The impact of central review and central therapy planning on the treatment of children and adolescents with Hodgkin lymphoma.

PURPOSE: The multicentre response-adapted paediatric Hodgkin lymphoma trial GPOH-HD95 (1995-2001, 925 patients) was followed by the 'HD-Interval' period (2001-2002, 203 patients). During this period, treatment was recommended according to GPOH-HD95 protocol with only minor changes. Central review and treatment planning as in HD95, however, had to be omitted in the absence of funding. Results of both periods were compared to evaluate the impact of central review on staging, stratification, treatment planning and outcome. METHODS: Pre- and post-chemotherapy computed tomography and magnetic resonance imaging of HD-Interval patients were evaluated with respect to reliability of staging, response assessment and subsequent treatment stratification. RESULTS: Despite more favourable patient characteristics and treatment group stratifications, the 10-year progression-free survival (PFS) was inferior in HD-Interval patients compared to GPOH-HD95 patients with nearly identical therapy (86% versus 91%, P=0.01). Of 142 patients without guidance by the reference centre, 56 (39%) received a treatment deviating from protocol recommendations: chemotherapy doses were either lower or higher than recommended in 17% of patients, and deviations concerning radiotherapy dose and treatment volume occurred in 25% and 20%, respectively. In both periods, the 10-year PFS was lower in patients with diminished therapy compared to those with adequate treatment according to the given recommendations (HD-Interval: 72% versus 89%, P=0.02; GPOH-HD95: 80% versus 92%, P=0.04). CONCLUSIONS: Deviations from protocol treatment may influence negatively the outcome in paediatric oncology. Protocol enrolment and compliance including timely and correct treatment are crucial. Central reference and consultation centres offer quality assurance, support protocol adherence, and hence influence PFS.

Treatment of children and adolescents with Hodgkin lymphoma without radiotherapy for patients in complete remission after chemotherapy: final results of the multinational trial GPOH-HD95.

UNLABELLED: PURPOSE To minimize the risk of late effects in pediatric Hodgkin lymphoma (HL) by omitting radiotherapy (RT) in patients in complete remission (CR) after chemotherapy and reducing the standard radiation dose to 20 Gy in patients in incomplete remission. PATIENTS AND METHODS: Between 1995 and 2001, 925 patients with classical HL (cHL) were registered from seven European countries in German Society of Pediatric Oncology and Hematology Hodgkin Lymphoma Trial 95. Patients in treatment group 1 (TG1; early stages) received two cycles of vincristine, prednisone, procarbazine, and doxorubicin or vincristine, prednisone, etoposide, and doxorubicin chemotherapy; additional two or four cycles of cyclophosphamide, vincristine, prednisone, and procarbazine were added in TG2 (intermediate stages) or TG3 (advanced stages), respectively. Patients in CR (assessed by computed tomography or magnetic resonance imaging) did not undergo RT. Those with tumor volume reduction more than 75% received reduced involved-field RT with 20 Gy and an additional 10- or 15-Gy boost only for larger residuals. RESULTS: Rates of overall survival, progression-free survival (PFS), and event-free survival at 10 years were (± SE) 96.3% ± 0.6%, 88.2% ± 1.1%, and 85.4% ± 1.3%, respectively. PFS for TG1 patients without or with RT was 97.0% ± 2.1% versus 92.2% ± 1.7% (P = .214) but was unsatisfactory for nonirradiated patients in TG2 (68.5% ± 7.4% v 91.4% ± 1.9%; P < .0001), with similar but not significant results in TG3 (82.6% ± 5.4% v 88.7% ± 2.0%, P = .259). Reduction of the standard radiation dose from 25 to 20 Gy did not increase failure rate. CONCLUSION: RT can be omitted in early stage HL in so defined CR following this chemotherapy. RT with 20(-35) Gy proved to be sufficient in patients with incomplete remission following chemotherapy.

Ocular symptoms in children treated with human-mouse chimeric anti-GD2 mAb ch14.18 for neuroblastoma.

Unusual ocular symptoms observed during intravenous treatment with anti-disialoganglioside antibody (Ab) in children suffering from neuroblastoma were analyzed and the results reported. Within the framework of the German Collaborative Neuroblastoma Study NB97, 85 children with high-risk neuroblastoma received anti-GD2 monoclonal antibody ch14.18 intravenously. Side effects were regularly reported to the study center. Ocular symptoms were recorded in clinical detail, duration and development over time. Symptoms of a parasympathetic deficit corresponding to internal ophthalmoplegia, i.e. mydriasis and accommodation deficit, were found in 10 patients. They were uni- or bilateral, began after the termination of Ab infusion and improved or disappeared in all surviving children. They did not reappear or worsen upon repeated Ab infusions. The pathophysiology of these disorders remains poorly understood. It is concluded that during systemic treatment with the anti-GD2 antibody ch14.18, reversible symptoms of parasympathetic denervation of the eye may occur which, however, do not warrant termination of this treatment.