bluuebunny/crossref_metadata_2025_split huggingface dataset:
P11.30.A Stereotactic Radiosurgery (SRS) for brain metastases in breast cancer: An evaluation of outcomes at a UK tertiary centre
Authors: Abdul Haris P , Brazil L , Blythe K , Chia K , Hassan S , Loganathan T , Smith D , Swampillai A , Al-Salihi O 
Published: September 2022

Abstract

Background
Brain metastases (BM) occur in approximately 10-30% of patients with breast cancer (BC). Patients with advanced breast cancer are living longer, and the incidence of BM are increasing. Stereotactic Radiosurgery (SRS) has emerged as a strategy to treat BM. We evaluated the outcomes and potential prognostic factors of patients with BM treated with SRS.

Material and Methods
Retrospective review of patients treated with linac-based SRS for BM from BC in a single tertiary centre between August 2017-September 2021. Overall survival (OS), intracranial progression-free survival (IPFS), and prognostic factors were evaluated using Kaplan-Meier analysis, log-rank test, and Cox proportional-hazards model.

Results
76 patients were included in the analysis. Out of these, 56 had first-line local treatment with SRS, either as primary (n=34) or adjuvant to surgery (n=22). Median age was 58 years old (range 37-86), and 88% had PS 0/1. One-year survival rate was 56%.
Median OS and IPFS from SRS was 16 months (95% CI 8-24) and 7 months (95% CI 2-12), respectively. However, there were significant differences in OS (p&lt;0.001) and IPFS (p=0.001) based on molecular subtypes. Patients with triple-negative breast cancer (TNBC) (n=14) had median OS of 7 months (95% CI 2-12), ER+/HER2- (n=22) median OS of 22 months, ER-/HER2+ (n=8) median OS of 4 months (95% CI 0-9), and ER+/HER2+ (n=11) median OS of 36 months. Similar trend was seen with IPFS.
Patients with progressive extracranial disease compared to stable disease had shorter median OS (4 months vs 23 months, HR 2.4, p=0.01) and median IPFS (4 months vs 13 months, HR 2, p=0.03). Age ≥65 years was associated with shorter median OS (4 vs 23 months, HR 2.3, p=0.02). Patients with ≥4 brain metastases had shorter IPFS (4 months vs 11 months, HR 2.4, p=0.012), but no significant difference in OS. Volume of metastases did not affect outcome in this series.
30% of patients progressed intracranially after first-line SRS. 94 % had out-of-field recurrences, and 6% in-field recurrences. 59% had further SRS, 12 % WBRT, 6% surgery, and 23% had no further local treatment.
26 patients had second-line local treatment with SRS after first-line SRS (n=9), WBRT (n=9), or surgery +/- WBRT (n=8). There were no significant differences in outcome based on the modality of first-line local treatment.

Conclusion
SRS is an effective treatment for BM from BC. There were significant differences in survival based on age, molecular subtypes, and extracranial disease status.
P11.31.B Pseudotumor Cerebri - a rare paraneoplastic manifestation
Authors: Ivan R , Nistor L C , Lipan C G , Mezei R M , Sirbu C A 
Published: September 2022

Abstract

Background
Pseudotumor Cerebri (PC) is defined by an elevated intracranial pressure of unidentified cause, associated with normal cerebrospinal fluid (CSF) composition and no cause for hypertension on the neuroimaging evaluations. The symptoms described in association are headache, papilledema, changes in vision, and sometimes tinnitus. Its pathophysiology is far from being elucidated and the mechanisms proposed are multiple. There are some cases described in the literature in which PC is the first manifestation of a systemic neoplasm, most probably due to an abnormal response of the immune system to cancerous growth. We aim to emphasize a possible connection between adenocarcinoma of the lung and PC as the first paraneoplastic manifestation.

Material and Methods
We present the case of a 59-year-old patient, female, non-obese, who presented to the hospital for severe headache, blurred vision, tinnitus, and paresthesia on both her upper limbs. On the first evaluation, the usual blood tests showed an increased creatinine level, and the subsequent abdominal echography and CT scan revealed bilateral ureter hydronephrosis, without an obvious obstacle, for which nephrostomies were implanted. On the ophthalmological evaluation bilateral papillary edema was described, although the cerebral CT with angiography and MRI showed no pathological modifications. A lumbar puncture with manometry was performed, that showed a CSF pressure of approximately 500 mmH2O.

Results
Following the clinical, imagistic, and biological manifestations, the diagnosis of PC was established. The decision to start the corticotherapy was made, followed by the addition of acetazolamide. Although the treatment tented was not efficient, the neurosurgery team decided that she is not a suitable candidate for a CSF shunting procedure and the ophthalmologist advised against an optic nerve sheath fenestration. The evolution was unfavorable, with the persistence of the symptoms. She underwent extensive investigations, the second cerebral MRI showing a slight dilation of the ventricles. On the thoracic-abdominal-pelvic CT, a pulmonary nodule with a malignant aspect was described, the histopathological results pleading for adenocarcinoma. The decision to excise the lesion was made, but after the surgery, the patient developed a cardiorespiratory arrest, without response to resuscitation.

Conclusion
Although there is scarce evidence of PC as a paraneoplastic syndrome, the evolution and investigations results support the possibility of a causal relationship. This is, to our knowledge, the second case of adenocarcinoma of the lung that primarily presents with PC. Further studies must be conducted to understand the underlying pathophysiology of this condition and to develop new treatment possibilities.
P11.32.A EGFR expression and non-methylated MGMT predict distant recurrence in glioblastoma patients treated with standard therapy
Authors: Urup T , Trip A K , Chiranth S B , Christensen I J , Grunnet K , Møller S , Hasselbalch B , Muhic A , Lassen U , Poulsen H S 
Published: September 2022

Abstract

Background
Infiltrative growth within the central nervous system is hallmark of glioblastoma (GBM) at time of diagnosis. Targeting infiltrative glioma cells by adding chemotherapy to local treatment (surgical resection and radiotherapy) has led to improved tumor control and survival. Still, infiltrative growth is a major factor in therapeutic failure and tumor recurrence is almost inevitable. Herein, we hypothesize that distant recurrence represents a more migratory phenotype and that biomarkers associated with distant recurrence can be used to personalize the treatment. The aim of this study was to identify clinical and molecular factors associated with distance recurrence in glioblastoma patients treated with standard therapy.

Material and Methods
A prospective cohort of consecutive, non-selected GBM patients administered standard therapy as primary treatment between 2005-2020 at Rigshospitalet, Copenhagen, Denmark. Distant recurrence was defined as a new contrast-enhancing tumor lesion outside the radiation field (&gt; 2 cm from the gross tumor volume). Clinical and molecular factors were screened for association with time to distant recurrence (p &lt; 0.30) using univariate analysis. The final model was generated employing multivariate Cox regression analysis to model the association with time to distant recurrence. It was chosen to maintain known prognostic factors in the model and subsequently add significantly associated factors (p &lt; 0.05). Competing risk adjusted analysis were performed with death as a competing risk.

Results
A total of 897 patients were included and at a median follow-up time of 73 (range: 12-198) months, 733 patients were evaluable for recurrence pattern. Out of 733 patients, 146 patients (20%) had distant recurrence. Median time to tumor progression was 7.0 months for patients with a local recurrence and 8.0 months for those with a distant recurrence (p=0.31). The following prognostic factors were not associated with distant recurrence by multivariate analysis: Corticosteroid use (p=0.84), age (p=0.20), multifocal disease (p=0.81), ECOG performance status (p=0.99) and degree of tumor resection (p=0.20). In multivariate analysis, factors independently associated with a higher likelihood of distant recurrence were: Non-methylated promoter of the MGMT gene (HR=1.93; 95% CI: 1.27-2.95; p=0.002) and positive expression of Epidermal Growth Factor Receptor (EGFR) by immunohistochemistry (HR=3.70; 95% CI: 1.61-8.33; p=0.002).

Conclusion
Non-methylated MGMT and positive expression of EGFR were independently associated with a higher likelihood of distant recurrence in GBM patients treated with standard-of-care. These factors, if validated, can be used for risk stratification and to enrich clinical treatment protocols aiming at improved local or distant tumor control.
P11.34.A Pseudoprogression in cases of brain metastases and its neurooncological pitfalls under PD-1 inhibitor therapy in the era of personalized medicine
Authors: Schulz T , Cattaneo A , Löhr M , Dufner V , Monoranu C , Keßler A 
Published: September 2022

Abstract

Background
Immunotherapy plays an increasing role in combating malignant cancers. Recently, there has been a noticeable uptick of pseudoprogression mimicking true tumor growth or even intracranial abscess. PD-1 inhibitors especially have come under scrutiny for imitating progressive diseases. Here, we summarize our departmental findings to this regard.

Material and Methods
We analyzed the clinical, intraoperative and neuropathological findings as well as perioperative radiological imaging in four cases.

Results
Four patients (three males and one female, ranged 52-74 years) underwent resection for brain metastases and were subsequently treated with radiotherapy and with PD-1 inhibitors. Within one-year post-surgery, cranial MRI-imaging showed space-occupying, contrast enhanced lesions in all four patients. In two cases FET-PETs were performed pre-operatively. They showed a significant increase in aminoacid uptake. In two cases, 5-aminolevulineacid (5-ALA) was applied pre-operatively. In one case, there was considerable 5-ALA uptake. The fourth patient presented radiological signs of an abscess and underwent emergency surgery. The neuropathological workup of all tissues in question depicted highly increased activity of lymphocytes and microglia, accompanied by necrosis. All cases were classified as pseudoprogression, which, on top, had developed supramarginally in previously healthy tissue.

Conclusion
Neurooncologists face crescent challenges in the increasing cases of pseudoprogression under/after immunotherapy. Radiological imaging doesn’t seem to be able to clearly differentiate between true and pseudoprogression. Even FET-PETs, in general a valid diagnostic tool, seem to be fooled by checkpoint inhibitors. Furthermore, pseudoprogressive tissue after PD-1 inhibitor therapy might mimic tumor tissue intra-operatively by increased 5-ALA uptake. All these characteristics increase the risk of overly aggressive resection of the suspected cancerous or infectious, but in the end pseudo-progressive tissue. Brain edema and clinical symptoms spurred by pseudoprogression may be an indication for surgery, but the risk of performing possibly unnecessary surgery based on radiological findings fooled by PD-1 inhibitors should be taken into consideration. At this point, there does not seem to be a foolproof diagnostic method to differentiate pseudo- from true progression. And there is the possibility that the pseudoprogression is happening in tissue adjacent to the previously resected lesion. Neurooncologists need to acknowledge that pseudoprogression under/after immunotherapy will become only more prevalent in the future and take this message to their patients.
P11.38.A Case reports on aggressive Pilocytic astrocytoma in TYA and adults: patient tailored approach or standard of care?
Authors: Gupta S , Brazil L , Swampillai A , Al-Salihi O 
Published: September 2022

Abstract

Background
Pilocytic astrocytoma (piloA) is a low grade brain tumour and most of the literature is based on paediatric patients with limited data on adults. Surgical resection followed by adjuvant treatment for recurrent lesions is standard of care. While previous literature was mainly based on historical classification, molecular analysis of tumour is adding to the subgroup classification.

Material and Methods
We are reporting 3 cases of adult piloA treated at our institute.

Results: Case1
31y female with headaches and visual problems was diagnosed with optic nerve glioma, biopsy confirmed piloA, and was treated with conventional radiotherapy 50Gy/30fr. A month later developed CSF dissemination requiring 10xTemozolamide. Two years later, developed L5 and S2 deposits which were resected and confirmed piloA. 5 years later there was progression of primary disease treated with 12xTemozolamide and a year later developed further progression and hydrocephalus. She received 1xPCV and succumbed to disease at the age of 42. Case 2: 29y female with severe dizziness on moving head, worsening headaches, word finding difficulty, and positive family history of anaplastic astrocytoma, was diagnosed with Tectal plate lesion. Surgical debulking was performed and pathology showed piloA with Methylated MGMT promoter, IDH wild-type, H3K27M negative, and no BRAF fusion. 3 years later developed recurrence which was treated with chemotherapy (5xPCV: 6th omitted due to recurrent infections) as patient was reluctant for radiotherapy. Follow up scans 6 months post chemotherapy remain stable. Case 3: 24y female with background of 2 haemorrhagic strokes, left spastic hemi-paralysis and left hemianopia, and negative family history, had a biopsy performed for Right Mesotemopral Cavenous Angioma. Pathology showed low grade neoplasm favouring Ganglioglioma with CD34 and IDH1 negative, ATRX retained, KI-67 focal index 5%, and no BRAF fusion or mutation. Surveillance imaging showed progressively increasing suprasellar mass and right temporal region enhancement which was surgically debulked at the age of 27. Repeat pathology examination favoured piloA considering the radiological progression. Methylation array failed but immunohistochemistry showed tumour cells positive with synaptophysin, ATRX and trimethylated H3K27 retained, H3K27M, NeuN, H3G34R and CD34 negative, p53 negative, and Ki-67 3-4%. Repeat imaging 10 months later showed further progressive suprasellar tumour and enhancing lesion in the right temporal area accompanied by rapid loss of right side vision. We have planned for radical radiotherapy 54Gy/30fr with IMRT.

Conclusion
There is a gap in management of piloA in adults with treatment extrapolated from paediatrics and does require further research. We want to approach other centres to establish consensus on treating such cases.
P11.44.A The impact of heme biosynthesis regulation on glioma aggressiveness: correlations with most recent diagnostic molecular markers
Authors: Mischkulnig M , Kiesel B , Rötzer-Pejrimovsky T , Borkovec M , Lang A , Millesi M , Wadiura L I , Hervey-Jumper S , Penninger J M , Berger M S , Widhalm G , Erhart F 
Published: September 2022

Abstract

Background
The prognosis of patients with diffusely infiltrating gliomas is dismal but varies greatly between individuals. While characterization of gliomas was primarily relied on typical histopathological features, specific molecular markers increasingly gained importance and play a key role in the recently published 5th edition of the World Health Organization (WHO) classification. Heme biosynthesis represents a crucial pathway due to its key role in oxygen transport, energy production or drug metabolism. Recently, we described a “heme biosynthesis mRNA expression signature” that correlates with histopathological glioma grades and patient survival. The aim of the current study was to correlate the heme biosynthesis mRNA expression signature with the most recent diagnostic molecular markers for glioma stratification.

Material and Methods
In this study, patient data were derived from the “The Cancer Genome Atlas” (TCGA) lower-grade glioma and glioblastoma cohorts. We identified diffusely infiltrating gliomas correlating molecular tumor diagnosis according to the most recent WHO classification with heme biosynthesis mRNA expression. The following molecular markers were analyzed: EGFR amplification, TERT promoter mutation, CDKN2A/B homozygous loss, concurrent chromosome 7 gain/10 loss, MGMT methylation, IDH mutation, ATRX loss, p53 mutation and 1p19q co-deletion. Subsequently, we calculated the heme biosynthesis mRNA expression signature and correlated this signature with distinct molecular glioma markers as well as the resulting molecular subgroups.

Results
A total of 649 patients with available data on up-to-date molecular markers and heme biosynthesis mRNA expression were included. According to analysis of individual molecular markers, we found a significantly higher heme biosynthesis mRNA expression signature in gliomas with IDH wildtype (p&lt;0.0005), without 1p19q co-deletion (p&lt;0.0005), with homozygous CDKN2A/B loss (p&lt;0.0005) and with EGFR amplification (p=0.001). Furthermore, we observed that the heme biosynthesis mRNA expression signature increased with the aggressiveness of the molecular subgroups (p&lt;0.0005), being lowest in WHO grade 2 oligodendrogliomas and highest in WHO grade 4 glioblastomas.

Conclusion
Our data demonstrate a significant correlation between diagnostic molecular markers and heme biosynthesis regulation in diffusely infiltrating gliomas. Consequently, heme biosynthesis expression is a promising biomarker for glioma aggressiveness and might constitute a potential target for novel therapeutic approaches.
P11.45.B Improved overall survival following Stereotactic Radiosurgery for brain metastases - a single institution experience
Authors: May C , Forshaw M , Wong H , Brass R , Corns A , Shenoy A , Mehta S 
Published: September 2022

Abstract

Background
Brain metastases are increasingly common due to longer survival associated with advancements in treatment. Approximately 40% of cancer patients are diagnosed with brain metastases at some point during their disease. Stereotactic radiosurgery (SRS) avoids the neuro-cognitive toxicity associated with whole brain radiotherapy and has been increasingly offered as a treatment alternative for brain metastases. Combined with developments in systemic treatments, this approach has resulted in improved overall survival (OS). This study reviewed patients treated with single fraction SRS at our institution with a primary endpoint of overall survival.

Material and Methods
A retrospective review determined overall survival for 237 patients who received single fraction SRS for 451 brain metastases from solid tumours between 1st January 2017 and 31st December 2021. Primary tumour sites were classified as breast, kidney, colorectal, melanoma, lung or other. SPSS v.27 was used for Kaplan Meier OS determination. The median follow up was 10.3 months. Cox regression analysis assessed the association between Gross Tumour Volume (GTV) and OS.

Results
In this patient cohort, 60% (N=142) were female and 40% (N=95) were male, with a median age of 63 [32-85]. 63.7% (N = 151) had a solitary metastasis. Patients received a single fraction of 15, 17.5 or 20 Gy (prescribed to 80% isodose) dependent on the planning target volume (PTV) size and whether it was initial treatment or re-treatment. 71% of all patients were alive at 6 months with median OS of 12.0 months [10.6-13.4]. Primary tumour site significantly affected OS (Log rank, Chi squared 15.656, p0.008) with breast cancer patients (N=58) surviving longest with a median OS 16.0 months [13.6-18.4] followed by melanoma median OS 15.0 months [7.6-22.4], kidney cancer patients (N = 24) median OS 12.0 months [8.3-15.7] and lung patients (N=87) median OS 10.0 months [8.9-11.3]. The lowest median OS was for colorectal patients at 7.0 months [1.4-12.6]. However, considering the small sample size, N = 15, more data is needed to confirm the significance. The larger the GTV volume the lower the survival time (Chi squared 8.692, p 0.003).

Conclusion
71% of patients had an OS of 6.0 months or more with a median of 12.0 months. As expected, primary tumour site has a significant impact on OS, with breast cancer patients living longest. In addition, increasing GTV size is associated with significantly worse survival. Given the improved survival for these patients, the avoidance of neuro cognitive decline remains of paramount importance and outcomes for these patients need to be reported in future work.
P11.49.B MOG antibody positive paraneoplastic brain stem encephalitis associated with cervical cancer: a rare case report
Authors: Bieler L , Hecker C , Machegger L , Wolfrum-Ristau P , Trinka E , Kleindienst W 
Published: September 2022

Abstract

Background
Paraneoplastic neurological syndromes are a rare complication of malignant tumors. Myelin oligodendrocyte glycoprotein (MOG) is an important marker on the surface of oligodendrocytes and is associated with many demyelinating diseases. There are only few reports of MOG antibody positive paraneoplastic syndromes. Here we present the first case of MOG-antibody positive brain stem encephalitis associated with cervical cancer.
Material and Methods: Case report.

Results
A 58-year-old female presented with headache, fever and acute cerebellar signs. 13 months earlier she was diagnosed with cervical cancer and ovarian metastases. Adnexectomy was performed and she received adjuvant chemo- and radiotherapy. At admission cerebrospinal fluid (CSF) analysis showed pleocytosis (90 cells/µl) with a mixed cell profile but no malignant cells could be detected. Protein and lactate were highly elevated. The patient was treated with aciclovir and ceftriaxone until serology and liquor PCR showed no evidence of systemic or cerebral infections. Initial magnetic resonance imaging (MRI) of the brain was unremarkable. The patient was symptomatically treated. CSF two weeks later showed 53 cells/µl, protein and lactate almost normal. Contrary to the mild improvement of CSF parameters, cerebellar symptoms worsened, and the patient complained about impaired vision and diplopia. MRI revealed gadolinium enhancing lesions of the left mesencephalon and the right N. opticus. Visual evoked potentials confirmed a demyelinating lesion of the right N. opticus. We then assumed paraneoplastic brain stem encephalitis and the patient received high dose methylprednisolone and immunoglobulins. Ultimately, lab results came back positive for anti-MOG-antibodies, while paraneoplastic panels were negative. At follow-up three weeks later, CSF analysis showed normal cell count and brain MRI was unremarkable again. MOG-antibodies however remained positive. Since then, the patient has received monthly immunoglobulins leading to a stable neurological status. Unfortunately, the cancer itself is progressive with a local relapse and metastases of liver, lung and bones.

Conclusion
Our patient had an acute presentation of a rare brain stem encephalitis. However, infectious workup as well as all well-known onconeural antibodies showed negative results. This shows that pleocytosis in patients with a history of malignant disease is highly suggestive for paraneoplastic neurological syndromes even if common antibodies show negative results. Clinicians should be aware of other autoimmune antibodies like anti-MOG-antibodies and should extend workup if necessary. Vice versa it is worth considering tumor workup in patients with neurological symptoms and anti-MOG-positivity. Furthermore, the appearance of paraneoplastic neurological syndromes is always suspicious for progressive disease.