Oral anticancer agents (OAAs) are commonly prescribed for patients with primary brain tumors, but adherence can be challenging due to cognitive impairment and discontinuous treatment schedules. This subgroup analysis of the randomized phase 3 CAPRI trial evaluated the impact of a nurse navigator-led intervention combined with a digital platform (web portal and mobile app) versus standard care in patients with primary brain tumors treated with OAAs. The primary endpoint was Relative Dose Intensity (RDI), with secondary endpoints including adherence, toxicity, healthcare utilization, and patient-reported experience. Fifty-one patients were included between October 2016 and May 2019, 63% of whom had glioblastoma. Twenty-six patients received the intervention. RDI was significantly higher in the intervention group compared to the control group (105% ± 12 vs. 97.6% ± 13, p = 0.04). The intervention also resulted in fewer emergency room visits, reduced hospitalizations, greater use of supportive care services, and improved patient-reported experience (all p < 0.05). Remote monitoring allowed early corticosteroid adjustments in cases suggestive of intracranial hypertension, helping to prevent hospitalizations. No significant differences were observed in treatment-related toxicity. These findings suggest that a nurse navigator-led digital intervention can improve care continuity and outcomes in this population and merit further investigation.

e13885 Background: Remote patient monitoring (RPM) using electronic Patient Reported Outcomes (ePROs) offers a unique opportunity to detect actionable symptoms commonly experienced by patients undergoing anticancer therapy. RPM demonstrated effectiveness in reducing morbidity, while improving quality of life in phase 3 trials. Therefore, the European Society for Medical Oncology (ESMO) recommended the use of RPM based on ePROs in routine care in the 2022 clinical practice guidelines. However, the implementation and the patient adherence of RPM in neuro-oncology remain largely unknown. Methods: Data from all neuro-oncology patients treated and monitored using the RPM solution between January 2022 and November 2024 were included in this study. The RPM pathway included four steps: (i) medical prescription, (ii) patients onboarding by a nurse, (iii) weekly collection of tailored symptoms survey (iv), severe (grades 3-4) or worsening symptoms (moving from a grade 0 to 2) triggered an alert notification to the care team. Results: A total of 261 patients diagnosed with primary CNS tumor were enrolled across 20 healthcare centers in France and Belgium. The average age was 58 years (ranging from 22 to 87). The gender distribution was 59% male and 41% female. The median response time to process questionnaires was 23h for patients and 1h30 for HCPs. The rate of processed questionnaires by healthcare professionals was 99.6%. Overall adherence to the weekly questionnaire was 83% for a total of 4626 questionnaires sent. The most frequent severe PROs (grade ≥3) reported were pain (37%), constipation (26%) and decreased performance status (25%). After the alerts, symptom assessment over a two-week period showed that 96% of patients experienced an improvement of at least 1 grade point, and 88% saw an improvement of 2 to 3 grade points. Conclusions: The implementation of a Remote Patient Monitoring (RPM) pathway in routine care for neuro-oncology patients is feasible and shows high adherence from both patients and healthcare professionals. These results suggest that integrating RPM into neuro-oncology could offer significant benefits and support its adoption as a standard practice in routine care.

INTRODUCTION:H3K27-altered diffuse midline gliomas (DMG) have limited therapeutic options and a very poor prognosis. Encouraging responses were observed in early clinical trials with ONC201. As ONC201 was unavailable in Europe, a compassionate use program supported by the French Authorities was launched for patients at progression after standard of care radiotherapy. METHODS:This program was developed by the French Society of Pediatric Oncology (SFCE) and Association des Neuro-Oncologues d'Expression Française in collaboration with the French National Agency For Medicines and Health Products Safety and Parents Associations. RESULTS:174 patients (102 children, 72 adults) from 14 countries were treated from November 2021 to August 2023 at Gustave Roussy Institut (Villejuif, France). 37 % received a second course of irradiation at the time of relapse. Median duration of treatment was 57 days or 1,9 months (mo) (range 1-456 days). Median OS since diagnosis for the whole cohort was 466 days or 15,5 mo (112-2612 days); 426 or 14,2 mo (112-2612 days) and 590 or 19,6 mo (range 160-1881) for children and adults, respectively (p = 0.001). Median OS after ONC201 start was 143 days or 4,7 mo (1-711 days) for the whole cohort. Univariate and multivariable analysis identified site (thalamus) and age (older) as favorable prognostic factors. Reirradiation was associated with significantly longer survival after ONC201 start only in children. CONCLUSION:While the efficacy of ONC201 needs validation in a controlled randomized clinical trial, our real-life data support a better outcome for patients with thalamic tumors treated with ONC201. We demonstrated furthermore the feasibility of a successful academia-driven compassionate use program.

In non-small cell lung cancer (NSCLC) patients without oncogenic addiction, the frequency of thromboembolic events varies from 5-15%. However, the occurrence of such events significantly increases to 30-48% when ALK or ROS1 fusion is present. Due to the infrequency of the RET fusion population, the incidence of thromboembolic events in these patients remains unknown.

We report the case of a patient with metastatic breast cancer who presented with an orthostatic headache. After a comprehensive diagnostic workup including MRI and lumbar puncture, we maintained the diagnosis of intracranial hypotension (IH). The patient was therefore treated with two consecutive non targeted epidural blood patches, resulting in the remission of IH symptoms for 6 months. IH in cancer patients is a rarer cause of headache than carcinomatous meningitis. As the diagnosis can be made by standard examination and the treatment is relatively simple and effective, IH deserves to be better known by oncologists.

Glioblastoma (GBM) is the most common malignant primary brain tumor in adults. It remains a relatively rare disease with an incidence of 3/100.000 in France, and an age-related peak in incidence at 70 years of age, which corresponds to the age limit inclusion criteria of the Stupp Trial on 2005, cornerstone of the GBM strategy. Therefore, treatment of GBM in elderly patients is not standardized and depends on several clinical and biological factors. The aim of this study is to compare survival outcome of elderly patients with glioblastoma treated with standard radiotherapy (SRT) versus hypofractionated radiotherapy (HRT) versus no radiotherapy (RT), with or without Temozolomide. A single-center retrospective case series analysis was conducted, including newly diagnosed GB patients older than 70 from January 2010 to December 2021. The Log-Rank test was used to compare the PFS and OS of patients treated with SRT versus HRT versus no RT. Furthermore, a Cox regression analysis was performed to identify risk factors associated with OS. Statistical significance was considered when p<0.05. A total of 304 patients were included with a median age of 74.36 years [71.63, 78.62], among whom, 142 were women. Most patients had a performans status of 0 or 1. Median OS was 11.4 months [95% CI 10.4 – 12.3] while median PFS was 8.1 months [95% CI 7.4 – 9.1]. Overall, 231 patients (76%) were treated with RT, 94 (30.9%) with SRT, 129 (42.4%) with HRT and 73 (24%) did not receive RT. On univariate analysis, the SRT group showed a better OS compared to the HRT and no RT groups (23.1 months, 11.1 months and 4.7 months, respectively, p<0.01). Same trend was observed for median PFS (SRT 13.6 months, 8.08 months and 3.7 months respectively, p<0.05). While previous randomized trials showed a benefit or non-inferiority of HRT over SRT in elderly glioblastoma patients, this large retrospective “real-life” cohort shows on the contrary a benefit in terms of OS of the standard normo fractionated RT regimen. Standard treatment should not always be degraded in elderly patient, and a proportion of them may still benefit from standard RT if their clinical status allows it.

Angiogenesis plays a key role in glioblastoma, but most anti-angiogenic therapy trials have failed to change the poor outcome of this disease. Despite this, and because bevacizumab is known to alleviate symptoms, it is used in daily practice. We aimed to assess the real-life benefit in terms of overall survival, time to treatment failure, objective response, and clinical benefit in patients with recurrent glioblastoma treated with bevacizumab. This was a monocentric, retrospective study including patients treated between 2006 and 2016 in our institution. 202 patients were included. The median duration of bevacizumab treatment was 6 months. Median time to treatment failure was 6.8 months (95%CI 5.3–8.2) and median overall survival was 23.7 months (95%CI 20.6–26.8). Fifty percent of patients had a radiological response at first MRI evaluation, and 56% experienced symptom amelioration. Grade 1/2 hypertension (n = 34, 17%) and grade one proteinuria (n = 20, 10%) were the most common side effects. This study reports a clinical benefit and an acceptable toxicity profile in patients with recurrent glioblastoma treated with bevacizumab. As the panel of therapies is still very limited for these tumors, this work supports the use of bevacizumab as a therapeutic option.

Patients (pts) with primary CNS tumors are often excluded from early phase clinical trials because of doubts regarding the blood brain penetration, adherence to study treatment and use of corticosteroids in immunotherapy clinical trials. Scores built to help selectection of pts that would be good candidates for early phase clinical trials such as the Royal Marsden Score (RMH) or the Gustave Roussy Immune Score (GRIm) are not relevant to pts with primary CNS. We aimed to determine factors associated with prognosis to help physicians referring pts. We conducted a retrospective analysis of all pts treated for a CNS tumor and enrolled in an early phase clinical trials at the Drug Development Department at Gustave Roussy between January 2013 and December 2022. Descriptive statistics were used to present the population and a multivariate Cox regression was used to determine prognostic factors in uni and multivariate analysis on overall survival (OS). A total of 108 pts were included in the study. Median age was 47 (18-82), most males (F/M=35/73), 44% were symptomatic in the three months before study entry, 46% had a multifocal disease at C1D1. The ratio between low grade glioma (LGG) and high grade glioma (HGG) according to the new molecular classification of 2021 were 24/84. Molecular alterations were: IDH mutation (59%), MGMT methylation (14.2%, 94 unknown), 1p19q codeletion (19.7%, 53 unkown). Targeted therapies were the most common drug used (44%), followed by immunotherapy (33.%) and epigenetic drugs (8.4%). Pts harbouring a BRAF mutation treated with a specific target therapy were 12; pts with an FGFR mutation or fusion treated in the same setting were 18. Median progression free survival (PFS) was 9.7 months, 40% of pts were progressing at 3 months. Altogether, 34% of pts were alive at 6 months. In multivariate analysis, lymphocyte counts ≥900/mm3 (HR=0.7 95% CI 0.46 - 1.07), absence of steroids at baseline (HR=2.3 95% CI 1.5 - 3.5), absence of antiepileptic drugs at baseline (HR=2.06 95%CI 1.2 - 3.7) were associated with a better overall survival. Corticosteroid use, lymphocyte count and use of antiepileptics will be used to build a new score that will be presented at the conference.

In the last 10 years, immune checkpoint inhibitor (ICI) immunotherapies have become a pivotal treatment in many types of cancer and the management of immune-related adverse events is now well codified [ [1] Schneider B.J. Naidoo J. Santomasso B.D. Lacchetti C. Adkins S. Anadkat M. et al. Management of immune-related adverse events in patients treated with immune checkpoint inhibitor therapy: ASCO guideline update. J Clin Oncol. 2021; 39: 4073-4126 Crossref PubMed Scopus (284) Google Scholar ]. At the beginning of ICI utilisation, patients with a history of autoimmune diseases were initially contraindicated to receive ICI, subsequently safety data accumulated in favour of using ICI in patients with controlled and inactive autoimmune diseases [ 2 Michot J.M. Lappara A. Le Pavec J. Simonaggio A. Collins M. De Martin E. et al. The 2016-2019 ImmunoTOX assessment board report of collaborative management of immune-related adverse events, an observational clinical study. Eur J Cancer. 2020; 130: 39-50 Abstract Full Text Full Text PDF PubMed Scopus (27) Google Scholar , 3 Naidoo J. Zhang J. Lipson E.J. Forde P.M. Suresh K. Moseley K.F. et al. A multidisciplinary toxicity team for cancer immunotherapy-related adverse events. J Natl Compr Canc Netw. 2019; 17: 712-720 Crossref PubMed Scopus (54) Google Scholar ]. A risk of usually mild autoimmune flare (up to 75%) is reported in patients with autoimmune diseases such as rheumatoid arthritis, polymyalgia rheumatica, psoriatic arthritis and autoimmune colitis, after initiation of ICI [ [4] Tison A. Garaud S. Chiche L. Cornec D. Kostine M. Immune-checkpoint inhibitor use in patients with cancer and pre-existing autoimmune diseases. Nat Rev Rheumatol. 2022; 18: 641-656 Crossref PubMed Scopus (9) Google Scholar ], however the level of this flare risk remains unknown for multiple sclerosis (MS).

Speculative execution can significantly improve the performance of Big Data applications by launching other copies of stragglers (slow tasks). Stragglers detection plays an important role in the effectiveness of speculative execution. The methods employed to detect stragglers use the information extracted from the last received heartbeats which may be outdated when triggering detection. This, in turn, can mislead Big Data analytic systems to make wrong detection with high inaccuracy. To shed the light on this issue, we carry out extensive simulations to identify how heartbeat arrival, task starting times, and detection methods impact the accuracy of stragglers detection in Big Data analytic systems. We reveal that the asynchrony in heartbeat arrivals not only lead to marking normal tasks as stragglers (false positives) but can also result in overlooking real stragglers (false negatives).

Diffuse gliomas, the most frequent and aggressive primary central nervous system neoplasms, currently lack effective curative treatments, particularly for cases lacking the favorable prognostic marker IDH mutation. Nonetheless, advances in molecular biology allowed to identify several druggable alterations in a subset of IDH wild-type gliomas, such as NTRK and FGFR-TACC fusions, and BRAF hotspot mutations. Multi-tyrosine kinase inhibitors, such as regorafenib, also showed efficacy in the setting of recurrent glioblastoma. IDH inhibitors are currently in the advanced phase of clinical evaluation for patients with IDH-mutant gliomas. Several immunotherapeutic approaches, such as tumor vaccines or checkpoint inhibitors, failed to improve patients' outcomes. Even so, they may be still beneficial in a subset of them. New methods, such as using pulsed ultrasound to disrupt the blood-brain barrier, gene therapy, and oncolytic virotherapy, are well tolerated and may be included in the therapeutic armamentarium soon.

Objective To assess whether RAF and MEK inhibitors (RAFi/MEKi) can provide long-term clinical benefit in adult patients with BRAF V600–mutant glial and glioneuronal tumors (GGNTs), we analyzed tumor response and long-term outcome in a retrospective cohort. Methods We performed a retrospective search in the institutional databases of 6 neuro-oncology departments for adult patients with recurrent or disseminated BRAF V600–mutant GGNTs treated with RAFi/MEKi. Results Twenty-eight adults with recurrent or disseminated BRAF V600–mutant gangliogliomas (n = 9), pleomorphic xanthoastrocytomas (n = 9), and diffuse gliomas (n = 10) were included in the study. At the time that treatment with RAFi/MEKi was started, all tumors displayed radiologic features of high-grade neoplasms. Thirteen patients received RAFi as single agents (vemurafenib [n = 11], dabrafenib [n = 2]), and 15 received combinations of RAFi/MEKi (vemurafenib + cobimetinib [n = 5], dabrafenib + trametinib [n = 10]). Eleven patients achieved a partial or complete response (11 of 28, 39%), with a median reduction of −78% in their tumor burden. Responders experienced a median increase of 10 points in their Karnofsky Performance Status (KPS) score and a median progression-free survival of 18 months, which was longer than achieved with first-line treatment (i.e., 7 months, p = 0.047). Responders had better KPS score (p = 0.018) and tended to be younger (p = 0.061) and to be treated earlier (p = 0.099) compared to nonresponders. Five patients were rechallenged with RAFi/MEKi at progression, with novel tumor responses in 2. On univariate and multivariate analyses, response to RAFi/MEKi was an independent predictor of overall survival. Conclusions Our study highlights the long-term clinical benefits of RAFi/MEKi in adult patients with BRAF V600–mutant GGNTs and encourages rechallenge in responders. Classification of Evidence This study provides Class III evidence that, for adult patients with BRAF V600-mutant GGNT, RAFi/MEKi can reduce tumor burden and provide clinical benefit.

Maximum Sustainable Throughput (MST) refers to the amount of data that a Data Stream Processing (DSP) system can ingest while keeping stable performance. It has been acknowledged as an accurate metric to evaluate the performance of stream data processing. Yet, existing operators placements continue to focus on latency and throughput, not MST, as main performance objective when deploying stream data applications in the Edge. In this paper, we argue that MST should be used as an optimization objective when placing operators. This is specially important in the Edge, where network bandwidth and data streams are highly dynamic. We demonstrate that through the design and evaluation of a MST-driven operators placement (based on constraint programming) for stream data applications. Through simulations, we show how existing placement strategies that target overall communications reduction often fail to keep up with the rate of data streams. Importantly, the constraint programming-based operators placement is able to sustain up to 5x increased data ingestion compared to baseline strategies.

BRAF -activating mutations detected in craniopharyngiomas of the papillary subtype, 1 with in-teresting implications for patients with suboptimal tumor control. we that combined treatment with and MEK inhibitors in major clinical benefit in the case of a patient with a BRAF V600E-mutant papillary craniopharyngioma rapidly progressing after surgery. Combined short-course BRAFi/MEKi therapy produced an efficient tumor debulking and allowed the dramatic reduction of the volume treated with local radiotherapy. Interestingly, close imaging follow-up showed an initial cystic recurrence 7 days after BRAFi/MEKi discontinuation, suggesting that some patients may present a BRAFi/MEKi dependent evolution requiring adequate treatment planning. While treatment with BRAFi/MEKi should be considered a potential life-saving strategy in relapsing patients, neoadjuvant approaches should also be discussed in order to reduce the morbidity associated with local treatments and to contribute to functional sparing.

Services offered by cloud computing are convenient to users for reasons such as their ease of use, flexibility, and financial model. Yet data centres used for their execution are known to consume massive amounts of energy. The growing resource utilisation following the cloud success highlights the importance of the reduction of its energy consumption. This paper investigates a way to reduce the footprint of HPC cloud users by varying the size of the virtual resources they request. We analyse the influence of concurrent applications with different resources sizes on the system energy consumption. Simulation results show that resources with larger size are more energy consuming regardless of faster completion of applications. Although smaller-sized resources offer energy savings, it is not always favourable in terms of energy to reduce too much the size. High energy savings depend on the user profiles' distribution.

Zika virus (ZIKV) infection has been associated with neurologic disorders including Guillain-Barré syndrome (GBS). In New Caledonia during the ZIKV outbreak (2014–2015), case-control and retrospective studies have been performed to assess the link between ZIKV and GBS. Among the 15 cases included, 33% had evidence of a recent ZIKV infection compared to only 3.3% in the 30 controls involved. All patients were Melanesian, had facial diplegia and similar neurophysiological pattern consistent with acute inflammatory demyelinating polyneuropathy, and recovered well. Furthermore, during the peak of ZIKV transmission, we observed a number of GBS cases higher than the calculated upper limit, emphasizing the fact that ZIKV is now a major trigger of GBS.

Reducing the energy consumed by datacenters becomes of major importance due to the current climate changes and the increasing success of cloud computing. Studies to optimize the energy consumption of cloud systems exist but do not take into account the end-user. The goal of this paper is to understand and quantify the link between the PaaS parameters a user can configure and the application energy consumption. In this work we summarize the parameters available at the PaaS layer and measure their influence on the energy consumed by RUBiS, a web application benchmark. Different database technologies and programming languages are compared as well as their software versions. Experimentation results show that by themselves the existing PaaS parameters can variate the application energy consumption. Although it shows that different programming languages do not consume the same, we discovered that a wider energy difference exists between database technologies which means higher energy savings is possible when the less consuming technology is used. Thus, users could optimize the energy impact of their applications by carefully configuring on-hand PaaS parameters.

Reducing the massive amount of energy consumed by cloud datacenters becomes of major importance. In the usual approach where resources are consolidated into fewer servers in order to power down the others, it still remains periods of time when servers are not fully utilized. Consequently, it exists unused resources that are not exploited although they could be used to execute applications compatible with the variable availability of these resources. In this work, we propose a cloud system where the Platform-as-a-Service (PaaS) and Infrastructure-as-a-Service (IaaS) layers interact to find execution trade-offs that exploit the unused resources at IaaS level. PaaS users are involved in the energy optimization by proposing to delay their executions and adapt resource sizes in order to fit with the available unused resources. Our evaluation by simulation is based on real data and expresses a realistic large scale cloud scenario. Results show that according to the proportion of energy-aware users, this system is able to reduce the amount of servers by using resources that would have been wasted otherwise. Therefore, our solution allows datacenters to consume less energy than with usual resource managers where all applications start their execution at submission time with their initial resource size.