bluuebunny/crossref_metadata_2025_split huggingface dataset:
P14.27 Exploring end-of-life care in the GlioCova national brain tumour patient cohort
Authors: Mauricaite R , Le Calvez K , Droney J , Caldano M , Alam M , Williams M 
Published: September 2021

Abstract

BACKGROUND
Brain tumours are the leading cause of cancer deaths in the under-40s. Research on end-of-life care, especially in brain tumour patients is rare, yet important to patients and carers. The GlioCova project holds data on all adult brain tumour patients in England diagnosed between 2013 and 2018. Using this linked data set, we performed preliminary analysis on end-of-life care, focusing on treatment close to death and place of death.

MATERIAL AND METHODS
We used data from the English National Cancer Registry and identified all patients with a primary CNS tumour (ICD-10: C70, C71, C72) who were diagnosed between 2013 - 2018. We examined demographics, tumour morphology and grade, primary cause of death, treatment received within the last 3 and 1 month of life, and the location of death. For patients with unclear location of death (‘unknown’, ‘other’, ‘NA’), we looked at their final destination of discharge recorded in their last inpatient admission.

RESULTS
We identified 26,239 brain tumour patients of whom 20,715 had died. 41.7% were female and median age was 68 (IQR=19). Most patients had a malignant neoplasm of brain (98.6%), followed by meninges (0.7%) and spinal cord, cranial nerves and other parts of central nervous system (0.7%). The most common primary cause of death was malignant neoplasm (70%). Of the 10,021(48.4%) patients who received radiotherapy at any time between diagnosis and death, 1,341 (6.5%) received it within the last three months of life and 254 (1.3%) received it within the last month of life. Of the 5,957 (28.8%) patients who received chemotherapy, 1,358 (6.6%) started a chemotherapy regimen 3 months and 200 (0.97%) 1 month before death. 36.0% of all patients died at home, 23.8% at hospital, 14.7% in a hospice and 8.8% in a nursing home. For 16.7% of patients with an unclear location of death, the most common destination of discharge during their last hospital admission was usual place of residence (54.5%), non-NHS run Care Home (13.9%), NHS run Care Home (11.2%).

CONCLUSION
To the best of our knowledge, this is the first national analysis of end-of-life care in brain tumour patients. Active treatment towards the end of life and in a hospital deaths appear lower in brain tumour patients than in studies of other cancer groups.
P14.62 Overall survival from glioblastoma: partial resection versus biopsy
Authors: Bjorland L S , Fluge Ø , Kurz K D , Gilje B , Mahesparan R , Ushakova A , Farbu E 
Published: September 2021

Abstract

BACKGROUND
Maximal safe resection is standard of care in patients with glioblastoma. Partial resection or biopsy are alternative surgical approaches when macroscopic complete resection is unachievable. Survival benefit from partial resection remains uncertain. We aimed to evaluate overall survival from glioblastoma in patients having undergone partial resection compared to biopsy.

MATERIAL AND METHODS
We retrospectively identified all patients with histologically confirmed glioblastoma having undergone partial resection or biopsy in Western Norway between 1.1.2007 and 31.12.2014. Clinical characteristics and radiology reports were extracted from electronic medical records. Categorical data were compared by chi square test or Fishers exact test, and continuous data by non-parametric tests. Kaplan Meier method and log rank test were used for survival analyses.

RESULTS
We identified 158 patients diagnosed with glioblastoma and having undergone biopsy or partial resection. Biopsy was performed in 52 patients (32.9%) and partial resection in 106 patients (67.1%). Median age (range) was 62.5 (18.1–82.3) in the biopsy group and 62.2 (27.9–85.1) in the partial resection group (p=0.90). Median Charlson comorbidity score was four in both groups. Multifocality was observed in 46.2% of patients in the biopsy group, compared to 27.4% of patients in the partial resection group (p=0.02). Deep-seated tumour localisation was also more frequent in the biopsy group than in the partial resection group, seen in 17.3% vs 5.7% of the patients (p=0.04). There was no difference in chemoradiotherapy (CRT) treatment between the groups. CRT according to the Stupp protocol, less intensive CRT and best supportive care was performed in 36.5%, 50.0% and 13.5% of patients in the biopsy group, compared to 45.3%, 49.1% and 5.7% in the partial resection group (p=0.20). Median overall survival in the biopsy group was 8.1 months (95% CI 5.2–11.1) compared to 11.1 months (95% CI 9.4–12.8) in the partial resection group (p=0.19). Median survival in the biopsy group was 13.8 months (95% CI 10.1–17.5), 6.5 months (95% CI 3.6–9.4), and 3.5 months (95% CI 0.0–7.7) for patients receiving CRT according to Stupp protocol, less-intensive CRT and best supportive care, respectively (p&lt;0.001). The corresponding numbers in the partial resection group were 15.1 months (95% CI 13.2–16.9), 9.1 months (95% CI 7.5–10.6), and 1.5 month (95% CI 0.0–4.7) (p&lt;0.001).

CONCLUSION
Median overall survival was slightly longer in patients having undergone partial resection compared to biopsy, however not statistically significant. Prospective studies are needed to evaluate the survival benefit from partial resection.
P14.66 Re-operation for recurrent meningioma - are we helping patients?
Authors: Richardson G E , Mustafa M A , Gillespie C S , Keshwara S M , Taweel B A , Millward C P , Islim A I , Jenkinson M D 
Published: September 2021

Abstract

BACKGROUND
Meningioma is the commonest primary brain tumour. Despite surgery, meningiomas can recur. Surgery is usually the first line treatment for recurrent meningioma. The aim was to determine the risk factors associated with clinical outcomes (performance status, morbidity, mortality, recurrence) following re-operation for recurrence of intracranial meningioma.

MATERIAL AND METHODS
Retrospective cohort study (1998–2018). Eligible patients had reoperation for local recurrence of a previously operated meningioma. Collected data included baseline clinical and imaging characteristic. Primary outcome measure was performance status after each reoperation. Secondary outcome measures were medical and surgical morbidity, recurrence-free survival (RFS) and overall survival (OS).

RESULTS
Fifty-eight patients were eligible (37 female, mean age at 1st re-operation 56.1 years (SD=11.6)). Eleven patients (19.6%) had 2 re-operations and 3 patients (5.4%) had 3 re-operations. Median follow up was 128.5 months (IQR=73–194.5). Median time to 1st recurrence and 1st re-operation were 36.5 (IQR=24.3–81.0) and 43.8 months (IQR=20.3–103.4), respectively. Fifteen patients (26.8%) had worse performance status after 1st reoperation, compared to 5.4% (n=3) after the primary operation. Complication rate was 32.1% (n=18) after the primary operation compared to 48.2% (n=27) after 1st reoperation. At primary operation, there were 29 (51.8%) grade 1, 24 (42.9%) grade 2, and 1 (1.8%) grade 3 tumours. Median RFS after first re-operation was 36.5 months (95% CI 29.3–43.9). Median OS was 312 months (95 % CI 257.8–366.2). Increased number of post-operative complications were a risk factor for worsened performance status following reoperation (OR 2.2 [95% CI 1.1–4.6], P=0.029).

CONCLUSION
Re-operation is associated with a worse performance status and increased risk of complications. Re-operating meningiomas for radiological recurrence without symptoms increases patient morbidity. Shared-care management decision should be made with patients when considering operating for radiological recurrence only.
P14.85 Impact of the neuro-radiologist and neuro-surgeon in contouring with the neuro-oncologist on local relapse rates for brain metastases treated with stereotactic radiosurgery
Authors: Robinson M , Sayal K , Tunstall C , Padmanaban S , Watson R , Pretorius P , Joseph R , Jeyaretna S , Hobbs C 
Published: September 2021

Abstract

BACKGROUND
The audit evaluates the value of MDT, including neuro-radiologist and neuro-surgeon, review of contouring carried out by a clinical oncologist in stereotactic radiosurgery (SRS).

MATERIAL AND METHODS
A sequential audit was conducted of all patients receiving intracranial SRS at our local institution for the first 22 months of a new SRS service. Lesions were contoured first by clinical oncologist then reviewed/edited by the MDT. The initial contour was compared with final contour using Jaccard conformity and geographical miss indices. The dosimetric impact of a contouring change was assessed using plan metrics to both original and final contour. The impact of the contouring review on local relapse, overall survival and radio necrosis rate was evaluated with at least 24 months follow up (24–46 months).

RESULTS
113 patients and 142 lesions treated over 22 months were identified. Mean JCI was 0.92 (0.32–1.00) and 38% needed significant editing (JCI&lt;0.95). Mean GMI was 0.03 (0.0–0.65) and 17% showed significant miss (GMI&gt;0.05). Resection cavities showed more changes, with lower JCI and higher GMI (p&lt;0.05). There was no significant improvement on JCI or GMI shown over time. Dosimetric analysis indicated a strong association of conformity metrics with PTV dose metrics; a 0.1 change in GTV conformity metric association with 6–17% change in dose to 95% of resulting PTV. Greater association was seen in resection cavity suggesting the geographical nature of a typical contouring error gives rise to greater potential change in dose. Clinical outcomes compared well with published series. Median survival was 20 months and local relapse free rate in the treated areas of 0.89 (0.8–0.94) at 40 months, and 0.9 (0.83–0.95) radio-necrosis free rate at 40 months with a median 17 months to developing radio-necrosis for those that did.

CONCLUSION
This work highlights that a MDT contour review adds significant value to SRS and the approach translates into reduced local recurrence rates at our local institution compared with previously published data. Radio-necrosis rates are below 10%. No improvement in clinical oncologist contouring over time was shown indicating a collaborative approach is needed regardless of experience of clinical oncologist. MDT input is recommended in particular in contouring of resection cavities.
P14.87 Significance of clinical and molecular-genetic factors for prognosis in 574 adult patients with primary glioblastoma
Authors: Zolotova S , Kurmukov A , Dalechina A , Belyashova A , Golanov A 
Published: September 2021

Abstract

BACKGROUND
Despite advances in the characterization of genomic alterations in glioblastoma patient survival remains poor. The aim of this single center retrospective study was to estimate prognostic factors affecting to survival for optimizing personalized treatment strategy in glioblastoma patients.

MATERIAL AND METHODS
574 consecutive patients with primary glioblastoma treated at the Burdenko National Medical Research Center of Neurosurgery from 2014 to 2019 were included in this study (314 male /260 female). Survival data was analyzed using Kaplan-Meier with log-rank tests to assess statistical significance. A linear regression model was built to predict overall survival.

RESULTS
Older patients (&gt; 45 years) had the worse prognosis than patients ≤ 45 (p = 2.37 * 10^-6). Female patients had advantages in overall survival (p = 0.014). Time interval from surgery to the starting of radiotherapy longer than 4 weeks was associated with worse overall survival (p = 0.062). Patients with positive IDH1/2 and MGMT had better prognosis than patients with wild type and MGMT negative (p = 0.000841, p = 0.000138, respectively). We revealed that there were significant differences in overall survival between patients who had progression on the first (p = 0.000312), second (p = 0.001046) and third (p = 0.00223) follow-up MRI after radiotherapy. Median survival times (from the date of surgery) were 17, 20, 23 months, respectively. The feature importance in the linear regression model was patient’s age, IDH1/2 mutation, MGMT promoter methylation status, progression on the first follow-up MRI and sex.

CONCLUSION
Older patient’s age, prolonged time between surgery and RT starting, male sex, negative IDH1/2 and MGMT, progression on the first MRI were associated with poor overall survival in glioblastoma patients. Our results suggested additional clinical, radiomics and molecular-genetic data should be added to improve the overall survival prediction.
The results have been obtained under the support of the RFBR grant 18-29-01054
P14.90 Survival outcomes and prognostic factors in glioblastoma patients treated with radiotherapy plus concomitant and adjuvant temozolomide - real-world study
Authors: Sousa M J , Magalhães J , Basto R , Costa C , Pego A , Sousa G 
Published: September 2021

Abstract

BACKGROUND
Glioblastoma (GBM) is the most common and aggressive primary malignant brain tumour in adults. The current standard of care for newly diagnosed GBM is maximal surgical resection, followed by radiotherapy plus concomitant and adjuvant temozolomide (TMZ). This study aimed to evaluate the survival outcomes and identify predictors of survival among these patients.

MATERIAL AND METHODS
We performed a single-centre retrospective analysis of GBM patients treated with radiotherapy plus concomitant and adjuvant TMZ from 2013 to 2020. The analyses of progression-free survival (PFS) and overall survival (OS), each one evaluated starting from initial diagnosis, were performed. Survival curves were estimated with the Kaplan- Meier method and compared using the log-rank test.

RESULTS
Fifty-eight patients were identified. The median age was 61 years (range 18- 80), 51 (88%) patients were in ECOG-PS 0–1, 6 (10%) patients had isocitrate dehydrogenase (IDH) mutation and 53 (91%) of patients had undergone debulking surgery. At a median follow-up of 21 months, median OS was 12.8 months (95% confidence interval [CI] 9.7–15.9), whereas median PFS was 9.5 months (95% CI 8.5–10.5). The 1-year survival rate was 42% and the 2-year survival rate was 10%. Grade 3 or 4 hematologic toxicity occurred in 11 (19%) patients. Twenty-five (42%) patients completed at least 6 cycles of TMZ monotherapy with statistically significant differences between this sub-group and those who weren’t able to continue TMZ monotherapy [median OS 19.3 months (95% CI 14.4–24.2) vs 10.6 months (95% CI 7.8–13.4) p&lt;0.001]. ECOG-PS = 0 [median OS 16.7 months (95% CI 13.4–20.0, p=0.001)] and patients under 65 years of age [median OS 15.6 months (95% CI 12.3–18.9, p=0.02) were associated with significantly better median OS.

CONCLUSION
The current standard of care treatment for GBM remains poor. An important factor predictor of survival is the completion of the 6 maintenance cycles of TMZ. At baseline, ECOG PS and the patient’s age could be used to define patient prognosis.
P16.08 Inhibition of melanoma brain metastasis by targeting miR-146a
Authors: Wang J , Rigg E K , Lunavat T R , Zhou W , Feng Z , Hoang T , Bjerkvig R , Thorsen F 
Published: September 2021

Abstract

BACKGROUND
Melanoma has the highest propensity of any cancer to metastasize to the brain, with late-stage patients developing brain metastasis (MBM) in 40% of cases. Survival of patients with MBM is around 8 months with current therapies, illustrating the need for new treatments. MBM development is likely caused by molecular interactions between tumor cells and the brain, constituting the brain metastatic niche. miRNAs delivered by exosomes released from the primary tumor cells may play a role in niche establishment, yet the mechanisms are poorly understood. Here, the aim was to identify miRNAs released by exosomes from melanomas, which may be important in niche establishment and MBM progression.

MATERIAL AND METHODS
miRNAs in exosomes collected from human astrocytes, melanocytes, and MBM cell lines were profiled to determine differential expression. Functional in vitro validation was performed by cell growth and migration assays, cytokine arrays, qPCR and Western blots. Functional in vivo studies were performed after miR knockdown in MBM cell lines. An in silico docking study was performed to determine drugs that potentially inhibit transcription of miR-146a to impede MBM development.

RESULTS
miR-146a was the most upregulated miRNA in exosomes from MBM cells and was highly expressed in human and animal MBM samples. miR-146a mimics activated human astrocytes, shown by increased proliferation and migration, elevated expression of GFAP in vitro and in mouse brain tumor samples, and increased cytokine production. In animal studies, knockdown of miR-146 in MBM cells injected intracardially into mice reduced BM burden and increased animal survival. Based on the docking studies, deserpidine was found to be an effective inhibitor of MBM growth in vitro and in vivo.

CONCLUSION
miR-146a may play an important role in MBM development, and deserpidine is a promising candidate for clinical use.
P16.09 Regulation of chromatin accessibility in the hypoxic tumor microenvironment of glioblastoma
Authors: Dzwigonska M , Mieczkowski J , Pilanc P , Cyranowski S , Kominek A , Piwocka K , Kaminska B , Leszczynska K B 
Published: September 2021

Abstract

BACKGROUND
Chromatin structure is often dysregulated in cancers, including glioblastoma (GBM), the most aggressive type of primary brain tumor. GBM has the poorest prognosis with no efficient cure to date due to diffusive growth into the brain, resistance to treatments and the immunosuppressive tumor microenvironment (TME). The growth and invasiveness of GBM is supported by the heterogeneous TME including local microglia and bone-marrow-derived macrophages (collectively known as glioma-associated microglia and macrophages, GAMs). In addition, tumor hypoxia is a key factor in the progression of GBM, as it can globally and rapidly alter gene expression, induce cancer cell invasiveness, stemness and lead to therapy resistance. Hypoxia can influence the pro-tumorigenic function of GAMs by inducing the expression of cytokines and cell surface receptors. However, little is known on the hypoxia-imposed chromatin changes of GAMs and GBM cells, which can in turn impact the interaction between these cell populations. Here we analyze these changes using a single-cell method, which preserves in situ hypoxia within the TME of GBM.

MATERIAL AND METHODS
Single-cell Pi-ATAC-seq (Protein-indexed Assay of Transposase Accessible Chromatin with sequencing) method in a GL261 murine glioma model was used to simultaneously assess genome-wide chromatin accessibility and expression of intracellular protein markers in single cells, enabling accurate selection of hypoxic and non-hypoxic tumor cells and GAMs. Pi-ATAC-seq is used on paraformaldehyde-perfused tumors and therefore allows capturing unaltered hypoxia-dependent cellular states, that often become distorted during dissociation and preparation of fresh material in most common single-cell methods.

RESULTS
We optimized Pi-ATAC method in a GL261 GBM mouse model, with specific sorting of GAMs using CD11b+ immunosorting followed by separation of microglia and macrophages, based on intensity of CD45 staining. HIF-1α induction and binding of pimonidazole were used to mark hypoxic populations. Currently, we are investigating the chromatin accessibility profiles of cancer cells and GAMs within the hypoxic tumor microenvironment of GBM. Exploring open chromatin profiles in GAMs and glioma-microglia co-cultures will allow to unravel the mechanisms of chromatin accessibility modulation in the oxygen-dependent manner.

CONCLUSION
In summary, we optimized the Pi-ATAC method in a mouse GBM model to characterize the chromatin openness changes in GAMs and cancer cells in response to hypoxic stress. Further validation of these results will provide the potential to identify novel markers for GAMs/glioma interactions in hypoxic GBMs and develop novel therapeutic targets.
Long COVID and Post-infective Fatigue Syndrome: A Review
Authors: Sandler Carolina X , Wyller Vegard B B , Moss-Morris Rona , Buchwald Dedra , Crawley Esther , Hautvast Jeannine , Katz Ben Z , Knoop Hans , Little Paul , Taylor Renee , Wensaas Knut-Arne , Lloyd Andrew R 
Published: September 2021

Abstract
Fatigue is a dominant feature of both acute and convalescent coronavirus disease 2019 (COVID-19) (sometimes termed “long-COVID”), with up to 46% of patients reporting fatigue that lasts from weeks to months. The investigators of the international Collaborative on Fatigue Following Infection (COFFI) conducted a systematic review of post-COVID fatigue and a narrative review on fatigue after other infections, and made recommendations for clinical and research approaches to assessing fatigue after COVID-19.
In the majority of COVID-19 cohort studies, persistent fatigue was reported by a significant minority of patients, ranging from 13% to 33% at 16–20 weeks post-symptom onset. Data from the prospective cohort studies in COFFI and others indicate that fatigue is also a prevalent outcome from many acute systemic infections, notably infectious mononucleosis, with a case rate for clinically significant Post-infective fatigue after exclusion of recognized medical and psychiatric causes, ranging from 10%–35% at 6 months.
To better characterize post-COVID fatigue, the COFFI investigators recommend the following: application of validated screening questionnaires for case detection; standardized interviews encompassing fatigue, mood, and other symptoms; and investigative approaches to identify end-organ damage and mental health conditions.
Retrospective Review on the Safety and Efficacy of Nitrofurantoin for the Treatment of Cystitis in the Veteran Population With or Without Renal Insufficiency
Authors: Welch Elwyn , Sheth Shaila , Ashong Chester N , Pham Caroline 
Published: September 2021

Abstract

Background
The emergence of antimicrobial resistance in uropathogens has generated interest in the use of nitrofurantoin in controversial populations, such as in males and those with renal dysfunction. The purpose of this study was to compare the efficacy and safety of nitrofurantoin for the treatment of cystitis in males and females with variable degrees of renal dysfunction.

Methods
A retrospective chart review was conducted in adult patients who received nitrofurantoin for acute cystitis in the outpatient setting. The primary outcome was clinical cure compared between males and females and across various renal function groups (creatinine clearances [CrCl] &gt;60 mL/min, 30–60 mL/min, and &lt;30 mL/min) following nitrofurantoin treatment. The secondary outcome was adverse events.

Results
A total of 446 patients were included, with 278 females and 168 males. The overall clinical cure rate was 86.5% (95% CI, 83.0%–89.4%; n = 386). The clinical cure rate did not vary between genders (odds ratio [OR], 0.6; 95% CI 0.35–1.04; P = .085) or between patients with a CrCl &gt;60 mL/min compared with those with CrCl 30–60 mL/min (OR, 1.01; 95% CI, 0.40–2.44; P = 1). The 1 patient with a CrCl &lt;30 mL/min was not included in the analysis. A history of benign prostatic hyperplasia (OR, 0.5; 95% CI, 0.26–0.99; P = .045) or cirrhosis (OR, 0.21; 95% CI, 0.06–0.82; P = .025) was associated with decreased odds of clinical cure. Adverse events occurred in 2% (n = 9) of patients.

Conclusions
There was no statistically significant difference in clinical cure with nitrofurantoin between genders or various renal functions.