Roger Stupp

• Northwestern University

Background: The blood-brain barrier (BBB) impedes the passage of most circulating drugs into the brain. Low-intensity pulsed ultrasound with microbubbles (LIPU/MB) transiently opens the BBB, improving parenchymal drug penetration. Parenchymal drug retention following short-lived BBB opening is unknown. We investigated the effect of LIPU/MB on the c...

While chimeric antigen receptor (CAR) T-cell therapies present novel therapeutic opportunities, their clinical success has been limited when targeting malignant brain tumors, such as malignant gliomas. Marked antigenic heterogeneity of those tumors underlies their treatment resistance. Ultimately, it is crucial to promote endogenous T cell response...

Sequential multiplex methodologies such as Akoya CODEX, Miltenyi MACSima, Rarecyte Orion, and others require modification of the antibodies by conjugation to an oligo or a specific fluorophore which means the use of off-the-shelf reagents is not possible. Modifications of these antibodies are typically performed via reduction chemistry and thus req...

Advances in molecular biology, genetics, and epigenetics have refined our understanding of metastatic brain cancer and underscored the need for better classification and targeted approaches. The heterogeneity of brain metastases highlights the differences from their primary source of origin and contributes to therapeutic resistance. Before colonisi...

Background: The blood-brain barrier (BBB) impedes the passage of most circulating drugs into the brain. Low-intensity pulsed ultrasound with microbubbles (LIPU/MB) transiently opens the BBB, improving parenchymal drug penetration. Parenchymal drug permanence upon short-lived BBB opening is unknown. We compared the parenchymal permanence of temozolo...

Background Preclinical work and retrospective studies suggest that temozolomide chemotherapy in glioblastoma may be more effective when administered in the morning rather than the evening. Here we examine the effect of timing in a large cohort of patients in 2 contemporaneous randomized clinical trials. Methods We assessed toxicity and survival da...

Seizures are a frequent complication in glioma. Incidence of brain tumor-related epilepsy (BTRE) in high-grade glioma (HGG) is an estimated > 25% and in low-grade glioma (LGG) is approximately 72%. Two first-line antiseizure medications (ASMs) for BTRE include levetiracetam (LEV) and valproic acid (VPA). Use of VPA has decreased because of a broade...

Cerebral endothelial cell (EC) injury and blood-brain barrier (BBB) permeability contribute to neuronal injury in acute neurological disease states. Preclinical experiments have used animal models to study this phenomenon, yet the response of human cerebral ECs to BBB disruption remains unclear. In our Phase 1 clinical trial (NCT04528680), we used...

INTRODUCTION Diffuse midline gliomas, H3 K27-altered (DMG) are rare, grade 4 tumors localized to the diencephalon, brainstem, and cervical spine. DMGs, characterized by a K27M missense mutation in histone H3, often cannot be safely resected and predominantly present with poor outcomes in children. Few prognostic factors for DMGs have been identifie...

BACKGROUND We previously reported on progression-free survival of our randomized phase 3 trial [Lancet Oncol. 2016;17:1521-1532]. Here we report results of long-term follow-up (FU) including overall survival (OS) and molecular subgroup analyses. METHODS 487 patients were randomized between 2005-2012 to either standard radiotherapy (RT, 50.4 Gy/ 28...

Immunotherapies targeting glioma, such as chimeric antigen receptor (CAR) T cell therapies, offer new therapeutic avenues; however, their application has yielded limited success in clinical trials so far. Due to the antigenic heterogeneity of gliomas, targeting a few or several antigens still results in recurrence with “antigen-loss” tumors, indica...

The blood-brain barrier (BBB) impedes the passage of most circulating drugs into the brain. Low-intensity pulsed ultrasound with microbubbles (LIPU/MB) transiently opens the BBB, improving drug delivery to the brain. The implication of this transient BBB opening on parenchymal drug permanence is unknown. We compared the parenchymal levels and perma...

BACKGROUND Yttrium-90 (Y90) microsphere treatment is an FDA-approved endovascular radiotherapy for Hepatocellular Carcinoma; however, extra-hepatic experience is limited. The FRONTIER trial (NCT05303467) is a first-in-human study conducted under an IDE from the FDA evaluating the safety and feasibility of intra-arterial Y90 endovascular radiotherap...

Glioblastoma (GBM) presents as a highly aggressive and malignant brain tumor with limited treatment options. Despite the availability of existing therapies, the invasive characteristics of GBM frequently result in tumor recurrence and poor prognosis. We previously developed a B-cell-based therapy (BVax) that has shown promising results in its abili...

Despite being the leading cause of childhood mortality, pediatric gliomas have been relatively understudied. Repurposing of adult brain tumor immunotherapies in pediatric patients has not been successful, highlighting the need for pediatric-specific immunotherapies. Pilocytic astrocytomas (PA) are the most common pediatric glioma. While surgical re...

The field of immunology has traditionally focused on immune checkpoint modulation of adaptive immune cells. However, many malignancies such as glioblastoma are mostly devoid of T cells and rather are enriched with immunosuppressive myeloid cells of the innate immune system. While some immune checkpoint targets are shared between adaptive and innate...

BACKGROUND Immunotherapies targeting glioma, such as chimeric antigen receptor (CAR) T cell therapies, offer new therapeutic opportunities; however, their application has yielded limited success. Due to the antigenic heterogeneity of gliomas, targeting a few or several antigens may still result in the recurrence with “antigen-loss” tumors, indicati...

BACKGROUND Chronotherapy, an innovative approach to improve survival or limit toxicity through timed administration of treatment, is of increasing in interest in cancer. In glioblastoma, preclinical models show that temozolomide activity depends on the time of the day it has been given. A retrospective study suggests improved outcomes for glioblast...

Glioblastoma (GBM) is a highly aggressive and malignant brain tumor with limited therapeutic options and a poor prognosis. Despite current treatments, the invasive nature of GBM often leads to recurrence. A promising alternative strategy is to harness the potential of the immune system against tumor cells. Our previous data showed that the Bvax (B-...

Despite being the leading cause of cancer-related childhood mortality, pediatric gliomas have been relatively understudied, and the repurposing of immunotherapies has not been successful. Whole-transcriptome sequencing, single-cell sequencing, and sequential multiplex immunofluorescence were used to identify an immunotherapeutic strategy that could...

Background Glioblastoma is a highly aggressive brain cancer that is resistant to conventional immunotherapy strategies. Botensilimab, an Fc-enhanced anti-CTLA-4 antibody (FcE-aCTLA-4), has shown durable activity in “cold” and immunotherapy-refractory cancers. Method We evaluated the efficacy and immune microenvironment phenotype of a mouse analogu...

Radiographic assessment plays a crucial role in the management of patients with central nervous system (CNS) tumors, aiding in treatment planning and evaluation of therapeutic efficacy by quantifying response. Recently, an updated version of the Response Assessment in Neuro-Oncology (RANO) criteria (RANO 2.0) was developed to improve upon prior cri...

STING agonists can reprogram the tumor microenvironment to induce immunological clearance within the central nervous system. Using multiplexed sequential immunofluorescence (SeqIF) and the Ivy Glioblastoma Atlas, STING expression was found in myeloid populations and in the perivascular space. The STING agonist 8803 increased median survival in mult...

Introduction Central Neurocytoma (CN) is a rare, WHO grade 2 brain tumor that predominantly affects young adults. Gross total resection (GTR) is often curative for CNs, but the optimal treatment paradigm including incorporation of RT, following subtotal resection (STR) and for scarcer pediatric cases has yet to be established. Methods Patients bet...

Given the marginal penetration of most drugs across the blood-brain barrier, the efficacy of various agents remains limited for glioblastoma (GBM). Here we employ low-intensity pulsed ultrasound (LIPU) and intravenously administered microbubbles (MB) to open the blood-brain barrier and increase the concentration of liposomal doxorubicin and PD-1 bl...

Background Tumor Treating Fields (TTFields) Therapy is an FDA-approved therapy in the first line and recurrent setting for glioblastoma. Despite Phase 3 evidence showing improved survival with TTFields, it is not uniformly utilized. We aimed to examine patient and clinician views of TTFields and factors shaping utilization of TTFields through a uni...

INTRODUCTION We recently participated in Phase 1/2 clinical trials where patients with recurrent glioblastoma received surgery for resection of the tumor followed by implantation of an ultrasound device (SonoCloud-9, Carthera, Lyon, France) into a window in the skull for subsequent repeated blood-brain barrier (BBB) opening and concomitant delivery...

INTRODUCTION Chordomas are rare tumors that arise from remnants of the notochord. The standard of care for chordoma remains only surgery and radiotherapy. Though checkpoint inhibition therapy shows promise, recent immunotherapy trials failed to reach endpoints. This emphasizes the need to comprehensively understand the tumor and peripheral immune l...

INTRODUCTION Chordomas, a rare type of tumor, originate from residual notochord tissue. These tumors present important challenges due to the limited treatment options. Investigating the intricacies of T-cell composition and function in chordoma immunity holds the potential to advance immunotherapy strategies for these patients. METHODS We generate...

INTRODUCTION Glioblastoma patients exhibit variable clinical responses to anti-PD-1 immunotherapy. Our previous work identified ERK1/2 phosphorylation (p-ERK) in pre-treatment tumor samples as a predictive biomarker of overall survival in two independent cohorts of recurrent glioblastoma patients undergoing adjuvant anti-PD-1 therapy (Arrieta et al...

INTRODUCTION The limited drug penetration across the blood-brain barrier (BBB) represents a challenge for the treatment of glioblastoma patients. A novel drug delivery technology based on low-intensity pulsed ultrasound combined with intravenous microbubbles (LIPU/MB) overcomes this challenge by opening the BBB. In this study, we hypothesize that L...

Gliomas, the most common primary brain tumors, remain largely incurable despite advancements in surgical and adjuvant therapies. While immunotherapies offer promising avenues, their efficacy has been limited by formidable anatomical barriers, such as the blood-brain barrier (BBB), which restricts the migration of immune cells into the brain and imp...

Glioblastoma (GBM) is a highly aggressive tumor of the brain. Current techniques of detection like magnetic resonance imaging and tissue biopsy are inaccurate or highly invasive, requiring alternatives like liquid biopsy. Exosomes are nanosized vesicles that contain cargo, reflective of their cellular origin and have been used for early diagnosis o...

Here, the results of a phase 1/2 single-arm trial (NCT03744026) assessing the safety and efficacy of blood-brain barrier (BBB) disruption with an implantable ultrasound system in recurrent glioblastoma patients receiving carboplatin are reported. A nine-emitter ultrasound implant was placed at the end of tumor resection replacing the bone flap. Aft...

Background A significant unmet need exists for the treatment of glioblastoma, IDH-wildtype (GBM). Preclinical work shows that acetazolamide sensitizes GBM to temozolomide (TMZ) by overcoming TMZ resistance due to BCL-3-dependent upregulation of carbonic anhydrase. Acetazolamide is Food and Drug Administration-approved for the treatment of altitude...

Purpose We recently reported on clinical trials for patients with recurrent glioblastoma where low-intensity pulsed ultrasound and microbubbles (LIPU/MB) improved paclitaxel or carboplatin delivery into the brain. Here, we report variable local tumor control with paclitaxel at the maximal/target dose in our phase I trial (NCT04528680). To address t...

Despite the recent success of immune checkpoint blockade in various cancer types, glioblastoma (GBM) remains resistant to immunotherapy due to its immunosuppressive features and the poor penetration of systemic agents across the blood-brain barrier (BBB). Recent clinical trials demonstrated the unprecedented efficacy of Fc enhanced anti-CTLA-4, an...

The central nervous system, immunologically unique due to specialized lymphatics and anatomical barriers, often conceals brain neoplasm from the peripheral immune system. Low-intensity pulsed ultrasound with microbubbles (LIPU/MB) enables transient opening of the BBB, allowing drug transport and immune cell trafficking into brain tumors. However, i...

INTRODUCTION Central Neurocytoma (CN) is a rare, WHO grade 2 brain tumor that predominantly affects young adults. Gross total resection (GTR) is often curative for CN, but the optimal treatment paradigm following subtotal resection (STR) and or scarcer pediatric cases has yet to be established—including the role of radiation therapy (RT). Herein, w...

We recently participated in phase 1/2 clinical trials where patients with recurrent glioblastoma received surgery for tumor resection followed by implantation of an ultrasound device into a skull window for subsequent repeated blood-brain barrier opening and concomitant delivery of chemotherapy (Sonabend et al., Lancet Oncology). Intraoperative exp...

In a phase I clinical trial for patients with recurrent glioblastoma, we used an implantable ultrasound device for low-intensity pulsed ultrasound and microbubbles (LIPU/MB) to open the blood-brain barrier (BBB). This strategy increased parenchymal drug concentrations by 3.7- to 5.9-fold. Magnetic resonance imaging analysis with gadolinium injectio...

Immune-mediated anti-tumoral responses, elicited by oncolytic viruses and augmented with checkpoint inhibition, may be an effective treatment approach for glioblastoma. Here in this multicenter phase 1/2 study we evaluated the combination of intratumoral delivery of oncolytic virus DNX-2401 followed by intravenous anti-PD-1 antibody pembrolizumab i...

Chordomas are rare tumors that arise from remnants of the notochord. The standard of care for chordoma remains only surgery and radiotherapy. Though checkpoint inhibition therapy shows promise, recent immunotherapy trials failed to reach endpoints. This emphasizes the need to comprehensively understand the tumor and peripheral immune landscape of c...

MGMT promoter methylation predicts favorable temozolomide (TMZ) response in gliomas. Accurate test results depend on adequate tumor cellularity in analyzed samples, which is usually estimated (with sub-optimal accuracy) via light microscopy. We evaluated driver mutation variant allelic frequency (VAF) as a quantitative metric for tumor cellularity...

Non-invasive methods to detect progression of glioblastoma (GBM) are needed to optimize patient management. Circulating blood-based biomarkers for GBM progression are limited by the blood-brain barrier, which restricts leakage of tumor-related elements into circulation. To address this, we investigated circulating GBM-associated exosomes using samp...

Purpose: Evidence suggests that MAPK pathway activation, as measured by ERK1/2 phosphorylation (p-ERK), predicts overall survival (OS) in recurrent glioblastoma patients receiving anti-PD-1 therapy. We aimed to validate these findings in independent cohorts. Experimental design: In a 24-patient clinical trial on recurrent glioblastoma and high-g...

MGMT promoter methylation testing is required for prognosis and predicting temozolomide response in gliomas. Accurate results depend on sufficient tumor cellularity, but histologic estimates of cellularity are subjective. We sought to determine whether driver mutation variant allelic frequency (VAF) could serve as a more objective metric for cellul...

PURPOSE The Response Assessment in Neuro-Oncology (RANO) criteria for high-grade gliomas (RANO-HGG) and low-grade gliomas (RANO-LGG) were developed to improve reliability of response assessment in glioma trials. Over time, some limitations of these criteria were identified, and challenges emerged regarding integrating features of the modified RANO...

BACKGROUND The Response Assessment in Neuro-Oncology (RANO) criteria for high-grade gliomas (RANO-HGG) and low-grade gliomas (RANO-LGG) were developed to improve reliability of response assessment in glioma trials. Over time some limitations of these criteria were identified, and uncertainty emerged regarding integrating features of the modified RA...

BACKGROUND Chordomas, rare indolent neoplasms, mainly occur in the skull base or lower spine. Therapies, including surgery and radiotherapy, often fail to impede local recurrence. Though checkpoint inhibition therapy shows promise, recent immunotherapy trials failed to reach endpoints. Here, we aim to investigate the immunological landscape of chor...

The Response Assessment in Neuro-Oncology (RANO) criteria for high-grade gliomas (RANO-HGG) and low-grade gliomas (RANO-LGG) were developed to improve the reliability of response assessment in glioma trials. Over time some limitations of these criteria were identified, and uncertainty emerged regarding integrating features of the modified RANO (mRA...

BACKGROUND: Glioblastoma (GBM) is the most aggressive primary brain tumor that virtually always recurs with no established standard therapy at recurrence. Median survival after recurrence is 7-12 months. Selective internal radiation therapy (SIRT) with Yttrium-90 (Y90) glass microspheres (TheraSphere™, Boston Scientific, Marlborough, MA) is an FDA...

Background: The inclusion of immune checkpoint inhibitors (ICIs) in the treatment of operable stage III non-small-cell lung cancer is becoming a new standard. Programmed death-ligand 1 (PD-L1) protein expression on tumor cells has emerged as the most important biomarker for sensitivity to ICIs targeting the programmed cell death protein 1 (PD-1)-P...

CNS metastases are often terminal for cancer patients and occur at an approximately 10-fold higher rate than primary CNS tumors. The incidence of these tumors is approximately 70,000–400,000 cases annually in the US. Advances that have occurred over the past two decades have led to more personalized treatment approaches. Newer surgical and radiatio...

3008 Background: PRMT5 catalyzes symmetric arginine dimethylation of protein substrates and is involved in histone modification, transcription, and spliceosome assembly. PRT811 is a potent, selective, brain-penetrant PRMT5 inhibitor being studied in a phase 1, multicenter, open-label, dose-escalation and -expansion study in pts with advanced solid...

Immune-mediated anti-tumoral responses, elicited by oncolytic viruses and augmented with checkpoint inhibition, may be an effective treatment approach for glioblastoma. Here in this multicenter phase 1/2 study we evaluated the combination of intratumoral delivery of oncolytic virus DNX-2401 followed by intravenous anti-PD-1 antibody pembrolizumab i...

Background: Low-intensity pulsed ultrasound with concomitant administration of intravenous microbubbles (LIPU-MB) can be used to open the blood-brain barrier. We aimed to assess the safety and pharmacokinetics of LIPU-MB to enhance the delivery of albumin-bound paclitaxel to the peritumoural brain of patients with recurrent glioblastoma. Methods:...

INTRODUCTION The blood-brain barrier (BBB) is a major impediment to pharmacological treatment of gliomas, as these infiltrate the brain. Low-intensity pulsed ultrasound with concomitant intravenous microbubbles (LIPU/MB), opens the BBB. METHODS To perform LIPU/MB-based BBB opening prior to ABX infusions, we used a novel 6 x 6 cm device with 9 ultr...

Purpose: We retrospectively evaluated the association between postoperative pre-radiotherapy tumour burden and overall survival (OS) adjusted for the prognostic value of O6-methylguanine DNA methyltransferase (MGMT) promoter methylation in patients with newly diagnosed glioblastoma treated with radio-/chemotherapy with temozolomide. Materials and...

Immune checkpoint blockade (ICB) has revolutionized modern cancer therapy, arousing great interest in the neuro-oncology community. While several reports show that subsets of patients with glioma exhibit durable responses to immunotherapy, the efficacy of this treatment has not been observed for unselected patient populations, preventing its broad...

Background Gliomas with IDH1/2 mutations without 1p19q codeletion have been identified as the distinct diagnostic entity of IDH mutant astrocytoma (IDHmut astrocytoma). Homozygous deletion of Cyclin-dependent kinase 4 inhibitor A/B (CDKN2A/B) has recently been incorporated in the grading of these tumors. The question of whether histologic parameter...

OBJECTIVE Surgical treatment of locally advanced non-small cell lung cancer including single or multilevel N2 remains a matter of debate. Several trials demonstrate that selected patients benefit from surgery if R0 resection is achieved. We aimed to assess resectability and outcome of patients with locally advanced clinical T3/T4 (American Joint Co...

Depressive symptoms are common among patients with glioblastoma, but patients are often not treated with antidepressants. There is only limited evidence on the association of antidepressant drug use with survival in glioblastoma. We performed a pooled analysis of patients treated within the CENTRIC, CORE, AVAglio and ACT‐IV trials to explore the re...

INTRODUCTION Anti-PD-1 immunotherapy induces clinical responses in a subset of glioblastoma (GBM) patients. We previously reported that ERK1/2 phosphorylation (p-ERK) in pre-treatment tumor samples is predictive of overall survival (OS) following adjuvant anti-PD-1 therapy in two independent cohorts of recurrent GBM patients. METHODS Following the...

Glioblastoma (GBM) continues to retain its dismal prognosis despite numerous new therapeutic modalities to target various aspects of the tumor. There is a need to identify new, and even personalized, targetable GBM specific antigens. Our B-cell-based vaccine (BVax) is generated by isolating immune experienced B cells, identified by 4-1BBL, from mur...

BACKGROUND Advancements in bioengineering have allowed bispecific Abs to develop with therapeutic applications in immuno-oncology. Here we describe a fully humanized bispecific t cell engager (BiTE) that binds the GBM-associated antigen interleukin 13 receptor alpha 2 (IL13Rα2) and the T Cell receptor CD3 epsilon (CD3ε) to elicit an anti-tumor immu...

The use of low-intensity pulsed ultrasound with concomitant injection of microbubbles (LIPU/MB) achieves local and reversible opening the blood-brain barrier (BBB), enhancing the delivery of systemically administered drugs to the brain parenchyma. Electron microscopic studies conducted in animals proposed that LIPU/MB enhances paracellular diffusio...

Low intensity pulsed ultrasound in combination with microbubbles can be used to temporarily disrupt the blood-brain barrier (BBB). A phase 1/2 clinical study (NCT03744026) was initiated to demonstrate the safety and efficacy of BBB disruption using an implantable ultrasound system (SonoCloud-9) in patients with recurrent glioblastoma receiving carb...

BACKGROUND The blood-brain barrier (BBB) is a major impediment to pharmacological treatment of gliomas. Low-intensity pulsed ultrasound with concomitant administration of intravenous microbubbles (LIPU/MB), temporarily opens the BBB. Here we investigate the pharmacokinetics and safety of this approach of repeated delivery of albumin-bound paclitaxe...

INTRODUCTION Given the limited drug penetration across the blood-brain barrier (BBB), the therapeutic potential of new and existing therapies has not been fully exploited for the benefit of glioblastoma (GBM) patients. METHODS Here we employed a novel drug delivery technology based on low-intensity pulsed ultrasound combined with intravenous micro...

Exposing cancer cells to alternating electric fields of frequency 100-300 kHz and strength 1-4 V/cm has been shown to significantly reduce cancer growth in cell culture and in human patients. This form of anti-cancer therapy is more commonly referred to as tumor treating fields (TTFields), a novel treatment modality that has been approved by the U....

Background Low intensity pulsed ultrasound (LIPU) in combination with microbubbles is a promising approach for brain drug delivery. A phase 1/2 clinical study (NCT03744026) was initiated to demonstrate the safety and efficacy of blood-brain barrier (BBB) disruption over a large volume using an implantable ultrasound system (SonoCloud-9) in patients...

Background Levetiracetam (LEV) is one of the most frequently used antiepileptic drugs (AED) for brain tumor patients with seizures. We hypothesized that toxicity of LEV and temozolomide-based chemoradiotherapy may overlap. Patients and Methods In a retrospective analysis of individual patient data using a pooled cohort of patients with newly diagn...

Background Levetiracetam (LEV) is one of the most frequently used antiepileptic drugs (AED) for brain tumor patients with seizures. We hypothesized that toxicity of LEV and temozolomide-based chemoradiotherapy may overlap. Methods Using a pooled cohort of patients with newly diagnosed glioblastoma included in clinical trials prior to chemoradiothe...

2055 Background: Myelosuppression is the major toxicity encountered during temozolomide chemoradiotherapy for newly diagnosed glioblastoma. Methods: We assessed the association of myelosuppression (neutropenia, thrombocytopenia, anemia, lymphopenia) during temozolomide chemoradiotherapy alone or in combination with experimental agents with progress...

2016 Background: The blood-brain barrier (BBB) is a major impediment to pharmacological treatment of gliomas, a diffuse tumor infiltrating the peri-tumoral normal brain. Low-intensity pulsed ultrasound directed at the brain with concomitant administration of intravenous microbubbles (LIPU/MB), temporarily opens the BBB. This technique was previousl...

This abstract is being presented as a short talk in the scientific program. A full abstract is available in the Proffered Abstracts section (PR011) of the Conference Proceedings. Citation Format: Atique U. Ahmed, Jack M. Shireman, Fatemeh Atash, Gina Lee, Eunus S. Ali, Miranda R. Saathoff, Cheol H. Park, Sol Savchuk, Shivani Baisiwala, Jason Miska,...

Glioblastoma is an incredibly aggressive primary brain tumor that is universally lethal due to 100% recurrence. Recent research has pointed to the existence of a population of cells that possess stem cell-like characteristics that are resistant to conventional therapy and can initiate recurrence. Our laboratory, along with others, has demonstrated...

Purpose: Paclitaxel (PTX) is one the most potent and commonly used chemotherapies for breast and pancreatic cancer. Several ongoing clinical trials are investigating means of enhancing delivery of PTX across the blood-brain barrier for glioblastomas (GBMs). Despite the widespread use of PTX for breast cancer, and the initiative to repurpose this d...

Background Maintenance of functioning and wellbeing during the progression-free survival (PFS) period is important for glioma patients. This study aimed to determine whether health-related quality of life (HRQoL) can be maintained during progression-free time, and factors associated with HRQoL deterioration in this period. Methods We included long...

Background Chemoradiotherapy with durvalumab consolidation has yielded excellent results in stage III non-small-cell lung cancer (NSCLC). Therefore, it is essential to identify patients who might benefit from a surgical approach. Material and methods Data from 437 patients with operable stage III NSCLC enrolled in four consecutive Swiss Group for...

Objective Surgical treatment of locally advanced NSCLC including single or multilevel-N2 remains a matter of debate. Several trials demonstrate that selected patients benefit from surgery, if R0 resection is achieved. We aimed to assess resectability and outcome of patients with locally advanced clinical T3/T4 (AJCC 8th-edition) tumors after induct...

Elderly patients represent a growing proportion of individuals with glioblastoma, who however, are often excluded from clinical trials owing to poor expected prognosis. We aimed at identifying age-related molecular differences that would justify and guide distinct treatment decisions in elderly glioblastoma patients. The combined DNA methylome (450...

Background: Myelosuppression is the major toxicity encountered during temozolomide chemoradiotherapy for newly diagnosed glioblastoma. Methods: We assessed the association of myelosuppression (neutropenia, thrombocytopenia, anemia, lymphopenia) during temozolomide chemoradiotherapy alone or in combination with experimental agents with progressio...

Elderly patients represent a growing proportion of individuals with glioblastoma, who however, are often excluded from clinical trials owing to poor expected prognosis. Little is known about molecular features that would justify different treatment modalities, not related to frailty and co-morbidities. We investigated the DNA methylome (450k) for a...

Leptomeningeal metastases (LM) constitute an involvement of cancer which is associated with marked morbidity and mortality. The contemporary diagnostic and therapeutic management of LM from solid tumors is reviewed. Therapeutic modalities including systemic therapies, cerebrospinal fluid (CSF)-directed therapies, and radiation therapy are discussed...

Only a subset of recurrent glioblastoma (rGBM) responds to anti-PD-1 immunotherapy. Previously, we reported enrichment of BRAF/PTPN11 mutations in 30% of rGBM that responded to PD-1 blockade. Given that BRAF and PTPN11 promote MAPK/ERK signaling, we investigated whether activation of this pathway is associated with response to PD-1 inhibitors in rG...

Background Tumor-treating fields (TTFields) is an antimitotic treatment modality that interferes with glioblastoma cell division and organelle assembly by delivering low-intensity alternating electric fields to the tumor. A previous analysis from the pivotal EF-14 trial demonstrated a clear correlation between TTFields dose-density at the tumor bed...

The use of ultrasound (US) in conjunction with microbubbles (MB) to transiently open the blood-brain barrier (BBB) has been used to increase drug delivery to the brain. Recently, US- mediated BBB opening has been demonstrated to increase the release of biomarkers such as DNA, RNA, and proteins from the central nervous system (CNS) compartment into...