Locoregional Therapies for Hepatocellular Carcinoma prior to Liver Transplant: Comparative Pathologic Necrosis, Radiologic Response, and Recurrence.

PURPOSE: To compare pathologic tumor necrosis rates after locoregional therapies (LRTs) for hepatocellular carcinoma (HCC) prior to liver transplantation and evaluate radiologic-pathologic correlation along with posttransplant HCC recurrence. MATERIALS AND METHODS: Consecutive patients with solitary HCC bridged or downstaged with LRT from 2010 to 2022 were included. LRTs were transarterial chemoembolization (TACE), radioembolization (yttrium-90 [90Y]), ablation, and stereotactic body radiotherapy (SBRT). Upfront combination therapy options were TACE/ablation and TACE/SBRT. Subsequent therapy crossover due to local recurrence was allowed. Posttreatment imaging closest to the time of transplant, explant histopathologic necrosis, and tumor recurrence after transplant were reviewed. RESULTS: Seventy-three patients met inclusion criteria, of whom 5 (7%) required downstaging. 90Y alone (n = 36) and multimodal therapy (pooled upfront combination and crossover therapy, n = 23) resulted in significantly greater pathologic necrosis compared with TACE alone (n = 14; P = .01). High dose 90Y radiation segmentectomy (≥190 Gy; n = 27) and TACE/ablation (n = 7) showed highest rates of complete pathologic necrosis (CPN)-63% (n = 17) and 71% (n = 5), respectively. Patients with CPN had a mean lesion size of 2.5 cm, compared with 3.2 cm without CPN (P = .04), irrespective of LRT modality. HCC recurrence was more common in patients without CPN (16%, 6/37) than in those with CPN (3%, 1/36; P = .11). Using Liver Imaging Reporting and Data System (LI-RADS), a nonviable imaging response was 75% sensitive and 57% specific for CPN. CONCLUSIONS: Radiation segmentectomy and multimodal therapy significantly improved CPN rates compared with TACE alone. A LI-RADS treatment response of nonviable did not confidently predict CPN.

Pilot Study Demonstrating the Value of Interdisciplinary Education on the Integration of Radiation Therapy in Lung Cancer Management.

This study aimed to understand baseline knowledge of basic principles of radiation therapy for lung cancer among medical oncology, thoracic surgery, and pulmonology trainees and practicing physicians and also assess whether a didactic lecture will improve objective knowledge and perceived comfort level in making appropriate referrals to radiation oncology (RO). Radiation oncologists at 8 academic institutions offered a presentation covering indications, logistics, efficacy, and toxicity of thoracic radiation. Participants completed a survey to assess their prior exposures to RO and perceived value of the lecture, and objective knowledge gained based on pre/post-lecture questions. Among 121 attendees, 76 completed the pre-test, and 25 the post-test (response rates 62.8% and 20.7%, respectively). Fifty-seven (75.0%) had never previously experienced a RO didactic about lung cancer, 62 (81.6%) had never seen a linear accelerator, and 65 (85.5%) had never rotated in a RO department. The mean pre-test score was 53.5% (SD 17.6%), with a trend (p = 0.066) towards thoracic surgeons (61.5%) performing better than medical oncologists (55.5%) or pulmonologists (48.3%). Level of training (p = 0.130), and prior RO exposures (p = 0.240), did not significantly impact pre-test scores. The mean post-test score of 75.1% (SD 3.6%) was significantly higher than mean pre-test score (p < 0.001). After the lecture, 25 participants (100%) felt more knowledgeable about RO, and 24 (96%) felt more comfortable making appropriate referrals to RO. A didactic lecture about RO for trainees and physicians who treat lung cancer at 8 academic institutions was feasible, filled a gap in exposure, and improved knowledge.

Outcomes following stereotactic radiosurgery for foramen magnum meningiomas: a single-center experience and systematic review of the literature.

OBJECTIVE: Foramen magnum meningiomas (FMMs) pose a unique challenge given their intimate anatomical relationship with the craniovertebral junction. While resection has been studied extensively, much less has been reported about the use of stereotactic radiosurgery (SRS) for FMMs. This study includes what is to the authors' knowledge the first systematic review in the literature that summarizes patient and treatment characteristics and synthesizes outcomes following SRS for FMMs. METHODS: A retrospective chart review was conducted at a single major academic institution, and a systematic review was performed according to PRISMA guidelines. The initial search on the PubMed and Scopus databases yielded 530 results. Key data extracted from both databases included Karnofsky Performance Status (KPS) score and neurological deficits at presentation, tumor location, treatment indication, target volume, single versus multiple fractions, marginal and maximum doses, isodose line, clinical and radiographic follow-up times, and primary (clinical stability and local control at last follow-up) and secondary (mortality, adverse radiation events, time to regression, progression-free survival) outcomes. RESULTS: The study patients included 9 patients from the authors' institution and 165 patients across 4 studies who received SRS for FMMs. The weighted median age at treatment was 60.2 years, and 73.9% of patients were female. Common presenting symptoms included headache (33.9%), dizziness/ataxia (29.7%), cranial nerve deficit(s) (27.9%), numbness (22.4%), weakness (15.2%), and hydrocephalus (4.2%). Lateral/ventrolateral (64.2%) was the most common tumor location. SRS was utilized as the primary therapy in 63.6% of patients and as salvage (21.8%) or adjuvant (14.5%) therapy for the rest of the patients. Most patients (91.5%) were treated with a single fraction. A tumor with a weighted median target volume of 2.9 cm3 was treated with a weighted median marginal dose, maximum dose, and isodose line of 12.9 Gy, 22.8 Gy, and 58%, respectively. Clinical stability and local control at last follow-up were achieved in 98.8% and 97.0% of patients, respectively. Only one possible adverse radiation event occurred, and no mortality directly related to the tumor or SRS was reported. CONCLUSIONS: In this retrospective analysis and systematic review, the authors demonstrate SRS to be an effective and safe treatment option for carefully selected patients with FMMs.

Feasibility of using Clinical Practice Research Datalink data to identify patients with chronic obstructive pulmonary disease to enrol into real-world trials.

PURPOSE: To assess the feasibility of using Clinical Practice Research Datalink (CPRD) data for identifying populations of patients with chronic obstructive pulmonary disease (COPD) eligible for a hypothetical pragmatic trial. METHODS: A retrospective multidatabase cohort study using CPRD primary care and linked secondary care data to describe the characteristics of populations of patients with COPD. Patients' demographic and lifestyle factors, comorbidity profile, spirometry measurements and treatment changes were evaluated, as was the distribution of follow-up time and types of losses during follow-up. Characteristics were evaluated using descriptive statistics. RESULTS: A total of 322 991 patients from 1148 primary care practices in the United Kingdom across two CPRD primary care databases, CPRD GOLD and CPRD Aurum, were potentially eligible to participate in a hypothetical trial using CPRD, starting on 31 December 2017. Patients with COPD in CPRD GOLD and CPRD Aurum were comparable in terms of age (median age 70 vs. 68 years), gender (50% vs. 52% male), disease severity (e.g., 25% vs. 24% Medical Research Council [MRC] dyspnoea score grades 3-5) and history of respiratory conditions (e.g., 43% vs. 38% asthma). High proportions of patients with COPD in CPRD GOLD and CPRD Aurum were available on 31 December 2012 for follow-up at 1, 2, and 5 years (92%, 85% and 67%, respectively). CONCLUSIONS: Patients and data from CPRD GOLD and CPRD Aurum were comparable across key aspects relevant to COPD trials. A pragmatic trial using CPRD to recruit patients with COPD is scientifically feasible.

Limitations for health research with restricted data collection from UK primary care.

PURPOSE: UK primary care provides a rich data source for research. The impact of proposed data collection restrictions is unknown. This study aimed to assess the impact of restricting the scope of electronic health record (EHR) data collection on the ability to conduct research. The study estimated the consequences of restricted data collection on published Clinical Practice Research Datalink studies from high impact journals or referenced in clinical guidelines. METHODS: A structured form was used to systematically analyse the extent to which individual studies would have been possible using a database with data collection restrictions in place: (1) retrospective collection of specified diseases only; (2) retrospective collection restricted to a 6- or 12-year period; (3) prospective and retrospective collection restricted to non-sensitive data. Outcomes were categorised as unfeasible (not reproducible without major bias); compromised (feasible with design modification); or unaffected. RESULTS: Overall, 91% studies were compromised with all restrictions in place; 56% studies were unfeasible even with design modification. With restrictions on diseases alone, 74% studies were compromised; 51% were unfeasible. Restricting collection to 6/12 years had a major impact, with 67 and 22% of studies compromised, respectively. Restricting collection of sensitive data had a lesser but marked impact with 10% studies compromised. CONCLUSION: EHR data collection restrictions can profoundly reduce the capacity for public health research that underpins evidence-based medicine and clinical guidance. National initiatives seeking to collect EHRs should consider the implications of restricting data collection on the ability to address vital public health questions.

SBRT vs. Y90: HCC Treatment Outcomes and Costs.

OBJECTIVES: Stereotactic Body Radiotherapy (SBRT) and Yttrium-90 (Y90) are among the ablative therapies used as treatment options for localized hepatocellular carcinoma (HCC). To date, direct comparisons of the 2 modalities' outcomes and costs are lacking. This study aimed to analyze demographic, treatment, and cost information for patients with HCC treated with SBRT and Y90. METHODS: Patients with HCC treated with SBRT or Y90 radioembolization between January 2018 and January 2020 at one institution were retrospectively reviewed. Demographic and treatment data were compared utilizing χ 2 tests. Kaplan-Meier curves and log-rank tests were applied to compare overall survival and progression-free survival in different treatment groups. Cox proportional hazard models were applied to analyze the unadjusted and adjusted survival differences. Ten SBRT and 10 Y90 patients were randomly selected for Medicare cost analysis. RESULTS: Sixty-three patients received Y90, and 21 received SBRT. On univariable and multivariable analysis, there was no significant difference in overall survival or progression-free survival between the Y90 and SBRT cohorts. SBRT patients had higher American Joint Committee on Cancer staging ( P =0.039), greater tumor size (4.07 vs. 2.96 cm, P =0.013), and greater rates of prior liver-directed therapy (71.4% SBRT vs. 12.7% Y90, P <0.001). The average cost for SBRT was $15,148, and Y90 was $41,360. CONCLUSIONS: SBRT and Y90 are effective therapies in the treatment of HCC, specifically having similar overall survival and progression-free survival. Y90 was found to have a significantly higher cost than SBRT. This study demonstrates the need for prospective studies to assess these modalities in treating HCC.

The Physician Fee Schedule Was Not Built for High-Cost Supplies and Equipment.

As reimbursement from the Medicare Physician Fee Schedule (PFS) continues to decline, cuts to practice expense relative value units disproportionately impact office-based interventionalists and private practices that rely on high-cost equipment. For 195 codes, specialties such as radiation oncology, vascular surgery, and interventional radiology are paid at rates less than their direct costs calculated by the Centers for Medicare and Medicaid Services itself. While reimbursement in the office-based setting continues to decline, high-cost hospital settings receive more payment for the same services. This disparity aligns with trends in care moving to the hospital setting and practice consolidation, resulting in increased costs to the healthcare system and decreased access to care. The current PFS is outdated, and the removal of high-cost supplies and equipment from the PFS is a critical step to reform.

GlioPredictor: a deep learning model for identification of high-risk adult IDH-mutant glioma towards adjuvant treatment planning.

Identification of isocitrate dehydrogenase (IDH)-mutant glioma patients at high risk of early progression is critical for radiotherapy treatment planning. Currently tools to stratify risk of early progression are lacking. We sought to identify a combination of molecular markers that could be used to identify patients who may have a greater need for adjuvant radiation therapy machine learning technology. 507 WHO Grade 2 and 3 glioma cases from The Cancer Genome Atlas, and 1309 cases from AACR GENIE v13.0 datasets were studied for genetic disparities between IDH1-wildtype and IDH1-mutant cohorts, and between different age groups. Genetic features such as mutations and copy number variations (CNVs) correlated with IDH1 mutation status were selected as potential inputs to train artificial neural networks (ANNs) to predict IDH1 mutation status. Grade 2 and 3 glioma cases from the Memorial Sloan Kettering dataset (n = 404) and Grade 3 glioma cases with subtotal resection (STR) from Northwestern University (NU) (n = 21) were used to further evaluate the best performing ANN model as independent datasets. IDH1 mutation is associated with decreased CNVs of EGFR (21% vs. 3%), CDKN2A (20% vs. 6%), PTEN (14% vs. 1.7%), and increased percentage of mutations for TP53 (15% vs. 63%), and ATRX (10% vs. 54%), which were all statistically significant (p < 0.001). Age > 40 was unable to identify high-risk IDH1-mutant with early progression. A glioma early progression risk prediction (GlioPredictor) score generated from the best performing ANN model (6/6/6/6/2/1) with 6 inputs, including CNVs of EGFR, PTEN and CDKN2A, mutation status of TP53 and ATRX, patient's age can predict IDH1 mutation status with over 90% accuracy. The GlioPredictor score identified a subgroup of high-risk IDH1-mutant in TCGA and NU datasets with early disease progression (p = 0.0019, 0.0238, respectively). The GlioPredictor that integrates age at diagnosis, CNVs of EGFR, CDKN2A, PTEN and mutation status of TP53, and ATRX can identify a small cohort of IDH-mutant with high risk of early progression. The current version of GlioPredictor mainly incorporated clinically often tested genetic biomarkers. Considering complexity of clinical and genetic features that correlate with glioma progression, future derivatives of GlioPredictor incorporating more inputs can be a potential supplement for adjuvant radiotherapy patient selection of IDH-mutant glioma patients.

Quality of Large Language Model Responses to Radiation Oncology Patient Care Questions.

Importance: Artificial intelligence (AI) large language models (LLMs) demonstrate potential in simulating human-like dialogue. Their efficacy in accurate patient-clinician communication within radiation oncology has yet to be explored. Objective: To determine an LLM's quality of responses to radiation oncology patient care questions using both domain-specific expertise and domain-agnostic metrics. Design, Setting, and Participants: This cross-sectional study retrieved questions and answers from websites (accessed February 1 to March 20, 2023) affiliated with the National Cancer Institute and the Radiological Society of North America. These questions were used as queries for an AI LLM, ChatGPT version 3.5 (accessed February 20 to April 20, 2023), to prompt LLM-generated responses. Three radiation oncologists and 3 radiation physicists ranked the LLM-generated responses for relative factual correctness, relative completeness, and relative conciseness compared with online expert answers. Statistical analysis was performed from July to October 2023. Main Outcomes and Measures: The LLM's responses were ranked by experts using domain-specific metrics such as relative correctness, conciseness, completeness, and potential harm compared with online expert answers on a 5-point Likert scale. Domain-agnostic metrics encompassing cosine similarity scores, readability scores, word count, lexicon, and syllable counts were computed as independent quality checks for LLM-generated responses. Results: Of the 115 radiation oncology questions retrieved from 4 professional society websites, the LLM performed the same or better in 108 responses (94%) for relative correctness, 89 responses (77%) for completeness, and 105 responses (91%) for conciseness compared with expert answers. Only 2 LLM responses were ranked as having potential harm. The mean (SD) readability consensus score for expert answers was 10.63 (3.17) vs 13.64 (2.22) for LLM answers (P < .001), indicating 10th grade and college reading levels, respectively. The mean (SD) number of syllables was 327.35 (277.15) for expert vs 376.21 (107.89) for LLM answers (P = .07), the mean (SD) word count was 226.33 (191.92) for expert vs 246.26 (69.36) for LLM answers (P = .27), and the mean (SD) lexicon score was 200.15 (171.28) for expert vs 219.10 (61.59) for LLM answers (P = .24). Conclusions and Relevance: In this cross-sectional study, the LLM generated accurate, comprehensive, and concise responses with minimal risk of harm, using language similar to human experts but at a higher reading level. These findings suggest the LLM's potential, with some retraining, as a valuable resource for patient queries in radiation oncology and other medical fields.

Integrating POLE/POLD1 mutated for immunotherapy treatment planning of advanced stage non-small cell lung cancer.

BACKGROUND: In this study, we evaluated the potential of DNA polymerase epsilon (POLE) and DNA polymerase delta 1 (POLD1) as prognostic biomarkers for immune checkpoint inhibitor (ICI) treatment in patients with advanced stage non-small cell lung cancer (NSCLC). METHODS: Disease stage, PD-L1 positivity, histological subtypes, POLE/POLD1 mutation status, tumor mutation burden (TMB), and response to ICIs in NSCLC cases were derived from AACR GENIE dataset (n = 24 120), TCGA-Pan Lung Cancer dataset (n = 1144), AACR GENIE BPC NSCLC v2.0-public (n = 2004), and Memorial Sloan Kettering-Integrated Mutation Profiling of Actionable Cancer Targets dataset (n = 350). The smoking history from TCGA and AACR GENIE datasets was grouped into current, former or never-smokers. RESULTS: POLE and POLD1 genetic alterations were identified in 5% and 2.6% of NSCLC patients, respectively. Current smokers had 9% and 4% of POLE/POLD1 mutations, respectively, versus 1.7% for both POLE and POLD1 mutations prevalence in never-smokers. POLE/POLD1 mutations were associated with elevated mutation counts than those with wild-type (median mutation counts 16 vs. 7, p < 0.0001), more advanced disease stages (stage I disease 15.19% vs. 29.42%), more prevalent squamous histology subtype (21.69% vs. 9.05%, p = 0.0427), and a higher percentage of PD-L1 positivity (66.67% vs. 43.87%, p < 0.001). Treatment with ICIs improved survival in patients with both POLE/POLD1 mutated and those with TMB > 18 (p < 0.001). CONCLUSION: Current smokers have a five-fold increased risk of having POLE mutations than never-smokers. POLE/POLD1 mutation status and TMB > 18 can be a composite biomarker for selecting NSCLC patients with survival benefits to ICI treatment.