Metastatic Foci Research Articles

PET/CT with <sup>18</sup>F-Fluoroestradiol in First Diagnosed Breast Cancer. A Pilot Study

Purpose: To evaluate the informativity of PET/CT with 18F-FES in determining estrogen receptor (ER) positivity in breast tumor tissue, as well as in regional lymph nodes or distant metastatic foci. Material and methods: The data of 30 patients who underwent PET/CT with 18F-FES performed at the stage of primary diagnosis were retrospectively analyzed. The study included patients before the start of specific treatment or on the background of neoadjuvant hormone therapy, with previously determined expression of ER according to the results of IGC. 14 patients underwent 18F-FDG PET/CT with 2–7 days difference between both PET/CT. Results: In our study, the mean SUVmax value in the primary tumor focus was 4.8, the lowest SUVmax = 1.61, and the highest SUVmax = 18.86. 18F-FES accumulation considered suspicious for metastatic lesion in axillary lymph nodes on the affected side was detected in 16 patients (56 %), mean SUVmax = 5.2, lowest SUVmax = 0.99, highest SUVmax = 11.54. On subsequent histological examination, tumor changes in axillary lymph nodes were confirmed in 16/16 patients. Conclusion: PET/CT with 18F-FES is a diagnostic method for noninvasive evaluation of ER expression in tumor foci, which can complement the data of traditional diagnostic methods and has a significant clinical potential. In our study, the results of PET/CT with 18F-FES coincided with the data of immunohistochemical study in 100 % of cases.

Morphometric Analysis of Lateral Cervical Lymph Node Metastasis in Papillary Thyroid Carcinoma Using Digital Pathology.

Digital pathology uses digitized images for cancer research. We aimed to assess morphometric parameters using digital pathology for predicting recurrence in patients with papillary thyroid carcinoma (PTC) and lateral cervical lymph node (LN) metastasis. We analyzed 316 PTC patients and assessed the longest diameter and largest area of metastatic focus in LNs using a whole slide imaging scanner. In digital pathology assessment, the longest diameters and largest areas of metastatic foci in LNs were positively correlated with traditional optically measured diameters (R = 0.928 and R2 = 0.727, p < 0.001 and p < 0.001, respectively). The optimal cutoff diameter was 8.0mm in both traditional microscopic (p = 0.009) and digital pathology (p = 0.016) evaluations, with significant differences in progression-free survival (PFS) observed at this cutoff (p = 0.006 and p = 0.002, respectively). The predictive area's cutoff was 35.6 mm2 (p = 0.005), which significantly affected PFS (p = 0.015). Using an 8.0-mm cutoff in traditional microscopic evaluation and a 35.6-mm2 cutoff in digital pathology showed comparable predictive results using the proportion of variation explained (PVE) methods (2.6% vs. 2.4%). Excluding cases with predominant cystic changes in LNs, the largest metastatic areas by digital pathology had the highest PVE at 3.9%. Furthermore, high volume of LN metastasis (p = 0.001), extranodal extension (p = 0.047), and high ratio of metastatic LNs (p = 0.006) were associated with poor prognosis. Both traditional microscopic and digital pathology evaluations effectively measured the longest diameter of metastatic foci in LNs. Moreover, digital pathology offers limited advantages in predicting PFS of patients with lateral cervical LN metastasis of PTC, especially those without predominant cystic changes in LNs.

A follicle-stimulating hormone receptor-targeted near-infrared fluorescent probe for tumor-selective imaging and photothermal therapy

Late detection, peritoneal dissemination, chemoresistance and weak response to targeted therapeutics lead to high mortality in ovarian cancer. More efficient and specific tumor imaging and therapeutic agents are needed to improve the resection rate of surgery and to eliminate residual disease. The expression patterns of follicle-stimulating hormone (FSH) receptor make it a suitable target for ovarian cancer. Here, we report a strategy to develop an organic near-infrared probe for FSH receptor-targeted tumor imaging and photothermal therapy. The FSH-Rh760 probe was conjugated from the Rh760 fluorophore with the FSH β subunit 33–53 peptide. FSH-Rh760 specifically distinguished peritoneal metastatic ovarian cancerous foci from surrounding normal tissues with a high tumor-to-background ratio. The fluorescence signals in tumors peaked at 2 h and were cleared at 120 h postinjection. FSH-Rh760 treatment rapidly increased the abdomen temperature of mice up to ∼43 °C upon exposure to a near-infrared laser and effectively suppressed peritoneal tumor growth with tumor specificity. No significant systemic toxicities were observed. This study demonstrates the targeting ability and biocompatibility of FSH receptor-targeted theranostics and highlights its potential for clinical application in imaging-guided precision tumor resection and photothermal therapy to eliminate cancer lesions intraoperatively and postoperatively.

Chemokine Receptor 2 Targeted PET/CT Imaging Distant Metastases in Pancreatic Ductal Adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive and treatment-refractory malignancies. The lack of an effective screening tool results in the majority of patients being diagnosed at late stages, which underscores the urgent need to develop more sensitive and specific imaging modalities, particularly in detecting occult metastases, to aid clinical decision-making. The tumor microenvironment of PDAC is heavily infiltrated with myeloid-derived suppressor cells (MDSCs) that express C-C chemokine receptor type 2 (CCR2). These CCR2-expressing MDSCs accumulate at a very early stage of metastasis and greatly outnumber PDAC cells, making CCR2 a promising target for detecting early, small metastatic lesions that have scant PDAC cells. Herein, we evaluated a CCR2 targeting PET tracer (68Ga-DOTA-ECL1i) for PET imaging on PDAC metastasis in two mouse models. Positron emission tomography/computed tomography (PET/CT) imaging of 68Ga-DOTA-ECL1i was performed in a hemisplenic injection metastasis model (KI) and a genetically engineered orthotopic PDAC model (KPC), which were compared with 18F-FDG PET concurrently. Autoradiography, hematoxylin and eosin (H&E), and CCR2 immunohistochemical staining were performed to characterize the metastatic lesions. PET/CT images visualized the PDAC metastases in the liver/lung of KI mice and in the liver of KPC mice. Quantitative uptake analysis revealed increased metastasis uptake during disease progression in both models. In comparison, 18F-FDG PET failed to detect any metastases during the time course studies. H&E staining showed metastases in the liver and lung of KI mice, within which immunostaining clearly demonstrated the overexpression of CCR2 as well as CCR2+ cell infiltration into the normal liver. H&E staining, CCR2 staining, and autoradiography also confirmed the expression of CCR2 and the uptake of 68Ga-DOTA-ECL1i in the metastatic foci in KPC mice. Using our novel CCR2 targeted radiotracer 68Ga-DOTA-ECL1i and PET/CT, we demonstrated the sensitive and specific detection of CCR2 in the early PDAC metastases in two mouse models, indicating its potential in future clinical translation.

ИЗМЕРЯЕМЫЙ КОЭФФИЦИЕНТ ДИФФУЗИИ В ДИАГНОСТИКЕ МЕТАСТАТИЧЕСКОГО ПОРАЖЕНИЯ КОСТЕЙ СКЕЛЕТА

Aim: To evaluate the possibilities of absolute and relative values of the apparent diffusion coefficient (ADC) in the diagnosis of metastatic lesions of skeletal bones. Material and methods: The study included 12 patients with metastatic bone lesions, before any treatment was applied. The age of the patients ranged from 38 to 73 years, 3 men, 9 women. Among the morphological forms of tumors were presented: cancers of the breast (3), prostate (1) glands, colon (1), lung (2), body (1) and cervix (1) uterus, thyroid (1) and pancreas (2). The detected changes were classified on the basis of Bone scan, SPECT/CT and standard MRI. The ADC values of unchanged bone marrow (n=360), divided by anatomical zones, metastatic foci (n=117), as well as benign changes of various nature (n=19) were analyzed. The ratio of the ADC values of each of the metastatic and benign focal formations to the normal values for each of the localizations was calculated. Results: Unchanged bone marrow, depending on anatomical localization (cervical, thoracic, lumbar spine, pelvic bones, shoulder blades, collarbones, sternum, ribs, proximal humerus and femur bones) from the point of view of ADC, showed statistically significant heterogeneity. Statistical analysis has shown that there is no connection between the groups of ADC indicators in the foci of metastatic lesions, combined depending on the anatomical localization. With a similar comparison, but by belonging to the primary tumor, an even greater intergroup difference was found. ADC values in the foci of metastatic lesions turned out to be dependent on the morphological type of the primary tumor and significantly differ both from metastases of other morphological affiliation and from normal red bone marrow parameters. The use of relative values allowed to increase the specificity from 15 to 19 %. Conclusion: This study showed that knowledge of the range of reference ADC values for unchanged red bone marrow and anomalies of various genesis is important in differential diagnosis. The differentiation of the skeleton into separate anatomical zones probably makes it possible to increase the effectiveness of the isolated application of the technique when it comes to absolute values. The morphological affiliation of metastatic foci is important in the formation of ADC values, rather than the bone marrow microenvironment, which is also supported by the low efficiency of the use of relative values.

A case report of early detection of rare femoral shaft bone metastasis in a penis cancer patient

Background. Bone metastasis is very common in the advanced stage of numerous carcinomas. In penile carcinoma, lymph nodes metastasis is somehow common but it is very rare reported to be secondary from penile cancer. till the date, there are only few cases of penis carcinoma reported bone metastasis in literature worldwide.Case Presentation. Herein, We presented a 51-year-old Nepalese male with squamous cell carcinoma of penis. computed tomography (ct) scan of the patient revealed that there was carcinoma involving glans penis and precure with bilateral external &amp; internal inguinal lymphadenopathies. After then, the patient was under gone for partial penectomy and bilateral inguinal lymphadenectomy and complete 6-cycle chemotherapy. After one year of treatment, patient developed thigh pain and headache and he advised to have magnetic Resonance imaging (mRi) of brain, 99mTc-MDP whole body bone scan and ct scan of pelvis and thigh. The examination report reveals that there was a sclerotic change in vertex of skull bone and moderate 99mTc-MDP uptake in right proximal shaft of femur just below the neck d/d metastasis. The histopathological examination of the true cut biopsy taken from the lesion of the femur showed metastatic keratinizing squamous cell carcinoma which is rare case of femoral shaft bone metastasis secondary from penile carcinoma. Then patient was sent for surgical reconstruction of femur. Based on the case studies review femur shaft bone metastasis from penile cancer is extremely rare.Conclusion. The best of our knowledge; this is the first early detected bone metastases to shaft of the femur in a patient with penile cancer. early diagnosis helps to radical treatment as well as palliative treatment. surgery is the preferred option of the treatments, especially for metastatic foci in the long bones.

CANCER AND NEW PROSPECTIVE TO TREAT CANCER

Cancer is a condition when a few of the body's cells grow out of control and spread across other bodily regions. In the millions of cells that make up the human body, cancer may develop practically anywhere. Human cells often divide (via a process known as cell growth and multiplication) to create new cells when the body requires them. New cells replace old ones when they die as a result of ageing or injury. Aside from recent significant advancements in stem cell treatment, targeted therapy, ablation therapy, nanoparticles, natural antioxidants, radionics, chemodynamic therapy, sonodynamic therapy, and ferroptosis-based therapy, traditional treatment modalities like surgery, chemotherapy, and radiotherapy are still in use. Oncology practices today concentrate on creating effective and secure cancer nanomedicines. Targeting both primary and metastatic cancer foci, stem cell treatment has demonstrated remarkable success in regenerating and repairing sick or damaged tissues, and nanoparticles have introduced novel diagnostic and therapeutic possibilities. The development and spread of particular cancer cells can be prevented by targeted treatment, which also protects good cells from harm. Ablation treatment has become a less invasive method for freezing or burning tumours without performing open surgery. Natural antioxidants have shown promise in locating free radicals and counteracting their damaging effects, perhaps treating or preventing cancer. Clinical trials are being conducted on a number of innovative technologies, some of which have already received approval. A summary on current developments and discoveries in cancer therapy was provided in this review.

Bcl-xL mediates interferon-beta secretion by protease-activated receptor 2 deficiency through the mitochondrial permeability transition pore in colorectal cancer metastasis

Cellular plasticity and immune escape are synergistic drivers of tumor colonization in metastatic organs. Activation of protease-activated receptor 2 (PAR2) signaling promotes metastasis of colorectal carcinoma (CRC). The role of PAR2 in regulating the immune microenvironment and cancer progression remains unclear. We demonstrated that the regulation of liver metastasis by PAR2 requires a competent immune system. PAR2 knockdown enhanced liver infiltration of activated CD8+ T cells prior to metastatic foci formation in an interferon receptor-dependent manner. PAR2 depletion increased interferon (IFN)-β production via the cGAS-STING and RIG-1 pathways. PAR2 inhibition increased mitochondrial permeability and cytosolic accumulation of mitochondrial DNA, which was reversed by Bcl-xL expression. Strikingly, shRNA against PAR2 with an immune checkpoint blocker (ICB) acted synergistically to suppress liver metastasis. Analysis of single-cell sequence data and 24 paired samples confirmed the regulatory effect of PAR2 on the metastatic immune environment in human CRC. Therefore, PAR2 signaling is involved in stabilizing the mitochondrial membrane and regulating the immune microenvironment through IFN-β during liver metastasis in CRC. The synergistic effect of the PAR2 inhibitor and ICB provides a potential therapeutic strategy for metastatic CRC treatment.

Clinical Outcomes of Radioactive Iodine Redifferentiation Therapy in Previously Iodine Refractory Differentiated Thyroid Cancers.

Objective: Redifferentiation therapy (RDT) can restore radioactive iodine (RAI) uptake in differentiated thyroid cancer (DTC) cells to enable salvage 131I therapy for previously RAI refractory (RAIR) disease. This study evaluated the clinical outcomes of patients who underwent RDT and identified clinicopathologic characteristics predictive of RAI restoration following RDT. Methods: This is a retrospective case series of 33 patients with response evaluation criteria in solid tumors (RECIST)-progressive metastatic RAIR-DTC who underwent RDT between 2017 and 2022 at the Mayo Clinic (Rochester, MN). All patients underwent genomic profiling and received MEK, RET or ALK inhibitors alone, or combination BRAF-MEK inhibitors for 4 weeks. At week 3, those with increased RAI avidity in metastatic foci received high-dose 131I therapy. Baseline and clinicopathologic outcomes were comprehensively reviewed. Results: Of the 33 patients, 57.6% had restored RAI uptake following RDT (Redifferentiated subgroup). 42.1% (8/19) with papillary thyroid cancers (PTC), 100% (4/4) with invasive encapsulated follicular variant PTCs (IEFV-PTCs), and 100% (7/7) with follicular thyroid cancers (FTC) redifferentiated. All (11/11) RAS mutant tumors redifferentiated compared with 38.9% (7/18) with BRAF mutant disease (6 PTC and 1 IEFV-PTC). 76.5% (13/17) of redifferentiated and 66.7% (8/12) of non-redifferentiated patients achieved a best overall RECIST response of stable disease (SD) or non-complete response/non-progressive disease. Both subgroups had a median 12% tumor shrinkage at 3 weeks on drug(s) alone. The redifferentiated subgroup, following high-dose 131I therapy, achieved an additional median 20% tumor reduction at 6 months after RDT. There were no statistically significant differences between both groups in progression free survival (PFS), time to initiation of systemic therapy, and time to any additional therapy. Of the entire cohort, 6.1% (2/33) experienced histologic transformation to anaplastic thyroid cancer, 15.1% (5/33) died, and all had redifferentiated following RDT and received 131I therapy. Conclusion: RDT has the potential to restore RAI avidity and induce RECIST responses following 131I therapy in select patients with RAIR-DTC, particularly those with RAS-driven "follicular" phenotypes. In patients with PTC, none of the evaluated clinical outcomes differed statistically between the redifferentiated and non-redifferentiated subgroups. Further studies are needed to better characterize the long-term survival and/or safety outcomes of high-dose RAI following RDT, particularly whether it could be associated with histologic anaplastic transformation.

Crioablación de tumores de mama

Cryoablation is a percutaneous thermal ablation technique developed to destroy focal groups of cells using extreme cold. It is an outpatient and image-guided procedure, performed under local anaesthesia, with typically short recovery times and good outcomes. Percutaneous cryoablation has good success rates for treating breast fibroadenomas. It is used in cases of malignant tumours mainly when a patient refuses surgery or is not considered to be a suitable candidate. Some studies indicate that cryoablation could be as effective and safe as lumpectomy in cases of low-risk early-stage breast cancer. Moreover, some studies have reported a regression of metastatic foci after ablation of a primary tumour thanks to an anti-tumour immune response stimulated by cryoablation. This article describes the technique and its indications with regards to breast tumours according to the existing literature.

Comparative analysis of the use of B16 melanoma and epidermoid Lewis lung carcinoma models for preclinical studies of compounds with a putative antitumor effect

Introduction The search for new compounds with putative antitumor effects and the development of domestic anticancer and antimetastatic drugs based on them is a priority task for specialists in the field of medical chemistry, experimental pathophysiology and pharmacology. Melanoma B16 and Lewis lung epidermoid carcinoma are universal models for evaluating the effect of compounds with putative antitumor action on the primary focus of tumor growth and the process of tumor cells dissemination.The aim of the work is to determine the feasibility of using models of solid tumor growth and metastasis activity of Lewis lung epidermoid carcinoma and B16 melanoma for preclinical studies of antitumor and antimetastatic pharmacological activity of hybrid organotin compounds depending on experimental objectives.Materials and methods The experimental part was performed on C57B1/6 mice (females). Hybrid organotin compounds were administered five times, intraperitoneal, the beginning of treatment – 48 hours after tumor cells transplantation in the same regimes for both models. In this work, the most effective (375 mg/kg and 250 mg/kg, respectively) and toxic (500 mg/kg and 375 mg/kg, respectively) doses of the leader hybrid organotin compounds Me3 (bis(3,5-di-tert-butyl-4-hydroxyphenylthiolate) dimethytin) and Me5 ((3,5-di-tert-butyl-4-hydroxyphenylthiolate)triphenyltin) were used.Results At all stages of the experiment on both models of tumor growth we obtained similar results characterizing the pharmacological activity of the tested compounds: moderate antitumor and high antimetastatic effect. The rates of growth and tumor process development are comparable and convenient for planning preclinical studies in vivo and can be interchangeable.Discussion The Lewis lung model of epidermoid carcinoma has a higher degree of convenience for data interpretation (number of metastatic foci in the lungs) when conducting exploratory analysis of pharmacological activity in a wide range of doses. When studying pathogenetic peculiarities of metastasis under the action of compounds with presumed antitumor action due to the possibilities of contrast immunohistochemical staining of tumor cells, the B16 melanoma model has an advantage. In our experiment with immunohistochemical staining for Melan A the hematogenic pathway of metastasis through the bloodstream is clearly traced.Conclusion For exploratory screening studies to select promising candidates for in-depth study it is reasonable to use the Lewis lung epidermoid carcinoma model. The B16 melanoma model is more informative for in-depth study of compounds that have proven to be effective.

Intracranial hemangiopericytoma: long-term surgical outcomes

BACKGROUND: According to 2021 WHS Classification, intracranial hemangiopericytomas or solitary fibrous tumors are rare meningeal neoplasms involving blood vessels and soft tissues. Such neoplasms are commonly classified as malignant due to their aggressive growth, metastasizing beyond the cranial cavity, and frequent recurrencies. Since these tumors rarely occur in neurosurgical patients, publications in Russian do not cover big cohorts of patients whose conditions would be assessed during both early and late observation periods.&#x0D; AIM: The present study analyzed our experience in surgical treatment of hemangiopericytomas and its long-term results.&#x0D; METHODS: The study was arranged as a single-center, pro-and retrospective trial that included hemangiopericytomas patients (n=17), whose tumors of different grades of malignancy (13) were operated at the Federal Neurosurgical Center in Novosibirsk from 2013 to 2021. The follow-up estimates included survivability; physical status (Karnofskys Scale); radicality; metastatic foci; need for postoperative chemo-and radiation therapy; adjuvant therapy effect on patients survivability, and delaying time to relapse.&#x0D; RESULTS: In total, 17 patients were included. 11 of them underwent total hemangiopericytomas removal (65%), and 6 subtotal removal (35%). Their survivability within the first year after the operation was 100%. As for the 5-year follow up, only 8 patients out of 17 were available, their mean observation time comprising 64.7 months. The 5-year survivability was 75% (6 out of 8 patients). A relapse occured in 3 out of 17 (17.5%). The mean delaying time comprised 67 months. 6 out of 17 patients (35%) underwent radiation therapy. Among the patients with total and subtotal removals who underwent postoperative radiation treatment neither a relapse nor tumor growth nor metastases were found.&#x0D; CONCLUSION: Intracranial hemangiopericytoma is a rare malignant space-occupying neoplasm. Considering our experience and published data, its treatment requires aggressive tactics that includes a radical removal of the tumor followed by early irradiation of the tumors residual volume or bed either in a proton accelerator or a gamma-knife facility notwithstanding its malignancy grade. It is also recommended to extend the follow-up period for such patients to 1015 years that should include annual cancer screening to detect local relapses and metastases.

Cancer treatment therapies: traditional to modern approaches to combat cancers.

As far as health issues are concerned, cancer causes one out of every six deaths around the globe. As potent therapeutics are still awaited for the successful treatment of cancer, some unconventional treatments like radiotherapy, surgery, and chemotherapy and some advanced technologies like gene therapy, stem cell therapy, natural antioxidants, targeted therapy, photodynamic therapy, nanoparticles, and precision medicine are available to diagnose and treat cancer. In the present scenario, the prime focus is on developing efficient nanomedicines to treat cancer. Although stem cell therapy has the capability to target primary as well as metastatic cancer foci, it also has the ability to repair and regenerate injured tissues. However, nanoparticles are designed to have such novel therapeutic capabilities. Targeted therapy is also now available to arrest the growth and development of cancer cells without damaging healthy tissues. Another alternative approach in this direction is photodynamic therapy (PDT), which has more potential to treat cancer as it does minimal damage and does not limit other technologies, as in the case of chemotherapy and radiotherapy. The best possible way to treat cancer is by developing novel therapeutics through translational research. In the present scenario, an important event in modern oncology therapy is the shift from an organ-centric paradigm guiding therapy to complete molecular investigations. The lacunae in anticancer therapy may be addressed through the creation of contemporary and pertinent cancer therapeutic techniques. In the meantime, the growth of nanotechnology, material sciences, and biomedical sciences has revealed a wide range of contemporary therapies with intelligent features, adaptable functions, and modification potential. The development of numerous therapeutic techniques for the treatment of cancer is summarized in this article. Additionally, it can serve as a resource for oncology and immunology researchers.

Adrenocortical carcinoma (ACC) with massive liver metastases in a 4-year-old female patient: the significance of chemotherapy and imaging studies in treatment and diagnosis – a case report

Background: Adrenocortical carcinoma (ACC) is a retroperitoneal tumour, accounting for less than 0.2% of all malignancies in children. In pediatric patients, the most common clinical presentation is virilisation, either isolated or in combination with hypercortisolemia.&#x0D; Case report: A 4-year-old girl was admitted to the hospital for diagnostic evaluation of precocious puberty and features of hypercorticism. Ultrasonography revealed a heterogeneous neoplastic lesion between the left kidney and spleen. Computed tomography (CT) scan confirmed a pathological mass in the left adrenal region. The urine steroid profile was suggestive of adrenocortical carcinoma. The patient was qualified for surgery. Histopathological examination confirmed the diagnosis. A PET scan performed a few months later showed a metabolically active lesion in the left lobe of the liver. Due to the suspicion of a metastatic focus, it was proposed to implement systemic treatment, to which the patient's parents did not agree. After 15 months of no treatment and oncological follow-up, the girl was referred to the ED with symptoms of progression of the neoplastic process. In the face of a renewed lack of consent to the inclusion of treatment, the patient was referred to a home hospice, where she died a short time later.&#x0D; Conclusions: In the pediatric population, adrenocortical carcinoma is a rare neoplasm with a very poor prognosis. Prompt diagnosis enables early identification of the primary tumour and implementation of appropriate treatment. Imaging examinations are crucial in order to assess the size of the tumour, the extent of local invasion and the presence of potential metastases.

High Incidence of Metastatic Infections in Panton-Valentine Leucocidin-Negative, Community-Acquired Methicillin-Resistant Staphylococcus aureus Bacteremia: An 11-Year Retrospective Study in Japan.

Panton-Valentine leucocidin (PVL)-negative community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) was originally disseminated in Japan and has since replaced healthcare-associated MRSA (HA-MRSA). However, the clinical characteristics of CA-MRSA bacteremia (CA-MRSAB) compared with those of HA-MRSA bacteremia (HA-MRSAB) are unknown. We aim to clarify differences and investigate associations between the clinical manifestations and virulence genes associated with plasma-biofilm formation in PVL-negative CA-MRSA. From 2011 to 2021, when CA-MRSA dramatically replaced HA-MRSA, 79 MRSA strains were collected from blood cultures and analyzed via SCCmec typing and targeted virulence gene (lukSF-PV, cna, and fnbB) detection. The incidence of metastatic infection was significantly higher in CA-MRSAB than in HA-MRSAB. PVL genes were all negative, although cna and fnbB were positive in 55.6% (20/36) and 50% (18/36) of CA-MRSA strains and 3.7% (1/27) and 7.4% (2/27) of HA-MRSA strains, respectively. cna and fnbB carriage were not associated with the development of metastatic infections in MRSAB; however, the bacteremia duration was significantly longer in CA-MRSAB harboring cna. CA-MRSAB may be more likely to cause metastatic infections than HA-MRSAB. Since CA-MRSA is dominant in Japan, suspected metastatic infection foci should be identified by computed tomography, magnetic resonance imaging, and echocardiography when treating MRSAB.

SAT520 Efficacy of Radioactive Iodine Redifferentiation Therapy in Previously Iodine Refractory Differentiated Thyroid Cancers

Abstract Disclosure: D. Toro-Tobon: None. J.C. Morris: None. C. Hilger: None. C.S. Peskey: None. D.M. Jolanta: None. M.M. Ryder: None. Objective: Patients with metastatic differentiated thyroid cancer (DTC) that are radioactive iodine (RAI) refractory (RAIR) have a poor prognosis. Redifferentiation therapy (RDT) has emerged as a potential approach to restore RAI avidity in this disease. The aim of this study was to examine the efficacy and predictors of RAI restoration in RAIR disease, as well as examine the outcomes of patients re-treated with high dose RAI following RDT. Methods: A retrospective review was conducted of 33 patients with RECIST-progressive metastatic RAIR-DTC who underwent RDT between 2017 and 2022 at the Mayo Clinic. All patients underwent genomic profiling, and either MEK inhibitor alone or combination BRAF-MEK inhibitors were prescribed for 4 weeks. At week 3, Thyrogen-stimulated I-123 whole body scans were performed. Those with increased RAI avidity in metastatic foci received high dose I-131 therapy using a previously published modified dosimetry protocol. Baseline and clinicopathologic outcomes were comprehensively reviewed. Results: Of the 33 patients, 12 of 23 (52%) with papillary thyroid cancers (PTC), 4 of 4 (100%) with follicular variant PTCs (FV-PTC), and 7 of 7 (100%) with follicular thyroid cancers (FTC) had restored RAI avidity following RDT using dabrafenib/trametinib (7 for BRAF mutant disease) or trametinib monotherapy (12 for RAS mutant disease). All 11 (100%) RAS mutant tumors (2 PTC, 3 FV-PTC, and 6 FTC) had RAI avidity restoration compared to 7 (36%) with BRAF mutant disease (6 PTC, and 1 FV-PTC). Of the 19 patients (57%) with restored RAI avidity (responders), 18 (94%) received I-131 with a median dose of 294 mCi. The median thyroglobulin (Tg) in responders was 294 mIU/L as compared to 29 mIU/L in non-responders. Following RDT-facilitated I-131 treatment, 94.7% achieved RECIST defined objective response (complete or partial response, stable disease, non-complete response/non-progressive disease) with a median progression free survival of 18 months and an overall survival of 30 months. Overall, patients with FTC (p=0.01), RAS mutation (p&amp;lt;0.001), Tg of 294 mIU/L or more (p=0.03), largest tumor diameter of 1.7 cm or less (p=0.05), bone metastasis (p=0.007), and without locoregional nodal disease (p=0.04), were more likely to demonstrate restored RAI avidity following RDT. Of the entire cohort, 2 (6%) patients experienced histologic transformation to anaplastic thyroid cancer and 5 (15%) patients died, all had had RAI restoration and received high-dose RAI following RDT. Conclusion: RDT has the potential to restore RAI avidity and induce RECIST responses following I-131 therapy in select patients with RAIR-DTC, particularly those with RAS mutations and ‘follicular’ phenotypes. Further studies are needed to better characterize the long-term survival and/or safety outcomes of high-dose RAI following RDT, particularly whether it could be associated with histologic transformation. Presentation Date: Saturday, June 17, 2023

THU483 Role Of Excess GH On Breast Cancer Aggressiveness And Metastasis In Acromegaly

Abstract Disclosure: J. Oh: None. C. Kang: None. E. Wang: None. S. Lee: None. J. Nam: None. C. Ku: None. E. Lee: None. Introduction Acromegaly is a rare disease characterized by chronic growth hormone (GH) and insulin-like growth factor-1 hypersecretion. In previous studies, it is known that the incidence of breast cancer increases in patients with acromegaly. For breast cancers, autocrine GH and GHR are expressed in primary lesion, which is significantly increased in metastatic one. To date, however, the precise mechanism of endocrine GH in breast cancer metastasis has not been defined. This study aimed to investigate the role of endocrine excess GH facilitating breast cancer metastasis in acromegaly mice model. Method We used Aiplox/lox (Con) and rGHp-Cretg/+; Aiplox/lox mice (Acro), which was previously established to model the phenotype of human acromegaly. To generate orthotopic xenograft model, we used C57BL/6 female mouse derived breast cancer cell line Py230 cells. Py230 cells were injected into mammary gland and tumor volumes were measured every 2 days. Tumor growth and metastasis were confirmed by bioluminescent in vivo imaging system (IVIS). Also, we investigated the effects of GH on triple negative breast cancer cell lines, which have the higher expression of GHR. To define GH induced pathway, we performed RT2 array. Cell proliferation was investigated with MTT assay and cell migration was investigated with wound healing assay and transwell invasion assay. Results In mouse orthotopic xenograft studies, tumor volumes of Acro mice were higher than that of Con mice (increase of 310%, 846.04±290.7 vs. 205.97±33.7 mm3, p=0.001). The tumor volume and serum GH level showed positive correlation (R2= 0.4739, p=0.027). After 14 weeks, the Acro mice showed significantly increased bioluminescence activity in the lung (increase of 1023%, 494666.7±104668.2 vs. 44037.7±6641.9 AU, p=0.0127). When GHR antagonist was treated, tumor growth and lung metastasis were decreased. We excised primary tumor and lung metastatic foci and performed RT2 array. We found Tcf-20 gene, which is upregulated in both primary tumor and lung metastatic burden (increase of 216%, p=0.0153). We confirmed GH induced Tcf-20 gene induction (increase of 57% (p=0.043), 41% (p=0.05), 67% (p=0.0021) in Hs578T, Py230 (p=0.05), and Hcc1806 cells each). We knocked down Ghr or Tcf-20 genes and observed decrease of invasion and migration compared to GH treated siCON HCC1806 (decrease of 64.5% in siGHR, decrease of 83.3% in siTCF-20, compared to siCON cells, p=0.000819977) and Py230 cells (decrease of 47.3% in siGHR transfected, decrese of 49.3% in siTCF-20 transfected, compared to siCON cells, p=0.0012). Conclusion Excess GH in acromegaly possess a strong potential to promotes tumor development and metastasis. We identified a molecular mechanism by which GH-induced TCF-20 promote tumor aggression and metastasis. These findings can aid in the development of improved strategies for managing cancer in acromegalic patients. Presentation: Thursday, June 15, 2023

Malignant neoplasia in Meckel’s diverticulum — our experience

Meckel’s diverticulum is the most common congenital anomaly within the gastrointestinal tract, with a prevalence in the general population of 0.9–3 %. Among the malignant neoplasms associated with Meckel’s diverticulum, carcinoids and gastrointestinal stromal tumors predominate in percentage, with adenocarcinomas accounting for less than 6% of all associated malignancies. The authors present a rare case report of a 67-year-old patient with gastric-type adenocarcinoma in Meckel’s diverticulum, with metastatic foci in both lobes of the liver at the time of diagnosis. The case demonstrates diagnostic and therapeutic procedures that led to a correct diagnosis and a satisfactory treatment outcome. They emphasize the importance of using all the possibilities of diagnosis and treatment as well as the necessity of cooperation with other experts in the proper management of this disease, they express an opinion about considering prophylactic resection of intraoperatively detected Meckel’s diverticulum.

466P Integrated analysis of potential prognosis and differential expression between primary and metastatic foci for COL12A1 in breast cancer

466P Integrated analysis of potential prognosis and differential expression between primary and metastatic foci for COL12A1 in breast cancer

Pretreatment Clinical Parameters Associated with Intracranial Progression Burden Following an Initial Stereotactic Radiosurgery Course in a Multi-Institutional Brain Metastases Cohort

While brain metastasis (BM) velocity is a valuable prognostic metric at time of intracranial progression (ICP), pre-SRS risk factors for post-SRS high-burden intracranial progression (ICP) remain poorly characterized. We hypothesized that pre-SRS clinical parameters are associated with subsequent high-burden (ICP), defined as either ≥5 (ICP5) or new/progressive ≥11 BMs (ICP11). All patients completing an initial SRS course for BMs at two institutions from 1/2015-12/2020 were retrospectively identified. Patients with prior whole brain radiation therapy (WBRT) and/or BM resection were eligible. Demographic and clinical parameters were collected. ICP was defined as any radiographic concern for distant and/or in-field progression per multidisciplinary consensus. Overall survival (OS) and freedom from ICP were estimated via the Kaplan Meier method. Cox models assessed association between parameters and freedom from ICP5 and ICP11. We identified 1383 patients completed SRS, with a median follow up of 8.7 months. Patients were 54.8% female, 45.6% with KPS ≥90, and a median of 63.4 years old. Primary tumor types included non-small cell lung (48.7%), breast (14.7%), and melanoma (8.5%). 46.9% had oligometastatic disease (≤5 metastatic foci: including BMs) at SRS, and 53.4% underwent SRS for >1 BM. 10.3% of patients had undergone prior WBRT and 26.1% surgical resection. 555 patients (40.1%) experienced ICP following SRS, of whom 72.6% had 1-4, 11.5% had 5-10, and 15.9% had ≥11 new/progressive BMs. Among patients with ICP, 6-month freedom from ICP was 35.5% (95% CI: 31.1-40.5%) for those with 1-4 BMs at time of ICP, 29.7% (95% CI: 20.4-43.3%) for 5-10 BMs, and 20.5% (95% CI: 13.5-30.1%) for ≥11 BMs (p = 0.016). Respective 12-month OS rates were 56.8% (95% CI: 52.1-61.9%), 46.0% (95% CI: 35.1-60.1%), and 38.7% (95% CI: 29.4-50.9%; p<0.001). Neurologic symptoms at time of ICP were observed in 21.1% of patients with 1-4 BMs, 28.1% with 5-10 BMs, and 50.0% with new/progressive ≥11 BMs (p<0.001). On multivariable analysis, superior freedom from high-burden ICP was associated with the following pre-SRS parameters: oligometastatic burden (ICP5: HR 0.68, 95% CI: 0.47-0.99; ICP11: 0.59; 95% CI: 0.36-0.97), no prior immunotherapy (ICP11: HR 0.57, 95% CI: 0.34-0.57), and a single BM at time of initial SRS (1 vs 2 BM, ICP 5: HR 0.51, 95% CI: 0.31-0.82; ICP11: HR 0.45, 95% CI: 0.24-0.84), while primary tumor type was not associated with ICP5 or ICP11. Pre-SRS parameters including polymetastatic burden, prior receipt of immunotherapy, and >1 BM were associated with post-SRS high-burden ICP. High burden ICP developed earlier following SRS completion and was associated with higher rates of neurologic decline and inferior OS.