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Publications

Journal Article Ppublish

PubMed: 42497480 DOI: 10.1016/j.esmoop.2026.108313

Cancer treatments-related factors for subsequent soft-tissue sarcoma in childhood cancer survivors.

ESMO Open 11(8):108313

Authors: R S Allodji, R C Reulen, I Diallo, D L Winter, G Vu-Bezin, S Bolle, M Locquet, F Bagnasco, E Bárdi, E A M Feijen, D Alessi, M M Fidler-Benaoudia, S Høgsholt, C J Bright, H Linge, B Fresneau, N Haddy, C Veres, D Llanas, N Journy, C Demoor-Goldschmidt, J Byrne, D Bejarano-Quisoboni, D Grabow, W Zrafi, T Gudmundsdottir, G Michel, W Gunnes, P Kaatsch, C Rubino, H Jenkinson, M Kaiser, R Skinner, R Aho Glele, C Ducos, N Aba, T Cole, N Waespe, S Nordenfelt, T Charrier, M Zidane, M Jankovic, T Lähteenmäki, M M Maule, H J H van der Pal, C M Ronckers, F E van Leeuwen, J Teepen, M Terenziani, T Wiebe … and 11 other authors

Affiliations

  • Université Paris-Saclay, Gustave Roussy, Inserm, UVSQ, Center for Research in Epidemiology and Population Health - Unit 1018, EpiRad (Radiation Epidemiology team), Villejuif, France.
  • Centre for Childhood Cancer Survivor Studies, School of Health Sciences, University of Birmingham, Birmingham, UK.
  • Université Paris-Saclay, Gustave Roussy, INSERM U1030, Molecular Radiation Therapy and Therapeutic Innovation, Villejuif, France.
  • Université Paris-Saclay, Gustave Roussy, Inserm, UVSQ, Center for Research in Epidemiology and Population Health - Unit 1018, EpiRad (Radiation Epidemiology team), Villejuif, France.
  • Centro de Protonterapia Quironsalud, Pozuelo de Alarcon, Madrid, Spain.
  • Scientific Directorate, IRCCS Istituto Giannina Gaslini, Genova, Italy.
  • St Anna Children's Hospital, Vienna, Austria; Department of Paediatrics and Adolescent Medicine, Johannes Kepler University Linz, Kepler University Hospital, Linz, Austria.
  • Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands.
  • Childhood Cancer Registry of Piedmont, Cancer Epidemiology Unit, Department of Medical Sciences, University of Turin and CPO-Piemonte, AOU Città della Salute e della Scienza di Torino, Torino, Italy.
  • Cancer Epidemiology and Prevention Research, Alberta Health Services, Calgary, Alberta; Departments of Oncology and Community Health Sciences, University of Calgary, Calgary, Alberta, Canada.
  • Danish Cancer Society Research Center, Childhood Cancer Research Group, Copenhagen; Department of Pediatrics, Aarhus University Hospital, Aarhus, Denmark.
  • NHS Digital, Leeds, UK.
  • Department of Clinical Sciences Lund, Division of Pediatrics, Lund University, Skane University Hospital, Lund, Sweden.
  • Boyne Research Institute, Bettystown, Ireland.
  • German Childhood Cancer Registry, Division of Childhood Cancer Epidemiology, Institute of Medical Biostatistics, Epidemiology and Informatics (IMBEI), Johannes-Gutenberg University Mainz, Germany.
  • Danish Cancer Society Research Center, Childhood Cancer Research Group, Copenhagen; Childreńs Hospital, Landspitali University Hospital, Reykjavik, Iceland.
  • Faculty of Health Sciences and Medicine, University of Lucerne, Lucerne, Switzerland.
  • Norwegian National Advisory Unit on Solid Tumors in Children, Oslo, Norway; Norwegian Cancer Registry and Department of Pediatric Medicine, Oslo University Hospital and Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway.
  • Birmingham Children's Hospital, Birmingham, UK.
  • Great North Children's Hospital, Newcastle upon Tyne Hospitals NHS Foundation Trust, and Newcastle University Centre for Cancer, Newcastle University, Newcastle upon Tyne, UK.
  • Autorité de Sûreté Nucléaire et de Radioprotection (ASNR), PSE-SANTE/SERAMED/LRMED, Fontenay-aux-Roses, France.
  • West Midlands Regional Genetics Laboratory, Birmingham Women's Hospital, Birmingham, UK.
  • CANSEARCH Research Platform for Paediatric Oncology and Haematology, Department of Paediatrics, Gynaecology and Obstetrics, Faculty of Medicine, University of Geneva, Geneva, Switzerland; Childhood Cancer Research Group, Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland; Division of Pediatric Hematology/Oncology, Department of Pediatrics, University Children's Hospital of Bern, University of Bern, Bern, Switzerland.
  • Lund University Cancer Centre, Lund, Sweden.
  • Pediatric Clinic, University of Milano-Bicocca, Hospital San Gerardo, Monza, Italy.
  • Department of Pediatrics and Adolescent Medicine, Turku University and Turku University Hospital, Turku, Finland.
  • Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands; Division of CAYA Cancer Survivorship Research, German Cancer Research Center, Heidelberg, Germany.
  • Department of Epidemiology, Division of Psychosocial Research & Epidemiology, Netherlands Cancer Institute, Amsterdam, The Netherlands.
  • Pediatric Oncology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy.

Abstract

BACKGROUND

Previous studies of risk factors for subsequent soft-tissue sarcoma (STS) among childhood cancer survivors had small numbers and were unable to comprehensively investigate the dose-response relationships with radiation from radiotherapy and with cumulative exposure to specific cytotoxics.

PATIENTS AND METHODS

We conducted a nested case-control study, encompassing 275 subsequent STS cases and 275 matched controls, within the Pan-European cohort of 69 460 5-year survivors from 12 countries. Odds ratios (ORs) and 95% confidence intervals (CIs) for subsequent STS were calculated for different levels of radiation dose to the STS location (in Gy) and for cumulative doses of specific chemotherapeutic agents (in g/m 2). Additionally, excess ORs per Gy (EOR/Gy) or per g/m 2 (EOR/g/m 2) were calculated to assess dose-response relationships.

RESULTS

The OR for subsequent STS was 22-fold [95% CI 6.9-95.4] higher in soft tissue exposed to ≥30 Gy and remained in excess with exposure to 5-9 Gy [OR = 3.8, 95% CI 1.3-12.0] compared with no radiation. The EOR/Gy was 0.86 [95% CI 0.35-2.16], with a particularly high risk observed in survivors of neuroblastoma [EOR/Gy = 5.52, 95% CI 0.71-52.31] or bone sarcoma [EOR/Gy = 4.16, 95% CI 0.40-24.72], and in females [EOR/Gy = 2.35; 95% CI 0.65-8.14]. For patients who had received a cumulative procarbazine dose of ≥6.0 g/m 2, the OR was 4.7 [95% CI 1.3-25.1] compared with non-exposure after controlling for radiation. No association was found for other alkylating agents or other specific cytotoxic drugs.

CONCLUSION

Although high radiation doses remain the primary risk factor for secondary STS, our findings suggest a possible increase in risk at lower doses (5-9 Gy) and following procarbazine treatment among childhood cancer survivors. These observations warrant further investigation and may merit consideration in treatment planning and long-term follow-up guidelines for cancer survivors.

MeSH

Radiotherapy, Cancer Survivors, Neoplasms, Drug Therapy, Sarcoma, Risk Factors, Procarbazine, Therapeutics, Tissues, Chemotherapy