Synergistic and Additive Effects of Herbal Medicines in Combination with Chemotherapeutics: A Scoping Review.

BACKGROUND: Natural products are increasingly gaining interest as potential new drug candidates for cancer treatment. Herbal formula, which are combinations of several herbs, are primarily used in East Asia and have a long history of use that continues today. Recently, research exploring the combination of herbal formulas and chemotherapy for cancer treatment has been on the rise. METHODS: This study reviewed research on the co-administration of herbal formulas and chemotherapy for cancer treatment. The databases PubMed, Embase, and Cochrane Library were used for article searches. The following keywords were employed: "Antineoplastic agents," "Chemotherapy," "Phytotherapy," "Herbal medicine," "Drug synergism," and "Synergistic effect." The selection process focused on studies that investigated the synergistic interaction between herbal formulas and chemotherapeutic agents. RESULTS: Among the 30 studies included, 25 herbal formulas and 7 chemotherapies were used. The chemotherapy agents co-administered included cisplatin, 5-fluorouracil, docetaxel, doxorubicin, oxaliplatin, irinotecan, and gemcitabine. The types of cancer most frequently studied were lung, breast, and colon cancers. Most studies evaluating the anticancer efficacy of combined herbal formula and chemotherapy treatment were conducted in vitro or in vivo. DISCUSSION: Most studies reported synergistic effects on cytotoxicity, apoptosis, and tumor growth inhibition. These effects were found to be associated with cell cycle arrest, anti-angiogenesis, and gene expression regulation. Further studies leading to clinical trials are required. Clinical experiences in East Asian countries could provide insights for future research.

The Convergence of Sonodynamic Therapy and Cuproptosis in the Dual-Responsive Biomimetic CytoNano for Precision Mitochondrial Intervention in Cancer Treatment.

The integration of sonodynamic therapy (SDT) with cuproptosis for targeted cancer treatment epitomizes a significant advancement in oncology. Herein, we present a dual-responsive therapeutic system, "CytoNano", which combines a cationic liposome infused with copper-nitride nanoparticles and oxygen-rich perfluorocarbon (Lip@Cu3N/PFC-O2), all enveloped in a biomimetic coating of neutrophil membrane and acid-responsive carboxymethylcellulose. CytoNano leverages the cellular mimicry of neutrophils and acid-responsive materials, enabling precise targeting of tumors and their acidic microenvironment. This strategic design facilitates the targeted release of Lip@Cu3N/PFC-O2 within the tumor, enhancing cancer cell uptake and mitochondrial localization. Consequently, it amplifies the therapeutic efficacy of both Cu3N-driven SDT and cuproptosis while preserving healthy tissues. Additionally, CytoNano's ultrasound responsiveness enhances intratumoral oxygenation, overcoming physiological barriers and initiating a combined sonodynamic-cuproptotic effect that induces multiple cell death pathways. Thus, we pioneer a biomimetic approach in precise sonodynamic cuproptosis, revolutionizing cancer therapy.

Transcription factor EHF drives cholangiocarcinoma development through transcriptional activation of glioma-associated oncogene homolog 1 and chemokine CCL2.

Cholangiocarcinoma (CCA) is characterized by rapid onset and high chance of metastasis. Therefore, identification of novel therapeutic targets is imperative. E26 transformation-specific homologous factor (EHF), a member of the E26 transformation-specific transcription factor family, plays a pivotal role in epithelial cell differentiation and cancer progression. However, its precise role in CCA remains unclear. In this study, through in vitro and in vivo experiments, we demonstrated that EHF plays a profound role in promoting CCA by transcriptional activation of glioma-associated oncogene homolog 1 (GLI1). Moreover, EHF significantly recruited and activated tumor-associated macrophages (TAMs) through the C-C motif chemokine 2/C-C chemokine receptor type 2 (CCL2/CCR2) axis, thereby remodeling the tumor microenvironment. In human CCA tissues, EHF expression was positively correlated with GLI1 and CCL2 expression, and patients with co-expression of EHF/GLI1 or EHF/CCL2 had the most adverse prognosis. Furthermore, the combination of the GLI1 inhibitor, GANT58, and CCR2 inhibitor, INCB3344, substantially reduced the occurrence of EHF-mediated CCA. In summary, our findings suggest that EHF is a potential prognostic biomarker for patients with CCA, while also advocating the therapeutic approach of combined targeting of GLI1 and CCL2/CCR2-TAMs to inhibit EHF-driven CCA development.

Long-term Outcomes of Hepatic Resection Combined With Intraoperative Ablation Versus Hepatic Resection Alone for Multinodular Hepatocellular Carcinoma: Insights from a Single-center Study.

BACKGROUND/AIM: The efficacy of combining hepatic resection (HR) with ablation therapy in treating multinodular hepatocellular carcinoma (mHCC) remains uncertain. This study aimed to compare the long-term survival outcomes of patients with mHCC undergoing HR combined with intraoperative ablation (HRA) versus those undergoing HR alone. PATIENTS AND METHODS: A retrospective analysis was conducted on 296 patients diagnosed with early-stage [Barcelona Clinic Liver Cancer (BCLC)-A] or intermediate-stage (BCLC-B) mHCC who underwent initial HR. Patients were divided into two groups: those who received HRA (HRA group, n=159) and those who underwent HR alone (HR group, n=137). Propensity score (PS), estimated as the likelihood of undergoing HRA, was applied to adjust for between-group differences in baseline characteristics. Overall survival (OS) and relapse-free survival (RFS) were compared using Cox regression and Kaplan-Meier analyses. RESULTS: There were no significant differences in survival between the HRA and HR groups, with 5-year OS and RFS rates of 47.7% versus 51.9% (p=0.837) and 17.0% versus 25.9% (p=0.094), respectively. After adjusting for PS, the differences remained non-significant (p=0.579 for OS and p=0.410 for RFS). Consistent results were also observed in PS-adjusted subgroup analysis stratified by factors such as BCLC stage, "Up-to-7" criteria, and Child-Pugh class. CONCLUSION: HRA may offer comparable long-term efficacy to HR alone in mHCC, suggesting broader treatment options that challenge the guideline-based monotherapy.

Carbon dots as a novel photosensitizer for photodynamic therapy of cancer and bacterial infectious diseases: recent advances.

Carbon dots (CDs) are novel carbon-based nanomaterials that have been used as photosensitizer-mediated photodynamic therapy (PDT) in recent years due to their good photosensitizing activity. Photosensitizers (PSs) are main components of PDT that can produce large amounts of reactive oxygen species (ROS) when stimulated by light source, which have the advantages of low drug resistance and high therapeutic efficiency. CDs can generate ROS efficiently under irradiation and therefore have been extensively studied in disease local phototherapy. In tumor therapy, CDs can be used as PSs or PS carriers to participate in PDT and play an extremely important role. In bacterial infectious diseases, CDs exhibit high bactericidal activity as CDs are effective in disrupting bacterial cell membranes leading to bacterial death upon photoactivation. We focus on recent advances in the therapy of cancer and bacteria with CDs, and also briefly summarize the mechanisms and requirements for PSs in PDT of cancer, bacteria and other diseases. We also discuss the role CDs play in combination therapy and the potential for future applications against other pathogens.

High-tailored Anal Canal Radiotherapy (HIT-ART): Outcomes of a 10-Year Single Center Clinical Experience.

BACKGROUND/AIM: The current standard for anal cancer treatment is essentially a 'one size fits all' approach where the dose of radiotherapy is similar whether the tumor is very small or very large. Trials are ongoing to evaluate dose de-escalation or escalation in localized disease depending on tumor size. The aim of the study was to assess results of a personalized approach involving dose stratification by stage and boost dose adjusted according to tumor early response. PATIENTS AND METHODS: We retrospectively reviewed squamous cell anal cancer (SCAC) patients treated between 2011 and 2021 by long-course intensity-modulated radiotherapy (IMRT) and concomitant chemotherapy (CT); a sequential boost could be administered by IMRT or interventional radiotherapy (IRT) to obtain a total equivalent dose in 2 Gy (EQD2) of 54-60 Gy. RESULTS: We analyzed 110 patients (61% T3-4 stage, 71% node-positive). A total of 68.2% of patients received a sequential boost, mainly by IRT; median total EQD2 to primary site was 59.3 Gy. Acute ≥G3 toxicity rate was 36.4%. Median follow-up (FUP) was 35.4 months. A total of 83% of patients achieved clinical complete response (cCR); locoregional recurrence (LRR) occurred in 20.9% and distant metastases in 6.4% of cases. A total of 12.7% patients underwent salvage surgery. A total of 25.5% of patients reported ≥G2 and 4.5% ≥G3 late toxicity. The estimated 3-year overall survival, disease-free survival and colostomy-free survival were 92%, 72% and 84% respectively; 3-year-LRR was 22%. Nodal stage was associated with poorer cCR probability and higher LRR (p<0.05). CONCLUSION: Our results on a large cohort of patients with locally advanced SCAC and long FUP time confirmed the efficacy of IMRT; high local control and manageable toxicity also suggest IRT as a promising method in treatment personalization.

Hug sign in intraprocedural cone-beam-CT to predict short-term response to combined treatment of hepatocellular carcinoma.

OBJECTIVES: Combined treatment of ablation and chemoembolization for hepatocellular carcinoma represents a promising therapy to increase treatment efficacy and improve patient survival. The "hug sign" is a recently introduced radiological sign consisting in deposition of beads/contrast agent during transarterial chemoembolization in the hyperemic area surrounding the post-ablation volume, seen during intraprocedural unenhanced cone-beam CT, that may indicate intraprocedural success. Aim of our retrospective study was to analyze the usefulness of the "hug sign" at the intraprocedural unenhanced cone-beam CT as an early predictor of response to combined treatment, based on the hug sign angle. MATERIALS AND METHODS: Between January 2017 and September 2021 all patients with hepatocellular carcinoma which underwent a combined treatment of thermal ablation followed by chemoembolization were enrolled. All treated patients underwent immediate post-procedural unenhanced cone-beam CT to evaluate the deposition of contrast agent, lipiodol or radiopaque beads and to assess the percentage of coverage of the ablated area with the contrast agent (hug sign angle). Patients with missing pre-procedural, intra-procedural and/or post-procedural data/imaging, or with poor-quality post-procedural cone-beam CT images were excluded. RESULTS: 128 patients (mean age, 69.3 years ± 1.1 [standard deviation]; 87 men) were evaluated. Our study evidenced that 84.4% (81/85) of patients with a hug sign angle of 360° had no residual tumor at the first 1-/3-months follow-up examination. A hug sign angle of 360° also showed to be an independent protective factor against residual tumor at multivariate analysis. CONCLUSION: Unenhanced cone-beam CT performed at the end of a combined treatment with ablation plus chemoembolization can effectively predict an early treatment response on radiological images, when a hug sign angle of 360° was detected.

Combination of Sodium Nitroprusside and Controlled Atmosphere Maintains Postharvest Quality of Chestnuts through Enhancement of Antioxidant Capacity.

The purpose of this study was to clarify the effect of CA (controlled atmosphere, 2-3% O2 + 3% CO2) and NO (nitric oxide, generated by 0.4 nM sodium nitroprusside), alone or combined (CA + NO), on the physio-chemical properties, enzyme activities and antioxidant capacities of chestnuts during storage at 0 °C for 180 d. Compared with control (CT), CA and CA+NO both improved the storage quality of the samples, but only CA resulted in more ethanol production. Moreover, these improvements were further enhanced and ethanol synthesis was inhibited by the addition of NO. A spectrometer was used to assess the production of phenolic content (TPC) and activities of phenylalanine ammonia-lyase (PAL), superoxide dismutas (SOD), peroxidase (POD), catalase (CAT) and polyphenol oxidase (PPO) as influenced by CA or CA+NO treatments. Higher TPC, PAL, SOD, POD, CAT, and lower PPO were observed in CA alone, and more so in the combination with NO group. The increased antioxidant production and enhanced antioxidant activities contributed to scavenging reactive oxygen species (ROS) and reducing malondialdehyde (MDA). This study unveiled the correlations and differences between the effects of CA and CA+NO on storage quality, providing valuable insights into postharvest preservation and suggesting that the combination (CA+NO) was more beneficial for quality maintenance in chestnuts.

The CDK Inhibitor Dinaciclib Improves Cisplatin Response in Nonseminomatous Testicular Cancer: A Preclinical Study.

BACKGROUND: Most patients with testicular germ cell tumors (GCTs) are treated with cisplatin (CP)-based chemotherapy. However, some of them may develop CP resistance and therefore represent a clinical challenge. Cyclin-dependent kinase 5 (CDK5) is involved in chemotherapy resistance in different types of cancer. Here, we investigated the possible role of CDK5 and other CDKs targeted by dinaciclib in nonseminoma cell models (both CP-sensitive and CP-resistant), evaluating the potential of the CDK inhibitor dinaciclib as a single/combined agent for the treatment of advanced/metastatic testicular cancer (TC). METHODS: The effects of dinaciclib and CP on sensitive and resistant NT2/D1 and NCCIT cell viability and proliferation were evaluated using MTT assays and direct count methods. Flow cytometry cell-cycle analysis was performed. The protein expression was assessed via Western blotting. The in vivo experiments were conducted in zebrafish embryos xenografted with TC cells. RESULTS: Among all the CDKs analyzed, CDK5 protein expression was significantly higher in CP-resistant models. Dinaciclib reduced the cell viability and proliferation in each cell model, inducing changes in cell-cycle distribution. In drug combination experiments, dinaciclib enhances the CP effect both in vitro and in the zebrafish model. CONCLUSIONS: Dinaciclib, when combined with CP, could be useful for improving nonseminoma TC response to CP.

In Situ Reaction-Generated Aldehyde-Scavenging Polypeptides-Curcumin Conjugate Nanoassemblies for Combined Treatment of Spinal Cord Injury.

The microenvironment after traumatic spinal cord injury (SCI) involves complex pathological processes, including elevated oxidative stress, accumulated reactive aldehydes from lipid peroxidation, excessive immune cell infiltration, etc. Unfortunately, most of current neuroprotection therapies cannot cope with the intricate pathophysiology of SCI, leading to scant treatment efficacies. Here, we developed a facile in situ reaction-induced self-assembly method to prepare aldehyde-scavenging polypeptides (PAH)-curcumin conjugate nanoassemblies (named as PFCN) for combined neuroprotection in SCI. The prepared PFCN could release PAH and curcumin in response to oxidative and acidic SCI microenvironment. Subsequently, PFCN exhibited an effectively neuroprotective effect through scavenging toxic aldehydes as well as reactive nitrogen and oxygen species in neurons, modulating microglial M1/M2 polarization, and down-regulating the expression of inflammation-related cytokines to inhibit neuroinflammation. The intravenous administration of PFCN could significantly ameliorate the malignant microenvironment of injured spinal cord, protect the neurons, and promote the motor function recovery in the contusive SCI rat model.

[Surgical treatment and prognostic factors in perihilar tumors]. / Khirurgicheskoe lechenie i faktory prognoza pri perikhilyarnoi opukholi.

OBJECTIVE: To study the results of surgical treatment in patients with perihilar tumors. MATERIAL AND METHODS: We analyzed 98 patients with perihilar tumors who underwent surgery. RESULTS: We prefer percutaneous transhepatic biliary drainage (n=58) for jaundice. Retrograde interventions were performed in 18 cases (20.5%), complications grade III-IV were more common (p=0.037) in the last group. Postoperative mortality was 12%. Complications developed in 81 patients (82.7%), grade ≥3 - in 39 (39.8%) cases. Portal vein resection (n=26) increased the incidence of complications grade ≥III (p=0.035) and portal vein thrombosis (p=0.0001). Chemotherapy after surgery was performed in 47 patients (48.0%), photodynamic therapy - in 7 (7.1%) patients. A 5-year overall survival was 28.1%, the median survival - 29 months. R2 resection and/or M1 stage (n=12) significantly worsened the prognosis and overall survival (16.5 vs. 31 months, p=0.0055). Lymph node (LN) lesion, microscopic status (R0 vs. R1) of resection margin, technique of decompression and isolated resection of extrahepatic bile ducts did not affect the prognosis, and we combined appropriate patients (n=72) for analysis. SI resection and excision of ≥6 lymph nodes were independent positive factors for disease-free survival (p=0.042 and p=0.007, respectively). Blood transfusion and high preoperative neutrophil-lymphocyte index (NLI ≥2.15) worsened overall (p=0.009 and p=0.002, respectively) and disease-free survival (p=0.002 and 0.007, respectively). The absence of adjuvant therapy worsened disease-free survival alone (p=0.024). CONCLUSION: SI liver resection, adequate lymph node dissection and adjuvant therapy should be used for perihilar tumors. Isolated resection of extrahepatic bile ducts is permissible in some cases. Blood transfusion and NLI ≥2.15 are independent negative prognostic factors.

First-line treatment of driver gene-negative metastatic lung adenocarcinoma with malignant pleural effusion: Should chemotherapy be combined with an immune checkpoint inhibitor or bevacizumab?

Patients with metastatic lung adenocarcinoma (MLA) and malignant pleural effusion (MPE) without driver gene mutations have a poor prognosis. None of the standard treatment strategies is recommended for such patients. We retrospectively analyzed the efficacy of the first-line treatment for this specific population: standard platinum-based doublet chemotherapy (CT), CT plus an immune checkpoint inhibitor (CT plus ICI), and CT plus bevacizumab (CT plus Bev). A total of 323 eligible patients were enrolled: CT alone (n = 166), CT plus Bev (n = 72), and CT plus ICI (n = 85). Treatment efficacy assessments were performed every two cycles according to the RECIST guidelines. The endpoints were overall survival (OS) and progression-free survival (PFS). Kaplan-Meier (K‒M) curves and the log-rank test were used to compare OS and PFS. p < 0.05 was the threshold of significance (statistical software: SPSS). The median follow-up was 11.4 months (range, 2.1-49.6 months). PFS and OS in the CT plus ICI/CT plus Bev cohort were significantly longer than those in the CT group (PFS: 7.8/6.4/3.9 months, p < 0.0001; OS: 16.4/15.6/9.6 months, p < 0.0001, respectively). CT plus Bev had better PFS and OS than CT plus ICI/CT in PD-L1 < 1% patients (PFS: 8.4/5.0/3.8 months, p < 0.0001; OS: 15.6/12.9/9.3 months, p < 0.0001). Among patients with PD-L1 1-49%, CT plus ICI led to a longer PFS and OS (PFS: 8.9/5.8/4.2 months, p = 0.009; OS: 24.2/18.8/11.5 months, p = 0.03). In the cohort with PD-L1 ≥ 50%, CT plus ICI was still the best first-line treatment (PFS: 19.7/13.8/9.6 months, p = 0.033; OS: 27.2/19.6/14.9 months, p = 0.047). In driver gene-negative MLA with MPE, CT plus Bev or ICI better controlled MPE and significantly prolonged survival compared to CT alone. PD-L1 expression (negative/positive) may be a key factor influencing the choice of CT plus Bev or ICI.

Programmed Remodeling of the Tumor Milieu to Enhance NK Cell Immunotherapy Combined with Chemotherapy for Pancreatic Cancer.

Natural killer (NK) cell-based adoptive immunotherapy has demonstrated encouraging therapeutic effects in clinical trials for hematological cancers. However, the effectiveness of treatment for solid tumors remains a challenge due to insufficient recruitment and infiltration of NK cells into tumor tissues. Herein, a programmed nanoremodeler (DAS@P/H/pp) is designed to remodel dense physical stromal barriers and for dysregulation of the chemokine of the tumor environment to enhance the recruitment and infiltration of NK cells in tumors. The DAS@P/H/pp is triggered by the acidic tumor environment, resulting in charge reversal and subsequent hyaluronidase (HAase) release. HAase effectively degrades the extracellular matrix, promoting the delivery of immunoregulatory molecules and chemotherapy drugs into deep tumor tissues. In mouse models of pancreatic cancer, this nanomediated strategy for the programmed remodeling of the tumor microenvironment significantly boosts the recruitment of NK92 cells and their tumor cell-killing capabilities under the supervision of multiplexed near-infrared-II fluorescence.

Quercetin increases the antidepressant-like effects of sclareol and antagonizes diazepam in thiopental sodium-induced sleeping mice: A possible GABAergic transmission intervention.

Quercetin is the most common polyphenolic flavonoid present in fruits and vegetables demonstrating versatile health-promoting effects. This study aimed to examine the effects of quercetin (QR) and sclareol (SCL) on the thiopental sodium (TS)-induced sleeping and forced swimming test (FST) mouse models. SCL (1, 5, and 10 mg/kg, p.o.) or QR (50 mg/kg, p.o.) and/or diazepam (DZP) (3 mg/kg, i.p.) were employed. After 30 min of TS induction, individual or combined effects on the animals were checked. In the FST test, the animals were subjected to forced swimming after 30 min of administration of the test and/or controls for 5 min. In this case, immobility time was measured. In silico studies were conducted to evaluate the involvement of GABA receptors. SCL (5 and 10 mg/kg) significantly increased the latency and decreased sleeping time compared to the control in the TS-induced sleeping time study. DZP (3 mg/kg) showed a sedative-like effect in animals in both sleeping and FST studies. QR (50 mg/kg) exhibited a similar pattern of activity as SCL. However, its effects were more prominent than those of SCL groups. SCL (10 mg/kg) altered the DZP-3-mediated effects. SCL-10 co-treated with QR-50 significantly (p < 0.05) increased the latency and decreased sleep time and immobility time, suggesting possible synergistic antidepressant-like effects. In silico studies revealed that SCL and QR demonstrated better binding affinities with GABAA receptor, especially α2, α3, and α5 subunits. Both compounds also exhibited good ADMET and drug-like properties. In animal studies, the both compounds worked synergistically to provide antidepressant-like effects in a slightly different fashion. As a conclusion, the combined administration of SCL and QR may be used in upcoming neurological clinical trials, according to in vivo and in silico findings. However, additional investigation is necessary to verify this behavior and clarify the potential mechanism of action.

Patient-specific signaling signatures predict optimal therapeutic combinations for triple negative breast cancer.

Triple negative breast cancer (TNBC) is a heterogeneous group of tumors which lack estrogen receptor, progesterone receptor, and HER2 expression. Targeted therapies have limited success in treating TNBC, thus a strategy enabling effective targeted combinations is an unmet need. To tackle these challenges and discover individualized targeted combination therapies for TNBC, we integrated phosphoproteomic analysis of altered signaling networks with patient-specific signaling signature (PaSSS) analysis using an information-theoretic, thermodynamic-based approach. Using this method on a large number of TNBC patient-derived tumors (PDX), we were able to thoroughly characterize each PDX by computing a patient-specific set of unbalanced signaling processes and assigning a personalized therapy based on them. We discovered that each tumor has an average of two separate processes, and that, consistent with prior research, EGFR is a major core target in at least one of them in half of the tumors analyzed. However, anti-EGFR monotherapies were predicted to be ineffective, thus we developed personalized combination treatments based on PaSSS. These were predicted to induce anti-EGFR responses or to be used to develop an alternative therapy if EGFR was not present.In-vivo experimental validation of the predicted therapy showed that PaSSS predictions were more accurate than other therapies. Thus, we suggest that a detailed identification of molecular imbalances is necessary to tailor therapy for each TNBC. In summary, we propose a new strategy to design personalized therapy for TNBC using pY proteomics and PaSSS analysis. This method can be applied to different cancer types to improve response to the biomarker-based treatment.

Biodegradable Osmium Nanoantidotes for Photothermal-/Chemo- Combined Treatment and to Prevent Chemotherapy-Induced Acute Kidney Injury.

Acute kidney injury (AKI) is a common adverse event in chemotherapy patients. AKI is accompanied by the generation of reactive oxygen species (ROS) and inflammation. Therefore, the management of ROS and inflammation is a potential strategy for AKI mitigation. Herein, polyethylene glycol-coated osmium nanozyme-based antidotes (Os) are developed for imaging-guided photothermal therapy (PTT) in combination with cisplatin (Pt); while, avoiding AKI induced by high-dose Pt. Os nanoantidotes can enhance the efficiency of tumor treatment during combined PTT and chemotherapy and inhibit tumor metastasis by improving the hypoxic and inflammatory tumor microenvironment. Os nanoantidotes preferentially accumulate in the kidney because of their 2-nm size distribution; and then, regulate inflammation by scavenging ROS and generating oxygen to alleviate Pt-induced AKI. Os nanoantidotes can be cleared from the kidneys by urine excretion but can be degraded under hydrogen peroxide stimulation, reducing the bio-retention of these compounds. By integrating PTT with inflammatory regulation, Os nanoantidotes have the potential to reduce the side effects of chemotherapy, offering an alternative route for the clinical management of cancer patients with chemotherapy-induced AKI.

Combined BNCT-CIRT treatment planning for glioblastoma using the effect-based optimization.

Objective. Boron neutron capture therapy (BNCT) and carbon ion radiotherapy (CIRT) are emerging treatment modalities for glioblastoma. In this study, we investigated the methodology and feasibility to combine BNCT and CIRT treatments. The combined treatment plan illustrated how the synergistic utilization of BNCT's biological targeting and CIRT's intensity modulation capabilities could lead to optimized treatment outcomes.Approach. The Monte Carlo toolkit, TOPAS, was employed to calculate the dose distribution for BNCT, while matRad was utilized for the optimization of CIRT. The biological effect-based approach, instead of the dose-based approach, was adopted to develop the combined BNCT-CIRT treatment plans for six patients diagnosed with glioblastoma, considering the different radiosensitivity and fraction. Five optional combined treatment plans with specific BNCT effect proportions for each patient were evaluated to identify the optimal treatment that minimizes damage on normal tissue.Main results. Individual BNCT exhibits a significant effect gradient along with the beam direction in the large tumor, while combined BNCT-CIRT treatments can achieve uniform effect delivery within the clinical target volume (CTV) through the effect filling with reversed gradient by the CIRT part. In addition, the increasing BNCT effect proportion in combined treatments can reduce damage in the normal brain tissue near the CTV. Besides, the combined treatments effectively minimize damage to the skin compared to individual BNCT treatments.Significance. The initial endeavor to combine BNCT and CIRT treatment plans is achieved by the effect-based optimization. The observed advantages of the combined treatment suggest its potential applicability for tumors characterized by pleomorphic, infiltrative, radioresistant and voluminous features.