International Journal of Radiation Oncology Biology Physics最新文献

{"title":"Evaluating Neurocognitive Recovery Following Stereotactic Radiosurgery and Whole Brain Radiation Therapy: Insights from a Pooled Analysis of Three Phase III Trials","authors":"","doi":"10.1016/j.ijrobp.2024.07.057","DOIUrl":"10.1016/j.ijrobp.2024.07.057","url":null,"abstract":"<div><h3>Purpose/Objective(s)</h3><div>Neurocognitive changes following brain radiation therapy are significant concerns for patients (pts) with brain metastases (BM). Despite reductions in the rates of neurocognitive failure (NCF) with conformal radiation techniques such as stereotactic radiosurgery (SRS) and hippocampal-avoidance whole brain radiation therapy (HA-WBRT), a significant number of pts still experience NCF. Although there are data describing the onset and incidence of NCF, the long-term neurocognitive changes and potential functional recovery that pts experience after NCF have not been well described. Thus, we aimed to evaluate cognitive recovery (CR) following initial NCF in patients treated with SRS or WBRT by analyzing cognitive testing results from cooperative group trials.</div></div><div><h3>Materials/Methods</h3><div>Using the NCTN data archive, we conducted a pooled analysis of three phase III randomized clinical trials - NCCTG N107C/CEC.3 (comparing postoperative SRS vs. WBRT), NCCTG N0574 (comparing SRS vs. SRS+WBRT), and NRG Oncology CC001 (comparing HA-WBRT vs. WBRT) - and included pts who experienced NCF as predefined in each trial. Full CR was defined as pts no longer exhibiting a 1 or more standard deviation (SD) decline from baseline on any cognitive test, while recovery on individual tests was defined as at least a 1 SD improvement on a previously failed cognitive test. To estimate the incidence of CR, we used cumulative incidence function and Gray’s test. We analyzed prognostic variables associated with CR using multivariable Cox proportional hazards modeling.</div></div><div><h3>Results</h3><div>Two hundred eighty-eight pts who experienced trial-defined NCF were included. The pooled cumulative incidence of full CR was 38% and 42% at 6- and 12-months after onset of NCF, respectively. The incidence rates of improvement on any previously failed cognitive test were 73% and 76% for the same time points. Cumulative incidence of full CR was significantly greater with postoperative SRS vs. WBRT (HR = 2.68, Gray’s <em>P</em> = 0.002), as well as with SRS alone vs. SRS+WBRT (HR = 2.35, <em>P</em> = 0.008). There was a trend towards higher incidence of CR with HA-WBRT vs. WBRT (HR = 1.57, <em>P</em> = 0.059). There was no difference in rates of improvement in cognitive tests based on treatment. On multivariable pooled analysis, SRS was predictive of CR vs. WBRT (HR = 2.42, <em>P</em> < 0.0001). HA-WBRT demonstrated near significant association with CR vs. WBRT (HR = 1.56, <em>P</em> = 0.06). Age and performance status were not prognostic for CR.</div></div><div><h3>Conclusion</h3><div>Our analysis reveals that a sizeable proportion of pts who experience NCF following brain radiation therapy eventually demonstrate recovery. The use of conformal radiation techniques such as SRS and HA-WBRT result in greater rates of functional recovery. These findings may help counsel pts about the likelihood of meaningful neurocognitive im","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":"142358606","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":"Radiotherapy Target Volume Delineation Based on Post-Induction Chemotherapy Gross Tumor Volume vs. Pre-Induction Volume for Locoregionally Advanced Nasopharyngeal Carcinoma: An Open-label, Non-Inferiority, Multicenter, Randomized Phase III Trial","authors":"","doi":"10.1016/j.ijrobp.2024.08.023","DOIUrl":"10.1016/j.ijrobp.2024.08.023","url":null,"abstract":"<div><h3>Purpose/Objective(s)</h3><div>Radiotherapy target volume delineation based on pre-induction chemotherapy gross tumor volume (pre-IC GTV) is the standard principle in patients with locoregionally advanced nasopharyngeal carcinoma (LANPC) after IC. However, over 90% patients responded to IC, with a significant volume reduction in GTV. We aimed to address whether radiotherapy target volume delineation based on pre-IC GTV can be safely reduced to post-IC GTV for LANPC patients treated with intensity-modulated radiotherapy.</div></div><div><h3>Materials/Methods</h3><div>In this open-label, non-inferiority, randomized controlled, phase III trial, patients with newly diagnosed, non-keratinising, non-metastatic NPC were recruited from three Chinese medical centers. Key inclusion criteria were aged 18–70 years, stage III-IVa disease (AJCC 8th edition), and a Karnofsky performance status score of at least 70. Eligible patients were required to have completed 3 cycles of IC and then were randomly assigned (1:1; block size of four) to receive radiotherapy with target volume delineation either based on post-IC or pre-IC GTV. Randomization was centrally performed with a random number code stratified by treatment center and stage. The primary endpoint was locoregional relapse-free survival (LRRFS). Non-inferiority was indicated if the lower limit of the 95% confidence interval (CI) of the difference in 3-year LRRFS between 2 groups was greater than -8%. The secondary endpoints were overall survival (OS), distant metastasis-free survival (DMFS), adverse events (AEs) and quality of life (QoL).</div></div><div><h3>Results</h3><div>A total of 445 patients were recruited (225 patients in the post-IC GTV group and 220 patients in the pre-IC GTV group). After a median follow-up of 38.7 months till June 30, 2024, intention-to-treat analysis showed that the post-IC GTV group and pre-IC GTV group had similar 3-year LRRFS (89.9% [95% CI 85.6 to 93.8] <em>v</em> 89.6% [95%CI 85.9 to 94.2], difference 0.3% [lower limit of the one-sided 95% CI -5.3], P_{non-inferiority} 0.007), 3-year OS (96.7% <em>v</em> 96.6%, P=0.64) and DMFS (91.2% <em>v</em> 92.7%, P=0.62). In the safety population (n=442), the post-IC GTV group had lower incidence of acute grade 3-4 AEs (37.4% <em>v</em> 55.5%) and late radiation related grade 3-4 AEs (22.5% <em>v</em> 33.6%) to the pre-IC GTV group. During follow up, the post-IC GTV group had significantly better QoL scores for global health (82.1 <em>v</em> 73.4, P&lt;0.001) and emotional functioning (94.4 <em>v</em> 90.3, P=0.25).</div></div><div><h3>Conclusion</h3><div>Radiotherapy target volume delineation based on post-IC GTV was noninferior to that based on pre-IC GTV in LRRFS with less toxicities and better quality of life in LANPC. This study is registered with ClinicalTrials.gov, NCT04384627.</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":"142358594","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":"Neurocognition and Quality of Life for Hypofractionated Stereotactic Radiotherapy (HFSRT) of the Resection Cavity vs. Whole-Brain Radiotherapy (WBRT) Following Brain Metastasis Resection – Results of the ESTRON Randomized Phase 2 Trial","authors":"","doi":"10.1016/j.ijrobp.2024.07.058","DOIUrl":"10.1016/j.ijrobp.2024.07.058","url":null,"abstract":"<div><h3>Purpose/Objective(s)</h3><div>The ESTRON randomized phase 2 trial compared post-operative hypofractionated stereotactic radiotherapy (HFSRT) of the resection cavity following brain metastases (BM) resection with post-operative whole-brain radiotherapy (WBRT) in patients with 1-10 BM. We previously presented local control (LC), intracranial control (IC) and overall survival (OS). Neurocognitive function and quality of life were pre-specified secondary endpoints.</div></div><div><h3>Materials/Methods</h3><div>Neurocognitive testing included the Hopkins Verbal Learning Test-Revised (HVLT-R) total recall (TR) and delayed recall (DR). A drop of ≥ 5 points from baseline in HVLT-R total recall was considered clinically relevant. Health-related Quality of Life (hr-QoL) was assessed using the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C15 PAL questionnaire and brain module (BN-20). All Assessments were performed at baseline, 6-8 weeks after treatment and three-monthly afterwards for 12 months.</div></div><div><h3>Results</h3><div>Fifty-four patients were randomized; HFSRT <em>n</em> = 27, WBRT <em>n</em> = 27. HFSRT provided 3-year LC of 96% with similar IC and OS between groups, as reported previously. Median baseline HVLT-R score was 24.0 (Q1-Q3 = 18-27) in the HFSRT-group vs. 26.0 (Q1-Q3 = 22-28) in the WBRT-group for TR subscale and 8.0 (Q1-Q3 = 5-10, HFSRT-group) vs. 9.5 (Q1-Q3 = 8-12, WBRT-group) for DR subscale. A drop of ≥ 5 points from baseline occurred in 5 patients (18.5%) in the HFSRT-group vs. 8 patients (29.6%) in the WBRT group (risk difference 0.11, 95% CI = [-0.34 to 0.12], <em>P</em> = 0.34). Maximum change in median HVLT-R TR score was +8.3% (Q1-Q3 = 23-34, HFSRT-group) vs. -11.5% (Q1-Q3 = 18-28, WBRT-group) at 31 weeks from baseline (<em>P</em> = 0.079). At no timepoint did the median HVLT-R TR score decline from baseline in the HFSRT-group. For DR subscale, median change from baseline was +17.6% (Q1-Q3 = 8-12, HFSRT-group) vs. -15.8% (Q1-Q3 = 4-10, WBRT-group) at 31 weeks (<em>P</em> = 0.246). Overall hr-QoL (QLQ-C15 PAL) was similar in both groups. Regarding functional subscales, in the WBRT-group a relevant increase in nausea/vomiting (mean +33.3, standard deviation (SD) = 13.4 points, <em>P</em> = 0.001) and appetite loss (mean +40.3, SD = 32.6 points, <em>P</em> &lt; 0.001) was observed 7 weeks from baseline with no respective change in the HFSRT-group. The other functional scales of QLQ-C15 PAL and BN-20 were not relevantly different between groups.</div></div><div><h3>Conclusion</h3><div>While providing excellent local control, HFSRT following BM resection preserves neurocognition more effectively than WBRT, with differences most pronounced at 7 months from baseline. Overall hr-QoL was similar, although WBRT acutely worsened nausea and appetite loss.</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":"142358607","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 Abstract Awards","authors":"","doi":"10.1016/j.ijrobp.2024.06.027","DOIUrl":"10.1016/j.ijrobp.2024.06.027","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":"142358788","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Phase 3 Study of Pembrolizumab (Pembro) + Concurrent Chemoradiotherapy (CCRT) for High-Risk Locally Advanced Cervical Cancer (LACC): Safety Findings","authors":"","doi":"10.1016/j.ijrobp.2024.07.004","DOIUrl":"10.1016/j.ijrobp.2024.07.004","url":null,"abstract":"<div><h3>Purpose/Objective(s)</h3><div>In ENGOT-cx11/GOG-3047/KEYNOTE-A18 (NCT04221945), pembro + CCRT improved PFS (HR = 0.70 [95% CI = 0.55‒0.89]; <em>P</em> = 0.0020) and showed a favorable trend in OS (HR = 0.73 [95% CI = 0.49‒1.07]) vs placebo (pbo) + CCRT in high-risk LACC at interim analysis 1 (IA1). Here, we report IA1 safety data.</div></div><div><h3>Materials/Methods</h3><div>Patients (pts) with previously untreated, high-risk LACC (FIGO 2014 stage IB2‒IIB node-positive or stage III‒IVA) were randomized 1:1 to 5 cycles of pembro 200 mg or pbo Q3W + CCRT, then 15 cycles of pembro 400 mg or pbo Q6W. CCRT included 5 cycles (optional 6th dose) of cisplatin 40 mg/m² QW + EBRT followed by brachytherapy. Safety was evaluated in all randomized and treated pts.</div></div><div><h3>Results</h3><div>Of 1060 randomized pts, 1058 were included in the safety analysis. At data cutoff (Jan 9, 2023), median follow-up was 17.9 mo. AE rates were similar between the treatment arms (see the <strong>Table</strong>). AEs were more common during the pembro + CCRT combination therapy phase vs pembro monotherapy phase. Exposure-adjusted AE rates generally decreased after 3 mo; hypothyroidism was most common between 3-6 mo with pembro + CCRT. Event rates for genitourinary AEs were &lt; 10.0 events per 100 person-months of exposure during any period.</div></div><div><h3>Conclusion</h3><div>Pembro + CCRT had manageable safety that was consistent with the known profiles of pembro monotherapy and chemoradiotherapy. Most AEs occurred during the combination therapy phase.</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":"142358706","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":"Randomized Trial of Mindfulness during Radiation Therapy","authors":"","doi":"10.1016/j.ijrobp.2024.07.028","DOIUrl":"10.1016/j.ijrobp.2024.07.028","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Purpose/Objective(s)&lt;/h3&gt;&lt;div&gt;Many patients receiving cancer treatment experience decreased quality of life (QoL). Evidence-based strategies are needed to mitigate this decline. Mindfulness meditation demonstrates promise in improving QoL in many patient populations but has not been studied in the radiation oncology setting. We aimed to evaluate the effectiveness of a mindfulness-based intervention (MBI) on QoL during and after radiotherapy (RT) for cancer treatment.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Materials/Methods&lt;/h3&gt;&lt;div&gt;We conducted a randomized, phase 3 trial of weekly guided mindfulness meditation vs. standard of care (SOC) for patients undergoing RT. Patients and their caregivers were offered several 30-minute mindfulness sessions per week, as well as materials to practice mindfulness independently. Patients were meditation-naïve and scheduled for at least 3 weeks of curative-intent RT. Randomization was 1:1 using a permuted block design and stratified by baseline QoL (FACT-G &gt; or &lt; 90) and expected treatment intensity (high vs low). The primary endpoint was change in FACT-G score from baseline to end of RT. Secondary endpoints included change in LASA-6 score during RT, measure of relaxation during RT, and change in FACT-G, PROMIS 10, and LASA-6 scores in the year following RT. We estimated 190 patients were needed to provide 90% power to detect at least half a standard deviation change.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;We enrolled 53 patients over 9 months prior to a study pause in March 2020 due to COVID-19. After 6 months and implementation of COVID safety measures, the study reopened but only accrued 22 more patients in 10 months. Accrual closed at 75 patients. Sixty-eight patients completed the study – 31 in the MBI arm and 37 in SOC. Most patients in the MBI arm (58%) and the SOC arm (62%) underwent low intensity treatment (majority breast and prostate). Per recorded attendance, 42% of MBI patients were compliant with attending sessions at least once per week (average 0.8 sessions weekly). However, attendance may be under-recorded, as 94% of patients reported attending at least weekly. Of those receiving SOC, 43% reported use of independent wellness activities. There was no difference in QoL, as measured by change in FACT-G score, from baseline to end of RT, 3 months after, or 12 months after RT between arms. High intensity MBI patients trended toward greater improvement in FACT-G score between baseline and 12 months, and end of RT and 12 months (&lt;em&gt;P&lt;/em&gt; = 0.097 and &lt;em&gt;P&lt;/em&gt; = 0.095), than SOC patients. Per LASA-5 and PROMIS-10 QoL scores, the MBI group maintained QoL during RT, whereas the SOC group experienced decreased QoL (mean Δ0.0 vs -1.0, &lt;em&gt;P&lt;/em&gt; = 0.019 per LASA-5; mean Δ0.1 vs -2.3, &lt;em&gt;P&lt;/em&gt; = 0.042 per PROMIS-10). Patients in the MBI group reported greater improvement in relaxation from the start to end of RT (&lt;em&gt;P&lt;/em&gt; = 0.002).&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusion&lt;/h3&gt;&lt;div&gt;Participation in weekly 30-minute se","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":"142359419","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 Mentorship Award Recipients","authors":"","doi":"10.1016/j.ijrobp.2024.08.003","DOIUrl":"10.1016/j.ijrobp.2024.08.003","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":"142358785","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 - 25 Years of Membership","authors":"","doi":"10.1016/j.ijrobp.2024.08.004","DOIUrl":"10.1016/j.ijrobp.2024.08.004","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":"142358787","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":"From Face-to-Face to Digital Spaces: A Critical Look at Patient Satisfaction with Telehealth in Cancer Care","authors":"","doi":"10.1016/j.ijrobp.2024.07.026","DOIUrl":"10.1016/j.ijrobp.2024.07.026","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Purpose/Objective(s)&lt;/h3&gt;&lt;div&gt;Telehealth encounters offer a convenient alternative to traditional healthcare access, mitigating infection risk and providing a critical safeguard for immunocompromised patients, such as those undergoing oncology treatment. Despite its growing usage, there is a lack of research on telemedicine’s impact on the quality of healthcare delivery. In this study, we provide a comprehensive analysis of our institutional data, highlighting the impact of telehealth on patient satisfaction relative to a carefully matched cohort of in-person encounters.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Materials/Methods&lt;/h3&gt;&lt;div&gt;A 14-item CMS approved Patient Satisfaction (PS) survey was administered to patients at four outpatient academic radiation oncology centers from May 2021 to November 2023. Four survey questions were analyzed: team member listened, team member explained, enough input in care, and the likelihood of facility/provider recommendation. The likelihood of recommending the facility and/or provider was gauged on a 0-10 scale, with 9-10 indicating a higher likelihood of endorsement. Responses to the other questions were measured on a 0-4 Likert scale, where 4 signifies “Yes, definitely”, indicating satisfaction for the given question. A previous analysis has identified five key factors that independently influence PS: Area Deprivation Index (ADI), gender, cancer diagnosis, treatment intent, and survey visit type. Based on these findings, a matched pair analysis was conducted, ensuring participants were paired based on these criteria to accurately assess the impact of telehealth on PS. Univariate (UVA) and multivariable (MVA) logistic regression analyses determined the impact of these factors on recommendation scores.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;Out of 7,501 collected surveys, 528 (7%) were collected from telehealth encounters. After matching, patients in the telehealth group reported less satisfaction across all questions, including team member listened (&lt;em&gt;P&lt;/em&gt; &lt; 0.001), team member explained (&lt;em&gt;P&lt;/em&gt; &lt; 0.001), enough input in care (&lt;em&gt;P&lt;/em&gt; &lt; 0.001), facility recommendation (&lt;em&gt;P&lt;/em&gt; = 0.003), and provider recommendation (&lt;em&gt;P&lt;/em&gt; = 0.012) compared to in-person visits. MVA highlighted that patients who were satisfied with “enough input in care” (OR = 86.9, &lt;em&gt;P&lt;/em&gt; = 0.002) and “team member explained” (OR = 9.3, &lt;em&gt;P&lt;/em&gt; &lt; 0.001) were more likely to recommend the facility and the provider.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusion&lt;/h3&gt;&lt;div&gt;In this study, we found that patients are overall less likely to report high satisfaction with their telehealth compared to in-person encounters. The factors driving whether patients are likely to recommend the facility or the provider were higher satisfaction with the input they had in their care and whether the provider explained well. Further research is needed to address potential limitations of telemedicine encounters to increase access to health, particularly for pat","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":"142359415","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Precision Oncology Platform to Target CDK4/6 Inhibitor Resistance","authors":"","doi":"10.1016/j.ijrobp.2024.07.069","DOIUrl":"10.1016/j.ijrobp.2024.07.069","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Purpose/Objective(s)&lt;/h3&gt;&lt;div&gt;Cyclin-dependent kinase (CDK)4/6 inhibitors such as palbociclib, in combination with endocrine therapies, are commonly used as first line treatment in patients with metastatic Estrogen Receptor-positive (ER+) breast cancer (BC). While CDK4/6 inhibitors significantly improve survival, development of acquired resistance to these agents is nearly universal, commonly through loss of &lt;em&gt;RB1.&lt;/em&gt; Since new drug development is a time consuming and expensive endeavor, we hypothesized that high throughput screens (HTS) employing existing drugs and drug candidates is a rapid and cost-effective process for identifying novel targeted therapies that are effective against breast tumors that have developed resistance to current standard-of-care treatments such as CDK4/6 inhibitors.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Materials/Methods&lt;/h3&gt;&lt;div&gt;We used the CRISPR-Cas9 system to knockout &lt;em&gt;RB1&lt;/em&gt; in a panel of ER+ cell lines, including MCF-7, to generate palbociclib-resistant models of ER+ BC. For HTS, MCF-7 &lt;em&gt;RB1&lt;/em&gt;&lt;sup&gt;-/-&lt;/sup&gt; cells were plated to a final density of 600 cells per well in 60 μL of medium in 384-well microtiter plates and incubated with the drug library (one drug/well). Cell Tier Glo assay was used to measure cell viability after 48-hour incubation with the drug library. Top 100 hits from the primary screen were validated in a confirmatory screen using a multidose format. Xenograft studies in athymic nude mice were employed to study the &lt;em&gt;in vivo&lt;/em&gt; efficacy of top hits identified in HTS.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;We carried out a HTS using Selleck and Prestwick chemical libraries comprised of over 3000 compounds, many of which are FDA approved drugs and identified several “hits” that exhibited potent &lt;em&gt;in vitro&lt;/em&gt; activity in inhibiting the growth of palbociclib-resistant MCF-7 &lt;em&gt;RB1&lt;/em&gt;&lt;sup&gt;-/-&lt;/sup&gt; cells. One of the top hits, JIB-04 (a small molecule inhibitor of Jumonji histone demethylase) was further validated in &lt;em&gt;in vivo&lt;/em&gt; xenograft models. Thus, JIB-04 (50 mg/kg by oral gavage, 3 days/week) completely inhibited tumor growth (&lt;em&gt;P&lt;/em&gt; &lt; 0.05 for JIB-04 vs vehicle and &lt;em&gt;P&lt;/em&gt; &lt; 0.05 for JIB-04 vs palbociclib by unpaired, 2-tailed t-test), although palbociclib (100 mg/kg by oral gavage, daily) was completely ineffective in inhibiting growth of these tumors (&lt;em&gt;P&lt;/em&gt; &gt; 0.5 for palbociclib vs vehicle by unpaired, 2-tailed t-test). Mice did not show any evidence of toxicity or weight loss&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusion&lt;/h3&gt;&lt;div&gt;We used a HTS to rapidly identify JIB-04, a small molecule inhibitor of Jumonji histone demethylase, as a highly effective targeted therapy for treatment of ER+ breast cancers that have developed resistance to CDK4/6 inhibitors due to loss of &lt;em&gt;RB1&lt;/em&gt;. Since treatment options for patients with CDK4/6 inhibitor-resistant ER+ breast cancer are severely limited, our findings provide therapeutic rationale for developing new clinical trials fo","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":"142359497","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}