The Trend of Dental Check-Up And Incidence of Dental Complications Following The Use of Bone Modifying Agents In Patients With Metastatic Breast And Prostate Cancer: Analysis of Data From The Korean National Health Insurance Service

Purpose: Bone-modifying agents (BMAs) are key components in the management of cancer patients with bone metastasis. Despite their clinical benefits, the use of BMAs is associated with adverse dental events including medication-related osteonecrosis of the jaw (MRONJ). This study investigated the rate of preoperative dental surveillance to reduce the incidence of adverse dental events including MRONJ after BMA treatment in patients with bone metastasis from breast and prostate cancer. Methods: Data, including age, cancer diagnosis, administered BMAs, and adverse dental events during cancer treatment, of patients with bone metastasis from breast and prostate cancer who received at least one infusion of BMA between 2007 and 2019 were extracted from the Korean National Health Insurance Service (KNHIS) dataset. Results: Of the 15357 patients who received BMAs, 1706 patients (11.1%) underwent dental check-ups before BMA treatment. The proportion of patients receiving dental check-ups increased from 4.4% in 2007 to 16.7% in 2019. Referral for dental check-up was more frequent in clinics and primary hospitals than in tertiary hospitals, and from the departments of internal medicine and urology than from the department of general surgery, regardless of the patient's health insurance status. After BMA treatment, 3328 patients (21.6%) developed adverse dental events, including tooth extraction (73.0%), abscess (16.9%), acute periodontitis (5.3%), acute pericoronitis (2.6%), and MRONJ (2.2% of 3328, 0.5% of 15357). Conclusions: Considering the long treatment period in patients with metastatic cancer, coordination between dentists and oncologists is necessary to ensure appropriate dental treatment before the initiation of BMAs.

A Non-Endemic Analysis of the Patterns and Prognosis of De Novo Metastatic Nasopharyngeal Carcinomas in Old Patients Aged ≥65 years

This study aimed to investigate the prognostic factors related to overall survival (OS) and cancer-specific survival (CSS) in patients with de novo metastatic nasopharyngeal carcinoma (NPC) aged ≥65 years in non-endemic areas. The Surveillance, Epidemiology, and End Results (SEER) database was queried for elderly patients with M1 stage NPC at initial diagnosis between 2004 and 2016. This study examined 100 patients and evaluated the relationship of gender, age, race, pathological grade, T stage, N stage, number of primary tumors, site of metastasis, number of metastatic organs, and other related factors with OS and CSS. The median survival and follow-up time were 10 and 48 months, respectively. The survival curves of race, N stage, bone metastasis, radiation, and chemotherapy significantly affected OS on the log-rank test. Race, bone metastasis, and chemotherapy were independent prognostic factors of OS. Bone metastasis was associated with poor survival. The survival curves of CSS were significantly differed between races, the number of primary tumors, and bone metastasis. In Cox regression multivariate analysis, only the number of primary tumors had an independent effect on prognosis. This study revealed that chemotherapy prolonged survival in elderly patients with metastatic NPC, whereas bone metastasis shortened survival.

Tumor- and Osteoblast-Derived Periostin in Prostate Cancer bone Metastases

Exploring the biological function of periostin (POSTN) in prostate cancer (PCa) bone metastasis is of importance. It was observed that the expression of POSTN was high in PCa, especially highest in PCa metastasized to bone. In this study, we found that inhibiting POSTN in PCa cells could significantly alleviate PCa bone metastasis in vivo, suggesting POSTN is a promising therapeutic target. Since, due to the secreted expression of POSTN in osteoblasts and PCa, we hypothesized the positive feedback loop between osteoblasts and PCa mediated by POSTN in PCa bone metastasis. The in vitro experiments demonstrated that osteoblast-derived POSTN promoted PCa cell proliferation and invasion and PCa cell-derived POSTN promotes proliferation of osteoblasts. Furthermore, we found that POSTN regulated PCa and osteoblast function through integrin receptors. Finally, 18F-Alfatide II was used as the molecule probe of integrin αvβ3 in PET-CT, revealing high intake in metastatic lesions. Our findings together indicate that targeting POSTN in PCa cells as well as in the osteoblastic may be an effective treatment for PCa bone metastasis.

EGFL6 Promotes Bone Metastasis of Lung Adenocarcinoma by Enhancing Osteoclast Differentiation and Stimulating Cancer Cell Metastasis

Background Lung cancer is still the most fatal cancer today with approximately 30%-40% of these patients will develop bone metastasis. Lung adenocarcinoma (LUAD) is the most common and aggressive type of lung cancer. The relationship between LUAD and bone metastasis and its underlying mechanism remains unclear. This study proved that epidermal growth factor-like domain multiple 6 (EGFL6) was highly expressed in LUAD specimens of patients, and the expression level was positively correlated with bone metastasis of LUAD. Method The expression of EGFL6 in cancer tissues was detected by IHC. CCK-8, colony formation assay, migration and invasion assay, wound healing assay, immunocytochemistry, RT-PCR, Western blotting, ELISA, bone resorption, TRAP staining and H&E staining were performed. A nude mouse model of LUAD-induced bone destruction was established by injecting A549 cells in different EGFL6 expression levels. Results EGFL6 is elevated in LUAD and is associated with bone metastasis. In vivo, implantation of human adenocarcinoma A549 cells with a higher expression of EGFL6 not only increased tumor growth rate but also bone resorption of tibias in nude mice. In vitro, the secretion of EGFL6 from A549 cells increased osteoclast differentiation but had little effect on osteogenic differentiation. To reveal the underlying mechanism, we demonstrated that EGFL6 enhanced osteoclast differentiation through activating nuclear factor-kappa B (NF-κB) and downstream c-Fos/NFATc1 signaling pathways, and in addition promoted the proliferation, migration and invasion of A549 cells through enhancing the epithelial mesenchymal transformation (EMT) and promoting Wnt/β-catenin and PI3K/AKT/mTOR signaling pathways. Conclusions We unveil EGFL6 as a predictor in bone metastasis of LUAD and underscore the relevance of EGFL6 as a therapeutic target.

Unusual hypocalcaemia in breast cancer relapse with multiple bone metastasis

Severe hypocalcaemia in breast cancer with bone metastasis is a rare finding usually associated with an advanced stage of the disease. We report a case of a 45-year-old woman with a history of local ductal carcinoma in situ (DCIS) of the breast, who presented with muscle tremors and general weakness. Hypocalcaemia was evident, with a positive Chvostek sign and a serum calcium level of 5.9 mg/dL (1.47 mmol/L), phosphorus 5.9 mg/dL (normal range: 2.3–4.7 mg/dL) with normal levels of albumin, magnesium and parathyroid hormone. High oral doses of alpha calcitriol and calcium with i.v. infusion of high calcium doses were instituted, altogether sufficient to maintain only mild hypocalcaemia. A whole-body CT revealed bone lesions along the axial skeleton. A biopsy from a bone lesion revealed a metastasis of breast carcinoma. With this pathological finding, leuprolide (GNRH analogue) and chlorambucil (alkylating agent) were initiated, followed by prompt tapering of infused calcium down to full discontinuation. Serum calcium was kept stable close to the low normal range by high doses of oral alpha calcitriol and calcium. This course raises suspicion that breast metastases to the skeleton caused tumour-induced hypocalcaemia by a unique mechanism. We assume that hypocalcaemia in this case was promoted by a combination of hypoparathyroidism and bone metastasis. Learning points Severe hypocalcaemia can a presenting symptom for breast cancer relapse.