UCLA Department of Radiation Oncology

BACKGROUND/OBJECTIVES: 5DCT was first proposed in 2005 as a motion-compensated CT simulation approach for radiotherapy treatment planning to avoid sorting artifacts that arise in 4DCT when patients breathe irregularly. Since March 2019, 5DCT has been clinically implemented for routine use at our institution to leverage this technological advantage. The clinical workflow includes a quality assurance report that describes the output of primary workflow steps. This study reports on the challenges and quality of the clinical 5DCT workflow using these quality assurance reports. METHODS: We evaluated all thoracic 5DCT simulation datasets consecutively acquired at our institution between March 2019 and December 2022 for thoracic radiotherapy treatment planning. The 5DCT datasets utilized motion models constructed from 25 fast-helical free-breathing computed tomography (FHFBCTs) with simultaneous respiratory bellows signal monitoring to reconstruct individual, user-specified breathing-phase images (termed 5DCT phase images) for internal target volume contouring. Each 5DCT dataset was accompanied by a structured quality assurance report composed of qualitative and quantitative measures of the breathing pattern, image quality, DIR quality, model fitting accuracy, and a validation process by which the original FHFBCT scans were regenerated with the 5DCT model. Measures of breathing irregularity, image quality, and DIR quality were retrospectively categorized on a grading scale from 1 (regular breathing and accurate registration/modeling) to 4 (irregular breathing and inaccurate registration/modeling). The validation process was graded according to the same scale, and this grade was termed the suitability-for-treatment-planning (STP) grade. We correlated the graded variables to the STP grade. In addition to the quality assurance reports, we reviewed the contour sessions to determine how often 5DCT phase images were used for treatment planning and delivery. RESULTS: There were 169 5DCT simulation datasets available from 156 patients for analysis. The STP was moderately correlated with breathing irregularity, image quality, and DIR quality (Spearman coefficients: 0.26, 0.30, and 0.50, respectively). Multiple linear regression analysis demonstrated that STP was correlated with regular breathing patterns (p = 0.008), image quality (p < 0.001), and better DIR quality (p < 0.001). 5DCT datasets were used for treatment planning in 82% of cases, while in 12% of cases, a backup image process was used. In total, 6% of image datasets were not used for treatment planning due to factors unrelated to the 5DCT workflow quality. CONCLUSIONS: The strongest association with STP was with DIR quality grades, as indicated by both Spearman and multiple linear regression analysis, implying that improvements to DIR accuracy and evaluation may be the best route for further improvement to 5DCT. The high rate of 5DCT phase image use for treatment planning showed that the workflow was reliable, and this has encouraged us to continue to develop and improve the workflow steps.

PURPOSE: Gamma Knife radiosurgery (GKRS) is a precise and efficacious treatment modality for vestibular schwannoma (VS) with favorable cranial nerve preservation rates. This study aims to better characterize facial nerve (FN) outcomes in VS after GKRS. METHODS: A query of six medical databases was conducted following PRISMA guidelines. Eligible studies exclusively reported VS managed with single-fraction GKRS and included House-Brackmann (HB) scale assessments prior to and following GKRS. Data was analyzed using random-effects modeling, and FN preservation was defined as HB I or II at last follow-up. RESULTS: Data was analyzed from 15 articles with 3,155 patients at an mean age of 55.0 years. Mean tumor volume, radiation dose, follow-up, tumor control, and hearing preservation were 4.28 cm3, 13.3 Gy, 59.4 months, 92.7%, and 62.6%, respectively. The pooled FN preservation rate was 92.9%. Mean preoperative tumor volume > 2.5 cm3 and age > 60 years were significantly associated with worse preoperative FN function (p = 0.019, p = 0.023, respectively). Normal FN function (HB = 1) at last follow up was 95.8% for VS volume < 2.5 cm3 and 89.4% with larger volumes (p < 0.001). Doses ≤ 13 Gy were significantly associated with superior FN preservation (96.5%) compared to higher doses (p < 0.001). Tumor control and hearing preservation were not significantly associated with FN preservation. CONCLUSION: This meta-analysis identifies tumor volume and radiation dose as prognostic factors for FN preservation. A FN preservation rate of 93% may be expected at five years after GKRS. This study provides a unique characterization of FN outcome that should be considered in the management of VS.

Radiation therapy (RT) is a critical component of multidisciplinary cancer care, but has inconsistent curricular exposure. We characterize the radiation oncology (RO) content on the standardized undergraduate medical examinations by comparing its context and prevalence with other domains in oncology. National Board of Medical Examiners (NBME) self-assessments and sample questions for the United States Medical Licensing Exam (USMLE) Steps 1-3 and NBME clinical science shelf examinations were accessed (n = 3878). Questions were inductively analyzed for content pertaining to oncology and treatment modalities of RT, systemic therapy (ST), and surgical intervention (SI). Questions were coded using USMLE Physician Tasks/Competencies and thematic analysis. Descriptive statistics and analyses using the Kruskal-Wallis test are reported. A total of 337 questions (8.6%) within the USMLE and shelf exams included oncology content, with 101 questions (2.6%) referencing at least one cancer treatment modality (n = 35 RT, 45 ST, 57 SI). Treatment questions were more common on USMLE Step 2 CK (n = 35/101, 32%) compared to Step 1 (n = 23/101, 23%) and Step 3 (n = 8/101, 8%) (p < 0.001). RT was significantly less likely to be the correct answer (2/35, 6%) compared to ST (4/45, 9%) and SI (18/57, 32%) (p = 0.003). Therapeutic oncology questions are uncommon on the examination material, with an under-representation of radiation-related content, and contextual bias favoring surgical approaches. We advocate for greater RO involvement in the content creation of such examinations to help trainees better understand multidisciplinary cancer care.

PURPOSE: Lung cancer screening (LCS) has the potential to reduce mortality and detect lung cancer at its early stages, but the high false-positive rate associated with low-dose computed tomography (LDCT) for LCS acts as a barrier to its widespread adoption. This study aims to develop computable phenotype (CP) algorithms on the basis of electronic health records (EHRs) to identify individuals eligibility for LCS, thereby enhancing LCS utilization in real-world settings. MATERIALS AND METHODS: The study cohort included 5,778 individuals who underwent LDCT for LCS from 2012 to 2022, as recorded in the University of Florida Health Integrated Data Repository. CP rules derived from LCS guidelines were used to identify potential candidates, incorporating both structured EHR and clinical notes analyzed via natural language processing. We then conducted manual reviews of 453 randomly selected charts to refine and validate these rules, assessing CP performance using metrics, for example, F1 score, specificity, and sensitivity. RESULTS: We developed an optimal CP rule that integrates both structured and unstructured data, adhering to the US Preventive Services Task Force 2013 and 2020 guidelines. This rule focuses on age (55-80 years for 2013 and 50-80 years for 2020), smoking status (current, former, and others), and pack-years (≥30 for 2013 and ≥20 for 2020), achieving F1 scores of 0.75 and 0.84 for the respective guidelines. Including unstructured data improved the F1 score performance by up to 9.2% for 2013 and 12.9% for 2020, compared with using structured data alone. CONCLUSION: Our findings underscore the critical need for improved documentation of smoking information in EHRs, demonstrate the value of artificial intelligence techniques in enhancing CP performance, and confirm the effectiveness of EHR-based CP in identifying LCS-eligible individuals. This supports its potential to aid clinical decision making and optimize patient care.

Glioblastoma is immunologically cold and resistant to single-agent immune-checkpoint inhibitors (ICI). Our previous study of neoadjuvant pembrolizumab in surgically-accessible recurrent glioblastoma identified a molecular signature of response to ICI and suggested that neoadjuvant pembrolizumab may improve survival. To increase the power of this observation, we enrolled an additional 25 patients with a primary endpoint of evaluating the cell cycle gene signature associated with neoadjuvant pembrolizumab and performed bulk-RNA seq on resected tumor tissue (NCT02852655). Neoadjuvant pembrolizumab was associated with suppression of cell cycle/cancer proliferation genes and upregulation of T-cell/interferon-related gene expression. This signature was unique to patients treated with neoadjuvant pembrolizumab and was an independent positive risk factor for survival. Our results demonstrate a clear pharmacodynamic effect of anti-PD1 therapy in glioblastoma and identify pathways that may mediate resistance. However, we did not confirm a survival benefit to neoadjuvant pembrolizumab in recurrent glioblastoma and our secondary endpoint of PFS-6 was 19.5% (95% CI: 9.29-41.2%) for the pooled neoadjuvant cohorts. Our new data suggests some patients may exhibit innate resistance to pre-surgical ICI and require other concomitant therapies to sensitize effectively.

Exposure to ionizing radiation disrupts metabolic pathways and causes oxidative stress, which can lead to organ damage. In this study, urinary metabolites from mice exposed to high-dose and low-dose whole-body irradiation (WBI HDR, WBI LDR) or partial-body irradiation (PBI BM2.5) were analyzed using targeted and untargeted metabolomics approaches. Significant metabolic changes particularly in oxidative stress pathways were observed on Day 2 post-radiation. By Day 30, the WBI HDR group showed persistent metabolic dysregulation, while the WBI LDR and PBI BM2.5 groups were similar to control mice. Machine learning models identified metabolites that were predictive of the type of radiation exposure with high accuracy, highlighting their potential use as biomarkers for radiation damage and oxidative stress.

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This cross-sectional study compares the use of management tools and plan-level total costs for oral ondansetron between Part D independent prescription drug plans and Medicare Advantage prescription drug plans.

PURPOSE: Fibroblast Activation Protein (FAP) is an emerging theranostic target that is highly expressed on cancer-associated fibroblasts and on certain tumor cells including sarcoma. We investigated the anti-tumor efficacy of [225Ac]Ac-FAPI-46 as monotherapy or in combination with immune checkpoint blockade (ICB) in immunocompetent murine models of sarcoma sensitive or resistant to ICB. METHODS: [68Ga]Ga- and [225Ac]Ac-FAPI-46 were tested in subcutaneous FAP+ FSA fibrosarcoma bearing C3H/Sed/Kam mice. The efficacy of up to three cycles of 60 kBq [225Ac]Ac-FAPI-46 was evaluated as monotherapy and in combination with an anti-PD-1 antibody. Efficacy of [225Ac]Ac-FAPI-46 and/or ICB was further compared in FAP-overexpressing FSA (FSA-F) tumors that were sensitive to ICB or rendered ICB-resistant by tumor-induction in the presence of Abatacept. RESULTS: [225Ac]Ac-FAPI-46 was well tolerated up to 3 × 60 kBq but had minimal effect on FSA tumor growth. The combination of three cycles [225Ac]Ac-FAPI-46 and ICB resulted in growth delay in 55% of mice (6/11) and partial tumor regression in 18% (2/11) of mice. In FSA-F tumors with FAP overexpression, both [225Ac]Ac-FAPI-46 and ICB were effective without additional benefits from the combination. In locally immunosuppressed and ICB resistant FAP-F tumors, however, [225Ac]Ac-FAPI-46 restored responsiveness to ICB, resulting in significant tumor regression and tumor-free survival of 56% of mice in the combination group up to 60 days post treatment. CONCLUSION: [225Ac]Ac-FAPI-46 efficacy is correlated with tumoral FAP expression levels and can restore responsiveness to PD-1 ICB. These data illustrate that careful patient selection based on target expression and rationally designed combination therapies are critically important to maximize the therapeutic impact of FAP-targeting radioligands.

Treatment of the tumor and dural margin with surgery and sometimes radiation are cornerstones of therapy for meningioma. Molecular classifications have provided insights into the biology of disease; however, response to treatment remains heterogeneous. In this study, we used retrospective data on 2,824 meningiomas, including molecular data on 1,686 tumors and 100 prospective meningiomas, from the RTOG-0539 phase 2 trial to define molecular biomarkers of treatment response. Using propensity score matching, we found that gross tumor resection was associated with longer progression-free survival (PFS) across all molecular groups and longer overall survival in proliferative meningiomas. Dural margin treatment (Simpson grade 1/2) prolonged PFS compared to no treatment (Simpson grade 3). Molecular group classification predicted response to radiotherapy, including in the RTOG-0539 cohort. We subsequently developed a molecular model to predict response to radiotherapy that discriminates outcome better than standard-of-care classification. This study highlights the potential for molecular profiling to refine surgical and radiotherapy decision-making.