Abstract
Background
Gliomas are the most prevalent primary malignant brain tumors in adults, with high-grade gliomas (HGGs) characterized by elevated recurrence rates, aggressiveness, and mortality. Despite numerous therapies being assessed for rHGGs, most have not yielded satisfactory results. Bevacizumab inhibits tumor angiogenesis by targeting VEGF, and garnered significant attention for its efficacy. We conducted this retrospective study to analyze the prognosis of patients with rHGG undergoing bevacizumab-related therapy, and explored the influencing factors from the clinical, radiological, and molecular pathological perspectives.
Methods
Patients diagnosed with rHGGs who received bevacizumab-related therapy from January 2012 to January 2024 were included in this study. Patients were divided into bevacizumab monotherapy and combination therapy groups. Clinical, radiological, molecular pathological, and survival data were collected for analysis.
Results
A total of 162 patients diagnosed with rHGGs were enrolled, including 115 patients receiving bevacizumab monotherapy and 47 patients receiving combination therapy. The median overall survival (mOS) was 10.3 months, and the median progression-free survival (mPFS) was 5.6 months, with no statistical difference observed in mOS and mPFS between the two treatment groups. In both univariate and multivariate analysis, patients over 60 years old exhibited a worse mOS after bevacizumab-related therapy, while multiple tumors suggested a worse mPFS.
Conclusions
This study focused on bevacizumab-related therapy in rHGGs, and the result indicated no apparent survial advantage with the addition of combination therapies to bevacizumab. Younger patients and those with single recurrent lesion were more likely to benefit from bevacizumab-related therapy. Identification of subgroups that benefit from bevacizumab-related therapy may represent a promising avenue for future research.
Supplementary Information
The online version contains supplementary material available at 10.1186/s12883-026-04665-3.
Keywords: Glioma, Bevacizumab, Recurrent high-grade glioma, Survival analysis, Radiological characteristics
Introduction
Despite a combined regimen of maximal safe surgical resection, postoperative concurrent chemoradiation with temozolomide (TMZ), and adjuvant TMZ chemotherapy, the vast majority of patients with HGGs experience recurrence, while roughly 90% of glioblastomas (GBMs) recurring within 2 years [1]. Furthermore, recurrent HGGs (rHGGs) often develop resistance to chemotherapy and radiotherapy. Currently, there is a lack of high-quality evidence-based therapeutic recommendations for rHGGs [2, 3], particularly recurrent GBM (rGBMs) whose median overall survival (mOS) is generally 6 to 12 months [4].
Overexpression of vascular endothelial growth factor A (VEGF-A) and extensive microvascular proliferation are major features of HGGs and are associated with a poor prognosis [5]. Additionally, HGGs often exhibit a perivascular organization upon recurrence [6]. Bevacizumab (BEV), a recombinant humanized immunoglobulin G1 monoclonal antibody that binds to VEGF-A and inhibits tumor angiogenesis, was initially investigated as monotherapy or in combination with irinotecan in three phase II clinical trials of rGBM [7–9]. The superior results compared to historical controls in these trials led to the approval of BEV as a single agent for patients with rGBM by the United States Food and Drug Administration (FDA) in 2009. Later, the phase II BELOB trial demonstrated that combining CCNU with BEV offered significantly better mOS and median progression-free survival (mPFS) benefits for rGBM patients than CCNU or BEV alone [10]. However, the phase III EORTC26101 trial only demonstrated a significantly longer mPFS in the CCNU-BEV group than the CCNU-alone group [11]. Studies investigating the combination of BEV and other cytotoxic agents including temozolomide (TMZ) [12, 13] and carboplatin [14] have generally shown no additional survival benefit but increased toxicity. Therefore, the use of BEV alone or with CCNU is supported for prolonging mPFS and reducing steroid requirements [15, 16]. In contrast, data on BEV in recurrent WHO grade 3 gliomas is limited, with one phase II study showing unimproved mPFS and mOS with BEV and TMZ combination therapy versus TMZ monotherapy [17].
In real-world applications, the use of BEV in rHGGs is more complex due to variations in treatment regimens involving monotherapy and combination therapy. To better reflect the real-world role of BEV in rHGGs and identify the beneficial subgroup of patients, we retrospectively included 162 patients treated with BEV at our institution and conducted survival analysis using clinical, radiological, and molecular pathological information.
Method
Study population
Patients who underwent BEV-related therapy at the Department of Neurosurgery at Peking Union Medical College Hospital from January 2012 to January 2024 were screened for this study. The patient inclusion criteria were as follows: (1) age ≥ 18 years; (2) patients with surgical resection or biopsy specimens confirmed by pathological examination to be HGGs, and considered to show tumor recurrence based on the immunotherapy response assessment in neuro-oncology (iRANO) criteria [18], or patients who underwent a second surgery with pathological confirmation of HGG recurrence; (3) patients who received BEV-related therapy after recurrence. The exclusion criteria included: (1) age < 18 years; (2) pathological diagnosis ruling out rHGG and (3) patients diagnosed with other malignancies, serious underlying conditions such as cardiovascular diseases, liver and kidney diseases, or hematologic disorders that may interfere with treatment. This study was approved by the Institutional Ethics Review Board of Peking Union Medical College Hospital (S-424) and complied with the requirements of the Declaration of Helsinki as revised in 2013 (https://www.wma.net/wp-content/uploads/2024/10/DoH-Oct2013.pdf).
BEV-related therapy regimen
All enrolled patients received either BEV monotherapy or combination therapy. In both groups, patients received 5 mg/kg intravenous infusion of BEV every 14 days. In the combination therapy group, BEV was combined with cisplatin (DDP), irinotecan (CPT-11), lomustine (CCNU), or PD-1 inhibitor. The administration and dosage of BEV in the combination therapy group were the same as in the monotherapy group. Cisplatin was administered at 40 mg, 30 mg, and 30 mg intravenously for 3 days every 28 days. Irinotecan was administered at 125 mg/m2 intravenously once every 14 days. Lomustine was administered at 100 mg/m2/d orally every 28 days for 5 days. The PD-1 inhibitor was administered at 3 mg/kg intravenously every 28 days. The flow chart of this study was shown in Supplementary Fig. 1.
Clinical and radiological data collection
Clinical and radiological data was collected retrospectively from patients’ medical records and examinations. Clinical data included age at diagnosis, gender, Karnofsky Performance Status (KPS) at recurrence, the extent of surgical resection (EOR), tumor pathology, and postoperative comprehensive treatment regimen (radiotherapy, chemotherapy and steriod). EOR was divided into three categories, namely gross total resection (no radiographic evidence of residual tumor after surgery), subtotal resection (positive radiographic evidence of residual tumor), and biopsy only (tissue sampling via stereotactic needle or open craniotomy). Radiological information was collected from baseline magnetic resonance imaging (MRI), including tumor side and location, the number of tumors, peritumor edema, T1-based contrast enhancement, and intratumoral necrosis. Survival information and incidence of adverse events were collected through outpatient and telephone follow-up.
Evaluation criteria
OS is defined as the time from the date of first administration of BEV-related therapy to the patient’s death or last-recorded follow-up (censored values), and PFS is defined as the time from the date of first administration of BEV-related therapy to the patient’s disease progression. The mOS and mPFS was defined as the OS and PFS achieved by 50% of patients, separately. MRI was performed every 8 weeks to evaluate tumor progression according to iRANO criteria. Adverse events were assessed using the Common Toxicological Criteria for Adverse Events (CTCAE) version 5.0.
Statistical analysis
Normally distributed variables were presented as means ± standard deviations (SDs), with differences between groups assessed by the Student’s t-test. Non-normally distributed variables were illustrated as medians (first quartile, third quartile) [M (Q1, Q3)] and differences between groups were analyzed by the Kruskal-Wallis H test. Categorical variables were compared using the chi-squared test. Molecular pathology alterations were presented by waterfall heat maps. Survival analysis were performed using the Kaplan-Meier method and Log-Rank test, with Kaplan-Meier curves presenting the results. Correlation analysis was conducted with univariate and multivariate Cox proportional hazards regression. A significance level of P < 0.05 was used for all statistical tests. Statistical analyses were performed using SPSS (version 26.0, IBM, USA) and figures were created using R Studio (PBC & Certified B Corp, USA) and GraphPad Prism (version 9, GraphPad Software, USA).
Results
Baseline information of patients receiving BEV-related therapy
A total of 162 rHGG patients received BEV-related therapy and were included in this study. Among them, 115 patients received BEV monotherapy, while 47 patients received BEV combination therapy. The mean age at diagnosis was 53.0 years in the BEV monotherapy group and 54.0 in the combination therapy group. The median KPS at recurrence was 80 in the BEV monotherapy group and 90 in the combination therapy group. No statistically significant differences were observed in mean age at diagnosis, age stratification, median KPS at recurrence, adverse effect, EOR, history of chemoradiotherapy, steroid usage, and pathology between the two groups (P > 0.05). However, there was a statistically significant difference in gender ratio, which may be attributed to the limited sample size. Detailed information was presented in Table 1.
Table 1.
Baseline clinical characteristics of patients diagnosed with rHGGs in the BEV monotherapy and combination therapy groups. KPS, Karnofsky Performance Status; MRI, magnetic resonance imaging; T1WI, T1-weighed image; T2WI, T2-weighed image
| Bevacizumab monotherapy (n = 115, 107 with radiological information) | Bevacizumab combination therapy (n = 47, 44 with radiological information) | P value | |
|---|---|---|---|
| Age at diagnosis, year | 53.0 ± 13.1 | 54.0 ± 12.8 | 0.857 |
| Age at diagnosis ≥ 60, n/% | 39, 33.91% | 11, 23.40% | 0.189 |
| Male, n/% | 60, 52.17% | 30, 63.83% | 0.031 |
| KPS at recurrence, n | 80 (60, 100) | 90 (70, 100) | 0.259 |
| KPS at recurrence ≥ 60, n/% | 88/105, 83.81% | 30/32, 93.75% | 0.242 |
| Adverse effect, n/% | 17/54, 31.48% | 12/31, 38.71% | 0.499 |
| Radiological characteristics on MRI* | |||
| Tumor side | 0.934 | ||
| Left, n/% | 49, 45.79% | 19, 43.18% | |
| Right, n/% | 50, 46.72% | 22, 50.00% | |
| Bilateral, n/% | 8, 7.48% | 3, 6.82% | |
| Tumor location (if involved) | 0.700 | ||
| Frontal lobe, n/% | 37, 34.58% | 14, 31.82% | |
| Temporal lobe, n/% | 17, 15.89% | 10, 22.73% | |
| Parietal lobe, n/% | 15, 14.02% | 5, 11.64% | |
| Occipital lobe, n/% | 2, 1.87% | 3, 6.82% | |
| Insular lobe, n/% | 2, 1.87% | 0, 0% | |
| Basal ganglia region, n/% | 6, 5.61% | 3, 6.82% | |
| Subtentorial structures, n/% | 3, 2.80% | 1, 2.27% | |
| Multiple lobes, n/% | 25, 23.36% | 8, 18.18% | |
| Multiple tumors, n/% | 17, 15.89% | 3, 6.82% | 0.135 |
| Peritumor edema, n/% | 82, 76.64% | 34, 77.27% | 0.933 |
| Contrast enhancement, n/% | 94, 87.85% | 39, 88.64% | 0.892 |
| Intratumoral necrosis, n/% | 79, 73.83% | 26, 59.09% | 0.074 |
| Extent of surgical resection | 0.069 | ||
| Gross total resection, n/% | 84, 73.04% | 42, 89.36% | |
| Subtotal resection, n/% | 14, 12.17% | 3, 6.38% | |
| Biopsy, n/% | 17, 14.78% | 2, 4.26% | |
| Radiotherapy history, n/% | 107, 93.04% | 45, 95.74% | 0.517 |
| Chemotherapy history, n/% | 114, 99.13% | 46, 97.87% | 0.510 |
| Usage of steroid, n/% | 37, 32.17% | 14, 29.79% | 0.767 |
| Pathology | 0.784 | ||
| Glioblastoma, n/% | 76, 66.09% | 30, 63.83% | |
| Other high-grade gliomas, n/% | 39, 33.91% | 17, 36.17% | |
Radiological and molecular features of patients receiving BEV-related therapy
Radiological characteristics of patients undergoing BEV-related therapy were summarized and analysed. Due to incomplete radiological information for some patients, 107 patients in the BEV monotherapy group and 44 patients in the combination therapy group were included. Solitary tumors occurred more frequently than multiple tumors in both groups, and there were no significant differences in tumor side and specific lobar localization. No differences were observed between the monotherapy and combination therapy groups regarding the rate of peritumoral edema and contrast enhancement. The monotherapy group tended to exhibit a higher incidence of intratumoral necrosis, though statistical significance was not reached (p = 0.074). The radiological features were summarized in Table 1.
Molecular alterations, including mutations, amplifications, or deletions of genes and chromosomes, were analyzed. Due to the long time span of patient enrollment, only a portion of patients underwent molecular pathology examination. Fourteen patients in the monotherapy group and five in the combination therapy were included. Changes in molecular markers in both groups of patients were shown in Supplementary Fig. 2, alongside the histological pathological grade and OS of each patient. In addition to chromosome alterations, common genetic alterations in both groups included PIK3CA, CDK6, CDKN2B, EGFR, PDGFRA and PTEN.
Survival analysis of patients receiving BEV-related therapy
Survival analysis was conducted for patients in both treatment groups. The mOS for all enrolled patients was 10.3 months, and the mPFS was 5.6 months. The mOS of pateints receiving BEV monotherapy was 10.3 months, and the mPFS was 7.0 months (Fig. 1). For patients receiving combination therapy, the mOS was 11.6 months, and the mPFS was 5.7 months. No statistical difference was observed in mOS and mPFS between two treatment groups (p = 0.99 and 0.81, separately). The detailed survival information was presented in Fig. 2. Besides, no significant trend toward improved mOS and mPFS was observed for any specific combination therapy group compared with bevacizumab monotherapy (Supplementary Fig. 3).
Fig. 1.
Kaplan-Meier curve showing OS and PFS in enrolled patients with rHGG. A OS; B PFS
Fig. 2.
Kaplan-Meier curve showing OS and PFS between patients with rHGG receiving BEV monotherapy and combination therapy. A OS; B PFS; Blue curve: BEV monotherapy, Red curve: BEV combination therapy
Further subgroup analysis was performed to evaluate survival based on different clinical and radiological characteristics. Patients over 60 years old showed significantly worse mOS and mPFS compared to patients under 60 years old (p = 0.037 and 0.033, separately). Male patients tended to show better mPFS than female patients (p = 0.015), though no statistical difference was observed in mOS. Patients with KPS higher than 60 at recurrence showed significantly better mPFS than patients with KPS lower than 60 (p = 0.003), though statistical advantage was not achieved in mOS. Regarding radiological features, patients with multiple tumors demonstrated significant worse mPFS (p < 0.0001). Patients without peritumor edema showed better mPFS (p = 0.0035), and these patients also tended to have longer mOS, though statistical significance was not reached (p = 0.056). Additionally, patients without central necrosis had longer mOS and mPFS (p = 0.047 and 0.02, separately). There were no prognostic differences observed in pathology and contrast enhancement (Figs. 3 and 4).
Fig. 3.
Kaplan–Meier curve showing OS and PFS between patients with different clinical characteristics. A OS of patients with GBM and other HGG; B PFS of patients with GBM and other HGG; C OS of patients under 60 years old and over 60 years old; D PFS of patients under 60 years old and over 60 years old; E OS of male and female patients; F PFS of male and female patients; G OS of patients with KPS ≤ 60 and > 60; H PFS of patients with KPS ≤ 60 and > 60
Fig. 4.
Kaplan-Meier curve showing OS and PFS between patients with different radiological features. A OS of solitary and multiple tumors; B PFS of solitary and multiple tumors; C OS of patients with and without contrast enhancement; D PFS of patients with and without contrast enhancement; E OS of patients with and without peritumor edema; F PFS of patients with and without peritumor edema; G OS of patients with and without intratumoral necrosis; H PFS of patients with and without intratumoral necrosis
Implications of clinical and radiological features with survival of patients receiving BEV-related therapy
In order to delineate the subpopulations likely to benefit from BEV-related treatment and offer insights for prognosis prediction and clinical decision-making strategies, comprehensive analyses focusing on clinical, radiological and molecular markers pertinent to patient outcomes were conducted. Univariate Cox proportional hazards regression analysis revealed associations of age over 60, peritumoral edema, and intratumoral necrosis with poorer OS. The extent of surgical resection being total resection was associated with extended OS. Multivariate regression analysis suggested that the age group was an independent prognostic factor for OS. Regarding tumor progression, univariate regression analysis indicated that age over 60, KPS under 60, multiple tumors, peritumoral edema, and intratumoral necrosis were associated with poorer PFS, while the extent of surgical resection being total resection was related to prolonged PFS. Multivariate regression analysis underscored the presence of multiple tumors as an independent prognostic factor for PFS (Supplementary Fig. 4). Although the impact of molecular marker changes on the prognosis was analyzed, the limited data resulted in no clear statistical significance (Supplementary Fig. 5).
Discussion
This retrospective study summarized the response of patients with rHGGs to BEV monotherapy and combination therapy, and examined the impact of various influencing factors on patient survival. The mOS of all enrolled patients was 10.3 months and the mPFS was 5.6 months. For patients with rGBM, the mOS was 10.3 months and the mPFS was 5.9 months, which was consistent with previous studies and did not demonstrate a significant positive impact of BEV treatment on survival in patients with rHGGs [19, 20].
Survival analysis indicated that the clinical characteristics with significant differences were geriatric age, gender and KPS at recurrence. Geriatric age (> 60 years) was identified as an independent risk factor, consistent with the findings from previous studies on rHGGs [21]. Although age as a continuous variable was not a risk factor, geriatric age had a significant impact on prognosis. The prognostic impact of geriatric age has not been extensively explored in studies of BEV. However, considering the importance of geriatric (rather than age) factors in patients with gliomas, especially in pathologic subtypes with a poor prognosis [22, 23], it is necessary to further investigate the use of BEV by age group. Additionally, male patients exhibited significantly better PFS with bevacizumab treatment, suggesting a potential gender-based differential response to the therapy. Hiller et al. reported that male patients with GBM showed necroinflammatory phenotypes and difference in mOS, which may explain the result of this study [24]. Lastly, KPS at recurrence under 60 indicated significantly decresed mPFS, while no significant difference was found in mOS between KPS above 60 and KPS under 60. For fragil patients, BEV-related therapy may not be able to offset tumor burden and delay progression. Even for patients with good functional status, the PFS benefit from BEV-related therapy could not be translated into improved OS.
No significant differences were observed between monotherapy and combination therapy, or between different pathologic subgroups. Among the pathologic subgroups, the prognosis of GBM was only slightly worse than other HGGs, not as significant as in previous studies [25]. This finding suggested a possible sensitivity of GBM to BEV treatment [11]. Also, GBM was more dependent on VEGF-related pathways, which could enhance the benefit from bevacizumab and other immunotherapies [26]. Survival differences between different medication subgroups were not significant, and most of the previous studies have also shown little prognostic impact [27]. Depending on the mechanism of BEV, its clinical effect may also be reflected in other endpoints such as ORR.
In the radiological data, significant findings included the impact of multiple tumors and peritumoral edema on prognosis. Patients with multiple tumors had significantly worse PFS, suggesting that multifocality may indicate higher tumor activity and progression risk [28]. Peritumoral edema, often caused by overproduction of VEGF, was associated with shorter OS and PFS. Increased cerebral blood vessel permeability due to VEGF activation can lead to vasogenic brain edema and higher interstitial fluid pressure, therefore reducing the effectiveness of bevacizumab in these patients [29, 30].Overall, the association of radiological factors with progression and survival was related to angiogenesis, and tumour necrosis in the development of gliomas.
Our study has certain limitations. It is a single-center, retrospective study with a relatively small sample size, which may introduce potential systematic bias. Future studies should aim to expand the follow-up cohort and conduct prospective research in collaboration with multiple medical centers. Additionally, the variability in treatment regimens in the combination therapy group limits the ability to draw definitive conclusions. Future prospective studies focusing on certain regimen and using standardized safety and quality-of-life measures are warranted to better define the benefit and tolerability of bevacizumab combination therapies. Lastly, the small number of patients undergoing molecular pathological examination also limited the statistical significance of regression analyses for meaningfully prognostic molecular characteristics.
Conclusion
This study provided a comprehensive summary of the clinical prognosis of BEV-related therapies in patients with rHGGs. The findings indicated that no apparent survival advantage when combination chemotherapy or immunotherapy was added to bevacizumab. Younger patients and those with single recurrent lesion were more likely to benefit from BEV-related therapy. Further research is needed to explore the significance of BEV-related treatment regimens in managing rHGGs, to provide robust evidence for extending overall and progression-free survival, and to identify subgroups that may benefit from these therapies.
Supplementary Information
Supplementary Material 1.Supplementary Figure 1: Flowchart presenting the overall design of the study.
Supplementary Material 2.Supplementary Figure 2: Molecular characterization of rHGG patients treated with BEV. BEV monotherapy: n=14; BEV combination therapy: n=5.
Supplementary Material 3.Supplementary Figure 3: Kaplan-Meier curve showing OS and PFS between rHGG patients receiving BEV monotherapy and different combination therapy. A. OS; B. PFS. Blue curve: BEV monotherapy, Green curve: BEV plus CCNU therapy, Red curve: BEV plus DDP therapy, Orange curve: BEV plus CPT-11 therapy, Purple curve: BEV plus anti-PD-1 therapy. CCNU, Lomustine; DDP, Cisplatin; CPT-11, Irinotecan; PD-1, Programmed death-1.
Supplementary Material 4.Supplementary Figure 4: Univariate and multivariate cox regression analysis on OS and PFS of clinical and radiologic features. Age group: age at diagnosis over 60 VS age at diagnosis under 60; Gender: female VS male; KPS: KPS at recurrence ≥ 60 VS KPS at recurrence < 60; Pathology: GBM VS HGG; Bevacizumab treatment group: combination therapy VS monotherapy; Multiple tumors: multiple tumors VS solitary tumor; Peritumor edema: with peritumor edema VS without peritumor edema; Contrast enhancement: with contrast enhancement VS without contrast enhancement; Intratumoral necrosis: with intratumoral necrosis VS without intratumoral necrosis; Extent of surgical resection: gross total resection VS biopsy, subtotal resection VS gross total resection, subtotal resection VS biopsy; Usage of steroid: with steroid usage VS without steroid usage.
Supplementary Material 5. Supplementary Figure 5. Univariate cox regression analysis on OS and PFS of clinical and molecular features. Age group: age at diagnosis over 60 VS age at diagnosis under 60; Gender: female VS male; Pathology: GBM VS HGG; Bevacizumab treatment group: combination therapy VS monotherapy; Extent of surgical resection: gross total resection VS biopsy, subtotal resection VS gross total resection, subtotal resection VS biopsy; Usage of steroid: with steroid usage VS without steroid usage.
Acknowledgements
This work was funded by the National High Level Hospital Clinical Research Funding (2022-PUMCH-B-113) for Wenbin Ma, the CAMS Innovation Fund for Medical Sciences (CIFMS) (2024-I2M-C&T-B-021), Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences (2024-JKCS-23), Peking Union Medical College Hospital Talent Cultivation Program (Category C) (UBJ10254), Beijing Science And Technology Innovation Medical Development Foundation (KC2023-JX-0288-BZ83), and Beijing Municipal Natural Science Foundation (F252060) and the National High Level Hospital Clinical Research Funding (2025-PUMCH-A-158) for Yu Wang.
Novelty and impact
This study focused on bevacizumab-related therapy in rHGGs, and the beneficial subgroups of patients were investigated. We noticed that bevacizumab-based combination therapy failed to extend mOS and mPFS significantly compared to bevacizumab monotherapy in rHGG patients. Additionally, those over 60 years old had a worse mOS after bevacizumab-related therapy, while multiple tumors suggested a worse mPFS. Identification of subgroups that benefit from bevacizumab-related therapy may represent a promising avenue for future research.
Abbreviations
- BEV
Bevacizumab
- CTCAE
Common Toxicological Criteria for Adverse Events
- EOR
Extent of Surgical Resection
- FDA
Food and Drug Administration
- GBMs
Glioblastomas
- KPS
Karnofsky Performance Status
- HGGs
High-Grade Gliomas
- mOS
median Overall Survival
- mPFS
median Progression-Free Survival
- MRI
Magnetic Resonance Imaging
- rGBMs
recurrent GBM
- rHGGs
recurrent HGGs
- SDs
Standard Deviations
- TMZ
Temozolomide
- VEGF-A
Vascular Endothelial Growth Factor A
Authors’ contributions
Conceptualization: Hai Wang, Wenlin Chen, Xiaopeng Guo, Yu Wang, Wenbin Ma; Methodology: Hai Wang, Wenlin Chen, Yixuan Song, Yaning Cao; Formal analysis and investigation: Hai Wang, Wenlin Chen, Yixuan Song, Yaning Cao, Ling Zhang, Xin Zhang, Yulu Ge, Junlin Li; Writing - original draft preparation: Hai Wang, Wenlin Chen, Yixuan Song, Yaning Cao, Xiaopeng Guo, Ling Zhang, Xin Zhang, Yulu Ge, Junlin Li, Yilin Li, Xiaoman Kang, Jiahui Liu, Yijun Dong, Zihan Zhong, Shanmu Jin, Qianshu Liu; Writing - review and editing: Hai Wang, Wenlin Chen, Yixuan Song, Yaning Cao, Xiaopeng Guo, Yu Wang, Wenbin Ma; Funding acquisition: Yu Wang, Wenbin Ma; Resources: Hai Wang, Wenlin Chen, Xiaopeng Guo, Yu Wang, Wenbin Ma; Supervision: Yu Wang, Wenbin Ma.
Funding
This work was funded by the National High Level Hospital Clinical Research Funding (2022-PUMCH-B-113) for Wenbin Ma, the CAMS Innovation Fund for Medical Sciences (CIFMS) (2024-I2M-C&T-B-021), Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences (2024-JKCS-23), Peking Union Medical College Hospital Talent Cultivation Program (Category C) (UBJ10254), Beijing Science And Technology Innovation Medical Development Foundation (KC2023-JX-0288-BZ83), and Beijing Municipal Natural Science Foundation (F252060) and the National High Level Hospital Clinical Research Funding (2025-PUMCH-A-158) for Yu Wang.
Data availability
The datasets generated during and/or analysed during the current study were available from the corresponding author on reasonable request.
Declarations
Ethics approval and consent to participate
This study was approved by the Institutional Ethics Review Board of Peking Union Medical College Hospital (S-424) and complied with the requirements of the Declaration of Helsinki as revised in 2013 (https://www.wma.net/wp-content/uploads/2024/10/DoH-Oct2013.pdf).
Written informed consent was obtained from all individual participants included in the study.
Consent for publication
Not applicable.
Competing interests
The authors declare no competing interests.
Footnotes
Publisher’s Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Hai Wang, Wenlin Chen, Yixuan Song, Yaning Cao and Xiaopeng Guo contributed equally.
Contributor Information
Yu Wang, Email: ywang@pumch.cn.
Wenbin Ma, Email: mawb2001@hotmail.com.
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
Supplementary Material 1.Supplementary Figure 1: Flowchart presenting the overall design of the study.
Supplementary Material 2.Supplementary Figure 2: Molecular characterization of rHGG patients treated with BEV. BEV monotherapy: n=14; BEV combination therapy: n=5.
Supplementary Material 3.Supplementary Figure 3: Kaplan-Meier curve showing OS and PFS between rHGG patients receiving BEV monotherapy and different combination therapy. A. OS; B. PFS. Blue curve: BEV monotherapy, Green curve: BEV plus CCNU therapy, Red curve: BEV plus DDP therapy, Orange curve: BEV plus CPT-11 therapy, Purple curve: BEV plus anti-PD-1 therapy. CCNU, Lomustine; DDP, Cisplatin; CPT-11, Irinotecan; PD-1, Programmed death-1.
Supplementary Material 4.Supplementary Figure 4: Univariate and multivariate cox regression analysis on OS and PFS of clinical and radiologic features. Age group: age at diagnosis over 60 VS age at diagnosis under 60; Gender: female VS male; KPS: KPS at recurrence ≥ 60 VS KPS at recurrence < 60; Pathology: GBM VS HGG; Bevacizumab treatment group: combination therapy VS monotherapy; Multiple tumors: multiple tumors VS solitary tumor; Peritumor edema: with peritumor edema VS without peritumor edema; Contrast enhancement: with contrast enhancement VS without contrast enhancement; Intratumoral necrosis: with intratumoral necrosis VS without intratumoral necrosis; Extent of surgical resection: gross total resection VS biopsy, subtotal resection VS gross total resection, subtotal resection VS biopsy; Usage of steroid: with steroid usage VS without steroid usage.
Supplementary Material 5. Supplementary Figure 5. Univariate cox regression analysis on OS and PFS of clinical and molecular features. Age group: age at diagnosis over 60 VS age at diagnosis under 60; Gender: female VS male; Pathology: GBM VS HGG; Bevacizumab treatment group: combination therapy VS monotherapy; Extent of surgical resection: gross total resection VS biopsy, subtotal resection VS gross total resection, subtotal resection VS biopsy; Usage of steroid: with steroid usage VS without steroid usage.
Data Availability Statement
The datasets generated during and/or analysed during the current study were available from the corresponding author on reasonable request.