B-39/RTOG 0413 accelerated partial breast irradiation (APBI) trial. Presented at the American Society for Radiation Oncology 53rd Annual Meeting; October 2-6, 2011; Miami Beach, FL. 3. Olivotto I, Whelan T, Parpia S, et al. Interim cosmetic and toxicity results from RAPID: A randomized trial of accelerated partial breast irradiation using three-dimensional conformal external beam radiation therapy. J Clin Oncol 2013;31:4038-4045. 4. Vicini FA, Chen P, Wallace M, et al. Interim cosmetic results and toxicity using 3D conformal external beam radiotherapy to deliver accelerated partial breast irradiation in patients with early-stage breast cancer treated with breast-conserving therapy. Int J Radiat Oncol Biol Phys 2007;69:1124-1130. 5. Rosenstein BS, Lymberis SC, Formenti SC. Biologic comparison of partial breast irradiation protocols. Int J Radiat Oncol Biol Phys 2004; 60:1393-1404. 6. Owen JR, Ashton A, Bliss JM, et al. Effect of radiotherapy fraction size on tumour control in patients with early-stage breast cancer after local tumour excision: Long-term results of a randomised trial. Lancet Oncol 2006;7:467-471. 7. Livi L, Meattini I, Marrazzo L, et al. Accelerated partial breast irra- diation using intensity modulated radiotherapy versus whole breast irradiation: 5-year survival analysis of a phase 3 randomised controlled trial. Eur J Cancer 2015;51:451-463. 8. Formenti SC, Truong MT, Goldberg JD, et al. Prone accelerated partial breast irradiation after breast-conserving surgery: Preliminary clinical results and dose-volume histogram analysis. Int J Radiat Oncol Biol Phys 2004;60:493-504. 9. Formenti SC, Hsu H, Fenton-Kerimian M, et al. Prone accelerated partial breast irradiation after breast conserving surgery: Five-year results of 100 patients. Int J Radiat Oncol Biol Phys 2012;84:606-611. 10. Jozsef G, DeWyngaert JK, Becker SJ, et al. Prospective study of cone- beam computed tomography image-guided radiotherapy for prone accelerated partial breast irradiation. Int J Radiat Oncol Biol Phys 2011;81:568-574. In Reply to Gerber et al To the Editor: We appreciate this review (1) of our phase 1 stereotactic partial breast irradiation (2) (S-PBI) clinical trial. As the authors outlined, the previously assumed a/b for breast cancer has fallen within the range of 3 to 4 Gy, which has been used as the basis for some whole breast hypofractionation trials (3, 4). However, it has taken more than 20 years of follow-up from the early breast radiation therapy trials using conventional fractionation to ultimately obtain discernible differences in breast cancer mortality (5). There is no comparable long follow-up time to enable an adequate assessment of the newer dosing regimens used for accelerated PBI treatments. The a/b that we used in our trial was from the MCF-7 breast cancer cell line (6, 7) rather than the 2.8, which was quoted by Gerber et al. Our biological equivalent dose (BED) was calculated using this cell line with the universal survival curve (USC) radiobiological model (8), which has been shown to better approximate hypo- fractionated regimens. Based on this model, 40 Gy in 5 fractions is considered equivalent to 60 Gy in 30 frac- tions using the survival characteristics of the MCF-7 breast cancer cell line (6, 7) (Table E1; available online at www.redjournal.org). Our dose equivalent accounts for a 10-Gy boost, which we offer as a standard for early- stage breast cancer. For the MCF-7 cell line, the shoul- der of the curve ends just over 5 Gy per fraction, and the curve becomes linear with slope D 0 (1.34 Gy for MCF-7). The USC model, as opposed to the linear-quadratic model (LQM), accounts for this transition and includes not only a/b but also D 0 for calculation of the BED. Thus, the LQM, being evercurving, overestimates the BED of large dose per fraction treatments. Our proposed dosing regimen could arguably encompass a greater variety of breast cancers, possibly expanding the use of S-PBI to less favorable biological types. The observed fat necrosis frequency of 13.3% in our trial included both asymptomatic and symptomatic fat necrosis (5% asymptomatic, 8.3% symptomatic). This is comparable to the rates illustrated in the RAPID trial (3%) and SAVI brachy- therapy systems (1.9%) (9, 10) and is significantly lower than the rates from brachytherapy series that used balloon-based systems (86% asymptomatc, 14% symptomatic) (11) and multicathether high-dose-rate interstitial brachytherapy (10.1% asymptomatic, 7.6% symptomatic) (12). We are in agreement that the proper dosing for S-PBI will necessitate striking a balance between therapeutic gain and toxicity. Ultimately, radiobiological modeling has limited potential for determining optimal dosing, and clinical trial experiences with measured patient outcomes are far more relevant. Long-term follow-up and reporting of hypofractio- nated partial breast studies will be crucial in answering these questions. We hope this study can be evaluated as part of a continuum of dosing regimens to optimize this balance. Asal Rahimi, MD Robert Timmerman, MD Department of Radiation Oncology University of Texas Southwestern Medical Center Dallas, Texas http://dx.doi.org/10.1016/j.ijrobp.2017.05.043 References 1. Gerber NK, Formenti SC. In Regard to Rahimi et al. Int J Radiat Oncol Biol Phys 2017;99:498-499. 2. Rahimi A, Thomas K, Spangler A, et al. Preliminary results of a phase 1 dose-escalation trial for early-stage breast cancer using 5-fraction stereotactic body radiation therapy for partial-breast irradiation. Int J Radiat Oncol Biol Phys 2016;96:30-41. 3. START Trialists’ Group, Bentzen SM, Agrawal RK, Aird EG, et al. The UK Standardisation of Breast Radiotherapy (START) Trial A of radiotherapy hypofractionation for treatment of early breast cancer: A randomised trial. Lancet Oncol 2008;9:331-341. 4. Owen JR, Ashton A, Bliss JM, et al. Effect of radiotherapy fraction size on tumour control in patients with early-stage breast cancer after local tumour excision: Long-term results of a randomised trial. Lancet Oncol 2006;7:467-471. 5. Favourable and unfavourable effects on long-term survival of radio- therapy for early breast cancer: An overview of the randomised trials. Conflict of interest: This study was supported by a research grant from Accuray. Volume 99  Number 2  2017 Comments 499