Radiotherapy and Oncology最新文献

{"title":"A multidimensional deep ensemble learning model predicts pathological response and outcomes in esophageal squamous cell carcinoma treated with neoadjuvant chemoradiotherapy from pretreatment CT imaging: A multicenter study","authors":"Yunsong Liu ,&nbsp;Yang Su ,&nbsp;Jun Peng ,&nbsp;Wencheng Zhang ,&nbsp;Fangdong Zhao ,&nbsp;Yue Li ,&nbsp;Xinyun Song ,&nbsp;Zeliang Ma ,&nbsp;Wanting Zhang ,&nbsp;Jianrui Ji ,&nbsp;Ye Chen ,&nbsp;Yu Men ,&nbsp;Feng Ye ,&nbsp;Kuo Men ,&nbsp;Jianjun Qin ,&nbsp;Wenyang Liu ,&nbsp;Xin Wang ,&nbsp;Nan Bi ,&nbsp;Liyan Xue ,&nbsp;Wen Yu ,&nbsp;Zhouguang Hui","doi":"10.1016/j.radonc.2025.111133","DOIUrl":"10.1016/j.radonc.2025.111133","url":null,"abstract":"<div><h3>Purpose</h3><div>Neoadjuvant chemoradiotherapy (nCRT) followed by esophagectomy remains standard for locally advanced esophageal squamous cell carcinoma (ESCC). However, accurately predicting pathological complete response (pCR) and treatment outcomes remains challenging. This study aimed to develop and validate a multidimensional deep ensemble learning model (DELRN) using pretreatment CT imaging to predict pCR and stratify prognostic risk in ESCC patients undergoing nCRT.</div></div><div><h3>Methods</h3><div>In this multicenter, retrospective cohort study, 485 ESCC patients were enrolled from four hospitals (May 2009–August 2023, December 2017–September 2021, May 2014–September 2019, and March 2013–July 2019). Patients were divided into a discovery cohort (n = 194), an internal cohort (n = 49), and three external validation cohorts (n = 242). A multidimensional deep ensemble learning model (DELRN) integrating radiomics and 3D convolutional neural networks was developed based on pretreatment CT images to predict pCR and clinical outcomes. The model’s performance was evaluated by discrimination, calibration, and clinical utility. Kaplan-Meier analysis assessed overall survival (OS) and disease-free survival (DFS) at two follow-up centers.</div></div><div><h3>Results</h3><div>The DELRN model demonstrated robust predictive performance for pCR across the discovery, internal, and external validation cohorts, with area under the curve (AUC) values of 0.943 (95 % CI: 0.912–0.973), 0.796 (95 % CI: 0.661–0.930), 0.767 (95 % CI: 0.646–0.887), 0.829 (95 % CI: 0.715–0.942), and 0.782 (95 % CI: 0.664–0.900), respectively, surpassing single-domain radiomics or deep learning models. DELRN effectively stratified patients into high-risk and low-risk groups for OS (log-rank P = 0.018 and 0.0053) and DFS (log-rank P = 0.00042 and 0.035). Multivariate analysis confirmed DELRN as an independent prognostic factor for OS and DFS.</div></div><div><h3>Conclusion</h3><div>The DELRN model demonstrated promising clinical potential as an effective, non-invasive tool for predicting nCRT response and treatment outcome in ESCC patients, enabling personalized treatment strategies and improving clinical decision-making with future prospective multicenter validation.</div></div>","PeriodicalId":21041,"journal":{"name":"Radiotherapy and Oncology","volume":"212 ","pages":"Article 111133"},"PeriodicalIF":5.3,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145055563","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Staged Gamma Knife radiosurgery for large brain metastases: local control and the influence of systemic treatment","authors":"R.G. Huisman ,&nbsp;P. van Schie ,&nbsp;L.G. Merckel ,&nbsp;T. Wiersma ,&nbsp;J.L. Knegjens ,&nbsp;E.P.M. Jansen ,&nbsp;A. Compter ,&nbsp;D. Brandsma ,&nbsp;M. Bot ,&nbsp;J. Hoogmoed ,&nbsp;P.C. de Witt Hamer ,&nbsp;G.R. Borst ,&nbsp;R. Post","doi":"10.1016/j.radonc.2025.111127","DOIUrl":"10.1016/j.radonc.2025.111127","url":null,"abstract":"<div><h3>Background and purpose</h3><div>Staged Gamma Knife radiosurgery (SGKRS) delivers high-dose radiotherapy to large brain metastases (BM) in two or three fractions with a time interval of several weeks. Various systemic treatments have also demonstrated favorable intracranial responses. Therefore, the outcome of patients undergoing radiosurgery and systemic treatment for large BM is of high interest but unknown.</div></div><div><h3>Materials and methods</h3><div>A retrospective cohort study was conducted on patients with large BM treated with SGKRS without previous local treatment directed to the brain. The primary outcome measure was the probability of intracranial local control at 12 months, calculated by the Kaplan-Meier method. Univariable and multivariable Cox regression analyses were performed to identify variables associated with intracranial local control.</div></div><div><h3>Results</h3><div>295 patients were included. Intracranial local control probability at 12 months was 83 % and overall survival at 12 months was 39 %. In the multivariable Cox regression analysis, receiving any type of concurrent or adjuvant systemic treatment (adjusted hazard ratio [aHR] 0.30, 95 % confidence interval [CI] 0.15–0.61) and volume reduction between the first and second fraction (aHR 0.99, 95 % CI 0.98–0.998) were significantly associated with better intracranial local control. Larger total volume of all treated BM (aHR 1.02, 95 % CI 1.01–1.04) was significantly associated with worse intracranial local control. The probability of symptomatic cerebral radiation necrosis at 12 months was 26 %.</div></div><div><h3>Conclusion</h3><div>SGKRS results in high local control, with further improvement when systemic treatment is administered. However, overall survival remains limited, highlighting the importance of adequate patient selection.</div></div>","PeriodicalId":21041,"journal":{"name":"Radiotherapy and Oncology","volume":"212 ","pages":"Article 111127"},"PeriodicalIF":5.3,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145034037","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comment on: Radiographic classification of mandibular osteoradionecrosis: A blinded prospective multi-disciplinary interobserver diagnostic performance study”","authors":"Efsun Somay ,&nbsp;Erkan Topkan ,&nbsp;Ugur Selek","doi":"10.1016/j.radonc.2025.111131","DOIUrl":"10.1016/j.radonc.2025.111131","url":null,"abstract":"","PeriodicalId":21041,"journal":{"name":"Radiotherapy and Oncology","volume":"212 ","pages":"Article 111131"},"PeriodicalIF":5.3,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145027398","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A randomized Phase II trial of High Dose-Rate (HDR) and Low Dose-Rate (LDR) brachytherapy as monotherapy in localized prostate cancer: analysis of initial arms of Canadian cancer trials group PR19 (NCT02960087)","authors":"G. Morton ,&nbsp;E. Vigneault ,&nbsp;M. Barkati ,&nbsp;J. Helou ,&nbsp;T.M. Niazi ,&nbsp;J. Robinson ,&nbsp;D.A. Loblaw ,&nbsp;C.L. Tseng ,&nbsp;H.T. Chung ,&nbsp;G. Delouya ,&nbsp;C. Menard ,&nbsp;A.G. Martin ,&nbsp;P. Chung ,&nbsp;D. Batchelar ,&nbsp;M.D. Brundage ,&nbsp;K. Whelan ,&nbsp;K. Ding ,&nbsp;W. Parulekar","doi":"10.1016/j.radonc.2025.111124","DOIUrl":"10.1016/j.radonc.2025.111124","url":null,"abstract":"<div><h3>Purpose/objectives</h3><div>Low Dose-Rate Brachytherapy (LDR) and High Dose-Rate Brachytherapy (HDR) are options for favorable risk prostate cancer. We hypothesized that HDR provides comparable disease control with less urinary toxicity. Primary objective was to determine prostate cancer control at 48 months, defined as a PSA &lt; 0.4 ng/ml.</div></div><div><h3>Materials/methods</h3><div>Eligible patients had low and intermediate risk diseases. Randomization was to Arm 1 LDR with I-125 to 144 Gy, or Arm 2 HDR with 19 Gy x1 + intraprostatic boost. Follow-up included PSA, toxicity (CTCAE v 4.0), and Quality of Life (EPIC 26). Arm 2 was closed in May 2019 due to evidence of inferior outcomes, and a third arm (HDR 13.5 Gy x 2) was opened. We report outcomes of Arms 1 (LDR) and 2 (HDR single fraction) prior to study amendment.</div></div><div><h3>Results</h3><div>103 patients were randomized: 51 to LDR (Arm 1) and 52 to HDR (Arm 2). Median age 65 years; 76 % had Gleason 3 + 4, 90 % PSA &lt; 10, and 80 % stage T1c. Median follow-up 53 months. PSA control at 4 years was 78.4 % for LDR, and 21.2 % for HDR. Local progression rates: 2 % LDR, 13.5 % HDR. Grade 3 toxicity occurred in 6 patients for LDR and 2 patients Arm 2. Urinary irritative and bowel symptoms were worse in the first 6 months for LDR.</div></div><div><h3>Conclusions</h3><div>LDR brachytherapy has high prostate cancer disease control rate at 4 years, although with worse impact on urinary symptoms in the first 6 months. Single fraction HDR was associated with unacceptable cancer control.</div></div>","PeriodicalId":21041,"journal":{"name":"Radiotherapy and Oncology","volume":"212 ","pages":"Article 111124"},"PeriodicalIF":5.3,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145034094","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Intraoperative radiotherapy for resectable brain metastases: a systematic review and meta-analysis","authors":"Cas Stefaan Dejonckheere ,&nbsp;Matthias Schneider ,&nbsp;Anna-Laura Potthoff ,&nbsp;Motaz Hamed ,&nbsp;Davide Scafa ,&nbsp;Thomas Zeyen ,&nbsp;Lea L. Friker ,&nbsp;Molina Grimmer ,&nbsp;Fabian Kugel ,&nbsp;Stephan Garbe ,&nbsp;Alexander Radbruch ,&nbsp;Hartmut Vatter ,&nbsp;Frank Anton Giordano ,&nbsp;Ulrich Herrlinger ,&nbsp;Eleni Gkika ,&nbsp;Gustavo Renato Sarria ,&nbsp;Julian Philipp Layer","doi":"10.1016/j.radonc.2025.111128","DOIUrl":"10.1016/j.radonc.2025.111128","url":null,"abstract":"<div><h3>Background</h3><div>In recent years, intraoperative radiotherapy (IORT) with low-energy X-rays is emerging as an alternative to postoperative stereotactic radiotherapy (SRT) of the resection cavity in patients with resectable brain metastases (BMs).</div></div><div><h3>Methods</h3><div>We performed a systematic review of the MEDLINE, Embase, and Scopus databases, including all original articles on IORT for resectable BMs from 2015 to 2025. Data on safety, local control, and survival outcomes were collected.</div></div><div><h3>Results</h3><div>Ten records (5 prospective single-arm trials) were included, representing 261 patients (49 % lung primary) with a median follow-up (range) of 14 (0–79) months. 77 % of patients had a solitary BM at the time of surgery and IORT. The median applicator size was 2.0 cm and the median prescribed dose (range) 22.3 (20–30) Gy. The 1-year local control rate was 93 % and the 1-year distant brain control rate 48 %. Median overall survival was 19 months. Only 6 % of patients developed leptomeningeal disease and the cumulative rate of radiation necrosis was 2.6 % (grade 1 in 56 % of cases). The median time to next treatment beyond BM therapy (range) was 31 (1–136) days. This was significantly shorter compared to SRT control collectives.</div></div><div><h3>Conclusions</h3><div>IORT for patients with BMs has a favorable toxicity profile and yields excellent local control. A potential advantage is the rapid completion of interdisciplinary BM treatment, allowing a swift transition to subsequent cancer treatments. A planned registry and a prospective randomized phase 3 trial will establish the preferred radiotherapy modality in the context of resectable BMs.</div></div>","PeriodicalId":21041,"journal":{"name":"Radiotherapy and Oncology","volume":"212 ","pages":"Article 111128"},"PeriodicalIF":5.3,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145034122","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Minimum sample size calculation for radiomics-based binary outcome prediction models: Theoretical framework and practical example","authors":"Qian Cao ,&nbsp;Zhaoyu Jiang ,&nbsp;Zhixiang Wang ,&nbsp;Leonard Wee ,&nbsp;Andre Dekker ,&nbsp;Zhen Zhang ,&nbsp;Ji Zhu","doi":"10.1016/j.radonc.2025.111134","DOIUrl":"10.1016/j.radonc.2025.111134","url":null,"abstract":"<div><h3>Background and purpose</h3><div>Determining the appropriate sample size for developing robust radiomics-based binary outcome prediction models and identifying the maximum number of predictors safely allowable within a fixed dataset size remain critical yet challenging tasks. This study aims to propose and demonstrate a structured method for addressing these issues, enhancing methodological rigor and practicality in radiomics research.</div></div><div><h3>Materials and methods</h3><div>We introduce a comprehensive sample size calculation framework for binary outcome prediction models in radiomic studies. The proposed approach integrates three key criteria: (1) maintaining a global shrinkage factor (<em>S</em>) ≥ 0.9 to control model overfitting, (2) ensuring a minimal absolute difference between apparent and adjusted performance metrics, and (3) precisely estimating the overall outcome risk. Additionally, we develop an accessible online calculation tool enabling researchers to efficiently determine either the minimum sample size or the maximum number of predictors permissible, based on clearly defined statistical parameters.</div></div><div><h3>Results</h3><div>The presented method systematically addresses model overfitting by integrating a global shrinkage factor into the calculation, providing robust estimates compared with traditional heuristic approaches (“rules of thumb”). Practical examples demonstrate that this structured method effectively balances predictive accuracy and generalizability, while the online tool provides researchers with a user-friendly platform to perform the necessary calculations.</div></div><div><h3>Conclusion</h3><div>Clear justification of sample size decisions is essential for developing reliable predictive models in radiomics research. By adopting a structured and rigorous calculation method, researchers can effectively minimize overfitting, ensure accurate risk estimation, and substantially enhance the reliability and validity of their predictive models.</div></div>","PeriodicalId":21041,"journal":{"name":"Radiotherapy and Oncology","volume":"212 ","pages":"Article 111134"},"PeriodicalIF":5.3,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145034068","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In Response to Efsun Somay et al. “Integration of dosimetric parameters into radiographic classification of Osteoradionecrosis”","authors":"Zaphanlene Kaffey,&nbsp;Clifton D. Fuller,&nbsp;Amy C. Moreno,&nbsp;Laia Humbert-Vidan","doi":"10.1016/j.radonc.2025.111132","DOIUrl":"10.1016/j.radonc.2025.111132","url":null,"abstract":"","PeriodicalId":21041,"journal":{"name":"Radiotherapy and Oncology","volume":"212 ","pages":"Article 111132"},"PeriodicalIF":5.3,"publicationDate":"2025-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145030525","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Delineation of the post-operative primary tumour and nodal clinical target volumes in oral cavity squamous cell carcinoma: European Society for Radiotherapy and Oncology (ESTRO) clinical guidelines","authors":"Mererid Evans ,&nbsp;Pierluigi Bonomo ,&nbsp;Po Chung Chan ,&nbsp;Melvin L.K. Chua ,&nbsp;Jesper Grau Eriksen ,&nbsp;Keith Hunter ,&nbsp;Kenneth Jensen ,&nbsp;T.M. Jones ,&nbsp;Sarbani Ghosh Laskar ,&nbsp;Roberto Maroldi ,&nbsp;Brian O’Sullivan ,&nbsp;Claire Paterson ,&nbsp;Luca Tagliaferri ,&nbsp;Silke Tribius ,&nbsp;Sue S. Yom ,&nbsp;Vincent Gregoire","doi":"10.1016/j.radonc.2025.111135","DOIUrl":"10.1016/j.radonc.2025.111135","url":null,"abstract":"<div><h3>Background and purpose</h3><div>To date, no consensus guidelines have been published that systematically guide delineation of primary and nodal Clinical Target Volumes (CTVs) in patients who require post-operative radiotherapy (PORT) for mucosal Head and Neck squamous cell carcinoma (HNSCC). As a result, significant individual, institutional and national variation exists in the way that CTVs are delineated in the post-operative setting, leading to considerable heterogeneity in radiotherapy treatment.</div></div><div><h3>Methods</h3><div>A multi-disciplinary group of experts convened by the European Society for Radiotherapy and Oncology (ESTRO) set-out principles for the multi-disciplinary management of oral cavity squamous cell carcinoma (OCSCC). Building on these, and adapting the geometric expansion approach described in previous primary CTV delineation guidelines, new consensus guidelines for the delineation of post-operative CTVs, both for the primary tumour and nodal regions, were proposed by the expert group, before being shared with a second tier of international experts to ensure their worldwide acceptability and applicability.</div></div><div><h3>Results</h3><div>These guidelines propose that surrogate volumes representing the resected primary and nodal Gross Tumour Volumes (GTV-P and GTV-N respectively) are re-created on the radiotherapy planning scan, either by registration with diagnostic imaging or via reference to anatomical landmarks. A post-operative CTV for the primary tumour (CTV-P) is created as a composite volume that includes: i) geometric expansion around the surrogate GTV-P, and ii) geometric expansion around the surgical defect and/or reconstruction flap. A post-operative CTV for the nodal region (CTV-N) is created as a composite volume that includes: i) geometric expansion around the surrogate GTV-N, and ii) the involved nodal level (CTV-N1). Guidelines for delineating at-risk nodal levels in a prophylactic dose CTV (CTV-N2) are included, and for making decisions regarding the need for unilateral and/or bilateral neck treatment.</div></div><div><h3>Conclusions</h3><div>Implementation of these guidelines into clinical practice should reduce variation, and by promoting consistency of approach, facilitate multi-institutional audits and clinical trials including Radiation Therapy Quality Assurance (RTQA) in patients with OCSCC. It is anticipated that they will form the basis for future guidelines aiming to standardise post-operative CTV delineation in other head and neck subsites.</div></div>","PeriodicalId":21041,"journal":{"name":"Radiotherapy and Oncology","volume":"212 ","pages":"Article 111135"},"PeriodicalIF":5.3,"publicationDate":"2025-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145030579","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sparing effects of FLASH irradiation in patient-derived lung tissue","authors":"Maxime Dubail ,&nbsp;Chloé Lafouasse ,&nbsp;Sophie Heinrich ,&nbsp;Vincent Favaudon ,&nbsp;Arturo Londoño-Vallejo ,&nbsp;Marie Dutreix ,&nbsp;Delphine Colin ,&nbsp;Jean-François Côté ,&nbsp;Jérôme Didier ,&nbsp;Christelle Pouliquen ,&nbsp;Abdelali Benali ,&nbsp;Pierre Verrelle ,&nbsp;Marine Lefèvre ,&nbsp;Nicolas Girard ,&nbsp;Agathe Seguin-Givelet ,&nbsp;Gilles Créhange ,&nbsp;Charles Fouillade","doi":"10.1016/j.radonc.2025.111126","DOIUrl":"10.1016/j.radonc.2025.111126","url":null,"abstract":"<div><h3>Background and purpose</h3><div>Radiation toxicities, such as pneumonitis and fibrosis, are major limitations affecting patients’ quality of life. Developed a decade ago, FLASH radiotherapy is an innovative method that, by delivering radiation at ultrafast dose rate, reduces radiation toxicities on healthy tissue while preserving the anti-tumoral effect of radiotherapy. This so-called FLASH effect has been described in different preclinical models but has not been observed in human tissue. This study aims to determine if FLASH irradiation can induce a sparing effect on human healthy lung tissue.</div></div><div><h3>Materials and methods</h3><div>To address this question, precision-cut lung slices (Hu-PCLS) were prepared from healthy lung samples collected from 19 lung cancer patients undergoing lobectomy. These Hu-PCLS were irradiated <em>ex vivo</em> at a dose of 9 Gy using the ElectronFLASH (SIT) device operated either in conventional or FLASH mode. We monitored cell division for each patient and performed RNAseq analysis to uncover some mechanistic insights.</div></div><div><h3>Results</h3><div>Analysis of cell division 24 h after treatment with conventional or ultra-high dose rate showed a higher proportion of dividing cells in Hu-PCLS after FLASH irradiation. Consistently, RNAseq analysis from irradiated lung samples confirmed an attenuated cell cycle checkpoint inhibition, p53 pro-apoptotic genes, DNA damage, and antioxidant pathways after ultra-high dose rate compared to conventional treatment.</div></div><div><h3>Conclusion</h3><div>Altogether, this study shows that, using freshly isolated patient-derived lung samples, cell proliferation can serve as an early marker of the normal lung response to FLASH irradiation. These findings hold great promises for future applications of FLASH radiotherapy in the clinic.</div></div>","PeriodicalId":21041,"journal":{"name":"Radiotherapy and Oncology","volume":"212 ","pages":"Article 111126"},"PeriodicalIF":5.3,"publicationDate":"2025-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145024122","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dose, dose rate and split dose impacts murine skin responses following photon FLASH irradiation","authors":"Kathryn H. Brown ,&nbsp;Mihaela Ghita-Pettigrew ,&nbsp;Malachy P. McIvor ,&nbsp;Mark P. McDowell ,&nbsp;Owen McLaughlin ,&nbsp;Kevin M. Prise ,&nbsp;Daniel Sforza ,&nbsp;John W. Wong ,&nbsp;Mohammad Rezaee ,&nbsp;Stephen J. McMahon ,&nbsp;Karl T. Butterworth","doi":"10.1016/j.radonc.2025.111125","DOIUrl":"10.1016/j.radonc.2025.111125","url":null,"abstract":"<div><h3>Introduction</h3><div>Preclinical evidence has demonstrated the potential of FLASH radiotherapy (FLASH-RT) to spare normal tissues compared to conventional (CONV) exposures. Most FLASH studies have used ultra-high dose rate (&gt;40 Gy/sec) electrons and protons whilst comparatively few studies have reported photon FLASH responses. Given the widespread use of photons clinically, there is a need to characterise the FLASH effect using photons. In this study, we applied a novel photon FLASH system (FLASH-SARRP, Xstrahl) to investigate the effects of dose, dose rate and split dose on murine skin toxicity.</div></div><div><h3>Methods</h3><div>Skin toxicity was assessed at CONV (3.2 Gy/min) and FLASH (72 Gy/s) dose rates using the SARRP or FLASH-SARRP. CONV responses were investigated at a dose of 20.2 Gy and FLASH responses at doses of 18.1, 21.3 &amp; 25.8 Gy. Comparative studies were conducted using a split dose exposure with an average dose rate of 2.8 Gy/s. Skin toxicity on the hind leg of C57BL/6 mice was visually scored and histopathological analysis performed at 8–12 weeks. Tumour growth delay was also assessed using a melanoma (B16-F10) xenograft model irradiated at FLASH and CONV dose rates.</div></div><div><h3>Results</h3><div>Skin toxicity was delayed for FLASH exposures and tissue analysis showed hyperplasia and significant fibrosis deposition (p &lt; 0.01) in CONV mice compared to FLASH. Tissue recovery was observed for both dose rates from 8 weeks post RT. A dose dependent relationship for FLASH sparing was observed, while a split dose exposure resulted in loss of sparing. FLASH was equally effective for tumour control in comparison to CONV exposures (p = 0.99).</div></div><div><h3>Conclusions</h3><div>These results demonstrate it is feasible to deliver photon FLASH exposures with sparing consistent with observations from previous studies using proton and electron beams. Dose, average dose rate and beam structure are key parameters that modulate radiobiological responses to photon FLASH.</div></div>","PeriodicalId":21041,"journal":{"name":"Radiotherapy and Oncology","volume":"212 ","pages":"Article 111125"},"PeriodicalIF":5.3,"publicationDate":"2025-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145018445","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}