{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T03:26:18Z","timestamp":1782444378638,"version":"3.54.5"},"reference-count":29,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2025,7,1]],"date-time":"2025-07-01T00:00:00Z","timestamp":1751328000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Background: CDK4\/6 inhibitor plus ET is a standard treatment for advanced HR+ BC. This study evaluates the efficacy and safety of CDK4\/6 inhibitors with concurrent RT (SBRT and non-SBRT) in terms of pain, analgesic therapy changes, toxicities, and net clinical benefit (NCB). Methods: BC patients with bone metastases treated with RT and CDK4\/6 inhibitor in the prospective observational COMBART study were analyzed. Pain was measured with the NRS. The NCB was defined by pain reduction (NRS), toxicity, and treatment changes. Adverse events (AEs) were graded per CTCAE v5.0. Statistical tests included chi-square and t-test. Results: Forty patients were treated with CDK4\/6 inhibitor (palbociclib 30.8%, ribociclib 51.3%, abemaciclib 17.9%) and RT (131 lesions; 100 SBRT, 31 non-SBRT). The mean NRS score dropped from 3.52 (pre-treatment) to 1.31 (post-treatment) (p &lt; 0.001), with better outcomes for patients treated with moderate hypofractionation (58.6% vs. 39.9% pain relief, p = 0.016). Pain relief was independent of the type of CDK4\/6 inhibitor used (p = NS). Analgesic reduction was most common with palbociclib (35.4%, p = 0.001). Eight toxicities (grade 1\u20132) were reported. The NCB was 0.6 overall, higher with non-SBRT (0.74 vs. 0.52). Conclusions: RT plus CDK4\/6 inhibitor, especially with moderate hypofractionation, significantly reduced pain with manageable toxicity. Analgesic therapy can often continue without stopping CDK4\/6 inhibitor.<\/jats:p>","DOI":"10.3390\/jcm14134662","type":"journal-article","created":{"date-parts":[[2025,7,1]],"date-time":"2025-07-01T06:56:54Z","timestamp":1751353014000},"page":"4662","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Clinical Value of Bone Radiotherapy in a Prospective Cohort of Metastatic Breast Cancer Treated with Anti-CDK4\/6"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1775-2009","authenticated-orcid":false,"given":"Edy","family":"Ippolito","sequence":"first","affiliation":[{"name":"Research Unit of Radiation Oncology, Department of Medicine and Surgery, Universit\u00e0 Campus Bio-Medico di Roma, Via Alvaro del Portillo, 21, 00128 Rome, Italy"},{"name":"Operative Research Unit of Radiation Oncology, Fondazione Policlinico Universitario Campus Bio-Medico, Via Alvaro del Portillo, 200, 00128 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7029-2692","authenticated-orcid":false,"given":"Lucrezia","family":"Toppi","sequence":"additional","affiliation":[{"name":"Operative Research Unit of Radiation Oncology, Fondazione Policlinico Universitario Campus Bio-Medico, Via Alvaro del Portillo, 200, 00128 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sofia","family":"Carrafiello","sequence":"additional","affiliation":[{"name":"Research Unit of Radiation Oncology, Department of Medicine and Surgery, Universit\u00e0 Campus Bio-Medico di Roma, Via Alvaro del Portillo, 21, 00128 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlo","family":"Greco","sequence":"additional","affiliation":[{"name":"Research Unit of Radiation Oncology, Department of Medicine and Surgery, Universit\u00e0 Campus Bio-Medico di Roma, Via Alvaro del Portillo, 21, 00128 Rome, Italy"},{"name":"Operative Research Unit of Radiation Oncology, Fondazione Policlinico Universitario Campus Bio-Medico, Via Alvaro del Portillo, 200, 00128 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michele","family":"Fiore","sequence":"additional","affiliation":[{"name":"Research Unit of Radiation Oncology, Department of Medicine and Surgery, Universit\u00e0 Campus Bio-Medico di Roma, Via Alvaro del Portillo, 21, 00128 Rome, Italy"},{"name":"Operative Research Unit of Radiation Oncology, Fondazione Policlinico Universitario Campus Bio-Medico, Via Alvaro del Portillo, 200, 00128 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-6661-311X","authenticated-orcid":false,"given":"Rita","family":"Alaimo","sequence":"additional","affiliation":[{"name":"Operative Research Unit of Radiation Oncology, Fondazione Policlinico Universitario Campus Bio-Medico, Via Alvaro del Portillo, 200, 00128 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Salvatore","family":"Minuti","sequence":"additional","affiliation":[{"name":"Research Unit of Radiation Oncology, Department of Medicine and Surgery, Universit\u00e0 Campus Bio-Medico di Roma, Via Alvaro del Portillo, 21, 00128 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Pantano","sequence":"additional","affiliation":[{"name":"Research Unit of Medical Oncology, Department of Medicine and Surgery, Universit\u00e0 Campus Bio-Medico di Roma, Via Alvaro del Portillo 21, 00128 Rome, Italy"},{"name":"Operative Research Unit of Medical Oncology, Fondazione Policlinico Universitario Campus Bio-Medico, Via Alvaro del Portillo, 200, 00128 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe","family":"Casale","sequence":"additional","affiliation":[{"name":"Research Unit Nursing in Palliative Care, Fondazione Policlinico Universitario Campus Bio-Medico, 00128 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rolando Maria","family":"D\u2019Angelillo","sequence":"additional","affiliation":[{"name":"Radiation Oncology, Department of Biomedicine and Prevention, University of Rome \u201cTor Vergata\u201d, 00133 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adriana","family":"Turriziani","sequence":"additional","affiliation":[{"name":"Operative Research Unit of Radiation Oncology, Fondazione Policlinico Universitario Campus Bio-Medico, Via Alvaro del Portillo, 200, 00128 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Grazia","family":"De Marinis","sequence":"additional","affiliation":[{"name":"Research Unit Nursing in Palliative Care, Fondazione Policlinico Universitario Campus Bio-Medico, 00128 Rome, Italy"},{"name":"Research Unit of Nursing Science, Department of Medicine and Surgery, Universit\u00e0 Campus Bio-Medico di Roma, Via Alvaro del Portillo, 21, 00128 Roma, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5782-7717","authenticated-orcid":false,"given":"Sara","family":"Ramella","sequence":"additional","affiliation":[{"name":"Research Unit of Radiation Oncology, Department of Medicine and Surgery, Universit\u00e0 Campus Bio-Medico di Roma, Via Alvaro del Portillo, 21, 00128 Rome, Italy"},{"name":"Operative Research Unit of Radiation Oncology, Fondazione Policlinico Universitario Campus Bio-Medico, Via Alvaro del Portillo, 200, 00128 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1023","DOI":"10.1016\/S0140-6736(17)33326-3","article-title":"Global surveillance of trends in cancer survival 2000-14 (CONCORD-3): Analysis of individual records for 37,513,025 patients diagnosed with one of 18 cancers from 322 population-based registries in 71 countries","volume":"391","author":"Allemani","year":"2018","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Wang, R., Zhu, Y., Liu, X., Liao, X., He, J., and Niu, L. (2019). The Clinicopathological features and survival outcomes of patients with different metastatic sites in stage IV breast cancer. BMC Cancer, 19.","DOI":"10.1186\/s12885-019-6311-z"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"287","DOI":"10.2147\/CMAR.S155524","article-title":"Bone metastasis pattern in initial metastatic breast cancer: A population-based study","volume":"10","author":"Xiong","year":"2018","journal-title":"Cancer Manag. Res."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"26368","DOI":"10.18632\/oncotarget.14300","article-title":"The prognosis analysis of different metastasis pattern in patients with different breast cancer subtypes: A SEER based study","volume":"8","author":"Wang","year":"2017","journal-title":"Oncotarget"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Coleman, R., Brown, J., and Holen, I. (2020). Bone metastases. Abeloff\u2019s Clinical Oncology, Elsevier. [6th ed.].","DOI":"10.1016\/B978-0-323-47674-4.00056-6"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Ito, K., and Nakamura, N. (2025). Palliative stereotactic body radiotherapy for spinal and non-spinal bone metastases: Combining tradition and innovation. Int. J. Clin. Oncol., in press.","DOI":"10.1007\/s10147-025-02750-0"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1186\/s13014-022-02128-w","article-title":"Stereotactic body radiotherapy versus conventional radiotherapy for painful bone metastases: A systematic review and meta-analysis of randomised controlled trials","volume":"17","author":"Ito","year":"2022","journal-title":"Radiat. Oncol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1925","DOI":"10.1056\/NEJMoa1607303","article-title":"Palbociclib and Letrozole in Advanced Breast Cancer","volume":"375","author":"Finn","year":"2016","journal-title":"N. Engl. J. Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1738","DOI":"10.1056\/NEJMoa1609709","article-title":"Ribociclib as First-Line Therapy for HR-Positive, Advanced Breast Cancer","volume":"375","author":"Hortobagyi","year":"2016","journal-title":"N. Engl. J. Med."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"904","DOI":"10.1016\/S1470-2045(18)30292-4","article-title":"Ribociclib plus endocrine therapy for premenopausal women with hormone-receptor-positive, advanced breast cancer (MONALEESA-7): A randomised phase 3 trial","volume":"19","author":"Tripathy","year":"2018","journal-title":"Lancet Oncol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"3638","DOI":"10.1200\/JCO.2017.75.6155","article-title":"MONARCH 3: Abemaciclib as Initial Therapy for Advanced Breast Cancer","volume":"35","author":"Goetz","year":"2017","journal-title":"J. Clin. Oncol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"2875","DOI":"10.1200\/JCO.2017.73.7585","article-title":"MONARCH 2: Abemaciclib in Combination with Fulvestrant in Women with HR+\/HER2- Advanced Breast Cancer Who Had Progressed While Receiving Endocrine Therapy","volume":"35","author":"Sledge","year":"2017","journal-title":"J. Clin. Oncol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"3379","DOI":"10.1158\/1078-0432.CCR-13-1551","article-title":"Molecular pathways: CDK4 inhibitors for cancer therapy","volume":"20","author":"Dickson","year":"2014","journal-title":"Clin. Cancer Res."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"6568","DOI":"10.1158\/1078-0432.CCR-20-2269","article-title":"Short-term CDK4\/6 Inhibition Radiosensitizes Estrogen Receptor-Positive Breast Cancers","volume":"26","author":"Pesch","year":"2020","journal-title":"Clin. Cancer Res."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1186\/s13046-020-01693-w","article-title":"CDK4\/6 inhibitors: A novel strategy for tumor radiosensitization","volume":"39","author":"Yang","year":"2020","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"5485","DOI":"10.3390\/curroncol30060415","article-title":"Safety of CDK4\/6 Inhibitors Combined with Radiotherapy in Patients with Metastatic Breast Cancer: A Review of the Literature","volume":"30","author":"Franco","year":"2023","journal-title":"Curr. Oncol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"102586","DOI":"10.1016\/j.ctrv.2023.102586","article-title":"Safety profile of cyclin-dependent kinase (CDK) 4\/6 inhibitors with concurrent radiation therapy: A systematic review and meta-analysis","volume":"119","author":"Becherini","year":"2023","journal-title":"Cancer Treat Rev."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"iv166","DOI":"10.1093\/annonc\/mdy152","article-title":"Management of cancer pain in adult patients: ESMO Clinical Practice Guidelines","volume":"29","author":"Fallon","year":"2018","journal-title":"Ann. Oncol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1627","DOI":"10.1093\/bjr\/tqae138","article-title":"Cyclin-dependent kinase 4\/6 inhibitors combined with stereotactic ablative radiotherapy in oligometastatic HR-positive\/HER2-negative breast cancer patients","volume":"97","author":"Kubeczko","year":"2024","journal-title":"Br. J. Radiol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"110639","DOI":"10.1016\/j.radonc.2024.110639","article-title":"Efficacy of radiotherapy for bone metastasis in breast cancer patients treated with cyclin-dependent kinase 4\/6 inhibitors","volume":"202","author":"Kubeczko","year":"2025","journal-title":"Radiother. Oncol."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Trovarelli, G., Rizzo, A., Zinnarello, F.D., Cerchiaro, M., Angelini, A., Pala, E., and Ruggieri, P. (2025). Modern Treatment of Skeletal Metastases: Multidisciplinarity and the Concept of Oligometastasis in the Recent Literature. Curr. Oncol., 32.","DOI":"10.3390\/curroncol32040226"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1016\/j.prro.2024.04.018","article-title":"External Beam Radiation Therapy for Palliation of Symptomatic Bone Metastases: An ASTRO Clinical Practice Guideline","volume":"14","author":"Alcorn","year":"2024","journal-title":"Pract. Radiat. Oncol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"e2355409","DOI":"10.1001\/jamanetworkopen.2023.55409","article-title":"Stereotactic Body and Conventional Radiotherapy for Painful Bone Metastases: A Systematic Review and Meta-Analysis","volume":"7","author":"Bindels","year":"2024","journal-title":"JAMA Netw. Open."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Wang, Z., Li, L., Yang, X., Teng, H., Wu, X., Chen, Z., Wang, Z., and Chen, G. (2022). Efficacy and safety of stereotactic body radiotherapy for painful bone metastases: Evidence from randomized controlled trials. Front. Oncol., 12.","DOI":"10.3389\/fonc.2022.979201"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"102092","DOI":"10.1016\/j.tranon.2024.102092","article-title":"Radiosensitizing effects of CDK4\/6 inhibitors in hormone receptor-positive and HER2-negative breast cancer mediated downregulation of DNA repair mechanism and NF-\u03baB-signaling pathway","volume":"49","author":"Yang","year":"2024","journal-title":"Transl. Oncol."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Iuliani, M., Simonetti, S., Ribelli, G., Napolitano, A., Longo, U.G., Vincenzi, B., Orsaria, P., Denaro, V., Tonini, G., and Santini, D. (2022). Biological Effects of Cyclin-Dependent Kinase Inhibitors Ribociclib, Palbociclib and Abemaciclib on Breast Cancer Bone Microenvironment. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23052477"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"e143","DOI":"10.1016\/j.prro.2013.05.006","article-title":"Outcomes and toxicities of stereotactic body radiation therapy for non-spine bone oligometastases","volume":"4","author":"Owen","year":"2014","journal-title":"Pract. Radiat. Oncol."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Alomran, R., White, M., and Bruce, M. (2021). Stereotactic radiotherapy for oligoprogressive ER-positive breast cancer (AVATAR). BMC Cancer, 21.","DOI":"10.1186\/s12885-021-08042-w"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"S549","DOI":"10.1016\/S0167-8140(25)01366-0","article-title":"2919 clinical value of bone radiotherapy in a prospective cohort of metastatic breast cancer treated with anti-cdk 4\/","volume":"206","author":"Carrafiello","year":"2025","journal-title":"Radiother. Oncol."}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/14\/13\/4662\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:02:24Z","timestamp":1760032944000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/14\/13\/4662"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,1]]},"references-count":29,"journal-issue":{"issue":"13","published-online":{"date-parts":[[2025,7]]}},"alternative-id":["jcm14134662"],"URL":"https:\/\/doi.org\/10.3390\/jcm14134662","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,7,1]]}}}