oral cavity, large tumor size, tumor mandibular invasion). Therapeutic risk factors are also associated with a higher risk of ORN (primary tumor surgery, concomitant radio-chemotherapy, post-irradiation dental avulsion, preventive non-observance with the absence of stomatological follow-up and daily installation of gutters fluoride and, non-observance curative healing treatments). Finally, various dosimetric studies have specified the parameters in order to target the dose values distributed in the mandible, which increases the risk of ORN. An mean mandibular dose greater than 48-54Gy and high percentages of mandibular volume receiving 40 to 60Gy appear to be discriminating in the risk of developing an ORN.

[Proposal for the delineation of postoperative primary clinical target volumes in ethmoid cancers]. / Proposition de délinéation des volumes cibles anatomocliniques postopératoires de la tumeur primitive des cancers de l'ethmoïde.

It is proposed to delineate the anatomo-clinical target volumes of primary tumor (CTV-P) in ethmoid cancers treated with post-operative radiotherapy. This concept is based on the use of radioanatomy and the natural history of cancer. It is supported by the repositioning of the planning scanner with preoperative imaging for the replacement of the initial GTV and the creation of margins around it extended to the microscopic risk zones according to the anatomical concept. This article does not discuss the indications of external radiotherapy but specifies the volumes to be delineated if radiotherapy is considered.

Nuclear power plant: state of knowledge of the population living in the area of the Cattenom special intervention plan. A cross-sectional study.

In France information campaigns are periodically conducted within a 10 km radius of nuclear power plants on the protective actions to be adopted in the event of a nuclear accident. The aim of this study was to assess the knowledge of the inhabitants of the Cattenom PPI area on the recommended actions to be adopted in the event of a nuclear accident after the information campaign that took place from 2016 to 2017 and compare its results with a similar study carried out before the information campaign. We performed a cross-sectional study in the Cattenom PPI area after the 2016-2017 information campaign. We administered questionnaires in ten municipalities selected by lot. These questionnaires contained queries on the general protective actions and required approach to taking potassium iodide (KI). The results obtained were compared with the results of a study conducted before the information campaign in the same area. Out of 200 questionnaires administered, 122 people responded. Only 40% of respondents remembered the information campaign. Only 16% knew all of the recommended protective actions. 78% of households had KI and only 60% knew the objective of KI intake. Compared to the results of the study before the information campaign, KI coverage was better (69% versus 78%, p = 0.02) and the dosage was better known (16% versus 28%, p = 0.0003). This study provides an overview of the effectiveness of information campaigns on the procedure in the event of a nuclear accident. This study highlights the insufficient knowledge of people living in the Cattenom PPI area.

Surgery in reference centers improves survival of sarcoma patients: a nationwide study.

BACKGROUND: NETSARC (netsarc.org) is a network of 26 sarcoma reference centers with specialized multidisciplinary tumor boards (MDTB) aiming to improve the outcome of sarcoma patients. Since 2010, presentation to an MDTB and expert pathological review are mandatory for sarcoma patients nationwide. In the present work, the impact of surgery in a reference center on the survival of sarcoma patients investigated using this national NETSARC registry. PATIENTS AND METHODS: Patients' characteristics and follow-up are prospectively collected and data monitored. Descriptive, uni- and multivariate analysis of prognostic factors were conducted in the entire series (N = 35 784) and in the subgroup of incident patient population (N = 29 497). RESULTS: Among the 35 784 patients, 155 different histological subtypes were reported. 4310 (11.6%) patients were metastatic at diagnosis. Previous cancer, previous radiotherapy, neurofibromatosis type 1 (NF1), and Li-Fraumeni syndrome were reported in 12.5%, 3.6%, 0.7%, and 0.1% of patients respectively. Among the 29 497 incident patients, 25 851 (87.6%) patients had surgical removal of the sarcoma, including 9949 (33.7%) operated in a NETSARC center. Location, grade, age, size, depth, histotypes, gender, NF1, and surgery outside a NETSARC center all correlated to overall survival (OS), local relapse free survival (LRFS), and event-free survival (EFS) in the incident patient population. NF1 history was one of the strongest adverse prognostic factors for LRFS, EFS, and OS. Presentation to an MDTB was associated with an improved LRFS and EFS, but was an adverse prognostic factor for OS if surgery was not carried out in a reference center. In multivariate analysis, surgery in a NETSARC center was positively correlated with LRFS, EFS, and OS [P < 0.001 for all, with a hazard ratio of 0.681 (95% CI 0.618-0.749) for OS]. CONCLUSION: This nationwide registry of sarcoma patients shows that surgical treatment in a reference center reduces the risk of relapse and death.

Health resource use and costs of symptomatic knee and/or hip osteoarthritis.

BACKGROUND: Data on the economic consequences of hip and knee osteoarthritis (OA) are scarce. We aimed to estimate the annual direct and indirect costs for patients followed for hip and/or knee OA in the Knee and Hip Osteoarthritis Long term Assessment (KHOALA) cohort. METHODS: The KHOALA cohort, set up from 2007 to 2009, is a French multicenter study of 878 individuals with symptomatic knee/hip OA who were 40-75 years old. Resources used were collected annually for 5 years. Costs were assigned by using official sources and expressed in 2018 euros per patient. RESULTS: The mean annual total costs per patient over the 5-year study period were 2,180 ± 5,305€. The mean annual direct medical costs per patient were 2,120 ± 5,275€ and mean annual indirect costs per patient 180 ± 1,735€ for people of working age. Costs increased slightly over the study period. Drugs were the largest cost share, representing over 50% of all direct costs. However, the proportion attributable to OA drugs accounted for only 10.5% of drug costs. The second cost share was hospitalizations; hip and knee prosthetic surgery accounted for 27% of surgery hospitalization costs. Health professional visits were the third cost share, accounting for 3% of direct medical costs. The median costs induced could be as high as 2 billion €/year (IQR 0.7-4.3) in France. CONCLUSION: Hip and knee OA costs were substantial and increased over the study period in France. However, the costs attributable to OA represented only a small fraction of overall costs.

Clinical follow-up of 411 patients with relapsing and progressive multiple sclerosis 10 years after discontinuing mitoxantrone treatment: a real-life cohort study.

BACKGROUND AND PURPOSE: Mitoxantrone (MITOX) has been used to treat patients with aggressive multiple sclerosis (MS) for decades. We aimed to describe the effectiveness and adverse events over 10 years post-MITOX in patients with relapsing and progressive MS from an exhaustive real-life database. METHODS: Data from patients who received MITOX before 1 January 2006 were collected from the MS Lorraine registry. Expanded Disability Status Scale (EDSS) scores and annual relapse rates (ARRs) year by year during follow-up and the year prior to MITOX were compared. Time to the first relapse and a 1-point increase in EDSS score were used in Cox multivariate models to find associations with potential predictive factors. RESULTS: A total of 411 patients were included. The ARR for the 155 relapsing patients had decreased from 2.0 (SD 1.20) the year before treatment to 0.3 (SD 0.31) by year 10 (P < 0.0001). The EDSS score increased from 2.8 (SD 1.44) to 4.8 (SD 1.90) by year 10 (P < 0.0001). A high ARR at MITOX initiation was associated with a longer time to a 1-point increase in EDSS score (hazard ratio, 0.81; 95% confidence interval, 0.67-0.99; P = 0.04). The EDSS score in 256 progressive patients increased from 5.0 (SD 1.33) to 6.5 (SD 1.26) by year 10 (P < 0.0001). We identified four cases of acute myeloid leukemias. CONCLUSIONS: Patients with the most active forms of MS are the most likely to benefit from MITOX in the long term.

Adjuvant radiation therapy for malignant Abrikossoff's tumor: a case report about a femoral triangle localisation.

BACKGROUND: Granular cell or Abrikossoff's tumors are usually benign however rare malignant forms concern 1 to 3% of cases reported. Pelvic locations are exceptional. CASE PRESENTATION: We report a case of a 43-years-old patient who had a benign Abrikossoff's tumor localized in the right femoral triangle diagnosed at the biopsy. The patient underwent a surgical tumorectomy and inguinal lymph nodes resection. Histologically, the tumor showed enough criteria to give diagnosis of malignancy: nuclear pleomorphism, tumor cell spindling, vesicular nuclei with large nucleoli. Moreover, five lymph nodes were metastatic. Immunohistochemistry findings confirmed the diagnosis of granular cell tumor which is positive for S100 protein and CD68 antibodies. The mitotic index was nevertheless low with a Ki67 labeling index of 1-2%. A large surgical revision with an inguinal curage following radiotherapy were decided on oncology committee. Adjuvant radiotherapy on the tumor bed and right inguinal area of ​​50 Gy in conventional fractionation was delivered with the aim of reducing local recurrence risk. There was no recurrence on longer follow-up (10 months post radiotherapy). CONCLUSIONS: Adjuvant radiotherapy seems an appropriate therapeutic approach, even if controversial, given that some authors report effectiveness on local disease progression.

Cost utility modeling of early vs late total knee replacement in osteoarthritis patients.

Given the dramatic increase in the number of total knee replacement (TKR) surgeries in developed countries, the issue of the best time for surgery needs to be addressed from an economic perspective. OBJECTIVE: To assess, from the perspective of the healthcare payer, the cost-utility of two surgical strategies in which knee replacement is performed at the early or late stage of the disease in patients with knee osteoarthritis (OA). DESIGN: Patient data and evidence from published literature on economic costs and outcomes in OA, including utilities, non-pharmacological, pharmacological and surgical options, combined with population life tables were entered in a Markov model of OA. The model represented the lifetime experience of a cohort of patients following their therapeutic management, discounting costs (euros) and utilities (quality-adjusted life-years) at 4% annually. RESULTS: In the base-case scenario, early TKR cost €6,624 more than late TKR (€76,223 vs €69,599) with a 0.15 gain in QALYs (18.675 vs 18.524). This yielded an incremental cost-utility ratio (ICUR) of 43,631 €/QALY. Sensitivity analyses of the most influential uncertain parameters were performed and did not modify the direction of the conclusions: early TKR cost between €3,655 and €7,194 more than late TKR with a gain in QALYs between 0.15 and 0.39. The ICUR ranged from 17,131 €/QALY to 48,241 €/QALY. CONCLUSION: Our data do not support the early TKR strategy over the late TKR strategy in knee OA patients from a medico-economic perspective.

[Evaluation of breast HER2+ cancer pathologic response after a taxan plus trastuzumab-based chemotherapy]. / Étude de réponse histologique du cancer du sein HER2+ après chimiothérapie néoadjuvante associant taxane et trastuzumab.

OBJECTIVES: In our study, we aimed to assess the pathologic complete response after neo-additive chemotherapy that contains a taxan associated to trastuzumab for patients treated from breast cancer at the institute Jean-Godinot between 2012 and 2014, and to evaluate factors associated to this pathologic complete response. METHODS: Retrospective study with clinical, anatomopathologic and radiologic parameters analysis before and after new adjuvant chemotherapy. The statistical analysis was done on logiciel XL-STAT, the Mann-Whitney-Wilcoxon for quantitative variables and Fisher exact tests for qualitative variables, the Spearman rang test. RESULTS: The rate of pathologic complete response is 38.8%. The prognostic factor associated to pathologic complete response is a Ki-67>44%. CONCLUSION: The pathologic complete response rate corresponds to international lower rate; because of the lack of several data, we found out only one prognostic factor, Ki-67>44%.

[New approach of learning curve for robotic-assisted gynecologic oncology surgery]. / Nouvelle approche de la courbe d'apprentissage en chirurgie oncogynécologique robot-assistée.

OBJECTIVES: Define the phases composing the learning curve of total hysterectomy (TH) and radical hysterectomy with pelvic lymphadenectomy (RHPL) robot-assisted performed by a single surgeon with no prior experience in laparoscopic surgery. METHODS: We retrospectively analyzed 72 procedures (TH, n=34 and RHPL, n=38) conducted between 2002 and 2011. The surgeon console time (CT) was used to determine the learning curve of TH and RHPL using CUSUM analysis. Epidemiological data, perioperative and postoperative complications were compared from the different phases of the learning curve. RESULTS: CUSUM analysis of surgeon console time (CUSUMCT) identified two learning phases for the TH group (phase 1: initial learning, phase 2: surgical skill increase). For the RHPL group, three learning phases were identified (phase 1: initial learning, phase 2: extending surgical indications, phase 3: control of surgical skills). Perioperative and postoperative complication rates did not differ significantly between the learning phases. Surgeon CT decreased from the 9th case (P=0.01) for the TH group and from the 13th case (P=0.04) for the RHPL group. DISCUSSION: CUSUM analysis of the learning curve in robotic-assisted gynecologic oncology surgery identified two phases of learning curve for simple procedures such as total hysterectomy and three phases for more complex procedures as radical hysterectomy with pelvic lymphadenectomy.

The EULAR Outcome Measures Library: development and an example from a systematic review for systemic lupus erythematous instruments.

OBJECTIVES: Patient reported outcomes (PROs) are relevant in rheumatology. Variable accessibility and validity of commonly used PROs are obstacles to homogeneity in evidence synthesis. The objective of this project was to provide a comprehensive library of "validated PROs". METHODS: A launch meeting with rheumatologists, PROs methodological experts, and patients, was held to define the library's aims and scope, and basic requirements. To feed the library we performed systematic reviews on selected diseases and domains. Relevant information on PROs was collected using standardised data collection forms based on the COSMIN checklist. RESULTS: The EULAR Outcomes Measures Library (OML), whose aims are to provide and to advise on PROs on a user-friendly manner albeit based on scientific grounds, has been launched and made accessible to all. PROs currently included cover any domain and, are generic or specifically target to the following diseases: rheumatoid arthritis, osteoarthritis, spondyloarthritis, low back pain, systemic lupus erythematosus, gout, osteoporosis, juvenile idiopathic arthritis, and fibromyalgia. Up to 236 instruments (106 generic and 130 specific) have been identified, evaluated, and included. The systematic review for SLE, which yielded 10 specific instruments, is presented here as an example. The OML website includes, for each PRO, information on the construct being measured and the extent of validation, recommendations for use, and available versions; it also contains a glossary on common validation terms. CONCLUSIONS: The OML is an in progress library led by rheumatologists, related professionals and patients, that will help to better understand and apply PROs in rheumatic and musculoskeletal diseases.

Occult cancer in specimens of reduction mammaplasty aimed at symmetrization. A multicentric study of 2718 patients.

Women who have undergone surgical treatment for breast cancer often benefit from a contralateral reduction mammaplasty (CRM) aimed at symmetrization of the contralateral breast unaffected by the initial cancer. In our 7-year multicentric study (12 centers) of 2718 patients, incidence of CRM cancers (CRMc) was 1.47% (n = 40) [95% CI 1.05%-2.00%]. The CRMc group had significantly more initial mammary cancers of invasive lobular carcinoma (ILC, 22.5% vs 12.0%) and ductal carcinoma in situ (DCIS, 35.0% vs 21.6%) types than the healthy CRM group (p = 0.017). 35.0% (n = 14) of patients had en bloc resection; 25.0% (n = 10) of surgical specimens were correctly oriented. En bloc resection and orientation of surgical specimens enable precise pinpointing of the CRMc. A salvage lumpectomy may be proposed as an option when margins are invaded. The histological distribution of the 40 CRMc (mean size 12.7 mm) was carcinoma in situ (CIS) 70%, ILC 12.5%, invasive ductal carcinoma (IDC) 12.5% and tubular carcinoma (TC) 5.0%.

Response shift effects on measuring post-operative quality of life among breast cancer patients: a multicenter cohort study.

PURPOSE: To characterize response shift effects in patients with breast cancer (BC). METHODS: The QLQ-C30, BR23, and EurQOL-EQ-5D were assessed at baseline and at the end of the first hospitalization. We used the then-test approach to characterize changes in internal standards by calculating the mean difference between the then-test (retrospective measure) and pre-test baseline QoL assessments. The Ideal Scale Approach was also used to assess changes in standards by comparing health and QoL expectancies between baseline and the end of the first hospitalization. Successive Comparison Approach was used to assess changes in values through the longitudinal assessment of the relative importance of EuroQOL dimensions. RESULTS: The results of this study showed that recalibration RS effects occurred early after the first hospitalization for 6/15 dimensions of QLQ-C30 (emotional, cognitive, fatigue, insomnia, appetite loss, diarrhea) and 2/8 of BR-23 (future perspective, systemic therapy side effects). Moreover, health and QoL expectancies changed between the baseline and the end of the first hospitalization, and changes in values were seen for the self-care and usual activities dimensions of the EuroQOL-EQ-5D. CONCLUSIONS: The occurrence of RS early after the first hospitalization suggests that it needs to be taken into account to interpret QoL changes in BC.

[Surgery and postoperative radiation therapy in primary retroperitoneal sarcomas: experience of the cancer centre Alexis-Vautrin]. / Intérêt de la radiothérapie postopératoire dans la prise en charge des sarcomes rétropéritonéaux primitifs : expérience du centre Alexis-Vautrin.

PURPOSE: Surgical resection remains the standard treatment for patients with resectable retroperitoneal sarcomas. The aim of this study was to retrospectively analyse the outcomes of patients with primary retroperitoneal sarcoma. PATIENTS AND METHODS: We analysed data of 50 patients with primary retroperitoneal sarcoma who underwent curative-intent resection from 1975 to 2008. External beam radiotherapy and chemotherapy were delivered postoperatively. Demographics, surgical, pathological variables and chemo/radiation therapy were analysed as prognosis factors. RESULTS: There were 22 males and 28 females (mean age 54 ± 13 years). Surgery required visceral resections in 30 patients. There were 16 leiomyosarcomas, 25 liposarcomas and eight other sub-types. Twenty-one patients had clear surgical margins. Twenty-eight patients received postoperative external beam radiotherapy (median 45 Gy) and 15 received chemotherapy. At the end of the follow-up (median 55 months), local recurrence occurred in 39% (n=14) among R0/R1 resection group (n=36). Postoperative external beam radiotherapy tends to increase the time of local recurrence from surgery (27 vs. 13 months, P=0.05). The overall survival rates were 81%, 55% and 46% at 1, 3 and 5 years, respectively. Although R0 resection (P=0.01), well tumour differentiation (P=0.004) and postoperative external beam radiotherapy (P=0.02) significantly influenced overall survival in univariate analysis, only R0 resection was an independent prognostic factor in a multivariate analysis. CONCLUSION: We confirm the pre-eminence of radical surgery with negative margins as major prognostic factor and the benefit of postoperative radiotherapy.

Gender differences in the association between depressive mood and mortality: a 12-year follow-up population-based study.

BACKGROUND: Depressive mood has been associated with all-cause mortality in both men and women. This study aimed at exploring gender differences in the association between depressive mood and specific causes of mortality as well as factors that may account for it, including education, marital status, social support, health behaviors, and chronic diseases. METHODS: A population-based survey including 6043 subjects (2892 men and 3151 women) was conducted in 1996 in the north-east of France with a questionnaire covering education, marital status, social support, health behaviors (smoking status, alcohol consumption, body mass index), and chronic diseases. Depressive mood was measured using the Duke Health Profile questionnaire. Cox regression models were used to examine its association with subsequent natural all-cause mortality, and cardiovascular and cancer mortality. RESULTS: During a follow-up of 12.5 years, 406 men and 303 women died from a natural cause. Adjusting for all covariates, depressive mood predicted natural mortality in both men [Hazard Ratio (HR)=1.30; 95% confidence interval (CI): 1.00-1.69] and women (HR=1.37; 95% CI: 1.06-1.77). However, this association was significant for cardiovascular mortality in men (HR=1.63; 95% CI: 1.00-2.65) whereas it was significant for cancer mortality in women (HR=1.71; 95% CI: 1.11-2.64). LIMITATIONS: Baseline data were self-reported and the response rate was low. DISCUSSION: Preventive strategies aiming at reducing the increased mortality associated with depressive mood should take gender into account. Depressed men may warrant a better screening for cardiovascular risk factors and diseases, whereas depressed women may benefit from better cancer prevention measures.