Bone Metastatic Sites Research Articles

Is surgery without curettage effective for periacetabular Metastasis? Insights from a survival study of 93 patients

BackgroundThe main aim of this study was to analyse the 6-month survival rates in peri-acetabular metastasis patients undergoing total hip arthroplasty (THA) with an acetabular cage and without curettage. The secondary objectives were to analyse the global survival rates, the factors influencing patient survival and to evaluate mechanical complication rates after THA. MethodsThis study was carried out on a cohort of 93 consecutive patients who underwent THA with an acetabular cage without curettage for acetabular metastasis or multiple myeloma lesions between 2010 and 2020. The National Death Registry was consulted to obtain the exact date of death of the patients; the minimum follow-up time was 2 years. ResultsThe 6-month survival rate for all types of cancer was 78 % [68 – 85], the 1-year survival rate was 66 % [55 – 74], and the 5-year survival rate was 26 % [17 – 36]. The median overall survival for the cohort was 24.37 months [16.10 – 32.63]. The mean overall survival was 46.02 months [32.89 – 59.16]. At last contact, 86 % of the operated patients were walking again.No patient died from surgery. The ECOG performance status score, the number of bone metastatic sites, the presence of visceral metastases and the number of lines of systemic therapy undertaken prior to surgery were negative survival factors. Three patients (3.2 %) had early prosthetic dislocation, 2 patients (2.2 %) showed aseptic loosening of her partial hip implant after 10 and 11 years respectively and 4 patients (4.3 %) had an early infection treated by debridement, antibiotics and implant retention to control the infection. During the follow-up period, no new femoral metastases were detected in any patient. ConclusionSurgery without curettage is an effective treatment for periacetabular metastasis. It gives reliable results, regardless of the type of acetabular lesion, allowing most patients to walk again and does not modify the patient’s survival.

Internal validation of modified Mirels’ scoring system for pathologic femur fractures

BackgroundThe proximal femur is a common site of bone metastasis. The Mirels’ score is a frequently utilized system to identify patients at risk for pathologic fracture and while it has consistently demonstrated strong sensitivity, specificity has been relatively poor. Our group previously developed a Modified Mirels’ scoring system which demonstrated improved ability to predict cases at risk of fracture in this patient population through modification of the Mirels’ location score. The purpose of the present study is to internally validate this newly developed scoring system on an independent patient series.MethodsRetrospective review was performed to identify patients who were evaluated for proximal femoral bone lesions. Patients were stratified into one of two groups: 1) those who went on to fracture within 4 months after initial evaluation (Fracture Group) and 2) those who did not fracture within 4 months of initial evaluation (No Fracture Group). Retrospective chart review was performed to assign an Original Mirels’ (OM) Score and Modified Mirels’ (MM) score to each patient at the time of initial evaluation. Descriptive statistics, logistic regression, receiver operating curve, and net benefit analyses were performed to determine the predictability of fractures when utilizing both scoring systems.ResultsThe use of the MM scoring improved fracture prediction over OM scoring for patients observed over a 4 month follow up based on logistic regression. Decision curve analysis showed that there was a net benefit using the MM score over the OM scoring for a full range of fracture threshold probabilities. Fracture prevalence was similar for current internal validation dataset when compared to the dataset of our index study with a comparable reduction in misclassification of fracture prediction when utilizing the modified scoring system versus the original.ConclusionsUse of MM scoring was found to improve fracture prediction over OM scoring when tested on an internal validation set of patients with disseminated metastatic lesions to the proximal femur. The improvement in fracture prediction demonstrated in the present study mirrored the results of our index study during which the MM system was developed.

Phosphate Ion-Responsive and Calcium Peroxide-Based Nanomedicine for Bone-Targeted Treatment of Breast Cancer Bone Metastasis.

The treatment of breast cancer bone metastasis is an unresolved clinical challenge, mostly because currently therapeutic approaches cannot simultaneously block the tumor growth and repair the osteolytic bone injuries at the metastatic site. Herein, the study develops a novel nanomedicine to treat breast cancer bone metastasis. The nanomedicine is based on phosphate ion-responsive and calcium peroxide-based nanoparticles carrying the bone-targeting agent zoledronic acid on the surface and loaded with the photosensitizer indocyanine green. Following intravenous administration to a mouse model of breast cancer bone metastasis, the nanoparticles efficiently accumulate at the bone metastasis site, react with free phosphate ions, and form hydroxyapatite nanoaggregates and O2, while releasing the photosensitizer. Hydroxyapatite nanoaggregates elicit the remineralization of the collagenous bone matrix and trigger tumor cell apoptosis. Upon irradiating tumor-bearing legs with an 808nm laser source, the O2 and free photosensitizer produced 1O2 by the reaction of the nanoparticles with phosphate ions, further boosting the anti-tumor effect. Tumor killing hampers the vicious cycle at the site of bone metastasis, translating to osteolysis blockade and further encouraging the remineralization of bone matrix. This work sheds light on the development of a novel, safe, and efficient approach for the treatment of breast cancer bone metastasis.

Concurrent use of Radiotherapy and Ribociclib: Preliminary Results and Review of the Literature.

In the recent MONALEESA-2, MONALEESA-3, and MONALEESA-7 clinical trials, the addition of ribociclib, a CDK4/6 inhibitor, to standard endocrine therapy significantly improved progression-free survival (PFS) compared with hormone therapy alone in the treatment of locally advanced or metastatic estrogen receptor-positive (ER) and HER2-negative breast cancer. However, its toxicity raises concerns when administered concomitantly with radiotherapy, leading most radiotherapists and medical oncologists to prefer to discontinue Ribociclib during radiotherapy (RT). Although there are insufficient published data on this combination, our preliminary experience with the first 2 patients treated at Institut Curie suggests promising results when using Ribociclib with Letrozole or Fulvestrant concurrently with palliative radiotherapy in the treatment of metastatic breast cancer. Our study aimed to evaluate the safety of combining Ribociclib with palliative radiotherapy in patients with metastatic breast cancer, providing crucial insights for clinical decision-making. A retrospective analysis was conducted on patients treated for hormone receptor-positive metastatic breast cancer with Ribociclib and concurrent radiotherapy at the Institut Curie (Paris, France) between September 2023 and April 2024. Among 38 patients who received Ribociclib and underwent irradiation, 36 temporarily suspended Ribociclib during radiotherapy, while 2 continued Ribociclib concurrently and were included in the analysis. Palliative radiotherapy was administered using volumetric modulated arc therapy, delivering 20Gy in 5 fractions to bone metastatic sites. Ribociclib was given at 600mg/day with hormonotherapy. Follow-up was conducted from the last day of RT until the last medical consultation. Toxicities were graded using CTCAE V5.0. Two patients received Ribociclib concomitantly with radiotherapy, experiencing pain relief without interruptions in RT. However, Ribociclib treatment was halted in both cases due to grade 3 neutropenia and grade 1 QTc interval prolongation, respectively. One patient had a dose reduction to 400mg due to neutropenia, with favorable outcomes observed. Both patients continued Ribociclib treatment, with one achieving complete remission and the other partial remission of bone disease. No late toxicities were observed. Despite the need for further investigation, our results suggest safety consistent with pivotal trials, advocating for a prospective cooperative data collection initiative to explore this combined strategy further, potentially revolutionizing metastatic breast cancer management.

INCIDENTAL BONE METASTASIS FINDING FROM CT SIMULATION FOR BREAST CANCER RADIOTHERAPY

Breast cancer has the highest tendency for bone metastasis. This study aimed to evaluate bone metastasis using computed tomography (CT) simulation for breast cancer radiotherapy. We retrospectively reviewed the patient's CT images from September 2022 to February 2023. The median age was 48 (34–80), and almost half of the patients had T3-4 and N2-3 disease. Nine out of 53 patients (17%) had bone metastasis, and 8 had multiple lesions. The vertebral spine was the predominant site of bone metastasis. Due to the high rate of bone spreading, bone evaluation is mandatory during CT simulation for more appropriate treatment. Keywords: Bone metastasis, computed tomography, breast cancer

The Prognostic Significance Of Inflammation Associated Blood Cell Markers In Metastatic Colorectal Cancer

Objectives: The aim is to perform prognostic evaluation with overall survival (OS) and progression-free survival (PFS) in hematological parameter-based groups in patients with metastatic colorectal cancer (mCRC). Methods: In a single institution, 51 patients were retrospectively analyzed mCRC diagnosed between 2019 and 2022. Pretreatment hematological parameters of patients with mCRC receiving first-line chemotherapy in a single center were examined. The receiver operating characteristic curve was used to predict the tests. Median OS was calculated by the Kaplan-Meier method and compared with the log-rank test. Multivariate analyses were performed using a Cox regression model. Results: The median OS of the patients included in the study was 27 months (3-88 months) by statistical calculation; the median PFS was 19 months (2-84 months). The median could not be reached. Among the risk factors affecting OS, it was found effective to have a bone metastasis site and a pancreatic metastasis site (p values 0.003 and 0.027, respectively). In the analysis of the risk factors affecting PFS, bone and pancreatic metastases were found to be significant (p values 0.001 and 0.004, respectively). Patients receiving chemotherapy and anti-VEGF therapy have a significantly reduced risk of death of 0.06 times compared to those who do not receive chemotherapy, which indicates that OS is significantly longer in people receiving chemotherapy in question (p=0.020). It was observed that blood cell marker levels were not statistically significant in PFS and OS. Of the 51 patients included in the study, 30 of them were still being followed up, while 21 of them died. Conclusions: Chemotherapy plus anti-VEGF therapy is a treatment whose effectiveness has been determined in metastatic colorectal cancer. In the future, there is a need for more prospective and large patient group studies on this topic to measure the prognostic value of hematological parameters in metastatic colorectal cancer.

Abstract 6942: Single cell resolution of intrapatient drug resistance mechanisms in metastatic melanoma

Abstract Intrapatient heterogeneity among different metastatic sites contributes to immunotherapy (ICi) and targeted therapy resistance. Determining the evolution of metastatic melanoma lesions that develop within the same patient could help elucidate adaptive mechanisms that drive tumor progression during therapy. To assess how metastatic melanoma persists through immunotherapy and targeted inhibitor treatments, we utilized samples from a single patient who had received anti-CTLA4, BRAFi/MEKi, and BRAFi/MEKi+CDK4/6i treatments during the LOGIC2 clinical trial. Eight short-term cultures were established from different metastatic site biopsies at chronological time points throughout the patient’s treatment and subsequent post-mortem resection of the bone, ovary, and brain metastatic sites. While the initial treatment naïve metastatic tumor in the breast was BRAFV600E mutant, NRASQ61 mutations were acquired after treatment with CDK4/6i in the bone and ovary tumors. Tumors that persist through treatment and colonize distant organs adapt to and rely on organ-specific microenvironments. To assess treatment- and organ-specific adaptations, single-cell RNA sequencing was performed on seven of the short-term cultures to identify subpopulations that persist through each treatment. We analyzed samples and subpopulations of each culture to determine differences in their transcriptional cell states. The regulon transcriptional network of each sample and subpopulation was evaluated to determine site- and treatment-specific transcriptional regulation differences. In addition, we identified the treatment naïve culture is split into two major subpopulations by therapy resistance features which are further made up of six distinct subpopulations with heterogeneous regulatory networks. We determined the longitudinal evolution of subpopulations in response to treatment and organ site to evaluate how the pressure of therapies and the microenvironment influence metastatic progression. We further evaluated site-specific resistance mechanisms and detected increased HER3 expression in the melanoma brain metastasis (MBM) sample. Treatment with Neuregulin 1, a ligand for the HER3 receptor that is abundant in brain tissue, partially rescued the growth of MBM cells and restored MAPK and AKT-mTOR signaling in the presence of BRAFi/MEKi. Targeting the NRG1-HER3 signaling axis could have therapeutic potential in melanoma patients with active brain metastases. Additionally, we evaluated treatment-specific resistance mechanisms and identified high Brevican (BCAN) expression in an early emerging subpopulation that arises after ICi in this patient and in others. BCAN is implicated in both ICi- and cross-resistance. We will functionally investigate whether targeting BCAN sensitizes cells to ICi. Future studies aim to functionally examine novel site- and treatment-specific cross patient targets. Citation Format: Haley P. Wilson, Glenn L. Mersky, Jelan I. Haj, Jessica Teh, Phil F. Cheng, Signe Caksa, Casey D. Stefanski, Vivian Chua, Claudia Capparelli, Mitch P. Levesque, Reinhard Dummer, Timothy J. Purwin, Andrew E. Aplin. Single cell resolution of intrapatient drug resistance mechanisms in metastatic melanoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6942.

Abstract 6866: Investigating the role of Epha2 in breast cancer-mediated myeloid cell expansion and function

Abstract Bone metastases are present in over 70% of metastatic breast cancer patients, and current therapy reduces osteolysis in tumor-induced bone disease (TIBD) but does not improve overall survival. Frequently, TIBD is characterized by an increase in osteoclast proliferation and bone-resorbing activity, and patients often experience pain and pathologic fractures. Increased bone resorption releases growth factors that aid in the progression of tumor growth causing the ‘vicious cycle’. Additionally, bone metastatic patients are often resistant to first- and second-line therapies highlighting an importance for research in this area. The receptor tyrosine kinase, Ephrin-type-A 2 receptor (EphA2), participates in both forward and reverse signaling during receptor/ligand engagement and participates in many physiological and pathological processes, including bone homeostasis, immunity, and cancer. Interestingly, EphA2 is highly expressed in bone metastases, and previous evidence suggests that EphA2 can promote TIBD and reduce anti-tumor immunity. We therefore hypothesize that increased expression of EphA2 in breast cancer cells at the site of bone metastasis promotes expansion of myeloid cells, leading to TIBD. Previous data shows a reduction in osteoclast number and bone lesions following EphA2 knockout. However, the mechanism by which EphA2 mediates the expansion of osteoclasts is not well understood. In agreement with previous work, our data shows that EphA2 deletion in murine breast cancer (BC) cell line, 4T1, reduces bone lesion area and number and the presence of bone metastasis-associated macrophages. Additionally, we observed a significant reduction in Ly6Chi cells. To assess the effects of EphA2 deletion on the behavior of 4T1 cells, we conducted a wound healing assay and observed a decrease in wound healing capacity in 4T1 cells following EphA2 deletion. This suggests that EphA2 expression in 4T1 cells may increase their metastatic potential. We will repeat these studies and incorporate factors from the bone marrow. Our future studies will investigate the role of EphA2 signaling and reverse signaling in BC cell lines, myeloid progenitor cells, osteoclasts, and bone metastasis-associated macrophages. We will utilize murine and human BC cell lines to elucidate the effects of EphA2 deletion in BC on immune cell populations, bone metastasis, and tumor progression. Additionally, we will investigate how EphA2 reverse signaling impacts osteoclasts’ ability to modulate immune cells. We aim to reduce TIBD and tumor burden by reducing the expansion of osteoclasts and shifting the immune cells to an anti-tumorigenic phenotype. Our studies will provide additional insight into the underlying mechanisms of the vicious cycle which will offer new treatment strategies for patients with osteolytic breast cancer. Citation Format: Dominique Parker, Verra Ngwa, Jin Chen, Julie Rhoades. Investigating the role of Epha2 in breast cancer-mediated myeloid cell expansion and function [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6866.

Metastatic profiles and survival differences between infiltrating ductal carcinoma and infiltrating lobular carcinoma in invasive breast cancer

BackgroundIn this study, we conducted a comprehensive evaluation of metastatic profiles and survival outcomes in patients with infiltrating ductal carcinoma (IDC) and infiltrating lobular carcinoma (ILC) treated at our university hospital center. MethodsWe collected and analyzed data from all patients diagnosed with invasive breast cancer at our center between January 1, 2007, and 31 December 2014. We specifically compared three subgroups: patients with IDC, patients with ILC and patients with mixed carcinoma, which is a combination of IDC and ILC. ResultsAmong the 1963 patients treated for invasive breast cancer in our center during the study period, 1435 had IDC, 466 had ILC, and 59 had mixed carcinoma. The incidence of patients with at least one positive axillary lymph node differed significantly: 40 % for IDC, 36 % for ILC, and 45 % for mixed carcinoma (p = 0.001). However, there was no significant difference in the mean number of positive nodes (p = 0.1633). The occurrence of distant metastases was lower in patients with ILC (p = 0.04), particularly in the case of brain metastases (p = 0.01), although there was no difference in bone or visceral metastatic sites. Patients with ILC exhibited a longer mean time to metastasis from the initial diagnosis of invasive breast carcinoma. Overall survival (p = 0.0525) and survival without locoregional recurrence (p = 0.026) were significantly different. Specifically, the 5-year overall survival rates for IDC, ILC, and mixed carcinoma were approximately 95 %. Distance metastatic-free survival at 5 years was 85 % for IDC, 91 % for ILC, and 87 % for mixed carcinoma (p = 0.00506). ConclusionOur findings indicate variations in the distribution of distant metastatic sites among patients with IDC, ILC, and mixed carcinoma, as well as differences in survival outcomes. This study sheds light on the unique characteristics and clinical implications associated with these two distinct subtypes of invasive breast cancer.

Disease characteristics and prognostic factors of colorectal cancer patients with bone metastasis: A real-world data from Turkey.

Bone metastasis is rarely seen in colorectal cancer (CRC) patients, and there is insufficient data available regarding such cases. The study aimed to identify the prognostic factors and characteristics associated with overall survival in patients with bone metastatic CRC. Data from bone metastatic CRC patients referred to a high-volume tertiary cancer center in Turkey, between January 2018 and April 2021, were retrospectively collected. The records of 150 consecutive patients treated for bone metastases due to CRC were reviewed. Overall survival curves were generated by the Kaplan-Meier method and analyzed using the log-rank test. Median age was 55 years (19-86 years). Bone metastases were more common in men and those with metachronous metastases. The axial skeleton was the most commonly involved site, and patients were frequently presented with single bone metastasis. Peritoneal metastases were significantly correlated with extra-axial metastases (P = 0.002), and radiotherapy was applied to axial metastases significantly, more frequently (P = 0.02). Lung metastasis was also more prevalent in K-RAS mutated patients (P = 0.008). The median survival time from diagnosis of bone metastasis was 8.3 months (95% confidence interval (CI), 5.5-10.6), and the three-year survival rate was 76.9% (95% CI, 69.8-84.0). Multivariate analysis revealed that brain metastases, right-sided colon tumor, high serum ALP, and Ca 19-9 levels were independent poor prognostic factors (P = 0.01, 0.02, <0.001, and 0.04, respectively). The location of CRC correlates significantly with the site of bone metastasis; the prognosis of CRC patients with bone metastasis is very poor, and the significant poor prognostic factors are brain metastases, right-sidedness, high serum ALP, and Ca 19-9 levels. More attention should be paid to bone metastasis in CRC patients.

Rectal toxicity of 3-dimensional conformal radiation therapy following hydrogel spacer (Space OAR) injection for men with prostate cancer.

To evaluate whether hydrogel spacer injection, which increases the distance between the prostate and rectum, prior to local radiation therapy for prostate cancer reduces rectal and bladder toxicity. With institutional review board approval (05-004), we retrospectively reviewed rectal and bladder toxicity after local radiation therapy in patients with prostate cancer who were followed up for more than 1 year. We included 156 patients who had received local radiation therapy. Their ages ranged from 63 to 86 years, with an average of 75 years. Most patients were treated only on the prostate and seminal vesicles. All prostate sites were irradiated as follows: whole pelvis with prostate in 10 patients, whole pelvis with prostate and metastatic sites in six, and prostate and metastatic sites in eight. Radiation therapy (70-74 Gy) was performed for the prostate. Irradiation of 45-46.8 Gy was applied to whole pelvic and para-aortic lymph nodes, with 54-60 Gy applied to bone metastatic sites. In one case, stereotactic body radiation therapy (36 Gy) was performed for a sacral bone metastatic site. The hydrogel spacer was injected in 39 patients. Rectal toxicity was reported in 21 patients without (17.9%) and 3 patients with (7.7%) the hydrogel spacer. Bladder toxicity was reported in five patients without and only one patient with the hydrogel spacer. Hydrogel spacer injection prior to local radiation therapy for prostate cancer reduces rectal radiation exposure, lowers the risk of rectal complications, and may be a promising method for boosting the irradiation dose in the future.

Survival Outcomes in Malignancy-related Hypercalcemia: A Tertiary Care Single-center Experience.

Malignancy-related hypercalcemia is commonly observed in patients with advanced stages of cancer. It is intricately linked with an unfavorable prognosis among oncology patients. This study aimed to evaluate survival outcomes among individuals diagnosed with hypercalcemia associated with malignancy. This retrospective analysis of 173 cancer patients with hypercalcemia who sought treatment at Shaukat Khanum Memorial Cancer Hospital and Research Centre, Lahore, Pakistan, between July 2019 and June 2020. This cohort of patients underwent a longitudinal follow-up for 2.5 years. To assess survival outcomes, the Kaplan-Meier tool was used to construct survival curves and estimate the survival probability over time. The significance of potential survival factors was evaluated using the log-rank test. All patients exhibited elevated levels of calcium. At admission, the cohort demonstrated varying degrees of hypercalcemia severity attributable to malignancy: Mild hypercalcemia was observed in approximately 61.3% of patients, moderate hypercalcemia in 23.7%, and severe hypercalcemia in 15% of cases. Among the total sample, most patients were female (54.9%), with a median age of 54. The primary tumor site most frequently observed was in cases of breast cancer (35.3%), wherein the prevalent histological subtype was lobular/ductal invasive carcinoma (34.1%). Most of the patients (93.6%) had an Eastern Cooperative Oncology Group (ECOG) performance status (ECOG) >1. In addition, the median overall survival for patients diagnosed with hypercalcemia was 51 days. Notably, there was a significant association between survival factors, including the primary site of malignancy (P = 0.001), bone metastasis (P = 0.04), severity and symptoms of hypercalcemia (P = 0.001), altered mental state (P = 0.001), albumin levels (P = 0.001), and ECOG (P = 0.001). Malignancy-related hypercalcemia in patients with cancer is a significant predictor of an unfavorable prognosis. The aforementioned survival factors may have the potential to influence patient survival outcomes. Further studies on larger cohorts are warranted.

Prognostic impact of colorectal cancer patients with bone metastases: a single-center experience.

The incidence of bone metastasis (BM) in colorectal cancer (CRC) patients is low and the prognosis is poor. There is no clear conclusion on the risk factors affecting the survival of CRC patients with BM. The aim of this study was to investigate the factors that may affect the prognosis of CRC patients with BM. The clinical and pathological data of CRC patients with BM were retrospectively analyzed. The overall survival after BM diagnosis was estimated using the Kaplan-Meier method and Log-rank test, and a multivariable cox regression model was used to identify the prognostic factors of overall survival. This study included 178 CRC patients with BM, of whom 151 had left-sided CRC and 27 had right-sided colon cancer. 1124 CRC patients with BM from the SEER database were included to perform a sensitivity analysis of the primary outcome. Multivariate analysis showed that the N staging, site of BM, and primary tumor sidedness (PTS) were independent prognostic factors for CRC with BM. Among them, right-sided colon cancer patients with BM had a poorer prognosis. Sensitivity analyses showed that PTS was an independent prognostic factor in CRC patients with BM. Primary tumor sidedness and N stage may be potential prognostic markers for BM of CRC. The prognosis of N0 stage CRC with BM is better, while the prognosis of right-sided colon cancer is poor.

Reoperation after surgery for bone metastasis of renal cell carcinoma.

The prognosis of metastatic renal cell carcinoma (RCC) has markedly improved with the advent of molecular targeted therapies and immune checkpoint inhibitors. However, the therapeutic response in patients with bone metastasis remains low; therefore, surgery still plays a significant role in treatment of bone metastasis. It is important to maintain quality of life for patients with bone metastasis from RCC and avoid reoperation after surgery for bone metastasis. Therefore, we investigated the risk factors for reoperation after surgery in patients with bone metastasis from RCC. We retrospectively studied 103 bones of 97 patients who underwent surgery for bone metastasis of RCC from 2001 to 2023 at our institutions. Reoperation was performed in 10 (9.7%) of 103 bones. There was no correlation between reoperation-free survival and any of the following variables: preoperative and postoperative radiotherapy, site of bone metastasis, indication for surgery (solitary bone metastasis or impending or pathologic fractures), surgical method (intramedullary nailing fixation, curettage, or en bloc resection), preoperative embolization, or survival. The risk of reoperation for bone metastasis of RCC does not appear to be based on the surgical method.

High bone tumor burden to identify advanced non-small cell lung cancer patients with survival benefit upon bone targeted agents and immune checkpoint inhibitors

BackgroundBone-targeted agents (BTA), such as denosumab (DN) and zoledronic acid (ZA), have historically reduced the risk of skeletal related events in cancer patients with bone metastases (BM), with no improvement in survival outcomes. In the immunotherapy era, BM have been associated with poor prognosis upon immune-checkpoint inhibitors (ICI). Currently, the impact of bone tumor burden on survival upon BTAs in advanced non-small cell lung cancer (aNSCLC) patients treated with ICI remains unknown. MethodsData from ICI-treated aNSCLC patients with BM (4/2013-5/2022) in one institution were retrospectively collected. BTA-ICI concurrent treatment was defined as BTA administration at any time before or within 90 days from ICI start. High bone tumor burden (HBTB) was defined as ≥ 3 sites of BM. Median OS (mOS) was estimated with Kaplan-Meier. Aikaike’s information criterion (AIC) was used to select the best model for data analysis adjusted for clinical variables. ResultsOf 134 patients included, 51 (38 %) received BTA. At a mFU of 39.6 months (m), BTA-ICIs concurrent treatment did not significantly impact on mOS [8.3 m (95% CI 3.9–12.8) versus (vs) 6.8 m (95% CI 4.0–9.6) p = 0.36]; these results were confirmed after adjustment for clinical variables selected by AIC. A multivariate model showed a significant interaction between BTA use and HBTB or radiation therapy to BM. In subgroup analyses, only HBTB confirmed to be associated with significantly longer mOS [8.3 m (95% CI 2.4–14.2) vs 3.5 m (95% CI 2.9–4.1), p = 0.003] and mPFS [3.0 m (95% CI 1.6–4.4) vs 1.8 m (95% CI 1.6–2.0) p = 0.001] upon BTA-ICI concurrent treatment, with the most pronounced OS benefit observed for DN-ICI concurrent regimen [15.2 m (95% CI 0.1–30.7) vs 3.5 m (95% CI 2.9–4.1) p = 0.002]. ConclusionsIn the immunotherapy era, HBTB can identify patients experiencing survival benefit with BTA, especially with DN-ICI combination. HBTB should be included as a stratification factor in the upcoming trials assessing BTA and ICI combinations in patients with aNSCLC and BM.

Wnt1 induces osteoblastic changes in a well-established osteolytic skeletal metastatic model derived from breast cancer.

Osteoblastic skeletal metastasis is frequently observed in prostate cancer. An effective therapy has not been developed due to the unclear molecular mechanism. The Wnt family is involved in various biological phenomena including bone metabolism. There is no direct evidence that the family causes osteoblastic skeletal metastasis. The present study aims to evaluate whether overexpressed Wnt induces osteoblastic bone metastasis in a well-established osteolytic bone metastatic model. The breast cancer-derived 5a-D-Luc-ZsGreen cells were transfected with Wnt1, Wnt3A, and Wnt5A expression vectors, producing stably highly expressing cells. These cells were intracardially transplanted in nude mice. Bone metastasis development was confirmed by fluorescence imaging. Hind-limb bones including metastasis were dissected and visualized through micro-CT imaging. After imaging, sections were stained with hematoxylin and eosin (H&E), and immunohistochemically stained with an anti-SATB2 antibody. Luminescent imaging confirmed mice with bone metastases in the hind limbs. Micro-CT imaging found an osteoblastic change only in bone metastasis of mice transplanted with Wnt1-expressing cells. This was confirmed on H&E-stained sections. SATB2 immunostaining showed differentiated osteoblasts were at the site of bone metastases in the diaphysis. SATB2 in the Wnt/β-catenin pathway activated by overexpressed Wnt1 could induce osteoblastic change. Our findings provided direct evidence Wnt1 is involved in osteoblastic bone metastasis development. Our model would be a powerful tool for further elucidating molecular mechanisms underlying the disease and developing effective therapies.

Osteoblastic bone reaction in non-small cell lung cancer harboring epidermal growth factor receptor mutation treated with osimertinib

BackgroundOsteoblastic bone reaction (OBR) refers to an increase in bone density at the site of bone metastasis or the appearance of new sclerotic bone lesions after anticancer treatment. OBR can be misunderstood as disease progression. In this study, we aimed to investigate the prevalence and details of OBR and its association with clinical outcomes in patients with epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC) treated with osimertinib.MethodsThis was a single-center, retrospective cohort study. We reviewed patients who were diagnosed with EGFR-mutant NSCLC with bone metastasis and received osimertinib as a first-line treatment between February 2018 and October 2022. The OBR was evaluated by comparing baseline computed tomography (CT) scans with the first CT scan after treatment initiation.ResultsA total of 45 patients were included in this study. Thirty-seven patients (82%) developed OBR. OBR developed in 94% (n = 16) of patients with sclerotic bone lesions (n = 17) at baseline. Similarly, OBR developed in lytic and mixed bone lesions in 76% and 82% of patients with lytic and mixed lesions, respectively. Progression-free survival (PFS) did not differ significantly between patients with (OBR group) and without OBR (non-OBR group) (median PFS, 24 months vs. 17 months; hazard ratio (HR), 0.62; 95% CI, 0.24–1.6; p = 0.31). In univariate analysis, the OBR group showed a trend toward longer skeletal-related events-free survival (SRE-FS) than the non-OBR group (median SRE-FS, 26 months vs. 12 months; HR, 0.53; 95% CI, 0.21–1.33; p = 0.16). Multivariate analysis showed OBR was a significant independent predictor of SRE-FS (HR, 0.35; 95% CI, 0.13–0.92; p = 0.034).ConclusionsOBR developed in most patients with NSCLC and bone metastasis who received osimertinib treatment. The increased incidence of OBR in patients with EGFR-mutant NSCLC with bone metastasis treated with osimertinib should not be confused with disease progression, and treatment decisions should be made carefully.

Alcoholization of intercostal nerves for incident pain due to rib metastases.

Rib metastases may cause incident pain on coughing, deep respiration, or on specific thoracic wall movement. Proper titration of opioid doses relieves the background pain adequately, but does not allow a good pain control for incident pain. A patient with rib metastases presented incident pain due to minimal chest wall movement, limiting breathing. Alcoholization of intercostal nerves at T6,T7, T8, and T9, at level of ribs angle, RESULTS: Intercostal blocks were highly effective in relieving incident pain due to rib metastases. A simple and safe procedure may produce effective analgesia preventing incident pain due to rib metastases. Differently from other sites of bone metastases, ribs are easily localized and the neurolytic block results to be effective and safe.

A prognostic nomogram for the cancer-specific survival of white patients with invasive melanoma at BANS sites based on the Surveillance, Epidemiology, and End Results database.

The purpose of this study was to develop a comprehensive nomogram for the cancer-specific survival (CSS) of white patients with invasive melanoma at back, posterior arm, posterior neck, and posterior scalp (BANS) sites and to determine the validity of the nomogram by comparing it with the conventional American Joint Committee on Cancer (AJCC) staging system. This study analyzed the patients with invasive melanoma in the Surveillance, Epidemiology, and End Results (SEER) database. R software was used to randomly divide the patients into training and validation cohorts at a ratio of 7:3. Multivariable Cox regression was used to identify predictive variables. The new survival nomogram was compared with the AJCC prognosis model using the concordance index (C-index), area under the receiver operating characteristic (ROC) curve (AUC), net reclassification index (NRI), integrated discrimination index (IDI), calibration plotting, and decision-curve analysis (DCA). A novel nomogram was established to determine the 3-, 5-, and 8-year CSS probabilities of patients with invasive melanoma. According to the nomogram, the Age at Diagnosis had the greatest influence on CSS in invasive melanoma, followed by Bone Metastasis, AJCC, Stage, Liver Metastasis, Histologic Subtype, Brain Metastasis, Ulceration, and Primary Site. The nomogram had a higher C-index than the AJCC staging system in both the training (0.850 versus 0.799) and validation (0.829 versus 0.783) cohorts. Calibration plotting demonstrated that the model had good calibration ability. The nomogram outperformed the AJCC staging system in terms of AUC, NRI, IDI, and DCA. This was the first study to develop and evaluate a comprehensive nomogram for the CSS of white patients with invasive melanoma at BANS sites using the SEER database. The novel nomogram can assist clinical staff in predicting the 3-, 5-, and 8-year CSS probabilities of patients with invasive melanoma more accurately than can the AJCC staging system.

Factors Associated with Long-Term Prostate Cancer Survival after Palliative Radiotherapy to a Bone Metastasis and Contemporary Palliative Systemic Therapy: A Retrospective, Population-Based Study

Background: Radiation therapy (RT) is an established palliative treatment for bone metastases; however, little is known about post-radiation survival and factors which impact it. The aim of this study was to assess a population-based sample of metastatic prostate cancer patients receiving palliative radiation therapy to bone metastases and contemporary palliative systemic therapy and identify factors that impact long-term survival. Materials/methods: This retrospective, population-based, cohort study assessed all prostate cancer patients receiving palliative RT for bone metastases at a Canadian provincial Cancer program during a contemporary time period. Baseline patient, disease, and treatment characteristics were extracted from the provincial medical physics databases and the electronic medical record. Post-RT Survival intervals were defined as the time interval from the first fraction of palliative RT to death from any cause or date of the last known follow-up. The median survival of the cohort was used to dichotomize the cohort into short- and long-term survivors following RT. Univariable and multivariable hazard regression analyses were performed to identify variables associated with post-RT survival. Results: From 1 January 2018 until 31 December 2019, 545 palliative RT courses for bone metastases were delivered to n = 274 metastatic prostate cancer patients with a median age of 76 yrs (Interquartile range (IQR) 39–83) and a median follow-up of 10.6 months (range 0.2 to 47.9). The median survival of the cohort was 10.6 months (IQR 3.5–25 months). The ECOG performance status of the whole cohort was ≤2 in n = 200 (73%) and 3–4 in n = 67 (24.5%). The most commonly treated sites of bone metastasis were the pelvis and lower extremities n = 130 (47.4%), skull and spine n = 114 (41.6%), and chest and upper extremities n = 30 (10.9%). Most patients had CHAARTED high volume disease n = 239 (87.2%). On multivariable hazard regression analysis, an ECOG performance status of 3–4 (p = 0.02), CHAARTED high volume disease burden (p = 0.023), and non-receipt of systemic therapy (p = 0.006) were significantly associated with worse post-RT survival. Conclusion: Amongst metastatic prostate cancer patients treated with palliative radiotherapy to bone metastases and modern palliative systemic therapies, ECOG performance status, CHAARTED metastatic disease burden, and type of first-line palliative systemic therapy were significantly associated with post-RT survival durations.