Simultaneous integrated boost intensity-modulated radiotherapy for treatment of bone metastases: analysis of a breast cancer cohort

Authors

  • Fabio Marazzi Radioterapia Oncologica, Dipartimento di Diagnostica per Immagini, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
  • Valeria Masiello Radioterapia Oncologica, Dipartimento di Diagnostica per Immagini, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy https://orcid.org/0000-0001-7589-7623
  • Alessandra Fabi Unità Operativa Dipartimentale di Medicina di Precisione in senologia, Dipartimento di Scienze della salute della donna, del bambino e di sanità pubblica Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
  • Stefania Manfrida Radioterapia Oncologica, Dipartimento di Diagnostica per Immagini, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
  • Barbara Corvari Radioterapia Oncologica, Dipartimento di Diagnostica per Immagini, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
  • Valentina Lancellotta Radioterapia Oncologica, Dipartimento di Diagnostica per Immagini, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
  • Ciro Mazzarella Radioterapia Oncologica, Dipartimento di Diagnostica per Immagini, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
  • Silvia Longo Radioterapia Oncologica, Dipartimento di Diagnostica per Immagini, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
  • Martina De Angeli Radioterapia Oncologica, Dipartimento di Diagnostica per Immagini, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
  • Francesca Moschella Chirurgia Senologica, Dipartimento di Scienze della salute della donna, del bambino e di sanità pubblica Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
  • Alba Di Leone Chirurgia Senologica, Dipartimento di Scienze della salute della donna, del bambino e di sanità pubblica Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
  • Armando Orlandi Oncologia Medica, Dipartimento di Dipartimento di Scienze Gastroenterologiche, Endocrino-metaboliche e Nefro-urologiche, Comprehensive Cancer Center. Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
  • Serena Bracci Radioterapia Oncologica, Dipartimento di Diagnostica per Immagini, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
  • Giuseppe Ferdinando Colloca Radioterapia Oncologica, Dipartimento di Diagnostica per Immagini, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
  • Mariangela Massaccesi Radioterapia Oncologica, Dipartimento di Diagnostica per Immagini, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
  • Luca Boldrini Radioterapia Oncologica, Dipartimento di Diagnostica per Immagini, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
  • Luca Tagliaferri Radioterapia Oncologica, Dipartimento di Diagnostica per Immagini, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy; Istituto di Radiologia, Università Cattolica del Sacro Cuore, Rome, Italy
  • Emilio Bria Centro di Eccellenza Oncologia Radioterapica, Medica e Diagnostica per Immagini, Ospedale Isola Tiberina-Gemelli Isola, Rome, Italy
  • Riccardo Masetti Chirurgia Senologica, Dipartimento di Scienze della salute della donna, del bambino e di sanità pubblica Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy; Università Cattolica del Sacro Cuore, Rome, Italy
  • Gianluca Franceschini Chirurgia Senologica, Dipartimento di Scienze della salute della donna, del bambino e di sanità pubblica Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy; Dipartimento di Scienze Mediche e Chirurgiche, Università Cattolica del Sacro Cuore, Rome, Italy
  • Vincenzo Valentini Centro di Eccellenza Oncologia Radioterapica, Medica e Diagnostica per Immagini, Ospedale Isola Tiberina-Gemelli Isola, Rome, Italy
  • Maria Antonietta Gambacorta Radioterapia Oncologica, Dipartimento di Diagnostica per Immagini, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy; Istituto di Radiologia, Università Cattolica del Sacro Cuore, Rome, Italy
  • Francesco Cellini Radioterapia Oncologica, Dipartimento di Diagnostica per Immagini, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy; Istituto di Radiologia, Università Cattolica del Sacro Cuore, Rome, Italy

DOI:

https://doi.org/10.2340/1651-226X.2025.42933

Keywords:

breast cancer, SIB-IMRT, bone metastases, precision medicine

Abstract

Background: Bone metastases occur in up to 75% of metastatic breast cancer (MBC) cases. Advances in imaging now allow earlier detection, even during the oligometastatic phase. Radiotherapy (RT) is increasingly used in asymptomatic patients with ≤5 bone lesions, however standardised guidelines for dose and target volumes remain lacking. This study evaluates the outcomes of a simultaneous integrated boost (SIB) using intensity-modulated radiotherapy (IMRT) to deliver ablative doses to macroscopic bone lesions.

Methods: This retrospective study analysed MBC patients treated with SIB-IMRT for bone metastases between January 2014 and January 2022. The primary endpoint was freedom from local progression (FFLP); secondary endpoints included disease progression after radiotherapy (DP-AR) and overall survival (OS). Subgroup analyses were performed according to age, immunophenotype, and line of therapy.

Results: Among 954 patients treated with RT, 85 received SIB-IMRT (6–8 Gy per fraction, 5 fractions). Median follow-up was 41 months. Nineteen patients (22.4%) had a single bone metastasis, 23.5% were oligometastatic, and 54.1% were plurimetastatic. Median FFLP was 17 months; only 7% experienced local relapse at the SIB site. While DP-AR was 13.2 months, median OS reached 82.7 months. No significant correlation was found between local relapse and age, immunophenotype, or systemic therapy. Immunophenotype significantly influenced DP-AR (p = 0.002), while DP-AR and OS were not significantly associated with local progression.

Interpretation: SIB-IMRT for bone metastases in MBC is feasible and effective, with encouraging local control and minimal toxicity. Prospective studies are warranted to optimise dose escalation and explore synergistic effects with systemic therapies.

Downloads

Download data is not yet available.

References

Andre F, Slimane K, Bachelot T, Dunant A, Namer M, Barrelier A, et al. Breast cancer with synchronous metastases: trends in survival during a 14-year period. J Clin Oncol. 2004;22(16):3302–8.

https://doi.org/10.1200/JCO.2004.08.095 DOI: https://doi.org/10.1200/JCO.2004.08.095

Giordano SH, Buzdar AU, Smith TL, Kau S-W, Yang Y, Hortobagyi GN. Is breast cancer survival improving? Cancer. 2004;100(1):44–52.

https://doi.org/10.1002/cncr.11859 DOI: https://doi.org/10.1002/cncr.11859

Guckenberger M, Lievens Y, Bouma AB, Collette L, Dekker A, deSouza NM, et al. Characterisation and classification of oligometastatic disease: a European Society for Radiotherapy and Oncology and European Organisation for Research and Treatment of Cancer consensus recommendation. Lancet Oncol. 2020;21(1):e18–28.

https://doi.org/10.1016/S1470-2045(19)30718-1 DOI: https://doi.org/10.1016/S1470-2045(19)30718-1

Pagani O, Senkus E, Wood W, Colleoni M, Cufer T, Kyriakides S, et al. International guidelines for management of metastatic breast cancer: can metastatic breast cancer be cured? J Natl Cancer Inst. 2010;102(7):456–63.

https://doi.org/10.1093/jnci/djq029 DOI: https://doi.org/10.1093/jnci/djq029

Sofi AA, Mohamed I, Koumaya M, Kamaluddin Z. Local therapy in metastatic breast cancer is associated with improved survival. Am J Ther 2013;20(5):487–92.

https://doi.org/10.1097/MJT.0b013e31822119c5 DOI: https://doi.org/10.1097/MJT.0b013e31822119c5

Possanzini M, Greco C. Stereotactic radiotherapy in metastatic breast cancer. Breast. 2018;41:57–66.

https://doi.org/10.1016/j.breast.2018.06.011 DOI: https://doi.org/10.1016/j.breast.2018.06.011

Marazzi F, Orlandi A, Manfrida S, Masiello V, Di Leone A, Massaccesi M, et al. Diagnosis and treatment of bone metastases in breast cancer: radiotherapy, local approach and systemic therapy in a guidefor clinicians. Cancers. 2020;12(9):2390.

https://doi.org/10.3390/cancers12092390 DOI: https://doi.org/10.3390/cancers12092390

Palma A, Olson R, Harrow S, Gaede S, Louie AV, Haasbeck C, et al. Stereotactic Ablative Radiotherapy for the Comprehensive Treatment of Oligometastatic Cancers: Long-Term Results of the SABR-COMET Phase II Randomized Trial, J Clin Oncol, 2020;38(25): 2830-2838.

https://doi.org/10.1200/JCO.20.00818 DOI: https://doi.org/10.1200/JCO.20.00818

Hanna GG, Murray L, Patel R, Jain S, Aitken KL, Franks KN, et al. UK consensus on normal tissue dose constraints for stereotactic radiotherapy.Clin Oncol. 2018;30(1):5–14.

https://doi.org/10.1016/j.clon.2017.09.007 DOI: https://doi.org/10.1016/j.clon.2017.09.007

Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2009;45(2):228–47.

https://doi.org/10.1016/j.ejca.2008.10.026 DOI: https://doi.org/10.1016/j.ejca.2008.10.026

Wahl RL, Jacene H, Kasamon Y, Lodge MA. From RECIST to PERCIST: evolving considerations for PET response criteria in solid tumors. J Nucl Med. 2009;50(Suppl. 1):122S–50S.

https://doi.org/10.2967/jnumed.108.057307 DOI: https://doi.org/10.2967/jnumed.108.057307

Nesbit EG, Donnelly ED, Strauss JB. Treatment strategies for oligometastatic breast cancer. Curr Treat Options Oncol. 2021;22(10):94.

https://doi.org/10.1007/s11864-021-00889-2 DOI: https://doi.org/10.1007/s11864-021-00889-2

Barberi V, Pietragalla A, Franceschini G, Marazzi F, Paris I, Cognetti F, et al. Oligometastatic breast cancer: how to manage it? J Pers Med.2021;11(6):532.

https://doi.org/10.3390/jpm11060532 DOI: https://doi.org/10.3390/jpm11060532

Trovo M, Furlan C, Polesel J, Fiorica F, Arcangeli S, Giaj-Levra N, et al. Radical radiation therapy for oligometastatic breast cancer: results of a prospective phase II trial, Radiother Oncol. 2018;126(1):177–80.

https://doi.org/10.1016/j.radonc.2017.08.032 DOI: https://doi.org/10.1016/j.radonc.2017.08.032

Scorsetti M, Franceschini D, De Rose F, Comito T, Villa E, Iftode C, et al. Stereotactic body radiation therapy: a promising chance for oligometastatic breast cancer, Breast. 2016;26:11–17.

https://doi.org/10.1016/j.breast.2015.12.002 DOI: https://doi.org/10.1016/j.breast.2015.12.002

Gerszten PC, Burton SA, Welch WC, Brufsky AM, Lembersky BC, Ozhasoglu C, et al. Single-fraction radiosurgery for the treatment of spinal breast metastases. Cancer. 2005;104(10):2244–54.

https://doi.org/10.1002/cncr.21467 DOI: https://doi.org/10.1002/cncr.21467

Milano MT, Zang H, Metcalfe SK, Muhs AG, Okunieff P. Oligometastatic breast cancer treated with curative-intent stereotactic body radiation therapy. Breast Cancer Res Treat. 2009;115(3): 601–8.

https://doi.org/10.1007/s10549-008-0157-4 DOI: https://doi.org/10.1007/s10549-008-0157-4

Milano MT, Katz AW, Zhang H, Huggins CF, Aujla KS, Okunieff P. Oligometastatic breast cancer treated with hypofractionated stereotactic radiotherapy: some patients survive longer than a decade. Radiother Oncol. 2019;131:45–51.

https://doi.org/10.1016/j.radonc.2018.11.022 DOI: https://doi.org/10.1016/j.radonc.2018.11.022

Cellini F, Manfrida S, Deodato F, Cilla S, Maranzano E, Pergolizzi S, et al. Pain REduction with bone metastases STereotactic radiotherapy (PREST): a phase III randomized multicentric trial. Trials.2019;20(1):609.

https://doi.org/10.1186/s13063-019-3676-x DOI: https://doi.org/10.1186/s13063-019-3676-x

Chmura SJ, Winter KA, Woodward WA, Borges VF, Salama JK, Al-Hallaq HA, et al. NRG-BR002: a phase IIR/III trial of standard of care systemic therapy with or without stereotactic body radiotherapy (SBRT) and/or surgical resection (SR) for newly oligometastatic breast cancer(NCT02364557). J Clin Oncol. 2022;40(16 Suppl.):1007.

https://doi.org/10.1200/JCO.2022.40.16_suppl.1007 DOI: https://doi.org/10.1200/JCO.2022.40.16_suppl.1007

Jeong J. Local treatment in ER-positive/HER2-negative Oligometastatic breast cancer (CLEAR) [Internet]. 2018. [cited 2019 Feb 15]. Available from: https://clinicaltrials.gov/ct2/show/NCT03750396

Roussy G, Campus C, Paris G. Trial of superiority of stereotactic body radiation therapy in patients with breast cancer (STEREOSEIN) [Internet]. 2014 [cited 2018 Jul 23]. Available from: https:// clinicaltrials.gov/ct2/show/NCT02089100

Weill Medical College of Cornell University. CIMER: combined immunotherapies in metastatic ER+ breast cancer (CIMER) [Internet]. 2020 [cited 2020 Sept 20]. Available from: https://clinicaltrials.gov/ct2/show/NCT04220476

Mohan R, Wu Q, Manning M, Schmidt-Ullrich R. Radiobiological considerations in the design of fractionation strategies for intensity-modulated radiation therapy of head and neck cancers. Int J Radiat Oncol Biol Phys. 2000;46(3):619–30.

https://doi.org/10.1016/S0360-3016(99)00438-1 DOI: https://doi.org/10.1016/S0360-3016(99)00438-1

Ost P, Speleers B, De Meerleer G, De Neve W, Fonteyne V, Villeirs G, et al. Volumetric arc therapy and intensity-modulated radiotherapy for primary prostate radiotherapy with simultaneous integrated boost to intraprostatic lesion with 6 and 18 MV: a planning comparison study. Int J Radiat Oncol Biol Phys. 2011;79(3):920–6.

https://doi.org/10.1016/j.ijrobp.2010.04.025 DOI: https://doi.org/10.1016/j.ijrobp.2010.04.025

Jolly D, Alahakone D, Meyer J. A RapidArc planning strategy foprostate with simultaneous integrated boost. J Appl Clin Med Phys. 2010;12(1):3320.

https://doi.org/10.1120/jacmp.v12i1.3320 DOI: https://doi.org/10.1120/jacmp.v12i1.3320

Lee YK, Bedford JL, McNair HA, Hawkins MA. Comparison of deliverable IMRT and VMAT for spine metastases using a simultaneous integrated boost. Br J Radiol. 2013;86(1022):20120466.

https://doi.org/10.1259/bjr.20120466 DOI: https://doi.org/10.1259/bjr.20120466

Sprave T, Welte SE, Bruckner T, Forster R, Bostel T, Schlampp I, et al. Intensity-modulated radiotherapy with integrated-boost in patients with bone metastasis of the spine: study protocol for a randomized controlled trial. Trials. 2018;19(1):59.

https://doi.org/10.1186/s13063-018-2452-7 DOI: https://doi.org/10.1186/s13063-018-2452-7

Skrobala A, Kruszyna-Mochalska M, Graczyk K, Ryczkowski A, Fundowicz M, Milecki P et al. Radiotherapy planning in a prostate cancer phantom model with intraprostatic dominant lesions using stereotactic body radiotherapy with volumetric modulated arcs and a simultaneous integrated boost. Front Oncol. 2023, 28:13:1147593.

https://doi.org/10.3389/fonc.2023.1147593 DOI: https://doi.org/10.3389/fonc.2023.1147593

Whittaker S, Madani D, Joshi S, Chung SA, Johns T, Day B et al. Combination of palbociclib and radiotherapy for glioblastoma. Cell Death Discovery. 2017, 3;3:17033.

https://doi.org/10.1038/cddiscovery.2017.33 DOI: https://doi.org/10.1038/cddiscovery.2017.33

Sun C, Chu A, Song R, Liu S, Chai T, Wang X et al. PARP inhibitors combined with radiotherapy: are we ready? Front Pharmacol, 2023, 14:1234973.

https://doi.org/10.3389/fphar.2023.1234973 DOI: https://doi.org/10.3389/fphar.2023.1234973

Murai T, Murata R, Manabe Y, Sugie C, Tamura T, Ito H et al. Intensity modulated stereotactic body radiation therapy for single or multiple vertebral metastases with spinal cord compression. Pract Radiat Oncol. 2014, 4;6:e231-7.

https://doi.org/10.1016/j.prro.2014.02.005 DOI: https://doi.org/10.1016/j.prro.2014.02.005

Farroqi A, Bishop AJ, Narang S, Allen PK, Li J, McAleer MF et al. Outcomes After Hypofractionated Dose-Escalation using a Simultaneous Integrated Boost Technique for Treatment of Spine Metastases Not Amenable to Stereotactic Radiosurgery. Pract Radiat Oncol. 2019, 9; 2:e142-e148.

https://doi.org/10.1016/j.prro.2018.10.008 DOI: https://doi.org/10.1016/j.prro.2018.10.008

Jacobs CD, Palta M, Williamson H, Price JG, Czito BG, Salama JK et al. Hypofractionated Image-Guided Radiation Therapy With Simultaneous-Integrated Boost Technique for Limited Metastases: A Multi-Institutional Analysis. Front Oncol, 2019, 4; 9: 469.

https://doi.org/10.3389/fonc.2019.00469 DOI: https://doi.org/10.3389/fonc.2019.00469

Shenker RF, Price GJ, Jacobs CD, Palta M, Czito BG, Mowery YM et al. Comparing Outcomes of Oligometastases Treated with Hypofractionated Image-Guided Radiotherapy (HIGRT) with a Simultaneous Integrated Boost (SIB) Technique versus Metastasis Alone: A Multi-Institutional Analysis. Cancers (Basel), 2022, 10;2403:14.

https://doi.org/10.3390/cancers14102403 DOI: https://doi.org/10.3390/cancers14102403

Potkrajcic V, Mueller A-C, Frey B, Gani C, Zips D, Hoffmann R et al. Dose-escalated radiotherapy with simultaneous integrated boost for bone metastases in selected patients with assumed favourable prognosis. Radiol Oncol, 2022, 56;4:515-524.

https://doi.org/10.2478/raon-2022-0053 DOI: https://doi.org/10.2478/raon-2022-0053

Downloads

Published

2025-05-19

How to Cite

Marazzi, F., Masiello, V., Fabi, A., Manfrida, S., Corvari, B., Lancellotta, V., … Cellini, F. (2025). Simultaneous integrated boost intensity-modulated radiotherapy for treatment of bone metastases: analysis of a breast cancer cohort. Acta Oncologica, 64, 685–692. https://doi.org/10.2340/1651-226X.2025.42933

Issue

Vol. 64 (2025): Acta Oncologica

Section

Original article

Categories

License

Copyright (c) 2025 Fabio Marazzi, Valeria Masiello, Alessandra Fabi, Stefania Manfrida, Barbara Corvari, Valentina Lancellotta, Ciro Mazzarella, Silvia Longo, Martina De Angeli, Francesca Moschella, Alba Di Leone, Armando Orlandi, Serena Bracci, Giuseppe Ferdinando Colloca, Mariangela Massaccesi, Luca Boldrini, Luca Tagliaferri, Emilio Bria, Riccardo Masetti, Gianluca Franceschini, Vincenzo Valentini, Maria Antonietta Gambacorta, Francesco Cellini

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 International License.