International Journal of Radiation Oncology Biology Physics最新文献

{"title":"A Phase I Trial of Image-Guided, Risk-Volume-Adapted Post-Prostatectomy Radiotherapy.","authors":"Krishnan R Patel, Esther Mena, Lindsay S Rowe, Holly Ning, Jason Cheng, Kilian Salerno, Erica Schott, Debbie-Ann Nathan, Erich P Huang, Liza Lindenberg, Peter Choyke, Baris Turkbey, Deborah E Citrin","doi":"10.1016/j.ijrobp.2024.09.048","DOIUrl":"https://doi.org/10.1016/j.ijrobp.2024.09.048","url":null,"abstract":"<p><strong>Purpose: </strong>This is a phase I trial with the primary objective of identifying the most compressed dose schedule (DS) tolerable using risk-volume-adapted, hypofractionated, post-operative radiotherapy (PORT) for biochemically recurrent prostate cancer. Secondary endpoints included biochemical progression free survival (bPFS) and quality of life (QOL).</p><p><strong>Methods: </strong>Patients were treated with one of 3 isoeffective dose schedules (DS1: 20 fractions, DS2: 15 fractions, DS3: 10 fractions) that escalated dose to the imaging-defined local recurrence (73Gy₃ EQD2) and de-escalated dose to the remainder of the prostate bed (48Gy₃ EQD2). Escalation followed a standard 3+3 design with a 6-patient expansion at the maximally tolerated hypofractionated dose schedule (MTHDS). Dose limiting toxicity (DLT) was defined as CTCAE v.4.0 grade (G) 3 toxicity lasting >4 days within 21 days of PORT completion or grade 4 gastrointestinal (GI) or genitourinary (GU) toxicities thereafter. QOL was assessed longitudinally through 24 months with the EPIC-26.</p><p><strong>Results: </strong>Between 01/2018 and 12/2023, 15 patients were treated (3 with DS1, 3 with DS2, and 9 with DS3). The median follow-up was 48 months. No DLTs were observed on any DS, and, thus, expansion occurred at DS3. The cumulative incidence of G3 GI and GU toxicity was 7% and 9% at 24 months, respectively, with no G4 events observed. Transient, acute G2+ GI toxicity was most common. QOL worsened transiently during study follow-up in urinary incontinence, GI, and sexual subdomains but was similar to baseline by 24 months. The bPFS was 91% at both 24- and 60-months.</p><p><strong>Conclusions: </strong>The maximally tolerated hypofractionated dose schedule for hypofractionated, risk-volume-adapted PORT was determined to be DS3 (36.4Gy to the prostate bed and 47.1Gy to the imaging-defined recurrence in 10 daily fractions). No >G3 events were observed. Transient declines in QOL did not persist through 24 months.</p>","PeriodicalId":14215,"journal":{"name":"International Journal of Radiation Oncology Biology Physics","volume":null,"pages":null},"PeriodicalIF":6.4,"publicationDate":"2024-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142390487","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":"ORAI2 is Important for the Development of Early-Stage Post-Irradiation Fibrosis in Salivary Glands.","authors":"Honglin Li, Yubin Cao, Guile Zhao, Guanru Wang, Guangzhao Huang, Lei Wang, Zhangfan Ding, Patrick Mk Tang, Chunjie Li","doi":"10.1016/j.ijrobp.2024.09.047","DOIUrl":"https://doi.org/10.1016/j.ijrobp.2024.09.047","url":null,"abstract":"<p><strong>Purpose: </strong>Although post-irradiation hyposalivation significantly impairs patient quality of life, the underlying mechanisms driving radiation-induced salivary gland fibrosis and hyposalivation remain poorly understood. This study aims to explore the role of calcium-mediated signaling pathways in radiation-induced salivary gland fibrosis.</p><p><strong>Materials and methods: </strong>Primary human submandibular gland (SG) cells and C57BL/6J female mouse SGs were exposed to irradiation to model fibrosis development. Following 15 Gy irradiation exposure, RNA sequencing and bioinformatic analysis were conducted on mouse SGs. The effects of Store-Operated Calcium Entry (SOCE) inhibition using SKF96365 and YM58483 on fibrosis markers were assessed in vitro and in vivo. Additionally, the involvement of ORAI2 protein and the newly identified JNK/NFAT1/TGF-β1 signaling axis in SG fibrosis was explored.</p><p><strong>Results: </strong>We identified that the calcium release-activated calcium modulator ORAI2 was important in promoting early-stage post-irradiation fibrosis in SGs. Calcium channel signaling was activated in both human patients and irradiated C57BL/6J female mice SGs. Inhibition of SOCE signaling effectively blocked fibrosis in an ORAI2-dependent manner 30 days after irradiation. Our mechanistic studies revealed a novel ORAI2/JNK/NFAT1 axis within the SOCE pathway critical in driving TGF-β1-mediated fibrogenesis. Encouragingly, pharmacological inhibition of NFAT1 significantly mitigated radiation-induced SG fibrosis and restored saliva flow to 84.61% of normal levels in treated mice 30 days after irradiation, without detectable side effects.</p><p><strong>Conclusions: </strong>Our findings highlight the significance of the ORAI2-mediated calcium signaling pathway, specifically via the ORAI2/JNK/NFAT1 axis, in promoting TGF-β1 expression and contributing to the development of early-stage salivary gland fibrosis following irradiation exposure. Targeting the ORAI2/JNK/NFAT1 axis emerges as a promising therapeutic strategy to alleviate radiation-induced hyposalivation and fibrosis, potentially improving the quality of life for patients undergoing radiotherapy.</p>","PeriodicalId":14215,"journal":{"name":"International Journal of Radiation Oncology Biology Physics","volume":null,"pages":null},"PeriodicalIF":6.4,"publicationDate":"2024-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142390488","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":"DeepTuning: A Novel Deep Learning Approach for Interactive Plan Tuning and Trade-Off Exploration","authors":"","doi":"10.1016/j.ijrobp.2024.07.018","DOIUrl":"10.1016/j.ijrobp.2024.07.018","url":null,"abstract":"<div><h3>Purpose/Objective(s)</h3><div>Back-and-forth plan revisions between physicians and dosimetrists occur in the planning process. They collaborate to tune plans and explore desired trade-off. To reduce back-and-forth, we proposed a new deep learning framework called DeepTuning. It can predict dose distributions with varying trade-offs from contours, so physicians can complete contours and subsequently explore trade-offs before dosimetry planning</div></div><div><h3>Materials/Methods</h3><div>DeepTuning can predict doses with different trade-offs by manipulating deepest layer Z (a 1 x 1 x 1024 vector). DeepTuning leverages two encoders for prior and posterior inference respectively. Prior encoder takes contours as input and extracts geometric information for conventional dose prediction, which predicts average dose with no trade-off. Posterior encoder takes both contour and dose as input and extracts ΔZ encoding the trade-off of input dose. Given a template plan from a treated patient with desired trade-off, posterior inference can extract trade-off information ΔZ. When predicting dose for a new patient with just contours, prior inference route predicts not only an average dose, but also doses with desired tradeoffs when we apply the ΔZs extracted</div></div><div><h3>Results</h3><div>We validated DeepTuning with a prostate dataset of 99 cases. We retrospectively optimized two VMAT plans for each case, prioritizing PTV coverage (pro-ptv) and rectum sparing (pro-oar). DeepTuning was trained / tested by 70 / 29 cases. The baseline is prior inference route that predicts fixed “average” dose distributions. Mean rectum doses are 49.5 ± 9.0 Gy, -3.1 ± 5.3% cooler than ground truth (GT) pro-ptv doses (52.0 ± 10.6 Gy) and 6.6 ± 7.9% hotter than GT pro-oar doses (44.2 ± 12.2 Gy). Then we extracted ΔZs for pro-ptv trade-off and pro-oar trade-off from the two plans of a training case. With ΔZs applied, DeepTuning can predict doses with two different trade-offs. The mean rectum doses of the pro-ptv predictions are 51.8 ± 8.5 Gy, -0.27 ± 5.1% different from GT, while pro-oar predictions are 43.8 ± 10.1 Gy, -0.6 ± 7.5% away from GT. The deviations from GT are much lower than “average” dose prediction.</div></div><div><h3>Conclusion</h3><div>We introduced a novel deep learning framework, DeepTuning, capable of encoding trade-offs from treated plans and predicting doses with varying trade-offs for new cases. DeepTuning empowers physicians to tune doses and explore trade-offs immediately after contouring. As the trade-off selection occurs before dosimetry planning, back-and-forth can be minimized and treatment planning workflow can be revolutionized. Furthermore, it holds promise to clinical application of auto-planning. Physicians can generate the doses distributions they desired, which serve as optimization objectives for auto-planning better than templated objectives.</div></div>","PeriodicalId":14215,"journal":{"name":"International Journal of Radiation Oncology Biology Physics","volume":null,"pages":null},"PeriodicalIF":6.4,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142358655","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":"O-GlcNAcylation of PRDX1 and Radiation Resistance in Non-Small Cell Lung Cancer via Suppressing TRIM21 Mediated Ubiquitination","authors":"","doi":"10.1016/j.ijrobp.2024.07.041","DOIUrl":"10.1016/j.ijrobp.2024.07.041","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Purpose/Objective(s)&lt;/h3&gt;&lt;div&gt;The molecular mechanism underlying radiation resistance in non-small cell lung cancer (NSCLC) is not well understood. This study aimed to investigate the potential role of Peroxiredoxin-1 (PRDX1) O-GlcNAcylation and its specific regulatory mechanism in NSCLC radiotherapy resistance.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Materials/Methods&lt;/h3&gt;&lt;div&gt;To establish radiotherapy-resistant NSCLC cell lines, multiple radiotherapy treatments were administered. The radiosensitivity of cells was evaluated using colony formation assay, western blot, and immunofluorescence. Metabolic changes in response to irradiation challenge were comprehensively analyzed through a metabolomics assay comparing radioresistant NSCLC cell lines (A549R or LLCR) with their parental cell lines (A549 or LLC). The correlation between PRDX1 and O-GlcNAcylation expression was investigated using a tissue microarray (TMA) of human NSCLC tissue (&lt;em&gt;n&lt;/em&gt; = 90). Co-immunoprecipitation coupled with mass spectrometry (Co-IP-MS) was employed to identify proteins regulating PRDX1 expression. The functional role of PRDX1 O-GlyNAcylation in NSCLC radiotherapy resistance was validated through multicolor immunofluorescence staining in tissue samples from pre-radiotherapy biopsies (&lt;em&gt;n&lt;/em&gt; = 79). Lastly, a short peptide was designed to target PRDX1 glycosylation both in vitro and in vivo.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;Metabolomic analyses revealed a shift in metabolic flux to the hexosamine biosynthesis pathway (HBP) with higher levels of UDP-GlcNAc in radioresistant NSCLC cells, a substrate for O-GlcNAcylation. Subsequently, O-GlcNAcylation and PRDX1 were found to be significantly up-regulated in human NSCLC tissues compared to adjacent benign tissues. O-GlcNAcylation of PRDX1, mediated by OGT, was identified as critical for radioresistance in NSCLC. Specifically, PRDX1 was O-GlcNAcylated at the conserved serine 2/3, and radiation-resistant NSCLC cells exhibited elevated levels of O-GlcNAcylation of PRDX1. This post-translational modification protected the protein stability of PRDX1, while TRIM21 was discovered as an E3 ubiquitin ligase promoting PRDX1 degradation, with its interaction affected by O-GlcNAcylation. Conversely, pharmacological reduction in the O-GlcNAcylation of PRDX1 (OSMI treatment) enhanced the radiotherapy sensitivity of NSCLC. Notably, multicolor immunofluorescence staining of tissue samples from pre-radiotherapy biopsies (&lt;em&gt;n&lt;/em&gt; = 79) confirmed a positive correlation between PRDX1 O-GlyNAcylation levels and OGT expression, as well as radiotherapy tolerance, and a negative correlation with TRIM21 expression levels.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusion&lt;/h3&gt;&lt;div&gt;Our findings highlight the regulatory role of PRDX1 in NSCLC radiation resistance, emphasizing how O-GlcNAcylation stabilizes and shields PRDX1 from TRIM21-mediated ubiquitination. These results uncover a potential mechanism of NSCLC radiation resistance and propose a promising therapeutic ","PeriodicalId":14215,"journal":{"name":"International Journal of Radiation Oncology Biology Physics","volume":null,"pages":null},"PeriodicalIF":6.4,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142358589","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":"Patient-Reported Functional Decline Following Active Surveillance (AS), Radical Prostatectomy (RP), External Beam Radiation without Androgen Deprivation Therapy (EBRT w/o ADT), or Low-Dose-Rate Brachytherapy (LDR-BR) for Favorable-Risk Prostate Cancer","authors":"","doi":"10.1016/j.ijrobp.2024.07.023","DOIUrl":"10.1016/j.ijrobp.2024.07.023","url":null,"abstract":"<div><h3>Purpose/Objective(s)</h3><div>In the primary analysis of the Comparative Effectiveness Analysis of Surgery and Radiation (CEASAR) study, most comparative patient-reported functional differences between treatments for localized prostate cancer attenuated within five years. This secondary analysis describes clinically meaningful functional decline after treatment to better inform patients’ expectations.</div></div><div><h3>Materials/Methods</h3><div>Participants diagnosed with localized prostate cancer between 2011 and 2012 were prospectively enrolled from 5 United States Surveillance, Epidemiology and End Results Program Sites. The validated 26-item Expanded Prostate Index Composite questionnaire (range = 0-100) was administered at baseline and at 1-, 3-, 5-, and 10 years. Functional change from baseline was calculated at each time point. Established thresholds for clinically meaningful functional decline (CMFD) were used: 10 sexual function (fxn), 6 urinary incontinence (incon); 5 urinary irritative (irr); 4 bowel fxn. Descriptive statistics report function and problems for participants with favorable-risk (cT1 to cT2bN0M0, prostate-specific antigen ≤ 20 ng/mL, and Grade Group 1-2) prostate cancer selecting a specific treatment. Unadjusted analyses were performed; results should not be compared across treatment groups.</div></div><div><h3>Results</h3><div>Among 1,656 men with favorable-risk prostate cancer, 322 were treated with AS, 999 with RP, 252 with EBRT w/o ADT, and 83 with LDR-HR and completed the baseline and at least 1 postbaseline survey. Median [interquartile range] age, 63 [IQR = 58-69] years; 76.2% non-Hispanic white. Most RP was nerve-sparing (85.6%) and most EBRT was IMRT (77.6%) or proton (8.1%) with IGRT (83.9%). The proportion of participants with CMFD in each functional domain and with “moderate to big problem” (MTBP) with sexual, urinary, and bowel function at each time point are reported in the table below. Fewer patients reported a MTBP with function than those reporting CMFD.</div></div><div><h3>Conclusion</h3><div>Our findings highlight long-term clinically meaningful functional declines and functional problems that occur after these management approaches for favorable-risk prostate cancer. Patients should be counseled regarding risks of possible long-term functional impact to better inform them of expectations after treatment.</div></div>","PeriodicalId":14215,"journal":{"name":"International Journal of Radiation Oncology Biology Physics","volume":null,"pages":null},"PeriodicalIF":6.4,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142358949","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":"Applying Deep Learning Based Facial Age Phenotyping to Improve Life Expectancy Prediction in Metastatic Cancer Patients Receiving Palliative Radiotherapy","authors":"","doi":"10.1016/j.ijrobp.2024.07.034","DOIUrl":"10.1016/j.ijrobp.2024.07.034","url":null,"abstract":"<div><h3>Purpose/Objective(s)</h3><div>Prognostic tools such as the TEACHH model (risk scoring based on cancer <u>t</u>ype, <u>E</u>COG PS, <u>a</u>ge, prior palliative <u>c</u>hemotherapy, <u>h</u>ospitalization, and <u>h</u>epatic metastases) aim to predict life expectancy (LE) in metastatic cancer patients receiving palliative radiotherapy (RT). In our prior study, a deep learning model predicting biological age from facial photographs (FaceAge) was developed and showed prognostic potential in cancer patients. Here, we evaluated the prognostic significance of extreme discordance between FaceAge vs chronological age (FaceAge–Age) among patients receiving palliative RT and applied FaceAge to the TEACHH model.</div></div><div><h3>Materials/Methods</h3><div>A retrospective study of 690 patients with metastatic cancer treated by palliative RT between 2012 and 2018 at six clinic locations was conducted. FaceAge estimates were derived based on patients’ facial photographs taken before RT. Cox and logistic regression analyses were used to evaluate predictors of overall survival (OS) and early mortality (&lt;3 months), respectively. FaceAge was substituted for chronological age in the TEACHH model and model fitness was compared via likelihood ratio test (LRT).</div></div><div><h3>Results</h3><div>Median OS was 9 months and 41% died within 3 months. Fifty-five percent had ≥ 5 years of absolute difference in FaceAge vs chronological age. Twenty-one percent had a much older FaceAge with FaceAge–Age of ≥ 10 years. In multivariate analyses, FaceAge–Age ≥ 10 years was significantly associated with worse OS (HR = 1.38, <em>P</em> = 0.01) and increased risk of early mortality within 3 months (OR = 1.68, <em>P</em> = 0.02), even after adjusting for other significant predictors (primary cancer type, ECOG PS, chemotherapy, and hospitalization). For all patients, substituting FaceAge for chronological age in the TEACHH model improved LE group stratification (LRT = 6.1, <em>P</em> &lt; 0.01). Among patients with ≥ 5 years of FaceAge vs age discrepancy, the TEACHH model failed to significantly stratify into 3 expected LE groups, but substituting FaceAge for age allowed for significant stratification (Table; LRT = 7.0, <em>P</em> &lt; 0.01).</div></div><div><h3>Conclusion</h3><div>Extreme discordance in facial aging may be a valuable prognostic marker for metastatic cancer patients receiving palliative RT. Moreover, substituting FaceAge for chronological age improved the performance of an existing LE prediction model, especially in patients with extreme discordance, by more accurately capturing biological age at end-of-life. Such AI biomarker may enhance LE predictions and aid in end-of-life treatment decision making.</div></div>","PeriodicalId":14215,"journal":{"name":"International Journal of Radiation Oncology Biology Physics","volume":null,"pages":null},"PeriodicalIF":6.4,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142358603","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":"The Prognostic Value of Pretreatment Carbohydrate Antigen 125 Level in Cervical Cancer Patients Treated with Definitive Radiotherapy or Concurrent Chemoradiotherapy","authors":"","doi":"10.1016/j.ijrobp.2024.07.045","DOIUrl":"10.1016/j.ijrobp.2024.07.045","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Purpose/Objective(s)&lt;/h3&gt;&lt;div&gt;Carbohydrate antigen 125 (CA125) is a widely used tumor marker, but its relationship with the prognosis of cervical cancer is little known. The study aims to investigate the prognostic value of pretreatment CA125 levels in patients with cervical cancer receiving definitive radiotherapy or concurrent chemoradiotherapy (CCRT), to identify the optimal pretreatment CA125 cutoff value for predicting treatment failure, and to explore its association with survival outcomes.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Materials/Methods&lt;/h3&gt;&lt;div&gt;A total of 645 patients (543 squamous cell carcinoma [SCC] patients, 85 adenocarcinoma [ADC] patients, and 17 others) satisfying the eligibility criteria treated between 2007 and 2016 were included, with a median follow-up duration of 60.2 months. The primary endpoint was disease-free survival (DFS), and the secondary endpoints included overall survival (OS) and local control (LC). The optimal cutoff value for pretreatment CA125 levels was verified by the receiver operating characteristic (ROC) curve. Five-year OS, DFS, and LC rates were evaluated utilizing the Kaplan-Meier method. The log-rank test and Cox proportional hazards model were implemented to recognize independent prognostic predictors. After analyzing the whole cohort, we further conducted analyses of both SCC and ADC subgroups. All statistical analyses were performed using R software.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;In the whole cohort, the optimal pretreatment CA125 cutoff value was 26.1 U/mL, with elevated levels presenting significantly inferior five-year DFS (59.4% vs. 80.6%, &lt;em&gt;P&lt;/em&gt; &lt; 0.001), OS (66.1% vs. 86.2%, &lt;em&gt;P&lt;/em&gt; &lt; 0.001), and LC (75.4% vs. 91.4%, &lt;em&gt;P&lt;/em&gt; &lt; 0.001) compared to those with lower levels. Univariate and multivariate analyses identified the higher pretreatment CA125 level as an independent predictor of treatment failure (hazard ratio [HR] = 2.16 [1.57-2.98]; &lt;em&gt;P&lt;/em&gt; &lt; 0.001). Subgroup analysis yielded similar results. For the SCC subgroup, the optimal pretreatment CA125 cutoff value was 25.6 U/mL, with higher levels indicating poorer five-year DFS (64.9% vs. 81.7%, &lt;em&gt;P&lt;/em&gt; &lt; 0.001), OS (67.4% vs. 87.9%, &lt;em&gt;P&lt;/em&gt; &lt; 0.001), and LC (79.6% vs. 91.9%, &lt;em&gt;P&lt;/em&gt; &lt; 0.001). Pretreatment CA125 level independently predicted treatment failure (HR, = 1.85 [1.27, 2.68], &lt;em&gt;P&lt;/em&gt; = 0.001). In the ADC subgroup, the optimal pretreatment CA125 cutoff value was 27.6 U/mL, with higher CA125 levels associated with worse five-year DFS (41.8% vs. 75.0%, &lt;em&gt;P&lt;/em&gt; = 0.003) and LC (60.0% vs. 86.9%, &lt;em&gt;P&lt;/em&gt; = 0.003), and a trend towards decreased OS (65.0% vs. 75.9%, &lt;em&gt;P&lt;/em&gt; = 0.09) was observed. Pretreatment CA125 level remained an independent predictor of treatment failure (HR = 2.51 [1.11, 5.68], &lt;em&gt;P&lt;/em&gt; = 0.03).&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusion&lt;/h3&gt;&lt;div&gt;Pretreatment CA125 levels are associated with treatment outcomes in cervical cancer patients receiving definitive radiotherapy or","PeriodicalId":14215,"journal":{"name":"International Journal of Radiation Oncology Biology Physics","volume":null,"pages":null},"PeriodicalIF":6.4,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142358667","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":"Image Guided Brachytherapy Quality Assurance on NRG GY017, an NRG Oncology Clinical Trial Investigating the Sequencing of Immunotherapy and Chemoradiation for Locally Advanced Cervical Cancer","authors":"","doi":"10.1016/j.ijrobp.2024.07.016","DOIUrl":"10.1016/j.ijrobp.2024.07.016","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Purpose/Objective(s)&lt;/h3&gt;&lt;div&gt;NRG GY-017 is a randomized Phase I trial of the anti-PD-L1 antibody atezolizumab administered neoadjuvantly and concurrently (Arm A) or concurrently with chemo RT (Arm B) in patients with node positive locally advanced cervical cancer, with 3 total cycles on each arm. All subjects were treated with PALN extended field external beam radiation therapy (EBRT) and brachytherapy (BT) boost. This trial is a pharmacodynamics study, 3D image-based BT was strongly recommended, and a quality assurance workflow was specified in the protocol. Herein, we report the BT dosimetry results from the NRG GY-017 trial and practice patterns from the participating centers in this trial.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Materials/Methods&lt;/h3&gt;&lt;div&gt;All patients were to be treated with 3D image based HDR or PDR BT following EBRT either with point or volume directed plans. The 2D LDR BT was also allowed. CT or MR images were used to delineate the target volume. MRI based target delineation was recommended for identifying the GTV. The MRI could be reused by superimposition for CT based planning, if only CT images for subsequent fractions are used with the applicator in place. Each participating center was to submit brachytherapy plans via TRIAD after the BT course was complete. The clinical trial QA center compiled the BT fractions for each trial patient using the trial specific dosimetry evaluation template. The expert physician scored the contours and plans as per protocol, variation acceptable or major deviation.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;Forty patients were enrolled from 9 institutions among designated “safety lead-in” participating centers for this trial in the United States. But 32 patients from 7 institutions had evaluable BT dosimetry results. Twenty-one BT submissions (66%) were completed during the trial period and the rest of the data were submitted after the trial was closed. For the applicator use, 19 patients (59%) had intracavitary only, and 13 (41%) patients had supplemental interstitial (hybrid) or interstitial applications. Point dose directed planning was performed for 4 patients and 28 patients had volume directed plans (&lt;em&gt;n&lt;/em&gt; = 28; 87.5%). For imaging use, 2 patients had MRI plans submitted, and the rest of the patients had CT planning. 31 patients had HDR BT with 27.5 Gy-30 Gy in either 4 or 5 fractions, while 1 patient had LDR BT. For the dose constraints compliance per protocol, there were 7 patients with 9 events scored as major deviations (22%), 7 events exceeding critical organ dose limits and 2 events deviating from the target dose.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusion&lt;/h3&gt;&lt;div&gt;Brachytherapy on this trial showed a wide range of practice patterns and suggest that BT trial-specific quality assurance review and standardized data submission processes may have the potential to enhance quality and safety for clinical trials. This report presents the first modern GYN BT trial dosimetry results, guiding future GYN BT t","PeriodicalId":14215,"journal":{"name":"International Journal of Radiation Oncology Biology Physics","volume":null,"pages":null},"PeriodicalIF":6.4,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142359493","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":"2024 Fellows","authors":"","doi":"10.1016/j.ijrobp.2024.06.025","DOIUrl":"10.1016/j.ijrobp.2024.06.025","url":null,"abstract":"","PeriodicalId":14215,"journal":{"name":"International Journal of Radiation Oncology Biology Physics","volume":null,"pages":null},"PeriodicalIF":6.4,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142358784","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":"Short-Term Androgen Deprivation Therapy and High-Dose Radiotherapy in Intermediate- and High-Risk Localized Prostate Cancer: Results from the GETUG 14 Randomized Phase III Trial","authors":"","doi":"10.1016/j.ijrobp.2024.08.017","DOIUrl":"10.1016/j.ijrobp.2024.08.017","url":null,"abstract":"<div><h3>Purpose/Objective(s)</h3><div>Few studies compared short-term androgen deprivation (STADT) with high-dose radiotherapy (STADT-RT) versus high-dose radiotherapy (RT) alone in localized prostate cancer.</div></div><div><h3>Materials/Methods</h3><div>The GETUG 14 study randomized 376 patients between RT (n=191) and STADT-RT (n=179). RT dose was 80 Gy in both arms and STADT was monthly triptorelin and daily flutamide for a total duration of 4 months, starting 2 months before irradiation. Disease-free survival (DFS) was the primary endpoint. Secondary endpoints were overall survival (OS), biochemical failure (BF), metastasis failure (MF), toxicity and quality of life.</div></div><div><h3>Results</h3><div>With a median follow-up of 84 months, five-year DFS was 76% in RT arm versus 84% in STADT-RT arm (hazard ratio [HR] = 0.64; [95% CI 0.43 - 0.89]; P = .02). ADT decreased BF (HR = 0.45; P = .001) and MF (HR = 0.5; P = .09) but not OS (HR = 1.22; P = .54). No difference was found in terms of gastrointestinal (26% of grade ≥2 in both arm, P = .97) and genito-urinary acute toxicity (39% for RT and 42% for STADT-RT, P = .55). Similarly, no difference was found in late toxicity and quality of life.</div></div><div><h3>Conclusion</h3><div>STADT improves disease-free survival in intermediate and high-risk prostate cancer patients receiving high dose (80 Gy) RT, without any deterioration in the safety profile.</div></div>","PeriodicalId":14215,"journal":{"name":"International Journal of Radiation Oncology Biology Physics","volume":null,"pages":null},"PeriodicalIF":6.4,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142358705","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}