Estimation of Annual Secondary Lung Cancer Deaths Using Various Adjuvant Breast Radiotherapy Techniques for Early-Stage Cancers.

Nienke Hoekstra,Jean-Philippe Pignol,Maureen Nolan,Derek Wilke,Hannah Dahn,Frank Vicini

doi:10.3389/fonc.2021.713328

Abstract

PurposeSecondary lung cancer (SLC) can offset the benefit of adjuvant breast radiotherapy (RT), and risks compound sharply after 25 to 30 years. We hypothesized that SLC risk is mainly an issue for early-stage breast cancer, and that lives could be saved using different RT techniques.Patients and MethodsThe SEER database was used to extract breast patient age, stage survival, and radiotherapy utilization over time and per stage and to assess the factors associated with increased SLC risk with a multivariable competing risk Cox model. The number of SLC was calculated using the BEIR model modified with patient survival, age, and use of RT from the SEER database. Stage distribution and number of new breast cancer cases were obtained from the NAACCR. Mean lung dose for various irradiation techniques was obtained from measurement or literature.ResultsOut of the 765,697 non-metastatic breast cancers in the SEER database from 1988 to 2012, 49.8% received RT. RT significantly increased the SLC risk for longer follow-up (HR=1.58), early stage including DCIS, stage I and IIA (HR = 1.11), and younger age (HR=1.061) (all p<0.001). More advanced stages did not have significantly increased risk. In 2019, 104,743 early-stage breast patients received radiotherapy, and an estimated 3,413 will develop SLC (3.25%) leading to an excess of 2,900 deaths (2.77%). VMAT would reduce this mortality by 9.9%, hypofractionation 26 Gy in five fractions by 38.8%, a prone technique by 70.3%, 3D-CRT APBI by 43.3%, HDR brachytherapy by 71.1%, LDR by 80.7%, and robotic 4π APBI by 85.2%.ConclusionsSLC after breast RT remains a clinically significant issue for early-stage breast cancers. This mortality could be significantly reduced using a prone technique or APBI.

Highlights

volumetric modulated arc therapy (VMAT) would reduce this mortality by 9.9%, hypofractionation 26 Gy in five fractions by 38.8%, a prone technique by 70.3%, 3D-conformal radiotherapy (CRT) accelerated partial breast irradiation (APBI) by 43.3%, high-dose rate (HDR) brachytherapy by 71.1%, LDR by 80.7%, and robotic 4p APBI by 85.2%
With the generalization of mammography screening, breast cancer can be diagnosed at an early stage [1], and the treatment gold standard includes breast-conserving surgery followed by whole breast radiotherapy
Using a modified version of the BEIR VII model, we previously confirmed a delay of the lifetime attributable risk (LAR) of excess lung cancers, which would be 0.33% 10 years after radiotherapy, 0.7% after 15 years, and 3% after 25 years [11]

Summary

Introduction

With the generalization of mammography screening, breast cancer can be diagnosed at an early stage [1], and the treatment gold standard includes breast-conserving surgery followed by whole breast radiotherapy. Cardiac morbidity appears relatively soon after the radiation treatment, generally 5 to 10 years following exposure of the heart [5, 6]. It is well documented in long-term reports of randomized trials or meta-analysis [4, 5]. It has justified technique changes, including the generalization of breath-hold or gating techniques and the development of constraints for the mean heart dose [7, 8]. Using a modified version of the BEIR VII model, we previously confirmed a delay of the lifetime attributable risk (LAR) of excess lung cancers, which would be 0.33% 10 years after radiotherapy, 0.7% after 15 years, and 3% after 25 years [11]

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