Skeletal Tumor Research Articles

Osteosarcoma and Langerhans Cell Histiocytosis in a Pediatric Patient with Lynch Syndrome: A Case Report.

Lynch syndrome (hereditary nonpolyposis colorectal cancer) is associated with extracolonic manifestations, but skeletal tumors are rare. Our patient, a 12-year-old boy with Lynch syndrome, developed osteosarcoma of the left femur. Treatment included cytotoxic chemotherapy, wide resection, and pembrolizumab. Two years later, he developed an aggressive lesion in the contralateral femur that was thought to be metastatic osteosarcoma but which histology revealed to be Langerhans cell histiocytosis. This case underscores the importance of advanced testing in patients with osteosarcoma and poor response to chemotherapy, and of tissue sampling when patients with a primary malignancy develop new bone lesions. IV.

Abstract 3405: CT-assessed body composition and tumor immunologic characteristics in patients with non-small-cell lung cancer

Abstract Objectives: Obesity is associated with higher immunotherapy efficacy, but body mass index is a convoluted marker of adipose and muscle tissue. We conducted a discovery scale study to assess the association of skeletal muscle and adipose tissue areas annotated on computed tomography (CT) scan images with selected tumor immunologic characteristics among patients with non-small-cell lung cancer (NSCLC). Methods: We analyzed publicly available data from 102 patients (mean age = 67.2, 47.1% female, and 70.6% stage I-II) who had diagnostic CT images in The Cancer Image Archive. All patients had the 12th thoracic vertebra (T12) image, and a subset (62 patients) had the 3rd lumber vertebra (L3) image. Paravertebral muscle areas on T12 and skeletal muscle and adipose tissue areas on L3 were annotated using Slice-O-Matic. RNA-seq data were provided by The Cancer Genome Atlas and Clinical Proteomic Tumor Analysis Consortium; percentages of CD8, regulatory T cells, and activated NK cells were identified using the CIBERSORT. ESTIMATE algorithm was used to derive the stromal score and the immune score. Differences in the immune markers were examined using ANOVA adjusting for stage, histology, and study. Results and Conclusion: Patients with higher paravertebral muscle area (3rd tertile) had the lowest stromal scores, compared to the 2nd and 1st tertile (P<0.05). Patients in the 2nd tertile of paravertebral muscle areas had the highest immune score and CD274 (PD-L1) gene expression. Among the body composition types classified using L3 images, low muscle/high adiposity was associated with lower stromal scores, and low muscle was associated with lower immune scores, compared to high adiposity and high muscle/low adiposity types. Other immunological markers did not differ across the body composition types. Significance: These findings suggest associations between deconvoluted skeletal and adipose tissue components and tumor markers relevant to immune checkpoint inhibitor efficacies in NSCLC. Further validation using immune phenotyping in a large patient sample is warranted. Funding: The study is in part supported by NIH/NCI R37CA248371 and OSU Comprehensive Cancer Center - James. Citation Format: Ting-Yuan David Cheng, Cuthbert Mario Mahenge, Rand T. Akasheh, Ayse Selen Yilmaz, Ben Kinder, Xuan Nguyen, Maciej Pietrzak, Carolyn J. Presley, Peter G. Shields. CT-assessed body composition and tumor immunologic characteristics in patients with non-small-cell lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3405.

Vascular Neoplasms With NFATC1/C2 Gene Alterations : Expanding the Clinicopathologic and Molecular Characteristics of a Distinct Entity.

Despite significant advances in their molecular pathogenesis, skeletal vascular tumors remain diagnostically challenging due to their aggressive radiologic appearance and significant morphologic overlap. Within the epithelioid category and at the benign end of the spectrum, recurrent FOS/FOSB fusions have defined most epithelioid hemangiomas, distinguishing them from epithelioid hemangioendothelioma and angiosarcoma. More recently, the presence of EWSR1/FUS :: NFATC1/2 fusions emerged as the genetic hallmark of a novel group of unusual vascular proliferations, often displaying epithelioid morphology, with alternating vasoformative and solid growth, variable atypia, reminiscent of composite hemangioendothelioma. In this study, we further our understanding and morphologic spectrum of NFATC -fusion positive vascular neoplasms by describing 9 new cases, including soft tissue locations and novel fusion partners. Combining with the initial cohort of 5 cases, a total of 14 patients were analyzed, showing slight female predilection and an age range of 10 to 66 (mean 42y). Twelve patients had solitary lesions, while 2 had multifocal polyostotic (pelvic bones) disease. Overall, 12 lesions were intra-osseous and 2 in soft tissue. By targeted RNA Fusion panels or FISH, there were 6 cases of EWSR1::NFATC1 , 4 EWSR1::NFATC2 , 2 FUS::NFATC2 , 1 EWSR1 rearrangement, and 1 with a novel FABP4::NFATC2 fusion. Follow-up was available in 4 patients. One patient experienced 2 local recurrences, 11 and 15 years postdiagnosis, and one patient experienced progressive disease despite multimodality treatment (curettings, embolization, radiation) over 3 years. In summary, our extended investigation confirms that NFATC -related fusions define a distinct group of vascular neoplasms with variable architecture, epithelioid phenotype, and cytologic atypia, commonly located in the bone, occasionally multifocal and with potential for local recurrence and aggressive behavior but no metastatic potential. Molecular analysis is recommended in diagnostically challenging cases with atypical histology to exclude malignancy.

Pyroptosis-Related Gene Signature Predicts Prognosis and Response to Immunotherapy and Medication in Pediatric and Young Adult Osteosarcoma Patients.

Pyroptosis, a new form of inflammatory programmed cell death, has recently gained attention. However, the impact of the expression levels of pyroptosis-related genes (PRGs) on the overall survival (OS) of osteosarcoma patients remains unclear. This study aims to investigate the impact of the expression levels of PRGs on the OS of pediatric and young adult patients with osteosarcoma. Transcriptome matrix datasets of normal muscle or skeletal tissues from the Genotype-Tissue Expression (GTEx) project and osteosarcoma specimen the National Cancer Institute's (NCI) Therapeutically Applicable Research to Generate Effective Treatments (TARGET) database were used to identify pyroptosis-related genes (PRGs) associated with prognosis. The National Center for Biotechnology Information's (NCBI) GSE21257 dataset was employed to validate the predictive value of the pyroptosis-related signature (PRS). Additionally, reverse transcription polymerase chain reaction (RT-qPCR) experiment was performed in normal and osteosarcoma cell lines. The study identified 18 differentially expressed PRGs (DEPRGs) between normal muscle or skeletal tissues and tumor samples. Multiple machine learning techniques were used to select PRGs, resulting in the identification of four hub PRGs. A PRS-score was calculated for each sample based on the expression of these four hub PRGs, and samples were categorized into low and high PRS-score level groups. It was confirmed that metastatic status and PRS-score level are independent prognostic predictors. A nomogram model for predicting OS of osteosarcoma patients was constructed. Single-cell RNA-sequencing data display the expression patterns of the hub PRGs. RT-qPCR data results were found to be consistent with the differential expression analysis performed on TARGET and GTEx samples. The study developed a novel pyroptosis-related gene signature that can stratify pediatric and young adult osteosarcoma patients into different risk groups, thus predicting their response to immunotherapy and chemotherapy.

Management of Ipsilateral Fractures After Rotationplasty

Case: Rotationplasty is a surgical procedure used for restoring functionality after skeletal tumor resection. Multiple complications have been described, including the potential occurrence of fractures. Literature on fracture management after rotationplasty is limited. In this article, we present 2 cases of late ipsilateral fractures in rotated limbs successfully treated with intramedullary nailing. Conclusion: Effective management of fractures after rotationplasty requires thorough understanding of the rotated limb anatomy and careful planning. The clinical considerations presented in this article aim to provide guidance for surgeons to achieve successful outcomes in the management of fractures after rotationplasty.

The Use Carbon Composite Material For Replacement of Postresection Bone Defects

In studying the use of various implanted materials, the authors found no case reports of carbon composite material for children in the available literature. The boundaries of carbon composite material use are not clear, and indications and contraindications for its applying are not outlined. Therefore, the authors decided to share the initial experience of its use for the replacement of post-resection bone defects for children. The paper presents the results of surgical treatment of 8-16-year-old children with extensive bone defects after resection of pathological tissue with the use of highly porous cellular carbon in isolation and in combination with autografts. During the study, children with damage to long bone segments - tibia, shoulder, and femoral were operated on. The clinical and radiation results of this study have been evaluated based on the Musculo Skeletal Tumor Society Score Scale. 100% of treated patients were rated as good for period from 7 to 12 years after surgery. There were no complications in the operated patients. Full integration of the implantable materials was observed with good clinical and radiological results.

Inflammatory Rhabdomyoblastic Tumor: Clinicopathologic and Molecular Analysis of 13 Cases

Inflammatory rhabdomyoblastic tumors (IRMTs) are newly recognized skeletal muscle tumors with uncertain malignant potential. We investigated 13 IRMTs using clinicopathologic, genetic, and epigenetic methods. The cohort included 7 men and 6 women, aged 23 to 80 years (median, 50 years), of whom 2 had neurofibromatosis type 1. Most tumors occurred in the deep soft tissues of the lower limbs, head/neck, trunk wall, and retroperitoneum/pelvis. Two tumors involved the hypopharyngeal submucosa as polypoid masses. Eight tumors showed conventional histology of predominantly spindled cells with nuclear atypia, low mitotic activity, and massive inflammatory infiltrates. Three tumors showed atypical histology, including uniform epithelioid or plump cells and mitotically active histiocytes. The remaining 2 tumors demonstrated malignant progression to rhabdomyosarcoma; one had additional IRMT histology and the other was a pure sarcoma. All 11 IRMTs without malignant progression exhibited indolent behavior at a median follow-up of 43 months. One of the 2 patients with IRMTs with malignant progression died of lung metastases. All IRMTs were positive for desmin and PAX7, whereas myogenin and MyoD1 were expressed in a subset of cases. Targeted next-generation sequencing identified pathogenic mutations in NF1 (5/8) and TP53 (4/8). All TP53 mutations co-occurred with NF1 mutations. TP53 variant allele frequency was much lower than that of NF1 in 2 cases. These tumors showed geographic (subclonal) strong p53 immunoreactivity, suggesting the secondary emergence of a TP53-mutant clone. DNA methylation–based copy number analysis conducted in 11 tumors revealed characteristic flat patterns with relative gains, including chromosomes 5, 18, 20, 21, and/or 22 in most cases. Widespread loss of heterozygosity with retained biparental copies of these chromosomes was confirmed in 4 tumors analyzed via allele-specific profiling. Based on unsupervised DNA methylation analysis, none of the 11 tumors tested clustered with existing reference entities but formed a coherent group, although its specificity warrants further study.

Giant Cell Tumour of Bone: A Comprehensive Review of Pathogenesis, Diagnosis, and Treatment.

The benign aggressive tumour known as a giant cell tumour of bone (GCTB) frequently affects the knee bones.Patients suffering from GCTB present with pain, swelling, joint effusion, loss of ability to bear weight on the involved extremity and a restriction in the range of motion of the afflicted joint may also exist, depending on the tumour's size. GCTB makes up 20% of benign skeletal tumours and 5% of all primary bone tumours. Although it has an equal distribution of the sexes, the majority reveal a higher frequency among women. Eighty per centof GCTB instances were recorded in patients between the ages of 20 and 50 during the third decade. The femur, tibiaand radius are where GCTB is most frequently discovered. Lesions can be rated using the Campanacci grading method based on the plain radiograph's results. Plain radiography, CT and MRI are used to diagnose the tumour. Surgery is the only curative treatment which is determined by the Campanacci grade and the tumour's location. Recurrence of GCTB is observed in about 25% of patients, with curettage being associated with rates as high as 50%. We evaluated the GCTB-related articles and summarised the developments in diagnosis, treatment and reducing risk of recurrence.

Gorlin-Goltz Syndrome: A Comprehensive Analysis of the Clinical, Genetic and Therapeutic Manifestations of a Rare and Complex Disease

Gorlin-Goltz syndrome, also known as basal cell nevus syndrome or nevoid basal cell carcinoma syndrome, is a rare and heterogeneous genetic disease with a varied clinical presentation involving multiple systems and organs. This comprehensive review aims to provide an in-depth understanding of this syndrome from a medical and scientific perspective. Gorlin-Goltz syndrome is characterized by an inherited predisposition to the formation of skin and skeletal tumors, as well as the development of jaw cysts, cleft palates, facial deformities, ocular malformations and other anomalies. At the genetic level, this syndrome is linked to mutations in the PTCH1 gene, which regulates the hedgehog signaling pathway, playing a crucial role in the regulation of cell growth and differentiation. Early and accurate diagnosis of Gorlin-Goltz syndrome is essential to prevent serious complications, such as advanced basal cell carcinomas and facial disfigurement. Molecular diagnostic strategies and therapeutic options, including reconstructive surgery, hedgehog pathway inhibitor therapy, and multidisciplinary patient management will be addressed. This review will also explore the psychological and social impact on patients and their families, as well as advances in genetic and therapeutic research that may open new perspectives for the management and prevention of this complex disease. Ultimately, detailed knowledge of Gorlin-Goltz syndrome is essential to improve the quality of life of those affected and to promote future research in this evolving field.

A model based on adipose and muscle-related indicators evaluated by CT images for predicting microvascular invasion in HCC patients

Background and aimThe presence of microvascular invasion (MVI) will impair the surgical outcome of hepatocellular carcinoma (HCC). Adipose and muscle tissues have been confirmed to be associated with the prognosis of HCC. We aimed to develop and validate a nomogram based on adipose and muscle related-variables for preoperative prediction of MVI in HCC.MethodsOne hundred fifty-eight HCC patients from institution A (training cohort) and 53 HCC patients from institution B (validation cohort) were included, all of whom underwent preoperative CT scan and curative resection with confirmed pathological diagnoses. Least absolute shrinkage and selection operator (LASSO) logistic regression was applied to data dimensionality reduction and screening. Nomogram was constructed based on the independent variables, and evaluated by external validation, calibration curve, receiver operating characteristic (ROC) curve and decision curve analysis (DCA).ResultsHistopathologically identified MVI was found in 101 of 211 patients (47.9%). The preoperative imaging and clinical variables associated with MVI were visceral adipose tissue (VAT) density, intramuscular adipose tissue index (IMATI), skeletal muscle (SM) area, age, tumor size and cirrhosis. Incorporating these 6 factors, the nomogram achieved good concordance index of 0.79 (95%CI: 0.72–0.86) and 0.75 (95%CI: 0.62–0.89) in training and validation cohorts, respectively. In addition, calibration curve exhibited good consistency between predicted and actual MVI probabilities. ROC curve and DCA of the nomogram showed superior performance than that of models only depended on clinical or imaging variables. Based on the nomogram score, patients were divided into high (> 273.8) and low (< = 273.8) risk of MVI presence groups. For patients with high MVI risk, wide-margin resection or anatomical resection could significantly improve the 2-year recurrence free survival.ConclusionBy combining 6 preoperative independently predictive factors of MVI, a nomogram was constructed. This model provides an optimal preoperative estimation of MVI risk in HCC patients, and may help to stratify high-risk individuals and optimize clinical decision making.

Mesenchymal and Non-meningothelial Tumors Involving the Central Nervous System

In the World Health Organization Classification of Brain Tumors Fifth Edition, mesenchymal non-meningothelial tumors involving the central nervous system are divided into three major categories: soft tissue tumors, chondro-osseous tumors, and notochordal tumors. Soft tissue tumors are classified into four groups: fibroblastic and myofibroblastic tumors, vascular tumors, skeletal muscle tumors, and tumors of uncertain differentiation. This article will focus on solitary fibrous tumors(SFTs), which are frequently encountered clinically and continue to undergo classification revisions in the 5th edition, and outline the three newly added histological diagnoses. Although SFTs and hemangiopericytomas occur throughout the body, including the central nervous system, nomenclatures have been different between the classifications of "Tumours of Soft Tissue and Bone" and "Tumours of the Central Nervous System." The latest nomenclature is "SFT" in accordance with the nomenclature of bone and soft-tissue tumors. In addition, three new diagnoses, which are intracranial mesenchymal tumor FET-CREB fusion-positive, CIC-rearranged sarcoma, and primary intracranial sarcoma DICER1-mutant, have been defined based on genetic abnormalities in tumors of uncertain differentiation.

569 Resection of Massive Pelvic Chondrosarcoma Using Custom Made 3D Printed Jig: A Case Report

Abstract Background The pelvis is a complex structure associated with major neurovascular structures and so pelvic surgery can be challenging. In the field of skeletal tumours, the surgeon's main aim is to achieve adequate margins, which modern 3D printed technology can assist with. Method A 43-year-old man was found to have a 20(CC) x 13(AO) x 9.3(TR) cm chondrasarcoma at the inner aspect of the right iliac bone. The patient was consented for right sided type 1 hemipelvectomy and tumour resection using customised 3D Printed Jig. A 64-slice spiral CT pelvis was transferred to an image processing software (Materialise Mimics 21.0 and Materialise 3 Matic 13.0) to generate a 3D model. The Jig was printed by the FDM machine in ABS material and sterilised. Incision was made through standard ilioinguinal approach and tumour was visualised. Soft tissue was dissected over the posterior aspect of the Ilium for the placement of the jig and then fixed with k wire, following which osteotomy was done. Results Postoperatively the patient had no complications. At final follow up of 4 years, the patient was independently ambulant. Post op x-ray showed no signs of tumour recurrence at the operated site. Conclusions This case highlights the importance of preoperative planning and the use of modern technology in surgical resection. Customised 3D printed jigs help surgeons achieve good resections with R0 margins.

Advances in Management of Osteoid Osteoma by Radiofrequency Ablation

Background Osteoid Osteoma is a benign painful skeletal neoplasm which is usually smaller than 1.5 cm. Surgery has been considered its standard treatment, currently, Percutaneous CT-guided Radiofrequency Ablation is proved to be the treatment of choice in such cases. Objective To evaluate the effectiveness of CT-guided radiofrequency ablation for the treatment of spinal and non-spinal osteoid osteomas, technical requirements needed for safe radiofrequency ablation and recent advances in this respect. Patients and Methods This study is a retrospective study conducted on patients with osteoid osteoma who underwent Radiofrequency ablation from January 2019 till July 2020 at Ain Shams University Hospitals, Maadi Military Hospital and El Galaa Military Hospital, followed by postprocedure computed tomography (CT) follow up. Results Location, calcification of the nidus, coagulation time, lesion size, and previous treatment are dependent risk factors compared regarding outcome. Conclusion We concluded that CT-guided RFA is a feasible, safe, and effective treatment for spinal and extra-spinal osteoid osteoma and is easily repeatable after unsuccessful treatment. Surgery should be reserved for lesions causing nerve root compression in spinal lesions.

Limb Salvage Strategy Amendment for a Better Future in the Era of Bone Cancer Therapy: A Cross-Sectional Study in North India.

Bone tumors remain a formidable challenge for orthopedic surgeons. In developing countries, the challenge is exacerbated by limited diagnostic, therapeutic, and management facilitiesand ignorance. Patients with upper and lower-extremity muscle and skeletal tumors are candidates for amputation or surgical rescue of the limbs. Traditionally, limb rescue surgery by neo-adjuvant chemotherapy is the preferred surgery method for localized carcinoma. Amputations are usually reserved for patients with increased tumor size. The purpose of this study is to investigate health-related quality of life (HRQOL) and physical disability, focusing on surgical care, gender, and age, in adolescent and young adult survivors of malignant bone tumors treated surgically. This cross-sectional study consists of 38 long-term survivors who underwent amputation or limb-salvage surgery at King George's Medical University, Lucknow, from 2019 to 2022. After obtaining ethical clearance and informed consent, 38 patients which included 26 patients treated with limb salvage in Group A and 12 patients treated with amputation in Group B were included in the study. The SF-36 and HUI3 scores were used to assess the functional outcome and health-related QoL of these patients. After minimal six months of interventions, we have found a significant improvement in all the following factors: physical functioning (P=0.000), role limitations due to physical health (P=0.000) and emotional problems (P=0.001), energy/fatigue (P=0.000), emotional well-being (P=0.000), social functioning (P=0.000), pain (P=0.000), and general health (P=0.000). Group A showed a higher degree of significance than Group B through SF-36 (Short Form-36, patient-reported outcome), whereasHUI-3 did not show any significant outcomes (P=0.347). The overall quality of life of patients with salvaged limbs appears to be higher than that of the quality of life of amputee patients in tumor survivor patients. Further analyses must be carried out to verify the results and focus on areas that have a major impact on the overall quality of life using other assessmenttools. The impact of therapy on the quality of life depends on maintaining the necessary structures for functional functions, adjusting patient expectations to cancer treatments, and designing long-term rehabilitation programs to support functional functions.

Bisphosphonate treatment as a safe choice for treating lung metastases of recurrent giant cell tumor of bone

Giant cell tumor (GCT) accounts for 5% of all primary bone tumors and 20% of benign skeletal tumors. This case report presents the case of a 17-year-old female with a recurrent giant cell tumor and lung metastases. The patient received bisphosphonate therapy instead of surgery. The use of zoledronic acid for lung metastases from GCT may have conservatively improved clinical symptoms and radiological assessments can be achieved.

The role of myokines in cancer: crosstalk between skeletal muscle and tumor

Loss of skeletal muscle mass is a primary feature of sarcopenia and cancer cachexia. In cancer patients, tumor-derived inflammatory factors promote muscle atrophy via tumor-to-muscle effects, which is closely associated with poor prognosis. During the past decade, skeletal muscle has been considered to function as an autocrine, paracrine, and endocrine organ by releasing numerous myokines. The circulating myokines can modulate pathophysiology in the other organs, as well as in the tumor microenvironment, suggesting myokines function as muscleto-tumor signaling molecules. Here, we highlight the roles of myokines in tumorigenesis, particularly in terms of crosstalk between skeletal muscle and tumor. Better understanding of tumor-to-muscle and muscle-to-tumor effects will shed light on novel strategies for the diagnosis and treatment of cancer.

Symptomatic Neuroma Development following En Bloc Resection of Skeletal and Soft-Tissue Tumors: A Retrospective Analysis of 331 Cases.

Although symptomatic neuroma formation has been described in other patient populations, these data have not been studied in patients undergoing resection of musculoskeletal tumors. This study aimed to characterize the incidence and risk factors of symptomatic neuroma formation following en bloc resection in this population. The authors retrospectively reviewed adults undergoing en bloc resections for musculoskeletal tumors at a high-volume sarcoma center from 2014 to 2019. The authors included en bloc resections for an oncologic indication and excluded non-en bloc resections, primary amputations, and patients with insufficient follow-up. Data are provided as descriptive statistics, and multivariable regression modeling was performed. The authors included 231 patients undergoing 331 en bloc resections (female, 46%; mean age, 52 years). Nerve transection was documented in 87 resections (26%). There were 81 symptomatic neuromas (25%) meeting criteria of Tinel sign or pain on examination and neuropathy in the distribution of suspected nerve injury. Factors associated with symptomatic neuroma formation included age 18 to 39 [adjusted OR (aOR), 3.6; 95% CI, 1.5 to 8.4; P < 0.01] and 40 to 64 (aOR, 2.2; 95% CI, 1.1 to 4.6; P = 0.04), multiple resections (aOR, 3.2; 95% CI, 1.7 to 5.9; P < 0.001), preoperative neuromodulator requirement (aOR, 2.7; 95% CI, 1.2 to 6.0; P = 0.01), and resection of fascia or muscle (aOR, 0.5; 95% CI, 0.3 to 1.0; P = 0.045). The authors' results highlight the importance of adequate preoperative optimization of pain control and intraoperative prophylaxis for neuroma prevention following en bloc resection of tumors, particularly for younger patients with a recurrent tumor burden. Risk, III.

44. Symptomatic Neuroma Formation following Skeletal and Soft Tissue Tumor Resection

PURPOSE: While symptomatic neuroma formation has been described in other patient populations, these data have not been studied in patients undergoing resection of musculoskeletal tumors. This study aims to characterize the incidence and risk factors of symptomatic neuroma formation following en bloc resection in this population. METHODS: We retrospectively reviewed adults undergoing en bloc resections for musculoskeletal tumors at a high-volume sarcoma center from 2014-2019. We included en bloc resections for an oncologic indication and excluded non-en bloc resections, primary amputations, and patients with insufficient follow-up. Data are provided as descriptive statistics and multivariable regression modeling was performed. RESULTS: We included 231 patients undergoing 331 en bloc resections (46% female; mean age 52 years). Nerve transection was documented in 87 resections (26%). There were 81 symptomatic neuromas (25%) meeting criteria of Tinel sign or pain on exam and neuropathy in the distribution of suspected nerve injury. Factors associated with symptomatic neuroma formation included age 18-39 (aOR, 3.6; 95% CI, 1.5-8.4; p < 0.01) and 40-64 (aOR, 2.2; 95% CI, 1.1-4.6; p = 0.04), multiple resections (aOR, 3.2; 95% CI, 1.7-5.9; p < 0.001), preoperative neuromodulator requirement (aOR, 2.7; 95% CI 1.2-6.0; p = 0.01) and resection of fascia or muscle (aOR, 0.5; 95% CI, 0.3-1.0; p = 0.045). CONCLUSION: Our results highlight the importance of adequate preoperative optimization of pain control and intraoperative prophylaxis for neuroma prevention following en bloc resection of tumors, particularly for younger patients with a recurrent tumor burden.

Safety and effectiveness of continuous denosumab for unresectable or advanced giant cell tumor

Introduction. Giant cell tumor of bone is a relatively rare, locally aggressive osteolytic skeletal neoplasm with uncertain behavior: recurrence rates up to 70 % and distant metastases occur 2–6 % of cases. Nowadays denosumab is the choice of therapy for patients with unresectable or advanced disease. However, the efficiency, duration or administration and most of all safety of continuous denosumab are not established.Materials and methods. Fourty advanced or unresectable giant cell tumor cases were observed from 2005 till 2020 in N.N. Blokhin National Medical Research Center of Oncology. The average age of pts was 33,6 ± 13,1 years (18–64), and the women and men ratio was about 2,1 : 1. The most commonly affected sites were long bones of the lower extremities (22,5 %), sacrum (22,5 %), long bones of the upper extremities (17,5 %), spine (17,5 %), pelvis (10 %) and others. 70 % of cases were anatomically compounded due to tumor localization and 27,5 % of cases were primary disease. 37,5 % of cases were with pulmonary metastases. Patients underwent computed tomography / magnetic resonance imaging every 3 months during the first three years and then once every six months. Patient received subcutaneous denosumab 120 mg every 4 weeks with a loading dose of 120 mg subcutaneous on study days 8 and 15. After 2 years monthly therapy and confirmed stabilization effect patient then received maintenance therapy: once in three months injection. All patients received daily calcium and vitamin D supplement.Results. Median follow-up was 52,8 ± 41,3 months (3–219 months). The average denosumab injections were 25 ± 16 (4–85). Clinical and radiographically stabilization of the effect occurred on average at 12 ± 8 (4–32) injections. Hypocalcemia was registered in one case (2.5 %). There was significant improvement of Karnofsky scale, Visual analogue scale (VAS) and Watkins scale (p &lt;0.001). 5-year progression-free survival for was 70.1 % (95 % confidence interval 55.7–88.0), the median was not reached. Progression of disease was observed only in subgroup with violations in denosumab administration or its cancellation (32,5 %). 3-year progression-free survival in subgroup with violations in denosumab administration or its cancellation was 10 % (95 % confidence interval 15.5–64.1). In subgroup with continuous denosumab and once in three months injection after 2 years monthly therapy there was no signs of progression.Conclusions. In this study we showed evidence of safety and effectiveness of continuous denosumab for unresectable or advanced giant cell tumor even with once in three months injection therapy. Denosumab for advanced giant cell tumor of bone became a choice of treatment, but we need further investigation for observation long term denosumab effectiveness and complications.

The CDK4/6 Inhibitor Palbociclib Inhibits Estrogen-Positive and Triple Negative Breast Cancer Bone Metastasis In Vivo

CDK 4/6 inhibitors have demonstrated significant improved survival for patients with estrogen receptor (ER) positive breast cancer (BC). However, the ability of these promising agents to inhibit bone metastasis from either ER+ve or triple negative BC (TNBC) remains to be established. We therefore investigated the effects of the CDK 4/6 inhibitor, palbociclib, using in vivo models of breast cancer bone metastasis. In an ER+ve T47D model of spontaneous breast cancer metastasis from the mammary fat pad to bone, primary tumour growth and the number of hind limb skeletal tumours were significantly lower in palbociclib treated animals compared to vehicle controls. In the TNBC MDA-MB-231 model of metastatic outgrowth in bone (intracardiac route), continuous palbociclib treatment significantly inhibited tumour growth in bone compared to vehicle. When a 7-day break was introduced after 28 days (mimicking the clinical schedule), tumour growth resumed and was not inhibited by a second cycle of palbociclib, either alone or when combined with the bone-targeted agent, zoledronic acid (Zol), or a CDK7 inhibitor. Downstream phosphoprotein analysis of the MAPK pathway identified a number of phosphoproteins, such as p38, that may contribute to drug-insensitive tumour growth. These data encourage further investigation of targeting alternative pathways in CDK 4/6-insensitive tumour growth.