Skeletal-related Events Research Articles

Abstract 244: Limiting metastatic breast cancer progression by targeting MK2 stromal signaling

Abstract Breast cancer is now the most common cancer among women in the US and metastasis to distant organs is the major cause of death in these patients. Among metastatic sites, bone is the most frequent destination of breast cancer metastasis and once the disease is found in the bone, it is often refractory to standard therapy. In addition, bone metastasis is associated with significant skeletal related events that greatly impact quality of life. Thus, there is a significant need to develop novel therapies that extend survival and improve quality of life. Previously we found that MK2 inhibition (MK2i) limits metastatic growth by targeting the tumor stromal compartment. To determine which stromal cells are targeted by MK2i we isolated stromal cells from within a metastatic bone lesion and carried out single cell RNA sequencing (scRNA-Seq). Using this approach, we found numerous gene expression changes in both the immune (CD45+) and non-immune (CD45-) populations upon MK2i. Indeed, we found significant numbers of p16+ senescent fibroblasts were present inside the metastatic lesion. We also found vascular cancer-associated fibroblasts (vCAF) and matrix CAFs (mCAF) inside the metastatic lesion suggesting that CAFs are not limited to primary disease. Numerous changes in gene expression in CD45+ cells were also observed, and these changes are being used to identify viable immunotherapies to deploy in our model. Finally, we are using conditional MK2 mice to establish the cell type targeted by MK2i. Our data demonstrate that MK2i is as effective as chemotherapy at limiting metastatic progression and our approach to leverage the scRNA-Seq data may allow us to optimize MK2i therapy to improve patient outcomes and quality of life. Citation Format: Renata Ramalho Oliveira, Douglas V. Faget, Xianmin Luo, Jiayu Ye, Joseph B. Monahan, Sheila A. Stewart. Limiting metastatic breast cancer progression by targeting MK2 stromal signaling [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 244.

ESTRO ACROP guidelines for external beam radiotherapy of patients with complicated bone metastases

This is the second part of the guidelines on the management of bone metastases. In the first part, the diagnosis and management of uncomplicated bone metastases have been addressed.Bone metastases may significantly reduce quality of life due to related symptoms and possible complications. The most common symptoms include pain and neurologic deficits. The most serious complications of bone metastases are skeletal-related events (SRE), defined as pathologic fracture, spinal cord compression, pain, or other symptoms requiring an urgent intervention such as surgery or radiotherapy. Diffuse bone metastases may lead to hypercalcaemia that can be fatal if untreated. The growing access to modern diagnostic tools allows early detection of asymptomatic bone metastases that could be successfully managed with local treatment if oligometastatic or systemic treatment for diffuse bone metastases to try to avoid the development of SRE.

Minimally Invasive Interventional Procedures for Metastatic Bone Disease: A Comprehensive Review.

Metastases are the main type of malignancy involving bone, which is the third most frequent site of metastatic carcinoma, after lung and liver. Skeletal-related events such as intractable pain, spinal cord compression, and pathologic fractures pose a serious burden on patients’ quality of life. For this reason, mini-invasive treatments for the management of bone metastases were developed with the goal of pain relief and functional status improvement. These techniques include embolization, thermal ablation, electrochemotherapy, cementoplasty, and MRI-guided high-intensity focused ultrasound. In order to achieve durable pain palliation and disease control, mini-invasive procedures are combined with chemotherapy, radiation therapy, surgery, or analgesics. The purpose of this review is to summarize the recently published literature regarding interventional radiology procedures in the treatment of cancer patients with bone metastases, focusing on the efficacy, complications, local disease control and recurrence rate.

Influence of alcohol sensitivity on bone metastases and skeletal-related events in primary operable breast cancer: A retrospective cohort study.

BackgroundBone metastases in breast cancer patients are a common concern for medical doctors and dentists. Bone-modifying agents, which are necessary to prevent skeletal-related events (SREs), are associated with osteonecrosis of the jaw as an adverse side effect. Hypersensitivity to alcohol is an unfavorable response caused by deficiency of aldehyde dehydrogenase-2 (ALDH2) activity. Inactive ALDH2 is associated with osteoporosis, but its influence on bone metastases is unclear. The aim of our study was to evaluate the effects of alcohol sensitivity on bone metastases and SREs in primary operable breast cancer patients.MethodsWe retrospectively analyzed patients who were administered docetaxel, an anti-tumor agent, for histologically diagnosed breast cancer between April 2004 and September 2015. Alcohol sensitivity was assessed based on medical records of hypersensitivity to alcohol. The primary endpoint was time to bone metastases and the secondary endpoint was time to first SRE from the initial docetaxel administration. Data were stratified by alcohol sensitivity and tumor stages, and differences were estimated by the Kaplan-Meier method. Prognostic risk factors were analyzed by the multivariate Cox proportional hazards model.ResultsThe median follow-up period of patients with high sensitivity to alcohol (n = 45) was 54 months and that for those with low sensitivity (n = 287) was 64 months. Stratification by alcohol sensitivity revealed that tumor stage exhibited significant correlations with the cumulative incidence of bone metastases in low-sensitivity patients; however, no differences were found in high-sensitivity patients. In multivariate analysis, alcohol sensitivity was a significant prognostic risk factor for bone metastases (HR 2.721, 95% CI 1.268–5.841, P = 0.010).ConclusionAlcohol sensitivity may be a prognostic risk factor for bone metastases. More detailed genetic investigations and metabolic analyses are needed.

The effects of bone targeted therapy in patients with greater than two years survival with metastatic breast cancer and bone metastasis.

e13076 Background: Administration of bone targeted therapy such as zoledronic acid (ZA) or of denosumab (D) decrease the risk of skeletal related events (SRE) such as radiation to the bone, pathological bone fractures, and spinal cord compression in patients with a diagnosis of metastatic breast cancer (MBC) and bone metastasis. As these patients continue to live longer it is unknown what are the impacts from long-term administration of ZA or D among those who live longer than 2 years. Methods: This was a retrospective analysis of patients with MBC and bone metastasis who lived for more than 2 years since diagnosis and received treatment at MD Anderson Cancer Center for MBC in addition to ZA and/or D between 2015 and 2021. Patient demographics, date of diagnosis, tumor characteristics, bone targeted agent treatment plans and SRE were extracted from the institutional database and electronic health records. We defined 3 patterns of receipt of bone targeted therapy: Pattern A: ZA every 3-4 weeks; Pattern B: D every 4-6 weeks; Pattern C; D every 4-6 weeks for a period followed by every 3 months. The association between these patterns and SRE was assessed using Fisher’s exact test. Results: We included 178 patients: Pattern A with 49 patients, Pattern B with 85 patients, and Pattern C with 44 patients. The proportion of patients who suffered a SRE in Patterns A, B, and C were 22.4% (11/49), 20% (17/85), and 21.4% (10/44). There was no statistical difference in the proportion of SRE between these three groups (p = 0.92). Conclusions: We did not observe a difference in the rate of SRE between the three different patterns of bone targeted therapy administration in patients with MBC and bone metastasis. Other treatment patterns will be considered in future analysis.[Table: see text]

Real-world associations between bone-targeted agents and palliative bone radiotherapy in prostate cancer decedents: A province-wide population study.

e17043 Background: Palliative bone radiation is the predominant skeletal-related event (SRE) reported in advanced prostate cancer. Bone targeted agents (BTA), such as denosumab and zoledronic acid, are shown to both prevent and delay SREs including bone radiation. This study evaluated real-world use of BTA in a large provincial database in relation to palliative bone radiotherapy prior to prostate-cancer related death. Methods: Linked, province-wide administrative databases from Ontario, Canada identified patients with prostate cancer (2007-2018, n = 98646), who received continuous androgen deprivation therapy (n = 29453), died between 2013-2018 (n = 4184), and qualified for Ontario Drug Benefits (OBD; 65 years or older, n = 3788). Patients receiving novel life prolonging therapy (LPT) for metastatic castration-resistant prostate cancer (mCRPC; abiraterone, enzalutamide, docetaxel, cabazitaxel and radium-223) were selected, and use of BTA (denosumab, zoledronic acid) was identified. Demographic, health, and treatment characteristics were collected over a 2-year observation window looking back from the date of death. Multivariable analyses were conducted to identify factors important in use of palliative bone radiation. Results: 1769 patients received LPT for mCRPC, including abiraterone (n = 1094, 62%), docetaxel (n = 881, 60%), enzalutamide (n = 480, 27%), radium-223 (n = 250, 14%) and cabazitaxel (n = 108, 6%). Amongst patients receiving LPT, 57% received BTA and 60% received palliative radiation to bone. Factors associated with palliative bone radiation were receipt of BTA (OR 1.46; 95% confidence interval [CI] 1.13-1.91), metastatic disease at diagnosis (OR 1.48; CI: 1.11-1.97), radiation oncologist involvement (OR 103.11; CI: 47.03-226.25), whereas patients with fewer chronic diseases (OR 0.73; CI: 0.54-0.98) and who had prior prostatectomy (OR 0.54; CI: 0.36-0.84) were less likely to receive radiation. This relationship was maintained for both zoledronic acid (OR 1.68; CI: 1.09-2.58) and denosumab (OR 1.35, CI: 1.03-1.77). No specific LPT was associated with use of palliative bone radiation. Conclusions: Despite clinicians prescribing BTAs to prevent SREs, in this cohort, radiotherapy to bone was more likely in patients receiving BTAs. This suggests that clinicians are prescribing BTAs to patients at greater risk of SREs, but that patients dying of prostate cancer continue to have significant bone-related morbidity despite contemporary prostate cancer treatment. An analysis of primary (before bone radiotherapy) versus secondary (after bone radiotherapy) BTA prescriptions will be presented, as well as timing of BTA initiation in relation to death.

Therapeutic effects and clinical outcomes of immune checkpoint inhibitors on bone metastases in lung cancer.

e21118 Background: In recent years, advanced lung cancer patients who received immune checkpoint inhibitors (ICIs) reportedly had a more prolonged overall survival (OS) than those treated with conventional anticancer drugs. However, the therapeutic effect of ICIs on bone metastases remains unclear. The purpose of this study was to investigate the therapeutic effects of ICIs on advanced lung cancer with bone metastasis. Methods: This retrospective study included 58 lung cancer patients (42 men and 16 women; mean age, 66.2±7.8 years) who had been diagnosed with bone metastasis before the initiation of ICI treatment between 2016 and 2019, and the mean follow-up period was 23.2 months. The clinical data such as content of chemotherapy including the bone-modifying agent (BMA), skeletal-related events (SREs), and immune-related adverse events (irAEs) were investigated. The therapeutic effects of ICIs on the primary lung lesions and bone metastases were evaluated by the response evaluation criteria in solid tumors 1.1 (RECIST 1.1) and MD Anderson criteria, respectively. To assess the influence of ICI treatment on prognosis, OS from the diagnosis of bone metastases was compared to the prognostic prediction of Katagiri's score. Results: The most used ICI was pembrolizumab in 27 cases (46.6%). BMA was used in 38 cases (65.6%), and denosumab was used in 31 cases (81.6%). SREs and irAEs were observed in three cases (5.2%) and 13 cases (22.4%), respectively. In the primary lung lesions, the response rate (RR) and disease control rate (DCR) of ICIs were 14.3% and 38.1%, respectively, including one case in CR and 5 cases in PR. In the bone metastatic lesions, the RR and DCR were 38.6% and 75.0%, respectively, including 3 cases in CR and 14 cases in PR. In 17 cases that ICIs responded to bone metastases, nine cases were treated with pembrolizumab (52.9%), and all cases whose evaluations were CR had been treated with concomitant therapy of pembrolizumab and denosumab. The median survival time was 28.1 months and the 2-year OS rate was 51.7%. The 6-, 12-, and 24-month OS rates in this study were more favorable than the prognostic prediction of the Katagiri's score. Conclusions: ICI treatment showed favorable responses to bone metastases in NSCLC and better prognoses than conventional predictive prognosis. Particularly, pembrolizumab may be the most effective, and the therapeutic effect was enhanced by the concomitant use of denosumab.[Table: see text]

Use of 18F-NaF PET in the staging of skeletal metastases of newly diagnosed, high-risk prostate cancer patients: a nationwide cohort study

ObjectiveTo determine whether preoperative staging of high-risk prostate cancer with 18F-sodium-fluoride (18F-NaF) positron emission tomography (PET) reduces the risk of skeletal metastases.DesignNationwide, population-based cohort study using real-world data.SettingThe study used...

Determination of direct treatment costs of patients with metastatic and nonmetastatic castration-resistant (mCRPC, nmCRPC) and metastatic hormone-sensitive (mHSPC) prostate cancer in Colombia.

e18838 Background: The purpose of this study was to determine the direct costs associated with the management of patients with metastatic castration resistant (mCRPC), non-metastatic (nmCRPC) and metastatic hormone-sensitive (mHSPC) prostate cancer in the Colombian healthcare system. Methods: First, a literature review was carried out to identify the main clinical recommendations for the treatment and follow-up of patients with prostate cancer at local and international levels. Subsequently, a participation process was developed with clinical experts, through a modified Delphi panel, to validate the natural history of the disease, and identify treatment options, skeletal-related events management, resource utilization, and distribution of patients within stages. Based on the above, a cost analysis model was performed, using Colombian health technology assessment agency recommendations, to calculate direct cost of treatment for mCRPC, nmCRPC and mHSPC from payer’s perspective. Exchange rate used was USD $1 = COP $4,000. Finally, the results were estimated considering the cost per patient per year. Results: According to the cost analysis of each stage, in the non-metastatic castration resistant stage (nmCRPC) the associated yearly cost of a patient was lower than in the metastatic castration resistant stage (mCRPC) (USD $8,581 versus $24,590, respectively), with a difference of USD $16,008. The metastatic hormone-sensitive stage (mHSPC) had a lower yearly cost than the metastatic castration-resistant stage (mCRPC) (USD $15,030 versus $24,590, respectively), with a difference of USD $ 9,559. The event that generated the greatest impact on the cost is the incidence of skeletal-related events associated with disease metastasis (55%). The deterministic sensitivity analysis on key variables, such as the percentage of patients who responded to treatment and the incidence of skeletal-related events, showed consistency of results. Conclusions: Delaying or stopping disease progression to mCRPC could more than halve annual treatment costs for patients. Given the findings, advanced metastatic castration resistant stages demand more resource utilization associated with disease management. The Colombian healthcare system would benefit from risk management strategies that implement timely interventions associated with early diagnosis and screening. In this way, the resource utilization in health sector's institutions would be directly impacted through budget optimization, obtaining better results focused on the national follow-up indicators of the prostate cancer patient cohort.

The use of osteoclast inhibitors in metastatic breast cancer

Abstract Introduction: In most patients, metastatic breast cancer (MBC) is incurable. Consequently, the goal in this setting is life prolongation and quality of life improvement, although possible long-term effects of anticancer treatment need to be considered. Bone is the most common site of metastasis in breast cancer and its complex management includes minimizing the risk of skeletal-related events (SRE), maximizing pain control, stabilizing or even restoring function, preventing spinal cord compression, hypercalcemia of malignancy and fractures and reducing the need for radiotherapy and orthopedic surgery. Aim: The present paper aims to compare the efficacy and safety of zoledronic acid (and other bisphosphonates) with denosumab in the management of bone metastases in breast cancer patients. Materials and methods: In this article, required information was collected through literature review and keyword query using the PRISMA 2020 guideline. Conclusions: In the metastatic setting, it appears that denosumab is indeed superior to zoledronic acid in delaying and preventing skeletal related events, except for spinal cord compression and risk of surgery, and equally efficient in treatment of already present bone pain and hypercalcemia of malignancy, with similar adverse effects, overall survival and disease progression.

A phase 2 randomized study of oral docetaxel plus ritonavir (ModraDoc006/r) in patients with metastatic castration-resistant prostate cancer (mCRPC).

5016 Background: Intravenous (IV) docetaxel and oral prednisone is a standard of care regimen in patients (pts) with mCRPC. ModraDoc006 is an oral formulation of docetaxel. To enhance bioavailability of ModraDoc006, it is co-administered with ritonavir (/r). The ModraDoc006 and ritonavir combination is active in multiple docetaxel and cabazitaxel-resistant prostate cancer cell-lines The oral combination (ModraDoc006/r) was compared to IV docetaxel in a randomized phase 2b study in pts with mCRPC evaluating two doses of ModraDoc006/r (30-20/200-100 mg and 20-20/200-100 mg). Data on outcomes in the larger cohort, receiving the lower dose, are being presented. Methods: Eligible pts had mCRPC, performance status of 0-1 and no prior chemotherapy for mCRPC. Sixty-two pts were enrolled in open label 1:1 randomized study comparing ModraDoc006/r 20-20 mg combined with 200-100 mg ritonavir in a bi-daily weekly schedule (“20-20/200-100 mg”), with IV docetaxel 75 mg/m2 in 21-day cycles. All pts received 5 mg oral prednisone twice daily. Primary endpoint was radiographic progression free survival (rPFS) per PCWG-3 criteria. Secondary objectives included ORR, PSA-PFS, time to skeletal related events, disease control rate, duration of response, and safety assessments. Results: 31 pts were enrolled on IV docetaxel 75 mg/m2 and 31 on ModraDoc006/r 20-20/200-100 mg. Of these, 57 were included in the analysis for rPFS, and 32 pts with measurable disease were included in the ORR analysis. Median PSA was 46 (range 1 to 1460 ng/ml). Prior therapy with enzalutamide in 8 pts, abiraterone in 10 pts. ModraDoc006/r was better tolerated with 0% all grades neutropenia and anemia, as compared to 26% (19% ≥G3) and 16% respectively on IV docetaxel. Neuropathy was significantly reduced at 9.7% G1 only on ModraDoc006/r vs 9.7% G1 and 19.4% G2 on IV docetaxel, whereas alopecia was reduced to 16.1% G1 and 6.5% G2 on ModraDoc006/r vs. 22.6% G1 and 19.4% G2 on IV docetaxel. GI toxicities were broadly comparable with diarrhea 32% (3% ≥G3) vs 29%, nausea 29% vs 13% and stomatitis 3% (G3) vs 13% (3% ≥G3), respectively. Conclusions: ModraDoc006/r demonstrated a favorable safety profile and comparable efficacy to IV docetaxel in pts with mCRPC, thus providing a compelling rationale for conduct of an expanded pivotal program. A key clinical program focus is the comparison of ModraDoc006/r to best available therapy in refractory mCRPC. Studies of ModraDoc006/r in other malignancies are also in active development. Clinical trial information: NCT04028388. [Table: see text]

A multicenter, randomized, double-blind, phase III trial comparing denosumab biosimilar QL1206 and denosumab in patients with bone metastases from solid tumors.

2526 Background: This phase III study compared clinical efficacy, safety of the first biosimilar QL1206 with denosumab in solid tumor patients with bone metastases. Methods: Patients aged 18-80 years, with bone metastatic solid tumors and ECOG performance status of 0-2 were randomly assigned 1:1 to receive subcutaneous QL1206 or denosumab (120 mg Q4W, both) based on stratification factors (tumor types, previous skeletal-related event [SRE], and current systemic anti-tumor therapy). The primary efficacy endpoint was the percentage changes from baseline to week 13 in urinary N-telopeptide/creatinine ratio (uNTX/uCr); Clinical equivalence would be confirmed if the two-sided 90% confidence intervals (CI) of the least-squares mean (LSM) difference of natural log-transformed ratio of week 13 uNTX/uCr to baseline calculated by analysis of covariance were within the margins of ±0.135. The secondary endpoints included the percentage changes from baseline to week 25 and 53 in uNTX/uCr, the percentage changes from baseline to week 13, 25 and 53 in serum bone-specific alkaline phosphatase (s-BALP) and the time to on-study SRE. Adverse events (AE), immunogenicity (IG) and pharmacokinetics (PK) were also assessed. Population PK was analyzed using nonlinear mixed effects model. Results: 717 patients were randomized to the QL1206 (n = 357) and denosumab (n = 360) groups, respectively. The median percentage changes at week 13 in uNTX/uCr were -75.2% for QL1206 and -75.8% for denosumab. LSM of natural log-transformed ratio of week 13 uNTX/uCr to baseline were -1.429 (standard error 0.130) and -1.441 (0.130) in the two groups. The LSM difference between the two groups was 0.012 (90% CI -0.078 to 0.103; P = 0.8208), within the equivalence margins. Analyses for subgroups of sex, age, and randomization strata showed almost no significant differences. The secondary endpoints were also similar between the two groups (median percentage changes in s-BALP from baseline to week 13: -38.0% vs -37.1%; hazard ratio of time to SRE: 1.264 [95% CI 0.670 to 2.383]; both P > 0.05). In the safety set, treatment-emergent AE occurred in 332 of 356 patients (93.3%) in the QL1206 group and 348 of 361 (96.4%) in the denosumab group. The proportions of positive anti-drug antibody (14/345 [4.1%] vs 16/352 [4.5%]), neutralizing antibody (three [0.9%], each), and PK characteristics were similar between the two groups. Conclusions: The results suggest that QL1206, the first biosimilar denosumab, is similar to denosumab with respect to clinical efficacy, acceptable safety, IG, and PK characteristics. The totality of evidence supports clinical equivalence of QL1206 and denosumab. Clinical trial information: NCT04550949.

Hypocalcemia After the Administration of Denosumab in a Patient With Osteoporotic Fracture and Vitamin D Deficiency

Denosumab is a potent antiresorptive agent used for the treatment of osteoporosis and the prevention of skeletal-related events in patients with multiple myeloma or bone metastasis from solid tumors. Although denosumab generally seems to be safe and well tolerated, denosumab-associated hypocalcemia may occur, and the majority of cases are asymptomatic or mild. Underlying malignancy, renal failure, calcium or vitamin D deficiency, and high bone turnover have been reported as risk factors for hypocalcemia. Here, the author reports a case of hypocalcemia and hypophosphatemia following the administration of denosumab for the treatment of osteoporotic fracture in a patient with underlying but unrecognized severe vitamin D deficiency. Following the supplementation of calcium, vitamin D, and phosphorus, serum calcium and phosphorus levels returned to normal levels after about 2 weeks. To avoid denosumab-associated hypocalcemia, calcium and vitamin D status, as well as renal function should be assessed and corrected if appropriate. J Endocrinol Metab. 2022;12(3):111-115 doi: https://doi.org/10.14740/jem810

ESTRO ACROP guidelines for external beam radiotherapy of patients with uncomplicated bone metastases

After liver and lungs, bone is the third most common metastatic site (Nystrom et al., 1977). Almost all malignancies can metastasize to the skeleton but 80% of bone metastases originate from breast, prostate, lung, kidney and thyroid cancer (Mundy, 2002). Introduction of effective systemic treatment in many cancers has prolonged patients’ survival, including those with bone metastases.Bone metastases may significantly reduce quality of life due to related symptoms and possible complications, such as pain and neurologic compromise. The most serious complications of bone metastases are skeletal-related events (SRE), defined as pathologic fracture, spinal cord compression, pain, or other symptoms requiring an urgent intervention such as surgery or radiotherapy. In turn, growing access to modern diagnostic tools allows early detection of asymptomatic bone metastases that could be successfully managed with local treatment avoiding development of SRE.The treatment for bone metastases should focus on relieving existing symptoms and preventing new ones. Radiotherapy is the standard of care for patients with symptomatic bone metastases, providing durable pain relief with minimal toxicity and reasonable cost-effectiveness. Historically, the dose was prescribed in one to five fractions and delivered using simple planning techniques. While 3D-conformal radiotherapy is still widely used for treating bone metastases, introduction of highlyconformal radiotherapy techniques such as stereotactic body radiotherapy (SBRT) have opened new therapeutic possibilities that should be considered in selected patients with bone metastases.

Newly Diagnosed Multiple Myeloma Patients with Skeletal-Related Events and Abnormal MRI Pattern Have Poor Survival Outcomes: A Prospective Study on 370 Patients.

Contemporary information is sparse on the frequency of skeletal-related events (SREs) in multiple myeloma (MM) patients at a population-based level in the era of novel agents. In this context, we conducted this single-center, prospective, observational study to determine the incidence of SREs among newly diagnosed MMs (NDMM) and to explore the possible correlations with disease characteristics, imaging finding, and patient prognosis. A total of 370 patients with available baseline MRIs were included. Among them, 208 (56%) presented with at least one SRE at diagnosis. Fractures were the most common reported SREs (48%). The incidence of SREs at diagnosis was higher in patients with osteolytic lesions, abnormal MRI pattern, hypercalcemia, and at least 60% bone marrow infiltration by plasma cells. Importantly, the patients with normal MRI pattern, who did not present with SREs at diagnosis, had statistically significant improved median OS in comparison with the patients who had abnormal MRI patterns and/or the presence of SREs at diagnosis (9.3 vs. 6.6 years, p = 0.048). Our data, which represent one of a few systematic reports on the incidence and characteristics of SREs in the era of novel agents, was indicative of a high incidence of SREs at the time of MM diagnosis. Early detection of myeloma bone disease and tailored patient management are essential to optimize patient outcomes.

Retrospective study of EGFR-mutant lung adenocarcinoma with bone metastatic clinical features.

With more and more target medicine application in lung cancer, lots of patients take medicine at home, the treatment bone metastasis and screen of bone metastasis always has been neglected until skeletal-related events (SREs) such as bone pain, hypercalcemia of malignancy and pathologic fractures emerging which significantly impairs the patients' daily activity ability, seriously lower quality of life. To identify the clinical characteristics of patients which influence the overall survival (OS) of EGFR-TKIs effective in EGFR-mutant NSCLC with bone metastasis (BM) and the bone metastatic image features. We conducted a retrospective study in patients (treated with EGFR-TKIs ≥6 months) of lung adenocarcinoma with BM in our hospital from October 2014 to October 2017. The Kaplan-Meier survival curves were calculated using the log-rank univariate test. Multivariate regression analysis was conducted using Cox's regression model. Comparison between the different subgroups of bone metastasis was conducted using Pearson Chi-Square test. A total of 79 patients were diagnosed as EGFR-mutant lung adenocarcinoma with bone metastases. At univariate analysis, age < 65 years (p = .024), heavy smoking (p = .005), Osteolytic BM (p = .034), number of bone metastasis ≥3 (p = .032), EGFR-L858R mutated (p = .018) and bisphosphonate times <6 (p = .046), were significantly associated with worse overall survival (OS). At multivariate analysis, EGFR 19del was an independent predictor of better OS (p = .035). Osteolytic BM was more likely to occur in EGFR-mutant patients (osteolytic vs. sclerotic vs. mixed: 45.57% vs. 34.18% vs. 20.25%). Patients who had received bisphosphonate ≥6 times were less suffer from SRE compared to those treated with bisphosphonate <6 times (p = .019). In conclusions, this retrospective study suggests that for the patients, treated with EGFR-TKIs ≥6months, EGFR exon 19 del, osteogenic bone metastasis, bisphosphonate application times ≥6, smoking <400/day and the number of BM <3 were predictors of better OS (p < .05). Bisphosphonate times ≥9 should be considered to the patients with BM. SPECT-CT would be an effective correction of SPECT in the patient's bone metastasis examination. During the whole follow-up process, we found by chance that the change of bone mineral density in the follow-up process suggested that bisphosphonates need to be used for more than 1 year or more, and we can use local CT in the follow-up clinical practice to confirm the bone density changes to decide when we could stop or reduce bisphosphonate application.

Uptake of bone-modifying agents in patients with HER2+ metastatic breast cancer with bone metastases - prospective data from a multi-site Australian registry.

International practice guidelines recommend administration of bone-modifying agents (BMA) in metastatic breast cancer (MBC) patients with bone metastases to reduce skeletal-related events (SRE). Optimal delivery of BMA in routine clinical practice, including agent selection and prescribing intervals, remains unclear. To describe real-world practice of Australian breast oncologists. Prospective data from February 2015 to July 2020 on BMA delivery to MBC patients with bone metastases was analysed from Treatment of Advanced Breast Cancer in the Human Epidermal Growth Factor Receptor 2 (HER2)-Positive Australian Patient (TABITHA), a multi-site Australian HER2+ MBC registry. Of 333 HER2+ MBC patients, 171 (51%) had bone metastases at diagnosis, with a mean age of 58.1 years (range, 32-87). One hundred and thirty (76%) patients received a BMA, with 90 (69%) receiving denosumab and 40 (31%) receiving a bisphosphonate. Patients who received a BMA were more likely to have received concurrent first-line systemic anti-HER2 therapy (95% vs 83%; P = 0.04), to present with bone-only metastases at diagnosis (24% vs 7%; P = 0.02) and less likely to have visceral metastases (51% vs 71%; P = 0.03). Ten of 40 (25%) bisphosphonate patients and 45 of 90 (50%) denosumab patients received their BMA at the recommended 4-weekly interval. Prescribing intervals varied over time. Adverse events reported were consistent with clinical trial data. Three-quarters of Australian HER2+ MBC patients with bone metastases receive a BMA, often at different schedules than guidelines recommend. Further studies, including all MBC subtypes, are warranted to better understand clinicians' prescribing rationale and potential consequences of current prescribing practice on SRE incidence.

Ocular complications with the use of radium-223: a case series

BackgroundRadium-223 is used for the treatment of osseous metastases in castrate-resistant prostate cancer, and has been shown to increase time to the first skeletal-related event, reduce the rate of hospitalization, and improve quality of life. It is well tolerated, with hematologic toxicity as the main adverse event. Thus far, no ocular complication has been reported in the literature after initial administration of radium-223 with a single case reported of ocular complications after a patient’s second course of radium-223.Case presentationsWe present three cases of ocular complications after the use of radium-223 in patients with metastatic prostatic adenocarcinoma. Ocular complications presented as blurry vision, and formal diagnosis included uveitis and hyphema.ConclusionsDocumentation of adverse events is exceedingly important due to the high incidence of metastatic prostate cancer and increasing interest for the use of radium-223 in other osteoblastic disease. The authors postulate that these ocular complications may be a result of radiation’s potential effect on neovascularization, polypharmacy, or the biomolecular effects of radium-223 on integral signaling proteins, potentially coupled with poor underlying ocular health.

Bone metastases in non-small cell lung cancer: a narrative review.

Background and ObjectiveBone metastases are common in patients with non-small cell lung cancer (NSCLC) and remain a significant source of morbidity, mortality, and diminished quality of life, despite the considerable progress made in the overall management of patients with metastatic NSCLC over the last decade. Understanding the molecular pathogenesis of bone metastases is critical to improving survival, preserving function, and managing symptoms in this patient population. The objective of our review is to provide a comprehensive review of the pathophysiology, clinical presentation, management, and factors predicting the development and prognosis of patients with NSCLC with bone metastases.MethodsAn online electronic search was performed on PubMed and Google Scholar of all English-language literature using combinations of the following keywords: bone metastases, non-small cell lung cancer, pathophysiology, skeletal related events, response to therapy, predictive factors, and immunotherapy. Bibliographies of identified papers were reviewed for additional articles of interest. Observational cohort, retrospective studies, randomized controlled trials (RCTs), meta-analyses, and review articles were examined for this review.Key Content and FindingsBone metastases in lung cancer patients remain a common occurrence, impacting morbidity, mortality, and quality of life. Patients with skeletal related events (SREs) have worse prognosis. There is data supporting use of bisphosphonates and/or denosumab, and these should be considered in all patients with bone metastases. Novel studies comparing the genomic alterations of skeletal metastases and primary tumors are needed. As therapy for patients with advanced disease evolves, more studies are needed to evaluate the interplay between immunotherapy and bone metastases, and in determining the response to treatment in bone.ConclusionsPredicting development and progression of bone metastases could allow earlier and targeted therapy in patients with bone metastases. Predicting and evaluating response to conventional chemotherapy and immune checkpoint inhibitors in NSCLC patients with bone metastases remains an unmet need and merits further study.

MP55-18 A NATIONAL COHORT STUDY OF CANCER OUTCOMES FOLLOWING HIGH-INTENSITY FOCUSED ULTRASOUND TREATMENT OF CLINICALLY LOCALISED PROSTATE CANCER

You have accessJournal of UrologyCME1 May 2022MP55-18 A NATIONAL COHORT STUDY OF CANCER OUTCOMES FOLLOWING HIGH-INTENSITY FOCUSED ULTRASOUND TREATMENT OF CLINICALLY LOCALISED PROSTATE CANCER Matthew Parry, Arunan Sujenthiran, Julie Nossiter, Melanie Morris, Brendan Berry, Ajay Aggarwal, Heather Payne, Jan van der Meulen, and Noel Clarke Matthew ParryMatthew Parry More articles by this author , Arunan SujenthiranArunan Sujenthiran More articles by this author , Julie NossiterJulie Nossiter More articles by this author , Melanie MorrisMelanie Morris More articles by this author , Brendan BerryBrendan Berry More articles by this author , Ajay AggarwalAjay Aggarwal More articles by this author , Heather PayneHeather Payne More articles by this author , Jan van der MeulenJan van der Meulen More articles by this author , and Noel ClarkeNoel Clarke More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002634.18AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Focal high-intensity focused ultrasound (HIFU) has fewer treatment-related side effects compared to radical whole-gland therapy (i.e surgery and radiotherapy) but there are limited data on 5-year cancer control. We therefore aimed to report on 5-year prostate cancer control following HIFU. METHODS: This observational cohort study used linked national cancer registry data, radiotherapy data, administrative hospital data and mortality records of 1,381 men treated with HIFU for clinically localised prostate cancer in England. The primary outcome, failure-free survival (FFS), was defined as freedom from local salvage treatment and cancer-specific mortality. Secondary outcomes were freedom from repeat HIFU, freedom from skeletal-related events (SREs), prostate cancer-specific survival (CSS) and overall survival (OS). Cox regression was used to determine whether baseline characteristics, including age, treatment year, T-stage and cancer grade (in groups ranging from 1 [least aggressive] to 5 [most aggressive]) were associated with with FFS. RESULTS: The median follow-up was 37 months (IQR 20-62). The median age was 65 years (IQR 59-70) and 81% had a International Society of Urological Pathology (ISUP) grade group of 1 or 2. FFS was 96.5% (95% CI 95.4-97.4%) at 1 year, 86.0% (95% CI 83.7-87.9%) at 3 years and 77.5% (95% CI 74.4-80.3%) at 5 years. 5-year FFS for ISUP grade groups 1-5 were 82.9%, 76.6%, 72.2%, 52.3% and 30.8%, respectively (P <0.001). Freedom from repeat HIFU at 5 years was 79.1% (95% CI 75.7-82.1%). 172 (12.5%), 13 (0.9%) and three (0.2%) men required one, two and three repeat HIFU treatments during follow-up, respectively. Nine men experienced a SRE and there were 44 deaths, 13 of which were related to prostate cancer. CSS was 98.8% (95% CI 98-99%) and OS was 95.9% (95% CI 94.2-97.1%) at 5 years. CONCLUSIONS: These results suggest that about four in five men are free from local salvage treatment and cancer-specific mortality at 5 years. Treatment failure varied significantly according to ISUP grade group indicating patient selection remains key and patients should be appropriately informed with respect to salvage radical treatment. Source of Funding: M.G.P. was supported by the National Institute of Health Research (DRF-2018-11-ST2-036). T.E.C. was supported by the Medical Research Council (MR/S020470/1). B.B. was partly supported by the NHS National Institute for Health Research through an Academic Clinical Fellowship. H.P. was supported by the University College London Hospitals/University College London Comprehensive Biomedical Research Centre. J.v.d.M. was partly supported by the National Institute for Health Research Collaboration for Leadership in Applied Health Research and Care North Thames at Bart’s Health NHS Trust. The views expressed in this article are those of the authors and not necessarily those of the NHS, the National Institute for Health Research or the Department of Health and Social Care © 2022 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 207Issue Supplement 5May 2022Page: e945 Advertisement Copyright & Permissions© 2022 by American Urological Association Education and Research, Inc.MetricsAuthor Information Matthew Parry More articles by this author Arunan Sujenthiran More articles by this author Julie Nossiter More articles by this author Melanie Morris More articles by this author Brendan Berry More articles by this author Ajay Aggarwal More articles by this author Heather Payne More articles by this author Jan van der Meulen More articles by this author Noel Clarke More articles by this author Expand All Advertisement PDF DownloadLoading ...