Pub Date : 2025-11-09DOI: 10.1016/j.adro.2025.101954
Tess J. Snoeijink MSc , Jan L. van der Hoek MSc , Anne van den Brekel MSc , Gerhard van Wolfswinkel MSc , Marcel J.R. Janssen MD, PhD , Erik Groot Jebbink PhD , J. Frank W. Nijsen PhD
Purpose
This study aimed to experimentally investigate how injection technique affects the distribution of microspheres during transarterial radioembolization in a successively bifurcating in vitro model.
Methods and Materials
A symmetrical phantom, bifurcating 3 times into 8 outlets, was incorporated into a flow circuit. A blood-mimicking fluid was pumped through the phantom using a physiological representative waveform. A microcatheter was placed into the lumen of the phantom, and holmium-165 microspheres were administered with a conventional administration device and a newly designed controlled administration device, containing a rotating syringe to keep the microspheres in suspension during administration. Two clinicians performed manual injections to establish clinically relevant injection rates. Then, different injection profiles were tested using syringe pumps: pulsed vs continuous injections (24 mL/min), and reduced continuous injection rates (10 and 5 mL/min). Microspheres were collected at each outlet and their distribution over the 8 outlets was analyzed.
Results
Continuous high injection rates led to more homogeneous radial distributions of microspheres over the right side of the phantom (outlet 5-8 received 16.5%-23.1% of the microspheres per outlet) compared with the clinically standard used pulsed injections (outlet 5-8 received 11.3%-40.1% of the microspheres per outlet). In contrast, reduced continuous injection rates led to more selective distributions (outlet 5-8 received 2.5%-68.8% of the microspheres at 10 mL/min and 1.0%-80.0% at 5 mL/min).
Conclusions
Injection technique strongly influences the distribution of microspheres. During high continuous injections, more mixing between microspheres and blood-mimicking fluid was observed. This led to more uniform radial microsphere distributions, creating a more predictive setting for transarterial radioembolization.
{"title":"Impact of Injection Technique on Microsphere Distribution During Transarterial Radioembolization in a Successively Bifurcating In Vitro Model","authors":"Tess J. Snoeijink MSc , Jan L. van der Hoek MSc , Anne van den Brekel MSc , Gerhard van Wolfswinkel MSc , Marcel J.R. Janssen MD, PhD , Erik Groot Jebbink PhD , J. Frank W. Nijsen PhD","doi":"10.1016/j.adro.2025.101954","DOIUrl":"10.1016/j.adro.2025.101954","url":null,"abstract":"<div><h3>Purpose</h3><div>This study aimed to experimentally investigate how injection technique affects the distribution of microspheres during transarterial radioembolization in a successively bifurcating in vitro model.</div></div><div><h3>Methods and Materials</h3><div>A symmetrical phantom, bifurcating 3 times into 8 outlets, was incorporated into a flow circuit. A blood-mimicking fluid was pumped through the phantom using a physiological representative waveform. A microcatheter was placed into the lumen of the phantom, and holmium-165 microspheres were administered with a conventional administration device and a newly designed controlled administration device, containing a rotating syringe to keep the microspheres in suspension during administration. Two clinicians performed manual injections to establish clinically relevant injection rates. Then, different injection profiles were tested using syringe pumps: pulsed vs continuous injections (24 mL/min), and reduced continuous injection rates (10 and 5 mL/min). Microspheres were collected at each outlet and their distribution over the 8 outlets was analyzed.</div></div><div><h3>Results</h3><div>Continuous high injection rates led to more homogeneous radial distributions of microspheres over the right side of the phantom (outlet 5-8 received 16.5%-23.1% of the microspheres per outlet) compared with the clinically standard used pulsed injections (outlet 5-8 received 11.3%-40.1% of the microspheres per outlet). In contrast, reduced continuous injection rates led to more selective distributions (outlet 5-8 received 2.5%-68.8% of the microspheres at 10 mL/min and 1.0%-80.0% at 5 mL/min).</div></div><div><h3>Conclusions</h3><div>Injection technique strongly influences the distribution of microspheres. During high continuous injections, more mixing between microspheres and blood-mimicking fluid was observed. This led to more uniform radial microsphere distributions, creating a more predictive setting for transarterial radioembolization.</div></div>","PeriodicalId":7390,"journal":{"name":"Advances in Radiation Oncology","volume":"11 2","pages":"Article 101954"},"PeriodicalIF":2.7,"publicationDate":"2025-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145665620","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-09DOI: 10.1016/j.adro.2025.101952
Jordan McDonald MD , Ethan P. Damron MD , Prajnan Das MD, MS, MPH , Eugene J. Koay MD, PhD , Ethan B. Ludmir MD , Bruce D. Minsky MD , Sonal S. Noticewala MD , Grace L. Smith MD, PhD, MPH , Craig Messick MD , Van K. Morris MD , Emma B. Holliday MD
Purpose
Although salvage surgery is the standard of care for locoregionally recurrent anal cancer, few local options exist for inoperable pelvic recurrences. Newly diagnosed anal cancer arising in a previously irradiated field also provides a unique treatment challenge, as delivery of standard doses would result in unsafe cumulative dose to pelvic structures. We aimed to evaluate efficacy and toxicity of a hyperfractionated accelerated reirradiation (reRT) regimen for such patients.
Methods and Materials
Patients treated with hyperfractionated accelerated reRT at a single institution between 2005 and 2024 for nonmetastatic inoperable locoregionally recurrent anal cancer or primary anal cancer in a previously irradiated field were included. The reRT regimen consisted of 1.5 Gy in twice daily fractions separated by 6 hours to a median (range) of 39 (30-51) Gy. Complete clinical response rates, recurrence rates, and toxicities were reported.
Results
The median (IQR) follow-up was 13.4 (7.5-42.2) months. Twenty-six (74.3%) patients were treated with reRT for recurrent anal cancer, and 9 (25.7%) patients were treated with reRT for a new squamous cell carcinoma of the anus (SCCA) primary after prior pelvic radiation. The complete clinical response rate was 46.2% among patients with recurrent anal cancer and 77.8% among patients with a new SCCA primary after prior pelvic radiation. Two-year locoregional recurrence rate was 64.0% among patients with recurrent anal cancer and 22.0% among patients treated with reRT for a new SCCA primary after prior pelvic radiation. Eight patients (22.9%) developed acute grade 3 toxicity and 10 (28.6%) developed late grade 3-4 toxicity.
Conclusions
Hyperfractionated accelerated reRT results in promising complete clinical response rates that appear to translate into durable pelvic control for patients with recurrent anal cancer or a new SCCA primary after prior pelvic radiation. Acute toxicity appears similar to initial standard chemoradiation, but limiting reRT doses to 39 Gy may reduce the risk of serious late toxicity.
{"title":"Can Patients With Recurrent or Primary Squamous Cell Carcinoma of the Anus in a Previously Irradiated Pelvis Receive Definitive Reirradiation?","authors":"Jordan McDonald MD , Ethan P. Damron MD , Prajnan Das MD, MS, MPH , Eugene J. Koay MD, PhD , Ethan B. Ludmir MD , Bruce D. Minsky MD , Sonal S. Noticewala MD , Grace L. Smith MD, PhD, MPH , Craig Messick MD , Van K. Morris MD , Emma B. Holliday MD","doi":"10.1016/j.adro.2025.101952","DOIUrl":"10.1016/j.adro.2025.101952","url":null,"abstract":"<div><h3>Purpose</h3><div>Although salvage surgery is the standard of care for locoregionally recurrent anal cancer, few local options exist for inoperable pelvic recurrences. Newly diagnosed anal cancer arising in a previously irradiated field also provides a unique treatment challenge, as delivery of standard doses would result in unsafe cumulative dose to pelvic structures. We aimed to evaluate efficacy and toxicity of a hyperfractionated accelerated reirradiation (reRT) regimen for such patients.</div></div><div><h3>Methods and Materials</h3><div>Patients treated with hyperfractionated accelerated reRT at a single institution between 2005 and 2024 for nonmetastatic inoperable locoregionally recurrent anal cancer or primary anal cancer in a previously irradiated field were included. The reRT regimen consisted of 1.5 Gy in twice daily fractions separated by 6 hours to a median (range) of 39 (30-51) Gy. Complete clinical response rates, recurrence rates, and toxicities were reported.</div></div><div><h3>Results</h3><div>The median (IQR) follow-up was 13.4 (7.5-42.2) months. Twenty-six (74.3%) patients were treated with reRT for recurrent anal cancer, and 9 (25.7%) patients were treated with reRT for a new squamous cell carcinoma of the anus (SCCA) primary after prior pelvic radiation. The complete clinical response rate was 46.2% among patients with recurrent anal cancer and 77.8% among patients with a new SCCA primary after prior pelvic radiation. Two-year locoregional recurrence rate was 64.0% among patients with recurrent anal cancer and 22.0% among patients treated with reRT for a new SCCA primary after prior pelvic radiation. Eight patients (22.9%) developed acute grade 3 toxicity and 10 (28.6%) developed late grade 3-4 toxicity.</div></div><div><h3>Conclusions</h3><div>Hyperfractionated accelerated reRT results in promising complete clinical response rates that appear to translate into durable pelvic control for patients with recurrent anal cancer or a new SCCA primary after prior pelvic radiation. Acute toxicity appears similar to initial standard chemoradiation, but limiting reRT doses to 39 Gy may reduce the risk of serious late toxicity.</div></div>","PeriodicalId":7390,"journal":{"name":"Advances in Radiation Oncology","volume":"11 2","pages":"Article 101952"},"PeriodicalIF":2.7,"publicationDate":"2025-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145665621","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-08DOI: 10.1016/j.adro.2025.101951
Alexander Marwaha DO , Matthew J. Shepard MD , Yun Liang PhD , Alexander Yu MD , Stephen M. Karlovits MD , Rodney E. Wegner MD
Purpose
Brain metastases are a common occurrence in patients with advanced malignancy. Treatment ranges from surgical resection, stereotactic radiosurgery (SRS), whole-brain radiation therapy (WBRT), or some combination thereof. Traditionally, SRS has followed surgical resection to help reduce the risk of local recurrence. In recent years, interest has arisen in treating these patients in the preoperative setting to help reduce the risk of leptomeningeal disease (LMD) and radiation necrosis while preserving rates of local control. This prospective pilot study, originally planned as a phase 2 protocol, investigated the use of 3-fraction preoperative SRS on the Gamma Knife (GK) Icon with the goal of examining those outcomes.
Methods and Materials
Patients who had symptomatic and a limited number of brain metastases amenable to surgical resection were prospectively enrolled in this study. Patients were treated with fractionated SRS on the GK Icon to 24 to 27 Gy in 3 fractions followed by surgical resection within 2 weeks. Postoperative MRIs were obtained to assess the extent of resection. Patients were then followed up with standard-of-care MRIs every 3 months for the first 2 years. Rates of local control, distant brain failure, LMD, and delivery of WBRT were recorded on follow-up.
Results
Twenty patients were prospectively enrolled in the trial, and an additional 11 were treated off study using 1 to 3 fractions between April 2021 and June 2024. The median age was 64 (31-81), and 55% were females. Primary malignancies were mainly non-small cell lung cancer, melanoma, and esophageal cancer. The median prescription dose was 27 Gy (15-27 Gy) in 3 (1-3) fractions. Surgery was performed at a median of 1 day post-SRS (0-11). All available postoperative MRIs showed gross total resection. Median follow-up was 9 months. One patient experienced a local failure, yielding a 1-year local control rate of 95%. The rate of distant brain failure at 6 and 12 months was 38% at each time point. Three patients (9.6%) developed LMD in follow-up. Six patients ultimately received WBRT, yielding a 1-year WBRT-free survival of 78%. Overall survival at 1 year was 52%. There were no predictors of overall survival, local failure, or distant brain failure on Cox regression. Two patients experienced short-term toxicity, including grade 2 intracranial swelling and one grade 5 hemorrhagic stroke related to a hypertensive crisis. There was no recorded radionecrosis in follow-up.
Conclusions
Fractionated preoperative SRS appears to be safe and effective with high rates of local control and low rates of LMD and radionecrosis. Results of ongoing phase 3 studies directly comparing preoperative to postoperative SRS will help further define the appropriate sequencing of therapies.
{"title":"Preoperative Fractionated Stereotactic Radiosurgery for Brain Metastases: A Prospective Pilot Study at a Single Institution","authors":"Alexander Marwaha DO , Matthew J. Shepard MD , Yun Liang PhD , Alexander Yu MD , Stephen M. Karlovits MD , Rodney E. Wegner MD","doi":"10.1016/j.adro.2025.101951","DOIUrl":"10.1016/j.adro.2025.101951","url":null,"abstract":"<div><h3>Purpose</h3><div>Brain metastases are a common occurrence in patients with advanced malignancy. Treatment ranges from surgical resection, stereotactic radiosurgery (SRS), whole-brain radiation therapy (WBRT), or some combination thereof. Traditionally, SRS has followed surgical resection to help reduce the risk of local recurrence. In recent years, interest has arisen in treating these patients in the preoperative setting to help reduce the risk of leptomeningeal disease (LMD) and radiation necrosis while preserving rates of local control. This prospective pilot study, originally planned as a phase 2 protocol, investigated the use of 3-fraction preoperative SRS on the Gamma Knife (GK) Icon with the goal of examining those outcomes.</div></div><div><h3>Methods and Materials</h3><div>Patients who had symptomatic and a limited number of brain metastases amenable to surgical resection were prospectively enrolled in this study. Patients were treated with fractionated SRS on the GK Icon to 24 to 27 Gy in 3 fractions followed by surgical resection within 2 weeks. Postoperative MRIs were obtained to assess the extent of resection. Patients were then followed up with standard-of-care MRIs every 3 months for the first 2 years. Rates of local control, distant brain failure, LMD, and delivery of WBRT were recorded on follow-up.</div></div><div><h3>Results</h3><div>Twenty patients were prospectively enrolled in the trial, and an additional 11 were treated off study using 1 to 3 fractions between April 2021 and June 2024. The median age was 64 (31-81), and 55% were females. Primary malignancies were mainly non-small cell lung cancer, melanoma, and esophageal cancer. The median prescription dose was 27 Gy (15-27 Gy) in 3 (1-3) fractions. Surgery was performed at a median of 1 day post-SRS (0-11). All available postoperative MRIs showed gross total resection. Median follow-up was 9 months. One patient experienced a local failure, yielding a 1-year local control rate of 95%. The rate of distant brain failure at 6 and 12 months was 38% at each time point. Three patients (9.6%) developed LMD in follow-up. Six patients ultimately received WBRT, yielding a 1-year WBRT-free survival of 78%. Overall survival at 1 year was 52%. There were no predictors of overall survival, local failure, or distant brain failure on Cox regression. Two patients experienced short-term toxicity, including grade 2 intracranial swelling and one grade 5 hemorrhagic stroke related to a hypertensive crisis. There was no recorded radionecrosis in follow-up.</div></div><div><h3>Conclusions</h3><div>Fractionated preoperative SRS appears to be safe and effective with high rates of local control and low rates of LMD and radionecrosis. Results of ongoing phase 3 studies directly comparing preoperative to postoperative SRS will help further define the appropriate sequencing of therapies.</div></div>","PeriodicalId":7390,"journal":{"name":"Advances in Radiation Oncology","volume":"11 2","pages":"Article 101951"},"PeriodicalIF":2.7,"publicationDate":"2025-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145788097","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-07DOI: 10.1016/j.adro.2025.101949
Elette Engels PhD , Helen B. Forrester PhD , Verdiana Trappetti PhD , Kellie Mouchemore PhD , Mitzi Klein VMD , Alice H. Sprung , Kirsty Brunt , Micah J. Barnes PhD , Matthew Cameron PhD , Vincent de Rover BSc , Bettina de Breuyn Dietler BSc , Anatoly B. Rosenfeld PhD , Michael L.F. Lerch PhD , Robin L. Anderson PhD , Olga A. Martin PhD , Valentin G. Djonov MD
Purpose
The superior therapeutic index of preclinical synchrotron microbeam radiation therapy (MRT) over conventional broad-beam (BB) radiation therapy (RT) has been clearly established. Published data demonstrate that a combination of 1 MRT session with 2 consecutive daily BB-RT sessions effectively controls the primary tumor and triggers an antitumor immune response. Here, we aimed to establish whether an ultrahigh dose rate of MRT, available exclusively on the synchrotron, is essential for effective treatment of murine triple-negative mammary carcinoma.
Methods and Materials
The in vitro response of mammary tumor cells was investigated using a clonogenic survival assay at different MRT dose rates (∼1000, 100, or 10 Gy/s). The in vivo tumor responses at the same dose rates, with an MRT/BB/BB treatment schedule, were evaluated by measuring tumor volume and the induced immune response. Animal survival and normal skin reactions were also assessed.
Results
Clonogenic survival decreased with decreasing MRT dose rate, with most cell sparing at the highest dose rate (1000 Gy/s), indicating that lower dose rates could be more effective against tumors. However, no significant differences in in vivo tumor growth delay were observed in response to dose-rate variations. Decreased infiltration of irradiated tumors with leucocytes and their subpopulations was observed at the lower dose rates, including decreased expression of immune checkpoints PD-1/PD-L1 and prognostic marker CD103, which could impact the overall tumor response in vivo. The higher dose rates were associated with increased antitumor immunity. Early euthanasia of mice, as dictated by ethical endpoints, prevented long-term observation of differences in animal survival. Skin toxicity in the vicinity of irradiated tumors was mild and developed later at the highest MRT dose rate. Overall, MRT at 10 to 1000 Gy/s was tolerated similarly, despite dramatic changes in the dose rate.
Conclusions
These findings are promising for the clinical translation of MRT in combination with conventional RT, using emerging compact x-ray MRT sources with dose rates lower than those delivered by synchrotron sources.
{"title":"Is Ultrahigh Dose Rate Critical for the Effectiveness of Microbeam Radiation Therapy in a Broad-Beam Combined Treatment?","authors":"Elette Engels PhD , Helen B. Forrester PhD , Verdiana Trappetti PhD , Kellie Mouchemore PhD , Mitzi Klein VMD , Alice H. Sprung , Kirsty Brunt , Micah J. Barnes PhD , Matthew Cameron PhD , Vincent de Rover BSc , Bettina de Breuyn Dietler BSc , Anatoly B. Rosenfeld PhD , Michael L.F. Lerch PhD , Robin L. Anderson PhD , Olga A. Martin PhD , Valentin G. Djonov MD","doi":"10.1016/j.adro.2025.101949","DOIUrl":"10.1016/j.adro.2025.101949","url":null,"abstract":"<div><h3>Purpose</h3><div>The superior therapeutic index of preclinical synchrotron microbeam radiation therapy (MRT) over conventional broad-beam (BB) radiation therapy (RT) has been clearly established. Published data demonstrate that a combination of 1 MRT session with 2 consecutive daily BB-RT sessions effectively controls the primary tumor and triggers an antitumor immune response. Here, we aimed to establish whether an ultrahigh dose rate of MRT, available exclusively on the synchrotron, is essential for effective treatment of murine triple-negative mammary carcinoma.</div></div><div><h3>Methods and Materials</h3><div>The in vitro response of mammary tumor cells was investigated using a clonogenic survival assay at different MRT dose rates (∼1000, 100, or 10 Gy/s). The in vivo tumor responses at the same dose rates, with an MRT/BB/BB treatment schedule, were evaluated by measuring tumor volume and the induced immune response. Animal survival and normal skin reactions were also assessed.</div></div><div><h3>Results</h3><div>Clonogenic survival decreased with decreasing MRT dose rate, with most cell sparing at the highest dose rate (1000 Gy/s), indicating that lower dose rates could be more effective against tumors. However, no significant differences in in vivo tumor growth delay were observed in response to dose-rate variations. Decreased infiltration of irradiated tumors with leucocytes and their subpopulations was observed at the lower dose rates, including decreased expression of immune checkpoints PD-1/PD-L1 and prognostic marker CD103, which could impact the overall tumor response in vivo. The higher dose rates were associated with increased antitumor immunity. Early euthanasia of mice, as dictated by ethical endpoints, prevented long-term observation of differences in animal survival. Skin toxicity in the vicinity of irradiated tumors was mild and developed later at the highest MRT dose rate. Overall, MRT at 10 to 1000 Gy/s was tolerated similarly, despite dramatic changes in the dose rate.</div></div><div><h3>Conclusions</h3><div>These findings are promising for the clinical translation of MRT in combination with conventional RT, using emerging compact x-ray MRT sources with dose rates lower than those delivered by synchrotron sources.</div></div>","PeriodicalId":7390,"journal":{"name":"Advances in Radiation Oncology","volume":"11 2","pages":"Article 101949"},"PeriodicalIF":2.7,"publicationDate":"2025-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145735320","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-01DOI: 10.1016/j.adro.2025.101841
Rong-Tse Hsu MD, Ting-Chun Lin MD
{"title":"In Reply to Sengul and Sengul","authors":"Rong-Tse Hsu MD, Ting-Chun Lin MD","doi":"10.1016/j.adro.2025.101841","DOIUrl":"10.1016/j.adro.2025.101841","url":null,"abstract":"","PeriodicalId":7390,"journal":{"name":"Advances in Radiation Oncology","volume":"10 11","pages":"Article 101841"},"PeriodicalIF":2.7,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145517068","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-31DOI: 10.1016/j.adro.2025.101933
Alexander Heer MD , Malte Schneider MD , Jan P. Boström MD , Michael Pinkawa MD , Attila Kovács MD , Johannes Weller MD , Jenny Bischoff MD , Charlotte M. Fries MD , Azize Boström MD , Wiebke K. Fenske MD
Purpose
Radiation therapy-induced hypopituitarism (RIH) is a common complication of radiation therapy, even if the pituitary gland is not the primary target but lies within the irradiation field. This study aimed to investigate the impact of high-precision radiation therapy for benign sellar and perisellar tumors, using radiosurgery or fractionated/hypofractionated stereotactic radiation therapy with the Novalis System (Brainlab), on functional pituitary integrity.
Methods and Materials
Fifty-six patients who underwent stereotactic radiation therapy for meningiomas of the sellar or perisellar region of the skull base (n = 36) or pituitary adenomas (n = 20) were recruited between 2013 and 2021 at a single radiooncologic clinic. Fractionated stereotactic radiation therapy was the main irradiation technique (n = 42), followed by hypofractionated stereotactic radiation therapy (n = 4) and stereotactic radiosurgery (n = 10). Irradiation data were assessed retrospectively, and radiation exposure to the pituitary was measured by dose-volume histograms. Each patient received an endocrine diagnostic workup, including a comprehensive functional pituitary analysis.
Results
The median age was 57 years (IQR, 50-63 years), and 42 of 56 patients (75%) were women. RIH was present in 10.7% (n = 6) of patients after a median follow-up of 83.5 months. Gonadotroph function was affected in 7.1% (n = 4) of patients, followed by corticotroph, thyreotroph, somatotroph, and lactotroph function, each at 1.8% (n = 1). Only 1 patient received hormonal replacement for RIH at the study visit.
Conclusions
Awareness of radiation therapy-induced damage to the pituitary gland is essential in the follow-up after radiation therapy of the surrounding structures of the hypothalamic-pituitary axis. High-precision fractionated stereotactic radiation therapy holds a low risk of RIH after irradiation of benign lesions of the sellar and perisellar region.
{"title":"Low Incidence of New-Onset Hypopituitarism After High-Precision Stereotactic Radiation Therapy of Sellar and Perisellar Lesions","authors":"Alexander Heer MD , Malte Schneider MD , Jan P. Boström MD , Michael Pinkawa MD , Attila Kovács MD , Johannes Weller MD , Jenny Bischoff MD , Charlotte M. Fries MD , Azize Boström MD , Wiebke K. Fenske MD","doi":"10.1016/j.adro.2025.101933","DOIUrl":"10.1016/j.adro.2025.101933","url":null,"abstract":"<div><h3>Purpose</h3><div>Radiation therapy-induced hypopituitarism (RIH) is a common complication of radiation therapy, even if the pituitary gland is not the primary target but lies within the irradiation field. This study aimed to investigate the impact of high-precision radiation therapy for benign sellar and perisellar tumors, using radiosurgery or fractionated/hypofractionated stereotactic radiation therapy with the Novalis System (Brainlab), on functional pituitary integrity.</div></div><div><h3>Methods and Materials</h3><div>Fifty-six patients who underwent stereotactic radiation therapy for meningiomas of the sellar or perisellar region of the skull base (n = 36) or pituitary adenomas (n = 20) were recruited between 2013 and 2021 at a single radiooncologic clinic. Fractionated stereotactic radiation therapy was the main irradiation technique (n = 42), followed by hypofractionated stereotactic radiation therapy (n = 4) and stereotactic radiosurgery (n = 10). Irradiation data were assessed retrospectively, and radiation exposure to the pituitary was measured by dose-volume histograms. Each patient received an endocrine diagnostic workup, including a comprehensive functional pituitary analysis.</div></div><div><h3>Results</h3><div>The median age was 57 years (IQR, 50-63 years), and 42 of 56 patients (75%) were women. RIH was present in 10.7% (n = 6) of patients after a median follow-up of 83.5 months. Gonadotroph function was affected in 7.1% (n = 4) of patients, followed by corticotroph, thyreotroph, somatotroph, and lactotroph function, each at 1.8% (n = 1). Only 1 patient received hormonal replacement for RIH at the study visit.</div></div><div><h3>Conclusions</h3><div>Awareness of radiation therapy-induced damage to the pituitary gland is essential in the follow-up after radiation therapy of the surrounding structures of the hypothalamic-pituitary axis. High-precision fractionated stereotactic radiation therapy holds a low risk of RIH after irradiation of benign lesions of the sellar and perisellar region.</div></div>","PeriodicalId":7390,"journal":{"name":"Advances in Radiation Oncology","volume":"11 3","pages":"Article 101933"},"PeriodicalIF":2.7,"publicationDate":"2025-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145973880","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-30DOI: 10.1016/j.adro.2025.101937
Enrique Chajon MD, PhD , Marc Pracht MD , Yan Rolland MD, PhD , France Nguyen MD , Jean-Pierre Bronowicki MD, PhD , Jérôme Durand-Labrunie MD , Véronique Vendrely MD, PhD , Antonio Sa Cunha MD , Valérie Laurent MD, PhD , Emmanuel Rio MD , Samuel Le Sourd MD , Pierre Gustin MD , Patricia C. Said MSc , Mikaela Dimitriu PhD , Benjin D. Facer MD , Omar I. Vivar PhD , Didier Peiffert MD, PhD , Eric Deutsch MD, PhD , Thierry de Baère MD
Purpose
Stereotactic body radiation therapy (SBRT) is a common treatment for unresectable liver cancers; however, delivering ablative doses while minimizing normal tissue toxicity is challenging. NBTXR3, a novel radioenhancer, demonstrated enhanced radiation therapy (RT) efficacy with minimal toxicity in healthy tissue. We evaluated NBTXR3 intratumoral injection followed by SBRT for hepatocellular carcinoma (HCC) or liver metastases.
Methods and Materials
This phase 1, multicenter, dose-escalation trial enrolled adults with unresectable HCC or liver metastases. Five dose levels of NBTXR3 were evaluated (3 + 3 design): 10%, 15%, 22%, 33% and 42% of gross tumor volume (GTV) determined by magnetic resonance imaging. Patients received RT (15 Gy × 3 or 10 Gy × 5 over 5-15 days) starting 1 to 5 days after NBTXR3 injection. Primary endpoints included: incidence of early dose-limiting toxicities (DLTs) and determination of the recommended phase 2 dose (RP2D) of NBTXR3.
Results
Between December 2015 and May 2020, 26 liver lesions in 23 patients with HCC (17 lesions in 15 patients) or liver metastases (9 lesions in 8 patients) were treated. No early DLTs were reported, and the maximum tolerated dose was not reached. The RP2D of NBTXR3 was 42% of GTV. During the treatment period, 6 patients experienced grade ≥3 toxicities; none were NBTXR3-related, one was RT-related (grade 3 fatigue), and 2 were injection procedure–related (grade 3 abdominal pain). During the follow-up period, 2 patients experienced treatment-related grade ≥3 AEs (grade 3 bile duct stenosis related to cancer/RT/NBTXR3, and grade 3 anemia related to cancer/RT/underlying liver disease). No treatment-related deaths were reported. The 12-week objective response rate in treated lesions was 58.3% (7/12) in patients with HCC, and 50.0% (4/8) in patients with liver metastases.
Conclusions
NBTXR3 + RT has a manageable safety profile with no DLTs identified during dose escalation. The RP2D for treatment of HCC or liver metastases is 42% of GTV. Future studies will further evaluate efficacy.
{"title":"Radioenhancing Hafnium Oxide Nanoparticles (NBTXR3) Followed by Stereotactic Body Radiation Therapy in Patients With Hepatocellular Carcinoma and Liver Metastases (NBTXR3-103): Phase 1 Dose-Escalation Trial","authors":"Enrique Chajon MD, PhD , Marc Pracht MD , Yan Rolland MD, PhD , France Nguyen MD , Jean-Pierre Bronowicki MD, PhD , Jérôme Durand-Labrunie MD , Véronique Vendrely MD, PhD , Antonio Sa Cunha MD , Valérie Laurent MD, PhD , Emmanuel Rio MD , Samuel Le Sourd MD , Pierre Gustin MD , Patricia C. Said MSc , Mikaela Dimitriu PhD , Benjin D. Facer MD , Omar I. Vivar PhD , Didier Peiffert MD, PhD , Eric Deutsch MD, PhD , Thierry de Baère MD","doi":"10.1016/j.adro.2025.101937","DOIUrl":"10.1016/j.adro.2025.101937","url":null,"abstract":"<div><h3>Purpose</h3><div>Stereotactic body radiation therapy (SBRT) is a common treatment for unresectable liver cancers; however, delivering ablative doses while minimizing normal tissue toxicity is challenging. NBTXR3, a novel radioenhancer, demonstrated enhanced radiation therapy (RT) efficacy with minimal toxicity in healthy tissue. We evaluated NBTXR3 intratumoral injection followed by SBRT for hepatocellular carcinoma (HCC) or liver metastases.</div></div><div><h3>Methods and Materials</h3><div>This phase 1, multicenter, dose-escalation trial enrolled adults with unresectable HCC or liver metastases. Five dose levels of NBTXR3 were evaluated (3 + 3 design): 10%, 15%, 22%, 33% and 42% of gross tumor volume (GTV) determined by magnetic resonance imaging. Patients received RT (15 Gy × 3 or 10 Gy × 5 over 5-15 days) starting 1 to 5 days after NBTXR3 injection. Primary endpoints included: incidence of early dose-limiting toxicities (DLTs) and determination of the recommended phase 2 dose (RP2D) of NBTXR3.</div></div><div><h3>Results</h3><div>Between December 2015 and May 2020, 26 liver lesions in 23 patients with HCC (17 lesions in 15 patients) or liver metastases (9 lesions in 8 patients) were treated. No early DLTs were reported, and the maximum tolerated dose was not reached. The RP2D of NBTXR3 was 42% of GTV. During the treatment period, 6 patients experienced grade ≥3 toxicities; none were NBTXR3-related, one was RT-related (grade 3 fatigue), and 2 were injection procedure–related (grade 3 abdominal pain). During the follow-up period, 2 patients experienced treatment-related grade ≥3 AEs (grade 3 bile duct stenosis related to cancer/RT/NBTXR3, and grade 3 anemia related to cancer/RT/underlying liver disease). No treatment-related deaths were reported. The 12-week objective response rate in treated lesions was 58.3% (7/12) in patients with HCC, and 50.0% (4/8) in patients with liver metastases.</div></div><div><h3>Conclusions</h3><div>NBTXR3 + RT has a manageable safety profile with no DLTs identified during dose escalation. The RP2D for treatment of HCC or liver metastases is 42% of GTV. Future studies will further evaluate efficacy.</div></div>","PeriodicalId":7390,"journal":{"name":"Advances in Radiation Oncology","volume":"11 1","pages":"Article 101937"},"PeriodicalIF":2.7,"publicationDate":"2025-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145681751","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-30DOI: 10.1016/j.adro.2025.101947
Woohyoung Kim MD, PhD , Jae-Sung Park MD, PhD , Jin-Ho Song MD, PhD , Heon Yoo MD, PhD , Kawngwoo Park MD, PhD , Hyun Ju Kim MD , Dong-Won Shin MD, PhD , Sung Uk Lee MD, PhD , Stephen Ahn MD, PhD , Seunggyun Ha MD, PhD , JunGyu Yi MS , Kwan Cho MD , Hyo Jung Seo MD, PhD , Hyung-Seok Lim MD, PhD , Gi-Taek Yee MD, PhD
Purpose
Boron neutron capture therapy (BNCT) is an advanced radiation therapy delivering highly selective tumor cell destruction via localized fission reactions. This phase 1 study evaluated the safety and efficacy of BNCT using [B-10]L-4-boronophenylalanine (BPA) in patients with recurrent high-grade gliomas, mostly glioblastomas.
Methods and Materials
A 3 + 3 dose-escalation design was used to determine the maximum tolerated dose of BNCT across 3 planned cohorts (Dmax: 9, 11, and 13 Gy-Eq), with 3 additional subjects enrolled at any dose level where dose-limiting toxicity (DLT) occurred. DLT was defined as BNCT-related grade 3+ toxicities within 90 days posttreatment, with protocol-defined exclusions. Patients underwent a single session: intravenous BPA administration (500 mg/kg/3 h) and neutron irradiation 1 hour later. The primary endpoint was the recommended phase 2 radiation dose, based on DLT incidence. Secondary endpoint included safety, efficacy, and pharmacokinetics: treatment-emergent adverse events (TEAEs), progression-free survival, objective response rate, and overall survival (OS).
Results
Six patients were treated between December 2022 and January 2024: 3 in the 9 Gy-Eq and 3 in the 11 Gy-Eq cohort. No DLTs or grade ≥4 TEAEs occurred. Two patients experienced grade 3 TEAEs (brain edema, seizure). Common adverse events were alopecia, aphasia, brain edema, and seizures. One serious adverse event (grade 3 seizure) was reported. Median follow-up was 9.03 months. Median progression-free survival was 1.87 months by response assessment in neuro-oncology; not reached by modified response assessment in neuro-oncology. Objective response was not observed. All patients survived to study completion; median OS not reached, maximum OS was 16.56 months. BPA pharmacokinetics were within expected ranges. The safety monitoring committee selected 11 Gy-Eq as the recommended phase 2 radiation dose, balancing tumoricidal effects with risks of necrosis and bevacizumab requirements.
Conclusions
This study demonstrates the acceptable safety profile of BNCT and suggests potential survival benefits in recurrent high-grade glioma. However, given the limited sample size and follow-up period, extended observation is required to validate long-term efficacy and safety.
{"title":"Boron Neutron Capture Therapy in Recurrent High-Grade Gliomas: Safety, Efficacy, and Pharmacokinetics From a Multicenter, Dose-Escalation Phase 1 Trial","authors":"Woohyoung Kim MD, PhD , Jae-Sung Park MD, PhD , Jin-Ho Song MD, PhD , Heon Yoo MD, PhD , Kawngwoo Park MD, PhD , Hyun Ju Kim MD , Dong-Won Shin MD, PhD , Sung Uk Lee MD, PhD , Stephen Ahn MD, PhD , Seunggyun Ha MD, PhD , JunGyu Yi MS , Kwan Cho MD , Hyo Jung Seo MD, PhD , Hyung-Seok Lim MD, PhD , Gi-Taek Yee MD, PhD","doi":"10.1016/j.adro.2025.101947","DOIUrl":"10.1016/j.adro.2025.101947","url":null,"abstract":"<div><h3>Purpose</h3><div>Boron neutron capture therapy (BNCT) is an advanced radiation therapy delivering highly selective tumor cell destruction via localized fission reactions. This phase 1 study evaluated the safety and efficacy of BNCT using [B-10]L-4-boronophenylalanine (BPA) in patients with recurrent high-grade gliomas, mostly glioblastomas.</div></div><div><h3>Methods and Materials</h3><div>A 3 + 3 dose-escalation design was used to determine the maximum tolerated dose of BNCT across 3 planned cohorts (D<sub>max</sub>: 9, 11, and 13 Gy-Eq), with 3 additional subjects enrolled at any dose level where dose-limiting toxicity (DLT) occurred. DLT was defined as BNCT-related grade 3+ toxicities within 90 days posttreatment, with protocol-defined exclusions. Patients underwent a single session: intravenous BPA administration (500 mg/kg/3 h) and neutron irradiation 1 hour later. The primary endpoint was the recommended phase 2 radiation dose, based on DLT incidence. Secondary endpoint included safety, efficacy, and pharmacokinetics: treatment-emergent adverse events (TEAEs), progression-free survival, objective response rate, and overall survival (OS).</div></div><div><h3>Results</h3><div>Six patients were treated between December 2022 and January 2024: 3 in the 9 Gy-Eq and 3 in the 11 Gy-Eq cohort. No DLTs or grade ≥4 TEAEs occurred. Two patients experienced grade 3 TEAEs (brain edema, seizure). Common adverse events were alopecia, aphasia, brain edema, and seizures. One serious adverse event (grade 3 seizure) was reported. Median follow-up was 9.03 months. Median progression-free survival was 1.87 months by response assessment in neuro-oncology; not reached by modified response assessment in neuro-oncology. Objective response was not observed. All patients survived to study completion; median OS not reached, maximum OS was 16.56 months. BPA pharmacokinetics were within expected ranges. The safety monitoring committee selected 11 Gy-Eq as the recommended phase 2 radiation dose, balancing tumoricidal effects with risks of necrosis and bevacizumab requirements.</div></div><div><h3>Conclusions</h3><div>This study demonstrates the acceptable safety profile of BNCT and suggests potential survival benefits in recurrent high-grade glioma. However, given the limited sample size and follow-up period, extended observation is required to validate long-term efficacy and safety.</div></div>","PeriodicalId":7390,"journal":{"name":"Advances in Radiation Oncology","volume":"11 1","pages":"Article 101947"},"PeriodicalIF":2.7,"publicationDate":"2025-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145681752","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-27DOI: 10.1016/j.adro.2025.101936
Paul Riviere MD , Kylie M. Morgan BS , Tyler Nelson BS , Daniel Sabater Minarim BS , Leah Deshler MS , Matthew P. Banegas PhD , Tyler F. Stewart MD , Rana R. McKay MD , Juan Javier-DesLoges MD , John Kellogg Parsons MD , Brent S. Rose MD
Purpose
Among patients with biochemical recurrent (BCR) prostate cancer following radiation therapy, there is no validated method for identifying those at the highest risk for metastases or death from prostate cancer. We characterized the natural history of BCR after radiation therapy and validated the proposed European consensus guidelines for stratification.
Methods and Materials
This retrospective, multicenter, nationwide cohort study used data from patients having postradiation BCR treated in the United States Veterans Administration Health System. High-risk BCR was defined as either Gleason score ≥8 or BCR occurring within 18 months of radiation therapy, per guidelines.
Results
Among 7126 patients who experienced BCR, 35.5% of patients developed metastatic disease and 17.4% died of prostate cancer at 10 years. 38.5% of patients had a high-risk BCR. High-risk BCR resulted in higher 10-year incidence of metastatic disease (56.2% vs 42.0%, adjusted hazard ratio [aHR] = 1.83, 95% CI: 1.69-1.98) and worse prostate cancer-specific survival (69.5% vs 81.6%, aHR = 1.82, 95% CI: 1.63-2.03, P < .001) and all-cause death (67.8% vs 65.0%, aHR = 1.18, 95% CI: 1.11-1.26, P < .001).
Conclusions
A simple, 2-element risk stratification tool using existing clinical data is the first validated tool for identifying patients at risk of metastases or prostate cancer-specific mortality following postradiation BCR. Most patients experiencing BCR in this context do not develop metastases or lethal prostate cancer, making such stratification essential for treatment decision-making and refinement of patient populations for clinical trials.
目的：在放射治疗后生化复发（BCR）前列腺癌患者中，没有有效的方法来识别前列腺癌转移或死亡风险最高的患者。我们描述了放射治疗后BCR的自然病史，并验证了提出的欧洲共识分层指南。方法和材料这项回顾性、多中心、全国性队列研究使用了在美国退伍军人管理局卫生系统接受过BCR治疗的患者的数据。根据指南，高风险BCR定义为Gleason评分≥8或在放射治疗18个月内发生BCR。结果7126例BCR患者中，35.5%的患者发生转移性疾病，17.4%的患者在10年内死于前列腺癌。38.5%的患者存在高危BCR。高风险BCR导致更高的10年转移性疾病发生率（56.2% vs 42.0%，校正危险比[aHR] = 1.83, 95% CI: 1.69-1.98），更差的前列腺癌特异性生存率（69.5% vs 81.6%, aHR = 1.82, 95% CI: 1.63-2.03, P < 001）和全因死亡（67.8% vs 65.0%, aHR = 1.18, 95% CI: 1.11-1.26, P < 001）。结论：使用现有临床数据的简单的2因素风险分层工具是第一个经过验证的工具，用于识别患者在放疗后BCR后的转移风险或前列腺癌特异性死亡率。在这种情况下，大多数经历BCR的患者不会发展为转移性或致命性前列腺癌，因此这种分层对于治疗决策和临床试验患者群体的细化至关重要。
{"title":"Natural History and Risk Stratification of Biochemically Recurrent Prostate Cancer Following Definitive Radiation Therapy","authors":"Paul Riviere MD , Kylie M. Morgan BS , Tyler Nelson BS , Daniel Sabater Minarim BS , Leah Deshler MS , Matthew P. Banegas PhD , Tyler F. Stewart MD , Rana R. McKay MD , Juan Javier-DesLoges MD , John Kellogg Parsons MD , Brent S. Rose MD","doi":"10.1016/j.adro.2025.101936","DOIUrl":"10.1016/j.adro.2025.101936","url":null,"abstract":"<div><h3>Purpose</h3><div>Among patients with biochemical recurrent (BCR) prostate cancer following radiation therapy, there is no validated method for identifying those at the highest risk for metastases or death from prostate cancer. We characterized the natural history of BCR after radiation therapy and validated the proposed European consensus guidelines for stratification.</div></div><div><h3>Methods and Materials</h3><div>This retrospective, multicenter, nationwide cohort study used data from patients having postradiation BCR treated in the United States Veterans Administration Health System. High-risk BCR was defined as either Gleason score ≥8 or BCR occurring within 18 months of radiation therapy, per guidelines.</div></div><div><h3>Results</h3><div>Among 7126 patients who experienced BCR, 35.5% of patients developed metastatic disease and 17.4% died of prostate cancer at 10 years. 38.5% of patients had a high-risk BCR. High-risk BCR resulted in higher 10-year incidence of metastatic disease (56.2% vs 42.0%, adjusted hazard ratio [aHR] = 1.83, 95% CI: 1.69-1.98) and worse prostate cancer-specific survival (69.5% vs 81.6%, aHR = 1.82, 95% CI: 1.63-2.03, <em>P</em> < .001) and all-cause death (67.8% vs 65.0%, aHR = 1.18, 95% CI: 1.11-1.26, <em>P</em> < .001).</div></div><div><h3>Conclusions</h3><div>A simple, 2-element risk stratification tool using existing clinical data is the first validated tool for identifying patients at risk of metastases or prostate cancer-specific mortality following postradiation BCR. Most patients experiencing BCR in this context do not develop metastases or lethal prostate cancer, making such stratification essential for treatment decision-making and refinement of patient populations for clinical trials.</div></div>","PeriodicalId":7390,"journal":{"name":"Advances in Radiation Oncology","volume":"11 2","pages":"Article 101936"},"PeriodicalIF":2.7,"publicationDate":"2025-10-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145972998","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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