bluuebunny/crossref_metadata_2025_split huggingface dataset:
CTIM-33. IMMUNE BIOMARKERS OF TREATMENT RELATED IMAGING CHANGES IN GLIOBLASTOMA PATIENTS TREATED WITH STANDARD OF CARE PLUS PEMBROLIZUMAB
Authors: Claunch Cheryl , Barajas Ramon , Ambady Prakash 
Published: November 2024

Abstract
Pseudoprogression is a post-treatment imaging phenomenon in glioblastoma (GBM) that mimics true progression. Immune checkpoint inhibition with pembrolizumab has shown clinical benefits in multiple cancers and is a burgeoning treatment in GBM. Discerning pseudoprogression, or treatment-related imaging changes, from true progression is essential for appropriate treatment recommendations. However, there are no reliable biomarkers that can differentiate between pseudoprogression and true progression. Our prospective single-arm study (NCT 03347617) evaluated immune cell sub-populations (B-cells, T-cells, NK cells, monocytes, and myeloid cells) in newly diagnosed GBM patients who received standard-of-care chemoradiation plus concurrent pembrolizumab after maximal safe resection. Flow cytometry was performed on blood collected at predetermined timepoints (pre-treatment, post-radiation, suspected progression, and confirmed progression) and immune cell sub-populations were evaluated as covariates in univariable and multivariable logistic regression analysis. Of the 56 patients enrolled in this trial, 51 completed blood collection. Median survival was 13.84 months. Fifteen (29%) patients had pseudoprogression by modified RANO criteria and 36 (70.5%) had suspected or confirmed progression. Univariable analysis identified the following serum derived immune populations as being significantly associated with pseudoprogression: cytotoxic T-cell percentage (CD3+CD8+; HR: 1.10; p=0.045); total NK Cells percentage (CD3+CD56+; HR:0.912; p=0.0.053); IGD+CD27-naïve B-cells of B-cell percentage (HR: 0.976; p=0.014); IGD+CD27+non-switched B of B-cell percentage (HR:1.07; p=0.036). Backward selection multivariable logistic regression analysis confirmed the significant association of cytotoxic T-cell percentage (CD3+CD8+; HR:1.02; p=0.049) with pseudoprogression while controlling for IGD+CD27+non-switched B of B-cell percentage (HR:1.01, p=0.116). Increasing levels of serum cytotoxic T-cells in GBM patients treated with standard-of-care plus pembrolizumab is associated with pseudoprogression and may be used to differentiate between true progression. Validation of results is needed in a control population treated with standard-of-care prior to clinical implementation. Future studies will utilize serum immune biomarkers coupled with radiomic features to better characterize the pseudoprogression signature in GBM.
CTNI-05. A PROSPECTIVE STUDY OF TUMOR-TREATING FIELDS COMBINED WITH SYSTEMIC THERAPY IN RECURRENT GLIOBLASTOMA
Authors: Guo Chengcheng , Yang Qunying , He Zhenqiang , Duan Hao , Lu Jie , Cao Xi , Sai Ke , Ke Chao , Chen Zhenghe , Liu Ruhua , Zhang Xiangheng , Mou Yonggao 
Published: November 2024

Abstract

BACKGROUND
Tumor-treating Fields (TTFields) monotherapy was approved for recurrent glioblastoma. However, TTFields combined with systemic therapy has not been well studied in China. This study aims to explore the efficacy and safety of such combination therapy for recurrent GBM.

METHOD
This study is a prospective, single-arm, open-label clinical trial (NCT04689087) planning to enroll 40 recurrent supratentorial GBM patients and use TTFields combined with physician chose systemic therapy. Kaplan-Meier survival curve was used to estimate PFS, OS and survival rate. The primary endpoint was 6-months OS rate (OS6). Secondary endpoints were PFS, PFS6 and safety. OS and PFS were computed from the day of initiating TTFields.

RESULT
Fourty recurrent supratentorial GBM patients was enrolled from July 2020 to May 2023. The average age was 51 and median KPS score was 80. Sixty-eight percent (27/40) of them underwent total resection surgery and 5% (2/40) only experienced biopsy as their newly diagnosed GBM surgery. Eighty-eight percent (35/40) of patients started TTFields when they were first diagnosed as recurrence, while 12.5% (5/40) patients started TTFields at their second-time recurrence or latter. Median time from diagnosis of recurrence to initiating TTFields was 27 days. Median duration time of TTFields was 8.7 months and average compliance of TTFields was 87% (20.9 hours/day). As for molecular biomarkers, 50% (20/40) patients were MGMT protein positive and 32.5% (13/40) were TERT mutant. Chemotherapy was included in the systemic therapy in 80% (32/40) patients, antiangiogenic therapy in 60% (24/40) patients, BRAF inhibitor therapy in one patient and immune checkpoint inhibitor therapy in one patient. At data cut-off date of March 20, 2024, the median follow-up period was 20.8 months. The primary endpoint OS6 was 87.2%, the median OS was 20.2 months (95%CI 11.9-NR). Median PFS was 8.5months (95%CI 6.2-NR). PFS6 was 67.5% while the historical reference of physician’s best choice of active chemotherapy from EF-11 study showed a PFS6 of 15%. Scalp adverse events were the most common AE. Seventy-eight (31/40) of patients experienced grade 1 or 2 scalp adverse events which can be relieved by topical corticosteroids.

CONCLUSION
TTFields combined with systemic therapy showed favorable efficacy and safety in Chinese recurrent GBM patients. Key words: Recurrent GBM, TTFields, prospective study, systemic therapy
CTNI-12. TIRABRUTINIB FOR RECURRENT/REFRACTORY PRIMARY CENTRAL NERVOUS SYSTEM LYMPHOMA –A SINGLE-INSTITUTION RETROSPECTIVE ANALYSIS–
Authors: Yamasaki Fumiyuki , Yonezawa Ushio , Taguchi Akira , Onishi Shumpei , Ozono Iori , Khairunnisa Novita Ikbar , Horie Nobutaka 
Published: November 2024

Abstract

BACKGROUND
Tirabrutinib is a second-generation, highly selective oral Bruton’s tyrosine kinase inhibitor and approved for the treatment of recurrent/refractory primary central nervous system lymphoma (PCNSL) in Japan. We reviewed our single institution experiments of tirabrutinib.

MATERIALS AND METHODS
Our institutional review board approved this retrospective study. Twenty-eight patients with recurrent or refractory PCNSL treated with tirabrutinib at our institution between 2020 and 2024 were included. Information regarding the patient’s age, gender, imaging findings, pathological results, including immunostaining findings, and treatment information, including chemotherapy and radiation therapy, was obtained from medical records.

RESULTS
Tirabrutinib was administered to 14 patients with recurrent cases (20-85 years old, median 69.5 years old, 9 males and 5 females), 14 with refractory cases (59-87 years old, median 74 years old, 9 males and 5 females). Three male patients received rechallenge with tirabrutinib against re-relapsed. We assessed the effectiveness of tirabrutinib and observed complete response (CR) in 12 cases, partial response (PR) in 1 case, and progressive disease (PD) in 1 case among refractory patients. In recurrent cases, we observed CR in 8 cases, PR in 1 case, stable disease (SD) in 3 cases, and PD in 2 cases. In rechallenge for re-relapsed cases, we observed CR in 2 cases and PD in 1 case. The progression-free survival following beginning of tirabrutinib was 12.95 months for refractory cases and 8.2 months for recurrent cases. The overall survival was 25 months for refractory cases and 12.8 months for recurrent cases. One patient each experienced CTCAE grade 3 interstitial pneumonia or liver failure, both of which improved after discontinuing the medication. Four patients exhibited grade 1-2 skin rashes.

CONCLUSIONS
Tirabrutinib demonstrates efficacy and high tolerability for the treatment of recurrent/refractory PCNSL in real-world settings.
CTNI-16. MONOGERM, A NOVEL PROOF-OF-PRINCIPLE BAYESIAN PHASE II TRIAL DESIGN OF CARBOPLATIN OR VINBLASTINE MONOTHERAPY INDUCTION PRIOR TO RADIOTHERAPY FOR INTRACRANIAL GERMINOMA
Authors: Kirton Laura , Apps John , Lawson Anna , Arvanitis Theodoros , Mitra Dipayan , Gagan Richard , Patel Hiten , Peet Andrew , Fern Lorna , Williams Emma , Coleman Nicholas , Ajithkumar Thankamma , Bison Brigitte , Veal Gareth , Stark Daniel , Morana Giovanni , Nicholson James , Billingham Lucinda , Murray Matthew 
Published: November 2024

Abstract

BACKGROUND
Current European standard-of-care for localised intracranial germinoma is multi-agent chemotherapy (carboPEI: carboplatin/etoposide/ifosfamide) followed by definitive radiotherapy, with excellent survival. MonoGerm is a de-escalation, non-inferiority trial aiming to reduce toxicity. Twelve-week carboplatin (PMID:8039122) AUC10 or vinblastine (PMIDs:32642701/34520101) induction will be evaluated to test if as effective as carboPEI from SIOP-CNS-GCT-II. A novel trial design was required to answer this question pragmatically/safely.

METHODS
Clinical trials in rare diseases recruit slowly, allowing continuous monitoring of efficacy outcomes. Efficacy-transition-pathways (ETP) are innovative visual tools to aid determination of trial design parameters, and an extension of the dose-transition-pathways concept introduced for dose-finding trials (PMID:28733440).

RESULTS
MonoGerm includes two monotherapies, with each single arm recruiting six cohorts of three patients, with interim assessment after each recruited cohort and final analysis at 18 patients (total n=36). Insufficient tumour volume response (&lt;30%) at 6-week safety MRI results in 12-weeks carboPEI. Primary outcome is radiological complete response (CR) by 12-weeks of induction monotherapy. A beta-binomial conjugate analysis will generate posterior probability distributions, combining observed trial data as realisations from a binomial distribution with a minimally informative Beta (1,1) prior. Decision criteria to allow early stopping at interim analyses and go/no-go decisions at final analysis are based on probabilities from these posterior distributions. ETP visually maps out parameters used to assert decisions after each interim assessment as a pyramid decision tree. For each recruited cohort and every CR outcome, estimates of the true CR rate and probabilities with associated decisions are mapped out. ETP allows clear communication between statisticians, clinicians, and patient-public-involvement (PPI) teams, facilitating informed decisions in an efficient/realistic trial design.

CONCLUSION
MonoGerm, a novel Bayesian de-escalation trial, funded by Little Princess Trust (https://www.littleprincesses.org.uk/), uses ETP and continuous monitoring with built-in stopping rules to ensure patient safety in this treatment de-escalation trial.
CTNI-26. A PHASE II STUDY OF SACITUZUMAB GOVITECAN IN RECURRENT GLIOBLASTOMA
Authors: Kelly William , Cordova Christine , Vaillant Brian , Balinda Henriette , Michalek Joel , Gilbert Andrea , Floyd John , Brenner Andrew 
Published: November 2024

Abstract

BACKGROUND
Glioblastoma (GBM) is the most aggressive and common form of primary brain cancer. GBM expresses trophoblast cell-surface antigen 2 (Trop2) which correlates with proliferation rate, microvessel density, histological grade and clinical survival. Sacituzumab Govitecan (SG) is an antibody-drug conjugate targeting Trop2 with a chemotherapy payload, SN-38. This drug has been approved for triple-negative and hormone-receptor positive metastatic breast cancer.

METHODS
We conducted multi-center (UT Health San Antonio, Cleveland Clinic, Texas Oncology in Austin), open-label, single-arm phase 2 study using a 2-stage adaptive Bayesian design. Patients with recurrent GBM (rGBM), IDH wild-type, following standard-of-care chemoradiation, received SG (10mg/kg IV, days 1 and 8 every 21 days). Patients were assessed by RANO and CTCAE v5. The primary endpoint was PFS of patients on SG as compared to a historical control of lomustine.

RESULTS
As of interim analysis cutoff, 24 patients have been screened with 20 patients enrolled. The average age was 58.8 years. 65% of patients identified as male. 95% were Caucasian with 20% identifying as Spanish, Hispanic or Latino. Adverse events (AE) include lymphopenia (40%), neutropenia (40%), hypokalemia (35%), elevated alkaline phosphatase (30%), anemia (30%) with most AE being grade ≤ and no grade 5 observed. 4 patients had grade ≥3 neutropenia attributable to SG. 20% had stable disease as best response with the rest being progressive disease. The mean PFS and OS were 7.0 and 2.0 months, respectively. Of 19 evaluable samples, 63% had positive Trop2 expression (H-Score ≥100, mean 123.6±74 [0.6, 269.2]). A post-hoc analysis of OS log survival time vs H-Score (n=19) using an accelerated failure time model showed that survival correlated with H-Score (p=0.0361).

CONCLUSIONS
In the interim analysis of this study of patients with rGBM, Sacituzumab was found to be well-tolerated. Further study of those patients bearing tumors with elevated H-scores may be warranted.
CTNI-33. EARLY COMPLETE RESPONSE MIGHT NOT BE AN INDICATOR OF LONGER PROGRESSION-FREE SURVIVAL IN NEWLY-DIAGNOSED PRIMARY CENTRAL NERVOUS SYSTEM LYMPHOMA WITH A COMPLETE RESPONSE BY MTX-BASED INDUCTION THERAPY
Authors: Nagane Motoo , Sasaki Nobuyoshi , Saito Kuniaki , Kobayashi Keiichi , Kugasawa Kazuha , Onoda Ryo , Nakatomi Hirofumi 
Published: November 2024

Abstract
Primary central nervous system lymphoma (PCNSL) is an extra-nodal non-Hodgkin lymphoma solely arising from the central nervous system including eyes. While 70% of patients with newly-diagnosed PCNSL achieve a complete response (CR) after R-MPV, the current standard of care MTX-based induction therapy, recurrence yet frequently occurs (~50%) and clinical factors related to failure are not well defined. Early complete response is associated with lower recurrence rate in various cancers. In this study, we conducted a retrospective, single-institution study to investigate whether early complete response was associated with recurrence in PCNSL. Newly-diagnosed PCNSL patients treated with R-MPV at the authors’ institution between 2011 and 2022 were identified, and progression-free survival (PFS), overall survival (OS) were analyzed along with number of chemotherapy cycles required to achieve a CR or CR unconfirmed (CRu). In total of 92 patients treated with R-MPV identified, 68 (75%) patients achieved a CR or CRu. Among patients who achieved CR or CRu, a median total of seven (1-8) R-MPV cycles were delivered. The median cycle required to achieve CR or CRu was five (1-8). Consolidation whole brain radiation therapy (WBRT) was given to 29 younger patients (median age: 63), while 39 older patients (median age: 74) were treated without WBRT. The number of chemotherapy cycles required to achieve CR or CRu was not associated with PFS or OS in all ages. However, requiring six or more chemotherapy cycles to achieve CR or CRu was associated with longer PFS (p=0.046) in patients treated without WBRT. These data suggest that early complete response might not be indicative of superior survival outcome in newly-diagnosed PCNSL treated without consolidation WBRT. Persisting enhancing lesions during chemotherapy could lead to treatment intensification through delivering greater number of chemotherapy cycles, which might have conferred longer PFS in these patients.
CTNI-35. EVALUATE THE SAFETY AND PRELIMINARY EFFICACY OF THE COMBINATION OF NAVIFUS SYSTEM WITH RE-IRRADIATION FOR RGBM PATIENTS
Authors: Wei Kuochen , Chen Koting , Huang Chiungyin 
Published: November 2024

Abstract
The blood-brain barrier (BBB) remains the major obstacle in treating patients with malignant brain tumors. Radiation therapy (RT) is the mainstay adjuvant modality regardless of the BBB, but its effectiveness is hindered by the hypoxic microenvironment. Focused ultrasound (FUS) combined with systemic microbubbles has been shown to open the BBB and potentially increase regional perfusion. However, no clinical study has investigated the combination of RT with FUS-BBB opening (RT-FUS). Here, we report an interim analysis of an ongoing single-arm, prospective, pilot study (NCT04988750) combining RT-FUS for recurrent malignant high-grade glioma patients, where re-RT was considered for disease control. FUS-BBB opening was conducted within 2 hours before RT. Treatment responses were evaluated by objective response rate (ORR) using magnetic resonance imaging, progression-free survival, overall survival, and adverse events (AEs). In this pilot clinical trial, an interim analysis of six recurrent malignant high-grade glioma patients who underwent a total of 24 RT-FUS treatments was presented. Three patients experienced rapid disease progression after RT-FUS, while the other three patients had at least stable disease after RT-FUS, with or without salvage chemotherapy or targeted therapy. There were no FUS-related AEs, but re-RT-related grade three radiation necrosis was observed. The interim analysis of this ongoing clinical trial showed that the combination of RT-FUS was safe, with no FUS-related adverse effects. Two more cases will be recruited in this trial. A comprehensive analysis of radiation dosimetry and FUS energy distribution is expected after completing the final recruitment.
CTNI-36. THE FEASIBILITY OF USING BORTEZOMIB WITH CHEMOTHERAPY IN ATYPICAL TERATOID/RHABDOID TUMORS
Authors: Ho Wan-Ling , Hsieh Ming-Yun , Liao Yu-Mei , Chiou Shyh-Shin , Shiah Her-Shyong , Chiang Chang-Hsu , Jou Shiann-Tarng , Yen Hsu-Ju , Lee Yi-Yen , Liang Muh-Lii , Yeh Ting-Chi , Chou Yu-Cheng , Huang Fang-Liang , Chen Shu-Huey , Lee Hsin-Lun , Kuo Chia-Chun , Chen Shu-Mei , Tsai Min-Lan , Chang Hsi , Hsieh Kevin Li-Chun , Fang Chia-Lang , Chang Chia-Yau , Wang Jinn-Li , Chen Chu-Chin , Loh Joon-Khim , Lin Pei-Chin , Lin Tzu-Chin , Wang Shih-Chung , Tu Yi-Fang , Cheng Chao-Neng , Chuang Ming-Jung , Tran Huy Minh , Sung Shian-Ying , Lai Irving , Wu Kuo-Sheng , Miser James S , Liu Yen-Lin , Wong Tai-Tong 
Published: November 2024

Abstract
Atypical teratoid/rhabdoid tumors (ATRTs) are highly aggressive pediatric brain tumors with sensitivity to proteasome inhibitors in preclinical models. We evaluated the feasibility of combining the proteasome inhibitor bortezomib with chemotherapy. Patients aged 0-20 years with newly diagnosed ATRT were enrolled from January 2022 through December 2023. A modified Medical University of Vienna (MUV)-ATRT regimen was used. They were treated with bortezomib of 1.3 mg/m2/dose given intravenously or subcutaneously twice a week for 2 weeks concurrently with 6 cycles of chemotherapy and 2 additional cycles after high-dose chemotherapy. Radiation therapy was given prior to or at the end of chemotherapy. A total of 36 chemotherapy cycles with bortezomib in 6 patients were evaluated. The primary endpoint was grade 3 or higher non-hematologic toxicities. Numbers of cycles with grade 3+ toxicities included: AST/ALT elevation (1), hypokalemia (2), peripheral neuropathy (1), subdural hemorrhage (2), vomiting (2), oral mucositis (3), lung infection (2), urinary tract infection (8), sepsis (3), febrile neutropenia (20). No grade 3+ toxicities were considered bortezomib-related. Three patients completed 8 cycles of bortezomib treatment; 2 patients discontinued the study due to progressive disease after 2 and 4 cycles respectively; 1 patient completed 6 cycles of bortezomib and died of septic shock in complete remission after high-dose chemotherapy. Two patients had a surgical complete resection. Three patients were evaluable for response after bortezomib: 1 partial response and 2 stable disease. Two patients had progression-free survival for 16+ and 22+ months after diagnosis, respectively. Among the 3 patients with progressive disease, 2 had metastatic relapse and 1 had primary and metastatic relapse. There were 4 deaths due to metastatic PD (n=2), septic shock after high-dose chemotherapy (n=1), and septic shock after 2nd line treatment for PD (n=1). We conclude that adding bortezomib to standard and high-dose chemotherapy of ATRT was feasible with the occurrence of grade 3/4 toxicities no more than what was expected with chemotherapy alone. Metastatic relapse remains the major challenge of ATRT treatment.
CTNI-38. SINGLE-CENTER COMPARATIVE ANALYSIS ABOUT OUTCOMES OF MULTI-AGENTS CHEMOTHERAPY FOR PRIMARY CENTRAL NERVOUS SYSTEM LYMPHOMA; R-MPV SHOWED A FAVOR RESULT
Authors: Makino Yasuhide , Yamamoto Etsuko , Takada Shigeki , Sano Noritaka , Tanji Masahiro , Mineharu Yohei , Arakawa Yoshiki 
Published: November 2024

Abstract

BACKGROUND
Primary central nervous system lymphoma (PCNSL) is a malignant tumor in the brain, spinal cord, and eyes. Radiotherapy may cause delayed leukoencephalopathy so that the first-line treatment is methotrexate (MTX)-based multi-agent chemotherapy. We had used the Bonn protocol based on MTX and cytarabine, but since 2020, we have adopted the R-MPV protocol. This study analyzes the outcomes of patients treated initially at our institution.

METHODS AND RESULTS
We reviewed 57 out of 88 newly diagnosed PCNSL patients treated with chemotherapy alone between December 2005 and January 2023. Initial treatments included the Bonn protocol in 25 patients (12 with rituximab, forming R-Bonn) and R-MPV in 26 patients. High-dose chemotherapy with peripheral blood stem cell transplantation (PBSCT) was given as consolidation in 4 Bonn and 9 R-MPV patients. The Bonn protocol was completed by 20 patients (80%) with a complete response (CR) in 19 (76%). The R-MPV protocol was completed by 23 patients (88%) with CR in 22 (85%). Post-treatment outcomes were compared using survival analysis. Median progression-free survival (mPFS) had not been reached in the R-MPV group and was significantly better than 33.1 months in the Bonn protocol and 58.6 months in the R-Bonn protocol (log-rank test; p=0.0296, 0.0036). Overall survival (OS) did not show significant differences. PBSCT’s impact on outcomes suggested improvement in PFS and OS after R-MPV, but this was not statistically significant.

DISCUSSION
We examined the efficacy of different chemotherapy regimens for PCNSL at our institution. The R-MPV protocol showed superior completion rates, response rates, and treatment efficacy. Consolidation with PBSCT may improve outcomes, though further investigation with more cases and longer observation is necessary.