International Journal of Radiation Oncology Biology Physics最新文献

{"title":"5-year survival and safety of stereotactic ablative radiotherapy in unresectable locally advanced non-small cell lung cancer patients unfit for concurrent radio-chemotherapy:focus on patterns of local recurrence from the START-NEW-ERA non-randomized phase II trial.","authors":"Fabio Arcidiacono, Paola Anselmo, Michelina Casale, Cristina Zannori, Fabio Loreti, Benedetta Enrico, Valentina Tassi, Alessandro Di Marzo, Marco Italiani, Gustavo Arruda Viani, Ernesto Maranzano, Fabio Trippa","doi":"10.1016/j.ijrobp.2025.08.060","DOIUrl":"https://doi.org/10.1016/j.ijrobp.2025.08.060","url":null,"abstract":"<p><strong>Purpose: </strong>In the early analysis of XXXX phase II trial, SAbR had optimal local control (LC) and promising OS without ≥G3 toxicity in unresectable LA-NSCLC patients unfit for concurrent chemo-radiotherapy. We report the 5-year outcomes with focus on patterns of local recurrence (LR).</p><p><strong>Methods and materials: </strong>SAbR was delivered by V-MAT to primary tumor (T) and regional nodes (N) based on PET-CT. When thoracic failures occurred, we matched the SAbR planning with PET-CT images to accurately assess the LR location, precisely to determine in-field versus out-field recurrence, looking at the specific isodose line within which the LR occurred.</p><p><strong>Results: </strong>50 unresectable LA-NSCLC patients unfit for concurrent ChT-RT were enrolled. Median dose was 45 Gy and 40 Gy in 5 daily fractions to T and N, respectively. After a median follow-up of 72 months (range, 10-108) the 3-, 5-year PFS rates were 26 ± 6%, 26 ± 6%. The 3-, 5-year OS rates were 70 ± 6%, 46 ± 7%. No patients developed ≥G3 late toxicities. The 3-, 5-year LR-FS rates were 64 ± 7%, 64 ± 7%, respectively. Multivariate analysis revealed SCC (p 0.016) and SAbR dose <40 Gy (p 0.044) as significant predictors of LR. 17 patients experienced LR; 14/17 had SCC, 13/17 IIIA or IIIB. Tumors that recurred were all centrally or ultra-centrally located. The LR was higher in patients receiving 35 Gy compared to those receiving at least 40 Gy (p= 0.037).</p><p><strong>Conclusions: </strong>The 5-year outcomes of XXXX trial confirm robust and sustained benefit in terms of safety and effectiveness of SAbR in LA-NSCLC patients unfit for concurrent chemo-radiotherapy.</p>","PeriodicalId":14215,"journal":{"name":"International Journal of Radiation Oncology Biology Physics","volume":" ","pages":""},"PeriodicalIF":6.5,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145137436","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Industry Sponsorship and Disease Site Focus in Therapeutic Radiopharmaceutical Clinical Trials Over the Past Decade.","authors":"Jackson N Howell, Jacob Wilkes, Nichole M Maughan, Ravi B Patel, Brandon Barney, Neil K Taunk, Freddy E Escorcia, Skyler B Johnson, Dustin Boothe","doi":"10.1016/j.ijrobp.2025.09.028","DOIUrl":"10.1016/j.ijrobp.2025.09.028","url":null,"abstract":"<p><strong>Purpose: </strong>Recent regulatory approvals of radiopharmaceutical therapies (RPTs) have brought increased attention to the modality. Knowledge of the RPT clinical trial landscape and its evolution will help practicing radiation oncologists prepare for the next generation of RPTs as they enter routine clinical practice.</p><p><strong>Methods and materials: </strong>We queried ClinicalTrials.gov for therapeutic RPT clinical trials posted between 2014 and 2024. After excluding diagnostic and yttrium-90 [⁹⁰Y] microsphere therapeutic trials, we analyzed each posting. We characterized overall and temporal trends in primary disease site, trial phase, primary and secondary endpoints, industry sponsorship, and radioisotope/radioligand selection. Annual rates of change in trial postings and industry sponsorship were analyzed using Poisson and fractional logistic regression methods.</p><p><strong>Results: </strong>The initial searches yielded 856 RPT clinical trials. After screening, 254 RPT trials were analyzed. The total number of annual trial postings demonstrated considerable growth during this period, with an approximate 13.0% year-over-year increase between 2014 and 2024. Prostate and neuroendocrine gastrointestinal cancers were the most commonly studied disease sites, accounting for 61.8% of trials. Efficacy and safety endpoints were the most common primary and secondary endpoints; however, notably, 24.4% of trials used a patient-reported quality of life indicator as a secondary endpoint. Trials involving lutetium-177 [¹⁷⁷Lu]-based agents accounted for 52.8% of therapeutic RPT trials over the past decade, with iodine-131 [¹³¹I] trials being the second most common at 15.7%. Specifically, ¹⁷⁷Lu-DOTATATE (26.0%) and ¹⁷⁷Lu-PSMA (22.4%) were the most commonly studied RPTs, followed by ¹³¹I (7.5%), radium-223 (²²³Ra, 6.7%), actinium-225 [²²⁵Ac]-PSMA (3.9%), and ¹³¹I-MIBG (3.9%). Nearly half (49.6%) of therapeutic RPT trials reported industry sponsorship, and the proportion of industry-sponsored trials increased consistently after 2017.</p><p><strong>Conclusions: </strong>RPT trials demonstrated consistent growth over the past decade, largely driven by robust industry support, and have predominantly focused on targeted ¹⁷⁷Lu-based RPTs for the treatment of prostate adenocarcinoma and gastrointestinal neuroendocrine tumors.</p>","PeriodicalId":14215,"journal":{"name":"International Journal of Radiation Oncology Biology Physics","volume":" ","pages":""},"PeriodicalIF":6.5,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145113223","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cross-Cancer Analysis Reveals a Distinct Pattern of Immune Modulation During Curative Radiation Therapy.","authors":"Badr Id Said, Giselle M Boukhaled, Benjamin H Lok, Jelena Lukovic, Aruz Mesci, John Waldron, Philip Wong, Ben X Wang, David G Brooks, Michael Milosevic","doi":"10.1016/j.ijrobp.2025.08.039","DOIUrl":"https://doi.org/10.1016/j.ijrobp.2025.08.039","url":null,"abstract":"<p><strong>Purpose: </strong>Radiation therapy (RT) is a cornerstone of curative cancer treatment, yet its immune effects are not fully understood. This study examined systemic immune profile changes in patients undergoing RT for solid tumors.</p><p><strong>Methods and materials: </strong>Patients with localized head and neck cancer, non-small cell lung cancer, rectal cancer, or extremity soft tissue sarcoma treated with curative RT (>45 Gy, 1.8-3 Gy/fraction) were enrolled. Baseline and post-RT (after 45 Gy) blood samples were analyzed using multiplex Luminex cytokine assays and high-dimensional mass cytometry (cytometry by time-of-flight). Immune alterations were correlated with patient outcomes.</p><p><strong>Results: </strong>Thirty-seven patients treated with curative RT for head and neck cancer (n = 8), non-small cell lung cancer (n = 8), rectal cancer (n = 7) or soft tissue sarcoma (n = 14) were enrolled. Approximately 50% of patients received concurrent chemotherapy. At a median follow-up of 21 months, there were 3 local and 12 distant recurrences. Cytokine analysis showed increased C-X-C motif chemokine ligand 12 (P = .044) and monocyte chemoattractant protein-1 (P < .001), both important in monocyte trafficking and mobilization. Consistent with the cytokine changes, cytometry by time-of-flight demonstrated increased monocytes (P < .001) and reduced natural killer and B cells (P < .001). Circulating CD4 effector T cells decreased in patients who developed distant metastases (P = .049) but remained unchanged in recurrence-free patients. These effects were independent of tumor type and chemotherapy, indicating conserved immune changes following RT.</p><p><strong>Conclusions: </strong>We identified a distinct pattern of immune change across all tumor types analyzed in response to RT, with increases in protumoral myeloid cell populations, reductions in B cells and natural killer cells, and a significant decrease in CD4 effector T cells among patients who developed distant metastases.</p>","PeriodicalId":14215,"journal":{"name":"International Journal of Radiation Oncology Biology Physics","volume":" ","pages":""},"PeriodicalIF":6.5,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145085924","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dose reduction in 4D CT imaging: Breathing signal-guided deep learning-driven data acquisition.","authors":"Lukas Wimmert, Tobias Gauerd, Jannis Dickmanne, Christian Hofmanne, Thilo Sentkera, Rene Wernera","doi":"10.1016/j.ijrobp.2025.08.047","DOIUrl":"https://doi.org/10.1016/j.ijrobp.2025.08.047","url":null,"abstract":"<p><strong>Purpose: </strong>4D CT imaging is essential for radiotherapy planning in thoracic tumors. However, current protocols tend to acquire more projection data than is strictly necessary for reconstructing the 4D CT, potentially leading to unnecessary radiation exposure and misalignment with the ALARA (As Low As Reasonably Achievable) principle. We propose a deep learning (DL)-driven approach that uses the patient's breathing signal to guide data acquisition, aiming to acquire only necessary projection data.</p><p><strong>Material and methods: </strong>This retrospective study analyzed 1,415 breathing signals from 294 patients, with a 75/25 training/validation split at patient level. Based on the signals, a DL model was trained to predict optimal beam-on events for projection data acquisition. Model testing was performed on 104 independent clinical 4D CT scans. The performance of the model was assessed by measuring temporal alignment between predicted and optimal beam-on events. To assess the impact on the reconstructed images, each 4D dataset was reconstructed twice: (1) using all clinically acquired projections (reference) and (2) using only the model-selected projections (dose-reduced). Reference and dose-reduced images were compared using Dice coefficients for organ segmentations, deformable image registration (DIR)-based displacement fields, artifact frequency, and tumor segmentation agreement, the latter evaluated in terms of Hausdorff distance and tumor motion ranges.</p><p><strong>Results: </strong>The proposed approach reduced beam-on time and imaging dose by a median of 29% (IQR: 24-35%), corresponding to 11.6 mGy dose reduction for a standard 4D CT CTDIvol of 40 mGy. Temporal alignment between predicted and optimal beam-on events showed marginal differences. Similarly, reconstructed dose-reduced images showed only minimal differences to the reference images, demonstrated by high lung and liver segmentation Dice values, small-magnitude (DIR) displacement fields, and unchanged artifact frequency. Minor deviations of tumor segmentation and motion ranges compared to the reference suggest only minimal impact of the proposed approach on treatment planning.</p><p><strong>Conclusions: </strong>The proposed DL-driven data acquisition approach has the ability to reduce radiation exposure during 4D CT imaging while preserving diagnostic quality, offering a clinically viable, ALARA-adhering solution for 4D CT imaging.</p>","PeriodicalId":14215,"journal":{"name":"International Journal of Radiation Oncology Biology Physics","volume":" ","pages":""},"PeriodicalIF":6.5,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145102949","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nomogram for Risk-Adaptive Estimation of the Locoregional Control Benefit Following Postoperative Radiation Therapy for Pathologic N0 Oral Cavity Cancer: A Retrospective Analysis.","authors":"Max Gau, Jie Su, Shao Hui Huang, Fatimah A Alfaraj, Robert Olson, Gustavo N Marta, Luiz P Kowalski, Hugo F Kohler, Leandro Luongo de Matos, Fabio Y Moraes, Wei Xu, Enrique Sanz-Garcia, Ezra Hahn, John J Kim, Andrew McPartlin, Brian O'Sullivan, C Jillian Tsai, John Waldron, Eitan Prisman, Jonathan C Irish, Christopher M K L Yao, John R de Almeida, David P Goldstein, Andrew Hope, Ali Hosni","doi":"10.1016/j.ijrobp.2025.09.011","DOIUrl":"10.1016/j.ijrobp.2025.09.011","url":null,"abstract":"<p><strong>Purpose: </strong>We constructed a nomogram to define the risk of locoregional failure (LRF) and quantify the association between postoperative radiation therapy (PORT) and LRF, for patients with pathologic T (pT)1 to pT4 N0 oral cavity squamous cell carcinoma (OSCC).</p><p><strong>Methods and materials: </strong>pT1 to PT4N0M0 OSCC cases treated between 1994 and 2017 at 4 tertiary cancer centers were reviewed. Prognostic factors (P < .05) identified in multivariable analysis and clinicopathologically relevant characteristics were used to construct a nomogram to define LRF risk group classification. Subsequently, the association of PORT with outcomes was calculated for each individual risk group.</p><p><strong>Results: </strong>A total of 1094 patients were retrospectively reviewed. Median follow-up was 4.7 years (IQR, 2.9-6.4 years). The nomogram comprised 6 statistically significant factors (pT category, histologic grade, perineural invasion, compromised resection margin [close <5 mm, positive or undetermined], inadequate neck dissection [<18 lymph nodes resected at any side of the planned neck dissection], and nonutilization of PORT), and 3 clinicopathologically relevant factors (oral tongue subsite, lymphovascular invasion, and smoking history). Risk scores were generated by summing the points of the coefficients in the above model, excluding the coefficient of PORT. Four risk groups were identified based on the 3-year LRF probability: low, standard, intermediate, and high (3-year LRF: 6%, 12%, 23%, and 27%, respectively, P < .001). The model demonstrated a C-index of 0.66, indicating that approximately 1 in 3 patients may be misclassified. The use of PORT was associated with a significant reduction of the 3-year LRF in the intermediate- and high-risk groups (19% vs 28%, P = .02 and 22% vs 38%, P = .03, respectively), which translated into improved 3-year overall survival rates (78% vs 70%, P = .04 and 73% vs 45%, P < .001, in the intermediate- and high-risk groups, respectively).</p><p><strong>Conclusions: </strong>Our nomogram and risk group classification could be a clinically relevant tool to facilitate treatment-decision making in the adjuvant setting for individual pT1 to pT4N0M0 OSCC patients based on an estimation of PORT benefit for LRF. The results from this retrospective study must be interpreted with caution, and our proposed model requires validation using prospective data before it can be applied in practice.</p>","PeriodicalId":14215,"journal":{"name":"International Journal of Radiation Oncology Biology Physics","volume":" ","pages":""},"PeriodicalIF":6.5,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145091517","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A systematic study on local failure events post chemoradiotherapy for cervical cancer: understanding the impact of baseline lateral anatomical compartment involvement.","authors":"Lucas Gomes Sapienza, Gustavo Guitmann, Christopher G Morris, Paul G Okunieff, Michelle Suzanne Ludwig, Maria José Leite Gomes, Isidore Daniel Benrubi, Karina E Hew","doi":"10.1016/j.ijrobp.2025.09.015","DOIUrl":"https://doi.org/10.1016/j.ijrobp.2025.09.015","url":null,"abstract":"<p><strong>Purpose: </strong>To dissect the local failure (LF) events, including specific rates by anatomical compartments, after definitive chemoradiotherapy for locally advanced cervical cancer (LACC).</p><p><strong>Methods: </strong>Records of all consecutive women with LACC treated with definitive chemoradiotherapy and image-guided adaptive brachytherapy (IGABT) were reviewed, focusing on the local disease status. No patient received external-beam radiotherapy (EBRT) parametrial boost. Incidence estimations, timing analysis (true persistent disease [TP]) versus new recurrence [NR]), calculations of LF rates by anatomical compartments (at the time of LF detection), and test of association of compartment-specific LF with baseline (at diagnosis) involvement (adjusted odds ratio [aOR]), were performed.</p><p><strong>Results: </strong>Among the 225 patients included (75% FIGO III-IV; 32% IC/IS BT use; median FU 46.2 months), 34 LFs occurred (24 TP; 10 NR), involving 92 anatomical compartments. Isolated LF was the first relapse in 55.9% (19/34), with no events after 3 years, resulting in 6.2% 3-year/5-year overall NR and 16.3% 3-year/5-year overall LF (NR + TP) rates. TP had worse survival compared to NR (2y-OS: 19.1% vs. 72.9%, p=0.04). The most involved compartments were the cervix (79.4%), parametrium (PMT) (61.8%), uterine corpus (33.3%), bladder (14.7%), vagina (11.8%), and mesorectum (2.9%). Recurrence followed the cardinal (CL), uterosacral (USL), and pubocervical (PCL) directions in 58.8%, 35.3%, and 23.5% of cases, respectively. Only two intact PMT at diagnosis developed ipsilateral LF (1.1%, 2/181, CL only), while baseline ipsilateral PMT involvement with hydronephrosis was associated with ipsilateral LF (aOR 22.2, p<0.01, rate: 21.3%, 10/47, involving CL±PCL±USL), but not with contralateral LF (aOR 0.4, p=0.28).</p><p><strong>Conclusion: </strong>In the non-operative setting, the lateral PMT is the second most involved anatomical compartment by LF (>60%) after the cervix (80%). An intact baseline PMT has low frequency (1%) and limited extension (CL only) of ipsilateral failure. In contrast, baseline hydronephrosis is strongly associated with extensive ipsilateral PMT relapse, requiring side-specific treatment intensification.</p>","PeriodicalId":14215,"journal":{"name":"International Journal of Radiation Oncology Biology Physics","volume":" ","pages":""},"PeriodicalIF":6.5,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145091526","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Survival Benefit of Adjuvant Radiation Therapy Following Asparaginase-Based Chemotherapy in Patients With Chemoresponsive Advanced-Stage Extranodal NK/T Cell Lymphoma: A Multicenter Study Using the China Lymphoma Collaborative Group Database.","authors":"Ke Su, Xiao-Rong Hou, Qiu-Zi Zhong, Xin Liu, Li-Ting Qian, Xue-Ying Qiao, Hua Wang, Yuan Zhu, Jian-Zhong Cao, Jun-Xin Wu, Tao Wu, Su-Yu Zhu, Mei Shi, Hui-Lai Zhang, Xi-Mei Zhang, Hang Su, Yu-Qin Song, Jun Zhu, Yu-Jing Zhang, Hui-Qiang Huang, Ying Wang, Xia He, Li-Ling Zhang, Bao-Lin Qu, Yong Yang, Shu-Lian Wang, Shu-Nan Qi, Ye-Xiong Li","doi":"10.1016/j.ijrobp.2025.09.017","DOIUrl":"10.1016/j.ijrobp.2025.09.017","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Purpose: &lt;/strong&gt;Radiation therapy (RT) is an essential component in the first-line treatment of early-stage extranodal NK/T cell lymphoma (ENKTCL) who have received asparaginase (ASP)-based chemotherapy (CT), but its effects on advanced-stage disease are unclear. This study is to evaluate the potential role of adjuvant RT following ASP-based CT for advanced-stage ENKTCL.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods and materials: &lt;/strong&gt;Data for 170 patients with advanced-stage ENKTCL who received ASP-based CT from the China Lymphoma Collaborative Group database were prospectively reviewed. Initial response after CT was classified as complete response (CR), partial response (PR), stable disease (SD), and progressive disease (PD). CR and PR after CT were defined as \"chemoresponsive\" disease. One hundred and five patients received ASP-based CT alone (CT alone), whereas 65 patients received CT followed by RT (CT + RT). Of the 112 chemoresponsive patients achieving CR and PR after CT, 58 patients received additional RT, whereas 54 patients did not. Overall survival (OS) and progression-free survival (PFS) were estimated by the Kaplan-Meier method, and compared using the log-rank test. Univariable Cox regression analysis was initially performed to identify potential factors associated with OS and PFS. Factors with a Pvalue &lt;.2 in univariable analysis were then included in the multivariable analysis to determine the independent prognostic factors for OS and PFS.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;CR, PR, SD, and PD following CT were 32.9%, 32.9%, 4.1%, and 30.0%, respectively. Patients who achieved CR (OS: hazard ratio [HR], 0.14, 95% CI, 0.07-0.27, P &lt; .001; PFS: HR, 0.11, 95% CI, 0.06-0.20, P &lt; .001) and PR (OS: HR, 0.23, 95% CI, 0.13-0.39, P &lt; .001; PFS: HR, 0.18, 95% CI, 0.11-0.30, P &lt; .001) had significantly higher OS and PFS than those who achieved SD and PD. The 5-year OS and PFS rates were 60.6% and 49.0% for CR and PR, with 69.5% and 63.4% for CR, and 54.2% and 39.4% for PR, respectively. The median OS and PFS for SD + PD were 8.1 and 3.6 months, respectively. In 170 patients, CT + RT versus CT alone significantly improved OS and PFS. The OS rates at 2 and 5 years were 68.7% and 60.8% for CT + RT, compared with 44.6% and 26.7% for CT alone (HR, 0.36; 95% CI, 0.21-0.60; P &lt; .001). The corresponding PFS rates were 58.6% and 47.7% for CT + RT, compared with 33.6% and 23.0% for CT alone (HR, 0.41; 95% CI, 0.26-0.65; P &lt; .001). Moreover, in 112 chemoresponsive patients, CT + RT significantly improved OS, with 2- and 5-year OS rates of 77.8% and 69.0% for CT + RT versus 64.5% and 48.0% for CT alone (HR, 0.43; 95% CI, 0.21-0.90; P = .020). Multivariable Cox regression analyses confirmed that radical RT versus no RT was independently associated with improved OS both in all patients (HR, 0.32; 95% CI, 0.15-0.67; P = .002) and chemoresponsive patients (HR, 0.41; 95% CI, 0.17-0.94; P = .044).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;Addition of RT to ASP-based CT provid","PeriodicalId":14215,"journal":{"name":"International Journal of Radiation Oncology Biology Physics","volume":" ","pages":""},"PeriodicalIF":6.5,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145091564","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Adjuvant Chemoradiotherapy Versus Chemotherapy Alone After Resection of Gallbladder Carcinoma: A Real-World, IPTW-Based Cohort Study.","authors":"Qiuyi Zheng, Bei Lyu, Yixing Chen, Shujung Hsu, Yang Zhang, Siwei Wang, Houbao Liu, Tao Suo, Zhaochong Zeng, Shisuo Du","doi":"10.1016/j.ijrobp.2025.09.023","DOIUrl":"https://doi.org/10.1016/j.ijrobp.2025.09.023","url":null,"abstract":"<p><strong>Purpose: </strong>To compare overall survival (OS) and disease-free survival (DFS) in patients with advanced resectable gallbladder carcinoma (GBC) receiving radical resection followed by chemoradiotherapy (S+CRT) or chemotherapy alone (S+CT).</p><p><strong>Methods and materials: </strong>This real-world study included 239 patients (pT2-4, N0-2, M0) treated between February 2017 and November 2021. Inverse probability of treatment weighting (IPTW) was applied to balance baseline variables between S+CRT and S+CT groups. Kaplan-Meier analysis and Cox regression were used to evaluate survival. Predefined subgroups analyses were conducted for 77 patients with incidental GBC and 94 patients with nodal metastasis (pN+). Adverse events and recurrence patterns were recorded for the entire cohort.</p><p><strong>Results: </strong>Median follow-up was 57.4 months. IPTW created 472.6 weighted patients with well-balanced characteristics. S+CRT was associated with higher OS and DFS at 1, 3, and 5 years compared to S+CT (OS: 90.5%, 71.9%, 65.8% vs. 81.6%, 56.1%, 50.1%; DFS: 77.8%, 65.1%, 57.7% vs. 63.1%, 45.3%, 42.6%). Median OS and DFS were not reached in the S+CRT group. In the incidental GBC subgroup, survival differences were not statistically significant overall, but a landmark analysis beyond 24 months revealed improved OS favoring S+CRT (P=0.011). Similarly, in the subgroup with nodal metastasis (pN+), adjuvant CRT was associated with a significant improvement in DFS.</p><p><strong>Conclusions: </strong>Postoperative CRT significantly improved OS and DFS in balanced patients with stage II-IV GBC. A delayed OS benefit was observed in patients with incidental GBC, while patients with nodal metastasis also experienced significantly improved DFS. Although intrahepatic recurrence remained predominant, CRT notably reduced local failures without significantly increasing treatment-related toxicity.</p>","PeriodicalId":14215,"journal":{"name":"International Journal of Radiation Oncology Biology Physics","volume":" ","pages":""},"PeriodicalIF":6.5,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145085530","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Activation of Angiotensin Converting Enzyme 2 (ACE2) Mitigates Gastrointestinal Acute Radiation Syndrome (GI-ARS).","authors":"Guru Prasad Sharma, Austen Nissen, Tracy Gasperetti, Jamie Foeckler, Anne C Frei, Rachel Kuehn, Melany Gerhartz, Pete Heinzelman, Philip A Romero, Joseph Zenga, Heather A Himburg","doi":"10.1016/j.ijrobp.2025.09.021","DOIUrl":"https://doi.org/10.1016/j.ijrobp.2025.09.021","url":null,"abstract":"<p><strong>Purpose: </strong>In a radiation mass casualty event, exposed populations will suffer dose-dependent toxicity to multiple-organ systems. Although several therapies are FDA-approved for treatment of the hematopoietic acute radiation syndrome (H-ARS), there are no FDA-approved medical countermeasures (MCM) for either acute gastrointestinal injury (GI) or multi-organ delayed effects of acute radiation exposure (DEARE). Prior data suggest activation of the alternative renin angiotensin system (RAS) enzyme angiotensin-converting enzyme 2 (ACE2) has therapeutic potential for mitigating multi-organ radiation injury, including GI-ARS. Here, we evaluated whether activation of ACE2 mitigates GI-ARS in rodent models and protects against DEARE in GI-ARS survivors.</p><p><strong>Methods and materials: </strong>GI recovery was assessed following treatment with ACE2 activator diminazene aceturate (DIZE) or an engineered form of the ACE2 protein with enhanced catalytic activity (ACE2 T371L/Y510Ile) in rodent partial body irradiation (PBI) models. Single cell RNA sequencing was performed following irradiation and DIZE treatment to assess the cellular target of ACE2 activation. Mitigation of DEARE was assessed in a cohort of ARS survivors following DIZE-treatment.</p><p><strong>Results: </strong>Radiation induced a marked loss of GI ACE2 expression, most notably within mature enterocyte populations. ACE2 activation accelerated recovery of intestinal progenitor cells with high proliferative capacity and mucosal defense function. Following 13.5 Gy PBI, DIZE improved survival in male rats during both ARS (days 0-30; p=0.0008) and DEARE (days 30-200; p<0.0001) compared to vehicle control. In female rats exposed to 13.5 Gy PBI, DIZE-treatment improved all-cause morbidity through ARS and DEARE following 13.5 Gy PBI (p=0.0025). Treatment with catalytically enhanced ACE2 variant T371L/Y510Ile accelerated recovery of ACE2 expression and improved survival during GI-ARS in male C57BL/6 mice exposed to 12.5 Gy PBI (p=0.038).</p><p><strong>Conclusions: </strong>Activation of ACE2 promotes GI recovery during GI-ARS and mitigates lethal DEARE. Together, these data demonstrate alternative RAS enzyme ACE2 expression within the GI tract regulates radiation response and the alternative RAS axis is targetable for development of MCM.</p>","PeriodicalId":14215,"journal":{"name":"International Journal of Radiation Oncology Biology Physics","volume":" ","pages":""},"PeriodicalIF":6.5,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145085226","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Improving Radiation Therapy in Pancreatic Cancer Through Radiosensitization Strategies.","authors":"Julie Dardare, Nicolas Martz, Andréa Witz, Margaux Betz, Cassandra Michel, Pauline Gilson, Jean-Louis Merlin, Aurélien Lambert, Alexandre Harle","doi":"10.1016/j.ijrobp.2025.09.013","DOIUrl":"10.1016/j.ijrobp.2025.09.013","url":null,"abstract":"<p><p>Radiation therapy (RT) is a mainstay of treatment for a myriad of cancers; however, it remains a controversial option in the management of patients with pancreatic cancer. The prognosis for this disease remains one of the poorest, despite recent advances in chemotherapy, which still has limited efficacy and suffers from multiple forms of resistance. The application of RT in patients with pancreatic cancer remains largely institution and provider dependent. Despite advances in RT where higher doses can be delivered while sparing adjacent normal organs, local control remains a problem, highlighting the necessity for improvements in the current RT approach. Emerging strategies are currently being developed with the aim of improving the effects of RT using \"radiosensitization\" mechanisms. The objective of radiosensitization is to either enhance DNA damage induced by RT or to prevent its repair or to impair the RT-resistance-associated components of the tumor. The process of radiosensitization can be achieved through the use of conventional chemotherapy agents or by novel molecules that inhibit DNA damage response effectors, as well as cell cycle checkpoints. Additionally, nanoparticles with a high atomic number have the potential to act as radiosensitizers by enhancing the effects of RT specifically in tumor cells. Another avenue of radiosensitization entails the combination of immunotherapy with immune checkpoint inhibitors to increase the immunomodulatory impact of RT. The radiosensitivity of pancreatic ductal adenocarcinoma may also be enhanced by targeting components of the tumor microenvironment or metabolic characteristics associated with resistance to RT. This review aims to provide a comprehensive overview of cutting-edge radiosensitization strategies, from their initial preclinical studies to their current status in clinical trials.</p>","PeriodicalId":14215,"journal":{"name":"International Journal of Radiation Oncology Biology Physics","volume":" ","pages":""},"PeriodicalIF":6.5,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145085952","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}