Osteosarcoma stratification relies on clinical parameters and histological response. We developed a new personalized stratification using less invasive circulating tumor DNA (ctDNA) quantification.
...Plasma from patients homogeneously treated in the prospective protocol OS2006, at diagnosis, before surgery and end of treatment, were sequenced using low-passage whole-genome sequencing (lpWGS) for copy number alteration detection. We developed a prediction tool including ctDNA quantification and known clinical parameters to estimate patients’ individual risk of event.
ctDNA quantification at diagnosis (diagCPA) was evaluated for 183 patients of the protocol OS2006. diagCPA as a continuous variable was a major prognostic factor, independent of other clinical parameters, including metastatic status diagCPA hazard ratio (HR) = 3.5, P = 0.002 and 3.51, P = 0.012, for progression-free survival (PFS) and overall survival (OS). At the time of surgery and until the end of treatment, diagCPA was also a major prognostic factor independent of histological response (diagCPA HR = 9.2, P < 0.001 and 11.6, P < 0.001, for PFS and OS). Therefore, the addition of diagCPA to metastatic status at diagnosis or poor histological response after surgery improved the prognostic stratification of patients with osteosarcoma. We developed the prediction tool PRONOS to generate individual risk estimations, showing great performance ctDNA quantification at the time of surgery and the end of treatment still required improvement to overcome the low sensitivity of lpWGS and to enable the follow-up of disease progression.
The addition of ctDNA quantification to known risk factors improves the estimation of prognosis calculated by our prediction tool PRONOS. To confirm its value, an external validation in the Sarcoma 13 trial is underway.
•ctDNA detection is a non-invasive procedure.•The use of lpWGS is cost-effective.•This procedure represents a considerable step in reducing therapeutic burden and trauma for patients with cancer.•PRONOS is a tool that estimates relapse risk using ctDNA at diagnosis and known clinical risk factor in osteosarcoma.
L’association de lymphomes, principalement non hodgkiniens, et de manifestations auto-immunes a surtout été étudiée chez l’adulte. Les publications concernant la maladie de Hodgkin sont rares, en ...particulier chez l’enfant et l’adolescent. L’objectif principal de cette étude était de définir les caractéristiques de l’association maladie de Hodgkin et auto-immunité chez l’enfant. Une étude rétrospective portant sur les 25 dernières années a été réalisée auprès des centres membres de la Société française des cancers de l’enfant et de l’adolescent (SFCE). Nous rapportons 11 cas d’enfants porteurs d’une maladie de Hodgkin ayant présenté des manifestations dysimmunitaires précédant ou suivant le diagnostic. Quatre patients présentaient un purpura thrombopénique idiopathique et les 7 autres des manifestations auto-immunes différentes : syndrome lupique, syndrome des anticorps anti-phospholipides avec accident ischémique transitoire, syndrome d’Evans, vascularite leucocytoclasique, anémie hémolytique auto-immune, thyroïdite auto-immune et arthrite chronique juvénile idiopathique. Trois enfants avaient présenté une rechute de la maladie de Hodgkin et 2 étaient décédés, dont l’un directement d’une pathologie auto-immune associée (syndrome lupique). Nous constatons une morbidité importante liée à l’auto-immunité. Les mécanismes physiopathologiques pouvant expliquer cette association sont discutés : inflammation chronique et prolifération lymphocytaire, déficit immunitaire cellulaire dans la maladie de Hodgkin, mimétisme moléculaire et auto-immunité en tant que phénomène antinéoplasique. Afin de définir une population à risque pour laquelle des examens complémentaires et des adaptations de traitement seraient nécessaires, une étude comportant un plus grand nombre de patients serait souhaitable.
The association of lymphoma and autoimmune manifestations has been predominantly studied in adults affected by non-Hodgkin lymphoma. Few publications exist in the literature concerning Hodgkin lymphoma, particularly in children and adolescents. The objectives of this study were to define the characteristics of the link between Hodgkin disease and autoimmunity in childhood. The present 25-year retrospective study was conducted in all centers affiliated with the French Society of Paediatric Oncology (SFCE). Eleven children with Hodgkin disease presented manifestations of disimmunity preceding or following their diagnosis. Four patients had thrombocytopenic purpura, the remaining 7 each had a different autoimmune pathology: lupus syndrome, antiphospholipid syndrome with transient ischemic attack, Evans syndrome, leukocytoclastic vasculitis, autoimmune hemolytic anemia, autoimmune thyroiditis, and juvenile idiopathic arthritis. Lymphoma relapse occurred in 3 patients. Two children died, death being directly attributed to the autoimmune disease in 1 case. Our data suggest that development of autoimmunity is related to significant morbidity. Possible pathophysiological mechanisms include lymphocyte proliferation secondary to chronic inflammation, cell-mediated immune deficiency in Hodgkin disease, molecular mimetics, and antineoplastic phenomena are discussed. A study with a larger patient population is needed to identify the group of children at high risk of autoimmunity for whom additional investigations and modified therapy may be indicated.
With recent conservative strategies, prognosis of patients with desmoid-type fibromatosis (DTF) is about function preservation. We analyzed the long-term quality of life (QoL) of pediatric patients ...with DTF.
All French young patients (<21years) treated between 2005 and 2016 for a DTF in the EpSSG NRSTS-05 study were analyzed. A first wait-and-see strategy was recommended. Patients' QoL was analyzed with the internationally validated Child Health Questionnaire (CHQ). We focused on the relevant subscales scores: physical functioning (PF), role social limitations physical (RP), bodily pain (BP), general health perception (GH) and physical (PhS) and psychosocial (PsS) summary measures.
Among the 81 patients, 52 families answered the CHQ (median delay since diagnosis = 6.2years; min2.2-max13.3 years). Median age at diagnosis was 11.5 years. Primary site: limbs (52%), head/neck (27%), or trunk (21%). Five year-Progression Free Survival was 39.1% (95%CI: 27.7–50.5%). As initial management for these 52 patients, 30 patients were first observed (57%), 13 had surgery (25%) and 9 received chemotherapy (18%). Total burden of therapy was exclusive surgery (9pts/18%), exclusive chemotherapy (18pts/35%), surgery + chemotherapy (13pts/25%), chemotherapy + radiotherapy (1 pt), surgery + chemotherapy + radiotherapy (1 pt), wait and see (10 pt). Regarding the parent forms, patients have significant lower PF (86.0vs.96.1; p = 0.03), RP (82.0vs.93.6; p = 0.04), GH (60vs.73; p < 0.005) and PhS (46.2 vs.53; p = 0.02) scores compared to healthy population. Comparison of QoL subscales scores according to initial strategy (wait-and-see vs.surgery/chemotherapy) did not reveal any difference (PF = 87.3vs.84.9; p = 0.80/RP = 83.4vs.78.7; p = 0.72/BP = 78.9vs.78.2; p = 0.95/GH = 59.7vs60; p = 0.97). Similar results were found using the children or adult forms.
Initial wait-and-see strategy does not affect long term functional impairment.
Purpura thrombotique thrombocytopénique chez un nouveau-né Sudour, H.; Rouabah, M.; Mansuy, L. ...
Archives de pédiatrie : organe officiel de la Société française de pédiatrie,
2007, 2007-1-00, Letnik:
14, Številka:
1
Journal Article
Recenzirano
Un nouveau-né s'est présenté dès les premières heures de vie avec un tableau d'anémie hémolytique, de thrombopénie, d'hyperbilirubinémie et d'insuffisance rénale aiguë. La mise en route rapide d'une ...plasmathérapie a permis une évolution favorable. Le dosage de la protéase du facteur von Willebrand (métalloprotéase ADAMTS13) a retrouvé un taux inférieur à 5
% signant le diagnostic de purpura thrombotique thrombocytopénique congénital ou syndrome d'Upshaw-Schulman. Cette entité de microangiopathie thrombotique constitutionnelle n'est bien décrite et comprise que depuis quelques années. Affection rare, son diagnostic et son traitement sont une urgence pour préserver le pronostic fonctionnel et vital des patients.
A newborn presented with haemolytic anemia, thrombocytopenia, hyperbilirubinemia and renal failure as early as the first hours of life. An early plasmatherapy was undertaken, followed by good outcome. The specific von Willebrand factor–cleaving protease (ADAMTS 13) was found at less than 5%. This is the specific biologic diagnostic element of congenital thrombotic thrombocytopenic purpura or Upshaw - Schulman syndrome. This disease of constitutional thrombotic microangiopathy was well identified and understood only few years ago. It's a rare disease which early diagnosis and treatment are crucial in order to preserve functional and vital capacities of the patient.
Infection is the major cause of treatment-related mortality in childhood acute leukemia, mainly due to bacterial translocation across the intestinal mucosa. Only a few studies have reported the ...impact of different antibacterial prophylaxis treatments on digestive tract flora and infection-related mortality.
We performed a retrospective analysis of two different digestive tract decontamination modalities (selective or total digestive decontamination) in a large single-center series of 323 children during the induction treatment of acute leukemia between January 1995 and December 2014. We examined the impact of antibiotic prophylaxis and food regimen (sterile or selected) on the digestive tract flora during the period of antibacterial prophylaxis, on the frequency of bacteremia, and on antibiotic sensitivity.
Only one Gram-negative (Klebsiella pneumonia) translocation occurred in the SDD group. No infection-related death occurred. Extended-spectrum beta-lactamase (ESBL) bacteria were observed in seven of 170 (4%) patients in the SDD group. The faecal-flora total suppression and faecal-flora Gram-negative bacilli suppression was 67 and 77%, respectively, in the TDD group with sterile food, 0 and 58%, respectively, in the SDD group with sterile food, and 6 and 63%, respectively, in the SDD group with selective food.
This study gives a rationale not to use antibacterial prophylaxis systematically in children who receive induction treatment for acute leukemia; additionally, antibiotics should only be used in case of stool contamination by highly pathogenic bacteria with a high potential of translocation.
Le sarcome d’Ewing est une tumeur osseuse ou extra-osseuse maligne rare qui peut intéresser tous les os du squelette, mais plus particulièrement les os plats. La douleur est très souvent le symptôme ...révélateur, accompagnée ou non d’une tuméfaction et justifie la prescription d’imageries médicales loco-régionales complétées par une biopsie. Certaines présentations peuvent être trompeuses du fait de leur localisation atypique et/ou de l’absence de douleur. Nous présentons le cas d’un enfant de 7ans atteint d’un sarcome d’Ewing localisé à la mandibule, diagnostiqué devant une tuméfaction mandibulaire d’apparition progressive sans symptomatologie douloureuse.
Ewing sarcoma is the second most common primary malignant bone cancer in children and adolescents. Clinical presentation is usually dominated by local pain and a palpable mass. These symptoms justify imaging investigations: the first one, when an osseous lesion is suspected, is usually a conventional radiograph in two planes. Ewing sarcoma appears as a poorly defined osteolytic lesion that may frequently be associated with cortical erosion or laminar periosteal response (“onion skin”). However, this aspect is not pathognomonic and the definitive diagnosis is made by biopsy. Absence of pain or an unusual localization can lead to misdiagnosis. We report the case of a 7-year-old boy with Ewing sarcoma located in the mandible with a clinical picture including progressive mandibular swelling but no pain.
Pilomatrix Carcinoma (PC) is a rare and malignant dermo-hypodermic tumor. Only 11 cases were reported in patients younger than 18years old and only 13 cases were reported on the scalp.
We report the ...case of a 15-year-old woman who underwent cyst excision on the vertex. Anatomopathology shed light trichilemmal cyst. Five months later, she presented a first local recurrence. The tumor was removed with wide margin. Anatomopathology shed light PC. No adjuvant therapy was performed. The patient presented a second recurrence 3months later with a parietal bone and superior sagittal sinus invasion and a lung metastasis. She underwent a craniotomy and radiochemotherapy. A third local recurrence was detected 4months later. Three more lines of chemotherapy were performed without success.
PC is a locally aggressive tumour, with a high rate of local recurrences and metastases. PC arises de novo or through malignant transformation of a pilomatrixoma. PC were observed frequently in the white male over 50years old. The histological diagnosis is difficult to prove. Treatment consists of a wide surgical excision. Peritumoral margins are not codified. Because of most cases are on the face and neck, Mohs Micrographic Surgery seems to be a good modality to limit margins. Radiation therapy is an adjuvant treatment. Chemotherapy can be used in metastasis case.
PC is a rare malignant tumor with high rate of disease relapse. Histological diagnosis is difficult and treatment is not standardized. Surgical procedure with wide margins is recommended to avoid the large recurrence when the staging shows no metastasis.
Le carcinome pilomatriciel (CP) est une tumeur dermo-hypodermique rare et maligne. Seulement 11 cas sont rapportés chez les patients de moins de 18ans et seulement 13 cas sont rapportés sur le scalp.
Nous rapportons le cas d’une femme de 15ans qui a subi une exérèse d’un kyste du vertex. L’anatomopathologie rapportait un kyste trichilemmal. Après 5 mois, elle a présenté une première récurrence locale qui a été ôtée avec de larges marges. L’anatomopathologie rapportait un CP. Aucune thérapie adjuvante n’a été réalisée. La patiente a présenté une seconde récurrence 3 mois après, avec une invasion de l’os pariétal, du sinus sagittal supérieur ainsi qu’une métastase pulmonaire. Elle a subi une craniotomie et une radiochimiothérapie. Une troisième récurrence locale a été détectée 4 mois plus tard. Trois lignes de chimiothérapies supplémentaires ont été effectuées sans succès.
Le CP est une tumeur agressive avec un haut taux de récurrences locales et de métastases. Il peut survenir de novo ou d’une transformation maligne d’un pilomatrixome. Les CP sont souvent observés chez l’homme caucasien de plus de 50ans. Le diagnostic histologique est difficile à établir. Le traitement consiste en une exérèse chirurgicale large. Les marges péri-tumorales ne sont pas codifiées. La radiothérapie est un traitement adjuvant. La chimiothérapie peut être utilisée dans les cas métastatiques.
Le CP est une tumeur maligne rare avec un haut taux de rechute. Le diagnostic histologique est difficile et le traitement non standardisé. La chirurgie avec de larges marges est recommandée pour éviter les récurrences des cas non métastatiques.
Ewing sarcoma located in the mandible: A case report Hernandez, M; Droz, D; Mansuy, L ...
Archives de pédiatrie : organe officiel de la Société française de pédiatrie,
06/2015, Letnik:
22, Številka:
6
Journal Article
Recenzirano
Ewing sarcoma is the second most common primary malignant bone cancer in children and adolescents. Clinical presentation is usually dominated by local pain and a palpable mass. These symptoms justify ...imaging investigations: the first one, when an osseous lesion is suspected, is usually a conventional radiograph in two planes. Ewing sarcoma appears as a poorly defined osteolytic lesion that may frequently be associated with cortical erosion or laminar periosteal response ("onion skin"). However, this aspect is not pathognomonic and the definitive diagnosis is made by biopsy. Absence of pain or an unusual localization can lead to misdiagnosis. We report the case of a 7-year-old boy with Ewing sarcoma located in the mandible with a clinical picture including progressive mandibular swelling but no pain.
interventions are crucial as they offer simple and inexpensive public health solutions that will be useful over the long term use. A Task Force on designing trials of nutritional interventions to ...slow cognitive decline in older adults was held in Toulouse in September 2012. The aim of the Task Force was to bring together leading experts from academia, the food industry and regulatory agencies to determine the best trial designs that would enable us to reach our goal of maintaining or improving cognitive function in apparently healthy aging people. An associated challenge for this Task Force was to determine the type of trials required by the Public Food Agencies for assessing the impact of nutritional compounds in comparison to well established requirements for drug trials. Although the required quality of the study design, rationale and statistical analysis remains the same, the studies designed to show reduction of cognitive decline require a long duration and the objectives of this task force was to determine best design for these trials. Two specific needs were identified to support trials of nutritional interventions: 1- Risk-reduction strategies are needed to tackle the growing burden of cognitive decline that may lead to dementia, 2- Innovative study designs are needed to improve the quality of these studies.
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