High-Dose Radioembolization with Resin Microspheres Limited by Lung Shunt for Localized Hepatocellular Carcinoma: Virtual Tumor Absorbed Dose as a Predictor of Complete Response.

Lesional dosimetry in 131I refractory metastatic differentiated thyroid cancer with BRAFp.V600E or RAS mutation treated with trametinib +/- dabrafenib followed by radioactive iodine.

Effect of dose escalation in neoadjuvant chemoradiotherapy of locally advanced rectal cancer on clinical and pathologic Response: A Systematic review and meta-analysis of randomized controlled trials.

Talc fits the framework of poorly soluble low-toxicity particles - implications for hazard classification.

Integration of quantitative MRI and liver function indices to predict early tumor response after stereotactic body radiotherapy for hepatocellular carcinoma: A prospective study.

Neoadjuvant PD-1 Inhibition prior to Partial Cryoablation of Murine Hepatocellular Carcinoma Modulates the Tumor Microenvironment toward Favorable Immunological Profiles.

Proton radiotherapy is applied for various tumor sites, offering better dose distribution resulting in decreased excess radiation of healthy tissue. Furthermore, the biological effects of proton irradiation may be different from X-ray irradiation, depending on tumor characteristics. This is particularly relevant for head and neck squamous cell carcinoma (HNSCC), which displays high biological heterogeneity. However, this heterogeneous response to various radiation modalities is currently not included in clinical decision making due to lack of response prediction models. Nine oral cavity tumor specimens were obtained after surgical resection, cut into thin slices, irradiated with both X-ray and protons, and cultured ex vivo for up to five days. We subsequently analyzed proliferation, apoptosis, DNA repair and immune cell infiltration. Most tumors (five out of nine) showed similar response to proton and X-ray irradiation. However, in three tumors a significantly larger decrease in viability was measured upon proton irradiation. One of those tumors was homologous recombination deficient (HRD). The other two proton-sensitive tumors showed low numbers of infiltrating immune cells, including tumor infiltrating lymphocytes, while the most X-ray sensitive tumor had a particularly high immune cell infiltration. The ex vivo assay revealed heterogeneous response of HNSCC tumors to proton and X-ray irradiation. The tumors with increased sensitivity to proton irradiation either showed HR deficiency or low immune cell infiltration. However, not all immune-deserted tumors showed this skewing towards X-ray resistance. These findings require validation in a larger cohort of patients.

Portable microrobotic platform for non-prehensile mechanophenotyping of biopsy-derived human cancer tissues.

Outcomes of Gamma Knife radiosurgery for meningiomas overlying the motor cortex.

Liquiritigenin targets transferrin receptor to potentiate ferroptosis sensitivity in colorectal cancer cells.

Patients with advanced epidermal growth factor receptor (EGFR)-mutated adenocarcinoma often receive frontline first- and second-generation EGFR tyrosine kinase inhibitor (TKI) treatments in Taiwan. However, upon progression, not all patients undergo rebiopsy for molecular testing. In some cases, tumors are located in difficult-to-access areas, and some rebiopsy specimens are inadequate for pathological and molecular assessment. Our aim is to evaluate the efficacy of the third-generation EGFR TKI, osimertinib, in tumors with unknown T790M mutation status. This study retrospectively collected data from patients with EGFR-mutant advanced lung adenocarcinoma who received first-line first- or second-generation EGFR TKI therapy followed by the third-generation EGFR TKI osimertinib without rebiopsy to assess T790M mutation status between January 2015 and December 2024. Efficacy and survival outcomes are presented. A total of 160 patients with EGFR-mutated lung adenocarcinoma at clinical stages IIIB-IVB received first- or second-generation EGFR-TKI frontline therapy. After disease progression, 82 patients were treated with osimertinib as a second-line therapy with unknown T790M mutation status. Among them, 48 patients initially received afatinib as frontline treatment, while 34 patients received erlotinib. The best tumor response rate (RR) was 42.7%, with a median time on treatment (ToT) of 5.6 months (95% CI, 4.0-9.3). Swim-plot visualization highlighted a hierarchical pattern wherein longer first-line duration frequently co-occurred with longer empirical second-line duration. Osimertinib treatment is a viable option for patients who progress on frontline first- or second-generation EGFR TKI therapy without rebiopsy and have an unknown T790M mutation status. The RR of 42.7% and median ToT of 5.6 months appear consistent with historical outcomes reported for second-line platinum-based chemotherapy. Osimertinib provides an additional treatment line for patients whose tumors are difficult to access and have an unknown T790M status, making it a valuable treatment option for these patients.

Activation of the phosphatodylinositol-3-kinase/AKT (PI3K/AKT) signalling pathway promotes tumor immune evasion by suppressing effector T-cell infiltration and enhancing regulatory T-cell activity contributing to resistance to immune checkpoint inhibitors. Preclinical studies have demonstrated that inhibition of this pathway can restore anti-tumor immunity and synergize with PD-1/PD-L1 blockade. We explore the synergistic clinical potential of targeting the PI3K/AKT pathway in combination with atezolizumab to overcome immunotherapy resistance in recurrent glioblastoma and advanced solid tumors. Phase 1b, investigator-initiated, open-label study (NCT03673787) composed of a proof-of-concept dose escalation Part A of ipatasertib plus atezolizumab in a 3+3 design. Adult patients with treatment refractory advanced cancers were enrolled into Cohort A1 and recurrent glioblastoma onto Cohort A2. Part B enrolled patients into 6 exploratory cohorts. Study aims to evaluate the safety, immune-modulatory effects and preliminary efficacy of the combination of ipatasertib with atezolizumab. The combination was well tolerated, with no dose-limiting toxicities at the recommended phase 2 dose of ipatasertib 400 mg/daily plus atezolizumab 1200mg every 3 weeks. Pharmacodynamic analysis demonstrated depletion of FOXP3+ regulatory T cells and increased infiltration of CD8+ effector T cells within the tumor microenvironment. Durable exceptional responses were seen in some patients with treatment-refractory or recurrent glioblastoma. This is the first report in clinical samples showing that ipatasertib efficiently depletes FOXP3+ regulatory T cells and results in increased infiltration of effector CD8+ T cells in the tumor microenvironment. This was associated with preliminary efficacy in a subset of patients with treatment-refractory glioblastoma (GBM).

BACKGROUND There have been no comparative studies on doxorubicin (DOX), oxaliplatin (OXA) and gemcitabine (GEM) drug-eluting bead transarterial chemoembolisation (DEB-TACE) in treating patients with unresectable non-small cell lung cancer (NSCLC). AIM To compare the efficacy and safety of different loading drugs in the treatment of these patients. METHODS A total of 123 patients with unresectable NSCLC were enrolled, including the DOX-eluting DEB-TACE group (DOX group, n = 47), OXA-eluting DEB-TACE group (OXA group, n = 29) and GEM-eluting DEB-TACE (GEM group, n = 47). Treatment response, overall survival (OS), progression-free survival (PFS) and adverse events were evaluated. RESULTS The 1- and 3-month tumor response showed no significant change among the three groups. Both the 6-month objective response rate and disease control rate showed highest trends in the OXA group [objective response rate (ORR): 33.3%/disease control rate (DCR): 57.1%], followed by the GEM (ORR: 17.1%/DCR: 42.9%) and DOX groups (ORR: 17.6%/DCR: 41.2%), although not statistically significant (ORR: P = 0.29/DCR: P = 0.47). Both OS and PFS were highest in the OXA group [OS: 29.6 months, interquartile range (IQR): 4.6-18.5 months/PFS: 9.9 months, IQR: 2.5-13.4 months]. The OXA group exhibited prolonged PFS and increased OS compared with the DOX group (P = 0.10, χ 2 = 2.720, P = 0.03, χ 2 = 4.806) and GEM groups (P = 0.30, χ 2 = 1.095, P = 0.08, χ 2 = 3.165). The incidence rates of adverse events were comparable between the DOX and OXA groups but were lower in the GEM group; however, no statistical significance was observed (P = 0.63), and all adverse events were tolerable in the three groups. CONCLUSION DOX, OXA and GEM eluting DEB-TACE may be an effective and safe treatment approach for unresectable NSCLC, with patients in the OXA group potentially exhibiting a prolonged OS. Randomized controlled trials are required to further clarify the efficacy of different drug-eluting DEB-TACE in unresectable NSCLC.

Glucose-6-phosphate dehydrogenase (G6PD) deficiency impairs NADPH generation through the pentose phosphate pathway, resulting in reduced glutathione regeneration and increased vulnerability to oxidative stress. While its clinical significance is well described in hemolytic disorders, its impact on tumor biology and chemosensitivity remains poorly characterized. Cisplatin, a backbone agent in the management of nasopharyngeal carcinoma (NPC), exerts its cytotoxicity through the formation of DNA adducts and the robust induction of reactive oxygen species (ROS) activity. We report a patient with non-keratinizing NPC and a G6PD variant, a (class III) deficiency, who demonstrated a rapid and pronounced objective response to cisplatin-based induction and concurrent chemoradiotherapy. Unfortunately, the patient also exhibited signs of rapid and persistent hematologic (platelets and white cells) toxicity. Notably, no hemolytic events occurred. A narrative review of the available literature indicates that G6PD-deficient cells exhibit a reduced antioxidant reserve, increased cisplatin-induced DNA damage, and impaired activation of ROS-detoxifying pathways. A few clinical observations similarly report enhanced tumor responsiveness in G6PD-deficient individuals, although the evidence is sparse and heterogeneous. Preclinical data support the notion that diminished NADPH availability amplifies cisplatin-triggered oxidative injury, thereby increasing tumor susceptibility. This case adds to emerging evidence that G6PD deficiency may potentiate cisplatin efficacy in NPC by exploiting intrinsic redox vulnerabilities. While preliminary, these findings suggest the potential utility of metabolic phenotyping in treatment stratification. Prospective studies are needed to define the predictive value, safety, and therapeutic implications of G6PD status in cisplatin-based regimens.

Tumor response to radiotherapy is shaped by multiple factors including immune modulation, tumor microenvironment and genetic factors. Among these, the Y-box binding protein-1 (YB-1) is a multifunctional DNA/RNA-binding protein frequently overexpressed in tumors. YB-1 controls the activation of DNA damage response (DDR) signaling following radiotherapy. Emerging evidence suggests that the role of YB-1 extends beyond DDR regulation to shaping tumor-immune interactions by regulating cytokine production, promoting immune evasion, and altering immune checkpoint expression. Elucidating these immune-related functions of YB-1 may uncover novel mechanisms of tumor immune evasion and identify novel therapeutic targets to enhance cancer immunotherapy. This mini-review summarizes current insights into the role of YB-1 in immune regulation, highlighting its impact on tumor immunity and potential clinical applications.

Exercise during chemotherapy or chemoradiotherapy and treatment delivery and tumor response outcomes: a scoping review.

Spatially fractionated radiation therapy (SFRT) has therapeutic potential as a priming therapy which boosts tumor control. However, the optimal delivery and spatial fractionation parameters have not been deciphered and the mechanisms at play are not yet fully understood. This paper highlights our preclinical setups for mini-grid SFRT with 6 MeV electrons delivered at conventional to ultrahigh dose rates, using a flexible collimator system. These setups let us explore relevant spatial fractionation parameters to observe their effect on tumor growth and normal tissue toxicity. Preclinical studies here may reveal the parameters of highest clinical relevance for SFRT and combination therapies. For preclinical experiments with electron spatial fractionation, 6.5mm thick brass collimators were made with 7- (or 19-) hole hexagonally packed ∅ 0.65-2mm apertures, with 1.6-5mm CTC distances. Irradiated EBT-XD Gafchromic film downstream of collimators were analyzed to obtain peak-to-valley dose ratios (PVDR), full width at half maxima (FWHM), and peak doses at various depths in solid water, and at surface when increasing the separations from collimators in air. Male and female C57BL/6 mice were injected subcutaneously with UPPL1541 bladder cancer cells in the right flank. After 10-13 days, a single dose treatment was delivered to the tumors with either ∅14mm circular homogeneous field (10Gy delivered at 3 kGy s-1), or using a 7-hole (∅ of 2 and 5mm center-to-center distances) spatially fractionated field; peak doses of 30Gy delivered at 820Gy s-1, 20Gy at 860Gy s-1, and 20Gy at<0.1Gy s-1. Tumor growth and time to triple tumor volume (TTTV) were measured and compared between treatment regimens. Similar PVDRs were obtained with 7- and 19-hole inserts (35 and31 at surface, respectively). Peak widths increased with depth, and maximal peak dose rates were>1.8 kGy s-1. A displacement in air from the collimator exit decreased PVDRs at the phantom surface; from32 to16 at∼10mm distance,and to 6 at∼20mm distance. Peak doses also reduced to ∼57 % at 10mm distance, and to∼33% at 20mm distance. Film measurements at the mouse phantom surface produced peak and valley dose rates of>850Gy s-1 and ∼60Gy s-1 respectively, with a PVDR>14. Tumor growth delays for spatially fractionated FLASH 30Gy (peak dose, with a 2.1Gy valley dose, and a 10Gy average dose) and homogeneous FLASH 10Gy electron irradiation regimens were similar. Both regimens also demonstrated significantly longer TTTV compared to control and spatially fractionated conventional 20Gy (peak dose, with a 1.4Gy valley dose, and a 6.7Gy average dose) regimens (p<0.05). No significant differences in body weight and skin damage were observed, indicating acceptable treatment tolerability. Spatially fractionated electron FLASH treatments with 30Gy peak doses and 2.1Gy valley doses provide effective tumor growth delay and prolonged tumor control akin to 10Gy homogeneous irradiations. Here we demonstrate that combining spatial modulation, higher peak doses, and FLASH dose rates can produce favorable tumor response.

altered glucose metabolism plays a pivotal role in cancer cell proliferation and disease progression. However, there is limited information regarding the role of glycemic variability in metastatic colorectal cancer (mCRC). to analyze the association between glycemic variability and tumor response in patients with mCRC. a prospective pilot cohort study was conducted in patients with newly diagnosed mCRC. Patients were excluded if they had a previous chronic corticosteroid use, prior cancer treatment, or infection. At baseline and after a four-month follow-up, the glycemic coefficient of variation (CV %) was measured by the Free Style Libre sensor over a 15-day period. The outcome was disease control rate (DCR) according to RECIST version 1.1. Disease control rate was defined as the proportion of patients achieving complete response, partial response, or stable disease. Progressive disease was defined as the appearance of new lesions or tumor growth. among the eleven patients included, 63.6 % achieved DCR. Patients with a glycemic CV % above the 75th percentile had a higher proportion of patients aged ≥ 65 years, a diagnosis of type 2 diabetes mellitus, and progression events (75 %), showing a trend to significance. this pilot study suggests that glycemic variability may be associated with tumor response in patients with mCRC. However due to the exploratory design, larger prospective studies are needed to confirm the potential role of glycemic variability as a metabolic biomarker in mCRC.

Endometrial cancer is one of the most common gynecological malignancies, and advanced disease remains associated with poor clinical outcomes. Mucin 16 (MUC16), a transmembrane glycoprotein frequently mutated in multiple cancers, has been implicated in tumor progression. However, its functional role and molecular mechanism in endometrial cancer remain unclear. Somatic mutation data from The Cancer Genome Atlas (TCGA) and the International Cancer Genome Consortium (ICGC) were analyzed to evaluate the association between MUC16 mutation and tumor mutation burden (TMB). Functional assays were performed in endometrial cancer cell lines. Protein interactions and ubiquitination were examined using co-immunoprecipitation and ubiquitination assays. Xenograft mouse models and drug sensitivity assays were used to evaluate tumor growth and response to targeted therapy. MUC16 is frequently mutated in endometrial cancer and its mutation status is associated with increased tumor mutation burden and improved overall survival in endometrial cancer patients. Functional experiments further demonstrated that MUC16 protein expression promotes tumor cell proliferation, migration, and invasion. Mechanistically, MUC16 interacted with estrogen receptor 1 (ESR1) and enhanced its stability by inhibiting ubiquitin-mediated degradation, thereby activating the PI3K/AKT signaling pathway. In addition, MUC16 knockdown significantly increased the sensitivity of endometrial cancer cells to the targeted drug lapatinib. These findings reveal that MUC16 promotes endometrial cancer progression through the ESR1/PI3K/AKT axis and highlight MUC16 as a potential prognostic biomarker and therapeutic target.

The neutrophil to lymphocyte ratio (NLR) serves as a marker of systemic inflammation and is an established prognostic factor in non-small cell lung cancer (NSCLC). However, its predictive value for treatment response, particularly when evaluated through three-dimensional CT volumetry, remains ambiguous. This study investigates whether pretreatment NLR and treatment-related changes in NLR correlate with volumetric tumor response to platinum-based neoadjuvant chemotherapy (NACT). Adult patients with histologically confirmed NSCLC who received platinum-based NACT and had evaluable pre- and posttreatment CT imaging were included in the analysis. Tumor response was defined as a ≥30% reduction using three-dimensional CT volumetry. We analyzed pretreatment NLR, posttreatment NLR, changes in NLR (ΔNLR), and the NLR ratio. To enhance statistical stability, additional analyses utilized log-transformed NLR values. Associations were examined through non-parametric tests, correlation analysis, and both univariable and multivariable logistic regression models adjusted for age, sex, histology, disease stage, performance status, and baseline tumor volume. A total of 70 patients were included, with 33 (47.1%) achieving a volumetric response. NLR decreased during treatment (median ΔNLR = -0.42), yet no significant differences were noted between responders and non-responders regarding pretreatment NLR (p= 0.773), posttreatment NLR (p= 0.920), ΔNLR (p= 0.514), or NLR ratio (p= 0.630). None of the NLR-derived parameters showed significant associations with treatment response in univariable or multivariable models, including those utilizing log-transformed variables. Furthermore, the NLR ratio exhibited substantial instability, reflected in wide confidence intervals. In conclusion, within this cohort, neither pretreatment nor dynamic NLR parameters were significantly associated with CT-based volumetric tumor response following platinum-based NACT.