International Journal of Radiation Oncology Biology Physics最新文献

{"title":"Impact of Clinical Target Volume Utilization on Outcomes in Patients with Non-Spine Bone Oligometastases Treated with Stereotactic Ablative Radiation Therapy","authors":"","doi":"10.1016/j.ijrobp.2024.07.032","DOIUrl":"10.1016/j.ijrobp.2024.07.032","url":null,"abstract":"<div><h3>Purpose/Objective(s)</h3><div>Despite advancements in stereotactic ablative radiotherapy (SABR) for non-spine bone metastases (NSBMs), uncertainty remains surrounding target volumes. While expert consensus guidelines recommend a clinical target volume (CTV), patterns of failure analyses are lacking, and larger treatment volumes may be associated with higher toxicity. This study aims to compare local failure, marginal failure, and toxicity in NSBMs treated with versus without a CTV in a population-based cohort.</div></div><div><h3>Materials/Methods</h3><div>A retrospective review was conducted on all patients in British Columbia treated with SABR for NSBMs on the single-arm phase II SABR-5 trial (November 2016 – July 2020) and on the BC Oligometastases Registry (August 2020 - October 2022). Use of a CTV was optional for both SABR-5 and the Registry. NSBMs were stratified based on CTV use for treatment planning.</div></div><div><h3>Results</h3><div>A total of 158 patients (113 on SABR-5 and 45 on Registry) with 200 NSBMs were included. One hundred fifty-nine (80%) NSBMs were treated with a CTV and 41 (21%) without a CTV. The most common histologies were prostate (60%), breast (17%) and lung cancer (6%), and lesions received 35 Gy in 5 fractions (81%) or 24 Gy in 2 fractions (14%). Rib (34%) and pelvis (47%) were the most common lesion sites. Groups with vs without a CTV did not differ in baseline patient or tumor characteristics. After a median follow-up time of 33.7 months (interquartile range [IQR] = 19.5-48.9), local failure rates did not differ, with 2-year local failure 9.3% (95% confidence interval [CI] = 4.4 – 14.2) in lesions treated with a CTV and 7.6% (95% CI = 0 – 15.8) without a CTV (<em>P</em> = 0.39). Marginal failure, defined as disease recurrence outside of the GTV but within 1 cm of the PTV, occurred in 15 (8%) of lesions and 2-year cumulative incidence did not differ between groups (6.2% [95% CI = 2.3 – 10.1] and 2.6%, [95% CI = 0 – 7.5], respectively [<em>P</em> = 0.16]). Overall survival (OS) was also similar (2-year OS = 84.6%, 95% CI = 78.1 – 91.1, and 90.3%, 95% CI = 79.9 – 100, respectively; <em>P</em> = 0.64). The most common grade ≥ 2 toxicities were pain (<em>n</em> = 18, 9%) and fracture (<em>n</em> = 8, 4%). There were no grade 4 or 5 toxicities. The 2-year cumulative incidence of grade ≥ 2 toxicity did not differ between groups (14.9%, 95% CI = 3.9-25.9 and 15.6%, 95% CI = 9.9-21.3, respectively; <em>P</em> = 0.78). Due to low number of events, local and marginal failure events were collated for a multivariable regression analysis. On multivariable regression, use of a CTV was not associated with the risk of local-marginal failure (hazard ratio [HR] = 2.41, 95% CI = 0.81 – 7.18, <em>P</em> = 0.11). Extraosseous extension (HR = 2.62, 95% CI = 1.07-6.38, <em>P</em> = 0.035) and lack of receipt of systemic therapy (HR = 3.03, 95% CI = 1.40-6.67, <em>P</em> = 0.005) were associated with higher risk.</div></div><di","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":"142358653","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":"Outcomes and Immune Responses from INNATE: A Randomized Phase II Trial of Sotigalimab Immunotherapy during Neoadjuvant Therapy of Rectal Cancer","authors":"","doi":"10.1016/j.ijrobp.2024.08.019","DOIUrl":"10.1016/j.ijrobp.2024.08.019","url":null,"abstract":"<div><h3>Purpose/Objective(s)</h3><div>Immunotherapy benefit has yet to show benefit in unselected colorectal cancer. The addition of a CD40 agonist, sotigalimab (Sotiga), to short course radiotherapy (SCRT) and FOLFOX chemotherapy (CT) is hypothesized to improve pathologic complete response (pCR) in locally advanced rectal cancer (LARC).</div></div><div><h3>Materials/Methods</h3><div>INNATE (NCT04130854) is a multi-institutional Phase II randomized trial for patients with Stage III or high-risk Stage II LARD. Patients were randomized 3:2 to receive daily SCRT (5 Gy x 5) and 6 cycles of FOLFOX ± 6 infusions of Sotiga, followed by total mesorectal excision stratified by stage. Tumor tissue was collected including pre- and post-SCRT for single cell RNA sequencing and multiplex immunofluorescence. Target accrual was 58 patients with the primary pCR endpoint powered for a 22% difference.</div></div><div><h3>Results</h3><div>From 7/30/20 to 6/23/22, 30 patients were enrolled by 4 centers (19 randomized to Sotiga), after which accrual was held. Patients had unfavorable disease: all were T3/4, 20 (67%) had N2 disease and 21 (70%) had tumor involving or threatening the mesorectal fascia. Of 26 patients that underwent TME, pCR was achieved in 4/18 (22.2%) in the study arm and 1/7 (14.3%) in the control arm. Major response of pCR, near CR, or sustained 12-month clinical CR occurred in 7/19 (36.8%) in the study arm and 6/10 (60%) control arm patients. Average radiology contoured tumor volumes pre- and post-treatment were respectively: 52.2 cc (SD = 34.39) and 11.05 cc (-78.82%) in the study arm, and 36.46 cc (SD = 29.34) 16.77 cc (-54.00 %) in control arm. Grade 3-4 toxicities occurred in 5 (26%) study arm patients and 5 (45%) control arm patients. The most common toxicities were Grade 3 GI related (n=7), infection (n=5), and thromboembolism (n=2). Other toxicities included abdominal pain, rectal fistula, radiation proctitis, and perforation (n=1ea). The study arm had 1 Grade 4 (unrelated) postoperative stercoral perforation, and the control arm had a Grade 5 sepsis and cardiac arrest after perforation during CT. Comparisons pre-post SCRT revealed significant increases in infiltration of antigen-presenting cells in both arms (FDR < 0.05). Higher anti-tumor M1 macrophage signature after SCRT (p = 0.01) was more pronounced with SCRT+Sotiga (p = 5.74e-08). Type 1 dendritic cell activation and antigen presentation pathways and CD40 signaling were significantly increased after SCRT and SCRT+Sotiga. Anti-tumor effects extended to T cells, with increased cytotoxic activity in CD8 T cells (IL-2, GZMB, GZMK, NKG7) and NK cells (PRF1, GZMB). Expression of immune checkpoints shifted in each arm suggesting additional targets for combination therapy with SCRT or Sotiga.</div></div><div><h3>Conclusion</h3><div>Adding Sotiga to SCRT and CT in LARC appears to be safe and shows robust responses to unfavorable disease, with evidence of increased antitumor adaptive immune ","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":"142358704","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":"Longitudinal CT Feature-Based Model for Predicting Local Recurrence Free Survival in Esophageal Cancer Patients Treated with Definitive Chemoradiotherapy: A Multicenter Study","authors":"","doi":"10.1016/j.ijrobp.2024.07.065","DOIUrl":"10.1016/j.ijrobp.2024.07.065","url":null,"abstract":"<div><h3>Purpose/Objective(s)</h3><div>Accurate prediction of local recurrence-free survival (LRFS) remains a great challenge for esophageal squamous cell carcinoma (ESCC) patients receiving definitive chemoradiotherapy (dCRT). However, the integration of longitudinal data holds significant potential for improving predictive capabilities. This study aims to develop and validate a deep learning model that incorporates longitudinal CT scans to accurately predict LRFS in patients with ESCC following dCRT.</div></div><div><h3>Materials/Methods</h3><div>We retrospectively collected 321 ESCC patients who underwent dCRT at our hospital and randomly divided them into training set (224) and internal validation set (91). Additionally, 202 patients from three other cancer hospitals were divided into two external validation sets (111 and 91 patients). The patients’ computed tomography (CT) images before and after dCRT were utilized. LRFS-related intratumoral and peritumoral radiomic features were extracted and selected through LASSO-Cox. Subsequently, we developed a correlation-driven disentanglement survival network (CDDSN), which integrated a ResNet block, base transformer, and basic CNN to effectively fuse shared and unique deep features from longitudinal CT images. The selected radiomic and deep features were then integrated to establish the final CDDSN model, the performance of which was validated using external sets. Furthermore, we developed a multimodal nomogram using independent clinical factors and the CDDSN signature in the training set, which was subsequently tested in three validation sets.</div></div><div><h3>Results</h3><div>Compared to the models utilizing CT images acquired before or after dCRT, the CDDSN model based on longitudinal CT scans achieved the highest performance in LRFS predictive with the C-index of 0.796 (95% CI = 0.741-0.851), 0.738 (95% CI = 0.675-0.801), 0.712 (95% CI = 0.661-0.758) and 0.708 (95% CI = 0.657-0.748) in the training set, internal testing set and the two external validation sets, respectively. Moreover, the CDDSN model integrating both intratumoral and peritumoral features outperformed the model solely using intratumoral features in each dataset. Additionally, our CDDSN model demonstrated superior fusion and predictive power in LRFS compared to the early fusion and late fusion methods in the two external validation sets (C-index: 0.712 vs 0.690 vs 0.681; 0.708 vs 0.661 vs 0.684), respectively. Furthermore, multivariable Cox regression analysis revealed that age, T stage, and absolute lymphocyte count were significantly correlated with LRFS (P<0.05). The multimodal nomogram, incorporating clinical factors and the CDDSN signature, exhibited a favorable predictive power for LRFS with a C-index of 0.826 in the training set and 0.709-0.734 in the validation sets.</div></div><div><h3>Conclusion</h3><div>The CDDSN model, utilizing longitudinal CT images, can enhance the predictive power for LRFS in patients with ES","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":"142359163","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":"Long Term Rates of Lymphedema in Hypofractionated Nodal Regional Irradiation for Women with Breast Cancer: A Phase 2 Clinical Trial – “HeNRIetta”","authors":"","doi":"10.1016/j.ijrobp.2024.07.008","DOIUrl":"10.1016/j.ijrobp.2024.07.008","url":null,"abstract":"<div><h3>Purpose/Objective(s)</h3><div>Moderate hypofractionation in the management of localized breast cancer is considered standard of care. Data suggests its use in the setting of regional nodal irradiation (RNI) yields equivalent oncologic and cosmetic outcomes but has not yet achieved universal acceptance into practice. The risk of lymphedema (LA) has not been the focus of study in this setting and therefore, we sought to evaluate the risk and establish the rate of moderate or marked LA for patients treated with hypofractionated RNI utilizing an established and commonly used hypofractionation treatment scheme with standardized treatment volumes for patients with node-positive breast cancer.</div></div><div><h3>Materials/Methods</h3><div>Women with node positive breast cancer who underwent definitive surgical resection were eligible for enrollment. Breast surgery may have been lumpectomy (Lp), mastectomy without reconstruction (M-R), or mastectomy with reconstruction (M+R). Nodal staging by sentinel lymph node (SLN) or by axillary lymph node (ALN) dissection were included. Patients could undergo neoadjuvant or adjuvant chemotherapy at the discretion of the treating medical oncologist. Breast and RNI was administered to 42.56 Gy in 16 daily fractions. The dissected axilla was excluded as a target volume in patients who underwent ALN dissection. Primary endpoint was rate of LA at 3 years following RNI for two cohorts, SLN (cohort A) and ALN (cohort B). Lymphedema was defined as ≥ 10% increase in arm circumference over baseline circumference as compared to the contralateral arm measured every 6 months for the first 3 years. Per protocol-defined to declare moderate hypofractionation non-inferior to recent historical controls cohorts A and B rate of lymphedema were estimated to be 6% and 10% respectively, a non-inferiority margin of +/- 7% was used. Secondary objectives included 5-year oncologic outcomes, grade 3 or higher toxicities, cosmesis and patient reported outcomes.</div></div><div><h3>Results</h3><div>Between September 2015 and July 2021, a total of 134 women were enrolled, 84 underwent SLN only and 50 completed ALN dissection. Mean age was 58.1 years for cohort A and 62.5 years for cohort B. Lp, M+R, and M-R was performed in 58.2%, 19.4, and 30% respectively. LA was observed in 11 patients (13.1%) with SLN only (<em>P</em> = 0.5897) and 9 patients (18%) who underwent ALN dissection (<em>P</em> = 0.65971). Only 2 patients developed grade 2 LA (limiting instrumental activities of daily living) and no grade 3 (limiting self-care activities of daily living) was observed. At 36 month follow up 85.5% in the lumpectomy group and 75.9% in the mastectomy with reconstruction group had excellent or good cosmesis.</div></div><div><h3>Conclusion</h3><div>Moderate hypofractionation did not meet the criteria defined by the protocol for non-inferiority. However, the absolute rates of LA remain low and predominantly grade 1. Cosmetic outcomes in this adv","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":"142359155","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":"Acceleration of Overall Treatment Time by Mono-Application Multifractionated Brachytherapy over 48 Hours vs. Sequential Weekly Application Brachytherapy in Carcinoma Cervix – Multi-Institutional, Subcontinent Based Real World Non-Inferiority Study","authors":"","doi":"10.1016/j.ijrobp.2024.07.015","DOIUrl":"10.1016/j.ijrobp.2024.07.015","url":null,"abstract":"<div><h3>Purpose/Objective(s)</h3><div>Standard practice entails employing multifractionated high-dose-rate (HDR) BT, administered in 3 to 4 sessions over 3 weeks post Chemoradiation, keeping overall treatment time < 56 days. Mono-application fractionated brachytherapy accelerates the treatment timeline without escalating acute or late toxicities. Recent progress in image-guided brachytherapy in cervical cancer facilitates the attainment of optimal dose volume parameters for both the target and organs at risk. This is the first multinational, multi-institutional study comparing outcomes and toxicity of mono-application fractionated brachytherapy versus multiple-application brachytherapy in carcinoma cervix.</div></div><div><h3>Materials/Methods</h3><div>Enrolled 401 eligible patients with confirmed cervical cancer, FIGO stages IIA-IVA, intended definitive chemoradiation. Patients post 45-50 Gy external radiation with cisplatin either received mono-application fractionated brachytherapy or multiple-application for interstitial or intracavitary BT. Rectal and bladder doses were strictly maintained within 50% of prescription dose with adequate dosing to high-risk target volume. Demographic data, stage, histology, external radiation dose, brachytherapy dose and fractionation, D2 cc doses to bladder, rectum were recorded. Disease free survival and overall survival at 3 years were obtained along with data on acute and long-term bladder and rectal toxicities.</div></div><div><h3>Results</h3><div>Four hundred one patients, 203 received multiple applications spaced over 3 weeks and 198 received single application multiple deliveries < 48 hours. All patients underwent Intracavitary or Interstitial BT with most common fractionation of 7 Gyx3 or equivalent. Rectal and bladder 2 cc doses were 45% +/- 12% of prescription dose. HRCTV coverage of D90 of 95+/-7 was achieved in all cases. With a median follow up of 36 months (range = 22-37), 3 year disease-free was 0.78 and 0.76, The <em>P</em> value of 0.98 (> 0.05), showed difference in DFS between the two groups was not statistically significant. The 3-year overall survival was 0.72 and 0.71, <em>P</em> value of 0.1 (> 0.05), again statistically insignificant. Cox regression model analysis showed stage wise DFS and OS difference between the groups weren’t statistically significant, hence proving the non-inferiority. The 3 year Grade 2 or more bladder and rectal toxicity has been reported in 2.3% and 4.1% in mono application group and 2.9% and 6.3% of multi-application group, statistically insignificant, confirming the credibility of our approach.</div></div><div><h3>Conclusion</h3><div>Our study lays the foundation for a comprehensive investigation into the outcomes and efficacy of mono-application fractionated brachytherapy being non inferior to multiple-application with respect to outcomes and toxicity, providing valuable insights into the management of cervical cancer with reduced overall treatme","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":"142359492","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":"Synergistic Potential of CDK4/6 Inhibitors and Radiotherapy with Anti-PD-L1 Immunotherapy in Triple-Negative Breast Cancer","authors":"","doi":"10.1016/j.ijrobp.2024.07.071","DOIUrl":"10.1016/j.ijrobp.2024.07.071","url":null,"abstract":"<div><h3>Purpose/Objective(s)</h3><div>Triple-negative breast cancer (TNBC) represents the subtype with the poorest survival outcomes among all breast cancer molecular classifications. While immunotherapy has shown promising anti-tumor effects in TNBC treatment, its efficacy is not universal across all patients. CDK4/6 inhibitors have been recognized for their ability to radiosensitize and modulate the immune system. Additionally, high-dose radiotherapy (RT) has been observed to bolster the effects of immunotherapy. This study investigates the potential of enhancing immunotherapy effectiveness in TNBC by integrating RT with CDK4/6 inhibitors, focusing on modulating the tumor microenvironment.</div></div><div><h3>Materials/Methods</h3><div>We employed three human TNBC cell lines—MDA-MB-231, MDA-MB-453, and MDA-MB-468—along with the 4T1 mouse TNBC cell line to assess CDK4/6 inhibitor, abemaciclib, in radiosensitizing effects of TNBC using the clonogenic assays. We assessed the anti-tumor efficacy of RT, abemaciclib, and anti-PD-L1 antibody combination through the 4T1 cell line-derived immunocompetent mouse model. Interferon-γ (IFN-γ) levels in mouse blood were monitored before, during, and after treatment to gauge the immune response. Tumor-infiltrating lymphocytes (TILs) were analyzed in excised tumor samples through flow cytometry assays and immunohistochemical staining.</div></div><div><h3>Results</h3><div>Clonogenic assays showed that RT combined with abemaciclib pretreatment had synergistic effects across all tested TNBC cell lines. A single 8 Gy fraction of RT increased PD-L1 expression on the surface of tumor cells, while abemaciclib (at 100nm or 200nm concentrations) did not alter PD-L1 expression in all TNBC cell lines. The combination of abemaciclib, RT, and anti-PD-L1 in the 4T1 mouse model significantly decreased the tumor growth (<em>P</em> &lt; 0.05) and elevated circulating IFN-γ levels during treatment (<em>P</em> &lt; 0.001) when compared with control, RT alone, abemaciclib with anti-PD-L1, abemaciclib with RT, and anti-PD-L1 with RT. TILs assays showed the combination treatment of abemaciclib, RT, and anti PD-L1 increased CD4 and CD8 positive T cells proportion (<em>P</em> &lt; 0.05 and <em>P</em> &lt;0.01, respectively) as well as tumor associated macrophage (<em>P</em> &lt; 0.001) when compared to the control group. Immunohistochemical staining revealed an increase in CD8 positive T cells and <em>monocyte</em> chemoattractant protein (<em>MCP</em>)-1 positive macrophages in the triple-combination treatment group compared to the other four groups.</div></div><div><h3>Conclusion</h3><div>Combined CDK4/6 inhibitors with RT enhance anti-tumor effects of anti-PD-L1 immunotherapy in TNBC through increasing secretion of IFN-γ and modulation of tumor microenvironments via recruiting CD4 and CD8 positive T-cells, as well as M1 type tumor associated macrophage.</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":"142359566","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":"Novel Statistical-AI Method to Automate Discovery of Predictive Factors and Thresholds for 3 Year Survival, Dysphagia and Xerostomia for Patients with Head and Neck Cancers","authors":"","doi":"10.1016/j.ijrobp.2024.07.062","DOIUrl":"10.1016/j.ijrobp.2024.07.062","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Purpose/Objective(s)&lt;/h3&gt;&lt;div&gt;Clinicians iteratively adjust treatment approaches to improve outcomes, but to date, automatable approaches for continuous learning of risk factors as these adjustments are made are lacking. We combined a large-scale, comprehensive real-world Learning Health System infrastructure (LHSI), with automated statistical profiling, visualization, and artificial intelligence (AI) approach to test evidence-based discovery of clinical factors for three endpoints: dysphagia, xerostomia, and 3-year survival for head and neck cancer patients.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Materials/Methods&lt;/h3&gt;&lt;div&gt;Records for 964 patients treated for head and neck cancers with conventional fractionation between 2017 and 2022 were used. Combined information on demographics, diagnosis and staging, social determinants of health measures, chemotherapy, radiation therapy dose volume histogram curves, treatment details, laboratory values, and outcomes from the LHSI to winnow evidence for 485 candidate features. Univariate statistical profiling was performed using bootstrap resampling to detail confidence intervals for the following thresholds and metrics: area under the curve (AUC), sensitivity (SN), specificity (SP), F1, diagnostic odds ratio (DOR), &lt;em&gt;P&lt;/em&gt; values for Wilcoxon Rank Sum (WRS), Kolmogorov-Smirnov (KS), and logistic fits of distributions detailed predictive evidence of individual features. Parsimonious XGBoost models were constructed with 10-fold cross validation using training (70%), validation (10%), and test (20%) sets. Probabilistic models utilizing statistical profiling logistic fits of distributions were used to benchmark XGBoost models.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;Incidence of dysphagia ≥ grade 3 within 1 year of treatment was low (11%). Xerostomia ≥ grade 2 (39% to 16%) and survival ≤ 3 years decreased (25% to 15%) over the time range. The strongest grade 2 xerostomia predictor was Glnd_Submand_Low: D15% [Gy] ≥ 45.2 with a logistic model quantifying a gradual rather than an abrupt increase in probability (13.5 + 0.18 (x-41.0 Gy)). Strongest predictive factors for lower likelihood of death by 3 years were GTV_High: Volume [cc] ≤ 21.1, GTV_Low: Volume [cc] ≤ 57.5, Baseline Neutrophil-Lymphocyte Ratio (NLR) ≤ 5.6, Monocyte-Lymphocyte Ratio (MLR) ≤0.56, Platelet-Lymphocyte ratio (PLR) ≤ 202.5. All predictors had WRS and KS &lt;em&gt;P&lt;/em&gt; values &lt; 0.02. Statistical profiling enabled detailing gains of XGBoost models with respect to individual features. Time period reductions in distribution of GTV volumes correlated with reductions in death by 3 years.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusion&lt;/h3&gt;&lt;div&gt;Combined use of LHSI, Statistical Profiling and Artificial Intelligence provided a basis for automating evidence-based discovery. Benchmarking AI models with simple probabilistic models provided a means of understanding when results are driven by general areas of overall risk vs. more complex interactions. The method can form a new appr","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":"142359160","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":"Prostate Advanced Radiation Technologies Investigating Quality of Life (PARTIQoL): Phase III Randomized Clinical Trial of Proton Therapy vs. IMRT for Localized Prostate Cancer","authors":"","doi":"10.1016/j.ijrobp.2024.08.012","DOIUrl":"10.1016/j.ijrobp.2024.08.012","url":null,"abstract":"<div><h3>Purpose/Objective(s)</h3><div>Patients with localized prostate cancer have several treatment options including external beam radiotherapy with either photons or protons. Proton beam therapy (PBT) has certain dosimetric advantages with the potential to reduce treatment-associated morbidity and improve oncologic outcomes, but it is generally more resource intensive than intensity modulated radiation therapy (IMRT). To address the hypothesis that PBT results in improved patient-reported outcomes (PROs), PARTIQoL (NCT01617161) was conducted as a multi-center phase 3 randomized trial comparing the two modalities.</div></div><div><h3>Materials/Methods</h3><div>Patients with intermediate- or low-risk prostate cancer were randomized to PBT or IMRT, without hormonal therapy, stratified for institution, age, rectal spacer use, and fractionation (79.2 Gy/44 fractions vs 70 Gy/28 fractions). Participants were followed longitudinally to assess PROs of bowel, urinary, and sexual function for 60 months (mo) after completion of radiotherapy. Primary endpoint was to compare change from baseline in bowel quality of life (QOL) using the health care software score (range 0-100) at 24 mo. Secondary objectives include comparison of urinary and sexual functions, toxicity, and efficacy endpoints.</div></div><div><h3>Results</h3><div>Between 06/2012-11/2021, 450 patients from 30 recruiting centers were randomized: PBT (N=226) and IMRT (N=224), of whom 221 and 216 were eligible and started radiation on the respective arms. Median follow-up was 60.3 mo among 424 patients still alive. Median age was 68 yrs (range 46-89), 59% had intermediate-risk disease, 51% received hypofractionation, 48% used a rectal spacer, and 49% of PBT patients were treated with pencil beam scanning. There was no difference between PBT or IMRT in mean change of health care software bowel score at 24 mo (p=0.836), with both arms showing only small, clinically non-meaningful decline from baseline (see Table). Similarly, there was no difference in bowel function at earlier timepoints (3, 6, 9, 12, 18 mo) or later timepoints (36, 48, 60 mo). No differences were observed in other domains (urinary, sexual, hormonal) at any timepoint. There was no difference in progression-free survival (PFS) (93.4% vs 93.7% at 60 mo, HR 1.16 [0.53, 2.57], p=0.706). There was no sustained difference in any QOL domain or PFS between arms in subgroups defined by stratification variables.</div></div><div><h3>Conclusion</h3><div>This prospective randomized clinical trial shows that patients treated with contemporary radiotherapy for localized prostate cancer achieve excellent QOL with highly effective tumor control, without measurable differences between PBT and IMRT. We continue to monitor participants for longer follow-up and secondary endpoints.</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":"142358888","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":"Hypofractionated Whole-Breast Irradiation with Simultaneous Integrated Boost for Breast Cancer: Primary Analysis of the HYPOSIB-Trial (ARO 2013-05)","authors":"","doi":"10.1016/j.ijrobp.2024.07.005","DOIUrl":"10.1016/j.ijrobp.2024.07.005","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Purpose/Objective(s)&lt;/h3&gt;&lt;div&gt;Moderate hypofractionation (HF) is considered standard of care for adjuvant whole-breast radiotherapy in patients with breast cancer after breast-conserving surgery (BCS). The trials establishing HF used a sequential tumor bed boost (seqB). Prior studies have studied simultaneous integrated boost (SIB)-irradiation with conventional fractionation. The HYPOSIB-trial (NCT02474641) is one of three large trials that studied HF with SIB. Results for acute toxicity have been presented at a prior ASTRO-meeting and favored HF with SIB.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Materials/Methods&lt;/h3&gt;&lt;div&gt;HYPOSIB is a randomized-controlled, European, multi-center, non-inferiority trial. Randomization was performed 1:1 to the experimental arm (40 Gy to the breast and 48 Gy to the tumor bed in 16 fractions) or to the control arm (physician’s choice between conventional fractionation with SIB or seqB, or HF with seqB). The primary endpoint was disease-free survival (DFS). At trial initiation, a DFS of 86.4% at 5 years was assumed in the control arm with a non-inferiority margin of 5% (hazard ratio [HR] = 1.42). After a blinded interim analysis showed fewer events than expected, the design was changed to a time-driven analysis 3 years after enrollment of the final patient with an adapted non-inferiority boundary for the HR of 1.757. Secondary endpoints were local control, locoregional control, overall survival, toxicity, quality of life, and cosmesis.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;Between 2015 and 2019, a total of 2310 patients were randomized, of which 2179 were treated according to protocol and were part of this analysis. Median follow-up was 52.9 months (range = 42.0-61.7 months). There were 141 patients who had at least one DFS-event, of which 75 were in the experimental arm. Local recurrence occurred in 31 patients, of which 16 were in the experimental arm. DFS at 5 years was 92.0% (95% confidence interval [CI] = 89.9-93.6%) in the experimental arm and 92.2% (95% CI = 89.9-94.0%) in the control arm (HR = 1.10; 95% CI = 0.78-1.54; &lt;em&gt;P&lt;/em&gt; = 0.58). Thus, non-inferiority of the experimental arm was established. Local control at 5 years was 98.2% (95% CI = 97.0-98.9%) in the experimental arm and 98.0% (95% CI = 96.4-98.9%) in the control arm (HR = 1.08; 95% CI = 0.51-2.27; &lt;em&gt;P&lt;/em&gt; = 0.84). Overall survival at 5 years was 98.2% (95% CI = 96.9-98.9%) in the experimental arm and 97.9% (95% CI = 96.5-98.7%) in the standard arm (HR = 0.78; 95% CI = 0.39-1.55; &lt;em&gt;P&lt;/em&gt; = 0.48). Cumulative incidence of grade ≥ 2 fibrosis at 5 years was 7.3% in the experimental arm and 8.4% in the experimental arm (odds ratio = 0.86; 95% CI = 0.63-1.16; &lt;em&gt;P&lt;/em&gt; = 0.32). Telangiectasia grade ≥ 2 had occurred in 1.5% in the experimental arm and 1.5% in the control arm at 5 years (OR = 0.97; 95% CI = 0.50-1.88; &lt;em&gt;P&lt;/em&gt; = 0.92).&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusion&lt;/h3&gt;&lt;div&gt;Together with the findings of IMPORT HIGH and RTOG 1005, the results of HYPOSIB demo","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":"142359152","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":"Is the IROC H&N credentialing phantom an effective surrogate for different anatomical sites?: Using IROC's H&N phantom for various sites.","authors":"Fre'Etta M D Brooks, Mallory C Glenn, Victor Hernandez, Jordi Saez, Julianne M Pollard-Larkin, Christine B Peterson, Rebecca M Howell, Christopher L Nelson, Catharine H Clark, Stephen F Kry","doi":"10.1016/j.ijrobp.2024.09.053","DOIUrl":"https://doi.org/10.1016/j.ijrobp.2024.09.053","url":null,"abstract":"<p><strong>Purpose: </strong>The IROC head and neck phantom is used to credential institutions for IMRT delivery for all anatomical sites where delivery of modulated therapy is a primary challenge. This study evaluated how appropriate the use of this phantom is for varied clinical anatomy by evaluating how closely the IROC head and neck phantom described clinical dose errors from beam modeling compared to various anatomical sites.</p><p><strong>Methods: </strong>The MLC offset, transmission, PDD and seven additional beam modeling parameters for a Varian accelerator were modified in RayStation to match community data at the 2.5, 25, 50, 75 and 97.5 percentile levels. Modifications were evaluated on 25 H&N phantom cases and 25 clinical cases (H&N, prostate, lung, mesothelioma, and brain), generating 2,000 plan perturbations. Differences in mean dose delivered to clinical target volumes (CTV) and organs at risk (OAR) were compared between phantom and clinical plans to assess the relationship between dose deviations in phantom versus clinical CTVs, and as a function of 18 different complexity metrics.</p><p><strong>Results: </strong>Perturbations to MLC offset and transmission parameters demonstrated the greatest impact on dose accuracy for phantom and clinical plans (for all anatomic sites). The phantom demonstrated equivalent or greater sensitivity to these parameter perturbations when compared to clinical sites, largely aligning with treatment complexity. The mean MLC Gap best described the impact of errors in TPS beam modeling parameters in phantoms plan and clinical plans from various anatomical sites.</p><p><strong>Conclusion: </strong>When compared across various anatomical sites, the IROC H&N credentialing phantom exhibited similar or greater sensitivity to errors in the treatment planning system. As such, it is a suitable surrogate device for assessing institutional performance across various anatomical sites. If an institution successfully irradiates the phantom, that result confers confidence that IMRT to a wide range of anatomical sites can be successfully delivered by the institution.</p>","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":"142371819","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}