Efficacy Of Combined Treatment Research Articles

Abstract IA01: Moving forward translation of targeted therapy with external beam radiation

Radiotherapy is an anatomically highly targeted treatment modality capable of eradicating cancer cells, including cancer stem cells (CSC). This precision makes radiotherapy an ideal partner for synergistic treatment with targeted drugs, combining local effects on the tumor with systemic molecular interventions. To evaluate the efficacy of such combined treatments on inactivation of CSC in translational research, it is essential to select the appropriate clinical endpoints for preclinical experiments, most importantly inactivation of CSC in vitro or local tumor control in vivo. This ensures that preclinical findings are better translatable to the clinical setting, bridging the gap between experimental models and patient outcomes. A critical factor in this translational pipeline is the use of appropriate in vitro and animal or explant models that as accurate as possible mimic the clinical tumor microenvironment and response dynamics. To account for inter-tumor heterogeneity, it is necessary to apply a panel of models that are well characterized on a molecular biological level. With the right preclinical systems in place, combination strategies can be refined to optimize timing, dosing and sequencing of therapies to maximize tumor control while minimizing damage to normal tissues. Biomarker-driven approaches and molecular pathway analysis are increasingly guiding patient selection and therapeutic personalization, thereby improving the likelihood of clinical success. Examples include biomarker-based studies such as the DELPHI trial for dose de-escalation in post-op HPV-positive head and neck cancer (HNSCC) and the INDIRA Miso study on escalation of PET hypoxic HNSCC. Promising examples of novel combinations with radiotherapy include not only small molecule or Immunotherapeutics, but also the use of radiotherapy integration with novel theranostic radiopharmaceuticals, genomic and radiomic data for adaptive treatment planning. By aligning preclinical and clinical strategies, these efforts are advancing the integration of targeted therapies with radiotherapy and improve loco-regional control, overall survival and quality of life for patients. Citation Format: Michael Baumann. Moving forward translation of targeted therapy with external beam radiation. [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Translating Targeted Therapies in Combination with Radiotherapy; 2025 Jan 26-29; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(2_Suppl):Abstract nr IA01

CAR T-cell and oncolytic virus dynamics and determinants of combination therapy success for glioblastoma.

Glioblastoma is a highly aggressive and treatment-resistant primary brain cancer. While chimeric antigen receptor (CAR) T-cell therapy has demonstrated promising results in targeting these tumors, it has not yet been curative. An innovative approach to improve CAR T-cell efficacy is to combine them with other immune modulating therapies. In this study, we investigate in vitro combination of IL-13R α 2 targeted CAR T-cells with an oncolytic virus (OV) and study the complex interplay between tumor cells, CAR T-cells, and OV dynamics with a novel mathematical model. We fit the model to data collected from experiments with each therapy individually and in combination to reveal determinants of therapy synergy and improved efficacy. Our analysis reveals that the virus bursting size is a critical parameter in determining the net tumor infection rate and overall combination treatment efficacy. Moreover, the model predicts that administering the oncolytic virus simultaneously with, or prior to, CAR T-cells could maximize therapeutic efficacy.

Apoptosis induction and tumor growth suppression by hydroxyapatite nanoparticles–cisplatin combined treatment in Ehrlich solid carcinoma-bearing mice

BackgroundHydroxyapatite (HAP) resembles the components of biological hard tissue. Recent research has been interested in the biomedical application of HAP nanoparticles (HAP-NPs) in cancer treatment, HAP-NPs have high cytotoxic activity against cancerous cells, in addition, they are nontoxic to healthy normal cells, biocompatible, biodegradable, and have a high absorption rate within the tissue. Therefore, this study evaluated HAP-NPs' antitumoral activity in Ehrlich solid carcinoma (ESC)-bearing mice, in addition, we examined the anticancer efficacy of combined treatment of a common chemotherapeutic drug such as Cisplatin (CDDP) and HAP-NPs in ESC-bearing mice.MethodsForty female mice were inoculated with 200 µl of diluted ascites fluid containing approximately two million viable cancer cells in the mice's left thigh, after 14 days of inoculation, the mice were distributed into four groups: 10 mice in each. ESC group was administrated distilled water, the HAP-NPs group was treated orally with 100 mg/kg of hydroxyapatite nanoparticles, the CDDP group was administrated intraperitoneally with 5 mg/kg of Cisplatin, the HAP-NPs + CDDP group was treated with both doses of hydroxyapatite and cisplatin, the animal treatment was conducted for 20 days. Antitumor activity was assessed for two durations after 10 and 20 days. DNA damage assessment was performed using comet assay in ESC, in addition, we measured the expression of the following genes (P53, Bcl2, and Bax,) using quantitative real-time PCR, and the apoptotic-related proteins (P53 and Ki-67) using immunohistochemical analysis. A histopathological examination of ESC was performed.ResultsThe obtained data illustrated a promising anticancer activity of HAP-NPs, and the combined treatment of HAP-NPs and CDDP illustrated a higher anticancer efficacy. HAP-NPs, CDDP, and HAP-NPs + CDDP resulted in significant (P < 0.05) nucleic acid destruction, and significant (P < 0.05) overexpression of apoptotic-related genes (P53, Bax, and Bcl2) and proteins (Ki-67 and P53), causing the tumor bulk to be greatly reduced in HAP-NPs, CDDP, and HAP-NPs + CDDP (1100, 570, and 450 mm3), respectively, compared to ESC group was 2240 mm3.ConclusionHydroxyapatite nanoparticles can provoke DNA damage and regulate apoptosis, selectively eliminating tumor cells. The co-administration of HAP-NPs and CDDP resulted in a synergistic enhancement of cisplatin activity within the tumor tissue.

Synthesis and Biological Evaluation of a New Biphenyl-Based Organogold(III) Complex with In Vitro and In Vivo Anticancer Activity.

Despite recent advances in cancer treatment, there is still a need for novel compounds with antineoplastic activity. Among 11 biphenyl-based organogold(III) N-heterocyclic carbene (NHC) (BGC) complexes of general formula [(C^C)Au(NHC-pyr)X], where (C^C) = 4,4'-ditertbutylbiphenyl, X = Cl or phenylacetylide, and (NHC-pyr) is a pyridyl-substituted NHC ligand, the complex BGC4 bearing a 4-CF3-pyridyl substituent and a chloride ligand showed promising antineoplastic activity on the triple negative breast cancer cell line. BGC4 was able to induce cell apoptosis but had no effect on the cell cycle. In vivo, BGC4 reduced the tumor growth rate by increasing the necrosis area and decreasing the mitotic activity. Repeated injections of BGC4 did not induce common side effects. The present investigation shows that BGC4 is a promising antineoplastic candidate. Its potential as a future chemotherapy for the treatment of cancer will be strengthened by evaluating its efficacy in combined treatment with current chemotherapy.

Long-term results of primary and revision oncological endoprosthetics

BACKGROUND: Increased overall survival leads to a significant increase in the service life of implants. Currently, no joint replacement systems are failure-free, which reduces the service life. AIM: To assess and systematize the main complications of primary and revision joint replacement surgery, identify the main causes of these complications at various stages of joint replacement based on literature data and analysis of own findings in a large patient population, and develop treatment approaches. MATERIALS AND METHODS: The study included 1,292 patients with primary bone and soft tissue sarcomas, as well as metastatic and benign bone tumors, with 1,671 primary and revision joint replacement surgeries of varying extent performed between January 1992 and January 2020. The proportion of males and females who underwent joint replacement surgery was approximately equal. Joint replacement surgery was performed in 886 (68.6%) patients with primary cancer, 144 (11.1%) patients with metastases to long bones, and 262 (20.3%) patients with benign tumors. RESULTS: During the study period, the overall incidence of complications was 1.4 times higher in the revision joint replacement surgery group (38.1%) compared to the primary joint replacement surgery group (26.6%). The most common type I–IV complications included unstable implants two and more years post-surgery (type IIB) and broken implants (type IIIA). As a result of innovative modifications, the overall incidence of type I–IV complications in primary and revision joint replacement surgery decreased to 16.5% and 24.3%, respectively. The most common cancer-related complication of primary joint replacement surgery was tumor recurrence (type V), accounting for 9.5% of cases. Tapered and cylindrical stems were the best shapes for primary and revision joint replacement surgery. The best stability was observed for 60–100 mm long stems in upper extremity joint replacement and 110–150 mm long stems in lower extremity joint replacement. Stems longer than 160 mm can only be used in revision joint replacement surgery. Adequate perioperative antibiotic prophylaxis reduced the risk of implant site infections. CONCLUSION: High-quality cement mantle formation, stems that match the diameter and shape of the medullary canal, and optimal stem length decrease the incidence of early aseptic instability. The study used a set of preventive measures, including strict compliance with standardized antibiotic therapy regimens during and after surgery, surgical technique modifications, perioperative patient management, and informing patients about the risks of infectious complications. These measures decreased the incidence of early implant site infections after primary and revision joint replacement surgery for a period of 28 years. The efficacy of combination treatment for these diseases has a direct impact on the incidence of local tumor recurrence. Surgical technique modifications based on tumor grade significantly increased treatment efficacy.

Comparison of the efficacy of combination treatment of microneedling and topical Bleomycin with cryotherapy for the management of hand and foot refractory warts.

Several studies have looked into the effectiveness of bleomycin treatment for warts using various injection methods, such as intralesional injection, multiple puncture technique, jet injection, and moonlet needle prick method, in various concentrations and doses. However, injection methods have been linked to acute pain and bleeding. The purpose of this study is to examine the efficacy of microneedling combination with topical bleomycin and cryotherapy in the treatment of resistant warts on the hands and feet. This randomized clinical trial, conducted at Sina Hospital in Tabriz, involved 90 patients with treatment-resistant warts on their hands and feet. Treatment measures were repeated every two weeks in treatment-resistant patients who did not react to four cryotherapy sessions or whose lesions remained stable for six months. Each wart lesion was randomly assigned to one of two treatment groups: topical bleomycin with microneedling or cryotherapy. The effectiveness of the treatment in weeks 2, 4, 6, and 8 with PGA and PaGA, the amount of clearance, and side effects were evaluated in each session and the 8th week. Pain during therapy was assessed using a visual analog scale (VAS) ranging from 0 to 10. The patients' mean age was 33.65 ± 12.24 years, with 63.3% being female. A total of 186 resistant wart lesions were treated, with 98 (52.7%) situated in the palmar region and 88 (47.3%) in the plantar region. In palm lesions, the bleomycin micro-needling group had a considerably greater clearance rate than the cryotherapy group (86.4% vs. 61.9%; p = 0.001). In foot lesions, the bleomycin microneedling group had a greater clearance rate than the cryotherapy group, although there was no statistically significant difference (69.6% vs. 54.2%; p = 0.209). In the eighth week following the intervention, the number of lesions and the diameter of warts on the palms and feet decreased significantly in the bleomycin microneedling group when compared to the cryotherapy group. Bleomycin microneedling had no adverse effects; however, in patients undergoing cryotherapy, local pain, blisters, and scars were noted. Bleomycin microneedling has a higher therapeutic efficiency than cryotherapy for treating refractory hand and foot warts, and it removes lesions more effectively. In addition, this therapeutic method is safer and has fewer side effects than cryotherapy.

Brexpiprazole and Sertraline Combination Treatment in Posttraumatic Stress Disorder

New pharmacotherapy options are needed for posttraumatic stress disorder (PTSD). To investigate the efficacy, safety, and tolerability of brexpiprazole and sertraline combination treatment (brexpiprazole + sertraline) compared with sertraline + placebo for PTSD. This was a parallel-design, double-blind, randomized clinical trial conducted from October 2019 to August 2023. The study had a 1-week, placebo run-in period followed by an 11-week, double-blind, randomized, active-controlled, parallel-arm period (with 21-day follow-up) and took place at 86 clinical trial sites in the US. Adult outpatients with PTSD were enrolled (volunteer sample). Oral brexpiprazole 2 to 3 mg per day (flexible dose) + sertraline 150 mg per day or sertraline 150 mg per day + placebo (1:1 ratio) for 11 weeks. The primary end point was change in Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) total score (which measures the severity of 20 PTSD symptoms) from randomization (week 1) to week 10 for brexpiprazole + sertraline vs sertraline + placebo. Safety assessments included adverse events. A total of 1327 individuals were assessed for eligibility. After 878 screen failures, 416 participants (mean [SD] age, 37.4 [11.9] years; 310 female [74.5%]) were randomized. Completion rates were 137 of 214 participants (64.0%) for brexpiprazole + sertraline and 113 of 202 participants (55.9%) for sertraline + placebo. At week 10, brexpiprazole + sertraline demonstrated statistically significant greater improvement in CAPS-5 total score (mean [SD] at randomization, 38.4 [7.2]; LS mean [SE] change, -19.2 [1.2]; n = 148) than sertraline + placebo (randomization, 38.7 [7.8]; change, -13.6 [1.2]; n = 134), with LS mean difference, -5.59 (95% CI, -8.79 to -2.38; P < .001). All key secondary and other efficacy end points were also met. Treatment-emergent adverse events with incidence of 5% or greater for brexpiprazole + sertraline (and corresponding incidences for sertraline + placebo) were nausea (25 of 205 [12.2%] and 23 of 196 [11.7%]), fatigue (14 of 205 [6.8%] and 8 of 196 [4.1%]), weight increase (12 of 205 [5.9%] and 3 of 196 [1.5%]), and somnolence (11 of 205 [5.4%] and 5 of 196 [2.6%]). Discontinuation rates due to adverse events were 8 of 205 participants (3.9%) for brexpiprazole + sertraline and 20 of 196 participants (10.2%) for sertraline + placebo. Results of this randomized clinical trial show that brexpiprazole + sertraline combination treatment statistically significantly improved PTSD symptoms vs sertraline + placebo, indicating its potential as a new efficacious treatment for PTSD. Brexpiprazole + sertraline was tolerated by most participants, with a safety profile consistent with that of brexpiprazole in approved indications. ClinicalTrials.gov Identifier: NCT04124614.

A Pilot One and Two-Year Prospective, Blinded Clinical Evaluation of Efficacy, and Safety of Combined Treatment With Crosslinked Hyaluronic Acid Dermal Filler and Barbed Polydioxanone Suspension Threads for Mid-Face Contour Enhancement.

The combination of hyaluronic acid (HA) fillers and polydioxanone (PDO) thread lifting is gaining popularity for mid-face rejuvenation, especially among the Asian population. Despite the common use of these techniques, there is a paucity of long-term studies assessing their combined efficacy and safety. This study aims to evaluate the efficacy and safety of combined HA filler and PDO thread treatment for mid-face rejuvenation over a 24-month period in a Korean population. This prospective, blinded, single-center, open-label trial included 11 Korean subjects, aged 29-70 years, with mid-face volume loss graded 1-4 on the antero-medial cheek fullness scale. Participants were treated with crosslinked HA dermal fillers and PDO threads. Assessments were conducted using the Global Aesthetic Improvement Scale (GAIS), investigator-led clinical evaluations, and volumetric measurements using the Morpheus 3D system at baseline, 6, 12, and 24 months post-treatment. Quantitative analysis revealed a significant reduction in mid-face width from an average baseline of 149.27-145.00 mm at 24 months (p < 0.00001). Similarly, lower-face width decreased from 130.36 to 117.27 mm at 24 months (p < 0.00001). The GAIS scores demonstrated high levels of subject satisfaction, with 9 out of 11 patients reporting consistent satisfaction or improvement over 24 months. Minimal adverse events were reported, and no serious complications occurred. The combination of HA fillers and PDO threads was effective in achieving and maintaining long-term improvements in facial volume and contour. The Morpheus 3D system provided objective volumetric data, which supported the subjective improvements observed by patients and investigators. The study results highlight the benefits of ongoing neocollagenesis and tissue remodeling beyond the dissolution period of the materials. The combination of HA filler injections and PDO thread lifting offers a promising and minimally invasive option for long-term mid-face rejuvenation with high patient satisfaction and a favorable safety profile. Further studies are warranted to confirm these findings across diverse populations and compare this approach with other aesthetic treatments.

A pilot study of tofacitinib citrate with 308-nm excimer laser for the treatment of vitiligo.

Vitiligo is a clinically prevalent acquired skin disorder characterized by depigmentation. Currently, the therapeutic options for vitiligo are restricted, and numerous issues exist, such as a prolonged treatment course, unsatisfactory therapeutic efficacy, adverse reactions, and a high propensity for recurrence after treatment cessation. To assess the safety and efficacy of combined treatment involving oral tofacitinib citrate (TC) and a 308-nm excimer laser (EL), with the aim of discovering a rapid and effective treatment approach to minimize the side effects of various drugs. A total of 63 patients with progressive vitiligo and a Vitiligo Disease Activity Score (VIDA) score of four from January 2022 to January 2024 were enrolled and divided into three groups. The three groups were the TC combined with 308-nm EL and methylprednisolone treatment group, the TC and 308-nm EL treatment group, and the methylprednisolone treatment alone group. The treatment was continued for 24 weeks. Finally, assessment of therapy outcomes was performed. When TC was combined with 308-nm EL and methylprednisolone treatment, the effect was more rapid. When TC was combined with 308-nm EL, it had a more favorable treatment effect than that of methylprednisolone alone, despite having a slower effect onset. After 24 weeks of treatment, there was no significant difference between the two groups in terms of the total response rate or significant efficiency. However, when only methylprednisolone treatment was applied, the effect is relatively slow and inefficient. This study confirmed the rapid and efficient treatment of vitiligo through the combination of TC and 308-nm EL, and no serious adverse reactions were reported, which could offer an optimal treatment plan for patients with vitiligo.

Real-world efficacy and safety of combined first-line treatment with PARP inhibitors and novel hormonal therapy in mCRPC patients with HRR gene mutations.

This study evaluated the real-world efficacy and safety of combining PARP inhibitors with novel hormonal therapy (NHT) as a first-line treatment in Chinese patients with metastatic castration-resistant prostate cancer (mCRPC) harboring homologous recombination repair (HRR) gene mutations. We enrolled 41 mCRPC patients who received at least 1month of combined treatment with PARP inhibitors and NHT. Patients were divided into two groups: Cohort A (mutations in BRCA1, BRCA2, or ATM genes) and Cohort B (mutations in other HRR genes). The primary endpoint was imaging-based progression-free survival (PFS), with secondary endpoints including objective response rate (ORR), disease control rate (DCR), overall survival (OS), PSA50 response, and adverse events (AEs). To ensure accurate research results and control confounding factors, we will employ multivariate Cox proportional hazards models to evaluate key variables affecting mCRPC patient survival outcomes. This study enrolled 41 patients, 22 in Cohort A and 19 in Cohort B. The median PFS for all patients was 21.8months, and the median OS had yet to be reached. The overall ORR was 48.8%, and the DCR was 61.0%. Specifically, the median PFS for Cohort A was 21.8months compared to 14.5months for Cohort B. The median OS had yet to be reached for either cohort. Regarding efficacy, 81.8% of patients in Cohort A and 73.7% in Cohort B achieved a PSA50 response. Imaging assessments showed ORRs of 54.6% for Cohort A and 42.1% for Cohort B, with DCRs of 72.7% and 47.4%, respectively. 85.4% of patients experienced grade 1 or 2 adverse events, and 51.2% encountered grade 3 or 4. In the multivariate Cox regression analysis focusing on PFS, the Gleason score was identified as a significant predictor (HR = 5.8, 95% CI: 1.65-20.2, p = 0.006). Combined first-line treatment with PARP inhibitors and NHT is effective and well-tolerated in mCRPC patients with HRR gene mutations, particularly those with BRCA1, BRCA2, or ATM mutations. These findings underscore the potential of this therapeutic combination in managing mCRPC in the Chinese population, suggesting a favorable outcome for those with specific genetic backgrounds.

Ivermectin 1% Combined With Intense Pulsed Light Treatment for Dry Eye Disease Secondary to Demodex Blepharitis.

To examine the safety and efficacy of combined treatment with topical ivermectin 1% and intense pulsed light (IPL) for dry eye disease (DED) secondary to demodex blepharitis. A retrospective review of medical files of patients treated at a private clinic specializing in DED between November 2022 and February 2024 was performed. Sixty-one patients aged 18 years or older with DED because of demodex blepharitis, who received the IPL and ivermectin 1% combination therapy, were included. IPL was applied to the periocular area 4 times at 2- to 3-week intervals, and ivermectin 1% once daily for 1 to 2 months. Both eyes (n = 122) of each patient were evaluated before and immediately after treatment cessation. Blepharitis, meibomian gland secretion, corneal staining, patient satisfaction, and overall clinical improvement were recorded. Mean age was 59.6 ± 17.6 years and 50.8% (n = 31) were males. Meibomian gland secretion grading improved significantly after treatment from 2.74 ± 0.63 to 1.63 ± 0.63 (P < 0.001). Blepharitis was eliminated after treatment in 77.0% of patients (23.0% after treatment vs. 100.0% before, P < 0.001). The patient satisfaction rate was moderate to high (range 0-2, mean 1.54 ± 0.60). Clinical improvement rate was moderate to high as well (range 0-2, mean 1.52 ± 0.50). No significant side effects were observed. The combined application of topical ivermectin and IPL to the facial area induced significant improvement of demodex blepharitis and meibomian gland secretion grading along with a high rate of patient satisfaction. Further randomized controlled double-blinded studies are needed.

Synergistic Anticancer Efficacy of Curcumin and Doxorubicin Combination Treatment Inducing S-phase Cell Cycle Arrest in Triple-Negative Breast Cancer Cells: An In Vitro Study

Synergistic Anticancer Efficacy of Curcumin and Doxorubicin Combination Treatment Inducing S-phase Cell Cycle Arrest in Triple-Negative Breast Cancer Cells: An In Vitro Study

The Efficacy and Safety of Albumin-Bound Paclitaxel Combined With Anlotinib and PD-1/L1 Inhibitors For Treating Patients With Extensive-Stage Small Cell Lung Cancer and Brain Metastasis: A Retrospective Cohort Study.

Extensive-stage small cell lung cancer (ES-SCLC) suffering from brain metastases (BM) has a poor prognosis and lacks effective treatment selection. In this study, we explored the efficacy and safety of combination treatment of albumin-bound paclitaxel (nab-ptx), anlotinib, and PD-1/L1 inhibitors for such special population. A total of 55 patients diagnosed with ES-SCLC and BM were enrolled in this retrospective study. Patients received a combination therapy consisting of nab-ptx, anlotinib, and PD-1/L1 inhibitors. The primary endpoints included overall response rate (ORR), progression-free survival (PFS), overall survival (OS), and adverse events (AEs). The results demonstrated promising efficacy of the combination therapy for such patients, with an ORR of 36.36%, median PFS and OS of 5.0 and 10.0 m, correspondingly. Subgroup analyses indicated that treatment efficacy closely correlated with patients' Ds-GPA (Diagnosis-specified Graded Prognosis Assessment) scores. Mechanistic studies revealed that this regimen likely operates by reducing immune suppression to activate immune function, thereby exerting synergistic anti-tumor effects. The common AEs include decreased appetite, nausea, leukopenia, hypertension, proteinuria, hand-foot syndrome, peripheral neuropathy, rash, and thyroid toxicity, most of which are generally mild and can be alleviated with symptomatic treatment. The combination of nab-ptx, anlotinib, and PD-1/L1 inhibitors exhibited substantial efficacy and acceptable safety in the treatment of BM from ES-SCLC. This novel therapeutic approach holds promise for improving the outcomes for patients with this challenging disease. Further studies are needed to validate these findings and investigate the long-term benefits of this combination regimen.

Denosumab combined with radiotherapy as an alternative to surgery for advanced metastatic bone lesions and pathologic fractures: a retrospective case study of 38 patients.

Pathologic and impending fractures occur in patients with advanced metastatic disease and necessitate surgical interventions with high risk of complications. The aim of this study was to analyze the efficacy of combined treatment with denosumab and radiotherapy as an alternative to surgery in treating bone metastases of the pelvis and extremities. This retrospective cohort study included 38 patients with impending and pathologic fractures due to carcinoma metastases who received monthly injections of denosumab (120 mg/dose) and radiotherapy. Twenty-three patients received denosumab and single-dose radiotherapy of 8 Gy, and 15 patients received denosumab and fractionated radiotherapy. We assessed pain, radiographic signs of fracture healing, survival and complications. Of the 38 patients 36 experienced pain reduction. Callus formation was observed in 11/17 patients with pathologic fractures, and increased mineralization was found in 12/21 patients with impending fractures. In 23/38 patients, we found both pain reduction and callus formation or increased mineralization. There were no statistically significant differences in treatment outcomes between the patients who received denosumab and single-dose radiotherapy and those who received denosumab and fractionated radiotherapy. The survival rates at 30 days and 1 year were 95% and 56%, respectively. Combined treatment with denosumab and radiotherapy may reduce pain and promote bone healing in patients with metastatic impending and pathologic fractures. In this combined treatment, the effect of single-dose radiotherapy appears to be comparable to that of fractionated regimens.

Efficacy of combination treatment in a patient with temporomandibular joint dysfunction

Background: Muscle and joint dysfunction is a common complication, particularly in females over 40 years. It is strongly associated with age-related hormonal changes in the bones, as well as concomitant dentoalveolar deformities and tooth loss. Case description: The efficacy of combination treatment of dentoalveolar abnormalities and deformities complicated by temporomandibular joint (TMJ) dysfunction was demonstrated. The efficacy of combination treatment in patients with missing teeth, as well as dentoalveolar abnormalities and deformities complicated by TMJ dysfunction, was confirmed. To ensure a representative before-and-after comparison, the restoration of masticatory efficiency following orthodontic and orthopedic rehabilitation was assessed. A physical examination in patient M. revealed hypertonia of masticatory muscles, restricted mouth opening, jaw shifting to the left, partially absent dentition in distal sections, and prosthetic restoration failure. On MRI, there were signs of deforming arthrosis of both TMJs. The following observation methods were used to assess the efficacy of rehabilitation: questioning to identify symptoms of TMJ pain; follow-up examination for joint clicking when opening the mouth; palpation of the external pterygoid muscle, masticatory muscle, and internal pterygoid muscle; X-ray examination (TMJ CT and MRI) following treatment; masticatory efficiency assessment using a masticatory performance test (according to Trezubov) before and after treatment. Diagnostic testing following combination orthodontic and orthopedic treatment revealed that the patient’s left TMJ no longer felt heavy, and she could open her mouth easily; moreover, jaw shifting resolved, and masticatory muscle rigidity decreased. Conclusion: This clinical case demonstrates why orthopedic surgeons and orthodontists must collaborate in the diagnosis and treatment of TMJ dysfunction. The authors present a well-established approach to the treatment of patients with TMJ dysfunction that has been used successfully in clinical practice for several years.

Extracellular Matrix as a Target in Melanoma Therapy: From Hypothesis to Clinical Trials.

Melanoma is a malignant, highly metastatic neoplasm showing increasing morbidity and mortality. Tumor invasion and angiogenesis are based on remodeling of the extracellular matrix (ECM). Selective inhibition of functional components of cell-ECM interaction, such as hyaluronic acid (HA), matrix metalloproteinases (MMPs), and integrins, may inhibit tumor progression and enhance the efficacy of combination treatment with immune checkpoint inhibitors (ICIs), chemotherapy, or immunotherapy. In this review, we combine the results of different approaches targeting extracellular matrix elements in melanoma in preclinical and clinical studies. The identified limitations of many approaches, including side effects, low selectivity, and toxicity, indicate the need for further studies to optimize therapy. Nevertheless, significant progress in expanding our understanding of tumor biology and the development of targeted therapies holds great promise for the early approaches developed several decades ago to inhibit metastasis through ECM targeting.

EGFR-TKIs or EGFR-TKIs combination treatments for untreated advanced EGFR-mutated NSCLC: a network meta-analysis

BackgroundEpidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) and EGFR-TKI combination treatments have become the standard first-line treatments for EGFR-mutated non-small cell lung cancer (NSCLC) patients. However, the best option has yet to be determined. This study compares the efficacy and safety of various first-line EGFR-TKI monotherapies and combination treatments for advanced EGFR-mutated NSCLC.MethodsWe searched PubMed, Embase, the Cochrane Central Register of Controlled Clinical Trials databases, and several international conferences to identify randomized controlled trials reporting on first-line EGFR-TKI treatments for patients with advanced EGFR-mutated NSCLC. The study quality was assessed using the revised tool for risk of bias in randomized trials. The efficacy and safety outcomes of the included treatments were compared by network meta-analysis based on a frequentist approach.ResultsWe identified 26 trials (8,359 patients) investigating 14 treatment groups, including first, second, and third-generation EGFR-TKIs and their combination treatments. Osimertinib plus chemotherapy and lazertinib plus amivantamab showed the highest efficacy in improving progression-free survival. New third-generation EGFR-TKIs demonstrated comparable efficacy to osimertinib alone but did not surpass it. Subgroup analyses revealed slight variation in treatment efficacy based on mutation types and patient demographics. Combination treatments were associated with a higher incidence of adverse events.ConclusionThese results reveal that osimertinib plus chemotherapy and lazertinib plus amivantamab are superior first-line options for patients with advanced EGFR-mutated NSCLC. However, these combinations are associated with higher adverse event rates.

Camptothecin and Its Derivatives from Traditional Chinese Medicine in Combination with Anticancer Therapy Regimens: A Systematic Review and Meta-Analysis.

Background/Objectives: Camptothecin (CPT) and its derivatives, irinotecan and topotecan, are integral components of cancer chemotherapy, often used in combination therapies. This meta-analysis evaluates the efficacy of CPT-based combination treatments in cancer patients. Methods: We systematically searched the literature database using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses checklist for articles published between 2000 and 2022. Published studies were retrieved through an electronic search on the Web of Science, PubMed, and Google Scholar databases. A total of 138 studies were downloaded and examined, and 71 eligible studies were selected for meta-analysis after excluding studies that did not meet the inclusion criteria. Results: Ultimately, a total of 71 studies were included in the analysis, comprising non-small cell lung cancer (NSCLC), colorectal cancer (COLRC), oesophageal/gastric cancer (O/GC), and small cell lung cancer (SCLC). For NSCLC, the objective response rate (RR) was 31.8% (95% CI: 27.3-37.1%, p = 0.025), with irinotecan plus cisplatin showing significantly higher efficacy compared to other irinotecan-based combinations. In COLRC, irinotecan and 5-fluorouracil/leucovorin plus bevacizumab demonstrated superior efficacy with a RR of 44% (95% CI: 34-58, p < 0.001) and minimal haematological toxicity. In O/GC, irinotecan-based combinations showed an average RR of 43% (95% CI: 27-70, p < 0.001) and average overall survival (OS) and progression-free survival (PFS) rates of 10.2 and 5.5 months, respectively. For SCLC, irinotecan-based combinations had a higher control response than topotecan-based ones, while the latter exhibited higher rates of stable and progressive disease. The overall RR for SCLC was 45% (95% CI: 34.3-60.2, p < 0.001). Conclusions: The existing evidence underscored the potential of CPT-based combination therapy in various cancers. Among the various combinations discussed in this analysis, irinotecan plus cisplatin demonstrated the highest objective RR in 12 trials focused on NSCLC. This study provides valuable insights into potential treatment strategies for various types of cancer, emphasising the importance of personalised and tailored approaches to maximise efficacy and minimise adverse effects.

Intermediate results of efficacy and safety of combined treatment with brentuximab vedotin and bendamustine for refractory and relapsed forms of peripheral T-cell lymphoma: A retrospective study

Aim. To evaluate the efficacy and safety profile of the BvB combination in the treatment of R/R nPTCL, the complete response (CR) and partial response (PR) rates, overall survival (OS), and progression-free survival (PFS). Materials and methods. The analysis included 39 patients with R/R forms of nPTCL who underwent treatment in state budgetary institutions of the Moscow Department of Health (06.2008–08.2024). The efficacy (CR, PR, OS, PFS) and safety profile of the BvB combination were evaluated. Results. The best efficacy was noted when the BvB regimen was prescribed as a 2nd-line therapy compared to 3rd and subsequent lines. The overall response rate (ORR) when prescribed as 2nd-line therapy was 57% (n=13) of cases, CR – in 39.1% (n=9), PR – in 8.7% (n=2). The use of the BvB regimen as 3rd and subsequent lines of therapy led to ORR in 5 (31.3%) patients, CR – in 2 (12.5%), PR – in 2 (12.5%) patients. Statistically significant differences were obtained for the median PFS of patients who received the BvB regimen in the 2nd vs 3rd and subsequent lines of therapy: 6.5 and 2.5 months, respectively (p=0.0304). The BvB combination was characterized by an acceptable safety profile. Conclusion. The use of the BvB regimen in R/R forms of nPTCL demonstrated high efficacy and an optimal safety profile. The obtained results indicate the need to continue the study on a larger group of patients.

Treatment of Vedolizumab With Exclusive Enteral Nutrition in Adult Patients With Moderate to Severe Crohn's Disease (Crohn Exclusive Enteral Nutrition Study).

Despite increasing studies confirming the efficacy of vedolizumab (VDZ) in Crohn's disease (CD), improving the responses to this biologic agent remains challenging in clinical practice. In this article, we investigated the efficacy of combined treatment of VDZ and 16-week exclusive enteral nutrition (EEN) in moderately to severely active CD. From October 2020 to October 2023, 81 patients with moderately to severely active CD treated with VDZ from 2 inflammatory bowel disease centers were retrospectively selected. Forty-one patients received treatment of VDZ with concomitant 16-week EEN (VDZ + EEN cohort), and 40 patients received VDZ treatment alone (VDZ cohort). Clinical and biological outcomes were evaluated. Endoscopic response and mucosal healing were assessed by colonoscopy at weeks 16 and 52. There was no statistically significant difference between 2 groups at baseline for demographic and clinical characteristics. Compared with patients treated with VDZ alone, patients in the VDZ + EEN cohort achieved higher rates of clinical response (84.2% vs 40.0%), clinical remission (81.6% vs 30.0%), endoscopic response (91.4% vs 34.6%), including mucosal healing (85.7% vs 26.9%) at week 16. The superiority of VDZ + EEN treatment sustained in maintenance, with 76.7% (vs 33.3%) clinical response, 70.0% (vs 26.7%) clinical remission, 76.9% (vs 33.3%) endoscopic response, and 61.5% (vs 26.7%) mucosal healing at week 52. None of the patients experienced severe adverse events. VDZ with concomitant 16-week EEN might be an effective and optimized approach with solid efficacy in the induction and maintenance treatment of active CD.