Clarification of the radiobiological basis for the reported equivalence of a single 20-Gy fraction

Dear Editor, I read with interest the recent article by Hacımustafaoğlu et al., entitled ‘Radiobiological effects of flattening filter and flattening filter free radiotherapy X-ray on inflammatory and apoptotic pathways in cardiac and pulmonary tissues in an MCF-7 xenograft breast cancer model’ [1]. This study states that ‘a single fraction dose of 20 Gy corresponding to a conventional biological equivalent dose of ~60–70 Gy was administered’. This statement is ambiguous because it does not specify the dose-equivalence metric, the assumed α/β ratio or the biological endpoint. I respectfully suggest that this ambiguity may mislead readers and should be clarified. The two most commonly used metrics are biologically effective dose (BED) and equivalent dose in 2-Gy fractions (EQD2). Using the linear-quadratic model, BED and EQD2 are defined as [2]: For a single 20-Gy fraction (n = 1, d = 20 Gy): Table 1 shows the calculated BED and EQD2 values for a single 20-Gy fraction at α/β ratios of 10, 3 and 2 Gy. Dependence of BED and EQD2 on α/β for a single 20-Gy fraction Note: BED = nd[1 + d/(α/β)]; EQD2 = BED/[1 + 2/(α/β)]. For a single fraction, n = 1 and d = 20 Gy. Thus, even for α/β = 10 Gy, the EQD2 is 50 Gy, not 60–70 Gy. The reported range of 60–70 Gy appears to reflect only the BED₁₀ value (60 Gy₁₀) and does not correspond to an EQD2. Moreover, the upper end of the reported range (70 Gy) does not correspond to any standard BED or EQD2 calculation for a single 20-Gy fraction. For α/β = 10 Gy, BED₁₀ = 60 Gy₁₀ and EQD2₁₀ = 50 Gy; for α/β = 2–3 Gy, the corresponding values are substantially higher. Thus, neither 60 nor 70 Gy represents a conventional equivalent dose in 2-Gy fractions for cardiac or pulmonary tissues. For cardiac and pulmonary tissues, which are late-responding, α/β is typically 2–3 Gy, depending on the specific endpoint (e.g. fibrosis, vascular injury or functional loss) [3]. Using a single α/β value for all cardiopulmonary effects is therefore not appropriate, and the 60–70 Gy equivalence is particularly misleading for these tissues. It is also important to distinguish the prescribed 20-Gy dose from the actual organ-specific doses delivered to the heart and lungs. The original article does not report dosimetric verification of cardiac or pulmonary doses, so the biological impact on these organs cannot be directly inferred from the prescribed dose alone. In summary, I recommend that the authors clarify whether the 60–70 Gy figure refers to BED or EQD2, state the assumed α/β ratio and the biological endpoint, and provide the corresponding EQD2 calculation. They should also acknowledge that organ-specific doses to the heart and lungs were not measured. This clarification would significantly improve the interpretability of the study. The author declares no conflict of interest. None declared.