tbuckley/cabot-search huggingface dataset:
P27.12.B IMPACT OF SEQUENCING TEMOZOLOMIDE TO DEFINITIVE RADIOTHERAPY IN GRADE-II GLIOMA- A CLINICAL AUDIT
Authors: N Kumar, A Tiwari, R Madan, B Saroya, M Tripathi, D Chatterjee, C Ahuja, H Devi, N Singla, D Shah, A Singh, S Sahoo, R Chhabra
Journal: Neuro-Oncology (2024)

Abstract BACKGROUND For low-grade Gliomas (LGG), total surgery remains the cornerstone of treatment; recent studies have demonstrated a remarkable improvement in overall survival (OS) when PCV chemotherapy is added to the radiation therapy treatment regimen for patients with low-grade Gliomas. In clinical practice, multi-agent PCV chemotherapy is being replaced with the Alkylating and oral drug Temozolomide (TMZ) for its better compliance in terms of administration and side effects. Thus, we performed a clinical audit to evaluate the role of TMZ instead of PCV in treating patients with LGG. MATERIAL AND METHODS Objectives- 1-Τo understand the pattern of use of temozolomide along with adjuvant radiotherapy in Grade 2 Glioma and its impact on outcome. 2-Quantify the impact of concurrent and adjuvant chemotherapy on the survival of Grade II Gliomas 3-Difference in the survival of Oligodendroglioma and Astrocytoma with respect to adjuvant treatment. All patient data from 2014 to 2020 was extracted in this clinical audit. Patients with the diagnosis of Grade II oligodendroglioma and Grade II astrocytoma were recorded. Information was recorded regarding surgical details, radiotherapy, and concurrent and adjuvant therapy. The patient’s last follow-up date was recorded. These patients were divided into five groups depending on the adjuvant treatment received after surgery. Group 1: Received External Beam Radiotherapy with concurrent and adjuvant chemotherapy (XRT+CC+ACT) Group 2: Received External Beam Radiotherapy and concurrent Chemotherapy (XRT+ CCT) Group 3: Only External Beam Radiotherapy (XRT) Group 4: No Adjuvant treatment (No Treatment) Group 5: External Beam Radiotherapy followed by adjuvant chemotherapy (XRT + ACT) RESULTS There were 469 patients with grade 2 glioma, including both Astrocytoma (n=192) and Oligodendroglioma(n=223). There was no difference in survival between Grade 2 ODG and Astrocytoma, with mean survival of 29.33 (±28.03) months and 28.53(±28.3) months (p=0.4). In patients with Grade 2 astrocytoma, the highest estimated survival was seen in Group 5 (39.63±7.34 months) and the lowest in Group 4 (7.24±2.27 months) with significant p-value (0.0001). In Patients with Grade 2 Oligodendroglioma, the highest estimated survival was seen in Group 5 (44±6.49 months) and the lowest in Group 3 (32.98±3.49 months) with non-significant p-value (0.4). CONCLUSION In the lack of definitive data on the role of adjuvant treatment in grade II Glioma, our study provides convincing evidence for the use of adjuvant Temozolomide in low-grade Glioma. Our study revealed that adjuvant Chemotherapy with Temozolomide after Radiotherapy results in better overall survival
P27.08.B EVALUATING THE SURVIVAL OUTCOMES OF REPEAT SURGICAL RESECTIONS FOR RECURRENT PRIMARY BRAIN TUMOURS: A RETROSPECTIVE ANALYSIS
Authors: M choudhury, L Harris, G Sioftanos, B Vaqas
Journal: Neuro-Oncology (2024)

Abstract BACKGROUND Primary brain tumours (PBTs), particularly Glioblastoma Multiforme (GBM), are known for their aggressive nature and poor prognosis. This study evaluates the survival outcomes of patients undergoing repeat resections for PBTs at a tertiary neurosurgical centre. MATERIAL AND METHODS We conducted a retrospective analysis of consecutive cases of repeat surgical resections for PBTs from January 2000 to August 2022. Data included patient demographics, initial and subsequent treatments, and survival times up to August 31, 2023. Kaplan-Meier estimates were used to analyse survival rates and progression times from both initial and repeat surgeries. RESULTS The median follow-up (FUP) was 72.5 months. During this period 18 patients had a repeat resection (RR). 61% (11) were male. 10, 3 and 5 patients had confirmed GBM, G3 and G2 astrocytoma respectively. Postoperatively, 8/10 GBM patients completed 60Gy in 30 of concurrent chemo-radiotherapy (CRT) and one received 40Gy in 15 alone. 1 GBM patient was deemed too frail for Radiotherapy (RT). 8/10 went on to receive Temozolomide (TMZ). 5/10 of these had a positive MGMT status (&amp;gt;1-25%). The median time on TMZ before progression was 6 months. All G3 patients and 3/5 G2 patients completed postoperative RT following initial surgery. Median progression time following initial surgery was 12 months (IQR: 8.5), 97 months (IQR: 29.5) and 95 months (IQR: 45) for GBM, G3 and G2 astrocytoma respectively. The median time between initial and repeat resection (RR) was 13, 98 and 95 months for GBM, G3 and G2 astrocytoma respectively. Following RR one G3 and G2 cases was upgraded to a GBM and G3 diagnosis. 7/10 GBM and all G3 patients were fit enough to receive further chemotherapy following RR. 2/5 G2 patients who were RT naive received RT with receiving further chemotherapy post-RR. During the FUP period 7/10, 2/3, 2/5 GBM, G3, G2 patients died. Median OS from initial surgery was 21, 181 and 97 months with Median OS from RR 8, 85 and 29 months for GBM, G3 and G2 astrocytoma respectively. CONCLUSION Repeat resections may provide a survival benefit in a highly selective group of patients, particularly in the GBM cohort, where outcomes were favourable compared to published real-world population data. Repeat surgical resection is well-tolerated and could be considered as part of the management strategy for recurrent PBTs, especially in the context of prolonged survival observed in G3 and G2 astrocytoma cases.
P27.07.A EFFICACY AND SAFETY OF STUPP REGIMEN WITH OR WITHOUT ANLOTINIB FOR NEWLY DIAGNOSED GLIOBLASTOMA: A MULTICENTER, DOUBLE-BLIND, RANDOMIZED PHASE II TRIAL
Authors: Y Chen, G Liu, P Sun, M Li, X Yang, L Pan, L Wang, Y Hua, M Zhao, Y Liu, J Ran, H Cai, X Lu, H Jiang, X Li, W Zheng, Z Liu, S Lin, M Deng, Q Yang, C Guo, J Li, Z Chen
Journal: Neuro-Oncology (2024)

Abstract BACKGROUND The STUPP regimen, which consists of postoperative radiotherapy with concurrent temozolomide (TMZ) followed by up to six cycles of adjuvant TMZ chemotherapy, is the established standard treatment for newly diagnosed glioblastoma (GBM). However, its effectiveness is limited. Anlotinib, a multi-kinase inhibitor targeting tumor angiogenesis and cell proliferation, has demonstrated promising results in preclinical GBM models and phase I clinical trials. In order to assess the efficacy and safety of combining the STUPP regimen with anlotinib, we conducted a phase II trial aimed at evaluating their combined effects. (NCT 04959500). MATERIAL AND METHODS This study is a multicenter, double-blind, randomized, placebo-controlled trial with an expected 150 patients randomly assigned 1:1 ratio to receive TMZ-based radiochemotherapy with anlotinib or placebo. Eligibility criteria include histologically confirmed GBM, ECOG performance score ≤2, age ≥18 years, and lack of significant comorbidity. The primary endpoint is median progression-free survival (PFS), while secondary endpoints include 1-year overall survival rate, PFS at 6 months, overall response rate, duration of response, disease control rate, quality of life, and toxicity. RESULTS From July 2021 to April 28th, 2024, 153 patients were enrolled. The results in this abstract were all obtained without exposing the blind state. The median PFS was 10.22 months (95% CI, 9.43-11.93) in the overall patient population, while the predicted mPFS of placebo group was 7 months according to the results of STUPP and AVAGlio trials. The median OS was 18.69 months (95% CI, 15.90-26.71). The 1-year overall survival rate is 75.71% (95% CI, 64.82%-79.11%), and the 2-year overall survival rate is 42.04% (95% CI, 33.14%-50.67%). 26.8% of patients experienced at least one grade 3 or higher treatment-related adverse events (TRAEs). 11.1% of patients experienced serious treatment-related adverse events. The most frequent grade 3 or higher TRAEs were lymphocytopenia, thrombocytopenia, leukopenia, decreased neutrophil count. CONCLUSION The current research findings, conducted under the condition of data blinding, suggest that the combination of anlotinib with the STUPP regimen demonstrates promising therapeutic efficacy and favorable tolerability in the treatment of patients. These results indicate the potential of this treatment modality as a viable option in clinical practice.
P22.14.A REPORTING STANDARDS IN RANDOMIZED CONTROLLED TRIALS WITH FAMILY CAREGIVERS IN NEURO-ONCOLOGY: A SYSTEMATIC REVIEW FROM THE RANO-CARES WORKING GROUP
Authors: F W Boele, C Hertler, P Sherwood, D Cachia, L Dirven, J Young, T Walbert, M Stockdill, E Rodriguez Almaraz, K Piil
Journal: Neuro-Oncology (2024)

Abstract BACKGROUND Family caregivers in neuro-oncology consistently report high levels of unmet support needs, yet intervention trials and effective support options are scarce. To raise the standard of caregiver-related research reporting in neuro-oncology, the Response Assessment in Neuro-Oncology (RANO-) Cares working group has been established. We investigated the current state of methodological quality of reporting on neuro-oncology caregiver outcomes in randomized controlled trials (RCTs). MATERIAL AND METHODS A systematic literature review (PubMed/Medline, Embase, Web of Science, Emcare, Cochrane Library, PsycINFO; July 2023) was performed to evaluate to what extent RCTs assessing outcomes of family caregivers of adult primary brain tumour patients adhere to minimum reporting standards. Using Covidence, screening and data extraction was done by two researchers independently, with a third guiding consensus. A 33-item checklist (23 applicable to secondary analysis reports) based on the International Society for Quality of Life Research (ISOQOL) criteria for patient-reported outcome (PRO) reporting was used to review each article. Risk of bias was assessed per RCT. RESULTS Fifteen publications (12 RCTs) included 684 neuro-oncology caregivers, with low overall risk of bias. Ten publications (66%) reported on caregiver outcomes as a primary aim, of which eight (80%) satisfied ≥2/3 of the key methodological criteria. Of the five secondary analysis reports (33%) two (40%) met ≥2/3 of applicable key criteria. Criteria often not reported adequately included sample size calculations (reported adequately in n=8, 53%), participant flow (n=9, 60%) window for data collection (n=1, 6%), and extent of (n=10, 66%), reasons for (n=9, 60%), and statistical approaches in dealing with (n=4, 26%) missing data. Unpublished outcome measures were seldom supplied as supplementary material (2/12 publications, 16%). CONCLUSION Whilst there are opportunities to enhance reporting standards, RCTs that include neuro-oncology caregiver outcomes generally adhere to high quality reporting standards, and have low risk of bias, indicating good potential to impact evidence-based, clinical practice.
P18.17.B EFFECTIVENESS OF DABRAFENIB-TRAMETINIB AND LAROTRECTINIB IN ADULT RECURRENT GLIOBLASTOMA PATIENTS: A REAL-LIFE COHORT ANALYSIS FROM 3 ITALIAN CENTERS
Authors: M Padovan, E Cella, A Bosio, M Maccari, G Cerretti, M Caccese, M Corrà, P Giordano, E Bennicelli, G Lombardi
Journal: Neuro-Oncology (2024)

Abstract BACKGROUND Although less than 5% and 1.5% of glioblastomas (GBM) exhibit the BRAFV600E mutation and NRTK fusion, respectively, these cases are significant because some of these patients (pts) may respond well to BRAF/MEK and NTRK inhibitors. Given limited literature, this study aims to evaluate the efficacy of dabrafenib-trametinib and larotrectinib in treating adults with recurrent GBM. MATERIAL AND METHODS We retrospectively analyzed a cohort of adult pts with recurrent GBM (WHO 2021) treated in 3 italian centers: Veneto Institute of Oncology (Padua), Ospedale Policlinico San Martino (Genoa), Ospedale del Mare (Naples). Molecular analysis was obtained on formalin-fixed paraffin-embedded tissue samples with next-generation sequencing analysis, PCR or immunohistochemistry. Dabrafenib-trametinib was given as part of compassionate use program or off-label, while larotrectinib has an agnostic approval. Response assessment was based on RANO (Response Assessment in Neuro-Oncology) criteria. RESULTS Between March 2020 and November 2023, 17 recurrent GBM pts (12 males, 5 females, median age 52) received target therapy: 13 pts with dabrafenib-trametinib, 4 with larotrectinib. 12 pts had ECOG PS 0-1. All had prior radiotherapy and temozolomide. Median line of therapy with target therapy was 2 (range 2-4), with a median of 6 cycles (range 1-48) of treatment. As of April 2024, median follow-up was 7.6 months. In the entire cohort, median overall survival and progression-free survival (PFS) after starting target therapy were 8.8 and 2.8 months, respectively. Dabrafenib-trametinib subgroup showcased the most prolonged median PFS (5.09 m), alongside a notable disease control rate (DCR) of 77% and an objective response rate (ORR) of 30.7%. Among the 13 pts included, 9 had died while 3 pts are presently undergoing active treatment. Pts treated with larotrectinib exhibited a shorter median PFS (2.5 m), with a DCR of 50%; no patient reported a response (ORR 0%). 3/4 pts had passed away, one pt is currently continuing larotrectinib.No grade 3-4 drug-related adverse events were observed in either subgroups; in any case target therapy was interrupted for toxicity. CONCLUSIONS Our results confirm the activity of dabrafenib-trametinib in BRAFV600E mutant GBM pts. Larotrectinib appears to have less activity than data reported in the literature for the pediatric population. However, additional investigations on largest cohorts are needed to elucitate correlations among patient outcomes, molecular characteristics, other prognostic factors, and the timing of target therapy.
Efficacy and safety of infliximab or adalimumab in severe mucocutaneous Behçet’s syndrome refractory to traditional immunosuppressants: a 6-month, multicentre, randomised controlled, prospective, parallel group, single-blind trial
Authors: Rosaria Talarico, Nazzareno Italiano, Giacomo Emmi, Matteo Piga, Luca Cantarini, Irene Mattioli, Alberto Floris, Stefano Gentileschi, Federica Di Cianni, Maria Letizia Urban, Emanuele Chiara, Diana Marinello, Alessandra Del Bianco, Michele Figus, Chiara Posarelli, Claudia Fabiani, Sabrina Vagnani, Gianni Andreozzi, Valentina Lorenzoni, Giuseppe Turchetti, Alberto Cauli, Lorenzo Emmi, Carlo Salvarani, Ornella Della Casa Alberighi, Stefano Bombardieri, Marta Mosca
Journal: Annals of the Rheumatic Diseases (2024)

Evidence from randomised controlled trials on anti-tumour necrosis factor (TNF) agents in patients with Behçet's syndrome (BS) is low.
P18.15.B DRUG SENSITIVITY OF RECURRENT GBM PATIENT-DERIVED ORGANOIDS CORRELATES WITH PATIENTS’ RESPONSE TO SECOND LINE CHEMOTHERAPY
Authors: M Morelli, O Santonocito, F Lessi, S Franceschi, F Pieri, C Gambacciani, G Grimod, F Aquila, S Cupini, I Stasi, V Zucchi, A Giusti, F Vannozzi, E Franceschi, G Berzero, C Mazzanti, A Di Stefano
Journal: Neuro-Oncology (2024)

Abstract OBJECTIVE This study aimed to explore the correlation between the effectiveness of second-line chemotherapy in patients with recurrent glioblastoma (rGBM) who underwent a second surgery and drug treatment tests on patient-derived organoids. METHODS Sixteen adult patients diagnosed with IDH wild-type glioblastoma underwent a second surgery for recurrent GBM, with nine cases studied retrospectively and seven prospectively. Patient-derived 3D glioblastoma organoids (GBM-EXPs) were established from resected tumors and treated with chemotherapy agents. The response to treatment was evaluated using the NADH-FLIM method. RESULTS Among patients experiencing progression during first-line TMZ therapy (or within three months of discontinuation), a majority showed resistance to TMZ in the NADH-FLIM assay (p=0.02), with a longer PFS1 in TMZ-sensitive rGBM-EXPs compared to TMZ-resistant ones (15.9 versus 10.9 months; p=0.07). We did not observe different pMGMT hypermethylation between sensitive and resistant to TMZ rGBM-EXPs. Among patients treated with regorafenib in their second-line chemotherapy, those with regorafenib-sensitive rGBM-EXPs showed a significantly longer PFS2 compared to those with regorafenib-resistant organoids (PFS2 of 7.5 months versus 3.6 months respectively, p=0.04). In the prospective study, seven patients underwent ex-vivo testing before starting second-line therapy. Results from rGBM-EXP were considered by the multidisciplinary tumor board regarding second-line chemotherapy options among other clinical criteria. A trend for a longer median PFS2 was found in the prospective cohort compared to that of the retrospective cohort (7.4 vs 4.6 months, p=0.08) as well as a longer OS2 (defined as the interval from first recurrence and death/last evaluation 6.3 months versus not reached, p=0.03). pMGMT hypermethylation rate was not significantly different between the retrospective and prospective cohort. Paired analysis of specific longitudinal cases of untreated GBM-EXPs compared to rGBM-EXPs showed acquired resistance to TMZ in rGBM. The combination of TMZ and lomustine in ex-vivo testing showed better efficacy than monotherapies with TMZ and lomustine alone: mean % drug-sensitive tissue (DS%) respectively 51.4% vs 5.2% vs 35.8%, p=0.02. CONCLUSIONS This study shows that the sensitivity of rGBM-EXP to TMZ mirrors the timing of recurrence observed in vivo. Our findings suggest a potential role for NADH-FLIM-based drug response assessment in rGBM-EXP for predicting the efficacy of second-line therapies and improving the overall clinical outcome. Further prospective studies are warranted to validate these findings and potentially guide treatment decisions in clinical practice.
JS07.5.A CORRELATION BETWEEN TUMOR-INFILTRATING LYMPHOCYTE DISTRIBUTION AND CLINICAL OUTCOME IN PHASE I/II CLINICAL TRIAL OF DENDRITIC-CELL BASED IMMUNOTHERAPY IN GLIOBLASTOMA PATIENTS
Authors: S Pellegatta, N Di Ianni, E Anghileri, M Facciolla, V Cuccarini, M Milani, M Patane, D Acquino, B Pollo, F DiMeco, A Silvani, M Eoli
Journal: Neuro-Oncology (2024)

Abstract BACKGROUND Despite the first classification of glioblastoma as an immunologically “cold” tumor, accumulating evidence suggests that this cancer type is susceptible to T cell infiltration, providing a glimmer of hope for the development of effective immunotherapy approaches that until now had limited success in brain tumors. To explore the contribution of biomarkers that could identify groups of patients showing durable response to immunotherapy, we examined several clinical and biological finding in 69 newly-diagnosed glioblastoma patients treated with dendritic cell (DC) immunotherapy added to standard treatment (DENDR1 NCT04801147). MATERIAL AND METHODS Patients with post-surgery volume ≤10 cc underwent leukapheresis before radiotherapy and chemotherapy with temozolomide (TMZ). Three intradermal injections of mature DC loaded with whole tumor lysate were administrated before and four after adjuvant TMZ. In all patients peripheral immune effector subsets were assessed including T and NK cells,, In all tumor samples MGMT methylation status was evaluated, and in 36 cases an immunohistochemistry (IHC) analysis was performed on tumor specimen collected before DC immunotherapy. RESULTS After a median follow-up of 23months (mo) median progression-free survival (PFS) was 12 mo (CI 95%10.34-13.6) and median overall survival (OS) was 22.6 mo (CI 95%18.7-24.5) comparing favorably with OS expected from the literature. MGMT status and expansion of NK cells positively impacted PFS and OS. Furthermore, our preliminary results suggest an association between the density and localization of specific Tumor Infiltrating Lymphocytes (TILs) and patients’ response to immunotherapy. TIL spatial patterns revealed either an immune-excluded, or an immune-infiltrated scenario with either scattered, clustered, or widespread T cell infiltration. Notably, an abundant widespread infiltration of CD8 TILs was correlated with prolonged survival of DENDR1 patients (PFS 18.0 vs. 8.9; OS 33.6 vs. 11.0; p&amp;lt; 0.005 compared with excluded CD8+ TIL distribution), supporting that distribution can be predictive of immunotherapy responsiveness. CONCLUSION These findings suggest that in DENDR-1 improved clinical outcomes correlate with an increase in the number of active NK cells, MGMT status, and abundant widespread infiltration of CD8+ TILs.
P17.14.A OPTIMISATION OF THE STEREOTACTIC RADIOSURGERY (SRS) SERVICE AT THE BEATSON, WEST OF SCOTLAND CANCER CENTRE (BWOSCC)
Authors: S Walker, S Nowicki, A James, A Williamson
Journal: Neuro-Oncology (2024)

Abstract BACKGROUND Since 2017 HyperArc™ VMAT SRS has been offered at BWOSCC as a treatment option for patients with brain metastases. During this period, WBRT (whole brain radiotherapy) or PB(Partial Brain)RT for the treatment of brain metastases has correspondingly reduced. Given the reduction in side effects, improved local control and reduced visits with SRS over WB/PBRT, the dedicated neuro-oncology team want to ensure all patients eligible for SRS treatment are being offered it, identify barriers to referral and ways to optimise the service. MATERIAL AND METHODS 57 patients treated with WB/PBRT for brain metastases were identified via the RT database from August 2022-September 2023. Patients with primary small cell lung cancer, post-neurosurgical resection site or leptomeningeal disease were excluded. Patient demographics; primary site; number of brain metastases; diagnostic imaging; geographical location; RT dose and fractionation and survival post-treatment were documented and analysed. Diagnostic imaging for each patient was peer-reviewed by two consultant clinical oncologists, a SABR clinical research fellow and consultant neuro-oncology radiographer to determine whether SRS treatment was technically deliverable. Where it was felt SRS treatment was an option, the patient’s electronic record was interrogated to identify reasoning as to why SRS was not offered. RESULTS The majority of patients had either primary breast(26) or lung(22) cancer: gynaecological(3); colorectal(2); oesophageal(2); CUP(1); urothelial(1). All patients except 2 were treated with 20gy/5# (otherwise 30Gy/10#). Most were treated with WBRT(43). 14 had single brain metastasis; 20: 2-4 metastases; 9: 5-10 metastases; 14 patients had ≥11 brain metastases. 27 had MRI imaging in addition to CT. Most patients’ geographical location was outside of Glasgow(35). In 16 of the 57 patients identified(28%), SRS was technically deliverable. Median survival was 145 days(4.8months): within the technically deliverable SRS group, median survival was also 145days(4.8months).In these 16 patients, 7 were not offered SRS due to widespread systemic disease (not necessarily a barrier to SRS). There was no identifiable rationale in the remaining 9. CONCLUSION From this work we have identified up to 16 potential patients (28%) who could have been offered SRS treatment. As an innovative and committed centre, we want to optimise this service further. Moving forward, we will survey the consultant body to ask what they believe the potential barriers to SRS referral are, and deliver tumour-site-specific and hospital-wide education sessions on SRS treatment and delivery. After these educational interventions, we will review a further 6 months of patient data and compare to this work.