Tumor microenvironment is intrinsically hypoxic with abundant hypoxia-inducible factors-1α (HIF-1α), a primary regulator of the cellular response to hypoxia and various stresses imposed on the tumor cells. HIF-1α increases radioresistance and chemoresistance by reducing DNA damage, increasing repair of DNA damage, enhancing glycolysis that increases antioxidant capacity of tumors cells, and promoting angiogenesis. In addition, HIF-1α markedly enhances drug efflux, leading to multidrug resistance. Radiotherapy and certain chemotherapy drugs evoke profound anti-tumor immunity by inducing immunologic cell death that release tumor-associated antigens together with numerous pro-immunological factors, leading to priming of cytotoxic CD8+ T cells and enhancing the cytotoxicity of macrophages and natural killer cells. Radiotherapy and chemotherapy of tumors significantly increase HIF-1α activity in tumor cells. Unfortunately, HIF-1α effectively promotes various immune suppressive pathways including secretion of immune suppressive cytokines, activation of myeloid-derived suppressor cells, activation of regulatory T cells, inhibition of T cells priming and activity, and upregulation of immune checkpoints. Consequently, the anti-tumor immunity elevated by radiotherapy and chemotherapy is counterbalanced or masked by the potent immune suppression promoted by HIF-1α. Effective inhibition of HIF-1α may significantly increase the efficacy of radiotherapy and chemotherapy by increasing radiosensitivity and chemosensitivity of tumor cells and also by upregulating anti-tumor immunity.

Tumor microenvironment is intrinsically hypoxic with abundant hypoxia-inducible factors-1α (HIF-1α), a primary regulator of the cellular response to hypoxia and various stresses imposed on the tumor cells. HIF-1α increases radioresistance and chemoresistance by reducing DNA damage, increasing repair of DNA damage, enhancing glycolysis that increases antioxidant capacity of tumors cells, and promoting angiogenesis. In addition, HIF-1α markedly enhances drug efflux, leading to multidrug resistance. Radiotherapy and certain chemotherapy drugs evoke profound anti-tumor immunity by inducing immunologic cell death that release tumor-associated antigens together with numerous pro-immunological factors, leading to priming of cytotoxic CD8+ T cells and enhancing the cytotoxicity of macrophages and natural killer cells. Radiotherapy and chemotherapy of tumors significantly increase HIF-1α activity in tumor cells. Unfortunately, HIF-1α effectively promotes various immune suppressive pathways including secretion of immune suppressive cytokines, activation of myeloid-derived suppressor cells, activation of regulatory T cells, inhibition of T cells priming and activity, and upregulation of immune checkpoints. Consequently, the anti-tumor immunity elevated by radiotherapy and chemotherapy is counterbalanced or masked by the potent immune suppression promoted by HIF-1α. Effective inhibition of HIF-1α may significantly increase the efficacy of radiotherapy and chemotherapy by increasing radiosensitivity and chemosensitivity of tumor cells and also by upregulating anti-tumor immunity.

Tumor microenvironment is intrinsically hypoxic with abundant hypoxia-inducible factors-1α (HIF-1α), a primary regulator of the cellular response to hypoxia and various stresses imposed on the tumor cells. HIF-1α increases radioresistance and chemoresistance by reducing DNA damage, increasing repair of DNA damage, enhancing glycolysis that increases antioxidant capacity of tumors cells, and promoting angiogenesis. In addition, HIF-1α markedly enhances drug efflux, leading to multidrug resistance. Radiotherapy and certain chemotherapy drugs evoke profound anti-tumor immunity by inducing immunologic cell death that release tumor-associated antigens together with numerous pro-immunological factors, leading to priming of cytotoxic CD8+ T cells and enhancing the cytotoxicity of macrophages and natural killer cells. Radiotherapy and chemotherapy of tumors significantly increase HIF-1α activity in tumor cells. Unfortunately, HIF-1α effectively promotes various immune suppressive pathways including secretion of immune suppressive cytokines, activation of myeloid-derived suppressor cells, activation of regulatory T cells, inhibition of T cells priming and activity, and upregulation of immune checkpoints. Consequently, the anti-tumor immunity elevated by radiotherapy and chemotherapy is counterbalanced or masked by the potent immune suppression promoted by HIF-1α. Effective inhibition of HIF-1α may significantly increase the efficacy of radiotherapy and chemotherapy by increasing radiosensitivity and chemosensitivity of tumor cells and also by upregulating anti-tumor immunity.

Objective: This study was performed to evaluate the efficacy and safety of lurasidone (160 mg/day) compared to quetiapine XR (QXR; 600 mg/day) in the treatment of acutely psychotic patients with schizophrenia. Methods: Patients were randomly assigned to 6 weeks of double-blind treatment with lurasidone 160 mg/day (n=105) or QXR 600 mg/day (n=105). Primary efficacy measure was the change from baseline to week 6 in Positive and Negative Syndrome Scale (PANSS) total score and Clinical Global Impressions severity (CGI-S) score. Adverse events, body measurements, and laboratory parameters were assessed. Results: Lurasidone demonstrated non-inferiority to QXR on the PANSS total score. Adjusted mean±standard error change at week 6 on the PANSS total score was -26.42±2.02 and -27.33±2.01 in the lurasidone and QXR group, respectively. The mean difference score was -0.91 (95% confidence interval -6.35–4.53). The lurasidone group showed a greater reduction in PANSS total and negative subscale on week 1 and a greater reduction in end-point CGI-S score compared to the QXR group. Body weight, body mass index, and waist circumference in the lurasidone group were reduced, with significantly lower mean change compared to QXR. Endpoint changes in glucose, cholesterol, triglycerides, and low-density lipoprotein levels were also significantly lower. The most common adverse drug reactions with lurasidone were akathisia and nausea. Conclusion Lurasidone 160 mg/day was found to be non-inferior to QXR 600 mg/day in the treatment of schizophrenia with comparable efficacy and tolerability. Adverse effects of lurasidone were generally tolerable, and beneficial effects on metabolic parameters can be expected.

Background/Aims: Despite short-acting β2-agonist (SABA) overuse being associated with poor asthma outcomes, data on SABA use in South Korea is scarce. Herein, we describe prescription patterns of SABA and other asthma medications in patients from the South Korean cohort of the SABA use IN Asthma (SABINA) III study. Methods: This study included patients with asthma aged ≥ 12 years, who had ≥ 3 consultations with the same healthcare provider, and medical records containing data for ≥ 12 months prior to the study visit. Patients were classified by investigator-defined asthma severity (per 2017 Global Initiative for Asthma recommendations) and practice type (primary or specialist care). Data on disease characteristics, asthma treatments, and clinical outcomes in the 12 months before the study visit were collected using electronic case report forms. Results: Data from 476 patients (mean age, 55.4 years; female, 63.0%) were analyzed. Most patients were treated by specialists (83.7%) and had moderate-to-severe asthma (91.0%). Overall, 7.6% of patients were prescribed ≥ 3 SABA canisters (defined as over-prescription). In patients prescribed SABA in addition to maintenance therapy, 47.4% were over-prescribed SABA. Most patients (95.4%) were prescribed a fixed-dose combination of an inhaled corticosteroid and a long-acting β2-agonist as maintenance therapy. Although asthma was well-controlled/partly-controlled in 91.6% of patients, 29.6% experienced ≥ 1 severe asthma exacerbation. Conclusions SABA over-prescription was reported in nearly 50% of patients prescribed SABA in addition to maintenance therapy, underscoring the need to align clinical practices with the latest evidence-based recommendations and educate physicians and patients on appropriate SABA use.

Background/Aims: Epidermal growth factor receptor (EGFR) mutation is important in determining the treatment strategy for advanced lung cancer patients with malignant pleural effusion (MPE). Contrary to serum carcinoembryonic antigen (S-CEA) levels, the associations between pleural fluid CEA (PF-CEA) levels and EGFR mutation status as well as between PF-CEA levels and treatment efficacy have rarely been investigated in lung adenocarcinoma patients with MPE. Methods: This retrospective study enrolled lung adenocarcinoma patients with MPE and available PF-CEA levels and EGFR mutation results. The patients were categorized based on PF-CEA levels: < 10 ng/mL, 10–100 ng/mL, 100–500 ng/mL, and ≥ 500 ng/mL. The association between PF-CEA levels and EGFR mutation status as well as their therapeutic impact on overall survival was compared among the four groups. Results: This study included 188 patients. PF-CEA level was found to be an independent predictor of EGFR mutation but not S-CEA level. The EGFR mutation rates were higher as the PF-CEA levels increased, regardless of cytology results or sample types. Among EGFR-mutant lung adenocarcinoma patients receiving EGFR-tyrosine kinase inhibitor (TKI) treatment, those with high PF-CEA levels had significantly better survival outcomes than those with low PF-CEA levels. Conclusion High PF-CEA levels were associated with high EGFR mutation rate and may lead to a favorable clinical outcome of EGFR-TKI treatment in EGFR-mutant lung adenocarcinoma patients with MPE. These findings highlight the importance of actively investigating EGFR mutation detection in patients with suspected MPE and elevated PF-CEA levels despite negative cytology results.

Breast manifestations of autoimmune diseases are rare but may present as localized disease or as part of a systemic disease. The most common clinical presentations of autoimmune mastitis are palpable masses and mastalgia, but patients can also be asymptomatic. Its radiological features are nonspecific and varied; it usually appears as an irregular hypoechoic mass or ill-defined hypoechoic nonmass lesion that mimics malignancy, with or without duct ectasia on breast ultrasonography. On breast MRI, segmental or regional nonmass enhancement is observed. However, due to its nonspecific and rapid changes in its clinical and radiological features, its diagnosis is often challenging and delayed. Herein, we present a rare case of mastitis with mammary duct ectasia in a patient with Behcet’s syndrome and its rapid changes in imaging features on serial radiologic studies. Furthermore, we review the literature focusing on the radiologic and histopathologic characteristics of autoimmune mastitis.

Purpose: Conventional gonadal shields are manufactured in standardized sizes and shapes and do not conform to individual testicular contours, causing discomfort. We developed a novel patientspecific gonadal shield using thermoplastic sheets and tested its feasibility through dosimetric evaluations. Methods: During the computed tomography simulation, custom lead shields were fabricated using thermoplastic sheets that were molded to the testicular shape of the patient. The shielding efficacy was evaluated using optically stimulated luminescent dosimeters (OSLDs) for point dose measurements. Results: The thermoplastic sheet was molded to fit closely to the skin with a minimal air gap of approximately 8.4 cm³, providing comfort to the patient during treatment. The patient-specific shield effectively reduced the surface dose from 28 cGy to less than 15 cGy. By combining the OSLDs located in the same row and calculating the mean dose value, a shielding effect was achieved with a maximum dose reduction of 56.1%. Conclusions Customized gonadal shields were successfully created using thermoplastic sheets to minimize patient discomfort during application. However, further improvements in lead shield fabrication are needed to ensure full conformity.

Purpose: This study investigated the dose perturbation according to the size of the sensitive volume in the dosimeter in small-field dosimetry. Methods: The dose profiles with different field sizes were measured using three different dosimeters: the CC13, Razor ion chamber, and Edge solid-state detector. Both the open and wedged beams with different field sizes were employed in the measurement. The profiles were measured in a water phantom at maximum dose depths of 5, 10, and 20 cm. The penumbra and width of the open-beam profiles were compared according to the types of the dosimeters and beam. The dose fall-off between the peak and 20% dose was evaluated for the wedged beam profiles. Results: In the open-beam measurement, the fall-off of the profile was steeper with the Edge detector, which has the smallest sensitive volume. Meanwhile, the dose in the out-of-field region was the smallest with the Edge detector. The widths of the penumbra were 6.10, 4.47, and 4.03 mm for the profile of the 3×3 cm 2 field measured by the CC13 chamber, Razor chamber, and Edge detector, respectively. The width of the profile was not changed even if different dosimeters were used in the measurement. The wedged beam profiles showed more clear peaks at the field edge when a smaller dosimeter was used. Conclusions The results demonstrate the necessity of dosimeters with a small sensitive volume for measuring a small-field beam or a steep dose gradient.

Purpose: This study evaluated various methods for determining the half-value layer (HVL) of kilovoltage (kV) beams produced by the Varian TrueBeam STx on-board imager. By comparing these methods with the standard ionization chamber approach, the study aimed to identify practical solutions for HVL determination and dosimetric characterization of kV beams, particularly in resource-limited settings. Methods: HVLs for kV beams (40–140 kVp) were measured using an Exradin A12 ionization chamber and a Piranha MULTI meter. The ionization chamber measurements adhered to American Association of Physicists in Medicine Task Group 61 guidelines and served as the reference standard. Additionally, HVL values were calculated using two model-based approaches: SpekPy (a Python-based tool) and Monte Carlo (MC) simulations using Geant4 and GATE. The results from these methods were compared to assess consistency and reliability. Results: Deviations across all methods were generally below 4%. At 40 kV, the most significant discrepancies were attributed to lower signal levels from the ionization chamber. The consistency between the model-based methods and experimental measurements demonstrates the reliability of these alternative approaches for HVL determination. Conclusions Although the ionization chamber remains the gold standard, the Piranha MULTI meter and model-based methods, i.e., SpekPy and MC simulations, have shown promise as viable alternatives, especially in resource-constrained settings. These in silico approaches also offer advantages in convenience and accuracy, supporting their potential for broader future applications.