title: Longitudinal follow-up of adult survivors of Ewing sarcoma: A report from the Childhood Cancer Survivor Study.
abstract: BACKGROUND
  Ewing sarcoma survivors (ESSs) are at increased risk for treatment-related complications. The incidence of treatment-related morbidity and late mortality with aging is unknown.
  
  
  METHODS
  This study reports survival probabilities, estimated with the Kaplan-Meier method, and the cumulative incidence of cause-specific mortality and chronic conditions among ESSs in the Childhood Cancer Survivor Study who were treated between 1970 and 1986. Piecewise exponential models were used to estimate relative rates (RRs) and 95% confidence intervals (CIs) for these outcomes. Chronic conditions were graded with the Common Terminology Criteria for Adverse Events (version 4.03).
  
  
  RESULTS
  Among 404 5-year ESSs (median age at last follow-up, 34.8 years; range, 9.1-54.8 years), the 35-year survival rate was 70% (95% CI, 66%-74%). Late recurrence (cumulative incidence at 35 years, 15.1%) was the most common cause of death, and it was followed by treatment-related causes (11.2%). There were 53 patients with subsequent neoplasms (SNs; cumulative incidence at 35 years, 24.0%), and 38 were malignant (14.3% at 35 years). The standardized incidence ratios were 377.1 (95% CI, 172.1-715.9) for osteosarcoma, 28.9 (95% CI, 3.2-104.2) for acute myeloid leukemia, 14.9 (95% CI, 7.9-25.5) for breast cancer, and 13.1 (95% CI, 4.8-28.5) for thyroid cancer. Rates of chronic conditions were highest for musculoskeletal (RR, 18.1; 95% CI, 12.8-25.7) and cardiac complications (RR, 1.8; 95% CI, 1.4-2.3). Thirty-five years after the diagnosis, the cumulative incidences of any chronic conditions and 2 or more chronic conditions were 84.6% (95% CI, 80.4%-88.8%) and 73.8% (95% CI, 67.8%-79.9%), respectively.
  
  
  CONCLUSIONS
  With extended follow-up, ESSs' risk for late mortality and SNs does not plateau. Treatment-related chronic conditions develop years after therapy, and this supports the need for lifelong follow-up. Cancer 2017;123:2551-60. © 2017 American Cancer Society.
authors.affiliation: Department of Pediatrics, Stanford University and Lucile Packard Children's Hospital, Palo Alto, California.
authors.forename: Neyssa M
authors.initials: NM
authors.lastname: Marina
authors.affiliation: School of Public Health, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Qi
authors.initials: Q
authors.lastname: Liu
authors.affiliation: Depratment of Radiation Oncology, Stanford University, Stanford, California.
authors.forename: Sarah S
authors.initials: SS
authors.lastname: Donaldson
authors.affiliation: Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York.
authors.forename: Charles A
authors.initials: CA
authors.lastname: Sklar
authors.affiliation: Department of Epidemiology and Cancer Control, St. Jude Children's Research Hospital, Memphis, Tennessee.
authors.forename: Gregory T
authors.initials: GT
authors.lastname: Armstrong
authors.affiliation: Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York.
authors.forename: Kevin C
authors.initials: KC
authors.lastname: Oeffinger
authors.affiliation: Seattle Children's Hospital, Clinical Statistics, Seattle, Washington.
authors.forename: Wendy M
authors.initials: WM
authors.lastname: Leisenring
authors.affiliation: Department of Pediatric Oncology, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.
authors.forename: Jill P
authors.initials: JP
authors.lastname: Ginsberg
authors.affiliation: University of Chicago, Comprehensive Cancer Center, Pediatric Oncology, Chicago, Illinois.
authors.forename: Tara O
authors.initials: TO
authors.lastname: Henderson
authors.affiliation: University of Minnesota/Masonic Cancer Center, Pediatrics, Minneapolis, Minnesota, Minnesota.
authors.forename: Joseph P
authors.initials: JP
authors.lastname: Neglia
authors.affiliation: The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Marilyn A
authors.initials: MA
authors.lastname: Stovall
authors.affiliation: Department of Epidemiology and Cancer Control, St. Jude Children's Research Hospital, Memphis, Tennessee.
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Yasui
authors.affiliation: Department of Orthopedic Surgery, Primary Children's Hospital and Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah.
authors.forename: R Lor
authors.initials: RL
authors.lastname: Randall
authors.affiliation: Montefiore Medical Center-Moses Campus and Orthopedic Surgery, Children's Hospital at Montefiore, Bronx, New York.
authors.forename: David S
authors.initials: DS
authors.lastname: Geller
authors.affiliation: Department of Epidemiology and Cancer Control, St. Jude Children's Research Hospital, Memphis, Tennessee.
authors.forename: Leslie L
authors.initials: LL
authors.lastname: Robison
authors.affiliation: Department of Epidemiology and Cancer Control, St. Jude Children's Research Hospital, Memphis, Tennessee.
authors.forename: Kirsten K
authors.initials: KK
authors.lastname: Ness
mesh_terms: D000293:Adolescent; D000328:Adult; D018943:Anthracyclines / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000627:therapeutic use; D001859:Bone Neoplasms / Q000453:epidemiology / Q000401:mortality* / Q000628:therapy; D001943:Breast Neoplasms / Q000453:epidemiology; D002648:Child; D002908:Chronic Disease; D015331:Cohort Studies; D005260:Female; D005500:Follow-Up Studies; D006331:Heart Diseases / Q000453:epidemiology; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000453:epidemiology; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D009026:Mortality; D009140:Musculoskeletal Diseases / Q000453:epidemiology; D009364:Neoplasm Recurrence, Local / Q000401:mortality*; D016609:Neoplasms, Second Primary / Q000453:epidemiology*; D019637:Orthopedic Procedures; D012516:Osteosarcoma / Q000453:epidemiology; D011878:Radiotherapy; D012189:Retrospective Studies; D012512:Sarcoma, Ewing / Q000401:mortality* / Q000628:therapy; D017741:Survivors; D013964:Thyroid Neoplasms / Q000453:epidemiology; D055815:Young Adult
chemical_list: D018943:Anthracyclines; D000970:Antineoplastic Agents
keywords: Ewing sarcoma; childhood cancer survivors; chronic health conditions; late mortality; treatment-related complications