The expansion of heavy-ion radiotherapy toward multi-ion operation requires a reassessment of shielding design methods that have traditionally relied on particle-number-based workloads. In facilities employing multiple ion species, this approach becomes inconsistent because different ions require substantially different numbers of primary particles to deliver the same prescribed dose. In this study, neutron shielding characteristics for helium, carbon, oxygen, and neon ion beams were evaluated using dose-defined workloads that reflect actual clinical and operational practice. Shielding effectiveness was assessed per unit physical dose to represent quality assurance and commissioning activities, and per unit Relative Biological Effectiveness (RBE)-weighted dose to represent treatment-related workload, based on PHITS Monte Carlo simulations. Under physical-dose normalization, carbon consistently produced the largest neutron effective dose across all shielding configurations. Under RBE-weighted dose normalization, carbon generally remained the most conservative reference ion, although high-energy helium under metallic beam-loss target conditions approached the carbon reference in selected configurations. These findings demonstrate that shielding outcomes are strongly dependent on the dose quantity used to define workload and support the continued use of carbon as the primary reference ion for multi-ion shielding assessment, while indicating that high-energy helium may approach the carbon reference only under restricted treatment-related metallic-target conditions.

BACKGROUND:Osimertinib (OSI), a third-generation epidermal growth factor receptor tyrosine kinase inhibitor, is the standard first-line treatment for non-small cell lung cancer (NSCLC) patients harbouring epidermal growth factor receptor-activating mutations. Nevertheless, the emergence of acquired resistance to OSI in most patients limits long-term efficacy and yields only modest improvements in overall survival. We identified nucleoporin 62 (NUP62) knockdown as a potential strategy to overcome OSI resistance in NSCLC and investigated the underlying molecular mechanisms. METHODS:The role of NUP62 in OSI resistance was evaluated in parental and OSI-resistant NSCLC cell lines. mRNA expression of NUP62 was analysed in lung cancer patient cohorts, and survival rate of the patients was assessed using Kaplan Meier Plot. Mechanistic studies employed siRNA-mediated knockdown, CCK-8, clonogenic assays, immunohistochemistry, western blotting and flow cytometric assays in vitro. In vivo efficacy was examined in a xenograft mouse model. RESULTS:mRNA expression of NUP62 was significantly upregulated in lung cancer tissues and correlated with poor patient survival and increased recurrence. NUP62 knockdown using small interfering RNA (siRNA) sensitised OSI-resistant NSCLC cells to OSI, leading to reduced cell viability and impaired clonogenic potential. Combination of siRNA NUP62 and OSI induced apoptosis via activation of caspases, an effect abrogated by the pan-caspase inhibitor zVAD (carbobenzoxy-valyl-alanyl-aspartyl-[O-methyl]-fluoromethylketone). Mechanistically, NUP62 knockdown markedly reduced survivin, a member of the inhibitor of apoptosis protein family. Survivin downregulation occurred through the ubiquitin-proteasome system, as shown by enhanced ubiquitination and a shortened protein half-life. Overexpressing survivin attenuated siRNA NUP62 plus OSI-induced cell death by inhibiting caspase-3 activity in OSI-resistant NSCLC cell lines. Furthermore, silencing of NUP62 significantly enhanced the antitumor activity of OSI and suppressed tumour growth in vivo. CONCLUSION:NUP62 knockdown reverses OSI resistance by promoting ubiquitination of survivin in OSI-resistant NSCLC cell lines. Silencing of NUP62 may, therefore, be an effective strategy to overcome OSI resistance and enhance therapeutic efficacy.

BACKGROUND:We aimed to evaluate the efficacy of prophylactic cranial irradiation (PCI) in the contemporary management of limited-stage small cell lung cancer (LS-SCLC) and to identify optimal strategies for patient selection. PATIENTS AND METHODS:This multi-institutional cohort study included patients with LS-SCLC who underwent definitive chemoradiation between 2006 and 2022, all staged using brain MRI and PET. We compared the incidence of brain metastases (BM) and overall survival (OS) between patients who received PCI and those who did not. Additionally, we analyzed the differential effect of PCI across 22 subgroups. BM was classified as either isolated or nonisolated, with cumulative incidence calculated using a competing risk model. Outcomes of salvage treatments for isolated BM were also assessed. RESULTS:Among the 1,302 study patients, 672 (51.6%) received PCI and 630 (48.4%) did not. During a median follow-up of 30.5 months (range, 4.2-227.2), PCI significantly reduced the cumulative incidence of BM (17.4% vs 27.6% at 2 years; P<.001), primarily by decreasing isolated BM (6.5% vs 16.1% at 2 years; P<.001), but had no significant effect on nonisolated BM. PCI consistently reduced the incidence of isolated BM across all subgroups, which led to improved OS except among patients who achieved complete response (CR) to primary treatment (hazard ratio [HR], 1.03; P=.865). Patients experiencing CR who developed isolated BM and received local salvage treatment achieved an 81.8% remission rate, resulting in OS comparable to those without BM development (HR, 1.10; P=.631). Stereotactic radiosurgery for BM salvage treatment showed superior OS compared with whole-brain radiotherapy or systemic treatment alone. CONCLUSIONS:PCI did not improve OS in patients achieving CR, who demonstrated excellent outcomes with BM salvage treatment. Our findings suggest that MRI surveillance, combined with effective salvage treatment, may serve as a viable alternative for selected patients with LS-SCLC.

INTRODUCTION:The optimal radiotherapy strategy for inoperable node-negative non-small cell lung cancer (NSCLC) ≥5 cm remains undefined. This study compared clinical outcomes of stereotactic body radiation therapy (SBRT), hypofractionated radiation therapy (HFRT), and conventionally fractionated radiation therapy (CRT) in this population. METHODS:This retrospective study included 137 patients with node-negative NSCLC ≥5 cm treated with SBRT (n = 37), HFRT (n = 56), or CRT (n = 44) from 2011 to 2023. CRT was more common early in the study period, while hypofractionated regimen, particularly HFRT, became increasingly favored over time. For central tumors, SBRT was not administered due to concerns about toxicity. Freedom from local progression (FFLP), overall survival (OS), and treatment-related toxicities were assessed. RESULTS:The median tumor sizes were 5.3 cm (SBRT), 6.1 cm (HFRT), and 7.1 cm (CRT) (P < .001). With a median follow-up of 23.0 months, the 2-year FFLP rates were 87.7% (SBRT), 69.0% (HFRT), and 57.5% (CRT) (P = .021). Hypofractionated regimen (SBRT+HFRT) showed significantly higher FFLP rates than CRT (P = .010), though not significant in multivariate analysis. OS did not differ significantly between groups (P = .92). Distant metastasis was the predominant failure pattern. Grade ≥2 toxicities occurred more often with SBRT (37.8%) than HFRT (14.3%) or CRT (13.6%) (P = .028), mainly due to chest wall pain. Grade ≥3 toxicities were similar across groups (P = .46). CONCLUSIONS:HFRT and SBRT demonstrated favorable local control in node-negative NSCLC ≥5 cm. HFRT may be preferable for central tumors, while SBRT can be considered for peripheral tumors in selected patients.

Radiation therapy is actively utilized for superficial lesions. External beam radiotherapy for cutaneous lesions utilizes electrons with low transmittance. Conventional electron beam therapy uses Cerrobend blocks for field shaping; however, the Intraoperative Radiotherapy (IORT) applicator offers superior dosimetric characteristics. The dosimetric parameters were measured using 4 and 6 MeV electron beams delivered by a Trilogy linear accelerator, and percent depth dose and lateral dose profiles were compared under the presence of the IORT applicator and Cerrobend block. The dose calculations under various IORT applicator conditions and planning studies were performed using Monte Carlo simulation. Treatment plans for three sites were evaluated in terms of coverage of the planning target volume, dose to the surrounding normal tissue, and beam-on time for two treatment modalities. The results of the measured and calculated dosimetric parameters correspond. Scattered electrons along the IORT applicators resulted in shorter dmax and R50 and sharper penumbras compared to the blocks. Oblique IORT applicators also maintained sharp penumbras. Treatment-plan analysis indicated significant reductions in normal tissue dose using the IORT applicator. Implementing IORT in clinical practice requires deliberation of extended beam-on times and associated patient safety protocols; however, the potential benefits regarding dose distribution warrant further optimization in clinical use.

Purpose: Although there is a growing role for local therapy in patients with hepatocellular carcinoma (HCC) and pulmonary oligometastasis, it remains unclear whether metastatectomy or stereotactic body radiation therapy (SBRT) is the more effective treatment for these patients. We aimed to compare the oncologic outcomes of metastasectomy and SBRT for HCC with pulmonary oligometastasis. Methods and Materials: We retrospectively analyzed 209 patients with HCC with 322 metastatic lung lesions who underwent either metastasectomy (150 patients with 241 lesions) or SBRT (59 patients with 81 lesions) between January 2008 and December 2018. Propensity score-based inverse probability of treatment weighting was used to minimize potential bias between the 2 groups. Results: The median follow-up duration was 39.8 months (range, 2.3-166.9 months). The 2-year rate of freedom from local progression was 98.2% in the metastasectomy group and 97.0% in the SBRT group (P = .197). The 2-year rates of overt systemic progression-free survival (PFS) (51.0% vs 46.1%; P = .274), PFS (26.3% vs 9.1%; P = .074), and overall survival (OS, 74.0% vs 57.6%; P = .006) were higher in the metastasectomy group. After the probability of treatment weighting adjustment, the 2-year rates of overt systemic PFS (50.8% vs 52.7%; P = .396), PFS (23.0% vs 24.7%; P = .478), and OS (72.6% vs 83.0%, P = .428) were not significantly different between the 2 groups. In multivariate analysis, viable intrahepatic lesions and the number of prior liver-directed therapies were found to be significant prognostic factors for OS and PFS. The time interval between HCC diagnosis and the development of pulmonary metastases was also significantly associated with OS. Conclusions: Both metastasectomy and SBRT demonstrated excellent local control and comparable oncologic outcomes in patients with pulmonary oligometastasis from HCC. The treatment modality for these patients could be determined based on the individual patient's condition and intrahepatic disease status. (c) 2024 Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies.

This study evaluated the efficacy and safety of 20.0 Gy versus 30.6 Gy radiotherapy for conjunctival MALT lymphoma in 76 lesions treated between 2010 and 2022. The 30.6 Gy group showed a shorter median time to response (3.7 vs. 9.5 months, p < 0.001) and a higher complete response rate at 6 months (68.4% vs. 36.8%, p = 0.009). However, both doses achieved 100% local control at two years. Radiation-induced complications were minimal, with no grade 3 or higher events, and cataracts occurred in only 5.3% of patients in both groups. These results indicate that reducing the radiation dose to 20.0 Gy can achieve comparable long-term outcomes with minimal toxicity, offering an effective treatment alternative for localized conjunctival MALT lymphoma.

Background and purpose:A definitive treatment for radiation-induced pulmonary fibrosis (RIPF), a common side effect of radiation therapy for thoracic cancer, remains to be established. Pulmonary rehabilitation programs, including regular aerobic exercise, may ameliorate RIPF. However, a scientific basis supporting the protective effect of exercise against RIPF is lacking. Methods:Seven-week-old Sprague-Dawley rats were randomly allocated to the control (CON), training without irradiation (T), irradiation only (IR), and irradiation with training (IR + T) groups. Irradiation of the right lung was commenced at 40 Gy over five consecutive days, followed by regular aerobic exercise training using a treadmill for 7 weeks. The variables were assessed before and after irradiation. Pulmonary fibrosis was assessed using Masson's trichrome (MT) staining and hydroxyproline (HYP) assay. Behavioral tests were conducted to evaluate functional changes. In addition, potential molecular mechanisms were explored. Results:The body weights of the rats in the IR and IR + T groups were lower than those in the other two groups. The Rota-rod test revealed significantly higher exercise capacity in the IR + T group compared to that in the IR group, which was closer to that in the CON group. MT staining and HYP assay revealed that the amount of fibrosis in the IR + T group was significantly lower than that in the IR group (collagen area (%): IR, 28.00 ± 7.51, n = 7; IR + T, 24.03 ± 6.93, n = 9; HYP concentration (μg/mg): IR, 0.80 ± 0.09, n = 7; IR + T, 0.47 ± 0.14, n = 9; p < 0.05). Superoxide dismutase activity in the IR + T group was higher than that in the IR group (IR, 84.02 ± 12.56, n = 7; IR + T, 100.55 ± 11.18, n = 9; p < 0.05). Conclusions:Regular aerobic exercise ameliorated RIPF in rats, suggesting its potential utility in pulmonary rehabilitation programs for patients undergoing thoracic radiation therapy.

OBJECTIVES:Radiotherapy for lung cancer can cause lung injury, which may lead to decreased pulmonary function, worsened clinical symptoms, reduced quality of life, and poor prognosis. Given that patients with compromised lung function are more likely to undergo radiotherapy, adjunct treatments to enhance its safety should be explored. We performed this study to determine whether outpatient-based pulmonary rehabilitation (PR) provides positive clinical effects for patients with lung cancer undergoing radiotherapy. METHODS:A randomized controlled trial was conducted between June 2022 and May 2023. Patients were stratified by radiotherapy objectives and assigned to the PR or control groups. The outpatient-based PR program was implemented 2-3 times per week during radiotherapy. RESULTS:Improvements in 6-minute walking distance from baseline were significant in the PR group (16.9 ± 69.9 m vs. -26.1 ± 49.8 m at the end of radiotherapy, P = 0.008; 34.9 ± 39.4 m vs. -24.0 ± 48.3 m at 1-month post-radiotherapy, P < 0.001; 40.7 ± 75.7 m vs. -3.1 ± 47.5 m at 7-month post-radiotherapy, P = 0.043). Grip strength and muscle mass-related parameters showed similar trends. The incidence of radiation pneumonitis requiring steroid treatment was significantly lower in the PR group (9.4 % vs. 54.5 %, P < 0.001). CONCLUSION:PR during radiotherapy for patients with lung cancer improved the 6-minute walking distance and reduced the occurrence of radiation pneumonitis requiring medical intervention. These findings support the integration of PR into radiotherapy for patients with lung cancer. CLINICAL TRIAL REGISTRATION:NCT05414188 at ClinicalTrials.gov (2022-06-10).

PURPOSE:This study aimed to evaluate the efficacy of local ablative therapy (LAT) combined with pembrolizumab in patients with synchronous oligometastatic non-small cell lung cancer (NSCLC) and to identify patients who would most benefit from LAT. METHODS AND MATERIALS:We retrospectively identified patients who received diagnosis of synchronous oligometastatic NSCLC (≤5 metastatic lesions and ≤3 organs involved) and were treated with first-line pembrolizumab between January 2017 and December 2022. Patients who underwent LAT, including surgery or radiation therapy at all disease sites, were compared with those who did not undergo LAT. A recursive partitioning analysis (RPA) model was developed using prognostic factors for progression-free survival (PFS). RESULTS:Among the 258 patients included, 78 received LAT with pembrolizumab, and 180 received pembrolizumab alone. The median follow-up duration was 15.5 months (range, 3.0-71.2 months). In the entire cohort, LAT was independently associated with significantly improved PFS (hazard ratio [HR], 0.64; P = .015) and overall survival (OS) (HR, 0.61; P = .020). In the propensity score-matched cohort (N = 74 in each group), the median PFS was 19.9 months and 9.6 months, respectively (P = .003), and the median OS was 42.2 months and 20.5 months, respectively (P = .045), for the LAT and non-LAT groups. Based on the RPA model, incorporating the number of metastatic lesions, performance status, and programmed cell death-ligand 1 expression level, patients were stratified into 3 risk groups with distinct PFS. LAT significantly improved PFS and OS in the low- and intermediate-risk groups; however, no difference was observed in the high-risk group. LAT was more effective as a consolidative treatment after pembrolizumab initiation than as an upfront therapy. CONCLUSIONS:LAT combined with pembrolizumab was associated with higher PFS and OS compared with pembrolizumab alone in selected patients with synchronous oligometastatic NSCLC. The RPA model could serve as a valuable clinical tool for identifying appropriate patients for LAT.

We developed a deep learning model for distinguishing radiation therapy (RT)-related changes and tumour recurrence in patients with lung cancer who underwent RT, and evaluated its performance. We retrospectively recruited 308 patients with lung cancer with RT-related changes observed on 18F-fluorodeoxyglucose positron emission tomography–computed tomography (18F-FDG PET/CT) performed after RT. Patients were labelled as positive or negative for tumour recurrence through histologic diagnosis or clinical follow-up after 18F-FDG PET/CT. A two-dimensional (2D) slice-based convolutional neural network (CNN) model was created with a total of 3329 slices as input, and performance was evaluated with five independent test sets. For the five independent test sets, the area under the curve (AUC) of the receiver operating characteristic curve, sensitivity, and specificity were in the range of 0.98–0.99, 95–98

Triple-negative breast cancer (TNBC) accounts for approximately 15–20% of all breast cancer types, indicating a poor survival prognosis with a more aggressive biology of metastasis to the lung and a short response duration to available therapies. Ibulocydine (IB) is a novel (cyclin-dependent kinase) CDK7/9 inhibitor prodrug displaying potent anti-cancer effects against various cancer cell types. We performed in vitro and in vivo experiments to determine whether IB inhibits metastasis and eventually overcomes the poor drug response in TNBC. The result showed that IB inhibited the growth of TNBC cells by inducing caspase-mediated apoptosis and blocking metastasis by reducing MMP-9 expression in vitro. Concurrently, in vivo experiments using the metastasis model showed that IB inhibited metastasis of MDA-MB-231-Luc cells to the lung. Collectively, these results demonstrate that IB inhibited the growth of TNBC cells and blocked metastasis by regulating MMP-9 expression, suggesting a novel therapeutic agent for metastatic TNBC.

Background and purpose: No established early biomarkers currently exist to predict responses during concurrent chemoradiotherapy (CCRT) in patients with unresectable non-small cell lung cancer (NSCLC). This study investigated the potential of gross tumor volume (GTV) and its changes during CCRT as predictors of survival outcomes. Materials and methods: We identified 227 patients with unresectable stage III NSCLC who underwent definitive CCRT followed by durvalumab between November 2018 and December 2022. GTV was defined as the volume of the primary tumor, assessed at two time points: before starting CCRT for initial planning (GTV1), and at the fourth week of CCRT for adaptive planning (GTV2). Both relative and absolute regressions between GTV1 and GTV2 were calculated. Results: The median GTV1 volume was 90 mL (range, 5-840 mL), and the median GTV2 volume was 64 mL (range, 1-520 mL), resulting in median absolute and relative regressions of 18.6 mL and 25.0 %, respectively. Among the GTV parameters, relative GTV regression exhibited the strongest predictive value, with an area under the curve (AUC) of 0.804 for in-field progression and 0.711 for overall progression. The 1-year progression-free survival rates for the high (>30 %), intermediate (0-30 %), and low (<= 0%) relative regression groups were 88.0 %, 62.6 %, and 14.3 %, respectively (p = 0.006 for high vs. intermediate; p < 0.001 for intermediate vs. low). Additionally, GTV2 volume demonstrated stronger associations with survival outcomes than GTV1 volume. Conclusion: Relative GTV regression was identified as a promising early predictor for patients with unresectable stage III NSCLC. Further development of a multi-parametric predictive model is warranted to guide patienttailored therapeutic approaches.

We aimed to investigate the safety and efficacy of HL301, a standardized combination product of 7 medicinal plants, in radiation pneumonitis in patients with unresectable non-small cell lung cancer undergoing curative concurrent chemoradiotherapy.

Recent studies report excellent local control (LC) and favorable toxicities of stereotactic ablative radiotherapy (SABR) for pulmonary metastasis (PM) from sarcoma. This study compared the LC and survival of SABR and metastasectomy for sarcoma PM. We analyzed the LC rates of 54 PMs treated with SABR between 2008 and 2022. For survival analysis, we compared 14 patients who received SABR as first-line treatment with 61 patients who underwent metastatectomy. For SABR-treated PMs, a median total dose of 55 Gy (range, 48–60) was administered over 3–10 fractions. Median follow-up for LC in SABR-treated PMs was 19.2 months (range, 0.8–124.0), and the 2-year LC rate was 92.2

Purpose This study aimed to assess the real-world clinical outcomes of consolidative durvalumab in patients with unresectable locally advanced non–small cell lung cancer (LA-NSCLC) and to explore the role of radiotherapy in the era of immunotherapy.Materials and Methods This retrospective study assessed 171 patients with unresectable LA-NSCLC who underwent concurrent chemoradiotherapy (CCRT) with or without consolidative durvalumab at Asan Medical Center between May 2018 and May 2021. Primary outcomes included freedom from locoregional failure (FFLRF), distant metastasis-free survival (DMFS), progression-free survival (PFS), and overall survival (OS).Results Durvalumab following CCRT demonstrated a prolonged median PFS of 20.9 months (p=0.048) and a 3-year FFLRF rate of 57.3% (p=0.008), compared to 13.7 months and 38.8%, respectively, with CCRT alone. Furthermore, the incidence of in-field recurrence was significantly greater in the CCRT-alone group compared to the durvalumab group (26.8% vs. 12.4%, p=0.027). While median OS was not reached with durvalumab, it was 35.4 months in patients receiving CCRT alone (p=0.010). Patients positive for programmed cell death ligand 1 (PD-L1) expression showed notably better outcomes, including FFLRF, DMFS, PFS, and OS. Adherence to PACIFIC trial eligibility criteria identified 100 patients (58.5%) as ineligible. The use of durvalumab demonstrated better survival regardless of eligibility criteria.Conclusion The use of durvalumab consolidation following CCRT significantly enhanced locoregional control and OS in patients with unresectable LA-NSCLC, especially in those with PD-L1–positive tumors, thereby validating the role of durvalumab in standard care.

The real-world evidence about the efficacy of cytotoxic chemotherapy in desmoid tumors is still limited. We investigated the efficacy of chemotherapy in the treatment of recurrent or progressive desmoid tumors. The patients with desmoid tumors who had received cytotoxic chemotherapy between November 2007 and June 2020 in two tertiary hospitals in Korea were reviewed. A total of 25 patients were included in the analysis. The most common primary tumor site was the intra-abdominal or pelvic cavity (56