Assessment Of Response Research Articles

NIMG-48. MEASURABLE DISEASE AS BASELINE CRITERION FOR RESPONSE ASSESSMENT IN GLIOBLASTOMA TRIALS – A COMPARATIVE STUDY OF MRI-BASED (RANO 2.0) VERSUS PET-BASED (PET RANO 1.0) ASSESSMENT

Abstract Response assessment in glioblastoma relies on measuring contrast enhancement on MRI according to RANO 2.0 criteria, and ‘measurable disease’ often serves as inclusion criterion for clinical trials. Recently, criteria based on amino acid PET have been proposed for response assessment in clinical trials (PET RANO 1.0). Here, we compare ‘measurable disease’ as defined by PET RANO 1.0 with the standard MRI-based RANO 2.0 criteria in glioblastoma patients. In this retrospective single-center study, we identified patients with newly diagnosed IDH-wildtype glioblastoma who underwent [18F]FET PET and MRI after resection or biopsy and before chemoradiotherapy. Two independent investigators analyzed ‘measurable disease’ according to PET RANO 1.0 versus MRI-based RANO 2.0 criteria. Additionally, lesion size and uptake intensity, including maximal and mean target-to-background ratio, were assessed. We evaluated 136 patients with 76 cases after biopsy and 60 after microsurgical resection. Using RANO 2.0, 35/76 patients (46.1%) had measurable disease in the biopsy group, and 25/60 (41.6%) in the resected group (median sum of maximum cross-sectional diameters: 39.7mm and 28.0mm, respectively). Utilizing PET RANO 1.0, a significantly higher proportion (overall 123/136, 90.4%; 66/76 (86.8%) after biopsy; 57/60 (95.0%) after resection) had measurable disease (p<0.001). None of the 10 patients in the biopsy group nor of the 3 patients in the resected group without measurable disease on PET had measurable disease on MRI. Contrariwise, 32/41 patients (73.2%) in the biopsy group and 30/35 (85.7%) in the resected group without measurable disease on MRI exhibited measurable disease on PET. PET RANO 1.0 identifies a significantly higher number of patients with ‘measurable disease’ compared to conventional MRI-based criteria in the perioperative period of glioblastoma. PET-based assessment may thus serve as a novel baseline parameter for evaluating treatment response in glioblastoma trials, that may allow the enrollment of larger patient populations. Further validation in prospective trials is warranted.

CTNI-77. PHASE 1 DOSE FINDING STUDY EVALUATING THE SAFETY, TOLERABILITY, AND EFFICACY OF IOPOFOSINE I 131 IN CHILDREN, ADOLESCENTS, AND YOUNG ADULTS WITH INOPERABLE RELAPSED OR REFRACTORY HIGH-GRADE GLIOMAS: A TRIAL-IN-PROGRESS

Abstract Iopofosine I 131, a radioconjugate therapy targeting tumor lipid rafts, is being assessed in CLOVER-2 [NCT05610891]–an ongoing dose-finding study evaluating iopofosine in children, adolescents, and young adults with relapsed, refractory, recurrent high-grade gliomas (HGGs) and ependymoma. Major inclusion criteria include patients aged 10-25 years, previously confirmed HGGs or ependymoma, ≥1 measurable intracranial lesion (≥10 mm in longest diameter), and performance status ≥60. Patients are assigned 1:1 to 2 treatment arms which will be assessed in parallel. Arm 1 has 2 cycles, each composed of 2 doses of 20 mCi/m2 given 14 days apart (± 1 day). Cycle 2 is given 8 weeks (± 4 days) post-initial infusion. Arm 2 patients receive 3 cycles of 10 mCi/m2 per dose. Patients in either arm are eligible for 1 additional cycle at the physician’s discretion. If after the first 10 patients, Arm 1 is not tolerated, dosing is reduced to 15 mCi/m2 per infusion. If after the first 10 patients in Arm 2 are deemed to be ineffective and Arm 1 is deemed to be tolerated, dosing is increased to 15 mCi/m2 per infusion. Final visits occur 57 days following the last cycle initiation, with quarterly follow-ups in year 1 and annually in years 2 and 3. Primary endpoints include safety, tolerability, and progression-free survival (PFS). Secondary endpoints are dosimetry, recommended phase 2 dosing determination, overall survival, antitumor and therapeutic activity, and duration of response and clinical benefit. Safety analysis uses the Wilson score method and nonparametric Wilcoxon signed-rank test. Efficacy analyses use the Response Assessment in Pediatric Neuro-Oncology criteria and the Kaplan-Meier method to detect a median PFS of 5 months compared to a historical control of 2 months. For 90% power by a 1-sided, 1-sample log-rank test: ≥10 evaluable patients must be enrolled (≤90) across ≤15 sites.

CTNI-43. MULTI-CENTER PHASE I STUDY OF CONCURRENT PAXALISIB AND RADIATION THERAPY (RT) IN PATIENTS WITH SOLID TUMOR BRAIN METASTASES (BM) OR LEPTOMENINGEAL METASTASES (LM) HARBORING PI3K PATHWAY ALTERATIONS

Abstract INTRODUCTION Partial or whole brain RT is a standard treatment for solid tumor BM and LM. However, tumors harboring PI3K pathway mutations have poorer CNS control after RT alone. Combining RT with paxalisib, a CNS-penetrant PI3K/mTOR inhibitor, may overcome radioresistance. METHODS This multi-center, phase I trial (NCT04192981) studied concurrent paxalisib with cranial RT (30Gy in 10 fractions) for PI3K pathway-altered BM/LM. Part A was a 3 + 3 dose escalation cohort of paxalisib at 45, 60 or 75mg to establish maximum tolerated dose (MTD). Part B was an expansion at MTD to further validate safety and early efficacy. CNS response was assessed using Response Assessment in Neuro-Oncology Brain Metastases (RANO-BM) criteria. RESULTS From 3/2020-2/2024, 21 patients (median age 58y, n=18 with BM, n=10 with breast cancer) were enrolled. PIK3CA mutations were the most common pathway alteration (n=15, 71%) followed by PTEN deletion (n=3, 14%). Part A enrolled 12 patients of which 9 were evaluable (3 did not complete protocol therapy). There were no dose-limiting toxicities (DLTs) at 45mg, and 2 DLTs at 60mg: grade 3 nausea and grade 4 neutropenic enterocolitis. Subsequently, 9 additional patients were enrolled during Part B at MTD of 45mg, of which 1 withdrew consent prior to completion of study interventions. No additional DLTs were observed during Part B. In total, there were 14 evaluable patients who received 45mg/day paxalisib concurrently with RT, two of whom died of intercurrent extracranial progression prior to CNS restaging. Of the remaining 12, there was robust response signal. At 1-month post-treatment, 6/12 (50%) had partial response (PR) and the remaining had stable disease (SD). To date, best CNS response is 67% PR (8/12) and 33% SD (4/12). CONCLUSIONS A MTD of 45 mg/day has been confirmed for paxalisib with concurrent brain RT for PI3K pathway-altered BM/LM. Given significant unmet need, this novel therapeutic combination warrants further investigation given promising activity signal.

NIMG-77. MRI PHENOMENON OF PUNCTATE ENHANCING LESIONS IN PATIENTS TREATED WITH IDH INHIBITORS

Abstract BACKGROUND Magnetic Resonance Imaging (MRI) response assessment is essential in isocitrate dehydrogenase (IDH)-mutant gliomas and provides evidence of treatment efficacy. Ivosidenib, a mutant IDH1 inhibitor, and vorasidenib, a pan-mutant IDH inhibitor, may induce imaging stabilization or improvement. We describe an imaging phenomenon of punctate enhancing lesions in patients receiving ivosidenib or vorasidenib. METHODS From October 2020 to December 2023, we identified patients treated with IDH inhibitors who developed punctate enhancing lesions on imaging during their treatment course. We report their clinical and imaging characteristics. RESULTS In our cohort (n=5), patients age range was 29-47 years. Diagnoses included astrocytoma grades 2 (n=2) or 3 (n=1), and oligodendroglioma grades 2 (n=1) or 3 (n=1). Beside all having a prior resection, two had prior radiation therapy and temozolomide, one had prior temozolomide only and two were treatment-naïve. Before initiation of IDH inhibitor, all patients had some evidence of enhancement, albeit small (<1 cm) for most. Four patients received ivosidenib (500mg daily) and one received vorasidenib (40mg daily). The median time to develop punctate lesions from treatment initiation was 16 months (range 1-28 months). All but one lesion was < 1 cm and adjacent to the original tumor locations. Four had FLAIR correlation, and two had high DWI signal without associated restricted diffusion. Punctate lesions resolved on subsequent imaging, within 1-2 months, for all grade 2 tumors. Punctate lesions persisted in the grade 3 tumors, without further progression. Four patients remain on therapy. One discontinued treatment due to this enhancement, which resolved on subsequent imaging. CONCLUSIONS Punctate enhancing lesions may develop in patients on IDH inhibitors. We advocate for close interval imaging monitoring in these cases since they may not universally require treatment discontinuation. Future advanced imaging and tissue evaluations of punctate enhancement, to differentiate between inflammatory response and progression, would be of interest.

New Vistas for the Relationship between Empathy and Political Ideology.

The study of ideological asymmetries in empathy has consistently yielded inconclusive findings. Yet, until recently these inconsistencies relied exclusively on self-reports, which are known to be prone to biases and inaccuracies when evaluating empathy levels. Very recently, we reported ideological asymmetries in cognitive-affective empathy while relying on neuroimaging for the first time to address this question. In the present investigation which sampled a large cohort of human individuals from two distant countries and neuroimaging sites, we re-examine this question, but this time from the perspective of empathy to physical pain. The results are unambiguous at the neural and behavioral levels and showcase no asymmetry. This finding raises a novel premise: the question of whether empathy is ideologically asymmetrical depends on the targeted component of empathy (e.g., physical pain vs cognitive-affective) and requires explicit but also unobtrusive techniques for the measure of empathy. Moreover, the findings shed new light on another line of research investigating ideological (a)symmetries in physiological responses to vicarious pain, disgust, and threat.Significance Statement In this study, we challenge the historically inconclusive findings on ideological asymmetries in empathy. By employing neuroimaging techniques, we demonstrated that ideological asymmetry in physical pain empathy is absent. This research underscores the importance of considering various facets of empathy, societal contexts, and unbiased measurement methodologies, such as neuroimaging techniques, in the assessment of empathic responses.

Assessment of therapeutic response to photodynamic therapy with the Zn-Phthalocyanine RLP068/Cl versus topical Clindamycin in patients affected by Hidradenitis Suppurativa: a comparative clinical pilot study.

Hidradenitis suppurativa is a chronic skin disorder characterized by painful inflammatory nodules and abscesses, significantly impacting patients' quality of life. Current treatment strategies, including topical antibiotics, often yield limited efficacy and pose risks of antibiotic resistance. Photodynamic therapy has emerged as a potential option, with RLP068/Cl (ELKOFAST®, non-sterile formulation) showing promising efficacy due to its broad-spectrum bactericidal activity. We conducted a pilot study assessing the therapeutic response to photodynamic therapy with RLP068/Cl versus topical clindamycin gel in patients affected by hidradenitis suppurativa of Hurley score I, II, and III. Results revealed higher efficacy of photodynamic therapy in combination with RLP068/Cl, particularly in mild cases. Its efficacy remains reliable even in more severe cases when combined with adalimumab. The observed faster lesion improvement and pain relief were ascribed to the bactericidal effects of RLP068/Cl against Gram+ and Gram- bacteria. Furthermore, photoactivated RLP068/Cl was well tolerated with no adverse events reported. Therefore, photodynamic therapy following RLP068/Cl application represents a novel therapeutic option for hidradenitis suppurativa with potential implications for antibiotic stewardship in dermatology.

Assessment of Biofilm Formation and Anti-Inflammatory Response of a Probiotic Blend in a Cultured Canine Cell Model

Gut dysbiosis and an inflamed bowel are growing concerns in mammals, including dogs. Probiotic supplements have been used to restore the natural microbial community and improve gastrointestinal health. Biofilm formation, antimicrobial activities, and immunological responses of probiotics are crucial to improving gut health. Thus, we tested a commercial probiotic blend (LabMAX-3), a canine kibble additive comprising Lactobacillus acidophilus, Lacticaseibacillus casei, and Enterococcus faecium for their ability to inactivate common enteric pathogens; their ability to form biofilms; epithelial cell adhesion; and their anti-inflammatory response in the Madin-Darby Canine Kidney (MDCK) cell line. Probiotic LabMAX-3 blend or individual isolates showed a strong inhibitory effect against Salmonella enterica, Listeria monocytogenes, enterotoxigenic Escherichia coli, and Campylobacter jejuni. LabMAX-3 formed biofilms comparable to Staphylococcus aureus. LabMAX-3 adhesion to the MDCK cell line (with or without lipopolysaccharide (LPS) pretreatment) showed comparable adhesion and biofilm formation (p < 0.05) to L. casei ATCC 334 used as a control. LabMAX-3 had no cytotoxic effects on the MDCK cell line during 1 h exposure. The interleukin-10 (IL-10) and tumor necrosis factor alpha (TNFα) ratio of LabMAX-3, compared to the L. casei control, showed a significant increase (p < 0.05), indicating a more pronounced anti-inflammatory response. The data show that LabMAX-3, a canine kibble supplement, can improve gastrointestinal health.

BIOM-75. MRI FLAIR SIGNAL ASSESSMENT IN NEURO-ONCOLOGY (SANO) AS A MEASURABLE TIMEPOINT FOR INTERVENTIONAL THERAPY PRIOR TO PROGRESSION IN HIGH GRADE GLIOMAS: A WINDOW OF OPPORTUNITY

Abstract BACKGROUND There are no validated clinical or radiographic assessments for response to therapy in glioblastoma (GBM). Offering interventions at the time of progression using our current assessment tools is likely too late as second-line therapies have failed to significantly delay progression and extend survival. In 2020, our team was first in the US to publish the largest and most comprehensive retrospective review identifying the T2/FLAIR MRI signal assessment protocol as an early indicator of progressive GBM. We proposed that the time of FLAIR signal abnormality within the resection cavity (RC) anticipated GBM progression by nearly 4 months and if used as a timepoint for therapeutic intervention could reshape glioma clinical trial design. METHODS To support validation of SANO, a prospective assessment of 146 GBM patients between 2019-2021 yielded 71 cases meeting resection and imaging inclusion criteria. We analyzed sequential brain MRIs from initial diagnosis to first progression for development of T2 FLAIR signal intensity (SI) within the RC as previously reported (Gatson et al 2020) and included cases with ventricle associated surgery as a comparator. PFS and OS were evaluated using Kaplan-Meier curves stratified by SI. RESULTS Development of SI occurred in 80.3% (n=57) GBM patients on average 2.8 months before RANO-assessed progression. A faster time to progression from SI development occurred in cases with ventricle associated RC. SI-positivity again portended poorer outcomes for PFS and OS as compared to SI-negative cases. Use of the eye (globe) for FLAIR assessment, instead of the ventricles, to qualitatively discern the presence of SI in ventricle associated RC. CONCLUSIONS This small prospective review supports our initial findings to validate a highly sensitive brain tumor imaging biomarker, SI, and should at least supplement existing response assessment criteria to improve declaration of GBM progression. Furthermore, use of SANO might also offer an earlier window of opportunity for salvage therapy intervention and offer new avenues for glioma clinical trial design.

BIOM-50. SERIAL INTRACRANIAL CEREBROSPINAL CELL-FREE DNA FOR DISEASE MONITORING IN PATIENTS WITH GLIOMAS

Abstract Improved response assessment methods are needed for patients with gliomas. Intracranial cerebrospinal fluid (CSF) is longitudinally accessible and provides an abundance source of candidate biomarkers, such as cell-free DNA (cfDNA), for disease monitoring. To evaluate the clinical feasibility of molecular profiling from longitudinal intracranial CSF, CSF was acquired from patients with CSF access devices, including Ommaya reservoirs and ventriculoperitoneal shunts. cfDNA was extracted and analyzed via PredicineCARE (Next Generation sequencing) or PredicineSCORE (low pass whole genome sequencing). Five patients (2 females, 3 males; median age: 40 years, range 32-64 years) underwent longitudinal intracranial CSF collection via Ommaya reservoirs (n=4) or VP shunt (n=1). In total, forty-eight CSF samples were obtained (median volume: 4.00 mL; 0.5-5 mL), with 39 samples (81.3%) yielding sufficient cfDNA for variant profiling. Our initial findings suggest that tumor fraction increased by 6.28x, 2.87x, and 8.31x with radiographic progression in three patients. Tumor fraction decreased by 0.08x and 0.04x in two patients with paired immediate pre-versus-post chemoradiation samples. Despite ongoing pseudoprogression in one patient, tumor fraction decreased to unmeasurable levels from a post-resection baseline of 0.26. Patient-specific tumor-associated variant allelic frequencies (VAFs), including TP53, PTEN, TERT, and CDKN2A/B, decreased within individual patients after resection and chemoradiation. In two patients with isocitrate dehydrogenase (IDH) mutant gliomas, decreasing IDH1 VAF after resection and chemoradiation correlated with decreased CSF D-2-hydroxyglutarate (D-2-HG) levels (0.64x and 0.62x, respectively, for the first patient, and 0.01x and 0.07x for the other patient). Both CSF IDH1 VAF and CSF D-2-HG increased a patient who had radiographic progression (2.56x and 9.21x, respectively). Moreover, CNB decreased below the limit of quantification during treatment and increased above the limit at progression. In conclusion, longitudinal CSF cfDNA can feasibly be obtained via CSF access devices in patients with gliomas during their disease course toward evaluating candidate monitoring biomarkers.

NIMG-89. MULTI-THRESHOLD VOLUMETRIC MAPPING OF18F-FLUOROETHYLTYROSINE POSITRON EMISSION TOMOGRAPHY (18F-FET PET) IMPROVES TUMOR DETECTION IN PRIMARY MALIGNANT BRAIN TUMOR PATIENTS

Abstract PURPOSE The purpose of this study was to determine whether additional volumetric measurements yielded significant prognostic information than typically reported tumor-to-brain ratio thresholds (TBRmax) alone for accurately distinguishing progressive disease from treatment induced changes. METHODS Hybrid 18F-FET PET/MRI was obtained on pathology confirmed high-grade glioma in sixty patients from August 6th, 2022 to March 9th, 2023 at one US institution. We compared the diagnostic accuracy of various TBR thresholds and volumetric measurement combinations in identifying progressive disease. Specifically, we assessed TBR >1.6, 2.0, 2.5, 3.0, 3.5, 4, 4.5, and 5.0 alone and in combination with volumetric measurements greater than 1 mL. Survival data for all patients were analyzed using Kaplan-Meier curves. RESULTS Our analysis revealed that TBR > 2.5 and >1 mL yielded the highest diagnostic accuracy (100%) in distinguishing progressive disease from treatment induced changes. This was followed by the combination TBR >2.0 and >1 mL (98%), TBR > 2.5 alone (98%), TBR > 2.0 alone (86%), TBR >1.6 and >1 mL (84%), and TBR >1.6 alone (77%). TBR >3.0, 3.5, 4.0, 4.5, and 5.0 with and without volumetric measurements showed accuracies of 100%. Kaplan-Meier survival analysis showed significant results for all thresholds: TBR >1.6 alone (p = 0.047), TBR >1.6 and 1 mL (p = 0.003), TBR > 2.0 alone (p = 0.019), TBR >2.0 and >1 mL (p < 0.001), TBR >2.5 alone (p < 0.001), and TBR >2.5 and >1 mL (p = 0.002). CONCLUSION Our findings suggest that although TBRmax > 2.5 alone continues to be a reliable metric for distinguishing progressive disease from treatment induced changes, TBRmax >2.5 when volume is greater than 1 mL shows the greatest accuracy in detecting disease progression. Understanding the volumetric contribution to static FET TBRmax is important for tumor response assessment at TBRmax thresholds above 1.6 TBRmax.

BIOM-54. AI-DRIVEN RISK-OF-PROGRESSION (AIRIP) CLASSIFIER FOR DISTINGUISHING RECURRENT BRAIN METASTASES FROM RADIATION TREATMENT EFFECT: A MULTI-INSTITUTIONAL COMPARATIVE STUDY WITH ADVANCED MULTIMODAL IMAGING

Abstract Following radiation therapy, a significant challenge in brain metastases (BM) management is differentiating radiation-induced-treatment effect (TrE) from tumor recurrence (TuR). TrE can be indistinguishable from TuR using conventional MRI. Advanced imaging techniques (e.g., perfusion MRI, PET/MRI) are not consistently used, and the standardized Response Assessment in Neuro-Oncology for brain metastases (RANO-BM) is sensitive to inter-reader variability. The performance of an artificial intelligence (AI)-driven risk-of-progression (AiRiP) classifier, which has been shown to capture pathophysiologic differences between TrE and TuR on routine MRI, was compared to that of clinical assessments and advanced imaging methods, in a multi-institutional setting. A total of n=261 lesions with pathologically-confirmed diagnoses in n=189 patients were analyzed. 115 lesions (73 TuR, 42 TrE) from site 1, 86 lesions (38 TuR, 48 TrE) from site 2, and 60 lesions (33 TuR, 27 TrE) from site 3 were used for training and testing the AiRiP-model. Gd-T1w, T2w, FLAIR MRI were preprocessed, and lesions were segmented by experts. Texture features (n=856) were extracted from each lesion. Random-forest classifier was employed for 3-fold cross-validation. Top-performing AiRiP-features, RANO-BM criteria, perfusion MRI and PET/MRI were evaluated in a sub-group analysis. For n=51 lesions on the test-set (site 3), 14 were classified as stable disease and 37 as TuR using RANO-BM (accuracy=54.1%). AiRiP-model achieved an accuracy of 76.5% on the same test-set and accurately classified 78.6% of the stable lesions as TrE or TuR. For another subset of lesions (n=27) on the same test-set, perfusion MRI and AiRiP-model achieved an accuracy of 59.3% and 70.4%, respectively. Lastly, for a subset of lesions (n=35) on the test-set (site 2), multimodal (perfusion, PET) imaging and AiRiP-model accurately classified 60% and 74.3% of lesions, respectively. 15 lesions were considered indeterminate via multimodal imaging, 73.3% of which AiRiP-model accurately classified as TrE or TuR. Our results suggest AI-driven models on conventional MRI may reliably distinguish TuR from TrE.

Ki-67 With MRI in Predicting the Complete Pathological Response Post-neoadjuvant Chemotherapy.

Neoadjuvant chemotherapy (NAC) is increasingly used for high-risk breast cancer to achieve pathologic complete response (pCR), an indicator of event-free survival and favorable survival outcomes. Integrating MRI and Ki-67 biomarker analysis into predictive models offers a promising approach to optimize NAC response assessment and guide personalized treatment strategies. This study evaluates the validity of combined MRI and Ki-67 metrics for predicting pCR. We conducted a systematic review and meta-analysis following Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines, including studies on NAC-treated breast cancer patients assessed by MRI and Ki-67. The predictive models were evaluated based on key parameters, including MRI-based tumor size reduction and Ki-67 levels, with outcomes measured by area under the receiver operating characteristic curve (AUC) and calibration metrics. Findings across ten studies consistently show that high Ki-67 levels and significant tumor size reduction on MRI are predictive of pCR, achieving AUCs near 0.90. The analysis highlighted that models integrating MRI with Ki-67 metrics outperformed single-modality approaches, showing enhanced predictive accuracy and calibration. However, high heterogeneity (I² = 77%) was noted, suggesting variability in imaging and Ki-67 assessment protocols across studies. Thisstudy underscores the combined utility of MRI and Ki-67 for the non-invasive prediction of pCR, offering both structural and biological insights into tumor responsiveness. The results align with prior research, affirming the role of Radiomic-clinicopathological models in providing a more comprehensive assessment compared to individual markers. Further refinement of imaging and biomarker protocols could improve model reproducibility and applicability. Our findings highlight the robust predictive accuracy of MRI-Ki-67 integrated models for assessing pCR, marking a significant step toward personalized cancer care. Future studies should focus on refining these models with additional biomarkers and standardized protocols, facilitating their integration into routine clinical oncology to enhance treatment decision-making and patient outcomes.

CNSC-14. GLIOBLASTOMA MULTIFORME TUMOR VOLUME AND PERSISTENCE OF CHIMERIC ANTIGEN RECEPTOR T CELLS FOLLOWING TREATMENT

Abstract Glioblastoma Multiforme (GBM) is one of the most common and aggressive high-grade primary brain tumors that arises from the glial cells of the central nervous system and occurs most often in the frontal and temporal lobes. Despite current treatment options, long-term prognosis of GBM remains low with no significant improvement rates. Chimeric antigen receptor (CAR)-expressing T cells target the B cell marker CD19 and have shown increased efficacy in B cell lymphomas, and lymphoblastic leukemias suggesting benefits in GBM. This study aims to quantify the persistence of CAR-T cells in the context of GBM tumor volume following neurosurgical debulking procedure. A radiology software known as the mint Lesion was utilized to provide Tumor Response Assessment by Criteria (TRAC) reports that consist of volumetric measurements of the tumor lesions (target enhancing lesions, non-target enhancing lesions, and non-target non-enhancing lesions). Fluorescence-activated cell sorting (FACS) analysis takes a sample mixture of cells and sorts them into different populations based on specific biomarkers and characteristics. B7-H3 CAR-T cell persistence was increased in patients with a larger post-surgical tumor volume (3.04% Subject 001 with 2438 mm² volume and 2.38% Subject 003 with 224 mm² tumor volume). However, the number of CAR-T cells per 1 mm² was significantly reduced in patients with a larger post-surgical tumor volume (0.0012 cells/mm² Subject 001 and 0.010 cells/mm² Subject 003). This study shows that although there is an overall increased CAR-T cell persistence for a larger tumor volume, the number of CAR-T cells per 1 mm² is significantly smaller for larger tumor volumes, while illustrating that a larger post-surgical tumor bulk volume is correlated with an increased CAR-T cell persistence within 1-week post-infusion. These findings provide novel information and complement other correlative studies as part of the Phase 1 interventional clinical trial for glioblastoma patients.

NIMG-70. COMPARISON OF VOLUMETRIC AND CROSS-SECTIONAL MEASUREMENTS IN DIFFUSE MIDLINE GLIOMAS: RETHINKING RESPONSE ASSESSMENT

Abstract BACKGROUND The Response Assessment in Pediatric Neuro-Oncology (RAPNO) criteria, which are based on bidimensional or cross-sectional product (CP) measurements of tumor size, are the standard for assessing treatment response in diffuse midline glioma (DMG). This study aims to investigate the correlation between CP and volumetric measurements in progressive disease (PD) and compare their prognostic impact in pediatric patients with DMG. METHODS We retrospectively reviewed clinical and imaging data from 27 subjects with newly diagnosed DMG, encompassing 16 subjects from the PNOC003 and PNOC007 clinical trials and 11 subjects from the Children’s Hospital of Philadelphia. Tumors were segmented using a pretrained pediatric-specific autosegmentation model followed by manual revisions. Tumor volume and CP measurements were automatically derived from the outlined tumor. Cox regression analysis was used to compare the performance of CP and volumetric measurements in predicting overall survival (OS). The correlation between CP and volumetric thresholds for PD was assessed by linear regression. Comparison of survival of patients classified as PD versus non-PD by CP and volumetric measurements at 7 months post-baseline scan was performed using log-rank analysis. RESULTS Cox regression analysis demonstrated that volumetric measurements were significantly associated with OS (p=0.04), whereas CP measurements were not a significant predictor (p=0.07). An approximate 55% increase in segmented volume corresponded to a 25% increase in CP, which is the definition of PD according to RAPNO criteria (R2 = 0.71). At 7 months, volumetric classification of PD more accurately predicted survival than the CP method (p=0.06 for volumetric vs 0.14 for CP). CONCLUSION Our study showed that volumetric measurements are better predictors of survival compared to bidimensional measurements. We are extending this analysis to a larger sample size, examining survival at additional time points, and incorporating other factors influencing OS, such as treatment approaches.

Current technologies of response assessment in rectal cancer after neoadjuvant treatment: A review

Improvement of the multidisciplinary approach to the treatment of rectal cancer over recent years has led to the fact that in specialized high-volume oncology clinics it is possible to achieve a complete pathomorphological response to neoadjuvant therapy in a third of patients. The emergence of new knowledge about the development of tumor complete response and the accumulation of clinical experience opens up possibility for the wider use of an organ-sparing approach. Undoubtedly, making such a critical strategic decision requires reliable and effective tools for complete response predicting. This review is devoted to methods for assessing tumor response in patients diagnosed with rectal cancer. A look at the problem is presented from the perspective of modern methods of medical imaging, molecular and genetic studies, the study of the characteristics of the immune response, and a new look at clinical data. New data can form the basis for new patient selection algorithms for personalized treatment protocols for rectal cancer, thereby improving long-term results and quality of life for patients.

The alteration of lipid metabolism and its correlation with glycometabolism following laparoscopic sleeve gastrectomy: A meta-analysis

Abstract Background The LSG has been shown to be effective in consistently reducing the body weight and improve the metabolism of patients with excessive obesity. However, its long-term effect in lipid metabolism and the correlation with glycometabolism have not been well summarized and analyzed. Objective The aims of this meta-analysis were to establish the panorama of lipid metabolism following LSG, study its correlation with glycometabolism, and provide evidence for therapeutic response assessment and prognosis prediction. Methods The meta-analysis identified all available studies reporting the lipid metabolism alterations following LSG from January, 2011, to March, 2023. Using relevant key words, articles were searched from the MEDLINE, PubMed, and EMBASE databases and screened following the PRISMA guideline. A total of 46 studies reporting the levels of several lipid markers across time points up to 24 months following LSG were included in the final analysis. Results Significant level decrease was found with FBG, FBI, HbA1C, HOMA-IR, and TG, in parallel with the drop of BMI following LSG up to 24 months, and significant level increase was observed in HDL. In contrast, no significant level changes were observed with TC and LDL. FBI and HOMA-IR exhibited the earliest (3–7 days) significant alterations even before BMI changed, and they also showed the biggest percentage decrease in all markers, while HDL exhibited the biggest percentage increase. All markers except LDL showed significant linear correlation with BMI, and TC and TG showed significant correlation with individual glycometabolism markers. TC, TG, and HDL showed significant correlation with each other, while LDL showed no significant correlation with other lipid markers except TC. Conclusions Insulin-related markers, HDL and TG, could be early response markers for LSG. Good correlation was found between BMI change and glyco- or lipid markers, while only TC and TG appeared to correlate with glycomarkers.

CTNI-13. 18-FET-PET ENHANCED DIAGNOSIS OF PSEUDOPROGRESSION IN GLIOBLASTOMA IS AN INDEPENDENT PROGNOSTIC FACTOR FOR OVERALL SURVIVAL

Abstract INTRODUCTION Detecting pseudoprogression (PSP) in glioblastoma during first-line treatment remains challenging and has significant clinical implications for patient management. The detection of PSP has been shown feasible using FET-PET. The prognostic impact of FET-PET diagnosed PSP on overall survival is still uncertain, as retrospective studies provide limited insights due to the substantial differences in the distribution of prognostic factors between tumor progression (TP) and PSP groups. This study aims to address these uncertainties by leveraging advanced analysis techniques. METHODS Patients with newly diagnosed glioblastoma (WHO 2021) who underwent chemoradiation and contrast-enhanced MRI suspected for TP and subsequent FET-PET scan at Essen University Hospital were retrospectively evaluated. The modified Response Assessment in Neuro-Oncology (RANO) criteria were used to diagnose PSP. FET-PET analysis included mean (TBRmean) and maximum tumor-to-brain ratios (TBRmax). The two groups (TP/PSP) were balanced using a propensity score analysis including age at diagnosis, extent of resection, Karnofsky-Performance-Status Scale (KPS) and MGMT methylation status. Overall survival was predicted using Kaplan-Meier and multivariate analysis as well as conventional FET-PET parameters, PET/MRI volumetry, and FET/MRI-derived radiomics. An independent cohort was used for validation. RESULTS Out of the 165 patients analysed in this study, 38 were diagnosed with PSP. Following balancing analysis, our study cohort consisted of 40 patients (20 TP/20 PSP). Patients with PSP had a significantly longer mean overall survival (mOS) compared to those with TP (mOS TP 20.24 months; mOS PSP 33.25 months; p=0.0023). The multivariate Cox-Regression analysis confirmed PSP as a significant prognostic marker for overall survival (p=0.0153). Confirmation of these results on an independent validation cohort is pending and will be presented at the meeting. CONCLUSION This study shows that PSP is an independent prognostic factor for overall survival in newly diagnosed glioblastoma patients.

NIMG-34. CXCR4-TARGETED PET IMAGING OF CENTRAL NERVOUS SYSTEM LYMPHOMA AND GLIOMA USING [68GA]GA-PENTIXAFOR

Abstract BACKGROUND Initial results suggest that PET imaging of the chemokine receptor CXCR4 is of considerable interest for differential diagnosis and theranostic approaches. Here, we summarized findings of CXCR4 PET imaging in an institutional series of lymphoma of the central nervous system (CNSL) and glioma. METHODS Twenty-three patients with CNSL and 16 patients with glioma (IDH-wildtype, n=9) underwent PET imaging using the CXCR4-directed tracer [68Ga]Ga-Pentixafor. In 18 patients, serial PET imaging was performed (range, 2-14 scans), resulting in a total of 104 PET scans. For evaluation, PET scans were classified as [68Ga]Ga-Pentixafor-positive and -negative visually, and the maximum standardized uptake value (SUVmax) was obtained from [68Ga]Ga-Pentixafor-PET. RESULTS Twenty-four of all 39 patients (62%) had at least one [68Ga]Ga-Pentixafor-positive PET (CNSL, 57%; glioma, 69%). [68Ga]Ga-Pentixafor-positive PET scans were more common in patients with IDH-wildtype gliomas (89%) than in IDH-mutant gliomas (43%). In patients with [68Ga]Ga-Pentixafor-positive PET, the average SUVmax was 6.4±4.0 in CNSL, and 3.4±1.0 in gliomas (P=0.155). Besides visualization of tumors, [68Ga]Ga-Pentixafor uptake was observed in two patients with radionecrosis. In four CNSL patients who had undergone methotrexate/cytarabine-based first-line therapy, serial PET revealed a significant reduction of SUVmax after chemotherapy completion (average decrease of SUVmax from 4.5±3.8 to 0.6±0.7; P=0.044). In three of those four patients, tumor progression has not been reached (range of time after the follow-up PET, 4-55 months); one patient deceased 44 months after the follow-up PET. In contrast, another patient with an increase in SUVmax from 6.9 to 11.0 after first-line treatment died one month after the follow-up PET. DISCUSSION [68Ga]Ga-Pentixafor PET seems to be of value for non-invasively visualizing and quantifying CXCR4 receptor binding. In CNSL, changes in [68Ga]Ga-Pentixafor uptake following therapy may indicate potential for response assessment. CXCR4-targeting radioligand therapies might be more promising in CNSL than in glioma.

NIMG-65. SYNTHETIC MRI GENERATION TO FACILITATE AUTOSEGMENTATION OF PEDIATRIC BRAIN TUMORS IN LIMITED DATA SCENARIOS

Abstract BACKGROUND The availability of standard multiparametric MRI sequences, including pre-contrast T1w (T1w-pre), post-contrast T1w (T1w-post), T2w, and FLAIR images, is essential for accurate segmentation of tumor subregions and subsequent response assessment in pediatric brain tumors (PBTs). However, clinical MRI sets are often incomplete due to imaging artifacts or inconsistent acquisition protocols across different centers. This study leverages Generative Adversarial Networks (GANs) to synthesize missing FLAIR and T1w-pre images from T2w and T1w-post images, respectively, to facilitate tumor segmentation in PBTs. METHODS We developed two GAN models based on the pix2pix framework, trained, validated, and tested on FLAIR-T2w and T1w-post-T1w-pre pairs from a multi-histology and multi-institutional cohort of 476 subjects with PBTs from the Children’s Brain Tumor Network (CBTN). The perceptual quality of the synthesized T1w-pre and FLAIR images was evaluated using the Structural Similarity Index (SSI; ideal value = 1). The robustness of the synthesized sequences to replace missing MRI sequences was evaluated by comparing the segmentation performance (Dice score) of our pre-trained autosegmentation model using all real modalities versus replacing real sequences with their synthesized counterparts. RESULTS The T1w-pre and FLAIR synthesis GANs achieved mean SSI values of 0.95 and 0.93, respectively. Median Dice scores for segmentation of whole tumor (WT), enhancing tumor (ET), and tumor core (TC) were calculated for real sequences: 0.90, 0.83, 0.89, replacing real FLAIR with synthetic: 0.86, 0.81, 0.86, and replacing real T1w-pre with synthetic: 0.90, 0.75, 0.89. No statistical significance (p>0.05) was observed in segmentation performance for WT, TC, ET when replacing real T1w-pre with synthetic, and for ET when replacing real with synthetic FLAIR sequences. CONCLUSION This method achieves robust segmentation performance in limited data scenarios by synthesizing missing MRI sequences. Future work includes improving FLAIR synthesis and segmentation performance for WT and ET by implementing and comparing other GAN architectures.

Magnetic resonance imaging techniques for monitoring glioma response to chemoradiotherapy.

Treatment response assessment for gliomas currently uses changes in tumour size as measured with T1- and T2-weighted MRI. However, changes in tumour size may occur many weeks after therapy completion and are confounded by radiation treatment effects. Advanced MRI techniques sensitive to tumour physiology may provide complementary information to evaluate tumour response at early timepoints during therapy. The objective of this review is to provide a summary of the history and current knowledge regarding advanced MRI techniques for early treatment response evaluation in glioma. The literature survey included perfusion MRI, diffusion-weighted imaging, quantitative magnetization transfer imaging, and chemical exchange transfer MRI. Select articles spanning the history of each technique as applied to treatment response evaluation in glioma were chosen. This report is a narrative review, not formally systematic. Chemical exchange saturation transfer imaging potentially offers the earliest method to detect tumour response due to changes in metabolism. Diffusion-weighted imaging is sensitive to changes in tumour cellularity later during radiotherapy and is prognostic for progression-free and overall survival. Substantial evidence suggests that perfusion MRI can differentiate between tumour recurrence and treatment effect, but consensus regarding acquisition, processing, and interpretation is still lacking. Magnetization transfer imaging shows promise for detecting subtle white matter damage which could indicate tumour invasion, but more research in this area is needed. Advanced MRI techniques show potential for early treatment response assessment, but each technique alone lacks specificity. Multiparametric imaging may be necessary to aid biological interpretation and enable treatment guidance.