The low and disproportionate utilization of antiresorptive therapy in patients with osseous metastasis.

Introduction: Antiresorptive therapies are commonly utilized to mitigate and prevent skeletal-related-events in patients with metastatic osseous disease. However, limited data exists on the incidence or factors associated with prescription of antiresorptives or their effects on the incidence of pathologic fractures in patients with osseous metastatic disease. The aims of this study were to determine 1) the proportion of patients with osseous metastasis who receive antiresorptive therapy and sustain a pathologic fracture within 2-years of a new diagnosis, 2) factors associated with sustaining a pathologic fracture, and 3) factors are associated with the likelihood of receiving antiresorptive therapy. Methods: Between January 2010 and October 2021, 1,492,301 patients with a new diagnosis of osseous metastasis were captured in the Mariner dataset of the PearlDiver database. Patients were identified using International Classification of Disease (ICD) 10 codes for osseous metastasis. We excluded patients with a prior diagnosis of osseous metastasis and if they had less than two-years of follow-up. There were 696,459 patients (46.7 %) included for analysis. Of these patients, 63 % (N = 437,716) were over the age of 65, 46 % were women, and 5.6 % had Medicaid insurance. We identified patients who were prescribed antiresorptive therapy within 2-years of a new diagnosis of osseous metastasis. Cox proportional hazard ratio models were created to predict factors associated with 1) pathologic fracture and 2) receiving antiresorptive therapy within 2-years of a new diagnosis of osseous metastasis, respectively. Results: The incidence of antiresorptive therapy prescription was 7.7 % in our cohort. The incidence of pathologic fracture within 2-years of a new diagnosis was 7.3 %. The risk of sustaining a pathologic fracture was higher for patients aged 35-44 (HR 1.27 [95 % CI 1.08-1.51]; p = 0.004), those with primary kidney cancer (HR 1.78 [95 % CI 1.71-1.85]; p < 0.001), p = 0.005), multiple myeloma (HR 2.49 [95 % CI 2.39-2.59]; p < 0.001), and Medicaid insurance (HR 1.17 [95 % CI 1.13-1.21]; p < 0.001). The risk of sustaining a pathologic fracture was lower for patients on antiresorptive therapy (HR 0.71 [95 % CI 0.66-0.83]; p < 0.001). Increasing age was an independent predictor for antiresorptive therapy prescription (HR 1.77-16.38, all p < 0.05). Male sex as well as diagnosis of primary prostate, lung, or kidney cancer and Medicaid insurance were negative predictors for antiresorptive prescription (HR 0.15-0.87, all p < 0.001). Conclusions: The utilization of antiresorptive therapy in patients with osseous metastases remains unacceptably low, with only 7.7% patients being prescribed these therapies, despite shown efficacy in reduction of pathologic fractures incidences. This study identified younger patients, males, and those diagnosed with primary prostate, kidney, and lung cancers to be at increased risk of not being prescribed antiresorptive therapy, suggesting possible bias in prescription patterns. Greater efforts are needed by providers who care for this vulnerable population to increase the utilization and reduce disparities of prescribing antiresorptive therapy.

Colorectal adenocarcinoma presenting with a pathological fracture due to a solitary bone metastasis to the tibia: a case report and literature review.

Introduction: Solitary bone metastasis of colorectal carcinoma (CRC) without other metastasis sites is extremely rare and can be found in less than 1% of patients with CRC. Aim: In the present study, we report the first case of a solitary tibia metastasis and its pathologic fracture as the first presenting feature of a colorectal adenocarcinoma. Material and methods: A 78-year-old female patient presented to our emergency department due to atraumatic pretibial swelling. Plain radiography did not detect any pathology. The swelling was incised and serous-bloody collection was evacuated, and the patient was discharged. On the 17th postoperative day, during a regular walk, the patient fell down and broke her leg, which transpired to be a pathologic fracture of the proximal tibial diaphysis, confirmed by X-ray. A biopsy of the altered bone tissue from the fracture site revealed metastatic colorectal adenocarcinoma. On colonoscopy, a circular mass in the upper rectum was found. Conclusions: Solitary bone metastases are most commonly found in bones that are related to venous drainage via the paravertebral plexus of Batson - the pelvis, vertebrae, and sacrum. Long bones are extremely rare localizations of solitary CRC metastases, with only few cases published so far in medical literature. In our case, the patient`s first symptom was related to the osseous tibial metastasis - leg swelling. No tumour was suspected until the pathologic fracture occurred. It is important to consider osseous metastasis in every patient with unexplained swelling, haematoma, or pain of the extremities and make a bone scan to recognize the metastasis early.

Clear Cell Ovarian Carcinoma With C1 Lateral Mass Metastasis and Pathologic Fracture: A Case Report.

Osseous metastasis (OM) in ovarian cancer (OC) are rare, with an incidence ranging from 0.8% to 2.6%, and are associated with poor prognosis. The available literature on their management and associated complications is scarce. We report a case of International Federation of Gynecology and Obstetrics (FIGO) stage IVB clear cell epithelial OC (EOC) who presented with neck pain. Imaging revealed multiple cervical spine metastases with left vertebral artery encasement and concurrent C1 lateral mass compression fracture, without neurological deficit, requiring occiput to C2 posterior instrumentation and fusion. Early OM may be associated with shorter overall survival, and survival after OM diagnosis is on the order of months. Management of OM should include a multidisciplinary team and may require surgical stabilization in addition to systemic chemotherapy, local radiotherapy, and osteoclast inhibitors.

Practice patterns in the United States for ablation of osseous tumors using Medicare claims analysis.

OBJECTIVES: To describe national practice trends in bone radiofrequency ablation (RFA) and cryoablation for osseous lesions by physician specialty and site-of-service from 2015 to 2018. MATERIALS AND METHODS: This study used data from the US Centers for Medicare and Medicaid Services public use files for 2015-2018. Current Procedural Terminology (CPT) codes for bone RFA (20982) and cryoablation (20983) were analyzed. Based on the specialty code, the specialty was sorted into five categories: radiology (diagnostic and interventional), orthopedic surgery, neurosurgery, pain management (pain management, anesthesiology, physical medicine and rehabilitation, and interventional pain management), and all others. Annual volume of billed services was additionally evaluated by site of service and provider specialty. RESULTS: Aggregate claims dramatically increased from 2015 to 2018. The enrollment adjusted overall growth averaged 45.2.% year-over-year, strongly driven by growth in RFA. Annual market share for radiology decreased slightly from 80.6% to 73.3% with neurosurgery making the largest gain, increasing from 4.7% to 11.3% from 2015 to 2018. Clinical site-of-service analysis demonstrated that outpatient is the main site-of-service for ablation (62.7% cumulatively from 2015 to 2018). Growth rates of outpatient and inpatient services are about the same over this time. CONCLUSIONS: There has been significant growth in osseous ablation between 2015 and 2018, with the growth dominated by Radiologists, although the overall growth rate and the market share of radiology are declining as the growth is outstripped by neurosurgery and orthopedics. Further consideration of these trends will be important for interventional radiologists to assure their involvement and expertise in ablation procedures.

The Role of a Navigational Radiofrequency Ablation Device and Concurrent Vertebral Augmentation for Treatment of Difficult-to-Reach Spinal Metastases.

AIMS: The purpose of this study was to assess the effectiveness of a navigational radiofrequency ablation device with concurrent vertebral augmentation in the treatment of posterior vertebral body metastatic lesions, which are technically difficult to access. Primary outcomes of the study were evaluation of pain palliation and radiologic assessment of local tumor control. MATERIALS AND METHODS: Thirty-five patients with 41 vertebral spinal metastases involving the posterior vertebral body underwent computed tomography-guided percutaneous targeted radiofrequency ablation, with a navigational radiofrequency ablation device, associated with vertebral augmentation. Twenty-one patients (60%) had 1 or 2 metastatic lesions (Group A) and fourteen (40%) patients had multiple (>2) vertebral lesions (Group B). Changes in pain severity were evaluated by visual analog scale (VAS). Metastatic lesions were evaluated in terms of radiological local control. RESULTS: The procedure was technically successful in all the treated vertebrae. Among the symptomatic patients, the mean VAS score dropped from 5.7 (95% CI 4.9-6.5) before tRFA and to 0.9 (95% CI 0.4-1.3) after tRFA (p < 0.001). The mean decrease in VAS score between baseline and one week follow up was 4.8 (95% CI 4.2-5.4). VAS decrease over time between one week and one year following radiofrequency ablation was similar, suggesting that pain relief was immediate and durable. Neither patients with 1-2 vertebral metastases, nor those with multiple lesions, showed radiological signs of local progression or recurrence of the tumor in the index vertebrae during a median follow up of 19 months (4-46 months) and 10 months (4-37 months), respectively. CONCLUSION: Treatment of spinal metastases with a navigational radiofrequency ablation device and vertebral augmentation can be used to obtain local tumor control with immediate and durable pain relief, providing effective treatment in the multimodality management of difficult-to-reach spinal metastases.

Evaluation of Preventive Treatment Protocols for Patients under Antiresorptive Therapy Undergoing Tooth Extraction at a Swiss University Clinic.

Antiresorptive agent-related osteonecrosis of the jaw (ARONJ) is a dreaded complication in patients with compromised bone metabolism. The purpose of the present study was to examine the occurrence of ARONJ and its related factors among patients with a history of antiresorptive therapy undergoing tooth extraction using preventive protocols at a Swiss university clinic. Data were retrospectively pooled from health records of patients having received a surgical tooth extraction between January 2015 and April 2020 in the Clinic of Cranio-Maxillofacial and Oral surgery, University of Zurich. A total of 970 patients received an extraction with flap elevation or wound closure during this period. A total of 104 patients could be included in the study. Furthermore, variables including age, gender, smoking, risk profile, choice, indication and duration of antiresorptive therapy, number of extractions, extraction site, surgical technique, choice and duration of antibiotics as well as the presence of postoperative inflammatory complications were assessed. Overall, 4 patients developed ARONJ (incidence of 3.8%) after tooth extraction at the same location, without previous signs of osteonecrosis. Preventive methods included predominantly primary wound closure using a full thickness mucoperiosteal flap and prolonged perioperative antibiotic prophylaxis. In accordance with current literature, the applied protocol showed a reliable outcome in preventing ARONJ when a tooth extraction is required.

A rare case of extremely delayed osseous metastasis of pineoblastoma.

Pineoblastoma is a rare, primitive, and malignant tumor arising from the parenchyma of the pineal gland. It typically metastasizes along the cerebral neural axis, with rare extraneural metastasis and even more rare intraosseous extraneural metastasis. A patient with pineoblastoma, initially treated with chemotherapy, presented 10 years after initial diagnosis with multiple osseous metastases including his pelvis, femur, and vertebrae, and is currently undergoing chemotherapy.

Colorectal cancer with first known case of simultaneous bilateral tibial metastases.

The most common osseous metastatic regions for colorectal cancer are the lumbar and sacral vertebrae and the pelvis. There are few reported cases of isolated solitary tibial metastasis, and simultaneous bilateral solitary tibial metastases in colorectal cancer are even rarer. A 62-year-old female patient was admitted to our inpatient clinic 3 years after receiving initial chemotherapy for a rectosigmoid adenocarcinoma with liver metastasis. The patient complained of left leg pain. Radiographs and magnetic resonance imaging revealed a 3- × 3-cm mass in the right proximal tibia and a 2- × 7-cm mass in the middle third of the left tibia; both were highly suggestive of bone metastases. Bilateral tibial metastases were confirmed after tumor excision and prophylactic open reduction and internal fixation. The postoperative course was relatively uneventful. Colorectal cancer with bone metastases is uncommon, and most metastases are found at a single site in an extremity. We believe this is the first published case of simultaneous bilateral tibial metastases in a patient with colorectal cancer.

Detection of bone metastases in uterine cancer: How common are they and should PET/CT be the standard for diagnosis?

OBJECTIVES: Osseous metastases (OM) in endometrial cancer (EMCA) are thought to be rare. This study aimed to address the gap in present knowledge by defining the rate of OM in endometrial cancer (EMCA) as stratified by histology and ascertaining the best diagnostic modality for detection. METHODS: 435 consecutive cases of EMCA evaluated in tertiary care setting were reviewed. Clinico-pathologic data were abstracted and analyzed. RESULTS: 18/403 patients were found to have OM (4.6%). Majority were detected by PET/CT (13/18 (72%)), with conventional CT scans missing the diagnoses otherwise made by PET/CT scans in 2/9 patients. Patients with type II EMCA were at higher risk of developing OM compared with patients with type I EMCA; 2/234 patients with type I EMCA (0.85%) developed OM, as compared to 16/167 patients with type II EMCA (9.58%), OR = 12.3. Patients with serous histology had significantly higher odds of developing OM when compared to patients with non-serous histologies (OR 4, p = 0.001, 95% CI 1.54 to 10.76). Kaplan Myer survival function and log-rank analysis showed that the presence of OM was a significant negative prognosticator of survival, with median overall survival (mOS) of 16 months in OM patients vs. mOS undefined in non-OM patients (p < 0.0001). DISCUSSION: Incidence of detected OM was clinically significant, with most cases identified by PET/CT scans. Patients with type II EMCA, and in particular serous histology, were at a significantly higher risk of developing OM. OM when present, is an indicator of aggressive cancer biology and poor prognosis. Further studies are needed to ascertain the mechanism of predisposition to OM formation in serous EMCA and to confirm PET/CT as modality of choice for detection of OM.

Feasibility of Controlling Metastatic Osseous Pain Using Three Kinds of Image-Guided Procedures for Thermal Microwave Ablation: A Retrospective Study.

OBJECTIVES: To evaluate the feasibility and safety of treating painful osseous metastases using image-guided percutaneous thermal microwave ablation. METHODS: This is a retrospective study of patients treated from December 2016 to December 2019 in one institute. A total of 50 patients (35 men, 15 women; mean age 55.24 ± 11.03 years) with 56 osseous metastatic lesions underwent image-guided percutaneous microwave ablation. There were 7 patients with multiple and 43 patients with single metastases. The numbers of patients with primary cancer were as follows: lung, 13; liver, 17; kidney, 10; prostate, 1; breast, 3; osteosarcoma, 1; and thyroid, 5. Seventeen patients had cancer combined with soft tissue masses. The radiological images for the ablative procedures were obtained by CT, fluoroscopy with ultrasound, and fluoroscopy alone in 16, 11, and 23 patients, respectively. Pain severity was estimated using the visual analogue scale before and after treatment (1 week, 1 month, and 3 months after treatment). Radiological evaluations were performed at baseline and 3 months after the procedure. RESULTS: In all patients, pain reduction occurred from the first day after treatment. Pain did not recur during the 3 months of follow up. The mean total ablation time per microwave electrode was 3.99 ± 2.48 min (range, 1-15 min). The mean power of the microwave electrode was 66.40 ± 12.08 W. The average volume of bone (load-bearing bone, such as vertebra and acetabulum) cement after ablation was 2.82 ± 0.81 mL. There were no significant differences in visual analogue scale pain scores for different imaging techniques or ablation energies. No procedure-related complications occurred. CONCLUSION: Image-guided percutaneous thermal microwave ablation of osseous metastases relieves pain and improves mobility. CT remains the first choice for percutaneous ablation. Fluoroscopy combined with ultrasound is effective for cases with soft tissue masses; fluoroscopy is also suitable for combination with vertebroplasty. However, further investigations are required.

Angiosarcomas of Primary Gynecologic Origin - A Case Series and Review of the Literature.

BACKGROUND/AIM: Angiosarcoma of primary gynecologic origin is an extremely rare and highly malignant tumor of endothelial origin with a 5-year survival rate of less than 35%. To date, only 61 cases have been described in the literature. The aim of this study was to present more cases and discuss potential therapy options. CASE REPORT: The following case series presents three cases of gynecologic angiosarcomas that were under therapy at the Charité - University medicine of Berlin from June 2014 to February 2018. RESULTS: Two of the cases deal with primary angiosarcomas of the uterus whereas the third case was diagnosed after the suspicion of a recurrence of a poorly differentiated squamous cell carcinoma of the cervix uteri. In case one a 75-year old patient with initial postmenopausal bleeding and a tumor mass of the uterus is described. After surgery a hemangiosarcoma of the uterus was confirmed. After two months the patient presented with a presacral peritoneal sarcomatosis. Chemotherapy of weekly paclitaxel was administered. Case two deals with a patient presenting with abdominal pain. A uterine sarcoma with infiltration of the parametry and angiosarcomatosis peritonei was diagnosed during an emergency laparotomy because of spontaneous peritoneal bleeding. Moreover, osseous metastasis was found. The patient underwent weekly paclitaxel. Due to tumor progression, chemotherapy was changed to doxorubicin and olaratumab and radiotherapy was induced. The patient died 33 months after initial diagnosis. Case three describes a 34-year old patient with suspected local recurrence of cervical cancer with infiltration of the bladder. During TURB an angiosarcoma was found. Following laparoscopy revealed peritoneal metastasis. The patient underwent weekly paclitaxel followed by a paclitaxel and pazopanib maintainance therapy which showed a regression. Due to progression afterwards, chemotherapy was changed to gemcitabine and docetaxel and gemcitabine monotherapy. The patient died 33 months after initial diagnosis. CONCLUSION: Even though there is no evidence on standard treatment of this extremely rare and aggressive tumor entity of the female genital tract the patients showed the longest stability of disease during chemotherapy with weekly paclitaxel.

Synchronous osseous metastasis, degenerative changes, and incidental multifocal Paget's disease in a case of newly diagnosed prostatic carcinoma.

Tc-99m methylene diphosphonate bone scintigraphy (bone scan) is a highly sensitive technique for the evaluation of osseous pathology. However, the nonspecificity of the method can present diagnostic challenges in differentiating benign from malignant processes. Often, Paget's disease and osseous metastasis can coexist in elderly patients. Therefore, it is important to accurately distinguish the two pathologies, as each has a different prognosis and impacts clinical management. Obtaining the appropriate clinical diagnosis often involves a combination of laboratory, radiographic, and clinical data. We present a case of newly diagnosed prostatic carcinoma presenting with synchronous osseous metastasis, degenerative changes, and incidental multifocal Paget's disease.

Bone metabolism regulation: Implications for the treatment of bone diseases.

Bone cells in the human body are continuously engaged in cellular metabolism, including the interaction between bone cells, the interaction between the erythropoietic cells of the bone marrow and stromal cells, for the remodeling and reconstruction of bone. Osteoclasts and osteoblasts play an important role in bone metabolism. Diseases occur when bone metabolism is abnormal, but little is known about the signaling pathways that affect bone metabolism. The study of these signaling pathways will help us to use the relevant techniques to intervene, so as to improve the condition. The study of these signaling pathways will help us to use the relevant techniques to intervene, so as to improve the condition. I believe they will shine in the diagnosis and treatment of future clinical bone diseases.

Adult-onset ganglioneuroblastoma of the posterior mediastinum with osseous metastasis.

Ganglioneuroblastomas are a member of the neuroblastic family of tumors most commonly seen in children but they may also occur in adults. Ganglioneuroblastomas have metastatic potential and, like other neuroblastic tumors, osseous metastasis is possible. Imaging features of ganglioneuroblastomas tend to be variable. We describe a case of an adult female who developed a ganglioneuroblastoma of the posterior mediastinum that metastasized to the thoracolumbar spine, highlighting rarely documented osseous metastasis.

Factors Predicting Metastatic Disease in 68Ga-PSMA-11 PET-Positive Osseous Lesions in Prostate Cancer.

Bone is the most common site of distant metastatic spread in prostate adenocarcinoma. Prostate-specific membrane antigen (PSMA) uptake has been described in both benign and malignant bone lesions, which can lead to false-positive findings on 68Ga-PSMA-11 PET. The purpose of this study was to evaluate the diagnostic accuracy of 68Ga-PSMA-11 PET for osseous prostate cancer metastases and improve bone uptake interpretation using semiquantitative metrics. Methods: Fifty-six prostate cancer patients (18 before prostatectomy and 38 with biochemical recurrence) who underwent 68Ga-PSMA-11 PET/MRI or PET/CT examinations with osseous PSMA-ligand uptake were included in the study. Medical records were reviewed retrospectively by board-certified nuclear radiologists to determine true or false positivity based on a composite endpoint. For each avid osseous lesion, we measured biologic volume; size; PSMA Reporting and Data System (RADS) rating; SUVmax; and ratio of lesion SUVmax to liver, blood pool, and background bone SUVmax Differences between benign and malignant lesions were evaluated for statistical significance, and cutoffs for these parameters were determined to maximize diagnostic accuracy. Results: Among 56 participants, 13 (22.8%) had false-positive osseous 68Ga-PSMA-11 findings and 43 (76.8%) had true-positive osseous 68Ga-PSMA-11 findings. Twenty-two patients (39%) had 1 osseous lesion, 18 (32%) had 2-4 lesions, and 16 (29%) had 5 or more lesions. Cutoffs resulting in statistically significant (P < 0.005) differences between benign and malignant lesions were a PSMA RADS rating of at least 4, an SUVmax of at least 4.1, and SUVmax ratios of at least 2.11 for lesion to blood pool, at least 0.55 for lesion to liver, and at least 4.4 for lesion to bone. These measurements corresponded to a lesion-based 68Ga-PSMA-11 PET lesion detection rate of 80%, 93%, 89%, 21%, and 89%, respectively, for malignancy, and a specificity of 73%, 73%, 73%, 93%, and 60%, respectively. Conclusion: PSMA RADS rating, SUVmax, and SUVmax ratio for lesion to blood pool can help differentiate benign from malignant lesions on 68Ga-PSMA-11 PET. An SUVmax ratio of more than 2.2 for lesion to blood pool is a reasonable parameter to support image interpretation and presented a superior lesion detection rate and specificity when compared with visual interpretation by PSMA RADS. These parameters hold clinical value by improving diagnostic accuracy for metastatic prostate cancer on 68Ga-PSMA-11 PET/MRI and PET/CT.

18F-FDG PET-CT versus MRI for detection of skeletal metastasis in Ewing sarcoma.

OBJECTIVE: To determine the level of discrepancy between magnetic resonance imaging (MRI) and 18F-FDG PET-CT in detecting osseous metastases in patients with Ewing sarcoma. METHODS: Twenty patients with histopathologically confirmed Ewing sarcoma between 2000 and 2017 who underwent 18F-FDG PET-CT and MRI within a 4-week range were included. Each imaging modality was evaluated by a separate observer. Reference diagnosis of each lesion was based on histopathology or consensus of an expert panel using all available data, including at least 6 months' follow-up. Sensitivity, specificity, and predictive values were determined. Osseous lesions were analyzed on a patient and a lesion basis. Factors possibly related to false-negative findings were evaluated using Pearson's Chi-squared or Fisher's exact test. RESULTS: A total of 112 osseous lesions were diagnosed in 13 patients, 107 malignant and 5 benign. Seven patients showed no metastases on either 18F-FDG PET-CT or MRI. Forty-one skeletal metastases (39%) detected with MRI did not show increased 18F-FDG uptake on 18F-FDG PET-CT (false-negative). Lesion-based sensitivities and specificities were 62% (95%CI 52-71%) and 100% (48-100%) for 18F-FDG PET-CT; and 99% (97-100%) and 100% (48-100%) for MRI respectively. Bone lesions were more likely to be false-negative on 18F-FDG PET-CT if hematopoietic bone marrow extension was widespread and active (p = 0.001), during or after (neo)-adjuvant treatment (p = 0.001) or when the lesion was smaller than 10 mm (p < 0.001). CONCLUSION: Although no definite conclusions can be drawn from this small retrospective study, it shows that caution is needed when using 18F-FDG PET-CT for diagnosing skeletal metastases in Ewing sarcoma. Poor contrast between metastases and active hematopoietic bone marrow, chemotherapeutic treatment, and/or small size significantly decrease the diagnostic yield of 18F-FDG PET-CT, but not of MRI.

Construction and improvement of animal models with different positional osseous metastasis of prostate cancer in vivo / 北京大学学报(医学版)

Objective: To provide an important tool for the study of diagnose and treatment of prostate cancer (PCa) osseous metastasis and change of bone stress force on prostate cancer (PCa) osseous metastasis and a platform, which is more congruous to clinical process, for prevention and cure of neoplastic bone metastases, and to carry out the construction and improvement of animal models of PCa with different positional osseous metastasis in vivo.Methods: Different gradient concentrations of RM-1 cells were inoculated into the cavity of left femoral bone or lumbar vertebra of mice (C57BL/6) respectively.The change of mouse activity, tumor formation, tumor size and survival time were observed respectively.And the femur tissue and spinal tissue were obtained from the mice after death.The gray value of iconography were measured by imageological examination of femur tissue, and the final histopathological examination were taken to determine the tumor type in both femur and spinal tissue.Results: The tumor growth could be touched at the puncture site in all the mice after inoculated for 7 days.There were no obvious differences in the time of tumorigenesis, the rate of tumor growth and tumor size among the mice in the same group (P>0.05).As the result, the construction femoral bone and lumbar vertebra metastatic models of PCa had been confirmed by iconography and pathology detection.At the same time, the survival time of the mice inoculated with low concentrations of PCa cells was obviously longer than that of high concentrations of PCa cells (at least 2 weeks longer).Conclusion: The animal models with different positional osseous metastasis (limbs and axial skeleton) of PCa using the same PCa cells (RM-1) had been first constructed successfully in our study.At the same time, a high success rate of construction of PCa animal model with bone metastasis was obtained by femoral bone marrow cavity injection of PCa cells.The rate of tumor growth was rapid, animal survival time was appropriate, and the PCa animal model with bone metastasis can be stably reproduced by our method.These animal models can be used to explore the pathogenesis of different positional PCa bone metastasis and provide a new platform, which were more congruous to clinical process, for prevention and cure of neoplastic bone metastases.

A Freeze-Dried Kit for the Preparation of (188)Re-HEDP for Bone Pain Palliation: Preparation and Preliminary Clinical Evaluation.

(188)Re-HEDP is an established radiopharmaceutical used for pain palliation in patients with osseous metastasis. Considering commercial availability of (188)W/(188)Re generator, the accessibility to a lyophilized kit would make preparation of this radiopharmaceutical feasible at the hospital radiopharmacy having access to a generator. A protocol for the preparation of a single-vial lyophilized hydroxyethane 1,1-diphosphonic acid (HEDP) kit was developed and its consistency was checked by preparing six batches. Each sterile lyophilized kit prepared as per the protocol contained 9 mg of HEDP, 3 mg of gentisic acid, and 4 mg of SnCl2.2H2O. Randomly selected kits from all six batches were subjected to thorough quality control tests that were passed by all batches. (188)Re-HEDP could be prepared by addition of 1 mL of freshly eluted Na(188)ReO4 (up to 3700 MBq) containing 1 µmol of carrier ReO4(-) (perrhenate) and heating at 100°C for 15 minutes. (188)Re-HEDP with >95% radiochemical purity could be consistently prepared using the lyophilized kits. Sterile (188)Re-HEDP prepared using the lyophilized kit was evaluated in patients with osseous metastasis. Post-therapy images of the patient were compared with (99m)Tc-MDP bone scan and found to be satisfactory. The bone-to-background as well as tumor-to-normal bone uptake ratio was found to be significant. All patients who received therapy reported significant pain relief within a week to 10 days post-administration of (188)Re-HEDP.

Dramatic response to temozolomide, irinotecan, and bevacizumab for recurrent medulloblastoma with widespread osseous metastases.

There is little evidence to guide the choice of chemotherapeutic agents for osseous metastases in medulloblastoma. Recently, triple therapy with temozolomide, irinotecan, and bevacizumab has been reported to have efficacy in recurrent medulloblastoma, and this regimen alone and in combination with other agents has been tested in several early-phase clinical trials. Here we report a 20-year-old woman with multiply-relapsed medulloblastoma with numerous osseous metastases 8 years after original diagnosis who responded dramatically to temozolomide, irinotecan, and bevacizumab therapy. This case highlights the potential for this regimen in treating osseous metastases in medulloblastoma.