Radiotherapy for patient with cardiac implantable electronic device, consensus from French radiation oncology society.

Radiotherapy in patients with cardiac implantable electronic device such as pacemakers or defibrillators, is a clinical situation that is becoming increasingly common. There is a risk of interaction between the magnetic field induced by accelerators and the cardiac implantable electronic device, but also a risk of device dysfunction due to direct and/or indirect irradiation if the cardiac implantable electronic device is in the field of treatment. The risk can be dose-dependent, but it is most often independent of the total dose and occurs randomly in case of neutron production (stochastic effect). The presence of this type of device is therefore described as a contraindication for radiotherapy by the French national agency for the safety of medicines and health products (Agence nationale de sécurité du médicament et des produits de santé, ANSM). Nevertheless, since radiotherapy is often possible, it is advisable to respect the recommendations of good practice, in particular the eligibility criteria, the monitoring modalities before, during and after irradiation according to the type of treatment, the dose and the characteristics of the cardiac implantable electronic device. It is sometimes necessary to discuss repositioning the device and/or modifying the treatment plan to minimize the risk of cardiac implantable electronic device dysfunction. We present the update of the recommendations of the French society of oncological radiotherapy on in patients with cardiac implantable electronic device.

Clinical and dosimetric impact of totally implantable venous access devices in radiotherapy of supra diaphragmatic Hodgkin Lymphoma.

PURPOSE: To evaluate attenuation of the totally implantable vascular access device (TIVAD) and assess its clinical and dosimetric impact on radiotherapy (RT) of lymphoma patients. MATERIALS AND METHODS: The first part of the study consisted of an in vitro approach by irradiating the TIVAD with different electron and photon energies. The attenuation data measured were compared with data calculated by our treatment planning system. All patients treated by radiotherapy for Hodgkin's lymphoma with their TIVAD in the target volume were then reviewed to assess the clinical outcome and dosimetric comparison using different plan metrics. All patients were treated by 3D conformal radiotherapy (3DCRT) or intensity-modulated radiotherapy delivered by Helical Tomotherapy (HT). RESULTS: Nineteen patients treated for stage I-III HL were studied. Seven patients were treated exclusively on the side of TIVAD and 12 were treated bilaterally. Median prescription dose was 30Gy. No significant clinical or dosimetric differences were observed between the side of the TIVAD and the contralateral side in patients treated bilaterally. HT resulted in a significantly higher conformity index (P<0.0022) and a significantly lower healthy tissue coverage (P=0.0008) than 3DCRT. The observed attenuation was 79% for 6 MeV, 59% for 9 MeV, and 46% for 12 MeV for electrons and 9% for 4 MV, 8% for 6 MV, 5% for 10 MV and 15 MV and 3% for 20 MV for X photons. CONCLUSION: TIVADs induce significant beam attenuation when using electrons, which can be overcome by using high-energy photons or by creating an exclusion zone in when HT is used.

Genetic counseling for cystic fibrosis: A basic model with new challenges.

While the goals of genetic counseling for cystic fibrosis - delivering relevant information on the risk of recurrence and nondirectional support of couples at risk in their reproductive choices - have not changed fundamentally, the practice has evolved considerably in the last decade, growing more complex to face new challenges but also proving more effective. Many factors have contributed to this evolution: technical progress in the exploration of the genome (new generation sequencing) and in reproductive medicine, but also societal developments promoting access to genetic information and the professionalization of genetic counselors in France. The prospect of expanded pre-conception screening of at-risk couples makes genetic counselors major actors not only in medical care centers, but also in modern society by contributing to genetic education among citizens. © 2020 French Society of Pediatrics. Published by Elsevier Masson SAS. All rights reserved.

[Lung cancer and elective nodal irradiation: A solved issue?] / Cancer du poumon et irradiation ganglionnaire prophylactique : un débat clos ?

Lung cancer treatment is a heavy workload for radiation oncologist and that field showed many evolutions over the last two decades. The issue about target volume was raised when treatment delivery became more precise with the development of three-dimensional conformal radiotherapy. Initially based upon surgical series, numerous retrospective and prospective studies aimed to evaluate the risk of elective nodal failure of involved-field radiotherapy compared to standard large field elective nodal irradiation. In every setting, locally advanced non-small cell lung cancer, localized non-small cell lung cancer, localized small cell lung cancer, exclusive chemoradiation or postoperative radiotherapy, most of the studies showed no significant difference between involved-field radiotherapy or elective nodal irradiation with elective nodal failure rate under 5% at 2 years, provided staging had been done with modern imaging and diagnostic techniques (positron emission tomography scan, endoscopy, etc.). Moreover, if reducing irradiated volumes are safe regarding recurrences, involved-field radiotherapy allowed dose escalation while reducing acute and late oesophageal, cardiac and pulmonary toxicities. Consequently, major clinical trials involving radiotherapy initiated in the last two decades and international clinical guidelines recommended omission of elective nodal irradiation in favour of in-field radiotherapy.

Correlation between pelvic bone marrow radiation dose and acute hematological toxicity in cervical cancer patients treated with concurrent chemoradiation.

PURPOSE: To evaluate the association between pelvic bone marrow (BM) dose volume parameters and probability of acute hematological toxicity (HT), a cohort of cervical cancer patients receiving definitive chemoradiation (CRT) was assessed. MATERIALS AND METHODS: Medical records of patients treated by CRT (45 Gy in 25 fractions, without dose constraints applied to the BM) were reviewed. Baseline and weekly hematological parameters were collected. BM was retrospectively delineated and divided into sub-sites: iliac crests, lower pelvis, lumbosacral region. BM volumes (V) receiving 5, 10, 20, 30, 40 Gy (V5, V10, V20, V30, V40, respectively) and mean dose (Dm) were calculated. Logistic regression was used to analyze associations between HT and dose-volume histograms parameters. RESULTS: 114 patients were included. 75.4% were treated with 3D radiation therapy and 24.6% were receiving intensity modulated radiation therapy (IMRT). Neither age, chemotherapy regimen (cisplatin vs carboplatin), number of chemotherapy cycles, performance status, body mass index, or para-aortic irradiation were associated with HT. In univariate analysis, more frequent grade 3+ leukopenia was found in the IMRT group (odds ratio [OR]: 3.5; 95% CI, 1.4-9.1; p=0.007). In multivariate analysis, grade 4 HT was associated with lower pelvis V5>95% (OR 4.1; 95% CI, 1.6-14. p=0.02), lower pelvis V20>45% (OR 3.5; 95% CI, 1.1-13.4; p=0.05), total pelvic bone V20>65%, and iliac crests Dm >31 Gy (OR 4.5; 95% CI, 1.4-14.7; p=0.02). CONCLUSION: The following dose constraints could be proposed to decrease acute HT risk: lower pelvis V5<95%, lower pelvis V20≤45%, total pelvic bone V20<65%, and iliac crests Dm <31 Gy.

[Stereotactic body radiotherapy: Prospective study to evaluate asthenia and quality of life]. / Radiothérapie en conditions stéréotaxiques : étude prospective évaluant la fatigue et la qualité de vie.

PURPOSE: To evaluate prospectively asthenia and the quality of life in patients treated by stereotactic body irradiation and to determine their predictive factors. METHODS AND MATERIALS: Quality of life was assessed by the EORTC QLQ-C30 and asthenia was evaluated with the Brief Fatigue Inventory (BFI), on the first day (T1), last day (T2) and 1-3 weeks after the end of treatment (T3). RESULTS: Sixty-three patients were treated with stereotactic body irradiation from February 2017 to May 2017 and 41 were included in the analysis (22 patients excluded for lack of understanding, organization, psychologic disorders or refusal). The mean number of fractions was 5 (±2). The compliance to quality of life assessment was 98%, 95% was 81% at T1, T2 and T3, respectively. An increase of asthenia and a worsened quality of life were found in 12 (29%) and 14 (34%) patients between T1 and T2. Univariate analysis demonstrated a correlation between asthenia and quality of life were correlated with performans status (P=0.03 and 0.05 respectively), hemoglobin level (p=0.01 and 0.004), albumin level (P=0.01 and 0.06), distance between home and radiotherapy department (P=0.05 and 0.02). Multivariate analysis demonstrated a correlation between female gender (P=0.012), albumin level (P<0.001), distance over 25km (P<0.001) with asthenia, and albumin level (P=0.003), hemoglobin level (P=0.004) and previous chemotherapy (P=0.003) with quality of life. No influence of stereotactic body ratiotherapy parameters was seen. CONCLUSION: Despite hypofractionation, stereotactic body radiotherapy induced asthenia and deterioration of quality of life.

Charge transport through redox active [H7P8W48O184]33- polyoxometalates self-assembled onto gold surfaces and gold nanodots.

Polyoxometalates (POMs) are redox-active molecular oxides, which attract growing interest for their integration into nano-devices, such as high-density data storage non-volatile memories. In this work, we investigated the electrostatic deposition of the negatively charged [H7P8W48O184]33- POM onto positively charged 8-amino-1-octanethiol self-assembled monolayers (SAMs) preformed onto gold substrates or onto an array of gold nanodots. The ring-shaped [H7P8W48O184]33- POM was selected as an example of large POMs with high charge storage capacity. To avoid the formation of POM aggregates onto the substrates, which would introduce variability in the local electrical properties, special attention has to be paid to the preformed SAM seeding layer, which should itself be deprived of aggregates. Where necessary, rinsing steps were found to be crucial to eliminate these aggregates and to provide uniformly covered substrates for subsequent POM deposition and electrical characterizations. This especially holds for commercially available gold/glass substrates while these rinsing steps were not essential in the case of template stripped gold of very low roughness. Charge transport through the related molecular junctions and nanodot molecule junctions (NMJs) has been probed by conducting-AFM. We analyzed the current-voltage curves with different models: electron tunneling though the SAMs (Simmons model), transition voltage spectroscopy (TVS) method or molecular single energy level mediated transport (Landauer equation) and we discussed the energetics of the molecular junctions. We concluded to an energy level alignment of the alkyl spacer and POM lowest occupied molecular orbitals (LUMOs), probably due to dipolar effects.

[Management of patients with pacemakers or implantable cardioverter defibrillator undergoing radiotherapy]. / Prise en charge des patients porteurs de stimulateurs cardiaques ou défibrillateurs automatiques implantables traités par irradiation.

An increasing number of patients with cardiac implantable electronic devices benefit from radiotherapy, warranting specific collaborative management between both radiation oncologists and cardiologists. Interactions between electromagnetic fields, secondary particles and cardiac implantable electronic devices may result in transient and reversible malfunctions with significant consequences depending on the underlying cardiac pathology and the level of patient's cardiac implantable electronic devices dependency. Numerous international guidelines on patients' management have been proposed and all agree on a total cumulated dose limit at the battery of 5Gy and on the need for an initial as well as repeated evaluation over time, up to 6months after the last radiation. The analysis of the published data revealed relatively rare incidence of significant adverse events. The most recent international guidelines underline the feasibility and safety of radiotherapy for cardiac implantable electronic devices holders, with the need for systematic local protocol in all radiotherapy centers.

[Recommendations for the management of bone demineralization in cystic fibrosis]. / Recommandations pour la prise en charge de la déminéralisation osseuse dans la mucoviscidose.

A high prevalence of low bone mineralization is documented in adult patients with cystic fibrosis (CF). Osteopenia is present in as much as 85% of adult patients and osteoporosis in 13 to 57% of them. In children, studies are discordant probably because of different control database. Denutrition, inflammation, vitamin D and vitamin K deficiency, altered sex hormone production, glucocorticoid therapy, and physical inactivity are well known risk factors for poor bone health. Puberty is a critical period and requires a careful follow-up for an optimal bone peak mass. This review is a consensus statement established by the national working group of the French Federation of CF Centers to develop practice guidelines for optimizing bone health in patients with CF. Recommendations for screening and for calcium, vitamin D and K supplementation are given. Further work is needed to define indications for treatment with biphosphonates and anabolic agents.

Neonatal screening of cystic fibrosis: diagnostic problems with CFTR mild mutations.

Newborn screening (NBS) of cystic fibrosis (CF) was implemented throughout the whole of France in 2002, but it had been established earlier in three western French regions. It can reveal atypical CF with one or two known CFTR mild mutations, with an uncertain evolution. The sweat test can be normal or borderline. In Brittany, from 1989 to 2004, 196 CF cases were diagnosed (1/2885 births). The incidence of atypical CF diagnosed by NBS is 9.7% (19 from 196). The outcome of 17 (2 lost of view) has been studied, with 9 other atypical CF cases diagnosed by NBS in two other regions. The follow-up period extends from 0.25 to 19.8 years (NBS implemented in Normandy in 1980) with mean age 4.6 years. The most frequent mild mutation is R117H ISV8-7T (50%). At the time of the last visit, nutritional status is normal. All these CF patients are pancreatic sufficient. Only one patient exhibits respiratory infections, whereas 7 others have them intermittently. Two of them had intermittent Pseudomonas aeruginosa colonization at 2.8 and 6.5 years. Mean Shwachman score is 96.7, mean Brasfield score is 22.8. Eight children have had lung function tests (mean follow-up of 10 years): mean FVC was 99% of predicted, mean FEV1 101%, but one of them has FEV1 of 48%. Predicting the phenotype of these atypical CF patients remains difficult, thus complicating any genetic counselling. A regular clinical evaluation is necessary, if possible by a CF unit, because CF symptoms may appear later.

[Pseudomonas aeruginosa and cystic fibrosis: first colonization to chronic infection]. / Pseudomonas aeruginosa et mucoviscidose: "de la primocolonisation a l'infection chronique".

Pseudomonas aeruginosa (Pa) is the most common virulent respiratory pathogen in cystic fibrosis and is characterized by an important capacity of adaptation, adherence and communication. The factors of virulence of Pa play a major part in adherence with the respiratory epithelial cells and in occurrence of infectious episodes. The factors responsible for the transition of first Pa acquisition to the chronic infection are not elucidated yet. The system of secretion of type III and the quorum sensing (QS) play an important role. The QS would intervene in the maturation of the biofilm of Pa, responsible for the "mucoid" phenotype of Pa, associated to a degradation of the respiratory function. We made a retrospective study on the period 1984-2005 within the Center of Cystic fibrosis of Caen allow to determine the percentage of firstly-colonized and chronic infected patients with Pa according to age. At 6 months of life, 11% of the infants were colonized with Pa reaching 48% to 7 years and 85% at the 18 years age. The percentage of chronic children carrying Pa was 0% at 1 year, 11% at 4 years, 44% at 12 years and 74% at 18 years according to the method of Kaplan-Meier. Comparing the period 1984-1994 with that of 1995-2005, the firstly-colonization and the chronic carrying of Pa occurred earlier and significantly during the second period. The current objective, beside the respiratory care, comprises the maintenance of an optimal nutritional statute and, waiting for an effective vaccine, the development of new therapeutic targets in order to attenuate the virulence of the stocks of Pa and as much as possible to delay the age of firstly-colonization and the age of chronic colonization with mucoid Pa.

[Evaluation of diagnosis and follow-up in screened children with cystic fibrosis in Normandy]. / Evaluation du diagnostic et du suivi de la cohorte normande d'enfants dépistés atteints de mucoviscidose.

The neonatal screening programme in Normandy (France) allowed the formation of a homogenous cystic fibrosis (CF) cohort of 150 children diagnosed between 1980 and 1997. At the time of this retrospective study, 11 were deceased, out of which nine had meconium ileus (eight deaths after surgery, one at 5 years of age). Sixty children born between 1980 and 1993 in the Basse-Normandie region were followed up during a mean 80 months following similar protocols. The mean age at diagnosis was 41 days (SD = 27 d) for infants without meconium ileus. The occurrence of Pseudomonas aeruginosa (P. aeruginosa) infection and chronic colonization was studied using a monovariate followed by a multivariate analysis including the following variables: sex; meconium ileus; anthropometric data at birth and at diagnosis; pancreatic insufficiency; radiological data (Brasfield score); microbiology data at diagnosis; and genetic data. P. aeruginosa infection appeared earlier in children with pancreatic insufficiency (OR = 2.2; p < 0.05) or with radiological abnormalities (Brasfield score < 21) at diagnosis (OR = 3.9; p < 0.05). Meconium ileus (OR = 5.3; p < 0.01), pancreatic insufficiency (OR = 3.8; p < 0.01) and Brasfield score < 21 at diagnosis (OR = 5.6; p < 0.001) were prognosis factors for early chronic P. aeruginosa colonization. In CF children without meconium ileus, the major risk factor found through multivariate analysis for earlier infection and for earlier chronic colonization by P. aeruginosa was a diagnosis delay > 40 days (respectively OR = 4.6; p < 0.001 and OR = 10.4; p < 0.005). These results must be compared with the lower Brasfield score at diagnosis in infants diagnosed after 40 days of life (p < 0.01).

Reliability and validity of a chronic care facility adaptation of the Clinical Dementia Rating scale.

OBJECTIVE: This study investigated the reliability and validity of a chronic care facility adaptation of the Clinical Dementia Rating scale (CDR-CC). METHOD: Sixty-two residents in a chronic care facility participated in an inter-rater and 1 month test-retest reliability study. The instrument was validated against the Mini-Mental State Examination (MMSE). RESULTS: Inter-rater and 1 month test-retest reliability for the global CDR-CC score were excellent (intraclass correlation coefficients 0.99 and 0.92, respectively). The CDR-CC domain and global scores were negatively correlated with the MMSE. CONCLUSIONS: The CDR-CC is a global assessment tool that reliably and validly measures cognitive and functional impairment in a chronic care setting.

[Prevention of vitamin D deficiency in adolescents and pre-adolescents. An interventional multicenter study on the biological effect of repeated doses of 100,000 IU of vitamin D3]. / Prophylaxie de la carence en vitamine D chez l'adolescent et le préadolescent. Etude interventionnelle multicentrique sur les effets biologiques d'un apport répété de 100,000 UI de vitamin D3.

UNLABELLED: Recent studies have shown a high prevalence of calcium and vitamin D deficiencies in adolescents. The aim of this present study was to follow the changes in calcium status and 25 hydroxyvitamin D (25[OH]D) and parathyroid hormone (iPTH) levels during winter in preadolescents and adolescents from four university hospitals in northern France. SUBJECTS AND METHODS: Two groups of teenagers and adolescents (range: 10-15 years) were followed from October 1996 to June 1997. They were given either 100,000 IU of vitamin D (treated group n = 33) or a placebo (control group n = 35) in October, January and April. Serum calcium, phosphate, 25(OH)D and iPTH levels were measured at inclusion and every three months thereafter. RESULTS: At inclusion, plasma or serum 25(OH)D levels were < or = 10 ng/mL in 16 subjects and < 6 ng/mL in six. In control children, no significant change in 25(OH)D occurred during the study, while plasma or serum iPTH levels increased to 34 +/- 11 pg/mL. In the treated groups, 25(OH)D levels remained > 20 ng/mL in every subject; no hypercalcemia was observed; and the mean plasma or serum iPTH level was 25 +/- 14 pg/mL at the end of the study. CONCLUSION: Teenagers presented with a high prevalence of biological vitamin D deficiency at the end of summer. The increase of iPTH during winter in the unsupplemented group suggests that this has secondary consequences on their calcium homeostasis unless they are supplemented with vitamin D. We advocate a sufficient calcium supply and a 100,000 IU vitamin D supplement given two or three times during winter to preadolescents and adolescents living in northern France.

Differential effects of apolipoprotein E isoforms on metal-induced aggregation of A beta using physiological concentrations.

The epsilon 4 allele of apolipoprotein E (APOE) has been found to be a risk factor for late-onset Alzheimer's disease (AD). While the pathogenic mechanism of APOE in AD is not yet clear, APOE isoforms appear to differentially influence the aggregation of A beta, the principal component of Alzheimer-associated beta-amyloid deposits. To date, no data are available for the propensity of A beta to aggregate in the presence of APOE under conditions where these components are at physiological concentrations (in cerebrospinal fluid, APOE and A beta are approximately 100 nM and approximately 5 nM, respectively). We employed a novel in vitro filtration assay for detecting zinc(II)- and copper(II)-induced aggregation of A beta in solutions containing concentrations of the peptide that are similar to those reported for human cerebrospinal fluid. The potential for resolubilization with EDTA and the relative densities of zinc- and copper-induced A beta aggregates were also compared. Zinc-induced A beta aggregates were found to be denser and less easily resolubilized than copper-induced precipitates. Metal-induced aggregation of A beta was studied in the presence of purified apolipoprotein E2, apolipoprotein E3, and apolipoprotein E4 under conditions that approximate the physiological concentrations and ratios of these proteins. In the presence of all three APOE isoforms, zinc-induced aggregation of A beta was attenuated, while precipitation with copper was enhanced. Consistent with the increased risk for AD associated with the epsilon 4 allele of APOE, metal-induced aggregation of A beta was highest for both zinc and copper in the presence of apolipoprotein E4. Our data are consistent with a role for APOE as an in vivo molecular chaperone for A beta.