Background: Breast cancer is the most common malignancy in women, and adjuvant radiotherapy for left-sided disease raises important concerns regarding cardiac and pulmonary toxicity. Advanced techniques such as intensity-modulated radiotherapy (IMRT) and volumetric-modulated arc therapy (VMAT) may improve dose conformity compared with three-dimensional conformal radiotherapy (3DCRT), but can increase low-dose exposure to normal tissues. Methods: In this retrospective planning study, three techniques—3DCRT, IMRT, and VMAT—were compared for left-sided whole-breast irradiation using both conventional dosimetric metrics and Equivalent Uniform Dose (EUD)-based radiobiological modeling, where EUD represents the biologically equivalent uniform dose corresponding to a heterogeneous dose distribution. Sixteen women with left-sided breast cancer treated at a single institution underwent CT simulation and had three separate plans generated on the same dataset (3DCRT, IMRT, VMAT) with identical prescription dose and uniform dose-volume constraints. Planning target volume (PTV) indices and organs-at-risk (OAR) doses were extracted from dose-volume histograms. Tumor control probability (TCP) and normal tissue complication probability (NTCP) for the heart, ipsilateral and contralateral lungs, and contralateral breast were calculated using Niemierko-based EUD models. Results: PTV coverage, minimum dose, and 107% hot-spot volume did not differ significantly among the three techniques, indicating comparable target coverage. VMAT produced significantly higher low-dose cardiac exposure (Heart V10), whereas mean heart dose and Heart V25 were similar across techniques. Ipsilateral lung mean dose and V20 were broadly comparable, with only modest, non-significant numerical differences between modalities. VMAT yielded significantly higher maximum doses to the contralateral lung and contralateral breast compared with 3DCRT, while mean doses to these structures remained similar. Radiobiological modeling showed no significant difference in TCP between techniques; however, NTCP estimates for the heart and ipsilateral lung were lower with IMRT and VMAT than with 3DCRT, whereas NTCP for contralateral structures did not differ significantly. Conclusion: IMRT and VMAT offer radiobiological advantages for modeled cardiac and pulmonary toxicity compared with 3DCRT, while maintaining comparable target coverage, but VMAT is associated with a broader low-dose bath to contralateral structures. These exploratory findings support individualized technique
References
[1]
Sung, H., Ferlay, J., Siegel, R.L., Laversanne, M., Soerjomataram, I., Jemal, A., et al. (2021) Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA: ACancerJournalforClinicians, 71, 209-249. https://doi.org/10.3322/caac.21660
[2]
Early Breast Cancer Trialists’ Collaborative Group (2011) Effect of Radiotherapy after Breast-Conserving Surgery on 10-Year Recurrence and 15-Year Breast Cancer Death: Meta-Analysis of Individual Patient Data for 10801 Women in 17 Randomised Trials. TheLancet, 378, 1707-1716.
[3]
Whelan, T.J., Olivotto, I.A., Parulekar, W.R., Ackerman, I., Chua, B.H., Nabid, A., et al. (2015) Regional Nodal Irradiation in Early-Stage Breast Cancer. New England Journal of Medicine, 373, 307-316. https://doi.org/10.1056/nejmoa1415340
[4]
Offersen, B.V., Boersma, L.J., Kirkove, C., Hol, S., Aznar, M.C., Biete Sola, A., et al. (2015) ESTRO Consensus Guideline on Target Volume Delineation for Elective Radiation Therapy of Early Stage Breast Cancer. Radiotherapy and Oncology, 114, 3-10. https://doi.org/10.1016/j.radonc.2014.11.030
[5]
Aznar, M.C., Duane, F.K., Darby, S.C., Wang, Z. and Taylor, C.W. (2018) Exposure of the Lungs in Breast Cancer Radiotherapy: A Systematic Review of Lung Doses Published 2010-2015. Radiotherapy and Oncology, 126, 148-154. https://doi.org/10.1016/j.radonc.2017.11.022
[6]
Darby, S.C., Ewertz, M., McGale, P., Bennet, A.M., Blom-Goldman, U., Brønnum, D., et al. (2013) Risk of Ischemic Heart Disease in Women after Radiotherapy for Breast Cancer. New England Journal of Medicine, 368, 987-998. https://doi.org/10.1056/nejmoa1209825
[7]
Taylor, C.W. and Kirby, A.M. (2015) Cardiac Side-Effects from Breast Cancer Radiotherapy. Clinical Oncology, 27, 621-629. https://doi.org/10.1016/j.clon.2015.06.007
[8]
van den Bogaard, V.A.B., Ta, B.D.P., van der Schaaf, A., Bouma, A.B., Middag, A.M.H., Bantema-Joppe, E.J., et al. (2017) Validation and Modification of a Prediction Model for Acute Cardiac Events in Patients with Breast Cancer Treated with Radiotherapy Based on Three-Dimensional Dose Distributions to Cardiac Substructures. Journal of Clinical Oncology, 35, 1171-1178. https://doi.org/10.1200/jco.2016.69.8480
[9]
Marks, L.B., Bentzen, S.M., Deasy, J.O., Bradley, J.D., et al. (2010) Radiation Dose-Volume Effects in the Lung. InternationalJournalofRadiationOncology, Biology, Physics, 76, S70-S76. https://doi.org/10.1016/j.ijrobp.2009.06.091
[10]
Piroth, M.D., Baumann, R., Budach, W., Dunst, J., Feyer, P., Fietkau, R., et al. (2019) Heart Toxicity from Breast Cancer Radiotherapy: Current Findings, Assessment, and Prevention. StrahlentherapieundOnkologie, 195, 1-12. https://doi.org/10.1007/s00066-018-1378-z
[11]
Drost, L., Yee, C., Lam, H., Zhang, L., Wronski, M., McCann, C., et al. (2018) A Systematic Review of Heart Dose in Breast Radiotherapy. Clinical Breast Cancer, 18, e819-e824. https://doi.org/10.1016/j.clbc.2018.05.010
[12]
Merino Lara, T.R., Fleury, E., Mashouf, S., Helou, J., McCann, C., Ruschin, M., et al. (2014) Measurement of Mean Cardiac Dose for Various Breast Irradiation Techniques and Corresponding Risk of Major Cardiovascular Event. Frontiers in Oncology, 4, Article 284. https://doi.org/10.3389/fonc.2014.00284
[13]
Dillon, D., Guidi, A.J., Schnitt, S.J., Harris, J.R., Lippman, M.E., et al. (2014) Diseases of the Breast. 5th Edition, Lippincott Williams & Wilkins.
[14]
Schubert, L.K., Gondi, V., Sengbusch, E., Westerly, D.C., Soisson, E.T., Paliwal, B.R., et al. (2011) Dosimetric Comparison of Left-Sided Whole Breast Irradiation with 3DCRT, Forward-Planned IMRT, Inverse-Planned IMRT, Helical Tomotherapy, and Topotherapy. Radiotherapy and Oncology, 100, 241-246. https://doi.org/10.1016/j.radonc.2011.01.004
[15]
Adeneye, S., Akpochafor, M., Adedewe, N., Habeebu, M., Jubril, R., Adebayo, A., et al. (2023) A Dosimetric Comparison of Volumetric Modulated Arc Therapy and Intensity Modulated Radiotherapy in Patients Treated with Post-Mastectomy Radiotherapy. European Journal of Breast Health, 19, 92-98. https://doi.org/10.4274/ejbh.galenos.2022.2022-9-2
[16]
Murakami, Y., Murakami, Y., Kamima, T., Oguchi, M., Abo, N., Takahashi, T., et al. (2022) Dosimetric Comparison between Three-Dimensional Conformal Radiotherapy Followed by Electron Beam Boost and Volumetric Modulated Arc Therapy Using Concomitant Boost for the Heart and Cardiac Segments in Patients with Left-Sided Breast Cancer at Risk for Radiation-Induced Cardiac Toxicity. Physica Medica, 95, 126-132. https://doi.org/10.1016/j.ejmp.2022.02.003
[17]
Mansouri, S., Naim, A., Glaria, L. and Marsiglia, H. (2014) Dosimetric Evaluation of 3-D Conformal and Intensity-Modulated Radiotherapy for Breast Cancer after Conservative Surgery. Asian Pacific Journal of Cancer Prevention, 15, 4727-4732. https://doi.org/10.7314/apjcp.2014.15.11.4727
[18]
Niemierko, A. (1997) Reporting and Analyzing Dose Distributions: A Concept of Equivalent Uniform Dose. Medical Physics, 24, 103-110. https://doi.org/10.1118/1.598063
[19]
Balasubramanian, S. and Shobana, M.K. (2022) A Dosimetric and Radiobiological Comparison of Intensity Modulated Radiotherapy, Volumetric Modulated Arc Therapy and Helical Tomotherapy Planning Techniques in Synchronous Bilateral Breast Cancer. Asian Pacific Journal of Cancer Prevention, 23, 4233-4241. https://doi.org/10.31557/apjcp.2022.23.12.4233
[20]
Bentzen, S.M., Constine, L.S., Deasy, J.O., Eisbruch, A., Jackson, A., Marks, L.B., et al. (2010) Quantitative Analyses of Normal Tissue Effects in the Clinic (QUANTEC): An Introduction to the Scientific Issues. International Journal of Radiation Oncology, Biology, Physics, 76, S3-S9. https://doi.org/10.1016/j.ijrobp.2009.09.040
[21]
Gagliardi, G., Constine, L.S., Moiseenko, V., Correa, C., Pierce, L.J., Allen, A.M., et al. (2010) Radiation Dose-Volume Effects in the Heart. International Journal of Radiation Oncology, Biology, Physics, 76, S77-S85. https://doi.org/10.1016/j.ijrobp.2009.04.093
[22]
Haciislamoglu, E., Colak, F., Canyilmaz, E., Dirican, B., Gurdalli, S., Yilmaz, A.H., et al. (2015) Dosimetric Comparison of Left-Sided Whole-Breast Irradiation with 3DCRT, Forward-Planned IMRT, Inverse-Planned IMRT, Helical Tomotherapy, and Volumetric Arc Therapy. Physica Medica, 31, 360-367. https://doi.org/10.1016/j.ejmp.2015.02.005
[23]
Jackson, A., Marks, L.B., Bentzen, S.M., Eisbruch, A., Yorke, E.D., Ten Haken, R.K., et al. (2010) The Lessons of QUANTEC: Recommendations for Reporting and Gathering Data on Dose-Volume Dependencies of Treatment Outcome. International Journal of Radiation Oncology, Biology, Physics, 76, S155-S160. https://doi.org/10.1016/j.ijrobp.2009.08.074
[24]
Chaikh, A. and Balosso, J. (2016) The Use of Radiobiological TCP and NTCP Models to Validate the Dose Calculation Algorithm and Readjust the Prescribed Dose. Radiotherapy and Oncology, 118, S24. https://doi.org/10.1016/s0167-8140(16)30047-0
[25]
Lee, B., Lee, S., Sung, J. and Yoon, M. (2014) Radiotherapy-induced Secondary Cancer Risk for Breast Cancer: 3D Conformal Therapy versus IMRT versus VMAT. Journal of Radiological Protection, 34, 325-331. https://doi.org/10.1088/0952-4746/34/2/325
[26]
Attalla, E. (2022) Physical and Radiobiological Evaluation of Patient Setup Errors in the Radiotherapy Procedure for Prostate Cancer. Egyptian Journal of Biophysics and Biomedical Engineering, 24, 13-30.
