Cancer Bone Metastasis Research Articles

Tumor Burden of Iodine-Avid Bone Metastatic Thyroid Cancer Identified via 18F-Sodium Fluoride PET/CT Imaging.

Patients with differentiated thyroid cancer (DTC) are referred to radioactive 131I (RAI) therapy and post-therapy 131I whole-body scintigraphy (WBS) to identify local and/or remote metastases. Positron emission tomography (PET)/computed tomography (CT) imaging with 18F-fluoro-D-glucose (FDG) or 18F-sodium fluoride (NaF) may also be used with these patients for the evaluation of bone metastases. We compared the role of 18F-NaF PET/CT and 18F-FDG-PET/CT in patients with DTC and documented bone metastases at post-therapy WBS. Ten consecutive DTC patients with iodine avid bone metastasis at post-therapy WBS referred to 18F-NaF PET/CT and 18F-FDG PET/CT were studied. The findings of the three imaging procedures were compared for abnormal detection rates and concordance. At post-therapy 131I WBS, all patients had skeletal involvement with a total of 21 bone iodine avid lesions. At 18F-FDG PET/TC, 19 bone lesions demonstrated increased tracer uptake and CT pathological alterations, while 2 lesions did not show any pathological finding. At 18F-NaF PET/CT, the 19 bone lesions detected at 18F-FDG PET/TC also demonstrated abnormal tracer uptake, and the other 2 bone iodine avid foci did not show any pathological finding. In patients with DTC, 18F-NaF PET/CT did not obtain more information on the metastatic skeletal involvement than post-therapy 131I WBS and 18F-FDG PET/CT.

Epigenetic control of the vicious cycle

Epigenetic alterations, including DNA methylation and post translational modifications to histones, drive tumorigenesis and metastatic progression. In the context of bone metastasis, epigenetic modifications in tumor cells can modulate dissemination of cancer cells to the bone, tumor progression in the bone marrow, and may be associated with patient survival rates. Bone disseminated tumor cells may enter a dormant state or stimulate osteolysis through the “vicious cycle” of bone metastasis where bone disseminated tumor cells disrupt the bone microenvironment, which fuels tumor progression. Epigenetic alterations may either exacerbate or abrogate the vicious cycle by regulating tumor suppressors and oncogenes, which alter proliferation of bone-metastatic cancer cells. This review focuses on the specific epigenetic alterations that regulate bone metastasis, including DNA methylation, histone methylation, and histone acetylation. Here, we summarize key findings from researchers identifying epigenetic changes that drive tumor progression in the bone, along with pre-clinical and clinical studies investigating the utility of targeting aberrant epigenetic alterations to treat bone metastatic cancer.

Management and maintenance of oral health: Personalized primary prevention strategies and protocols in patients at risk of developing medication-related osteonecrosis of the jaw

Skeletal complications arising from osteoporosis or bone metastases are associated with considerable pain, increased mortality, and diminished quality of life. Agents that prevent bone resorption, such as bisphosphonates, denosumab, and antiangiogenic agents, prove effective in reducing fracture risk and find extensive use in patients with osteoporosis or bone cancer metastases. Medication-related osteonecrosis of the jaw (MRONJ) is a potentially serious adverse event associated with high cumulative doses of antiresorptive drugs. Other risk factors for osteonecrosis of the jaw include glucocorticoid use, maxillary or mandibular bone surgery, poor oral hygiene, chronic inflammation, diabetes mellitus, inappropriate dentures, and other MRONJ-related medications. Preventive strategies encompass completing necessary oral surgery before initiating antiresorptive drug therapy, administering antibiotics before and/or after the procedure, rinsing the mouth with chlorhexidine, ensuring adequate wound healing post-tooth extraction, and maintaining good oral hygiene. The primary goal of treatment is to improve the patient’s quality of life by managing pain and infection, preventing the development of new lesions, and decelerating disease progression. Dentists and dental hygienists, operating within a multi-professional team, play a key role in the primary prevention of MRONJ. However, a standardized multidisciplinary approach, fostering sustained dialog between specialists involved in the management of patients at risk for MRONJ, remains essential. This review describes the preventive and individualized oral hygiene management in patients at risk for this condition.

The Role of Osteocytes in Pre-metastatic Niche Formation.

The formation of a pre-metastatic niche (PMN), in which primary cancer cells prime the distant site to be favorable to their engraftment and survival, may help explain the strong osteotropism observed in multiple cancers, such as breast and prostate. PMN formation, which includes extracellular matrix remodeling, increased angiogenesis and vascular permeability, enhanced bone marrow-derived cell recruitment and immune suppression, has mostly been described in soft tissues. In this review, we summarize current literature of PMN formation in bone. We also present evidence of a potential role for osteocytes to be the primary mediators of PMN development. Osteocytes regulate the bone microenvironment in myriad ways beyond canonical bone tissue remodeling, including changes that contribute to PMN formation. Perilacunar tissue remodeling, which has been observed in both bone and non-bone metastatic cancers, is a potential mechanism by which osteocyte-cancer cell signaling stimulates changes to the bone microenvironment. Osteocytes also protect against endothelial permeability, including that induced by cancer cells, in a loading-mediated process. Finally, osteocytes are potent regulators of cells within the bone marrow, including progenitors and immune cells, and might be involved in this aspect of PMN formation. Osteocytes should be examined for their role in PMN formation.

Beyond boundaries: unraveling innovative approaches to combat bone-metastatic cancers.

Evidence demonstrated that bones, liver, and lungs are the most common metastasis sites in some human malignancies, especially in prostate and breast cancers. Bone is the third most frequent target for spreading tumor cells among these organs and tissues. Patients with bone-metastatic cancers face a grim prognosis characterized by short median survival time. Current treatments have proven insufficient, as they can only inhibit metastasis or tumor progression within the bone tissues rather than providing a curative solution. Gaining a more profound comprehension of the interplay between tumor cells and the bone microenvironment (BME) is of utmost importance in tackling this issue. This knowledge will pave the way for developing innovative diagnostic and therapeutic approaches. This review summarizes the mechanisms underlying bone metastasis and discusses the clinical aspects of this pathologic condition. Additionally, it highlights emerging therapeutic interventions aimed at enhancing the quality of life for patients affected by bone-metastatic cancers. By synthesizing current research, this review seeks to shed light on the complexities of bone metastasis and offer insights for future advancements in patient care.

From bone to nanoparticles: development of a novel generation of bone derived nanoparticles for image guided orthopedic regeneration.

Bone related diseases such as osteoporosis, osteoarthritis, metastatic bone cancer, osteogenesis imperfecta, and Paget's disease, are primarily treated with pharmacologic therapies that often exhibit limited efficacy and substantial side effects. Bone injuries or fractures are primarily repaired with biocompatible materials that produce mixed results in sufficiently regenerating healthy and homogenous bone tissue. Each of these bone conditions, both localized and systemic, use different strategies with the same goal of achieving a healthy and homeostatic bone environment. In this study, we developed a new type of bone-based nanoparticle (BPs) using the entire organic extracellular matrix (ECM) of decellularized porcine bone, additionally encapsulating indocyanine green dye (ICG) for an in vivo monitoring capability. Utilizing the regenerative capability of bone ECM and the functionality of nanoparticles, the ICG encapsulated BPs (ICG/BPs) have been demonstrated to be utilized as a therapeutic option for localized and systemic orthopedic conditions. Additionally, ICG enables an in situ monitoring capability in the Short-Wave Infrared (SWIR) spectrum, capturing the degradation or the biodistribution of the ICG/BPs after both local implantation and intravenous administration, respectively. The efficacy and safety of the ICG/BPs shown within this study lay the foundation for future investigations, which will delve into optimization for clinical translation.

LncRNA 51325 Alleviates Bone Cancer Induced Hyperalgesia Through Inhibition of Pum2.

Bone cancer pain (BCP) represents one of the most challenging comorbidities associated with cancer metastasis. Long non-coding RNAs (lncRNAs) have garnered attention as potential therapeutic agents in managing neuropathic pain. However, their role in the regulation of nociceptive information processing remains poorly understood. In this study, we observed a significant down-regulation of the spinal lncRNA ENSRNOG00000051325 (lncRNA51325) in a rat model of bone cancer pain. Our study sought to elucidate the potential involvement of lncRNA51325 in the development of BCP by modulating the expression of molecules associated with pain modulation. We established the BCP model by injecting Walker 256 cells into the tibial plateau of rats. We conducted tests on the pain behaviors and anxiety-like responses of rats through von-Frey test, Gait analysis, and Open Field Test. Spinal lumbar expansion was harvested for molecular biology experiments to explore the relationship between lncRNA51325 and Pumilio RNA binding family member 2 (Pum2). Notably, the overexpression of lncRNA51325 effectively attenuated mechanical allodynia in rats afflicted with BCP, whereas the knockdown of lncRNA51325 induced pain behaviors and anxiety-like responses in naïve rats. Additionally, we observed a time-dependent increase in the expression of Pum2 in BCP-afflicted rats, and intrathecal injection of Pum2-siRNA alleviated hyperalgesia. Furthermore, our investigations revealed that lncRNA51325 exerts a negative modulatory effect on Pum2 expression. The overexpression of lncRNA51325 significantly suppressed Pum2 expression in BCP rats, while the knockdown of lncRNA51325 led to elevated Pum2 protein levels in the spinal cord of naïve rats. Subsequent treatment with Pum2-siRNA mitigated the downregulation of lncRNA51325-induced mechanical allodynia in naïve rats. Our findings indicate that lncRNA51325 plays a role in regulating bone cancer pain by inhibiting Pum2 expression, offering a promising avenue for novel treatments targeting nociceptive hypersensitivity induced by bone metastatic cancer.

Chronic Pain and Bone-Related Pathologies: A Narrative Review.

Pain related to bone may occur as a result of trauma, bone fracture, genetic disease, arthritis, benign or malignant primary bone tumors and bone cancer metastases. We discuss the pathophysiology of chronic bone-related pain, treatment options and therapeutic perspectives. Using predefined terms, we searched PubMed, MEDLINE, and Google Scholar for meta-analyses, evidence-based reviews, and clinical practice guidelines. This narrative article reviews pathologies linked to chronic bone pain and discusses the preventive and therapeutic strategies for better bone pain management. Pathophysiology of bone-related pain is complex, especially in cancer conditions and missing gaps are underlined. Treatment of pain, after adequate evaluation, includes classical analgesics, adjuvants for neuropathic and refractory pain, specific bone drugs, surgery and non-pharmacological approaches. Prevention of chronic bone pain encompasses prevention of central sensitization and of causal diseases. Translational research, drug repurposing, an interdisciplinary approach and a person-centered assessment to evaluate, beyond pain, physical, social and functional abilities, are proposed future directions to improve chronic bone pain management and optimize independence and quality of life. Chronic bone-related pain is frequent and is associated with an impairment of quality of life. In this review, we summarize the pathophysiology of chronic bone pain, describe treatment approaches and envisage new avenues for pain alleviation. Our article will help doctors manage chronic bone pain and address unmet needs for future research to alleviate bone-related pain.

Kiosk 4Q-FA-06 - A Case of 51 Years Old Woman with Suspected Cardiac, Pulmonary, Bone and Renal Triple-negative Breast Cancer Metastasis

Kiosk 4Q-FA-06 - A Case of 51 Years Old Woman with Suspected Cardiac, Pulmonary, Bone and Renal Triple-negative Breast Cancer Metastasis

Abstract A007: Preclinical bone metastasis technology platform – Predictive evaluation of experimental therapies on bone metastasis

Abstract Most cancer deaths are due to metastases, and bone metastases are a considerable problem especially in breast and prostate cancer, being developed in 70-90% of advanced-stage patients. Despite major investments in oncology drug development, bone metastases are currently incurable and a high unmet medical need with only 5% of patients being alive 5 years after the diagnosis. Development of therapies for bone metastasis has been challenging due to lack of appropriate preclinical models available to support decision making in next phases of drug development. In the absence of clinically relevant preclinical bone metastasis models, the current strategy is to rely on preclinical efficacy data obtained with subcutaneous models that lack the clinically relevant local tissue microenvironment, which has a major impact on tumor growth. The use of clinically non-relevant models in preclinical-stage development may be one important reason for the current >95% failure rate of oncology drugs in clinical trials. To support predictive evaluation of therapies for bone metastatic cancers, we describe a preclinical bone metastasis technology platform for evaluating efficacy of novel therapies on bone metastases. The platform utilizes tumors growing in bone microenvironment, mimicking growth of bone metastases in patients. Syngeneic or humanized mouse models with tumor and immune cells of same species are needed for supporting development of immunotherapies, allowing interactions of tumor and immune cells in the bone metastatic microenvironment, according to the novel osteoimmuno-oncology concept. The platform provides a predictive tool for studying unique biological features associated with different types of bone metastases in cancer-type specific manner. Here we summarize case examples where results from preclinical bone metastasis studies align with clinical findings of different therapies approved or evaluated for bone metastasis. Zoledronic acid, an anti-resorptive bisphosphonate that is currently used in breast cancer patients with bone metastases to prevent cancer-induced bone loss, showed improved bone health but no effects on tumor growth. Radium-223 dichloride, an approved treatment for bone metastatic castration-resistant prostate cancer in patients, showed reduced prostate cancer growth and decreased tumor-induced bone changes. As for immunotherapies, an IDO1 inhibitor had no effects on breast cancer bone metastases and the anti-PD-1 antibody pembrolizumab had no effects on breast and prostate cancer bone metastases, predicting recent clinical findings that demonstrate lack of efficacy of anti-PD-1 in clinical prostate cancer trials. We conclude that the bone metastasis technology platform is a biologically relevant tool for preclinical evaluation of the efficacy of experimental therapies on bone metastasis, and it has been validated with positive and negative case examples, demonstrating its clinically predictive power. Citation Format: Tiina E Kähkönen, Jussi M Halleen, Jenni Bernoulli. Preclinical bone metastasis technology platform – Predictive evaluation of experimental therapies on bone metastasis [abstract]. In: Proceedings of the AACR-NCI-EORTC Virtual International Conference on Molecular Targets and Cancer Therapeutics; 2023 Oct 11-15; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2023;22(12 Suppl):Abstract nr A007.

Evaluation of pain related behaviors and disease related outcomes in an immunocompetent mouse model of prostate cancer induced bone pain

Cancer-induced bone pain (CIBP) is the most common and devastating symptom of bone metastatic cancer that substantially disrupts patients’ quality of life. Currently, there are few effective analgesic treatments for CIBP other than opioids which come with severe side effects. In order to better understand the factors and mechanisms responsible for CIBP it is essential to have clinically relevant animal models that mirror pain-related symptoms and disease progression observed in patients with bone metastatic cancer.In the current study, we characterize a syngeneic mouse model of prostate cancer induced bone pain. We transfected a prostate cancer cell line (RM1) with green fluorescent protein (GFP) and luciferase reporters in order to visualize tumor growth longitudinally in vivo and to assess the relationship between sensory neurons and tumor cells within the bone microenvironment. Following intra-femoral injection of the RM1 prostate cancer cell line into male C57BL/6 mice, we observed a progressive increase in spontaneous guarding of the inoculated limb between 12 and 21 days post inoculation in tumor bearing compared to sham operated mice. Daily running wheel performance was evaluated as a measure of functional impairment and potentially movement evoked pain. We observed a progressive reduction in the distance traveled and percentage of time at optimal velocity between 12 and 21 days post inoculation in tumor bearing compared to sham operated mice. We utilized histological, radiographic and μCT analysis to examine tumor induced bone remodeling and observed osteolytic lesions as well as extra-periosteal aberrant bone formation in the tumor bearing femur, similar to clinical findings in patients with bone metastatic prostate cancer. Within the tumor bearing femur, we observed reorganization of blood vessels, macrophage and nerve fibers within the intramedullary space and periosteum adjacent to tumor cells. Tumor bearing mice displayed significant increases in the injury marker ATF3 and upregulation of the neuropeptides SP and CGRP in the ipsilateral DRG as well as increased measures of central sensitization and glial activation in the ipsilateral spinal cord. This immunocompetent mouse model will be useful when combined with cell type selective transgenic mice to examine tumor, immune cell and sensory neuron interactions in the bone microenvironment and their role in pain and disease progression associated with bone metastatic prostate cancer.

Osteonecrosis in the jaws an alert to the use of bisphosphonates literature review

Bisphosphonates are a class of drugs widely used to treat bone conditions such as osteoporosis and metastatic bone cancer, they work by inhibiting the activity of osteoclasts, the cells responsible for bone resorption, resulting in an increase in bone density. However, prolonged use of these medications has been linked to the development of osteonecrosis, a condition in which a part of the bone loses its blood supply, resulting in pain, inflammation and, in severe cases, bone necrosis. Awareness of bisphosphonates and osteonecrosis is critical to ensuring that the benefits of these drugs outweigh the risks.

Peripheral but not axial muscle mass is associated with early mortality in bone metastatic lung cancer patients at diagnosis.

Identification of sarcopenia is a key issue in oncology. Several methods may be used to evaluate muscle mass in patients. Routine cancer follow-up computed tomography (CT) provides axial muscle mass whereas whole-body densitometry (DEXA) measures appendicular lean mass (ALM). Up to now, no studies have assessed, in cancer patients, the correlation between CT and DEXA muscle mass indicators and compared their prognostic value. We included patients with synchronous bone metastases from lung adenocarcinoma at diagnosis. Diagnosis was confirmed by bone biopsy. Skeletal muscle area was determined semi-automatically on initial CT scan at the T7, T12, and L3 vertebral level using Osirix® software. The skeletal muscle index (SMI) was calculated as the ratio of muscle area to height squared. Standardised ALM/height squared data were obtained by DEXA assessment within a 30-day window of CT. A total of 65 patients were included; 47 (72%) were male. Mean±SD age was 65±11.4years. DEXA was available for 46 patients. The performance status was good (<1) for 39 patients. SMI indicators were significantly correlated with each other (rho from 0.3 to 0.7) but moderately correlated with ALM (rho from 0.1 to 0.7). ALM had a good discriminatory ability on 6-month survival (AUC 0.87 [0.76; 0.97]). ALM was associated with early mortality (<6months) (HR=0.29, 95% CI [0.15; 0.57]; P<0.001) but not with later mortality (>6months). In contrast, no significant effect was found for SMI. Peripheral muscle mass (standardized ALM by DEXA) but not axial muscle mass (SMI assessed by CT) was associated with early mortality (<6months) suggesting that cancer-induced muscle loss would affect differently appendicular muscles and axial muscles.

Reconstruction After En Bloc Resection of a Distal Radius Tumor. An Updated and Concise Review.

The distal radius is rarely affected by either primary or metastatic bone cancers. The most frequent tumors of the distal radius are giant cell tumors, which are benign tumors with the propensity to invade. En bloc excision of giant cell tumors of the distal radius achieves a low recurrence rate but compromises the wrist joint, necessitates a significant reconstruction, and has functional consequences. Reconstruction after en bloc resection of a distal radius bone tumor is challenging. Furthermore, orthopedic oncologists disagree on treating such long bone anomalies most effectively. The present article summarizes the various biological and non-biological reconstruction techniques performed after en bloc resection of a distal radius tumor, discusses the advantages and disadvantages of each reconstruction strategy, and summarizes several case studies and case reports.

Nursing Care for Metastatic Bone Cancer: Trends for the Future.

To effectively treat patients and minimize viral exposure, oncology nurses and radiology departments during COVID-19 had to re-examine the ability to offer palliative radiation treatments to people with metastatic bone cancer. Decreasing potential exposure to the virus resulted in extra measures to keep patients and personnel safe. Limiting radiotherapy treatments, social distancing, and limiting caregivers were a few of the ways that oncology patients were impacted by the pandemic. Hypofractionated radiation therapy (HFRT), or the delivery of fewer higher-dose treatments, was a method of providing care but also limiting exposure to infection for immunocompromised patients as well as healthcare staff. As oncology radiation centers measure the impact of patient care during the pandemic, a trend toward HFRT may occur in treating the painful symptoms of bone cancer. In anticipation that HFRT may be increasingly used in patient treatment plans, oncology nurses should consider patient perspectives and outcomes from the pandemic to further determine how to manage future trends in giving personalized care, and supportive care.

Bone metastatic cancer of unknown primary at initial presentation.

Cancer of unknown primary (CUP) is a challenging malignancy. The purpose of this study was to investigate the clinical characteristics and prognosis of bone metastatic CUP using the population-based Surveillance, Epidemiology, and End Results (SEER) database. From the SEER database, we identified 1908 patients with bone metastatic CUP at initial presentation between 2010 and 2018. Histology was subdivided following International Classification of Diseases for Oncology codes as Adenocarcinoma, Squamous cell, Neuroendocrine, or Carcinoma not otherwise specified (NOS). Cox proportional hazard modeling was applied using factors of age, sex, ethnicity, histological subtype, and therapeutic intervention. Among the 1908 patients, histology was Neuroendocrine in 240 patients, Squamous cell in 201 patients, Adenocarcinoma in 810 patients and NOS in 657 patients. In each subtype, patients tended to be predominantly male and white. Chemotherapy was introduced for 28% of patients and radiation for 34% in the entire cohort. Survival in patients with bone metastatic CUP was unfavorable, with a median survival of 2months. Among the histological subtypes, Adenocarcinoma showed shorter survival than the other groups. In addition, treatment interventions such as chemotherapy and radiation therapy prolonged survival, particularly for Squamous cell, Adenocarcinoma and NOS, but not for Neuroendocrine. Bone metastatic CUP showed extremely poor prognosis, but treatment interventions such as chemotherapy and radiation generally offered survival benefits. Further randomized clinical research is needed to confirm the present results.

Plasma Therapy for Medication-Related Osteonecrosis of the Jaws- a Case Report

Medication-related osteonecrosis of the jaw (MRONJ) is a side effect of anti-bone resorption medications. Nowadays antiresorptive medications like bisphosphonate and monoclonal antibodies like denosumab that have been prescribed for bone disorders and metastatic cancer are becoming increasingly common. Although these medications are quite efficient at reducing bone resorption, they can develop osteomyelitis and jaw necrosis as a side effect. A 65-year-old woman was referred to the Oral Medicine Department of Semnan University of Medical Sciences with diffuse bilateral mandibular osteonecrosis, with a history of osteopetrosis and under-treatment of bisphosphonate. This complication started after tooth extraction and without any healing 5 years ago. After 3 sessions of plasma therapy, obvious improvement was seen. A proper medical history and a routine oral examination before treating with any invasive dental treatment are necessary to avoid any medication-related osteonecrosis of the jaw or mucosal abnormalities.

Nε-(1-Carboxymethyl)-L-lysine, an advanced glycation end product, exerts malignancy on chondrosarcoma via the activation of cancer stemness.

Despite epidemiological evidence that suggests diabetes mellitus is a risk factor for cancer, the link between diabetes mellitus and primary bone cancer is rarely discussed. Chondrosarcomas are primary malignant cartilage tumors with poor prognosis and high metastatic potential. It remains unclear whether hyperglycemia affects the stemness and malignancy of chondrosarcoma cells. Nε-(1-Carboxymethyl)-L-lysine (CML), an advanced glycation end product (AGE), is a major immunological epitope detected in the tissue proteins of diabetic patients. We hypothesized that CML could enhance cancer stemness in chondrosarcoma cells. CML enhanced tumor-sphere formation and the expression of cancer stem cell markers in human chondrosarcoma cell lines. Migration and invasion ability and the epithelial-mesenchymal transition (EMT) process were also induced by CML treatment. Moreover, CML increased the protein expression levels of the receptor for AGE (RAGE), phosphorylated NFκB-p65, and decreased the phosphorylation of AKT and GSK-3. We also found that hyperglycemia with high CML levels facilitated tumor metastasis, whereas tumor growth was not affected in the streptozotocin (STZ)-induced diabetic NOD/SCID tumor xenograft mouse models. Our results indicate that CML enhances chondrosarcoma stemness and metastasis, which may reveal the relationship between AGE and bone cancer metastasis.

An easy tool to predict survival in patients with bone metastatic lung cancer treated with palliative radiotherapy.

This study aimed to devise a simple assessment system for bone metastases (BMs) from lung cancer (LC). A total of 368 LC patients with BMs who underwent radiotherapy (RT) were retrospectively reviewed. Prognostic factors were evaluated using multivariate analysis, and a scoring system based on regression coefficients was devised. The median follow-up time for survival was 4.3 months, and the 0.5-year overall survival (OS) rate was 44.7%. In the multivariate analysis, the significant prognostic factors were performance status (PS), metastases to internal organs, and post-RT molecular-targeting therapies (MTs) (tyrosine kinase inhibitors, and/or immune checkpoint inhibitors). A scoring system aggregating points assigned to each risk factor was created (2 points; non-administration of post-RT MTs, 1 point; PS ≥3 and metastases to internal organs). The median OSs were 25.0 months, 12.8 months, and 2.5 months in patients with a total score of 0 (n = 22), 1-2 (n = 124), and 3-4 (n = 221), respectively (p < 0.01). This easy-to-use scoring system is useful for selecting patients who received comparatively high-dose fractionated RT for BMs from LC. Updates are required to follow the progress of systemic therapy.

Incidence rate of osteonecrosis of jaw after cancer treated with bisphosphonates and denosumab: A systematic review and meta-analysis.

This study aimed to assess the overall incidence of osteonecrosis of the jaw (ONJ) caused by bisphosphonates and denosumab when used for controlling bone cancer metastasis or as adjuvant therapy. A systematic search of the PubMed, Embase, and Cochrane Library databases and major meetings' proceedings as of July 30, 2022, identified randomized controlled trials (RCTs) and observational trials that evaluated ONJ caused by denosumab or bisphosphonates. The total incidence and risk ratio (RR) for ONJ were calculated using a random-effects model. A total of 42003 patients with various solid tumors reported in 23 RCTs were included. The overall ONJ incidence in cancer patients receiving denosumab or bisphosphonates was 2.08% (95% CI 1.37-2.91; p<.01; I2 =94.99%). Patients receiving denosumab had a higher ONJ incidence than those receiving bisphosphonates (RR 1.64, 95% CI 1.10-2.44; p<.05; I2 =65.4%). Subgroup analyses showed that prostate cancer patients receiving denosumab and receiving zoledronic acid had the highest ONJ incidences, 5.0% and 3.0%, respectively. The incidence of ONJ induced by different doses was also different. The incidence of ONJ caused by denosumab and bisphosphonates is low, the dose of the drug and the type of cancer have certain influence on ONJ. Therefore, clinicians should use the drug reasonably to improve the quality of life of patients.