Utilizing Large Language Models for Enhanced Clinical Trial Matching: A Study on Automation in Patient Screening.

Background Clinical trial matching, essential for advancing medical research, involves detailed screening of potential participants to ensure alignment with specific trial requirements. Research staff face challenges due to the high volume of eligible patients and the complexity of varying eligibility criteria. The traditional manual process, both time-consuming and error-prone, often leads to missed opportunities. Recently, large language models (LLMs), specifically generative pre-trained transformers (GPTs), have become impressive and impactful tools. Utilizing such tools from artificial intelligence (AI) and natural language processing (NLP) may enhance the accuracy and efficiency of this process through automated patient screening against established criteria. Methods Utilizing data from the National NLP Clinical Challenges (n2c2) 2018 Challenge, we utilized 202 longitudinal patient records. These records were annotated by medical professionals and evaluated against 13 selection criteria encompassing various health assessments. Our approach involved embedding medical documents into a vector database to determine relevant document sections and then using an LLM (OpenAI's GPT-3.5 Turbo and GPT-4) in tandem with structured and chain-of-thought prompting techniques for systematic document assessment against the criteria. Misclassified criteria were also examined to identify classification challenges. Results This study achieved an accuracy of 0.81, sensitivity of 0.80, specificity of 0.82, and a micro F1 score of 0.79 using GPT-3.5 Turbo, and an accuracy of 0.87, sensitivity of 0.85, specificity of 0.89, and micro F1 score of 0.86 using GPT-4. Notably, some criteria in the ground truth appeared mislabeled, an issue we couldn't explore further due to insufficient label generation guidelines on the website. Conclusion Our findings underscore the potential of AI and NLP technologies, including LLMs, in the clinical trial matching process. The study demonstrated strong capabilities in identifying eligible patients and minimizing false inclusions. Such automated systems promise to alleviate the workload of research staff and improve clinical trial enrollment, thus accelerating the process and enhancing the overall feasibility of clinical research. Further work is needed to determine the potential of this approach when implemented on real clinical data.

Preliminary Results of Multi-Institutional Phase 1 Dose Escalation Trial Using Single-Fraction Stereotactic Partial Breast Irradiation for Early Stage Breast Cancer.

PURPOSE: We report on our early experience of our prospective multicenter phase 1 dose- escalation study of single-fraction stereotactic partial breast irradiation (S-PBI) for early stage breast cancer after partial mastectomy using a robotic stereotactic radiation system. METHODS AND MATERIALS: Thirty women with in situ or invasive breast cancer stage 0, I, or II with tumor size <3 cm treated with lumpectomy were enrolled in this phase 1 single-fraction S-PBI dose-escalation trial. Women received either 22.5, 26.5, or 30 Gy in a single fraction using a robotic stereotactic radiation system. The primary outcome was to reach tumoricidal dose of 30 Gy in a single fraction to the lumpectomy cavity without exceeding the maximum tolerated dose. Secondary outcomes were to determine dose-limiting toxicity and cosmesis. Tertiary goals were ipsilateral breast recurrence rate, distant disease-free interval, recurrence-free survival, and overall survival. RESULTS: From June 2016 to January 2021, 11, 8, and 10 patients were treated to doses of 22.5, 26.5, or 30 Gy in a single fraction, respectively, with median follow-up being 47.9, 25.1, and 16.2 months. No patients experienced acute (<90 days) grade 3 or higher treatment-related toxicity, and maximum tolerated dose was not reached. There were 2 delayed grade 3 toxicities. Four patients (13.8%) developed fat necrosis across all 3 cohorts, which compares favorably with results from other PBI trials. No dose cohort had a statistically significant cosmetic detriment from baseline to 12 months or 24 months follow-up by patient- or physician-reported global cosmetic scores. There were no reports of disease recurrence. CONCLUSIONS: This phase 1 trial demonstrates that S-PBI can be used to safely escalate dose to 30 Gy in a single fraction with low toxicity and without detriment in cosmesis relative to baseline.

A Multi-Institutional Phase 2 Trial of High-Dose SAbR for Prostate Cancer Using Rectal Spacer.

PURPOSE: High-dose SABR for prostate cancer offers the radiobiologic potency of the most intensified radiation therapy regimens but was associated with >90% rates of ulceration of the anterior rectal wall on endoscopic assessment; this infrequently progressed to severe rectal toxicity in prior prospective series. A multi-institutional phase 2 prospective trial was conducted to assess whether placement of a perirectal hydrogel spacer would reduce acute periprostatic rectal ulcer events after high-dose (>40 Gy) SABR. METHODS AND MATERIALS: Eligible patients included men with stage ≤T2c localized grade group 1 to 3 prostate cancer, a prostate-specific antigen (PSA) level ≤15 ng/mL, American Urological Association Symptom Index = AUA-SI scores ≤18, and a gland volume ≤80 cm3. Patients underwent perirectal hydrogel spacer placement, followed by SABR of 45 Gy in 5 fractions every other day to the prostate only. Androgen deprivation was not allowed except for cytoreduction. The rectal wall was directly assessed by serial anoscopy during follow-up to determine whether the spacer would reduce acute periprostatic rectal ulcer events from >90% to <70% within 9 months of treatment. RESULTS: Forty-four men were enrolled and 43 were eligible for protocol analysis. The median follow-up for surviving patients was 48 months. Acute periprostatic ulcers were observed in 6 of 42 patients (14.3%; 95% confidence interval, 6.0%-27%; P < .001) at a median of 2.9 months posttreatment (range, 1.7-5.6 months). All ulcers (grade 1, 5 ulcers; grade 2, 1 ulcer) resolved on repeat anoscopy within 8 months of incidence. There were no grade ≥3 late gastrointestinal toxicities; the incidence of late grade-2 gastrointestinal toxicities was 14.3%, with a prevalence at 3 years of 0%. No toxicities greater than grade 3 occurred in any domain. Four-year freedom from biochemical failure was 93.8% (95% CI, 85.2%-100.0%). CONCLUSIONS: Temporary hydrogel spacer placement before high-dose SABR treatment for localized prostate cancer and use of strict dose constraints are associated with a significant reduction in the incidence of rectal ulcer events compared with prior phase 1/2 trial results.

Cosmetic Outcomes of a Phase 1 Dose Escalation Study of 5-Fraction Stereotactic Partial Breast Irradiation for Early Stage Breast Cancer.

PURPOSE: Our purpose was to evaluate cosmetic changes after 5-fraction adjuvant stereotactic partial breast irradiation (S-PBI). METHODS AND MATERIALS: Seventy-five women with in situ or invasive breast cancer stage 0, I, or II, with tumor size ≤3 cm, were enrolled after lumpectomy in a phase 1 dose escalation trial of S-PBI into cohorts receiving 30, 32.5, 35, 37.5, or 40 Gy in 5 fractions. Before S-PBI, 3 to 4 gold fiducial markers were placed in the lumpectomy cavity for tracking with the Synchrony respiratory tracking system. S-PBI was delivered with a CyberKnife robotic radiosurgery system. Patients and physicians evaluated global cosmesis using the Harvard Breast Cosmesis Scale. Eight independent panelists evaluated digital photography for global cosmesis and 10 subdomains at baseline and follow-up. McNemar tests were used to evaluate change in cosmesis, graded as excellent/good or fair/poor, from baseline to year 3. Wilcoxon signed rank tests were used to evaluate change in subdomains. Cohen's kappa (κ) statistic was used to estimate interobserver agreement (IOA) between raters, and Fleiss' κ was used to estimate IOA between panelists. RESULTS: Median cosmetic follow-up was 5, 5, 5, 4, and 3 years for the 30, 32.5, 35, 37.5, and 40 Gy cohorts. Most patients reported excellent/good cosmesis at both baseline (86.3%) and year 3 (89.8%). No dose cohort had significantly worsened cosmesis by year 3 on McNemar analysis. No cosmetic subdomain had significant worsening by year 3. IOA was fair for patient-physician (κ = 0.300, P < .001), patient-panel (κ = 0.295, P < .001), physician-panel (κ = 0.256, P < .001), and individual panelists (Fleiss κ = 0.327, P < .001). CONCLUSIONS: Dose escalation of S-PBI from 30 to 40 Gy in 5 fractions for early stage breast cancer was not associated with a detectable change in cosmesis by year 3. S-PBI is a promising modality for treatment of early stage breast cancer.