{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,9]],"date-time":"2026-04-09T14:00:18Z","timestamp":1775743218151,"version":"3.50.1"},"reference-count":28,"publisher":"Harborside Press, LLC","issue":"4","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,4]]},"abstract":"\n Background:<\/jats:bold>\n Early radiation therapy (RT) reduces the rate of skeletal-related events (SRE), which can affect patients\u2019 functionality and quality of life (QoL). We aimed to determine predictors of SRE and the effect of early RT on individual QoL dimensions.\n Methods:<\/jats:bold>\n We conducted a secondary analysis of a multicenter, randomized phase II trial (ClinicalTrials.gov identifier:\n NCT03523351<\/jats:ext-link>\n ) assessing early RT to asymptomatic, high-risk bone metastases. A competing risks analysis evaluated patient-level factors associated with SRE. Linear mixed models evaluated dimensions of the EuroQol 5-Dimension 5-Level (EQ-5D-5L) QoL assessment (mobility, self-care, usual activities, pain\/discomfort, anxiety\/depression) over time by study arm.\n Results:<\/jats:bold>\n Overall, 78 patients with 122 bone metastases were enrolled; 71 (91%) patients were evaluable for the primary endpoint of SRE (35 patients in the early RT arm vs 36 in the control arm). A total of 15 SREs occurred among 11 unique patients during the 1-year follow-up period. Receipt of early RT was statistically significantly correlated with a lower risk of SRE (hazard ratio, 0.09; 95% CI, 0.01\u20130.66;\n P<\/jats:italic>\n =.018). In the linear mixed model predicting self-care, the interaction between time and study arm was statistically significant (\n P<\/jats:italic>\n =.022). At 6 months, the control arm had a decline in self-care, whereas patients in the RT arm experienced an improvement. Anxiety\/depression was worse at 3 months in the RT arm, but this was not statistically significant (\n P<\/jats:italic>\n =.120).\n Conclusions:<\/jats:bold>\n Rates of SRE were high among patients with bone metastases, and these findings underscore the importance of early RT in their prevention. Patient-reported QoL suggests preservation of self-care with early RT, and that survival beyond 6 months may be needed to observe a benefit. Further research regarding patient selection and the impact of SRE on QoL and functionality are needed, and a phase III randomized trial (NRG CC014;\n NCT06745024<\/jats:ext-link>\n ) is in progress.\n <\/jats:p>\n \n ClinicalTrials.gov identifier:<\/jats:bold>\n NCT03523351<\/jats:ext-link>\n <\/jats:p>","DOI":"10.6004\/jnccn.2025.7126","type":"journal-article","created":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T20:37:29Z","timestamp":1773088649000},"source":"Crossref","is-referenced-by-count":0,"title":["Predictors of Skeletal-Related Events and Quality-of-Life Dimensions Among Patients With High-Risk Asymptomatic Bone Metastases With or Without Early Radiation Therapy: Secondary Analysis of a Multicenter Randomized Phase II Clinical Trial"],"prefix":"10.6004","volume":"24","author":[{"given":"Kaitlyn","family":"Lapen","sequence":"first","affiliation":[{"name":"Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhigang","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Charlie","family":"White","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christopher A.","family":"Barker","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rupesh","family":"Kotecha","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Miami Cancer Institute, Baptist Health South Florida, Miami, FL"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alyson F.","family":"McIntosh","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Lehigh Valley Cancer Institute, Allentown, PA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ryan D.","family":"Nipp","sequence":"additional","affiliation":[{"name":"Section of Hematology\/Oncology, Department of Medicine, University of Oklahoma Health Stephenson Cancer Center, Oklahoma City, OK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Puneeth","family":"Iyengar","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jonathan T.","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, New York University Grossman School of Medicine, New York, NY"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Divya","family":"Yerramilli","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Erin F.","family":"Gillespie","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, University of Washington, Seattle, WA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"4047","reference":[{"key":"B1","series-title":"Cancer","first-page":"1082","article-title":"Pamidronate prevents skeletal complications and is effective palliative treatment in women with breast carcinoma and osteolytic bone metastases: long term follow-up of two randomized, placebo-controlled trials","volume":"88","author":"Lipton A","year":"2000","unstructured":"Lipton A, Theriault RL, Hortobagyi GN, Pamidronate prevents skeletal complications and is effective palliative treatment in women with breast carcinoma and osteolytic bone metastases: long term follow-up of two randomized, placebo-controlled trials. Cancer 2000;88:1082\u20131090."},{"key":"B2","series-title":"J Thorac Oncol","first-page":"231","article-title":"Prospective study on the incidence of bone metastasis (BM) and skeletal-related events (SREs) in patients (pts) with stage IIIB and IV lung cancer-CSP-HOR 13","volume":"9","author":"Katakami N","year":"2014","unstructured":"Katakami N, Kunikane H, Takeda K, Prospective study on the incidence of bone metastasis (BM) and skeletal-related events (SREs) in patients (pts) with stage IIIB and IV lung cancer-CSP-HOR 13. J Thorac Oncol 2014;9:231\u2013238."},{"key":"B3","series-title":"Ann Oncol","first-page":"579","article-title":"The significance of skeletal-related events for the health-related quality of life of patients with metastatic prostate cancer","volume":"16","author":"Weinfurt KP","year":"2005","unstructured":"Weinfurt KP, Li Y, Castel LD, The significance of skeletal-related events for the health-related quality of life of patients with metastatic prostate cancer. Ann Oncol 2005;16:579\u2013584."},{"key":"B4","series-title":"Clin Cancer Res","first-page":"1684","article-title":"Oral bisphosphonates and improved survival of breast cancer","volume":"23","author":"Rennert G","year":"2017","unstructured":"Rennert G, Pinchev M, Gronich N, Oral bisphosphonates and improved survival of breast cancer. Clin Cancer Res 2017;23:1684\u20131689."},{"key":"B5","series-title":"J Clin Oncol","first-page":"38","article-title":"Prophylactic radiation therapy versus standard of care for patients with high-risk asymptomatic bone metastases: a multicenter, randomized phase II clinical trial","volume":"42","author":"Gillespie EF","year":"2024","unstructured":"Gillespie EF, Yang JC, Mathis NJ, Prophylactic radiation therapy versus standard of care for patients with high-risk asymptomatic bone metastases: a multicenter, randomized phase II clinical trial. 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J Clin Oncol 2025;43:2164\u20132172."},{"key":"B14","series-title":"Int J Radiat Oncol Biol Phys","first-page":"1730","article-title":"Update of the international consensus on palliative radiotherapy endpoints for future clinical trials in bone metastases","volume":"82","author":"Chow E","year":"2012","unstructured":"Chow E, Hoskin P, Mitera G, Update of the international consensus on palliative radiotherapy endpoints for future clinical trials in bone metastases. 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Cancer 2000;88:1082\u20131090."},{"key":"B2","series-title":"J Thorac Oncol","first-page":"231","article-title":"Prospective study on the incidence of bone metastasis (BM) and skeletal-related events (SREs) in patients (pts) with stage IIIB and IV lung cancer-CSP-HOR 13","volume":"9","author":"Katakami N","year":"2014","unstructured":"Katakami N, Kunikane H, Takeda K, Prospective study on the incidence of bone metastasis (BM) and skeletal-related events (SREs) in patients (pts) with stage IIIB and IV lung cancer-CSP-HOR 13. J Thorac Oncol 2014;9:231\u2013238."},{"key":"B3","series-title":"Ann Oncol","first-page":"579","article-title":"The significance of skeletal-related events for the health-related quality of life of patients with metastatic prostate cancer","volume":"16","author":"Weinfurt KP","year":"2005","unstructured":"Weinfurt KP, Li Y, Castel LD, The significance of skeletal-related events for the health-related quality of life of patients with metastatic prostate cancer. 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J Clin Oncol 2024;42:38\u201346."},{"key":"B6","series-title":"Oncologist","first-page":"508","article-title":"Risk factors for developing skeletal-related events in breast cancer patients with bone metastases undergoing treatment with bone-modifying agents","volume":"21","author":"Tanaka R","year":"2016","unstructured":"Tanaka R, Yonemori K, Hirakawa A, Risk factors for developing skeletal-related events in breast cancer patients with bone metastases undergoing treatment with bone-modifying agents. Oncologist 2016;21:508\u2013513."},{"key":"B7","series-title":"Qual Life Res","first-page":"1727","article-title":"Development and preliminary testing of the new five-level version of EQ-5D (EQ-5D-5L)","volume":"20","author":"Herdman M","year":"2011","unstructured":"Herdman M, Gudex C, Lloyd A, Development and preliminary testing of the new five-level version of EQ-5D (EQ-5D-5L). 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Cancer 2019;125:4003\u20134010."},{"key":"B10","series-title":"JAMA Oncol","first-page":"879","article-title":"Association of quality-of-life outcomes in cancer drug trials with survival outcomes and drug class","volume":"8","author":"Samuel JN","year":"2022","unstructured":"Samuel JN, Booth CM, Eisenhauer E, Association of quality-of-life outcomes in cancer drug trials with survival outcomes and drug class. JAMA Oncol 2022;8:879\u2013886."},{"key":"B11","series-title":"Value Health","first-page":"644","article-title":"Instrument-defined estimates of the minimally important difference for EQ-5D-5L index scores","volume":"20","author":"McClure NS","year":"2017","unstructured":"McClure NS, Sayah FA, Xie F, Instrument-defined estimates of the minimally important difference for EQ-5D-5L index scores. Value Health 2017;20:644\u2013650."},{"key":"B12","series-title":"Health Qual Life Outcomes","first-page":"81","article-title":"Estimating the minimally important difference for the EQ-5D-5L and EORTC QLQ-C30 in cancer","volume":"22","author":"Bourke S","year":"2024","unstructured":"Bourke S, Bennett B, Oluboyede Y, Estimating the minimally important difference for the EQ-5D-5L and EORTC QLQ-C30 in cancer. Health Qual Life Outcomes 2024;22:81."},{"key":"B13","series-title":"J Clin Oncol","first-page":"2164","article-title":"Dose-escalated stereotactic versus conventional radiotherapy for painful bone metastases (ROBOMET): a multicenter, patient-blinded randomized clinical trial","volume":"43","author":"Mercier C","year":"2025","unstructured":"Mercier C, Billiet C, Ost P, Dose-escalated stereotactic versus conventional radiotherapy for painful bone metastases (ROBOMET): a multicenter, patient-blinded randomized clinical trial. J Clin Oncol 2025;43:2164\u20132172."},{"key":"B14","series-title":"Int J Radiat Oncol Biol Phys","first-page":"1730","article-title":"Update of the international consensus on palliative radiotherapy endpoints for future clinical trials in bone metastases","volume":"82","author":"Chow E","year":"2012","unstructured":"Chow E, Hoskin P, Mitera G, Update of the international consensus on palliative radiotherapy endpoints for future clinical trials in bone metastases. Int J Radiat Oncol Biol Phys 2012;82:1730\u20131737."}],"container-title":["Journal of the National Comprehensive Cancer Network"],"original-title":[],"link":[{"URL":"https:\/\/jnccn.org\/view\/journals\/jnccn\/24\/4\/article-e257126.xml","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/jnccn.org\/downloadpdf\/journals\/jnccn\/24\/4\/article-e257126.xml","content-type":"text\/html","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/jnccn.org\/downloadpdf\/journals\/jnccn\/24\/4\/article-e257126.xml","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,9]],"date-time":"2026-04-09T13:08:01Z","timestamp":1775740081000},"score":1,"resource":{"primary":{"URL":"https:\/\/jnccn.org\/view\/journals\/jnccn\/24\/4\/article-e257126.xml"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4]]},"references-count":28,"journal-issue":{"issue":"4"},"URL":"https:\/\/doi.org\/10.6004\/jnccn.2025.7126","relation":{},"ISSN":["1540-1405","1540-1413"],"issn-type":[{"value":"1540-1405","type":"print"},{"value":"1540-1413","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4]]}}}