Pub Date : 2025-12-13DOI: 10.1016/j.radonc.2025.111327
E Alì , G Simontacchi , M Levis , F Iori , S Gambara , EM Cuffini , N Pimpinelli , V Grandi , A Botti , G Paolani , C Iotti , U Ricardi , P Ciammella
Background and purpose
Primary indolent cutaneous B-cell lymphomas (PCBCL) account for approximately 20% of all primary cutaneous lymphomas. Radiotherapy (RT) has a well-established therapeutic role in treating PCBCL, and recent evidence suggests that low-dose schedules may be effective as frontline treatment. In this multicenter retrospective observational study, we aimed to evaluate the efficacy and safety of low-dose RT (LDRT) in patients affected with PCBCL.
Methods and materials
We retrospectively reviewed 75 patients with 137 cutaneous lesions treated across three Italian Radiation Oncology Centers between 2010 and 2023. The lesions included 77 Marginal Zone Lymphomas (PCMZL), 55 Follicle Center Lymphomas (PCFCL), and 5 other low-grade lymphomas. All lesions were treated with LDRT. Fifteen lesions (11%) were treated with orthovoltage, 117 lesions (85%) with electrons, and 5 lesions (4%) with photons (3D-CRT).
Results
The median age was 60 years (range 25–89), with a median follow-up of 44.35 months (range 8.88–144.3). The overall progression free survival (PFS) at 12, 24, 36 and 48 months after LDRT was 83 % (95 % CI: 0.74–0.92), 59 % (95 % CI: 0.48–0.72), 49 % (95 % CI: 0.38–0.63), and 42 % (95 % CI: 0.31–0.57), respectively. The overall local control (LC) rate at 12, 24, 36 and 48 months was 87 % (95 % CI: 0.81–0.93), 80 % (95 % CI: 0.73–0.88), 79 % (95 % CI: 0.72–0.87), and 77 % (95 % CI: 0.70–0.86), respectively. Additionally, 64 recurrences (19 %) in 29 patients were documented at sites distant from the initially irradiated lesion. Larger lesions (>2.5 cm) and multifocal presentation were associated with worse progression-free survival (PFS) and LC. Histologic subtype, lesion site, and prior treatments did not significantly influence outcomes. LDRT was very well tolerated and no grade 3 + toxicity events were detected.
Conclusions
Our analysis reinforces the role of LDRT in the management of PCBCL, demonstrating excellent local control rates and a favorable toxicity profile. Further prospective studies are warranted to confirm these results and to optimize treatment protocols.
{"title":"Low-Dose Radiotherapy for Primary Cutaneous Indolent B-Cell Lymphomas: a Multicenter Retrospective Study","authors":"E Alì , G Simontacchi , M Levis , F Iori , S Gambara , EM Cuffini , N Pimpinelli , V Grandi , A Botti , G Paolani , C Iotti , U Ricardi , P Ciammella","doi":"10.1016/j.radonc.2025.111327","DOIUrl":"10.1016/j.radonc.2025.111327","url":null,"abstract":"<div><h3>Background and purpose</h3><div>Primary indolent cutaneous B-cell lymphomas (PCBCL) account for approximately 20% of all primary cutaneous lymphomas. Radiotherapy (RT) has a well-established therapeutic role in treating PCBCL, and recent evidence suggests that low-dose schedules may be effective as frontline treatment. In this multicenter retrospective observational study, we aimed to evaluate the efficacy and safety of low-dose RT (LDRT) in patients affected with PCBCL.</div></div><div><h3>Methods and materials</h3><div>We retrospectively reviewed 75 patients with 137 cutaneous lesions treated across three Italian Radiation Oncology Centers between 2010 and 2023. The lesions included 77 Marginal Zone Lymphomas (PCMZL), 55 Follicle Center Lymphomas (PCFCL), and 5 other low-grade lymphomas. All lesions were treated with LDRT. Fifteen lesions (11%) were treated with orthovoltage, 117 lesions (85%) with electrons, and 5 lesions (4%) with photons (3D-CRT).</div></div><div><h3>Results</h3><div>The median age was 60 years (range 25–89), with a median follow-up of 44.35 months (range 8.88–144.3). The overall progression free survival (PFS) at 12, 24, 36 and 48 months after LDRT was 83 % (95 % CI: 0.74–0.92), 59 % (95 % CI: 0.48–0.72), 49 % (95 % CI: 0.38–0.63), and 42 % (95 % CI: 0.31–0.57), respectively. The overall local control (LC) rate at 12, 24, 36 and 48 months was 87 % (95 % CI: 0.81–0.93), 80 % (95 % CI: 0.73–0.88), 79 % (95 % CI: 0.72–0.87), and 77 % (95 % CI: 0.70–0.86), respectively. Additionally, 64 recurrences (19 %) in 29 patients were documented at sites distant from the initially irradiated lesion. Larger lesions (>2.5 cm) and multifocal presentation were associated with worse progression-free survival (PFS) and LC. Histologic subtype, lesion site, and prior treatments did not significantly influence outcomes. LDRT was very well tolerated and no grade 3 + toxicity events were detected.</div></div><div><h3>Conclusions</h3><div>Our analysis reinforces the role of LDRT in the management of PCBCL, demonstrating excellent local control rates and a favorable toxicity profile. Further prospective studies are warranted to confirm these results and to optimize treatment protocols.</div></div>","PeriodicalId":21041,"journal":{"name":"Radiotherapy and Oncology","volume":"215 ","pages":"Article 111327"},"PeriodicalIF":5.3,"publicationDate":"2025-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145757562","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}
Pub Date : 2025-12-11DOI: 10.1016/j.radonc.2025.111330
Evert S M van Aken, Ajeet Kumar Gandhi, Sean M O'Cathail, Gerben Borst, Jorge Barriuso, Emmanouil Fokas, Luis Castelo-Branco, Anne Hansen Ree, Evandro de Azambuja, Stephanie Kroeze, Ilaria Colombo, Antonin Levy, Carmen Criscitiello, Maximilian Niyazi, Nadia Harbeck, Ewa Szutowicz, Gabor Liposits, Marcel Verheij, Isabelle Ray-Coquard, Paolo Tarantino, Dario Trapani, Paulien Boot, Claus Belka, Dirk De Ruysscher, George Pentheroudakis, Corrie A M Marijnen, Florian Lordick, Umberto Ricardi, Diogo Martins-Branco, Arsela Prelaj, Monique C de Jong, Bharti Devnani
Background: While combining radiotherapy (RT) with targeted agents or immunotherapy may improve outcomes, it may also increase toxicity. High-quality toxicity data and multidisciplinary, evidence-based guidelines on the combination of these treatment modalities are scarce.
Design: The European Society for Medical Oncology (ESMO) and the European SocieTy for Radiotherapy and Oncology (ESTRO) developed a series of systematic reviews with multidisciplinary, tumor-agnostic, evidence-based Delphi consensus statements regarding the safety of combining RT with targeted agents or immunotherapy. The current study addresses the safety of combining RT with CDK4/6 inhibitors, anti-HER2 monoclonal antibodies, PARP inhibitors, or mTOR-inhibitors. During the modified Delphi process, two digital voting rounds were organized with 18 international experts. By systematically evaluating the different drug classes and irradiated areas, 74 clinical scenarios were assessed. Safety statements were formulated for all scenarios, based on the evidence from the systematic literature reviews.
Results: A total of 1,341 records were screened during the systematic literature reviews, of which 107 studies were ultimately included in the final reviews and the literature database. After two Delphi voting rounds, agreement was reached on all 74 scenario-specific safety statements.
Conclusions: The expected combined toxicity is often low for anti-HER2 monoclonal antibodies. For most scenarios with CDK4/6, PARP, or mTOR inhibitors, exercising caution is recommended.
{"title":"ESMO-ESTRO consensus statements on the safety of combining radiotherapy with CDK4/6, HER2, PARP, or mTOR inhibitors.","authors":"Evert S M van Aken, Ajeet Kumar Gandhi, Sean M O'Cathail, Gerben Borst, Jorge Barriuso, Emmanouil Fokas, Luis Castelo-Branco, Anne Hansen Ree, Evandro de Azambuja, Stephanie Kroeze, Ilaria Colombo, Antonin Levy, Carmen Criscitiello, Maximilian Niyazi, Nadia Harbeck, Ewa Szutowicz, Gabor Liposits, Marcel Verheij, Isabelle Ray-Coquard, Paolo Tarantino, Dario Trapani, Paulien Boot, Claus Belka, Dirk De Ruysscher, George Pentheroudakis, Corrie A M Marijnen, Florian Lordick, Umberto Ricardi, Diogo Martins-Branco, Arsela Prelaj, Monique C de Jong, Bharti Devnani","doi":"10.1016/j.radonc.2025.111330","DOIUrl":"https://doi.org/10.1016/j.radonc.2025.111330","url":null,"abstract":"<p><strong>Background: </strong>While combining radiotherapy (RT) with targeted agents or immunotherapy may improve outcomes, it may also increase toxicity. High-quality toxicity data and multidisciplinary, evidence-based guidelines on the combination of these treatment modalities are scarce.</p><p><strong>Design: </strong>The European Society for Medical Oncology (ESMO) and the European SocieTy for Radiotherapy and Oncology (ESTRO) developed a series of systematic reviews with multidisciplinary, tumor-agnostic, evidence-based Delphi consensus statements regarding the safety of combining RT with targeted agents or immunotherapy. The current study addresses the safety of combining RT with CDK4/6 inhibitors, anti-HER2 monoclonal antibodies, PARP inhibitors, or mTOR-inhibitors. During the modified Delphi process, two digital voting rounds were organized with 18 international experts. By systematically evaluating the different drug classes and irradiated areas, 74 clinical scenarios were assessed. Safety statements were formulated for all scenarios, based on the evidence from the systematic literature reviews.</p><p><strong>Results: </strong>A total of 1,341 records were screened during the systematic literature reviews, of which 107 studies were ultimately included in the final reviews and the literature database. After two Delphi voting rounds, agreement was reached on all 74 scenario-specific safety statements.</p><p><strong>Conclusions: </strong>The expected combined toxicity is often low for anti-HER2 monoclonal antibodies. For most scenarios with CDK4/6, PARP, or mTOR inhibitors, exercising caution is recommended.</p>","PeriodicalId":21041,"journal":{"name":"Radiotherapy and Oncology","volume":" ","pages":"111330"},"PeriodicalIF":5.3,"publicationDate":"2025-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145752083","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}
Pub Date : 2025-12-11DOI: 10.1016/j.radonc.2025.111323
Astrid E. Persson , Elisabeth Kjellén , Hans Garmo , Gabriel Adrian , Pär Stattin , Anders Widmark , Per Nilsson , Adalsteinn Gunnlaugsson
Background and purpose
HYPO-RT-PC was the first phase 3 trial showing the long-term efficacy and safety of extremely hypofractionated radiotherapy schedules (ultra-hypofractionation or stereotactic body radiotherapy) compared with standard radiotherapy in localised prostate cancer. We aimed to verify their safety in the context of a clinical trial, by comparing events of potentially radiotherapy-related morbidity according to routinely collected health data between the arms and with men unexposed to prostate radiotherapy.
Materials and methods
We included Swedish residents in the per-protocol population and unexposed men matched with the ultra-hypofractionation group. Primary outcomes were genitourinary and gastrointestinal events defined by linking the Common Terminology Criteria for Adverse Events version 5.0 to diagnosis and intervention codes in broad (any related condition) and narrow code sets (strongly related conditions) tested separately. Inpatient care, interventions, and causes of death, identified in Swedish national healthcare registers, were events. Outcomes were analysed as time-to-event, adjusted for Charlson Comorbidity Index and socioeconomic status.
Results
Five hundred and forty-one participants (92%) from each trial arm and 2705 unexposed men were included. We found no statistically significant differences between the radiotherapy groups (broad code sets: genitourinary events, adjusted hazard ratio 0.95, 95% confidence interval 0.71–1.25; gastrointestinal events, 1.24, 0.91–1.69). Compared with the unexposed men, 10-year excess cumulative incidence was 8% and 5% for genitourinary and 5% and 4% for gastrointestinal events when applying the broad and narrow code sets, respectively, without excess mortality events.
Conclusion
The results support the HYPO-RT-PC findings by showing similar morbidity between ultra-hypofractionated and standard radiotherapy. Excess events were estimated to 4–8%, without increased associated mortality.
{"title":"Routinely collected health data on 10-year genitourinary and gastrointestinal morbidity after ultra-hypofractionated versus conventionally fractionated radiotherapy for localised prostate cancer in the randomised, non-inferiority, phase 3 trial HYPO-RT-PC","authors":"Astrid E. Persson , Elisabeth Kjellén , Hans Garmo , Gabriel Adrian , Pär Stattin , Anders Widmark , Per Nilsson , Adalsteinn Gunnlaugsson","doi":"10.1016/j.radonc.2025.111323","DOIUrl":"10.1016/j.radonc.2025.111323","url":null,"abstract":"<div><h3>Background and purpose</h3><div>HYPO-RT-PC was the first phase 3 trial showing the long-term efficacy and safety of extremely hypofractionated radiotherapy schedules (ultra-hypofractionation or stereotactic body radiotherapy) compared with standard radiotherapy in localised prostate cancer. We aimed to verify their safety in the context of a clinical trial, by comparing events of potentially radiotherapy-related morbidity according to routinely collected health data between the arms and with men unexposed to prostate radiotherapy.</div></div><div><h3>Materials and methods</h3><div>We included Swedish residents in the per-protocol population and unexposed men matched with the ultra-hypofractionation group. Primary outcomes were genitourinary and gastrointestinal events defined by linking the Common Terminology Criteria for Adverse Events version 5.0 to diagnosis and intervention codes in broad (any related condition) and narrow code sets (strongly related conditions) tested separately. Inpatient care, interventions, and causes of death, identified in Swedish national healthcare registers, were events. Outcomes were analysed as time-to-event, adjusted for Charlson Comorbidity Index and socioeconomic status.</div></div><div><h3>Results</h3><div>Five hundred and forty-one participants (92%) from each trial arm and 2705 unexposed men were included. We found no statistically significant differences between the radiotherapy groups (broad code sets: genitourinary events, adjusted hazard ratio 0.95, 95% confidence interval 0.71–1.25; gastrointestinal events, 1.24, 0.91–1.69). Compared with the unexposed men, 10-year excess cumulative incidence was 8% and 5% for genitourinary and 5% and 4% for gastrointestinal events when applying the broad and narrow code sets, respectively, without excess mortality events.</div></div><div><h3>Conclusion</h3><div>The results support the HYPO-RT-PC findings by showing similar morbidity between ultra-hypofractionated and standard radiotherapy. Excess events were estimated to 4–8%, without increased associated mortality.</div></div>","PeriodicalId":21041,"journal":{"name":"Radiotherapy and Oncology","volume":"215 ","pages":"Article 111323"},"PeriodicalIF":5.3,"publicationDate":"2025-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145751923","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}
Pub Date : 2025-12-11DOI: 10.1016/j.radonc.2025.111331
Alba Sanchez-Fernandez , Hermann Tenor , Claire Beckers , Chantal Pauli , Zuzana Garajova , Enni Markkanen , Irene Vetrugno , Lazaros Vasilikos , Tobias Braun , Esra Lone- Kapaklikaya , Yoshita Bhide , Reto Naef , Martin Pruschy
Purpose
Colorectal carcinoma is the third most common cancer globally and a major cause of cancer-related deaths. Many patients develop radiotherapy resistance, underscoring the urge for new therapies. The second messenger cGMP is crucial to maintain intestinal homeostasis, and its lack correlates with epithelial dysfunction and increased tumorigenesis. We investigated the role of TOP-V122, a dual-mode NO-releasing PDE-5 inhibitor, as an anti-tumoral drug alone and in combination with ionizing radiation.
Experimental design
The therapeutic effect of TOP-V122 alone and combined with radiotherapy was assessed using patient-derived colorectal cancer organoids in vitro and in an orthotopic murine tumor model.
Results
Preformed CRC organoids treated with TOP-V122 and radiotherapy showed smaller organoid size, lighter cystic structures, appeared less compact and covered a smaller area in the wells, with increased spacing between individual structures. ATP-based viability and luciferase assays confirmed enhanced anti-tumoral efficacy of the combined treatment. TOP-V122 alone did not induce DNA double-strand breaks or ROS, and while it did not prevent radiotherapy-induced double-strand breaks formation in the combined treatment, it significantly abrogated γH2AX foci formation, suggesting interference with early DNA damage signaling. KAP-1 phosphorylation was unaffected, indicating specificity for γH2AX pathways. Combined treatment further reduced the proliferative status (Ki67) and upregulated p57^Kip2 expression, whereas p21 and Wnt/β-catenin signaling (CCDN1, MYC, β-catenin) remained unchanged. In the orthotopic CRC model, oral TOP-V122 alone reduced tumor growth, and the combined treatment with radiotherapy further enhanced anti-tumoral efficacy. IVIS imaging showed a 55 % early tumor shrinkage rate with the combination, compared with 33 % and 23 % for TOP-V122 and radiotherapy alone, respectively. Terminal tumor weights confirmed these findings, with a 40 % reduction for the combined treatment versus controls. All treatments were well tolerated with stable body weight.
Conclusion
The PDE-5 inhibitor TOP-V122 represents a novel therapeutic option for colorectal cancer alone and in combination with radiotherapy.
{"title":"The combined treatment with TOP-V122, a dual-acting NO-releasing PDE-5 inhibitor, and ionizing irradiation as a novel therapeutical strategy for colorectal carcinoma","authors":"Alba Sanchez-Fernandez , Hermann Tenor , Claire Beckers , Chantal Pauli , Zuzana Garajova , Enni Markkanen , Irene Vetrugno , Lazaros Vasilikos , Tobias Braun , Esra Lone- Kapaklikaya , Yoshita Bhide , Reto Naef , Martin Pruschy","doi":"10.1016/j.radonc.2025.111331","DOIUrl":"10.1016/j.radonc.2025.111331","url":null,"abstract":"<div><h3>Purpose</h3><div>Colorectal carcinoma is the third most common cancer globally and a major cause of cancer-related deaths. Many patients develop radiotherapy resistance, underscoring the urge for new therapies. The second messenger cGMP is crucial to maintain intestinal homeostasis, and its lack correlates with epithelial dysfunction and increased tumorigenesis. We investigated the role of TOP-V122, a dual-mode NO-releasing PDE-5 inhibitor, as an anti-tumoral drug alone and in combination with ionizing radiation.</div></div><div><h3>Experimental design</h3><div>The therapeutic effect of TOP-V122 alone and combined with radiotherapy was assessed using patient-derived colorectal cancer organoids <em>in vitro</em> and in an orthotopic murine tumor model.</div></div><div><h3>Results</h3><div>Preformed CRC organoids treated with TOP-V122 and radiotherapy showed smaller organoid size, lighter cystic structures, appeared less compact and covered a smaller area in the wells, with increased spacing between individual structures. ATP-based viability and luciferase assays confirmed enhanced anti-tumoral efficacy of the combined treatment. TOP-V122 alone did not induce DNA double-strand breaks or ROS, and while it did not prevent radiotherapy-induced double-strand breaks formation in the combined treatment, it significantly abrogated γH2AX foci formation, suggesting interference with early DNA damage signaling. KAP-1 phosphorylation was unaffected, indicating specificity for γH2AX pathways. Combined treatment further reduced the proliferative status (Ki67) and upregulated p57^Kip2 expression, whereas p21 and Wnt/β-catenin signaling (CCDN1, MYC, β-catenin) remained unchanged. In the orthotopic CRC model, oral TOP-V122 alone reduced tumor growth, and the combined treatment with radiotherapy further enhanced anti-tumoral efficacy. IVIS imaging showed a 55 % early tumor shrinkage rate with the combination, compared with 33 % and 23 % for TOP-V122 and radiotherapy alone, respectively. Terminal tumor weights confirmed these findings, with a 40 % reduction for the combined treatment versus controls. All treatments were well tolerated with stable body weight.</div></div><div><h3>Conclusion</h3><div>The PDE-5 inhibitor TOP-V122 represents a novel therapeutic option for colorectal cancer alone and in combination with radiotherapy.</div></div>","PeriodicalId":21041,"journal":{"name":"Radiotherapy and Oncology","volume":"215 ","pages":"Article 111331"},"PeriodicalIF":5.3,"publicationDate":"2025-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145751996","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}
Pub Date : 2025-12-11DOI: 10.1016/j.radonc.2025.111329
Trey Waldrop , Grace Murley , Brett Velasquez , Elise Konradsson , Denae Neill , Luke Connell , Alan Lopez Hernandez , Abagail Delahoussaye , F. William Schuler , Jorge De La Cerda , Ziyi Li , Mark D. Pagel , Emil Schüler
Purpose
The FLASH effect occurs when radiation given at ultra-high dose rates spares healthy tissue while achieving isoeffective tumor control relative to conventional (CONV) dose rate irradiation. Limited data has implicated oxygen in the FLASH effect. This study investigated the effect of tissue oxygen tension (pO2) on gastrointestinal (GI) FLASH sparing in mice.
Methods
pO2 was quantified in vivo by electron paramagnetic resonance imaging (EPRI)— noninvasive oximetry through spin probe injection and magnetic resonance co-registration— and a phosphorescent quenching microsensor. B6(Cg)-Tyrc-2 J/J female mice were imaged while breathing 10%, 21%, and 95% oxygen. C57BL/6 mice of both sexes underwent microsensor probing and FLASH or CONV total abdominal irradiation under these conditions, and GI toxicity was quantified with regenerating crypt assay.
Results
EPRI-measured pO2 within the liver, bowel, and kidney positively correlated with breathing-gas oxygen concentration. In the liver, the microsensor further confirmed this correlation and demonstrated lower pO2's in male mice under 10% and 21% oxygen with a similar trend under 95% oxygen compared to female mice. In both sexes, GI toxicity decreased with decreasing pO2 after FLASH and CONV. Male mice showed significant FLASH GI sparing across breathing-gas conditions, but female mice showed nonsignificant trends. For all gas conditions and both dose-rate regimes, male mice had lower toxicity (more spared crypts) than female mice, except for CONV under 21% oxygen.
Conclusions
Our findings demonstrate that both CONV- and FLASH-induced GI toxicity correlate with in-vivo oxygen tension and that age-matched male and female mice differ in FLASH radiosensitivity across the breathing-gas conditions examined.
{"title":"Investigating the oxygen dependence of FLASH-RT using electron paramagnetic resonance imaging","authors":"Trey Waldrop , Grace Murley , Brett Velasquez , Elise Konradsson , Denae Neill , Luke Connell , Alan Lopez Hernandez , Abagail Delahoussaye , F. William Schuler , Jorge De La Cerda , Ziyi Li , Mark D. Pagel , Emil Schüler","doi":"10.1016/j.radonc.2025.111329","DOIUrl":"10.1016/j.radonc.2025.111329","url":null,"abstract":"<div><h3>Purpose</h3><div>The FLASH effect occurs when radiation given at ultra-high dose rates spares healthy tissue while achieving isoeffective tumor control relative to conventional (CONV) dose rate irradiation. Limited data has implicated oxygen in the FLASH effect. This study investigated the effect of tissue oxygen tension (pO<sub>2</sub>) on gastrointestinal (GI) FLASH sparing in mice.</div></div><div><h3>Methods</h3><div>pO<sub>2</sub> was quantified in vivo by electron paramagnetic resonance imaging (EPRI)— noninvasive oximetry through spin probe injection and magnetic resonance co-registration— and a phosphorescent quenching microsensor. B6(Cg)-Tyrc-2 J/J female mice were imaged while breathing 10%, 21%, and 95% oxygen. C57BL/6 mice of both sexes underwent microsensor probing and FLASH or CONV total abdominal irradiation under these conditions, and GI toxicity was quantified with regenerating crypt assay.</div></div><div><h3>Results</h3><div>EPRI-measured pO<sub>2</sub> within the liver, bowel, and kidney positively correlated with breathing-gas oxygen concentration. In the liver, the microsensor further confirmed this correlation and demonstrated lower pO<sub>2</sub>'s in male mice under 10% and 21% oxygen with a similar trend under 95% oxygen compared to female mice. In both sexes, GI toxicity decreased with decreasing pO<sub>2</sub> after FLASH and CONV. Male mice showed significant FLASH GI sparing across breathing-gas conditions, but female mice showed nonsignificant trends. For all gas conditions and both dose-rate regimes, male mice had lower toxicity (more spared crypts) than female mice, except for CONV under 21% oxygen.</div></div><div><h3>Conclusions</h3><div>Our findings demonstrate that both CONV- and FLASH-induced GI toxicity correlate with in-vivo oxygen tension and that age-matched male and female mice differ in FLASH radiosensitivity across the breathing-gas conditions examined.</div></div>","PeriodicalId":21041,"journal":{"name":"Radiotherapy and Oncology","volume":"215 ","pages":"Article 111329"},"PeriodicalIF":5.3,"publicationDate":"2025-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145752019","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}
Pub Date : 2025-12-11DOI: 10.1016/j.radonc.2025.111328
Dominik Wróbel , Bartosz Wojewoda , Wiktoria Ziółek , Paweł Michał Potocki , Jędrzej Borowczak
Background and purpose
Immunotherapy has redefined the therapeutic paradigm in extensive-stage small cell lung cancer (ES-SCLC). However, the potential role of consolidative thoracic radiotherapy (cTRT) in this context remains unresolved. This study evaluated the efficacy and safety of cTRT in patients with ES-SCLC treated with chemoimmunotherapy, with particular focus on patients with baseline liver and brain metastasis.
Methods
A systematic review and pairwise meta-analysis were conducted per PRISMA guidelines, including studies from PubMed, Embase, and Scopus up to September 1, 2025. Outcomes were reported as hazard ratios (HR) for overall survival (OS), progression-free survival (PFS), and brain metastasis-free survival (BMFS), and odds ratios (OR) for treatment-related adverse events (TRAEs) with 95 % confidence intervals (95 % CI).
Results
Twenty studies involving 5282 patients were included. cTRT combined with chemoimmunotherapy improved OS (HR: 0.57, 95 %CI: 0.48–0.66, p < 0.001) and PFS (HR: 0.53, 95 %CI: 0.45–0.63, p < 0.001). In patients with baseline brain metastasis, cTRT improved both OS (HR:0.57, 95 %CI: 0.39–0.84, p = 0.01) and PFS (HR:0.42, 95 %CI: 0.28–0.64, p < 0.001), whereas in patients with liver metastasis, there was no improvement. Furthermore, cTRT increased BMFS (HR: 0.46, 95 %CI: 0.33–0.64, p < 0.001). Grade ≥ 3 pneumonitis and esophagitis were observed in 3.86 % and 1.27 % of cTRT patients, respectively.
Conclusions
cTRT confers significant improvements in OS and PFS in the general population of patients with ES-SCLC, as well as in patients with baseline brain metastasis. Moreover, cTRT may be associated with prolonged BMFS, potentially reflecting an abscopal effect. The safety profile remains acceptable, given the substantial survival benefit.
{"title":"Consolidative thoracic radiotherapy in the immunotherapy era for extensive-stage small cell lung cancer: a systematic review and meta-analysis with emphasis on brain and liver metastases","authors":"Dominik Wróbel , Bartosz Wojewoda , Wiktoria Ziółek , Paweł Michał Potocki , Jędrzej Borowczak","doi":"10.1016/j.radonc.2025.111328","DOIUrl":"10.1016/j.radonc.2025.111328","url":null,"abstract":"<div><h3>Background and purpose</h3><div>Immunotherapy has redefined the therapeutic paradigm in extensive-stage small cell lung cancer (ES-SCLC). However, the potential role of consolidative thoracic radiotherapy (cTRT) in this context remains unresolved. This study evaluated the efficacy and safety of cTRT in patients with ES-SCLC treated with chemoimmunotherapy, with particular focus on patients with baseline liver and brain metastasis.</div></div><div><h3>Methods</h3><div>A systematic review and pairwise <em>meta</em>-analysis were conducted per PRISMA guidelines, including studies from PubMed, Embase, and Scopus up to September 1, 2025. Outcomes were reported as hazard ratios (HR) for overall survival (OS), progression-free survival (PFS), and brain metastasis-free survival (BMFS), and odds ratios (OR) for treatment-related adverse events (TRAEs) with 95 % confidence intervals (95 % CI).</div></div><div><h3>Results</h3><div>Twenty studies involving 5282 patients were included. cTRT combined with chemoimmunotherapy improved OS (HR: 0.57, 95 %CI: 0.48–0.66, p < 0.001) and PFS (HR: 0.53, 95 %CI: 0.45–0.63, p < 0.001). In patients with baseline brain metastasis, cTRT improved both OS (HR:0.57, 95 %CI: 0.39–0.84, p = 0.01) and PFS (HR:0.42, 95 %CI: 0.28–0.64, p < 0.001), whereas in patients with liver metastasis, there was no improvement. Furthermore, cTRT increased BMFS (HR: 0.46, 95 %CI: 0.33–0.64, p < 0.001). Grade ≥ 3 pneumonitis and esophagitis were observed in 3.86 % and 1.27 % of cTRT patients, respectively.</div></div><div><h3>Conclusions</h3><div>cTRT confers significant improvements in OS and PFS in the general population of patients with ES-SCLC, as well as in patients with baseline brain metastasis. Moreover, cTRT may be associated with prolonged BMFS, potentially reflecting an abscopal effect. The safety profile remains acceptable, given the substantial survival benefit.</div></div>","PeriodicalId":21041,"journal":{"name":"Radiotherapy and Oncology","volume":"216 ","pages":"Article 111328"},"PeriodicalIF":5.3,"publicationDate":"2025-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145744207","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}
Pub Date : 2025-12-09DOI: 10.1016/j.radonc.2025.111326
Paul Sargos , Géraldine Pignot , Carine Bellera , Pascal Pommier , Etienne Martin , Pierre Clavere , Christophe Hennequin , Jean-Luc Hoepffner , Gautier Marcq , Mathieu Roumiguié , Sébastien Crouzet , Luc Cormier , Vanessa Schartner , Noémie Huchet , David Pasquier , Jonathan Khalifa
Background and Purpose
Patients with muscle-invasive bladder cancer (MIBC) treated with radical cystectomy remain at significant risk of pelvic recurrence. We aim to report acute toxicity from a multicentric phase II randomized trial evaluating adjuvant radiotherapy (ART).
Materials and Methods
Patients with pathological high-risk urothelial MIBC, defined as pT3a-4b and/or pN1-2 and/or positive surgical margins, were randomized (3:1) between ART (arm A) and observation (arm B). ART consisted of IMRT (50.4 Gy / 28 fractions) to the pelvic lymph nodes ± cystectomy bed. The primary endpoint was pelvic recurrence-free survival. Herein, we report on acute toxicity (< 6 months after treatment) using the NCI CTCAE 4.0.
Results
From May 2018 to December 2023, 80 eligible patients from 19 centres across France were enrolled: 58 in arm A and 22 in arm B. The present safety analysis focuses on 74 patients: 52 patients in arm A who effectively initiated ART and 22 in arm B. The median age was 66 years. Chemotherapy (mostly neoadjuvant) was given in 62.2 %. All the patients in the arm A completed the treatment. The rate of grade ≥ 2 and grade ≥ 3 acute gastro-intestinal adverse events (AEs) was 28.8 % and 3.8 %, respectively in arm A, and 4.5 % and 0 % respectively in arm B. Of the two grade ≥ 3 GI AE observed in arm A, one was attributed to surgical complications and the other to disease progression. The rate of grade ≥ 2 and grade ≥ 3 acute urinary AEs was 5.8 % and 0 %, respectively in arm A, and 9.1 % and 4.5 % respectively in arm B. As exploratory analyses, when focusing on AE of grade ≥ 2, these proportions were greater for Arm A (28.8 % [n = 15] vs. 4.5 % [n = 1]; p = 0.028, Fisher’s exact test). Overall, no radiotherapy-related grade ≥ 3 AE was observed.
Conclusion
From a randomized multicentric phase II trial, despite a logical higher rate of radiotherapy-related AE in the experimental arm, low rates of moderate to severe acute toxicity suggest the safety of ART for pathological high-risk MIBC. Efficacy end-points results are awaited.
{"title":"Adjuvant radiotherapy in patients with pathological high-risk bladder cancer: Acute toxicity results from a randomized multicentre phase II trial (Bladder-ART/GETUG-AFU30)","authors":"Paul Sargos , Géraldine Pignot , Carine Bellera , Pascal Pommier , Etienne Martin , Pierre Clavere , Christophe Hennequin , Jean-Luc Hoepffner , Gautier Marcq , Mathieu Roumiguié , Sébastien Crouzet , Luc Cormier , Vanessa Schartner , Noémie Huchet , David Pasquier , Jonathan Khalifa","doi":"10.1016/j.radonc.2025.111326","DOIUrl":"10.1016/j.radonc.2025.111326","url":null,"abstract":"<div><h3>Background and Purpose</h3><div>Patients with muscle-invasive bladder cancer (MIBC) treated with radical cystectomy remain at significant risk of pelvic recurrence. We aim to report acute toxicity from a multicentric phase II randomized trial evaluating adjuvant radiotherapy (ART).</div></div><div><h3>Materials and Methods</h3><div>Patients with pathological high-risk urothelial MIBC, defined as pT3a-4b and/or pN1-2 and/or positive surgical margins, were randomized (3:1) between ART (arm A) and observation (arm B). ART consisted of IMRT (50.4 Gy / 28 fractions) to the pelvic lymph nodes ± cystectomy bed. The primary endpoint was pelvic recurrence-free survival. Herein, we report on acute toxicity (< 6 months after treatment) using the NCI CTCAE 4.0.</div></div><div><h3>Results</h3><div>From May 2018 to December 2023, 80 eligible patients from 19 centres across France were enrolled: 58 in arm A and 22 in arm B. The present safety analysis focuses on 74 patients: 52 patients in arm A who effectively initiated ART and 22 in arm B. The median age was 66 years. Chemotherapy (mostly neoadjuvant) was given in 62.2 %. All the patients in the arm A completed the treatment. The rate of grade ≥ 2 and grade ≥ 3 acute gastro-intestinal adverse events (AEs) was 28.8 % and 3.8 %, respectively in arm A, and 4.5 % and 0 % respectively in arm B. Of the two grade ≥ 3 GI AE observed in arm A, one was attributed to surgical complications and the other to disease progression. The rate of grade ≥ 2 and grade ≥ 3 acute urinary AEs was 5.8 % and 0 %, respectively in arm A, and 9.1 % and 4.5 % respectively in arm B. As exploratory analyses, when focusing on AE of grade ≥ 2, these proportions were greater for Arm A (28.8 % [n = 15] vs. 4.5 % [n = 1]; p = 0.028, Fisher’s exact test). Overall, no radiotherapy-related grade ≥ 3 AE was observed.</div></div><div><h3>Conclusion</h3><div>From a randomized multicentric phase II trial, despite a logical higher rate of radiotherapy-related AE in the experimental arm, low rates of moderate to severe acute toxicity suggest the safety of ART for pathological high-risk MIBC. Efficacy end-points results are awaited.</div></div>","PeriodicalId":21041,"journal":{"name":"Radiotherapy and Oncology","volume":"214 ","pages":"Article 111326"},"PeriodicalIF":5.3,"publicationDate":"2025-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145736728","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}
Pub Date : 2025-12-09DOI: 10.1016/j.radonc.2025.111311
S R Brown, M Van Hemelrijck, G Price, F B Oppong, J J C Verhoeff, C Faivre-Finn
Background: Traditional randomised controlled trials (RCTs) are foundational to clinical research, yet in radiation oncology, their limitations are increasingly evident. Rapid technological innovation, complex treatment protocols, and diverse patient populations challenge the feasibility, generalisability, and timeliness of RCTs. This has prompted exploration of alternative methodologies that better align with real-world practice and patient-centred care.
Methods: This narrative review was developed following a joint ESTRO-EORTC session at the May 2025 ESTRO meeting. It synthesises expert perspectives and recent literature to examine the limitations of RCTs and the potential of alternative designs, including real-world evidence (RWE), pragmatic trials, and Trials within Cohorts (TwiCs).
Findings: RCTs in radiation oncology face challenges including high cost, recruitment barriers, limited external validity, and ethical constraints. RWE, derived from registries and electronic health records, is increasingly used for regulatory decisions and post-market surveillance, though concerns about data quality and bias remain. Pragmatic trials offer inclusive, flexible designs that reflect routine care, but require robust infrastructure and statistical methods. TwiCs embed randomisation within observational cohorts, improving recruitment and reducing burden, yet raise ethical and methodological concerns. Examples such as OligoCARE, RAPID-RT and SPRINT illustrate how these designs can support scalable, patient-centred research.
Conclusion: To advance societal sustainability and equity in radiation oncology, methodological pluralism is essential. RWE, pragmatic trials, and TwiCs offer promising alternatives to traditional RCTs, enabling more responsive and inclusive research. Their success depends on investment in infrastructure, training, and ethical frameworks that support transparency and trust.
{"title":"Novel methodologies for clinical research in radiation oncology: Time to think outside of the box? A narrative review.","authors":"S R Brown, M Van Hemelrijck, G Price, F B Oppong, J J C Verhoeff, C Faivre-Finn","doi":"10.1016/j.radonc.2025.111311","DOIUrl":"https://doi.org/10.1016/j.radonc.2025.111311","url":null,"abstract":"<p><strong>Background: </strong>Traditional randomised controlled trials (RCTs) are foundational to clinical research, yet in radiation oncology, their limitations are increasingly evident. Rapid technological innovation, complex treatment protocols, and diverse patient populations challenge the feasibility, generalisability, and timeliness of RCTs. This has prompted exploration of alternative methodologies that better align with real-world practice and patient-centred care.</p><p><strong>Methods: </strong>This narrative review was developed following a joint ESTRO-EORTC session at the May 2025 ESTRO meeting. It synthesises expert perspectives and recent literature to examine the limitations of RCTs and the potential of alternative designs, including real-world evidence (RWE), pragmatic trials, and Trials within Cohorts (TwiCs).</p><p><strong>Findings: </strong>RCTs in radiation oncology face challenges including high cost, recruitment barriers, limited external validity, and ethical constraints. RWE, derived from registries and electronic health records, is increasingly used for regulatory decisions and post-market surveillance, though concerns about data quality and bias remain. Pragmatic trials offer inclusive, flexible designs that reflect routine care, but require robust infrastructure and statistical methods. TwiCs embed randomisation within observational cohorts, improving recruitment and reducing burden, yet raise ethical and methodological concerns. Examples such as OligoCARE, RAPID-RT and SPRINT illustrate how these designs can support scalable, patient-centred research.</p><p><strong>Conclusion: </strong>To advance societal sustainability and equity in radiation oncology, methodological pluralism is essential. RWE, pragmatic trials, and TwiCs offer promising alternatives to traditional RCTs, enabling more responsive and inclusive research. Their success depends on investment in infrastructure, training, and ethical frameworks that support transparency and trust.</p>","PeriodicalId":21041,"journal":{"name":"Radiotherapy and Oncology","volume":" ","pages":"111311"},"PeriodicalIF":5.3,"publicationDate":"2025-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145744153","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}
Pub Date : 2025-12-08DOI: 10.1016/j.radonc.2025.111320
Siming Zheng , Ting Liu , Jiaxiong Zhou, Ting Wang, Zhen Li, Jianrong Yu, Lei Wen, Minying Li
Background and purpose
To describe the clinical outcomes of patients with metastatic epidural spinal cord compression (MESCC) treated with hypofractionated stereotactic body radiation therapy (SBRT).
Materials and Methods
The outcomes of MESCC patients who underwent SBRT at our institution from January 2021 to September 2023 were retrospectively reviewed. The prescribed dose was 30–35 Gy delivered in five fractions over 7 days. Differences between complete pain relief, local control (LC), overall survival (OS), and adverse reaction rates between the groups were evaluated at different time points.
Results
The study cohort included 63 patients (91 lesions) with a median follow-up of 12 months. Complete pain relief rates at post-treatment months 1, 3, and 6 were 28.6 %, 44.4 %, and 45.3 %, respectively, with no significant difference between patients with low-grade vs. high-grade MESCC. The 1-year LC rate was 91.4 % (32/35) and the 1- and 2-year OS rates were 83.1 % and 46.1 %, respectively, with no significant difference between the low-grade and high-grade MESCC groups. Furthermore, 87.5 % (14/16) of patients with high-grade MESCC exhibited a decrease in Bilsky score at 3 months post-treatment, and the majority remained stabilized at 6 months. However, nine (14.3 %) patients developed new or worsening vertebral compression fractures.
Conclusion
Hypofractionated SBRT presents a feasible option for MESCC. For patients with high-grade MESCC who are unsuitable for surgery or refuse surgical intervention, SBRT can effectively relieve spinal cord compression.
{"title":"Hypofractionated stereotactic body radiation therapy for metastatic epidural spinal cord Compression: A case series study","authors":"Siming Zheng , Ting Liu , Jiaxiong Zhou, Ting Wang, Zhen Li, Jianrong Yu, Lei Wen, Minying Li","doi":"10.1016/j.radonc.2025.111320","DOIUrl":"10.1016/j.radonc.2025.111320","url":null,"abstract":"<div><h3>Background and purpose</h3><div>To describe the clinical outcomes of patients with metastatic epidural spinal cord compression (MESCC) treated with hypofractionated stereotactic body radiation therapy (SBRT).</div></div><div><h3>Materials and Methods</h3><div>The outcomes of MESCC patients who underwent SBRT at our institution from January 2021 to September 2023 were retrospectively reviewed. The prescribed dose was 30–35 Gy delivered in five fractions over 7 days. Differences between complete pain relief, local control (LC), overall survival (OS), and adverse reaction rates between the groups were evaluated at different time points.</div></div><div><h3>Results</h3><div>The study cohort included 63 patients (91 lesions) with a median follow-up of 12 months. Complete pain relief rates at post-treatment months 1, 3, and 6 were 28.6 %, 44.4 %, and 45.3 %, respectively, with no significant difference between patients with low-grade vs. high-grade MESCC. The 1-year LC rate was 91.4 % (32/35) and the 1- and 2-year OS rates were 83.1 % and 46.1 %, respectively, with no significant difference between the low-grade and high-grade MESCC groups. Furthermore, 87.5 % (14/16) of patients with high-grade MESCC exhibited a decrease in Bilsky score at 3 months post-treatment, and the majority remained stabilized at 6 months. However, nine (14.3 %) patients developed new or worsening vertebral compression fractures.</div></div><div><h3>Conclusion</h3><div>Hypofractionated SBRT presents a feasible option for MESCC. For patients with high-grade MESCC who are unsuitable for surgery or refuse surgical intervention, SBRT can effectively relieve spinal cord compression.</div></div>","PeriodicalId":21041,"journal":{"name":"Radiotherapy and Oncology","volume":"214 ","pages":"Article 111320"},"PeriodicalIF":5.3,"publicationDate":"2025-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145725555","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}
Pub Date : 2025-12-07DOI: 10.1016/j.radonc.2025.111321
Yunxiang Li, Xiao Liang, Jiacheng Xie, Jie Deng, Weiguo Lu, You Zhang
Purpose
We developed a universal image translation model—Translate Any Modality (TAM) model to synthesize MRI sequences and CT for brain and head-and-neck radiotherapy, facilitating downstream clinical tasks including multimodal registration and treatment dose calculation.
Methods and materials
We retrospectively curated multi-modal imaging from 90 patients (43 brain, and 47 head-and-neck), each with up to eight MRI sequences and a paired CT. TAM uses a two-stage translation strategy: a 3D U-Net to firstly segment soft tissues and bones to serve as anatomical anchors; and a conditional diffusion model, guided by these masks, to synthesize the target modality from any available input modalities. We evaluated 46 MRI-to-MRI and MRI-to-CT translation tasks against two comparison methods, CycleGAN and UNIT, using Frechet Inception Distance (FID), peak signal-to-noise-ratio (PSNR), structural similarity index (SSIM), and Hounsfield unit (HU)-based mean absolute error (MAE). Clinical relevance was tested via multi-modality registration with simulated B-spline deformations and dose calculation using clinical plans with Gamma criteria 1 %/1 mm and 2 %/2 mm.
Results
TAM improved image quality (PSNR 30.0 ± 3.7; SSIM 0.973 ± 0.024) versus UNIT (27.0 ± 3.2; 0.958 ± 0.026) and CycleGAN (25.4 ± 4.1; 0.949 ± 0.037). For synthesized CT, TAM-based CT achieved average Gamma indices of 99.1 ± 1.7 % (2 %/2 mm) and 94.1 ± 6.4 % (1 %/1 mm) versus CycleGAN 93.1 ± 7.5 %/84.0 ± 9.5 % and UNIT 93.8 ± 7.0 %/86.3 ± 9.4 %, with dose-volume histograms closely matching real-CT plans.
Conclusion
TAM is a novel any-to-any medical image modality translation model. It provides flexible, anatomically faithful translation among MRI sequences and CT, which subsequently improves the accuracy of downstream tasks, including registration and dose calculation.
{"title":"A universal medical imaging modality translation model in brain and head-and-neck radiotherapy","authors":"Yunxiang Li, Xiao Liang, Jiacheng Xie, Jie Deng, Weiguo Lu, You Zhang","doi":"10.1016/j.radonc.2025.111321","DOIUrl":"10.1016/j.radonc.2025.111321","url":null,"abstract":"<div><h3>Purpose</h3><div>We developed a universal image translation model—Translate Any Modality (TAM) model to synthesize MRI sequences and CT for brain and head-and-neck radiotherapy, facilitating downstream clinical tasks including multimodal registration and treatment dose calculation.</div></div><div><h3>Methods and materials</h3><div>We retrospectively curated multi-modal imaging from 90 patients (43 brain, and 47 head-and-neck), each with up to eight MRI sequences and a paired CT. TAM uses a two-stage translation strategy: a 3D U-Net to firstly segment soft tissues and bones to serve as anatomical anchors; and a conditional diffusion model, guided by these masks, to synthesize the target modality from any available input modalities. We evaluated 46 MRI-to-MRI and MRI-to-CT translation tasks against two comparison methods, CycleGAN and UNIT, using Frechet Inception Distance (FID), peak signal-to-noise-ratio (PSNR), structural similarity index (SSIM), and Hounsfield unit (HU)-based mean absolute error (MAE). Clinical relevance was tested via multi-modality registration with simulated B-spline deformations and dose calculation using clinical plans with Gamma criteria 1 %/1 mm and 2 %/2 mm.</div></div><div><h3>Results</h3><div>TAM improved image quality (PSNR 30.0 ± 3.7; SSIM 0.973 ± 0.024) versus UNIT (27.0 ± 3.2; 0.958 ± 0.026) and CycleGAN (25.4 ± 4.1; 0.949 ± 0.037). For synthesized CT, TAM-based CT achieved average Gamma indices of 99.1 ± 1.7 % (2 %/2 mm) and 94.1 ± 6.4 % (1 %/1 mm) versus CycleGAN 93.1 ± 7.5 %/84.0 ± 9.5 % and UNIT 93.8 ± 7.0 %/86.3 ± 9.4 %, with dose-volume histograms closely matching real-CT plans.</div></div><div><h3>Conclusion</h3><div>TAM is a novel any-to-any medical image modality translation model. It provides flexible, anatomically faithful translation among MRI sequences and CT, which subsequently improves the accuracy of downstream tasks, including registration and dose calculation.</div></div>","PeriodicalId":21041,"journal":{"name":"Radiotherapy and Oncology","volume":"214 ","pages":"Article 111321"},"PeriodicalIF":5.3,"publicationDate":"2025-12-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145715642","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}
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