Safety and efficacy of teniposide-based therapy for glioma: a single-center retrospective study

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This study aimed to evaluated the efficacy and safety of teniposide (VM-26)-based therapy in glioma patients. Methods : A retrospective analysis was conducted on glioma patients treated with teniposide-based therapy between 2022 and 2025. Safety assessments were performed using Common Terminology Criteria for Adverse Events (CTCAE). Efficacy was evaluated according to the Response Assessment in Neuro-Oncology (RANO) criteria. Kaplan-Meier analysis was utilized to estimate the prognosis of patients. Results : Thirty-eight patients were enrolled. Regarding adverse events (AEs), 39.5% of patients experienced no AEs, 44.7% developed AEs below grade 3, whereas 15.8% presented with grade 3 and 4 AEs. No treatment-related deaths occurred. In tumor-present gliomas patients, the objective response rate (ORR) was 33.3% and the disease control rate (DCR) was 62.5%. Among tumor-present glioblastomas (GBM) patients, the median progression-free survival (PFS) was 4.15 months versus 12.20 months in tumor-absent GBM. The median overall survival after VM-26 (OS-VM-26) was 7.57 months in tumor-present GBM, whereas the median value was not reached in tumor-absent GBM. The median OS-VM26 was 17.70 months for primary GBM and 6.63 months for recurrent GBM, respectively. Molecular subtypes analysis of the tumor-present GBM revealed that the MGMT-methylated group had superior OS-VM26 and overall survival (OS) (both p < 0.05), with no significant difference in PFS. One representative case illustrated durable response with manageable toxicity. Conclusion : Teniposide-based therapy demonstrated acceptable safety. This therapy may serve as a candidate treatment option for patients with GBM. Teniposide Glioblastoma Retrospective study Glioma Figures Figure 1 Figure 2 Figure 3 Introduction Glioblastoma, the most aggressive adult primary brain tumor classified as WHO CNS grade 4, accounts for 48% of all gliomas and 15% of intracranial neoplasms worldwide [ 1 ] . Typically diagnosed at a median age of 64 years with a male predominance (male-to-female ratio 1.6:1), GBM exhibits a marked increase after age 50 [ 2 ] . The current standard therapy for GBM comprises maximal safe resection, concurrent temozolomide (TMZ)-based chemoradiotherapy, and adjuvant TMZ, supplemented by tumor-treating fields [ 3 ] . Despite multimodal therapy, the median OS of GBM patients remains dismal, with a median OS of about 20 months and a 5-year survival rate below 10% [ 4 ] . Chemotherapy serves as a cornerstone of multimodal GBM management, primarily acting via direct tumor cell cytotoxicity, inhibition of DNA synthesis, or induction of apoptosis to retard disease progression. GBM chemotherapy centers on TMZ, which is hampered by notable limitations: approximately 50% of patients exhibit primary resistance, with nearly all ultimately experiencing disease recurrence [ 5 ] . Additional constraints include limited blood-brain barrier (BBB) penetration, MGMT promoter methylation-dependent efficacy [ 6 ] , and myelosuppression [ 4 ] . Consequently, exploration of novel therapeutic agents and strategies represents a critical approach to overcome the therapeutic impasse in GBM. In recent years, clinical trials targeting GBM have made incremental progress yet mostly ended in failure. Regarding immunotherapy, despite initial promise, candidates including nivolumab, the EGFRvIII-targeted peptide vaccine rindopepimut, and recombinant poliovirus PVSRIPO failed to maintain efficacy or achieve clinical endpoints in subsequent trials [ 7 ] . Vorasidenib, a mutant IDH1/IDH2 enzyme inhibitor, significantly improved PFS in Grade 2 IDH-mutant glioma patients, but its efficacy in high-grade gliomas remains undetermined [ 8 ] . Tyrosine kinase inhibitors (TKIs) targeting the EGFR pathway largely failed to show meaningful efficacy, with inconsistent evidence of target engagement [ 7 ] . To date, agents targeting the PI3K/mTOR pathway have also demonstrated limited utility: the pan-PI3K TKI buparlisib showed​ minimal single-agent activity in recurrent PI3K-activated GBM [ 9 ] , and mTOR inhibitors such as everolimus and temsirolimus similarly failed in phase 2 trials [ 10 , 11 ] . Anti-angiogenic therapies such as bevacizumab (Bev) improved PFS without extending OS in GBM [ 7 ] . Additionally, cediranib failed to prolong PFS or enhance survival in recurrent GBM in a randomized trial [ 12 ] . Teniposide (VM-26), a semi-synthetic podophyllotoxin derivative, functions as a topoisomerase II (Topo II) inhibitor. Its antitumor activity is mediated by selective binding to the Topo II-DNA complex, stabilizing enzyme-induced DNA double-strand breaks to inhibit DNA repair/replication and induce tumor cell apoptosis [ 13 ] . Compared to conventional Topo II inhibitors such as etoposide, teniposide exhibits greater lipophilicity, enhancing BBB penetration and conferring a unique distribution advantage in central nervous system tumors [ 14 ] . In glioma therapy, early trials demonstrated that single-agent teniposide yielded a modest 28% response rate in recurrent gliomas but synergized with other agents [ 15 ] . A subsequent phase 2 study reported a 6-month PFS rate of 34.8% using a teniposide-carboplatin combination in patients with recurrent oligodendroglioma or mixed oligoastrocytoma [ 16 ] . Despite its potential in brain tumor therapy, teniposide’s clinical application is constrained by several factors: first, its limited single-agent efficacy necessitates combination strategies; second, existing regimens predominantly focus on recurrent tumors, with standardized protocols for newly diagnosed GBM which are still lacking. More critically, teniposide underwent a global production suspension in recent years, resulting in drug shortages that substantially hindered clinical research progression. Its reintroduction in China in 2022 has alleviated supply constraints and revitalized opportunities for comprehensive clinical exploration. This study aims to address limited understanding of teniposide-based therapy through a retrospective analysis of clinical data from patients with newly diagnosed or recurrent high-grade gliomas receiving this therapy. The objective is to evaluate its safety and efficacy, thereby providing novel evidence-based insights for the management of​ gliomas. Material and method Participants This retrospective study consecutively enrolled glioma patients treated at the Department of Neurosurgery, Cancer Hospital, Chinese Academy of Medical Sciences, between September 2022 and December 2025. This study was reviewed and approved by the Ethics Committee of Cancer Hospital, Chinese Academy of Medical Sciences for implementation (approval number: NCC4687). Inclusion criteria were as follows: (1) patients ≥ 18 years; (2) diagnosis of primary, recurrent, or progressive gliomas confirmed by clinical and histopathological evaluation; (3) receipt of teniposide-based therapy, either as monotherapy or in combination with other agents; (4) completion of comprehensive baseline evaluations prior to treatment initiation, including complete blood count, serum biochemistry, thyroid function, immune function, and imaging studies. Exclusion criteria comprised: (1) patients < 18 years; (2) severe cardiopulmonary, hepatic, or renal dysfunction; acute cerebrovascular events; severe autoimmune disorders; or other systemic comorbidities precluding treatment tolerance; (3) incomplete follow-up data or loss to follow-up. Written informed consent was obtained from all participants for the use of their clinical data and biological samples. Observation indicators All patients received a 3-day course​ of VM-26 chemotherapy. During treatment, tumor response was assessed by imaging studies every 2–3 treatment cycles, and adverse events (AEs) were systematically recorded. Safety was assessed according to Common Terminology Criteria for Adverse Events (CTCAE; version 5.0, 2019). Clinical data included patient age, pathological type, initial treatment strategy, regimen at recurrence or metastasis, and survival follow-up status. Tumor response was evaluated according to the Response Assessment in Neuro-Oncology (RANO) criteria (version 2.0, 2023)​ and was classified as complete response (CR), partial response (PR), stable disease (SD), or progressive disease (PD). Subsequently, the objective response rate (ORR) and disease control rate (DCR) were calculated. Progression-free survival (PFS) was defined as the time from treatment initiation to disease progression or death. Overall survival from teniposide initiation (OS-VM26) was defined as the interval from teniposide initiation to death or follow-up date. Statistical analysis All statistical analyses were conducted using R software (version 4.4.3). Kaplan-Meier analysis was conducted by GraphPad Prism (version 10.0). Normally distributed continuous data are presented as mean ± standard deviation and compared using independent-sample t-tests. Non-normally distributed data were compared with the Mann-Whitney U test. Categorical variables were analyzed using the chi-square test or Fisher’s exact test, as appropriate. Median survival time was estimated via the Kaplan-Meier method, with differences between survival curves compared via the log-rank test. Statistical significance was set at P < 0.05. Result Clinical features of patients The clinical characteristics of the 38 enrolled patients are summarized in Table 1 . The cohort included 21 males (55.3%) and 17 females (44.7%). A total of 27 patients (71.1%) were aged 18–60 years, and 11 (28.9%) were over 60 years of age. Primary and recurrent cases accounted for 21 (55.3%) and 17 (44.7%), respectively. According to the RANO criteria, measurable tumor burden was present in 24 patients (63.2%), while the remaining 14 patients (36.8%) showing no measurable lesions. Most tumors were WHO grade 4 (33 cases, 86.8%), followed by​ WHO grade 3 (3 cases, 7.9%) and WHO grade 2 (2 cases, 5.3%). Histopathologically, glioblastoma was the most common subtype (28 cases, 73.7%), followed by astrocytoma (5 cases, 13.1%), diffuse midline glioma (3 cases, 7.9%), and anaplastic oligodendroglioma (2 cases, 5.3%). Regarding treatment, the median number of VM-26 cycles administered was 4.5 (range 1–26). Dosage distribution showed that 32 patients (84.2%) received 50 mg/d and 6 (15.8%) received 100 mg/d. The combination regimens were as follows: VM-26 + TMZ + Bev (n = 20), VM-26 + TMZ (n = 8), VM-26 + cisplatin (CDDP) + Bev (n = 4), VM-26 + TMZ + anlotinib (Anl) (n = 2), VM-26 + TMZ + intrathecal methotrexate (MTX) (n = 1), VM-26 + CDDP + TMZ (n = 1), VM-26 + CDDP (n = 1), and VM-26 + Bev (n = 1). Table 1 Clinical characteristics of patients Characteristic Case (n = 38) Gender Male 21 Female 17 Age 18–60 27 >60 11 Primary/non-primary status Primary 21 Recurrent 17 Tumor burden status Presence 24 Absence 14 Grade 2 2 3 3 4 33 Pathological type Glioblastoma 28 Astrocytoma 5 Diffuse midline glioma 3 Anaplastic Oligodendroglioma 2 Number of administrations (VM-26) Median (range from 1 to 26) 4.5 Dosage of VM-26 50mg 32 100mg 6 Treatment protocol VM-26 + Bev 1 VM-26 + CDDP 1 VM-26 + CDDP + Bev 4 VM-26 + CDDP + TMZ 1 VM-26 + TMZ 8 VM-26 + TMZ + Anl 2 VM-26 + TMZ + Bev 20 VM-26 + TMZ + MTX (intrathecal) 1 VM-26: Teniposide; Bev: Bevacizumab; CDDP: Cisplatin; TMZ: Temozolomide; Anl, Anlotinib; MTX, Intrathecal methotrexate (MTX) injection. Safety assessment The safety assessment of all treatment regimens is detailed in Table 2 . Among the 19 patients receiving VM-26 (50 mg/d) combined with TMZ and bevacizumab, 52.63% (10/19) experienced adverse events, including one case of grade 1 fatigue, seven cases of grade 2 neutropenia, one case of grade 3 neutropenia, and one case of grade 4 neutropenia. One additional patient treated with the same regimen but at VM-26 (100 mg/d) reported grade 1 myelosuppression. In the cohort receiving VM-26 (50 mg/d) plus TMZ (n = 7), 42.9% (3/7) developed AEs: one case of grade 2 neutropenia, one case of grade 2 myelosuppression, and one case of grade 1 vomiting. One case of grade 2 leukopenia was observed in the regimen of VM-26 (100 mg/d) plus TMZ. For the cohort receiving VM-26 (50 mg/d) combined with TMZ and anlotinib (n = 2), AEs comprised one case of grade 2 neutropenia and one case presenting with both grade 2 neutropenia and drug-induced liver injury. The patient receiving VM-26 (50 mg/d) plus TMZ and intrathecal methotrexate experienced grade 2 neutropenia and thrombocytopenia. In the VM-26 (50 mg/d) combined with CDDP and bevacizumab cohort (n = 2), no AEs were observed. However, patients receiving​ VM-26 (100 mg/d) combined with CDDP (including VM-26 + CDDP + TMZ, VM-26 + CDDP, and VM-26 + CDDP + Bev) developed severe AEs: three cases of grade 3 neutropenia and one case of grade 4 neutropenia. Table 2 Safety Assessment of treatment protocol Treatment protocol Incidence rate of adverse reactions Incidence rate of grade ≥ 3 adverse reactions VM-26 + Bev (n = 1) 50mg (n = 1) 100% (1/1) 0% (0/1) VM-26 + CDDP (n = 1) 100mg (n = 1) 100% (1/1) 100% (1/1) VM-26 + CDDP + Bev (n = 4) 50mg (n = 2) 0% (0/2) 0% (0/2) 100mg (n = 2) 100% (2/2) 100% (2/2) VM-26 + CDDP + TMZ (n = 1) 100mg (n = 1) 100% (1/1) 100% (1/1) VM-26 + TMZ (n = 8) 50mg (n = 7) 42.86% (3/7) 0% (0/7) 100mg (n = 1) 100% (1/1) 0% (0/1) VM-26 + TMZ + Anl (n = 2) 50mg (n = 2) 100% (2/2) 0% (0/2) VM-26 + TMZ + Bev (n = 20) 50mg (n = 19) 52.63% (10/19) 10.53% (2/19) 100mg (n = 1) 100% (1/1) 0% (0/1) VM-26 + TMZ + MTX (n = 1) 50mg (n = 1) 100% (1/1) 0% (0/1) VM-26: Teniposide; Bev: Bevacizumab; CDDP: Cisplatin; TMZ: Temozolomide; Anl, Anlotinib; MTX, Intrathecal methotrexate injection. Efficacy assessment of glioma patients with tumor burden Table 3 summarizes outcomes in the 24 glioma patients with measurable tumor burden. No complete responses (CR) were observed. Partial responses (PR), stable disease (SD), and progressive disease (PD) occurred in 8 (33.3%), 7 (29.2%), and 9 (37.5%) patients, respectively. The ORR was 33.3%, and the DCR was 62.5%. Table 3 Efficacy assessment of the tumor present group Efficacy indicators Tumor-present group (n = 24) CR 0 PR 8 SD 7 PD 9 ORR/% 33.3% DCR/% 62.5% CR: Complete response; PR: partial response; SD: stable disease; PD: Progressive disease; ORR: Objective response rate; DCR: Disease control rate. Prognosis among different groups of GBM Patients Table 4 and Fig. 1 summarize survival outcomes of four distinct GBM cohorts stratified by tumor burden and disease status. Among patients with measurable tumor burden (n = 20), the median PFS was 4.15 months​ (Fig. 1 a), while those without measurable tumor burden (n = 13) exhibited a longer median PFS of 12.20 months (Fig. 1 d). The median OS-VM26 in the tumor-present group was 7.57 months​ (Fig. 1 b), and the median OS-total was 15.30 months (Fig. 1 c). Neither the OS-VM26 nor the OS-total reached the median values observed in the tumor-absent cohort (Fig. 1 e-f). By disease status, patients with de novo primary GBM (n = 20, including 9 tumor-present cases and 11 tumor-absent cases) demonstrated superior outcomes: median PFS was 7.70 months (Fig. 1 g), median OS-VM26 was 17.70 months (Fig. 1 h), and median OS-total was 18.53 months (Fig. 1 i). Recurrent GBM patients (n = 13, including 11 tumor-present cases, and 2 tumor-absent cases after second surgery) showed inferior survival, with a median PFS of 3.17 months (Fig. 1 j), a median OS-VM26 of 6.63 months (Fig. 1 k), and a median OS-total of 23.90 months (Fig. 1 l). Table 4 The prognosis of different groups of GBM patients clinical feature Present group (n = 20) Absent group (n = 13) Primary group (n = 20) Recurrent group (n = 13) PFS median 4.15 12.20 7.70 3.17 OS-VM26 median 7.57 / 17.70 6.63 OS-total median 15.30 / 18.53 23.90 PFS: Progression-free survival; OS-VM-26: Overall survival from VM-26 initiation; OS-total: Overall survival. Prognostic analysis of molecular subgroups in patients with GBM Survival outcomes across molecular subgroups in patients with tumor burden were presented in Table 5 and Fig. 2 . In the TERT subgroup, patients with TERT mutation (n = 9) showed a median PFS of 6.13 months, a median OS-VM26 of 8.63 months, and a median OS-total of 18.53 months, whereas wild-type TERT (n = 7) showed inferior median values (PFS = 5.77 months; OS-VM26 = 6.53 months; OS-total = 10.47 months). However, these clinical indicators did not reach statistical significance (Fig. 2 .a-c, p = 0.73 for PFS, p = 0.31 for OS-VM26, p = 0.64 for OS-total). In the MGMT subgroup (Fig. 2 .d-f), patients with MGMT promoter methylation (n = 5) demonstrated significantly prolonged OS-VM26 (median 17.70 months) and OS-total (median 38.42 months) compared to those with unmethylated MGMT (n = 10, median OS-VM26 = 6.22 months, p = 0.007; median OS-total = 10.84 months, p = 0.008), though PFS did not differ significantly between the two groups ( p = 0.056). In the CDKN2A/B subgroup, no significant differences in survival were observed between patients with CDKN2A/B loss (n = 4) and those with wild-type CDKN2A/B (n = 10) (Fig. 2 .g-i, p = 0.39 for PFS, p = 0.60 for OS-VM26, p = 0.17 for OS-total). Table 5 The prognosis of genetic subtypes in GBM patients with tumor burden Subtype PFS OS-VM-26 OS-total TERT Mut (n = 9) 6.13 8.63 18.53 Wild (n = 7) 5.77 6.53 10.47 P -value ns ns ns MGMT Met (n = 5) 11.73 17.70 38.42 Wild (n = 10) 4.87 6.22 10.84 P -value ns P < 0.05 P < 0.05 CDKN2A/B Lost (n = 4) 4.00 8.60 27.12 Wild (n = 10) 5.05 6.58 11.73 P -value ns ns ns PFS: Progression-free survival; OS-VM-26: Overall survival from VM-26 initiation; OS-total: Overall survival. TERT: Telomerase reverse transcriptase; MGMT: O-6-methylguanine-DNA methyltransferase; CDKN2A/B: Cyclin-dependent kinase inhibitor 2A/B. Efficacy assessment of 3 patients with diffuse midline glioma This study included three patients with pathologically confirmed grade 4 diffuse midline gliomas (DMG) who received teniposide-based therapy (Table 6 ). Baseline characteristics revealed that all cases were primary tumors. DMG1​ exhibited multiple lesions, a Karnofsky Performance Status (KPS) score of 50, and measurable tumor burden. DMG2​ manifested as a solitary tumor with a KPS score of 90 and lacked initial measurable tumor burden. DMG3​ presented as a solitary tumor with a KPS score of 80 and had initial measurable tumor burden. Treatment regimens varied among the patients: DMG1 received VM‑26 (100 mg/d for 7 cycles) plus TMZ; DMG2 received VM‑26 (50 mg/d for 6 cycles) plus TMZ, followed by long‑term anlotinib; and DMG3 received VM‑26 (50 mg/d for 5 cycles) combined with TMZ and bevacizumab. Regarding efficacy, DMG1 achieved a partial response (PR) but had a PFS of only 7 months, an OS‑VM26 of 9.03 months, and an OS-total of 9.63 months, accompanied by grade 2 treatment‑related adverse events. DMG2 attained stable disease (SD), with a PFS of 13.20 months, an OS‑VM26 of 19.37 months, and an OS-total of 20.27 months, and only grade 1 adverse events. Despite the addition of bevacizumab, DMG3 showed a PFS of 5.77 months, an OS‑VM26 of 6.53 months, and an OS-total of 8.03 months, accompanied by grade 2 adverse events. Table 6 Efficacy Assessment Table of 3 Patients with Diffuse Midline Glioma Clinical feature DMG1 DMG2 DMG3 Grade 4 4 4 Primary/non-primary status Primary Primary Primary Solitary/Multiple Tumors Multiple Solitary Solitary Tumor burden status Presence Absence Presence Number of administrations (VM-26) 7 6 5 Treatment protocol VM-26 + TMZ VM-26 + TMZ + Anl VM-26 + TMZ + Bev Dosage of VM-26 100mg 50mg 50mg KPS 50 90 80 Tumor response PR SD SD Survival status Dead Alive Dead PFS 7.00 13.20 5.77 OS-VM26 9.03 19.37 6.53 OS-total 9.63 20.27 8.03 Grade of adverse events 2 1 2 VM-26: Teniposide; KPS: Karnofsky performance status; PFS: Progression-free survival; OS-VM-26: Overall survival from VM-26 initiation; OS: Overall survival; VM-26: Teniposide; TMZ: Temozolomide; Anl, Anlotinib; Bev: Bevacizumab. Efficacy assessment of one representative patient Table 7 illustrates the therapeutic efficacy in one representative GBM patient receiving VM-26-based therapy.​ The patient, a case of recurrent GBM with widespread metastases (including leptomeningeal and cervical spinal cord involvement; positive cerebrospinal fluid cytology), underwent an 8-cycle regimen of VM-26 (50 mg/day, days 1–3) combined with TMZ (200 mg/m 2 , days 1–5), Bev (5 mg/kg, day 1), and intrathecal thiotepa (10mg/d, day 1), administered in 28-day cycles (Fig. 3 . a&c). The patient achieved a partial response (characterized by significant tumor shrinkage from baseline and negative cerebrospinal fluid cytology), with a PFS of 11.73 months and an OS-VM26 of 19.97 months (Fig. 3 . b&d). Notably, the patient remained alive at the last follow-up, with manageable grade 2 adverse events. Table 7 One representative patients’ efficacy assessment Clinical features Grade 4 Primary/Recurrent status Recurrent Solitary/Multiple tumors Solitary Tumor burden status Presence Number of administrations (VM-26) 8 Treatment protocol VM-26 + TMZ + Bev Dosage of VM-26 50mg/m2 KPS 80 Tumor response PR Survival status Alive PFS 11.73 OS-VM26 19.97 OS-total 41.13 Grade of adverse reactions 2 VM-26: Teniposide; KPS: Karnofsky performance status; PFS: Progression-free survival; OS-VM-26: Overall survival from VM-26 initiation; OS-total: Overall survival. Discussion Despite current standard-of-care therapies, the prognosis for GBM patients remains dismal, driving intensive efforts to integrate novel therapeutic agents into clinical regimens. After teniposide was reintroduced in China in 2022, we implemented teniposide-based therapy for glioma treatment, particularly focusing on​ medically challenging patients, including patients with recurrence or progression after standard therapy, a large residual tumor volume, MGMT promoter unmethylated status, or poor performance status. In this study, we demonstrated acceptable safety for teniposide-based therapy and observed its efficacy in glioma patients. This study evaluated the safety profile of teniposide-based therapies. The low-dose VM-26 (50 mg/d) regimen exhibited manageable hematological toxicity (incidence of grade 1–2 AEs: 46.87%, grade 3–4 AEs: 6.25%), underscoring its feasibility as an alternative for elderly or frail patients. Similarly, a previous study assessing the safety of​ intra-arterial chemotherapy​ (BCNU 100 mg/m² + cisplatin 60 mg/m² + VM-26​ 150 mg/m²) in patients with primary or metastatic intracranial tumors found that only 9% of patients receiving lower-dose​ VM-26 experienced permanent severe toxicity [ 17 ] . In contrast, the high-dose VM-26 (100 mg/d) regimen combined with platinum-based agents (e.g., VM-26 + CDDP, VM-26 + CDDP + Bev, VM-26 + CDDP + TMZ) warranted caution owing to the risk of severe myelosuppression, given that all such combinations were associated with grade ≥ 3 AEs. The higher incidence of severe AEs in this regimen was potentially due to three factors: the limited sample size (only 4 cases), use of salvage therapy, and the impaired functional status (KPS < 70) of enrolled patients. These findings suggested that VM-26-based therapy (without platinum agents) exhibited an acceptable safety profile in GBM patients, even in those with fragile status. Our study examined the efficacy of teniposide-based regimens in GBM patients with measurable​ tumor burden, demonstrating​ an ORR of 36.4% and a DCR of 68.2%. While a study assessing the lomustine-bevacizumab combination for progressive GBM [ 18 ] reported an ORR of 41.5%, teniposide-based therapy covered a broader patient population by providing an alternative with lower economic burden, and applicability to patients with lower KPS scores or even fragile status. Compared with the 28% ORR reported for teniposide monotherapy in recurrent gliomas [ 16 ] , the combination regimen in our study achieved a higher ORR, thereby supporting its synergistic potential. As an innovative therapy, immunotherapies necessitate rigorous clinical investigation to validate their clinical utility, since systematic reviews report they remain investigational with most clinical trials yielding suboptimal results (ORR typically below 20%) [ 7 , 19 ] . Our study reported the median PFS of 7.7 months for the primary GBM group. Given that TTFields is not yet widely available and is costly, a phase 2 study reported a PFS of 5.8 months [ 20 ] in newly diagnosed GBM patients treated with TTFields and temozolomide alone following chemoradiotherapy, thereby highlighting the potential cost-effectiveness advantages of the teniposide-based regimen. Additionally, phase 1 results of OLA-TMZ-RTE-01 revealed that olaparib, temozolomide, and concurrent radiotherapy yielded a PFS of 6.2 months in GBM patients undergoing partial resection or biopsy-only [ 21 ] . As the related phase 2 study remains incomplete, clinical application of this regimen requires a prolonged wait, which further underscores the teniposide-based regimen’s superior outcomes and broad application potential. GBM recurrence is an inevitable event, with primary GBM showing a median PFS of approximately 7 months [ 22 ] . We further focused on the PFS of recurrent GBM patients receiving a teniposide-based regimen and reported a median PFS of 3.17 months and median OS‑VM26 of 6.63 months. In comparison with the bevacizumab monotherapy group for recurrent glioblastoma (median PFS of 3.7 months, median OS of 7.9 months) [ 23 ] , our study showed​ more favorable outcomes in tumor-present GBM patients (mostly with large tumors): a median PFS of 4.15 months, a median OS‑VM26 of 7.57 months, and a median OS-total of 15.30 months. Molecular subtype analysis in the tumor-present group revealed that overall survival, including both OS-VM26 and OS-total, was significantly better in the MGMT methylated subgroup than in the unmethylated subgroup (both p < 0.05). This result may be attributed to the underlying mechanism: MGMT promoter methylation reduces DNA repair capacity in tumor cells, thereby increasing the sensitivity to teniposide-an inhibitor of topoisomerase II activity. For the tumor-absent group, the majority in our study were newly diagnosed GBM patients who underwent gross total resection, and no significant difference in prognostic outcomes was detected between the MGMT unmethylated and methylated subgroups. As is known, newly diagnosed GBM patients with MGMT unmethylated status generally have a poorer prognosis when treated with the Stupp protocol than those with MGMT methylated status [ 24 ] . This suggests that VM-26-based therapy should be actively adopted for newly diagnosed GBM patients with unmethylated MGMT. This study is subject to several limitations inherent to its design and scope. The single-center retrospective design is prone to inherent selection biases, including potential confounding by treatment timing within tumor burden subgroups. The modest sample size constrains statistical power, particularly in subgroup analyses where certain molecular cohorts have inadequate representation for robust conclusions. Additionally, therapeutic heterogeneity poses challenges: heterogeneous combination regimens (e.g., VM-26 + TMZ + Bev, VM-26 + CDDP) and variable dosing schedules (50 mg vs. 100 mg) complicate the attribution of outcomes to specific agents, while temporal variations in treatment duration further obscure dose-response relationships. This study addresses critical gaps in glioblastoma therapeutics through two transformative advancements. Amid a global hiatus in teniposide (VM-26) production, our work presents the inaugural clinical dataset from China following its reintroduction, establishing a foundational reference for future VM-26-based combination therapies in GBM. We systematically evaluated the adverse events of VM-26-based combinations and demonstrated acceptable safety. Furthermore, our results suggested this therapy could represent a candidate therapeutic option for GBM patients, especially with tumor presence and newly diagnosed GBM patients with unmethylated MGMT status. Statements & Declarations Funding This study was supported by the National Natural Science Foundation of China (No. 82472722) and Beijing Hope Run Special Fund of Cancer Foundation of China (No. LC2022B18). Competing interests The authors declare no competing interests. Author contributions Jinghai Wan and Hongqing Cai designed the study and revised the manuscript. Zekun Deng and Yujia Chen drafted the manuscript. Huaixu Li, Qi Liu, and Chang Fang collected the data. Jinghai Wan, Haipeng Qian, and Ming Yang reviewed the paper. All authors made substantial contributions to the study and approved the submitted version. Data availability No datasets were generated or analysed during the current study. Ethics approval and consent to participate This study was conducted in accordance with the ethical principles of the Declaration of Helsinkiand was reviewed and approved by the Ethics Committee of Cancer Hospital, Chinese Academy of Medical Sciences for implementation (approval number: NCC4687). Consent to participate Informed consent was obtained from all individual participants included in the study. Consent to publish The authors affirm that human research participants provided informed consent for publication of the images in Figure 3A-D. References Louis, D.N. et al (2021) The 2021 WHO Classification of Tumors of the Central Nervous System: a summary. Neuro Oncol 23(8): p. 1231-1251. Ostrom, Q.T. et al (2021) CBTRUS Statistical Report: Primary Brain and Other Central Nervous System Tumors Diagnosed in the United States in 2014-2018. Neuro Oncol 23(12 Suppl 2): p. iii1-iii105. Stupp, R. et al (2017) Effect of Tumor-Treating Fields Plus Maintenance Temozolomide vs Maintenance Temozolomide Alone on Survival in Patients With Glioblastoma: A Randomized Clinical Trial. JAMA 318(23): p. 2306-2316. Lim, M. et al (2022) Phase III trial of chemoradiotherapy with temozolomide plus nivolumab or placebo for newly diagnosed glioblastoma with methylated MGMT promoter. Neuro Oncol 24(11): p. 1935-1949. Hegi, M.E. et al (2005) MGMT gene silencing and benefit from temozolomide in glioblastoma. N Engl J Med 352(10): p. 997-1003. Wick, W. et al (2014) MGMT testing--the challenges for biomarker-based glioma treatment. Nat Rev Neurol 10(7): p. 372-85. Tan, A.C. et al (2020) Management of glioblastoma: State of the art and future directions. CA Cancer J Clin 70(4): p. 299-312. Mellinghoff, I.K. et al (2023) Vorasidenib in IDH1- or IDH2-Mutant Low-Grade Glioma. N Engl J Med 389(7): p. 589-601. Wen, P.Y. et al (2019) Buparlisib in Patients With Recurrent Glioblastoma Harboring Phosphatidylinositol 3-Kinase Pathway Activation: An Open-Label, Multicenter, Multi-Arm, Phase II Trial. J Clin Oncol 37(9): p. 741-750. Ma, D.J. et al (2015) A phase II trial of everolimus, temozolomide, and radiotherapy in patients with newly diagnosed glioblastoma: NCCTG N057K. Neuro Oncol 17(9): p. 1261-9. Wick, W. et al (2016) Phase II Study of Radiotherapy and Temsirolimus versus Radiochemotherapy with Temozolomide in Patients with Newly Diagnosed Glioblastoma without MGMT Promoter Hypermethylation (EORTC 26082). Clin Cancer Res 22(19): p. 4797-4806. Batchelor, T.T. et al (2013) Phase III randomized trial comparing the efficacy of cediranib as monotherapy, and in combination with lomustine, versus lomustine alone in patients with recurrent glioblastoma. J Clin Oncol 31(26): p. 3212-8. Pommier, Y. et al (2006) Topoisomerase I inhibitors: camptothecins and beyond. Nat Rev Cancer 6(10): p. 789-802. Bogdahn, U. et al (1987) Vidarabin-monophosphate, BCNU, VM26--an in vitro comparative study of active agents in the treatment of malignant human brain tumours. Br J Cancer 55(2): p. 153-8. Stewart, D.J. et al (1989) The role of chemotherapy in the treatment of gliomas in adults. Cancer Treat Rev 16(3): p. 129-60. Brandes, A.A. et al (2003) Carboplatin and teniposide as third-line chemotherapy in patients with recurrent oligodendroglioma or oligoastrocytoma: a phase II study. Ann Oncol 14(12): p. 1727-31. Stewart, D.J. et al (1984) Intracarotid chemotherapy with a combination of 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU), cis-diaminedichloroplatinum (cisplatin), and 4'-O-demethyl-1-O-(4,6-O-2-thenylidene-beta-D-glucopyranosyl) epipodophyllotoxin (VM-26) in the treatment of primary and metastatic brain tumors. Neurosurgery 15(6): p. 828-33. Wick, W. et al (2017) Lomustine and Bevacizumab in Progressive Glioblastoma. N Engl J Med 377(20): p. 1954-1963. Schalper, K.A. et al (2019) Neoadjuvant nivolumab modifies the tumor immune microenvironment in resectable glioblastoma. Nat Med 25(3): p. 470-476. Chen, D. et al (2025) Efficacy and safety of adjuvant TTFields plus pembrolizumab and temozolomide in newly diagnosed glioblastoma: A phase 2 study. Med 6(9): p. 100708. Stefan, D. et al (2025) Olaparib, Temozolomide, and Concomitant Radiotherapy for Partially Resected or Biopsy-Only Glioblastoma First-Line Treatment: Results from the OLA-TMZ-RTE-01 Phase I Study. Clin Cancer Res 31(7): p. 1212-1222. Schaff, L.R. and I.K. Mellinghoff (2023) Glioblastoma and Other Primary Brain Malignancies in Adults: A Review. JAMA 329(7): p. 574-587. Brandner, S. et al (2021) MGMT promoter methylation testing to predict overall survival in people with glioblastoma treated with temozolomide: a comprehensive meta-analysis based on a Cochrane Systematic Review. Neuro Oncol 23(9): p. 1457-1469. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-9311229","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Case Report","associatedPublications":[],"authors":[{"id":620473793,"identity":"03645a05-09f1-4500-9aa3-d28292ab45ab","order_by":0,"name":"Zekun Deng","email":"","orcid":"","institution":"Chinese Academy of Medical Sciences \u0026 Peking Union Medical College","correspondingAuthor":false,"prefix":"","firstName":"Zekun","middleName":"","lastName":"Deng","suffix":""},{"id":620473796,"identity":"7a3cbd44-1633-4330-b4b6-862658be9c50","order_by":1,"name":"Hongqing Cai","email":"","orcid":"","institution":"Chinese Academy of Medical Sciences \u0026 Peking Union Medical College","correspondingAuthor":false,"prefix":"","firstName":"Hongqing","middleName":"","lastName":"Cai","suffix":""},{"id":620473799,"identity":"77476627-3fe0-4ee8-a479-78a45e660a0e","order_by":2,"name":"Yujia Chen","email":"","orcid":"","institution":"Chinese Academy of Medical Sciences \u0026 Peking Union Medical College","correspondingAuthor":false,"prefix":"","firstName":"Yujia","middleName":"","lastName":"Chen","suffix":""},{"id":620473801,"identity":"12cdb581-1fae-42b8-bfcb-be38d56ccd3c","order_by":3,"name":"Qi Liu","email":"","orcid":"","institution":"Chinese Academy of Medical Sciences \u0026 Peking Union Medical College","correspondingAuthor":false,"prefix":"","firstName":"Qi","middleName":"","lastName":"Liu","suffix":""},{"id":620473804,"identity":"014f7335-78b4-46b9-a6b4-d3148d53caf4","order_by":4,"name":"Huaixu Li","email":"","orcid":"","institution":"Chinese Academy of Medical Sciences \u0026 Peking Union Medical College","correspondingAuthor":false,"prefix":"","firstName":"Huaixu","middleName":"","lastName":"Li","suffix":""},{"id":620473808,"identity":"abfad11f-aba5-460b-8500-7bbc104834c7","order_by":5,"name":"Cheng Fang","email":"","orcid":"","institution":"Chinese Academy of Medical Sciences \u0026 Peking Union Medical College","correspondingAuthor":false,"prefix":"","firstName":"Cheng","middleName":"","lastName":"Fang","suffix":""},{"id":620473813,"identity":"68a9a222-88dd-4604-a8a0-e66d2b6d24ce","order_by":6,"name":"Ming Yang","email":"","orcid":"","institution":"Chinese Academy of Medical Sciences \u0026 Peking Union Medical College","correspondingAuthor":false,"prefix":"","firstName":"Ming","middleName":"","lastName":"Yang","suffix":""},{"id":620473817,"identity":"4cfba010-e021-403c-8ebe-87f6feda9a59","order_by":7,"name":"Haipeng Qian","email":"","orcid":"","institution":"Chinese Academy of Medical Sciences \u0026 Peking Union Medical College","correspondingAuthor":false,"prefix":"","firstName":"Haipeng","middleName":"","lastName":"Qian","suffix":""},{"id":620473821,"identity":"698e85f4-6f7f-46f8-8744-051d83fbe073","order_by":8,"name":"Jinghai Wan","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA1UlEQVRIiWNgGAWjYJACgwQGhgQGZuYDQJI0LWwJxGsBAaBiHgMibTh+9kDBwx21efztPJ8/PNxhx8Df3o3fMoMzeQkGiWeOF0sc5t0mkXgmmUHizNkNeLWYHcgxMEhsO5bYANTCkNjGzGAgkUtAy/k3EC3zD/M8/pDYVk+ElhtgW2oSNxzmYZBIbDtMWIv9DbAtBxI3HmYzA2o5zkPQL5L9OWaGP9vqEuedP/z448+2ajn+9l78WoCADRgfh+E8HkLKQYD5AQNDHTEKR8EoGAWjYKQCALr0TRkAy3qvAAAAAElFTkSuQmCC","orcid":"","institution":"Chinese Academy of Medical Sciences \u0026 Peking Union Medical College","correspondingAuthor":true,"prefix":"","firstName":"Jinghai","middleName":"","lastName":"Wan","suffix":""}],"badges":[],"createdAt":"2026-04-03 09:23:34","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-9311229/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-9311229/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":106636235,"identity":"b64e0aa3-a323-472e-8d13-d2696560f96b","added_by":"auto","created_at":"2026-04-10 16:53:03","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":197714,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eThe prognosis of four distinct GBM cohorts\u003c/strong\u003e. \u003cstrong\u003ea-c\u003c/strong\u003e. The PFS, OS-VM26, OS-total curve of GBM present group. \u003cstrong\u003ed-f\u003c/strong\u003e. The PFS, OS-VM26, OS-total curve of GBM absent group. \u003cstrong\u003eg-i\u003c/strong\u003e. The PFS, OS-VM26, OS-total curve of GBM primary group. \u003cstrong\u003ej-l\u003c/strong\u003e. The PFS, OS-VM26, OS-total curve of GBM recurrent group. PFS: Progression-free survival; OS-VM-26: Overall survival from VM-26 initiation; OS-total: Overall survival.\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-9311229/v1/7e43dbc9380e341147592afc.png"},{"id":106726503,"identity":"897920f2-077b-470f-a6d0-fecf76402b9f","added_by":"auto","created_at":"2026-04-12 18:36:22","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":204963,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eThe Kaplan-Meier analysis of genetic subtypes in GBM patients with tumor burden\u003c/strong\u003e. \u003cstrong\u003ea-c\u003c/strong\u003e. The PFS, OS-VM26, OS-total curve of TERT subgroup. \u003cstrong\u003ed-f\u003c/strong\u003e. The PFS, OS-VM26, OS-total curve of MGMT subgroup. \u003cstrong\u003eg-i\u003c/strong\u003e. The PFS, OS-VM26, OS-total curve of CDKN2 subgroup. PFS: Progression-free survival; OS-VM-26: Overall survival from VM-26 initiation; OS: Overall survival; TERT: Telomerase reverse transcriptase; MGMT: O-6-methylguanine-DNA methyltransferase; CDKN2A/B: Cyclin-dependent kinase inhibitor 2A/B.\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-9311229/v1/50b0a41d7fddd95036315d48.png"},{"id":106726339,"identity":"f8660a4f-21db-4e22-a368-232a6ca1e75f","added_by":"auto","created_at":"2026-04-12 18:35:50","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":442054,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eComparison of pre- and post-treatment imaging studies in the patient receiving 8-cycle VM-26-based therapy\u003c/strong\u003e. \u003cstrong\u003ea-b\u003c/strong\u003e. The pre- and post-treatment imaging of leptomeningeal and cervical spinal cord; \u003cstrong\u003ec-d\u003c/strong\u003e. The pre- and post-treatment imaging of left temporoparietal lobe.\u003c/p\u003e","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-9311229/v1/8762fb7a3d251fcf5d6d2a78.png"},{"id":108376525,"identity":"2159b323-03d7-4abc-8976-9f851ab45e61","added_by":"auto","created_at":"2026-05-04 02:40:58","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1283097,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-9311229/v1/91f1954f-5cd5-45cc-ab49-a3998f8cf6a2.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Safety and efficacy of teniposide-based therapy for glioma: a single-center retrospective study","fulltext":[{"header":"Introduction","content":"\u003cp\u003eGlioblastoma, the most aggressive adult primary brain tumor classified as WHO CNS grade 4, accounts for 48% of all gliomas and 15% of intracranial neoplasms worldwide \u003csup\u003e[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]\u003c/sup\u003e. Typically diagnosed at a median age of 64 years with a male predominance (male-to-female ratio 1.6:1), GBM exhibits a marked increase after age 50 \u003csup\u003e[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]\u003c/sup\u003e. The current standard therapy for GBM comprises maximal safe resection, concurrent temozolomide (TMZ)-based chemoradiotherapy, and adjuvant TMZ, supplemented by tumor-treating fields \u003csup\u003e[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]\u003c/sup\u003e. Despite multimodal therapy, the median OS of GBM patients remains dismal, with a median OS of about 20 months and a 5-year survival rate below 10% \u003csup\u003e[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eChemotherapy serves as a cornerstone of multimodal GBM management, primarily acting via direct tumor cell cytotoxicity, inhibition of DNA synthesis, or induction of apoptosis to retard disease progression. GBM chemotherapy centers on TMZ, which is hampered by notable limitations: approximately 50% of patients exhibit primary resistance, with nearly all ultimately experiencing disease recurrence \u003csup\u003e[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]\u003c/sup\u003e. Additional constraints include limited blood-brain barrier (BBB) penetration, MGMT promoter methylation-dependent efficacy \u003csup\u003e[\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]\u003c/sup\u003e, and myelosuppression \u003csup\u003e[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]\u003c/sup\u003e. Consequently, exploration of novel therapeutic agents and strategies represents a critical approach to overcome the therapeutic impasse in GBM.\u003c/p\u003e \u003cp\u003eIn recent years, clinical trials targeting GBM have made incremental progress yet mostly ended in failure. Regarding immunotherapy, despite initial promise, candidates including nivolumab, the EGFRvIII-targeted peptide vaccine rindopepimut, and recombinant poliovirus PVSRIPO failed to maintain efficacy or achieve clinical endpoints in subsequent trials \u003csup\u003e[\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]\u003c/sup\u003e. Vorasidenib, a mutant IDH1/IDH2 enzyme inhibitor, significantly improved PFS in Grade 2 IDH-mutant glioma patients, but its efficacy in high-grade gliomas remains undetermined \u003csup\u003e[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]\u003c/sup\u003e. Tyrosine kinase inhibitors (TKIs) targeting the EGFR pathway largely failed to show meaningful efficacy, with inconsistent evidence of target engagement \u003csup\u003e[\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]\u003c/sup\u003e. To date, agents targeting the PI3K/mTOR pathway have also demonstrated limited utility: the pan-PI3K TKI buparlisib showed​ minimal single-agent activity in recurrent PI3K-activated GBM \u003csup\u003e[\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]\u003c/sup\u003e, and mTOR inhibitors such as everolimus and temsirolimus similarly failed in phase 2 trials \u003csup\u003e[\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]\u003c/sup\u003e. Anti-angiogenic therapies such as bevacizumab (Bev) improved PFS without extending OS in GBM \u003csup\u003e[\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]\u003c/sup\u003e. Additionally, cediranib failed to prolong PFS or enhance survival in recurrent GBM in a randomized trial \u003csup\u003e[\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eTeniposide (VM-26), a semi-synthetic podophyllotoxin derivative, functions as a topoisomerase II (Topo II) inhibitor. Its antitumor activity is mediated by selective binding to the Topo II-DNA complex, stabilizing enzyme-induced DNA double-strand breaks to inhibit DNA repair/replication and induce tumor cell apoptosis \u003csup\u003e[\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]\u003c/sup\u003e. Compared to conventional Topo II inhibitors such as etoposide, teniposide exhibits greater lipophilicity, enhancing BBB penetration and conferring a unique distribution advantage in central nervous system tumors \u003csup\u003e[\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]\u003c/sup\u003e. In glioma therapy, early trials demonstrated that single-agent teniposide yielded a modest 28% response rate in recurrent gliomas but synergized with other agents \u003csup\u003e[\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]\u003c/sup\u003e. A subsequent phase 2 study reported a 6-month PFS rate of 34.8% using a teniposide-carboplatin combination in patients with recurrent oligodendroglioma or mixed oligoastrocytoma \u003csup\u003e[\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eDespite its potential in brain tumor therapy, teniposide\u0026rsquo;s clinical application is constrained by several factors: first, its limited single-agent efficacy necessitates combination strategies; second, existing regimens predominantly focus on recurrent tumors, with standardized protocols for newly diagnosed GBM which are still lacking. More critically, teniposide underwent a global production suspension in recent years, resulting in drug shortages that substantially hindered clinical research progression. Its reintroduction in China in 2022 has alleviated supply constraints and revitalized opportunities for comprehensive clinical exploration.\u003c/p\u003e \u003cp\u003eThis study aims to address limited understanding of teniposide-based therapy through a retrospective analysis of clinical data from patients with newly diagnosed or recurrent high-grade gliomas receiving this therapy. The objective is to evaluate its safety and efficacy, thereby providing novel evidence-based insights for the management of​ gliomas.\u003c/p\u003e"},{"header":"Material and method","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eParticipants\u003c/h2\u003e \u003cp\u003eThis retrospective study consecutively enrolled glioma patients treated at the Department of Neurosurgery, Cancer Hospital, Chinese Academy of Medical Sciences, between September 2022 and December 2025. This study was reviewed and approved by the Ethics Committee of Cancer Hospital, Chinese Academy of Medical Sciences for implementation (approval number: NCC4687). Inclusion criteria were as follows: (1) patients\u0026thinsp;\u0026ge;\u0026thinsp;18 years; (2) diagnosis of primary, recurrent, or progressive gliomas confirmed by clinical and histopathological evaluation; (3) receipt of teniposide-based therapy, either as monotherapy or in combination with other agents; (4) completion of comprehensive baseline evaluations prior to treatment initiation, including complete blood count, serum biochemistry, thyroid function, immune function, and imaging studies. Exclusion criteria comprised: (1) patients\u0026thinsp;\u0026lt;\u0026thinsp;18 years; (2) severe cardiopulmonary, hepatic, or renal dysfunction; acute cerebrovascular events; severe autoimmune disorders; or other systemic comorbidities precluding treatment tolerance; (3) incomplete follow-up data or loss to follow-up. Written informed consent was obtained from all participants for the use of their clinical data and biological samples.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eObservation indicators\u003c/h3\u003e\n\u003cp\u003eAll patients received a 3-day course​ of VM-26 chemotherapy. During treatment, tumor response was assessed by imaging studies every 2\u0026ndash;3 treatment cycles, and adverse events (AEs) were systematically recorded. Safety was assessed according to Common Terminology Criteria for Adverse Events (CTCAE; version 5.0, 2019). Clinical data included patient age, pathological type, initial treatment strategy, regimen at recurrence or metastasis, and survival follow-up status. Tumor response was evaluated according to the Response Assessment in Neuro-Oncology (RANO) criteria (version 2.0, 2023)​ and was classified as complete response (CR), partial response (PR), stable disease (SD), or progressive disease (PD). Subsequently, the objective response rate (ORR) and disease control rate (DCR) were calculated. Progression-free survival (PFS) was defined as the time from treatment initiation to disease progression or death. Overall survival from teniposide initiation (OS-VM26) was defined as the interval from teniposide initiation to death or follow-up date.\u003c/p\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analysis\u003c/h2\u003e \u003cp\u003eAll statistical analyses were conducted using R software (version 4.4.3). Kaplan-Meier analysis was conducted by GraphPad Prism (version 10.0). Normally distributed continuous data are presented as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation and compared using independent-sample t-tests. Non-normally distributed data were compared with the Mann-Whitney U test. Categorical variables were analyzed using the chi-square test or Fisher\u0026rsquo;s exact test, as appropriate. Median survival time was estimated via the Kaplan-Meier method, with differences between survival curves compared via the log-rank test. Statistical significance was set at \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05.\u003c/p\u003e \u003c/div\u003e"},{"header":"Result","content":"\u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003eClinical features of patients\u003c/h2\u003e \u003cp\u003eThe clinical characteristics of the 38 enrolled patients are summarized in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. The cohort included 21 males (55.3%) and 17 females (44.7%). A total of 27 patients (71.1%) were aged 18\u0026ndash;60 years, and 11 (28.9%) were over 60 years of age. Primary and recurrent cases accounted for 21 (55.3%) and 17 (44.7%), respectively. According to the RANO criteria, measurable tumor burden was present in 24 patients (63.2%), while the remaining 14 patients (36.8%) showing no measurable lesions. Most tumors were WHO grade 4 (33 cases, 86.8%), followed by​ WHO grade 3 (3 cases, 7.9%) and WHO grade 2 (2 cases, 5.3%). Histopathologically, glioblastoma was the most common subtype (28 cases, 73.7%), followed by astrocytoma (5 cases, 13.1%), diffuse midline glioma (3 cases, 7.9%), and anaplastic oligodendroglioma (2 cases, 5.3%).\u003c/p\u003e \u003cp\u003eRegarding treatment, the median number of VM-26 cycles administered was 4.5 (range 1\u0026ndash;26). Dosage distribution showed that 32 patients (84.2%) received 50 mg/d and 6 (15.8%) received 100 mg/d. The combination regimens were as follows: VM-26\u0026thinsp;+\u0026thinsp;TMZ\u0026thinsp;+\u0026thinsp;Bev (n\u0026thinsp;=\u0026thinsp;20), VM-26\u0026thinsp;+\u0026thinsp;TMZ (n\u0026thinsp;=\u0026thinsp;8), VM-26\u0026thinsp;+\u0026thinsp;cisplatin (CDDP)\u0026thinsp;+\u0026thinsp;Bev (n\u0026thinsp;=\u0026thinsp;4), VM-26\u0026thinsp;+\u0026thinsp;TMZ\u0026thinsp;+\u0026thinsp;anlotinib (Anl) (n\u0026thinsp;=\u0026thinsp;2), VM-26\u0026thinsp;+\u0026thinsp;TMZ\u0026thinsp;+\u0026thinsp;intrathecal methotrexate (MTX) (n\u0026thinsp;=\u0026thinsp;1), VM-26\u0026thinsp;+\u0026thinsp;CDDP\u0026thinsp;+\u0026thinsp;TMZ (n\u0026thinsp;=\u0026thinsp;1), VM-26\u0026thinsp;+\u0026thinsp;CDDP (n\u0026thinsp;=\u0026thinsp;1), and VM-26\u0026thinsp;+\u0026thinsp;Bev (n\u0026thinsp;=\u0026thinsp;1).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eClinical characteristics of patients\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"2\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCharacteristic\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCase (n\u0026thinsp;=\u0026thinsp;38)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGender\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e21\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e17\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e18\u0026ndash;60\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e27\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026gt;60\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e11\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePrimary/non-primary status\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePrimary\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e21\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRecurrent\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e17\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTumor burden status\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePresence\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e24\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAbsence\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e14\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGrade\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e33\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePathological type\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGlioblastoma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e28\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAstrocytoma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDiffuse midline glioma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAnaplastic Oligodendroglioma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNumber of administrations (VM-26)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMedian (range from 1 to 26)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4.5\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDosage of VM-26\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e50mg\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e32\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e100mg\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTreatment protocol\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVM-26\u0026thinsp;+\u0026thinsp;Bev\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVM-26\u0026thinsp;+\u0026thinsp;CDDP\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVM-26\u0026thinsp;+\u0026thinsp;CDDP\u0026thinsp;+\u0026thinsp;Bev\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVM-26\u0026thinsp;+\u0026thinsp;CDDP\u0026thinsp;+\u0026thinsp;TMZ\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVM-26\u0026thinsp;+\u0026thinsp;TMZ\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVM-26\u0026thinsp;+\u0026thinsp;TMZ\u0026thinsp;+\u0026thinsp;Anl\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVM-26\u0026thinsp;+\u0026thinsp;TMZ\u0026thinsp;+\u0026thinsp;Bev\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e20\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVM-26\u0026thinsp;+\u0026thinsp;TMZ\u0026thinsp;+\u0026thinsp;MTX (intrathecal)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"2\"\u003eVM-26: Teniposide; Bev: Bevacizumab; CDDP: Cisplatin;\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"2\"\u003eTMZ: Temozolomide; Anl, Anlotinib; MTX, Intrathecal methotrexate\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e(MTX) injection.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eSafety assessment\u003c/h2\u003e \u003cp\u003eThe safety assessment of all treatment regimens is detailed in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e. Among the 19 patients receiving VM-26 (50 mg/d) combined with TMZ and bevacizumab, 52.63% (10/19) experienced adverse events, including one case of grade 1 fatigue, seven cases of grade 2 neutropenia, one case of grade 3 neutropenia, and one case of grade 4 neutropenia. One additional patient treated with the same regimen but at VM-26 (100 mg/d) reported grade 1 myelosuppression.\u003c/p\u003e \u003cp\u003eIn the cohort receiving VM-26 (50 mg/d) plus TMZ (n\u0026thinsp;=\u0026thinsp;7), 42.9% (3/7) developed AEs: one case of grade 2 neutropenia, one case of grade 2 myelosuppression, and one case of grade 1 vomiting. One case of grade 2 leukopenia was observed in the regimen of VM-26 (100 mg/d) plus TMZ. For the cohort receiving VM-26 (50 mg/d) combined with TMZ and anlotinib (n\u0026thinsp;=\u0026thinsp;2), AEs comprised one case of grade 2 neutropenia and one case presenting with both grade 2 neutropenia and drug-induced liver injury. The patient receiving VM-26 (50 mg/d) plus TMZ and intrathecal methotrexate experienced grade 2 neutropenia and thrombocytopenia.\u003c/p\u003e \u003cp\u003eIn the VM-26 (50 mg/d) combined with CDDP and bevacizumab cohort (n\u0026thinsp;=\u0026thinsp;2), no AEs were observed. However, patients receiving​ VM-26 (100 mg/d) combined with CDDP (including VM-26\u0026thinsp;+\u0026thinsp;CDDP\u0026thinsp;+\u0026thinsp;TMZ, VM-26\u0026thinsp;+\u0026thinsp;CDDP, and VM-26\u0026thinsp;+\u0026thinsp;CDDP\u0026thinsp;+\u0026thinsp;Bev) developed severe AEs: three cases of grade 3 neutropenia and one case of grade 4 neutropenia.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eSafety Assessment of treatment protocol\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"3\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTreatment protocol\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eIncidence rate of adverse reactions\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eIncidence rate of grade\u0026thinsp;\u0026ge;\u0026thinsp;3 adverse reactions\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVM-26\u0026thinsp;+\u0026thinsp;Bev (n\u0026thinsp;=\u0026thinsp;1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e50mg (n\u0026thinsp;=\u0026thinsp;1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e100% (1/1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0% (0/1)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVM-26\u0026thinsp;+\u0026thinsp;CDDP (n\u0026thinsp;=\u0026thinsp;1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e100mg (n\u0026thinsp;=\u0026thinsp;1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e100% (1/1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e100% (1/1)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVM-26\u0026thinsp;+\u0026thinsp;CDDP\u0026thinsp;+\u0026thinsp;Bev (n\u0026thinsp;=\u0026thinsp;4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e50mg (n\u0026thinsp;=\u0026thinsp;2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0% (0/2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0% (0/2)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e100mg (n\u0026thinsp;=\u0026thinsp;2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e100% (2/2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e100% (2/2)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVM-26\u0026thinsp;+\u0026thinsp;CDDP\u0026thinsp;+\u0026thinsp;TMZ (n\u0026thinsp;=\u0026thinsp;1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e100mg (n\u0026thinsp;=\u0026thinsp;1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e100% (1/1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e100% (1/1)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVM-26\u0026thinsp;+\u0026thinsp;TMZ (n\u0026thinsp;=\u0026thinsp;8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e50mg (n\u0026thinsp;=\u0026thinsp;7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e42.86% (3/7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0% (0/7)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e100mg (n\u0026thinsp;=\u0026thinsp;1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e100% (1/1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0% (0/1)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVM-26\u0026thinsp;+\u0026thinsp;TMZ\u0026thinsp;+\u0026thinsp;Anl (n\u0026thinsp;=\u0026thinsp;2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e50mg (n\u0026thinsp;=\u0026thinsp;2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e100% (2/2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0% (0/2)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVM-26\u0026thinsp;+\u0026thinsp;TMZ\u0026thinsp;+\u0026thinsp;Bev (n\u0026thinsp;=\u0026thinsp;20)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e50mg (n\u0026thinsp;=\u0026thinsp;19)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e52.63% (10/19)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10.53% (2/19)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e100mg (n\u0026thinsp;=\u0026thinsp;1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e100% (1/1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0% (0/1)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVM-26\u0026thinsp;+\u0026thinsp;TMZ\u0026thinsp;+\u0026thinsp;MTX (n\u0026thinsp;=\u0026thinsp;1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e50mg (n\u0026thinsp;=\u0026thinsp;1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e100% (1/1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0% (0/1)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eVM-26: Teniposide; Bev: Bevacizumab; CDDP: Cisplatin; TMZ: Temozolomide; Anl, Anlotinib; MTX, Intrathecal methotrexate injection.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003e\u003c/h3\u003e\n\u003cdiv class=\"Heading\"\u003e\u003cb\u003eEfficacy assessment of glioma patients with tumor burden\u003c/b\u003e\u003c/div\u003e \u003cp\u003eTable\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e summarizes outcomes in the 24 glioma patients with measurable tumor burden. No complete responses (CR) were observed. Partial responses (PR), stable disease (SD), and progressive disease (PD) occurred in 8 (33.3%), 7 (29.2%), and 9 (37.5%) patients, respectively. The ORR was 33.3%, and the DCR was 62.5%.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eEfficacy assessment of the tumor present group\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"2\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEfficacy indicators\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eTumor-present group (n\u0026thinsp;=\u0026thinsp;24)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eORR/%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e33.3%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDCR/%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e62.5%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"2\"\u003eCR: Complete response; PR: partial response; SD: stable disease;\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"2\"\u003ePD: Progressive disease; ORR: Objective response rate;\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eDCR: Disease control rate.\u003c/p\u003e\n\u003ch3\u003ePrognosis among different groups of GBM Patients\u003c/h3\u003e\n\u003cp\u003eTable\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e and Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e summarize survival outcomes of four distinct GBM cohorts stratified by tumor burden and disease status. Among patients with measurable tumor burden (n\u0026thinsp;=\u0026thinsp;20), the median PFS was 4.15 months​ (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003ea), while those without measurable tumor burden (n\u0026thinsp;=\u0026thinsp;13) exhibited a longer median PFS of 12.20 months (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003ed). The median OS-VM26 in the tumor-present group was 7.57 months​ (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eb), and the median OS-total was 15.30 months (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003ec). Neither the OS-VM26 nor the OS-total reached the median values observed in the tumor-absent cohort (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003ee-f).\u003c/p\u003e \u003cp\u003eBy disease status, patients with de novo primary GBM (n\u0026thinsp;=\u0026thinsp;20, including 9 tumor-present cases and 11 tumor-absent cases) demonstrated superior outcomes: median PFS was 7.70 months (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eg), median OS-VM26 was 17.70 months (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eh), and median OS-total was 18.53 months (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003ei). Recurrent GBM patients (n\u0026thinsp;=\u0026thinsp;13, including 11 tumor-present cases, and 2 tumor-absent cases after second surgery) showed inferior survival, with a median PFS of 3.17 months (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003ej), a median OS-VM26 of 6.63 months (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003ek), and a median OS-total of 23.90 months (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003el).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eThe prognosis of different groups of GBM patients\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eclinical feature\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePresent group (n\u0026thinsp;=\u0026thinsp;20)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eAbsent group (n\u0026thinsp;=\u0026thinsp;13)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003ePrimary group (n\u0026thinsp;=\u0026thinsp;20)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eRecurrent group (n\u0026thinsp;=\u0026thinsp;13)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePFS median\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e4.15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e12.20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e7.70\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e3.17\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOS-VM26 median\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e7.57\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e/\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e17.70\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e6.63\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOS-total median\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e15.30\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e/\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e18.53\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e23.90\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003ePFS: Progression-free survival; OS-VM-26: Overall survival from VM-26 initiation; OS-total: Overall survival.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003ePrognostic analysis of molecular subgroups in patients with GBM\u003c/h2\u003e \u003cp\u003eSurvival outcomes across molecular subgroups in patients with tumor burden were presented in Table\u0026nbsp;\u003cspan refid=\"Tab5\" class=\"InternalRef\"\u003e5\u003c/span\u003e and Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e. In the TERT subgroup, patients with TERT mutation (n\u0026thinsp;=\u0026thinsp;9) showed a median PFS of 6.13 months, a median OS-VM26 of 8.63 months, and a median OS-total of 18.53 months, whereas wild-type TERT (n\u0026thinsp;=\u0026thinsp;7) showed inferior median values (PFS\u0026thinsp;=\u0026thinsp;5.77 months; OS-VM26\u0026thinsp;=\u0026thinsp;6.53 months; OS-total\u0026thinsp;=\u0026thinsp;10.47 months). However, these clinical indicators did not reach statistical significance (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e.a-c, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.73 for PFS, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.31 for OS-VM26, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.64 for OS-total). In the MGMT subgroup (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e.d-f), patients with MGMT promoter methylation (n\u0026thinsp;=\u0026thinsp;5) demonstrated significantly prolonged OS-VM26 (median 17.70 months) and OS-total (median 38.42 months) compared to those with unmethylated MGMT (n\u0026thinsp;=\u0026thinsp;10, median OS-VM26\u0026thinsp;=\u0026thinsp;6.22 months, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.007; median OS-total\u0026thinsp;=\u0026thinsp;10.84 months, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.008), though PFS did not differ significantly between the two groups (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.056). In the CDKN2A/B subgroup, no significant differences in survival were observed between patients with CDKN2A/B loss (n\u0026thinsp;=\u0026thinsp;4) and those with wild-type CDKN2A/B (n\u0026thinsp;=\u0026thinsp;10) (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e.g-i, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.39 for PFS, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.60 for OS-VM26, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.17 for OS-total).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab5\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 5\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eThe prognosis of genetic subtypes in GBM patients with tumor burden\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSubtype\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePFS\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eOS-VM-26\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eOS-total\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTERT\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMut (n\u0026thinsp;=\u0026thinsp;9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6.13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8.63\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e18.53\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eWild (n\u0026thinsp;=\u0026thinsp;7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5.77\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6.53\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e10.47\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eP\u003c/em\u003e-value\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ens\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003ens\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003ens\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMGMT\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMet (n\u0026thinsp;=\u0026thinsp;5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e11.73\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e17.70\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e38.42\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eWild (n\u0026thinsp;=\u0026thinsp;10)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4.87\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6.22\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e10.84\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eP\u003c/em\u003e-value\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ens\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCDKN2A/B\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLost (n\u0026thinsp;=\u0026thinsp;4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4.00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8.60\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e27.12\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eWild (n\u0026thinsp;=\u0026thinsp;10)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5.05\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6.58\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e11.73\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eP\u003c/em\u003e-value\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ens\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003ens\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003ens\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003ePFS: Progression-free survival; OS-VM-26: Overall survival from VM-26 initiation;\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003eOS-total: Overall survival. TERT: Telomerase reverse transcriptase; MGMT:\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003eO-6-methylguanine-DNA methyltransferase; CDKN2A/B: Cyclin-dependent\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003ekinase inhibitor 2A/B.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec12\" class=\"Section2\"\u003e \u003ch2\u003eEfficacy assessment of 3 patients with diffuse midline glioma\u003c/h2\u003e \u003cp\u003eThis study included three patients with pathologically confirmed grade 4 diffuse midline gliomas (DMG) who received teniposide-based therapy (Table\u0026nbsp;\u003cspan refid=\"Tab6\" class=\"InternalRef\"\u003e6\u003c/span\u003e). Baseline characteristics revealed that all cases were primary tumors. DMG1​ exhibited multiple lesions, a Karnofsky Performance Status (KPS) score of 50, and measurable tumor burden. DMG2​ manifested as a solitary tumor with a KPS score of 90 and lacked initial measurable tumor burden. DMG3​ presented as a solitary tumor with a KPS score of 80 and had initial measurable tumor burden.\u003c/p\u003e \u003cp\u003eTreatment regimens varied among the patients: DMG1 received VM‑26 (100 mg/d for 7 cycles) plus TMZ; DMG2 received VM‑26 (50 mg/d for 6 cycles) plus TMZ, followed by long‑term anlotinib; and DMG3 received VM‑26 (50 mg/d for 5 cycles) combined with TMZ and bevacizumab.\u003c/p\u003e \u003cp\u003eRegarding efficacy, DMG1 achieved a partial response (PR) but had a PFS of only 7 months, an OS‑VM26 of 9.03 months, and an OS-total of 9.63 months, accompanied by grade 2 treatment‑related adverse events. DMG2 attained stable disease (SD), with a PFS of 13.20 months, an OS‑VM26 of 19.37 months, and an OS-total of 20.27 months, and only grade 1 adverse events. Despite the addition of bevacizumab, DMG3 showed a PFS of 5.77 months, an OS‑VM26 of 6.53 months, and an OS-total of 8.03 months, accompanied by grade 2 adverse events.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab6\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 6\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eEfficacy Assessment Table of 3 Patients with Diffuse Midline Glioma\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eClinical feature\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eDMG1\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eDMG2\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eDMG3\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGrade\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePrimary/non-primary status\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePrimary\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003ePrimary\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003ePrimary\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSolitary/Multiple Tumors\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMultiple\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eSolitary\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eSolitary\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTumor burden status\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePresence\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eAbsence\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003ePresence\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNumber of administrations (VM-26)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTreatment protocol\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eVM-26\u0026thinsp;+\u0026thinsp;TMZ\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eVM-26\u0026thinsp;+\u0026thinsp;TMZ\u0026thinsp;+\u0026thinsp;Anl\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eVM-26\u0026thinsp;+\u0026thinsp;TMZ\u0026thinsp;+\u0026thinsp;Bev\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDosage of VM-26\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e100mg\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e50mg\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e50mg\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eKPS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e50\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e90\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e80\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTumor response\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eSD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eSD\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSurvival status\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eDead\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eAlive\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eDead\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePFS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7.00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e13.20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5.77\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOS-VM26\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9.03\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e19.37\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e6.53\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOS-total\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9.63\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e20.27\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e8.03\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGrade of adverse events\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eVM-26: Teniposide; KPS: Karnofsky performance status; PFS: Progression-free survival; OS-VM-26: Overall survival from VM-26 initiation; OS: Overall survival; VM-26: Teniposide; TMZ: Temozolomide; Anl, Anlotinib; Bev: Bevacizumab.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec13\" class=\"Section2\"\u003e \u003ch2\u003eEfficacy assessment of one representative patient\u003c/h2\u003e \u003cp\u003eTable\u0026nbsp;\u003cspan refid=\"Tab7\" class=\"InternalRef\"\u003e7\u003c/span\u003e illustrates the therapeutic efficacy in one representative GBM patient receiving VM-26-based therapy.​ The patient, a case of recurrent GBM with widespread metastases (including leptomeningeal and cervical spinal cord involvement; positive cerebrospinal fluid cytology), underwent an 8-cycle regimen of VM-26 (50 mg/day, days 1\u0026ndash;3) combined with TMZ (200 mg/m\u003csup\u003e2\u003c/sup\u003e, days 1\u0026ndash;5), Bev (5 mg/kg, day 1), and intrathecal thiotepa (10mg/d, day 1), administered in 28-day cycles (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e. a\u0026amp;c). The patient achieved a partial response (characterized by significant tumor shrinkage from baseline and negative cerebrospinal fluid cytology), with a PFS of 11.73 months and an OS-VM26 of 19.97 months (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e. b\u0026amp;d). Notably, the patient remained alive at the last follow-up, with manageable grade 2 adverse events.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab7\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 7\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eOne representative patients\u0026rsquo; efficacy assessment\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"2\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eClinical features\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGrade\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePrimary/Recurrent status\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eRecurrent\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSolitary/Multiple tumors\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSolitary\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTumor burden status\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePresence\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNumber of administrations (VM-26)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTreatment protocol\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eVM-26\u0026thinsp;+\u0026thinsp;TMZ\u0026thinsp;+\u0026thinsp;Bev\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDosage of VM-26\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e50mg/m2\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eKPS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e80\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTumor response\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePR\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSurvival status\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAlive\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePFS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e11.73\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOS-VM26\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e19.97\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOS-total\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e41.13\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGrade of adverse reactions\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"2\"\u003eVM-26: Teniposide; KPS: Karnofsky performance status; PFS:\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"2\"\u003eProgression-free survival; OS-VM-26: Overall survival from\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eVM-26 initiation; OS-total: Overall survival.\u003c/p\u003e \u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eDespite current standard-of-care therapies, the prognosis for GBM patients remains dismal, driving intensive efforts to integrate novel therapeutic agents into clinical regimens. After teniposide was reintroduced in China in 2022, we implemented teniposide-based therapy for glioma treatment, particularly focusing on​ medically challenging patients, including patients with recurrence or progression after standard therapy, a large residual tumor volume, MGMT promoter unmethylated status, or poor performance status. In this study, we demonstrated acceptable safety for teniposide-based therapy and observed its efficacy in glioma patients.\u003c/p\u003e \u003cp\u003eThis study evaluated the safety profile of teniposide-based therapies. The low-dose VM-26 (50 mg/d) regimen exhibited manageable hematological toxicity (incidence of grade 1\u0026ndash;2 AEs: 46.87%, grade 3\u0026ndash;4 AEs: 6.25%), underscoring its feasibility as an alternative for elderly or frail patients. Similarly, a previous study assessing the safety of​ intra-arterial chemotherapy​ (BCNU 100 mg/m\u0026sup2; + cisplatin 60 mg/m\u0026sup2; + VM-26​ 150 mg/m\u0026sup2;) in patients with primary or metastatic intracranial tumors found that only 9% of patients receiving lower-dose​ VM-26 experienced permanent severe toxicity \u003csup\u003e[\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]\u003c/sup\u003e. In contrast, the high-dose VM-26 (100 mg/d) regimen combined with platinum-based agents (e.g., VM-26\u0026thinsp;+\u0026thinsp;CDDP, VM-26\u0026thinsp;+\u0026thinsp;CDDP\u0026thinsp;+\u0026thinsp;Bev, VM-26\u0026thinsp;+\u0026thinsp;CDDP\u0026thinsp;+\u0026thinsp;TMZ) warranted caution owing to the risk of severe myelosuppression, given that all such combinations were associated with grade\u0026thinsp;\u0026ge;\u0026thinsp;3 AEs. The higher incidence of severe AEs in this regimen was potentially due to three factors: the limited sample size (only 4 cases), use of salvage therapy, and the impaired functional status (KPS\u0026thinsp;\u0026lt;\u0026thinsp;70) of enrolled patients. These findings suggested that VM-26-based therapy (without platinum agents) exhibited an acceptable safety profile in GBM patients, even in those with fragile status.\u003c/p\u003e \u003cp\u003eOur study examined the efficacy of teniposide-based regimens in GBM patients with measurable​ tumor burden, demonstrating​ an ORR of 36.4% and a DCR of 68.2%. While a study assessing the lomustine-bevacizumab combination for progressive GBM \u003csup\u003e[\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]\u003c/sup\u003e reported an ORR of 41.5%, teniposide-based therapy covered a broader patient population by providing an alternative with lower economic burden, and applicability to patients with lower KPS scores or even fragile status. Compared with the 28% ORR reported for teniposide monotherapy in recurrent gliomas \u003csup\u003e[\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]\u003c/sup\u003e, the combination regimen in our study achieved a higher ORR, thereby supporting its synergistic potential. As an innovative therapy, immunotherapies necessitate rigorous clinical investigation to validate their clinical utility, since systematic reviews report they remain investigational with most clinical trials yielding suboptimal results (ORR typically below 20%) \u003csup\u003e[\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eOur study reported the median PFS of 7.7 months for the primary GBM group. Given that TTFields is not yet widely available and is costly, a phase 2 study reported a PFS of 5.8 months \u003csup\u003e[\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]\u003c/sup\u003e in newly diagnosed GBM patients treated with TTFields and temozolomide alone following chemoradiotherapy, thereby highlighting the potential cost-effectiveness advantages of the teniposide-based regimen. Additionally, phase 1 results of OLA-TMZ-RTE-01 revealed that olaparib, temozolomide, and concurrent radiotherapy yielded a PFS of 6.2 months in GBM patients undergoing partial resection or biopsy-only \u003csup\u003e[\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]\u003c/sup\u003e. As the related phase 2 study remains incomplete, clinical application of this regimen requires a prolonged wait, which further underscores the teniposide-based regimen\u0026rsquo;s superior outcomes and broad application potential.\u003c/p\u003e \u003cp\u003eGBM recurrence is an inevitable event, with primary GBM showing a median PFS of approximately 7 months \u003csup\u003e[\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]\u003c/sup\u003e. We further focused on the PFS of recurrent GBM patients receiving a teniposide-based regimen and reported a median PFS of 3.17 months and median OS‑VM26 of 6.63 months. In comparison with the bevacizumab monotherapy group for recurrent glioblastoma (median PFS of 3.7 months, median OS of 7.9 months) \u003csup\u003e[\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]\u003c/sup\u003e, our study showed​ more favorable outcomes in tumor-present GBM patients (mostly with large tumors): a median PFS of 4.15 months, a median OS‑VM26 of 7.57 months, and a median OS-total of 15.30 months.\u003c/p\u003e \u003cp\u003eMolecular subtype analysis in the tumor-present group revealed that overall survival, including both OS-VM26 and OS-total, was significantly better in the MGMT methylated subgroup than in the unmethylated subgroup (both \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05). This result may be attributed to the underlying mechanism: MGMT promoter methylation reduces DNA repair capacity in tumor cells, thereby increasing the sensitivity to teniposide-an inhibitor of topoisomerase II activity. For the tumor-absent group, the majority in our study were newly diagnosed GBM patients who underwent gross total resection, and no significant difference in prognostic outcomes was detected between the MGMT unmethylated and methylated subgroups. As is known, newly diagnosed GBM patients with MGMT unmethylated status generally have a poorer prognosis when treated with the Stupp protocol than those with MGMT methylated status \u003csup\u003e[\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]\u003c/sup\u003e. This suggests that VM-26-based therapy should be actively adopted for newly diagnosed GBM patients with unmethylated MGMT.\u003c/p\u003e \u003cp\u003eThis study is subject to several limitations inherent to its design and scope. The single-center retrospective design is prone to inherent selection biases, including potential confounding by treatment timing within tumor burden subgroups. The modest sample size constrains statistical power, particularly in subgroup analyses where certain molecular cohorts have inadequate representation for robust conclusions. Additionally, therapeutic heterogeneity poses challenges: heterogeneous combination regimens (e.g., VM-26\u0026thinsp;+\u0026thinsp;TMZ\u0026thinsp;+\u0026thinsp;Bev, VM-26\u0026thinsp;+\u0026thinsp;CDDP) and variable dosing schedules (50 mg vs. 100 mg) complicate the attribution of outcomes to specific agents, while temporal variations in treatment duration further obscure dose-response relationships.\u003c/p\u003e \u003cp\u003eThis study addresses critical gaps in glioblastoma therapeutics through two transformative advancements. Amid a global hiatus in teniposide (VM-26) production, our work presents the inaugural clinical dataset from China following its reintroduction, establishing a foundational reference for future VM-26-based combination therapies in GBM. We systematically evaluated the adverse events of VM-26-based combinations and demonstrated acceptable safety. Furthermore, our results suggested this therapy could represent a candidate therapeutic option for GBM patients, especially with tumor presence and newly diagnosed GBM patients with unmethylated MGMT status.\u003c/p\u003e"},{"header":"Statements \u0026 Declarations","content":"\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was supported by the National Natural Science Foundation of China (No. 82472722) and Beijing Hope Run Special Fund of Cancer Foundation of China (No. LC2022B18).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eJinghai Wan and Hongqing Cai designed the study and revised the manuscript. Zekun Deng and Yujia Chen drafted the manuscript. Huaixu Li, Qi Liu, and Chang Fang collected the data. Jinghai Wan, Haipeng Qian, and Ming Yang reviewed the paper. All authors made substantial contributions to the study and approved the submitted version.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData availability\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNo datasets were generated or analysed during the current study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was conducted in accordance with the ethical principles of the Declaration of Helsinkiand was reviewed and approved by the Ethics Committee of Cancer Hospital, Chinese Academy of Medical Sciences for implementation (approval number: NCC4687). \u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eInformed consent was obtained from all individual participants included in the study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent to publish\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors affirm that human research participants provided informed consent for publication of the images in Figure 3A-D.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n \u003cli\u003eLouis, D.N. et al (2021) The 2021 WHO Classification of Tumors of the Central Nervous System: a summary. Neuro Oncol 23(8): p. 1231-1251.\u003c/li\u003e\n \u003cli\u003eOstrom, Q.T. et al (2021) CBTRUS Statistical Report: Primary Brain and Other Central Nervous System Tumors Diagnosed in the United States in 2014-2018. Neuro Oncol 23(12 Suppl 2): p. iii1-iii105.\u003c/li\u003e\n \u003cli\u003eStupp, R. et al (2017) Effect of Tumor-Treating Fields Plus Maintenance Temozolomide vs Maintenance Temozolomide Alone on Survival in Patients With Glioblastoma: A Randomized Clinical Trial. JAMA 318(23): p. 2306-2316.\u003c/li\u003e\n \u003cli\u003eLim, M. et al (2022) Phase III trial of chemoradiotherapy with temozolomide plus nivolumab or placebo for newly diagnosed glioblastoma with methylated MGMT promoter. Neuro Oncol 24(11): p. 1935-1949.\u003c/li\u003e\n \u003cli\u003eHegi, M.E. et al (2005) MGMT gene silencing and benefit from temozolomide in glioblastoma. N Engl J Med 352(10): p. 997-1003.\u003c/li\u003e\n \u003cli\u003eWick, W. et al (2014) MGMT testing--the challenges for biomarker-based glioma treatment. Nat Rev Neurol 10(7): p. 372-85.\u003c/li\u003e\n \u003cli\u003eTan, A.C. et al (2020) Management of glioblastoma: State of the art and future directions. CA Cancer J Clin 70(4): p. 299-312.\u003c/li\u003e\n \u003cli\u003eMellinghoff, I.K. et al (2023) Vorasidenib in IDH1- or IDH2-Mutant Low-Grade Glioma. N Engl J Med 389(7): p. 589-601.\u003c/li\u003e\n \u003cli\u003eWen, P.Y. et al (2019) Buparlisib in Patients With Recurrent Glioblastoma Harboring Phosphatidylinositol 3-Kinase Pathway Activation: An Open-Label, Multicenter, Multi-Arm, Phase II Trial. J Clin Oncol 37(9): p. 741-750.\u003c/li\u003e\n \u003cli\u003eMa, D.J. et al (2015) A phase II trial of everolimus, temozolomide, and radiotherapy in patients with newly diagnosed glioblastoma: NCCTG N057K. Neuro Oncol 17(9): p. 1261-9.\u003c/li\u003e\n \u003cli\u003eWick, W. et al (2016) Phase II Study of Radiotherapy and Temsirolimus versus Radiochemotherapy with Temozolomide in Patients with Newly Diagnosed Glioblastoma without MGMT Promoter Hypermethylation (EORTC 26082). Clin Cancer Res 22(19): p. 4797-4806.\u003c/li\u003e\n \u003cli\u003eBatchelor, T.T. et al (2013) Phase III randomized trial comparing the efficacy of cediranib as monotherapy, and in combination with lomustine, versus lomustine alone in patients with recurrent glioblastoma. J Clin Oncol 31(26): p. 3212-8.\u003c/li\u003e\n \u003cli\u003ePommier, Y. et al (2006) Topoisomerase I inhibitors: camptothecins and beyond. Nat Rev Cancer 6(10): p. 789-802.\u003c/li\u003e\n \u003cli\u003eBogdahn, U. et al (1987) Vidarabin-monophosphate, BCNU, VM26--an in vitro comparative study of active agents in the treatment of malignant human brain tumours. Br J Cancer 55(2): p. 153-8.\u003c/li\u003e\n \u003cli\u003eStewart, D.J. et al (1989) The role of chemotherapy in the treatment of gliomas in adults. Cancer Treat Rev 16(3): p. 129-60.\u003c/li\u003e\n \u003cli\u003eBrandes, A.A. et al (2003) Carboplatin and teniposide as third-line chemotherapy in patients with recurrent oligodendroglioma or oligoastrocytoma: a phase II study. Ann Oncol 14(12): p. 1727-31.\u003c/li\u003e\n \u003cli\u003eStewart, D.J. et al (1984) Intracarotid chemotherapy with a combination of 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU), cis-diaminedichloroplatinum (cisplatin), and 4\u0026apos;-O-demethyl-1-O-(4,6-O-2-thenylidene-beta-D-glucopyranosyl) epipodophyllotoxin (VM-26) in the treatment of primary and metastatic brain tumors. Neurosurgery 15(6): p. 828-33.\u003c/li\u003e\n \u003cli\u003eWick, W. et al (2017) Lomustine and Bevacizumab in Progressive Glioblastoma. N Engl J Med 377(20): p. 1954-1963.\u003c/li\u003e\n \u003cli\u003eSchalper, K.A. et al (2019) Neoadjuvant nivolumab modifies the tumor immune microenvironment in resectable glioblastoma. Nat Med 25(3): p. 470-476.\u003c/li\u003e\n \u003cli\u003eChen, D. et al (2025) Efficacy and safety of adjuvant TTFields plus pembrolizumab and temozolomide in newly diagnosed glioblastoma: A phase 2 study. Med 6(9): p. 100708.\u003c/li\u003e\n \u003cli\u003eStefan, D. et al (2025) Olaparib, Temozolomide, and Concomitant Radiotherapy for Partially Resected or Biopsy-Only Glioblastoma First-Line Treatment: Results from the OLA-TMZ-RTE-01 Phase I Study. Clin Cancer Res 31(7): p. 1212-1222.\u003c/li\u003e\n \u003cli\u003eSchaff, L.R. and I.K. Mellinghoff (2023) Glioblastoma and Other Primary Brain Malignancies in Adults: A Review. JAMA 329(7): p. 574-587.\u003c/li\u003e\n \u003cli\u003eBrandner, S. et al (2021) MGMT promoter methylation testing to predict overall survival in people with glioblastoma treated with temozolomide: a comprehensive meta-analysis based on a Cochrane Systematic Review. Neuro Oncol 23(9): p. 1457-1469.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Teniposide, Glioblastoma, Retrospective study, Glioma","lastPublishedDoi":"10.21203/rs.3.rs-9311229/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-9311229/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003ePurpose\u003c/strong\u003e: Glioma remains challenging despite standard therapy, necessitating novel treatment strategies. This study aimed to evaluated the efficacy and safety of teniposide (VM-26)-based therapy in glioma patients.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods\u003c/strong\u003e: A retrospective analysis was conducted on glioma patients treated with teniposide-based therapy between 2022 and 2025. Safety assessments were performed using Common Terminology Criteria for Adverse Events (CTCAE). Efficacy was evaluated according to the Response Assessment in Neuro-Oncology (RANO) criteria. Kaplan-Meier analysis was utilized to estimate the prognosis of patients.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults\u003c/strong\u003e: Thirty-eight patients were enrolled. Regarding adverse events (AEs), 39.5% of patients experienced no AEs, 44.7% developed AEs below grade 3, whereas 15.8% presented with grade 3 and 4 AEs. No treatment-related deaths occurred. In tumor-present gliomas patients, the objective response rate (ORR) was 33.3% and the disease control rate (DCR) was 62.5%. Among tumor-present glioblastomas (GBM) patients, the median progression-free survival (PFS) was 4.15 months versus 12.20 months in tumor-absent GBM. The median overall survival after VM-26 (OS-VM-26) was 7.57 months in tumor-present GBM, whereas the median value was not reached in tumor-absent GBM. The median OS-VM26 was 17.70 months for primary GBM and 6.63 months for recurrent GBM, respectively. Molecular subtypes analysis of the tumor-present GBM revealed that the MGMT-methylated group had superior OS-VM26 and overall survival (OS) (both \u003cem\u003ep\u003c/em\u003e \u0026lt; 0.05), with no significant difference in PFS. One representative case illustrated durable response with manageable toxicity.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion\u003c/strong\u003e: Teniposide-based therapy demonstrated acceptable safety. This therapy may serve as a candidate treatment option for patients with GBM.\u003c/p\u003e","manuscriptTitle":"Safety and efficacy of teniposide-based therapy for glioma: a single-center retrospective study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-04-10 16:52:59","doi":"10.21203/rs.3.rs-9311229/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"28d6d542-35a3-4c08-9095-2fe06649becc","owner":[],"postedDate":"April 10th, 2026","published":true,"recentEditorialEvents":[{"type":"decision","content":"Rejected","date":"2026-05-04T02:34:51+00:00","index":"","fulltext":""}],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2026-05-04T02:40:32+00:00","versionOfRecord":[],"versionCreatedAt":"2026-04-10 16:52:59","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-9311229","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-9311229","identity":"rs-9311229","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}