bluuebunny/crossref_metadata_2025 huggingface dataset:
P16.04.B LONG TERM SURVIVAL AND TOXICITY OUTCOMES IN PEDIATRIC MEDULLOBLASTOMA: SINGLE CENTER EXPERIENCE
Authors: Kamer S , Karaman E , Acar M S , Anacak Y
Published: October 2024

BACKGROUND

Craniospinal radiotherapy(CSRT) is a crucial part of medulloblastoma treatment. Due to the diverse age range of patients and large treatment fields, long term toxicity results, as well as survival outcomes, must be evaluated. This study aims to assess treatment outcomes of CSRT in medulloblastoma patients at a single tertiary center, considering both long-term toxicity and survival.

MATERIAL AND METHODS

Pediatric medulloblastoma patients who underwent postoperative CSRT between 2000-2021 were included in the analysis. CSRT was planned with 3D CRT technique for all patiens. Craniospinal axis doses were 23,4 Gy for standard risk and 36 Gy for high risk group. Patients received posterior fossa or tumor bed boost according to their risk status. Clinical characteristics and survival outcomes were obtained from follow-up visits. For late toxicity analysis, patients with less than 2 years of follow-up were excluded. Assessments included educational issues, neurological deficits, hearing impairment, endocrinopathy, and growth impairment.

RESULTS

120 cases (median age: 7 (2-17)) were analyzed with %61,7 being male. Gross total resection was achieved in 80,8% of cases. Most common histopathologic subtype was classical histology (76.7%). Forty-eight case (40%) was diagnosed in metastatic stage (M+) according to Chang’s classification. 52.5% of the cases were classified as high-risk group. Median follow-up was 64 months (4-252). 5- and 10-year overall survival was estimated to be 71.6% and 63.3% respectively. For the recurrence free survival; 5- and 10-year estimates were 68.5% and 61.6%. High risk group correlated adversely with overall survival (p<0.01). In follow-up, recurrence was detected in 41 cases (34.2%) with a median of 16 months (1-52). Recurrence sites included 22 cases in the primary site, 8 cases in the spinal region, and 11 cases in both region. Although a higher recurrence rate was observed in the high-risk group (41.2% vs. 26.3%), difference was not statistically significant. Seventy-five cases underwent late toxicity analysis, with 72% exhibiting at least one late toxicity. Educational issues were found in 36% of cases, permanent neurological deficit in 34.7%, hearing impairment in 32%, endocrine insufficiency in 40%, and growth impairment in 49.3%.Higher spinal dose (p:0,019), age ≤8 (p:0,011) and female sex (p:0,034) correlated with growth impairment. Endocrinopathy was significantly more prevalent in children over 12 years of age (p=0.032). During follow-up, three cases developed secondary malignancies: one meningioma and two papillary thyroid carcinomas.

CONCLUSION

CSRT is an effective treatment modality for pediatric medulloblastoma and must be meticulously administered in order to achieve acceptable survival outcomes and minimize late toxicity. Long-term follow-up is crucial for monitoring late adverse effects and recurrences in patients.
P16.08.B TARGETING MYELOID CELLS IN COMBINATION IMMUNOTHERAPIES FOR PAEDIATRIC MEDULLOBLASTOMA
Authors: Abbas Z , Hii H , Buck J , Byrne J , Johnson I , Howlett M , Johns T , Gottardo N G , Endersby R
Published: October 2024

BACKGROUND

Stagnation in clinical outcomes, as well as severe side-effects of current treatments for high-risk medulloblastoma, have prompted the search for novel therapies. To date, immunotherapies have not demonstrated success in medulloblastoma. Due to the highly aggressive nature of relapsed medulloblastoma, we posit that immunotherapies have the greatest chance of success if applied first-line, alongside conventional therapies. We have previously shown that while conventional therapies deplete adaptive immune cells from the medulloblastoma microenvironment, macrophages persist following treatment. Moreover, medulloblastomas are myeloid dominant tumours and blocking the anti-phagocytic CD47-SIRPa interaction has demonstrated preclinical efficacy as a monotherapy.

MATERIAL AND METHODS

We tested the combination of anti-CD47 immunotherapy with craniospinal irradiation in patient-derived xenograft models of medulloblastoma and have characterised treatment responses using flow cytometry, RNA sequencing, and immunohistochemistry.

RESULTS

We found that the combination of anti-CD47 and radiotherapy is remarkably effective in radiosensitive tumours, resulting in long-term tumour-free survival. We found that the combination therapy results in enhanced macrophage infiltration and phagocytic activation in radiosensitive tumours compared to either monotherapy. However, we found this combination to be ineffective in tumours which do not regress in response to irradiation.

CONCLUSION

Although this combination treatment may not be a one-size-fits-all approach, biomarkers of radiosensitivity may allow for the identification of patients most likely to benefit from this combination.
P17.22.B SILMET TRIAL: A RANDOMIZED, PLACEBO-CONTROLLED STUDY TO EVALUATE THE STAT3 INHIBITOR SILIBININ IN PREVENTING INTRACRANIAL RECURRENCE AFTER COMPLETE RESECTION OF A SINGLE BRAIN METASTASIS FROM NON-SMALL-CELL LUNG CANCER (NSCLC) OR BREAST CANCER
Authors: Pellerino A , Pace A , Angileri F , Caffo M , Gatti M , Benicelli E , Bertero L , Ricci A , Mangherini L , Garbossa D , Priego N , Bosch-Barrera J , Valiente M , Rudà R , Soffietti R
Published: October 2024

BACKGROUND

A subpopulation of reactive astrocytes (RAs) with activated signal transducer and activator of transcription 3 (STAT3) signalling in peritumoral tissue of brain metastases (BM) has been shown to favor a pro-metastatic microenvironment. High-pSTAT3 expression in RAs of BM has been correlated with a shorter intracranial progression-free survival (i-PFS) as compared with low-pSTAT3 BM. Pharmacological inhibition of the STAT3 pathway with silibinin has been suggested to be active in preliminary cohort of patients with BM.

PATIENTS AND METHODS

A new “prevention” trial has been initiated in June 2023 to investigate the efficacy of silibinin in comparison to placebo (PCB) to prevent a secondary intracranial relapse in a multicentric cohort of patients with gross-total resected BM from NSCLC and breast cancer. Inclusion criteria are as follows: histologically confirmed BM from NSCLC or BC; single BM who underwent a complete resection; systemic disease not requiring a change of antineoplastic therapy; pSTAT3 presence in RAs of peritumoral tissue confirmed by central assessment; ≥ 18 - 70 years of age; KPS ≥ 70. The primary endpoint is to demonstrate a superiority of silibinin in prolonging time to local recurrence as compared to PCB. The secondary endpoints are time to distant recurrence of BM in the brain, i-PFS, overall PFS (intracranial and/or systemic), overall survival, tolerability, quality of life. Collection of blood and CSF samples for the analysis of STAT3 downstream pathways is an exploratory objective. The sample size (70 patients) was calculated by assuming a median time to local recurrence of BM of 7.5 months for PCB (control arm) according to Mahajan [1] and ≥15 months for silibinin arm. Clinical trial information: NCT05689619 [1] Mahajan A et al. Post-operative stereotactic radiosurgery versus observation for completely resected brain metastases: a single-centre, randomised, controlled, phase 3 trial. Lancet Oncol. 2017
P17.23.B SINGLE INSTITUTION RETROSPECTIVE ANALYSIS OF COMPLICATIONS ASSOCIATED WITH SURGICAL DEBULKING OF BRAIN METASTASIS: SINGLE VS MULTIPLE LESIONS
Authors: Kannan S , Liew Y , Ray A , Hall G , Phang I , Hazra A
Published: October 2024

BACKGROUND

Surgical resection of brain metastasis is associated with complications, which worsens patient’s quality of life, resulting in oncological treatment delays and death. Surgical complication data aids decision making, leads to objective risk benefit analysis and informed consent. The aim of this study is to quantify the impact of the number of intracranial metastases on the rate and types of post-operative complications.

MATERIAL AND METHODS

Retrospective analysis on adult patients with brain metastasis, who underwent surgical debulking between 2017 and 2023 at Royal Preston Hospital. Data collected included demographics, primary tumour, number of lesions, 30-days post-operative complications, 30-days post-operative mortality and palliation, Karnofsky-Performance Score (KPS), and first vs. repeat resection. Univariate analysis carried out using R studio software.

RESULTS

Our patient cohort (n=226), 80 (35.6%) experienced post-operative complications. Top-five most common complications were Hospital-acquired pneumonia (HAP) (n=30, 13.3%), surgical site infection (SSI) (n=23, 10.2%), wound dehiscence (n=11, 4.9%), thromboembolic events (n=14,6.2%) and CSF leak (n=8, 3.5%). Average length of admission was 19.9 days (1-120) for patients with complications compared to 6.9 days (2-31) for patients without complications. Thirty (37.5%) patients with complications were readmitted. One-hundred twenty-seven patients (56.1%) had solitary lesion and 99 patients (43.9%) had multiple lesions. The most common primaries for patients with solitary lesion were lung (n=51, 40.2%), breast (n=25, 19.7%), and gastrointestinal (n=21, 16.5%). Whereas the most common primaries for multiple metastases were lung (n=41, 41.4%), breast (n=18, 18.2%), and skin (n=18, 18.2%). Amongst patients with complications, 45 (45.5%) had multiple metastases whilst 35 (27.6%) had solitary. The most common complications for patients with solitary lesion were HAP (n=10, 7.9%), SSI (n=9, 7.1%) and thromboembolism (n=8, 6.3%). Common complications for multiple lesions were HAP (n=20, 20.2%), SSI (n=14, 14.1%) and wound complications (n=10,10.1%). Patients with multiple metastases had higher 30-days post-operative palliation [(n=12) 12.1% vs (n=0) 0% solitary) and higher 30-days mortality [(n=4) 4% vs (n=4) 3.1% solitary). Multiple metastases were statistically significant for complications (p=0.005), HAP (p=0.006) and 30-days palliation (n=0.0001) but not statistically significant for SSI, 30-days mortality or thromboembolism. Conclusion: Surgical debulking is associated with significant post-operative complications, especially patients with multiple metastases with 16% either dying or not receiving any further treatment. Furthermore, 14.1% develop serious complications requiring further surgical interventions whilst 34.3% requires medical treatment.
P18.09.A CLINICAL AND MOLECULAR CHARACTERIZATION OF ADULT DIFFUSE MIDLINE GLIOMAS, H3 K27M-MUTANT
Authors: Grassl N , Suwala A , Kessler T , Etminan N , Unterberg A , Breckwoldt M , Bendszus M , Groden C , Debus J , Ehmann M , Wick W , Sahm F , Platten M , Sahm K
Published: October 2024

BACKGROUND

Diffuse midline glioma (DMG), H3 K27M-altered is a central nervous system tumor that occurs predominantly in children and young adults. They are characterized by distinct epigenetic features, whose therapeutic consequences remain ill defined.

MATERIAL AND METHODS

In this retrospective multicenter cohort study 52 adult patients with H3 K27M-mutant DMG and matched H3-wildtype glioma were characterized with respect to location, radiological features, methylation profile and clinical course.

RESULTS

DMGs were predominantly located in the thalamus, brainstem or spinal cord, but also occurred in the cerebellum and cerebral hemispheres. 35% of H3 K27M-mutant gliomas did not show contrast enhancement on MRI and only 43% had central necrosis. A third of adult H3 K27M-mutant gliomas, especially in spinal location, had distant progression resulting in shorter progression free survival (PFS). Addition of alkylating chemotherapy with temozolomide to radiotherapy did not result in prolonged PFS or overall survival (OS). A distinct methylation signature on the q arm of chromosome 15 differentiated patients with favorable OS form patients with short OS.

CONCLUSION

Adult DMGs occur throughout the CNS and are characterized by distinct epigenetic, radiological and clinical features.
P18.15.B DRUG SENSITIVITY OF RECURRENT GBM PATIENT-DERIVED ORGANOIDS CORRELATES WITH PATIENTS’ RESPONSE TO SECOND LINE CHEMOTHERAPY
Authors: Morelli M , Santonocito O , Lessi F , Franceschi S , Pieri F , Gambacciani C , Grimod G , Aquila F , Cupini S , Stasi I , Zucchi V , Giusti A , Vannozzi F , Franceschi E , Berzero G , Mazzanti C , Di Stefano A
Published: October 2024

OBJECTIVE

This study aimed to explore the correlation between the effectiveness of second-line chemotherapy in patients with recurrent glioblastoma (rGBM) who underwent a second surgery and drug treatment tests on patient-derived organoids.

METHODS

Sixteen adult patients diagnosed with IDH wild-type glioblastoma underwent a second surgery for recurrent GBM, with nine cases studied retrospectively and seven prospectively. Patient-derived 3D glioblastoma organoids (GBM-EXPs) were established from resected tumors and treated with chemotherapy agents. The response to treatment was evaluated using the NADH-FLIM method.

RESULTS

Among patients experiencing progression during first-line TMZ therapy (or within three months of discontinuation), a majority showed resistance to TMZ in the NADH-FLIM assay (p=0.02), with a longer PFS1 in TMZ-sensitive rGBM-EXPs compared to TMZ-resistant ones (15.9 versus 10.9 months; p=0.07). We did not observe different pMGMT hypermethylation between sensitive and resistant to TMZ rGBM-EXPs. Among patients treated with regorafenib in their second-line chemotherapy, those with regorafenib-sensitive rGBM-EXPs showed a significantly longer PFS2 compared to those with regorafenib-resistant organoids (PFS2 of 7.5 months versus 3.6 months respectively, p=0.04). In the prospective study, seven patients underwent ex-vivo testing before starting second-line therapy. Results from rGBM-EXP were considered by the multidisciplinary tumor board regarding second-line chemotherapy options among other clinical criteria. A trend for a longer median PFS2 was found in the prospective cohort compared to that of the retrospective cohort (7.4 vs 4.6 months, p=0.08) as well as a longer OS2 (defined as the interval from first recurrence and death/last evaluation 6.3 months versus not reached, p=0.03). pMGMT hypermethylation rate was not significantly different between the retrospective and prospective cohort. Paired analysis of specific longitudinal cases of untreated GBM-EXPs compared to rGBM-EXPs showed acquired resistance to TMZ in rGBM. The combination of TMZ and lomustine in ex-vivo testing showed better efficacy than monotherapies with TMZ and lomustine alone: mean % drug-sensitive tissue (DS%) respectively 51.4% vs 5.2% vs 35.8%, p=0.02.

CONCLUSIONS

This study shows that the sensitivity of rGBM-EXP to TMZ mirrors the timing of recurrence observed in vivo. Our findings suggest a potential role for NADH-FLIM-based drug response assessment in rGBM-EXP for predicting the efficacy of second-line therapies and improving the overall clinical outcome. Further prospective studies are warranted to validate these findings and potentially guide treatment decisions in clinical practice.
P18.45.A THE INCONSISTENT TERMINOLOGY FOR EXTENT OF RESECTION IN GLIOBLASTOMA: A SYSTEMATIC REVIEW ON SIX DECADES OF NEURO-ONCOLOGICAL STUDIES
Authors: Teske N C , Jung L B , Teske N , Thon N , Tonn J , Karschnia P
Published: October 2024

BACKGROUND

More extensive resection translates into improved outcome in patients with newly diagnosed glioblastoma. Insufficient acknowledgment of extent of resection may therefore introduce substantial bias in clinical trials. We herein aimed to systemically characterize the terminology used to describe resection in the context of neuro-oncological studies.

MATERIAL AND METHODS

A thorough review of the PubMed database was conducted to identify neuro-oncological trials between January 1966, and January 2024. Only studies which included information on extent of resection for newly diagnosed glioblastoma in adult patients were selected for our analysis. A standardized set of semantic and clinical variables was extracted for each study.

RESULTS

A total of 1862 neuro-oncological studies were screened, and 117 studies including 44 prospective interventional trials and 73 retrospective studies met our inclusion criteria. While a favorable association between outcome and more extensive resection was virtually uniformly reported, a broad range of 15 different semantic terms were used to describe the extent of resection (e.g., “complete/incomplete”, “gross-total/subtotal”, or “total/partial” resection). In line with this inconsistent terminology, only 60 studies (60/117, 51%) provided explicit definitions on how much tumor needed to be removed in order for a patient to match into a category corresponding to more extensive resection. Of these 60 studies, 17 (17/60, 28%) relied on subjective measurements including intraoperative estimations for extent of resection, while 43 studies (43/60, 72%) required objective measurements of volumetrics on pre- and post-operative imaging. There was no difference in the number of objective definitions between prospective and retrospective studies. However, the number of studies with objective definitions were significantly higher in surgical studies compared to medical neuro-oncological studies and increased over the last years (before 2010: 21%; after 2010: 41%).

CONCLUSION

The terminology used to describe the extent of resection is highly inconsistent across different clinical studies in neuro-oncology. To reduce potential imbalances between study arms and enable comparisons across different institutions, adaption of a standardized surgical nomenclature appears crucial. The recent RANO resect classification for extent of resection might form the basis for such a standardized terminology.
P19.04.B CHROMOGRANIN A IN HUMAN MENINGIOMAS
Authors: Tollefsen S E , Solheim O , Mjønes P , Torp S H
Published: October 2024

BACKGROUND

Meningiomas are the most common intracranial tumor. The neoplasms are usually benign and slow-growing, but the recurrence rates are substantial. There is currently no established pharmaceutical treatment for patients suffering from meningioma, marking the need for a further understanding of tumor biology and investigation of treatment options. Somatostatin receptors are well-known to be present in human meningiomas and somatostatin analogs are investigated as a potential targeted treatment. The presence of somatostatin receptors may suggest a possible expression of other neuroendocrine proteins in human meningiomas. The neuroendocrine glycoprotein chromogranin A is a precursor for several biologically active peptides and contributes to the intracellular formation of secretory granules. Chromogranin A is a well-established neuroendocrine differentiation marker. To our knowledge the immunohistochemical expression of chromogranin A in human meningiomas is not previously investigated. The aim of this study was to investigate neuroendocrine differentiation in human meningiomas by using chromogranin A as an immunohistochemical marker.

MATERIAL AND METHODS

The immunohistochemical expression of chromogranin A were measured in tissue specimens from 162 patients operated for primary World Health Organization 2016 classification grade 1 or 2 meningioma in the period of 1991 to 2000 at St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway. Sections were incubated for 40 minutes in room temperature with a monoclonal chromogranin A antibody (clone DAK-A3, dilution 1:100).

RESULTS

None of the 162 tissue specimens of meningioma were immunoreactive for chromogranin A.

CONCLUSION

Chromogranin A was not immunohistochemically expressed in our series of 162 meningioma specimens, thus not supporting neuroendocrine differentiation in human meningiomas. However, as other neuroendocrine peptides (such as somatostatin receptors) are previously detected in meningiomas, further investigations are needed to conclude on the matter of neuroendocrine differentiation in meningiomas.
P19.05.B CHROMOSOME 1P DELETION IS A NEGATIVE, INDEPENDENT, PROGNOSTIC FACTOR IN ATYPICAL MENINGIOMAS
Authors: Mulone D , Pedron S , Alberti S , Zanconato G , Caffo M , Barresi V
Published: October 2024

BACKGROUND

The treatment of patients with meningiomas is based on the degree of surgical excision and the tumor histological grade, which is determined according to the World Health Organization (WHO) classification of tumors of the central nervous system (CNS). Meningiomas are classified into three grades of malignancy, based on the presence of histopathological and molecular features. Grade 1 meningiomas do not require adjuvant treatment, while grade 3 tumors are generally treated with radiotherapy. For grade 2 meningiomas, which have a 50% 5-year recurrence-free survival rate and an uncertain prognosis, both radiotherapy and observation have been proposed. Consequently, identifying molecular factors that can predict the recurrence risk of grade 2 meningiomas and detect cases requiring adjuvant treatment has been a significant research issue in recent years. Several studies have found that chromosomal copy number variations, particularly the deletion of chromosome 1p, may be prognostically relevant in meningiomas. In this study, we examined 1p deletion in 79 grade 2 meningiomas of the atypical subtype and its correlation with clinico-pathological features and molecular group.

MATERIAL AND METHODS

Using Fluorescent In Situ Hybridization (FISH) and 1p36/1q25 dual color FISH probes, we analyzed 1p chromosome deletion in 79 meningiomas, which were histologically classified as atypical subtype and treated with gross total resection. Cases were classified as “1p deleted” when at least 50% of the nuclei had one signal for 1p and 2 signals for 1q. Data on recurrence-free survival (RFS) were available in 70 meningiomas. Molecular groups (MGs) were established using immunohistochemistry for MCM2 and ACADL as surrogates for proliferative and hypermetabolic MGs. Kaplan-Meier curves and the Mantel-Cox log-rank test were used to evaluate the association between 1p deletion and other clinical-pathological or molecular parameters and RFS. A chi-squared test was utilized to investigate correlations between 1p deletion and clinical-pathological features.

RESULTS

Chi-squared test revealed that 1p deletion was significantly associated with proliferative and hypermetabolic MG (P= 0.0128), mitotic index ≥6/1.6 mm2 (P= 0.0101), presence of necrosis (P= 0.0076) and recurrence (P= 0.0072). In addition, chromosome 1p deletion was significantly associated with a shorter RFS (P= 0.0196), and was an independent negative prognostic variable (P= 0.0159), along with necrosis (P= 0.0006) in multivariate analysis.

CONCLUSION

Chromosome 1p deletion, detected using FISH, is a robust negative prognostic factor, associated with high proliferation, in atypical meningiomas. Therefore, it could be used to identify cases at a higher risk of recurrence and which could benefit of adjuvant treatments.
P20.11.A DIAGNOSTIC DELAY OF PRIMARY CENTRAL NERVOUS SYSTEM LYMPHOMA (PCNSL) MAY BE CAUSED BY INFLAMMATORY DIFFERENTIAL DIAGNOSES
Authors: Beyer I , Proescholdt M , Wiesinger I , Bumes E , Haedenkamp T , Fischl A , Lee D , Koelbl O , Schmidt N O , Wendl C , Pukrop T , Mayer S , Riemenschneider M J , Linker R , Hau P
Published: October 2024

BACKGROUND

PCNSL is a rare extranodal subtype of B-cell non-Hodgkin lymphoma initially located in the central nervous system. It can only be finally diagnosed with tissue sampling. Therefore, tumor biopsy and staging examinations beforehand can delay diagnosis. Consequently, PCNSL at histological diagnosis has often already evolved for a prolonged time. However, late therapy start may worsen treatment outcomes. A clearer delineation of PCNSL-specific clinical and imaging features that leads to an earlier diagnosis might accelerate start of therapy and improve prognosis. We here performed a retrospective analysis to construct a pathway that enhances this process.

MATERIAL AND METHODS

Clinical and imaging data of patients with histologically confirmed PCNSL diagnosed between 2012 and 2022 and hospitalized in the University Hospital Regensburg, was collected retrospectively from the local clinical management systems and tumor registry. Data included demographic, prognostic and clinical data incl. neurocognitive function (NCF), neuropathological and laboratory data, and magnetic resonance imaging (MRI). Descriptive analyses and univariate and multivariate analyses were performed. Survival data was calculated using the Kaplan Meier-method.

RESULTS

A retrospective cohort of 108 patients was investigated. Median time to diagnosis (TTD) was 40 (range, 6-1,100) days and median time to hospitalization (TTH) was 14 (range, 0-700) days. Median overall survival (OS) was 20 months (range, 0.5-125+). There was no significant correlation between TTD and OS (r= 0.001, p=0.990) nor between TTD and progression free survival (PFS) (r=0.031, p=0.756). However, TTH correlated significantly to TTD (r=0.429, p<0.001). Most common symptoms at incidence were cognitive decline (N=63, 59%) and psychiatric symptoms (N=41, 38%). Together, 6% of patients had positive McDonald criteria that would have defined autoimmune disease. MRI was the diagnostic technique with the greatest variation of differential diagnoses, including primary brain tumors in 44% of patients. Abnormal memory in NCF was detected as risk factor for decreased OS (HR=3.237, CI=1.111-9.434; p=0.023) and increased TTH (partial eta squared=0.279; p=0.024).

CONCLUSION

We conclude from our data that a delayed diagnosis of PCNSL cannot be verified as a causal factor for decreased OS or PFS. The relevance of a delayed diagnosis therefore may be restricted to certain subgroups who show a more dynamic disease. In relation to this hypothesis, the positive correlation of TTH to TTD suggests, that a subgroup of PCNSL may have a less dynamic course leading to a prolonged diagnostic period. Whereas symptoms like cognitive decline and psychiatric symptoms are typical for PCNSL, typical patterns in MRI do not occur and the rate of false negative diagnoses is high.
P22.02.B ACCOMMODATING LIFE DISRUPTION: AN INTERPRETIVE EXPLORATION OF LIVING WITH LOW-GRADE GLIOMA
Authors: Legge D M , Langbecker D , Yates P
Published: October 2024

BACKGROUND

Significant treatment and resource allocation are directed towards improving the support and services for people with high-grade glioma, recognising this diagnosis brings significant care burden and high supportive care needs. People diagnosed with the less common low-grade glioma (LGG) often live for an extended period of time following diagnosis, needing to find ways to manage family, work, health, and relationships. In this study, we explored social processes these people undertake to accommodate a diagnosis of LGG.

MATERIAL AND METHODS

Symbolic interactionism was used as a lens for this work, incorporating Charmaz’s grounded theory methods to identify the social processes undertaken in accommodating LGG. Semi-structured interviews were conducted with adults diagnosed with LGG, purposively selected for their rich contribution to the data. Interviews were audio-recorded and transcribed verbatim. Data analysis occurred concurrently with interviews to enable co-construction of social processes, ensuring the emerging concepts remained grounded in the data. Concepts were confirmed through coding and constant comparison. Data analysis was managed using NVivo v11.4 software.

RESULTS

Interviews were conducted with 13 people with grades 2 and 3 glioma between June and December 2016, lasting a median of 67 (range: 52-82) minutes. Participants were from Australia, rural and urban areas, aged between 21 - 65 years with a median of 4.5 years since diagnosis. A core concept of ‘Accommodating Life Disruption’ emerged with three supporting social processes describing how people dealt with a diagnosis of LGG: 1) Dealing with contradictions; identifying the ambiguous clinical context and the language and narrative used in LGG; 2) Defining time; where LGG marks a point in time, with people taking stock of their resources and values; and 3) Re-negotiating identity; describing how people with LGG take control, make connections and go about creating a good life.

CONCLUSION

This interpretive study highlights the nuanced social processes people undertake to accommodate the diagnosis of LGG and identifies clear targets for improving supportive care resources and survivorship practices for people with LGG. The findings also offer an opportunity to consider and improve how health professionals interact and communicate the diagnosis for people with LGG and their families.
P22.03.A ASSESSING PALLIATIVE CARE APPROACHES IN NEUROONCOLOGY: INSIGHTS FROM GERMANY
Authors: Lawson McLean A , Lawson McLean A , Ernst T , Forster M , Freyschlag C , Gempt J , Goldbrunner R , Grau S , Jungk C , von Oorschot B , Rosahl S , Wedding U , Neumeister A , Senft C , Kamp M
Published: October 2024

BACKGROUND

This study aims to assess the palliative care practices across neurooncology centres in Germany, focusing on the variations in integration, timing, and involvement in tumour board discussions. By pinpointing gaps in care, it seeks to contribute to discussions on refining optimal palliative care strategies.

MATERIAL AND METHODS

Surveys were distributed to both DKG-certified neurooncology centres and non-certified university neurooncology centres in Germany to investigate their palliative care frameworks and practices. The survey examined department availability, participation in tumour boards, timing of integration, and the use of standardised screening tools for assessing palliative burden and psycho-oncological distress.

RESULTS

Out of 57 centres contacted, 46 responded (81% response rate). The findings indicate that 76.1% of centres have dedicated palliative care departments, but only 34.8% include specialists in tumour board discussions. There is notable variability in the initiation of palliative care, with early integration occurring in only 30.4% of centres at the diagnosis stage. The survey also reveals a lack of standardised spiritual care assessments and minimal use of advanced care planning. Discrepancies in documenting and treating palliative care symptoms and social complaints highlight the need for comprehensive care approaches.

CONCLUSION

This study underscores the diverse landscape of palliative care provision within German neurooncology centres and stresses the importance of standardised practices and early integration. It suggests the imperative need for developing standard protocols and guidelines to enhance the quality and uniformity of palliative care, ultimately improving patient-centred care in neurooncology.
P22.14.A REPORTING STANDARDS IN RANDOMIZED CONTROLLED TRIALS WITH FAMILY CAREGIVERS IN NEURO-ONCOLOGY: A SYSTEMATIC REVIEW FROM THE RANO-CARES WORKING GROUP
Authors: Boele F W , Hertler C , Sherwood P , Cachia D , Dirven L , Young J , Walbert T , Stockdill M , Rodriguez Almaraz E , Piil K
Published: October 2024

BACKGROUND

Family caregivers in neuro-oncology consistently report high levels of unmet support needs, yet intervention trials and effective support options are scarce. To raise the standard of caregiver-related research reporting in neuro-oncology, the Response Assessment in Neuro-Oncology (RANO-) Cares working group has been established. We investigated the current state of methodological quality of reporting on neuro-oncology caregiver outcomes in randomized controlled trials (RCTs).

MATERIAL AND METHODS

A systematic literature review (PubMed/Medline, Embase, Web of Science, Emcare, Cochrane Library, PsycINFO; July 2023) was performed to evaluate to what extent RCTs assessing outcomes of family caregivers of adult primary brain tumour patients adhere to minimum reporting standards. Using Covidence, screening and data extraction was done by two researchers independently, with a third guiding consensus. A 33-item checklist (23 applicable to secondary analysis reports) based on the International Society for Quality of Life Research (ISOQOL) criteria for patient-reported outcome (PRO) reporting was used to review each article. Risk of bias was assessed per RCT.

RESULTS

Fifteen publications (12 RCTs) included 684 neuro-oncology caregivers, with low overall risk of bias. Ten publications (66%) reported on caregiver outcomes as a primary aim, of which eight (80%) satisfied ≥2/3 of the key methodological criteria. Of the five secondary analysis reports (33%) two (40%) met ≥2/3 of applicable key criteria. Criteria often not reported adequately included sample size calculations (reported adequately in n=8, 53%), participant flow (n=9, 60%) window for data collection (n=1, 6%), and extent of (n=10, 66%), reasons for (n=9, 60%), and statistical approaches in dealing with (n=4, 26%) missing data. Unpublished outcome measures were seldom supplied as supplementary material (2/12 publications, 16%).

CONCLUSION

Whilst there are opportunities to enhance reporting standards, RCTs that include neuro-oncology caregiver outcomes generally adhere to high quality reporting standards, and have low risk of bias, indicating good potential to impact evidence-based, clinical practice.
P23.07.B POSTOPERATIVE TRAJECTORIES OF SELF-PERCEIVED COGNITIVE FUNCTION AND ASSOCIATED FACTORS IN PATIENTS WITH PRIMARY BRAIN TUMORS
Authors: Butterbrod E , Rutten G , Sitskoorn M , Gehring K
Published: October 2024

BACKGROUND

Cognitive dysfunction profoundly impacts daily lives of patients with brain tumors. Standardized tests are key to its objective assessment, but fail to fully capture patients’ experience of cognitive (dys-)function in day-to-day activities. The way in which this self-perceived cognitive function (SPCF) changes over the disease course is not clear, and limited insights into factors that contribute to SPCF trajectories hinder early risk identification and intervention. This study aimed to identify latent trajectories of SPCF and associated factors in patients with meningioma or glioma.

MATERIAL AND METHODS

Patients with meningioma or glioma reported SPCF through the Cognitive Failures Questionnaire (CFQ) as part of a neuropsychological screening within two weeks before surgery, three months post-surgery and one year post-surgery. A higher CFQ score indicated more severe complaints. An unsupervised latent class growth (LCG) model was used to identify classes of patients based on the longitudinal trajectory of their CFQ scores. For comparative purposes, a second LCG model was applied to longitudinal data with similar intervals from healthy controls (n=158). Diagnosis, sociodemographics, anxiety and depression symptomatology, general and activity-related fatigue, and the presence of cognitive impairment (Z-score <-1.5 on ≥ 1 cognitive test) before surgery were adopted as external predictors of patients’ trajectories, based on proportional classification.

RESULTS

In total, 159 patients (meningioma, n=103; glioma, n=56 [60% IDH-1 mutated]) were included based on availability of ≥2 consecutive CFQ assessments. A four-class LCG model, i.e., four distinct trajectories, showed the best fit among patients. Trajectories were interpreted as follows: a moderate complaint load showing a mild increase across each timepoint (62% of the sample), a low and stable complaint load (20%), a high load with a late increase between 3 and 12 month follow-up (11%) and a low load with a similarly late increase (8%). In controls, three trajectories with low (46%), low-moderate (31%) and moderate (23%) complaint loads existed, all of which showing a mild decrease over time. After false discovery rate correction, pre-surgical general and activity-related fatigue were related to patients’ CFQ trajectories, with stronger fatigue particularly distinguishing the two trajectories with late increases from the others.

CONCLUSION

Patients showed four distinct trajectories of SPCF up to one year after surgery. Trajectories were characterized by different, but mostly increasing, complaint loads. While similar across diagnoses, patients’ trajectories were seemingly different from those of controls. Among early factors, fatigue types seem particularly related to the course of SPCF. Potentially diverse trajectories of domain-specific complaints should be investigated.
P25.02.A GLIOBLASTOMA RESEARCH FROM 1938 TO 2021: INCREASED SURVIVAL, CHANGING TREATMENT REGIMES, AND GENDER DISPARITIES IN AUTHORSHIP
Authors: Breu J , Nenning K , Baumann B , Nam D , Woehrer A
Published: October 2024

BACKGROUND

Glioblastoma is the most common and aggressive malignant brain tumor in adults with continued poor prognosis. While the long-lasting gold standard RT-TMZ was eventually refined by incorporating tumor treating fields as well as lomustine for subsets of patients, patient outcomes showed only modest improvements over the decades. Here, we set out to map patient outcomes according to type of study, treatment approach and publication year. Additionally, we explore geographic origin and sex differences in authorship per study type to track disparities in glioblastoma research.

MATERIAL AND METHODS

We conducted a systematic literature search using the terms “glioblastoma” AND “overall survival” at PubMed.gov. We manually reviewed 20,047 articles from 1938 to 2021 and included 2,232 ones that reported median overall survival for human subjects. Study type was categorized as case series, clinical trials (CTs), randomized controlled trials (RCTs), meta-analysis and population-based studies. For each study, treatment, number of subjects, and authorship details were extracted.

RESULTS

65.5% of articles were case series followed by 23.9% CTs. Overall, median OS was 13.1 months for all studies and increased from 11.3 months in 1938-2000 to 14.3 months in 2001-2021. Population-based studies reported the lowest median OS (9.0 months). Survival increases were similar for studies reporting radiotherapy (r=0.32), chemotherapy (r=0.27) and temozolomide (r=0.20). No significant survival increases were observed in studies reporting targeted therapies (r=0.22), tumor treating fields (r=0.23), bevacizumab (r=0.02) and immunotherapies (r=-0.10). Despite making up only 5.6% of all studies, RCTs had the highest cumulative impact factor and citation count. While US-based researchers dominated across all study types, 25.2% of articles were authored by females as first and 18.5% as last authors. Only for meta analysis, gender parity seemed to be achieved in first authorship (46.2% female first). Women continued to be under-represented, particularly as last authors in range from 15.4% to 22.5% across study types.

CONCLUSION

Almost 100 years of reported survival of patients with glioblastoma document a consistent, but slow increase in survival, with overly optimistic survival reported in non-population-based studies. Research by women as first authors shows an upward trend, although gender equality has not been achieved yet, particularly in last authorship.
P27.08.B EVALUATING THE SURVIVAL OUTCOMES OF REPEAT SURGICAL RESECTIONS FOR RECURRENT PRIMARY BRAIN TUMOURS: A RETROSPECTIVE ANALYSIS
Authors: choudhury M , Harris L , Sioftanos G , Vaqas B
Published: October 2024

BACKGROUND

Primary brain tumours (PBTs), particularly Glioblastoma Multiforme (GBM), are known for their aggressive nature and poor prognosis. This study evaluates the survival outcomes of patients undergoing repeat resections for PBTs at a tertiary neurosurgical centre.

MATERIAL AND METHODS

We conducted a retrospective analysis of consecutive cases of repeat surgical resections for PBTs from January 2000 to August 2022. Data included patient demographics, initial and subsequent treatments, and survival times up to August 31, 2023. Kaplan-Meier estimates were used to analyse survival rates and progression times from both initial and repeat surgeries.

RESULTS

The median follow-up (FUP) was 72.5 months. During this period 18 patients had a repeat resection (RR). 61% (11) were male. 10, 3 and 5 patients had confirmed GBM, G3 and G2 astrocytoma respectively. Postoperatively, 8/10 GBM patients completed 60Gy in 30 of concurrent chemo-radiotherapy (CRT) and one received 40Gy in 15 alone. 1 GBM patient was deemed too frail for Radiotherapy (RT). 8/10 went on to receive Temozolomide (TMZ). 5/10 of these had a positive MGMT status (>1-25%). The median time on TMZ before progression was 6 months. All G3 patients and 3/5 G2 patients completed postoperative RT following initial surgery. Median progression time following initial surgery was 12 months (IQR: 8.5), 97 months (IQR: 29.5) and 95 months (IQR: 45) for GBM, G3 and G2 astrocytoma respectively. The median time between initial and repeat resection (RR) was 13, 98 and 95 months for GBM, G3 and G2 astrocytoma respectively. Following RR one G3 and G2 cases was upgraded to a GBM and G3 diagnosis. 7/10 GBM and all G3 patients were fit enough to receive further chemotherapy following RR. 2/5 G2 patients who were RT naive received RT with receiving further chemotherapy post-RR. During the FUP period 7/10, 2/3, 2/5 GBM, G3, G2 patients died. Median OS from initial surgery was 21, 181 and 97 months with Median OS from RR 8, 85 and 29 months for GBM, G3 and G2 astrocytoma respectively.

CONCLUSION

Repeat resections may provide a survival benefit in a highly selective group of patients, particularly in the GBM cohort, where outcomes were favourable compared to published real-world population data. Repeat surgical resection is well-tolerated and could be considered as part of the management strategy for recurrent PBTs, especially in the context of prolonged survival observed in G3 and G2 astrocytoma cases.
P27.17.B PRIMARY CNS LYMPHOMA IN YOUNGER PATIENTS: ANALYSIS OF A MONOCENTRIC COHORT RECEIVING THE MODIFIED BONN PROTOCOL AS PRIMARY THERAPY
Authors: Zeyen T , Weller J , Schneider M , Potthoff A , Schaub C , Röver L , Herrlinger U , Schäfer N
Published: October 2024

BACKGROUND

Polychemotherapy based on high-dose methotrexate (HD-MTX) is generally regarded ad standard therapy for newly diagnosed, younger patients with primary CNS lymphoma (PCNSL). Combination partners for HD-MTX vary between protocols (rituximab, ifosfamid (IFO), cytarabine (AraC), thiotepa (TT)). The type of consolidation therapy is even more variable (whole brain radiotherapy, high-dose therapy with stem cell rescue (HD-ASCT), continuation of standard-dose chemotherapy +/- intrathecal therapy). Successfull protocols are associated with a long-term survival (>5years) rate of substantially more than 50%. We here report the retrospective analysis of our monocentric cohort treated with the modified Bonn protocol.

MATERIAL AND METHODS

All consecutive patients aged <65 years who were newly diagnosed with PCNSL between 2012-2021 and recieved at least 1 cycle of the modified Bonn protocol as first-line therapy were included in this retrospective analysis. The modified Bonn protocol comprised 3 courses of rituximab/HD-MTX/IFO, implantation of an intraventricular catheter followed by consolidation therapy with 2 courses of HD-AraC and 2 courses of HD-MTX/IFO including intrathecal MTX and AraC in each course. Progression-free survival and overall survival were evaluated.

RESULTS

Forty patients with a median age of 58 years (range 38-64) and a median KPS of 80% (range 30-100) were included. Twenty-three patients (57.5%) had multiple cerebral lesions. Thirty-eight patients (95%) reached intrathecal consolidation therapy and 36 (90%) completed all seven courses of therapy. Grade 3/4 toxicity (CTCAE v5) was observed in 21 patients (52.5%); among those, nine had an infection grade 3/4 (22.5%). After a median follow-up (mFU) of 54.7 months (IQR 25-99.5 months), the median progression-free survival was 102.8 months (95%CI 0-211.5) and the 2-year progression-free survival rate was 55%. The 5-year overall survival rate was 80% (median not reached). Sixteen patients developing refractory/relapsed PCNSL received second line therapy using the modified Freiburg protocol (AraC/TT +/- HD-MTX/rituximab followed by HD-ASCT). A second relapse has been observed in 6 of these 16 patients so far (mFU 48.7 months).

CONCLUSION

First line treatment of PCNSL with the modified Bonn protocol is highly effective. Overall survival rates compare well with other seemingly more toxic PCNSL protocols in younger patients. In patients with relapsed/refractory disease, second line therapy according to the modified Freiburg protocol appears to be affective.
Increased access to pediatric specialist healthcare using eConsult: A retrospective observational cohort and case–control study
Authors: Lai Lillian , Roubos Sophia , Radhakrishnan Dhenuka , Benchimol Eric I , Wang Xuesong , Matai Lavina , Keely Erin , Liddy Clare , Murto Kimmo
Published: October 2024

Objectives

Primary care practitioners (PCPs) report that using the Champlain BASE™ eConsult service (eConsult) averts one-third of face-to-face (FTF) specialist referrals, however, there are concerns about duplication of services and adverse patient outcomes. Following an eConsult, we evaluated patient healthcare utilization and associated treatment costs.

Methods

Retrospective cohort study (2014 to 2018) of patients (<18 years old) for whom an eConsult visit averted a FTF specialist referral. Patients were linked to provincial health administrative databases and hospital electronic medical records for healthcare use for the same diagnosis and specialty for the 18 months following the eConsult. Concurrently, a retrospective case–control study compared utilization and costs between an eConsult versus a matched FTF visit for the same diagnosis. We also assessed PCP satisfaction.

Results

In follow-up, <5% of the study cohort of eConsult patients (n = 242) later accessed the healthcare system for the identical diagnosis and specialty type. FTF visits generate more frequent outpatient visits (12.6 times more [95% CI: 2.28 to 69.66, P = 0.002]) and higher costs compared to eConsult visits. There were no hospital admissions or deaths in patients with eConsult. PCPs (98%) described eConsult as an excellent service.

Conclusions

Using eConsult is associated with <5% of patients subsequently having a FTF visit for the same reason. Matched FTF visits generated more healthcare utilization and higher costs compared with eConsult. eConsult in pediatrics is safe and can minimize FTF specialist visits in elective cases and increase capacity, towards a more efficient and cost-effective healthcare system.
Curvature-directed anchoring and defect structure of colloidal smectic liquid crystals in confinement
Authors: Jull Ethan I L , Campos-Villalobos Gerardo , Tang Qianjing , Dijkstra Marjolein , Tran Lisa
Published: October 2024

Rod-like objects at high packing fractions can exhibit liquid crystalline ordering. By controlling how the rods align near a boundary, i.e. the anchoring, the defects of a liquid crystal can be selected and tuned. For smectic phases, the rods break rotational and translational symmetry by forming lamellae. Smectic defects thereby include both discontinuities in the rod orientational order (disclinations), as well as in the positional order (dislocations). In this work, we use experiments and simulations to uncover the geometrical conditions necessary for a boundary to set the anchoring of a confined, particle-resolved, smectic liquid crystal. We confine a colloidal smectic within elliptical wells of varying size and shape for a smooth variation of the boundary curvature. We find that the anchoring depends upon the local boundary curvature, with an anchoring transition observed at a critical radius of curvature approximately twice the rod length. Surprisingly, the critical radius of curvature for an anchoring transition holds across a wide range of rod lengths and packing fractions. The anchoring controls the defect structure. By analyzing topological charges and networks composed of maximum density (rod centers) and minimum density (rod ends), we quantify disclinations and dislocations formed with varying confinement geometry. Circular confinements, characterized by planar anchoring, promote disclinations, whereas elliptical confinements, featuring antipodal regions of homeotropic anchoring, promote long-range smectic order and dislocations. Our findings demonstrate how geometrical constraints can control the anchoring and defect structures of liquid crystals—a principle that is applicable from molecular to colloidal length scales.