Citations

Importance Tumor-infiltrating lymphocytes (TILs) are a provocative biomarker in melanoma, influencing diagnosis, prognosis, and immunotherapy outcomes; however, traditional pathologist-read TIL assessment on hematoxylin and eosin–stained slides is prone to interobserver variability, leading to inconsistent clinical decisions. Therefore, development of newer TIL scoring approaches that produce more reliable and consistent readouts is important. Objective To evaluate the analytical and clinical validity of a machine learning algorithm for TIL quantification in melanoma compared with traditional pathologist-read methods. Design, Setting, and Participants This multioperator, global, multi-institutional prognostic study compared TIL scoring reproducibility between traditional pathologist-read methods and an artificial intelligence (AI)-driven approach. The study was conducted using retrospective cohorts of patients with melanoma between January 2022 and June 2023 across 45 institutions, with tissue evaluated by participants from academic, clinical, and research institutions. Participants were selected to ensure diverse expertise and professional backgrounds. Main Outcomes and Measures Intraclass correlation coefficient (ICC) values were calculated for the manual and AI-assisted arms using log-transformed data. Kendall W values were calculated for Clark scores (brisk = 3, nonbrisk = 2, and sparse = 1). Reliabilities of ICC and W values were classified as moderate (0.40-0.60), good (0.61-0.80), or excellent (>0.80). AI TIL measurements were dichotomized using the 16.6 and median cutoffs. Univariable and multivariable Cox regression analyses assessed the prognostic value of TIL scores adjusted for clinicopathologic variables. Results There were 111 patients with melanoma in the independent testing cohort (median [range] age at diagnosis, 61.0 [25.0-87.0] years; 56 [50.5%] male) who contributed melanoma whole tissue sections. A total of 98 participants evaluated TILs on 60 hematoxylin and eosin–stained melanoma tissue sections. All 40 participants in the manual arm were pathologists, while the AI-assisted arm included 11 pathologists and 47 nonpathologists (scientists). The AI algorithm demonstrated superior reproducibility, with ICCs higher than 0.90 for all machine learning TIL variables, significantly outperforming manual assessments (ICC, 0.61 for AI-derived stromal TILs vs Kendall W , 0.44 for manual Clark TIL scoring). AI-based TIL scores showed prognostic associations with patient outcomes (n = 111) using the median cutoff approach with a hazard ratio (HR) of 0.45 (95% CI, 0.26-0.80; P = .005), and using the cutoff of 16.6, with an HR of 0.56 (95% CI, 0.32-0.98; P = .04). Conclusions and Relevance In this prognostic study of TIL quantification in melanoma, the AI algorithm demonstrated superior reproducibility and prognostic associations compared with traditional methods. Although the retrospective nature of the cohorts limits demonstration of clinical utility, the publicly available dataset and open-source AI tool offer a foundation for future validation and integration into melanoma management.

Lymphoscintigraphy, which is commonly used for sentinel lymph node mapping, can help diagnose lymphedema, lymphatic leakage, and lymphatic malformations and provides valuable information for surgical planning and treatment.

Objectives: This practice parameter was revised collaboratively by the American College of Radiology (ACR), and American Radium Society (ARS). Image-guided radiation therapy (IGRT) uses various imaging modalities to maximize the accuracy and precision of radiation treatment delivery. 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 ACR Commission on Radiation Oncology in collaboration with the ARS. Results: This practice parameter for IGRT addresses qualifications and responsibilities of personnel, clinical IGRT implementation, documentation, quality control and improvement, safety, and patient education. Since the publication of the ACR–ASTRO Practice Parameter in 2019, there is now more clarity as to what criteria and parameters need to be documented in the medical record, a better appreciation of the large amount of imaging data, how to interpret such data, as well as the complex interactions of multiple systems in the implementation of IGRT. Conclusions: This practice parameter assists practitioners in the clinical use of IGRT. IGRT should complement and be used in combination with other quality assurance processes. IGRT is a rapidly evolving field, and practitioners should have a thorough understanding of its strengths and potential limitations.

Breast cancer is one of the most common cancers in females. In low- and middle-income countries like Pakistan, reported incidence and prevalence remain unreliable. The aim was to evaluate Pakistani women’s knowledge, attitude, and perception of breast cancer. This cross-sectional study was conducted among Pakistani women from Punjab, Pakistan. A self-administered online questionnaire was formulated to collect data from the participants from September 24, 2022, to October 24, 2022. The questionnaire included sociodemographic data, knowledge questions regarding breast cancer risk factors, knowledge questions about symptoms of breast cancer, and questions assessing the participants’ attitudes toward mammography screening. For knowledge questions, a score of more than 7 out of 13 was considered good knowledge. For attitude questions, regression analysis was done and a score of more than 5 out of 11 was considered a positive attitude. Data was analyzed using SPSS version 25 (Chicago). 796 women participated in this study. Out of 796 participants, 543 (68.2%) were between 20 and 30 years of age, and 43 (5.4%) were more than 40 years old. The level of knowledge regarding breast cancer risk factors was suboptimal. 523 (65.7%) of the participants thought that breast cancer risk increases with advancing age and 218 (27.4%) thought that early menarche increases the risk of developing breast cancer. 471 (59.2%) mentioned that mammography is an effective tool for detecting breast cancer, and 30 (3.8%) thought that there is a cure for breast cancer. According to regression analysis, higher education, higher monthly household income, and married marital status were significantly associated with good knowledge related to breast cancer. Although most of the population is aware of breast cancer’s risk factors and symptoms, they avoid screening such as mammography. Public awareness projects could help increase women’s knowledge of breast cancer signs, symptoms, and screening.

Gastroesophageal reflux disease (GERD) is a prevalent condition impacting physical and mental health, characterized by symptoms like heartburn and acid regurgitation. GERD affects 18.1–27.8% of North Americans, rising to ~ 50% under less strict criteria. Effective management of GERD is critical to improving patients’ quality of life. Traditional treatments range from lifestyle modifications and pharmacological interventions to surgical approaches like laparoscopic anti-reflux surgery (LARS). Patients with erosive esophagitis receive a near 70–80% rate of “complete” symptom relief by 4 weeks using PPIs, in contrast to patients with non-erosive reflux disease (NERD), who demonstrate an intermediate response on the order of 50–60%. However, the invasiveness and associated side effects of surgical options have spurred the development of endoscopic techniques, including anti-reflux mucosectomy (ARMS) and transoral incisionless fundoplication (TIF). This review evaluates ARMS and TIF as therapeutic interventions for GERD, focusing on their risks, benefits, outcomes, and complications. ARMS is noted for shorter procedure times and fewer complications, particularly dysphagia and bleeding, making it an efficient choice for symptom control. TIF, while associated with a higher recurrence and reoperation rate, demonstrates superior long-term efficacy in medication reduction and sustained quality-of-life improvements, especially in patients without prior anti-reflux surgeries. Emerging advancements in endoscopic technologies, such as improved suturing techniques and refinements in mucosal resection, hold promise for reducing recurrence rates and enhancing procedural durability. The choice between ARMS and TIF should be tailored to individual patient needs, taking into account GERD severity, comorbidities, and surgical history. Both procedures exemplify significant advancements in minimally invasive GERD management, and ongoing innovations in endoscopic technologies are expected to further refine their safety and effectiveness. This comparative analysis provides insights into optimizing treatment selection and underscores the importance of personalized care in managing GERD.

e13162 Background: BRCA1/2 mutations impair homologous recombination repair, forcing cancer cells to rely on alternative DNA repair pathways, such as those mediated by poly(ADP-ribose) polymerase (PARP). PARP inhibitors (PARPis), like iniparib, olaparib, talazoparib, niraparib, and veliparib, exploit this dependency, inducing lethality in cells of BRCA-mutated, HER2-negative breast cancers (BRCAm, HER2-BC). Only 2 PARPis, talazoparib and olaparib, are FDA-approved for BRCAm, HER2-BC. However, the treatment with the highest efficacy remains unclear. We conducted a network meta-analysis (NMA) of randomised controlled trials (RCTs) to compare the efficacy of PARPis in treating BRCAm, HER2-BC. Methods: We systematically searched PubMed, Cochrane CENTRAL, SCOPUS, and ClinicalTrials.gov (up to December 2024) for randomized controlled trials (RCTs) following PRISMA-NMA guidelines. Primary outcome was overall survival(OS), with hazard ratios (HRs) and 95% confidence intervals (CIs). Secondary outcome was progression-free survival (PFS). Survival times were converted to HRs under the assumption of exponential distribution. Standard of care (SOC) was defined as taxane/anthracycline-based regimens with additional platinum-based chemotherapy. Physician's choice chemotherapy (PCT) included capecitabine, eribulin, gemcitabine, or vinorelbine. A frequentist approach with random-effects modeling was used to pool estimates, and P-scores ranked treatment efficacy. Heterogeneity and inconsistency were assessed using τ², I², and Q-statistics. Analyses were conducted in R version 4.4.1. Results: 8 studies including 4432 participants incorporating 8 pairwise comparisons and 7 treatments were analyzed for OS. Compared to SOC (reference), HRs of OS were significantly reduced with talazoparib+SOC (HR = 0.49, 95% CI: 0.32–0.74; P = 0.64), olaparib+SOC (HR = 0.46, 95% CI: 0.36–0.59; P = 0.69), niraparib+SOC (HR = 0.44, 95% CI: 0.26–0.76; P = 0.76), and veliparib+SOC (HR = 0.38, 95% CI: 0.29–0.48; P = 0.91). No heterogeneity or inconsistency was detected (τ² = 0; I² = 0; Q = 1.27, p = 0.53). For PFS, iniparib/gemcitabine, talazoparib, olaparib, and niraparib showed significant reduction in HR with increasing order of P-scores, in combination with SOC. Conclusions: Veliparib combined with SOC showed the highest OS improvement, while niraparib ranked highest for PFS, followed by talazoparib and olaparib. Further trials are needed to confirm these findings and refine treatment strategies for BRCAm, HER2-BC.

e24020 Background: Transcatheter aortic valve replacement (TAVR) is a widely adopted treatment for severe aortic stenosis, but outcomes in cancer survivors with prior chest radiation therapy (C-XRT) remain uncertain. This study compares the clinical outcomes of TAVR between patients with a history of C-XRT and those without prior radiation exposure (control group). Methods: Patients with prior chest radiation therapy (C-XRT) were compared to a control group without radiation exposure to evaluate key clinical endpoints. For each endpoint, odds ratios (OR) and 95% confidence intervals (CI) were determined, and heterogeneity was analyzed using the I² statistic. A p-value of <0.05 was considered statistically significant. Results: Nine studies were included in the meta-analysis, encompassing 3083 C-XRT and 8891 control patients. Patients with prior C-XRT showed significantly higher long-term mortality (OR 1.84, 95% CI [1.08, 3.13], p=0.02) compared to controls. Other outcomes, including access-related vascular complications, Acute Kidney Injury, Congestive heart failure, major bleeding, need for pacemaker, short-term mortality, and stroke, did not demonstrate significant differences between the groups. Conclusions: Cancer survivors with prior chest radiation therapy undergoing TAVR may experience higher long-term mortality compared to patients without radiation exposure. However, no significant differences were observed in other major outcomes. These findings suggest that while TAVR is a viable treatment for C-XRT patients, long-term risks require further investigation to optimize patient selection and management strategies. Outcomes. Outcome OR 95% Confidence Interval P value Access related vascular complications 1.12 [0.85, 1.48] 0.43 Acute kidney injury 0.54 [0.20, 1.50] 0.24 Congestive heart failure 1.38 [0.88, 2.17] 0.16 Long term mortality 1.84 [1.08, 3.13] 0.02 Major bleeding 0.96 [0.78, 1.17] 0.67 Need for pacemaker 1.05 [0.88, 1.26] 0.57 Short term mortality 1.66 [0.97, 2.84] 0.06 Stroke 1.25 [0.74, 2.11] 0.39

e24024 Background: Patients with active cancer undergoing trans catheter aortic valvular replacement (TAVR) face a higher risk of adverse outcomes due to the interplay between cancer and cardiovascular disease. Although TAVR is increasingly used in high-risk populations, data on outcomes for these patients remain limited. This systematic review and meta-analysis aim to evaluate the clinical outcomes associated with TAVR in patients with active cancer compared to non-cancer controls, providing insights to inform clinical decision-making in this unique group. Methods: A systematic search of major databases (PubMed, Embase, OVID, Web of Science, Scopus) was conducted to identify studies comparing clinical outcomes of TAVR between patients with active cancer and those without cancer. Key outcomes included measures of mortality, procedural complications, and post-procedure adverse events. The Mantel-Haenszel method was used for pooled analysis, applying random-effects or fixed-effects modeling based on heterogeneity assessed by Higgins I². Statistical significance was set at a p-value < 0.05. Results: Twelve studies involving 5,73,192 patients (67,684 active cancer, 505508 control) were included. Patients with active cancer undergoing TAVR have significantly higher risks of short-term mortality (OR 1.31, 95% CI [1.15, 1.49], p < 0.0001), long-term mortality (OR 2.24, 95% CI [1.85, 2.70], p < 0.0001), and major bleeding complications (OR 1.80, 95% CI [1.68, 1.92], p < 0.0001). There were no statistically significant differences in cardiovascular mortality (OR 1.33, 95% CI [0.94, 1.89], p = 0.11), myocardial infarction (OR 1.60, 95% CI [0.82, 3.11], p = 0.17), stroke (OR 0.61, 95% CI [0.28, 1.35], p = 0.22), AKI (OR 0.92, 95% CI [0.49, 1.73], p = 0.80), or the need for permanent pacemaker implantation (OR 1.12, 95% CI [0.85, 1.48], p = 0.42). Conclusions: Patients with active cancer undergoing TAVR face significantly higher risks of mortality and major bleeding compared to non-cancer controls. However, the risks of cardiovascular mortality, MI, stroke, AKI, and the need for permanent pacemaker implantation are comparable to those of non-cancer controls. Careful risk assessment and management are crucial for optimizing outcomes in this vulnerable population, and further studies are needed to refine treatment strategies. Odds ratios of all outcomes. Outcomes OR Confidence Interval (95% CI) p-value Short term mortality 1.31 [1.15, 1.49] < 0.0001 Long term mortality 2.24 [1.85, 2.70] < 0.00001 Major bleeding 1.8 [1.68, 1.92] < 0.00001 Cardiovascular mortality 1.33 [0.94, 1.89] 0.11 Myocardial Infarction 1.6 [0.82, 3.11] 0.17 Stroke 0.61 [0.28, 1.35] 0.22 Acute Kidney Injury 0.92 [0.49, 1.73] 0.8 Need for permanent pacemaker implantation 1.12 [0.85, 1.48] 0.42

e16001 Background: Esophageal carcinoma ranks among the top 10 malignancies in the world, contributing to high morbidity and mortality. With radiotherapy being one of the most administered treatment options, different variations of administration have evolved. Two such variations include intensity-modulated radiotherapy and 3D conformational radiotherapy. These modalities have been investigated for their efficacy and rate of adverse events. However, conclusions from the trials conducted have been variable. In this systematic review and meta-analysis, we aim to collate these findings to assess the exposure of cancerous cells and rates of adverse events following IMRT or 3D-CRT. Methods: A comprehensive literature search was conducted across three databases for all articles published from inception till September 2024. All primary studies evaluating the comparative efficacy of IMRT vs 3D-CRT were included. Outcomes assessed include dose volume histograms (DVHs) at heart and lung, Dmax at the spinal cord, and irradiation toxicity. Data analysis was conducted in RevMan 5.4 using a random-effects model. Results: A total of twenty records were included in the study, with a sample size of 3090 patients. Radiation dosage, estimated as DVHs, was equal across both regimens at heart (MD: 2.67; 95%CI: –0.15 to 5.48; P = 0.06), except at 40 Gy of radiation, where a lower DVH was noted among patients being administered IMRT (MD: 6.64; 95%CI: 0.25 to 13.03; P = 0.04). At the lung, a higher DVH was noted, especially for doses of 20 Gy or above, on using IMRT. Similarly, a lower dosage in the spinal cord was noted in the IMRT group (MD: 2.87; 95%CI: 1.04 to 4.70; P = .002). Consequently, a lower risk of esophagitis was noted among the IMRT group (OR: 1.54; 95%CI: 1.14 to 2.07; p = 0.009]). While considering patient outcomes, the odds of survival were higher in the IMRT group at 3 years post-treatment (OR: 0.53; 95%CI: 0.31 to 0.92; P = 0.02). Conclusions: IMRT was superior to 3D-CRT in terms of volume of tissue irradiated and lower spinal toxicity. A higher chance of survival was noted in the IMRT group. Further trials are needed to strengthen these findings. Outcome Mean Difference (MD) 95% confidence interval (CI) P value Mean dosage at lung 1.14 0.6, 1.68 <0.0001 Mean dosage at heart 2.67 -0.15, 5.48 0.06 Radiation esophagitis Odds ratio, OR: 1.38 1.09, 1.76 0.009 Radiation pneumonitis OR:1.37 0.62, 3.01 0.43 3-year OS OR: 0.69 0.56, 0.84 0.0003 5-year OS OR: 0.53 0.31, 0.92 0.02 Maximum dosage at spinal cord 2.87 1.04, 4.7 0.0002

e12615 Background: Breast MRI after completion of neoadjuvant chemotherapy (NAC) has demonstrated high sensitivity and positive predictive value in evaluating response to NAC. It is widely recognized as the most accurate imaging technique for assessing tumor response, outperforming mammography and ultrasound. However, there remains a knowledge gap in its potential as an early predictor of pathological response, when performed at the midpoint of NAC. Here, we investigated the correlation between MRI findings at the midpoint of NAC and subsequent pathological response at definitive surgery. Methods: A retrospective study was performed of patients with breast cancer who received NAC at Mayo Clinic, Florida and had at least 2 breast MRIs, one at midpoint and one either pre- or post-treatment. Patients with prior ipsilateral breast cancer were excluded. Participants were stratified into three molecular subtypes: hormone receptor-positive (HR+), HER2-positive (HER2+), and triple-negative breast cancer (TNBC). All MRIs were re-reviewed by dedicated breast radiologists, with tumor response classified as complete response (CR), partial response (PR), stable disease (SD), or progressive disease (PD) based on RECIST criteria. Pathological outcomes, including pathologic complete response (pCR) and residual cancer burden (RCB), were extracted from pathology reports and confirmed by a single breast pathologist, as indicated. pCR was defined as the absence of residual invasive tumor in both the breast and axillary lymph nodes. Results: A total of 154 patients met inclusion criteria from 2012 to 2022. Similar to previous studies, the positive predictive value for the post-treatment MRI was high at 82.4%, with 14 of 17 patients with imaging complete responses (iCR) achieving pCR. For the midpoint MRI, the positive predictive value for patients with iCR was 100%, with 8 out of 8 patients achieving pCR. Patients with certain subtypes of breast cancer with at least PR in both breast and axillary lymph nodes at midpoint MRI had numerically higher pCR rate, specifically HER2+ (22/37, 59.5%) and TNBC (8/13, 61.5%) but not HR+ tumors (12/45, 26.7%). In contrast, patients with less than PR in either breast or axillary lymph nodes showed numerically lower rate pCR in TNBC (7/18, 38.9%) and HR+ tumors (3/18, 16.7%). However, 15/23 (65.2%) patients with HER2+ tumors achieved pCR despite having less than PR at midpoint MRI. Conclusions: Midpoint breast MRI may serve as an early predictor of pathological response, particularly in patients with iCR. Patients with less than PR, especially those with HR+ and TNBC, have lower chances of achieving pCR. These findings highlight the importance of considering additional therapies for these subgroups of patients to improve the treatment outcomes, as they are less likely to achieve pCR with the current standard neoadjuvant chemotherapy regimen.