Cyrus Chargari1, Christine Haie-Meder2, Sophie Espenel2, Max-Adrien Garcia3, Myriam Ben-Arush4, Stéphanie Bolle2, Anna Borjesson5, Maja Cesen6, Rita Costa Lago7, Anne-Sophie Defachelles8, Barbara De Moerloose9, Christine Devalck10, Pernille Edslev11, Nuno Jorge Farinha12, Nadine Francotte13, Heidi Glosli14, Sebastien Gouy15, Gabriela Guillen Burrieza16, Sylvie Helfre17, Sabine Irtan18, Antonis Kattamis19, Ana Lacerda20, Antonin Levy2, Lisa Lyngsie Hjalgrim21, Ludovic Mansuy22, Eric Mascard23, Salma Moalla24, Daniel Orbach25, Cormac Owens26, Pascale Philippe-Chomette27, Barry Pizer28, Claire Pluchart29, Marleen Renard30, Anne Gro Wesenberg Rognlien14, Angélique Rome31, Sabine Sarnacki23, Akmal Safwat32, Amalia Schiavetti33, Jill Serre34, Cécile Verite35, Nicolas Von Der Weid36, Mariusz Wysocki37, Dominique Valteay-Couanet38, Eric Deutsch2, Véronique Minard-Colin38, Hélène Martelli39, Florent Guérin39. 1. Radiation Oncology, Gustave Roussy Cancer Campus, Villejuif, France. Electronic address: cyrus.chargari@gustaveroussy.fr. 2. Radiation Oncology, Gustave Roussy Cancer Campus, Villejuif, France. 3. Centre Hygée, Saint Etienne, France. 4. Ruth Rappaport Children's Hospital, Haifa, Israel. 5. Department of Pediatric Surgery, Lund University Hospital, Lund, Sweden. 6. University Children's Hospital Ljubljana, Ljubljana, Slovenia. 7. Radiation Oncology Department, Centro Hospitalar Universitário de São João, Porto, Portugal. 8. Pediatric Oncology, Centre Oscar Lambret, Lille, France. 9. Department of Pediatric Hemato-Oncology, Ghent University Hospital, Ghent, Belgium. 10. Hôpital Universitaire des Enfants Reine Fabiola, Brussels, Belgium. 11. Child and Adolescent Health, Division for Hematology and Oncology, Aarhus University Hospital, Aarhus, Denmark. 12. Pediatric Oncology Department, Centro Hospitalar Universitário de São João, Porto, Portugal. 13. Service Interhospitalier Universitaire d'Hématologie et d'Oncologie Pédiatrique Liégeois, Liège, Belgium. 14. Division of Paediatric and Adolescent Medicine, Oslo University Hospital, Oslo, Norway. 15. Gynecological Surgery, Gustave Roussy Cancer Campus, Villejuif, France. 16. Hospital Universitario Vall d'Hebron, Barcelona, Spain. 17. Radiation Oncology, Institut Curie, Paris, France. 18. Sorbonne Université, Visceral and Neonatal Pediatric Surgery, Centre Hospitalier Universitaire Armand Trousseau, Assistance Publique-Hôpitaux de Paris, Paris, France. 19. Division of Pediatric Hematology-Oncology, First Department of Pediatrics, National and Kapodistrian University of Athens, Athens, Greece. 20. Pediatric Oncology, Instituto Portugues de Oncologia de Lisboa Francisco Gentil, Lisboa, Portugal. 21. Department of Pediatrics and Adolescent Medicine, University Hospital Rigshospitalet, Copenhagen, Denmark. 22. Pediatric Oncology, Centre Hospitalier Universitaire de Nancy, Nancy, France. 23. Pediatric Surgery, Centre Hospitalier Universitaire Necker, Paris, France. 24. Department of Radiology, Gustave Roussy Cancer Campus, Villejuif, France. 25. SIREDO Oncology Center (Care, Innovation and Research for Children, Adolescents and Young Adults with Cancer), Paris Sciences et Lettres University, Institut Curie, Paris, France. 26. National Pediatric Oncology Unit, Our Lady's Children's Hospital, Crumlin, Dublin, Ireland. 27. Pediatric Surgery, Hôpital Universitaire Robert-Debré, Assistance Publique de Hôpitaux de Paris, Paris, France. 28. Department of Paediatric Oncology, Alder Hey Children's Hospital, Liverpool, United Kingdom. 29. Service d'Oncologie Pédiatrique, Centre Hospitalier Universitaire de Reims, Reims, France. 30. Kinderhemato-Oncologie, University Hospital, Leuven, Belgium. 31. Pediatric Oncology, Hôpital La Timone, Marseille, France. 32. Oncology Department and Danish Center for Particle Therapy, Aarhus University Hospital, Aarhus, Denmark. 33. Pediatric Oncology Unit, Sapienza University of Rome, Rome, Italy. 34. Centre Hospitalier Regional et Universitaire Clocheville, Tours, France. 35. Pediatric Oncology, Groupe Hospitalier Pellegrin Hôpital des Enfants, Bordeaux, France. 36. Pediatric Oncology, Universitäts-Kinderspital Beider Basel, University of Basel, Basel, Switzerland. 37. Department of Pediatric Hematology and Oncology, Dr Antoni Jurasz Memorial University Hospital, Bydgoszcz, Poland. 38. Department of Pediatric and Adolescent Oncology, Gustave Roussy, Université Paris-Saclay, Villejuif, France. 39. Paris-Saclay University, Assistance Publique-Hôpitaux de Paris, Bicêtre Hospital, Department of Pediatric Surgery, Le Kremlin Bicêtre, France.
Abstract
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.
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.