Citations

Importance Postdural puncture headache (PDPH) can follow unintentional dural puncture during epidural techniques or intentional dural puncture during neuraxial procedures, such as a lumbar puncture or spinal anesthesia. Evidence-based guidance on the prevention, diagnosis, and management of this condition is, however, currently lacking. Objective To fill the practice guidelines void and provide comprehensive information and patient-centric recommendations for preventing, diagnosing, and managing PDPH. Evidence Review With input from committee members and stakeholders of 6 participating professional societies, 10 review questions that were deemed important for the prevention, diagnosis, and management of PDPH were developed. A literature search for each question was performed in MEDLINE on March 2, 2022. Additional relevant clinical trials, systematic reviews, and research studies published through March 2022 were also considered for practice guideline development and shared with collaborator groups. Each group submitted a structured narrative review along with recommendations that were rated according to the US Preventive Services Task Force grading of evidence. Collaborators were asked to vote anonymously on each recommendation using 2 rounds of a modified Delphi approach. Findings After 2 rounds of electronic voting by a 21-member multidisciplinary collaborator team, 47 recommendations were generated to provide guidance on the risk factors for and the prevention, diagnosis, and management of PDPH, along with ratings for the strength and certainty of evidence. A 90% to 100% consensus was obtained for almost all recommendations. Several recommendations were rated as having moderate to low certainty. Opportunities for future research were identified. Conclusions and Relevance Results of this consensus statement suggest that current approaches to the treatment and management of PDPH are not uniform due to the paucity of evidence. The practice guidelines, however, provide a framework for individual clinicians to assess PDPH risk, confirm the diagnosis, and adopt a systematic approach to its management.

Abstract Studying cardiovascular senescence is crucial for understanding disease-related changes in the cardiovascular system and their impact on health and disease. To systematically investigate the heterogeneity of senescent vascular cells in atherosclerosis, we employed the senescence reporter mouse p16tdTomato+/-, overexpressed PCSK9 and fed a high-fat diet (HFD) to induce atherosclerosis, and treated them with the senolytic drug ABT-737. Whole-aorta, single-cell RNA-sequencing (scRNA-seq) and Gene Set Enrichment Analysis (GSEA) using the SenMayo panel uncovered 10 cell clusters displaying senescent features, although not ‘classical’ senescence markers, that were reduced by treatment with ABT-737. Unbiased subclustering revealed subsets of cells increasing by HFD and reduced by ABT-737 treatment that expressed unique transcripts Spp1, Ctsb, and Tnfrsf11b mRNAs. Spatial analysis of these RNAs identified senescent cells in the cap and core of brachiocephalic arteries from atherosclerotic mice. Our results uncover a vascular-specific transcriptomic signature that may be exploited for therapeutic targeting in age-related vascular diseases.

In this study, we investigated whether radiomics features from pre-treatment positron emission tomography (PET) images could be used to predict disease progression in patients with HPV-positive oropharyngeal cancer treated with definitive proton or x-ray radiotherapy. Machine learning models were built using a dataset from Mayo Clinic, Rochester, Minnesota (n = 72) and tested on a dataset from Mayo Clinic, Phoenix, Arizona (n = 22). A total of 71 clinical and radiomics features were considered. The Mann–Whitney U test was used to identify the top 2 clinical and top 20 radiomics features that were significantly different between progression and progression-free patients. Two dimensionality reduction methods were used to define two feature sets (manually filtered or machine-driven). A forward feature selection scheme was conducted on each feature set to build models of increased complexity (number of input features from 1 to 6) and evaluate model robustness and overfitting. The machine-driven features had superior performance and were less prone to overfitting compared to the manually filtered features. The four-variable Gaussian Naïve Bayes model using the ‘Radiation Type’ clinical feature and three machine-driven features achieved a training accuracy of 79% and testing accuracy of 77%. These results demonstrate that radiomics features can provide risk stratification beyond HPV-status to formulate individualized treatment and follow-up strategies.

Abstract Background: While cigarette smoking has declined among the U.S. general population, sale and use of non-cigarette alternative tobacco products (ATP; e.g., e-cigarettes, cigars) and dual use of cigarettes/ATPs are rising. Little is known about ATP use patterns in cancer survivors enrolled in clinical trials. We investigated prevalence of tobacco product use, and factors associated with past 30-day use, among patients with cancer in national trials. Methods: Cancer survivors (N = 756) enrolled in 9 ECOG-ACRIN clinical trials (2017–2021) completed a modified Cancer Patient Tobacco Use Questionnaire (C-TUQ) which assessed baseline cigarette and ATP use since cancer diagnosis and in the past 30 days. Results: Patients were on average 59 years old, 70% male, and the mean time since cancer diagnosis was 26 months. Since diagnosis, cigarettes (21%) were the most common tobacco product used, followed by smokeless tobacco use (5%), cigars (4%), and e-cigarettes (2%). In the past 30 days, 12% of patients reported smoking cigarettes, 4% cigars, 4% using smokeless tobacco, and 2% e-cigarettes. Since cancer diagnosis, 5.5% of the sample reported multiple tobacco product use, and 3.0% reported multiple product use in the past 30 days. Males (vs. females; OR 4.33; P = 0 < 0.01) and individuals not living with another person who smokes (vs. living with; OR, 8.07; P = 0 < 0.01) were more likely to use ATPs only versus cigarettes only in the past 30 days. Conclusions: Among patients with cancer, cigarettes were the most prevalent tobacco product reported. Impact: Regardless, ATPs and multiple tobacco product use should be routinely assessed in cancer care settings.

Objective: We sought to evaluate symptomatic adverse event (AE) rates among patients with pancreatic cancer receiving neoadjuvant therapy on clinical trial (A021501) using the Patient-Reported Outcomes Common Terminology Criteria for Adverse Events (PRO-CTCAE). Background: To date, pancreatic cancer clinical trials have measured AEs using standard physician reporting [Common Terminology Criteria for Adverse Events (CTCAE)]. Patient-reported symptomatic AEs have been incompletely characterized. Methods: A021501 (December 31, 2016–January 1, 2019) randomized patients with borderline resectable pancreatic ductal adenocarcinoma to 8 doses of mFOLFIRINOX (Arm 1) or 7 doses of mFOLFIRINOX+hypofractionated radiotherapy (Arm 2), followed by pancreatectomy and adjuvant FOLFOX6. Patients completed PRO-CTCAE assessments at baseline, on day 1 of each chemotherapy cycle, and daily during radiotherapy. Results: Of 126 patients, 96 (76%) initiated treatment and completed a baseline plus at least 1 postbaseline PRO-CTCAE assessment. Diarrhea and fatigue were the only symptomatic grade 3 or higher AEs identified in at least 10% of patients using CTCAE. At least 10% of all patients reported an adjusted PRO-CTCAE composite grade 3 AE during neoadjuvant treatment for 10 of 15 items: anxiety (10%), bloating of abdomen (16%), decreased appetite (18%), diarrhea (13%), dry mouth (21%), fatigue (36%), nausea (18%), generalized pain (16%), abdominal pain (21%), and problems tasting (32%). Decreased appetite was higher in Arm 2 than in Arm 1 (P=0.0497); no other differences between study arms were observed. Conclusion: Symptomatic AEs during neoadjuvant therapy were common and were reported more frequently by patients using PRO-CTCAE than were recorded by clinicians using standard CTCAE.

6551 Background: Despite recent advances in lung cancer therapeutics leading to considerable improvement in survival, disparities continue to persist among socially disadvantaged populations. Although the reasons underlying this phenomenon are uncertain, we posit that neighborhood-level factors could play a role. Furthermore, neighborhood disadvantage may lead to epigenetic changes which promote malignant progression. This study aimed to determine the effects of neighborhood-deprivation index (NDI), a validated 13-factor-based measure, that combines income, education, employment, and housing in a neighborhood, on lung cancer mortality. Methods: A retrospective cohort study assessed the relationship of NDI with survival weighted by age, stage, and DNA methylation among biopsy-proven lung cancer from two U.S. medical centers, Johns Hopkins University and the University of Illinois Chicago, between 2008-2020. In our analysis, U.S.-standardized NDI values for each year of sample collection were computed at the U.S. census tract level and categorized into quartiles. Participants’ residential addresses were geocoded to U.S. census tracts and linked to NDI quartiles. DNA extraction from liquid biopsy samples was performed for quantification of DNA methylation. Results: The study included 184 lung cancer patients, with 89 in the low-deprivation group and 95 in the high-deprivation group. The high-deprivation group had a higher percentage of females (57% vs. 48%), a higher percentage of African Americans (AA) (50% vs. 36%), a lower pack-year smoking history (30 vs. 39 median pack-years), and a higher percentage with stage IV disease (28% vs. 20%) than the low-deprivation group. Overall, NDI was significantly higher among AA when compared with Whites (p=0.003) and associated with lung cancer stage at diagnosis with an odds ratio of 1.17 (p=0.02). There was a significant correlation between DNA methylation and stage for HOXA7, SOX17, ZPF42, TAC1 and HOXA9. Only HOXA7 DNA methylation correlated with NDI (p=0.003).The high-deprivation group had a significantly shorter survival duration compared to the low-deprivation group, with a 1-year survival rate of 79% vs. 90%, a 2-year survival rate of 70% vs. 84%, and a 5-year-survival rate of 51% vs. 73% (p=0.02). After adjusting for age at diagnosis, stage, and DNA methylation status, belonging to the high-deprivation group was associated with a higher mortality risk with a hazard ratio of 2.02 (p=0.04). Conclusions: Neighborhood-level socioeconomic status and DNA methylation may be associated with late stage lung cancer at diagnosis; whereas NDI shows a potential association with shorter survival and increased mortality risk. Higher neighborhood deprivation among AA suggests that changes in health care policy that account for neighborhood-level indices of socioeconomic deprivation may enable more equitable improvement of lung cancer mortality.

Background: Particle therapy is a noninvasive, catheter-free modality for cardiac ablation. We previously demonstrated the efficacy for creating ablation lesions in the porcine heart. Despite several earlier studies, the exact mechanism of early biophysical effects of proton and photon beam delivery on the myocardium remain incompletely resolved. Methods: Ten normal and 9 infarcted in situ porcine hearts received proton beam irradiation (40 Gy) delivered to the left ventricular myocardium with follow-up for 8 weeks. High-resolution electroanatomical mapping of the left ventricular was performed at baseline and follow-up. Bipolar voltage amplitude, conduction velocity, and connexin-43 were determined within the irradiated and nonirradiated areas. Results: The irradiated area in normal hearts showed a significant reduction of bipolar voltage amplitude (10.1±4.9 mV versus 5.7±3.2, P <0.0001) and conduction velocity (85±26 versus 55±13 cm/s, P =0.03) beginning at 4 weeks after irradiation. In infarcted myocardium after irradiation, bipolar voltage amplitude of the infarct scar (2.0±2.9 versus 0.8±0.7 mV, P =0.008) was significantly reduced as well as the conduction velocity in the infarcted heart (43.7±15.7 versus 26.3±11.4 cm/s, P =0.02). There were no significant changes in bipolar voltage amplitude and conduction velocity in nonirradiated myocardium. Myocytolysis, capillary hyperplasia, and dilation were seen in the irradiated myocardium 8 weeks after irradiation. Active caspase-3 and reduction of connexin-43 expression began in irradiated myocardium 1 week after irradiation and decreased over 8 weeks. Conclusions: Irradiation of the myocardium with proton beams reduce connexin-43 expression, conduction velocity, and bipolar conducted electrogram amplitude in a large porcine model. The changes in biomarkers preceded electrophysiological changes after proton beam therapy.

Abstract Introduction: The utilization of self reported chemotherapy treatment data is common in epidemiologic research but there is little understanding of its accuracy and limitations. Methods: The Mayo Clinic Breast Disease Registry (MCBDR) has over 9,600 participants enrolled within one year of a first breast cancer diagnosis. Participants receive annual follow up surveys through the mail to capture data on breast cancer treatments and outcomes. We compared nurse abstracted medical record chemotherapy data to self reported chemotherapy data from women diagnosed with stage 0 to 3 breast cancer that completed five consecutive annual follow up surveys. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) statistics were assessed for the report of broad chemotherapy receipt (yes, no, DK) within each yearly survey compared to the gold standard medical record data. To assess the accuracy of the self reported use of specific chemotherapy regimens, a sub cohort known as the “congruent sub cohort” was created for each survey year that included subjects that agreed with the nurse abstractors report of their broad chemotherapy usage. Sensitivity, specificity, PPV, NPV, and concordance statistics were calculated for the congruent sub cohorts followed by an assessment of the proportion of subjects providing correct responses for all chemotherapy regimens queried compared to those that had at least one discrepancy with the nurse abstracted data and the proportion of subjects with 0, 1, 2 and 3 or more discrepancies within each survey year. Results: For the 430 survey respondents, the average age was 59.5 years (SD 11.7) with a range of 29 to 94. The mean time between diagnosis and the year 1 follow up survey was 13.5 months, with an average of 61.2 months between diagnosis and the year 5 survey. The respondents were 97% white, 100% female, and 53.5% had a bachelor’s degree or higher. The self-reported receipt of chemotherapy had substantial agreement across all 5 follow up surveys with the nurse abstracted treatment data from the medical record with kappa values ranging from 0.70 (0.63 to 0.76) to 0.64 (0.57 to 0.71). For subjects in the congruent sub cohort (N=125, 120, 122, 121, and 121 subjects across the 5 survey years, respectively), self reported use of specific chemotherapy regimens were reported with an average concordance of 90% across the 5 annual surveys, however only 23% had perfect agreement with nurse abstracted data. The average number of discrepant responses provided by subjects was 1.2, with at least 12% of subjects reporting 3 or more erroneous responses for the specific chemotherapy regimens each survey year. Discussion: This study supports previous findings that self-reported chemotherapy usage may be utilized when resources are unavailable for medical record abstraction, but may have less utility when analyzing specific chemotherapy regimens. Citation Format: Nicole L. Larson, Kathryn J. Ruddy, Feven Abraha, Denise M. Herman, Fergus J. Couch, Janet E. Olson. Accuracy of self reported chemotherapy usage in annual follow up surveys for a breast cancer registry [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 748.

Purpose: This study evaluates beam angles used to generate highly individualized proton therapy treatment plans for patients eligible for carbon ion radiotherapy (CIRT). Methods and Materials: We retrospectively evaluated patients treated with pencil beam scanning intensity modulated proton therapy from 2015 to 2020 who had indications for CIRT. Patients were treated with a 190° rotating gantry with a robotic patient positioning system. Treatment plans were individualized to provide maximal prescription dose delivery to the tumor target volume while sparing organs at risk. The utilized beam angles were grouped, and anatomic sites with at least 10 different beam angles were sorted into histograms. Results: A total of 467 patients with 484 plans and 1196 unique beam angles were evaluated and characterized by anatomic treatment site and the number of beam angles utilized. The most common beam angles used were 0° and 180°. A wide range of beam angles were used in treating almost all anatomic sites. Only esophageal cancers had a predominantly unimodal grouping of beam angles. Pancreas cancers showed a modest grouping of beam angles. Conclusions: The wide distribution of beam angles used to treat CIRT-eligible patients suggests that a rotating gantry is optimal to provide highly individualized beam arrangements.