Intraventricular Chemotherapy Research Articles

BIOM-08. LEVERAGING CSF PROTEOMICS TO OPTIMIZE CNS LYMPHOMA MANAGEMENT

Abstract INTRODUCTION Despite exquisite responses to initial therapy for CNS lymphoma (CNSL), relapse is common and overall responses are disappointing compared to other non-CNS diffuse large B-cell lymphomas. Incorporation of multi-agent intraventricular chemotherapy (MAIVC) alongside systemic therapy is novel. Identification of minimally-invasive biomarkers of response to MAIVC are necessary but lacking. The objectives of this study were to 1) identify baseline cerebrospinal fluid (CSF)-based proteomic predictive biomarkers of MAIVC treatment response and 2) identify tumor burden markers for longitudinal monitoring of MAIVC treatment response in CNSL. METHODS A cohort of patients with primary or secondary CNSL that were treated with MAIVC at Penn State Health (2015-2021) was included. Each MAIVC cycle was administered via Ommaya reservoir and included a 2-drug combination comprised of methotrexate, rituximab, cytarabine, etoposide, topotecan, gemcitabine, or thiotepa. Patient-matched CSF was sampled at pre- and post-therapeutic endpoints and profiled using shotgun proteomics. Patients were grouped by treatment response status. Early responders were defined as patients that achieved malignant cell-free CSF within 6 MAIVC cycles, whereas never responders were those patients that i) did not achieve malignant cell-free CSF by endpoint or ii) required salvage surgery or radiation during MAIVC. RESULTS 59 patients were included (21 primary; 38 secondary CNSL) with a median age of 66 years (range 25-90) and median number of MAIVC cycles of 8 (range 2-23). A proteomic-based classifier, comprised of SGCE, LCP1 and AGRN, discriminated between early and never responders with an AUROC of 0.95. Comparison of CSF at baseline (<3 cycles MAIVC) vs. post-treatment (>12 cycles MAIVC) identified H3F3A, YWHAE, LCP1, CA1 and GAPDH as tumor burden biomarkers. CONCLUSION Here we developed a proteomic signature capable of predicting CNSL patient response to MAIVC, with potential to improve clinical decision making. Furthermore, the biomarkers associated with tumor burden represent important indicators of treatment response. Ongoing efforts are underway to evaluate these candidates as actionable therapeutic targets.

1369P Trilaciclib combined with intraventricular injection chemotherapy in the treatment of advanced NSCLC with leptomeningeal metastasis: A prospective, single-arm, phase II clinical trial

1369P Trilaciclib combined with intraventricular injection chemotherapy in the treatment of advanced NSCLC with leptomeningeal metastasis: A prospective, single-arm, phase II clinical trial

High-dose furmonertinib combined with intraventricular chemotherapy as salvage therapy for leptomeningeal metastasis from EGFR exon 20 insertion-mutated lung cancer.

The treatment of leptomeningeal metastasis (LM), a serious complication of advanced non-small cell lung cancer (NSCLC), presents challenges, particularly in patients with EGFR exon 20 insertion (ex20ins) mutations. This study retrospectively analyzed data from 10 EGFR ex20ins-mutated NSCLC patients with LM admitted at our institution from May 2011 to June 2023. Circulating tumor DNA (ctDNA) from cerebrospinal fluid (CSF) and matched plasma samples was analyzed using next-generation sequencing. All patients received high-dose furmonertinib combined with intraventricular chemotherapy (IVC) as salvage therapy. Data on patient demographics, treatment efficacy, and safety outcomes were collected. The most common insertion mutation identified in this study was p.A767_V769dup (n = 4, 40%), followed by D770-N771insY (n = 2, 20%). Nine patients had EGFR ex20ins occurring in the EGFR loop region following the C-helix, whereas only one patient had an EGFR ex20ins (A763_Y764insFQEA) occurring in the C-helix of the tyrosine kinase domain. LM response assessment using the RANO-LM criteria revealed that 6 patients (60%, 95% CI 26.2-87.8%) achieved a response, 3 had stable disease, and 1 had progressive disease. The median progression-free survival and overall survival were estimated to be 6.5 months and 8.8 months, respectively. The most commonly reported treatment-related adverse events were rash (n = 7) and diarrhea (n = 7), with no treatment-related deaths occurring. The current study demonstrated that high-dose furmonertinib plus IVC as salvage treatment for patients with LM harboring EGFR ex20ins mutations had promising clinical benefits and a manageable safety profile.

LMIC-16. PRE-IRRADIATION CHEMOTHERAPY AND DELAYED RADIATION THERAPY IN INFANTS AND YOUNG CHILDREN WITH WITH CENTRAL NERVOUS SYSTEM EMBRYONAL TUMOURS

Abstract BACKGROUND Established strategies for infants and young children(IYC) with embryonal tumours of the central nervous system(CNSET) - autologous stem-cell rescue(ASCT) and intraventricular chemotherapy(IVCT) – are not universally available. We report the outcomes of IYC with CNSET treated using the strategy of surgery, pre-irradiation chemotherapy and delayed radiation. METHODS Children <3years diagnosed with CNSET- medulloblastoma(MB), atypical teratoid/rhabdoid tumour(ATRT), embryonal tumour with multilayered rosettes(ETMR), CNS primitive neuroectodermal tumours(PNET)- and pineoblastoma(PB),underwent standard evaluation and staging, maximal safe excision, pre-irradiation chemotherapy(cyclophosphamide, etoposide and carboplatin;CEJ) upto 36months of age and either ris-adapted craniospinal with boost or focal irradiation. We performed a retrospective intention-to-treat outcome analysis. RESULTS Of 117children <3years with CNSET treated January2011- December2022, 72 were treated with this strategy.The median age was 25months (range6-35), 49males,histology medulloblastoma-42(58%), ATRT-9(12.5%), PNET-8(11.1%), ETMR-8(11.1%) and PB-5(6.8%); 23(32%) metastatic.The median chemotherapy cycles were 6(range 1-15). 36 children went on to receive RT; CSI in 33 (20standard-dose,13reduced-dose) and focal in 3. At last follow-up, 27children are in remission, 43 have relapsed/progressed (9 received salvage treatment) and 2 died due to chemotherapy toxicity. The 3-year and 5-year event-free-survival(EFS) are 35% and 3-year and 5-year overall-survival(OS) are 41.8% and 40.2%. The 3-year EFS/OS for MB are 51.1%/ 62.8%,PNET 25%/25%,ATRT 11.1%/11.1%,ETMR 12.5%/12.5% and PB 0%. Only metastasis was prognostic in medulloblastoma (HR 2;95% CI 0.86-4.6 for EFS and HR 1.7;95% CI 0.67-4.5 for OS); age, molecular group and histology were not prognostic. Long-term follow-up (n=17) documented >grade2 late effects in all (endocrine-16, neurocognitive-8, vision-3, hearing -8 and neurological-10). CONCLUSION The use of moderate-intensity pre-irradiation chemotherapy is feasible and effective in infants and young children with CNSETs. Despite inferior outcomes compared to ASCT or IVCT,this strategy could be used in resource-limited settings.

LMIC-11. OUTCOMES OF INFANTS WITH CNS TUMORS: REPORT OF 85 CASES FROM 6 MEXICAN HOSPITALS

Abstract INTRODUCTION Reports on central nervous system (CNS) tumors in infants from low- and middle-income countries are scarce. This is a high-risk population, we sought to analyze their outcomes in Mexico. METHODS Patients <36 months diagnosed CNS tumors between January 2014 to December 2023 from 6 hospitals in Mexico were included. Demographic, treatment, and outcomes were collected. RESULTS In total, 85 patients with a median age of 21 months were included. Of these, 51 (60%) were male. Diagnoses included low-grade glioma (LGG) in 26 (33%), medulloblastoma (MB) in 19 (22%), other embryonal tumors in 12 (14%), ependymoma (EPN) in 11 (13%), high-grade glioma (HGG) in 6 (7%), and other tumors in 11 (13%). Regarding surgery, a near or gross total resection was achieved in 22 patients (26%). For LGG it was 23%, while it was 37% for for MB, 36% for for EPN, and 17% for HGG. Ten patients (12%) died from postoperative complications. Overall, 12 (14%) patients, including 4 patients with MB, had metastasis at diagnosis. In total, 19 (22%) patients received radiotherapy, including 10 patients who received CSI (average age 35 months) and 9 who received focal radiotherapy, including 6 with EPN, 2 with LGG, and 1 with ATRT. Of patients with MB, 18 (95%) received chemotherapy, including 1 with autologous stem cell transplant and 3 with intraventricular chemotherapy. The 5-year event-free survival was 38±11%, while the 5-year overall survival (OS) was 52±10%. The 5-year OS were: 84±10% for LGG, 43±21% for MB, 55±23% for EPN, 9±25% for other embryonal tumors, and 17±35% for HGG. CONCLUSIONS These data show low survival rates, associated with very poor surgical outcomes. A fraction of patients received CSI radiotherapy, showing deviation from international standards. Further analyses are needed to identify factors that lead to better prognosis.

DIPG-03. VENTRICULAR CEREBROSPINAL FLUID SAMPLING IN PEDIATRIC DIFFUSE MIDLINE GLIOMA PATIENTS: INSTITUTIONAL EXPERIENCE AND REVIEW OF THE LITERATURE

Abstract BACKGROUND Increasing evidence suggests that circulating biomarkers may serve diagnostic and longitudinal monitoring purposes in pediatric neuro-oncology. Mutant tumor DNA is detectable in the cerebrospinal fluid (CSF) of pediatric diffuse midline glioma (DMG) patients and quantity can reflect disease burden. CSF sampling (“liquid biopsy”) via a CSF access device could therefore play a role in DMG management. Therefore, we set to evaluate the incidence of hydrocephalus (HCP) in DMG patients, and to characterize ventricular reservoir placement and access practices. METHODS A single institution retrospective review of DMG patients <21-years-old was performed (1984-2019). MEDLINE searches for reports of ventricular reservoir or shunt placement in DMG, and reservoir access for intraventricular chemotherapy (IVC) were performed. RESULTS At our institution, 62.6% of DMG patients (67/108) required intervention for HCP: 19.4% provided transient CSF access (ETV alone n=3, EVD n=8, unspecified n=2), and 80.6% permanent CSF access (ETV + reservoir n=13, shunt n=41). Further, 22/34 patients with initially transient CSF devices required conversion to a permanent device. Five devices were revised for malfunction, one for infection. Seventeen articles cited HCP in 22% to 100% of DMG patients. IVC administration was described in 632 patients (seven articles), with 42 infectious and 63 non-infectious complications. CONCLUSIONS Management of HCP is often necessary in children with DMG. Given the low rate of clinical risk associated with VAD placement and access, and the potential utility of longitudinal disease monitoring via CSF analysis, VAD placement could be considered in future clinical trials to guide DMG treatment.

High-dose furmonertinib in combination with intraventricular chemotherapy for EGFR exon 20 insertion mutated lung adenocarcinoma with leptomeningeal metastasis.

e20555 Background: Leptomeningeal metastasis (LM) is a severe complication of advanced lung adenocarcinoma (LUAD) and always has a dismal prognosis. EGFR exon 20 insertion ( EGFR 20ins) is the third most common EGFR mutations; however, there are currently no reports focusing on LM with EGFR 20ins, and the optimal therapy for these patients remains unclear. This retrospective study aimed to evaluate the efficacy and safety of high-dose furmonertinib in combination with intraventricular chemotherapy in EGFR 20ins mutated LUAD patients with LM. Methods: Weretrospectively enrolled 10 LUAD patients with LM who had failed multiline treatment between May 2021 and June 2023 at Nanjing Chest Hospital. All of them had confirmed EGFR 20ins by next generation sequencing. All patients received furmonertinib in combination with intraventricular chemotherapy via the Ommaya reservoir. Furmonertinib was taken at 160 mg once daily. The chemotherapy regimen consisted of 30mg pemetrexed and 5 mg dexamethasone administered twice weekly for 2 weeks during the consolidation phase, followed by a maintenance phase every 3-4 weeks until disease progression or unacceptable toxicity, or patient refusal. Results: The median age was 53.5 years (range: 39-66), and six (60%) were males. Four patients (40%) had an ECOG of 3, and six patients (60%) had an ECOG of 4. The intracranial ORR (iORR) was 60% (6/10) and intracranial DCR (iDCR) was 90% (9/10). The ECOG PS improved in 80% patients after treatment. With a median follow-up of 9.3 months, the median intracranial progression-free survival (iPFS) was 7.3 months (95% CI, 3.3-NR) and the median overall survival (OS) was 8.8 months (95% CI, 4.9-NR), respectively. Treatment related adverse events of ≥ grade 3 occurred in only 2 patients, which were nausea and rash. Conclusions: Furmonertinib in combination with intraventricular chemotherapy is a tolerable treatment with breakthrough clinical efficacy for LUAD patients with LM harboring EGFR 20ins.

The study protocol of the winners project: a randomized and controlled trial using a videogame-based training program in pediatric cancer survivors

IntroductionChildhood cancer survivors have neurocognitive sequelae that in most survivor follow-up programs are underdiagnosed and for which there is usually no treatment plan.Video games have demonstrated various psychological and neurocognitive benefits in different subpopulations, such as patients with organic neurological deficits or children with ADHD. However, few studies have been carried out using video games-based interventions in the paediatric oncology population.ObjectivesThe aim of this work is to present the WINNERS study protocol, the objectives of which are to diagnose the neurological and cognitive sequelae in child cancer survivors, and to demonstrate the benefit in these areas of a training program based on video games.MethodsA randomized controlled and unblinded trial is presented. Fifty-six patients aged 8 to 17 years stratified into two age groups (8-12 and 13-17) who had received any of the following treatments 1 to 6 years before the enrolment will be selected: high-dose chemotherapy with blood-brain barrier crossing, intrathecal or intraventricular chemotherapy, CNS radiotherapy or hematopoietic stem cell transplantation. A neuropsychological evaluation will be performed consisting of a battery of neuropsychological tests to assess parameters such as attention, memory, visuospatial ability or speed of response, as well as a neuroimaging evaluation by structural and functional magnetic resonance imaging. The evaluation will be repeated 3 months and 6 months after the enrolment. Patients will be randomized to a treatment group or to a recycled waiting group. Intervention will consist on a 12-week training at home using 3 video games: a brain training game, an exergaming game and a skill training game.ResultsAccording to the hypotheses of this study, it is expected that the proposed program of videogame-based interventions will improve neurocognitive and other wellbeing parameters in the intervention group.ConclusionsThis study aims to improve the quality of care for patients who have survived a cancer disease by detecting sequelae that have so far been poorly attended, and by proposing a gamification-based intervention program that is effective and attractive for this population.Disclosure of InterestNone Declared

Ommaya reservoir use in pediatric ALL and NHL: a review at St. Jude Children's Research Hospital.

The intraventricular route of chemotherapy administration, via an Ommaya Reservoir (OmR) improves drug distribution in the central nervous system (CNS) compared to the more commonly used intrathecal administration. We retrospectively reviewed our experience with intraventricular chemotherapy, focused on methotrexate, in patients with Acute Lymphoblastic Leukemia (ALL) and Non-Hodgkin Lymphoma (NHL). Twenty-four patients (aged 7 days - 22.2 years) with 26 OmR placements were identified for a total of 25,009 OmR days between 1990 and 2019. Methotrexate cerebrospinal fluid (CSF) concentrations (n = 124) were analyzed from 59 courses of OmR therapy in 15 patients. Twenty-one courses involved methotrexate dosing on day 0 only, whereas 38 courses involved booster dosing on days 1, 2, or both. We simulated the time CSF methotrexate concentrations remained > 1 µM for 3 days given various dosing regimens. CSF methotrexate exposure was higher in those who concurrently received systemic methotrexate than via OmR alone (p < 10- 7). Our simulations showed that current intraventricular methotrexate boosting strategy for patients ≥ 3 years of age maintained CSF methotrexate concentrations ≥ 1 µM for 72h 40% of the time. Alternatively, other boosting strategies were predicted to achieve CSF methotrexate concentrations ≥ 1 µM for 72h between 46 and 72% of the time. OmR were able to be safely placed and administer intraventricular methotrexate with and without boost doses in patients from 7 days to 22 years old. Boosting strategies are predicted to increase CSF methotrexate concentrations ≥ 1 µM for 72h.

Clinical Safety and Efficiency of the H-Port for Treatment of Leptomeningeal Metastasis.

To evaluate the usefulness of a cranial implantable chemoport, the H-port, as an alternative to the Ommaya reservoir for intraventricular chemotherapy/cerebrospinal fluid (CSF) access in patients with leptomeningeal metastasis (LM). One hundred fifty-two consecutive patients with a diagnosis of LM and who underwent H-port installation between 2015 and 2021 were evaluated. Adverse events associated with installation and intraventricular chemotherapy, and the rate of increased intracranial pressure (ICP) control via the port were evaluated for safety and efficacy. These indices were compared with published data of Ommaya (n=89), from our institution. Time-to-install and installation-related complications of intracranial hemorrhage (n=2) and catheter malposition (n=5) were not significantly different between the two groups. Intraventricular chemotherapy-related complications of CSF leakage occurred more frequently in the Ommaya than in the H-port group (13/89 vs. 3/152, respectively, p<0.001). Intracranial hemorrhage during chemotherapy occurred only in the Ommaya group (n=4). The CSF infection rate was not statistically different between groups (14/152 vs. 12/89, respectively). The ICP control rate according to reservoir type revealed a significantly higher ICP control rate with the H-port (40/67), compared with the Ommaya result (12/58, p<0.001). Analyzing the ICP control rate based on the CSF drainage method, continuous extraventricular drainage (implemented only with the H-port), found a significantly higher ICP control rate than with intermittent CSF drainage (33/40 vs. 6/56, respectively, p<0.0001). The H-port for intraventricular chemotherapy in patients with LM was superior for ICP control; it had equal or lower complication rates than the Ommaya reservoir.

SURG-44. VENTRICULAR CEREBROSPINAL FLUID SAMPLING IN PEDIATRIC DIFFUSE MIDLINE GLIOMA PATIENTS: INSTITUTIONAL EXPERIENCE AND REVIEW OF THE LITERATURE

Abstract BACKGROUND Increasing evidence suggests that circulating biomarkers may serve diagnostic and longitudinal monitoring purposes in pediatric neuro-oncology. Mutant tumor DNA is detectable in the cerebrospinal fluid (CSF) of pediatric diffuse midline glioma (DMG) patients and quantity can reflect disease burden. CSF sampling (“liquid biopsy”) via a CSF access device could therefore play a role in DMG management. Therefore, we set to evaluate the incidence of hydrocephalus (HCP) in DMG patients, and to characterize ventricular reservoir placement and access practices. METHODS A single institution retrospective review of DMG patients &amp;lt;21-years-old was performed (1984-2019). MEDLINE searches for reports of ventricular reservoir or shunt placement in DMG, and reservoir access for intraventricular chemotherapy (IVC) were performed. RESULTS At our institution, 62.6% of DMG patients (67/108) required intervention for HCP: 19.4% provided transient CSF access (ETV alone n = 3, EVD n = 8, unspecified n = 2), and 80.6% permanent CSF access (ETV + reservoir n = 13, shunt n = 41). Further, 22/34 patients with initially transient CSF devices required conversion to a permanent device. Five devices were revised for malfunction, one for infection. Seventeen articles cited HCP in 22% to 100% of DMG patients. IVC administration was described in 632 patients (seven articles), with 42 infectious and 63 non-infectious complications. CONCLUSIONS Management of HCP is often necessary in children with DMG. Given the low rate of clinical risk associated with VAD placement and access, and the potential utility of longitudinal disease monitoring via CSF analysis, VAD placement could be considered in future clinical trials to guide DMG treatment.

527P Efficacy of intraventricular chemotherapy with pemetrexed for leptomeningeal metastasis from lung adenocarcinoma: A retrospective study

527P Efficacy of intraventricular chemotherapy with pemetrexed for leptomeningeal metastasis from lung adenocarcinoma: A retrospective study

P16.05.B SAFETY AND EFFICACY OF INTRA-CSF BIOLOGIC AGENTS IN TREATMENT OF NEOPLASTIC MENINGITIS

Abstract BACKGROUND Neoplastic meningitis (NM) is an increasingly frequent, profoundly morbid, and almost invariably fatal complication of solid and hematologic malignancies. Despite multimodal therapy, median survival in randomized trials is approximately 4 months. Biologic agents are widely utilized in management of extra-CSF disease, but often have limited ability to penetrate the CSF. Intra-CSF administration of biologic agents has not been widely investigated. We describe the safety and efficacy of tumor-specific, intra-CSF biologic therapy in a large group of patients with neoplastic meningitis. MATERIAL AND METHODS We queried the database of a large, international neoplastic meningitis registry (NeMeRe) to identify patients with neoplastic meningitis who received at least one dose of neoplastic meningitis-directed therapy with a biologic agent. Detailed patient demographic, treatment, toxicity and outcome data was extracted and analyzed for the first 140 consecutive patients treated at our institution. RESULTS These 140 patients received an intrathecal biologic agent as part of a histology- and molecular profile-directed intraventricular chemotherapy treatment approach. Agents included rituximab (58 patients with lymphoma, 224 cycles), trastuzumab (42 patients with malignant primary brain tumors, 211 cycles; 15 patients with breast cancer, 149 cycles; 1 patient with esophageal cancer, 9 cycles), panitumumab (4 patients with lung cancer, 9 cycles), nivolumab (1 patient with melanoma, 5 cycles; 2 patients with breast cancer, 2 cycles; 2 patients with GBM 12 cycles; 2 patients with lung cancer, 4 cycles; 2 patients with gastric adenocarcinoma, 17 cycles; 2 patients with renal clear cell carcinoma, 17 cycles; 1 patient with AML, 2 cycles; 1 patient with multiple myeloma, 8 cycles) and alpha-interferon (10 patients with melanoma, 31 cycles; 2 patients with renal clear cell carcinoma, 18 cycles). Grade I/II toxicity occurred in 5.8% of rituximab, 3.2% of trastuzumab, 0% of panitumumab, 16.3% of nivolumab, and 3.2% of alpha-interferon containing cycles. There was no grade III toxicity. Median survivals in patients with lymphomatous meningitis (304 days), solid tumor NM from primary brain tumors (243 days), HER2 -positive breast cancer (not reached, &amp;gt;315 days), lung cancer (192 days), and melanoma (307 days) were encouraging. No difference in survival was seen between patients with and without treatment-related toxicity in any histologic group. CONCLUSION This large registry-based cohort study suggests that rituximab, trastuzumab, panitumumab, nivolumab, and alpha interferon may be safely administered into the CSF as part of a multi-agent intra-CSF treatment regimen. Survival, while very tentative, is encouraging. A prospective, multi-center evaluation of these agents in patients with neoplastic meningitis is warranted.

OUTC-06. BEST PRACTICES FOR THE SUCCESSFUL ADMINISTRATION OF COMBINATION METRONOMIC ANTI-ANGIOGENIC AND INTRAVENTRICULAR THERAPY

Abstract BACKGROUND Combination metronomic anti-angiogenic and intraventricular therapy incorporates a customized administration of a five-drug oral antiangiogenic regimen with intravenous bevacizumab and intraventricular chemotherapy and is an effective treatment regimen for children with recurrent central nervous system embryonal tumors. This treatment can be administered while maintaining quality of life and avoiding severe side effects through personalized therapy schedules; however, dosing modifications, available dosage formulations, and complexity of medication administration creates challenges for families and clinical staff. METHODS A retrospective chart review was completed on 11 patients who received this treatment with various combinations of oral medications (thalidomide, etoposide, cyclophosphamide, celecoxib, and fenofibrate), intravenous (IV) medication (bevacizumab), and intraventricular chemotherapy (cytarabine, etoposide, and topotecan). We implemented successful nursing interventions, family education, variable scheduling options, dosage formulation selections, and innovative oral and intraventricular administration techniques. RESULTS Patients were able to successfully receive therapy for an average of 14 months and no patient came off for toxicity. Treatment was generally well-tolerated, with most toxicities being hematologic or gastrointestinal in nature. CONCLUSION Education, innovative dosing schedules, recognition of potential side effects, and medication administration allow for successful administration of this complex therapy.

Retrospective National “Real Life” Experience of the SFCE with the Metronomic MEMMAT and MEMMAT-like Protocol

Relapses in pediatric high-risk brain tumors remain unmet medical needs. Over the last 15 years, metronomic chemotherapy has gradually emerged as an alternative therapeutic approach. This is a national retrospective study of patients with relapsing pediatric brain tumors treated according to the MEMMAT or MEMMAT-like regimen from 2010 to 2022. Treatment consisted of daily oral thalidomide, fenofibrate, and celecoxib, and alternating 21-day cycles of metronomic etoposide and cyclophosphamide associated with bevacizumab and intraventricular chemotherapy. Forty-one patients were included. The most frequent malignancies were medulloblastoma (22) and ATRT (8). Overall, the best responses were CR in eight patients (20%), PR in three patients (7%), and SD in three patients (7%), for a clinical benefit rate of 34%. The median overall survival was 26 months (IC95% = 12.4-42.7), and median EFS was 9.7 months (IC95% = 6.0-18.6). The most frequent grade ¾ toxicities were hematological. Dose had to be adjusted in 27% of the cases. There was no statistical difference in outcome between full or modified MEMMAT. The best setting seems to be when MEMMAT is used as a maintenance and at first relapse. The metronomic MEMMAT combination can lead to sustained control of relapsed high-risk pediatric brain tumors.

How I treat recurrent pediatric high-grade glioma (pHGG): a Europe-wide survey study

PurposeAs there is no standard of care treatment for recurrent/progressing pediatric high-grade gliomas (pHGG), we aimed to gain an overview of different treatment strategies.MethodsIn a web-based questionnaire, members of the SIOPE-BTG and the GPOH were surveyed on therapeutic options in four case scenarios (children/adolescents with recurrent/progressing HGG).Results139 clinicians with experience in pediatric neuro-oncology from 22 European countries participated in the survey. Most respondents preferred further oncological treatment in three out of four cases and chose palliative care in one case with marked symptoms. Depending on the case, 8–92% would initiate a re-resection (preferably hemispheric pHGG), combined with molecular diagnostics. Throughout all case scenarios, 55–77% recommended (re-)irradiation, preferably local radiotherapy > 20 Gy. Most respondents would participate in clinical trials and use targeted therapy (79–99%), depending on molecular genetic findings (BRAF alterations: BRAF/MEK inhibitor, 64–88%; EGFR overexpression: anti-EGFR treatment, 46%; CDKN2A deletion: CDK inhibitor, 18%; SMARCB1 deletion: EZH2 inhibitor, 12%). 31–72% would administer chemotherapy (CCNU, 17%; PCV, 8%; temozolomide, 19%; oral etoposide/trofosfamide, 8%), and 20–69% proposed immunotherapy (checkpoint inhibitors, 30%; tumor vaccines, 16%). Depending on the individual case, respondents would also include bevacizumab (6–18%), HDAC inhibitors (4–15%), tumor-treating fields (1–26%), and intraventricular chemotherapy (4–24%).ConclusionIn each case, experts would combine conventional multimodal treatment concepts, including re-irradiation, with targeted therapy based on molecular genetic findings. International cooperative trials combining a (chemo-)therapy backbone with targeted therapy approaches for defined subgroups may help to gain valid clinical data and improve treatment in pediatric patients with recurrent/progressing HGG.

QLTI-17. PROPHYLACTIC VANCOMYCIN REDUCES OMMAYA RESERVOIR-ASSOCIATED BACTERIAL MENINGITIS: A 12-MONTH PROSPECTIVE STUDY

Abstract INTRODUCTION Intraventricular chemotherapy administered through an Ommaya reservoir (OR) constitutes the mainstay of therapy for adults with leptomeningeal metastases from solid and hematologic malignancies. Unfortunately, OR-associated bacterial meningitis remains a relatively frequent, costly, often morbid, and occasionally fatal complication, limiting the benefit of this approach. We investigated the potential efficacy, cost savings, and toxicity of intraventricular vancomycin co-administered with intraventricular chemotherapy. METHODS Detailed demographic, treatment, and outcome data were collected prospectively between 5/1/21 and 4/30/22 for 63 consecutive patients at our institution who underwent OR placement and subsequent intraventricular chemotherapy, co-administered with 10 mg of intraventricular vancomycin at each treatment. Reservoir-associated bacterial meningitis was defined as 2 consecutive positive cultures from the cerebrospinal fluid of the same organism or 1 positive culture in the presence of any other clinical or laboratory evidence of infection, or signs of infection at the surgical site. RESULTS The infection rate was 0% [95% CI 0-6.75%] among the 63 patients and 0% [0-0.76%] in the 501 consecutive treatments administered over the 12-month study period compared to 10.25% [7.39- 14.0%] in 322 patients and 1.71% [1.22-2.39%] in 1932 treatments over the preceding 5 years. The absolute risk reduction was 10.3% [3.83 - 14.04], p = 0.0049. The number needed to treat was 10 [7-26]. Cost per vancomycin dose was $10.00 ($5,010 over 12 months). The cost of non-surgical treatment of one OR-associated infection is $88,337.70, which translates into a $618,363.90 savings for the estimated 7 patients over 12 months spared an OR-associated infection. Savings were even further increased if OR removal and subsequent replacement was required. The only other covariate associated with (increased) infection risk on multivariable analysis was treatment number. No treatment-associated toxicity was observed. CONCLUSION Prophylactic intraventricular vancomycin eliminated OR-associated infection in patients receiving intraventricular chemotherapy. Dramatic cost savings were achieved without added toxicity.

NCMP-10. NEURO-OPHTHALMOLOGICAL FINDINGS IN CHILDREN AND ADOLESCENTS WITH MEDULLOBLASTOMA - A RETROSPECTIVE ANALYSIS

Abstract BACKGROUND Medulloblastoma represents the most common malignant pediatric brain tumor. Ophthalmic complications are possible sequelae. METHODS Pediatric medulloblastoma (MB) patients treated at the Medical University of Vienna from January 2012 to August 2021 were analyzed and their last ophthalmic assessment was reviewed. RESULTS Fifty-six MB patients could be included (71.4% non-WNT/non-SHH, 16.1% SHH-activated, 8.9% WNT-activated, 3.6% non-specified). Mean age at diagnosis was 7.2 years (range 0-19). Median follow-up to last ophthalmological assessment was 19.7 months (range 0.1-93.2). Thirty-four children underwent tumor resection at our hospital, their tumor localizations were: vermis (55.9%), floor of the 4th ventricle (26.5%), cerebellar hemispheres (11.8%), lateral recess (5.9%). Symptoms at presentation were evaluable for 51 children: 92.2% had symptoms of elevated intracranial pressure, 76.5% ataxia and 21.6% visual disturbances. Postoperative posterior fossa syndrome was observed in 11.1% of 54 children. 98.2% had chemotherapy as part of their initial treatment and all children older than four years (85.7%) received postoperative irradiation of the posterior fossa. In 13 (23.2%) intraventricular chemotherapy was applied. At the last follow-up 21 patients experienced relapse after primary treatment. At the final assessment, frequent neuro-ophthalmological abnormalities included: oculomotor disturbance (75%), esotropia (35.7%) including abducens palsy (12.5%), other cranial nerve palsies (21.4%), horizontal gaze-evoked nystagmus (51.8%), spontaneous nystagmus (16.1%), ocular tilt reaction (21.4%), and optic disc abnormalities (14.3%). Good visual acuity (≥20/25) was maintained in 62.5% patients. Visual field and optical coherence tomography was successfully performed in 75% and 66.1% of patients, respectively. Optic pathway lesions were detected in 4 patients (7.1%), including two cases with occipital metastases, one with optic nerve metastasis and one with leptomeningeal carcinomatosis. Orthoptic treatment with prisms and strabismus surgery was required in 14.3% and 7.7% of children, respectively. CONCLUSION Children with MB frequently suffer from neuro-ophthalmological late-effects. Regular monitoring is warranted to initiate appropriate management.

LOCL-11 EGFR-MUTATED NON-SMALL CELL LUNG CANCER (NSCLC) LEPTOMENINGEAL DISEASE (LMD) IN A LARGE STEREOTACTIC RADIOSURGERY PATIENT COHORT: INCIDENCE AND OUTCOME

Abstract AIM Patients with EGFR-mutated NSCLC brain metastases (BM) treated with targeted agents +/- radiosurgery (SRS) have increasing life expectancies. Systemic treatment may become less effective in preventing CNS progression as survival is prolonged. We sought to identify subsequent LMD in patients with EGFR-mutated NSCLC treated initially with SRS for BM and describe the associated features, treatment, and outcome. METHODS Review of our prospective Gamma Knife registry identified 177 patients with EGFR-mutated NSCLC between 2005 and 2021 treated with SRS. The EMR was queried for development of LMD, and type of LMD was recorded (focal/nodular or diffuse). RESULTS 38 (21%) of the 177 patients developed LMD at a median of 10 months (range 1-25 IQR) following SRS. 27 (71%) of these were on tyrosine kinase inhibitors (TKI) at time of LMD diagnosis. Median overall survival (OS) from initial SRS for the entire cohort was 21 months (18-27 95%CI). Median OS after LMD diagnosis was 5 months (2-32 95%CI). LMD was diagnosed radiographically in 35 patients (92%); 20 patients had diffuse, 15 had focal/nodular, and 3 had positive CSF cytology. 26 (68%) had systemic progression synchronously with LMD. 33 (87%) had treatment for LMD including 19 with whole brain radiation therapy, 16 with the addition of or increased dosing of TKI, 6 with SRS for nodular disease, and 9 with intraventricular chemotherapy. The one- and two-year survival rates following the diagnosis of LMD was 21% and 3%, respectively. CONCLUSION LMD developed in a substantial subset of our patients, and despite the use of a variety of salvage therapies, survival was poor. Investigation to identify factors correlating with the development of LMD and those related to outcome are ongoing. The development of LMD on TKI in several of our patients supports efforts to pursue development of therapeutic agents with long-lasting CNS efficacy.

Sellar Atypical Teratoid/Rhabdoid Tumors (AT/RT): A Systematic Review and Case Illustration.

Introduction: Atypical Teratoid/Rhabdoid tumors are rare, highly malignant tumors in adults, with a median survival of 20 months. We report a case of a sellar atypical teratoid/rhabdoid tumor in a 70-year-old female treated with intraventricular chemotherapy, followed by a systematic review of the current management of sellar AT/RTs.Methods: A comprehensive systematic literature search was conducted on Web of Science, Scopus, and PubMed Central using the key terms “sellar” and “atypical teratoid/rhabdoid tumors”, following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Data, including patient demographics, histology, treatments, and overall survival were extracted and analyzed. Kaplan-Meier survival curves and log-rank analysis were used to compare survival outcomes between different treatment regimens.Results: Our literature search disclosed 123 publications. After prespecified exclusions, 41 patients with sellar AT/RT from 30 manuscripts were identified, and 38 were included in the final analysis. Including our patient, the median age was 44 (range: 20-70) with a substantial female predominance (94.7%). Collectively, patients who received combined chemoradiation therapy had a significantly increased overall survival compared to those who received single modality or no adjuvant therapies (median OS 27 vs. 1.25 months; p=0.0052).Conclusion: Atypical teratoid/rhabdoid tumor in the sellar region carries a poor prognosis. Adjuvant chemotherapy and radiation therapy were associated with significantly increased overall survival. Early consideration of neuro-oncology and radiation-oncology referral and management is likely beneficial in this patient population. Intrathecal chemotherapy is a treatment modality that requires further exploration given the limited options and current dismal prognosis of adult sellar AT/RT.