title: Long-term follow-up of patients treated with primary radiotherapy for supradiaphragmatic Hodgkin's disease at St. Jude Children's Research Hospital.
abstract: OBJECTIVE
  To assess disease control, patterns of relapse, factors predictive of relapse, and late effects of treatment, we reviewed all cases of supradiaphragmatic (SD) Hodgkin's disease (HD) treated with primary radiation therapy (RT) at our institution.
  
  
  METHODS
  We retrospectively reviewed the disease characteristics, treatment history, and long-term outcome of the 106 patients with Stage I and II supradiaphragmatic HD who received definitive irradiation at St. Jude Children's Research Hospital between 1970 and 1995. As of the date of analysis, 95 patients are alive, with a median follow-up of 13.3 years (range, 1.9-24.2 years).
  
  
  RESULTS
  The median age at diagnosis was 14.7 years (range, 3.7-22.7). Involved-field RT was given to 13 patients (12%), whereas 37 (35%) had mantle RT, 51 patients (48%) had subtotal nodal irradiation, and 5 (5%) had total nodal irradiation. Relapsed disease developed in 26 patients at a median of 1.8 years (range, 0.2-9.3 years). The 5- and 10-year estimated cumulative incidences of relapse were 20.9% +/- 4.0% and 25.1% +/- 4.3%, respectively. With a median dose of 36 Gy (range, 32-40), in-field failure rate was 6.2%, whereas subdiaphragmatic relapse in sites irradiated prophylactically was 1.5%. There was a trend toward an increased incidence of relapse with higher ESR (p = 0.088) and greater number of sites of disease (p = 0.087). Age, stage, histology, nodal disease > or = 6 cm, the presence of bulky mediastinal disease, and the method of staging did not affect the incidence of relapse. The pattern of failure could not be predicted based on the stage of disease, the extent of subdiaphragmatic staging, the extent of radiation therapy, or the sequence of RT fields-"ping pong" vs. sequential. Subset analysis of Stage II patients revealed significantly more relapses in clinically staged patients. Excluding Stage IA patients with high cervical disease or peripheral nodal disease, nodal extension failures were more common for patients undergoing limited-volume RT, whereas extranodal relapses were likely after STNI or TNI. The estimated 10- and 15-year cumulative incidences of second malignancies were 2.9% +/- 1.6% and 7.9% +/- 3.3%, respectively. Our patients are at increased risk of second malignancies (11-fold), and fatal cardiac (68-fold) and infectious (33-fold) complications. Overall survival at 10 years was 90.8% +/- 3.2%; event-free survival was 72.1% +/- 5.0%.
  
  
  CONCLUSIONS
  The current analysis confirms the curative potential of RT for HD in children and adolescents. Despite successful salvage therapy, relapsed disease remained the principal cause of death in our cohort. Excess risk of septic death in asplenic patients, fatal heart disease, and second malignancies may further compromise the ultimate cure of HD in long-term survivors.
authors.affiliation: Department of Radiation Oncology, St. Jude Children's Research Hospital, Memphis, TN, USA.
authors.forename: A B
authors.initials: AB
authors.lastname: Shah
authors.forename: M M
authors.initials: MM
authors.lastname: Hudson
authors.forename: C A
authors.initials: CA
authors.lastname: Poquette
authors.forename: X
authors.initials: X
authors.lastname: Luo
authors.forename: J A
authors.initials: JA
authors.lastname: Wilimas
authors.forename: L E
authors.initials: LE
authors.lastname: Kun
mesh_terms: D000293:Adolescent; D000328:Adult; D000704:Analysis of Variance; D002423:Cause of Death; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D005260:Female; D005500:Follow-Up Studies; D006689:Hodgkin Disease / Q000188:drug therapy / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy*; D006801:Humans; D007223:Infant; D008297:Male; D009367:Neoplasm Staging; D016609:Neoplasms, Second Primary / Q000453:epidemiology; D011379:Prognosis; D011879:Radiotherapy Dosage; D012008:Recurrence; D012189:Retrospective Studies; D016879:Salvage Therapy; D017211:Treatment Failure