Search Results (71)

Mediastinal radiotherapy plays a central role in the treatment of several malignancies, particularly Hodgkin lymphoma and breast cancer. However, exposure to thoracic radiation is associated with long-term cardiovascular complications, among which valvular heart disease (VHD) is increasingly recognized. Radiation-induced VHD typically presents after a latency period of 10–20 years and is characterized by progressive valve fibrosis, thickening, and calcification, most commonly affecting the left-sided valves. Management of radiation-induced VHD generally follows standard guidelines but remains challenging due to extensive calcification and coexisting radiation-related cardiac or pulmonary injury. A history of thoracic radiotherapy is associated with increased perioperative risk and may negatively impact surgical outcomes, which often alters the risk–benefit balance and favors less invasive therapeutic approaches. Advances in the transcatheter approach have expanded treatment options for this high-risk population; however, data on long-term outcomes remain limited. Evolving dose-reduction techniques, such as deep-inspiration breath-hold, intensity-modulated radiotherapy, and proton therapy, together with predictive dosimetric models, aim to minimize future cardiac toxicity. Given the delayed onset and progressive nature of radiation-associated VHD, structured long-term surveillance is essential to enable early detection and timely intervention in cancer survivors at risk. Full article

Background: The role of pulmonary metastasectomy has been increasingly questioned in the surgical community after the PulMiCC trial challenged its benefit in colorectal cancer. However, the view on pulmonary metastasectomy among people in non-surgical disciplines remains unclear. This study explored interdisciplinary attitudes toward pulmonary metastasectomy and identified the clinical expectations shaping its future role. Methods: An anonymous online survey of active board-certified physicians in oncology, urology, gynecology and dermatology was conducted (December 2024–June 2025). Twenty items covered attitudes to local ablative therapy, referral criteria, preferred modalities and future relevance. Group comparisons used Pearson’s χ²; ordinal ratings were compared by one-way ANOVA; associations were explored with Spearman’s ρ. Results: Of 2884 contacted physicians, 165 participated (≈5.7%), and 106 completed the questionnaire. All 106 (100%) endorsed local ablative therapy as meaningful; 92/106 (86.8%) favored routine integration into multimodal care. Surgical metastasectomy was selected by 49/106 (46.2%), SBRT was selected by 27/106 (25.5%) and image-guided ablation was selected by 7/106 (6.6%); preference for surgery differed by specialty (χ²(4) = 15.31, p = 0.004), while institutional availability (in-house thoracic surgery or radiation oncology) showed no association with selecting surgery or SBRT. Key referral determinants were number of lesions (105/106; 99.1%), anatomical location (86/106; 81.1%; p < 0.02 across specialties), and lesion size (81/106; 76.4%; p < 0.05); other factors showed no consistent inter-specialty differences. The perceived usefulness of metastasectomy was high (mode 8/10) and showed a weak, non-significant correlation with referral experience (ρ = 0.172, p = 0.077). Looking ahead, 46/106 (43.4%) anticipated a declining role of local ablative therapy with novel systemic therapies; interest in biomarker analysis from metastatic tissue compared to primary tumor tissue was very high 97/106 (91.5%). Conclusions: Local ablative therapy, particularly pulmonary metastasectomy, continues to be viewed as an integral and trusted element of metastatic disease management across specialties. Despite limited prospective evidence, clinicians maintain strong confidence in its clinical value and foresee its evolution toward biologically and patient-tailored indications. However, the interpretation of these findings is limited by a low response rate and potential selection bias toward European, academically affiliated respondents. To our knowledge, this is the first study to systematically capture perceptions of pulmonary metastasectomy among non-surgical oncology-related specialists. Full article

Background and Objectives: The axillary lateral vessel thoracic junction (ALTJ) is a key lymphatic drainage pathway for the arm and a potential structure to spare during regional nodal irradiation (RNI) to reduce lymphedema risk in breast cancer patients. This study aims to demonstrate the feasibility of ALTJ-sparing radiation therapy (RT) planning using Tomotherapy. Materials and Methods: Ten breast cancer patients who had undergone axillary lymph node dissection and whose dissected axillary levels were excluded from the RNI target volume were included. A TomoDirect intensity-modulated RT plan was generated at a dose of 50 Gy in 25 fractions. The dissected axilla was not designated as an organ at risk (OAR) in the original treatment plan. For this study, the axillary lymph node level I (AXL1) and the ALTJ were delineated retrospectively, with the ALTJ considered an OAR in the newly generated study plan. A total of 20 RT plans (10 per group) were statistically compared using various dose-volume parameters. Results: Compared to the original plans, the study plans with ALTJ as an OAR significantly reduced the incidental dose to both the ALTJ (mean: 41.7 ± 3.4 Gy vs. 27.2 ± 1.3 Gy; p = 0.005) and the AXL1 (mean: 43.9 ± 2.0 Gy vs. 37.7 ± 1.9 Gy; p = 0.005). All other dosimetric parameters (V25Gy, V35Gy, V40Gy, Dmin, Dmax) for the ALTJ were also significantly lower in the study plans. This ALTJ sparing was achieved while maintaining all required dose-volume constraints for target volumes and standard OARs such as the lung and heart. Conclusions: This study demonstrates that simply excluding the dissected axilla from the target volume without designating it as an OAR still results in a substantial incidental dose to this region. Our findings also show the feasibility of using Tomotherapy to selectively spare the axilla, particularly the ALTJ subregion of AXL1, which is critical for lymphedema risk in breast cancer patients. Full article

Radiation-induced lung inflammation (RILI) is a major complication of thoracic radiotherapy, characterized by excessive inflammation and subsequent fibrosis that compromise pulmonary function and treatment outcomes. This study explores the pharmacological properties of a newly synthesized Lipoxin A4 analogue (CYNC-2) to mitigate RILI by modulating the AMP-activated protein kinase (AMPK)/NOD-like receptor family pyrin domain containing 3(NLRP3) inflammasome pathway. A murine RILI model was established in mice by delivering a single high-dose (ablative) X-ray irradiation to the left lung. Mice in the treatment group received CYNC-2 via tail-vein injection three times per week for 2 weeks. The effects of CYNC-2 on RILI were evaluated histological, immunohistochemical analysis of lung tissues, cytokine profiling, lung function testing using a FlexiVent system, and micro-computed tomography (micro-CT) imaging of lung damage. In parallel, two human lung cell lines—L132 (normal bronchial epithelial cells) and A549 (lung carcinoma cells)—were irradiated with 6 Gy X-rays and treated with CYNC-2 to assess cell viability and changes in AMPK/NLRP3 pathway markers via qPCR and immunofluorescence. Lung tissue sample from patients who underwent thoracic radiotherapy were also examined to validate key findings. CYNC-2 activated AMPK and inhibited mTOR signaling, which suppressed NLRP3 inflammasome activation and led to reduced secretion of pro-inflammatory cytokines (IL-1β, IL-6, and TGF-β1). In vitro, CYNC-2 mitigated radiation-induced inflammatory responses and preserved cellular viability. Overall, CYNC-2 effectively dampened acute pulmonary in the RILI model. These findings suggest that targeting the AMPK/NLRP3 inflammasome pathway via a stable LXA4 analogue such as CYNC-2 is a promising therapeutic strategy to improve clinical outcomes for patients receiving thoracic radiation therapy. Full article

Immune checkpoint inhibitors (ICIs) and thoracic radiotherapy are standard treatments for advanced non-small-cell lung cancer (NSCLC), especially in patients with high PD-L1 expression or symptoms such as superior vena cava syndrome (SVCS). Both therapies carry a risk of pulmonary toxicity, which may be exacerbated by opportunistic infections due to corticosteroid use. We report a unique case of a 65-year-old man with squamous-cell NSCLC and high PD-L1 expression (80%), who developed a rare complication: radiation recall pneumonitis (RRP), with superimposed Pneumocystis jirovecii pneumonia and severe symptomatic hyponatremia induced by trimethoprim/sulfamethoxazole (TMP-SMX). The coexistence of these three complications—radiotherapy- and immunotherapy-associated lung injury, opportunistic infection, and electrolyte imbalance—represents an exceptional clinical scenario not previously described in the literature. This report highlights the importance of differential diagnosis, early recognition of complications, and close monitoring of electrolytes in NSCLC patients undergoing complex treatment regimens. Full article

Background: Trastuzumab deruxtecan (T-DXd), a HER2-directed antibody-drug conjugate, has significantly advanced the management of HER2-expressing malignancies. However, interstitial lung disease (ILD) remains a clinically significant adverse effect. Despite increasing clinical use of T-DXd, real-world data on ILD incidence, characteristics, and outcomes—particularly in Middle Eastern populations remain limited. Methods: This retrospective study analyzed medical records of patients who received trastuzumab deruxtecan (T-DXd) at a tertiary care hospital. Data collected included demographics, tumor characteristics, prior treatments, and interstitial lung disease (ILD)-related outcomes. ILD events were identified and graded according to the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Descriptive statistics were used to summarize baseline characteristics and ILD features. Univariate logistic regression was performed to assess potential risk factors associated with ILD development. Kaplan–Meier survival analysis was used to evaluate time-to-event outcomes, including time to ILD onset and resolution. Results: Among 65 patients with advanced stage IV cancer (90.8% with breast cancer), 16 (24.6%) developed ILD following T-DXd therapy. The median time to ILD onset was 125.5 days. The most common presenting symptoms were dyspnea and cough (50%). A history of ground-glass opacities was associated with increased odds of ILD (OR 2.7; p = 0.236), though not statistically significant. Patients with Grade ≥ 3 ILD had significantly lower oxygen saturation levels compared to those with milder grades (88.3% vs. 97.7%, p = 0.049). Median time to clinical resolution was 297 days (95% CI: 77.5–516). No significant associations were observed with smoking history, pulmonary metastases, or prior thoracic radiation. Conclusions: In this real-world cohort, ILD occurred in nearly one-quarter of patients receiving T-DXd, predominantly within the first six months of treatment. The findings highlight the importance of early respiratory symptom monitoring and pulse oximetry—particularly in patients with pre-existing pulmonary abnormalities. These results underscore the need for vigilant ILD surveillance strategies and further prospective studies to validate predictive risk factors and optimize management protocols. Full article

Purpose: The liver is susceptible to adverse effects from radiation therapy (RT) and systemic therapy (ST) for breast cancer, given its anatomical proximity. Thus, we evaluated hepatotoxicity after RT and ST for breast cancer. Methods: This multicenter retrospective study included breast cancer patients treated with RT in 2021 and underwent a liver function test (LFT) before and after RT. Patients with bilateral breast cancer or a history of thoracic or abdominal RT and liver disease were excluded. Changes in Common Terminology Criteria for Adverse Events (CTCAE) grading of liver enzyme elevation (LEE) of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP) and its associations with Dose-volume histogram (DVH) parameters and other clinical factors were analyzed. Results: In total, 529 patients were included in the analysis. Median values of mean liver dose, V5Gy, V10Gy, and V20Gy dose to the liver were 1.37 Gy, 4.3%, 2.1%, and 0.9%, respectively. In the post-RT LFT, 6 (1.1%), 9 (1.7%), and 25 (4.7%) patients showed CTCAE grade elevation of AST, ALT and ALP, respectively, with most cases being grade 1. Three patients (0.6%) met the diagnostic criteria for radiation-induced liver disease (RILD). In multivariate logistic regressions including various DVH parameters, neoadjuvant therapy was associated with LEE. Conclusions: The incidences of LEE and RILD after multimodal therapy for breast cancer were limited, suggesting that RT and ST can be considered safe in terms of hepatotoxicity. Nevertheless, caution in treating patients who underwent neoadjuvant therapy, especially to those with underlying liver disease, might help minimize LEE. Full article

Background: Lattice Radiation Therapy (LRT), a spatially fractionated stereotactic radiotherapy (SBRT) technique, has shown promising results in the palliative treatment of large tumors. The focus of our first analysis of 56 lesions ≥7 cm was on the extent of shrinkage following palliative LRT (mean 50%) and assessment of its effect duration (: mean 6 months). Herewith we present an updated analysis of our single-center LRT cohort, with a focus on LRT outcome across diagnoses and applied LRT regimens. Methods: We assessed the clinical outcome following LRT in 66 patients treated for 81 lesions between 01.2022 and 05.2025. LRT protocols included simultaneous integrated boost (sib-) LRT in 49 lesions (5 × 4–5 Gy to the entire mass with sib of 9–13 Gy to lattice vertices). Alternatively mainly in pre-irradiated and/or very large lesions—a single-fraction stereotactic LRT (SBRT-LRT) of 1 × 20 Gy to vertices only was delivered to 26 lesions. In six cases with modest response to single fraction SBRT-LRT, the sib-LRT schedule was added 4–8 weeks later. Results: The median age was 68 years (18–93). Main tumor locations were abdomino-pelvic (n = 34) and thoracic (n = 17). Histopathological diagnoses included carcinoma (n = 34), sarcoma (n = 31), and melanoma (n = 16). 31% of all lesions have been previously irradiated. 73% of cases underwent concurrent or peri-LRT systemic therapy. The mean/median overall survival (OS) time of the cohort was 7.6/4.6 months (0.4–40.2), 11.9/5.8 months in 16/66 alive, and 6.4/4.3 months in deceased patients, respectively. 82% of symptomatic patients reported immediate subjective improvement (PROM), with a lifelong response duration in most cases. Progressive disease (PD: >10% increase in initial volume) was found in 9%, stable disease (SD +/−10% of initial volume) in 19% of scanned lesions, and shrinkage (>10% reduction in initial volume) in 75%, with a mean/median tumor volume reduction of 51/60%. The extent of shrinkage was found to be 11–30%/31–60%/61–100% in 38/24/38% of lesions. Response rates (PD, SD, shrinkage) following the two applied LRT regimens, as well as those related to sarcoma and carcinoma diagnoses, were found to be comparable. Treatment tolerance was excellent (G0-1). Conclusions: Palliative LRT provides rapid subjective relief in ~80% of symptomatic patients. Radiologic shrinkage was stated in 75% of FU-scanned lesions, with a lifelong effect duration in most patients. LRT was found effective across histologies, with a similar extent of shrinkage in carcinoma and sarcoma following 1F SBRT- and 5F sib-LRT regimens, respectively. Full article

Objectives: We investigated the performance of a slow computed tomography (CT) protocol to reduce alignment errors arising from motion when using CT-on-rail (CTOR) for image guidance for patients receiving thoracic stereotactic body radiation therapy (SBRT). Methods: A Quasar lung phantom with a moving tumor was programmed with three breathing rates and three motion amplitudes. MIP and average 4DCT images were used for contouring and alignment, respectively. Ten CTOR images were obtained for each of the breathing rates and amplitudes, under both CT protocols. We used in-house CAT software for image guidance, centering the tumor in the lung window within the gross tumor volume contour. Longitudinal coordinate reproducibility was compared between the two protocols. We also retrospectively analyzed CBCT SBRT image guidance alignment data from 31 patients to evaluate the systematic error in the longitudinal direction between simulation and daily treatments. Results: The mean (standard deviation) alignments (mm) for the standard and slow CT protocol ranged from 0.7 (0.68) and 1.0 (0.0), respectively, for the 28 BPM breathing rate and 5 mm amplitude combination to 5.2 (2.0) and 1.6 (0.52) for the 8 BPM breathing rate and 15 mm amplitude combination. Our retrospective analysis of patient alignment data showed a notable systematic difference in the relative bone and gross tumor volume alignment between the simulation and daily cone beam CT datasets. The mean longitudinal difference was −0.19 cm (standard deviation, 0.17 cm; range, 0.28 cm to −1.14 cm). Therefore, the position of the vertebral body cannot be used as a surrogate for mean tumor position in the longitudinal direction. Longitudinal position must be accurately determined for each patient using multiple CT images. Conclusions: A slow CT protocol improved the alignment with slower breathing rates being more challenging. A 5 mm PTV is not sufficient for tumor motion greater than 9 mm. Averaging the coordinates from multiple CTOR images is recommended. Full article

Background and Objectives: Small-cell lung cancer (SCLC) is an exceedingly aggressive neoplasm distinguished by an unfavorable prognosis. Recent studies have confirmed chemo-immunotherapy as the conventional first treatment for extensive-stage small-cell lung cancer (ES-SCLC), but the impact of treatment duration remains unclear. The goal of this study was to find out how the length of treatment affected progression-free survival (PFS) and overall survival (OS) in patients with ES-SCLC who were receiving first-line atezolizumab plus chemotherapy. Materials and Methods: This retrospective multicenter study comprised 82 patients from six oncology centers in Turkey between 2017 and 2024. Patients were categorized into two categories according to the quantity of chemotherapy cycles they had undergone: standard treatment (≤4 cycles) and extended treatment (≥5 cycles). For the purpose of analyzing survival outcomes and related clinical determinants, as well as the demographic structures and features of the patients, both univariate and multivariate Cox regression models were utilized. Results: The median number of atezolizumab cycles was 8 (1–63). OS was 29.46 months after 15.8 months of follow-up, while PFS was 10.63 months. When comparing the two groups, we found no statistically significant differences in either PFS (p = 0.952) or OS (p = 0.374). Significant associations with OS were seen in the standard therapy group for both ECOG PS 1 (p = 0.028). Thoracic radiation considerably decreased progression risk (HR = 0.41, p = 0.031) in the extended group. Conclusions: While prolonging chemo-immunotherapy beyond four cycles did not significantly improve survival, the selected patient subgroups may benefit from personalized approaches. Thoracic radiotherapy emerged as a key modifier of outcome. Full article

Background: The re-irradiation of centrally located lung tumors poses substantial risks due to prior dose exposure and proximity to critical structures. Accurate target delineation is crucial to minimize toxicity and ensure tumor coverage. Four-dimensional positron emission tomography/computed tomography (4D-PET/CT) integrates respiratory motion and metabolic data, offering improved delineation over static imaging. Its clinical utility in re-irradiation remains under-reported. Methods: A 67-year-old male presented with the central recurrence of squamous cell carcinoma in the right upper lobe, embedded in radiation-induced fibrosis, following prior chemoradiotherapy. Delineation using static PET underestimated tumor motion. A 4D-PET/CT-guided Stereotactic Body Radiation Therapy (SBRT) plan was developed with a prescription of 60 Gy in eight fractions. A comparative plan using static PET was generated to assess the dosimetric differences. Results: The internal target volume (ITV) from 4D-PET/CT was nearly double the size of the GTV from static PET, with a 5.1 mm discrepancy in the craniocaudal axis. The 4D-PET-based plan achieved 95.0% PTV coverage, while the static PET-based plan covered only 61.7%, illustrating the risk of underdosage without motion-resolved imaging. The patient completed the treatment without acute or late toxicity and showed a sustained metabolic response at one year (SUVmax from 13.4 to 5.8). Conclusions: This case demonstrates the clinical value of 4D-PET/CT in the SBRT re-irradiation of centrally located lung tumors, particularly in fibrotic regions where anatomical imaging is insufficient. It enabled accurate delineation, improved dosimetric coverage, and safe, effective retreatment. These findings support its integration into planning for complex thoracic re-irradiation. Full article

Radiation therapy (RT) plays a vital role in managing thoracic cancers, though it can lead to adverse effects, including significant cardiotoxicity. Understanding the risk factors like hypertension in RT is important for patient prognosis and management. A Dahl salt-sensitive (SS) female rat model was used to study hypertension effect on RT-induced cardiotoxicity. Rats were fed a high-salt diet to induce hypertension and then divided into RT and sham groups. The RT group received 24 Gy of whole-heart irradiation. Cardiac function was evaluated using MRI and blood pressure measurements at baseline, 8 weeks and 12 weeks post-RT. Histological examination was performed after the last timepoint or animal death. The hypertensive RT rats demonstrated significant decreases in left-ventricular ejection fraction (EF) (45 ± 7.2%) compared to sham (68 ± 7.3%). Furthermore, circumferential (Ecc) and radial (Err) myocardial strains were significantly reduced (Ecc: −7.4 ± 2.0% RT rats vs. −11 ± 2.4% sham; Err: 15 ± 6.5% RT rats vs. 23 ± 8.9% sham). Histological analysis revealed significant pathophysiological remodeling post-RT, including nuclear size, interstitial fibrosis, necrosis, and the presence of inflammatory cells. This study provides valuable insights into the cardiotoxic effects of RT in the context of hypertension, highlighting the potential of using MRI for improved risk assessment with potential for future clinical translation. Full article

Objectives: Extensive-stage small-cell lung cancer (SCLC) has a poor prognosis, but recently, the combination of immunotherapy and chemotherapy has improved treatment outcomes in some patients, and treatment plans may vary depending on the individual’s general condition and tumor response. In addition, intrathoracic tumor control remains a major challenge for this disease. In the current study, we aim to share our clinical experience and demonstrate that consolidative high-dose thoracic radiotherapy effectively reduces intrathoracic tumor recurrence while maintaining acceptable treatment-related toxicities. Materials and Methods: The medical records of 81 SCLC patients treated at Korea University Guro Hospital from January 2019 to December 2023 were reviewed retrospectively. Among them, 22 patients with extensive-stage SCLC who had a favorable tumor response after systemic therapy, including those with oligo-progressive disease limited to the thoracic region and suitable for curative local therapy, received consolidative radiotherapy. A total dose of 52.5 Gy in 25 fractions was administered over 5 weeks to all patients with extensive-stage SCLC. Results and Conclusions: The median follow-up time was 22 months (range: 8–59 months), with the median follow-up period after completing consolidative radiotherapy being 13 months (range: 4–35 months). In-field local recurrence occurred in only one patient after consolidative thoracic radiotherapy. Most importantly, 10 patients with oligo-progressive disease at the thoracic site, at the time of tumor response, remained stable without further intrathoracic in-field recurrence. Additionally, no severe cases of radiation pneumonitis or esophagitis were observed. Based on our institution’s experience, consolidative high-dose thoracic radiotherapy is well-tolerated and associated with fewer intrathoracic recurrences, leading to improved long-term survival in carefully selected patients with extensive-stage SCLC. Given these findings, we believe consolidative radiotherapy should be considered more proactively in clinical practice. Furthermore, these results may help guide the design of future clinical trials. Full article

Background: Approximately 50% of all oncological patients undergo radiation therapy, where personalized planning of treatment relies on gross tumor volume (GTV) delineation. Manual delineation of GTV is time-consuming, operator-dependent, and prone to variability. An increasing number of studies apply artificial intelligence (AI) techniques to automate such delineation processes. Methods: To perform a systematic review comparing the performance of AI models in tumor delineations within the body (thoracic cavity, esophagus, abdomen, and pelvis, or soft tissue and bone). A retrospective search of five electronic databases was performed between January 2017 and February 2025. Original research studies developing and/or validating algorithms delineating GTV in CT, MRI, and/or PET were included. The Checklist for Artificial Intelligence in Medical Imaging (CLAIM) and Transparent Reporting of a multivariable prediction model for Individual Prognosis Or Diagnosis statement and checklist (TRIPOD) were used to assess the risk, bias, and reporting adherence. Results: After screening 2430 articles, 48 were included. The pooled diagnostic performance from the use of AI algorithms across different tumors and topological areas ranged 0.62–0.92 in dice similarity coefficient (DSC) and 1.33–47.10 mm in Hausdorff distance (HD). The algorithms with the highest DSC deployed an encoder–decoder architecture. Conclusions: AI algorithms demonstrate a high level of concordance with clinicians in GTV delineation. Translation to clinical settings requires the building of trust, improvement in performance and robustness of results, and testing in prospective studies and randomized controlled trials. Full article