Search Results (488)

Chemotherapy-Induced Peripheral Neuropathy (CIPN) is a dose-limiting complication of paclitaxel (PTX) therapy, for which effective treatments are still lacking. This study evaluated the neuroprotective potential of Thymoquinone (TQ), a bioactive derivative of Nigella sativa, in mitigating chronic PTX-induced neurotoxicity without compromising antineoplastic activity. We first performed in vitro experiments using Sprague–Dawley rat embryonic (E15) Dorsal Root Ganglia (DRG) (Envigo Laboratory (Udine, Italy))to assess neurotoxicity through neurite outgrowth evaluation. To investigate the molecular mechanisms underlying TQ’s putative neuroprotective mechanisms, SIRT1 protein expression was additionally evaluated by western blot, while MCF-7 and MDA-MB-231 breast cancer cells were used to monitor cytotoxicity via MTT assay. We then moved to in vivo experiments, in which chronic neuropathy was induced in rats using PTX (10 mg/kg, i.v., weekly for 4 weeks). TQ was co-administered orally (5–10 mg/kg/day). The effects of TQ on peripheral neuropathy were assessed through behavioral testing, neurophysiological assessments, and histological analysis of Intraepidermal Nerve Fibre density (IENF), DRG and peripheral nerves. In vitro, TQ (5 μM) significantly attenuated PTX-induced neurite shortening at 24 h; TQ co-treatment fully prevented PTX-induced SIRT1 downregulation in embryonic DRG neurons and did not compromise PTX cytotoxicity in MCF-7 cells, while significantly potentiating it in MDA-MB-231 triple-negative breast cancer cells. In vivo results demonstrated that PTX-treated animals exhibited mild erythroid myelosuppression at the end of treatment. Regarding efficacy, TQ consistently prevented PTX-induced mechanical allodynia throughout the treatment period, and TQ (10 mg/kg) transiently mitigated IENF depletion at mid-treatment; however, no improvement in neurophysiological parameters or peripheral nerve morphology was observed at either time point. Collectively, these findings suggest that, under conditions of chronic PTX exposure, TQ exerts a predominantly analgesic effect in vivo, without conferring meaningful structural neuroprotection against PTX-induced peripheral nerve degeneration. Full article

Background: Comorbidity is an important determinant of treatment selection and in-hospital complications in patients with head and neck cancer (HNC) and thyroid cancer (TC), yet population-based evidence on this relationship remains limited. Methods: We analyzed nationwide Diagnosis-Related Groups (DRG) data from 1,552,028 inpatient HNC and TC treatments of patients aged ≥30 years in Germany between 2005 and 2021. The aim was to characterize the association of comorbidity and severe treatment-related procedure-coded inpatient events (IEs) with gender, age, tumor subsite, and treatment type. Results: The largest proportion of treatments occurred in patients aged 60–69 years (33.5%). The most frequent tumor subsites were the oropharynx, thyroid gland, oral cavity, larynx, and hypopharynx, with 35.52, 33.84, 33.60, 26.12, and 15.76 treatments per 100,000 population per year, respectively. Overall, 38% of cases had a Charlson Comorbidity Index (CCI) ≥ 1, with the highest mean CCI observed for C14 (other sites of the lip, oral cavity and pharynx) and C12 (piriform sinus). IEs requiring additional in-hospital treatment occurred in 19.3% of cases. After adjustment for age, tumor location, and treatment type, men had a lower risk of IEs than women (OR 0.929; CI 0.919–0.939; p < 0.001). Increasing comorbidity was associated with a higher IE risk, reaching a plateau at CCI ≥ 4 (OR 2.135; CI 2.029–2.246; p < 0.001). IE risk was high during chemotherapy/immunotherapy (OR 29.527; CI 28.897–30.170; p < 0.001), followed by surgery (OR 3.465; CI 3.433–3.498; p < 0.001), whereas radiotherapy showed the lowest risk (OR 1.339; CI 1.313–1.366; p < 0.001). Conclusions: These findings highlight substantial heterogeneity in comorbidity and IE risk among patients with HNC or TC. Full article

Background: Oral cavity cancer is a clinically relevant subgroup of head and neck malignancies and is associated with substantial treatment burden and healthcare utilization. Hospital length of stay (LOS) is an important indicator of inpatient resource use and complexity of care, yet large multicenter data from Germany are limited. Methods: This retrospective multicenter analysis used anonymized inpatient administrative data from 49 German hospitals; eligible oral cavity cancer hospitalizations were contributed by 34 of these hospitals. Adult inpatient hospitalizations (≥18 years) with malignant neoplasms of the oral cavity, defined using ICD-10-GM codes C00–C06, recorded between January 1 2019 and 31 December 2024 were included. The primary outcome was hospital LOS in days. Multimorbidity was quantified using the van Walraven-weighted Elixhauser Comorbidity Score. Prolonged hospitalization was defined as LOS ≥ 7 days and LOS ≥ 14 days. Associations between demographic, clinical, and treatment-related variables and LOS were examined using multivariable Poisson regression models. Because overdispersion was present, a negative binomial mixed model was additionally fitted as a sensitivity analysis. To account for inter-hospital variability, hospital was included as a random intercept in all multivariable models. Associations with prolonged LOS were analyzed using multivariable logistic regression models. All analyses were performed at the hospitalization level. Results: A total of 3957 inpatient hospitalizations for oral cavity cancer were included. Mean age was 65.6 years, and 66.2% of hospitalizations involved male patients. The median LOS was 6 days (interquartile range [IQR] 3–13; mean 10.2 days, standard deviation 11.8). Overall, 49.4% of hospitalizations had an LOS ≥ 7 days and 23.5% had an LOS ≥ 14 days. Older age, particularly >80 years, and higher comorbidity burden were associated with longer LOS (adjusted Poisson rate ratio [RR] for age > 80 years 1.17, 95% CI 1.13–1.21; high comorbidity burden RR 1.58, 95% CI 1.54–1.63). Several treatment-related variables, including surgical procedures in the oral and facial region, lymphatic system operations, blood transfusions, and complex intensive care treatment, were associated with prolonged hospitalization (e.g., blood transfusion RR 1.80, 95% CI 1.76–1.85; complex intensive care RR 1.70, 95% CI 1.65–1.75). Chemotherapy-related hospitalizations were associated with shorter LOS. Conclusions: LOS varied substantially across inpatient hospitalizations for oral cavity cancer in Germany. Older age, higher comorbidity burden, and markers of more complex inpatient treatment were associated with extended hospital stay. These findings may help identify hospitalizations at increased risk of prolonged LOS and inform inpatient planning and resource allocation. Full article

Background: Immunotherapy and targeted therapy have gained ground over conventional chemotherapy in treating various cancers. While pulmonary toxicity associated with these agents is rare, it represents a significant factor in both mortality and morbidity and may influence the overall success of cancer treatment. This case series report adds to the emerging evidence of cancer therapy-induced pneumonitis features and corticotherapy outcomes. Patients and methods: This single-center, retrospective case series analyzed 12 consecutive cases of patients undergoing immunotherapy (four receiving nivolumab, four receiving pembrolizumab) or targeted therapy (three receiving obinutuzumab, one receiving abemaciclib) for cancer (seven with lung cancer, three with non-Hodgkin lymphoma, one with breast cancer, one with renal cancer) who developed pneumonitis during their follow-up. Results: The interval from oncological treatment initiation to pneumonitis onset ranged from 6 to 48 months (median = 18.5), and in four patients it occurred after discontinuation of oncologic therapy. In most patients, the diagnosis was established with high probability based only on the clinical presentation, radiologic pattern, and concomitant oncologic therapy. Bronchoscopy with bronchoalveolar lavage analysis was performed in eight of the 12 patients, particularly when onset followed treatment discontinuation. The main symptom was dyspnea (10/12 cases), and three of 12 patients had respiratory failure (SpO₂ ≤ 88%). The CTCAE severity grades were: one mild, seven moderate, three severe, and one life-threatening. The CT scan showed different patterns (7 OP, 4 NSIP-like, and 1 HP). Eleven patients received oral methylprednisolone (0.40 to 0.82 mg/kg) for 5 to 16 weeks. Two patients continued oncologic treatment, and six discontinued. Pneumonitis improved or resolved in 11 of the 12 patients; one patient deteriorated after reintroduction of immunotherapy and subsequently died from cancer-related complications. Conclusions: Immunotherapy- and targeted therapy-induced pneumonitis can express various features and severities, and prompt recognition and diagnosis based on clinical, radiologic and contextual elements are mandatory. In this small, heterogeneous series the individualized corticosteroid regimens used were followed by favorable outcomes. Our observations suggest that, in selected clinically improving patients, follow-up may rely only on clinical assessment and chest X-ray, and extensive tests may be reserved for non-responsive cases. Full article

Background: Pleomorphic rhabdomyosarcoma (RMS) is a rare, adult-predominant high-grade sarcoma that usually arises in the deep soft tissues of the extremities. Primary oral pleomorphic RMS is exceptionally rare, and detailed CT and MRI characteristics of oral pleomorphic RMS remain sparsely documented. Case Presentation: A 66-year-old woman presented with a two-month history of lower anterior tooth pain and progressive mandibular swelling, initially misdiagnosed and treated as a dental infection. CT and MRI revealed a 3.8-cm heterogeneously enhancing mass centered in the mandibular gingiva, with aggressive cortical destruction, diffusion restriction, and anterior floor-of-mouth extension; oral cavity cancer (squamous cell carcinoma) was initially favored on imaging. The patient underwent wide excision with segmental mandibulectomy and fibular osteocutaneous free-flap reconstruction. Histopathologic examination confirmed a high-grade pleomorphic RMS with immunoreactivity for desmin and MyoD1. The patient received adjuvant chemotherapy and radiotherapy, with no recurrence at 8-month follow-up. Conclusions: Pleomorphic RMS of mandibular gingiva may be mistaken clinically for odontogenic infection and radiologically for squamous cell carcinoma. Although imaging findings are nonspecific, CT and MRI are essential for defining mandibular and floor-of-mouth involvement and planning resection; definitive diagnosis requires histopathologic and immunohistochemical confirmation. Full article

Triple-negative breast cancer (TNBC) is a highly aggressive subtype of breast cancer with limited therapeutic options for patients at high risk of disease recurrence and metastasis. The cyclic nucleotide-degrading enzyme, phosphodiesterase 10A (PDE10), that hydrolyzes both cAMP and cGMP has been previously reported to be expressed in multiple cancers and regulates key cellular signaling pathways involved in cancer cell proliferation, survival, and maintenance of stem cell-like properties. We found that PDE10 overexpression was associated with poor relapse-free survival of TNBC patients and identified its potential as a therapeutic target for TNBC using a novel inhibitor, ADT-030. Our results showed that ADT-030 inhibited the growth of TNBC cells, reduced colony-forming efficiency and enhanced the therapeutic efficacy of paclitaxel. A TNBC mouse model demonstrated that oral administration of ADT-030 significantly suppressed syngeneic tumor growth and enhanced the antitumor efficacy of paclitaxel. ADT-030 treatment altered differentially expressed genes (DEGs), signaling pathways, and cellular processes. Overall, our findings suggest that ADT-030, as a monotherapy or in combination with standard-of-care chemotherapy, may be an effective therapeutic approach for TNBC. Further studies are warranted to better understand the oncogenic role of PDE10 in TNBC and the mechanisms by which ADT-030 modulates the tumor microenvironment (TME) and enhances chemotherapy response. Full article

Background/Objectives: Triple-negative breast cancer (TNBC) is one of the most aggressive breast cancer subtypes and remains associated with limited therapeutic options and high systemic toxicity from conventional chemotherapy. Ipomoea pes-caprae is a coastal medicinal plant traditionally consumed in Mexico for inflammatory and renal disorders and contains bioactive metabolites with reported antioxidant and pharmacological properties. However, its antitumoral activity and systemic safety profile remain poorly understood. This study aimed to characterize the phytochemical composition, antioxidant capacity, antitumoral activity, and toxicity of a traditionally prepared aqueous infusion of I. pes-caprae leaves (IPCAE). Methods: IPCAE was characterized using phytochemical screening and complementary instrumental analyses. Antioxidant activity was evaluated using the DPPH assay. A randomized preclinical study was performed in mice bearing MDA-MB-231 xenografts treated with IPCAE, cisplatin, or saline control. Results: The infusion showed measurable antioxidant activity (72.25 ± 1.25% DPPH inhibition at 1 mg/mL) and a total polyphenol content of 7.29 µg/mg gallic acid equivalents. Phytochemical screening revealed abundant flavonoids and reducing sugars, with moderate saponin content. In vivo, IPCAE produced only a transient and non-significant trend toward slower tumor progression compared with control (p = 0.214) and cisplatin (p = 0.377). However, marked systemic toxicity was observed, including severe thoracic dermal lesions in 40% of animals and 70% mortality by day 15. Survival was significantly reduced compared with control and cisplatin groups (p < 0.001). Conclusions: Although IPCAE exhibited antioxidant activity, no statistically significant antitumoral effect was observed under the evaluated conditions. Furthermore, repeated oral administration resulted in marked systemic toxicity, characterized by visible dermal lesions, clinical deterioration, and increased mortality. Therefore, the present findings do not support the use of the evaluated crude preparation as an anticancer intervention. Future studies should focus on detailed toxicological characterization, bioassay-guided fractionation, dose optimization, and identification of the individual metabolites responsible for the observed biological effects. The antioxidant activity demonstrated in this study should be interpreted independently from antitumoral activity, as no causal relationship between these findings was established. Full article

Background: Cancer treatment-induced ulcerative mucositis (UM) is a debilitating toxicity in patients with cancers of the lip, oral cavity, and pharynx (CLOP). This study evaluated the association of chemotherapy-induced (CT-UM) and radiotherapy-induced ulcerative mucositis (RT-UM) with burden of illness (BOI), focusing on hospital length of stay (LOS) and total charges, and examined disparities in outcomes. Methods: This retrospective cohort study analyzed 2019 National Inpatient Sample (NIS) data. Adult patients (≥18 years) hospitalized with CLOP (ICD-10-CM C00–C14) undergoing inpatient surgery, chemotherapy, or radiotherapy were included. CT-UM (K12.31) and RT-UM (K12.33) were identified as secondary diagnoses. Survey-weighted generalized linear models (negative binomial for LOS; gamma for charges) adjusted for demographics, comorbidities (Elixhauser score), insurance, income, and Diagnosis-Related Groups (DRG; surgical vs. medical) were used. Results: Among 59,710 weighted CLOP hospitalizations, 820 had CT-UM and 1010 had RT-UM. Patients with UM were younger and had varying comorbidity burdens. Unadjusted analyses showed prolonged geometric mean LOS for CT-UM (5.66 vs. 3.81 days, p < 0.001) and RT-UM (4.95 vs. 3.81 days, p = 0.001), with lower total charges ($48,645 and $42,938 vs. $56,267). Multivariable analyses confirmed RT-UM was associated with increased LOS (adjusted coefficient 1.33, 95% CI 1.14–1.55) but lower charges (0.67, 95% CI 0.56–0.81). In patients >50 years, CT-UM showed stronger effects (LOS 1.80, 95% CI 1.49–2.15; charges 0.79, 95% CI 0.65–0.98). Significant disparities were observed: females, Black and Hispanic patients, and Medicaid beneficiaries experienced greater BOI (prolonged LOS and/or higher charges in subgroups). Associations persisted in DRG- and procedure-stratified sensitivity analyses, suggesting treatment interruptions as a key driver. Conclusions: Ulcerative mucositis in hospitalized CLOP patients is associated with prolonged LOS but lower charges, likely due to treatment modifications, and disproportionately affects vulnerable populations. These findings highlight the need for proactive oral care protocols, multidisciplinary integration, and equity-focused interventions to reduce the burden of this toxicity and improve cancer treatment outcomes. Full article

Background/Objectives: Oral mucositis is a frequent and clinically significant acute toxicity in patients undergoing radiotherapy or chemoradiotherapy for head and neck cancer, with substantial consequences for swallowing function, nutritional status, and quality of life. Conventional clinician-reported toxicity grading may not fully capture the multidimensional burden experienced by patients. This study aimed to perform a longitudinal multidimensional assessment of treatment-related oral mucositis by evaluating the relationship between clinician-reported toxicity, objective mucosal injury, patient-reported swallowing-related quality of life, and nutritional status. Methods: In this retrospective observational study, 32 of 54 consecutively screened patients with locally advanced head and neck cancer treated with curative-intent radiotherapy, with or without concurrent chemotherapy, were included. Oral mucositis was assessed using the Common Terminology Criteria for Adverse Events (CTCAE) and the Oral Mucositis Assessment Scale (OMAS). Swallowing-related quality of life was evaluated using the MD Anderson Dysphagia Inventory (MDADI). Body weight was recorded longitudinally as an indicator of nutritional status. Correlations between OMAS scores and clinical outcome measures were analyzed at predefined timepoints using Spearman’s rank correlation coefficient. Results: All patients developed treatment-related oral mucositis, with peak severity occurring during the acute treatment phase. During the acute treatment phase, OMAS scores demonstrated a moderate positive correlation with clinician-reported toxicity (CTCAE) and inverse correlations with MDADI scores. A significant inverse association between OMAS and MDADI composite score persisted at treatment completion (ρ = −0.41, p = 0.022). Body weight progressively declined during treatment, although no statistically significant correlation with OMAS severity was observed. Conclusions: A multidimensional assessment integrating clinician-reported toxicity, objective mucosal evaluation, and patient-reported functional outcomes provides a broader characterization of oral mucositis burden in patients undergoing radiotherapy-based treatment for head and neck cancer. These findings support the potential value of integrated toxicity assessment strategies to improve supportive care monitoring in clinical practice. Full article

Background: Therapeutic resistance following cyclin-dependent kinase 4/6 inhibitor (CDK4/6i) plus endocrine therapy (ET) represents a key unmet need in hormone receptor-positive, human epidermal growth factor receptor 2-negative (HR+/HER2−) metastatic breast cancer (mBC). Treatment paradigms have advanced from non-targeted options, such as fulvestrant monotherapy or everolimus-based combinations, to precision medicine strategies, including inhibitors of the PI3K/AKT pathway, oral selective estrogen receptor degraders (SERDs), and novel ER-modulating agents, often guided by biomarkers and molecular surveillance. Methods: This narrative review synthesizes evidence from randomized clinical trials, real-world studies, and biomarker-driven analyses published from 2010 to 2026, with emphasis on next-generation sequencing (NGS)-guided genomic profiling, targeted pathway therapies, and circulating tumor DNA (ctDNA)-based proactive interventions in the post-CDK4/6i setting. This review was conducted and reported in accordance with the SANRA recommendations for narrative reviews. Results: Early second-line standards, including fulvestrant and alpelisib for PIK3CA-mutated tumors, established the basis for biomarker-guided treatment in hormone receptor–positive, HER2-negative metastatic breast cancer. With the widespread use of CDK4/6 inhibitors in the first-line setting, the optimal post-progression strategy has shifted toward molecularly selected combination approaches rather than single-agent endocrine therapy, as endocrine monotherapy has shown limited efficacy in acquired resistance. Multiple randomized studies have demonstrated that adding targeted agents to endocrine therapy improves progression-free survival compared with hormonal therapy alone, supporting combination regimens as the preferred strategy after CDK4/6 inhibitor progression, except in carefully selected patients with low disease burden, indolent biology, or frailty where tolerability is a major concern. Precision-based trials have further refined this approach. Elacestrant improved progression-free survival in ESR1-mutated disease in the EMERALD trial, capivasertib plus fulvestrant demonstrated significant benefit in tumors harboring AKT/PIK3CA/PTEN pathway alterations in CAPItello-291, and inavolisib plus palbociclib and fulvestrant achieved both progression-free and overall survival improvement in PIK3CA-mutated patients with early relapse in INAVO120. Real-world analyses further support the effectiveness of these biomarker-directed strategies across diverse clinical subgroups. Comprehensive genomic profiling has identified multiple resistance mechanisms, including ESR1 mutations, PI3K/AKT/mTOR pathway activation, RB1 loss, and FGFR alterations, which may co-occur and reduce sensitivity to endocrine monotherapy. While ESR1 and PI3K pathway alterations now guide approved therapies, FGFR alterations remain investigational targets, with ongoing trials evaluating selective FGFR inhibitors. Proactive switching approaches evaluated in SERENA-6 and PADA-1 demonstrate that serial circulating tumor DNA (ctDNA) monitoring can detect emergent ESR1 mutations before radiographic progression, providing a clinically actionable lead time for early therapeutic modification and extending endocrine-based disease control by approximately 5 to 7 months. Conclusions: Post-CDK4/6i management increasingly relies on NGS-guided precision approaches, integrating pathway-specific therapies and ctDNA surveillance to tailor sequencing based on resistance profiles, prior ET response, and tumor heterogeneity. Future investigations into novel ER degraders and multi-targeted combinations hold potential to further optimize algorithms, extend non-chemotherapy options, and enhance survival in HR+/HER2− mBC. Full article

Background/Objectives. Breast cancer is the most frequently diagnosed cancer worldwide, with approximately 15% classified as Triple-Negative Breast Cancer (TNBC). TNBC is characterized by the absence of estrogen receptor (ER) and progesterone receptor (PR), and the lack of HER2 overexpression, limiting use of targeted therapies. Current TNBC treatment relies heavily on chemotherapy, most commonly taxanes including paclitaxel that stabilize microtubules, disrupt chromosome separation and induce apoptosis. TNBCs frequently develop chemoresistance after multiple treatment cycles, highlighting a critical unmet need for novel therapeutic strategies. This study addresses this challenge by targeting salt-inducible kinase 2 (SIK2), which is overexpressed in 85% of TNBCs compared to normal breast tissue. Methodes. In collaboration with Arrien Pharmaceuticals and Greenfire Biologics, we developed ARN-3261/GRN-300, a novel orally bioavailable SIK2 inhibitor and evaluated its ability to sensitize TNBC cells to paclitaxel in vitro and in vivo. Results. GRN-300 demonstrated strong synergy with paclitaxel in all eight TNBC cell lines tested, as indicated by favorable combination indices. In xenograft models, the combination therapy significantly enhanced tumor growth inhibition and prolonged survival compared to either agent alone. Mechanistic studies showed that GRN-300 disrupts the anaphase-promoting complex/cyclosome (APC/C) pathway by downregulating key mitotic regulators, including CDC27, CDK1, and PLK1, thereby potentiating G2/M cell cycle arrest and apoptosis. Conclusions. Together, these findings establish GRN-300 as a promising therapeutic agent that enhances paclitaxel efficacy through complementary disruption of mitotic regulatory pathways, providing strong preclinical rationale for clinical development in TNBC. Full article

Background. This study aimed to evaluate the efficacy and safety of low-dose neoadjuvant chemotherapy with an oral fluoropyrimidine containing tegafur, gimeracil, and oteracil (S-1) and oxaliplatin (NAC-SOX) in improving resectability and long-term outcomes in patients with advanced gastric cancer. Methods. This was a single-center, retrospective study analyzing patients with advanced gastric cancer or esophagogastric junction cancer who received NAC-SOX. (S-1: 80–120 mg/m², oxaliplatin: 100 mg/m²) followed by gastrectomy with D2 lymphadenectomy. Clinical background, chemotherapy-related adverse effects, surgical outcomes, pathological response, and survival were assessed. Results. A total of 34 patients underwent NAC-SOX, with a median age of 74 years. The most common surgical procedure was total gastrectomy (n = 16). Peripheral neuropathy was the most frequent adverse effect, but no grade 4 toxicities were observed. Postoperative complications (≥CD grade 3a) occurred in 8.8% of cases, with no treatment-related deaths. R0 resection was achieved in 85.3% of cases, and the pathological complete response rate was 20.6%. The 3-year recurrence-free and overall survival rates were 71.3% and 83.2%, respectively. Conclusions. Low-dose NAC-SOX demonstrated favorable efficacy and safety, achieving high R0 resection and pathological response rates. Further prospective studies are needed to optimize treatment strategies. Full article

Background: Oral delivery of chemotherapeutic agents remains challenging due to gastrointestinal degradation, poor intestinal permeability, and extensive first-pass metabolism, which collectively limit bioavailability. Lipid-based drug delivery systems offer a promising strategy to overcome these barriers. This study aimed to develop a freeze-dried, solid-dispersible self-emulsifying drug delivery system (SEDDS) using a water-in-oil-in-water (w/o/w) double emulsion approach for the co-encapsulation of hydrophilic (doxorubicin) and lipophilic (ellipticine) agents to enhance oral delivery. Methods: Double-emulsion SEDDS were prepared via a two-stage emulsification process to enable compartmentalized drug loading within aqueous and oil phases. The formulations were freeze-dried to improve stability and storage. Physicochemical properties were characterized using dynamic light scattering for droplet size and polydispersity index (PDI), zeta potential analysis for colloidal stability, and differential scanning calorimetry for thermal behavior. Drug encapsulation efficiency was determined, and cellular uptake was evaluated in breast cancer cells using fluorescence microscopy. Results: Optimized SEDDS exhibited droplet sizes of 90–347 nm with low PDI values (0.005–0.336), indicating uniform and stable dispersions. Zeta potential values (−10.64 to 2.38 mV) supported colloidal stability, while freeze-dried formulations retained dispersion characteristics upon reconstitution over extended storage. Both drugs demonstrated high encapsulation efficiency (>97%), and thermal analysis confirmed the formation of stable amorphous systems. Fluorescence imaging revealed enhanced intracellular uptake of both agents. Conclusions: This study demonstrates that freeze-dried double-emulsion SEDDS enable efficient co-delivery of hydrophilic and lipophilic drugs, improving stability and cellular uptake. This platform shows strong potential for overcoming key barriers in oral chemotherapy and provides a promising strategy for combination drug delivery. Full article

Background/Objectives: The neutrophil-to-lymphocyte ratio (NLR) is a simple biomarker reflecting systemic inflammatory status and has been investigated in head and neck cancer (HNC) as a potential prognostic indicator. Its role in relation to radiotherapy-related toxicity remains uncertain. The aim of this study was to provide a descriptive evaluation of NLR values in relation to oral mucositis severity and swallowing-related quality of life in patients undergoing radiotherapy-based treatment. Methods: We retrospectively evaluated 32 patients with locally advanced HNC treated with radiotherapy, with or without concomitant chemotherapy, in the definitive or adjuvant setting (March 2025–January 2026). NLR was calculated at baseline (T0), at a predefined mid-treatment timepoint (T3), and during week 6 of treatment (T6). Mucositis severity was assessed using CTCAE and the Oral Mucositis Assessment Scale (OMAS), while swallowing-related quality of life was measured using the MD Anderson Dysphagia Inventory (MDADI). Relationships between NLR values and toxicity endpoints were descriptively assessed using Spearman correlation analysis. Results: No statistically significant correlations were observed between NLR values and OM severity or swallowing-related outcomes at any evaluated timepoint. At T3, non-significant correlations were observed between NLR and CTCAE mucositis grade and between NLR and MDADI global score. No statistically significant correlations were observed between NLR values and OMAS at any evaluated timepoint. Conclusions: In this retrospective cohort, no association between NLR and radiotherapy-related mucositis severity or swallowing-related quality of life was demonstrated. These findings are descriptive and limited by the small sample size, the retrospective design, and the absence of control for potential confounding factors. No inferential or causal conclusions can be drawn. Further prospective studies with larger and more homogeneous cohorts are required to better characterize NLR behavior in this clinical setting. Full article

Metabolic changes in saliva are known to be closely associated with the presence of non-oral cancers, particularly breast cancer. The diagnostic and prognostic potential of salivary biomarkers in breast cancer has been demonstrated, but their applicability for assessing therapy response has not yet been established. The aim of this study was to comprehensively analyze clinical, pathological, molecular, and salivary characteristics when assessing the response to neoadjuvant chemotherapy for breast cancer. The study included 361 breast cancer patients undergoing their first course of chemotherapy and 127 healthy volunteers without breast pathologies. Saliva samples were collected from all volunteers before treatment. Saliva analysis results for amino acids, lipids, and tumor markers were compared with tumor pathomorphism assessment after breast cancer surgery. The proportion of patients with a complete response to therapy was statistically significantly lower after menopause, and in those with HER2-negative breast cancer, moderate tumor differentiation, and high estrogen and progesterone receptor expression. For the first time, a body mass index (BMI) greater than 25 and low HER2 expression (HER2-low) were shown to have an unfavorable prognosis. The criterion for selecting informative salivary metabolites was a multidirectional change in minimal and complete pathological responses to therapy compared to healthy controls. Thus, prognostically favorable signs were a decrease in the concentration of urea below 7.5 mmol/L (OR = 1.921; 95% CI 1.061–4.270; p = 0.0342), a decrease in the area of the absorption band at 2957 cm⁻¹ below 24 (OR = 3.875; 95% CI 1.160–12.70; p = 0.0003), and an increase in the concentration of cancer antigen CA27.29 above 3 U/L (OR = 2.138; 95% CI 1.021–7.273; p = 0.0343) and CA-15-3 above 39 U/L (OR = 3.896; 95% CI 1.062–14.07; p = 0.0072). With a simultaneous increase in both CA27.29 and CA15-3, the probability of a complete response to therapy increased (OR = 4.288; 95% CI 1.056–17.09; p = 0.0013). Multivariate analysis showed that an independent prognostic indicator, along with the expression status of HER2, estrogen receptors, differentiation degree, BMI, and menopause status, was the concentration of CA15-3 in saliva (AUC = 0.789, 95% CI: 0.737–0.842, p = 0.0001). Identifying new markers will help physicians formulate treatment plans tailored to a patient’s individual risk factors, leading to increased survival and improved quality of life. Full article