bluuebunny/crossref_metadata_2025_split huggingface dataset:
P11.50.A Surgical results and long-term outcome in supratentorial intraventricular tumors
Authors: Teske N , Chiquillo M , Skrap B , Blobner J , von Baumgarten L , Kunz M , Tonn J , Thon N , Karschnia P 
Published: September 2022

Abstract

Background
Intraventricular tumors (IVTs) are rare lesions of various entities, which pose a surgical challenge. We aimed to elaborate on surgical approaches and outcomes, postoperative morbidity, and elucidate whether preoperative hydrocephalus necessitates shunting despite surgical resection.

Material and Methods
We retrospectively searched the institutional database for patients with supratentorial intraventricular tumours that were treated in the Department of Neurosurgery of the Ludwig-Maximilians-University Munich, Germany between 2014 and 2022.

Results
We identified 60 patients with supratentorial intraventricular tumors comprising over 10 different tumor entities, most often subependymoma (8/60 patients, 13.4%). Median age at diagnosis was 45.5 ± 3.0 years with 31 male patients (51.6%) and 29 female patients (48.3%). Microsurgical tumor resection was completed in 44 patients (45/60 patients, 75%; gross total resection: 36/45 patients, 80%; subtotal resection: 9/45 patients, 20%). In cases where neurosurgical tumor resection was not feasible, stereotactic biopsy was provided in 15/60 patients (25%), often combined with stereotactic internal shunt implantation (8/60 patients, 13.3%). Mean follow-up was 17 months; median overall survival was not reached. Postoperative persistent hydrocephalus necessitating ventriculoperitoneal shunt placement was rare (4/60 patients, 6.7%). Ventriculocisternostomy was performed in one patient. New postoperative focal neurological deficits - mostly transient - were encountered in 16/60 patients (26.6%) at discharge. Postoperative adverse events rate was 11.7%.

Conclusion
Complete resection of IVT can often be achieved and forms the basis for favourable outcome. Permanent neurological deficits are rare, and hydrocephalus can almost always be alleviated which prevents the need for long-term shunting. If microsurgical resection is not feasible, stereotactic biopsy along with internal shunting represents an effective approach to establish diagnosis and ameliorate symptoms.
P11.52.A Peripheral neuropathies after BRAF and/or MEK inhibitors treatment: a pharmacovigilance study
Authors: Picca A , Birzu C , Berzero G , Sanchez-Pena P , Gaboriau L , Vidil F , Lenglet T , Tafani C , Ricard D , Psimaras D , Bihan K 
Published: September 2022

Abstract

Background
BRAF (BRAFi) and MEK inhibitors (MEKi) demonstrated significant efficacy in the treatment of BRAF-activated tumours, firstly melanoma. Nevertheless, they are not devoid of adverse events. Sparse reports in the literature suggest the potential occurrence of peripheral neuropathies (PN) under BRAFi/MEKi treatment, but their characteristics remain poorly defined. We aimed to characterize the clinical phenotypes of PN occurring under BRAFi/MEKi treatment using a national pharmacovigilance database.

Material and Methods
We queried the French pharmacovigilance database for all cases of PN toxicity attributed to at least one BRAFi or MEKi compound. Only cases with a least symptoms description and nerve conduction studies (NCS) conclusion were included.

Results
Sixteen cases of PN occurred in 15 patients were identified. All patients had underlying melanoma. Two main phenotypes were seen. Six patients (dabrafenib-trametinib, n=3; vemurafenib, n=2; vemurafenib-cobimetinib, n=1) presented a length-dependent axonal polyneuropathy: symptoms were mostly sensory at lower limbs; NCS disclosed an axonal neuropathy; management and outcome were variable. Nine patients (dabrafenib-trametinib, n=5, encorafenib-binimetinib, n=3, and vemurafenib-cobimetinib, n=1) developed a demyelinating polyradiculoneuropathy: symptoms affected the four limbs and included hypoesthesia, weakness, and ataxia; cranial nerves were involved in four; NCS showed predominantly demyelinating features; most patients received intravenous immunoglobulins (n=6) or glucocorticoids (n=5), but the outcome was variable; one patient was rechallenged with a different BRAFi/MEKi with a rapid relapse.

Conclusion
Patients under treatment with BRAFi/MEKi may develop treatment-induced PN. Two main phenotypes are seen: a symmetric, axonal, length-dependent polyneuropathy, and a demyelinating polyradiculoneuropathy.
P11.56.A Shared and personalized decision-making in pre-surgical consultations of brain tumor patients and neurosurgeons
Authors: Bras I J M , Sitskoorn M M , van Vugt I J M , Joosen M C W , Hoogendoorn A P Y , Rutten G J , Gehring K 
Published: September 2022

Abstract

Background
In order to assess whether the oncological benefits outweigh the functional risks of treatment for an individual patient, it is important that physicians involve patients in decision-making and personalize the process. This is especially important for brain tumor patients considering the limited treatment options available. The aim of this study is to evaluate shared decision-making and the personalization of the decision-making process during consultations of brain tumor patients and their neurosurgeons.

Material and Methods
For this observational study we collected 66 audio-recordings of pre-surgical consultations of adult brain tumor patients (glioma, meningioma) and their neurosurgeons. A preliminary analysis based on a shared decision-making template was conducted on 14/66 transcribed audio-recordings to assess in how many consultations the following key elements of shared decision-making were present, namely 1) offering a choice to the patient and emphasizing that the patient’s perspective is important in making the decision, 2) discussing treatment options with benefits and risks and 3) asking about treatment preferences and personal goals. Next, thematic analysis will be performed by two independent researchers until data saturation is reached to gain insight into personalization of the decision-making process as an integral part of shared decision-making.

Results
Preliminary findings show that 1) offering the patient a choice and emphasizing that the perspective of the patient is important in decisions was done in 12/14 consultations; 2) discussing treatment options with benefits and risks was present in every consultation (14/14); and 3) in 12/14 consultations the neurosurgeon asked the patient about his or her treatment preference. However, explicitly asking the patient about personal goals occurred only in 3/14 consultations. By the time of the conference, we expect to have explored the decision-making process more in-depth and will be able to share the themes we have identified related to personalization of the decision-making process.

Conclusion
Key elements of shared decision-making were present in most pre-surgical consultations, except for asking patients about their personal goals. Discussing personal goals that patients have concerning daily life may facilitate personalization of the decision-making process.
P11.58.A Case of a complex neurocutaneous syndrome characterized by extensive peripheral nerve sheath tumors and somatic ERBB2 mutation
Authors: Barden M , Baehring J 
Published: September 2022

Abstract
Schwannomatosis is a rare genetic tumor predisposition syndrome characterized by the presence of multiple non-intradermal schwannomas and the definitive absence of vestibular nerve involvement. Though considered benign, the burden of tumors can cause significant morbidity in the form of motor dysfunction and refractory neuropathic pain. Treatment is focused on mitigating these symptoms, which includes resection of offending tumors when feasible and anti-angiogenesis therapy with bevacizumab. Options for targeted medical therapies are lacking. Schwannomatosis is molecularly distinct from the other neurofibromatoses and by definition lacks constitutional mutations in NF1 and NF2. Instead, constitutional mutations in SMARCB1 or LZTR1 are often the “first hit” in tumorigenesis. Activating mutations in ERBB2 (also designated HER2) have been identified as oncogenic drivers in peripheral nerve sheath tumors in patients who lack these typical constitutional tumor suppressor gene mutations.
Here we report a case of extensive peripheral nerve sheath tumors in the setting of apparent somatic mosaicism of an ERBB2 mutation. A 48-year-old man with history of chronic back pain presented with diffuse enlarging soft tissues masses primarily involving the left neck and occiput. Examination revealed areas of cutaneous heterogeneous hyperpigmentation, decreased muscle bulk and dorsiflexor weakness in the bilateral lower extremities, and steppage gait. Neuroimaging showed extensive T2 hyperintense, mildly enhancing masses within the bilateral thoracic and lumbar spine neuroforamina, intercostal nerves, paraspinal musculature, and lumbosacral plexus. Tissue from two separate tumor sites was morphologically consistent with schwannoma with some features of neurofibroma. Immunohistochemistry revealed partial loss of staining for SMARCB1. Whole exome sequencing (WES) on blood and tumor tissue did not show pathogenic germline or somatic variants for NF1, NF2, SMARCB1, LZTR1, or an array of tumor predisposition syndromes. WES on tumor tissue from both sites however did reveal a somatic ERBB2 variant (p.D769Y), suggesting mosaicism. ERBB2 D769Y has previously been classified as an activating mutation that confers sensitivity to some small molecule receptor tyrosine kinase inhibitors. Patients with ERRB2-mutated peripheral nerve sheath tumors may have broader therapeutic options in the variety of available tyrosine kinase inhibitors studied in other cancers.
P11.60.A Quantitative analysis of the MGMT methylation status of glioblastomas in the light of the 2021 WHO classification
Authors: Häni L , Kopcic M , Branca M , Schütz A , Murek M , Söll N , Raabe A , Hewer E , Schucht P 
Published: September 2022

Abstract

Background
Glioblastomas with methylation of the promotor region of the O(6)-methylguanine-DNA methyltransferase (MGMT) gene exhibit increased sensitivity to alkylating chemotherapy. Quantitative assessment of the MGMT promotor methylation status might provide additional prognostic information. The aim of our study was to determine a quantitative threshold of MGMT methylation for better survival among patients with isocitrate dehydrogenase (IDH) wildtype glioblastomas.

Material and Methods
We included consecutive patients treated at our department between 11/2010 and 08/2018. Inclusion criteria were i) diagnosis of glioblastoma, IDH wildtype according to the 2021 WHO classification of tumors of the central nervous system, ii) availability of a quantitative MGMT promotor methylation analysis, iii) absence of an IDH mutation as determined by immunohistochemistry and/or sequencing, and iii) age ≥ 18 years. The primary endpoint was overall survival. To evaluate a threshold for a benefit from temozolomide (TMZ), a secondary analysis included only tumors exposed to TMZ, which were compared to a historical cohort treated by radiotherapy only with a median survival of 13.0 months.

Results
Between 11/2010 and 08/2018, 321 patients diagnosed with a glioblastoma, IDH wildtype meeting our inclusion criteria were included. Mean age at diagnosis was 64.1 years (± 11.4). Median overall survival was 12.6 months. Kaplan-Meier analysis showed better survival for all groups with ≥ 16% methylation. Similarly, Cox regression analysis confirmed significantly better survival in the groups with 16-30%, 31-60%, and 61-100% methylation. In contrast, survival in the group with 1-15% methylation was similar to that with unmethylated promotor regions. When the percentage of methylation of each patient treated with TMZ was plotted on an ROC curve using survival &gt; 13.0 months as outcome parameter, the Youden index was maximal at ≥ 16% methylation.

Conclusion
Better survival is seen in patients with glioblastomas with ≥ 16% methylation of the MGMT promotor region than with &lt; 16% methylation. Survival with tumors with 1-15% methylation is similar to with unmethylated tumors. Above 16% methylation, we found no additional benefit with increasing methylation.
P11.61.B Capecitabine treatment of CNS metastases from breast cancer: intracranial response and survival
Authors: Luitse M J A , Boles G , Sonke G S , Brandsma D 
Published: September 2022

Abstract

Background
20-30% of breast cancer patients develop brain metastases (BM) and 5% leptomeningeal metastases (LM). Incidence of BM and/or LM is dependent on breast cancer subtype. Treatment of BM consists of local treatment (resection and/or radiotherapy) and if possible systemic therapy. LM can be treated with radiotherapy of the symptomatic location of the nervous system and/or systemic therapy. Capecitabin is effective for both systemic metastases and BM of HER2-positive breast cancer. The effect of capecitabine in the non-HER2-positive breast cancers and in the LM group is largely unknown. The goal of this study is to determine the intracranial response of capecitabine and survival in HM and/or LM of the various breast cancer subtypes.

Material and Methods
breast cancer patients with HM and/or LM treated with capecitabine were selected retrospectively from a breast cancer patient cohort treated at the Netherlands Cancer Institute - Antoni van Leeuwenhoek between 2005 and 2020. Follow-up MRI scans of the brains were performed in all patients. The primary endpoints were intracranial response, intracranial progression-free survival (PFS) and overall survival (OS). Subgroup analyses for breast cancer subtypes and BM and LM patient groups were done.

Results
93 of 381 patients treated for CNS metastases of breast cancer fulfilled the inclusion criteria. Sixty-one patients (66%) had HM only, 13 (14%) had LM only and 19 patients (20%) had both HM and LM. Forty-six percent of patients had HER2-positive breast cancer, 26% had hormone receptor-positive breast cancer and 28% of patients had a triple negative subtype. After three months of capecitabine treatment intracranial response was 53%. Median OS in the patient group with intracranial response was 16.5 months versus 4.5 months in the non-response group. The hazard ratio (HR) for the median OS, corrected for radiotherapy and concurrently administered, other systemic therapy was 0.33 (95% CI: 0.17-0.67). Median intracranial PFS was 7.3 months in the response group versus 1.4 months in the non-response group (p&lt;0.001).The corrected HR for median intracranial PFS 0.13 (95% CI 0.06-0.27). The HER2-positive subtype group showed the longest median OS (22 months) as compared to the other subtypes (OS in hormone-receptor positive and triple negative subtype both 12 months)

Conclusion
Fifty-three percent of breast cancer patients with HM and/or LM treated with capecitabine demonstrate an intracranial response after three months of treatment. HER2+ breast cancer patients with HM and/or LM have a longer survival than patients with hormone receptor-positive or triple negative breast cancer subtypes.
P11.66.A Immune checkpoint inhibitors related peripheral nerve disorders: clinical and electrophysiological particularities
Authors: Birzu C , Farina A , Pegat A , Devic P , Lenglet T , Viala K , Debs R , Fargeot G , Picca A , Le Guennec L , Mongin M , Villette B , Joubert B , Maisonobe T , Psimaras D 
Published: September 2022

Abstract

Background
The immune-checkpoint inhibitors (ICIs) announced a new era in cancer treatment allowing long-term survival in advanced cancers. However, immune related adverse events impose treatment limitations being one of the main challenges when dealing with ICI treated patients. Neurologic toxicities have unique presentations and can progress rapidly, requiring prompt recognition. Among them, ICI-related peripheral nerve disorders are highly heterogeneous, profoundly debilitating, and insufficiently explored.

Material and Methods
We reviewed the clinical and electrodiagnostic features of a retrospective cohort of patients hospitalized in our centre for ICI related neuropathies. We applied the EFNS 2021 electrodiagnostic criteria for neuropathies and we researched the outcome according to the treatment received.

Results
We included 16 patients: 4 men and 12 women, median age 61 years (31-72) treated by anti-PD1 monotherapy (10) or antiCTLA4-antiPD1 combination (6). Median delay from ICIs initiation to neuropathy symptoms was 58,5 days (4 cycles), it seemed lower in combination group (median 33,5 days vs 81,5 days in monotherapy patients p=0,02). Half of patients presented with concurrent non-neurological irAE. CSF was inflammatory in 56% of cases, pleocytosis was seen in 57% of these. Cranial nerve involvement was rare (3/16) the most frequent phenotype was demyelinating polyneuropathy fulfilling EFNS 2021 EMG criteria in 10 cases. The other 6 presented with non-length dependent sensory neuropathy, (3) dysautonomic neuropathy (1) or sensory motor neuropathy with incomplete EFNS 2021 EMG criteria (2). ICI treatment was stopped, and steroids were the first line of treatment for all patients. However, 12/16 patients received additional iv immunoglobulin. Supplementary immunomodulation (cyclophosphamide, tocilizumab) was required in 2 cases. 75% of patients improved within a median of 4.5 months, median decrease in mRS was 2 points. Noteworthy, the rechallenge by antiPD1 monotherapy was proposed in 4 patients with a single neuropathy relapse.

Conclusion
Our series expand the knowledge on the clinical and electrophysiological phenotype of ICI related neuropathies improving their recognition in clinical practice. Moreover, our findings argue for the benefit of adding iv immunoglobulin to steroids as a first line treatment for different phenotypes of ICI related neuropathies.
P11.70.A The yield of screening brain MRI among stage IV non small cell lung cancer patients
Authors: Waizman E , Lavie I , Amiel A , Siegal T , Dudnick E , Yust-Katz S 
Published: September 2022

Abstract

Background
Brain metastases are a common complication of non small cell lung cancer (NSCLC). Approximately 10 percent of newly diagnosed patients with advanced NSCLC have brain metastases. The purpose of this study was to determine whether using magnetic resonance imaging (MRI) for early screening of brain metastases can improve survival.

Material and Methods
A retrospective analysis of newly diagnosed stage IV NSCLC treated at Davidoff Cancer Center, Israel, between the years 2019-2020. Only patients who were neurologically asymptomatic were included in the study. The study population was divided into two groups. Group A included patients who underwent screening MRI within 12 weeks form diagnosis and group B included those who did not undergo screening MRI. Clinical and radiographic data were collected form the medical records.

Results
379 patients were included in the study, of whom 170 underwent screening MRI. Of the patients who underwent screening MRI 54 were diagnosed with brain metastases. On univariate analysis screening MRI was correlated with better survival [group A median survival 24 month, group B median survival 18 month, p=0.003 HR 1.4 CI 1.12-1.75]. On multivariate analysis that included functional status (ECOG 0-2 compared to 3 and above) and age- screening MRI correlated with survival (p=0.04 HR 1.28 CI 1.02-1.6). Subgroup analysis according to molecular subgroup will be presented in the conference.

Conclusion
In this study screening MRI among stage IV NSCLC correlated with better survival even when adjusted to functional status and age.
P11.72.A Glioblastoma in elderly patients. Which is the best treatment option?
Authors: Costa C A , Sousa M , Pires M R , Monteiro J C , Caetano A , Póvoa S , Pêgo A , Sousa G 
Published: September 2022

Abstract

Background
Glioblastoma (GBM) is the most common and aggressive primary malignant brain tumor in adults, and it is associated with a poor prognosis in the elderly. The current standard of care for newly diagnosed GBM is maximal surgical resection, followed by radiotherapy plus concomitant and adjuvant temozolomide (TMZ). In elderly patients with GBM, short-courses of radiotherapy with TMZ are used.

Material and Methods
We performed a single-center retrospective analysis of elderly GBM patients treated from 2013 to 2020. The primary endpoint was to evaluate progression free survival (PFS) and overall survival (OS) according to treatment received (TMZ and standard radiotherapy (60 Gy over a period of 6 weeks) vs TMZ and short-course radiotherapy (40 Gy in 15 fractions)). Secondary endpoints were analysis of population demographics and major toxicities associated to treatment.

Results
Twenty-two patients were identified. The median age was 72 years (range 65- 80), 18 (85.7%) patients were in ECOG-PS 0-1, 12 (57.1%) were males and all patients had undergone partial or complete resection surgery. Eleven (52.4%) patients received TMZ and standard radiotherapy and 10 (47.6%) patients received TMZ and short-course radiotherapy. Three (14.3%) patients had complete remission, 11 (52.4%) patients had partial response, 2 (9.5%) patients presented stable disease and 5 (23.8%) patients had disease progression. Median OS was 9 months (95% CI, 3.6 to 14.4) with TMZ with standard radiotherapy and 8 months (95% CI, 1.8 to 14.2) with TMZ and short-course radiotherapy (p=0.322). Median PFS was 5 months (95% CI, 2.8 to 7.2) with TMZ with standard radiotherapy and 6 months (95% CI, 3.1 to 8.9) with TMZ and short-course radiotherapy (p=0.944). Most common toxicities were hematological, with 5 (23.8%) patients presented thrombocytopenia grade 2 or higher. Five (23.8%) patients presented grade 3/4 toxicities (2 (9.5%) patients presented thrombocytopenia grade 4, 1 (4.8%) patient presented thrombocytopenia grade 3, and 2 (9.5%) patients presented anemia grade 3.

Conclusion
The prognosis of GBM remains poor besides standard therapy. TMZ and short-course radiotherapy should be an option in elderly patients due to its non-inferiority. Elderly patients should undergo a careful geriatric evaluation before starting treatment.