Radiotherapy and Oncology最新文献

{"title":"Low-dose radiation as a potential strategy for alleviating lung injury caused by radiotherapy combined with immunotherapy: A preclinical study","authors":"Yu Wang ,&nbsp;Jing Zhang ,&nbsp;Yao Liu ,&nbsp;Han Jiang ,&nbsp;Bibo Wu ,&nbsp;Shasha Zhao ,&nbsp;WeiWei Ouyang ,&nbsp;Yinxiang Hu ,&nbsp;Bing Lu ,&nbsp;Shengfa Su","doi":"10.1016/j.radonc.2025.110823","DOIUrl":"10.1016/j.radonc.2025.110823","url":null,"abstract":"<div><h3>Background and Purpose</h3><div>Radiotherapy combined with immunotherapy has been shown to improve thoracic tumor outcomes while increasing the risk of lung injury. Low-dose radiotherapy (LD-RT) has been proven efficient in managing inflammatory diseases. This study aims to investigate whether LD-RT might alleviate lung injury induced by radiotherapy combined with immunotherapy, and attempt to explore its underlying mechanisms thereby offering novel insights for clinical application.</div></div><div><h3>Methods</h3><div>To establish a mouse model of lung injury caused by radiotherapy combined with immunotherapy, C57 BL/6J mice received intraperitoneal injections of programmed death 1(PD-1) inhibitor weekly and a single dose of 15 Gy whole thoracic irradiation. Then they received a single dose of LD-RT at 1.0 Gy or 1.5 Gy on Day 14 or 28. The mice were euthanized on Day 42, and lung tissue samples were collected for HE, Masson’s trichrome, and immunohistochemical staining to evaluate lung tissue damage, fibrosis, and lymphocyte infiltration. The expression levels of cytokine were quantified by the enzyme-linked immunosorbent assay.</div></div><div><h3>Results</h3><div>Both low-dose of 1.0 Gy and 1.5 Gy attenuated lung injury caused by radiotherapy combined with PD-1 inhibitors, but 1.5 Gy was more effective. Compared with Day 14, LD-RT at 1.5 Gy on Day 28 was more effective in alleviating alveolar inflammation and reducing collagen deposition, and inhibiting lymphocyte infiltration and secretion of inflammatory cytokine in lung tissue.</div></div><div><h3>Conclusion</h3><div>Low-dose radiation alleviated lung injury caused by radiotherapy combined with PD-1 inhibitor, and the alleviating effect is closely related to the timing and dose of the radiotherapy administered.</div></div>","PeriodicalId":21041,"journal":{"name":"Radiotherapy and Oncology","volume":"206 ","pages":"Article 110823"},"PeriodicalIF":4.9,"publicationDate":"2025-02-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143493429","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":"An ultra-high dose rate Bragg peak tracking technique provides more affordable proton radiotherapy for cancer patients: From principle to experimental validation","authors":"Shouyi Wei ,&nbsp;Haibo Lin ,&nbsp;Chingyun Cheng ,&nbsp;J. Isabelle Choi ,&nbsp;Charles B. Simone II ,&nbsp;Minglei Kang","doi":"10.1016/j.radonc.2025.110800","DOIUrl":"10.1016/j.radonc.2025.110800","url":null,"abstract":"<div><h3>Purpose</h3><div>This work aims to experimentally validate a novel cost-effective solution for achieving both conventional dose-rate and ultra-high dose rate (UHDR) deliveries in pencil beam scanning proton therapy.</div></div><div><h3>Methods</h3><div>A proton therapy delivery solution was previously developed by our group using only a single pristine Bragg peak of the highest energy proton beams from a cyclotron. This approach streamlines upstream beam modifiers, including energy degrader, selection and focusing systems, while utilizing of universal range shifters (URS) and range compensators (RCs) to preserve high beam transmission efficiency for UHDR beam delivery. It achieves the Bragg peak tracking and target dose conformity, making it potentially suitable for FLASH radiation therapy. In the current study, we highlighted the realization of the solution by using URS and customized beam-specific RCs via simulation in an in-house treatment planning software (TPS) which is then fabricated by a 3D printer, facilitating precise beam shaping and Bragg peak tracking. Experimental validation of this method was conducted using a clinical proton system to showcase a practical solution that can be translated into realistic operation. Both dose and dose rate were measured and compared to treatment planning results.</div></div><div><h3>Results</h3><div>The proton convolution superposition (PCS) dose calculation was benchmarked by the Monte Carlo calculation. Matrixx PT measured the delivered dose in the uniform and head-neck (HN) phantom, and the gamma passing rates were &gt; 99 % in the water phantom. The gamma rate was &gt; 98 % for the HN phantom for this distal tracking method. The measured dose difference between the TPS and HN phantom was &lt; 2 %. The implementation of a high temporal resolution strip ion chamber detector array enabled accurate measurement of the spot time structure, facilitating 3D dose rate reconstruction across various beam currents.</div></div><div><h3>Conclusion</h3><div>The experimental validation successfully demonstrated the dosimetric accuracy and robustness of this proposed delivery method. The employment of the Bragg peak tracking method holds great promise for reducing treatment delivery costs for future UHDR and conventional dose rate proton radiation therapy, ultimately benefiting a larger population of patients.</div></div>","PeriodicalId":21041,"journal":{"name":"Radiotherapy and Oncology","volume":"206 ","pages":"Article 110800"},"PeriodicalIF":4.9,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143484035","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":"Incorporating indirect MRI information in a CT-based deep learning model for prostate auto-segmentation","authors":"Daan Stas ,&nbsp;Geert De Kerf ,&nbsp;Michaël Claessens ,&nbsp;Anna Karlhede ,&nbsp;Jonas Söderberg ,&nbsp;Piet Dirix ,&nbsp;Piet Ost","doi":"10.1016/j.radonc.2025.110806","DOIUrl":"10.1016/j.radonc.2025.110806","url":null,"abstract":"<div><h3>Background and purpose</h3><div>Computed tomography (CT) imaging poses challenges for delineation of soft tissue structures for prostate cancer external beam radiotherapy. Guidelines require the input of magnetic resonance imaging (MRI) information. We developed a deep learning (DL) prostate and organ-at-risk contouring model designed to find the MRI-truth in CT imaging.</div></div><div><h3>Material and Methods</h3><div>The study utilized CT-scan data from 165 prostate cancer patients, with 136 scans for training and 29 for testing. The research focused on contouring five regions of interest (ROIs): clinical target volume of the prostate including the venous plexus (VP) (CTV-iVP) and excluding the VP (CTV-eVP), bladder, anorectum and the whole seminal vesicles (SV) according to The European Society for Radiotherapy and Oncology (ESTRO) and Advisory Committee on Radiation Oncology Practice (ACROP) contouring guidelines. Human delineation included fusion of MRI-imaging with the planning CT-scans in the process, but the model itself has never been shown MRI-images during its development. Model training involved a three-dimensional U-Net architecture. A qualitative review was independently performed by two clinicians scoring the model on time-based criteria and the DL segmentation results were compared to manual adaptations using the Dice similarity coefficient (DSC) and the 95th percentile Hausdorff distance (HD95).</div></div><div><h3>Results</h3><div>The qualitative review of DL segmentations for CTV-iVP and CTV-eVP showed 2 or 3 out of 3 in 96 % of cases, indicating minimal manual adjustments were needed by clinicians. The DL model demonstrated comparable quantitative performance in delineating CTV-iVP and CTV-eVP with a DSC of 89 % with a standard deviation of 3.3 %. HD95 is 4 mm for CTV-iVP and 4.1 mm CTV-eVP with a standard deviation of 2.1 mm for both contours. Anorectum, bladder and SV scored 3 out of 3 in the qualitative analysis in 62 %, 72 % and 55 % of cases respectively. DSC and HD95 are 90 % and 5.5 mm for anorectum, 96 % and 2.9 mm for bladder, and 81 % and 4.6 mm for the seminal vesicles.</div></div><div><h3>Conclusion</h3><div>To our knowledge, this is the first DL model designed to implement MRI contouring guidelines in CT imaging and the first model trained according to ESTRO-ACROP contouring guidelines. This CT-based DL model presents a valuable tool for aiding prostate delineation without requiring the actual MRI information.</div></div>","PeriodicalId":21041,"journal":{"name":"Radiotherapy and Oncology","volume":"206 ","pages":"Article 110806"},"PeriodicalIF":4.9,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143484052","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 performance in radiation oncology: An international systematic review of quality improvement interventions","authors":"Joanna Dodkins ,&nbsp;Georgia Zachou ,&nbsp;Adil Rashid ,&nbsp;Jan van der Meulen ,&nbsp;Julie Nossiter ,&nbsp;Alison Tree ,&nbsp;Ajay Aggarwal","doi":"10.1016/j.radonc.2025.110798","DOIUrl":"10.1016/j.radonc.2025.110798","url":null,"abstract":"<div><div>National cancer audits and registers have highlighted significant national and international variation in patient care and outcomes. Quality Improvement (QI) is mandated in radiation oncology but the interventions designed to support QI in this field remain poorly understood. This paper seeks to assess the types of QI interventions in radiation oncology, the QI evaluation design and their impact on process of care measures and patient-related outcomes. MEDLINE and EMBASE were searched systematically for studies of QI interventions in radiation oncology between 2000 and 2024. The studies needed to identify the quantitative or qualitative impact of the QI intervention on process of care measures or patient-related outcomes. Study results were summarised using narrative synthesis and appraised using the Quality Improvement Minimum Quality Criteria Set (QI-MQCS). 26 papers were included in the analysis. The majority of studies were conducted in the USA (n = 13) and in Europe (n = 7), with only two studies conducted at a national level. Ten studies covered all tumour types, with six specifically focusing on head and neck cancers, two each on prostate and nasopharyngeal cancers, and one study each examining lung, cervical, rectal, and breast cancers. The aspects of care evaluated most frequently were those relating to reducing waiting times or increasing utilisation of radiotherapy as per guidelines (n = 15), followed by those seeking to reduce radiotherapy contouring variability (n = 5) and those involving the management of symptoms during or after radiotherapy treatment (n = 6). Only 42 % of studies reported funding, with the most frequent funding source being national, government or federal (n = 6). All QI interventions across the 26 studies were successful as they resulted in an improvement in a process or patient-related outcome measure. The studies scored between 10 and 15 out of 16, according to the QI-MQCS criteria. Despite substantial investments in cancer research and development, there is a scarcity of information on how to enhance the quality of care in radiation oncology. While there are examples of national cancer audits and registers in a number of countries, much of the research in QI interventions is being conducted in the USA. This situation underscores the need for more comprehensive, well-funded studies and improved training for clinicians to conduct high-quality improvement activities and research. There should be a greater emphasis on the substantial gains that can be achieved by improving existing care in terms of access and outcomes, rather than solely focusing on innovation.</div></div>","PeriodicalId":21041,"journal":{"name":"Radiotherapy and Oncology","volume":"206 ","pages":"Article 110798"},"PeriodicalIF":4.9,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143477110","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum to “GEC-ESTRO ACROP prostate brachytherapy guidelines” [Radiother Oncol. 2022; 167: 244–251]","authors":"Ann Henry ,&nbsp;Bradley R. Pieters ,&nbsp;Frank André Siebert ,&nbsp;Peter Hoskin ,&nbsp;UROGEC group of GEC ESTRO with endorsement by the European Association of Urology","doi":"10.1016/j.radonc.2025.110791","DOIUrl":"10.1016/j.radonc.2025.110791","url":null,"abstract":"","PeriodicalId":21041,"journal":{"name":"Radiotherapy and Oncology","volume":"206 ","pages":"Article 110791"},"PeriodicalIF":4.9,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143444585","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Consensus for a postoperative atlas of sinonasal substructures from a modified Delphi study to guide radiotherapy in sinonasal malignancies","authors":"Florent Carsuzaa ,&nbsp;Valentin Favier ,&nbsp;Lise Seguin ,&nbsp;Mario Turri-Zanoni ,&nbsp;Anna-Maria Camarda ,&nbsp;Benjamin Verillaud ,&nbsp;Philippe Herman ,&nbsp;Daniele Borsetto ,&nbsp;Alberto Schreiber ,&nbsp;Stefano Taboni ,&nbsp;Vittorio Rampinelli ,&nbsp;Alessandro Vinciguerra ,&nbsp;Alperen Vural ,&nbsp;Xavier Liem ,&nbsp;Fabio Busato ,&nbsp;Sophie Renard ,&nbsp;Charles Dupin ,&nbsp;Mélanie Doré ,&nbsp;Pierre Graff ,&nbsp;Yungan Tao ,&nbsp;Juliette Thariat","doi":"10.1016/j.radonc.2025.110784","DOIUrl":"10.1016/j.radonc.2025.110784","url":null,"abstract":"<div><h3>Background</h3><div>Sinonasal and skull base tumor surgery-related morbidity has been reduced by the use of endoscopic endonasal skull base surgery (EESBS). Postoperative radiation therapy (poRT) requires precise definition of target volumes. To enhance the accuracy of poRT planning, histological and radiological correlations are necessary to locate the tumor attachment on poRT CT scans. An accurate atlas of structures resected or identified during EESBS could serve for the interdisciplinary postoperative management of patients, personalizing poRT by adequate radiation dose delivery. The objective of this study was to achieve a consensual segmentation atlas on CT scan with surgeons practicing EESBS and radiation oncologists.</div></div><div><h3>Methods</h3><div>The sinonasal structures relevant for poRT of sinonasal malignancies were determined by a two-round Delphi process. A rating group of 25 European experts in sinonasal malignancies was set up. Consensual structures emerged and were used to determine the anatomical limits of the retained structures to draft an atlas with expert based relevant structures. The atlas was then critically reviewed, discussed, and edited by another 2 skull base surgeons and 2 radiation oncologists.</div></div><div><h3>Results</h3><div>After the two rating rounds, 46 structures obtained a strong agreement, 7 an agreement, 5 were rejected and 5 did not reach consensus. The atlas integrating all the selected structures is presented attached.</div></div><div><h3>Conclusion</h3><div>Consensual segmentation atlas on CT scan might allow, through careful poRT planning to limit the morbidity of poRT while maintaining good local control. Prospective studies are necessary to validate this potential precision medicine-based approach.</div></div>","PeriodicalId":21041,"journal":{"name":"Radiotherapy and Oncology","volume":"206 ","pages":"Article 110784"},"PeriodicalIF":4.9,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143477109","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Electron vs proton FLASH radiation on murine skin toxicity","authors":"Line Kristensen ,&nbsp;Sky Rohrer ,&nbsp;Lone Hoffmann ,&nbsp;Lars H Præstegaard ,&nbsp;Christina Ankjærgaard ,&nbsp;Claus E Andersen ,&nbsp;Eleni Kanouta ,&nbsp;Jacob Graversen Johansen ,&nbsp;Morten Sahlertz ,&nbsp;Jasper Nijkamp ,&nbsp;Per Rugaard Poulsen ,&nbsp;Brita Singers Sørensen","doi":"10.1016/j.radonc.2025.110796","DOIUrl":"10.1016/j.radonc.2025.110796","url":null,"abstract":"<div><h3>Background and purpose</h3><div>Dose-response modification of FLASH has previously been established for acute skin toxicity in protons. This study used a similar experimental setup to quantify the dose–response modification of electron FLASH irradiation for acute skin- and late fibrotic toxicity in mice. The setup similarity enabled quantitative comparison of the acute skin response for electrons to protons.</div></div><div><h3>Method</h3><div>Female unanaesthetised C3D2F1 mice were restrained with the right hindleg fixated and submerged in a water bath for horizontal electron irradiation at 16 MeV. Mice were randomised in groups of varying single doses (19.4–57.6 Gy) and irradiated with either 0.162 Gy/s conventional (CONV) or 233 Gy/s FLASH dose rate using 8–10 mice per group. Acute skin toxicity was assessed daily from the 8th to the 28th day post-irradiation. The same mice were kept for a fibrotic assay of leg extension assessment done biweekly until 52 weeks post-irradiation. The dose-modifying factor (DMF) of FLASH was quantified from dose-response curves.</div></div><div><h3>Results and discussion</h3><div>Electron FLASH irradiated mice showed a considerable skin-sparing effect with a DMF of 1.45–1.54 and a smaller fibrotic-sparing effect with a DMF of 1.15. The development of acute skin toxicity was similar between CONV and FLASH groups with biological equivalent doses based on the DMF. The acute response of the electron irradiations was similar to previous reports on protons.</div></div><div><h3>Conclusion</h3><div>Despite apparent differences, e.g. average and instantaneous dose rates, the acute skin toxicity of electron beams and previously published proton beams were remarkably similar regarding both biological response and quantified acute skin DMFs.</div></div>","PeriodicalId":21041,"journal":{"name":"Radiotherapy and Oncology","volume":"206 ","pages":"Article 110796"},"PeriodicalIF":4.9,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143472886","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dosimetric predictors of toxicity for brainstem metastases and AVMs treated with stereotactic radiosurgery: An international, multi-institutional analysis","authors":"Raj Singh ,&nbsp;Samantha Dayawansa ,&nbsp;Duy Pham ,&nbsp;Georgios Mantziaris ,&nbsp;Selcuk Peker ,&nbsp;Yavuz Samanci ,&nbsp;Ali Haluk Duzkalir ,&nbsp;David Mathieu ,&nbsp;Anne-Marie Langlois ,&nbsp;Molly L. Egnot ,&nbsp;Ronald E. Warnick ,&nbsp;Herwin Speckter ,&nbsp;Erwin Lazo ,&nbsp;Laura Mendez ,&nbsp;Angel I. Blanco ,&nbsp;Mark J. Amsbaugh ,&nbsp;Collin Liu ,&nbsp;Andrea Becerril-Gaitan ,&nbsp;Yoshua Esquenazi ,&nbsp;Ching-Jen Chen ,&nbsp;Jason P. Sheehan","doi":"10.1016/j.radonc.2025.110795","DOIUrl":"10.1016/j.radonc.2025.110795","url":null,"abstract":"<div><h3>Background</h3><div>There are limited data on dosimetric predictors of radiation-induced changes (RICs) for brainstem metastases or arteriovenous malformations (AVMs) following single-fraction stereotactic radiosurgery (SRS).</div></div><div><h3>Methods</h3><div>We examined a multi-institutional cohort of patients with brainstem metastases or AVMs treated with SRS. We evaluated predictors of RICs graded per CTCAE(Common Terminology Criteria for Adverse Events), including D5%, D95%, D0.03 cc, and D0.5 cc (brainstem minus lesion). Univariate logistic regressions were initially performed with independent variables trending towards significance included on multivariate logistic regression.</div></div><div><h3>Results</h3><div>A total of 124 brainstem lesions treated with SRS were analyzed (21 AVMs and 103 metastases). The median prescription dose was 16 Gy(range: 13–23 Gy), and the median treatment volume was 0.48 cc(range: 0.002–11.19 cc). The incidence of RICs was 9.7 % (with 3/12 being Grade 3–4 and no Grade 5). All cases occurred in brainstem metastases, with no cases among those of the midbrain-pons transition. Treatment volumes ≥ 1cc were correlated with a higher symptomatic RIC incidence(6/57 vs. 6/65; <em>p</em> = 0.04). Notably, all RIC cases had a D0.5 cc ≥ 15 Gy(12/87 vs. 0/32). Both D5%≥6 Gy(9/55 vs. 3/69; <em>p</em> = 0.04) and D95%≥1 Gy(7/31 vs. 5/93; <em>p</em> = 0.01) were significantly correlated with higher incidence of RICs and D0.03 cc ≥ 22 Gy was correlated with a lower risk(2/61 vs. 9/63; <em>p</em> = 0.03). On MVA, D0.03 cc ≥ 22 Gy remained a significant predictor of a lower incidence of RICs(odds ratio = -1.72 (95 % CI: −3.32 to −0.12; <em>p</em> = 0.04).</div></div><div><h3>Conclusions</h3><div>Incidence of RICs was low following SRS for brainstem metastases and AVMs. We recommend optimizing radiosurgical plans for D0.5 cc &lt; 15 Gy with consideration of D5% and D95%, with less emphasis on D0.03 cc to allow to meet the former metrics as feasible.</div></div>","PeriodicalId":21041,"journal":{"name":"Radiotherapy and Oncology","volume":"206 ","pages":"Article 110795"},"PeriodicalIF":4.9,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143472884","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PIM kinase inhibition counters resistance to radiotherapy and chemotherapy in human prostate cancer","authors":"Anne Rajkumar-Calkins ,&nbsp;Vinay Sagar ,&nbsp;Jian Wang ,&nbsp;Shania Bailey ,&nbsp;Philip Anderson ,&nbsp;Sarki A. Abdulkadir ,&nbsp;Austin N. Kirschner","doi":"10.1016/j.radonc.2025.110794","DOIUrl":"10.1016/j.radonc.2025.110794","url":null,"abstract":"<div><h3>Purpose</h3><div>PIM kinases are associated with treatment resistance and poor prognosis in prostate cancer through roles in DNA damage response, cellular metabolism, proliferation, and survival. We hypothesized PIM inhibition addresses treatment resistance to radiotherapy and docetaxel in prostate cancer.</div></div><div><h3>Methods</h3><div>PIM inhibition in prostate cancer cell lines was examined by phosphorylated H2AX and colony formations assays. In normal and castrated mice with prostate tumor xenografts, tumor growth was monitored with daily oral PIM inhibition +/- fractionated radiotherapy (RT) or docetaxel. Radiotherapy was given 30 Gy in 15 treatments, mimicking clinical conventional daily treatment over 3 weeks in a translational murine model system.</div></div><div><h3>Results</h3><div>PIM inhibition decreased radiotherapy-induced DNA-damage repair and decreased cell proliferation and survival. In mice, PIM inhibition increased the efficacy of both radiation and docetaxel to reduce tumor size in hormone-dependent and −independent xenografts. Xenografts showed altered gene expression changes, including downregulation of ribosomal pathways and upregulation of cardiomyocyte signaling pathways, due to PIM inhibition as analyzed by RNA-Seq. Immunostaining of multiple proteins, including COX-2 and MDM2, was altered by PIM inhibition.</div></div><div><h3>Conclusions</h3><div>PIM inhibition addresses treatment resistance to docetaxel and radiotherapy in multiple prostate cancer models. Our data provide a strong rationale for testing PIM inhibitors in combination with standard therapies for treatment-resistant high-risk localized or metastatic prostate cancer in clinical trials.</div></div>","PeriodicalId":21041,"journal":{"name":"Radiotherapy and Oncology","volume":"206 ","pages":"Article 110794"},"PeriodicalIF":4.9,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143463443","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neoadjuvant chemoradiotherapy plus sequential tislelizumab followed by surgery for esophageal carcinoma (CRISEC study): A single-arm, bicentric, phase 2 trial","authors":"Jinsong Yang ,&nbsp;Cui Liu ,&nbsp;Zhigang Zuo ,&nbsp;Fengjun Cao ,&nbsp;Zhanjie Zhang ,&nbsp;Bian Wu ,&nbsp;You Qin ,&nbsp;Lu Wen ,&nbsp;Jielin Wei ,&nbsp;Guangqin Xiao ,&nbsp;Shijie Xing ,&nbsp;Yue Qu ,&nbsp;Lei Huang ,&nbsp;Xiaolin Wang ,&nbsp;Buhai Wang ,&nbsp;Kunyu Yang ,&nbsp;Ke Jiang","doi":"10.1016/j.radonc.2025.110797","DOIUrl":"10.1016/j.radonc.2025.110797","url":null,"abstract":"<div><h3>Background and purpose</h3><div>To explore the efficacy and safety of neoadjuvant chemoradiotherapy (NCRT) plus sequential tislelizumab followed by surgery for esophageal squamous cell carcinoma (ESCC).</div></div><div><h3>Materials and methods</h3><div>This single-arm, bicentric, phase 2 trial enrolled patients with resectable or potentially resectable thoracic ESCC to receive neoadjuvant radiotherapy (41.4 Gy in 23 fractions) with concurrent chemotherapy (albumin-bound paclitaxel, 50–100 mg/m², and carboplatin, area under the curve of 2 mg/ml/min, once weekly, five times) plus sequential tislelizumab (200 mg Q3W, three cycles) followed by surgery. The primary endpoint was pathologic complete response (pCR) rate. The secondary endpoints included safety, R0 resection rate, major pathologic response (MPR) rate, disease-free survival (DFS), and overall survival (OS).</div></div><div><h3>Results</h3><div>Of the 30 patients enrolled from January 2021 to October 2022, 24 (80.0 %) completed planned surgery and gained R0 resection (100 %). Among the 24 patients, nine (37.5 %) achieved pCR and 21 (87.5 %) achieved MPR. Ten patients (35.7 %) developed grade 3–4 toxicities during tislelizumab therapy, including lymphopenia (32.1 %), neutropenia (3.6 %), and thrombocytopenia (3.6 %). Grade 5 hematemesis occurred in two patients and both were attributed to aortic invasion. Three patients (12.5 %) developed grade 3 postoperative complications, including pulmonary infection (8.3 %) and hoarseness (4.2 %). After a median follow-up of 35.4 months, the 2-year OS and DFS rates were 83.3 % and 79.2 %, respectively.</div></div><div><h3>Conclusion</h3><div>Sequential tislelizumab after NCRT in ESCC is safe and feasible. Further study is warranted to validate the efficacy of this combination mode.</div></div>","PeriodicalId":21041,"journal":{"name":"Radiotherapy and Oncology","volume":"206 ","pages":"Article 110797"},"PeriodicalIF":4.9,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143468956","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}