Short-term outcomes associated with temozolomide or PCV chemotherapy for 1p/19q-codeleted WHO grade 3 oligodendrogliomas: a national evaluation

Background The optimal chemotherapy regimen between temozolomide and procarbazine, lomustine, and vincristine (PCV) remains uncertain for W.H.O. grade 3 oligodendroglioma (Olig3) patients. We therefore investigated this question using national data. Methods Patients diagnosed with radiotherapy-treated 1p/19q-codeleted Olig3 between 2010-2018 were identified from the National Cancer Database. The OS associated with first-line single-agent temozolomide vs. multi-agent PCV was estimated by Kaplan-Meier techniques and evaluated by multivariable Cox regression. Results 1,596 radiotherapy-treated 1p/19q-codeleted Olig3 patients were identified: 88.6% (n=1,414) treated with temozolomide and 11.4% (n=182) with PCV (from 5.4% in 2010 to 12.0% in 2018) in the first-line setting. The median follow-up was 35.5 months (interquartile range [IQR] 20.7-60.6 months) with 63.3% of patients alive at time of analysis. There was a significant difference in unadjusted OS between temozolomide (5yr-OS 58.9%, 95%CI: 55.6-62.0) and PCV (5yr-OS 65.1%, 95%CI: 54.8-73.5; p=0.04). However, a significant OS difference between temozolomide and PCV was not observed in the Cox regression analysis adjusted by age and extent of resection (PCV vs. temozolomide HR 0.81, 95%CI: 0.59-1.11, p=0.18). PCV was more frequently used for younger Olig3s, but otherwise was not associated with patient’s insurance status or care setting. Conclusions In a national analysis of Olig3s, first-line PCV chemotherapy was associated with a slightly improved unadjusted short-term OS compared to temozolomide; but not following adjustment by patient age and extent of resection. There has been an increase in PCV utilization since 2010. These findings provide preliminary data while we await the definitive results from the CODEL trial.

Primary Central Nervous System Lymphoma: A Real-World Comparison of Therapy Access and Outcomes by Hospital Setting

Background This study analyzes sociodemographic barriers for primary CNS lymphoma (PCNSL) treatment and outcomes at a public safety-net hospital versus a private tertiary academic institution. We hypothesized that these barriers would lead to access disparities and poorer outcomes in the safety-net population. Methods We reviewed records of PCNSL patients from 2007-2020 (n = 95) at a public safety-net hospital (n = 33) and a private academic center (n = 62) staffed by the same university. Demographics, treatment patterns, and outcomes were analyzed. Results Patients at the safety-net hospital were significantly younger, more commonly Black or Hispanic, and had a higher prevalence of HIV/AIDS. They were significantly less likely to receive induction chemotherapy (67% vs 86%, p = 0.003) or consolidation autologous stem cell transplantation (0% vs. 44%, p = 0.001), but received more whole-brain radiation therapy (35% vs 15%, p = 0.001). Younger age and receiving any consolidation therapy were associated with improved progression-free (PFS, p = 0.001) and overall survival (OS, p = 0.001). Hospital location had no statistical impact on PFS (p = 0.725) or OS (p = 0.226) on an age-adjusted analysis. Conclusions Our study shows significant differences in treatment patterns for PCNSL between a public safety-net hospital and an academic cancer center. A significant survival difference was not demonstrated, which is likely multifactorial, but likely was positively impacted by the shared multidisciplinary care delivery between the institutions. As personalized therapies for PCNSL are being developed, equitable access including clinical trials should be advocated for resource-limited settings.

Convection-enhanced delivery for high-grade glioma

Glioblastoma (GBM) is the most common adult primary malignant brain tumor and is associated with a dire prognosis. Despite multi-modality therapies of surgery, radiation, and chemotherapy, its 5-year survival rate is 6.8%. The presence of the blood-brain barrier (BBB) is one factor that has made GBM difficult to treat. Convection-enhanced delivery (CED) is a modality that bypasses the BBB, which allows the intracranial delivery of therapies that would not otherwise cross the BBB and avoids systemic toxicities. This review will summarize prior and ongoing studies and highlights practical considerations related to clinical care to aid providers caring for a high-grade glioma patient being treated with CED. Although not the main scope of this paper, this review also touches upon relevant technical considerations of using CED, an area still under much development.

Metabolic risk factors in NZ Glioblastoma cohort 2005-2020: A retrospective analysis

Background Glioblastoma multiforme (GBM) is the most aggressive form of glioma. There is growing recognition that mitochondrial metabolism plays a role in cancer development. Metabolic syndrome is a risk factor for several cancers; however, the prevalence in GBM patients in New Zealand (NZ) is unknown. We hypothesised that patients with GBM would show a higher prevalence of metabolic syndrome compared to the general NZ population and that metabolic syndrome may be associated with worsened overall survival (OS) in GBM. Methods We performed a retrospective analysis in 170 patients diagnosed and treated for GBM between 2005-2020. Clinical and biochemical data were collected with regards to five metabolic criteria. OS was determined from the date of initial surgical diagnosis to the date of death or date of data acquisition. Results 31 (18.2%) of GBM patients met the diagnostic criteria for metabolic syndrome. The prevalence of metabolic syndrome in our cohort did not significantly differ from that of the general NZ population. However, OS in patients with metabolic syndrome was significantly worse compared to patients without metabolic syndrome [8.0 vs 13.0 months, P = 0.016]. Patients who received a lower dexamethasone dose had significantly better survival outcomes (15.0 vs 5.0 months, P < 0.01). Differences in OS did not differ by gender or ethnicity. Conclusions We have shown that metabolic syndrome is associated with reduced OS in a New Zealand cohort of GBM patients. This finding further strengthens the possibility that a metabolic pathogenesis may underpin GBM. However, prospective clinical trials are needed.

Long-term impact of adult WHO grade II or III gliomas on health-related quality of life: a systematic review

Background Glioma diagnosis can be devastating and result in a range of symptoms. Relatively little is known about the long-term health-related quality of life (HRQOL) challenges faced by these patients. Establishing the impact of diagnosis on HRQOL could help positively tailor clinical decision making regarding patient support and treatment. The aim of this review is to identify the long-term HRQOL issues reported at least two years following diagnosis of WHO grade II/III glioma. Method Systematic literature searches were carried out using Medline, EMBASE, CINAHL, PsycINFO, and Web of Science Core Collection. Searches were designed to identify patient self-reports on HRQOL aspects defined as physical, mental or social issues. Quality assessment was conducted using the Mixed Methods Appraisal Tool (MMAT). Narrative synthesis was used to collate findings. Results The search returned 8923 articles. 278 titles remained after title and abstract screening, with twenty-one full text articles included in the final analysis. The majority of studies used quantitative methods, with three articles reporting mixed methodology. Negative emotional/psychological/cognitive changes were the most commonly reported. Physical complaints included fatigue, seizures and restricted daily activity. Social challenges included strained social relationships and financial problems. Patient coping strategies were suggested to influence patient’s survival quality. Conclusion The consequences of a glioma diagnosis and treatment can have substantial implications for patients’ long-term HRQOL and daily functioning. Findings from this review lay the groundwork for efforts to improve patient HRQOL in long-term survivorship.

Classical and disease-specific quality indicators in glioma surgery – Development of a quality checklist to improve treatment quality in glioma patients

Background There is a pressing demand for more accurate, disease-specific quality measures in the field of neurosurgery. Aiming at most adequately measuring and reflecting the quality of glioma therapy, we developed a novel quality indicator bundle in form of a checklist for all patients that are treated operatively for glioma. Methods On the basis of possible glioma-specific quality indicators retrieved from the literature and quality guidelines, a multidisciplinary team developed a checklist containing 13 patient-need-specific outcome measures. Subsequently, the checklist was prospectively applied to a total of 78 patients compared with a control group consisting of 322 patients. A score was generated based on the maximum of quality measures achieved. Results Significant improvements in quality after prospectively introducing the checklist were achieved for supplemental physical and occupational therapy during inpatient stay (89.4% vs. 100%, p= 0.002), consultation of a social worker during inpatient stay (64% vs. 92.3%, p< 0.001), psycho-oncological screening (14.3% vs. 70.5%, p< 0.001), psycho-oncological consultation (31.1% vs. 82.1%, p< 0.001), and consultation of the palliative care team (20% vs. 40%, p= 0.031). Overall, after introduction of the checklist one third (n= 23) of patients reached best-practice measures in all categories, and over half of the patients (n= 44) achieved above 90% with respect to the outcome measures. Conclusions Aiming at ensuring comprehensive, consistent and timely care of glioma patients the implementation of the checklist for routine use in glioma surgery represents an efficient, easily reproducible and powerful tool for significant improvements.

Frequency, etiologies, risk factors, and sequelae of falls among patients with brain metastases: a population- and institutional-level analysis

Background Falls in patients with cancer harbor potential for serious sequelae. Patients with brain metastases (BrM) may be especially susceptible to falls but supporting investigations are lacking. We assessed the frequency, etiologies, risk factors, and sequelae of falls in patients with BrM using two data sources. Methods We identified 42,648 and 111 patients with BrM utilizing Surveillance, Epidemiology, and End Results (SEER)-Medicare data (2008-2016) and Brigham/Dana Farber (BWH/DFCI) institutional data (2015), respectively, and characterized falls in these populations. Results Among SEER-Medicare patients, 10,267 (24.1%) experienced a fall that prompted medical evaluation, with cumulative incidences at 3, 6, and 12 months of 18.0%, 24.3%, and 34.1%, respectively. On multivariable Fine/Gray’s regression, older age (>81 or 76-80 vs. 66-70 years, hazard ratio [HR] 1.18 [95% CI, 1.11-1.25], p<0.001 and HR 1.10 [95% CI, 1.04-1.17], p<0.001, respectively), Charlson comorbidity score of >2 vs. 0-2 (HR 1.08 [95% CI, 1.03-1.13], p=0.002) and urban residence (HR 1.08 [95% CI, 1.01-1.16], p=0.03) were associated with falls. Married status (HR 0.94 [95% CI, 0.90-0.98], p=0.004) and Asian vs. white race (HR 0.90 [95% CI, 0.81-0.99], p=0.03) were associated with reduced fall-risk. Identified falls were more common among BWH/DFCI patients (N=56, 50.4% of cohort), resulting in emergency department visits, hospitalizations, fractures, and intracranial hemorrhage in 33%, 23%, 11%, and 4% of patients, respectively. Conclusions Falls are common among patients with BrM, especially older/sicker patients, and can have deleterious consequences. Risk-reduction measures, such as home safety checks, physical therapy, and medication optimization, should be considered in this population.

Prescription preferences of antiepileptic drugs in brain tumor patients: an international survey among EANO members

Background This study aimed at investigating antiepileptic drug (AED) prescription preferences in patients with brain tumor-related epilepsy (BTRE) among the European neuro-oncology community, the considerations that play a role when initiating AED treatment, the organization of care, and practices with regard to AED withdrawal. Methods A digital survey containing 31 questions about prescription preferences of AEDs was set out among members of the European Association of Neuro-Oncology (EANO). Results A total of 198 respondents treating patients with BTRE participated of whom 179 completed the entire survey. Levetiracetam was the first choice in patients with BTRE for almost all respondents (90% [162/181]). Levetiracetam was considered the most effective AED in reducing seizure frequency (72% [131/181]) and having the least adverse effects (48% [87/181]). Common alternatives for levetiracetam as equivalent first choice included lacosamide (33% [59/181]), lamotrigine (22% [40/181]), and valproic acid (21% [38/181]). Most crucial factors to choose a specific AED were potential adverse effects (82% [148/181]) and interactions with antitumor treatments (76% [137/181]). In the majority of patients neuro-oncologists were involved in the treatment of seizures (73% [132/181])). Other relevant findings were that a minority of respondents ever prescribe AEDs in brain tumor patients without epilepsy solely as prophylaxis (29% [53/181]), but a majority routinely considers complete AED withdrawal in BTRE patients who are seizure free after antitumor treatment (79% [141/179]). Conclusions Our results show that among European professionals treating patients with BTRE levetiracetam is considered the first choice AED, with the presumed highest efficacy and least adverse effects.