Metastatic Tumor Lesions Research Articles

OUTCOMES OF SHOULDER JOINT ENDOPROSTHETICS AFTER REMOVAL OF TUMORS IN THE HUMERUS

Introduction. The use of endoprostheses of the shoulder joint is possible with primary and secondary (metastatic) tumor lesions of the proximal part of the humerus. The possibility of using both individual oncological endoprostheses and modular oncological endoprostheses for tumors of the proximal part of the humerus is reported. Aim. To assess the effectiveness of restoring the function of the shoulder joint and upper limb and improving the patient's quality of life after shoulder joint arthroplasty for tumors of the proximal part of the humerus. Materials and methods. The results of the treatment of 27 patients who underwent shoulder arthroplasty in the conditions of the clinical departments of the "Institute of Traumatology and Orthopedics of the National Academy of Medical Sciences of Ukraine" for tumors of the proximal part of the humerus from 2014 to 2024 were evaluated. Endoprosthesis was performed in 22 (81.5%) patients with primary tumors of the proximal part of the humerus and in 5 (18.5%) with metastatic tumors. Endoprosthesis of the shoulder joint was performed with individual oncological endoprostheses in 24 (88.9%) patients and modular oncological endoprostheses in 3 (11.1%) patients. Arthroplasty was primary in 25 (92.6%) patients and secondary in 2 (7.4%) patients. Results. During follow-up, 3 (11.1%) patients died with an average follow-up period of 10.3±1.9 months, the other 24 (88.9%) were alive, with an average follow-up period of 88.1±8.7 months. The overall frequency of complications in our study was 6 (22.2%) cases, 3 (11.1%) patients had an infectious complication in the late postoperative period after 12, 24 and 36 months, 1 (3.7%) patient had aseptic loosening of the leg of the endoprosthesis after 36 months, in 2 (7.4%) patients after 5 and 6 months, dislocation of the head of the endoprosthesis from the joint cavity was noted. Local tumor recurrence was observed in 2 (7.4%) patients. The overall mean MSTS total limb functional outcome after shoulder arthroplasty for all 27 patients was 74.2%, and of the 24 patients who survived, the mean limb functional outcome after shoulder arthroplasty was 78.4%. The patients' quality of life (according to the EORTQ-QLQ-С30 questionnaire) increased from 32 points in the preoperative period to 78 points after shoulder joint replacement. Conclusions. Endoprosthetics is a modern method for reconstructing bone segments in the surgical treatment of tumors of long bones in the limbs. This method allows for the replacement of bone defects of any size (volume) and length. Shoulder joint endoprosthetics within the framework of combination and multimodal treatment of primary and metastatic tumors of the proximal part of the humerus provides restoration of both shoulder joint functions and the upper limb as a whole, thereby improving the quality of life for this group of patients.

Human Biodistribution and Radiation Dosimetry of the Targeting Fibroblast Growth Factor Receptor 1-Positive Tumors Tracer [68Ga]Ga-DOTA-FGFR1-Peptide.

Objective: [68Ga]Ga-DOTA-FGFR1-peptide is a novel positron emission tomography (PET) radiotracer targeting fibroblast growth factor receptor 1 (FGFR1). This study aimed to evaluate the safety, biodistribution, radiation dosimetry, and imaging potential of [68Ga]Ga-DOTA-FGFR1-peptide. Methods: The FGFR1-targeting peptide DOTA-(PEG2)-KAEWKSLGEEAWHSK was synthesized by manual solid-phase peptide synthesis and high-performance liquid chromatography purification, and labeled with 68Ga with DOTA as chelating agent. We recruited 14 participants and calculated the radiation dose of 4 of these pathologically confirmed nontumor subjects using OLINDA/EXM 2.2.0 software. At the same time, the imaging potential in 10 of these lung cancer patients was evaluated. Results: The biodistribution of [68Ga]Ga-DOTA-FGFR1-peptide in 4 subjects showed the highest uptake in the bladder and kidney. Dosimetry analysis indicated that the bladder wall received the highest effective dose (3.73E-02 mSv/MBq), followed by the lungs (2.36E-03 mSv/MBq) and red bone marrow (2.09E-03 mSv/MBq). No normal organs were found to have excess specific absorbed doses. The average systemic effective dose was 4.97E-02 mSv/MBq. The primary and metastatic tumor lesions were clearly visible on PET/computed tomography (CT) images in 10 patients. Conclusion: Our results indicate that [68Ga]Ga-DOTA-FGFR1-peptide has a good dosimetry profile and can be used safely in humans, and it has significant potential value for clinical PET/CT imaging.

Prognosis and tumor-infiltrating lymphocytes (TILs) in estrogen receptor (ER)-low metastatic breast cancer (MBC): Analysis from a large multi-institutional cohort and the TONIC phase II trial with nivolumab.

1100 Background: Although 1% as ER cutoff to discriminate ER+/HER2- from triple-negative (TN) BC serves the purpose of maximizing access to endocrine therapy, it may be suboptimally informative in terms of prognosis and immune checkpoint inhibitor (ICI) benefit. In the early setting, we reported that ER-low BC (ER 1-9%/HER2-) is immunologically and prognostically similar to TN (ER 0%) [Massa, 2023]. Here we focus on MBC and aim to assess prognosis of ER-low BC, including the conversion from ER+(≥10%)/HER2- to ER-low at relapse. We also compared ER-low and TN in terms of outcome after ICI, and TILs. Methods: We included two cohorts of MBC patients (pts): a multicentric retrospective cohort and pts with ER<10%/HER2- MBC enrolled in the TONIC trial testing nivolumab +/- induction therapy. All pts had ER and HER2 status assessed on metastatic tumor lesion; in the retrospective cohort ER and HER2 status on primary tumor was also available. Survival endpoints in the retrospective cohort: overall survival (OS, from BC diagnosis), post-relapse survival (PRS, from BC relapse). Exploratory endpoints from the TONIC trial: clinical benefit rate (CBR), OS and PFS (both from randomization). TILs were assessed on MBC samples (both cohorts) and on matched primary tumor (retrospective cohort). Results: We included 1112 pts in the retrospective cohort: the prevalence of ER-low BC was 3.6% in primary tumor and 5.9% in MBC lesions. In the TONIC trial, 15/110 pts had ER-low MBC. In the retrospective cohort, ER-low and TN MBC showed similar outcome, and significantly unfavorable vs ER+/HER2- MBC (Table). Among pts with ER+/HER2- primary BC, 6.7% converted to ER-low and 14.7% to TN at relapse. ER+/HER2- BC pts converting to ER-low had similar outcome than those converted to TN, and significantly poorer than pts with stable ER+/HER2- (Table). In the TONIC trial, ER-low MBC pts, compared to TN, showed similar response to ICI (CBR: 20.0% vs 22.1%, p=1), similar PFS and numerically worse OS (Table). TIL levels on MBC samples were similar between ER-low and TN both in the retrospective (median: 6% vs 5%, p=0.83) and the TONIC cohorts (median: 5.5% vs 5.0%, p=0.56) and were higher than ER+/HER2- (median: 3%). Conclusions: We confirmed that ER-low and TN MBC show similar poor outcome and the shift from ER+/HER2- to ER-low has a comparable unfavorable prognostic impact compared to conversion to TN. Our results support the hypothesis that ER-low and TN are immunologically akin and similarly prone to respond to ICI. [Table: see text]

Syringeable Near-Infrared Light-Activated In Situ Immunogenic Hydrogel Boosts the Cancer-Immunity Cycle to Enhance Anticancer Immunity.

Effective anticancer immunity depends on properly activating multiple stepwise events in the cancer-immunity cycle. An immunologically "cold" tumor microenvironment (TME) engenders immune evasion and refractoriness to conventional checkpoint blockade immunotherapy. Here, we combine nanoparticle formulations and an in situ formed hydrogel scaffold to treat accessible tumors locally and to stimulate systemic immunity against metastatic tumor lesions. The nanoparticles encapsulate poly(ε-caprolactone)-derived cytotoxic chemotherapy and adjuvant of Toll-like receptor 7/8 through a reactive oxygen species (ROS)-cleavable linker that can be self-activated by the coassembled neighboring photosensitizer following near-infrared (NIR) laser irradiation. Further development results in syringeable, NIR light-responsive, and immunogenic hydrogel (iGEL) that can be implanted peritumorally and deposited into the tumor surgical bed. Upon NIR laser irradiation, the generated ROS induces iGEL degradation and bond cleavage in the polymer-drug conjugates, triggering the immunogenic cell death cascade in cancer cells and spontaneously releasing encapsulated agents to rewire the cancer-immunity cycle. Notably, upon application in multiple preclinical models of melanoma and triple-negative breast cancer, which are aggressive and refractory to conventional immunotherapy, iGEL induces durable remission of established tumors, extends postsurgical tumor-free survival, and inhibits metastatic burden. The result of this study is a locally administrable immunogenic hydrogel for triggering host systemic immunity to improve immunotherapeutic efficacy with minimal off-target side effects.

Objective response after immune checkpoint inhibitors in a chemotherapy-refractory pMMR/MSS metastatic rectal cancer patient primed with experimental AlloStim® immunotherapy

BackgroundImmune Checkpoint Inhibitor (ICI) immunotherapy is most effective in immune effector cell infiltrated ‘hot’ tumor lesions, such as occurs in deficient mismatch repair, microsatellite instability high (dMMR/MSI-H) colorectal cancer (CRC). However, most all metastatic CRC tumors are mismatch repair proficient/microsatellite stable (pMMR/MSS) ‘cold’ lesions, without significant immune cell infiltration, and are unresponsive to ICI. AlloStim®, is an experimental, allogeneic immunomodulatory cell therapy designed to convert ‘cold’ metastatic tumor lesions to ‘hot’ inflamed lesions. After AlloStim® immunotherapy, this cold to hot inflammatory mechanism can make it difficult to distinguish between pseudoprogression and actual progression on restaging CT scans, as inflamed metastatic lesions can appear larger and occult disease can appear as new small lesions.MethodsTo explore whether radiological progression after AlloStim® immunotherapy is due to immune-flare or disease progression, we administered a short course of a combination ICI therapy to a pMMR/MSS chemotherapy-refractory metastatic colorectal cancer patient enrolled in the StimVax Phase IIb clinical study that presented with radiological progression after AlloStim® immunotherapy. Our rationale was that an accelerated response to ICI should occur if the lesions were inflamed, while if the enlarged lesions were due to disease progression there would not be a response.ResultsHere we report a rapid, significant reduction in tumor burden in response to ICI administration in an AlloStim® primed pMMR/MSS mCRC patient with retroperitoneal and lung metastases.ConclusionThis rare objective response to ICIs in a pMMR/MSS mCRC patient supports further evaluation of the combination of AlloStim® with ICI immunotherapy in MSS mCRC and other cold or ICI refractory tumors.Trial registrationNational Library of Medicine (NLM) at the National Institutes of Health (NIH). Registered 22 June 2020, https://clinicaltrials.gov/study/NCT04444622.

Sentinel Node Navigation Surgery for Early Gastric Cancer: A Narrative Review.

Early gastric cancer (EGC) refers to malignant tumor lesions that are limited to the mucosa and submucosa layers, regardless of the presence of lymph node metastasis. Typically, EGC has a low rate of perigastric lymph node metastasis, and long-term survival outcomes are good after radical surgical treatment. The primary objective of surgical treatment for EGC is to achieve functional preservation while ensuring a radical cure. Sentinel node navigation surgery (SNNS) is a surgical technique used in the treatment of EGC. This approach achieves functional preservation by limiting lymph node dissection and performing restrictive gastrectomy guided by intraoperative negative sentinel node (SN) biopsy. Despite the apparent improvement in the detection rate of SN with the emergence of various tracing dyes and laparoscopic fluorescence systems, the oncological safety of SNNS remains a controversial research topic. SNNS, as a true form of stomach preservation surgery that enhances the quality of life, has become a topic of interest in the EGC field. In recent years, scholars from Japan and South Korea have conducted extensive research on the feasibility and safety of SNNS in the treatment of EGC. This article aims to provide reference choices for surgeons treating EGC by reviewing relevant research on SNNS for EGC in recent years.

3-[18F]Fluoro-para-hydroxyphenethylguanidine (3-[18F]pHPG) PET-A Novel Imaging Modality for Paraganglioma.

Functional positron emission tomography (PET) imaging for the characterization of pheochromocytoma and paraganglioma (PCC/PGL) and for detection of metastases in malignant disease, offers valuable clinical insights that can significantly guide patient treatment. This work aimed to evaluate a novel PET radiotracer, 3-[18F]fluoro-para-hydroxyphenethylguanidine (3-[18F]pHPG), a norepinephrine analogue, for its ability to localize PCC/PGL. 3-[18F]pHPG PET/CT whole-body scans were performed on 16 patients (8 male:8 female; mean age 47.6 ± 17.6 years; range, 19-74 years) with pathologically confirmed or clinically diagnosed PCC/PGL. After intravenous administration of 304 to 475 MBq (8.2-12.8 mCi) of 3-[18F]pHPG, whole-body PET scans were performed at 90 minutes in all patients. 3-[18F]pHPG PET was interpreted for abnormal findings consistent with primary tumor or metastasis, and biodistribution in normal organs recorded. Standardized uptake value (SUV) measurements were obtained for target lesions and physiological organ distributions. 3-[18F]pHPG PET showed high radiotracer uptake and trapping in primary tumors, and metastatic tumor lesions that included bone, lymph nodes, and other solid organ sites. Physiological biodistribution was universally present in salivary glands (parotid, submandibular, sublingual), thyroid, heart, liver, adrenals, kidneys, and bladder. Comparison [68Ga]DOTATATE PET/CT was available in 10 patients and in all cases showed concordant distribution. Comparison [123I]meta-iodobenzylguanidine [123I]mIBG planar scintigraphy and SPECT/CT scans were available for 4 patients, with 3-[18F]pHPG showing a greater number of metastatic lesions. We found the kinetic profile of 3-[18F]pHPG PET affords high activity retention within benign and metastatic PCC/PGL. Therefore, 3-[18F]pHPG PET imaging provides a novel modality for functional imaging and staging of malignant paraganglioma with advantages of high lesion affinity, whole-body coregistered computed tomography, and rapid same-day imaging.

Abstract 1419: Locoregional delivery with engineered stem cells modulates immunosuppressive tumor microenvironment in brain leptomeningeal metastasis

Abstract Leptomeningeal metastasis (LM) is one of the severe disease conditions in brain metastasis (BM) and results in poor prognosis and reduction of quality of life. Immunotherapies such as anti-Programmed cell Death (PD)-1 antibodies have shown improved overall survival against non-small cell lung cancer (NSCLC).. However, the clinical benefit of patients with NSCLC derived LM is still limited due to poor penetration of therapeutic agents into the brain and cerebrospinal fluid (CSF) and lack of understanding of the tumor microenvironment in LM. In this study, we first developed immune-competent mouse models of LM which show significantly decreased immune cells and increased PD-1+ T cells in the tumor microenvironment as compared to primary NSCLC tumors, thus mimicking primary and LM NSCL in patients. Next, we explored the use of oncolytic herpes simplex virus (oHSV) that selectively replicate in tumor cells and illicit an antitumor effect via oncolysis and production of neoantigens for targeting LM NSCLC. Given that virus neutralization, and inefficient extravasation are the major barriers to the effective systemic delivery of oHSV to target metastatic tumor lesions in the brain, we utilized mesenchymal stem cells (SC) and created two population of mesenchymal SC types: one for loading oncolytic herpes simplex virus (oHSV) and another one, engineered with knockout of Nectin-1 receptor by CRISPR/Cas9 technique to be resistant to oHSV, for secreting single-chain variable fragment (scFv) anti-PD-1. We show that locoregional treatment improved therapeutic outcomes by inducing oHSV-mediated immunogenic cell death, and activation of anti-tumor T cell signaling in mouse NSCLC LM tumors. Our novel SCs based immunotherapeutic strategy provides a roadmap towards treatment of lung to brain leptomeningeal metastatic patients. Citation Format: Nobuhiko Kanaya, Waleed Seddiq, Kok-Siong Chen, Yoshinori Kajiwara, Lucia Moreno Lama, Shinji Kuroda, Toshiyoshi Fujiwara, Hiroaki Wakimoto, Khalid Shah. Locoregional delivery with engineered stem cells modulates immunosuppressive tumor microenvironment in brain leptomeningeal metastasis [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 1419.

Pulmonary abscess with atypical topography - computed tomography assessment before and after treatment.

We present a clinical case of a patient with neurological sequelae, dementia, gastrostomy and tracheostomy with a metal canula, who developed a lung abscess in an atypical topography, in the anterior segment of the left upper lobe, being attended to in the emergency department. A 79-year-old man who was bedridden and with neurological sequelae resulting from a hemorrhagic stroke, with gastrostomy and tracheostomy with a metal canula, was attended for daily fever and increased secretion trough the canula, and a diagnosis of bronchoaspiration pneumonia was made. The chest X-ray was unremarkable with an evaluation impaired by the patient's posture. The chest CT showed a characteristic image of an abscess in the topography of the anterior segment of the upper lobe. Improvement in the patient`s clinical condition was accompanied by an improvement in the CT imaging results. And the other exams carried out did not show any other associated lung disease. Chest X-ray is still the initial method for studying infectious lung lesions, and CT is indicated in cases where the appearance of the lesion is not well defined, if doubts persist, whether the patient is immunosuppressed or oncological. CT can provide better definition of abscess imaging findings and is particularly useful for visualizing cavities not well delineated by X-ray, especially when a malignant neoplastic tumor lesion is suspected or when there is an associated pleural collection.

Diagnosis of skull-base invasion by nasopharyngeal tumors on CT with a deep-learning approach

PurposeTo develop a convolutional neural network (CNN) model to diagnose skull-base invasion by nasopharyngeal malignancies in CT images and evaluate the model’s diagnostic performance.Materials and methodsWe divided 100 malignant nasopharyngeal tumor lesions into a training (n = 70) and a test (n = 30) dataset. Two head/neck radiologists reviewed CT and MRI images and determined the positive/negative skull-base invasion status of each case (training dataset: 29 invasion-positive and 41 invasion-negative; test dataset: 13 invasion-positive and 17 invasion-negative). Preprocessing involved extracting continuous slices of the nasopharynx and clivus. The preprocessed training dataset was used for transfer learning with Residual Neural Networks 50 to create a diagnostic CNN model, which was then tested on the preprocessed test dataset to determine the invasion status and model performance. Original CT images from the test dataset were reviewed by a radiologist with extensive head/neck imaging experience (senior reader: SR) and another less-experienced radiologist (junior reader: JR). Gradient-weighted class activation maps (Grad-CAMs) were created to visualize the explainability of the invasion status classification.ResultsThe CNN model’s diagnostic accuracy was 0.973, significantly higher than those of the two radiologists (SR: 0.838; JR: 0.595). Receiver operating characteristic curve analysis gave an area under the curve of 0.953 for the CNN model (versus 0.832 and 0.617 for SR and JR; both p < 0.05). The Grad-CAMs suggested that the invasion-negative cases were present predominantly in bone marrow, while the invasion-positive cases exhibited osteosclerosis and nasopharyngeal masses.ConclusionsThis CNN technique would be useful for CT-based diagnosis of skull-base invasion by nasopharyngeal malignancies.

Deep learning algorithm for the automated detection and classification of nasal cavity mass in nasal endoscopic images.

Nasal endoscopy is routinely performed to distinguish the pathological types of masses. There is a lack of studies on deep learning algorithms for discriminating a wide range of endoscopic nasal cavity mass lesions. Therefore, we aimed to develop an endoscopic-examination-based deep learning model to detect and classify nasal cavity mass lesions, including nasal polyps (NPs), benign tumors, and malignant tumors. The clinical feasibility of the model was evaluated by comparing the results to those of manual assessment. Biopsy-confirmed nasal endoscopic images were obtained from 17 hospitals in South Korea. Here, 400 images were used for the test set. The training and validation datasets consisted of 149,043 normal nasal cavity, 311,043 NP, 9,271 benign tumor, and 5,323 malignant tumor lesion images. The proposed Xception architecture achieved an overall accuracy of 0.792 with the following class accuracies on the test set: normal = 0.978 ± 0.016, NP = 0.790 ± 0.016, benign = 0.708 ± 0.100, and malignant = 0.698 ± 0.116. With an average area under the receiver operating characteristic curve (AUC) of 0.947, the AUC values and F1 score were highest in the order of normal, NP, malignant tumor, and benign tumor classes. The classification performances of the proposed model were comparable with those of manual assessment in the normal and NP classes. The proposed model outperformed manual assessment in the benign and malignant tumor classes (sensitivities of 0.708 ± 0.100 vs. 0.549 ± 0.172, 0.698 ± 0.116 vs. 0.518 ± 0.153, respectively). In urgent (malignant) versus nonurgent binary predictions, the deep learning model achieved superior diagnostic accuracy. The developed model based on endoscopic images achieved satisfactory performance in classifying four classes of nasal cavity mass lesions, namely normal, NP, benign tumor, and malignant tumor. The developed model can therefore be used to screen nasal cavity lesions accurately and rapidly.

Patlak Reconstruction Using Dynamic 18 F-FDG PET Imaging for Evaluation of Malignant Liver Tumors : A Comparison of HCC, ICC, and Metastatic Liver Tumors.

The aim of this study was to explore the different patterns of dynamic whole-body (D-WB) FDG PET/CT parameters among liver malignancy types as potential diagnostic clues and investigate the association between static and dynamic PET/CT parameters for each tumor histology. Seventy-one patients with intrahepatic cholangiocarcinoma (ICC), metastatic liver tumor (MLT), or hepatocellular carcinoma (HCC) who underwent D-WB and static dual-time-point FDG PET/CT were enrolled. We obtained Pearson correlation coefficients between the metabolic rate of FDG (MR FDG ; mg/min/ 100ml) or distribution volume of free FDG (DV FDG , %) and static PET/CT parameters. We compared MR FDG and DV FDG values by tumor type and performed receiver operating characteristic analyses for MR FDG and static images. A total of 12 ICC, 116 MLT, and 36 HCC lesions were analyzed. MR FDG and DV FDG showed excellent correlation with early (SUV e ) and delayed SUV max (SUV d ) ( r = 0.71~0.97), but DV FDG in the HCC lesions did not ( r = 0.62 and 0.69 for SUV e and SUV d , respectively) ( P < 0.001 for all). HCC lesions showed significantly lower MR FDG (2.43 ± 1.98) and DV FDG (139.95 ± 62.58) than ICC (5.02 ± 3.56, 207.06 ± 97.13) and MLT lesions (4.51 ± 2.47, 180.13 ± 75.58) ( P < 0.01 for all). The optimal MR FDG could differentiate HCC from ICC and MLT with areas under the curve of 0.84 and 0.80, respectively. Metastatic liver tumor lesions showed the widest distribution of MR FDG and DV FDG values but with no significant difference among most primary sites. MR FDG was strongly correlated with SUV max in the 3 malignancies and showed utility for differentiating HCC from ICC and MLT. Each tumor type has a different glucose metabolism, and D-WB FDG PET/CT imaging has the potential to visualize those differences.

Initial Evaluation of [18F]FAPI-74 PET for Various Histopathologically Confirmed Cancers and Benign Lesions.

The 18F-labeled fibroblast activation protein inhibitor (FAPI) [18F]FAPI-74 has the benefit of a higher synthetic yield and better image resolution than 68Ga-labeled FAPI. We preliminarily evaluated the diagnostic performance of [18F]FAPI-74 PET in patients with various histopathologically confirmed cancers or suspected malignancies. Methods: We enrolled 31 patients (17 men and 14 women) with lung cancer (n = 7), breast cancer (n = 5), gastric cancer (n = 5), pancreatic cancer (n = 3), other cancers (n = 5), and benign tumors (n = 6). Twenty-seven of the 31 patients were treatment-naïve or preoperative, whereas recurrence was suspected in the remaining 4 patients. Histopathologic confirmation was obtained for the primary lesions of 29 of the 31 patients. In the remaining 2 patients, the final diagnosis was based on the clinical course. [18F]FAPI-74 PET scanning was performed 60 min after the intravenous injection of [18F]FAPI-74 (240 ± 31 MBq). The [18F]FAPI-74 PET images were compared between the primary or local recurrent lesions of malignant tumors (n = 21) and nonmalignant lesions (n = 8: type-B1 thymomas, granuloma, solitary fibrous tumor, and postoperative or posttherapeutic changes). The uptake and number of detected lesions on [18F]FAPI-74 PET were also compared with those on [18F]FDG PET for available patients (n = 19). Results: [18F]FAPI-74 PET showed higher uptake in primary lesions of various cancers than in nonmalignant lesions (median SUVmax, 9.39 [range, 1.83-25.28] vs. 3.49 [range, 2.21-15.58]; P = 0.053), but some of the nonmalignant lesions showed high uptake. [18F]FAPI-74 PET also showed significantly higher uptake than [18F]FDG PET (median SUVmax, 9.44 [range, 2.50-25.28] vs. 5.45 [range, 1.22-15.06] in primary lesions [P = 0.010], 8.86 [range, 3.51-23.33] vs. 3.84 [range, 1.01-9.75] in lymph node metastases [P = 0.002], and 6.39 [range, 0.55-12.78] vs. 1.88 [range, 0.73-8.35] in other metastases [P = 0.046], respectively). In 6 patients, [18F]FAPI-74 PET detected more metastatic lesions than [18F]FDG PET. Conclusion: [18F]FAPI-74 PET showed higher uptake and detection rates in primary and metastatic lesions than did [18F]FDG PET. [18F]FAPI-74 PET is a promising novel diagnostic modality for various tumors, especially for precise staging before treatment, including characterization of tumor lesions before surgery. Moreover, 18F-labeled FAPI ligand might serve a higher demand in clinical care in the future.

Abstract 1816: Locoregional delivery with gene edited and engineered stem cells modulates unique immune profiling in leptomeningeal metastasis

Abstract Patients with advanced melanoma have a high propensity to metastasize to the brain and numerous investigational treatments with targeted agents have shown modest response in melanoma brain metastatic patients. Leptomeningeal metastasis (LM) is one of the severe disease conditions in brain metastasis. Recently, phase I/II clinical studies with immune-checkpoint inhibitors (ICIs) are promising however the clinical benefit of patients with LM is limited mainly due to poor penetration of anti-PD-1 antibodies into the brain and cerebrospinal fluid. Therefore, there is an urgent need to develop innovative therapies for such tumors. Oncolytic herpes simplex virus (oHSV) that selectively replicate in tumor cells and illicit an antitumor effect via oncolysis and production of neoantigens are among the recently approved promising therapies for primary melanoma patients. However, virus neutralization, and inefficient extravasation are the major barriers to the effective systemic delivery of oHSV to target metastatic tumor lesions in the brain. We first established and characterized PTEN deficient metastatic melanoma tumor model and show that brain metastatic tumors are more immunosuppressive compared to primary melanoma and therefore mimics the clinical settings. Next, we developed a multimodal approach by creating tumor-tropic allogeneic twin (T) stem cells (SC): one for producing oncolytic herpes simplex virus (oHSV) and the other one engineered with CRISPR/Cas9 mediated knockout of Nectin 1 (N1) receptor (N1KO) to acquire resistance to oHSV and releasing immunomodulators. Utilizing mouse models of brain metastatic PTEN deficient melanomas, we show that locoregional delivery of twin stem cells releasing oHSV and cytokine, GM-CSF (TSC-G) activated dendritic cell and T cell-mediated immune responses in both syngeneic and patient derived-humanized mouse models. Importantly, our strategy exhibited greater therapeutic efficacy when compared with the existing oncolytic viral therapeutic approaches. Moreover, the use of SC-oHSV with SCN1KO releasing both GM-CSF and single-chain variable fragment (scFv) anti-PD-1 (TSC-G/P) effectively suppressed immunosuppressive PTEN deficient LM. Our findings provide a novel allogeneic SC based immunotherapeutic strategy against melanomas and a roadmap towards clinical application particularly for leptomeningeal disease. Citation Format: Nobuhiko Kanaya, Kok Siong Chen, Yoshinori Kajiwara, Waleed Seddiq, Thijs A. van Schaik, Touraj Aligholipour Farzani, Paulo Borges, Shah Khalid. Locoregional delivery with gene edited and engineered stem cells modulates unique immune profiling in leptomeningeal metastasis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1816.

Engineered Macrophages-Based uPA-Scavenger Load Gemcitabine to Prompt Robust Treating Cancer Metastasis.

The majority of cancer patients die of metastasis rather than primary tumors, and most patients may have already completed the cryptic metastatic process at the time of diagnosis, making them intractable for therapeutic intervention. The urokinase-type plasminogen activator (uPA) system is proved to drive cancer metastasis. However, current blocking agents such as uPA inhibitors or antibodies are far from satisfactory due to poor pharmacokinetics and especially have to face multiplex mechanisms of metastasis. Herein, an effective strategy is proposed to develop a uPA-scavenger macrophage (uPAR-MΦ), followed by loading chemotherapeutics with nanoparticles (GEM@PLGA) to confront cancer metastasis. Interestingly, significant elimination of uPA by uPAR-MΦ is demonstrated by transwell analysis on tumor cells in vitro and enzyme-linked immunosorbent assay detection in peripheral blood of mice with metastatic tumors, contributing to significant inhibition of migration of tumor cells and occurrence of metastatic tumor lesions in mice. Moreover, uPAR-MΦ loaded with GEM@PLGA shows a robust antimetastasis effect and significantly prolonged survival in 4T1-tumor-bearing mice models. This work provides a novel living drug platform for realizing a potent treatment strategy to patients suffering from cancer metastasis, which can be further expanded to handle other tumor metastasis markers mediating cancer metastasis.

HISTOPATHOLOGICAL EVALUATION OF BONE TUMORS IN A TERTIARY CARE HOSPITAL IN GWALIOR, INDIA

Background : Bone lesions are diagnostic challenges to surgical pathologists. Correlation of Histopathological study enables us to understand the spectrum of bone lesions and gives an idea of different bone tumors and tumor-like lesions in population among different age group and sex. To determine the spectrum of various bone tumors a Objective: nd their relative frequency at Gajraraja Medicsl College , Gwalior (M.P.). A retrospective review Materials and Methods: of histopathological reports of all bone specimens received in the Department of Pathology gajra raja medical college, gwalior for a period of 1years from August 2021- July 2022 was done. Results: Of the 55 histopathologically diagnosed bone lesions, male to female ratio was of 2.77:1. Age ranged from 6-83 years. Nonneoplastic lesions accounted for 38.18%, while neoplastic lesions accounted for 61.82%. Osteomyelitis was the most common and only nonneoplastic lesion encountered with 21cases (38.18%). Out of 34 cases of bone tumors, benign tumors made up to 67.65%, while the malignant tumor and tumor-like lesions made up 8.82% and 23.52%, respectively. Giant cell tumours with 10 cases (29.41%) and Ewing sarcoma with 3 cases (8.82%) were the most common benign and malignant tumors, respectively; while non ossifying fibroma with six cases (17.64%) was the most common tumor-like lesion. Femur was the most common site with 13(38.23%) occurrences followed by tibia with 6 (17.64%). Chronic osteomyelitis was Conclusion: the commonest nonneoplastic lesion. Among the bone tumors, giant cell tumour and Ewing sarcoma was the most common benign and malignant bone tumor, respectively

Aspects of vertebral column resection in patients with rigid kyphotic and kyphoscoliotic deformities of different genesis of the thoracolumbar spine: multicenter retrospective observational cohort study

BACKGROUND: Vertebral column resection (VCR) as a type of spinal osteotomy is characterized by maximum possibilities of three-dimensional correction of various etiologies: congenital, post-tuberculous, iatrogenic (after other interventions on the spine), degenerative, and vertebral spondyloptosis caused by Kmmels disease, and primary, and metastatic tumor lesions of the spine. Nowadays, the use of single-level VCR is far beyond its initial purpose.&#x0D; OBJECTIVE: The study aimed to compare features of VCR for rigid deformities of various etiologies and management of erythrocyte blood products in the perioperative period.&#x0D; MATERIALS AND METHODS: A multicenter retrospective observational cohort study analyzed data from 53 adult (aged 18 years) patients with kyphotic and kyphoscoliotic deformities of the thoracic and lumbar spine, distributed into four comparison groups according to the deformity genesis, namely, impaired spinal development, traumatic genesis, degenerative or idiopathic, and neoplasms of the vertebral bodies. The characteristics of VCR in these patients were compared.&#x0D; RESULTS: The surgery duration was longer in VCR for spinal neoplasms (p 0.05) than for high-energy burst compression fractures of vertebral bodies and scoliotic deformities (grade IV). On average, this group also had the most cranial osteotomy level among the study groups. VCR for idiopathic scoliotic deformities is characterized by a larger intraoperative blood loss volume than other nosologies, and the differences were statistically significant. In male patients of this group, the hemoglobin level on day 1 after surgery was statistically significantly lower than in those who underwent VCR for compression fractures of the vertebral bodies or impaired vertebral development. During resection of the vertebral column for burst compression fractures of the vertebral bodies, the fixation length was less (p 0.05), with a similar intervention for developmental anomalies, deformities of postoperative genesis, and grade IV idiopathic scoliosis. VCR for grade IV idiopathic scoliosis requires a larger (p 0.05) volume of the reinfused autologous blood than for intervention for acute traumatic pathologies (burst compression fractures of the vertebral bodies).&#x0D; CONCLUSION: The versatility of clinical tasks for which resection of the spinal column can be performed using the VCR technique also determines the significant heterogeneity of the patients who undergo such treatment. Knowledge of the interventions in various nosologies is very useful in vertebrological practice.

Asociación entre las características radiográficas y los tumores óseos de rodilla.

Bone neoplasms require an adequate clinical-radiographic evaluation for their diagnosis. Plain radiographs are the usual method to establish the diagnosis and evaluate differential diagnoses in the study of bone tumor pathology. To recognize the frequency of radiographic characteristics and associate them with bone tumor pathology. Radiographic data were collected from 132 patients with tumor pathology confirmed by biopsy from bone tumors service of the Traumatology and Orthopedics Hospital Unidades Médicas de Alta Especialidad Dr. Victorio de la Fuente Narváez, Instituto Mexicano del Seguro Social, Ciudad de México, during 2019. 132 patients were registered. The most frequent benign tumor was osteochondroma (27.3%), and malignant was osteosarcoma (9.8%). Active lytic lesions (odds ratio [OR]: 6.9; 95% confidence interval [95% CI]: 2.83-16.85) or aggressive (OR: 26.85; 95% CI: 3.21-224) were associated with giant cells tumors. Poorly differentiated intraosseous blast lesions of bone lineage (OR: 36.15; 95% CI: 4.4-295.5) were associated with osteosarcoma. The periosteal reaction (OR: 36.15; 95% CI: 4.4-295.5), the moth-eaten or permeative pattern (OR: 11.75; 95% CI: 1.26-109) and the central location of the lesion (OR: 3.03; 95% CI: 1.37-6.69) were associated with malignant tumor lesions. Poorly defined intraosseous blast lesions of bone lineage, periosteal reaction, and moth-eaten or permeative pattern of destruction are associated with malignant lesions.

An Intelligent Auxiliary Framework for Bone Malignant Tumor Lesion Segmentation in Medical Image Analysis.

Bone malignant tumors are metastatic and aggressive, with poor treatment outcomes and prognosis. Rapid and accurate diagnosis is crucial for limb salvage and increasing the survival rate. There is a lack of research on deep learning to segment bone malignant tumor lesions in medical images with complex backgrounds and blurred boundaries. Therefore, we propose a new intelligent auxiliary framework for the medical image segmentation of bone malignant tumor lesions, which consists of a supervised edge-attention guidance segmentation network (SEAGNET). We design a boundary key points selection module to supervise the learning of edge attention in the model to retain fine-grained edge feature information. We precisely locate malignant tumors by instance segmentation networks while extracting feature maps of tumor lesions in medical images. The rich contextual-dependent information in the feature map is captured by mixed attention to better understand the uncertainty and ambiguity of the boundary, and edge attention learning is used to guide the segmentation network to focus on the fuzzy boundary of the tumor region. We implement extensive experiments on real-world medical data to validate our model. It validates the superiority of our method over the latest segmentation methods, achieving the best performance in terms of the Dice similarity coefficient (0.967), precision (0.968), and accuracy (0.996). The results prove the important contribution of the framework in assisting doctors to improve the accuracy of diagnosis and clinical efficiency.

Results of Application of Saturable Microspheres of Domestic Production in Locoregional Endovascular Treatment of Inoperable Patients with Malignant Liver Tumors

The incidence of malignant liver tumors is steadily increasing. Most patients are considered inoperable at the time of detection of a malignant liver lesion. In general, unsatisfactory liver function, comorbidities, bilobar lesion, extrahepatic metastasis allow performing radical treatment in not more than 20 % of cases. Thus, the majority of patients are indicated for other types of treatment, including endovascular locoregional techniques. Taking into account the implementation of the federal program for state support of import substitution in Russia, the creation and production of competitive products in the field of medicine, including for endovascular surgery, becomes relevant. The aim of this article was to study the properties, tolerability and safety of domestically produced saturable microspheres and evaluate the immediate results of transarterial chemoembolization in the treatment of inoperable patients with primary and metastatic liver cancer. Within the framework of the State Scientific Program, clinical studies on the use of saturable microspheres produced in Russia were conducted. The results of treatment of 32 patients who underwent transarterial chemoembolization (TACE) with the use of domestic microspheres “Sphere-Spectrum” at the N.N. Blokhin Research Institute of Oncology from January 2020 to October 2022 were analyzed. Of these, TACE was performed in 24 patients diagnosed with HCC, 5 patients with liver metastases of neuroendocrine tumors, and 3 patients with melanoma metastases. TACE was performed using microspheres with sizes 35–40 in dry (210–240 μm in saturated) 50–60 μm in dry (300–360 μm in saturated), 25 mg or 50 mg in one vial. A total of 40 endovascular procedures were performed in all 32 patients with malignant liver tumor lesions. In 11 of them (34.3 %) a single TACE session was sufficient to achieve an objective response. Partial response was observed in 21 (65.7 %) patients, including those with bilobar metastatic liver lesion. All patients tolerated treatment satisfactorily, the desired therapeutic effect was achieved in 26 (81.2 %) cases (taking into account repeated interventions). One patient (3.1 %) diagnosed with HCC had a complication in the form of liver abscess formation.