Site-specific patterns of early-stage cancer diagnosis during the COVID-19 pandemic.

The COVID-19 pandemic caused widespread disruptions in cancer care. We hypothesized that the greatest disruptions in diagnosis occurred in screen-detected cancers. We identified patients (≥18 years of age) with newly diagnosed cancer from 2019 to 2020 in the US National Cancer Database and calculated the change in proportion of early-stage to late-stage cancers using a weighted linear regression. Disruptions in early-stage diagnosis were greater than in late-stage diagnosis (17% vs 12.5%). Melanoma demonstrated the greatest relative decrease in early-stage vs late-stage diagnosis (22.9% vs 9.2%), whereas the decrease was similar for pancreatic cancer. Compared with breast cancer, cervical, melanoma, prostate, colorectal, and lung cancers showed the greatest disruptions in early-stage diagnosis. Uninsured patients experienced greater disruptions than privately insured patients. Disruptions in cancer diagnosis in 2020 had a larger impact on early-stage disease, particularly screen-detected cancers. Our study supports emerging evidence that primary care visits may play a critical role in early melanoma detection.

Updated Analysis of Comparative Toxicity of Proton and Photon Radiation for Prostate Cancer.

PURPOSE: Previous comparative effectiveness studies have not demonstrated a benefit of proton beam therapy (PBT) compared with intensity-modulated radiation therapy (IMRT) for prostate cancer. An updated comparison of GI and genitourinary (GU) toxicity is needed. METHODS: We investigated the SEER-Medicare linked database, identifying patients with localized prostate cancer diagnosed from 2010 to 2017. Procedure and diagnosis codes indicative of treatment-related toxicity were identified. As a sensitivity analysis, we also identified toxicity based only on procedure codes. Patients who underwent IMRT and PBT were matched 2:1 on the basis of clinical and sociodemographic characteristics. We then compared GI and GU toxicity at 6, 12, and 24 months after treatment. RESULTS: The final sample included 772 PBT patients matched to 1,544 IMRT patients. The frequency of GI toxicity for IMRT versus PBT was 3.5% versus 2.5% at 6 months (P = .18), 9.5% versus 10.2% at 12 months (P = .18), and 20.5% versus 23.4% at 24 months (P = .11). The frequency of only procedure codes indicative of GI toxicity for IMRT versus PBT was too low to be reported and not significantly different. The frequency of GU toxicity for IMRT versus PBT was 6.8% versus 5.7% (P = .30), 14.3% versus 12.2% (P = .13), and 28.2% versus 25.8% (P = .21) at 6, 12, and 24 months, respectively. When looking only at procedure codes, the frequency of GU toxicity for IMRT was 1.0% at 6 months, whereas it was too infrequent to report for PBT (P = .64). GU toxicity for IMRT versus PBT was 3.3% versus 2.1% (P = .10), and 8.7% versus 6.7% (P = .10) at 12 and 24 months, respectively. CONCLUSION: In this observational study, there were no statistically significant differences between PBT and IMRT in terms of GI or GU toxicity.

Enhancing Safety in AI-Driven Cone Beam CT-based Online Adaptive Radiation Therapy: Development and Implementation of an Interdisciplinary Workflow.

Purpose: The emerging online adaptive radiation therapy (OART) treatment strategy based on cone beam computed tomography allows for real-time replanning according to a patient's current anatomy. However, implementing this procedure requires a new approach across the patient's care path and monitoring of the "black box" adaptation process. This study identifies high-risk failure modes (FMs) associated with AI-driven OART and proposes an interdisciplinary workflow to mitigate potential medical errors from highly automated processes, enhance treatment efficiency, and reduce the burden on clinicians. Methods and Materials: An interdisciplinary working group was formed to identify safety concerns in each process step using failure mode and effects analysis (FMEA). Based on the FMEA results, the team designed standardized procedures and safety checklists to prevent errors and ensure successful task completion. The Risk Priority Numbers (RPNs) for the top twenty FMs were calculated before and after implementing the proposed workflow to evaluate its effectiveness. Three hundred seventy-four adaptive sessions across 5 treatment sites were performed, and each session was evaluated for treatment safety and FMEA assessment. Results: The OART workflow has 4 components, each with 4, 8, 13, and 4 sequentially executed tasks and safety checklists. Site-specific template preparation, which includes disease-specific physician directives and Intelligent Optimization Engine template testing, is one of the new procedures introduced. The interdisciplinary workflow significantly reduced the RPNs of the high-risk FMs, with an average decrease of 110 (maximum reduction of 305.5 and minimum reduction of 27.4). Conclusions: This study underscores the importance of addressing high-risk FMs associated with AI-driven OART and emphasizes the significance of safety measures in its implementation. By proposing a structured interdisciplinary workflow and integrated checklists, the study provides valuable insights into ensuring the safe and efficient delivery of OART while facilitating its effective integration into clinical practice.

Prognosis and risk of suicide after cancer diagnosis.

INTRODUCTION: Suicide rates are elevated after cancer diagnosis. Existential distress caused by awareness of one's impending death is well-described in patients with cancer. The authors hypothesized that suicide risk is associated with cancer prognosis, and the impact of prognosis on suicide risk is greatest for populations with higher baseline suicide risk. METHODS: The authors identified patients (≥16 years old) with newly diagnosed cancers from 2000 to 2019 in the Surveillance, Epidemiology, and End Results database, representing 27% of US cancers. Multiple primary-standardized mortality ratios (SMR) were used to estimate the relative risk of suicide within 6 months of diagnosis compared to the general US population, adjusted for age, sex, race, and year of follow-up. Suicide rates by 20 most common cancer sites were compared with respective 2-year overall survival rates (i.e., prognosis) using a weighted linear regression model. RESULTS: Among 6,754,704 persons diagnosed with cancer, there were 1610 suicide deaths within 6 months of diagnosis, three times higher than the general population (SMR = 3.1; 95% confidence interval, 3.0-3.3). Suicide risk by cancer site was closely associated with overall prognosis (9.5%/percent survival deficit, R2  = 0.88, p < .0001). The association of prognosis with suicide risk became attenuated over time. For men, the risk of suicide increased by 2.8 suicide deaths per 100,000 person-years (p < .0001) versus 0.3 in women (p < .0001). The risk was also higher for persons ≥60 old and for the White (vs. Black) race. CONCLUSIONS: Poorer prognosis was closely associated with suicide risk early after cancer diagnosis and had a greater effect on populations with higher baseline risks of suicide. This model highlights the need for enhanced psychiatric surveillance and continued research in this patient population.

Acute and Chronic Complications After Treatment of Locoregional Anal Cancer: Prevention and Management Strategies.

Definitive chemoradiotherapy (CRT) for anal cancer spares patients the morbidity of a colostomy surgery and optimizes cancer outcomes. CRT, however, has introduced a unique acute and chronic toxicity profile, which has greatly improved over the years with the introduction of advanced radiotherapy techniques. This article provides the multidisciplinary care team with practical tools to mitigate and manage acute and chronic complications from definitive treatment of anal cancer.

MGMT Promoter Methylation Predicts Overall Survival after Chemotherapy for 1p/19q-Codeleted Gliomas.

PURPOSE: While MGMT promoter methylation (mMGMT) is predictive of response to alkylating chemotherapy and guides treatment decisions in glioblastoma, its role in grade 2 and 3 glioma remains unclear. Recent data suggest that mMGMT is prognostic of progression-free survival in 1p/19q-codeleted oligodendrogliomas, but an effect on overall survival (OS) has not been demonstrated. EXPERIMENTAL DESIGN: We identified patients with newly diagnosed 1p/19q-codeleted gliomas and known MGMT promoter status in the National Cancer Database from 2010 to 2019. Multivariable Cox proportional hazards regression modeling was used to assess the effect of mMGMT on OS after adjusting for age, sex, race, comorbidity, grade, extent of resection, chemotherapy, and radiotherapy. RESULTS: We identified 1,297 eligible patients, 938 (72.3%) of whom received chemotherapy in their initial course of treatment. The MGMT promoter was methylated in 1,009 (77.8%) patients. Unmethylated MGMT (uMGMT) was associated with worse survival compared with mMGMT [70% {95% confidence interval (CI), 64%-77%} vs. 81% (95% CI, 78%-85%); P < 0.001; adjusted HR (aHR), 2.35 (95% CI, 1.77-3.14)]. uMGMT was associated with worse survival in patients who received chemotherapy [63% (95% CI, 55-73%) vs. 80% (95% CI, 76%-84%); P < 0.001; aHR, 2.61 (95% CI, 1.89-3.60)] but not in patients who did not receive chemotherapy [P = 0.38; HR, 1.31 (95% CI, 0.71-2.42)]. Similar results were observed regardless of World Health Organization grade and after single- or multiagent chemotherapy. CONCLUSIONS: Our study demonstrates an association between mMGMT and OS in 1p/19q-codeleted gliomas. MGMT promoter status should be considered as a stratification factor in future clinical trials of 1p/19q-codeleted gliomas that use OS as an endpoint.

Adaptive Radiation Therapy: A Review of CT-based Techniques.

Adaptive radiation therapy is a feedback process by which imaging information acquired over the course of treatment, such as changes in patient anatomy, can be used to reoptimize the treatment plan, with the end goal of improving target coverage and reducing treatment toxicity. This review describes different types of adaptive radiation therapy and their clinical implementation with a focus on CT-guided online adaptive radiation therapy. Depending on local anatomic changes and clinical context, different anatomic sites and/or disease stages and presentations benefit from different adaptation strategies. Online adaptive radiation therapy, where images acquired in-room before each fraction are used to adjust the treatment plan while the patient remains on the treatment table, has emerged to address unpredictable anatomic changes between treatment fractions. Online treatment adaptation places unique pressures on the radiation therapy workflow, requiring high-quality daily imaging and rapid recontouring, replanning, plan review, and quality assurance. Generating a new plan with every fraction is resource intensive and time sensitive, emphasizing the need for workflow efficiency and clinical resource allocation. Cone-beam CT is widely used for image-guided radiation therapy, so implementing cone-beam CT-guided online adaptive radiation therapy can be easily integrated into the radiation therapy workflow and potentially allow for rapid imaging and replanning. The major challenge of this approach is the reduced image quality due to poor resolution, scatter, and artifacts. Keywords: Adaptive Radiation Therapy, Cone-Beam CT, Organs at Risk, Oncology © RSNA, 2023.

Scorecards: Quantifying Dosimetric Plan Quality in Pancreatic Ductal Adenocarcinoma Stereotactic Body Radiation Therapy.

Purpose: A scoring mechanism called the scorecard that objectively quantifies the dosimetric plan quality of pancreas stereotactic body radiation therapy treatment plans is introduced. Methods and Materials: A retrospective analysis of patients with pancreatic ductal adenocarcinoma receiving stereotactic body radiation therapy at our institution between November 2019 and November 2020 was performed. Ten patients were identified. All patients were treated to 36 Gy in 5 fractions, and organs at risk (OARs) were constrained based on Alliance A021501. The scorecard awarded points for OAR doses lower than those cited in Alliance A021501. A team of 3 treatment planners and 2 radiation oncologists, including a physician resident without plan optimization experience, discussed the relative importance of the goals of the treatment plan and added additional metrics for OARs and plan quality indexes to create a more rigorous scoring mechanism. The scorecard for this study consisted of 42 metrics, each with a unique piecewise linear scoring function which is summed to calculate the total score (maximum possible score of 365). The scorecard-guided plan, the planning and optimization for which were done exclusively by the physician resident with no prior plan optimization experience, was compared with the clinical plan, the planning and optimization for which were done by expert dosimetrists, using the Sign test. Results: Scorecard-guided plans had, on average, higher total scores than those clinically delivered for each patient, averaging 280.1 for plans clinically delivered and 311.7 for plans made using the scorecard (P = .003). Additionally, for most metrics, the average score of each metric across all 10 patients was higher for scorecard-guided plans than for clinically delivered plans. The scorecard guided the planner toward higher coverage, conformality, and OAR sparing. Conclusions: A scorecard tool can help clarify the goals of a treatment plan and provide an objective method for comparing the results of different plans. Our study suggests that a completely novice treatment planner can use a scorecard to create treatment plans with enhanced coverage, conformality, and improved OAR sparing, which may have significant effects on both tumor control and toxicity. These tools, including the scorecard used in this study, have been made freely available.

Risk of Squamous Cell Carcinoma of the Breast Following Postmastectomy Implant Reconstruction in Women With Breast Cancer and Carcinoma in Situ.

This cohort study uses national surveillance data to describe the incidence and risk of squamous cell carcinoma after postmastectomy implant reconstruction in women with breast cancer.

National Patterns of Early Adoption of Magnetic Resonance Imaging-Guided Linear Accelerators in 2018 to 2019.

Purpose: Adaptive magnetic resonance imaging-guided linear accelerators (aMRI-LINACs) are an emerging technology with the potential to improve radiation treatment for cancer through improved visualization and adaptive treatment. Given the competing forces of the increased cost, knowledge, and staff required for aMRI-LINAC therapy, it is unpredictable how rapidly and for whom aMRI-LINAC therapy is being adopted. Therefore, given that aMRI-LINAC therapy was granted approval from the Food and Drug Administration in late 2017, we evaluated the National Cancer Database (NCDB) to obtain a nationwide view of early aMRI-LINAC adoption in 2018 to 2019. Methods and Materials: Forty-three disease sites were aggregated. A sample of patients who underwent intensity modulated radiation therapy (IMRT) from 2018 to 2019 were matched 1:1 by stage for the top 4 cancer sites. We then compared 9 characteristics of interest (age, % White [vs non-White], % residing in metro areas, % living in the greatest income quartile, % insured by Medicare, % uninsured or unknown insurance status, % treated at a comprehensive cancer center or academic center, % with no recorded Charlson-Deyo comorbidities, and % residing in an area with highest educational) between the 2 samples (aMRI-LINAC and matched IMRT). Results: Only 171 patients were recorded as having been treated with aMRI-LINACs in the NCDB in 2018 to 2019. Fifty-six percent were male, 89% White, and 54% enrolled in Medicare. The most common sites of disease treated were lung (33 patients), pancreas (30 patients), prostate (29 patients), and breast (23 patients). There were no significant differences between aMRI-LINAC- and IMRT-matched patients except that patients with lung or breast cancer treated with aMRI-LINAC were significantly more likely to be treated at a comprehensive cancer center or academic center. Conclusions: aMRI-LINAC adoption recorded in the NCDB after Food and Drug Administration approval was potentially underreported, slow, and attributed to academic sites of practice. Further longitudinal study will be needed to assess how practice patterns evolve with greater adoption.

Adjuvant Chemoradiation in Patients with Lymph Node-Positive Biliary Tract Cancers: Secondary Analysis of a Single-Arm Clinical Trial (SWOG 0809).

BACKGROUND: SWOG 0809 is the only prospective study of adjuvant chemotherapy followed by chemoradiation focusing on margin status in patients with extrahepatic cholangiocarcinoma (EHCC) and gallbladder cancer (GBCA); however, the effects of adjuvant therapy by nodal status have never been reported in this population. METHODS: Patients with resected EHCC and GBCA, stage pT2-4, node-positive (N+) or margin-positive (R1) who completed four cycles of chemotherapy followed by radiotherapy were included. Cox regression was used to compare overall survival (OS), disease-free survival (DFS), local recurrence, and distant metastasis by nodal status. DFS rates were compared with historical data via a one-sample t-test. RESULTS: Sixty-nine patients [EHCC, n = 46 (66%); GBCA, n = 23 (33%)] were evaluated, with a median age of 61.7 years and an R0 rate of 66.7% and R1 rate of 33.3%. EHCC versus GBCA was more likely to be N+ (73.9% vs. 47.8%, p = 0.03). Nodal status did not significantly impact OS (hazard ratio [HR] 1.98, 95% confidence interval [CI] 0.86-4.54, p = 0.11) or DFS (HR 1.63, 95% CI 0.77-3.44, p = 0.20). Two-year OS was 70.6% for node-negative (N0) disease and 60.9% for N+ disease, while 2-year DFS was 62.5% for N0 tumors and 49.8% for N+ tumors. N+ versus N0 tumors showed higher rates of distant failure (42.2% vs. 25.0%, p = 0.04). The 2-year DFS rate in N+ tumors was significantly higher than in historical controls (49.8% vs. 29.7%, p = 0.004). CONCLUSIONS: Adjuvant therapy is associated with favorable outcome independent of nodal status and may impact local control in N+ patients. These data could serve as a benchmark for future adjuvant trials, including molecular-targeted agents.

Impact of Adapted Radiotherapy Schedules on Bowel Sparing in Node-Positive Cervical Cancer.

PURPOSE: Definitive radiation therapy (RT) for locally advanced node-positive cervical cancer confers significant toxicity to pelvic organs including the small bowel. Gross nodal disease exhibits significant shrinkage during RT, and yet conventional RT does not account for this change. We evaluated the reduction in absorbed bowel dose using various adaptive RT schedules. METHODS AND MATERIALS: We obtained 130 evaluable scans (computed tomography simulation and 25 cone beam computed tomography scans per patient) of 5 patients who had received definitive external beam RT for lymph node positive cervical cancer daily over 5 weeks. Using a single universal volumetric modulated arc therapy plan with predefined optimization priorities, we created adapted RT plans in 4 schedules: Daily, Weekly, Twice, and NoAdapt (mimicking conventional nonadapted RT). The in silico (computer modeled) patients were treated to 45 Gy to primary cervical disease with a simultaneous integrated boost to 55 Gy to involved lymph nodes. We evaluated dose metrics including D2cc, D15cc, and V45 to determine the impact of adapted RT schedules on bowel sparing. Statistical tests included the Student t test, analysis of variance, and the Spearman rank correlation. RESULTS: The quantity of reduced bowel dose was significantly associated with the chosen planning schedule in all evaluated metrics and was proportional to the frequency of adaptive RT with significant moderate-to-strong monotonicity. Both D2cc and D15cc were reduced an average of 2.7 Gy using daily replanning compared with a nonadapted approach. A minimally adapted strategy of only 2 replans also confers a significant dosimetric benefit over a nonadapted approach. Reduced standard deviations of D2cc and V45 bowel doses over the treatment courses were significantly associated with the choice of planning schedule with strong monotonicity. CONCLUSIONS: All adaptive RT schedules evaluated confer significant dosimetric advantages in bowel sparing over a conventional nonadapted technique, with greater sparing seen with more frequent replanning schedules. These findings warrant future trials of adaptive RT for pelvic malignancies.

Risk of Anaplastic Large Cell Lymphoma Following Postmastectomy Implant Reconstruction in Women With Breast Cancer and Ductal Carcinoma in Situ.

This cohort study examines the risk of anaplastic large cell lymphoma (ALCL) following postmastectomy implant reconstruction among US women with breast cancer and ductal carcinoma in situ (DCIS).

Long-term follow-up experience with adjuvant therapy after irreversible electroporation of locally advanced pancreatic cancer.

BACKGROUND: Irreversible electroporation (IRE) expands the surgical options for patients with unresectable pancreatic cancer. This study evaluated for differences in survival stratified by type of IRE and receipt of adjuvant chemotherapy. METHODS: Patients with locally advanced pancreatic cancer treated by IRE (2012-2020) were retrospectively included. Overall survival (OS) and recurrence-free survival (RFS) were compared by type of IRE (in situ for local tumor control or IRE of potentially positive margins with resection) and by receipt of adjuvant chemotherapy. RESULTS: Thirty-nine patients had IRE in situ, 61 had IRE for margin extension, and 19 received adjuvant chemotherapy. Most (97.00%) underwent induction chemotherapy. OS was 28.71 months (interquartile range [IQR] 19.17, 51.19) from diagnosis, with no difference by IRE type (hazard ratio [HR] 1.05 for margin extension [p = 0.85]) or adjuvant chemotherapy (HR 1.14 [p = 0.639]). RFS was 8.51 months (IQR 4.95, 20.17) with no difference by IRE type (HR 0.90 for margin extension [p = 0.694]) or adjuvant chemotherapy (HR 0.90 [p = 0.711]). CONCLUSION: These findings suggest that adjuvant therapy may have limited benefit for patients treated with induction chemotherapy followed by local control with IRE for unresectable pancreatic cancer. Further study of the duration and timing of systemic therapy is warranted to maximize benefit and limit toxicity.

Anal Cancer: Emerging Standards in a Rare Disease.

The social stigma surrounding an anal cancer diagnosis has traditionally prevented open discussions about this disease. However, as recent treatment options and an increasing rate of diagnoses are made worldwide, awareness is growing. In the United States alone, 9,090 individuals were expected to be diagnosed with anal cancer in 2021. The US annual incidence of squamous cell carcinoma of the anus continues to increase by 2.7% yearly, whereas the mortality rate increases by 3.1%. The main risk factor for anal cancer is a human papillomavirus infection; those with chronic immunosuppression are also at risk. Patients with HIV are 19 times more likely to develop anal cancer compared with the general population. In this review, we have provided an overview of the carcinoma of the anal canal, the role of screening, advancements in radiation therapy, and current trials investigating acute and chronic treatment-related toxicities. This article is a comprehensive approach to presenting the existing data in an effort to encourage continuous international interest in anal cancer.

Neoadjuvant chemoradiation alters the immune microenvironment in pancreatic ductal adenocarcinoma.

Patients with pancreatic ductal adenocarcinoma (PDAC) have a grim prognosis despite complete surgical resection and intense systemic therapies. While immunotherapies have been beneficial with many different types of solid tumors, they have almost uniformly failed in the treatment of PDAC. Understanding how therapies affect the tumor immune microenvironment (TIME) can provide insights for the development of strategies to treat PDAC. We used quantitative multiplexed immunofluorescence (qmIF) quantitative spatial analysis (qSA), and immunogenomic (IG) analysis to analyze formalin-fixed paraffin embedded (FFPE) primary tumor specimens from 44 patients with PDAC including 18 treated with neoadjuvant chemoradiation (CRT) and 26 patients receiving no treatment (NT) and compared them with tissues from 40 treatment-naïve melanoma patients. We find that relative to NT tumors, CD3+ T cell infiltration was increased in CRT treated tumors (p = .0006), including increases in CD3+CD8+ cytotoxic T cells (CTLs, p = .0079), CD3+CD4+FOXP3- T helper cells (Th, p = .0010), and CD3+CD4+FOXP3+ regulatory T cells (Tregs, p = .0089) with no difference in CD68+ macrophages. IG analysis from micro-dissected tissues indicated overexpression of genes involved in antigen presentation, T cell activation, and inflammation in CRT treated tumors. Among treated patients, a higher ratio of Tregs to total T cells was associated with shorter survival time (p = .0121). Despite comparable levels of infiltrating T cells in CRT PDACs to melanoma, PDACs displayed distinct spatial profiles with less T cell clustering as defined by nearest neighbor analysis (p < .001). These findings demonstrate that, while CRT can achieve high T cell densities in PDAC compared to melanoma, phenotype and spatial organization of T cells may limit benefit of T cell infiltration in this immunotherapy-resistant tumor.

Dosimetric assessment of patient dose calculation on a deep learning-based synthesized computed tomography image for adaptive radiotherapy.

PURPOSE: Dose computation using cone beam computed tomography (CBCT) images is inaccurate for the purpose of adaptive treatment planning. The main goal of this study is to assess the dosimetric accuracy of synthetic computed tomography (CT)-based calculation for adaptive planning in the upper abdominal region. We hypothesized that deep learning-based synthetically generated CT images will produce comparable results to a deformed CT (CTdef) in terms of dose calculation, while displaying a more accurate representation of the daily anatomy and therefore superior dosimetric accuracy. METHODS: We have implemented a cycle-consistent generative adversarial networks (CycleGANs) architecture to synthesize CT images from the daily acquired CBCT image with minimal error. CBCT and CT images from 17 liver stereotactic body radiation therapy (SBRT) patients were used to train, test, and validate the algorithm. RESULTS: The synthetically generated images showed increased signal-to-noise ratio, contrast resolution, and reduced root mean square error, mean absolute error, noise, and artifact severity. Superior edge matching, sharpness, and preservation of anatomical structures from the CBCT images were observed for the synthetic images when compared to the CTdef registration method. Three verification plans (CBCT, CTdef, and synthetic) were created from the original treatment plan and dose volume histogram (DVH) statistics were calculated. The synthetic-based calculation shows comparatively similar results to the CTdef-based calculation with a maximum mean deviation of 1.5%. CONCLUSIONS: Our findings show that CycleGANs can produce reliable synthetic images for the adaptive delivery framework. Dose calculations can be performed on synthetic images with minimal error. Additionally, enhanced image quality should translate into better daily alignment, increasing treatment delivery accuracy.

Readability of Patient Education Materials From High-Impact Medical Journals: A 20-Year Analysis.

Comprehensive patient education is necessary for shared decision-making. While patient-provider conversations primarily drive patient education, patients also use published materials to enhance their understanding. In this investigation, we evaluated the readability of 2585 patient education materials published in high-impact medical journals from 1998 to 2018 and compared our findings to readability recommendations from national groups. For all materials, mean readability grade levels ranged from 11.2 to 13.8 by various metrics. Fifty-four (2.1%) materials met the American Medical Association recommendation of sixth grade reading level, and 215 (8.2%) met the National Institutes of Health recommendation of eighth grade level. When stratified by journal and material type, general medical education materials from Annals of Internal Medicine were the most readable (P < .001), with 79.8% meeting the eighth grade level. Readability did not differ significantly over time. Efforts to standardize publication practice with the incorporation of readability evaluation during the review process may improve patients' understanding of their disease processes and treatment options.