Toxicity Evaluation of Dose-Escalation in Hypofractionated Regional Nodal Irradiation for Breast Cancer: A Retrospective Study

Int J Radiat Oncol Biol Phys. 2024 Nov 1;120(3):823-834. doi: 10.1016/j.ijrobp.2024.04.014. Epub 2024 Apr 15.

Abstract

Purpose: Regional nodal irradiation (RNI) to the axilla and supraclavicular area presents distinct toxicities, such as lymphedema and shoulder stiffness, compared with whole-breast irradiation. There is insufficient evidence on the safety of dose-escalation in hypofractionated RNI. We aimed to evaluate and compare toxicity rates in patients with breast cancer who received hypofractionated RNI with and without dose-escalation.

Methods and materials: We retrospectively analyzed 381 patients with breast cancer treated with hypofractionated RNI between March 2015 and February 2017. Patients received either the standard-dose to the regional nodal area (43.2 Gy/16 fx; 48.7 Gy3.5 equivalent dose [EQD2], 2 Gy equivalent dose with α/β= 3.5 Gy) or dose-escalation with a median dose of 54.8 Gy3.5 EQD2 (range, 51.7-60.9 Gy3.5 EQD2), depending on clinical and pathologic nodal stage. Toxicity rates of lymphedema and shoulder stiffness were assessed, and statistical analyses were conducted to identify associated factors.

Results: The median follow-up time was 32.3 months (5.7-47.0 months). After radiation therapy, 71 (18.6%) patients developed lymphedema, and 48 (12.6%) developed shoulder stiffness. Patients who received dose-escalation exhibited significantly higher rates of lymphedema (32.1% vs 14.8%; odds ratio, 2.72, P = .0004) and shoulder stiffness (23.8% vs 9.4%; odds ratio, 2.01, P = .0205) compared with the standard-dose group. Moreover, dose-escalation showed a tendency to increase the severity of lymphedema and shoulder stiffness.

Conclusions: Patients who received dose-escalation in hypofractionated RNI face a higher risk of developing lymphedema and shoulder stiffness compared with those who received standard-dose hypofractionated RNI. Therefore, it is crucial to implement close and frequent monitoring for early detection, along with timely rehabilitation interventions for these patients.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Axilla
  • Breast Neoplasms* / pathology
  • Breast Neoplasms* / radiotherapy
  • Female
  • Humans
  • Lymphatic Irradiation* / adverse effects
  • Lymphedema / etiology
  • Middle Aged
  • Radiation Dose Hypofractionation*
  • Radiation Injuries / etiology
  • Retrospective Studies
  • Shoulder / radiation effects