Metastatic Bone Lesions Research Articles

Long-term oncological results of patients with primary and metastatic tumors of the musculoskeletal system who underwent arthroplasty

Introduction. Primary malignant tumors of the skeletal system mostly develop in young and middle-aged people. Morbidity in this age group amounts to between 75 and 80 % of overall morbidity. Due to low survival caused by patient death in the first 5 years mostly because of metastases of primary malignant tumors, the main focus of treatment was on prolongation of life, study and development of new methods of conservative therapy. Therefore, until the early 1970 amputation surgery was the generally accepted standard of surgical intervention. Positive oncological results required revision of the surgical concept of treatment in this patient group. This problem was solved through active development of oncological endoprosthesis started in the second half of the 1970s and led to shaping of orthopedic oncology into a separate oncological specialty. The study objective is to study long-term oncological results of treatment of patients with primary and metastatic tumors of the locomotor system after oncological endoprosthesis.Materials and methods. The study included 1292 patients with primary sarcomas of the bones, soft tissues and patients with metastatic and benign bone tumors who underwent 1200 bone resections/extirpations of varying scale with endoprosthetic replacement between January of 1992 and January of 2020. In the total group of patients who underwent endoprosthesis, the number of men and women was approximately the same: 677 (52.4 %) and 615 (47.6 %), respectively. At the time of surgery, age of the patients in the total group varied between 10 and 81 years. Mean patient age was 34.7 years. Most commonly, endoprosthetic replacement was performed in patients between the ages of 21 and 30 years (in 29 % of cases). Oncological endoprosthesic replacement was performed in 814 (67.8 %) patients with primary malignant tumors, 143 (11.9 %) patients with metastatic lesions in long bones, and 243 (20.3 %) patients with benign neoplasms. Mean follow-up period after endoprosthesis of different bone segments was 82.8 months (between 0 and 335.7 months).Results. In 27 years of observations, total frequency of recurrences after endoprosthesis for various tumor locations (type V complication per the International Society of Limb Salvage system (2013) (ISOLS 2013)) was 8.8 % (86/979); among them recurrence in the bone (type VA complication) was observed in 1.7 % (17/979) of cases, recurrence in the soft tissues (type VB complication) in 7.0 % (69/979) of cases. Primary endoprosthetic replacement due to recurrence after previous surgical treatment leads to 2.2-time increase in the risk of development of this complication. The obtained results show that repeat recurrence significantly increases the risk of recurrence in soft tissues and does not affect the risk of recurrence in the bone. The most recurrences developed in patients with non-differentiated pleomorphic sarcoma (15.4 % of cases), chondrosarcoma (15.0 % of cases) and parosteal osteosarcoma (14.3 % of cases). Frequency of recurrences in patients with giant cell bone tumors and aneurysmal bone cysts was 4.0 and 3.8 %, respectively. In cases of tumor recurrence after endoprosthesis, limb amputation was the most common treatment: 33.7 % (28/83) of cases. In this study, recurrence mostly developed after femur resection with knee joint endoprosthesis: in 45.8 % (38/83) of cases. Frequency of oncological complications in patients with bone sarcomas who underwent endoprosthetic replacement was 31.9 % (283/886). In the total patient group in 27 years of observations, in 25.3 % (224/886) of patients disease progression in the form of metastases was observed. Local tumor recurrence was accompanied by metastases in 6.7 % (59/886) of cases.Conclusion. Decreased risk of development of local recurrences depends on the effectiveness of complex approach to therapy in this disease group. Changes in surgical endoprosthesis techniques in tumors of varying differentiation levels allowed to achieve significant radicalness of treatment. Progression risk for bone sarcomas, level of response to specialized therapy and, as a result, patient’s prognosis depend on the presence of epigenetic, genetic, molecular and chromosomal abnormalities.

PP122 Magnetic Resonance-guided High-intensity Focused Ultrasound For Non-surgical Treatment Of Prostate Cancer, Uterine Fibroids, Adenomyosis And Pain In Bone Metastases

IntroductionMagnetic resonance imaging guided high-intensity focused ultrasound (MR-HIFU) is a non-invasive technique with a low risk of complications for the patient and few side effects. Integration with MRI allows monitoring of the temperature regime of thermal doses, which protects important structures from overheating, and at the same time directing a high thermal dose to the target tissue.MR-HIFU in the treatment of uterine fibroids, prostate cancer and the treatment of pain in bone metastases is compared with both traditional methods of treatment (uterine artery embolization, hysterectomy, prostatectomy, etc.).MethodsTo assess the clinical effectiveness and safety of non-invasive MR-HIFU, a literature search was performed in the MEDLINE database using the following keywords:“MRgFUS” “MR-HIFU”. The following filters were used: (i) article type: meta-analysis, systematic review, guidance; (ii) date of publication: no later than 5 years (from 2016).ResultsAccording to the search terms, 104 publications were submitted to MEDLINE for keywords. After using filters, 57 publications were identified to familiarize themselves with research abstracts. The analysis included six publications according to PICO criteria.The use of non-invasive MR-HIFU therapy for the treatment of uterine fibroids, prostate cancer and various forms of metastatic bone lesions does not have convincing evidence of advantages over standard treatment methods (surgical resection, embolization, etc.) and may be used only as an alternative technique or in addition to standard therapy.ConclusionsDespite some advantages of the MR-HIFU technology, it is experimental and should only be used as an alternative to surgical treatment. Convincing evidence of the efficacy of MR-HIFU treatment in meta-analyses, systematic reviews, and randomized controlled trials has not yet been published.

ODP085 Denosumab Induced Severe Hypophosphatemia

Abstract Introduction Denosumab is a receptor activator of nuclear factor kappa-B (RANK) ligand inhibitor used for treatment of osteoporosis and bone metastases in patients with solid tumors. Denosumab induced hypophosphatemia has been reported in less than 1% of patients, and in most cases described as mild to moderate in severity. We present a case of severe hypophosphatemia after denosumab treatment for diffuse bone metastases due to prostate cancer. Case report A 78-year-old male patient with history of diffuse bone metastases due to prostate cancer, schizophrenia on treatment and intermittent alcohol use, presented to the hospital with suicidal ideation and worsening fatigue. Patient was found to have a phosphorus levels of <1. 0 mg/dL (2.5-4.6 mg/dL), corrected calcium of 8.2 mg/dL (8.4-10.5 mg/dl), vitamin D 25 OH of 36.34 ng/mL (30-100 ng/mL), magnesium of 2.3 mg/dL (1.7-2.5 mg/dL), parathyroid hormone (iPTH) level of 379 pg/mL (10-65pg/mL) and serum creatinine of 1.1 mg/dL (0.5-1.2 mg/dL). Urinary studies showed 24 hour urinary phosphate 1282 mg/24h (360-1600 mg/24h), urine creatinine 1570 mg/24h (500-2150 mg/24h). There was no evidence of acidosis, chronic kidney disease, preexisting osteomalacia or vitamin D deficiency. The patient had no recent alcohol consumption and his alcohol level was undetectable. After reviewing the outside medical records it was noted that the patient had received denosumab 120 mg, 11 days prior to the hospital admission, as part of the management of bone metastases due to prostate cancer. The patient's baseline phosphorus prior to denosumab was in the low normal range. The severe hypophosphatemia and secondary hyperparathyroidism were attributed to denosumab administration. Patient was initially treated with intravenous phosphate and then transitioned to oral phosphate along with elemental calcium and calcitriol during the course of his hospitalization. Patient's phosphorus improved to 2.3 mg/dL by the time of discharge. Discussion In patients treated with denosumab, the primary concern is potential post-treatment hypocalcemia, however, our case brings attention to severe hypophosphatemia as a serious side effect to treatment with denosumab. Multiple specialties are involved in the treatment of osteoporosis and metastatic bone lesions, and each should be aware that denosumab can lead to lower serum phosphate levels due to its effects on bone resorption and reduction of proximal tubular reabsorption of the phosphate resulting in clinical symptoms of muscle weakness, bone pain, fractures and even stupor, coma and death. We therefore conclude that monitoring phosphate levels should be part of the pre- and post-treatment evaluation in patients who are candidates for treatment with denosumab, particularly high-dose denosumab. Presentation: No date and time listed

О ЦЕЛЕСООБРАЗНОСТИ ПРОВЕДЕНИЯ ПОВТОРНОЙ РАДИОТЕРАПИИ ПРИ РЕЦИДИВАХ И ПРОДОЛЖЕННОМ РОСТЕ РАНЕЕ ОБЛУЧЕННЫХ ОПУХОЛЕЙ РАЗЛИЧНОЙ ЛОКАЛИЗАЦИИ

Introduction: The development of a recurrence or a second tumor in previously irradiated patients requires, in some cases, repeated radiotherapy (reirradiation) of the previously irradiated tissue volume. In the past decades, it was widely believed that it was possible to irradiate one anatomical zone in curative doses only once (taking into account the tolerance of healthy tissues) and the issue of repeated irradiation was practically not discussed (there are only a few studies). This approach was due to the fact that the use of old technologies did not allow sufficient protection of healthy tissues surrounding the tumor, which led to severe complications. Due to the development of radiotherapy technologies and new advances in radiobiology, the number of studies on the re-irradiation of recurrent tumors has recently increased significantly, however, they are mainly retrospective in nature and do not have a sufficient evidence compared to indications for primary radiotherapy. However, reirradiation can be used not only for palliative purposes, but also to achieve long-term local control. Modern medical approaches and technical capabilities make it possible to re-irradiate tumors of any localization, up to the second curative dose. Purpose: To investigate the expediency of repeated irradiation of patients with different tumor localizations, taking into account the survival rates of patients, possible complications and subsequent quality of life. Materials and methods: For the first time in Armenia, an analysis of the results of reirradiation is carried out on the basis of the experience of one clinic. The results of treatment of 1300 patients, who received radiotherapy at the IRA MEDICAL Group Radiotherapy Center from March 2019 to March 2022 were studied. The study included 52 patients, who received the second course of RT, which accounted for 4% of the total number of patients. The median age of patients was 60.5 years (22 - 81), including 22 men, 30 women, based on pathologies: CNS tumors - 17 patients, brain metastasis - 10, gynecology - 6, head and neck tumors - 6, metastatic skeletal bone lesions - 4, breast cancer - 3, other localizations - 6. Stage of the disease: III - 7 patients, IV - 37, unclassified - 8. The mean interval between two courses of radiotherapy was 34.5 months (1.5 - 252). The median total equivalent dose from two irradiation courses is 99 Gy (56-121). Except of the patients, who received reirradiation for metastatic relapse, the total equivalent dose was 102 Gy (84–121), and the median follow-up time after reirradiation was 9 months (4–29.5). Results: The average life expectancy of patients, who died during the observation period was 6.5 months (1-23). In 7 out of 52 patients, who initially had low KPS (60%), survival was up to 3.5 months or less. After excluding these patients from further statistical analysis, the median survival of the remaining patients was 10 months (4 – 23). As of March 31, 2022, 31 patients (59.6%) are alive, with an average follow-up of 13 months (5 – 29.5). The number of post-radiation complications and the quality of life of patients were also assessed. There were no treatment related deaths or reduced quality of life in the early stages. The results of this prospective study demonstrate that the use of the latest technologies in repeat radiotherapy can improve survival and quality of life in these patients. Thanks to new technologies, it is possible to conduct a repeated course of radiotherapy even in curative doses. When planning the second therapeutic or palliative course of radiotherapy, it is necessary to carefully select patients, taking into account a number of factors related to the previous treatment and the individual characteristics of the patient. After completion of the study, we plan to create recommendations on the criteria for selecting candidates for re-irradiation.

Semi-supervised segmentation of metastasis lesions in bone scan images.

To develop a deep image segmentation model that automatically identifies and delineates lesions of skeletal metastasis in bone scan images, facilitating clinical diagnosis of lung cancer-caused bone metastasis by nuclear medicine physicians. A semi-supervised segmentation model is proposed, comprising the feature extraction subtask and pixel classification subtask. During the feature extraction stage, cascaded layers which include the dilated residual convolution, inception connection, and feature aggregation learn the hierarchal representations of low-resolution bone scan images. During the pixel classification stage, each pixel is first classified into categories in a semi-supervised manner, and the boundary of pixels belonging to an individual lesion is then delineated using a closed curve. Experimental evaluation conducted on 2,280 augmented samples (112 original images) demonstrates that the proposed model performs well for automated segmentation of metastasis lesions, with a score of 0.692 for DSC if the model is trained using 37% of the labeled samples. The self-defined semi-supervised segmentation model can be utilized as an automated clinical tool to detect and delineate metastasis lesions in bone scan images, using only a few manually labeled image samples. Nuclear medicine physicians need only attend to those segmented lesions while ignoring the background when they diagnose bone metastasis using low-resolution images. More images of patients from multiple centers are typically needed to further improve the scalability and performance of the model via mitigating the impacts of variability in size, shape, and intensity of bone metastasis lesions.

Efficacy of SBRT in High Volume Metastatic Carcinoma Breast – A Berry Picking Approach in the Era of High Precision Radiotherapy

<h3>Purpose/Objective(s)</h3> Treatment of metastatic breast cancer is always challenging. Management mainly involves chemotherapy, targeted therapy and immunotherapy. Though novel conformal techniques have evolved in the field of radiotherapy, the same has not been optimally tried in metastatic carcinoma breast patients except for low burden oligometastatic disease. Systemic therapy has been the cornerstone of management till date. In the present study we evaluate the role of SABR in high volume metastatic breast carcinoma in regards with efficacy and feasibility. <h3>Materials/Methods</h3> 47 patients with biopsy proven carcinoma breast were prospectively analyzed (age > 18 years, ECOG ≤2). SBRT was delivered to metastatic lesions in brain, liver, lung, bone and adrenal. Median dose of 30 Gy (25 to 35) in 3 to 5 sessions. PETCT based planning was done in all patients. Robotic assisted SABR was done using real time tumor tracking during treatment. All patients were continued on systemic therapy. Clinical outcomes were studied in regards with local control, overall and progression free survival. Survival analysis was performed using Kaplan-Meier method. <h3>Results</h3> 47 patients with metastatic carcinoma breast (median age: 51 years, range: 29 to 70 years) ER positive 60%, PR positive in 45%, HER2 over expression was seen in 25%, Triple negative (34%) were included in our study. All patients were treated with SBRT to a total of 103 metastatic sites, including brain (27%); bone (20.3%); lung (17.4%); lymph node (17.4%); liver (12.6%); and adrenal (4%) from the years 2009 - 2021. OS at the end of 1, 3 and 5 years was 78.37, 43.24 and 21.62 respectively. Local control (LC) - sitewise has been mentioned below. <h3>Conclusion</h3> SABR is feasible option in high volume metastatic carcinoma breast with good local control, improved survival and well tolerable approach and can be considered as an adjunct to systemic therapy. Further randomized trials are needed to validate the same.

S3016 Hepatocellular Carcinoma as an Uncommon Cause of PTHrP-Mediated Hypercalcemia

Introduction: Humoral hypercalcemia of malignancy driven by PTHrP is a syndrome frequently associated with squamous cell carcinoma. We present a case of humoral hypercalcemia as a rare manifestation of hepatocellular carcinoma and describe the impact of early diagnosis on patient care. Case Description/Methods: A 67-year-old male with HCC presented to the emergency department with subacute confusion, constipation, and lower extremity weakness. Physical exam revealed tangential thinking and no asterixis. Serum calcium was 14.8 (corrected to 15.3), creatinine 1.36 (baseline 0.8), AST 141, ALT 32, and AFP 135 (all previously normal). Imaging revealed new liver lesions in multiple segments, enlarged lymph nodes in the porta hepatis, widespread lytic lesions in the spine, calvarium, and facial bones with a 3.4 cm x 2.4 cm left orbital wall mass consistent with metastatic disease. Serum calcium levels normalized with IV fluids, calcitonin, and zolendronic acid. The PTHrP was elevated at 79. Vitamin D levels, SPEP and UPEP were normal. He returned one week later with recurrent severe hypercalcemia. No further cancer treatment options were available so the patient elected for hospice services and died at home. Discussion: Malignancy is the most common cause of hypercalcemia in the inpatient setting. Malignancy-associated hypercalcemia occurs through three distinct mechanisms – humoral (PTHrP mediated), lytic bone lesions, and increased absorption due to excess 1,25 vitamin D production by the cancer. Most cases of HCC-associated hypercalcemia are due to metastatic lytic bone lesions. Less than 10% of cases are attributable to PTHrP, which is severe and often refractory. The mechanism for this is unknown but may be related to an underlying paraneoplastic syndrome and downstream metabolic derangements. Humoral hypercalcemia in patients with HCC is associated with a more advanced TNM stage and higher tumor burden. In a study of 534 patients with HCC, 6.3% had humoral hypercalcemia and had worse prognoses by Child-Pugh scores. Another study of 165 patients with HCC and PTHrP-mediated hypercalcemia found a median survival time of 15 days. Early recognition of humoral hypercalcemia in patients with HCC is essential given its association with higher mortality. Doing so can help providers expedite locoregional therapy or guide goals of care discussions with their patients.

Factors Associated with Revision Surgery in Long Bones Metastases

Background. Bones as an organ are one of the most common targets for tumor metastasis. Currently, the number of patients undergoing surgical treatment for metastatic bone lesions is steadily increasing. In most patients, after surgical treatment, the manifestation of clinical symptoms decreases, primarily pain syndrome, which improves their quality of life. However, it should be noted that the number of patients with bone metastases who underwent revision surgery is also increasing. This article retrospectively analyzes the factors leading to revision after surgical treatment of metastases in long bones.&#x0D; The aim of this study was to identify factors leading to revision after surgical treatment of patients with metastases in long bones.&#x0D; Methods. A retrospective medical records analysis of 247 patients who underwent surgical treatment for metastases in long bones on the basis of the P.A. Herzen Moscow Research Institute of Oncology in 20062020 was performed. Of these, 33 patients underwent revision surgery. The median age was 62 years. The localization of the primary tumor was as follows: breast cancer 10 cases, kidney cancer 13, lung cancer 3, prostate cancer 2, rectal cancer 3, liver cancer and Ewings sarcoma with bone metastases 1 case each.&#x0D; Results. The following factors led to revision surgery: mistakes in preoperative diagnosis (3 patients); postoperative infectious complication (6 patients); dislocation of the endoprosthesis (4 patients); continued growth of solitary metastasis after osteosynthesis (5 cases); aseptic instability after intramedullary osteosynthesis (14 patients); traumatic fracture of the endoprosthesis stem (1 patient).&#x0D; Conclusions. Revision after surgical treatment of metastases in long bones, in addition to postoperative complications, lead to mistakes in diagnosis and incorrect choice of surgical treatment method. To reduce the risk of revision surgical interventions, a multidisciplinary approach is needed with the development of surgical treatment tactics in consultation and the use of specialized scales of oncological prognosis.

The value of 18F-NaF PET/CT in the diagnosis of bone metastases in patients with nasopharyngeal carcinoma using visual and quantitative analyses.

To assess the diagnostic value of 18F-NaF PET/CT in diagnosing bone metastases in patients with nasopharyngeal carcinoma (NPC) using visual and quantitative analyses. 164 patients with NPC who underwent 18F-NaF PET/CT between 2017 and 2021 were included. The sensitivity, specificity, and accuracy were calculated. All bone lesions were divided into metastatic bone lesion group and benign lesion group; the benign lesion group was further subdivided into benign lesion without osteophyte and fracture group (CT images showing no osteophyte, no fracture), and benign lesion with osteophyte and fracture group (CT images showing typical osteophytes and fractures), the differences in maximum standardized uptake value (SUVmax) were compared between every two groups, and the diagnostic cut-off values were derived from receiver operating characteristic curves (ROC). Quantitative data were expressed as mean ± SD, multiple continuous variables were compared using one-way analysis of variance (ANOVA), and multiple comparisons among more than two groups were made using the Bonferroni method. The sensitivity, specificity, and overall accuracy of 18F-NaF PET/CT for the diagnosis of bone metastases in NPC were 97.1%, 94.6%, and 95.1% based on the patient level and 99.5%, 91.5%, and 96.4% based on the lesion level, respectively. The SUVmax was significantly different between the metastatic bone lesion group and the benign lesion without osteophyte and fracture group (p < 0.05); the area under the curve was 0.865, the threshold was 12.5, the sensitivity was 0.912, and the specificity was 0.656. Visual analysis of 18F-NaF PET/CT has high sensitivity and specificity for diagnosing bone metastases in NPC. After excluding osteophytes and fracture lesions based on CT findings, using SUVmax ≥12.5 as the threshold can be an important reference for the differential diagnosis of bone metastases and benign bone lesions in patients with NPC.

INTER- AND INTRA-OBSERVER RELIABILITY OF THE MIRELS’ SCORING SYSTEM FOR THE DETERMINATION OF PATHOLOGICAL FRACTURE RISK IN METASTATIC BONE LESIONS AMONG ORTHOPEDIC SURGEONS WITH DIFFERENT LEVELS OF EXPERTISE

Objective: To assess inter- and intra-observer reliability of Mirels scoring for the determination of pathological fracture risk in metastatic bone lesions of 30 patients among six different levels of experienced orthopedic surgeons who were trained in the same university clinic. Material and Methods: Thirty patients were randomly selected from oncology unit consultations. Six observers were selected in accordance to their orthopedic experience. Mirels parameters except pain were evaluated by observers on two different times without the observers being aware of each other. Results: The Fleiss’ Kappa values were detected as κ=0.21, p&lt;0.0001, and κ=0.15, p&lt;0.0001 by inter-observers at the first and second observational points, respectively. The Kappa values were in perfect (κ=0.95), fair (κ=0.27) and fair (κ=0.10) agreements for the region, size and type of the metastatic involvement by inter-observers at the first observational point. The same parameters had similiar scores as κ=0.83, κ=0.13 and κ=0.28 for region, size and type for the second observation. Fair (κ=0.333), moderate (κ=0.413), fair (κ=0.225), slight (κ=0.035), fair (κ=0.369 and poor (κ=0.030) evidence of agreements were detected in the comparison of the first and second observations for total scores in seniority order. Conclusions: Kappa analysis showed perfect agreement for region, but slight to fair for size and type. There was a significant difference in overall scores across experience levels for the most and least experienced observers. A new rating system with revised parameters may be required to predict impending fractures.

Recent topics of the clinical utility of PET/MRI in oncology and neuroscience.

Since the inline positron emission tomography (PET)/magnetic resonance imaging (MRI) system appeared in clinical, more than a decade has passed. In this article, we have reviewed recently-published articles about PET/MRI. There have been articles about staging in rectal and breast cancers by PET/MRI using fluorodeoxyglucose (FDG) with higher diagnostic performance in oncology. Assessing possible metastatic bone lesions is considered a proper target by FDG PET/MRI. Other than FDG, PET/MRI with prostate specific membrane antigen (PSMA)-targeted tracers or fibroblast activation protein inhibitor have been reported. Especially, PSMA PET/MRI has been reported to be a promising tool for determining appropriate sites in biopsy. Independent of tracers, the clinical application of artificial intelligence (AI) for images obtained by PET/MRI is one of the current topics in this field, suggesting clinical usefulness for differentiating breast lesions or grading prostate cancer. In addition, AI has been reported to be helpful for noise reduction for reconstructing images, which would be promising for reducing radiation exposure. Furthermore, PET/MRI has a clinical role in neuroscience, including localization of the epileptogenic zone. PET/MRI with new PET tracers could be useful for differentiation among neurological disorders. Clinical applications of integrated PET/MRI in various fields are expected to be reported in the future.

Retinoic Acid Receptor Activation Reduces Metastatic Prostate Cancer Bone Lesions by Blocking the Endothelial-to-Osteoblast Transition.

This study provides mechanistic insights into how RAR agonists suppress prostate cancer-induced bone formation and offers a rationale for developing RAR agonists for prostate cancer bone metastasis therapy. See related commentary by Bhowmick and Bhowmick, p. 2975.

GL2-5 Criteria for treatment efficacy, analgesics, RI therapy, rehabilitation, and nursing

How to determine the effect of pharmacotherapy and radiotherapy on bone metastases is an important issue. Bone metastatic lesions are often not measurable, and RECIST ver 1.1 is often not applicable. In this revised guideline, attempts to determine the efficacy of whole-body diffusion-weighted MRI and FDG-PET/CT are introduced. As palliative therapy for pain associated with bone metastasis, non-opioid analgesics (NSAIDs and acetaminophen) and opioid analgesics have been established as standard treatments and are listed as BQ (Background Question).

STERNUM TUMOR SURGICAL TREATMENT METHOD: A CLINICAL CASE

Relevance: Sarcomas are relatively rare tumors. They make up 1% of all malignant neoplasms in adults, of which about 10-15% appear in the chest wall. Unlike primary tumors, metastatic bone tumors occur 2-4 times more often, while the sternum is affected in 9% of&#x0D; all metastatic bone lesions. A review of the literature and analysis of patients with chest wall tumors showed that surgical treatment might&#x0D; be the best option for primary and secondary chest wall tumors.&#x0D; Chondrosarcoma is the most common primary chest bone sarcoma and originates from the anterior segment of the ribs, less often from&#x0D; the sternum, scapula, or clavicle.&#x0D; The study aimed to present the outcome of a sternum sarcoma surgical treatment with a simultaneous reconstruction of an extensive&#x0D; postoperative defect at the Kazakh Institute of Oncology and Radiology (Almaty, Kazakhstan).&#x0D; Methods: The article reviews the literature on the treatment of chest wall tumors and describes a clinical case of a patient with&#x0D; chondrosarcoma of the sternum. After subtotal resection of the sternum 2-3 cm away from the tumor margins, the patient underwent&#x0D; reconstructive plastic surgery. Synthetic material was used to stabilize the chest wall, prevent paradoxical breathing, and replace&#x0D; the defect.&#x0D; Results: No recurrence of the primary process was registered after radical removal of the sternum tumor with the simultaneous reconstruction of the defect with synthetic material. Given the prevalence of the tumor, intraoperative suturing of the subclavian vein was&#x0D; performed, which led to vein thrombosis in the postoperative period.&#x0D; Conclusions: Early recognition and radical removal with adequate margins are essential to successful sternum tumor treatment. Complete excision with broadly negative microscopic margins at the first operation is paramount since local recurrence increases the risk of&#x0D; systemic metastasis and death. Thus, standard guidelines are required to ensure the proper treatment of chest wall sarcomas.

STERNUM TUMOR SURGICAL TREATMENT METHOD: A CLINICAL CASE

Relevance: Sarcomas are relatively rare. They make up 1% of all malignant neoplasms in adults, of which about 10-15% appear in the chest&#x0D; wall. Unlike primary tumors, metastatic bone tumors occur 2-4 times more often, while the sternum is affected in 9% of all metastatic bone lesions.&#x0D; A review of the literature and analysis of patients with chest wall tumors showed that surgical treatment might be the best option for primary tumors&#x0D; and some secondary chest wall tumors.&#x0D; Chondrosarcoma (12%) is the most common primary chest bone sarcoma and originates from the anterior segment of the ribs, less often from&#x0D; the sternum, scapula, or clavicle.&#x0D; The purpose was to present the outcome of a sternum sarcoma surgical treatment with a simultaneous reconstruction of an extensive postoperative defect at the Kazakh Institute of Oncology and Radiology (Almaty, Kazakhstan).&#x0D; Methods: The article reviews the literature on the treatment of chest wall tumors and describes a clinical case of a patient with chondrosarcoma of the sternum. After subtotal resection of the sternum 2-3 cm away from the tumor margins, the patient underwent reconstructive plastic&#x0D; surgery. Synthetic material was used to stabilize the chest wall, prevent paradoxical breathing, and replace the defect.&#x0D; Result: No recurrence of the main process was registered after radical removal of the sternum tumor with the simultaneous reconstruction of&#x0D; the defect with synthetic material. Given the prevalence of the tumor, intraoperative suturing of the subclavian vein was performed, which led to&#x0D; vein thrombosis in the postoperative period.&#x0D; Conclusions: The key to successful sternum tumor treatment is early recognition and radical removal with adequate margins. Complete excision with broadly negative microscopic margins at the first operation is paramount since local recurrence increases the risk of systemic metastasis&#x0D; and death. Thus, standard guidelines are required to ensure chest wall sarcomas proper treatment.

Abstract 244: Limiting metastatic breast cancer progression by targeting MK2 stromal signaling

Abstract Breast cancer is now the most common cancer among women in the US and metastasis to distant organs is the major cause of death in these patients. Among metastatic sites, bone is the most frequent destination of breast cancer metastasis and once the disease is found in the bone, it is often refractory to standard therapy. In addition, bone metastasis is associated with significant skeletal related events that greatly impact quality of life. Thus, there is a significant need to develop novel therapies that extend survival and improve quality of life. Previously we found that MK2 inhibition (MK2i) limits metastatic growth by targeting the tumor stromal compartment. To determine which stromal cells are targeted by MK2i we isolated stromal cells from within a metastatic bone lesion and carried out single cell RNA sequencing (scRNA-Seq). Using this approach, we found numerous gene expression changes in both the immune (CD45+) and non-immune (CD45-) populations upon MK2i. Indeed, we found significant numbers of p16+ senescent fibroblasts were present inside the metastatic lesion. We also found vascular cancer-associated fibroblasts (vCAF) and matrix CAFs (mCAF) inside the metastatic lesion suggesting that CAFs are not limited to primary disease. Numerous changes in gene expression in CD45+ cells were also observed, and these changes are being used to identify viable immunotherapies to deploy in our model. Finally, we are using conditional MK2 mice to establish the cell type targeted by MK2i. Our data demonstrate that MK2i is as effective as chemotherapy at limiting metastatic progression and our approach to leverage the scRNA-Seq data may allow us to optimize MK2i therapy to improve patient outcomes and quality of life. Citation Format: Renata Ramalho Oliveira, Douglas V. Faget, Xianmin Luo, Jiayu Ye, Joseph B. Monahan, Sheila A. Stewart. Limiting metastatic breast cancer progression by targeting MK2 stromal signaling [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 244.

Abstract CT152: Phase I study of MT-6402, a novel engineered toxin body (ETB) targeting PD-L1, in patients with PD-L1 expressing advanced solid tumors

Abstract This is the first-in-human study of MT-6402, a unique, first-in-class potent PD-L1-targeted engineered toxin body (ETB) capable of direct killing of PD-L1 expressing cells via rapid PD-L1-mediated internalization of a fused Shiga-like toxin A subunit (SLTA) resulting in permanent ribosomal inactivation. MT-6402 also delivers an HLA-A*02 restricted pp65 cytomegalovirus (CMV) antigen into PD-L1 expressing tumor cells leading to MHC-I presentation to existing CMV-specific cytotoxic T cells (antigen seeding). MT-6402 functions by targeting tumor and inhibitory immune cells directly and altering tumor immunophenotype to re-direct antiviral cytotoxic T cells into the tumor microenvironment. MT-6402 shows picomolar cytotoxic activity across several PD-L1 expressing cancer cell lines and treatment of human PBMCs results in selective depletion of PD-L1 positive cells. MT-6402 was well tolerated in non-human primates at doses above those which induce pharmacodynamic (PD) effect (reduction of CD14+ monocytes) in humans. This first-in-human study in patients with PD-L1-expressing advanced solid tumors will employ a modified toxicity probability interval design to determine MTD and will then enroll additional subjects at the MTD, to further explore safety and efficacy and determine RP2D. Results of the first dose cohort (16 micrograms/kg) are presented. Six patients received MT-6402. A significant and sustained reduction in CD14+ monocytes starting in cycle 2 was observed in patients on therapy beyond one cycle and was maintained with each MT-6402 administration, indicating HLA-independent PD effect consistent with preclinical observations. One HLA-A*02 and CMV+ patient with osseous metastases from NSCLC showed marked CMV-specific T-cell extravasation at day 8 and serum cytokine signatures consistent with antigen dependent responses and T cell mobilizations, suggesting engagement of MT-6402 antigen seeding. This patient has reduced intensity of metastatic bone lesions with 3/4 lesions resolving; the remaining lesion showing reduced uptake. Two patients had cytokine elevations at day 15, manifested by transient (1-12h), grade 2 infusion-related reactions and grade 2 cytokine release syndrome, which were subsequently prevented by steroid premedication. These results describe a novel approach to checkpoint modulation, leveraging direct PD-L1 cell kill and antigen seeding technology by the ETB. The results support further dose escalation and hold promise for development of MT-6402 for solid tumors, including in the R/R setting. Citation Format: David R. Spigel, Eugene Ahn, Herbert L. Duvivier, Drew Rasco, Agnes Rethy, Chris Moore, Amy Yuet, Sandra Hankins, Swati Khanna, Joseph Dekker, Brian Van Tine. Phase I study of MT-6402, a novel engineered toxin body (ETB) targeting PD-L1, in patients with PD-L1 expressing advanced solid tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr CT152.

Is it sufficient to evaluate metastatic bone involvement in breast cancer using SPECT/CT? A new approach of SPECT/CT-guided targeted bone marrow biopsy

ObjectiveTo investigate the feasibility, safety, and clinical application value of single photon emission computed tomography/computed tomography (SPECT/CT)-guided bone marrow biopsy (BMB) in breast cancer (BC) patients with suspected bone metastases (BM) and compare its diagnostic performance for detection of BM with SPECT/CT.MethodsThe records of breast cancer patients referred for bone scintigraphy (BS), SPECT/CT and SPECT/CT-guided BMB from January of 2018 to June of 2021 in our hospital were retrospectively reviewed. 49 Patients were consecutively included in this study, all 49 specimens were analyzed by pathological and immunohistochemical studies.The biopsy success rate, total examination time, biopsy operation time, complications, CT radiation dose, and pathological and immunohistochemical results were recorded. The diagnostic performance based on SPECT/CT and SPECT/CT-guided BMB were compared with pathological, immunohistochemical examinations and the results of subsequent follow-up.ResultsBone samples of the sites with high uptake were obtained in all 49 patients under BMB. No severe postoperative complications occurred. Among all 49 cases, 34 specimens were positive for metastatic breast cancer (69%, 34/49), and positive for benign tissue in 15 cases (31%, 15/49). 1 case of 15 cases was subsequently diagnosed as metastatic breast cancer according to the follow-up result. SPECT/CT-guided BMB demonstrated significantly higher negative predictive value (NPV) when compared to SPECT/CT (p = 0.021 < 0.05). Patients with differential expression of ER, PR, and HER-2 between primary lesions and metastatic lesions accounted for 12, 17, and 5 cases, respectively, and the changing rates were 35.2% (12/34), 50% (17/34), and 14.7% (5/34), respectively. Molecular subtype changes occurred in 7 patients, accounting for 47% (16/34) of metastatic patients.ConclusionIt is insufficient to evaluate BM in BC patients using SPECT/CT imaging. SPECT/CT-guided BMB provided significantly higher sensitivity and NPV than SPECT/CT for detection of BM in BC patients. Our research redefines a new approach which can confirm diagnosis and potential molecular subtype changes for suspected bone metastatic lesions in BC patients, which can offer important opportunities for precision treatment and improved quality of life of BC patients with BM.

A Radiologists' Guide to En Bloc Resection of Primary Tumors in the Spine: What Does the Surgeon Want to Know?

En bloc resection in the spine is performed for both primary and metastatic bone lesions and has been proven to lengthen disease-free survival and decrease the likelihood of local recurrence. It is a complex procedure, which requires a thorough multi-disciplinary approach. This article will discuss the role of the radiologist in characterizing the underlying tumor pathology, staging the tumor and helping to predict possible intraoperative challenges for en bloc resection of primary bone lesions. The postoperative appearances and complications following en bloc resection in the spine will be considered in subsequent articles.

Therapeutic effects and clinical outcomes of immune checkpoint inhibitors on bone metastases in lung cancer.

e21118 Background: In recent years, advanced lung cancer patients who received immune checkpoint inhibitors (ICIs) reportedly had a more prolonged overall survival (OS) than those treated with conventional anticancer drugs. However, the therapeutic effect of ICIs on bone metastases remains unclear. The purpose of this study was to investigate the therapeutic effects of ICIs on advanced lung cancer with bone metastasis. Methods: This retrospective study included 58 lung cancer patients (42 men and 16 women; mean age, 66.2±7.8 years) who had been diagnosed with bone metastasis before the initiation of ICI treatment between 2016 and 2019, and the mean follow-up period was 23.2 months. The clinical data such as content of chemotherapy including the bone-modifying agent (BMA), skeletal-related events (SREs), and immune-related adverse events (irAEs) were investigated. The therapeutic effects of ICIs on the primary lung lesions and bone metastases were evaluated by the response evaluation criteria in solid tumors 1.1 (RECIST 1.1) and MD Anderson criteria, respectively. To assess the influence of ICI treatment on prognosis, OS from the diagnosis of bone metastases was compared to the prognostic prediction of Katagiri's score. Results: The most used ICI was pembrolizumab in 27 cases (46.6%). BMA was used in 38 cases (65.6%), and denosumab was used in 31 cases (81.6%). SREs and irAEs were observed in three cases (5.2%) and 13 cases (22.4%), respectively. In the primary lung lesions, the response rate (RR) and disease control rate (DCR) of ICIs were 14.3% and 38.1%, respectively, including one case in CR and 5 cases in PR. In the bone metastatic lesions, the RR and DCR were 38.6% and 75.0%, respectively, including 3 cases in CR and 14 cases in PR. In 17 cases that ICIs responded to bone metastases, nine cases were treated with pembrolizumab (52.9%), and all cases whose evaluations were CR had been treated with concomitant therapy of pembrolizumab and denosumab. The median survival time was 28.1 months and the 2-year OS rate was 51.7%. The 6-, 12-, and 24-month OS rates in this study were more favorable than the prognostic prediction of the Katagiri's score. Conclusions: ICI treatment showed favorable responses to bone metastases in NSCLC and better prognoses than conventional predictive prognosis. Particularly, pembrolizumab may be the most effective, and the therapeutic effect was enhanced by the concomitant use of denosumab.[Table: see text]