Showalter, Timothy N.

Background: The rapid adoption of digital pathology and artificial intelligence (AI) in oncology creates multiple opportunities for precision diagnostics but also creates an urgent need for evidence-based standards to ensure safe and effective implementation. Goal: This article, developed by the Digital Pathology Association, presents recommendations for digital pathology as well as the validation and clinical utility of AI-enabled digital pathology tools in clinical practice. This guidance addresses analytical and clinical validation, algorithm reliability, and criteria for establishing clinical utility attributed to test use. Key recommendations emphasize separate validation of scanning processes and AI algorithms, concordance studies to support interscanner generalizability, rigorous assessment of accuracy and reliability in real-world settings, and clear description of algorithmic use limitations. These recommendations further provide frameworks for when AI may replace or augment existing diagnostic approaches, such as biomarker scoring, cancer diagnosis, and prognostic risk assessment. Conclusions: By considering payer, regulatory, and clinical perspectives, the recommendations promote transparency, trust, and reproducibility in digital pathology while encouraging value-based care delivery. We support responsible innovation in computational pathology, ensuring that AI applications achieve not only technical performance goals but also deliver measurable clinical benefit to patients.

LBA5012 Background: There is a critical evidence gap on the relative benefits and harms of proton therapy (PT) compared with photon-based intensity-modulated radiation therapy (IMRT) in prostate cancer. Herein we report early results from COMPPARE, a non-randomized comparative study of outcomes with PT and IMRT in prostate cancer. Methods: Between 2018-2022, 2524 patients from 51 facilities (28 PT and 23 IMRT) enrolled in COMPPARE, including 1501 treated with PT and 1023 treated with IMRT, and were followed prospectively. Treatment naïve patients with localized prostate cancer except those with very high-risk disease were eligible. Treatment was pragmatic with daily standard fractionation (1.8-2.1 Gy) and moderate hypofractionation (2.4-3.1 Gy) permitted. Use of rectal spacers and androgen deprivation were at physician discretion. Patient-reported quality of life data and treatment team-reported toxicity and disease control outcomes were collected at baseline and pre-specified time intervals via VisionTreeOptimalCare; treatment planning and delivery data were collected via the Advanced Treatment Consortium. We analyzed 1404 PT patients and 939 IMRT patients. We report the early primary endpoint of the study, a comparison of patient reported bowel urgency and bowel frequency at 2-years using the EPIC tool, and the secondary endpoints of 2-year CTCAE v5 ≥ grade 2 gastrointestinal toxicity outcomes and 3-year freedom from biochemical progression (FFBP) results reported by the study teams. Results: Study sample size was targeted at 1,500 PT patients and 1,000 IMRT patients, and median follow-up time was 4.0 years. The primary endpoint and secondary toxicity 2-year endpoints focused on the alternative hypothesis of PT superiority. All results include inverse probability of treatment weighting. Using generalized linear mixed effects models, we found there to be no significant difference in EPIC bowel urgency scores (p = 0.324) or bowel frequency scores (p = 0.514) between PT and IMRT cohorts over time up to the 2-year endpoint. For grade 2 gastrointestinal toxicity, the 2-year cumulative incidence was 5.2% for PT and 5.6% for IMRT. Gray’s Test for competing risks showed a hazard ratio (HR) of 0.91 [95% confidence interval (CI): 0.65-1.28, p = 0.6] for PT versus IMRT. The exploratory non-inferiority endpoint of 3-year FFBP was 98.0% for PT and 97.9% for IMRT, and Gray’s Test showed a HR of 0.95 (95% CI: 0.52-1.71, p = 0.90). Conclusions: Analysis of early results of COMPPARE show no significant differences between PT and IMRT in patient reported bowel frequency and urgency, grade ≥2 gastrointestinal toxicity, or FFBP. Assessment of long-term disease control, late toxicity and secondary malignancy will require longer follow-up. Clinical trial information: NCT03561220 .

Retrieval-augmented generation (RAG) is rapidly emerging as a transformative paradigm for large language models (LLMs), especially in high-stakes domains like oncology that demand precision, factual grounding, and up-to-date knowledge. By pairing LLMs with external knowledge repositories, RAG systems explicitly ground model outputs in relevant retrieved documents, helping to reduce hallucinations and ensure responses reflect current evidence. In oncology, where clinical knowledge evolves continually with new research and drug approvals, RAG offers a way to integrate the latest data (e.g., trial results, guidelines, genomic databases) into decision-making. This review synthesizes the technical foundations of RAG, including its architecture and key components, and examines current applications in oncology such as clinical decision support, patient education, radiology reporting, pathology analysis, and genomics-driven precision medicine. We highlight recent studies that demonstrate RAG’s potential—for instance, improving treatment recommendations by incorporating genetic profiles and literature, and enhancing diagnostic accuracy by integrating guidelines. We also discuss emerging developments like multimodal RAG (combining text with imaging or other data), ensemble model approaches, and new explainability tools that trace model outputs to sources. Finally, we critically analyze the limitations and challenges of deploying RAG in healthcare, including computational costs, retrieval errors, noise or conflicts in retrieved information, and ethical and regulatory considerations. While RAG-based systems show promise in augmenting oncologists’ expertise with timely knowledge, careful implementation, high-quality curation of knowledge bases, and human oversight will be crucial for safe and effective adoption in clinical practice.

Aim/Objectives/Background: The American College of Radiology (ACR), American Brachytherapy Society (ABS), and American Society for Radiation Oncology (ASTRO) have jointly developed the following practice parameter for transperineal permanent brachytherapy of prostate cancer. Transperineal permanent brachytherapy of prostate cancer is the interstitial implantation of low-dose rate radioactive seeds into the prostate gland for the purpose of treating localized prostate cancer. Methods: This practice parameter was developed according to the process described under the heading The Process for Developing ACR Practice Parameters and Technical Standards on the ACR website (https://www.acr.org/Clinical-Resources/Practice-Parameters-and-Technical-Standards) by the Committee on Practice Parameters—Radiation Oncology of the Commission on Radiation Oncology, in collaboration with ABS and ASTRO. Results: This practice parameter provides a framework for the appropriate use of low-dose rate brachytherapy in the treatment of prostate cancer either as monotherapy or as part of a treatment regimen combined with external-beam radiation therapy. The practice parameter defines the qualifications and responsibilities of all involved radiation oncology personnel, including the radiation oncologist, medical physicist, dosimetrist, radiation therapist, and nursing staff. Patient selection criteria and the utilization of supplemental therapies such as external-beam radiation therapy and androgen deprivation therapy are discussed. The logistics of the implant procedure, postimplant dosimetry assessment, and best practices with regard to safety and quality control are presented. Conclusions: Adherence to established standards can help to ensure that permanent prostate brachytherapy is delivered in a safe and efficacious manner.

AbstractAlthough cancer is highly heterogeneous, all metastatic cancer is considered American Joint Committee on Cancer (AJCC) Stage IV disease. The purpose of this project was to redefine staging of metastatic cancer. Internal validation of nationally representative patient data from the National Cancer Database (n = 461 357; 2010‐2013), and external validation using the Surveillance, Epidemiology and End Results database (n = 106 595; 2014‐2015) were assessed using the concordance index for evaluation of survival prediction. A Cox proportional hazards model was used for overall survival by considering identified phenotypes (latent classes) and other confounding variables. Latent class analysis was performed for phenotype identification, where Bayesian information criterion (BIC) and sample‐size‐adjusted BIC were used to select the optimal number of distinct clusters. Kappa coefficients assessed external cluster validation. Latent class analysis identified five metastatic phenotypes with differences in overall survival (P < .0001): (Stage IVA) nearly exclusive bone‐only metastases (n = 59 049, 12.8%; median survival 12.7 months; common in lung, breast and prostate cancers); (IVB) predominant lung metastases (n = 62 491, 13.5%; 11.4 months; common in breast, stomach, kidney, ovary, uterus, thyroid, cervix and soft tissue cancers); (IVC) predominant liver/lung metastases (n = 130 014, 28.2%; 7.0 months; common in colorectum, pancreatic, lung, esophagus and stomach cancers); (IVD) bone/liver/lung metastases predominant over brain (n = 61 004, 13.2%; 5.9 months; common in lung and breast cancers); and (IVE) brain/lung metastases predominant over bone/liver (n = 148 799, 32.3%; 5.7 months; lung cancer and melanoma). Long‐term survivors were identified, particularly in Stages IVA‐B. A pan‐cancer nomogram model to predict survival (STARS: site, tumor, age, race, sex) was created, validated and provides 13% better prognostication than AJCC: 1‐month concordance index of 0.67 (95% confidence interval [CI]: 0.66‐0.67) vs 0.61 (95% CI: 0.60‐0.61). STARS is simple, uses easily accessible variables, better prognosticates survival outcomes and provides a platform to develop novel metastasis‐directed clinical trials.

AbstractIntroductionWe evaluated the impact of MRI‐based target delineation on toxicity and tumour control after implementation of a protocol to incorporate MRI while minimizing impact on overall procedural time.MethodsWe retrospectively reviewed outcomes for a cohort of 96 consecutive patients who received intracavitary brachytherapy for cervical cancer at our institution during 2012–2016. Starting in October 2014, an outpatient MRI was obtained for patients after Smit sleeve placement and first insertion to assess concurrent chemoradiotherapy tumour response. Then, for subsequent fractions, the MRI was co‐registered by the Smit sleeve to the planning CT for target volume delineation. The primary and secondary outcomes were toxicity and local control, respectively.ResultsMedian follow‐up for the pre‐ (n = 50) and post‐MRI‐based (n = 46) planning groups was 24.6 and 14.7 months, respectively. Median treatment duration for patients before and after MRI implementation was 56 and 58 days (P = 0.052), respectively. Cumulative rectal D2 cc was less for those with MRI‐based target delineation (P = 0.005). On multivariable analysis, patients with MRI‐based target delineation experienced fewer severe late (CTCAE grade ≥ 3) toxicities (P = 0.025, hazard ratio = 0.25). Local control was 86% and 91% of the pre‐ and post‐MRI groups, respectively (P = 0.959).ConclusionsPreliminary findings using this technique, which is applicable to other institutions without in‐room MRI availability, are associated with lower radiation prescription doses, lower rectal doses and favourable toxicity rates while maintaining a rapid workflow. Longer follow‐up is required to confirm equivalent local control.

Purpose: To present the most updated American College of Radiology consensus guidelines formed from an expert panel on treatment of locally advanced, high-risk prostate cancer Methods: The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer-reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment. Results: The panel summarized the most recent and relevant literature on the topic and voted on 4 clinical variants illustrating the appropriate management of locally advanced, high-risk cancer. Numerical rating and commentary reflecting the panel consensus was given for each treatment approach in each variant. Conclusions: Aggressive local approaches including surgery followed by adjuvant XRT, beam combined with androgen deprivation therapy, and beam combined with brachytherapy have resulted in unpresented success in locally advanced, high-risk prostate cancer. By combining most recent medical literature and expert opinion, this guideline can aid clinicians in the appropriate integration of available therapeutic modalities.