Search

Nous avons mene une etude pilote sur l’evaluation de l’interet d’un groupe de paroles pilote, fonde sur l’analyse existentielle et la logotherapie (therapie centree sur le sens existentiel), parallelement au traitement medical du cancer du sein. Un groupe de femmes suivi a l’institut de cancerologie Hartmann, en derniere phase de traitement d’un cancer du sein, dans ce moment tres particulier de transition entre maladie et reprise d’une vie « normale », a ete selectionne pour participer au groupe de paroles. Entre decembre 2015 et juin 2016, huit femmes ont participe au groupe de paroles. Les resultats extraits d’une seance de bilan ainsi que d’un questionnaire de satisfaction auquel ont repondu toutes les participantes montrent l’importance de la parole, des liens crees, seance apres seance, au sein du groupe et du soutien apporte par la synergie groupe–animateurs pour affirmer une nouvelle dynamique de vie — une noodynamique — selon les termes de Viktor Frankl (1905–1997), psychiatre et fondateur de la logotherapie, et redonner du sens a son existence. Les resultats des groupes de paroles sur la qualite de vie des patientes traitees pour un cancer du sein sont encourageants, et l’instauration de ces groupes de paroles et de logotherapie serait strategique pour un plus grand nombre de patientes.

Resume Analyse de la litterature medicale scientifique consacree au bilan, a l’epidemiologie, au controle local, a la survie ainsi qu’aux complications et sequelles apres traitement conservateur des carcinomes epidermoides de stade « precoce » de la region amygdalienne. Analyse de la base de donnees PubMed (1975–2016) avec les mots cles et les associations qui suivent : « amygdale/loge amygdalienne/oropharynx » et « cancer epidermoide » et « stade precoce (I–II ; T1-T2N0M0) » et « radiotherapie » ou « chirurgie conservatrice/oropharyngectomie/chirurgie transorale/amygdalectomie radicale ». Cette recherche electronique trouvait dix articles retrospectifs qui analysaient specifiquement survie et controle local au sein de series de plus de 50 patients avec un recul minimum de 2 ans apres traitement conservateur et aucun article prospectif, meta-analyse et/ou etude Cochrane. L’imagerie par resonance magnetique nucleaire est l’examen radiologique clef du bilan d’extension locale. L’infestation par l’ human papilloma virus est un facteur de risque a rechercher systematiquement, car il favorise la radiosensibilite tumorale et expose a des secondes localisations synchrones et metachrones specifiques. Quel que soit le traitement conservateur realise, des taux de controle local et de survie superieure a 85 % etaient notes. La modulation d’intensite reduisait la morbidite de la radiotherapie. La chirurgie transorale avait une faible morbidite/mortalite tout en permettant la realisation d‘un evidement ganglionnaire ipsilateral et en preservant la radiotherapie pour le traitement des secondes localisations metachrones. La chirurgie transorale semble l’option therapeutique a privilegier dans la majorite des cas. Un suivi a vie adapte au statut HPV doit etre realise. La mise en place de vaccination anti-HPV ne doit pas faire perdre de vue l’importance de la lutte contre le tabagisme et l’enolisme.

Purpose There are only scarce data on the place of brachytherapy (BT) for treatment of vulvar carcinoma. Our institutional experience of interstitial BT for vulvar carcinoma patients is reported. Methods and Materials Clinical records of patients receiving low-dose-rate or pulsed-dose-rate BT as part of the primary treatment for primary/recurrent vulvar squamous cell carcinoma or as part of postoperative treatment between 2000 and 2015 were included. Patients, tumors, and treatment characteristics as well as clinical outcome were examined. Results A total of 26 patients treated with BT were identified. BT was delivered as part of primary intent treatment for locally advanced/recurrent cancer in 11 patients and as part of postoperative treatment in 15 patients. Median age at time of BT was 63 years (range, 41–88 years). Pulsed-dose-rate and low-dose-rate were used in 15 patients and 11 patients, respectively. BT was performed as a boost to the tumor bed following external beam radiotherapy ( n = 13) or as the sole irradiation modality ( n = 13). Total median dose at the level of primary tumor was 60 GyEQD2 (range, 55–60 GyEQD2). With mean followup of 41 months (range, 5 months–11.3 years), 11 patients experienced tumor relapse, and in two of them, site of relapse was only local. Three-year estimated disease-free survival and overall survival rates were 57% (95% confidence interval: 45–69%) and 81% (95% confidence interval: 72–90%), respectively. All toxicities were Grade 2 or less. Conclusions Interstitial BT used as part of the primary or postoperative treatment of vulvar carcinoma is feasible with a satisfactory toxicity profile. Prognosis remains, however, dismal, with a high frequency of failures in patients with locally advanced tumors.

Along with the surgeon, the gastroenterologist and the general practitioner, the radiation oncologist is involved in the follow-up of patients with rectal cancer treated by radiation. Post-treatment follow-up is recommended by major professional expert groups and consists of clinical examination, monitoring of carcinoembryonic antigen, colonoscopy and computed tomography of the abdomen and pelvis. Three recent large phase III randomized trials demonstrated a lack of survival benefit from intensive follow-up strategies in comparison with minimal follow-up. However, a follow-up program is not only important for the detection of an early disease relapse but it can be also used for the identification and the management of long-term toxicity and sequalae related to rectal cancer treatment.

Along with the surgeon, the gastroenterologist and the general practitioner, the radiation oncologist is involved in the follow-up of patients with rectal cancer treated by radiation. Post-treatment follow-up is recommended by major professional expert groups and consists of clinical examination, monitoring of carcinoembryonic antigen, colonoscopy and computed tomography of the abdomen and pelvis. Three recent large phase III randomized trials demonstrated a lack of survival benefit from intensive follow-up strategies in comparison with minimal follow-up. However, a follow-up program is not only important for the detection of an early disease relapse but it can be also used for the identification and the management of long-term toxicity and sequalae related to rectal cancer treatment.

Image-guided adaptive brachytherapy (IGABT) is a high-precision radiation that allows defining accurately treatment targets and optimizing their coverage whereas sparing efficiently the surrounding organs at risk. Ten years ago, in a will of harmonizing the reporting of brachytherapy, the Groupe Européen de Curiethérapie - European Society for Radiation Oncology (GEC-ESTRO) published recommendations on target definitions and dosimetric parameters. During the last years, clinical and dosimetric studies supporting their relevance led the International Commission on Radiation Units and Measurements to propose a report on prescribing and reporting. This review aims to highlight the recent advances in IGABT and its future developments.Clinical evidence demonstrating the superiority of IGABT over radiographs-based brachytherapy is accumulating. In parallel, dose-volume effects have been established between dose-volume parameters and tumor response or the occurrence of late radiation morbidity. Preliminary studies indicate that planning aims could be adapted to clinical situations and cofactors. The first publications from the large studies led by the GEC-ESTRO enforce these findings.A trend emerges toward a personalization of treatment with the adaptation of planning aims to prognostic features and the development of individualized applicators. Image-guidance modalities are developed with a better use of MRI or conversely the use of more accessible modalities such as transrectal ultrasound.

Image-guided adaptive brachytherapy is a high precision technique that allows dose escalation and adaptation to tumor response. Two monocentric studies reported continuous dose-volume response relationships, however, burdened by large confidence intervals. The aim was to refine these estimations by performing a meta-regression analysis based on published series.Eligibility was limited to series reporting dosimetric parameters according to the Groupe Européen de Curiethérapie-European SocieTy for Radiation Oncology recommendations. The local control rates reported at 2-3 years were confronted to the mean D90 clinical target volume (CTV) in 2-Gy equivalent using the probit model. The impact of each series on the relationships was pondered according to the number of patients reported.An exhaustive literature search retrieved 13 series reporting on 1299 patients. D90 high-risk CTV ranged from 70.9 to 93.1 Gy. The probit model showed a significant correlation between the D90 and the probability of achieving local control (p0.0001). The D90 associated to a 90% probability of achieving local control was 81.4 Gy (78.3-83.8 Gy). The planning aim of 90 Gy corresponded to a 95.0% probability (92.8-96.3%). For the intermediate-risk CTV, less data were available, with 873 patients from eight institutions. Reported mean D90 intermediate-risk CTV ranged from 61.7 to 69.1 Gy. A significant dose-volume effect was observed (p = 0.009). The D90 of 60 Gy was associated to a 79.4% (60.2-86.0%) local control probability.Based on published data from a high number of patients, significant dose-volume effect relationships were confirmed and refined between the D90 of both CTV and the probability of achieving local control. Further studies based on individual data are required to develop nomograms including nondosimetric prognostic criteria.

Objective To examine the clinical results of a preoperative image-guided pulse-dose-rate brachytherapy (PDR-BT) in early stage cervical cancer. Materials/methods We examined the outcome of consecutive patients with early stage cervical cancer undergoing preoperative image-guided PDR-BT between 2004 and 2013 because of risk factors (lymphovascular embols and/or tumour>2cm). The objective was to deliver 60Gy to 100% of the intermediate risk clinical target volume. Brachytherapy was followed, 6–8weeks later, by a radical hysterectomy/bilateral salpingo-oophorectomy plus pelvic +/− para-aortic lymph node dissection. Patients with positive lymph nodes had postoperative chemoradiation. Results 77 patients met the above criteria of preoperative PDR-BT. On hysterectomy specimen, 54 (70.1%) presented a complete histological response. Four (5.2%) had a tumour residuum⩾1cm. Median follow-up was 46.8months. 5-Year disease-free survival (DFS) rate was 84.4%. Only one local recurrence was observed. The presence of lymph nodal metastases, a tumour size>3cm and a brachytherapy/surgery time interval⩾9weeks correlated with a poorer DFS. Six postoperative complications were encountered (7.8%). Total reference air kerma correlated with late vaginal toxicity ( p =0.02). Conclusions A preoperative image-guided PDR-BT was safe and effective. Predictive factors for survival and toxicity were evidenced.

ObjectiveThe aim of this study was to report our institutional experience of a multimodal approach for treatment of locally advanced high-grade neuroendocrine cervical cancer.Methods and MaterialsPatients with primary locally advanced neuroendocrine cervical cancer diagnosed between 2001 and 2014 were included. The scheduled treatment sequence was as follows: pelvic +/− para-aortic radiotherapy (according to tumor stage), associated with chemotherapy based on platine-derivate and etoposide regimen, followed with a brachytherapy boost, then completion surgery if there was no progression +/− consolidation etoposide chemotherapy (for a total of 5–6 cycles). Disease-free survival (DFS) and overall survival (OS) were reported and prognostic factors were searched.ResultsA total of 24 patients fulfilled inclusion criteria. Median age was 48 (range 22–77 years). Fourteen patients (58%) had pelvic lymph node metastases. After chemoradiation/brachytherapy, a radical hysterectomy could be performed in 18 of 24 patients (75%). Histologically complete resection was achieved in 14 (78%) of 18 patients. Complete pathological response was reported in 7 (39%) of 18. With median follow-up of 29.7 months, 10 (42%) of 24 patients experienced tumor relapse, all associated with distant failure, including one local failure. The DFS and OS rates estimated at 3 years were 55% and 63%, respectively. Lymph node metastases and tumor stage were prognostic for DFS (P = 0.016 and P = 0.022, respectively). Complete resection was associated with a lower incidence of relapses, as compared with microscopically incomplete resection (P = 0.04). A total of 12 (86%) of 14 patients with histologically complete resection were in complete remission at last follow-up. Apart from manageable acute hematological toxicities, most treatment complications were mild to moderate.ConclusionsThis series based on a multimodal management compares favorably with previously published data. Most patients could be eligible to surgery, and complete remission was achieved in 85% of those amenable to complete resection.

To report the outcomes and late toxicities of patients with locally advanced cervical cancer treated with concomitant chemoradiation (CRT) followed by intracavitary image-guided adaptive brachytherapy (IGABT).Data from consecutive patients with histologically proven stage IB-IVA cervical cancer treated with curative intent in a single institution were analyzed. After pelvic +/- para-aortic external-beam radiation therapy, they received pulsed-dose rate IGABT following GEC-ESTRO recommendations.Two hundred and twenty-five patients were enrolled. Sixty-five percent were stage≥IIB according to FIGO classification. Ninety-five percent received CRT. Mean D90 to HR and IR-CTV were 80.4+/-10.3Gy and 67.7+/-6.1Gy. After a median follow-up of 38.8months, 3-year local control and overall survival rates were 86.4% and 76.1%, respectively. A trend for a detrimental effect of tumor stage on local control rates was observed with 3-year local control rates of 100% for stages IB1 and IIA, 90.5 for IB2, 85.8% for IIB, 50% for IIIA, 77.1 for IIIB, and 66.7% for IVA tumors (p=0.06). Local control rates at 3years were 95.6% in the group of patients with D90 of HR-CTV≥85Gy, 88.8% in those with D90 between 80 and 85Gy, and 80% when D9080Gy (p=0.018). Eighteen severe late gastrointestinal and urinary effects affecting 14 patients were reported corresponding with a crude incidence of 6.6%.CRT followed by IGABT provides high local control rates with limited toxicity. Reaching high doses is mandatory to achieve local control and interstitial brachytherapy is necessary in advanced diseases.

To analyze the medical literature devoted to work-up, epidemiology, local control, survival, complications and sequelae after conservative treatment for early-stage squamous cell carcinoma of the tonsillar region. An analysis of the PubMed (1975-2016) database was performed using the following keywords and associations: "tonsil/tonsillar region/oropharynx" AND "squamous cell carcinoma" AND "early-stage (I-II; T1-2N0M0)" AND "radiation therapy/radiotherapy" OR "conservative surgery/oropharyngectomy/transoral surgery/radical tonsillectomy". The search retrieved 10 retrospective series documenting local control and/or survival in series with more than 50 cases and a minimum 2 years' follow-up after conservative treatment; no prospective studies, meta-analyses and/or Cochrane analyses were found. Magnetic resonance imaging is the key radiological exam for local extension assessment. Human papilloma virus infection (HPV) is a risk factor that must be screened for systematically, since it induces tumoral radio-sensitivity and increases the risk of specific synchronous and metachronous second primaries. Whatever conservative treatment used, local control and survival rates higher than 85% were achieved. Implementing intensity-modulated radiation therapy reduced the incidence and severity of radiation-related complications and sequelae. Transoral surgery yielded very low morbidity/mortality rates, enabled association to ipsilateral neck dissection, and allowed radiation therapy to be reserved for the management of metachronous second primaries. Transoral surgery appeared to be the first-line option in the majority of cases. Lifetime follow-up adapted to HPV status is mandatory. The development of HPV vaccination does not mean that campaigns against smoking and alcohol abuse are of diminished importance.

Introduction L’exposition aux UV, artificiels ou naturels, constitue un des elements majeurs du traitement du vitiligo (V) alors meme que certains phenotypes de V pourraient etre photo-declenches. A ce jour cependant, on sait peu de choses sur les habitudes de protection solaire chez les patients atteints de V. Materiel et methodes A partir du 20/4/17, une etude prospective transversale sur auto-questionnaire a ete initiee aupres des patients adultes consentants adherents de l’Association francaise du Vitiligo et des patients souffrant de V consultant spontanement au sein de 2 CHU francais (Creteil – Bordeaux). Deux questionnaires valides etaient administres : l’un permettant de determiner le phototype (PT) (I a III = peau claire [PC] et IV a VI = peau mate [PM]) ; l’autre la severite auto-percue. Resultats Au 31 mai 2017, un total de 196 patients avec un V avaient repondu au questionnaire : PC : 61,7 % vs PM : 38,3 % ; 78 % etaient des femmes. Seule la frequence de localisation sur le visage etait differente entre les 2 groupes : 89,2 % chez les PC vs 98 % chez les PM (p = 0,006). Au total, 14,8 % declarent avoir pele au cours des 12 derniers mois pour 14,2 % ayant declare un coup de soleil. En termes de connaissance des risques, 86,7 % pensent qu’il existe un risque augmente de brulure de la peau atteinte de V par rapport a la peau normale (90,3 % pour les PC vs 81,3 % pour les PM (p = 0,039)) alors qu’il n’y avait pas de difference observee en ce qui concerne la perception d’un risque accru de cancer cutane (47,96 %). De la meme maniere, 73,53 % des PC vs 61,13 % des PM declarent eviter de s’exposer au soleil entre 11 h et 17 h (p = 0,03). Enfin, 76,8 % des PC declarent eviter le soleil a cause de leur V vs 54,6 % chez les PM (p Discussion Il semblerait selon nos resultats preliminaires que la declaration d’un coup de soleil au cours de l’annee passee soit associee a un usage plus strict des moyens de protection solaire chez les sujets atteints de V. Par ailleurs, la perception d’un risque accru de cancer cutane chez ces derniers concerne pres d’un participant sur 2 alors meme qu’il existe desormais de forts arguments epidemiologiques et physiopathologiques qui vont dans le sens d’un risque moindre de cancer cutane dans la population atteinte de V, et ce meme apres ajustement sur la protection solaire. Conclusion Enfin, nous prevoyons d’analyser de maniere plus fine le lien entre severite du V et attitude de protection solaire.

Long-chain 3-hydroxyacyl CoA dehydrogenase deficiency and choroidal neovascularization D. Stopek, E. Gitteau Lala, F. Labarthe, M.L. Le Lez, S. Majzoub, P. Castelnau, P.J. Pisella We report the case of a 9-year-old girl with a long-chain 3-hydroxyacyl CoA dehydrogenase (LCHAD) deficiency. This enzyme participates in mitochondrial fatty acid β-oxidation. Genetic fatty acid oxidation defects induce cellular energetic deficiency, and thus early life-threatening manifestations. An appropriate diet prevents these severe disorders. Nevertheless, LCHAD deficiency is the only β-oxidation enzymatic disorder that induces a chorioretinopathy, predominating at the posterior pole. We describe the first case of bilateral macular choroidal neovascularization. One eye presented a fibrovascular lesion. The other eye presented an active neovascularization stabilized by two dynamic phototherapies. The specificity of choroidal degeneration related to LCHAD deficiency remains unknown. Reviewing of literature and biochemical mechanisms suggests that fatty acid oxidative stress rather than a mitochondrial energetic defect is involved. For practical purposes, this report emphasizes the importance of ophthalmological follow-up of these patients.

Purpose To establish dose–volume effect correlations for late bladder and rectum side effects in patients treated for locally advanced cervical cancer with concomitant chemoradiation followed by pulsed-dose rate image-guided adaptive brachytherapy. Material and methods The dosimetric data, converted in 2Gy equivalent, from 217 patients were confronted to late morbidity defined as any event lasting or occurring 90days after treatment initiation. Toxicity was assessed using the CTC-AE 3.0. Probit analyses and Log rank tests were performed to assess relationships. Results One hundred and sixty-one urinary and 58 rectal events were reported, affecting 98 (45.1%) and 51 (23.5%) patients, respectively. Cumulative incidences for grade 2–4 bladder and rectal morbidity were 24.3% and 9.6% at 3years, respectively. Significant relationships were observed between grade 2–4 and 3–4 events and D0.1cm 3 and D2cm 3 for the bladder and between grade 1–4 and 2–4 event probability and rectal D2cm 3 . The effective doses for 10% grade 2–4 morbidity were 65.3Gy (59.8–81.3), and 55.4Gy (15.7–63.6), respectively, for the rectum and bladder. Without considering urinary and rectal incontinence, for which the pertinence of correlating them with D2cm 3 is questionable, ED10 were 68.5Gy (62.9–110.6) and 65.5Gy (51.4–71.6Gy). When sorting patients according to D2cm 3 levels, patients with high D2cm 3 had significantly lower morbidity free survival rates for grade 1–4 and 2–4 urinary and rectal morbidity. Conclusion Significant dose–volume effect relationships were demonstrated between the modern dosimetric parameters and the occurrence of late rectal and urinary morbidity in patients treated with pulsed-dose-rate brachytherapy. Further studies are required to refine these relationships according to clinical cofactors, such as comorbidities.

Purpose Concomitant chemoradiation followed by brachytherapy is the standard treatment for locally advanced cervical cancers. The place of adjuvant hysterectomy remains unclear but tends to be limited to incomplete responses to radiotherapy or local relapse. The aim was to analyse the benefit from immediate salvage surgery following radiation therapy in incomplete responders. Methods Among the patients with locally advanced cervical cancer treated with concomitant chemoradiation followed by 3D image-guided adaptive brachytherapy and hysterectomy, cases with genuine macroscopic remnant, defined as at least 1 cm in width, were identified. Their clinical data and outcomes were retrospectively reviewed and compared to the patients treated with the same modalities. Results Fifty-eight patients were included, with a median follow-up of 4.2 years. After hysterectomy, 9 patients had macroscopic residual disease, 10 microscopic and the remaining 39 patients were considered in complete histological response. The 4-year overall survival and disease-free survival rates were significantly decreased in patients with macroscopic residual disease: 50 and 51% versus 92% and 93%, respectively. Intestinal grades 3–4 toxicities were reported in 10.4% and urinary grades 3–4 in 8.6% in the whole population without distinctive histological features. Planning aims were reached in only one patient with macroscopic residuum (11.1%). In univariate analysis, overall treatment time (> 55 days) and histological subtype (adenocarcinomas or adenosquamous carcinomas) appeared to be significant predictive factors for macroscopic remnant after treatment completion (P = 0.021 and P = 0.017, respectively). In multivariate analysis, treatment time was the only independent factor (P = 0.046, odds ratio = 7.0). Conclusions Although immediate salvage hysterectomy in incomplete responders provided a 4-year disease-free survival of 51%, its impact on late morbidity is significant. Efforts should focus on respect of treatment time and dose escalation. Adenocarcinoma might require higher high-risk clinical target volume planning aims.

Purpose To report the prognostic factors for local control in patients treated for locally advanced cervical cancer with image guided pulsed-dose rate brachytherapy. Materials/methods Patients treated with curative intent by a combination of external beam radiotherapy and pulsed-dose rate brachytherapy were selected. Local failure was defined as any relapse in the cervix, vagina, parametria, or uterus during follow-up. Prognostic factors were selected based on log rank tests and then analyzed with a Cox model. Dose/effect correlations were performed using the probit model. Results Two hundred and twenty-five patients treated from 2006 to 2011 were included. According to the FIGO classification, 29% were stage IB, 58% stage II, 10% stage III, and 3% stage IVA; 95% received concomitant chemotherapy. Thirty patients were considered having incomplete response or local failure. Among the selected parameters, D90 for HR-CTV, D90 for IR-CTV, the overall treatment time, the TRAK, and the HR-CTV volume appeared significantly correlated with local control in univariate analysis. In multivariate analysis, overall treatment time >55days and HR-CTV volume >30cm 3 appeared as independent. The probit analysis showed significant correlations between the D90 for both CTVs, and the probability of achieving local control ( p =0.008 and 0.024). The thresholds to reach to warrant a probability of 90% of local control were 85Gy to the D90 of the HR-CTV and 75Gy to 90% of the IR-CTV (in 2Gy equivalent, α / β =10). To warrant the same local control rate, the D90 HR-CTV should be significantly increased in stage III–IV tumors, in case of HR-CTV >30cm 3 , excessive treatment time, or tumor width at diagnosis >5cm (97, 92, 105, and 92Gy respectively). Conclusions Overall treatment time and HR-CTV volume were independent prognostic factors for local control. The D90 for HR and IR CTV were significantly correlated with local control, and D90 HR-CTV should be adapted to clinical criteria.

Objectifs Rapporter les resultats cliniques et la toxicite tardive chez des patientes atteintes de cancer du col uterin localement evolue apres chimioradiotherapie concomitante suivie de curietherapie endocavitaire adaptative guidee par l’image. Materiels et methodes Les donnees de patientes atteintes de lesions de stade IB1N + -IVA du col uterin ont ete retrospectivement analysees. Apres radiotherapie externe pelvienne et ou non lombo-aortique, toutes ont recu une curietherapie endocavitaire adaptative guidee par l’image de debit de dose pulse suivant les recommandations du Groupe europeen de curietherapie–European Society for Therapeutic Radiology and Oncology (Gec-ESTRO). Resultats Deux cent vingt-cinq patientes ont ete incluses. Soixante-cinq pour cent des lesions ont ete classees au moins IIB selon les recommandations de la Federation de gynecologie-obstetrique (Figo). Quatre-vingt-cinq pour cent ont recu une chimiotherapie concomitante. Les doses delivrees a 90 % des volumes cibles anatomocliniques de haut risque et de risque intermediaire etaient respectivement de 80,4 ± 10,3 Gy et de 67,7 ± 6,1 Gy. Apres un suivi median de 38,8 mois, les taux de controle local et de survie globale a 3 ans etaient respectivement de 86,4 et 76,1 %. Un effet deletere du stade tumoral sur le taux de controle local a ete note (de 92,0 % pour les cancers de stade 1B a 66,7 % pour ceux de stade IVA, p = 0,038), parallele a une diminution de la D90 (dose dans 90 % du volume cible anatomoclinique de haut risque) avec le stade tumoral (de 84,6 Gy a 65,4 Gy). Les taux de controle local a 3 ans variaient significativement avec cette D90 : 95,6 % a 3 ans si 85 Gy ou plus, 88,8 % entre 80 et 85 Gy, et 80 % si moins de 80 Gy (p = 0,018). Quatorze patientes ont souffert d’une toxicite tardive de grade 3–4 gastro-intestinale ou urinaire, ce qui correspond a une incidence de 6,6 % a 3 ans. Conclusion La chimioradiotherapie concomitante suivie de curietherapie endocavitaire adaptative guidee par l’image fournit des taux de controle local eleves avec une toxicite limitee. La necessite d’atteindre des doses elevees pour obtenir le controle local rend la curietherapie interstitielle necessaire pour les tumeurs localement evoluees.

Anti-N-methyl-D-aspartate receptor (NMDA-R) encephalitis is little known to pediatricians and likely underdiagnosed. The child's vital and cognitive prognosis is at stake. The use of immunomodulatory drugs, such as rituximab has led to spectacular results, but many questions remain about its mode of action in this type of pathology.We report the case of a 6-year-old girl with no medical history, admitted for status epilepticus preceded by behavior symptoms and sleep disorders. Gradually, the child became bedridden, mute, and animated by predominantly orofacial dyskinesia. Examinations were normal (cerebrospinal fluid [CSF] analysis, brain MRI). The diagnosis was established by the presence of NMDA-R antibodies in the CSF. After exclusion of a tumor-associated syndrome, treatment was started initially by intravenous immunoglobulins, then by plasma exchange, and finally rituximab. The patient was cured with rituximab despite an unusually early recovery of the B-cell pool.Anti-N-methyl-D-aspartate receptor (NMDA-R) encephalitis is a severe but potentially reversible neurologic disorder only recently described, even in childhood. It may be reversible without sequelae if diagnosed and treated early. The use of immunomodulatory therapy, such as rituximab seemingly improves the outcome. Immunological monitoring is needed to better understand its mechanism of action in autoimmune diseases of the nervous system in childhood.

Objectif de l’etude La curietherapie adaptative guidee par l’image est une technique de haute precision qui autorise escalade de dose et adaptation a la reponse tumorale. Des etudes monocentriques ont permis d’etablir des relations dose–volume reponse. Celles-ci sont cependant grevees d’intervalles de confiance larges. L’objectif etait d’affiner ces estimations en effectuant une meta-regression sur donnees publiees. Materiels et methode L’eligibilite etait limitee aux series rapportant des resultats selon les recommandations du Groupe europeen de curietherapie – European Society for Therapeutic Radiology and Oncology (Gec-ESTRO). En se basant sur le modele Probit, les taux de controle local evalues a 2 a 3 ans, ont ete confrontes aux doses recues par 90 % du volume (D90) moyennes converties en equivalent 2 Gy (α/β = 10 Gy). L’impact de chaque serie a ete pondere en fonction du nombre de patientes incluses. Resultats Une recherche exhaustive a permis d’identifier 13 series rapportant les donnees de 1299 patientes. Les D90 moyennes du volume cible anatomoclinique a haut risque (CTVHR) variaient de 70,9 a 93,1 Gy. Le modele probit a montre une forte relation entre la D90 et la probabilite d’obtenir le controle local ( p p = 0,009). Le seuil de 60 Gy etait associe a une probabilite de controle local de 79,4 % (60,2 a 86,0 %). Conclusion Les relations d’effet dose–volume ont ete entre les D90 et la probabilite d’obtenir un controle local confirmees et affinees. Des etudes basees sur donnees individuelles sont necessaires pour developper des nomogrammes prenant en compte donnees dosimetriques et cofacteurs cliniques.

Objectif de l’etude La place des traitements locaux de rattrapage apres radiotherapie pour un cancer de prostate n’est actuellement pas bien definie. L’hormonotherapie demeure le traitement de reference, mais plusieurs donnees suggerent la possibilite d’une re-irradiation a visee curative. Nous rapportons notre experience de curietherapie de haut debit de dose de rattrapage apres radiotherapie. Materiel et methode Entre mai 2013 et fevrier 2015, huit patients nous ont ete adresses pour la realisation d’une curietherapie de rattrapage dans le cadre du traitement de rattrapage d’un adenocarcinome prostatique en rechute biochimique apres radiotherapie externe. Le temps median ecoule entre la fin de la radiotherapie et la realisation de la curietherapie etait de 9,9 annees (6–14). La concentration mediane de PSA total au moment de la curietherapie etait de 6,7 ng/mL (4–11). Trois patients ont ete traites en situation d’echappement sous hormonotherapie et trois autres avaient ete prealablement pris en charge par cryotherapie. La dose mediane de curietherapie etait de 25,5 Gy (24–26 Gy) en deux fractions de haut debit de dose. Resultats Avec un suivi median apres le traitement de 13 mois (8,7–32,4), quatre patients ont souffert d’une toxicite urinaire de grade 2 ou plus. Aucune toxicite rectale de grade 2 ou plus n’a ete rapportee. Le nadir du PSA median etait de 1,95 ng/mL (0,24–5,87). La duree mediane de survie sans traitement etait de 13 mois (4,6–20,9). Cinq patients ont ete atteints d’une rechute biochimique, associee pour un patient a une rechute ganglionnaire obturatrice et deux autres patients de rechutes metastatiques osseuses prises en charge par hormonotherapie. Conclusion La curietherapie de haut debit de dose est techniquement faisable dans le cadre du rattrapage d’un cancer de prostate recidivant apres radiotherapie, avec une toxicite acceptable. Il demeure necessaire d’ameliorer la selection des patients et de mieux definir les criteres de realisation de ce traitement.

Congenital myasthenia syndromes (CMS) are a group of genetic disorders responsible for neuromuscular junction dysfunction. Usually beginning before 2 years of age, they are revealed by fatigability and muscle weakness, especially after stress, and often prevent the child's normal development. Over recent years, major advances in therapeutic strategies have been made following the discovery of numerous mutations responsible for CMS and the understanding of their pathogenic role. Here we report a pediatric CMS case caused by a mutation of the ɛ subunit of the acetylcholine receptor. The initial treatment with acetylcholinesterase inhibitor rapidly showed its limits in terms of both effectiveness and tolerance. The association with 3.4 diaminopyridine (DAP), a new drug available to treat such conditions, has transformed the motor outcome of our patient and allowed psychomotor development. In addition to 3.4 DAP, other molecules adapted to other types of CMS are now available. Three major groups of CMS can be distinguished depending on whether the deficit is at the presynaptic, synaptic, or postsynaptic level of the neuromuscular junction. Depending on the type of CMS, therapeutic management may include acetylcholinesterase inhibitors, 3.4 DAP, fluoxetine, quinidine sulfate, or ephedrine. With the case report, we provide a recent review of the literature on such new therapeutic options, their indications and restrictions, their mechanism of action, and prescription modalities. Knowing the precise CMS type and the appropriate therapeutic options available is essential for the proper management of such chronic and severe but relatively treatable childhood disorders.

Objectif Identifier les facteurs pronostiques du controle local apres curietherapie optimisee pour cancer du col de l’uterus localement evolue. Patientes et methodes Les patientes dont le traitement a visee curative etait une chimioradiotherapie puis une curietherapie de debit pulse ont ete selectionnees. Dans un premier temps, une hysterectomie de cloture etait realisee pour les lesions de stade I-II. L’echec local etait retenu en cas de maladie residuelle de 1 cm ou plus sur la piece d’hysterectomie ou en cas de rechute au cours du suivi. Les facteurs pronostiques ont ete identifies par regression lineaire. Des correlations dose/effet ont ete effectuees en utilisant le modele Probit. Resultats Au total, 286 patientes ont ete incluses. Selon la classification de la Federation internationale des gynecologues-accoucheurs (Figo), 29 % des tumeurs etaient de stade IB, 58 % de stade II, 10 % de stade III et 3 % de stade IVA. Soixante et une patientes ont eu une hysterectomie. Avec un recul median de 37 mois, 45 patientes ont ete considerees en situation d’echec local. Parmi les parametres testes, les D90 (doses dans 90 % du volume) du volume cible anatomoclinique a haut risque, et du volume cible anatomoclinique a risque intermediaire, l’etalement du traitement, et le volume du volume cible anatomoclinique a haut risque sont apparus significativement correles avec la probabilite de controle local en analyse unifactorielle. En analyse multifactorielle, ces memes parametres, hormis la D90 du volume cible anatomoclinique a risque intermediaire, semblaient independants. L’allongement de l’etalement du traitement au-dela de 56 jours engendrait une perte de 0,5 % de la probabilite de controle local par jour supplementaire. Des correlations entre la D90 des volumes cibles anatomocliniques a haut risque et a risque intermediaire, et la probabilite de controle local ( p = 0,008 et 0,024) ont ete observees. Les seuils a atteindre pour garantir un taux de 90 % de controle local etaient de 90 Gy pour le volume cible anatomoclinique a haut risque et de 75 Gy pour celui a risque intermediaire. Conclusion L’etalement reste un facteur pronostique primordial du controle local. La D90 du volume cible anatomoclinique a haut risque a ete identifiee comme facteur pronostique independant.

We report the case of a 9-year-old girl with a long-chain 3-hydroxyacyl CoA dehydrogenase (LCHAD) deficiency. This enzyme participates in mitochondrial fatty acid B-oxidation. Genetic fatty acid oxidation defects induce cellular energetic deficiency, and thus early life-threatening manifestations. An appropriate diet prevents these severe disorders. Nevertheless, LCHAD deficiency is the only B-oxidation enzymatic disorder that induces a chorioretinopathy, predominating at the posterior pole. We describe the first case of bilateral macular choroidal neovascularization. One eye presented a fibrovascular lesion. The other eye presented an active neovascularization stabilized by two dynamic phototherapies. The specificity of choroidal degeneration related to LCHAD deficiency remains unknown. Reviewing of literature and biochemical mechanisms suggests that fatty acid oxidative stress rather than a mitochondrial energetic defect is involved. For practical purposes, this report emphasizes the importance of ophthalmological follow-up of these patients.

Mitochondrial respiratory chain deficiencies are known for their high clinical variability. Difficult to diagnose, the prevalence of these diseases is probably underestimated.We report 18 children diagnosed with respiratory chain deficiency at the Tours University Hospital over the past 10 years.Three clinical profiles can be distinguished depending on the age at onset of the first symptoms: the neonatal period (4 cases), between 1 month and 2 years of age (10 cases), and after 10 years (4 cases). However, no clinical feature appears specific of any age group. In contrast, respiratory chain analysis on liver biopsy was very informative for all our patients at any age and with any clinical presentation, even with predominant neurological symptoms.These biochemical analyses support the diagnosis of mitochondrial disorders in view of molecular analysis, which nevertheless frequently remains inconclusive. These investigations should benefit from the new molecular screening technologies based on DNA chips that can identify the genomic mutations responsible for these severe and relatively frequent diseases.

Objectifs Etablir des correlations dose–volume–effets pour la morbidite tardive de la vessie et du rectum chez les patientes atteintes d’un cancer localement evolue du col uterin dont le traitement etait une chimioradiotherapie concomitante suivie de curietherapie adaptative guidee par l’image. Materiels et methodes Les donnees dosimetriques, converties en equivalent 2 Gy, de 217 patientes ont ete confrontees aux donnees cliniques de morbidite tardive definie comme tout evenement survenant ou persistant au-dela de 90 jours apres le debut du traitement. La toxicite a ete evaluee en utilisant la Common Terminology Criteria for Adverse Events version 3.0. Resultats Un total de 219 evenements a ete rapporte : 161 vesicaux et 58 rectaux. Les D0,1 cm3 et D2 cm3 (doses dans 0,1 et 0,2 cm3) du rectum et de la vessie etaient significativement plus elevees chez les patientes atteintes de morbidite de grade 2–4 par rapport a celles dont la morbidite etaient de grade 0–1. Des relations significatives ont ete observees entre la probabilite de survenue d’une morbidite vesicale de grade 2–4 ou 3–4 et les D0,1 cm3 (p = 0,01 et 0,05) et D2 cm3 (p = 0,007 et 0,02), et entre la probabilite de survenue d’evenements de grade 1–4 et 2–4 et la D2 cm3 du rectum (p = 0,02 et 0,01). Les D2 cm3 theoriques engendrant des risques de 10 % et 50 % de survenue d’un evenement de grade 2–4 etaient de 65,3 et 90,1 Gy pour le rectum et de 55,4 et 99,4 Gy pour la vessie. Apres repartition des patientes en sous-groupes en fonction de cinq niveaux de D2 cm3, les patientes ayant recu des D2 cm3 elevees avaient des taux de survie sans toxicite de grade 1–4 et 2–4 significativement reduits. Conclusion Des relations dose–volume–effets ont ete etablies entre parametres dosimetriques modernes et morbidite tardive rectale et vesicale chez des patientes dont le traitement etait une curietherapie de debit de dose pulse. Des etudes supplementaires sont necessaires pour affiner ces relations en fonction de cofacteurs cliniques, tels que les maladies associees.

Neurofibromatosis 1 (NF1) is a frequent genetic disease. Diagnostic criterias were established in 1988. The patients can exhibit various and unpredictable complications.To check the efficiency of a coordinated follow-up in specialized multidisciplinary centers providing a higher quality of management and to have a better knowledge of the complications including their true frequencies.We report a serie of 100 NF1 children who were followed-up during 4 years in a specialized center at the Tours University Hospital. Three hospital check-up at 2-5, 6-7, 14-15 years of age were performed as well as an annual physical examination.In our serie, the mean age was 7.8 years old with a sex ratio of 1. The mean age at diagnosis was 3.8 years old and the main diagnosis criteria were the café-au-lait spots and the family history for 80% of the patients. The optic nerve glioma has a low frequency of 5%. Learning disabilities clearly represent the most frequent complication (46% of the patients).An early detection of these difficulties is a priority for the appropriate management of these children.

Methylphenidate (MPH) is a potential therapeutic tool for Attention Deficit with Hyperactivity Disorders (ADHD). In addition to the immediate-release formulation, Ritalin, two extended-release formulations, Ritalin LA and Concerta are available and allow a once-daily administration. We compared the respective benefits of both formulations for the patients and their family in terms of efficacy, handling and tolerance.This prospective study was based on 30 children aged 6 to 15 years. All patients had a confirmed ADHD and were efficiently treated with Ritalin. The children were consecutively treated with Ritalin LA and Concerta, with a comparable MPH daily dosage, during 2 months for each molecule. The 3 drugs were evaluated individually and comparatively through a battery of questionnaires submitted to the parents and the teachers of each child.Extended-release MPH efficacy was comparable to the immediate-release formulation, Ritalin. For both of them, the once-daily administration appeared beneficial. Concerta was finally prescribed in 18 children, Ritalin LA in 8 cases and Ritalin in 4 cases. In each case the medical choice was consistent with the parents preference. Concerta was appreciated for its persisting efficacy in late afternoon during homework. Concerta and Ritalin LA did not induce significant adverse effects, especially regarding alimentation and sleep.MPH therapy in ADHD carries an excellent risk/benefit ratio without addictive induced behaviours. The extended-release MPH formulations provide an improvement for the patients in keeping with Ritalin efficacy through a once-daily administration. Regardless of its formulation, MPH indications and guidelines must be respected.

Ischemic strokes represent a rare condition in childhood, mostly revealed by a motor deficit. In the pediatric age, strokes are different than in adulthood where atherosclerosis is the major cause. The etiologies of stroke in childhood are rather multiple and each of them is rare. In nearly half of the pediatric cases no cause can be found and usually no recurrence occurs. The aim of this presentation is to propose a diagnosis strategy for ischemic strokes in children. An extensive search should be performed in every children presenting a stroke episode even if the initial outcome appears favorable. Such investigations could improve our understanding and therapeutic strategies of stroke in childhood, a condition where the cognitive and functional prognosis can be severely compromised.

Objectifs Comparer les differentes modalites de RMN (imagerie et spectroscopie) pour la caracterisation des hamartomes intracerebraux dans une population d’enfants suivis pour une NF1 et comparaison avec les donnees parfois contradictoires de la litterature. Materiels et methodes L’etude est realisee sur une population de 20 enfants suivis pour une NF1 sans complication tumorale cerebrale. Une exploration cerebrale est effectuee pour chaque patient a l’aide d’un spectro-imageur GE de 1,5 Tesla. Les sequences suivantes sont realisees : TSE T2 axiale, T2 FLAIR axiale suivies d’acquisitions spectroscopiques monovoxel de type PRESS avec un VOI de 8 ml place sur les zones en hypersignal T2 et sur la localisation controlaterale saine. Une imagerie spectroscopique multivoxel est realisee sur la region thalamo-striee. Resultats L’etude a permis le recensement et la caracterisation des hamartomes intra-cerebraux par les differentes modalites de RMN. Les resultats ont ete confrontes a ceux de la litterature. Conclusion Les techniques de RMN permettent la detection et la caracterisation des hamartomes chez des enfants suivis pour une NF1.

The control of Graves' disease patients treated with antithyroid drugs (ATD) involves monitoring the dose of ATD, the duration of therapy and the prediction of the long-term outcome of the disease. The sequential follow-up of free thyroid hormones and ultrasensitive TSH (USTSH) helps in monitoring of ATD therapy, except in patients complemented with thyroid hormones. The normalization of early thyroid uptake of radioiodine or pertechnetate, which seems to be closely related to circulating thyroid-stimulating immunoglobulins, confirms the remission that leads to stopping ATD therapy. The raise of plasma USTSH in a normal range within the six months following ATD withdrawal is another indicator of remission. However, the post therapeutic course of Graves' patients remains unpredictable: late relapses and hypothyroidism may occur despite the normalization of the pituitary-thyroid axis, leading to a yearly clinical control with USTSH evaluation.