bluuebunny/crossref_metadata_2025_split huggingface dataset:
INNV-23. LIFESTYLE COACHING IS FEASIBLE AND IMPROVES PILOT OUTCOMES IN FATIGUED BRAIN TUMOUR PATIENTS: THE BT-LIFE (BRAIN TUMOURS, LIFESTYLE INTERVENTIONS, AND FATIGUE EVALUATION) MULTI-CENTRE, PHASE II RCT
Authors: G Rooney Alasdair , Hewins William , Walker Amie , Withington Lisa , Mackinnon Mairi , Robson Sara , Green Aimee , Anderson Garry , Bulbeck Helen , Cochrane Carol , Gillespie David , Hewitt Christopher , Day Julia , Torrens Claire , Emerson Julie , Dunlop Jo , Welsh Michelle , Hopcroft Lisa , Wells Mary , McBain Catherine , Chalmers Anthony , Grant Robin 
Published: December 2020

Abstract

BACKGROUND
Fatigue is common and disabling for brain tumour patients. We studied the feasibility of two innovative lifestyle coaching interventions for high fatigue.

METHODS
Multi-centre phase II feasibility RCT (ISRCTN17883425). Adult primary brain tumour outpatients reporting significant fatigue (Brief Fatigue Inventory [BFI] score 4+), were randomised to one of three arms: Control; Health Coaching (“HC”, comprising eight structured coaching sessions on lifestyle behaviours); or HC plus Activation Coaching (“HC+AC”, adding two structured interviews targeting motivation to change). Outcomes were measured at baseline (T0), after interventions (T1), and at 16 weeks (T2). The primary outcome of feasibility was required for both recruitment (aim: average n= 5 fatigued patients recruited/month) and retention (aim: minimum 60% retention at T2). Secondary pilot outcomes included change in fatigue, depressive symptom, and QOL measures.

RESULTS
Over a nine-month recruitment period, n= 46 fatigued brain tumour patients were recruited (average n=5.1/month) and n= 34 were retained to endpoint (retention at T2= 73%), meeting the primary outcome of feasibility. Surprisingly, fatigue reduced significantly after HC (T1 mean change in BFI score from T0 baseline, relative to the equivalent change in control group: HC= -2.3 points [95%CI -3.4/-0.3]; HC+AC= -2.0 [-2.9/+0.1]; ANOVA p= 0.02) and was reduced in magnitude in both intervention groups at T2 (p= N.S). Both interventions also improved depressive symptoms (T1 mean change in HADS-Depression: HC= -2.0 points [-5.6/-0.1]; HC+AC= -2.9 [-6.5/-1.0]; Kruskal-Wallis p= 0.02). Patient-nominated QOL outcomes improved persistently after HC+AC (T2 mean change in PSYCHLOPS score: HC= -2.4 points [-5.4/+2.8]; HC+AC= -6.1 [-9.2/-0.8]; ANOVA p= 0.01).

CONCLUSION
Innovative coaching interventions, focused on lifestyle factors, are feasible to deliver to fatigued brain tumour patients. Preliminary signals suggest that these non-drug approaches may benefit several mediators of quality of life and warrant further study.
INNV-24. THE EXPERIENCE OF FATIGUED BRAIN TUMOUR PATIENTS RECEIVING INNOVATIVE LIFESTYLE INTERVENTIONS: QUALITATIVE RESULTS FROM THE BT-LIFE RANDOMISED CONTROLLED TRIAL
Authors: Torrens Claire , Emerson Julie , Hewins William , Walker Amie , Withington Lisa , Mackinnon Mairi , Robson Sara , Dunlop Jo , Welsh Michelle , McBain Catherine , Chalmers Anthony , Grant Robin , Rooney Alasdair G , Wells Mary 
Published: December 2020

Abstract

BACKGROUND
Most brain tumour patients report clinically significant fatigue. Here, we aimed to explore patients’ views of the experience, acceptability and usefulness of participating in a trial of novel lifestyle interventions for fatigue.

METHODS
Qualitative sub-study within the ‘BT-LIFE’ multi-centre phase II RCT (submitted separately). Fatigued adult primary brain tumour patients in receipt of one of the trial interventions (‘Health Coaching’: eight coaching sessions targeting lifestyle behaviours; plus or minus ‘Activation Coaching’: two additional interviews targeting motivation to change) took part in a semi-structured interview following completion of the interventions. A realist approach to the ‘framework’ method was used to analyse verbatim transcripts, with inductive and deductive codes assigned to the realist domains of Context-Mechanism-Outcome.

RESULTS
Twenty themes and 53 sub-themes were derived from the data. Patients’ (n= 21) understanding of and engagement with the interventions were influenced by their expectations, attitudes to life, and experience of living with a brain tumour. Behaviour change was supported by goal-setting, monitoring using a weekly diary, the motivational ‘push’ by coaches, and family/ social support where available. Barriers to engagement included technical diary difficulties, time limitations including work and holiday schedules, and interference from life events. Most patients described beneficial changes in health behaviours, self-efficacy, and general health and wellbeing. About half indicated actual improvement in fatigue levels; others reported no direct change but they could now cope better with fatigue. A minority experienced no change or worsening fatigue.

CONCLUSION
Most fatigued brain tumour patients were able to make positive changes after lifestyle coaching, despite physical and cognitive impairments. However, their experiences were varied. Those for whom the interventions were a good ‘fit’ with their pre-existing outlook, lifestyle, and physical and emotional capabilities, appeared to achieve most benefit. These qualitative findings will inform further work addressing the disabling symptom of brain tumour-related fatigue.
NCMP-03. INTRATHECAL TRASTUZUMAB TREATMENT OF HER-2 POSITIVE LEPTOMENINGEAL BREAST CANCER: THE UNIVERSITY OF MICHIGAN EXPERIENCE
Authors: Peters Kelsey , Robell Lindsay , Morikawa Aki , Umemura Yoshie , Sun Yilun , Leung Denise , Mammoser Aaron , Gill Anoop , Junck Larry 
Published: December 2020

Abstract

PURPOSE
Breast cancer is the most common solid tumor to metastasize to the leptomeninges, affecting up to 5% of breast cancer patients. Overall survival for patients with leptomeningeal metastases (LM) is poor, with median survival of 4–6 months following diagnosis. There is limited data available on the efficacy of intrathecal (IT) trastuzumab in the treatment of Her-2 positive LM.

METHODS
A total of 30 patients with Her-2 positive breast cancer with LM treated at the University of Michigan from 2008–2020 were identified retrospectively. Of these, 13 patients were treated with IT trastuzumab beginning in June 2010 and followed through April 2020. Initial dose was 50–80 mg twice weekly for a minimum of 4 weeks, followed by slow taper. The 17 patients with Her-2 positive breast cancer with LM who did not receive IT trastuzumab served as control.

RESULTS
The median age of patients in the treatment group was 42 and 52 in the control group. Whole brain radiation therapy was received by 92% of patients in the treatment group and 76% in the control group. The median overall survival from diagnosis of LM to death was 20 months (interquartile range [IQR] 13–60 months) in the treatment group and 6 months (IQR 2–17 months) in the control group. Survival at 3 years and 5 years was 40% and 13%, respectively for the treatment group and 8% and 0% (no data available at 60 months), for the control group. Hazard ratio for death with IT trastuzumab 0.38 (95% CI 0.16–0.91, p=0.024). IT trastuzumab was overall well-tolerated (one patient developed meningitis, while another had shunt malfunction necessitating removal of the reservoir).

CONCLUSIONS
Patients with HER2+ LM who received IT trastuzumab demonstrated significantly improved OS compared to control with minimal toxicity.
NCMP-04. INCIDENCE AND OUTCOMES OF BRAIN METASTASES IN PATIENTS WITH EXTRA-PULMONARY NEUROENDOCRINE NEOPLASMS
Authors: Abedin Kapacee Zainul , Dawod Mohammed , Allison Jennifer , Frizziero Dr Melissa , Chakrabarty Bipasha , Manoharan Prakash , McBain Catherine , Mansoor Was , Lamarca Angela , Hubner Richard , Valle Juan , McNamara Mairead 
Published: December 2020

Abstract

BACKGROUND
Brain metastases (BMs) incidence in patients with extra-pulmonary neuroendocrine neoplasms (EP-NENs) is unclear, with no available management recommendations. This study aimed to review the clinical presentation, management and survival outcomes of patients with EP-NENs and BMs at a European Centre of Excellence.

METHODS
A retrospective single-centre analysis of consecutive patients with EP-NENs (Aug 2004-Feb 2020) was conducted. Median overall survival (OS)/survival from BMs diagnosis were estimated (Kaplan Meier).

RESULTS
Of 786 patients, 15 (1.9%) had BMs, median age 61y (range 15–77); 8 (53%) male, primary NEN site: unknown 40%; oesophageal 13%; small bowel 13%; pancreas 13%; gastric 7%; cervix 7% and bladder 7%. Most patients with BMs had grade 3 (G3) NENs (11, 73%), 3 (20%) were G2 and 1 (7%)G1. Eight (53%) had poorly-differentiated NENs, 6 well-differentiated and 1 not recorded. Two (13%) patients had synchronous BMs at diagnosis, whilst 13 (87%) developed BMs metachronously. Median time to development of BMs after initial NEN diagnosis: 15.9 months (range 2.5–139.5). Five patients had a solitary BM, 4 had 2–9 lesions and 6 had &gt;10 BMs. The most commonly affected sites were the cerebrum (13, 87%), cerebellum (6, 40%), leptomeninges (2, 13%) and orbit (1, 7%). The most common presenting symptoms were limb weakness, headache, confusion, visual disturbance (each n=3, 20%), seizures (2, 13%), word-finding difficulty (2, 13%) and facial weakness/ptosis (1, 7%). Median OS from initial NEN diagnosis was 23.6-months [95%-CI 15.2–31.3]; median time to death from BMs diagnosis was 3.0-months [95%-CI 0.0–8.3]. Treatment of BMs was surgery (n=3); radiotherapy (n=6); 5 had WBRT, one localised radiotherapy (orbit). Six (40%) had best supportive care.

CONCLUSION
BMs in patients with EP-NENs are rare and predominantly in G3 NENs, with diverse intracranial distribution. Although uncommon, BMs from NENs behave aggressively and greater understanding is needed to improve therapeutic outcomes.
NCMP-05. DECODING THE IMMUNE SYSTEM RESPONSE TO LEPTOMENINGEAL METASTASIS
Authors: Remsik Jan , Tong Xinran , Sener Ugur , Isakov Danille , Chi Yudan , Iacobuzio-Donahue Christine , Pe’er Dana , Schietinger Andrea , Boire Adrienne 
Published: December 2020

Abstract
For decades, the central nervous system was considered to be an immune privileged organ with limited access to systemic immunity. However, the leptomeninges, the cerebrospinal fluid (CSF)-filled anatomical structure that protects the brain and spinal cord, represent a relatively immune-rich environment. Despite the presence of immune cells, complications in the CSF, such as infectious meningitis and a neurological development of cancer known as leptomeningeal metastasis, are difficult to treat and are frequently fatal. We show that immune cells entering the CSF are held in an ‘idle’ state that limits their cytotoxic arsenal and antigen presentation machinery. To understand this underappreciated neuroanatomic niche, we used unique mouse models and rare patient samples to characterize its cellular composition and critical signaling events in health and disease at a single-cell resolution. Revealing the mediators of CSF immune response will allow us to re-evaluate current therapeutic protocols and employ rational combinations with immunotherapies, therefore turning the patient’s own immune system into an active weapon against pathogens and cancer.
NCMP-08. EFFICACY OF ANTIEPILEPTIC DRUGS IN GLIOMA PATIENTS WITH EPILEPSY: A SYSTEMATIC REVIEW
Authors: de Bruin Marjolein , van der Meer Pim , Dirven Linda , Taphoorn Martin , Koekkoek Johan 
Published: December 2020

Abstract

BACKGROUND
Epilepsy is a common symptom in glioma patients, requiring antiepileptic drug (AED) treatment. However, comprehensive data on the efficacy and tolerability of AED treatment is currently lacking. In this systematic review we specifically assessed the efficacy of AEDs in patients with a grade II-IV glioma.

METHODS
Electronic databases PubMed/MEDLINE, EMBASE, Web of Science, and Cochrane library were searched up to April 2020. Three different outcomes were extracted from all eligible articles: (I) seizure freedom; (II) ≥50% reduction in seizure frequency; and (III) treatment failure. To overcome variation with respect to sample sizes, weighted averages (WA) were calculated for outcomes at 6 and 12 months.

RESULT
A total of 64 studies were included. For monotherapy, the 6-months seizure freedom rate was highest for phenytoin (WA=72%), whereas the 12-months seizure freedom rate was highest for pregabalin (WA=75%). For achieving ≥ 50% seizure reduction, levetiracetam was the most effective AED at 6 and 12 months, with WA of 82 and 97% respectively. Considering the provided polytherapy combinations, levetiracetam combined with phenytoin was most effective followed by levetiracetam with valproic acid. Seizure freedom rates with polytherapy at 6 months and 12 months were highest for combinations with phenytoin and topiramate, respectively. For achieving a ≥ 50% seizure reduction, combinations with perampanel were found to be the most effective at 6 and 12 months.

CONCLUSION
Based on the current literature, phenytoin, levetiracetam and pregabalin are most effective as AED monotherapy in glioma patients with epilepsy. Well-controlled prospective studies are needed to help further guide clinician’s treatment choices.
NCMP-18. NEUROTOXICITY AS A POTENTIAL SURROGATE MARKER FOR THERAPEUTIC RESPONSE WITH COMMERCIAL ANTI-CD19 CAR T-CELL THERAPY
Authors: Yuen Carlen , Riedell Peter , Artz Andrew , Kosuri Satyajit , Kelly Thomas , Wu Shasha , Reder Anthony , Rezania Kourosh , Soliven Betty , Xie Tao , Mastrianni James , Park Deric , Klejch Wesley , Ali Saad , Bishop Michael 
Published: December 2020

Abstract
Neurotoxicity is a common occurrence and a major form of morbidity in adult patients with relapsed or refractory (R/R) diffuse large B cell lymphoma (DLBCL) patients treated with anti-CD19 directed chimeric antigen receptor (CAR) T-cell therapy. Variables related to the incidence and severity of neurotoxicity have been relatively well delineated, but the association between neurotoxicity and the efficacy of CAR T-cell therapy has not been well studied. We performed a retrospective analysis of the outcomes of DLBCL patients who developed neurotoxicity following anti-CD19 CAR T-cell treatment. The analysis included 26 patients with R/R DLBCL who received commercial anti-CD19 CAR T-cell therapy. All patients received a lymphodepleting chemotherapy regimen consisting of fludarabine and cyclophosphamide. Twenty-five patients received axicabtagene ciloleucel, and 1 received tisagenlecleucel. The overall incidence of neurotoxicity was 88%; 31% developed severe neurotoxicity (Grade III-IV by CTCAE). Higher neurotoxicity was associated with better PFS by both CTCAE (CR 2.4 ± 1.1 vs. PD 1.4 ± 1.3, p = 0.051) and CARTOX-10 (CR 3.78 ± 4.6 vs. PD 7.7 ± 3.8, p = 0.044) grading systems. Higher neurotoxicity continued to show a trend at 6, 9, and 12 months by the CTCAE grading system (CR 2.4 ± 1.0 vs. PD 1.7 ± 1.3, p = 0.085), and no patients had disease recurrence after 6 months. In this limited cohort, neurotoxicity severity was paradoxically positively correlated with progression-free survival with commercial CAR T-cell therapy and may therefore indicate an effective therapeutic response.
NCMP-26. RECOGNITION OF PARANEOPLASTIC SYNDROMES TRIGGERED BY TRADITIONAL CYTOTOXIC CANCER TREATMENT, TUMOR RECURRENCE AND DEVELOPMENT OF SECOND CANCER
Authors: Tummala Sudhakar 
Published: December 2020

Abstract

BACKGROUND
Paraneoplastic syndromes traditionally precede tumor diagnosis. With recent greater use of immune checkpoint blockade therapy there is ever-increasing recognition of various immune related adverse effects. This abstract highlights PCA 1 paraneoplastic syndrome triggered by non-immune based chemotherapy, surgery, tumor recurrence and prior to development of second cancer.

METHODS
This is retrospective case review of patients seen at MD Anderson Cancer Center who developed PCA 1 paraneoplastic syndrome.

RESULTS
64 yr old female with ovarian cancer on ERK inhibitor develops lower extremity weakness, ataxia and difficulty ambulation. Serum and CSF showed positive PCA-1 antibody. 59 yr old female with ovarian serous carcinoma develops cerebellar dysfunction after receiving caroboplatin and doxil. Serum and CSF were positive for PCA-1 antibody. 57 yr old female with ovarian carcinoma develops tremors, progressive ataxia after second cycle of carboplatin,taxol and avastin. Serum was positive for PCA-1 antibody. 45 yr old female with ovarian carcinoma completes 6 cycles of taxol and carboplatin. 3 months later develops gait ataxia. CSF was positive for PCA-1 antibody. Workup showed progressive ovarian carcinoma. 59 yr old with invasive ductal breast cancer develops lower extremity weakness and ataxia. Serum and CSF were positive for PCA-1 antibody. Work up revealed ovarian carcinoma. 63 yr old female with newly diagnosed breast cancer undergoes mastectomy. In the immediate postoperative time period develops diplopia, gait ataxia. Serum and CSF were positive for PCA-A antibody. All patients were aggressively treated with steroids. Most received additional therapies including plasma exchange, IVIG, tacrolimus, Rituxan, Cytoxan. All patients remained with permanent cerebellar dysfunction.

CONCLUSIONS
Case series highlights the recognition of paraneoplastic syndrome following traditional cytotoxic chemotherapy. There is need for early recognition of this neurological urgency. Work up includes prompt LP, serum and CSF paraneoplastic antibody panel, and evaluation for primary tumor recurrence or development of second cancer.
NCMP-27. THE USE OF INTRAVENOUS IMMUNOGLOBULIN (IVIG) DURING SEVERE NEUROTOXICITY AMONG THE RECIPIENTS OF CHIMERIC ANTIGEN RECEPTOR T-CELLS (CAR-T) THERAPY
Authors: Mokhtari Sepideh , Asquith Justin , Bachmeier Christina , Faramand Rawan , Kim Youngchul , Peguero Edwin , Sahebjam Solmaz , Jain Michael , Vogelbaum Michael , Davila Marco , Forsyth Peter , Locke Frederick , Aleksandr Lazaryan 
Published: December 2020

Abstract

INTRODUCTION
Severe Immune effector Cell-Associated Neurotoxicity Syndrome (ICANS) occurs in ~ 30% of Diffuse Large B Cell Lymphoma (DLBCL) patients treated with CAR-T cell therapy. The current treatment for severe ICANS is glucocorticoids, and this may be combined with tocilizumab for concurrent cytokine release syndrome. Even with these treatments, neurotoxicity can persist. It is essential, therefore, to find additional treatments to more effectively reverse CAR-T neurotoxicity.

OBJECTIVE
We summarize our institutional experience using IVIG to treat severe or refractory ICANS after glucocorticoids alone.

METHOD
This is a single center retrospective cohort study of neurologic and oncologic outcomes among patients who received axicabtagene ciloleucel (axi-cel) for DLBCL or its variants from May 2015 to February 2019. We identified those patients who developed severe ICANS subsequently treated with glucocorticoids alone (n = 10) or glucocorticoids plus IVIG (n = 9).

RESULTS
The median age of all 19 patients was 63 (range 47-75, and 68% were males). All IVIG recipients received glucocorticoids prior to IVIG administration. There was no significant difference in time to resolution (TTR) of severe ICANS between both groups (median 3 vs. 3 days, Log-rank p = 0.331). However, we found that all IVIG recipients had experienced either escalation of their neurotoxicity grade or persistent severe neurotoxicity after initiation of steroids (p = 0.001). Moreover, IVIG recipients had worse ECOG performance status prior to axi-cel therapy (p = 0.03).

CONCLUSION
Although we found no difference in TTR of severe ICANS with addition of IVIG to glucocorticoids, our analysis suggests that the addition of IVIG blunted the effects of steroid-refractory neurotoxicity. Patients who received IVIG had worsening ICANS despite administration of steroids and therefore might have benefited from the earlier addition of IVIG. Controlled studies may clarify the potential efficacy of IVIG in severe neurotoxicity after CAR-T therapy.
NCMP-28. BEVACIZUMAB ASSOCIATED INTRACEREBRAL HEMORRHAGE IN PATIENTS WITH PRIMARY CNS MALIGNANCY
Authors: Clarke Nathan 
Published: December 2020

Abstract
The risk of intracranial hemorrhage (ICH) associated with the use of bevacizumab (BEV) has been a topic of several reviews in the literature, and is considered to be a potential adverse effect of BEV when used in patients with malignant glioma. We performed a single-center retrospective chart-review identifying glioma patients treated with BEV at our institution. 595 unique patients who received BEV with documented follow up were identified. Of these patients, 23 (3.9%) developed ICH within 12 weeks (five half-lives) of a BEV infusion (median 9 days post infusion, 1-24 days IQR). There was a trend towards statistical significance between dose administered and the incidence of hemorrhage (P=0.06), with all 23 hemorrhages occurring in patients treated with 10 mg/kg (n=21/490) per infusion or 15 mg/kg per infusion (n=2/35) (n=525, 88.2% of cohort). No patient on dosing regimens of 7.5 mg/kg (n=72) or 5 mg/kg per infusion (n=16) (n=88, 14.7% of cohort) developed ICH. Therapeutic anticoagulation and concomitant BEV therapy was observed in 103 (17%) patients with 10 patients (10/93, 9.7%) developing an ICH (n=10), at a rate significantly higher than in patients treated with bevacizumab alone (13/479, 2.6%) (p=0.0025). When hemorrhages occurred (with or without concomitant anticoagulation) they were associated with high morbidity and mortality (ECOG 3.54 versus 1.26, p = &lt; 0.0001), with 12 patients (52%) suffering severe debility (n=2) or death (n=10). CONCLUSION: Bevacizumab associated intracerebral hemorrhages remain uncommon events, similar to the baseline rate of spontaneous hemorrhage associated with malignant glioma. We observed a trend towards significance with higher doses per infusion associated with an increased rate of intracerebral hemorrhage. The combination of anticoagulation and BEV appears to confer a greater risk of hemorrhage than BEV alone.