High-grade glioma case series

120 patients who were hospitalized in the Department of Neurosurgery, Renmin Hospital, Shiyan from January 2018 to January 2021 were selected and then divided into a control and a study group using the random number table method, with 60 cases in each group. To compare the clinical efficacy of patients in both groups, neuronavigation microsurgery was used in the control group and neuronavigation microsurgery combined with Fluorescein sodium guided resection of high-grade glioma

The Gross Total Resection Rate (GTRR) of the study group was significantly higher than that of the control group. There was no significant difference in intraoperative bleeding loss or hospital stay between the two groups, and the study group had a much shorter operation time than the control group. The Karnofsky Performance Score (KPS) and the National Institutes of Health Stroke Scale (NIHSS) scores did not significantly differ between the two groups prior to surgery but declined significantly in the study group compared to the control group following treatment. In terms of adverse effects, there was no significant difference between the two groups. In the control group, the median progression-free survival (PFS) was 7.5 months, and the median overall survival (OS) was 9.6 months, whereas in the study group, the median PFS was 9.5 months, and the median OS was 11.5 months. PFS did not significantly differ between the two groups (HR=1.389, 95% CI=0.926-2.085, p=0.079); however, OS was significantly higher in the study group compared to the control group (HR=1.758, 95% CI=1.119-2.762, p=0.013).

Fluorescein-guided microsurgery can dramatically improve total resection rate, postoperative neurological functional status, and overall survival with higher efficacy and safety in patients with high-grade gliomas ¹⁾.

Patients with DHGGs, who received prophylactic anticonvulsant for three months following surgery, were enrolled into the study. The patients were assigned randomly into training (n = 166) and validation (n = 42) cohorts. Differentially expressed genes (DEGs) were identified based on preoperative glioma-related epilepsy (GRE) history. Least absolute shrinkage and selection operator (LASSO) logistic regression analysis was used to construct a predictive gene-signature for the occurrence of postoperative seizures. The final integrated prediction model was generated using the gene-signature and clinical data. Receiver operating characteristic analysis and calibration curve method were used to evaluate the accuracy of the gene-signature and prediction model using the training and validation cohorts.

Results: A seven-gene signature for predicting the occurrence of postoperative seizures was developed using LASSO logistic regression analysis of 623 DEGs. The gene-signature showed satisfactory predictive capacity in the training cohort [area under the curve (AUC) = 0.842] and validation cohort (AUC = 0.751). The final integrated prediction model included age, temporal lobe involvement, preoperative GRE history, and gene-signature-derived risk score. The AUCs of the integrated prediction model were 0.878 and 0.845 for the training and validation cohorts, respectively.

Conclusion: We developed an integrated prediction model for the occurrence of postoperative seizures in patients with DHGG using clinical and RNA-Seq data. The findings of this study may contribute to the development of personalized management strategies for patients with DHGGs and improve our understanding of the mechanisms underlying GRE in these patients ²⁾.

Between 2001 and 2021, 52 patients underwent re-irradiation for a diagnosis of recurrent high-grade glioma. 36 patients (69.2%) had a histologic diagnosis of glioblastoma at the time of re-irradiation. The median BED10 (biological equivalent dose 10 Gy) of re-irradiation was 53.1 Gy. Twenty-one patients (40.4%) received concurrent bevacizumab with re-irradiation. Median survival for the entire cohort and for glioblastoma at the time of recurrence patients was 6.7 months and 6.0 months, respectively. For patients with glioblastoma at the time of recurrence, completing re-irradiation (HR 0.03, P < .001), use of concurrent bevacizumab (HR 0.3, P = .009), and the BED10 (HR 0.9, P = .005) were predictive of overall survival. Nine patients developed grade 3-5 toxicity; of these, 2 received concurrent bevacizumab and 7 did not (P = .15).

High-dose re-irradiation with concurrent bevacizumab is feasible in patients with recurrent gliomas. Concurrent bevacizumab and increasing radiation dose may improve survival in patients with recurrent glioblastoma ³⁾.

120 High-grade glioma patients admitted to Zibo Central Hospital. (January 2019-January 2020) were chosen as the research objects and were randomly divided into group A (n = 60) and group B (n = 60). All patients were treated with radiotherapy, and patients in group A were additionally treated with temozolomide. The clinical efficacy, quality of life, incidence of adverse reactions, incidence of postoperative complications, survival rates, and average survival time of the two groups were compared. The objective remission rate (ORR), disease control rate (DCR), survival rates after one year and two years of follow-up, and the number of patients with improved quality of life in group A were markedly higher compared with group B (P < 0.05). The incidence of postoperative complications in group A was remarkably lower compared with group B (P < 0.05). The average survival time of group A was dramatically longer compared with group B (P < 0.001). There was no significant difference in the incidence of adverse reactions between the two groups (P > 0.05), and no new adverse reactions occurred in the patients. Temozolomide combined with radiotherapy can effectively improve the quality of life, treatment effect, and survival rate of MG patients, with a lower incidence of postoperative complications and better tolerance. The finding indicates that temozolomide combined with radiotherapy has a high clinical application value. In addition, it indicates that this treatment method should be promoted in practice ⁴⁾.

In a longitudinal multi-methods study, adult patients with high-grade glioma (n = 17) and their family caregivers (n = 16) completed a 4-day residential program and a 2-day follow-up program 3 months later. Participants completed questionnaires after each program, scoring relevance and satisfaction on a 5-point Likert scale. Qualitative data were collected during four evaluation group interviews with patients and caregivers.

The mean overall satisfaction score was 4.80 (standard deviation [SD], 0.55) for the initial 4-day program and 4.28 (SD, 0.83) for the follow-up program. Three themes emerged in the evaluation group interviews: (1) meeting peers strengthen social well-being, (2) the value of information and focusing on individual needs, and (3) accepting life as an unpredictable passage.

Participants found completing the REHPA-HGG program feasible and rated all sessions highly for relevance and satisfaction. Qualitative findings confirm the value of individualized information, acceptance, and peer interactions.

A multimodal rehabilitative palliative care program addressed unmet patient and caregiver needs. Peer-to-peer interventions for family caregivers may address individual support needs. Similar programs may maximize the benefit by avoiding planned behavior changes and enhancing palliative approaches ⁵⁾.

Outcomes in children and adolescents with recurrent or progressive high-grade glioma are poor, with a historical median overall survival of 5.6 months. Pediatric high-grade gliomas are largely immunologically silent or “cold,” with few tumor-infiltrating lymphocytes. Preclinically, pediatric brain tumors are highly sensitive to oncolytic virotherapy with genetically engineered herpes simplex virus type 1 (HSV-1) G207, which lacks genes essential for replication in normal brain tissue.

Friedman et al. conducted a phase 1 trial of G207, which used a 3+3 design with four dose cohorts of children and adolescents with biopsy-confirmed recurrent or progressive supratentorial brain tumors. Patients underwent stereotactic placement of up to four intratumoral catheters. The following day, they received G207 (107 or 108 plaque-forming units) by controlled-rate infusion over a period of 6 hours. Cohorts 3 and 4 received radiation (5 Gy) to the gross tumor volume within 24 hours after G207 administration. Viral shedding from saliva, conjunctiva, and blood was assessed by culture and polymerase-chain-reaction assay. Matched pre-and post-treatment tissue samples were examined for tumor-infiltrating lymphocytes by immunohistologic analysis.

Twelve patients 7 to 18 years of age with high-grade glioma received G207. No dose-limiting toxic effects or serious adverse events were attributed to G207 by the investigators. Twenty grade 1 adverse events were possibly related to G207. No virus shedding was detected. Radiographic, neuropathological, or clinical responses were seen in 11 patients. The median overall survival was 12.2 months (95% confidence interval, 8.0 to 16.4); as of June 5, 2020, a total of 4 of 11 patients were still alive 18 months after G207 treatment. G207 markedly increased the number of tumor-infiltrating lymphocytes.

Intratumoral G207 alone and with radiation had an acceptable adverse-event profile with evidence of responses in patients with recurrent or progressive pediatric high-grade glioma. G207 converted immunologically “cold” tumors to “hot.” (Supported by the Food and Drug Administration and others; ClinicalTrials.gov number, NCT02457845.) ⁶⁾.

Kwon et al. retrospectively reviewed the medical records of patients with HGG (World Health Organization grade III or IV) between 2004 and 2019, and patients with primary leptomeningeal seeding (PLS) at the initial diagnosis were enrolled in the study. Clinical features, such as the location of leptomeningeal seeding, surgical methods, and degree of resection, were sorted based on electronic medical records also containing performance scale, and hematological and serological evaluations. Radiological findings and immunohistochemical categories were confirmed. Furthermore, they sought to determine whether controlling intracranial pressure (ICP) via early cerebrospinal fluid (CSF) diversion increases overall survival (OS) after the initial diagnosis.

Of the 469 patients with HGG in our institution, less than 2% had PLS at the initial diagnosis. Most patients suffered from headache, diplopia, and dizziness. Pathological findings included 7 glioblastomas and 2 anaplastic astrocytomas. Seven of the 9 patients underwent CSF diversion. All patients were administered concurrent chemoradiotherapy (CCRT) with temozolomide, 89% of which started adjuvant temozolomide and 33% of which completed the six cycles of adjuvant temozolomide. The OS of patients with HGG and PLS was 8.7 months (range, 4-37), an extremely poor result compared to that of other studies. Also, the 1-year and 2-year OS rates were 44.4% and 16.7%, respectively.

Diagnosis and treatment of high-grade glioma with leptomeningeal seeding (PLS) are challenging. Aggressive control of ICP followed by early initiation of standard concurrent chemoradiotherapy (CCRT) seems to be helpful in improving symptoms. However, despite aggressive treatment, the prognosis is poor. A multicenter trial and research may be necessary to create a standardized protocol for this disease ⁷⁾.

Renovanz et al. used baseline data of a prospective study where High-grade glioma (HGG) patients were enrolled from 4 hospitals. Distress was measured using the distress thermometer (DT), HRQoL using the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Core Questionnaire (QLQ-C30) plus brain module (BN20). We compared distress and HRQoL by age (≥ 65 vs. < 65 years), gender, performance score, and time since diagnosis using multivariate linear and logistic regressions.

A total of n = 93 (30%) out of n = 309 patients were ≥ 65 years (mean 70 years, range 65-86 years). Mean DT score of elderly patients (5.2, SD 2.6) was comparable with younger patients (4.9, SD 2.6). Elderly patients reported significantly lower global health (GHS, mean elderly vs. younger; 50.8 vs. 60.5, p = 0.003), worse physical (56.8 vs. 73.3, p < 0.001) and lower cognitive functioning (51.1 vs. 63.2, p = 0.002), worse fatigue (52.5 vs. 43.5, p = 0.042), and worse motor dysfunction (34.9 vs. 23.6, p = 0.030). KPS and not age was consistently associated with HRQoL.

Physical functioning was significantly reduced in the elderly compared with younger HGG patients, and at the same time, emotional functioning and DT scores were comparable. KPS shows a greater association with HRQoL than with calendric age in HGG patients reflecting the particular importance for adequate assessment of HRQoL and general condition in elderly patients ⁸⁾.

Hwang et al. investigated the efficacy of temozolomide during and after radiotherapy in Korean adults with anaplastic gliomas without 1p/19q co-deletion.

This was a randomized, open-label, phase 2 study and notably the first multicenter trial for Korean grade III glioma patients. Eligible patients were aged 18 years or older and had newly diagnosed non-co-deleted anaplastic glioma with an Eastern Cooperative Oncology Group performance status of 0-2. Patients were randomized 1:1 to receive radiotherapy alone (60 Gy in 30 fractions of 2 Gy) (control group, n=44) or to receive radiotherapy with concurrent temozolomide (75 mg/m2/day) followed by adjuvant temozolomide (150-200 mg/m2/day for 5 days during 6 28-day cycles) (treatment group, n=40). The primary endpoint was 2-year progression-free survival (PFS). Seventy patients (83.3%) were available for the analysis of the isocitrate dehydrogenase 1 gene (IDH1) mutation status.

The two-year PFS was 42.2% in the treatment group and 37.2% in the control group. Overall survival (OS) did not reach to significant difference between the groups. In multivariable analysis, age was a significant risk factor for PFS (hazard ratio [HR], 2.08; 95% confidence interval [CI], 1.04 to 4.16). The IDH1 mutation was the only significant prognostic factor for PFS (HR, 0.28; 95% CI, 0.13 to 0.59) and OS (HR, 0.19; 95% CI, 0.07 to 0.50). Adverse events over grade 3 were seen in 16 patients (40.0%) in the treatment group and were reversible.

Concurrent and adjuvant temozolomide in Korean adults with newly diagnosed non-co-deleted anaplastic gliomas showed improved 2-year PFS. The survival benefit of this regimen needs further analysis with long-term follow-up at least more than 10 years ⁹⁾.

Twenty-three patients with high-grade gliomas were retrospectively analyzed. White et al., measured the perfusion at the resection area and evaluated the presence or absence of the restricted diffusion in residual tumor masses. The associations of the perfusion, diffusion and contrast enhancement (delayed static enhancement (DSE)) characteristics with time to tumor progression were statistically calculated. White et al., also evaluated if the location of the tumor progression was concordant to the areas of the elevated perfusion, tumor type restricted diffusion and enhancement.

Patients with >200 days to progression are more likely to have no elevated relative cerebral blood volume (rCBV) ratio (p = 0.0004), no tumor restriction (p = 0.024), and no DSE (p = 0.052). The elevated mean rCBV ratio (p<0.001) and tumor type restricted diffusion (p = 0.002) were significantly associated with a higher risk of progression. All cases with rCBV ratio of >1.5 progressed in 275 days or earlier. Tumors tended to progress at the area where patients with post-operative MRIs showed elevated perfusion (p = 0.006), tumor-type restricted diffusion (p = 0.005) and DSE (p = 0.008).

Post-operative analysis of rCBV, tumor type restricted diffusion and enhancement characteristics are predictive of time to progression, risk of progression and where tumor progression is likely to occur ¹⁰⁾.

The clinical data of 198 patients surgically treated for primary anaplastic glioma in Henan Provincial People's Hospital between Jan 2009 and Jan 2018 were reviewed. Univariate and multivariate analyses were used to identify prognostic factors with methods of Kaplan-Meier plot and Cox proportional hazards model, respectively. Based on the prognostic factors, a scoring scale was thereby proposed.

Univariate analysis results showed age, tumor location, tumor diameter, preoperative KPS, extent of resection, radiotherapy, chemotherapy, pathology with oligodendroglial components, 1p/19q co-deletion, IDH, MGMT were significantly correlated with survival (P<0.05). Multivariate analysis results showed age ≥45 years old, tumor diameter ≥6 cm, preoperative KPS<70, without radiotherapy, 1p/19q intact, MGMT promoter unmethylation were independent prognostic risk factors (P<0.05). Patients were scored with 0-6 points based on the formulation that each independent prognostic risk factor was assigned with 1 point. Then patients were further grouped according to the score. Those with less than 2 points were low-risk group, equal to 2 points were medium-risk group, equal to 3 points were high-risk group, more than or equal to 4 points were extremely high-risk group. There were significant differences in survival between the different groups (P<0.000 1).

The higher score, the shorter survival time. This prognostic scoring scale can provide a theoretical basis for the prognosis estimation of patients with anaplastic glioma and help to carry out personalized clinical treatment ¹¹⁾.

Wu et al., retrospectively evaluated intraoperative data obtained from 16 patients diagnosed with high-grade glioma (HGG).

Overall, 18 nodules observed in 15 patients were examined. HGG images from ultrasound and contrast-enhanced ultrasound (CEUS) were compared to those from preoperative reconstructive coplanar enhanced T1-weighted MRI using automatic V Nav fusion image technology.

All HGG tumours were detected. Images of 13 of 18 tumours (72.2%) with obscure margins using B-mode ultrasound were improved with clear tumour boundaries using CEUS imaging. The relative difference in tumour area between CEUS and enhanced MRI modalities in 14 mainly solid component lesions was considered statistically significant (p-value < 0.05). There was a perfect correlation of the enhanced area (EA) between coplanar CEUS and enhanced MRI.

The V Nav fusion image system combining intraoperative real-time ultrasound imaging with reconstructive preoperative coplanar MRI is valuable for image-guided HGG resection. It is suitable for neurosurgeons who lack the expertise in ultrasound technology to discern the brain structure and allows better recognition of tumour and oedema tissues compared with reconstructive preoperative coplanar-enhanced MRI in real-time and in multiplane from different angles. In addition, CEUS combined with B-mode ultrasound could improve tumour detection and resection control in neurosurgery, even in single ultrasound-guided operations ¹²⁾.

In a study of Senders et al. from Boston and Utrecht, patients were extracted from the National Surgical Quality Improvement Program registry (2005-2015) and analyzed using multivariable logistic regression.

A total of 7376 patients were identified, of which 948 (12.9%) experienced a major complication. The most common major complications were reoperation (5.1%), venous thromboembolism (3.5%), and death (2.6%). Furthermore, 15.6% stayed longer than 10 d, and 11.5% were readmitted within 30 d after surgery. The most common reasons for reoperation and readmission were intracranial hemorrhage (18.5%) and wound-related complications (11.9%), respectively. Multivariable analysis identified older age, higher body mass index, higher American Society of Anesthesiologists (ASA) classification, dependent functional status, elevated preoperative white blood cell count (white blood cell count WBC, >12 000 cells/mm3), and longer operative time as predictors of major complication (all P < .001). Higher ASA classification, dependent functional status, elevated WBC, and ventilator dependence were predictors of extended length of stay (all P < .001). Higher ASA classification and elevated WBC were predictors of reoperation (both P < .001). Higher ASA classification and dependent functional status were predictors of readmission (both P < .001). Older age, higher ASA classification, and dependent functional status were predictors of death (all P < .001).

This study provides a descriptive analysis and identifies predictors for short-term complications, including death, after craniotomy for primary malignant brain tumors ¹³⁾.

Preibisch et al. performed a study in 12 patients with high-grade glioma, where they directly compared the two currently most promising techniques, namely the MR-based relative oxygen extraction fraction (MR-rOEF) and the PET hypoxia marker H-1-(3-[18 F]-fluoro-2-hydroxypropyl)-2-nitroimidazole ([18 F]-FMISO). MR-rOEF was determined from separate measurements of T2 , T2 * and relative cerebral blood volume (rCBV) employing a multi-parametric approach for quantification of the blood-oxygenation-level-dependent (BOLD) effect. With respect to [18 F]-FMISO-PET, besides the commonly used late uptake between 120 and 130 min ([18 F]-FMISO120-130 min ), we also analyzed the hypoxia specific uptake rate [18 F]-FMISO-k3 , as obtained by pharmacokinetic modeling of dynamic uptake data. Since pharmacokinetic modeling of partially acquired dynamic [18 F]-FMISO data was sensitive to a low signal-to-noise-ratio, analysis was restricted to high-uptake tumor regions. Individual spatial analyses of deoxygenation and hypoxia-related parameter maps revealed that high MR-rOEF values clustered in (edematous) peritumoral tissue, while areas with high [18 F]-FMISO120-130 min concentrated in and around active tumor with disrupted blood-brain barrier, i.e. contrast enhancement in T1 -weighted MRI. Volume-of-interest-based correlations between MR-rOEF and [18 F]-FMISO120-130 min as well as [18 F]-FMISO-k3 , and voxel-wise analyses in individual patients, yielded limited correlations, supporting the notion that [18 F]-FMISO uptake, even after 2 h, might still be influenced by perfusion while [18 F]-FMISO-k3 was severely hampered by noise. According to these results, vascular deoxygenation, as measured by MR-rOEF, and severe tissue hypoxia, as measured by [18 F]-FMISO, show a poor spatial correspondence. Overall, the two methods appear to rather provide complementary than redundant information about high-grade glioma biology ¹⁴⁾.

Data of 47 consecutive patients with HGG have been collected in our study (25 males, 22 females; mean age: 60.3 years, range: 27-86 years). Fluorescein (5 mg/kg of body weight) was injected intravenously right after the induction of general anesthesia. A YELLOW 560 filter was used on an OPMI Pentero 900 microscope (Carl Zeiss Meditec, Oberkochen, Germany) to complete a microsurgical tumor removal. Glioma resection and quality of life were evaluated preoperative and postoperatively.

Gross total resection (GTR) was achieved in 53.2% (n = 25) of patients. A subtotal resection (STR) (>95%) was achieved in 29.8% (n = 14), while a partial resection (PR) (<95%) was obtained in 17% (n = 8) of patients. Overall, in 83% (n = 39) of patients who underwent fluorescence-guided surgery the resection rate achieved was >95%. No adverse effects correlated to fluorescein have been recorded.

Fluorescein seems to be safe and effective in the resection of HGGs, allowing a high rate of gross total removal of contrast enhanced areas ¹⁵⁾.

A retrospective study of 125 HGG patients used three different classification standards of age-groups (≤50 and >50years old, ≤60 and >60years old, ≤45 and 45-65 and ≥65years old) to evaluate the impact of age on prognosis. The primary end-point was overall survival (OS). The Kaplan Meier method was applied for univariate analysis and Cox proportional hazards model for multivariate analysis. Univariate analysis showed a significant correlation between OS and all three classification standards of age-groups as well as between OS and pathological grade, gender, location of glioma, and regular chemotherapy and radiotherapy treatment. Multivariate analysis showed that the only independent predictors of OS were classification standard of age-groups ≤50 and >50years old, pathological grade and regular chemotherapy. In summary, the most appropriate classification standard of age-groups as an independent prognostic factor was ≤50 and >50years old. Pathological grade and chemotherapy were also independent predictors of OS in post-operative HGG patients ¹⁶⁾.

Malignant glioma, ie, anaplastic astrocytoma and glioblastoma, is the most common type of primary malignant brain tumor in the People's Republic of China, and is particularly aggressive.

The median survival of patients with newly diagnosed glioblastoma is only 12-14 months despite advanced therapeutic strategies.

Treatment of malignant glioma consists mainly of surgical resection followed by adjuvant radiation and chemotherapy. Temozolomide (TMZ), a second-generation oral alkylating agent, is playing an increasingly important role in the treatment of malignant glioma in Chinese patients. Since the publication of a study by Stupp et al in 2005, which used a protocol of conventional fractionated irradiation with concomitant TMZ followed by standard TMZ for six cycles, many clinical studies in the People's Republic of China have demonstrated that such a treatment strategy has significantly improved efficacy with limited side effects for newly diagnosed glioblastoma after surgery as compared with strategies that do not contain TMZ. However, as a relatively new agent, the history and development of TMZ for malignant glioma is not well documented in Chinese patients. Multicenter, randomized controlled trials including appropriately sized patient populations investigating multiple aspects of TMZ therapy and related combination therapies are warranted in patients with malignant glioma ¹⁷⁾.

The Nationwide Inpatient Sample (NIS) database was queried from 2002 to 2011. All adult patients who underwent elective brain surgery for a malignant brain tumor were included. Surgical complications included wrong side surgery, retention of a foreign object, iatrogenic stroke, meningitis, hemorrhage/hematoma complicating a procedure, and neurological complications. A regression model was conducted to estimate the odds ratios (OR) with their 95% confidence intervals (95% CI) of in-hospital mortality for each surgical complication.

A total of 16,530 admissions were analyzed, with 601 (36.2 events per 1000 cases) surgical complications occurring in 567 patients. Over the examined 10-year period, the overall incidence of surgical complications did not change (P=0.061) except for iatrogenic strokes, which increased in incidence from 14.1 to 19.8 events per 1000 between 2002 and 2011 (P=0.023). Patients who developed a surgical complication had significantly longer lengths of stay, total hospital costs, and higher rates of other complications. Patients who experienced an iatrogenic stroke had a significantly increased risk of mortality (OR 9.6; 95% 6.3-14.8) and so were patients with a hemorrhage/hematoma (OR 3.3; 95% CI 1.6-6.6).

In this study of an administrative database, patients undergoing surgery for a malignant brain tumor who suffered from a surgical complication had significantly longer lengths of stay, total hospital charges, and complication rates. Having a surgical complication was also an independent risk factor for in-hospital mortality. Nonetheless, it is unclear whether all surgical complications were clinically relevant, and further research is encouraged ¹⁸⁾.