Lymph Node Research Articles

NCMP-22. CO-OCCURRENCE OF MULTIPLE SCLEROSIS AND HODGKIN LYMPHOMA. IS THERE A COMMON PATHOPHYSIOLOGY?

Abstract BACKGROUND Multiple sclerosis (MS) and Hodgkin lymphoma (HL) share common epidemiology, genetics and immunological factors. Both affect immune activation, cell proliferation and lymphocyte-mediated immunity. However, occurrence of these two distinct clinical conditions is rare. We present a case of a woman with transverse myelitis fulfilling criteria for MS with synchronous HL. CASE REPORT A 37-year-old woman presented to the emergency room with bilateral leg weakness, numbness and urinary retention. A contrasted MRI of the brain and thoracic spine showed non-specific, non-enhancing white-matter lesions in the brain, and patchy areas of peripheral contrast-enhancement with T2-hyperintensity in the thoracic cord. Treatment with steroid infusion resulted in mild improvements of leg weakness and numbness. Cerebrospinal fluid (CSF) demonstrated oligoclonal bands (OCB) and increased IgG index. Serum was positive for JCV antibody. Due to the atypical MRI findings, namely the peripheral nature of thoracic contrast-enhancement, we were concerned for other inflammatory or autoimmune etiologies. A computed tomography of the chest, abdomen and pelvis revealed a large mediastinal mass and enlarged lymph nodes. A biopsy revealed classic HL. Three-months later, a follow-up MRI brain showed worsening contrast-enhanced lesions. A repeat CSF study revealed normal OCBs and IgG index. CSF was negative for malignant cells and JC virus DNA. To rule out a rare possibility of central nervous system HL, a biopsy of an enhancing brain lesion was obtained, which showed focal gliosis and focal perivascular lymphocytic infiltrates. No malignant cells were observed. She was diagnosed with multiple sclerosis and started systemic chemotherapy (doxorubicin, bleomycin, dacarbazine and vinblastine) for HL. CONCLUSIONS We report a case of an atypical transverse myelitis with HL. Although familial genetic clustering has been described, other potential common risk-factors between MS and HL are Epstein-Barr Virus infection and immunologic overlap, particularly in the context of lymphocyte-mediated immunity.

CTIM-27. DOC1021 CELL-BASED VACCINATION AS ADJUVANT THERAPY FOR GLIOBLASTOMA: PHASE I CLINICAL TRIAL ANALYSIS

Abstract Glioblastoma is an aggressive tumor for which median survival remains 14-18 months despite aggressive standard of care. Cellular immunotherapy approaches have recently shown promise. Homologous antigenic loading is an ex-vivo technique that leverages p38MAPK and mTORC1 signaling cascades to initiate powerful cDC1-like skewing in monocyte-derived dendritic cells, leading to downstream induction of tissue-infiltrating, cytolytic effector memory T-cells. This open-label phase I clinical trial evaluated the autologous dendritic cell vaccine DOC1021 prepared through homologous antigenic loading and administered bilaterally near the deep cervical lymph nodes. Three courses of vaccine were administered every 2 weeks after completion of chemoradiation, adjuvanted concurrently with six weeks of weekly type I interferon. Four dose levels from 3.5x106 to 3.6x107 total vaccine cells were tested. Tumor progression prior to vaccination was not an exclusion criterion. Sixteen newly diagnosed IDH-WT patients completed treatment, median age 63 years and 94% MGMTp unmethylated. The most common related AEs were grade 1 injection-site reactions and grade 1-3 fatigue and urticaria. No DLTs were observed. Immunohistochemistry of tumors derived from early post-vaccination second resections showed enhanced CD8+ T-cell infiltration and pathologic findings consistent with residual rather than relapsed GBM in 2/3 patients. Analysis of post-vaccination PBMC in dose level cohorts 2-4 indicated expansion of both CD4+ (13/13) and CD8+ (11/13) central memory T-cell compartments (p<0.002 and p<0.05, respectively) as well as expansion of CD8+CD127+ T-cells (12/13; p<0.001). Among three patients for whom tissue was obtained pre- and post-vaccination, clinical outcomes correlated with Visium spatial transcriptomic analysis. Median survival for the MGMTp unmethylated cohort (n=15) has not yet been reached but is statistically greater (p<0.05) than that of matched historic controls. The results indicate that DOC1021 is safe, can be effectively integrated within existing standards of care and is potentially efficacious in a challenging patient population.

The enhanced-view totally extraperitoneal repair of abdominal bulge after DIEP flap breast reconstruction for breast cancer: a case report.

The deep inferior epigastric perforator (DIEP) flap for autologous breast reconstruction is associated with higher patient satisfaction and fewer abdominal morbidities at the donor site than the transverse rectus abdominis myocutaneous flap. However, abdominal bulging occurs at a certain frequency, and there is no established treatment. Here, we present a case of laparoscopic hernia repair using the enhanced-view totally extraperitoneal (eTEP) method in a patient with a lower abdominal bulge after DIEP flap reconstruction. A 53-year-old woman underwent left nipple-sparing mastectomy, left axillary lymph node dissection, and breast reconstruction with a DIEP flap for left breast cancer 3years previously. We performed an eTEP method for an abdominal bulge. The absence of a hernia sac facilitated dissection of the retrorectal space, and a left-sided transversus abdominis release was performed, followed by mesh placement. No postoperative abdominal bulging was observed. Using the eTEP method for repairing an abdominal bulge after DIEP flap reconstruction is advantageous because it facilitates a relatively straightforward dissection of a wide area of the retrorectal space without a hernia sac.

IMMU-28. LOW-INTENSITY PULSED ULTRASOUND COMBINED WITH POLY-ICLC AND INTERLEUKIN-2 UNLOCKS THE IMMUNE PRIVILEGE OF THE BRAIN BY PROMOTING EPITOPE SPREADING AND ACTIVATION OF CNS-SPECIFIC NAÏVE T CELLS

Abstract Immunotherapies targeting glioma, such as chimeric antigen receptor (CAR) T cell therapies, offer new therapeutic avenues; however, their application has yielded limited success in clinical trials so far. Due to the antigenic heterogeneity of gliomas, targeting a few or several antigens still results in recurrence with “antigen-loss” tumors, indicating the need to engage the endogenous immune system to eliminate these therapy-resistant tumor cells. However, natural anatomical barriers and an immunosuppressive environment allow brain tumors to evade detection by the endogenous immune system. Low-intensity pulsed ultrasound combined with microbubbles (LIPU/MB) has recently been shown to transiently open the blood-brain barrier (BBB), enabling penetration of cells and drugs into the CNS. Using intravital two-photon imaging, two-photon microscopy, multiparametric spectral flow cytometry, and bone marrow chimera mice, alongside blood samples from glioblastoma patients treated with LIPU/MB, we observed that LIPU/MB promotes migration of CNS antigen-presenting cells from the perivascular space into the periphery. To assess the immunological relevance of LIPU/MB-mediated CNS antigen presentation to the peripheral immune system, we have developed new transgenic mice (GFAP-minigene mice) with an intact BBB expressing four immunogenic peptides under the CNS-specific GFAP promoter. In GFAP-minigene mice, LIPU/MB combined with toll-like receptor 3 agonist poly-ICLC and Interleukin-2 promoted priming, activation, and homing of naïve CNS-specific T cells into the brain parenchyma. Cytotoxic T cell activity in the brain was accompanied by MHC-I and MHC-II epitope spreading, mirrored by the occurrence of endogenous T cells in the brain, deep cervical lymph nodes, and spleen harboring other CNS-(minigene) antigen-specific T cell receptors. Collectively, our findings suggest that LIPU/MB combined with poly-ICLC can overcome inherent limitations of immunotherapy by enhancing CNS epitope spreading and activation of naïve CNS-antigen-specific T cells within the context of an intact blood-brain barrier.

Modern aspects of treatment of acute tonsillopharyngitis

Introduction. Primary referral for infectious and inflammatory diseases of the pharynx reaches 30%.Aim. To study the effectiveness of ambazon in patients with acute tonsillopharyngitis.Materials and methods. The study was conducted at the SCDC Clinics of the Samara State Medical University and the CDC “Persona-Med” LLC in 75 patients (45.9 ± 11.2 years old) with acute tonsillopharyngitis (ATP). The main group (Group I, n = 48) additionally received ambazon, 1 tablet for resorption 15 minutes after meals 4 times a day for 4 days. The control group (Group II, n = 27) received symptomatic therapy. On the 1st, 2nd and 4th day, the complaint of sore throat was assessed using a visual analogue scale (VAS), the frequency of additional complaints, and the pharyngoscopic picture using a 4-point scale.Results and discussion. On the 2nd day, the severity of sore throat according to VAS in group I was 3.5 ± 0.2 points, in group II 4.9 ± 0.3 points (p < 0.05). On the 4th day, the severity of sore throat in group I had lower values 1.1 ± 0.1 points, in group II 2.9 ± 0.1 points (p < 0.05). On the 2nd day, complaints of a sensation of a foreign body in the oropharynx and discomfort when swallowing in group I amounted to 27.1% and 45.8%, and in group II 77.8% and 66.7%, respectively. The pharyngoscopic picture in group I was characterized by a decrease in the severity of edema and hyperemia of the pharyngeal mucosa (score of 1.3 ± 0.3 points and 1.1 ± 0.2 points), in group II 2.1 ± 0.3 points and 2.9 ± 0.4 points, respectively. On the 4th day, the pharyngoscopic picture in group I returned to normal, while in group II, hyperemia and edema of the mucosa and an increase in regional lymph nodes persisted.Conclusions. The use of ambazon in the treatment of ATP allows to reduce the severity of the pain symptom, reduce the frequency of additional complaints and normalize the pharyngoscopic picture.

A rare presentation of isolated intraosseous Rosai-Dorfman disease of the tibia – The role of whole-body magnetic resonance imaging in management

Rosai–Dorfman disease (RDD) is a rare non-Langerhans histiocytic disorder, usually presenting with enlarged cervical lymph nodes. Extranodal involvement is quite common and synchronously involves the nasal cavity, paranasal sinuses, skin, orbit, central nervous system, and rarely bones. Isolated bone involvement is rare and can present with local symptoms such as pain, swelling, restriction of activity, and occasionally pathological fracture. The most common sites of osseous RDD are the cranium, facial bones, and tibia, in decreasing order of frequency. Imaging findings of primary osseous RDD can be variable and there are no key features to diagnose this entity with certainty. Hence, the primary role of imaging is to plan the management and post-treatment follow-up. Here, we present a case of primary osseous RDD involving tibial diaphysis and emphasize the importance of whole-body magnetic resonance imaging in ruling out systemic involvement.

TMIC-63. DUAL IMMUNE CHECKPOINT BLOCKADE IN A NOVEL EGFR-DRIVEN MURINE GLIOMA MODEL INCREASES PERIPHERAL T CELL PROLIFERATION BUT FAILS TO PROLONG SURVIVAL

Abstract Patients with glioblastoma (GBM) survive only 15-18 months following standard-of-care surgical resection and radio-chemotherapy. Immune checkpoint blockade (ICB), effective in extracranial cancers, failed to improve survival in patients with recurrent GBM in a multi-center phase III clinical trial. As such, we are interested in the molecular mechanisms that drive ICB resistance. Oncogenic EGFR activation is observed in ~50% of GBMs and is associated with immunosuppression; however, whether EGFR signaling impairs T cell function in GBM resulting in limited ICB efficacy remains unclear. Therefore, we leveraged the novel MADR-mEGFRvIII glioma model, which expresses murine EGFRvIII under a tetracycline-off system, to investigate the relationship between EGFR activation and responsiveness to dual anti-PD-1 and anti-CTLA-4 (10mg/kg) in vivo. Mice were bled prior to enrollment and weekly thereafter, which confirmed anti-PD-1-PD-1 binding via competitive flow cytometric assay. Following two weeks on treatment, animals were euthanized for immunophenotypic analyses of tumors and tumor-draining lymph nodes. These analyses revealed a significantly increased prevalence of peripheral CD11b+ myeloid cells and enhanced peripheral T cell proliferation, indicated by Ki67 positivity, after treatment with dual ICB compared to isotype control. However, these shifts did not translate to effective ICB-mediated recruitment of peripheral T cells to the tumor microenvironment and no significant survival benefit was observed (p=0.68, n=15/treatment arm). Given our previous findings that EGFR ablation via doxycycline enhanced intratumoral T cell infiltration, we hypothesize the rational combination of EGFR-targeted therapy and ICB will have a synergistic effect; thus, future directions include a study combining the two treatment regimens consisting of a lead-in with doxycycline to increase intratumoral T cell trafficking, followed by treatment with dual ICB. This work will provide insight into the interplay between oncogenic signaling and immunosuppression, contributing to the development of novel combination therapies in treating this lethal disease.

Prognosis analysis and nomogram for predicting lateral lymph node metastasis in Medullary Thyroid Microcarcinoma.

Currently, the incidence rate of Medullary Thyroid Microcarcinoma (micro-MTC) has an increasing trend, but the incidence of LNM and prognosis were still ambiguous. We analyzed the status of neck LNM of micro-MTC patients and created a prognostic nomogram to predict the probability of lateral lymph node metastasis (LLNM) for clinical practice. This is a retrospective study included patients with micro-MTC from SEER database for the period from 2004 to 2017 and patients from our medical center for the period from 2011 to 2019. A nomogram was constructed and the accuracy and clinical practicability were separately tested by Harrell's C-indexes, calibration plots, Receiver operating characteristic curve (ROC) and decision curve analyses (DCA). A total of 413 patients with micro-MTC from SEER database and 64 patients with micro-MTC from our department enrolled in the study. There were 16.0% and 9.4% cases in SEER database and 39.1% and 25.0% cases in our department appeared LNM and LLNM, respectively. Besides, a nomogram was constructed to assess the incidence of LLNM with good C-index, which was 0.850 in training cohort and 0.856 in validation cohort. The results of the area under the curve (AUC) were 0.830 in training cohort, 0.801 in validation cohort and 0.832 in external testing cohort, respectively. A relatively high rate of LLNM than expected was found, which should be emphasized. The prediction model could facilitate clinicians to assess the probability of LLNM and make a personalized treatment strategy.

EXTH-57. EXPLORING NOVEL ROUTES FOR NON-INVASIVE DRUG ADMINISTRATION: INTRADERMAL DELIVERY FOR THE TREATMENT OF BRAIN TUMORS

Abstract Effective non-invasive drug delivery to brain tumors remains challenging, despite extensive exploration of these methods, due to the blood-brain barrier (BBB). Intranasal drug delivery has emerged as a promising alternative approach, as it circumvents limitations on tumor access imposed by the BBB when administering therapeutics systemically and limits the occurrence of systemic toxic responses to treatment. The intranasal route of administration allows therapeutic access to brain tumors through pathways involving the olfactory and trigeminal nerves (TNs) that connect the nasal passage to the brain. However, effective nose-to-brain delivery is impeded by rapid mucosal drug clearance in the nasal cavity, drug aspiration, and ingestion. Since the TN arises from the brainstem and its branches innervate the facial skin, in addition to muscles, meninges, and respiratory mucosa, we tested the hypothesis that facial intradermal administration targeting the V2 branch of the TN could be an alternative strategy to harness TN-mediated brain delivery to bypass the BBB. Here, we developed Spherical Nucleic Acids (SNAs) consisting of a 15nm spherical gold nanoparticle core functionalized with radially oriented fluorophore-tagged ssDNA as a model therapeutic. We observed the delivery of the SNAs to the brain starting 4 hours post intradermal injection, with the SNA accumulation in the tumor persisting over time. Using ex vivo fluorescent imaging, comprehensive immunofluorescence microscopy, and flow cytometry we confirmed the SNA accumulation in the brain, dura, TN, and cervical lymph nodes. In particular, we demonstrated that SNAs were enriched in the neuronal cell bodies of the trigeminal ganglia and within the epineurium and perineurium of the TN. The SNAs were also enriched in CD45-positive immune cells. In conclusion, this study credentialed facial intradermal administration of SNAs as a promising non-invasive method for brain drug delivery to target intracranial tumors.

Clinicopathologic Features of Oral Verrucous Carcinoma: A Systematic Review and Meta-Analysis.

To further characterize the clinicopathologic features of oral verrucous carcinoma. In accordance with PRISMA guidelines, a systematic review of the Medline, Web of Science, Embase, and Cochrane databases was performed in search of articles evaluating clinicopathologic features of oral verrucous carcinoma. Primary outcomes of interest included tumor subsites, T-staging, rates of cervical lymph node metastases, rates of distant metastases, 5-year survival (overall, disease-free, or disease-specific), and recurrence rates. Meta-analysis was performed using a random effects model. Nineteen articles with a total of 1458 subjects were ultimately included in the analysis. There were 17 studies with a total of 1353 patients reporting verrucous carcinoma subsites and the buccal mucosa (59.2%, 55.1%-63.3%) (I2 = 98.1%) had the highest incidence of involvement. There were 10 papers with 277 patients reporting on rates of cervical lymph node metastases from surgical pathology yielding a pooled rate of 0% (0%-2.3%) (I2 = 1%). There were 14 studies with a collective 712 patients commenting on rates of distant metastases and collectively, none were reported, yielding a pooled rate of 0% (0%-0%) (I2 = 0%). Five year survival data was generally favorable relative to oral squamous cell carcinoma but was insufficient for meta-analysis. An international collection of evidence supports that pure oral verrucous carcinoma is a relatively indolent, non-metastasizing malignancy associated with areca nut consumption. A reliance on traditional squamous cell carcinoma staging and treatment algorithms for verrucous carcinoma patients can predispose to overtreatment.

Analysis of METTL14 expression in pancreatic cancer and adjacent tissues and its prognostic value for patient outcomes.

This study aims to analyze the differential expression of METTL14 in pancreatic cancer (PC) tissues and adjacent normal tissues, and its correlation with clinical outcomes. According to the inclusion and exclusion criteria, a total of 80 patients diagnosed in our hospital from January 2021 to January 2023 were chosen as research subjects. RTQ-PCR has detected the mRNA level expression of METTL14 in cancer and para-cancerous tissues. Immunohistochemistry was used to detect the protein expression of METTL14 in cancer and para-cancerous tissues. To compare the relationship between METTL14 expression and clinicopathological parameters in different PC patients. Kaplan-Meier survival analysis of the relationship between METTL14 expression in PC tissues and patient survival prognosis. The Multifactor COX model evaluates factors affecting the prognosis of PC. The expression level of METTL14 mRNA in PC tissues was 5.51 ± 0.35 (kDa), and the positive rate of METTL14 protein expression in PC tissues of all patients was 73.75 (59/80). Tumor location (P = 0.012), tumor differentiation degree (P = 0.028), tumor AJCC stage (P = 0.000), and lymph node metastasis (P = 0.000) were significantly related to the positive rate of METTL14 protein expression in PC tissue. Follow-up results showed that among 80 patients, 63 died. The three-year survival rate of the METTL14 positive group was 13.56% (8/59), and the three-year survival rate of the negative group was 42.86% (9/21). The difference in the three-year survival rate between METTL14 positive and negative expression groups was statistically significant (P = 0.031). Multivariate COX regression analysis results showed that METTL14 was positive (OR 2.797, 95% CI 1.233-5.877), tumor AJCC stage II-III (OR 1.628, 95% CI 1.435-3.859) and lymph node metastasis (OR 1.733, 95% CI 1.122-2.372) were substantive risk factors for poor prognosis in patients with PC. METTL14 expression increases in PC tissue, which is related to tumor AJCC stage, tumor differentiation, and lymph node metastasis, and can be evaluated in the survival prognosis of patients with PC.

Screening high-risk individuals for primary gastric adenocarcinoma: evaluating progression-free survival probability score in the presence and absence of Rictor expression after gastrectomy

ObjectiveDeveloping nomogram-based risk stratification model to determine 3-year and 5-year progression-free survival (PFS) and to identify high-risk patients with gastric adenocarcinoma based on different Rictor statuses.Methods1366 individuals who underwent radical gastric surgery to treat gastric adenocarcinoma at Shanxi Cancer Hospital from May 2002 to December 2020 were analyzed. Cox regression analysis was employed to create the nomograms. The nomograms’ performance was assessed using C-index, time receiver operating characteristic (t-ROC) curves, calibration curves, and decision curve analysis (DCA) curves in training and validation cohorts. Subsequently, patients were categorized into high-risk and low-risk groups based on the nomogram’s risk scores.ResultsThe Rictor (-) nomogram for predicting PFS included variables such as age, number of positive lymph nodes, vascular invasion, maximum diameter of the tumor, omentum metastasis, and expression of MSH2. In the internal validation, the C-index of the Rictor (-) nomogram was 0.760 (95%CI: 0.720-0.799), which was superior to the C-index of the American Joint Committee on Cancer (AJCC) 8th edition TNM staging (0.683, 95%CI: 0.646-0.721). Similarly, the Rictor (+) nomogram for predicting PFS included variables such as gender, age, pT stage, number of positive lymph nodes, neural invasion, maximum diameter of the tumor, omentum metastasis, Clavien-Dindo classification for complications, and CGA expression. The C-index of the Rictor (+) nomogram was 0.795 (95%CI: 0.764-0.825), which outperformed the C-index of the AJCC 8th edition TNM staging (0.693, 95%CI: 0.662-0.723). The calibration curves, t-ROC curves, and decision curve analysis for both nomogram models demonstrated their excellent prediction ability.ConclusionThis study presents the first risk stratification for Rictor status in gastric adenocarcinoma. Our model identifies low-risk patients who may not require additional postoperative treatment, while high-risk patients should consider targeted therapies that specifically target Rictor-positive indicators.

Clinical Utility of Bioimpedance Analysis for Upper Limb Lymphedema with Surgical Treatment.

Background: In lymphedema, the accumulation of subcutaneous interstitial fluid is the most characteristic feature. Bioimpedance analysis (BIA) is a promising technique to measure the amount of body components using a noninvasive method. In this study, we determined the clinical significance of BIA parameters in upper limb lymphedema with surgical treatment such as lymphovenous anastomosis or vascularized lymph node transfer. Methods and Results: A single-center retrospective study using a multifrequency BIA. Perioperative BIA parameters such as extracellular water ratio or fat-free mass (FFM) ratio and limb volume defined as percentage of excess volume (PEV) were measured. The relationships between the magnitude of change in PEV and BIA parameters during surgery were evaluated. Out of 48 unilateral lymphedema patients, 46 were female and the average age was 55.4 years. PEV and all BIA parameters showed a significant decrease after surgery (p < 0.001). There were significant correlations between ΔPEV and the degree of changes in all BIA parameters. ΔFFM ratio showed the highest correlation with the amount of change in PEV (r = 0.599, p < 0.001). Conclusion: BIA parameters correlated well with the volume change after surgery. BIA could be useful as a quick and easy tool for follow-up after lymphedema surgery.

EXTH-40. IMMUNOPHENOTYPING OF RWTC-MBTA AUTOLOGOUS CANCER VACCINE IN PRECLINICAL GLIOBLASTOMA MODELS

Abstract Despite advances in immunotherapy, glioblastoma multiforme (GBM) remains challenging to treat due to its low inherent immunogenicity and a suppressive tumor microenvironment. Converting “cold” GBMs to “hot” tumors is crucial for effective immune activation and improved patient outcomes. We comprehensively characterized the rWTC-MBTA autologous cancer vaccine, consisting of Mannan-BAM-anchored irradiated whole tumor cells, Toll-like receptor ligands (LTA, Poly(I:C), R-848), and an anti-CD40 agonistic antibody, in preclinical GL261 and SB28 GBM models. A substantial number of vaccinated mice exhibited complete regression of GBM tumors in a T-cell-dependent manner, with no significant toxicity. Long-term tumor-specific immune memory was confirmed upon tumor rechallenge. In the vaccine-draining lymph nodes of the SB28 model, rWTC-MBTA vaccination triggered a major rise in cDC1 12 hours post-treatment, followed by an increase in cDC2, moDC, and pDC on Days 5 and 13. Enhanced cytotoxicity of CD4+ and CD8+ T cells in vaccinated mice was verified in co-culture with tumor cells. Comprehensive immunophenotyping in the GL261 and SB28 GBM microenvironments confirmed decreased regulatory T cells and increased CD4+ and CD8+ T cell infiltration in vaccinated mice. T-cell exhaustion analyses revealed an increase in the Tim3+CD8+ T cells. No significant differences were observed in the quantification of M-MDSC and PMN-MDSC between control and vaccinated mice, but PD-L1 expression significantly increased in M2 macrophages in vaccinated mice. Our findings demonstrate that rWTC-MBTA induces potent and long-term adaptive immune responses against GBM, warranting further investigation of combinations with other immunotherapies for enhanced efficacy.

Giant pelvic dermoid cyst in a 17-year-old girl

BACKGROUND: Dermoid cysts in the presacral and retrorectal space in children are relatively rare. However, even more rarely, they have clinical manifestations at patient’s early age and so, can be silent for a long time. CLINICAL CASE DESCRIPTION: The article describes a rare clinical observation — a giant dermoid cyst in the retrorectal space in a 17-year-old girl. The child had a tendency to constipation from her early childhood. Menses started at age 13, painful. During the last year, disorders in her menstrual cycle were noticed. The girl was examined by a gynecologist. Ultrasound examination revealed a cystic formation in the pelvic cavity up to 9 cm in diameter. Non-malignant nature of the process was confirmed by: normal level of cancer markers (α-fetoprotein, β-human chorionic gonadotropin), single node, clearly defined formation capsule, homogeneous nature of its contents, no invasive growth and lesions in the regional lymph nodes. Magnetic resonance imaging with intravenous contrasting defined a true relationship of the cystic formation with other organs and structures of the pelvic cavity. The cystic formation caused deformation of the cervix, vagina, and rectum. The obtained findings allowed to plan surgical intervention correctly. Surgical access-transverse in the coccyx projection up to 10 cm long. The cystic formation was a thin-walled connective tissue capsule with a yellowish content. Due to very large cyst dimensions, first it was opened in a limited area and emptied. Then the capsule was isolated and completely removed. The cyst intimately adhere to rectum, vagina, and cervix walls. Histological conclusion: "Capsule of a dermoid cyst with hemorrhages". The postoperative period was smooth. The patient recovered, all disease manifestations disappeared. She was discharged home in a satisfactory state. Follow-up visits were in 6 and 12 months after surgery. No evidence of possible relapse. CONCLUSION: There are only few descriptions of such cases in the available literature. Ultrasound and MRI examinations allowed to have a full picture of dermoid cyst position and its connection with other pelvic organs due to which surgeons could develop a correct plan for surgical intervention.

Predicting ipsilateral supraclavicular lymph node pathological complete response: nomogram based on the inflammatory markers

BackgroundThe prediction of ISLN pCR after neoadjuvant chemotherapy (NAC) based on inflammatory markers and its prognostic value have rarely been investigated.MethodsPatients diagnosed with ISLN-involved breast cancer who received NAC in West China Hospital between September 2009 and December 2020 were enrolled in the derivation cohort for model construction and survival analysis, and patients with the same criteria between January 2021 and July 2024 were involved in validation cohort for external validation. After randomly dividing patients into training and testing groups at 7:3 ratio, a nomogram predicting ISLN pCR was constructed based on logistic regression in training group. Internal validation was performed in the testing group and external validation was performed in the independent validation cohort. The ROC curves were applied to validate the accuracy of the model. Survival analysis was performed using Kaplan−Meier plots.ResultsA total of 120 eligible patients were involved in the derivation cohort to establish the nomogram (84 patients in training group and 36 patients in testing group), and 45 patients were involved in the independent validation cohort for external validation of the nomogram. Pretreatment NLR and hormone receptor (HR) status, as well as preoperative SII, CEA, CA15-3 and anti-HER2 therapy were included in the nomogram predicting ISLN pCR. The AUC were 0.906 (95% CI 0.837-0.975, P&amp;lt;0.001), 0.888 (95% CI 0.751-1.000, P&amp;lt;0.001) and 0.828 (95% CI 0.703-0.953, P&amp;lt; 0.001) in training, testing groups and the validation cohort respectively. ISLN pCR was significantly associated with better prognosis (all P&amp;lt;0.05).ConclusionInflammatory factors combined with tumor makers, hormone receptor status and anti-HER2 therapy could predict ISLN pCR effectively, which was significantly associated with improved survival outcomes.

Systematic review of risk prediction tools for primary cutaneous melanoma outcomes and validation of sentinel lymph node positivity prediction in a UK tertiary cohort.

It is difficult for clinicians to make predictions for cancer progression or outcomes based on AJCC staging for individual patients. Models individualising risk prediction for clinical outcomes are developed using patient level data, advanced statistical techniques, and artificial intelligence. A systematic search identified cutaneous melanoma prognostic prediction tools published between January 1985-March 2023. Population comparisons of key clinico-pathological variables, external prediction of receiver operating characteristics and calibration analysis are applied to an unselected group of patients undergoing sentinel lymph node biopsy in a UK University hospital setting (n = 1564). Twenty-nine models were identified which predicted survival, disease recurrence or sentinel lymph node positivity (Internal validation n = 19 and external validation n = 14). 3 out of 7 tools for sentinel node positivity were contemporaneous with available characteristics for external validation. External validation of models by Lo et al. Friedman et al. & Bertolli et al. highlighted good discriminative performance (AUC 68.1% (64.5-71.8%), 77.1% (66.8-85.7%) & 68.6% (63.3-74.1%) respectively) but were sub-optimally calibrated for the UK patient cohort (Calibration intercept & slope Friedman: -4.01 & 32.92, Lo: -1.17 & 0.44, Bertolli: -2.75 & 4.88). This work highlights the complexity of predictive modelling and the rigorous validation process necessary to ensure accurate predictions. Our search highlights a tendency to focus on discriminative performance over calibration, and the possibility for inconsistent predictions when tools are applied to populations with differing characteristics.

Case report: Radical robotic nephroureterectomy after chemotherapy followed by avelumab in a patient with node-positive UTUC

IntroductionPlatinum-based chemotherapy followed by the immune checkpoint inhibitor avelumab represents an intensified upfront therapy regimen that may result in significant downstaging and, subsequently, potentially radical robotic nephroureterectomy with a lymph node dissection, an uncommon approach with an unexpectedly favorable outcome.Case presentationWe report a case of a 70-year-old female presented with a sizeable cN2+ tumor of the left renal pelvis and achieved deep partial radiologic response after systemic therapy with four cycles of gemcitabine-cisplatin chemotherapy followed by avelumab maintenance therapy and subsequent robotic resection of the tumor. The patient continued with adjuvant nivolumab therapy once recovered after surgery and remained tumor-free on the subsequent follow-up. The systemic treatment was without any severe adverse reaction.ConclusionWe highlight the feasibility of the upfront systemic therapy with four cycles of gemcitabine-cisplatin chemotherapy followed by avelumab maintenance, robotic-assisted removal of the tumor, and adjuvant immunotherapy with nivolumab. This intensification of the upfront systemic therapy, and the actual treatment sequence significantly increase the chances of prolonged survival or even a cure. This type of personalized therapeutic approach can accelerate future advanced immunotherapeutic strategies.

IMMU-38. LEVERAGING INNATE IMMUNE SENSORS TO GENERATE DURABLE ANTI-GLIOMA ADAPTIVE IMMUNE RESPONSES

Abstract Glioblastoma harbors a tumor microenvironment (TME) that is mostly devoid of T cell effector infiltration but is dominated by immune suppressive microglia, macrophages, and myeloid-derived suppresser cells. The innate immune cells in the TME have impaired phagocytosis and antigen presentation and are inadequate for triggering the subsequent immune activating signals needed for anti-tumor effector responses. Phagocytic activity can also be blocked by the upregulation of CD47 on the tumor cells. In the immune checkpoint resistant Qki-/- Pten-/- P53-/- (QPP) glioma model, intratumoral treatment with the synthetic cyclic di-nucleotide STING agonist IACS-8803 (8803) induces global immunological reprogramming and long-term survival resistant to tumor rechallenge. More specifically, in the infiltrating myeloid stroma 8803 increases costimulatory protein CD86 while reducing the expression of suppressive markers CD163 and CD206. Conventional type 1 dendritic cells are increased in both the TME (p&amp;lt;0.05) and the draining cervical lymph node (p&amp;lt;0.01). Intratumoral infiltration of both CD8 T (p&amp;lt;0.05) and NK (p&amp;lt;0.001) cells increases. However, only T cells, but not NK cells, are necessary for 8803 therapeutic activity when assessed with in vivo NK cell depletion studies and treatment in the RAG-/- background. STING activation increases microglial phagocytic capacity, but also induces a compensatory increase in SIRPα expression (p&amp;lt;0.001) – the ligand for CD47. 8803 synergizes with anti-CD47 blockade to enhance microglia phagocytosis of QPP glioblastoma cells in vitro. Finally, the combination of 8803 and anti-CD47 synergizes to extend both median survival and the fraction of long-term survivors in orthotopic QPP-bearing mice (QPP8v; vehicle control MS=39d, anti-CD47 MS=40d, 8803 MS=67d 20% long-term survival, 8803 + anti-CD47 MS=107.5d 40% long-term survival). These data demonstrate that 8803 induces proinflammatory conversion of the glioblastoma TME, generates T cell-dependent survival benefits in QPP-bearing mice, and synergizes with anti-CD47 blockade to enhance microglia phagocytosis of glioblastoma cells and extend survival in QPP-bearing mice.

CTIM-13. D2C7-IT IN COMBINATION WITH AN FC-ENGINEERED ANTI-HUMANCD40 MONOCLONAL ANTIBODY (2141-V11) ADMINISTERED INTRATUMORALLY VIA CONVECTION-ENHANCED DELIVERY (CED) FOLLOWED BY CERVICAL PERILYMPHATIC INJECTIONS (CPLIS) OF 2141-V11 IN PATIENTS WITH RECURRENT GLIOBLASTOMA (RGBM)

Abstract BACKGROUND The combination of D2C7-IT, an antibody toxin conjugate, and anti-mouseCD40 via CED generates robust antitumor immunity by killing tumor cells, activating microglia, reversing glioma-associated microglia and macrophage (GAMM)-mediated immune suppression, and empowering polyfunctional tumor antigen-specific CD8 T cells in glioma models. In addition to reprogramming GAMMs, anti-CD40 also activated dendritic cells and induced glioma-specific T cell responses in tumor draining lymph nodes. After establishing the phase 2 dose of the combination of D2C7-IT+2141-V11 when infused via CED, we initiated an assessment of the safety and efficacy of the combination of D2C7-IT+2141-V11 CED followed by repeated subcutaneous CPLIs of 2141-V11 ipsilateral to the tumor in patients with rGBM, IDH wild-type (NCT04547777). METHODS Eligible are adult patients with solitary supratentorial rGBM; ≥4weeks after chemotherapy, bevacizumab, or investigational agent; adequate organ function; and KPS ≥70%. Patients are treated with D2C7-IT (166μg) and 2141-V11 (3mg), both infused via CED, followed by CPLI of 2141-V11 at 2mg at weeks 2 and 4 post D2C7-IT+2141-V11 CED, followed by every 3 weeks for 1 year and then every 4-6 weeks. RESULTS As of May 22, 2024, 18 patients with rGBM (median age of 54) were treated with D2C7-IT+2141-V11 CED followed by CPLIs of 2141-V11. 83% patients remain alive (range 3.3-14.8 months from start of D2C7-IT CED infusion) with a median of 8 CPLIs of 2141-V11 received (range 3-19). No study related grade 4 or 5 adverse events (AEs) were observed. Grade 3 AEs related to D2C7-IT and/or 2141-V11 include one each of hydrocephalus, headache, seizure, and cerebral edema. AEs related exclusively to CPLIs of 2141-V11 consist of grade 1 injection site reaction (n=16). CONCLUSIONS The addition of CPLIs of 2141-V11 post CED of D2C7-IT+2141-V11 is feasible and has shown an acceptable toxicity profile. The safety and efficacy results will be updated.