Brachytherapy for Pediatric Patients at Gustave Roussy Cancer Campus: A Model of International Cooperation for Highly Specialized Treatments.

PURPOSE: Childhood cancer is rare, and treatment is frequently associated with long-term morbidity. Disparities in survival and long-term side effects encourage the establishment of networks to increase access to complex organ-conservative strategies, such as brachytherapy. We report our experience of an international cooperation model in childhood cancers. METHODS AND MATERIALS: We examined the outcome of all children referred to our center from national or international networks to be treated according to a multimodal organ-conservative approach, including brachytherapy. RESULTS: We identified 305 patients whose median age at diagnosis was 2.2 years (range, 1.4 months to 17.2 years). Among these patients, 99 (32.4%) were treated between 2015 and 2020; 172 (56.4%) were referred from national centers; and 133 (43.6%) were international patients from 31 countries (mainly Europe). Also, 263 patients were referred for primary treatment and 42 patients were referred for salvage treatment. Genitourinary tumors were the most frequent sites, with 56.4% bladder/prostate rhabdomyosarcoma and 28.5% gynecologic tumors. In addition to brachytherapy, local treatment consisted of partial tumor resection in 207 patients (67.9%), and 39 patients (13%) had additional external radiation therapy. Median follow-up was 58 months (range, 1 month to 48 years), 93 months for national patients, and 37 months for international patients (P < .0001). Five-year local control, disease-free survival, and overall survival rates were 90.8% (95% confidence interval [CI], 87.3%-94.4%), 84.4% (95% CI, 80.1%-89.0%), and 93.3% (95% CI, 90.1%-96.5%), respectively. Patients referred for salvage treatment had poorer disease-free survival (P < .01). Implementation of image guided pulse-dose-rate brachytherapy was associated with better local control among patients with rhabdomyosarcoma referred for primary treatment (hazard ratio, 9.72; 95% CI, 1.24-71.0). At last follow-up, 16.7% patients had long-term severe treatment-related complications, and 2 patients (0.7%) had developed second malignancy. CONCLUSIONS: This retrospective series shows the feasibility of a multinational referral network for brachytherapy allowing high patient numbers in rare pediatric cancers. High local control probability and acceptable late severe complication probability could be achieved despite very challenging situations. This cooperation model could serve as a basis for generating international reference networks for high-tech radiation such as brachytherapy to increase treatment care opportunities and cure probability.

A clinical prediction score for transient versus persistent childhood immune thrombocytopenia.

Essentials There is a need for improved tools to predict persistent and chronic immune thrombocytopenia (ITP). We developed and validated a clinical prediction model for recovery from newly diagnosed ITP. The Childhood ITP Recovery Score predicts transient vs. persistent ITP and response to intravenous immunoglobulins. The score may serve as a useful tool for clinicians to individualize patient care. ABSTRACT: Background Childhood immune thrombocytopenia (ITP) is an autoimmune bleeding disorder. The prognosis (transient, persistent, or chronic ITP) remains difficult to predict. The morbidity is most pronounced in children with persistent and chronic ITP. Clinical characteristics are associated with ITP outcomes, but there are no validated multivariate prediction models. Objective Development and external validatation of the Childhood ITP Recovery Score to predict transient versus persistent ITP in children with newly diagnosed ITP. Methods Patients with a diagnosis platelet count ≤ 20 × 109 /L and age below 16 years were included from two prospective multicenter studies (NOPHO ITP study, N = 377 [development cohort]; TIKI trial, N = 194 [external validation]). The primary outcome was transient ITP (complete recovery with platelets ≥100 × 109 /L 3 months after diagnosis) versus persistent ITP. Age, sex, mucosal bleeding, preceding infection/vaccination, insidious onset, and diagnosis platelet count were used as predictors. Results In external validation, the score predicted transient versus persistent ITP at 3 months follow-up with an area under the receiver operating characteristic curve of 0.71. In patients predicted to have a high chance of recovery, we observed 85%, 90%, and 95% recovered 3, 6, and 12 months after the diagnosis. For patients predicted to have a low chance of recovery, this was 32%, 46%, and 71%. The score also predicted cessation of bleeding symptoms and the response to intravenous immunoglobulins (IVIg). Conclusion The Childhood ITP Recovery Score predicts prognosis and may be useful to individualize clinical management. In future research, the additional predictive value of biomarkers can be compared to this score. A risk calculator is available (http://www.itprecoveryscore.org).

Acute Myeloid Leukemia in Adolescents and Young Adults Treated in Pediatric and Adult Departments in the Nordic Countries.

BACKGROUND: Studies on adolescents and young adults with acute lymphoblastic leukemia suggest better results when using pediatric protocols for adult patients, while corresponding data for acute myeloid leukemia (AML) are limited. PROCEDURE: We investigated disease characteristics and outcome for de novo AML patients 10-30 years old treated in pediatric or adult departments. We included 166 patients 10-18 years of age with AML treated according to the pediatric NOPHO-protocols (1993-2009) compared with 253 patients aged 15-30 years treated in hematology departments (1996-2009) in the Nordic countries. RESULTS: The incidence of AML was 4.9/million/year for the age group 10-14 years, 6.5 for 15-18 years, and 6.9 for 19-30 years. Acute promyelocytic leukemia (APL) was more frequent in adults and in females of all ages. Pediatric patients with APL had similar overall survival as pediatric patients without APL. Overall survival at 5 years was 60% (52-68%) for pediatric patients compared to 65% (58-70%) for adult patients. Cytogenetics and presenting white blood cell count were the only independent prognostic factors for overall survival. Age was not an independent prognostic factor. CONCLUSIONS: No difference was found in outcome for AML patients age 10-30 years treated according to pediatric as compared to adult protocols.

[Differences in the treatment of idiopathic thrombocytopenic purpura in children]. / Forskelle i behandling af børn med idiopatisk trombocytopenisk purpura.

INTRODUCTION: Idiopathic thrombocytopenic purpura (ITP) is a rare immune-mediated bleeding disorder that usually takes a self-limiting and benign course. Due to the risk of intracranial haemorrhage, treatment regimens tend to be active. We present treatment data from 17 paediatric departments in Denmark (1998-2000), focusing on regional differences in treatment strategy. MATERIAL AND METHODS: As part of a prospective Nordic study, clinical findings and treatment were recorded for 109 children with newly diagnosed ITP. The course in the following six months was reported for 91 children. Results are compared for three geographical regions: East, North and South. RESULTS: Pharmacotherapy, almost exclusively intravenous immunoglobulin, was given within 14 days of diagnosis to 89%, 70%, and 48% in regions East, North, and South, respectively. A very low platelet count was the main indication. Platelet transfusion was given to 24%, 0% and 4%, respectively. There were no differences in remission rates or frequency of mucosal bleeding during follow-up, but treatment rates were 6.3, 4.7, and 3.0 per patient-year with severe thrombocytopenia. Chronic ITP lasting more than six months developed in 26%, 33%, and 18%, respectively. CONCLUSION: We found obvious regional differences in treatment strategy which reflect differences in international clinical guidelines. The initial treatment approach had no influence on morbidity, time of remission or risk of chronic course.

Subcutaneous anti-D treatment of idiopathic thrombocytopenic purpura in children.

We investigated the effect of subcutaneous anti-D IgG as platelet enhancing therapy in children with idiopathic thrombocytopenic purpura (ITP). Twenty-three children were treated with subcutaneous anti-D 50 microg/kg. The median platelet count increased from 7 x 10(9) to 31 x 10(9)/L on day 3 (P < 0.01). The median decline in hemoglobin was 1.3 g/dl. Two children experienced minor fever and chills within 24 hr of treatment. Pain at the injection site was common but self-limiting with no effect on activity level. These results suggest subcutaneous anti-D IgG 50 microg/kg as an effective and well-tolerated treatment option in childhood ITP.

[Epidemiology, disease presentation and course of idiopathic thrombocytopenic purpura in Danish children from 1998-2000]. / Epidemiologi, sygdomspraesentation og forløb af idiopatisk trombocytopenisk purpura hos børn i Danmark 1998-2000.

INTRODUCTION: Idopathic Thrombocytopenic Purpura (ITP) is a condition with isolated thrombocytopenia and bleeding symptoms in skin and mucous membranes. It is easy to establish the diagnosis, but treatment is controversial, possibly due to different estimates of the risk for serious bleeding. We present the epidemiology and clinical course of ITP during the first 6 months after diagnosis in Danish children diagnosed from 1998-2000. MATERIALS AND METHODS: The Nordic Society of Paediatric Haematology and Oncology conducted a prospective registration study of children with newly diagnosed ITP from 1998-2000. The study included children < 15 years of age with newly diagnosed, untreated ITP and platelet count (TBC) < 30 x 10(9) /l. Information about bleeding symptoms, TBC, treatment and ITP related episodes was recorded at diagnosis and during the first six months. RESULTS: Of 109 included children 81% had a short symptom history, 46% a preceding viral infection. At diagnosis 62% had TBC < 10 x 10(9) /l, 41% mucosal bleeding, and 72% received medical treatment. Follow-up was available for 91 children. Sixty seven children with acute ITP had TBC < 150 x 10(9) /l for 11 days (median). Twenty four children suffered chronic ITP, 8 of them had persistent TBC < 20 x 10(9) /l. Insidious onset had a 64% predictive value for chronic ITP. Of the 57 registered ITP-related episodes, 45 occurred in chronic cases, 23 of them in six of the children with persistent TBC < 20 x 10(9) /l. CONCLUSION: It is likely that children with newly diagnosed ITP recover quickly, and the risk of serious bleeding is low. A small group of children with persistent severe thrombocytopenia experience significant morbidity.

A clinical score predicting a brief and uneventful course of newly diagnosed idiopathic thrombocytopenic purpura in children.

The Nordic idiopathic thrombocytopenic purpura study data showed that morbidity occurred mainly in children with thrombocytopenia lasting >3 months, whereas, the risk period with platelet counts <20 x 10(9)/l was short and the number of bleeding events low in children with shorter disease duration. These brief, uneventful courses were predicted by developing a scoring system based on six clinical features: abrupt onset (weight 5), age <10 years (3), preceding infection (2), platelet count <5 x 10(9)/l, wet purpura (1) and male gender (1). The score was derived and validated in two different cohorts of children. High scores (10-14) clearly identified low-risk patients. The score provides valid prognostic information and may be useful in clinical decision-making.