Twenty years of experience of a tertiary cancer center in total body irradiation with focus on oncological outcome and secondary malignancies

Abstract

Purpose: Total body irradiation (TBI) is a common part of the myelo- and immuno-ablative conditioning regimen prior to an allogeneic hematopoietic stem cell transplantation (allo-HSCT). Due to concerns regarding acute and long-term complications, there is currently a decline in otherwise successfully established TBI-based conditioning regimens. Here we present an analysis of patient and treatment data with focus on survival and long-term toxicity.

Methods: Patients with hematologic diseases who received TBI as part of their conditioning regimen prior to allo-HSCT at Frankfurt University Hospital between 1997 and 2015 were identified and retrospectively analyzed.

Results: In all, 285 patients with a median age of 45 years were identified. Median radiotherapy dose applied was 10.5 Gy. Overall survival at 1, 2, 5, and 10 years was 72.6, 64.6, 54.4, and 51.6%, respectively. Median follow-up of patients alive was 102 months. The cumulative incidence of secondary malignancies was 12.3% (n = 35), with hematologic malignancies and skin cancer predominating. A TBI dose ≥ 8 Gy resulted in significantly improved event-free (p = 0.030) and overall survival (p = 0.025), whereas a total dose ≤ 8 Gy and acute myeloid leukemia (AML) diagnosis were associated with significantly increased rates of secondary malignancies (p = 0.003, p = 0.048) in univariate analysis. No significant correlation was observed between impaired renal or pulmonary function and TBI dose.

Conclusion: TBI remains an effective and well-established treatment, associated with distinct late-toxicity. However, in the present study we cannot confirm a dose-response relationship in intermediate dose ranges. Survival, occurrence of secondary malignancies, and late toxicities appear to be subject to substantial confounding in this context.

Keywords: Hematopoietic stem cell transplant; Long-term follow-up; Sequelae; TBI; Toxicity.

Fig. 1

Overall survival of all patients (a) and cumulative incidence of secondary malignancies during the observation period (b). ALL acute lymphoblastic leukemia, AML acute myeloid leukemia

Fig. 2

Overall survival and event-free survival according to primary disease (a, c) and applicated dose (b, d). ALL acute lymphoblastic leukemia, AML acute myeloid leukemia

Fig. 3

The frequency of secondary malignancies in our cohort of patients who underwent a total body irradiation as a part of their conditioning regimen in prior to hematopoietic stem cell transplantation (HSCT). HNSCC head and neck squamous cell carcinoma

Fig. 4

Cumulative incidence of secondary malignancies stratified by total dose (a, b and c) and by primary disease (d). The numbers of patients at risk are given below. ALL acute lymphoblastic leukemia, AML acute myeloid leukemia

Fig. 5

Total number of chronic disorders after treatment