Dose-volume effects of breast cancer radiation therapy on the risk of second oesophageal cancer

Neige Journy; Sara J Schonfeld; Michael Hauptmann; Sander Roberti; Rebecca M Howell; Susan A Smith; Leila Vaalavirta; Marilyn Stovall; Flora E van Leeuwen; Rita E Weathers; David Hodgson; Ethel S Gilbert; Amy Berrington de Gonzalez; Lindsay M Morton

doi:10.1016/j.radonc.2020.07.022

Dose-volume effects of breast cancer radiation therapy on the risk of second oesophageal cancer

Radiother Oncol. 2020 Oct:151:33-39. doi: 10.1016/j.radonc.2020.07.022. Epub 2020 Jul 15.

Affiliations

¹ INSERM U1018, Centre for Research in Epidemiology and Population Health, Laboratory "Radiation Epidemiology & Cancer Survivorship", Gustave Roussy Cancer Campus, Villejuif, France. Electronic address: neige.journy@gustaveroussy.fr.
² Radiation Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, United States.
³ Department of Epidemiology and Biostatistics, Netherlands Cancer Institute, Amsterdam, The Netherlands; Institute of Biostatistics and Registry Research, Brandenburg Medical School Theodor Fontane, Neuruppin, Germany.
⁴ Department of Epidemiology and Biostatistics, Netherlands Cancer Institute, Amsterdam, The Netherlands.
⁵ Department of Radiation Physics, The University of Texas MD Anderson Cancer Center, Houston, United States.
⁶ Department of Oncology, Helsinki University Central Hospital and University of Helsinki, Helsinki, Finland.
⁷ Department of Radiation Oncology, University of Toronto, and Radiation Medicine Program, Princess Margaret Hospital, Toronto, Canada.

PMID: 32679305
DOI: 10.1016/j.radonc.2020.07.022

Abstract

Purpose: To investigate the relationship between oesophagus dose-volume distribution and long-term risk of oesophageal cancer after radiation therapy for breast cancer.

Materials and methods: In a case-control study nested within a cohort of 289,748 ≥5-year survivors of female breast cancer treated in 1943-2003 in five countries, doses to the second primary cancer (D_SPC) and individual dose-volume histograms (DVH) to the entire oesophagus were reconstructed for 252 oesophageal cancer cases and 488 matched controls (median follow-up time: 13, range: 5-37 years). Using conditional logistic regression, we estimated excess odds ratios (EOR) of oesophageal cancer associated with DVH metrics. We also investigated whether DVH metrics confounded or modified D_SPC-related -risk estimates.

Results: Among the DVH metrics evaluated, median dose (D_median) to the entire oesophagus had the best statistical performance for estimating risk of all histological types combined (EOR/Gy = 0.071, 95% confidence interval [CI]: 0.018 to 0.206). For squamous cell carcinoma, the most common subtype, the EOR/Gy for D_median increased by 31% (95% CI: 3% to 205%) for each increment of 10% of V30 (p = 0.02). Adjusting for DVH metrics did not materially change the EOR/Gy for D_SPC, but there was a borderline significant positive interaction between D_SPC and V30 (p = 0.07).

Conclusion: This first study investigating the relationship between oesophagus dose-volume distribution and oesophageal cancer risk showed an increased risk per Gy for D_median with larger volumes irradiated at high doses. While current techniques allows better oesophagus sparing, constraints applied to D_median and V30 could potentially further reduce the risk of oesophageal cancer.

Keywords: Breast cancer; Dose-volume constraint; Oesophageal cancer; Risk modelling; Second cancer.

Publication types

Research Support, N.I.H., Intramural
Research Support, Non-U.S. Gov't

MeSH terms

Breast Neoplasms* / epidemiology
Breast Neoplasms* / etiology
Breast Neoplasms* / radiotherapy
Case-Control Studies
Esophageal Neoplasms* / epidemiology
Esophageal Neoplasms* / etiology
Esophageal Neoplasms* / radiotherapy
Female
Humans
Radiotherapy, Conformal*
Survivors