Treatment Of Tumors Research Articles

Percutaneous cryoablation in soft tissue tumor management: an educational review

Abstract Background Percutaneous cryoablation (PCA), having shown effectiveness in treating liver, lung, prostate, breast, and kidney tumors, is now gaining attention for the treatment of soft tissue tumors. PCA functions by freezing tissue, which induces ice crystal formation and cell death without damaging collagen structures. Technical considerations include the selection and handling of cryoprobes and cryogenic agents, procedural duration, and choice of image guidance for precision. This review aims to synthesize the mechanisms, applications, and technical aspects of PCA in the treatment of soft tissue tumors. Methods Adhering to PRISMA 2020 guidelines, a review was conducted of studies published prior to March 2024 that investigated PCA of soft tissue tumors. The review focused on technical and procedural aspects of cryoablation, cryobiological principles, cellular and tissue responses to extreme cold, intra- and post-procedure physiological mechanisms during and post-procedure, and main clinical applications. Results PCA is efficient in treating soft tissue tumors, including desmoid tumors, vascular malformations, and abdominal wall endometriosis. Several cryobiological mechanisms are involved, notably ice crystal formation, cellular dehydration, osmotic effects, and the inflammatory response, all of which contribute to its efficacy. Key technical aspects include the choice of cryoprobes, cryogenic agents (argon gas or liquid nitrogen), and the duration and control of freezing/thawing cycles. PCA also frequently outperformed traditional treatments like surgery and radiotherapy in terms of pain reduction, tumor size reduction, and patient outcomes. Moreover, its nerve sideration properties make it effective under local anesthesia. Conclusion Demonstrating substantial pain reduction, tumor size decrease, and high technical success rates, PCA offers a promising and minimally invasive alternative for soft tissue tumor treatment. Critical relevance statement Percutaneous cryoablation provides a minimally invasive, precise alternative for soft tissue tumor management, advancing clinical radiology by offering effective treatment with reduced patient risk and enhanced outcomes through image-guided procedures. Key Points Percutaneous cryoablation (PCA) offers a promising, minimally invasive alternative for managing soft tissue tumors. PCA employs image-guided techniques to accurately target and treat tumors, ensuring high precision and control. PCA preserves structures like collagen, reduces pain, decreases tumor size, and generally enhances patient outcomes. Graphical Abstract

Comparison of robotic vs. laparoscopic treatment in pediatric ovarian benign tumors

Comparison of robotic vs. laparoscopic treatment in pediatric ovarian benign tumors

Abstract PR001: An immunomodulatory crosstalk between cancer cells and the hepatic microenvironment underlies mutant estrogen receptor-driven breast cancer-to-liver metastasis

Abstract While major advancements have been made in treatment of primary tumors in estrogen receptor-positive (ER+) breast cancer, reducing mortality from metastatic breast cancer (mBC) in treated patients who develop endocrine resistance to first line therapies remains an unmet clinical need. Wild-type ER activity or availability of its cognate ligand 17-beta estradiol (E2) are major factors in primary tumor progression, which are lost/reduced due to endocrine treatments, such as use of selective estrogen degraders (SERDs) and aromatase inhibitors (AIs), respectively. Over time, this leads to selection of rare cancer cells bearing point mutations in ESR1, the gene encoding ER-alpha, which become the dominant population at metastatic sites, and such mutations are now recognized as a frequent driver of endocrine resistance and metastasis, especially in patients with advanced ER+ breast cancer who have been heavily pre-treated with AIs. Analyses of clinical samples have shown a statistically significant association enrichment of ESR1 mutations in liver metastases, compared to the primary tumor. Other distant tissues commonly colonized by breast cancer cells, such as bones, lungs, or brain, although prevalent, do not display this strong association. While this might be due to ease of biopsy sampling in the liver compared to other sites, an alternate and intriguing hypothesis is that the liver offers a fertile soil for metastatic colonization by mutant ER-expressing cells, compared to other distant sites, such as lungs. Using a combination of pre-clinical models, we assessed if mutant ER could drive metastatic colonization at distant sites, such as the liver. We have uncovered a novel link between cancer cell-intrinsic immunomodulatory signaling pathways that are specifically upregulated in mutant ER-expressing breast cancer cells, which represents at least one major molecular mechanism underlying the observed liver tropism of mutant ER-associated, endocrine resistant ER+ breast cancer. We show that disseminated, mutant ER-expressing BC cells engage in crosstalk with the liver stromal and immune populations post-extravasation to further fuel metastatic outgrowth. Citation Format: Sunny Das, Joana Liu Donaher, Lisa Verhoeven, Ranjan Mishra, Ferenc Reinhardt, Sumeet Gupta, Zheqi Li, Kornelia Polyak, Robert A. Weinberg. An immunomodulatory crosstalk between cancer cells and the hepatic microenvironment underlies mutant estrogen receptor-driven breast cancer-to-liver metastasis [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Tumor-body Interactions: The Roles of Micro- and Macroenvironment in Cancer; 2024 Nov 17-20; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2024;84(22_Suppl):Abstract nr PR001.

Engineered Platelets for Cancer Therapy

ABSTRACTWhile nanomedicine research shows a great progress in the treatment of cancer, it still faces challenges of tumor recurrence and metastasis. Numerous studies have demonstrated intricate crosstalk between platelets and tumor cells. The re‐education of platelets by tumor cells enables these platelets to provide critical assistance for tumor proliferation, recurrence, and metastasis. Engineered platelets have shown promising potential in the treatment of tumors, postoperative tumor recurrence, and tumor metastasis. Different engineering technologies such as surface modification, gene editing, membrane coating, and loading into hydrogels can produce multifunctional and customized engineered platelets. These engineered platelets inherit the key properties of platelets, including long blood circulation, tumor targeting, and thrombus targeting, and can be stimulated to generate derivatized particles. In this review, we elucidate the critical role of platelets in the complex processes of tumorigenesis and tumor progression and summarize the emerging paradigm of engineered platelets in tumor therapy. The purpose of this review is to comprehensively explore the potential value of engineered platelets toward the clinical treatment of cancer, providing a valuable reference for the further development of engineered platelets and their broader applications in the field of cancer therapy.

Repurposing of PSMA-targeted diagnostic and therapeutic agents for the detection and treatment of giant cell tumors of bone

Giant cell tumor of bone (GCTB) is a rare bone tumor often necessitating surgical intervention, radiation therapy, or treatment with bisphosphonates or denosumab. 99mTc-MDP bone scintigraphy for GCTB has limited specificity, and the relatively high uptake of 18F-FDG in GCTB makes it challenging to differentiate it from other benign bone tumors. More specific detection and treatment modalities for GCTB are needed to enhance patient monitoring and outcomes. Prostate Specific Membrane Antigen (PSMA) is present in the neovasculature of various tumors, yet unexplored in GCTB. PSMA-targeted imaging and radiotherapeutic agents Locametz and Pluvicto are a powerful theranostic pair for detecting and treating PSMA-positive metastatic tumors, including those in bone, and thus have considerable potential to be repurposed for GCTB. This study aimed to determine if the vasculature of GCTB was PSMA-positive and whether targeting it with PSMA-specific agents was feasible. Using bone core samples from 28 GCTB patients and 9 negative controls, we present the first robust detection of PSMA on the tumor vasculature of GCTB. To demonstrate the potential repurposed use of PSMA-targeted agents in detecting and treating GCTB, we used a PSMA-specific fluorescent probe (FAM-C6-1298) as a model for these radiopharmaceutical agents. Incubation of fresh GCTB tissue samples with FAM-C6-1298 showed increased fluorescence intensity compared to controls, indicating successful targeting of PSMA in GCTB tissue. In conclusion, our data established that PSMA is not only present in the tumor vasculature of GCTB patient tissue but can be effectively targeted with repurposed PSMA-specific radiopharmaceuticals for diagnosis and therapy.

Rehabilitation Management of a Pediatric Patient with Modified Van Nes Prosthesis after Type B-IIIA Hip Rotationplasty: A Case Report

Van Nes rotationplasty has gained popularity as a surgical treatment for malignant bone tumors without resorting to amputation. However, the nature of the surgery poses unique challenges in the rehabilitation management in order to optimize safety and functional mobility. We describe a case of a 6-year-old female with Ewing’s sarcoma of the right femur who underwent Van Nes Type BIIIA rotationplasty. This procedure involved a complete femoral resection, with the tibia and the foot rotated by 180 degrees and the lateral tibial plateau placed into the acetabulum that is expected to remodel to form a neo-hip joint. The patient was referred to rehabilitation medicine and was eventually admitted due to impairment in mobility secondary to the surgery. The goal was to achieve K-1 level of function. This case demonstrates that the rehabilitation management of a child with Type B-IIIA rotationplasty using a modified Van Nes prosthesis requires a comprehensive multidisciplinary approach.

NOT THE USUAL SUSPECTS: GLIOBLASTOMA OF THE CEREBELLOPONTINE ANGLE MASQUERADING AS A VESTIBULAR SCHWANNOMA

Introduction Most tumoral processes involving the cerebellopontine angle (CPA) are extraneuraxial and usually comprise of vestibular schwannomas and meningiomas, followed by less common lesions such as epidermoid cysts, metastases and arachnoid cysts. Glioblastomas located in the CPA are rarely diagnosed. Uncommonly, intraneuraxial tumors in the CPA may grow in an exophytic manner compressing the surrounding cranial nerves, resembling the clinical picture of a more common extraneuraxial tumour. Clinical Case A 47 year old male presented to our department accusing gait imbalance, vertigo, vomiting and nausea, symptoms that started 2 months prior to admission. Upon neurological examination, the patient additionally presented right facial paresis and hypoesthesia, right sided hypoacusis, hypogeusia and diplopia. A contrast enhanced cerebral MRI revealed a right cerebellopontine angle mass with inhomogenous contrast enhancement, relatively well delineated, exerting mass effect on the cerebellum and pons with reduced perilesional edema but with involvement of the internal acoustic meatus. The indication for surgical removal of the tumour was made. The patient was placed in sitting position and a right retrosigmoid approach was performed using the operating microscope. Upon retraction of the cerebellar hemisphere, a greyish, highly vascularized and soft lesion was seen, exhibiting a spread growth, engulfing the V, VII and VIII nerves, without infiltrating them, resembling anything but a schwannoma. A frozen section of the tumour revealed a surprising result: high grade glioma. The surgical excision continued in a piece-meal fashion, using the ultrasonic aspirator with preservation of the cranial nerves until an almost complete removal was achieved. The immediate postop evolution of the patient was favourable. Nevertheless, the final histopathological diagnosis confirmed a grade IV glioblastoma. Oncological treatmend followed, but the tumour relapsed in 2 months after surgery, the control MRI revealing a multilocular tumoral dissemination in the cerebellum and brainstem which was surgically unsalvageable. Conclusion Glioblastoma of the CPA, manifesting both imagistically and clinically as a vestibular schwannoma is a rare entity but nevertheless extant, that dramatically changes the prognosis and postop evolution of a patient. Physicians involved in the diagnosis and treatment of such tumours must always be suspicious of the usual suspects in the CPA.

Abstract PR001: Targeting mRNA methyltransferase in RNA-dependent DNA repair in cancer therapy

Abstract The treatment of many solid tumors presents significant challenges with chemotherapy, radiation therapy, and the limited effectiveness of immunotherapy. Targeted therapy offers a promising approach, yet the lack of validated targets limits its applicability across the spectrum of solid tumors. Our past studies have revealed that an R-loop and mRNA-dependent DNA repair (RDDR) pathway, induced by damage at the transcribed regions of the genome, contributes to cell survival and drug resistance in cancer cells. This is particularly due to the high levels of transcription and DNA damage in these cells. We identified the RNA methyltransferase TRDMT1 as the primary modifier of mRNA methyl-5-cytosine in the RDDR pathway. Overcoming technical difficulties in monitoring RNA modifications, we developed the first TRDMT1 inhibitor (TRDMT1i) using in-house built cell-based and in vitro assays. We have identified highly potent and specific lead compounds that significantly reduce TRDMT1 activity at nanomolar concentrations. Our current lead TRDMT1 inhibitors meets most of the criteria that are required for optimal lead. Initial assessments involving the screening of normal and cancer cell lines, xenograft models, and patient specimens indicate that TRDMT1i sensitizes tumors with genomic instability when used as monotherapy. We aim to develop TRDMT1i as an investigational new drug (IND) for future clinical trials, initially targeting ovarian cancer as a monotherapy or in combination therapy for first-line maintenance and systematic therapy. Our goal is to pioneer the discovery of the RDDR pathway, leading to the development of innovative platforms and next-generation medications to revolutionize the targeting of mRNA modifications in cancer treatment. Citation Format: Li Lan. Targeting mRNA methyltransferase in RNA-dependent DNA repair in cancer therapy [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: RNAs as Drivers, Targets, and Therapeutics in Cancer; 2024 Nov 14-17; Bellevue, Washington. Philadelphia (PA): AACR; Mol Cancer Ther 2024;23(11_Suppl):Abstract nr PR001.

Ifosfamide-Induced Encephalopathy Managed Successfully with Methylene Blue in a Child with Wilms Tumor: A Case Report and Review of the Literature

Introduction: Ifosfamide is a crucial element in various chemotherapy protocols for the treatment of diverse solid tumors in both children and adults. Despite its efficacy, ifosfamide is associated with a rare yet severe adverse effect known as ifosfamide-induced encephalopathy (IIE), with a spectrum of signs and symptoms spanning from mild lethargy to coma or death. While approximately 13% of pediatric patients undergoing ifosfamide treatment experience IIE, consensus regarding its management remains controversial. Case Presentation: We present the case of a 4-year-old girl with stage 4 Wilms tumor and lung metastases who underwent radical nephrectomy followed by UH-1 chemotherapy. Imaging post-chemotherapy initially showed tumor clearance but later revealed relapse and lung metastasis. Following the initiation of the adjusted ICE protocol (ifosfamide, etoposide), the patient developed IIE, which was successfully treated with methylene blue. Conclusions: We strongly advise pediatric oncologists and hematologists to proactively consider the potential occurrence of IIE. Before starting ifosfamide therapy, patients should be assessed for possible risk factors associated with IIE. Considering methylene blue as a prophylactic measure is recommended for patients with significant risk factors. In cases where IIE manifests, using Methylene Blue to alleviate and reverse its signs and symptoms should be considered. Moreover, we highly encourage further research endeavors to validate methylene blue's effectiveness and determine its optimal dosage range, especially concerning pediatric patients.

Update from d-uo: what can healthcare research contribute to renal cell carcinoma?

Renal cell carcinoma (RCC) accounts for about 13.5% of all urological tumors. Healthcare research analyzes whether treatment recommendations from controlled studies or guidelines are being implemented in routine care. Aprerequisite for the assessment and scientific study of the quality of care in the treatment of urological tumors is standardized documentation. This article illustrates healthcare research in RCC by presenting current data from the prospective of the VERSUS study (VERSorgUngsStudie) by d‑uo (Deutsche Uro-Onkologen). The VERSUS study is anoninterventional, prospective, multicentric study for the documentation and descriptive statistical analysis of the diagnosis, treatment, and aftercare of uro-oncological patients. Of 25,065 patients currently included in the VERSUS study, 1976 have a diagnosis of RCC. Data regarding stage distribution, reason leading to initial diagnosis, distribution of symptomatic vs. asymptomatic patients as well as surgical margins from surgical treatment of RCC are presented. Despite providing interesting results, the VERSUS study remains limited with regard to the depth of the data, since it relies on the same dataset as the German cancer registry. In order to provide more comprehensive healthcare research, organ-related cancer registries like the Urothelial Cancer National Registry (UroNAT) and the Prostate Cancer National Registry (ProNAT) by d‑uo are necessary. These national cancer registries by d‑uo are unique in that they comprise all tumor stages. The Renal Cancer National Registry (ReNAT) by d‑uo is in preparation and will be avaluable contribution to quality assurance of oncological care in Germany.

GAMMA KNIFE AND QUALITY OF LIFE: A REVIEW ON THE USE OF RADIOSURGERY IN BRAIN TUMORS

INTRODUCTION: Considering the quality of life of patients with brain tumors, several treatment alternatives have been developed over time, aiming at a less invasive potential and providing a permanent functional capacity for the individual. In this regard, in recent decades there has been debate about radiosurgery for the treatment of brain tumors. OBJECTIVE: The objective of this study was to evaluate the feasibility of Gamma Knife radiosurgery, considering patient safety. METHODS: This article is characterized as an integrative literature review of an exploratory nature, in the PubMED and Cochrane databases, the search was restricted to observational studies and randomized clinical trials as primary data to contemplate the outcomes Quality of life, neurological preservation, recurrence, cerebral complications and overall survival. RESULTS: The analysis of the collected data demonstrated that, in general, radiosurgery by the Gamma Knife platform preserves quality of life in several cases, mainly in smaller benign brain tumors. The disease recurrence rate after 3 years of radiosurgery ranged from 20 to 40%, depending on the type of tumor and treatment, with the highest recurrence rate in grade III meningiomas and high-grade gliomas. The 5-year recurrence rate ranged from 60 to 80%, and was therefore higher than that of more invasive treatments. CONCLUSION: The qualitative synthesis of these data proves the efficacy of radiosurgery and may suggest to neurosurgeons the possibility of treating brain tumors in patients who are not eligible for conventional surgery or in patients with non-bulky tumors.

In Situ Tumor-Infiltrating Lymphocyte Therapy by Local Delivery of an mRNA Encoding Membrane-Anchored Anti-CD3 Single-Chain Variable Fragment.

Tumor-infiltrating lymphocyte (TIL) therapy has shown promising responses in clinical trials for highly aggressive cancers such as advanced melanoma and metastatic colorectal cancer. However, TIL therapy is still limited in clinical practice due to the complex ex vivo cell preparation process. Here, we report an "in situ TIL therapy" for the treatment of solid tumors. We utilized lipid nanoparticles for the delivery of an mRNA encoding membrane-anchored anti-CD3 single-chain variable fragment (scFv) (MA-aCD3), efficiently engineering both tumor-associated macrophages (TAMs) and tumor cells following intratumoral delivery. Expression of MA-aCD3 resulted in enhanced TIL activation, proliferation, and tumor cell engagement directly within the tumor microenvironment. In B16F10 and MC38 tumor models, concurrent expression of MA-aCD3 on TAMs and tumor cells mediated by mRNA delivery resulted in significant antitumor effects via in situ polyclonal CD8+ TIL expansion and directed cytotoxic effector functions. In addition, combinatorial treatment of MA-aCD3-encoding mRNA and antiprogrammed cell death 1 (anti-PD-1) antibodies exhibited synergistic antitumor effects on anti-PD-1 refractory B16F10 tumors. Together, our findings suggest that in situ TIL therapy is a practical and effective mRNA-based therapeutic modality for the treatment of solid tumors.

DDEL-01. ENGINEERING MRNA THERAPIES FOR BRAIN TUMORS

Abstract Safe delivery of mRNA to the brain will revolutionize the treatment of brain tumors. While lipid nanoparticles (LNPs) are clinically most advanced non-viral delivery vehicles for therapeutic mRNA, LNP-mediated mRNA delivery to the brain remains challenging. We hypothesized that rationally designed LNPs based on extracellular vesicle mimicry would enable efficient delivery of RNA therapeutics to brain cells without undue toxicity. We engineered LNPs consisting of four components similar to the formulation used in the mRNA COVID-19 vaccines (Moderna and Pfizer-BioNTech): ionizable lipid, cholesterol, helper lipid and polyethylene glycol (PEG)-lipid. We screened ten classes of helper lipids based on lipids enriched in extracellular vesicles to engineer biomimetic LNPs and tested their GFP mRNA delivery efficacy in SIM-A9 mouse microglia cell line. Several unique LNP formulations with potent delivery efficacy (>90% cells transfected) and stable GFP expression kinetics (5 days) were identified. LNP formulations with high transfection efficacy were then tested in vivo for luciferase mRNA delivery via intrathecal injection in C57BL/6 mice. Luciferase expression in vivo confirmed widespread mRNA delivery in the brain. We then tested Cre recombinase mRNA delivery in Ai9 mouse to identify LNP-targeted cells via flow cytometry and histology. Flow cytometry and expansion microscopy confirmed Cre recombinase mRNA delivery to a variety of brain cells, including microglia (75-90%), neurons (31-40%), neural stem cells (39-62%), oligodendrocytes (70-90%), and astrocytes (44-76%). LNPs were further evaluated for Cas9 mRNA and CD81 sgRNA delivery in C57BL/6 mouse brains to assess brain-targeted gene editing. Sanger sequencing showed that CRISPR-Cas9 editing was successful in ~40% of cells in the mouse brain. In summary, we engineered extracellular vesicle-based LNP library that can deliver RNA therapeutics to a variety of brain cells in vivo. With further development, this technology could potentially enable genetic and epigenetic therapies targeting drivers of brain tumors.

INNV-10. ULTRA-RAPID INTRAOPERATIVE GLIOMA TUMOR CELL QUANTIFICATION

Abstract The diagnosis and treatment of brain tumors often depends on molecular-genetic data. To date, however, there has been no intraoperative method to rapidly and iteratively utilize tumor-specific genetic alterations to guide brain tumor surgical resections, complicating intraoperative diagnosis and precluding measurement of tumor cell burdens at surgical margins. To address this gap, we developed Ultra-Rapid droplet digital PCR (UR-ddPCR), which can be completed in 15 minutes from tissue to result with an accuracy and sensitivity comparable to standard ddPCR. We demonstrate an UR-ddPCR assay for the IDH1 R132H clonal mutation that is present in many low-grade gliomas. We illustrate the clinical feasibility of UR-ddPCR by performing it intraoperatively for 49 samples from 13 glioma cases, achieving intraoperative quantification in an average of 14 minutes and 54 seconds spanning a wide dynamic range from 0.1% to 94% tumor cell percentages. We further combine UR-ddPCR measurements with UR-stimulated Raman histology intraoperatively to estimate tumor cell densities in addition to tumor cell percentages, across a wide range from < 1 to 1332 cells/mm2. We anticipate that UR-ddPCR, along with future refinements in assay instrumentation, will enable novel point-of-care diagnostics and the development of molecularly-guided brain tumor surgeries that improve clinical outcomes.

EXTH-71. A MECHANISTIC INVESTIGATION INTO AUGER THERAPY: 2-DIMENSIONAL THIN-FILMS TO CHARACTERIZE THERAPEUTIC RANGEIN VITRO

Abstract Metallic nanoparticles can improve the accuracy and effectiveness of conventional radiotherapy in the treatment of solid tumors through a light-matter interaction known as the Auger effect. In this work, we present the assembly of an iron oxide (Fe3O4) nanoparticle (NPs) layer within a biocompatible polyelectrolyte film using ionic self-assembly to enable the spatial separation of NPs from their target cells. Films exhibited uniform nanoparticle coverage as well as strong stability in cell culture conditions. To investigate the applicability of NMDR with non-internalized NPs, conditions with (NP-PEM) and without (PEM) embedded nanoparticles were used to evaluate the therapeutic effect of physically separated nanoparticles on cells cultured on the film surface via a measure of intracellular reactive oxygen (ROS) generation and histone phosphorylation (yH2AX) after irradiation from a 137Cesium source. Cells cultured on NP-PEM demonstrated a 78.4% increase in ROS generation when compared to cells cultured on PEM films. When adjusting for cell count, NP-PEM films induce 70.5% greater ROS generation. In investigating nanoparticle-mediated deposition of radiation (NMDR), these films allow for the determination of the extent of the therapeutic effect when NPs are not internalized into their targeted cells, potentially providing indications with respect to off-target effects. Cells were irradiated on films with nanoparticle distances from 25.9 nm to 97.5 nm to interrogate the NMDR effect size at a range of distances. yH2AX phosphorylation exhibited an exponential decay until 69.8 nm, where there was no difference when compared to nanoparticle-free films. This work highlights the ability of iron oxide NPs to deliver NMDR at a known, quantifiable distance, providing insights for further translational applications.

Local Endoscopic Treatment of Low-Grade Urothelial Tumors in the Upper Urinary Tract—Oncological Outcome of a Consecutive Single-Center Series of 118 Patients

Background: Upper urinary tract urothelial tumors are mostly treated with the use of endoscopic laser ablation. The treatment is recommended when the tumor is low grade and non-invasive. Objective: The aim of the present study was to investigate the oncological outcome of patients treated endoscopically for low-grade (LG) upper tract urothelial carcinoma (UTUC). Methods: One hundred and eighteen consecutive patients with pTa LG UTUC initially treated with laser ablation from 2012–2022 at a single university hospital were included. Patient and tumor characteristics, treatment, and oncological outcomes were retrospectively registered from electronic medical journals. Survival analysis was performed using Kaplan–Meier and Nelson–Aalen plots. Results: The median number of local recurrences was 2 with a median time to first recurrence of 5 months (IQR: 2–46). The 2-year share of patients having no recurrence was 28.8%. The risk of recurrence was highest within the first 3 years following initial treatment. Two-year survival function with no progression and preserved renal unit was 67.9%. The two-year overall survival (OS) and disease-specific survival (DSS) were 84.2% and 97.1%. The 5-year OS and DSS were 59.1% and 94.1%. The median follow-up time for OS was 36 months (IQR: 20.3–58.8). Conclusions: In the patient series, we found that the risk of recurrence following laser ablation of LG UTUC was high; however, it was associated with a low risk of progression and high OS and DSS. Therefore, we conclude that treatment with laser ablation in patients with LG UTUC is safe, although frequent follow-up is needed to detect recurrence.

SURG-28. THE IMPACT OF PERILESIONAL HEATSINK STRUCTURES ON ABLATION VOLUMES AND SYMMETRY IN LASER INTERSTITIAL THERMAL THERAPY FOR THE TREATMENT OF PRIMARY CENTRAL NERVOUS SYSTEM TUMORS

Abstract BACKGROUND Laser Interstitial Thermal Therapy (LITT) has emerged as a minimally invasive treatment for primary CNS tumors. While LITT offers advantages over traditional approaches, perilesional intracranial heatsinks can lead to asymmetric ablation, impacting patient outcomes. Understanding heatsink effects is crucial for optimizing LITT efficacy. METHODS We retrospectively analyzed primary CNS tumors treated with LITT at a single tertiary care center. Ablation outcomes were quantified using the Heatsink Effect Index (HEI) measured on a scale of 0-1 (0=total symmetry; 1=complete asymmetry), and extent of ablation (EOA). Heatsink types evaluated were sulci, meninges, vasculature, and cerebrospinal fluid (CSF) spaces, inclusive of ventricles, surgical resection cavities, and CSF cisterns. Statistical analyses assessed the relationship between heatsink proximity and ablation outcomes. RESULTS A total of 99 patients satisfied all selection criteria. The cohort was 53% female, with a mean age of 61 years. Glioblastoma was the most predominant tumor type (78%), followed by low grade gliomas (15%), and meningiomas (4%). Heatsink proximity significantly correlated with ablation asymmetry (HEI) (p < 0.001), particularly at the midpoint of the catheter trajectory. The correlation between closest heatsink distance and HEI varied across the different heatsink types, with distance to vasculature and CSF spaces correlating the strongest with ablation asymmetry. When assessing the relationship between EOA and medial HEI during suboptimal ablations (EOA < 100%), we demonstrated a negative correlation showing improved EOA as HEI was reduced. Optimal cutoff catheter-heatsink distances for predicting ablation asymmetry ranged from 6.6-13.0 mm, emphasizing the impact of heatsink proximity on LITT efficacy. CONCLUSION We show that proximity to heatsinks, especially within a threshold distance of 13.0mm from the laser catheter, significantly predicts ablation asymmetry and volume in the setting of primary CNS tumors. Neurosurgeons should consider heatsink effects in pre- and intraoperative planning to optimize LITT outcomes and preserve normal brain tissue.

Cremastrae Pseudobulbus Pleiones Pseudobulbus (CPPP) Against Non-Small-Cell Lung Cancer: Elucidating Effective Ingredients and Mechanism of Action

Cremastrae Pseudobulbus Pleiones Pseudobulbus (CPPP) is derived from the dried pseudobulb of the orchid family plants Cremastra appendiculata (D.Don) Makino, Pleione bulbocodioides (Franch.) Rolfe, or Pleione yunnanensis Rolfe, and has the properties of clearing heat, detoxification, resolving phlegm, and dispersing nodules. It is frequently used for the treatment of various malignant tumors in clinical practice, especially lung cancer. CPPP is divided into two commercial specifications in the market, Maocigu (MCG) and Bingqiuzi (BQZ). However, owing to a lack of appropriate research strategies, the active ingredients and molecular mechanisms involved have not yet been clarified. This study intended to discover the combination of effective anti-lung-cancer ingredients in CPPP and explore their potential mechanisms of action. In this study, UHPLC-MS fingerprints of MCG and BQZ were established separately. Inhibitory effects on the proliferative viability and migratory ability of A459 and H1299 cells were evaluated as pharmacodynamic indicators. GRA and BCA were used to determine spectrum–effect relationships. Next, the identification and analysis of components of drug-containing serum were performed using UHPLC-Q-Exactive Orbitrap MS. Then, the results of the two analyses were combined to jointly screen out the anti-lung-cancer candidate active monomers of CPPP, and their in vitro activities were verified. Afterward, all effective ingredient combinations of MCG (MCGC) and BQZ (BQZC) were prepared according to their contents in the original medicinal materials. Their anti-lung-cancer activities in vitro and in vivo were compared and verified. Finally, we used the human lung cancer cell line A549 and the Lewis tumor xenograft model to investigate how BQZC would influence autophagy and apoptosis processes and the mechanisms involved. Overall, 11 predominant anti-lung-cancer active ingredients from CPPP were screened. Next, MCGC and BQZC were prepared according to their contents in the original medicinal materials, respectively, and their anti-tumor effects were equivalent to those of the original materials in vitro and in vivo. We found that BQZC could inhibit lung cancer cell growth and induce protective autophagy and apoptosis in lung cancer cells by activating the AMPK–mTOR–ULK1/BMF signaling pathway. These results provide important evidence for the clinical application and deep development of CPPP against tumors.

QOL-27. PATIENT REPORTED OUTCOME AND PREFERENCE AFTER CRANIOTOMY AND LASER THERMAL ABLATION: A PILOT STUDY

Abstract BACKGROUND Laser interstitial thermal therapy (LITT) is a minimally invasive procedure that allows cytoreduction in the treatment of brain tumors and can be considered by both surgeons and patients as an alternative to craniotomy. OBJECTIVE We surveyed 27 patients who underwent both craniotomy and LITT during distinct stages of their oncology journey to assess patient reported outcomes comparing both procedures. METHODS A nine question survey was developed and validated to assess patient reported post-operative recovery, pain level, narcotic use, and procedure preference. The survey was administered to patients with WHO II-IV gliomas who underwent both craniotomy and LITT. RESULTS The survey was reviewed by independent surgeons, patient advocates, and patients in terms of face validity and showed >90% correlation in test-retest reliability. Our cohort had a mean age of 57 (+/- 12 years), 78% had glioblastoma. There was no significant difference in symptomatic improvement post-craniotomy or post-LITT (30% versus 4%, p=0.17). Similarly, no significance was detected in patient-reported recovery time from craniotomy (time required to return to pre-operative state, 4.3 +/- 9.1 weeks, median 2 weeks) or LITT (2 ± 2.3 weeks, median 1 week)(p=0.21). Notably, post-surgical pain (1-10 pain scale) and need for narcotic use in the first week (yes/no) after the procedure were significantly lower post-LITT (average pain score 1.7 versus 5 points, narcotic use 4% versus 81%, p<0.0005 for both comparisons). When asked which procedure they would choose – having experienced both craniotomy and LITT, surveyed patients overwhelmingly chose LITT over craniotomy (89% versus 11%, p<0.0005). Of note, the patients who preferred craniotomy experienced improved neurologic function post-craniotomy or suffered new deficits post-LITT. CONCLUSION In this pilot study, patients reported less pain and narcotic use post-LITT relative to craniotomy and generally preferred the former procedure if given the choice. Validation of these results in future studies can help inform decision making in clinical scenarios where there is equipoise between LITT and craniotomy.

IMMU-67. INTRACRANIAL IL12 SECRETING CAR-T CELLS OBVIATE THE NEED FOR LYMPHODEPLETION AND COMBAT HETEROGENEITY VIA MICROGLIAL INTERACTIONS

Abstract INTRODUCTION Epidermal growth factor receptor variant III (EGFRvIII) is a tumor-specific antigen distinctively expressed in glioblastoma multiforme (GBM). However, its heterogeneous expression in GBM complicates its application as a target for Chimeric Antigen Receptor (CAR) T cells. Additionally, Interleukin-12 (IL12) has recently been identified as a potent cytokine in the treatment of solid tumors. In this study, we investigate the potential synergy between CAR-T cells and IL12 in targeting heterogeneous tumor antigens. METHODS To model tumor heterogeneity, mice were injected with a 50/50 mix of CT2A and CT2A EGFRvIII+ cells. EGFRvIII-specific third-generation CAR T cells, engineered with or without single-chain IL12, were cloned using an MSGV retrovirus backbone and transduced into murine T cells. The antitumor efficacy of CAR-T cells was evaluated through survival analysis. Additionally, the capability of CAR-T cells with or without IL12 to prolong survival and alter the tumor microenvironment was analyzed using single-cell sequencing. RESULTS EGFRvIII CARs alone were insufficient to cure mice with heterogeneous tumors, whereas EGFRvIII CARs co-expressing IL12 achieved a 60% cure rate. Interestingly, EGFRvIII CARs secreting IL12 demonstrated longer persistence in vivo compared to EGFRvIII CARs alone and did not require lymphodepletion before administration. We found that EGFRvIII CARs expressing IL12 promoted the elimination of EGFRvIII-negative tumor cells by recruiting endogenous CD8 T cells. Furthermore, among all Antigen Presenting Cell (APC) populations in the tumor microenvironment, we found that IL12 primarily acted on microglia to enhance antigen presentation pathways and support epitope spreading. CONCLUSION EGFRvIII CARs engineered to secrete IL12 effectively treat antigen-heterogeneous tumors by modulating local APCs and recruiting endogenous T cells. IL12-secreting CARs demonstrate longer persistence without the need for lymphodepletion compared to traditional EGFRvIII CARs. Employing CAR-T cells that secrete IL12 is a promising strategy to address tumor heterogeneity, offering therapeutic potential against GBM in clinical settings.