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Bone Pain in Cancer Patients: Mechanisms and Current Treatment.

The skeletal system is the third most common site for cancer metastases, surpassed only by the lungs and liver. Many tumors, especially those of the breast, prostate, lungs, and kidneys, have a strong predilection to metastasize to bone, which causes pain, hypercalcemia, pathological skeletal fractures, compression of the spinal cord or other nervous structures, decreased mobility, and increased mortality. Metastatic cancer-induced bone pain (CIBP) is a type of chronic pain with unique and complex pathophysiology characterized by nociceptive and neuropathic components. Its treatment should be

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… Systemic administration of radiopharmaceuticals (e.g., strontium-89, samarium-153, rhenium, radium-223) may be offered to patients with diffuse bone pain due to osteoblastic or mixed osteoblastic–osteolytic metastases, which cannot be treated efficaciously with EBRT. … RT with radium-223 may be recommended for patients with castration-resistant cancer of the prostate because it reduces SREs, decreases pain, and improves QoL and survival [ 44 , 50 ]. …

Skeletal metastasis: treatments, mouse models, and the Wnt signaling.

Skeletal metastases result in significant morbidity and mortality. This is particularly true of cancers with a strong predilection for the bone, such as breast, prostate, and lung cancers. There is currently no reliable cure for skeletal metastasis, and palliative therapy options are limited. The Wnt signaling pathway has been found to play an integral role in the process of skeletal metastasis and may be an important clinical target. Several experimental models of skeletal metastasis have been used to find new biomarkers and test new treatments. In this review, we discuss pathologic process o

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… inhibition | Cabazantinib | Clinical trials | [95] – [97] Src inhibition | Dasatinib / saracatinib / bosutinib | Clinical trials | [99] Vitamin D analogues | Calcitriol / EB1089 | Clinical trials | [190] , [191] Proteasome inhibition | Bortezomib | Clinical trials | [192] , [193] Radiopharmaceuticals | Radium … Radium-223 is the first alpha-emitting radiopharmaceutical to reach clinical trials and has been shown in phases I and II trials to improve survival in patients with skeletal metastases from prostate cancer [38] . …

Current Overview of Treatment for Metastatic Bone Disease.

The number of patients with bone metastasis increases as medical management and surgery improve the overall survival of patients with cancer. Bone metastasis can cause skeletal complications, including bone pain, pathological fractures, spinal cord or nerve root compression, and hypercalcemia. Before initiation of treatment for bone metastasis, it is important to exclude primary bone malignancy, which would require a completely different therapeutic approach. It is essential to select surgical methods considering the patient's prognosis, quality of life, postoperative function, and risk of pos

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… Radionuclides, including beta-emitters such as Strontium-89 ( 89 Sr) and Samarium-153 ( 153 Sa), and alpha-emitters such as Radium-223 ( 223 Ra) can be selectively delivered towards bone areas of amplified osteoblastic activity, sparing healthy organs from irradiation [ 143 ]. … Alpha emitter Radium-223 and survival in metastatic prostate cancer N. Engl. J. Med. 2013 369 213 223 10.1056/NEJMoa1213755 23863050 145. Terrisse S. Karamouza E. Parker C.C. Sartor A.O. James N.D. Pirrie S. Collette L. Tombal B.F. Chahoud J. Smeland S. …

Use of imaging-based dosimetry for personalising radiopharmaceutical therapy of cancer.

Theranostics - i.e., the combination of molecular imaging and radiopharmaceutical therapy of cancer targeting a common biological feature - is a rapidly expanding field owing the recent successes of novel radiopharmaceutical therapies, such as 177Lu-based prostate-specific membrane antigen radioligand therapy of prostate cancer and peptide receptor radionuclide therapy of neuroendocrine tumours. Despite the ongoing technical developments in imaging-based dosimetry, the existence of tumour absorbed dose-efficacy and organ absorbed dose-toxicity relationships, as well as the high interpatient va

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… Alpha emitter radium-223 and survival in metastatic prostate cancer. N Engl J Med. 2013;369(3):213–223. doi: 10.1056/NEJMoa1213755. 21. GE Healthcare. Metastron (strontium-89 chloride injection) [package insert]. U.S. … Xofigo (radium-223 dichloride injection) [package insert]. U.S. Food and Drug Administration website. https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/209607s000lbl.pdf . Revised December 2019. Accessed 11 Nov 2022. 24. Sartor O, Reid RH, Hoskin PJ, Quick DP, Ell PJ, Coleman RE, et al. …

Current landscape and future directions of targeted-alpha-therapy for glioblastoma treatment.

Glioblastoma (GB) is the most aggressive malignancy of the central nervous system. Despite two decades of intensive research since the establishment of the standard of care, emerging strategies have yet to produce consistent satisfactory outcomes. Because of its specific localisation and intricate characteristics, GB is a uniquely regulated solid tumour with a strong resistance to therapy. Advances in targeted radionuclide therapy (TRT), particularly with the introduction of a-emitting radionuclides, have unveiled potential avenues for the management of GB. Recent preclinical and clinical stud

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… Significant clinical outcomes have already been demonstrated, leading to the FDA approval of the radium-223 dichloride ( 223 Ra; Xofigo ® ) in 2013 for the treatment of mCRPC 33 . …

Medication-Related Osteonecrosis of the Jaw (MRONJ): A Review of Pathophysiology, Risk Factors, Preventive Measures and Treatment Strategies.

Medication-related osteonecrosis of the jaw (MRONJ) is a major problem that can occur in people taking certain medications such bisphosphonates and denosumab. It can be used to treat osteoporosis or cancer. Bisphosphonate exposure, dental diseases and procedures, age, sex, anatomical factors, medical issues, and hereditary factors are all variables that enhance the risk of MRONJ. Even though MRONJ and antiresorptive medications have a close association, the pathophysiology of MRONJ is unknown. Careful dental preparation and oral hygiene instructions significantly minimize the risk of osteonecr

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… However, all of these patients have a history of use of antiresorptive drugs and radiopharmaceuticals (Radium 223) in bone metastases management. … Based on current reports, the chance of MRONJ incidence in patients receiving radium 223 therapy is low and is considered to have an additive effect with antiresorptive drugs and mammalian target of rapamycin inhibitors (temsirolimus) in the treatment of advanced cases of renal cell carcinomas. …

Targeted treatments of bone metastases in patients with lung cancer.

Until now ~30-40% of patients with advanced lung cancer develop bone metastases, but as the newer therapies are extending survival, the chance of developing bone metastases increases. Bone metastases cause skeletal-related events (SREs) such as pathologic fractures, spinal cord compression, radiation therapy or surgery to bone, or hypercalcemia, which can have debilitating consequences affecting patients' health-related quality of life (HR-QOL) and performance status (PS). Poor PS then prevents the patients to receive further lines of treatments, which are available today. SREs are associated

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… Promising New Bone Targeting Agents Targeting bone agents in the early stage of investigation in NSCLC are Dasatinib (i.e., anti-src activity) ( 66 ), ACE-011 (Sotatercept – Activin TRAP) ( 67 , 68 ), Cabozantinib (anti-RET agent) ( 69 ), and Radium 223 (targeted alpha emitter) ( 70 ). … J Clin Oncol ( 2012 ) 30 ( Suppl 15 ): 7514 70 Parker C Nilsson S Heinrich D Helle SI O’Sullivan JM Fosså SD Alpha emitter radium-223 and survival in metastatic prostate cancer . N Engl J Med ( 2013 ) 369 ( 3 ): 213 – 23 10.1056/NEJMoa1213755 23863050 …

Psychometric properties and clinical utility of the EORTC QLQ-BM22 in patients with bone metastases: a systematic review.

BackgroundThe European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire for bone metastases 22 (EORTC QLQ-BM22) is a site-specific health-related quality-of-life instrument for patients with bone metastases. However, modern treatments and extended survivorship have introduced new toxicity profiles and clinical challenges. We systematically assessed the measurement performance of QLQ-BM22 to determine if contemporary evidence supports updating the module.MethodsA search was conducted using Medline, Embase, and Cochrane Central Register of Controlled Trials from in

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… After strontium-89, improvements were observed in Painful Characteristics, Functional Interference, and Psychosocial Aspects within 1–3 months in a Japanese study. 13 With radium-223 dichloride, an Italian study reported fluctuations in QLQ-BM22 scores over time, indicating sensitivity to both improvement … Alpha emitter radium-223 and survival in metastatic prostate cancer. N Engl J Med. 2013;369(3):213–223. doi: 10.1056/NEJMoa1213755. 11. Rajeswaran T., Wong H.C.Y., Zhang E., et al. Quality of life issues in patients with bone metastases: a systematic review. …

Beyond Palliation: Therapeutic Applications of 153Samarium-EDTMP.

Primary and metastatic malignant bone lesions result in significant pain and disability in oncology patients. Targeted bone-seeking radioisotopes including 153Samarium ethylene-diamine-tetramethylene-phosphonic acid (153Sm-EDTMP) have been shown to effectively palliate bone pain, often when external beam radiotherapy (EBRT) is not feasible. However, recent evidence also suggests 153Sm-EDTMP has cytotoxic activity either alone or in combination with chemotherapy or EBRT. 153Sm-EDTMP may be useful as anti-neoplastic therapy apart from pain palliation in a variety of malignancies. For prostate ca

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… Two are approved in Europe and the United States ( 89 strontium and 153 samarium) and others are still in the experimental phase but appear promising ( 186 rhenium, 188 rhenium, 223 radium, 166 holmium). … Am J Roentgenol Radium Ther Nucl Med. 1954;72:813–818. 4. Jenkin RD, Allt WE, Fitzpatrick PJ. Osteosarcoma. An assessment of management with particular reference to primary irradiation and selective delayed amputation. …

A New Generation of Vaccines in the Age of Immunotherapy.

Purpose of reviewCancer vaccines are one of the most extensively studied immunotherapy type in solid tumors. Despite favorable presuppositions, so far, the use of cancer vaccines has been associated with disappointing results. However, a new generation of vaccines has been developed, promising to revolutionize the immunotherapy field.Recent findingsIn this review, we aim to highlight the advances in cancer vaccines and the remaining hurdles to overcome. Cancer vaccination has experienced tremendous progress in the last decade, with myriad promising developments. Future efforts should focus on

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… Provenge®) Autologous peripheral-blood mononuclear cells (PBMCs) Autologous PBMCs, including APCs, that have been activated ex vivo with a recombinant fusion protein (PA2024) that consists of a prostate antigen, prostatic acid phosphatase, that is fused to GM-CSF FDA approved Phases 1–3 Sipuleucel-T + / − radium … Autologous peripheral-blood mononuclear cells (PBMCs) | Autologous PBMCs, including APCs, that have been activated ex vivo with a recombinant fusion protein (PA2024) that consists of a prostate antigen, prostatic acid phosphatase, that is fused to GM-CSF | FDA approved Phases 1–3 | Sipuleucel-T + / − radium …

Inconsistent approaches of the G-BA regarding acceptance of primary study endpoints as being relevant to patients - an analysis of three disease areas: oncological, metabolic, and infectious diseases.

BackgroundPrevious evaluations of oncological medicines in the German early benefit assessment (EBA) procedure have demonstrated inconsistent acceptance of endpoints by regulatory authorities and the Federal Joint Committee (G-BA). Accepted standard endpoints for regulatory purposes are frequently not considered as patient-relevant in the German EBA system. In this study the acceptance of clinically acknowledged primary endpoints (PEPs) from regulatory trials in EBAs conducted by the G-BA was evaluated across three therapeutic areas.MethodsMedicines for oncological, metabolic and infectious di

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… Grosshansdorf Nivolumab Melanoma OS, PFS ADO, DGHO Obinutuzumab Chronic lymphocytic leukaemia PFS DGHO Olaparib Ovarian cancer PFS DGHO Pertuzumab Breast cancer PFS, ORR AGO, DGHO Pomalidomide Multiple myeloma PFS DGHO, representatives from the University Hospitals of Heidelberg, Tübingen and Würzburg Radium … Melanoma | OS, PFS | ADO, DGHO Obinutuzumab | Chronic lymphocytic leukaemia | PFS | DGHO Olaparib | Ovarian cancer | PFS | DGHO Pertuzumab | Breast cancer | PFS, ORR | AGO, DGHO Pomalidomide | Multiple myeloma | PFS | DGHO, representatives from the University Hospitals of Heidelberg, Tübingen and Würzburg Radium …

Metastatic Spread in Prostate Cancer Patients Influencing Radiotherapy Response.

Radiotherapy and surgery are curative treatment options for localized prostate cancer (PCa) with a 5-year survival rate of nearly 100%. Once PCa cells spread into distant organs, such as bone, the overall survival rate of patients drops dramatically. The metastatic cascade and organotropism of PCa cells are regulated by different cellular subtypes, organ microenvironment, and their interactions. This cross-talk leads to pre-metastatic niche formation that releases chemo-attractive factors enforcing the formation of distant metastasis. Biological characteristics of PCa metastasis impacting on m

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… On the other hand, alpha-emitting particles including agents such as radium-223 dichloride ( 223 RaCl2, Xofigo ® , Bayer Healthcare) revealed overall survival benefit and reduced symptomatic skeletal events ( 131 ). … These agents include bone homeostasis targeting compounds affecting osteoclast-osteoblast equilibrium e.g., bisphosphonates, the anti-RANKL antibody denosumab, or radiopharmaceuticals such as radium-223. …

Cancer Metastases to Bone: Concepts, Mechanisms, and Interactions with Bone Osteoblasts.

The skeleton is a unique structure capable of providing support for the body. Bone resorption and deposition are controlled in a tightly regulated balance between osteoblasts and osteoclasts with no net bone gain or loss. However, under conditions of disease, the balance between bone resorption and deposition is upset. Osteoblasts play an important role in bone homeostasis by depositing new bone osteoid into resorption pits. It is becoming increasingly evident that osteoblasts additionally play key roles in cancer cell dissemination to bone and subsequent metastasis. Our laboratory has evidenc

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… In addition to atrasentan, radium-223 has been investigated as a treatment for patients with bone metastatic prostate cancer. Radium-223 is an alpha particle emitter that accumulates preferentially at sites with increased osteoblast activity and bone deposition [ 127 ]. … Moreover, use of radium-223 preserved bone volume and bone architecture [ 127 ]. Ongoing and future clinical trials will help to determine the optimal treatment modalities for patients with bone metastatic prostate cancer. 4. …

Modern Treatment of Skeletal Metastases: Multidisciplinarity and the Concept of Oligometastasis in the Recent Literature.

Bone metastases are a major concern in cancer management since they significantly contribute to morbidity and mortality. Metastatic lesions, commonly arising from breast, prostate, lung, and kidney cancers, affect approximately 25% of cancer patients, leading to severe complications such as pain, fractures, and neurological deficits. This narrative review explores contemporary approaches to bone metastases, emphasizing a multidisciplinary strategy and the evolving concept of oligometastatic disease. Oligometastases, defined by limited metastatic spread (1-5 lesions), offer a potential window f

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… Another practical approach is radium-223, a radiopharmaceutical that selectively targets bone metastases. By emitting high-energy alpha particles, radium-223 destroys cancer cells and limits its damage to surrounding healthy tissue [ 73 ]. … Stereotactic Ablative Radiotherapy (SABR/SBRT) | High-dose radiation to a small, precise area | Oligometastatic disease, bone metastases in controlled primary tumors | Improves survival, systemic immune activation | Requires specialized equipment, potential treatment-related toxicity Radiopharmaceuticals | Radium …

The Link Between the Gut Microbiome and Bone Metastasis.

The gut microbiome is essential for regulating host metabolism, defending against pathogens, and shaping the host's immune system. Mounting evidence highlights that disruption in gut microbial communities significantly impacts cancer development and treatment. Moreover, tumor-associated microbiota, along with its metabolites and toxins, may contribute to cancer progression by promoting epithelial-to-mesenchymal transition, angiogenesis, and metastatic spread to distant organs. Bones, in particular, are common sites for metastasis due to a rich supply of growth and neovascularization factors an

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… In castration-resistant prostate cancer patients with two or more bone metastases, the therapy based on radium-223 (Ra-223) led to gut microbiome changes, and the results showed that levels of Clostridium coccoides , Clostridium leptum , and Bacteroides fragilis were decreased in fecal samples after … Effect of Radium-223 on the Gut Microbiota of Prostate Cancer Patients: A Pilot Case Series Study. Curr. Issues Mol. Biol. 2022;44:4950–4959. doi: 10.3390/cimb44100336. 115. Chen W., Li J., Sun Z., Wu C., Ma J., Wang J., Liu S., Han X. …

New thoughts concerning xanthogranulomatous pyelonephritis (X-P).

A clinical and roentgenographic analysis of 13 patients with pathologically proved xanthogranulomatous pyelonephritis (X-P) has demonstrated that many previously accepted truisms associated with this disease may not be valid. As a result of this study it is suggested that X-P: 1. Does have a prominant female distribution. 2. May arise relatively acutely. 3. Can be associated with a well-functioning kidney. 4. May destroy the kidney and collecting system. 5. Does not demonstrate neovascularity. 6. Can be distinguished angiographically from hypernephroma. 7. May be associated with diabetes. Othe

Mediastinal neuroblastoma and ganglioneuroma. The differentiation between primary and secondary involvement on the chest roentgenogram.

The roentgenologic diagnosis and differentiation of mediastinal neurogenic tumors are possible on the chest roentgenogram as a rule. The soft tissue mass may be ill-defined and the tumor "ghost-like" in the case of primary neuroblastoma, but it is usually obvious in ganglioneuroma and metastatic disease. The presence of calcifications differentiates neurogenic tumors from other posterior mediastinal tumors of childhood. They are common in primary and rare in secondary disease. Rib erosions and displacement are striking in neuroblastoma (after a few months of age), more subtle in ganglioneuroma

The role of lymphangiography in chylothorax. A report of six nontraumatic cases.

Six cases of nontraumatic chylothorax secondary to filariasis, postinflammatory thoracic duct obstruction, idiopathic lymphangiectasis with lymph node hypoplasia, lymphangioma and lymphoma (2 cases) are reported. All cases were studied by lymphangiography, which provided considerable diagnostic information. In those cases which are undiagnosed at the time the chylothorax is discovered, a lymphangiogram should be carried out prior to any therapeutic measures.

Submucosal hemorrhage of the renal collecting system.

Two cases of submucosal hemorrhage in the renal pelvis and ureter are presented. The roentgenographic appearance was identical to that of pyeloureteritis cystica but without evidence of urinary tract infection and, in 1 case, the submucosal impression resolved rapidly. When nodular, submucosal filling defects are demonstrated in the renal collecting system in the clinical setting of anticoagulant therapy or trauma, a diagnosis of submucosal hemorrhage should be considered.

Tomography of the kidney bed as an aid in differentiating renal pelvic tumor and stone.

Plain film tomography is of value in detecting small amounts of calcium in "non-opaque" stones. The use of this technique to help differentiate renal pelvic tumor from stone in patients presenting with a filling defect in the renal pelvis is suggested. Four cases in which plain film tomography detected calcium in a renal pelvic stone that could not be seen on routine roentgenograms are presented.