Radiotherapy and Oncology最新文献

{"title":"In vivo measurements of change in tissue oxygen level during irradiation reveal novel dose rate dependence","authors":"Veljko Grilj ,&nbsp;Ron J. Leavitt ,&nbsp;Mirna El Khatib ,&nbsp;Ryan Paisley ,&nbsp;Javier Franco-Perez ,&nbsp;Benoit Petit ,&nbsp;Paola Ballesteros-Zebadua ,&nbsp;Marie-Catherine Vozenin","doi":"10.1016/j.radonc.2024.110539","DOIUrl":"10.1016/j.radonc.2024.110539","url":null,"abstract":"<div><h3>Background and purpose</h3><p>This study aimed to investigate the radiochemical oxygen depletion (ROD) <em>in vivo</em> by directly measuring oxygen levels in various mouse tissues during ultra-high dose rate (UHDR) irradiation at clinically relevant doses and dose rates.</p></div><div><h3>Materials and methods</h3><p>Mice bearing subcutaneous human glioblastoma (U-87 MG) tumors were used for tumor and normal tissue (skin, muscle, brain) measurements. An oxygen-sensitive phosphorescent probe (Oxyphor PtG4) was injected into the tissues, and oxygen levels were monitored using a fiberoptic phosphorometer during UHDR irradiation with a 6 MeV electron linear accelerator (LINAC). Dose escalation experiments (10–40 Gy) were performed at a dose rate of 1300 Gy/s, and dose rate escalation experiments were conducted at a fixed dose of 40 Gy with dose rates ranging from 2 to 101 Gy/s.</p></div><div><h3>Results</h3><p>Radiation-induced change in tissue oxygenation (ΔpO₂) increased linearly with dose and correlated with baseline tissue oxygenation levels in the range of 0 – 30 mmHg. At higher baseline tissue oxygenation levels, such as those observed in muscle and brain, there was no corresponding increase in ΔpO₂. When we modulated dose rate, ΔpO₂ increased steeply up to ∼ 20 Gy/s and plateaued thereafter. The relationship between ΔpO₂ and dose rate showcases the interplay between ROD and reoxygenation.</p></div><div><h3>Conclusion</h3><p>While UHDR irradiation induces measurable oxygen depletion in tissues, the observed changes in oxygenation levels do not support the hypothesis that ROD-induced radioresistance is responsible for the FLASH tissue-sparing effect at clinically relevant doses and dose rates. These findings highlight the need for further investigation into alternative mechanisms underlying the FLASH effect.</p></div>","PeriodicalId":21041,"journal":{"name":"Radiotherapy and Oncology","volume":"201 ","pages":"Article 110539"},"PeriodicalIF":4.9,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0167814024035175/pdfft?md5=b4337bb6a3f261242773e43998625d1b&pid=1-s2.0-S0167814024035175-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142270939","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":"Artificial intelligence uncertainty quantification in radiotherapy applications − A scoping review","authors":"Kareem A. Wahid ,&nbsp;Zaphanlene Y. Kaffey ,&nbsp;David P. Farris ,&nbsp;Laia Humbert-Vidan ,&nbsp;Amy C. Moreno ,&nbsp;Mathis Rasmussen ,&nbsp;Jintao Ren ,&nbsp;Mohamed A. Naser ,&nbsp;Tucker J. Netherton ,&nbsp;Stine Korreman ,&nbsp;Guha Balakrishnan ,&nbsp;Clifton D. Fuller ,&nbsp;David Fuentes ,&nbsp;Michael J. Dohopolski","doi":"10.1016/j.radonc.2024.110542","DOIUrl":"10.1016/j.radonc.2024.110542","url":null,"abstract":"<div><h3>Background/purpose</h3><p>The use of artificial intelligence (AI) in radiotherapy (RT) is expanding rapidly. However, there exists a notable lack of clinician trust in AI models, underscoring the need for effective uncertainty quantification (UQ) methods. The purpose of this study was to scope existing literature related to UQ in RT, identify areas of improvement, and determine future directions.</p></div><div><h3>Methods</h3><p>We followed the PRISMA-ScR scoping review reporting guidelines. We utilized the population (human cancer patients), concept (utilization of AI UQ), context (radiotherapy applications) framework to structure our search and screening process. We conducted a systematic search spanning seven databases, supplemented by manual curation, up to January 2024. Our search yielded a total of 8980 articles for initial review. Manuscript screening and data extraction was performed in Covidence. Data extraction categories included general study characteristics, RT characteristics, AI characteristics, and UQ characteristics.</p></div><div><h3>Results</h3><p>We identified 56 articles published from 2015 to 2024. 10 domains of RT applications were represented; most studies evaluated auto-contouring (50 %), followed by image-synthesis (13 %), and multiple applications simultaneously (11 %). 12 disease sites were represented, with head and neck cancer being the most common disease site independent of application space (32 %). Imaging data was used in 91 % of studies, while only 13 % incorporated RT dose information. Most studies focused on failure detection as the main application of UQ (60 %), with Monte Carlo dropout being the most commonly implemented UQ method (32 %) followed by ensembling (16 %). 55 % of studies did not share code or datasets.</p></div><div><h3>Conclusion</h3><p>Our review revealed a lack of diversity in UQ for RT applications beyond auto-contouring. Moreover, we identified a clear need to study additional UQ methods, such as conformal prediction. Our results may incentivize the development of guidelines for reporting and implementation of UQ in RT.</p></div>","PeriodicalId":21041,"journal":{"name":"Radiotherapy and Oncology","volume":"201 ","pages":"Article 110542"},"PeriodicalIF":4.9,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0167814024035205/pdfft?md5=3b2ec20e65e19cce054e8f3257230cf7&pid=1-s2.0-S0167814024035205-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142270958","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":"Local control and toxicity after stereotactic radiotherapy in brain metastases patients and the impact of novel systemic treatments","authors":"P. van Schie ,&nbsp;R.G. Huisman ,&nbsp;T. Wiersma ,&nbsp;J.L. Knegjens ,&nbsp;A. Navran ,&nbsp;D. Brandsma ,&nbsp;A. Compter ,&nbsp;M. Bot ,&nbsp;J. Hoogmoed ,&nbsp;P.C. de Witt Hamer ,&nbsp;R. Post ,&nbsp;G.R. Borst","doi":"10.1016/j.radonc.2024.110540","DOIUrl":"10.1016/j.radonc.2024.110540","url":null,"abstract":"<div><h3>Background and purpose</h3><p>Treatment modalities for patients with brain metastases consist of surgery, radiotherapy, and systemic treatments such as immunotherapy and targeted therapy. Although much is known about local control of brain metastases after radiotherapy and surgery alone, more understanding is needed of the additional effect of new systemic treatments. Our study presents real-world data about the combined effects of different local and systemic treatment strategies on local response of irradiated brain metastases.</p></div><div><h3>Materials and methods</h3><p>We performed a retrospective consecutive cohort study of patients that presented with brain metastases in our institution between June 2018 and May 2020, reporting the impact of radiotherapy alone versus radiotherapy combined with systemic treatment on local control of irradiated brain metastases and toxicity. Chemotherapy and targeted therapy were temporarily discontinued around irradiation.</p></div><div><h3>Results</h3><p>262 consecutively treated patients were included in the study. Median time to local failure of irradiated brain metastases was 18 months (IQR 9–34), median overall survival was 20 months (IQR 10–36). 211 (81 %) patients received systemic treatment. Patients with breast cancer had a worse local control (HR 2.3, 95 % CI 1.0–5.0, p = 0.038), as did patients without any systemic treatment (HR 2.1, 95 % CI 1.1–4.3, p = 0.034). Symptomatic radiation necrosis occurred in 36 (14 %) patients. A diameter &gt; 2.5 cm was associated with a higher risk of radiation necrosis. No association was found between systemic treatment in combination with local radiotherapy and symptomatic radiation necrosis.</p></div><div><h3>Conclusion</h3><p>Patients who received any form of systemic treatment had better local control after stereotactic radiosurgery for brain metastases. We did not find an association between systemic treatment and the incidence of radiation necrosis.</p></div>","PeriodicalId":21041,"journal":{"name":"Radiotherapy and Oncology","volume":"200 ","pages":"Article 110540"},"PeriodicalIF":4.9,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0167814024035187/pdfft?md5=d1d5cb2c7fa1eb95fb3ac660af350f97&pid=1-s2.0-S0167814024035187-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142238041","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":"A multi-institutional study to investigate the sparing effect after whole brain electron FLASH in mice: Reproducibility and temporal evolution of functional, electrophysiological, and neurogenic endpoints","authors":"Olivia G.G. Drayson ,&nbsp;Stavros Melemenidis ,&nbsp;Nikita Katila ,&nbsp;Vignesh Viswanathan ,&nbsp;Enikö A. Kramár ,&nbsp;Richard Zhang ,&nbsp;Rachel Kim ,&nbsp;Ning Ru ,&nbsp;Benoit Petit ,&nbsp;Suparna Dutt ,&nbsp;Rakesh Manjappa ,&nbsp;M. Ramish Ashraf ,&nbsp;Brianna Lau ,&nbsp;Luis Soto ,&nbsp;Lawrie Skinner ,&nbsp;Amu S. Yu ,&nbsp;Murat Surucu ,&nbsp;Peter G. Maxim ,&nbsp;Paola Zebadua-Ballasteros ,&nbsp;Marcelo A. Wood ,&nbsp;Charles L. Limoli","doi":"10.1016/j.radonc.2024.110534","DOIUrl":"10.1016/j.radonc.2024.110534","url":null,"abstract":"<div><h3>Background and Purpose</h3><div>Ultra-high dose-rate radiotherapy (FLASH) has been shown to mitigate normal tissue toxicities associated with conventional dose rate radiotherapy (CONV) without compromising tumor killing in preclinical models. A prominent challenge in preclinical radiation research, including FLASH, is validating both the physical dosimetry and the biological effects across multiple institutions.</div></div><div><h3>Materials and Methods</h3><div>We previously demonstrated dosimetric reproducibility of two different electron FLASH devices at separate institutions using standardized phantoms and dosimeters. In this study, tumor-free adult female mice were given 10 Gy whole brain FLASH and CONV irradiation at both institutions and evaluated for the reproducibility and temporal evolution of multiple neurobiological endpoints.</div></div><div><h3>Results</h3><div>FLASH sparing of behavioral performance on novel object recognition (4 months post-irradiation) and of electrophysiologic long-term potentiation (LTP, 5 months post-irradiation) was reproduced between institutions. Differences between FLASH and CONV on the endpoints of hippocampal neurogenesis (Sox2, doublecortin), neuroinflammation (microglial activation), and electrophysiology (LTP) were not observed at early times (48 h to 2 weeks), but recovery of immature neurons by 3 weeks was greater with FLASH.</div></div><div><h3>Conclusion</h3><div>In summary, we demonstrated reproducible FLASH sparing effects on the brain between two different beams at two different institutions with validated dosimetry. FLASH sparing effects on the endpoints evaluated manifested at later but not the earliest time points.</div></div>","PeriodicalId":21041,"journal":{"name":"Radiotherapy and Oncology","volume":"201 ","pages":"Article 110534"},"PeriodicalIF":4.9,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142294140","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":"Automated dose evaluation on daily cone-beam computed tomography for breast cancer patients","authors":"Maureen Groot Koerkamp ,&nbsp;Peter Stijnman ,&nbsp;Antonetta Houweling,&nbsp;Cornel Zachiu,&nbsp;Alexis Kotte,&nbsp;Bas Raaymakers","doi":"10.1016/j.radonc.2024.110541","DOIUrl":"10.1016/j.radonc.2024.110541","url":null,"abstract":"<div><h3>Background and purpose</h3><p>Our goal was to develop a workflow to automatically evaluate delivered dose on daily cone beam computed tomography (CBCT) in all breast cancer patients to assess dosimetric impact of anatomical changes and guide decision-making for offline plan adaptation.</p></div><div><h3>Materials and methods</h3><p>The workflow automatically processes the daily CBCTs of all breast cancer patients receiving local and locoregional radiotherapy. The planning-CT is registered to the CBCT to create a synthetic CT and propagate contours. A forward dose calculation is performed, and DVH parameters are extracted and printed in a report. We evaluated the workflow on a group level and in a subset of 30 patients on a patient-specific level, including comparison to clinical evaluation on additional planning-CT in 10 patients.</p></div><div><h3>Results</h3><p>7454 fractions in 647 patients were analyzed over a period of seven months. Median breast clinical target volume V95% was ≥ 95 % for 97 % of the patients. The workflow would have provided useful additional insights for decision-making for the requirement of plan adaptation, based on debatable disagreement with the clinical decision in half of the cases with an additional planning-CT. The workflow also identified cases with suboptimal coverage not identified in the clinical procedure.</p></div><div><h3>Conclusion</h3><p>We developed a fully automated workflow for dose evaluation on daily CBCT for local and locoregional breast radiotherapy. We have demonstrated its potential for aiding decision-making for plan adaptation in patients with changing anatomy and its capability to highlight patients that may receive suboptimal treatment and require closer clinical evaluation of treatment quality.</p></div>","PeriodicalId":21041,"journal":{"name":"Radiotherapy and Oncology","volume":"200 ","pages":"Article 110541"},"PeriodicalIF":4.9,"publicationDate":"2024-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0167814024035199/pdfft?md5=feba6d707e3cb0e09256ed74d3bc288b&pid=1-s2.0-S0167814024035199-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142238836","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":"GEC-ESTRO recommendations for head & neck cancer brachytherapy (interventional radiotherapy): 2nd update with focus on HDR and PDR","authors":"J.L. Guinot ,&nbsp;W. Bacorro ,&nbsp;A. Budrukkar ,&nbsp;F. Bussu ,&nbsp;V. Gonzalez-Perez ,&nbsp;R. Jaberi ,&nbsp;R. Martinez-Monge ,&nbsp;A. Rembielak ,&nbsp;A. Rovirosa ,&nbsp;V. Strnad ,&nbsp;Z. Takácsi-Nagy ,&nbsp;L. Tagliaferri ,&nbsp;the Head & Neck and Skin Working Group of GEC-ESTRO","doi":"10.1016/j.radonc.2024.110533","DOIUrl":"10.1016/j.radonc.2024.110533","url":null,"abstract":"<div><div>Modern brachytherapy (BT) is playing an important role in the multidisciplinary treatment of Head and Neck (H&amp;N) cancer, as an organ- and function-preserving therapy. Low-dose-rate (LDR) technology has been replaced by modern remote afterloading and stepping source equipment using pulsed dose rate (PDR) or high dose rate (HDR) sources, improved image guidance and 3D treatment planning systems. This is an update of the previous GEC-ESTRO recommendations for H&amp;N tumors, mainly applied to squamous carcinomas. Indications, results and recommended doses for different tumor sites are presented according to the published studies.</div></div>","PeriodicalId":21041,"journal":{"name":"Radiotherapy and Oncology","volume":"201 ","pages":"Article 110533"},"PeriodicalIF":4.9,"publicationDate":"2024-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142294142","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":"Fructose 1,6-bisphosphate aldolase: A promising prognostic marker for oral cancer and its role in radiotherapy response","authors":"Rekha Thiruvengadam ,&nbsp;Seung-Hyun Kim ,&nbsp;Muthu Thiruvengadam","doi":"10.1016/j.radonc.2024.110537","DOIUrl":"10.1016/j.radonc.2024.110537","url":null,"abstract":"<div><p>Oral cancer remains a significant global health concern and its early detection plays a crucial role in improving patient outcomes. Identifying reliable prognostic markers is essential to guide treatment decisions and enhance survival rates. Fructose 1,6-bisphosphate aldolase (FBA), a glycolytic enzyme, has emerged as a promising candidate for prognostic assessment of oral cancer. This review highlights the role of FBA in tumorigenesis, its potential utility in predicting disease progression and patient survival, and its influence on response to radiotherapy. Recent studies have suggested that dysregulated metabolic pathways involving FBA may contribute to radiation resistance in oral cancer, emphasizing the need for further exploration of FBA-targeted therapeutic strategies. Understanding the role of FBA in oral cancer pathogenesis could pave the way for the development of personalized treatment strategies, including combined radiotherapy.</p></div>","PeriodicalId":21041,"journal":{"name":"Radiotherapy and Oncology","volume":"200 ","pages":"Article 110537"},"PeriodicalIF":4.9,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142238047","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":"Intra-prostatic recurrences after radiotherapy with focal boost: Location and dose mapping in the FLAME trial","authors":"K. Menne Guricová ,&nbsp;F.J. Pos ,&nbsp;I.G. Schoots ,&nbsp;W.V. Vogel ,&nbsp;L.G.W. Kerkmeijer ,&nbsp;E.M. Monninkhof ,&nbsp;J.C.J. de Boer ,&nbsp;J.R.N. van der Voort van Zyp ,&nbsp;M. Kunze-Busch ,&nbsp;R.J. Smeenk ,&nbsp;C. Draulans ,&nbsp;K. Haustermans ,&nbsp;P.J. van Houdt ,&nbsp;U.A. van der Heide","doi":"10.1016/j.radonc.2024.110535","DOIUrl":"10.1016/j.radonc.2024.110535","url":null,"abstract":"<div><h3>Introduction</h3><div>The FLAME trial demonstrated that the dose to the gross tumor volume (GTV) is associated with tumour control in prostate cancer patients. This raises the question if dose de-escalation to the remaining prostate gland can be considered. Therefore, we investigated if intraprostatic recurrences occur at the location of the GTV and which dose was delivered at that location.</div></div><div><h3>Materials and methods</h3><div>For FLAME trial patients with an intra-prostatic recurrence, we collected pre-treatment images, GTV delineations, dose distributions and post-recurrence images. Pre-treatment images were registered to the post-recurrence images (PSMA-PET CT). An overlap between GTV and PSMA-PET activity was considered an intra-prostatic recurrence at the location of the primary tumor.</div></div><div><h3>Results</h3><div>Twenty eight out of 535 patients in the FLAME trial had an intra-prostatic recurrence. Its location could be determined for 24 patients. One patient recurred in the prostate gland outside the GTV. The median near-minimum dose to the GTV (D98%) was 76.5 Gy (range: 73.3–86.5 Gy). Only one patient with a recurrence in the GTV received a substantial focal boost of 86.5 Gy. The D98% of all remaining patients was &lt; 81 Gy.</div></div><div><h3>Conclusion</h3><div>Intra-prostatic recurrences of intermediate- and high-risk prostate cancer patients treated with radiotherapy appeared predominantly at the location of the primary tumor. All but one patient did not receive a high dose to the GTV. Intra-prostatic failure is likely a consequence of the undertreatment of the primary tumor rather than the undertreatment of the remaining prostate gland.</div></div>","PeriodicalId":21041,"journal":{"name":"Radiotherapy and Oncology","volume":"201 ","pages":"Article 110535"},"PeriodicalIF":4.9,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142294143","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":"Prognostic factors in post-prostatectomy salvage radiotherapy setting with and without hormonotherapy: An individual patient data analysis of randomized trials from ICECaP database","authors":"Pascal Pommier ,&nbsp;Wanling Xie ,&nbsp;Praful Ravi ,&nbsp;Christian Carrie ,&nbsp;James J. Dignam ,&nbsp;Felix Feng ,&nbsp;Paul Sargos ,&nbsp;Silke Gillessen Sommer ,&nbsp;Daniel E. Spratt ,&nbsp;Bertrand Tombal ,&nbsp;Hendrik Van Poppel ,&nbsp;Christopher Sweeney","doi":"10.1016/j.radonc.2024.110532","DOIUrl":"10.1016/j.radonc.2024.110532","url":null,"abstract":"<div><h3>Background</h3><p>Early salvage radiotherapy (SRT) is the standard of care for biochemical recurrence post-prostatectomy but outcomes are heterogeneous.</p></div><div><h3>Objective</h3><p>To develop a risk scoring system based on relevant standard-of-care clinico-pathological prognostic factors for patients treated with SRT with and without hormonal therapy (HT).</p></div><div><h3>Design, setting, and participants</h3><p>The Intermediate Clinical Endpoints in Cancer of the Prostate (ICECaP) database included three randomized trials (Individual patients’ data from 1647 subjects) assessing SRT (GETUG-AFU-16; NRG/RTOG-9601, and a subset of EORTC-22911).</p></div><div><h3>Outcome measurements and statistical analysis</h3><p>Outcomes were clinical progression (CP). metastasis free-survival (MFS) and overall survival (OS). Clinico-pathological factors, including pathological Gleason Score (GS), PSA at SRT start, margin status, persistent PSA post-RP and time from RP to SRT were evaluated by multivariable models stratified by type of treatment.</p></div><div><h3>Results and limitations</h3><p>On multivariable analysis PSA ≥ 0.5 ng/mL at SRT start, GS ≥ 8 and negative margin status were the three strongest prognostic factors. Three prognostic groups defined by number of these risk features (high risk: 2 or 3; intermediate risk: 1 and low risk: 0) were strongly associated with OS, MFS and CP outcomes with SRT alone or with HT. This prognostic group definition was also relevant for patients with persistent PSA post RP and for patients treated &lt; 1 year from RP to SRT and with and without HT.</p></div><div><h3>Conclusion</h3><p>A risk score for patients receiving SRT with or without HT, using three standard-of-care clinico-pathological risk factors provides refined prognostic information for individual patient counselling.</p></div><div><h3>Patient summary</h3><p>By using a composite score of pathology grading (Gleason Score), PSA at start of salvage radiation and margin status data, physicians can provide patients with more refined information on the risk of a second relapse after receiving radiation to the prostate bed after a prostatectomy for a rising or persistent PSA, both with and without hormonal therapy.</p></div>","PeriodicalId":21041,"journal":{"name":"Radiotherapy and Oncology","volume":"201 ","pages":"Article 110532"},"PeriodicalIF":4.9,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0167814024035102/pdfft?md5=7cda79fcf2d454970bd27af483cccf5b&pid=1-s2.0-S0167814024035102-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142270938","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":"Enhanced radiosensitivity of pancreatic cancer achieved through inhibition of Cyclin-dependent kinase 1","authors":"Stetson Van Matre ,&nbsp;Saaimatul Huq ,&nbsp;Lokesh Akana ,&nbsp;Daniel E. Eldridge ,&nbsp;Oscar Zuniga ,&nbsp;Henrique Rodrigues ,&nbsp;Adam R. Wolfe","doi":"10.1016/j.radonc.2024.110531","DOIUrl":"10.1016/j.radonc.2024.110531","url":null,"abstract":"<div><h3>Background and purpose</h3><p>Overcoming radioresistance is a critical challenge in pancreatic ductal adenocarcinoma (PDAC). Our study investigates the targeting of Cyclin-dependent kinase-1 (CDK1) through genetic and pharmaceutical inhibition to radiosensitize PDAC cells.</p></div><div><h3>Materials and Methods</h3><p>Mass spectrometry and phosphoproteomics were used to analyze engineered radiation-resistant PDAC cell lines (MIA PaCa-2 and PANC-1) compared to parental controls. The TCGA PDAC database was queried for clinical outcomes and patients were dichotomized based on the median CDK1 mRNA expression. We generated a microRNA-based TET-on inducible shRNA to inhibit CDK1 expression in two PDAC cell lines. We used an orthotopic model of PDAC to test the radiation sensitivity of PDAC tumors with or without doxycycline treatment. We targeted CDK1 activation with a selective CDK1 inhibitor, RO-3306, followed by in vitro experiments employing immunoblotting, immunocytochemistry, and clonogenic assays.</p></div><div><h3>Results</h3><p>Phosphoproteomics analysis revealed that phospho-CDK1 (Tyr15) was significantly elevated in the resistant clones. We found that high CDK1 expression was associated with worse OS in PDAC patients. Radiation exposure increased CDK1 phosphorylation. In MIA PaCa-2 and PANC-1 cells, CDK1 inhibition synergized with radiation therapy to delay tumor growth in vivo. CDK1 inhibition via. RO-3306 resulted in a significant shift of cells into the G2/M phase and disrupted DNA repair after radiation exposure. In vitro, pre-treatment with RO-3306 led to enhanced radiosensitivity of PDAC cells.</p></div><div><h3>Conclusion</h3><p>CDK1 plays a crucial role in PDAC radioresistance. Targeting CDK1 with radiotherapy holds promise for further investigation in PDAC treatment.</p></div>","PeriodicalId":21041,"journal":{"name":"Radiotherapy and Oncology","volume":"200 ","pages":"Article 110531"},"PeriodicalIF":4.9,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142230238","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}