BACKGROUND: Skeletal-related events (SREs), including the pathological fracture, surgical treatment or radiation of bone lesions, malignant spinal cord compression, hypercalcemia, are important considerations when managing metastatic bone tumors; however, owing to their rarity, the incidence of SREs in patients with Ewing sarcoma remains unknown.
METHODS: We retrospectively reviewed the clinical data from 146 patients with Ewing sarcoma treated at a single institution from 2005 to 2019. The median age at diagnosis was 22.7 years. Fifty patients (34.2%) had metastatic disease at diagnosis. The primary outcome was the SRE-free rate among patients with Ewing sarcoma. Moreover, we identified the risk factors for SREs using univariate or multivariate analyses.
RESULTS: During the observational period (median, 2.6 years), SREs occurred in 23 patients. Radiation to the bone, malignant spinal cord compression, and hypercalcemia were documented as the initial SREs in 12 patients (52.2%), 10 patients (43.5%), and one patient (4.3%), respectively. The SRE-free rate was 94.2 ± 2.0, 87.3 ± 3.0, and 79.6 ± 3.8% at 1, 2, and 3 years after the initial visit, respectively. Multivariate analysis revealed bone metastasis at diagnosis (hazard ratio [HR] = 4.41, p = 0.007), bone marrow invasion (HR = 34.08, p < 0.001), and local progression or recurrence after definitive treatment (HR = 3.98, p = 0.012) as independent risk factors for SREs.
CONCLUSIONS: SREs are non-rare events that can occur during the treatment course for Ewing sarcoma, with an especially high incidence of malignant spinal cord compression. Patients with metastatic disease at diagnosis, especially in the bone or bone marrow, or with local progression or recurrence after definitive treatment, should be carefully monitored for the occurrence of SREs. The most effective methods to monitor the occurrence of SREs and new preventative therapies for SREs should be investigated in the future.

In the absence of early detection and initial treatment, prostate cancer often progresses to an advanced stage, frequently spreading to the bones and significantly impacting patients\' well-being and healthcare resources. Therefore, managing patients with prostate cancer that has spread to the bones often involves using bone-targeted medications like bisphosphonates and denosumab to enhance bone structure and minimize skeletal complications. Additionally, researchers are studying the tumor microenvironment and biomarkers to understand the mechanisms and potential treatment targets for bone metastases in prostate cancer. A literature search was conducted to identify clinical studies from 2013 to 2023 that focused on pain, performance status, or quality of life as primary outcomes. The analysis included details such as patient recruitment, prior palliative therapies, baseline characteristics, follow-up, and outcome reporting. The goal was to highlight the advancements and trends in bone metastasis research in prostate cancer over the past decade, with the aim of developing strategies to prevent and treat bone metastases and improve the quality of life and survival rates for prostate cancer patients.

BACKGROUND: Early palliative/pre-emptive intervention improves clinical outcomes and quality of life for patients with metastatic cancer. A previous signal-seeking randomized controlled trial (RCT) demonstrated that early upfront radiotherapy to asymptomatic or minimally symptomatic high-risk osseous metastases led to reduction in skeletal-related events (SREs), a benefit driven primarily by subgroup of high-risk spine metastasis. The current RCT aims to determine whether early palliative/pre-emptive radiotherapy in patients with high-risk, asymptomatic or minimally symptomatic spine metastases will lead to fewer SREs within 1 year.
METHODS: This is a single-center, parallel-arm, in-progress RCT in adults (≥ 18 years) with ECOG performance status 0-2 and asymptomatic or minimally symptomatic (not requiring opioids) high-risk spine metastases from histologically confirmed solid tumor malignancies with > 5 sites of metastatic disease on cross-sectional imaging. High-risk spine metastases are defined by the following: (a) bulkiest disease sites ≥ 2 cm; (b) junctional disease (occiput to C2, C7-T1, T12-L2, L5-S1); (c) posterior element involvement; or (d) vertebral body compression deformity > 50%. Patients are randomized 1:1 to receive either standard-of-care systemic therapy (arm 1) or upfront, early radiotherapy to ≤ 5 high-risk spine lesions plus standard-of-care systemic therapy (arm 2), in the form of 20-30 Gy of radiation in 2-10 fractions. The primary endpoint is SRE, a composite outcome including spinal fracture, spinal cord compression, need for palliative radiotherapy, interventional procedures, or spinal surgery. Secondary endpoints include (1) surrogates of health care cost, including the number and duration of SRE-related hospitalizations; (2) overall survival; (3) pain-free survival; and (4) quality of life. Study instruments will be captured pre-treatment, at baseline, during treatment, and at 1, 3, 6, 12, and 24 months post-treatment. The trial aims to accrue 74 patients over 2 years to achieve > 80% power in detecting difference using two-sample proportion test with alpha < 0.05.
CONCLUSIONS: The results of this RCT will demonstrate the value, if any, of early radiotherapy for high-risk spine metastases. The trial has received IRB approval, funding, and prospective registration (NCT05534321) and has been open to accrual since August 19, 2022. If positive, the trial will expand the scope and utility of spine radiotherapy.
BACKGROUND: ClinicalTrials.Gov NCT05534321 . Registered September 9, 2022.
METHODS: Version 2.0 of the protocol (2021-KOT-002), revised last on September 2, 2022, was approved by the WCG institutional review board (Study Number 1337188, IRB tracking number 20223735). The trial was first posted on ClinicalTrials.Gov on September 9, 2022 (NCT05534321). Patient enrollment commenced on August 19, 2022, and is expected to be completed in 2 years, likely by August 2024.

BACKGROUND: Bone modifying agents (BMAs) have been used to prevent skeletal-related events (SRE) in cancer patients with bone metastases. In this meta-analysis, efficacy and adverse events (AEs) were studied based on a de-escalation strategy in which the BMA dosing interval was prolonged from 4 to 12 weeks.
METHODS: PubMed, Cochrane, ICHUSHI, and CINAHL were searched for articles on BMA dosing intervals from outcomes measured were the incidence of SRE and related various AEs. A quantitative meta-analysis was performed using a random-effects model to calculate relative risk ratios (RRs) and 95% confidence intervals (CIs).
RESULTS: The meta-analysis included three randomized controlled studies (RCTs) of Zoledronic acid hydrate (ZA) (n = 2663) and six RCTs (n = 141) on BMA other than ZA. There was no difference in the incidence of SREs when comparing the dosing frequency of 12 versus 4 weeks for BMA (RR = 1.21, 95% CI [0.82-1.78], p = 0.33). Further, AEs related to treatment discontinuation were significantly less frequent with ZA given every 12 weeks than when given every 4 weeks (RR = 0.51 [0.30-0.89], p = 0.02). In particular, renal dysfunction leading to grade ≥3 or discontinuation of treatment with ZA occurred significantly less frequently with every 12-week dosing (RR = 0.33 [0.12-0.91], p = 0.33).
CONCLUSIONS: This meta-analysis showed no influence of BMA de-escalation on the incidence of SRE; nevertheless, AEs appeared to reduce with the de-escalated usage of ZA.

BACKGROUND: Real-world data on optimal cancer pain management remain scarce. We describe prescription patterns of analgesics in Japanese cancer patients with bone metastases.
METHODS: National hospital-based claims data were analyzed. Adults with first diagnosis of cancer during 2015-2019 and first diagnosis of bone metastasis after the initial cancer diagnosis were included. Skeletal-related events (SREs) were identified with disease and receipt codes.
RESULTS: Among the 40,507 eligible patients (age [mean ± SD], 69.7 ± 11.7 years), lung (25.3%), prostate (15.6%), breast (10.9%), and colorectal (10.7%) cancers were common primary tumors. Time (mean ± SD) between primary cancer diagnosis and bone metastases was 306.9 ± 490.4 days; median survival time from bone metastases was 483.0 days. Most patients used acetaminophen (62.7%, 117.5 days/year) and nonsteroidal anti-inflammatory drugs (NSAIDs; 75.3%, 170.0 days/year). Commonly used opioids included oxycodone (39.4%; 479.3 days/year), fentanyl (32.5%; 52.6 days/year), morphine (22.1%; 130.9 days/year), and tramadol (15.3%; 143.0 days/year). Internal medicine, surgery, respiratory, urology, and orthopedics treated 19.4%, 18.5%, 17.6%, 17.3%, and 13.0% of patients, respectively. Prescription patterns varied inter-department. Overall, 44.9% of patients developed SRE (bone pain requiring radiation [39.6%] or orthopedic surgery [2.9%]; hypercalcemia, 4.9%; pathological fracture, 3.3%; spinal cord compression, 0.4%). Analgesics use by patients with SREs was 1.8- to 2.2-fold in the postsymptomatic vs the presymptomatic period. SRE patients had numerically lower survival probabilities than non-SRE patients. Opioid use increased considerably in the month before death.
CONCLUSIONS: In Japanese cancer patients with bone metastases, acetaminophen, NSAIDs, and weak or strong opioids were commonly used; their use increased after SREs developed. Opioid use increased closer to death.

Progression of bone metastases is the primary cause of death in prostate cancer, and skeletal-related events (SREs), including pathologic fractures, spinal cord compression, radiation, or surgery to bone can impair patients\' quality of life. Over the past decade, the development of cytotoxic agents, androgen-receptor-axis-targeted therapies (ARATs), and radioligand therapies has prolonged overall survival of prostate cancer patients with bone metastases and reduced the risk of SREs. The use of bone-modifying agents has also contributed to the reduced risk of SREs. Initial use of a cytotoxic agent, docetaxel, or an ARAT agent with androgen deprivation therapy (ADT) is the current approach to metastatic castration-sensitive prostate cancer. However, there is no consensus on the optimal medication for upfront use in combination with ADT, or on specific patient selection. Recently, next-generation imaging modalities, such as whole-body magnetic resonance imaging and prostate-specific membrane antigen-positron emission tomography have been utilized to detect bone metastases at an early stage. In addition, metastasis-directed therapy, such as stereotactic body radiation therapy, has been attempted. In the future, patients with bone metastatic prostate cancer will be divided into subgroups and their treatment options will be tailored to their specific characteristics.

Bone metastases are common in advanced breast cancer (BC) patients and increase the risk for skeletal-related events (SREs), which present a significant health and economic burden. Bone targeting agents (BTAs) can improve health-related quality of life by delaying or preventing SREs; nevertheless, a significant portion of eligible BC patients are not receiving this therapy. A bone health education needs assessment survey was conducted to examine cancer-related bone health awareness and to identify opportunities to improve bone health education. Direct-to-patient outreach was used to recruit adult BC patients in the USA self-reporting a diagnosis of bone metastasis within the past 3 years. Of the 200 patients, 59% experienced at least one SRE prior to survey participation (44% radiation to bone, 29% bone fracture, 17% spinal cord compression, 15% surgery to bone), and 83% were currently receiving a BTA. Awareness of general cancer bone health, protection strategies against SREs, and screening tests were low to moderate. Patients currently not receiving a BTA were least knowledgeable about cancer bone health, with only 40% aware of BTAs as a protective strategy, and only 26% were very or extremely satisfied with the information received from healthcare providers. Sixty-two percent of patients wanted to receive information by more than one mode of communication. Notable gaps in bone health education were observed in bone metastatic BC patients at risk for SREs, suggesting the need for earlier and more effective communication and education strategies to promote appropriate BTA use and better health outcomes.

BACKGROUND: Prognostic indicators, treatments, and survival estimates vary by cancer type. Therefore, disease-specific models are needed to estimate patient survival. Our primary aim was to develop models to estimate survival duration after treatment for skeletal-related events (SREs) (symptomatic bone metastasis, including impending or actual pathologic fractures) in men with metastatic bone disease due to prostate cancer. Such disease-specific models could be added to the PATHFx clinical-decision support tool, which is available worldwide, free of charge. Our secondary aim was to determine disease-specific factors that should be included in an international cancer registry.
METHODS: We analyzed records of 438 men with metastatic prostate cancer who sustained SREs that required treatment with radiotherapy or surgery from 1989-2017. We developed and validated 6 models for 1-, 2-, 3-, 4-, 5-, and 10-year survival after treatment. Model performance was evaluated using calibration analysis, Brier scores, area under the receiver operator characteristic curve (AUC), and decision curve analysis to determine the models\' clinical utility. We characterized the magnitude and direction of model features.
RESULTS: The models exhibited acceptable calibration, accuracy (Brier scores < 0.20), and classification ability (AUCs > 0.73). Decision curve analysis determined that all 6 models were suitable for clinical use. The order of feature importance was distinct for each model. In all models, 3 factors were positively associated with survival duration: younger age at metastasis diagnosis, proximal prostate-specific antigen (PSA) < 10 ng/mL, and slow-rising alkaline phosphatase velocity (APV).
CONCLUSIONS: We developed models that estimate survival duration in patients with metastatic bone disease due to prostate cancer. These models require external validation but should meanwhile be included in the PATHFx tool. PSA and APV data should be recorded in an international cancer registry.

Background and Objectives: There have been numerous advances in spine surgery for metastatic spinal tumors, and minimally invasive spine stabilization (MISt) is becoming increasingly popular in Japan. MISt is a minimally invasive fixation procedure that temporarily stabilizes the spine, thereby reducing pain, preventing pathological fractures, and improving activities of daily living at an early stage. MISt may be useful given the recent shift toward outpatient cancer treatment. Materials and Methods: This study enrolled 51 patients with metastatic spinal tumors who underwent surgery using MISt between December 2013 and October 2020. The Spinal Instability Neoplastic Score, an assessment of spinal instability, was used to determine the indication for surgery, and the Epidural Spinal Cord Compression scale was used for additional decompression. Results: The patients comprised 34 men and 17 women, and the mean age at surgery was 68.9 years. The mean postoperative follow-up period was 20.8 months, and 35 of 51 patients (67%) had died by the last survey. The mean operative time was 159.8 min, mean blood loss was 115.7 mL, and mean time to ambulation was 3.2 days. No perioperative complications were observed, although two patients required refixation surgery. Preoperatively, 37 patients (72.5%) were classified as Frankel grade E. There were no cases of postoperative exacerbation, and six patients showed improvement of one or more Frankel grades after surgery. The median duration of patient survival was about 22.0 months. Patients with breast, prostate, renal, and thyroid cancers had a good prognosis, whereas those with gastrointestinal and head and neck cancers had a poor prognosis. Conclusions: MISt can benefit patients who are ineligible for conventional, highly invasive surgery and is also suitable because cancer treatment is increasingly performed on an outpatient basis. Furthermore, choosing the right surgery for the right patient at the right time can significantly affect life expectancy.

BACKGROUND: There is a growing momentum for the collaboration between multiple disciplines for the prevention and treatment of skeletal-related events (SREs) in patients with metastatic spinal tumors. However, the effectiveness of multidisciplinary approaches remains unclear. Hence, we conducted an exploratory study to examine the impact of liaison treatment for metastatic spinal tumor (LMST) on the prevention of SREs among patients with a metastatic spinal tumor.
METHODS: This study was an exploratory interrupted time series conducted in a single medical center. Overall, 1,043 patients with a metastatic spinal tumor diagnosed between January 2011 and December 2020 were included. The LMST was implemented in January 2014. The LMST team consisted of the orthopedic surgery, thoracic surgery, breast and thyroid surgery, clinical oncology, urology, and radiology departments. Monthly joint conferences were held for patients with spinal instability, and the incidence of SRE was measured at 6-month intervals.
RESULTS: Throughout the study period, we identified 66 SRE incidences. After the implementation of the LMST, a level change of -5.2% (95% confidence interval [CI]: -11.7 to 1.3, p = 0.11) was observed. Subsequently, a post-implementation trend change of -0.3% (95% CI: -2.0 to 1.5, p = 0.75) beyond the baseline was noted.
CONCLUSIONS: We suggest both immediate and gradual effects of the introduction of the LMST on deterring the development of SREs. Our results support the global trend of introducing a multidisciplinary approach for the treatment of metastatic spinal tumors.