ctDNA quantification improves estimation of outcomes in patients with high-grade osteosarcoma: a translational study from the OS2006 trial.

BACKGROUND: Osteosarcoma stratification relies on clinical parameters and histological response. We developed a new personalized stratification using less invasive circulating tumor DNA (ctDNA) quantification. PATIENTS AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

[Kikuchi-Fujimoto disease mimicking malignant lymphoma in adolescents]. / La maladie de Kikuchi-Fujimoto ; un diagnostic différentiel méconnu du lymphome chez l'adolescent.

Kikuchi-Fujimoto disease, also known as histiocytic necrotizing lymphadenitis, is a rare cause of lymphadenopathy in children. This benign disease can mimic lymphoma and misleads doctors. It was first described in Asia, where it occurred especially in young women. Recent publications show that it can also affect teenagers and young adults in Caucasian populations. The pathophysiology remains unknown. Three hypotheses have been raised for this disease: the role of viruses (in particular HHV-8), genetic predisposition (two alleles in HLA class II genes were found more frequently in patients with Kikuchi disease), and an autoimmune cause because of the correlation with lupus erythematosus. Few cases have been reported in Europe so far. In this article, we report three cases of Kikuchi disease observed in less than 2 months in a single hospital in France. All three patients were teenagers who presented with lymphadenopathy, either isolated or combined with fever, weakness, and weight loss. In all of them, the hypermetabolic activity of the lymph node on the PET scanner misled us to suspect lymphoma. The diagnosis of Kikuchi disease was finally made, for all patients, after 2 weeks in the hospital based on lymph node biopsy. Based on this report, we highlight that early biopsy in presence of lymphadenopathy can avoid unnecessary extensive investigations. Moreover, in this rare disease, it is very surprising to come across three cases that are not family-related, in such a short period of time. This strengthens the hypothesis of the possible implication of an environmental factor in the pathophysiology of Kikuchi disease.

Combined therapy in children and adolescents with classical Hodgkin's lymphoma: A report from the SFCE on MDH-03 national guidelines.

Hodgkin's lymphoma (HL) in children and adolescents is highly curable, but children are at risk of long-term toxicity. The MDH-03 guidelines were established in order to decrease the burden of treatment in good-responder patients, and this report should be considered a step toward further optimization of treatment within large collaborative trials. We report the therapy and long-term outcomes of 417 children and adolescents treated according to the national guidelines, which were applied between 2003 and 2007 in France. The patients were stratified into three groups according to disease extension. Chemotherapy consisted of four cycles of VBVP (vinblastine, bleomycin, VP16, prednisone) in localized stages (G1/95 pts/23%), four cycles of COPP/ABV (cyclophosphamide, vincristine, procarbazine, prednisone, adriamycin, bleomycin, vinblastine) cycles in intermediate stages (G2/184 pts/44%) and three cycles of OPPA (vincristine, procarbazine, prednisone, adriamycin) plus three cycles of COPP in advanced stages (G3/138 pts/33%). Radiation therapy of the involved field was given to 97% of the patients, with the dose limited to 20 Gy in good responders (88%). With a median follow-up of 6.6 years, the 5-year event-free survival (EFS) and overall survival (OS) were 86.7% (83.1-89.7%) and 97% (94.5-98.1%), respectively. EFS and OS for G1, G2, and G3 were 98% and 100%, 81% and 97%, and 87% and 95%, respectively. Low-risk patients treated without alkylating agents and anthracycline had excellent outcomes and a low expected incidence of late effects. Intensification with a third OPPA cycle in high-risk group patients, including stage IV patients, allowed for very good outcomes, without increased toxicity.

[Primary cervico-facial amylosis. Apropos of a case]. / Amylose cervico-faciale primitive. A propos d'une observation.

Diagnosis in a case of primary localized amylosis of the sinuses and cervical nodes was from the discovery of nasal obstruction with conductive hearing loss and cervical nodes. Biopsy confirmed the presence of amyloid deposits in the maxillary sinuses mucosa and the cervical nodes. This case illustrates the value of typing of the amylosis, rectal biopsy and investigation to detect a myeloma, thus providing confirmation of a primary localized amylosis. A literature review confirmed the rarity of this localization of amyloidosis.

[Alpha-fetoproteins in maternal serum. Radioimmunologic determination in current obstetrical practice. Analysis of 669 determinations]. / Alpha-foetoprotéine dans le sérum maternel. Dosage radio-immunologique en pratique obstétricale courante. Analyse de 669 dosages.

The analysis of 669 levels of maternal serum alpha-fetoproteins carried out using a radio-immunological technique with double antibodies has enabled a diagram of normal values to be established on the one hand has shown up certain modifications of levels when different pathological conditions arise in pregnancy on the other hand. Raised levels were found in: intra-uterine fetal death. In some cases the rise preceded death, in twin pregnancies. Low levels were found in: severe pre-eclamptic pregnancies, in low intra-uterine fetal growth after the 32nd week, in threatened premature labour. Finally, the levels of AFP in the maternal serum were found to be normal in two cases where there were neural tube malformations. The existence of variations in the levels of AFP in maternal serum in a variety of pathological features suggests that these levels could be used as a new parameter in the biochemical monitoring of the fetus.

[Malignant cyto-trophoblastic tumors following the abortion of a mole. Their treatment with methotrexate alone or in conjunction with surgery].

We report six case histories of malignant tumours following abortion of moles. In three cases their surgical removal allowed us to control them by histology: two of these were destruens chorio-adenomata, one case only was a choriocarcinoma. In the three other cases the cure was obtained by the sole use of anti-mitotic drugs. This treatment was undertaken on bioclinical evidence of malignancy which is certainly not foolproof, but which is practical in use, when one appreciates how difficult it is to diagnose some of these post-mole tumours histologically. There is a place for the surgical treatment of these cases in spite of the usefulness of Methotrexate. This place varies according to the age of the patients and the resistance of the tumours to treatment with anti-mitotic drugs.