Pub Date : 2025-11-22DOI: 10.1016/j.radonc.2025.111300
Eva Oldenburger , Jane Jomy , Inmaculada Navarro-Domenech , Shing Fung Lee , Joanne M. Van der Velden , Henry C.Y. Wong , Mateusz Spalek , Gustavo N. Marta , Peter Hoskin , Yvette M. Van der Linden , Johan Menten , Charles B. Simone II , Daniel Roos , Francesca De Felice , Dirk Rades , Edward Chow , Philip Wong , Srinivas Raman , On behalf of the International Bone Metastases Consensus Working Party
Background and purpose
External beam radiotherapy (EBRT) is a well-established and effective intervention for pain palliation in patients with bone metastases. Variability in trial endpoints, however, has limited comparability and synthesis of available evidence. To address this, the International Bone Metastases Consensus Working Party published endpoint guidelines in 2002 and updated them in 2012. This study aims to review, re-evaluate, and update the existing consensus to reflect contemporary clinical practice and technological advances.
Materials and methods
A modified Delphi process was undertaken, informed by a systematic literature review and post-2012 guideline publications. An electronic survey was distributed to previous contributors and internationally recognized bone EBRT experts. In Phase I, statements achieving ≥ 75 % agreement were accepted. Items not reaching consensus were refined by the Working Party, discussed by a core panel of eight experts, and recirculated in Phase II. Descriptive statistics summarized response rates and agreement levels.
Results
Of 125 experts invited, 58 participated in Phase I, and 44 in Phase II. Consensus was achieved for 38 out of 49 statements (78%), including 18 new or revised items. Key recommendations addressed eligibility criteria for trial enrolment, standardized pain and analgesic assessments, specification of radiation techniques and dose schedules, follow-up intervals, assessment timing and modalities, and incorporation of cost-effectiveness analyses.
Conclusion
This updated consensus provides a contemporary, standardized framework for EBRT trial design and reporting in bone metastases. Adoption will improve cross-study comparability and guide future research priorities. Regular updates are planned to ensure alignment with evolving clinical practice and technology.
{"title":"International consensus on palliative radiotherapy endpoints for future clinical trials in bone metastases: A second update","authors":"Eva Oldenburger , Jane Jomy , Inmaculada Navarro-Domenech , Shing Fung Lee , Joanne M. Van der Velden , Henry C.Y. Wong , Mateusz Spalek , Gustavo N. Marta , Peter Hoskin , Yvette M. Van der Linden , Johan Menten , Charles B. Simone II , Daniel Roos , Francesca De Felice , Dirk Rades , Edward Chow , Philip Wong , Srinivas Raman , On behalf of the International Bone Metastases Consensus Working Party","doi":"10.1016/j.radonc.2025.111300","DOIUrl":"10.1016/j.radonc.2025.111300","url":null,"abstract":"<div><h3>Background and purpose</h3><div>External beam radiotherapy (EBRT) is a well-established and effective intervention for pain palliation in patients with bone metastases. Variability in trial endpoints, however, has limited comparability and synthesis of available evidence. To address this, the International Bone Metastases Consensus Working Party published endpoint guidelines in 2002 and updated them in 2012. This study aims to review, re-evaluate, and update the existing consensus to reflect contemporary clinical practice and technological advances.</div></div><div><h3>Materials and methods</h3><div>A modified Delphi process was undertaken, informed by a systematic literature review and post-2012 guideline publications. An electronic survey was distributed to previous contributors and internationally recognized bone EBRT experts. In Phase I, statements achieving ≥ 75 % agreement were accepted. Items not reaching consensus were refined by the Working Party, discussed by a core panel of eight experts, and recirculated in Phase II. Descriptive statistics summarized response rates and agreement levels.</div></div><div><h3>Results</h3><div>Of 125 experts invited, 58 participated in Phase I, and 44 in Phase II. Consensus was achieved for 38 out of 49 statements (78%), including 18 new or revised items. Key recommendations addressed eligibility criteria for trial enrolment, standardized pain and analgesic assessments, specification of radiation techniques and dose schedules, follow-up intervals, assessment timing and modalities, and incorporation of cost-effectiveness analyses.</div></div><div><h3>Conclusion</h3><div>This updated consensus provides a contemporary, standardized framework for EBRT trial design and reporting in bone metastases. Adoption will improve cross-study comparability and guide future research priorities. Regular updates are planned to ensure alignment with evolving clinical practice and technology.</div></div>","PeriodicalId":21041,"journal":{"name":"Radiotherapy and Oncology","volume":"214 ","pages":"Article 111300"},"PeriodicalIF":5.3,"publicationDate":"2025-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145597275","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 : 2025-11-22DOI: 10.1016/j.radonc.2025.111303
Mengqi Zhou , Dania Abu Awwad , Geoffrey Paul Delaney , Vikneswary Batumalai , Aba Scott , Eduardo Zubizarreta , Yavuz Anacak , Soehartati Gondhowiardjo , Tiara B. Mayang Permata , Mei Ling Yap
Background
Radiotherapy is a vital component of cancer care, yet access is limited. Global estimates often overlook cancer stage variability across countries with different income levels. This study assesses the supply–demand gap for megavoltage radiotherapy machines (MVMs) from 2012 to 2022 and projects the survival and local control benefits achievable by meeting optimal radiotherapy needs by 2050.
Methods
Global cancer data were from GLOBOCAN 2022. A validated, stage-adjusted radiotherapy utilisation model was adapted using available cancer stage data from LMICs for each geographical region. Population-based models estimating local control and survival benefit from radiotherapy were also stage-adjusted. The overall shortfall was calculated as patients not receiving treatment due to limited MVM availability. Corresponding outcome gaps were estimated by multiplying shortfall cases by their respective benefit percentages.
Results
Radiotherapy demand increased by 2.4 million cases from 2012 to 2022. Optimising access would yield survival benefits for >860,000 people annually and improved local control for 3.5 million cases annually. Lower-middle-income countries are estimated to derive the highest population-based benefits in local control (10.65 %) and survival (4.94 %). The number of patients missing radiotherapy is projected to reach 7.9 million by 2050, creating a global local control gap of 1.2 million and a survival gap of 500,000 cases per year.
Conclusion
This study highlights the urgent need for enhanced policies and expanded infrastructure to address radiotherapy disparities, particularly in LMICs, to improve local control and survival outcomes.
{"title":"Stage-adjusted forecasting of radiotherapy demand and outcome benefits across income groups: Estimating survival and local control gains by 2050","authors":"Mengqi Zhou , Dania Abu Awwad , Geoffrey Paul Delaney , Vikneswary Batumalai , Aba Scott , Eduardo Zubizarreta , Yavuz Anacak , Soehartati Gondhowiardjo , Tiara B. Mayang Permata , Mei Ling Yap","doi":"10.1016/j.radonc.2025.111303","DOIUrl":"10.1016/j.radonc.2025.111303","url":null,"abstract":"<div><h3>Background</h3><div>Radiotherapy is a vital component of cancer care, yet access is limited. Global estimates often overlook cancer stage variability across countries with different income levels. This study assesses the supply–demand gap for megavoltage radiotherapy machines (MVMs) from 2012 to 2022 and projects the survival and local control benefits achievable by meeting optimal radiotherapy needs by 2050.</div></div><div><h3>Methods</h3><div>Global cancer data were from GLOBOCAN 2022. A validated, stage-adjusted radiotherapy utilisation model was adapted using available cancer stage data from LMICs for each geographical region. Population-based models estimating local control and survival benefit from radiotherapy were also stage-adjusted. The overall shortfall was calculated as patients not receiving treatment due to limited MVM availability. Corresponding outcome gaps were estimated by multiplying shortfall cases by their respective benefit percentages.</div></div><div><h3>Results</h3><div>Radiotherapy demand increased by 2.4 million cases from 2012 to 2022. Optimising access would yield survival benefits for >860,000 people annually and improved local control for 3.5 million cases annually. Lower-middle-income countries are estimated to derive the highest population-based benefits in local control (10.65 %) and survival (4.94 %). The number of patients missing radiotherapy is projected to reach 7.9 million by 2050, creating a global local control gap of 1.2 million and a survival gap of 500,000 cases per year.</div></div><div><h3>Conclusion</h3><div>This study highlights the urgent need for enhanced policies and expanded infrastructure to address radiotherapy disparities, particularly in LMICs, to improve local control and survival outcomes.</div></div>","PeriodicalId":21041,"journal":{"name":"Radiotherapy and Oncology","volume":"216 ","pages":"Article 111303"},"PeriodicalIF":5.3,"publicationDate":"2025-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145597250","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 : 2025-11-22DOI: 10.1016/j.radonc.2025.111302
Lukas Schröder , Erik van der Bijl , Lisa Wiersema , Anja Betgen , Baukelien van Triest , Femke Peters , Alice Couwenberg , Uulke A. van der Heide , Jan-Jakob Sonke , Tomas Janssen
Background and purpose
Online adaptive radiotherapy (OART) allows for a reduction of geometric uncertainties and therefore smaller PTV margins. In this work we take the next step and introduce online dose-adaptive radiotherapy (DART), where the treatment plan is adapted not only to the geometry of the day but also to the accumulated dose delivered in previous fractions.
Materials and methods
14 rectal cancer patients that were treated with OART with 5x5Gy on a 1.5 T MR-Linac were retrospectively included. For fractions 1–4, a daily treatment plan using 1 mm PTV margin was generated. Actual delivered dose was estimated by recalculation of this plan on the post-treatment scan. By means of deformable image registration, the delivered doses were accumulated on the adaptation scan of fraction 5. For fraction 5, a plan was optimized to the prescribed dose, using the accumulated dose of fractions 1–4 as background. Target coverage and irradiated volume of the final accumulated delivered dose was compared with the accumulated delivered dose from conventional OART using clinical PTV margins.
Results
After dose accumulation, DART led to a mean decrease in CTV D99% of 0.5 Gy compared to conventional OART, however, conform protocol, target coverage was sufficient in >90 % of patients. The median dose in the 1 cm ring around the clinical PTV was reduced by 3.6 Gy and the patient volume that received 95 % of the prescribed dose decreased by 32 % (221 cm3) on average.
Conclusion
Online DART is technically feasible, achieving adequate delivered accumulated CTV dose, while substantially sparing the healthy tissue.
背景和目的：在线自适应放疗（OART）允许减少几何不确定性，因此更小的PTV边缘。在这项工作中，我们采取了下一步，并引入在线剂量适应性放疗（DART），其中治疗计划不仅适用于当天的几何形状，而且适用于先前部分交付的累积剂量。材料和方法：回顾性分析14例经1.5 T MR-Linac上5x5Gy OART治疗的直肠癌患者。对于分数1-4，产生1 mm PTV裕量的每日治疗计划。在治疗后的扫描中，通过重新计算该计划来估计实际递送剂量。采用可变形配准的方法，将传递的剂量累积到5分的自适应扫描上。对于分数5，以分数1-4的累积剂量为背景，将计划优化为规定剂量。使用临床PTV边缘将最终累积递送剂量的靶覆盖率和照射体积与常规OART的累积递送剂量进行比较。结果：经剂量积累后，与常规OART相比，DART使CTV D99%平均降低0.5 Gy，然而，符合方案，bbb90 %的患者的目标覆盖率是足够的。临床PTV周围1 cm环内的中位剂量减少3.6 Gy，接受95 %处方剂量的患者体积平均减少32 %（221 cm3）。结论：在线DART在技术上是可行的，可以获得足够的CTV累积剂量，同时基本上保留健康组织。
{"title":"Online dose-adaptive radiotherapy considerably reduces irradiated volume in rectal cancer radiotherapy","authors":"Lukas Schröder , Erik van der Bijl , Lisa Wiersema , Anja Betgen , Baukelien van Triest , Femke Peters , Alice Couwenberg , Uulke A. van der Heide , Jan-Jakob Sonke , Tomas Janssen","doi":"10.1016/j.radonc.2025.111302","DOIUrl":"10.1016/j.radonc.2025.111302","url":null,"abstract":"<div><h3>Background and purpose</h3><div>Online adaptive radiotherapy (OART) allows for a reduction of geometric uncertainties and therefore smaller PTV margins. In this work we take the next step and introduce online dose-adaptive radiotherapy (DART), where the treatment plan is adapted not only to the geometry of the day but also to the accumulated dose delivered in previous fractions.</div></div><div><h3>Materials and methods</h3><div>14 rectal cancer patients that were treated with OART with 5x5Gy on a 1.5 T MR-Linac were retrospectively included. For fractions 1–4, a daily treatment plan using 1 mm PTV margin was generated. Actual delivered dose was estimated by recalculation of this plan on the post-treatment scan. By means of deformable image registration, the delivered doses were accumulated on the adaptation scan of fraction 5. For fraction 5, a plan was optimized to the prescribed dose, using the accumulated dose of fractions 1–4 as background. Target coverage and irradiated volume of the final accumulated delivered dose was compared with the accumulated delivered dose from conventional OART using clinical PTV margins.</div></div><div><h3>Results</h3><div>After dose accumulation, DART led to a mean decrease in CTV D<sub>99%</sub> of 0.5 Gy compared to conventional OART, however, conform protocol, target coverage was sufficient in >90 % of patients. The median dose in the 1 cm ring around the clinical PTV was reduced by 3.6 Gy and the patient volume that received 95 % of the prescribed dose decreased by 32 % (221 cm<sup>3</sup>) on average.</div></div><div><h3>Conclusion</h3><div>Online DART is technically feasible, achieving adequate delivered accumulated CTV dose, while substantially sparing the healthy tissue.</div></div>","PeriodicalId":21041,"journal":{"name":"Radiotherapy and Oncology","volume":"214 ","pages":"Article 111302"},"PeriodicalIF":5.3,"publicationDate":"2025-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145597213","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 : 2025-11-22DOI: 10.1016/j.radonc.2025.111298
Karolina Klucznik , Thomas Ravkilde , Simon Skouboe , Paul Keall , Laura Happersett , Hai Pham , Brian Leong , Pengpeng Zhang , Grace Tang , Per R. Poulsen
Background and motivation
Organ motion can distort prostate radiotherapy doses. This study presents the first real-time calculation of the motion-induced dose distortions performed online during prostate radiotherapy.
Methods
Twenty patients were treated with stereotactic prostate radiotherapy of 35 Gy or 40 Gy in 5 fractions using intrafractional image guidance for real-time prostate localization and patient repositioning upon prostate misalignments exceeding 1.5 mm. In-house developed software performed motion-including prostate and bladder dose reconstruction during treatment. The reconstructed doses were retrospectively validated against a clinical treatment planning system (TPS) where motion was encoded in treatment plans as multiple 3D isocenter shifts. Hypothetical doses delivered without intra-treatment repositioning were reconstructed post-treatment for comparison to illustrate how the dose reconstruction allows easy assessment of the effectiveness of the used motion mitigation method.
Results
Dose reconstruction was performed for 91 fractions either online during treatment (n = 41) or retrospectively using recorded motion (n = 50). The real-time calculated doses (calculated by the in-house software using a simplified algorithm) agreed with TPS calculations with mean (±std) differences of 0.1 % (±0.9 %) for clinical target volume (CTV) D95% and 0.2 % (±0.2 %) for bladder V36Gy. The mean time per online dose-reconstruction (±std) was 336 ± 86 ms, proving the real-time applicability of the proposed method. The average (±std) motion-induced dose distortions for individual fractions with intrafractional image guidance were –0.5 % (±1.0 %) for CTV D95% and +0.1 % (±0.5 %) for bladder V36Gy for individual fractions. Accumulated across all fractions of each patient, these deviations decreased to 0.0 % (±0.7 %) for the CTV and +0.1 % (±0.2 %) for the bladder. In contrast, without intratreatment repositioning, deviations would have been –1.3 % (±5.0 %) for CTV D95% and +0.5 % (±1.5 %) for bladder V36Gy, with individual fractions exhibiting clinically unacceptable CTV D95% decreases of up to 42.5 %.
Conclusion
This study marks the first clinical realization of real-time motion-including dose reconstruction for both target and organ-at-risk structures paving the way for real-time dose-guided radiotherapy.
{"title":"First online real-time motion-including prostate and bladder dose reconstruction during prostate radiotherapy","authors":"Karolina Klucznik , Thomas Ravkilde , Simon Skouboe , Paul Keall , Laura Happersett , Hai Pham , Brian Leong , Pengpeng Zhang , Grace Tang , Per R. Poulsen","doi":"10.1016/j.radonc.2025.111298","DOIUrl":"10.1016/j.radonc.2025.111298","url":null,"abstract":"<div><h3>Background and motivation</h3><div>Organ motion can distort prostate radiotherapy doses. This study presents the first real-time calculation of the motion-induced dose distortions performed online during prostate radiotherapy.</div></div><div><h3>Methods</h3><div>Twenty patients were treated with stereotactic prostate radiotherapy of 35 Gy or 40 Gy in 5 fractions using intrafractional image guidance for real-time prostate localization and patient repositioning upon prostate misalignments exceeding 1.5 mm. In-house developed software performed motion-including prostate and bladder dose reconstruction during treatment. The reconstructed doses were retrospectively validated against a clinical treatment planning system (TPS) where motion was encoded in treatment plans as multiple 3D isocenter shifts. Hypothetical doses delivered without intra-treatment repositioning were reconstructed post-treatment for comparison to illustrate how the dose reconstruction allows easy assessment of the effectiveness of the used motion mitigation method.</div></div><div><h3>Results</h3><div>Dose reconstruction was performed for 91 fractions either online during treatment (n = 41) or retrospectively using recorded motion (n = 50). The real-time calculated doses (calculated by the in-house software using a simplified algorithm) agreed with TPS calculations with mean (±std) differences of 0.1 % (±0.9 %) for clinical target volume (CTV) D<sub>95%</sub> and 0.2 % (±0.2 %) for bladder V<sub>36Gy</sub>. The mean time per online dose-reconstruction (±std) was 336 ± 86 ms, proving the real-time applicability of the proposed method. The average (±std) motion-induced dose distortions for individual fractions with intrafractional image guidance were –0.5 % (±1.0 %) for CTV D<sub>95%</sub> and +0.1 % (±0.5 %) for bladder V<sub>36Gy</sub> for individual fractions. Accumulated across all fractions of each patient, these deviations decreased to 0.0 % (±0.7 %) for the CTV and +0.1 % (±0.2 %) for the bladder. In contrast, without intratreatment repositioning, deviations would have been –1.3 % (±5.0 %) for CTV D<sub>95%</sub> and +0.5 % (±1.5 %) for bladder V<sub>36Gy</sub>, with individual fractions exhibiting clinically unacceptable CTV D<sub>95%</sub> decreases of up to 42.5 %.</div></div><div><h3>Conclusion</h3><div>This study marks the first clinical realization of real-time motion-including dose reconstruction for both target and organ-at-risk structures paving the way for real-time dose-guided radiotherapy.</div></div>","PeriodicalId":21041,"journal":{"name":"Radiotherapy and Oncology","volume":"214 ","pages":"Article 111298"},"PeriodicalIF":5.3,"publicationDate":"2025-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145597206","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 : 2025-11-21DOI: 10.1016/j.radonc.2025.111275
Siyer Roohani , Peter W.M. Chung , Brendan C. Dickson , Peter C. Ferguson , Anthony M. Griffin , David G. Kirsch , Reinhardt Krcek , Brian O’Sullivan , David B. Shultz , Kim M. Tsoi , Philip Wong , Jay S. Wunder , Charles N. Catton
Purpose
To assess oncologic, functional outcomes, and recurrence patterns in a large cohort of prospectively collected patients with localized extremity/trunk myxoid liposarcoma with long-term follow-up.
Methods
Analysis of 186 patients (1992–2025) treated with surgery ± perioperative radiotherapy. Data were drawn from prospective institutional registries with central pathology/radiology review. Outcomes: wound complications, late toxicity, functional scores, overall survival (OS), cancer-specific survival (CSS), and local (LR) and distant metastatic recurrence (DM).
Results
Median age was 44.5 years; median follow-up 77 months. All had surgery; 86.6 % received radiotherapy (73.7 % preoperatively). Wound complications occurred in 33.3 %. Late ≥ Grade 2 toxicities: skin (7.5 %), subcutaneous fibrosis (14.5 %), joint stiffness (2.2 %), edema (9.1 %). Functional scores at last follow-up: median TESS: 97 (mean 91.3), MSTS-87: 35 (mean 33.1), MSTS-93: 100 (mean 94.7). LR: 3 cases (1.6 %, 5-year cumulative incidence: 1.4 %). DM: 31 patients (16.7 %), involving 40 sites (42.5 % soft tissue, 22.5 % lung, 17.5 % bone, 7.5 % liver, 5 % lymph nodes). Cumulative incidence of DM: 1-year 0.6 %, 5-year 10.8 %, 10-year 23.4 %. CSS was 100 %, 96.4 %, and 80 % at 1, 5, and 10 years, respectively. OS was 98.8 %, 92 %, and 74.2 % at the same time points.
Conclusions
Local control was high, and long-term function were favorable. Distant recurrences were more frequent, occurred at a constant rate beyond 5 years, without plateau, often involved extra-pulmonary sites, and drove late cancer-related mortality. These findings support the consideration of continued annual follow-up through at least 10 years, with imaging of pulmonary and extra-pulmonary sites to adequately capture the full spectrum of metastatic risk.
{"title":"Refining surveillance in Myxoid liposarcoma: long-term recurrence patterns and functional outcomes after surgery ± radiotherapy in 186 patients","authors":"Siyer Roohani , Peter W.M. Chung , Brendan C. Dickson , Peter C. Ferguson , Anthony M. Griffin , David G. Kirsch , Reinhardt Krcek , Brian O’Sullivan , David B. Shultz , Kim M. Tsoi , Philip Wong , Jay S. Wunder , Charles N. Catton","doi":"10.1016/j.radonc.2025.111275","DOIUrl":"10.1016/j.radonc.2025.111275","url":null,"abstract":"<div><h3>Purpose</h3><div>To assess oncologic, functional outcomes, and recurrence patterns in a large cohort of prospectively collected patients with localized extremity/trunk myxoid liposarcoma with long-term follow-up.</div></div><div><h3>Methods</h3><div>Analysis of 186 patients (1992–2025) treated with surgery ± perioperative radiotherapy. Data were drawn from prospective institutional registries with central pathology/radiology review. Outcomes: wound complications, late toxicity, functional scores, overall survival (OS), cancer-specific survival (CSS), and local (LR) and distant metastatic recurrence (DM).</div></div><div><h3>Results</h3><div>Median age was 44.5 years; median follow-up 77 months. All had surgery; 86.6 % received radiotherapy (73.7 % preoperatively). Wound complications occurred in 33.3 %. Late ≥ Grade 2 toxicities: skin (7.5 %), subcutaneous fibrosis (14.5 %), joint stiffness (2.2 %), edema (9.1 %). Functional scores at last follow-up: median TESS: 97 (mean 91.3), MSTS-87: 35 (mean 33.1), MSTS-93: 100 (mean 94.7). LR: 3 cases (1.6 %, 5-year cumulative incidence: 1.4 %). DM: 31 patients (16.7 %), involving 40 sites (42.5 % soft tissue, 22.5 % lung, 17.5 % bone, 7.5 % liver, 5 % lymph nodes). Cumulative incidence of DM: 1-year 0.6 %, 5-year 10.8 %, 10-year 23.4 %. CSS was 100 %, 96.4 %, and 80 % at 1, 5, and 10 years, respectively. OS was 98.8 %, 92 %, and 74.2 % at the same time points.</div></div><div><h3>Conclusions</h3><div>Local control was high, and long-term function were favorable. Distant recurrences were more frequent, occurred at a constant rate beyond 5 years, without plateau, often involved extra-pulmonary sites, and drove late cancer-related mortality. These findings support the consideration of continued annual follow-up through at least 10 years, with imaging of pulmonary and extra-pulmonary sites to adequately capture the full spectrum of metastatic risk.</div></div>","PeriodicalId":21041,"journal":{"name":"Radiotherapy and Oncology","volume":"214 ","pages":"Article 111275"},"PeriodicalIF":5.3,"publicationDate":"2025-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145588394","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 : 2025-11-19DOI: 10.1016/j.radonc.2025.111293
Lone Hoffmann , Mai-Britt Linaa , Mai Lykkegaard Ehmsen , Maria Fuglsang Jensen , Sarah Eckholdt , Christina Larsen , Mikkel Drøgemüller Lund , Laura Patricia Kaplan , Morten Nielsen , Wiviann Ottosson , Cécile Peucelle , Arpit Saini , Hella Sand , Simon Nyberg Thomsen , Stine Fredslund , Torben Schjødt Hansen , Vladimira Horvat , Marianne Marquard Knap , Lotte Holm Land , Hanna Mortensen , Ane Appelt
Introduction
High-dose lung cancer reirradiation is promising but associated with high toxicity risk. Development of and adherence to consensus guidelines will support safe use.
Materials and methods
Literature review and live workshops were conducted to develop treatment planning guidelines in preparation for the Scandinavian CURE Lung trial. Relevant OARs, dose metrics, constraints, and priorities were considered. For six high-dose reirradiation lung cancer cases, the physical 3D dose distribution of previous treatment was mapped to current CT. The cases were distributed to eight radiotherapy centres, which optimised plans on current CT respecting equieffective cumulative dose constraints. Mapped previous dose and current dose were rescaled to EQD2Gy (α/β = 3 Gy, spinal cord: α/β = 2 Gy), summed by each centre, and reviewed centrally. After cases 1–4 were completed, prioritisation between OAR constraints and target coverage was clarified.
Results
Consensus agreement on guidelines for treatment planning, equieffective cumulative dose constraints, and priorities was established. For cases 1–3, centres complied with constraints. For case 4, covering PTV while respecting OAR constraints was difficult, and major variations were identified, underscoring the need for clearer prioritisation guidance. Consensus was reached to prioritise OAR constraints, and centres re-optimised case 4 accordingly. For cases 5 and 6, all centres underdosed PTV, to comply with OAR constraints. Generally, considerable variation in cumulative OAR doses was observed.
Conclusions
A treatment planning protocol was developed. The pre-trial multi-centre treatment planning study identified and resolved key missing guidance to facilitate common conception of consensus guidelines. Feasibility and compliance with the proposed equieffective cumulative dose constraints were established.
{"title":"Development of a treatment planning protocol for the multi-centre reirradiation CURE Lung trial","authors":"Lone Hoffmann , Mai-Britt Linaa , Mai Lykkegaard Ehmsen , Maria Fuglsang Jensen , Sarah Eckholdt , Christina Larsen , Mikkel Drøgemüller Lund , Laura Patricia Kaplan , Morten Nielsen , Wiviann Ottosson , Cécile Peucelle , Arpit Saini , Hella Sand , Simon Nyberg Thomsen , Stine Fredslund , Torben Schjødt Hansen , Vladimira Horvat , Marianne Marquard Knap , Lotte Holm Land , Hanna Mortensen , Ane Appelt","doi":"10.1016/j.radonc.2025.111293","DOIUrl":"10.1016/j.radonc.2025.111293","url":null,"abstract":"<div><h3>Introduction</h3><div>High-dose lung cancer reirradiation is promising but associated with high toxicity risk. Development of and adherence to consensus guidelines will support safe use.</div></div><div><h3>Materials and methods</h3><div>Literature review and live workshops were conducted to develop treatment planning guidelines in preparation for the Scandinavian CURE Lung trial. Relevant OARs, dose metrics, constraints, and priorities were considered. For six high-dose reirradiation lung cancer cases, the physical 3D dose distribution of previous treatment was mapped to current CT. The cases were distributed to eight radiotherapy centres, which optimised plans on current CT respecting equieffective cumulative dose constraints. Mapped previous dose and current dose were rescaled to EQD2Gy (α/β = 3 Gy, spinal cord: α/β = 2 Gy), summed by each centre, and reviewed centrally. After cases 1–4 were completed, prioritisation between OAR constraints and target coverage was clarified.</div></div><div><h3>Results</h3><div>Consensus agreement on guidelines for treatment planning, equieffective cumulative dose constraints, and priorities was established. For cases 1–3, centres complied with constraints. For case 4, covering PTV while respecting OAR constraints was difficult, and major variations were identified, underscoring the need for clearer prioritisation guidance. Consensus was reached to prioritise OAR constraints, and centres re-optimised case 4 accordingly. For cases 5 and 6, all centres underdosed PTV, to comply with OAR constraints. Generally, considerable variation in cumulative OAR doses was observed.</div></div><div><h3>Conclusions</h3><div>A treatment planning protocol was developed. The pre-trial multi-centre treatment planning study identified and resolved key missing guidance to facilitate common conception of consensus guidelines. Feasibility and compliance with the proposed equieffective cumulative dose constraints were established.</div></div>","PeriodicalId":21041,"journal":{"name":"Radiotherapy and Oncology","volume":"214 ","pages":"Article 111293"},"PeriodicalIF":5.3,"publicationDate":"2025-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145574210","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 : 2025-11-19DOI: 10.1016/j.radonc.2025.111294
Colin Niaudet , Thibaud Mathis , Thao-Nguyen Pham , Jean-Claude Quintyn , François Paris , Juliette Thariat
Optic tissue toxicity remains a major limitation of radiation therapy for ocular, brain, skull base, and head and neck tumors. Among the most frequent complications, radiation retinopathy (RR) occurs in 6% of patients treated for extraocular tumors and in more than 40% of those with ocular tumors. After an initial asymptomatic stage characterized by vascular remodeling and chronic retinal ischemia, RR may progress to irreversible vision loss and significantly impaired quality of life. Advances in non-invasive, high-resolution imaging have improved our understanding of the molecular and cellular mechanisms underlying RR in both preclinical and clinical models. In particular, multimodal imaging—and especially optical coherence tomography angiography (OCTA)—has enabled earlier detection of RR in humans. Animal studies have highlighted vascular obstruction and rarefaction, together with early neurovascular dysfunction, as central features of the clinical phase. Beyond preventive measures such as dose constraints, biological and imaging biomarkers may help guide targeted interventions. In this review, we summarize current evidence on the sequential endothelial and neuronal alterations that drive RR and discuss molecular and cellular pathways that could inform the development of potential therapeutic strategies.
{"title":"Vascular dysfunctions during radiation retinopathy","authors":"Colin Niaudet , Thibaud Mathis , Thao-Nguyen Pham , Jean-Claude Quintyn , François Paris , Juliette Thariat","doi":"10.1016/j.radonc.2025.111294","DOIUrl":"10.1016/j.radonc.2025.111294","url":null,"abstract":"<div><div>Optic tissue toxicity remains a major limitation of radiation therapy for ocular, brain, skull base, and head and neck tumors. Among the most frequent complications, radiation retinopathy (RR) occurs in 6% of patients treated for extraocular tumors and in more than 40% of those with ocular tumors. After an initial asymptomatic stage characterized by vascular remodeling and chronic retinal ischemia, RR may progress to irreversible vision loss and significantly impaired quality of life. Advances in non-invasive, high-resolution imaging have improved our understanding of the molecular and cellular mechanisms underlying RR in both preclinical and clinical models. In particular, multimodal imaging—and especially optical coherence tomography angiography (OCTA)—has enabled earlier detection of RR in humans. Animal studies have highlighted vascular obstruction and rarefaction, together with early neurovascular dysfunction, as central features of the clinical phase. Beyond preventive measures such as dose constraints, biological and imaging biomarkers may help guide targeted interventions. In this review, we summarize current evidence on the sequential endothelial and neuronal alterations that drive RR and discuss molecular and cellular pathways that could inform the development of potential therapeutic strategies.</div></div>","PeriodicalId":21041,"journal":{"name":"Radiotherapy and Oncology","volume":"214 ","pages":"Article 111294"},"PeriodicalIF":5.3,"publicationDate":"2025-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145573796","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 : 2025-11-19DOI: 10.1016/j.radonc.2025.111291
Longfei Diao , Xingyi Zhao , Chingyun Cheng , Tengda Zhang , Shouyi Wei , Dongdong Meng , Zhizhen Wei , Yangguang Ma , Kun Zhu , Hui Wu , Benjamin Durkee , Haibo Lin , Charles B. Simone , Xueqing Yan , Minglei Kang
Purpose
To evaluate the impact of key treatment planning parameters—including beam arrangement, minimum monitor unit (MMU) settings, and anatomical site variability—on the ability to achieve ultra-high dose rate (UHDR) delivery in Bragg peak FLASH radiotherapy.
Methods
FLASH dose rate coverage can be assessed by dose-rate volume histogram (DRVH), thus objective functions based on DRVH can be constructed to optimize the dose rate distribution for individual regions of interest (ROIs). The optimization of each ROI, as part of the final objective function, is integrated into a multi-objective optimization problem that can be solved using a heuristic algorithm. A phantom-based study was conducted to investigate the effect of beam number on optimization performance in proton therapy planning. Treatment plans of 8 consecutive node-negative non-small cell lung cancer and 5 consecutive liver cancer patients were initially optimized, followed by optimizing the spot delivery sequence to enhance dose rate ratios without compromising dose performance. A thorough evaluation was conducted to assess the optimization of the scanning pattern in improving the FLASH ratio of critical OARs in Bragg peak FLASH-RT, considering beam currents, beam arrangement, MMU constraints, and anatomical sites in lung and liver cases.
Results
The phantom study demonstrated that the effectiveness of the spot pattern in dose rate depends on the number of beams and beam arrangement, and the 3-field arrangement can achieve better optimization effects. In lung cases, using a MMU of 600 (nozzle current of 252nA), scanning pattern optimization increased the average dose rate (V40Gy/s) for the esophagus, heart, spinal cord, and lung-GTV from 38.3 %, 62.8 %, 59.6 % and 61.9 % to 74.4 %, 85.5 %, 83.3 % and 78.6 %, respectively (all p-values < 0.001). When a higher MMU of 1200 (nozzle current of 504nA) was used, the benefits brought by optimization are not as obvious as the previous situation. For all liver cases with an MMU of 600, the average FLASH dose rate (V40Gy/s) for the esophagus, heart, spinal cord, and liver-GTV increased from 60.5 %, 52.7 %, 60.3 %, and 59.1 % to 75.1 %, 69.4 %, 80.2 %, and 75.9 %, respectively, after optimization (all p-values < 0.001). However, when a higher MMU of 1200 was used, the V40Gy/s for all four OARs increased from approximately 93.3 % to 97.0 %, showing only limited additional improvement.
Conclusion
This approach successfully optimized FLASH dose rate coverage for specific OARs, enhancing BP-FLASH effectiveness by improving OAR protection while maintaining dosimetric quality. However, the impact of spot pattern optimization is influenced by factors such as the number of beams, MMU constraints, and spot distribution, with limited effectiveness in significantly increasing the FLASH ratio.
{"title":"Assessing the potential and pitfalls of spot sequence optimization for OAR-specific dose rate control in proton PBS Bragg peak FLASH radiotherapy","authors":"Longfei Diao , Xingyi Zhao , Chingyun Cheng , Tengda Zhang , Shouyi Wei , Dongdong Meng , Zhizhen Wei , Yangguang Ma , Kun Zhu , Hui Wu , Benjamin Durkee , Haibo Lin , Charles B. Simone , Xueqing Yan , Minglei Kang","doi":"10.1016/j.radonc.2025.111291","DOIUrl":"10.1016/j.radonc.2025.111291","url":null,"abstract":"<div><h3>Purpose</h3><div>To evaluate the impact of key treatment planning parameters—including beam arrangement, minimum monitor unit (MMU) settings, and anatomical site variability—on the ability to achieve ultra-high dose rate (UHDR) delivery in Bragg peak FLASH radiotherapy.</div></div><div><h3>Methods</h3><div>FLASH dose rate coverage can be assessed by dose-rate volume histogram (DRVH), thus objective functions based on DRVH can be constructed to optimize the dose rate distribution for individual regions of interest (ROIs). The optimization of each ROI, as part of the final objective function, is integrated into a multi-objective optimization problem that can be solved using a heuristic algorithm. A phantom-based study was conducted to investigate the effect of beam number on optimization performance in proton therapy planning. Treatment plans of 8 consecutive node-negative non-small cell lung cancer and 5 consecutive liver cancer patients were initially optimized, followed by optimizing the spot delivery sequence to enhance dose rate ratios without compromising dose performance. A thorough evaluation was conducted to assess the optimization of the scanning pattern in improving the FLASH ratio of critical OARs in Bragg peak FLASH-RT, considering beam currents, beam arrangement, MMU constraints, and anatomical sites in lung and liver cases.</div></div><div><h3>Results</h3><div>The phantom study demonstrated that the effectiveness of the spot pattern in dose rate depends on the number of beams and beam arrangement, and the 3-field arrangement can achieve better optimization effects. In lung cases, using a MMU of 600 (nozzle current of 252nA), scanning pattern optimization increased the average dose rate (V40Gy/s) for the esophagus, heart, spinal cord, and lung-GTV from 38.3 %, 62.8 %, 59.6 % and 61.9 % to 74.4 %, 85.5 %, 83.3 % and 78.6 %, respectively (all p-values < 0.001). When a higher MMU of 1200 (nozzle current of 504nA) was used, the benefits brought by optimization are not as obvious as the previous situation. For all liver cases with an MMU of 600, the average FLASH dose rate (V40Gy/s) for the esophagus, heart, spinal cord, and liver-GTV increased from 60.5 %, 52.7 %, 60.3 %, and 59.1 % to 75.1 %, 69.4 %, 80.2 %, and 75.9 %, respectively, after optimization (all p-values < 0.001). However, when a higher MMU of 1200 was used, the V40Gy/s for all four OARs increased from approximately 93.3 % to 97.0 %, showing only limited additional improvement.</div></div><div><h3>Conclusion</h3><div>This approach successfully optimized FLASH dose rate coverage for specific OARs, enhancing BP-FLASH effectiveness by improving OAR protection while maintaining dosimetric quality. However, the impact of spot pattern optimization is influenced by factors such as the number of beams, MMU constraints, and spot distribution, with limited effectiveness in significantly increasing the FLASH ratio.</div></div>","PeriodicalId":21041,"journal":{"name":"Radiotherapy and Oncology","volume":"214 ","pages":"Article 111291"},"PeriodicalIF":5.3,"publicationDate":"2025-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145574168","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 : 2025-11-19DOI: 10.1016/j.radonc.2025.111297
Junxian Li , Renhe Liu , Yuchen Xing , Ximin Gao , Qiang Yin , Qian Su
Objectives
This study aims to develop a self-supervised foundational model based on routine MRI and to evaluate its performance in tasks of brain tumor grading and pathological subtype classification.
Methods
We developed the Unified Multimodal Brain Imaging Foundation (UMBIF) model by performing self-supervised learning on 51,029 MRI images from multiple institutions. The model was first trained using a contrastive masked image modeling task to extract robust feature representations. Next, UMBIF was fine-tuned for downstream tasks—glioma grading and histological classification—using multi-center cohorts. Finally, we compared UMBIF model with mainstream convolutional neural networks and machine learning algorithms, evaluating accuracy, sensitivity, specificity, and area under the curve (AUC).
Results
Compared to self-supervised pretraining methods applied to natural images or single large tumor region images, the UMBIF architecture effectively extracted more comprehensive feature representations, leading to superior model performance. The optimal classifier with pretrained weights demonstrated outstanding results on independent test datasets, achieving accuracies of 0.840 (AUC: 0.723) for grade II, 0.684 (AUC: 0.854) for grade III, 0.775 (AUC: 0.743) for grade IV gliomas and 0.903 (AUC: 0.966) for histological classification, respectively, highlighting its potential in clinical decision-making.
Conclusions
The UMBIF model demonstrated robust applicability across clinically relevant glioma-grading formulations and LGG/HGG subtype classification. By enhancing classification performance with pretrained weights and reducing reliance on annotated data, it holds strong clinical potential for improving diagnostic efficiency and decision-making.
{"title":"A foundation model for brain tumor MRI analysis: WHO grading and subtype classification","authors":"Junxian Li , Renhe Liu , Yuchen Xing , Ximin Gao , Qiang Yin , Qian Su","doi":"10.1016/j.radonc.2025.111297","DOIUrl":"10.1016/j.radonc.2025.111297","url":null,"abstract":"<div><h3>Objectives</h3><div>This study aims to develop a self-supervised foundational model based on routine MRI and to evaluate its performance in tasks of brain tumor grading and pathological subtype classification.</div></div><div><h3>Methods</h3><div>We developed the Unified Multimodal Brain Imaging Foundation (UMBIF) model by performing self-supervised learning on 51,029 MRI images from multiple institutions. The model was first trained using a contrastive masked image modeling task to extract robust feature representations. Next, UMBIF was fine-tuned for downstream tasks—glioma grading and histological classification—using multi-center cohorts. Finally, we compared UMBIF model with mainstream convolutional neural networks and machine learning algorithms, evaluating accuracy, sensitivity, specificity, and area under the curve (AUC).</div></div><div><h3>Results</h3><div>Compared to self-supervised pretraining methods applied to natural images or single large tumor region images, the UMBIF architecture effectively extracted more comprehensive feature representations, leading to superior model performance. The optimal classifier with pretrained weights demonstrated outstanding results on independent test datasets, achieving accuracies of 0.840 (AUC: 0.723) for grade II, 0.684 (AUC: 0.854) for grade III, 0.775 (AUC: 0.743) for grade IV gliomas and 0.903 (AUC: 0.966) for histological classification, respectively, highlighting its potential in clinical decision-making.</div></div><div><h3>Conclusions</h3><div>The UMBIF model demonstrated robust applicability across clinically relevant glioma-grading formulations and LGG/HGG subtype classification. By enhancing classification performance with pretrained weights and reducing reliance on annotated data, it holds strong clinical potential for improving diagnostic efficiency and decision-making.</div></div>","PeriodicalId":21041,"journal":{"name":"Radiotherapy and Oncology","volume":"214 ","pages":"Article 111297"},"PeriodicalIF":5.3,"publicationDate":"2025-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145574217","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 : 2025-11-19DOI: 10.1016/j.radonc.2025.111295
Tae Hyun Kim , Jung Won Chun , Sang Myung Woo , Joo-Hyun Chung , Min Hee Lee , Sung-Sik Han , Sang-Jae Park , Sung Uk Lee , Yang-Gun Suh , Sung Ho Moon , Sang Soo Kim , Woo Jin Lee
Purpose
To evaluate the efficacy and safety of hypofractionated simultaneous integrated boost (SIB) − proton beam therapy (PBT) with systemic treatment and also to explore survival-related prognostic factors, including treatment sequencing and dose–response.
Methods
We reviewed 225 consecutive patients with LAPC treated with SIB-PBT (45–50 Gy[RBE] for PTV1 and 30 Gy[RBE] for PTV2 in 10 fractions). The patients were grouped by treatment sequence as follows: PBT after stable disease post-induction chemotherapy (Group I, 48.9 %), PBT after progression post-induction chemotherapy (Group II, 15.6 %), and PBT followed by maintenance chemotherapy (Group III, 35.6 %).
Results
Median overall survival (OS) from first treatment and PBT was 24.2 (95 % CI, 21.7–26.7) and 19.5 (95 % CI, 17.4–21.7) months, respectively. Group I had significantly longer OS than Groups II and III from first treatment (31.1 vs. 21.1 and 19.1 months) and PBT (23.7 vs. 9.9 and 19.1 months) (p < 0.05 each). Patients receiving 50 Gy(RBE) had significantly better OS from first treatment (25.6 vs. 19.3 months; p = 0.001) and a trend towards better OS from PBT (20.3 vs. 18.3 months; p = 0.062). Most acute adverse events were grade 1–2, with late grade ≥ 3 gastrointestinal events in 4 %.
Conclusion
This largest to-date study on PBT for LAPC suggests that hypofractionated SIB-PBT could be a safe and effective local treatment for LAPC. Favorable outcomes were observed with PBT after stable disease following induction chemotherapy, and a potential dose–response relationship was suggested. However, further prospective studies are required to validate our findings.
{"title":"Impact of treatment sequence and dose response on outcomes in locally advanced pancreatic cancer treated with hypofractionated proton beam therapy using simultaneous integrated boost technique","authors":"Tae Hyun Kim , Jung Won Chun , Sang Myung Woo , Joo-Hyun Chung , Min Hee Lee , Sung-Sik Han , Sang-Jae Park , Sung Uk Lee , Yang-Gun Suh , Sung Ho Moon , Sang Soo Kim , Woo Jin Lee","doi":"10.1016/j.radonc.2025.111295","DOIUrl":"10.1016/j.radonc.2025.111295","url":null,"abstract":"<div><h3>Purpose</h3><div>To evaluate the efficacy and safety of hypofractionated simultaneous integrated boost (SIB) − proton beam therapy (PBT) with systemic treatment and also to explore survival-related prognostic factors, including treatment sequencing and dose–response.</div></div><div><h3>Methods</h3><div>We reviewed 225 consecutive patients with LAPC treated with SIB-PBT (45–50 Gy[RBE] for PTV1 and 30 Gy[RBE] for PTV2 in 10 fractions). The patients were grouped by treatment sequence as follows: PBT after stable disease post-induction chemotherapy (Group I, 48.9 %), PBT after progression post-induction chemotherapy (Group II, 15.6 %), and PBT followed by maintenance chemotherapy (Group III, 35.6 %).</div></div><div><h3>Results</h3><div>Median overall survival (OS) from first treatment and PBT was 24.2 (95 % CI, 21.7–26.7) and 19.5 (95 % CI, 17.4–21.7) months, respectively. Group I had significantly longer OS than Groups II and III from first treatment (31.1 vs. 21.1 and 19.1 months) and PBT (23.7 vs. 9.9 and 19.1 months) (<em>p</em> < 0.05 each). Patients receiving 50 Gy(RBE) had significantly better OS from first treatment (25.6 vs. 19.3 months; <em>p</em> = 0.001) and a trend towards better OS from PBT (20.3 vs. 18.3 months; <em>p</em> = 0.062). Most acute adverse events were grade 1–2, with late grade ≥ 3 gastrointestinal events in 4 %.</div></div><div><h3>Conclusion</h3><div>This largest to-date study on PBT for LAPC suggests that hypofractionated SIB-PBT could be a safe and effective local treatment for LAPC. Favorable outcomes were observed with PBT after stable disease following induction chemotherapy, and a potential dose–response relationship was suggested. However, further prospective studies are required to validate our findings.</div></div>","PeriodicalId":21041,"journal":{"name":"Radiotherapy and Oncology","volume":"214 ","pages":"Article 111295"},"PeriodicalIF":5.3,"publicationDate":"2025-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145574237","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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