Differences in Tumor Microenvironment Dictate T Helper Lineage Polarization and Response to Immune Checkpoint Therapy.

Immune checkpoint therapy (ICT) shows encouraging results in a subset of patients with metastatic castration-resistant prostate cancer (mCRPC) but still elicits a sub-optimal response among those with bone metastases. Analysis of patients' bone marrow samples revealed increased Th17 instead of Th1 subsets after ICT. To further evaluate the different tumor microenvironments, we injected mice with prostate tumor cells either subcutaneously or intraosseously. ICT in the subcutaneous CRPC model significantly increases intra-tumoral Th1 subsets and improves survival. However, ICT fails to elicit an anti-tumor response in the bone CRPC model despite an increase in the intra-tumoral CD4 T cells, which are polarized to Th17 rather than Th1 lineage. Mechanistically, tumors in the bone promote osteoclast-mediated bone resorption that releases TGF-ß, which restrains Th1 lineage development. Blocking TGF-ß along with ICT increases Th1 subsets and promotes clonal expansion of CD8 T cells and subsequent regression of bone CRPC and improves survival.

Dose-intensified stereotactic body radiotherapy for painful vertebral metastases: A randomized phase 3 trial.

BACKGROUND: The purpose of this randomised study was to determine whether dose-intensified stereotactic body radiotherapy (SBRT) for painful vertebral metastases results in increased rates of pain improvement compared with conventional external beam radiotherapy (cEBRT) (control) 6 months after treatment. METHODS: This randomized, controlled phase 3 trial was conducted between November 2016 and January 2023, when it was stopped early. Patients were eligible if they were aged 18 years or older; had one or two painful, stable, or potentially unstable vertebral metastases; and had a life expectancy of 1 year or longer according to the investigator's estimates. Patients received 48.5 grays (Gy) in 10 fractions (with epidural involvement) or 40 Gy in five fractions (without epidural involvement) in the SBRT group and 30 Gy in 10 fractions or 20 Gy in five fractions in the cEBRT group, respectively. The primary end point was an improvement in the pain score at the treated site by at least 2 points (on a visual analog scale from 0 to 10 points) at 6-month follow-up. Data were analyzed on an intention-to-treat and per-protocol basis. RESULTS: Of 214 patients who were screened for eligibility, 63 were randomized 1:1 between SBRT (33 patients with 36 metastases) and cEBRT (30 patients with 31 metastases). The median age of all patients was 66 years, and 40 patients were men (63.5%). In the intention-to-treat analysis, the 6-month proportion of patients who had metastases with pain reduction by 2 or more points was significantly higher in the SBRT group versus the control group (69.4% vs. 41.9%, respectively; two-sided p = .02). Changes in opioid medication intake relative to baseline were nonsignificant between the groups. No differences were observed in vertebral compression fracture or adverse event rates between the groups. CONCLUSIONS: Dose-intensified SBRT improved pain score more effectively than cEBRT at 6 months.

Spinal and cervical nodal metastases in a patient with glioblastoma.

This article presents the rare case of a 54-year-old gentleman with primary glioblastoma developing multiple extracranial metastases 7 months after diagnosis. Initially, the patient complained of progressive headaches, confusion, and weakness of the left arm. Magnetic resonance imaging of the brain showed a right temporoparietal tumor with substantial surrounding subcortical edema and midline shift to the left. Two consecutive craniotomies resulted in complete microsurgical resection of the lesion. Histology was consistent with a World Health Organization grade IV, IDH-wildtype glioblastoma. Further treatment was standard chemoradiation including intensity-modulated radiotherapy with oral temozolomide chemotherapy. Seven months after diagnosis, the cranial lesion progressed, and the patient developed painful metastases in multiple bones and suspicious right-sided cervical lymph nodes. Immunohistochemistry and molecular signature supported the case of a metastatic glioblastoma. Further treatment was palliative radiotherapy of the spinal lesions along with symptomatic pain management. Extracranial metastasis of glioblastoma is a rare complication of which only a few cases have been reported in the literature. Little is known about the precise mechanisms of tumor dissemination and the appropriate treatment.

Denosumab-induced hypocalcemia in patients with solid tumors and renal dysfunction: a multicenter, retrospective, observational study.

BACKGROUND: Bone metastases are frequently observed in advanced cancer, and bone modifying agents are used to prevent or treat skeletal-related events. Zoledronic acid is contraindicated in patients with severe renal impairment (Ccr < 30 mL/min), but it is not completely known whether denosumab can be used in them. We aimed to determine the association between renal function and hypocalcemia development during denosumab treatment. METHODS: We included patients with solid cancer and bone metastases who started denosumab treatment between April 2017 and March 2019. They were classified into four groups based on creatinine clearance (Ccr; mL/min): normal (Ccr ≥ 80), mild (50 ≤ Ccr ˂80), moderate (30 ≤ Ccr ˂50), and severe (Ccr ˂30). Hypocalcemia was evaluated using the Common Terminology Criteria for Adverse Events (v5.0) based on the albumin-adjusted serum calcium levels; its incidence (stratified by renal function) and risk factors were investigated using a Chi-square test and logistic regression analysis. RESULTS: Of 524 patients (age: 69 ± 11 years; 303 men), 153 had a normal renal function and 222, 117, and 32 had mild, moderate, and severe renal dysfunction. The albumin-adjusted serum calcium level was higher than the measured (total) calcium level in most patients. The incidence of grade ≥ 1 hypocalcemia was 32.0% in the normal group and 37.4%, 29.9%, and 62.5% in the mild, moderate, and severe renal dysfunction groups, respectively. It was, therefore, higher in the severe renal dysfunction groups than in the normal group (P = 0.002). The incidence of grade ≥ 3 hypocalcemia did not differ significantly among the groups. Pre-treatment low serum calcium levels and severe renal dysfunction were risk factors for hypocalcemia. CONCLUSIONS: Evaluating denosumab-induced hypocalcemia required albumin adjustment, and its incidence was high among patients with severe renal dysfunction. Reduced serum calcium levels and severely impaired renal function were associated with an elevated hypocalcemia risk.

Paget Disease of Bone Harboring Bone Metastatic Neuroendocrine Cancer: A Case Report.

In this case report, we describe an uncommon case of neuroendocrine cancer of unknown origin began with cauda equina syndrome in a patient affected by Paget disease of bone (PDB). A 76-year-old man with diagnosis of PDB, without history of pain or bone deformity, developed sudden severe low back pain. Bone alkaline phosphatase was increased and MRI and whole-body scintigraphy confirmed the localization of the disease at the third vertebra of the lumbar spine. Treatment with Neridronic Acid was started, but after only 2 weeks of therapy anuria and bowel occlusion occurred together with lower limb weakness and walking impairment. Cauda equina syndrome consequent to spinal stenosis at the level of L2-L3 was diagnosed after admission to Emergency Department and the patient underwent neurosurgery for spinal medulla decompression. The histologic results showed a complete subversion of bone structure in neoplastic tissue, consistent with metastatic neuroendocrine carcinoma of unknown origin. In conclusion, low back pain in the elderly may require deep investigation to individuate rare diseases. In asymptomatic patients with apparently stable PDB, the sudden appearance of pain or neurologic symptoms may alert the clinician for the possibility of other superimposing diseases, like bone metastases.

Synthesis and Evaluation of Radiogallium Labeled Bone-Imaging Probes Using Oligo-γ-Carboxy Glutamic Acid Peptides as Carriers to Bone.

We investigated the importance of the carboxy group density in bone affinity during the development of peptide-based bone-seeking radiopharmaceuticals and carriers. Oligo-γ-carboxy glutamic acid peptides [(Gla)n] with higher carboxy group density than oligo-glutamic acid peptides [(Glu)n] and oligo-aspartic acid peptides [(Asp)n] were chosen. Using the radiogallium chelator N,N'-bis-[2-hydroxy-5-(carboxyethyl)benzyl]ethylenediamine-N,N'-diacetic acid (HBED-CC), we synthesized [67Ga]Ga-HBED-CC-(Gla)n (n = 1, 2, 5, 8, 11, or 14) with high yields. Hydroxyapatite-binding assays, biodistribution, and SPECT imaging showed higher affinity and bone accumulation for [67Ga]Ga-HBED-CC-(Gla)n compared to [67Ga]Ga-HBED-CC-(Glu)n. Notably, [67Ga]Ga-HBED-CC-(Gla)8 and [67Ga]Ga-HBED-CC-(Gla)11 exhibited superior bone accumulation and rapid blood clearance. SPECT/CT imaging with [67Ga]Ga-HBED-CC-(Gla)8 exclusively visualized the bone tissue. These findings support the potential use of [67Ga]Ga-HBED-CC-(Gla)n as excellent bone-imaging PET probes, suggesting (Gla)n peptides are superior bone-seeking carriers.

Optimizing Oxygen-Production Kinetics of Manganese Dioxide Nanoparticles Improves Hypoxia Reversal and Survival in Mice with Bone Metastases.

Persistent hypoxia in bone metastases induces an immunosuppressive environment, limiting the effectiveness of immunotherapies. To address chronic hypoxia, we have developed manganese dioxide (MnO2) nanoparticles with tunable oxygen production kinetics for sustained oxygenation in bone metastases lesions. Using polyethylene glycol (PEG)-stabilized MnO2 or poly(lactic[50]-co-glycolic[50] acid) (50:50 PLGA), poly(lactic[75]-co-glycolic[25] acid) (75:25 PLGA), and polylactic acid (PLA)-encapsulated MnO2 NPs, we demonstrate that polymer hydrophobicity attenuates burst oxygen production and enables tunable oxygen production kinetics. The PEG-MnO2 NPs resulted in rapid hypoxia reduction in spheroids, which was rapidly attenuated, while the PLA-MnO2 NPs exhibited delayed hypoxia control in cancer spheroids. The 50:50 PLGA-MnO2 NPs exhibited the best short- and long-term control of hypoxia in cancer spheroids, resulting in sustained regulation of the expression of HIF-1α and immunosuppressive genes. The sustained control of hypoxia by the 50:50 PLGA-MnO2 NPs enhanced the cytotoxicity of natural killer cells against cancer spheroids. In vivo, 50:50 PLGA-MnO2 showed greater accumulation in the long bones and pelvis, common sites for bone metastases. The NPs decreased hypoxia in bone metastases and decreased regulatory T cell levels, resulting in enhanced survival of mice with established bone metastases.

An Update on the Management of Bone Metastases.

PURPOSE OF REVIEW: Increasing life expectancy among patients with advanced cancer has placed a greater emphasis on optimizing pain control and quality of life. Concurrently, significant advancements in radiotherapy for bone metastases have permitted for dose escalation strategies such as stereotactic radiotherapy. This review aims to provide updated information on the management of bone metastases in light of these developments. RECENT FINDINGS: We reviewed recent studies regarding the role and details of external beam radiotherapy for bone metastases, with emphasis on differences by treatment site as well as intention (palliative versus ablative for oligometastases). Conventional palliative radiotherapy remains a mainstay of management. While stereotactic radiotherapy may augment durability of pain relief and even survival time, there are significant questions remaining regarding optimal dosing and patient selection. Radiotherapy for bone metastases continues to evolve, particularly with increasing use of stereotactic radiotherapy. Future studies are needed to clarify optimal dose, fractionation, modality, and patient selection criteria among different radiotherapy approaches.

Treatment of bone metastases from solid tumors with bone-modifying agents: a web survey of Italian oncologists investigating patterns of practice drug prescription and prevention of side effects.

PURPOSE: Optimal use of bone-modifying agents (BMAs) in patients with bone metastases from solid tumors is uncertain in some aspects: the drug choice; the planned treatment duration and long-term therapy; the prevention and management of possible side effects, including renal toxicity, hypocalcaemia, and medication-related osteonecrosis of the jaw (MRONJ). METHODS: Italian oncologists were invited to fulfil a 24-question web survey about prescription of BMAs for bone metastases of breast cancer, prostate cancer, and other solid tumors. Prevention and management of side effects were also investigated. RESULTS: Answers of 191 oncologists were collected. BMAs are usually prescribed at the time of diagnosis of bone metastases by 87.0% (breast cancer) and 76.1% (solid tumors except breast and prostate cancers) of oncologists; the decision is more articulated for prostate cancer (endocrine-sensitive versus castration-resistant). The creatinine level (32.3%), the availability of patient venous access (15.8%), and the type of primary neoplasm (13.6%) are the most reported factors involved in choice between bisphosphonates and denosumab. Zoledronic acid every 3 months was considered as a valid alternative to monthly administration by 94% of Italian oncologists. Oncologists reported a good confidence with measures aimed to prevent MRONJ, whereas uncertainness about prevention and management of hypocalcemia was registered. CONCLUSION: Italian oncologists showed a high attitude in prescribing bisphosphonates or denosumab at the time of diagnosis of bone metastases, with a large application of preventive measures of side effects. Further studies are needed to investigate some controversial aspects, such as optimal drug treatment duration and long-term drug schedules.

Limited utility of routine bone scintigraphy in the staging of patients with hepatocellular carcinoma: A cross-sectional study.

INTRODUCTION AND OBJECTIVES: The most widely used staging system for hepatocellular carcinoma (HCC) is the Barcelona Liver Clinic Cancer (BCLC) system, which considers tumor burden, performance status, and liver function. Tumor burden is assessed with cross sectional imaging of the abdomen and chest, controversy surrounds the routine use of bone scintigraphy (BS) for detecting extrahepatic metastases. This study evaluated the role of BS in staging HCC in Mexican patients. PATIENTS AND METHODS: Retrospective cross-sectional study of all adults with HCC at a Mexican referral center from 2000 to 2018. Staging included abdominal computed tomography (CT) or magnetic resonance imaging, chest CT, and BS. The main outcome was the impact of BS on staging and/or therapy plans. RESULTS: Among 238 patients, 2 with fibrolamellar variant and 44 with incomplete data were excluded. Median age was 66 years, 84 % had cirrhosis, and the predominant etiology was hepatitis C virus (43 %). BCLC stages were distributed as follows: A (14 %), B (7 %), C (68 %), and D (11 %). Extrahepatic disease was present in 18 %; only 8 % patients had a positive BS. Among the positive cases, 4 were true positives, but they did not alter staging or therapy plans. CONCLUSIONS: Routine BS in HCC staging demonstrated low yield, with a notable rate of false positives. Considering the implications of extrahepatic disease, BS may be justified for liver transplant candidates outside conventional criteria. Our study highlights the limited role of BS in early-stage HCC and advocates for a more selective utilization.

Bone metastases among newly diagnosed cancer patients: a population-based study.

PURPOSE: (i) To analyze age-adjusted incidence rates of synchronous bone metastases diagnosed alongside primary malignancy from 2010 to 2018 in the US population, (ii) determine the incidence proportions (IPs) and characteristics of synchronous bone metastases among newly diagnosed cancer patients in the USA especially pediatric cases, and (iii) assess the implications of synchronous bone metastases on cancer patient's survival, and identify the survival risk factors for these cancer patients. METHODS: Utilizing data from the Surveillance, Epidemiology, and End Results (SEER) program (2010-2018), we calculated age-adjusted IPs and annual percentage change (APC), and employed logistic regression and Cox regression models for our analysis. RESULTS: 3 300 736 cancer patients were identified. The age-adjusted incidence rates of synchronous bone metastases increased from 2010 (18.04/100 000) to 2018 (20.89/100 000; APC: 2.3, 95% confidence interval [CI], 1.4-3.1), but decreased in lung cancer (average APC: -1.0, 95% CI, -1.8 to -0.3). The highest IPs were observed in pediatric neuroblastoma (43.2%; 95% CI, 39.8%-46.7%) and adult small cell carcinoma (23.1%; 95% CI, 22.7%-23.4%). Multivariate logistic analyses revealed that primary tumor characteristics were correlated with higher bone metastases risk. Survival analyses also showed varied prognostic outcomes based on metastasis sites and demographics among cancer patients. Landmark analyses further indicated among long-term cancer survivors (≥3 and ≥5 years), patients with de novo bone metastases had the poorest survival rates compared with those with other synchronous metastases (P < 0.001). CONCLUSION: This study provides a population-based estimation of the incidence and prognosis for synchronous bone metastases. Our findings highlight the need for early identification of high-risk groups and multidisciplinary approaches to improve prognosis of cancer patients with de novo bone metastases.

Radiomics based on multiple machine learning methods for diagnosing early bone metastases not visible on CT images.

OBJECTIVES: This study utilizes [99mTc]-methylene diphosphate (MDP) single photon emission computed tomography (SPECT) images as a reference standard to evaluate whether the integration of radiomics features from computed tomography (CT) and machine learning algorithms can identify microscopic early bone metastases. Additionally, we also determine the optimal machine learning approach. MATERIALS AND METHODS: We retrospectively studied 63 patients with early bone metastasis from July 2020 to March 2023. The ITK-SNAP software was used to delineate early bone metastases and normal bone tissue in SPECT images of each patient, which were then registered onto CT images to outline the volume of interest (VOI). The VOI includes 63 early bone metastasis volumes and 63 normal bone tissue volumes. 126 VOIs were randomly distributed in a 7:3 ratio between the training and testing groups, and 944 radiomics features were extracted from every VOI. We established 20 machine learning models using 5 feature selection algorithms and 4 classification methods. Evaluate the performance of the model using the area under the receiver operating characteristic curve (AUC). RESULTS: Most machine learning models demonstrated outstanding discriminative capacity, with AUCs higher than 0.70. Notably, the K-Nearest Neighbors (KNN) classifier exhibited significant performance improvement compared to the other four classifiers. Specifically, the model constructed utilizing eXtreme Gradient Boosting (XGBoost) feature selection method integrated with KNN classifier achieved the maximum AUC, which is 0.989 in the training set and 0.975 in the testing set. CONCLUSIONS: Radiomics features integrated with machine learning methods can identify early bone metastases that are not visible on CT images. In our analysis, KNN is considered the optimal classification method.

Update on musculoskeletal applications of magnetic resonance-guided focused ultrasound.

Magnetic resonance-guided focused ultrasound (MRgFUS) is a noninvasive, incisionless, radiation-free technology used to ablate tissue deep within the body. This technique has gained increased popularity following FDA approval for treatment of pain related to bone metastases and limited approval for treatment of osteoid osteoma. MRgFUS delivers superior visualization of soft tissue targets in unlimited imaging planes and precision in targeting and delivery of thermal dose which is all provided during real-time monitoring using MR thermometry. This paper provides an overview of the common musculoskeletal applications of MRgFUS along with updates on clinical outcomes and discussion of future applications.

Magnetic resonance-guided focused ultrasound versus percutaneous thermal ablation in local control of bone oligometastases: a systematic review and meta-analysis.

BACKGROUND: The percutaneous thermal ablation techniques (pTA) are radiofrequency ablation, cryoablation, and microwave ablation, suitable for the treatment of bone oligometastases. Magnetic resonance-guided focused ultrasound (MRgFUS) is a noninvasive ablation technique. OBJECTIVES: To compare the effectiveness and safety of MRgFUS and pTA for treating bone oligometastases and their complications. METHODS: Studies were selected with a PICO/PRISMA protocol: pTA or MRgFUS in patients with bone oligometastases; non-exclusive curative treatment. Exclusion criteria were: primary bone tumor; concurrent radiation therapy; palliative therapy; and absence of imaging at follow-up. PubMed, BioMed Central, and Scopus were searched. The modified Newcastle-Ottawa Scale assessed articles quality. For each treatment (pTA and MRgFUS), we conducted two separate random-effects meta-analyses to estimate the pooled effectiveness and safety. The effectiveness was assessed by combining the proportions of treated lesions achieving local tumor control (LTC); the safety by combining the complications rates of treated patients. Meta-regression analyses were performed to identify any outcome predictor. RESULTS: A total of 24 articles were included. Pooled LTC rate for MRgFUS was 84% (N = 7, 95% CI 66-97%, I2 = 74.7%) compared to 65% of pTA (N = 17, 95% CI 51-78%, I2 = 89.3%). Pooled complications rate was similar, respectively, 13% (95% CI 1-32%, I2 = 81.0%) for MRgFUS and 12% (95% CI 8-18%, I2 = 39.9%) for pTA, but major complications were recorded with pTA only. The meta-regression analyses, including technique type, study design, tumor, and follow-up, found no significant predictors. DISCUSSION: The effectiveness and safety of the two techniques were found comparable, even though MRgFUS is a noninvasive treatment that did not cause any major complication. Limited data availability on MRgFUS and the lack of direct comparisons with pTA may affect these findings. CONCLUSIONS: MRgFUS can be a valid, safe, and noninvasive treatment for bone oligometastases. Direct comparison studies are needed to confirm its promising benefits.

Combined chemotherapy of zoledronic acid and pamidronate in the treatment of bone metastases from nonsmall cell lung cancer and the effects on pain stress and bone metabolic indices.

OBJECTIVE: We conducted this paper to decipher the efficacy of the combined chemotherapy of zoledronic acid and pamidronate in treating bone metastases from nonsmall cell lung cancer (NSCLC) and the effects on pain stress and bone metabolic indices. METHODS: Patients with bone metastases from NSCLC were allocated into Group A and Group B. Patients in the Group A were administrated with pamidronate combined chemotherapy and patients in the Group B were administrated with zoledronic acid combined chemotherapy. The efficacy, pain symptom scores, quality of life scores, serum inflammatory factor, serum bone metabolic indices, serum pain stress indicators, and the occurrence of adverse effects were compared in patients of the two groups. RESULTS: The total effective rate of treatment was higher in the Group B than in the Group A. After treatment, reduced Numerical Rating Scale scores and elevated Karnofsky Performance Score score, reduced serum levels of N-terminal mid-fragment of osteocalcin, N-terminal propeptide of type I procollagen, bone-specific alkaline phosphatase, and type I collagen hydroxyl terminal peptide ß special sequence, reduced serum levels of C-reactive protein, procalcitonin, tumor necrosis factor-α, and interleukin-6, as well as decreased levels of bradykinin, substance P, neuropeptide Y, and ß-endorphin were found in the Group B versus the Group A. No notable difference was witnessed in the rate of adverse reactions between the Group A and the Group B. CONCLUSION: Zoledronic acid combined with chemotherapy can effectively treat bone metastases of NSCLC and improve pain stress and bone metabolic status, which has value that can be promoted and applied in clinical treatment.

Bridging the Gap in Understanding Bone Metastasis: A Multifaceted Perspective.

The treatment of patients with advanced cancer poses clinical problems due to the complications that arise as the disease progresses. Bone metastases are a common problem that cancer patients may face, and currently, there are no effective drugs to treat these individuals. Prostate, breast, and lung cancers often spread to the bone, causing significant and disabling health conditions. The bone is a highly active and dynamic tissue and is considered a favorable environment for the growth of cancer. The role of osteoblasts and osteoclasts in the process of bone remodeling and the way in which their interactions change during the progression of metastasis is critical to understanding the pathophysiology of this disease. These interactions create a self-perpetuating loop that stimulates the growth of metastatic cells in the bone. The metabolic reprogramming of both cancer cells and cells in the bone microenvironment has serious implications for the development and progression of metastasis. Insight into the process of bone remodeling and the systemic elements that regulate this process, as well as the cellular changes that occur during the progression of bone metastases, is critical to the discovery of a cure for this disease. It is crucial to explore different therapeutic options that focus specifically on malignancy in the bone microenvironment in order to effectively treat this disease. This review will focus on the bone remodeling process and the effects of metabolic disorders as well as systemic factors like hormones and cytokines on the development of bone metastases. We will also examine the various therapeutic alternatives available today and the upcoming advances in novel treatments.

Role of Bone Metastases in Lung Neuroendocrine Neoplasms: Clinical Presentation, Treatment and Impact on Prognosis.

Lung neuroendocrine neoplasms (L-NEN) are heterogeneous tumors. While bone metastases (BM) have been associated with worse prognosis in other NEN, their role in L-NEN deserves in-depth analysis. This study analyzes the clinical presentation, treatment and survival outcomes of L-NEN, focusing on patients with BM compared with patients without metastases or with metastases in other sites (OtherMtx). The clinicopathological and survival data of L-NEN admitted to the Federico II University were retrospectively evaluated. Fifty L-NEN were included. Among 27 metastatic patients (54%), 13 (26%) had BM, more commonly occurring in males than females and in primary bilateral L-NEN or L-NEN > 26 mm, with higher Ki67. Atypical carcinoid and hypovitaminosis D were associated with BM. The number of metastatic sites was higher in patients with BM than OtherMtx. Synchronous metastases were associated with shorter overall survival (OS). The median progression-free survival (PFS) and OS in patients with BM were similar to OtherMtx, but a two-times increased risk of shorter OS was detected. BM do not impact PFS or OS more than OtherMtx, but the increased risk of shorter OS in patients with BM should be considered. Periodic bone evaluation in L-NEN should be recommended.

Differences in the Renal Accumulation of Radiogallium-Labeled (Glu)14 Peptides Containing Different Optical Isomers of Glutamic Acid.

Acidic amino acid peptides have a high affinity for bone. Previously, we demonstrated that radiogallium complex-conjugated oligo-acidic amino acids possess promising properties as bone-seeking radiopharmaceuticals. Here, to elucidate the effect of stereoisomers of Glu in Glu-containing peptides [(Glu)14] on their accumulation in the kidney, the biodistributions of [67Ga]Ga-N,N'-bis-[2-hydroxy-5-(carboxyethyl)benzyl]ethylenediamine-N,N'-diacetic acid-conjugated (l-Glu)14 ([67Ga]Ga-HBED-CC-(l-Glu)14), [67Ga]Ga-HBED-CC-(d-Glu)14, [67Ga]Ga-HBED-CC-(dl-Glu)14, and [67Ga]Ga-HBED-CC-(d-Glu-l-Glu)7 were compared. Although the accumulation of these compounds in the bone was comparable, their kidney accumulation and retention were strikingly different, with [67Ga]Ga-HBED-CC-(d-Glu-l-Glu)7 exhibiting the lowest level of kidney accumulation among these compounds. Repeated d- and l-peptides may be a useful method for reducing renal accumulation in some cases.

Multimodal Treatment of Metastatic Rectal Cancer in a Young Patient: Case Report and Literature Review.

Metastatic colorectal cancer requires a multidisciplinary and individualized approach. Herein, we reported the case of a young woman diagnosed with metastatic rectal cancer who received an individualized multimodal treatment strategy that resulted in a remarkable survival. There were several particular aspects of this case, such as the early onset of the disease, the successful use of conversion therapy, the application of liquid biopsy to guide treatment, and the specific nature of the bone metastasis. To offer more insights for navigating such challenges in patients with metastatic colorectal cancer, we have conducted a literature review to find more data related to the particularities of this case. The incidence of early onset colorectal cancer is on the rise. Data suggests that it differs from older-onset colorectal cancer in terms of its pathological, epidemiological, anatomical, metabolic, and biological characteristics. Conversion therapy and surgical intervention provide an opportunity for cure and improve outcomes in metastatic colorectal cancer. It is important to approach each case individually, as every patient with limited liver disease should be considered as a candidate for secondary resection. Moreover, liquid biopsy has an important role in the individualized management of metastatic colorectal cancer patients, as it offers additional information for treatment decisions.

[Medication-related osteonecrosis of the jaws associated with the use of bone-modifying agents]. / Medikamentoznyi osteonekroz chelyustei, svyazannyi s priemom osteomodifitsiruyushchikh preparatov.

The relevance of the study is associated with the widespread use of osteomodifying agents in patients with bone metastases and osteoporosis. Bisphosphonates and other osteo-modifying agents are widely used in oncology and prevention of age-related changes in the human bone system. The use, therapeutic effects and complications of therapy with osteo modifying agents are being investigated all over the world. However, the etiology and pathogenesis of drug-induced osteonecrosis of the jaws (MONCH) have not been fully studied, in this regard, the study of risk factors and mechanisms of its development remains relevant. New data on the etiology and pathogenesis of drug-induced osteonecrosis are presented. The literature review is carried out on the electronic resource PubMed.