bluuebunny/crossref_metadata_2025 huggingface dataset:
Racial disparities in acute myocardial infarction outcomes in patients with cancer: A nationwide analysis.
Authors: Winn Soe , Kansakar Sajog , Shikhrakar Shreeja , Guragain Ashish , Chudy-Onwugaje Dilichukwu
Published: June 2024

e24031

Background: Cancer patients and survivors face an elevated risk of coronary artery disease due to shared risk factors. Risk is further heightened by cancer itself as well as its treatment. Acute myocardial infarction (AMI) is becoming a leading cause of death among this demographic, owing to significant advancements in cancer survival in recent decades. While racial disparities in outcomes and resource utilization in AMI hospitalizations are well-documented, data on patients with cancer remain limited. Methods: We extracted data from the National Inpatient Sample (NIS) Database from 2016 to 2020. We included all admissions with a principal diagnosis of AMI and a cancer diagnosis using ICD-10 codes. Patients were stratified by their race as – White, Black, Hispanic, Asian and others. Multivariate logistic regression was performed to assess outcomes while adjusting for hospital characteristics, patient demographics and comorbidities between the groups. The primary outcome was inpatient mortality. Results: Out of 3,190,929 admissions for AMI, 93,279 (2.9%) had co-morbid cancer. Among this subset, the majority were White patients (70.9%), followed by Black (11.0%), Hispanic (8.5%), Asian (2.7%), and others (6.9%). Asian patients, compared to White patients, had higher in-hospital mortality (adjusted odds ratio [aOR] 1.52, 95% CI 1.12-2.07, p < 0.01). There was no difference in mortality among other racial groups. There were no differences in complications such as respiratory failure, acute kidney injury, stroke, and vascular complications between the cohorts, although Black patients had lower odds of cardiogenic shock (aOR 0.78, 95% CI 0.62-0.98, p = 0.03) compared to White patients. Compared to White patients, there were lower odds of undergoing coronary angiogram in Black (aOR 0.75, 95% CI 0.68-0.83, p < 0.01), Hispanic (aOR 0.87, 95% CI 0.76-0.99, p = 0.43), and Asian patients (aOR 0.64, 95% CI 0.53-0.79, p < 0.01). Similarly, there were lower odds of undergoing percutaneous coronary intervention (PCI) in Black (aOR 0.64, 95% CI 0.57-0.72, p < 0.01), Hispanic (aOR 0.79, 95% CI 0.68-0.91, p < 0.01), and Asian patients (aOR 0.71, 95% CI 0.56-0.88, p > 0.01). Likewise, there were lower odds of undergoing coronary artery bypass grafting (CABG) in Black (aOR 0.58, 95% CI 0.45-0.76, p < 0.01) and Hispanic patients (aOR 0.70, 95% CI 0.50-0.98, p < 0.04). Conclusions: Cancer patients presenting with AMI experience similar mortality and complications across all races, although in-hospital mortality for Asian was higher compared to White patients. However, significant racial disparities exist in interventions being performed in this patient population. Coronary angiogram, PCI and CABG was performed more often in White patients than other races. Additional research is required to identify the factors contributing to this racial disparity and provide guidance for interventions aimed at improving outcomes.
Analysis of the fecal metagenome in pelvic radiation survivors with or without chronic gastrointestinal toxicity.
Authors: Nelson Bailey , Apewokin Senu , Esslinger Hope , Kharofa Jordan
Published: June 2024

e24041

Background: Whole pelvis radiation therapy (WPRT) is often used as a definitive or adjuvant treatment in patients with genitourinary, gynecologic, and gastrointestinal (GI) malignancies. Irradiation of nearby bowel can cause acute and chronic GI symptoms, which can affect patients’ quality of life. Radiation therapy has been shown to alter the microbial flora and may select for pathogenic species, which may enhance toxicity. Characteristics of the fecal metagenome in patients with or without chronic GI toxicity is unknown. Severity of GI symptoms can vary between patients who receive a similar radiation dose to normal bowel; therefore, there is a critical need to evaluate the interaction of RT and microbial species in the development of toxicity. Methods: An institutional database was used to identify survivors that completed WPRT for prostate, gynecologic, and anal cancer within the last 5 years. Patients were excluded if they had evidence of recurrent disease requiring additional therapy. Eligible patients were asked to participate via telephone. Consenting patients provided a stool sample and completed a customized PRO-CTCAE form (scale 1-5) assessing chronic GI symptoms. Comprehensive shotgun metagenomics were performed on stool. Stool was sequenced using an Illumina NextSeq500. The fecal metagenome in patients with or without chronic GI symptoms were compared. Patients were dichotomized by PRO-CTCAE diarrhea score (0-1 [mild] vs ≥2 [moderate-severe]). Raw reads were processed with Kneaddata for trimming, Kracken2 for taxonomic profiling, and Bracken for abundance estimation for bacterial, fungal and viral genomes using sequences from the National Center for Bioinformatics to determine quantitative genus and species differences. For microbial diversity assessments, estimated inverse Simpson and Shannon indices were performed. Results: Fecal metagenome and PRO-CTCAE results were available for 13 survivors. Thirty percent (n = 4) of patients reported moderate to severe diarrhea. The mean age was 66 years, 38% were male, 46% received concurrent or adjuvant chemotherapy, and the mean time from completion of WPRT to stool analysis was 34 months (range 14-62 months). Conventional radiation bowel constraints were met for each patient. Several species were enriched in patients with mild GI toxicity. Notably, Akkermansia muciniphilia had the largest differential enrichment in patients with without chronic GI toxicity. Conclusions: In this cohort of patients, A. muciniphilia, a mucin-degrading bacteria that modulates the gut barrier integrity and mucin layer thickness, was enriched in patients with no to mild diarrhea compared to patients with moderate to severe diarrhea. A. muciniphilia supplementation has been shown to decrease systemic inflammation in Western diet-fed mice. Evaluation of A. muciniphilia as a radioprotective gut bacterium warrants further evaluation.
Psychoneurological symptoms, inflammatory biomarkers and gut microbiome richness and diversity in individuals receiving hematopoietic cell transplantation (HCT).
Authors: Samami Elham , Starkweather Angela , Lyon Debra , Lynch Kelly Debra , Weaver Michael T.
Published: June 2024

e24053

Background: Hematopoietic Stem Cell Transplantation (HCT) is a potentially curative treatment for certain hematologic cancers. Although survival rates are markedly higher than in the past, there are a growing number of long-term HCT survivors who are at risk for short and long-term sequela, which can negatively affect quality of life. Psychoneurological (PN) symptoms are common occurrences associated with heightened inflammation in other cancers and chronic conditions. Emerging research links the gut microbiota to inflammatory biomarkers and suggests that gut-microbiota-brain crosstalk impacts the severity of psychoneurological symptoms among HCT recipients. Methods: This longitudinal descriptive study investigated the relationship among a cluster of PN symptoms (pain, fatigue, and depression), inflammatory biomarkers (IL-6, IL-10, C-reactive protein (CRP), and microbiota diversity measures (Shannon and Chao Beta diversity indexes) in 55 individuals receiving HCT for a hematologic malignancy. The time periods examined covered pre-transplant, 30-days, and 100-days following transplant. The PN symptoms were collected through self-reported questionnaires via computer with assistance from study staff, along with blood samples and stool specimens obtained at each study visit. Inflammatory marker values were log-transformed when used as dependent variables. Gut microbiota samples were analyzed using 16S ribosomal gene (V4 region) amplicons using Illumina MiSeq. Data analysis was performed using SAS 9.4, with PROC MIXED used for the mixed model analyses. Results: The analysis characterized mean changes in microbiota diversity over time for both Shannon and Chao indexes. IL6 levels were consistent over time, with an inverse association with Chao but not Shannon index. IL10 and CRP levels changed over time, but without associations with either Shannon or Chao. Pain severity and interference changed over time, but with no associations with inflammatory markers or gut microbiome beta diversity. Fatigue severity and interference changed over time and were positively associated with IL10. Depression did not change over time and was not associated with inflammatory markers or diversity. Conclusions: This study provides preliminary information related to associations between PN symptoms, inflammatory markers, and selected measures of gut microbiome diversity in HCT recipients. Further research is needed to explore and validate these findings to examine the implications for microbiota diversity on inflammatory factors and PN symptoms. Clinical trial information: NCT02398708 .
Comparison of concurrent care and traditional hospice at a regional VA.
Authors: Zhang Jeremy Shi , Hadler Rachel A. , Broderick Ann , Zeitler William Andrew
Published: June 2024

e24065

Background: While hospice care offers many patients services promoting comfort and quality of life, the traditional hospice model described in Medicare policy presents numerous barriers to utilization. Notably, since hospice pays for all therapies related to a terminal illness, patients are often forced to make a difficult choice to stop disease-directed therapies in order to enroll in hospice. Poor provider understanding of hospice also contributes to the common scenario in which hospice is offered too late to make a meaningful impact for patients and their families. These issues were prominent in the VA population in 2006, when only 5% of eligible Veterans received hospice services. Consequently, the VA Comprehensive End-of-Life Care Initiative in 2009 created the concurrent care hospice model in where Veterans no longer had to stop all disease-directed therapies to enroll. Initial national VA data in lung cancer suggested that concurrent care may be better than traditional hospice by decreasing aggressive treatments, ICU hospitalizations, and medical costs. Our regional VA developed a Hospice Flag system that tagged patients in the electronic medical record who had either a concurrent or traditional hospice enrollment to better inform health care providers. This project investigates how the concurrent care hospice model may help achieve an important Veteran-centered outcome, which is to die in the home setting and improve access to hospice care. Methods: We retrospectively reviewed all Veterans with a hospice flag from October 2017 to July 2021 and cancer as the primary hospice diagnosis. Our primary aim was to establish correlation between hospice type and Veterans’ ultimate location of death with the percentage at home versus institution (e.g. care center, hospital, or hospice house). A secondary measure was median length-of-stay (LOS) in hospice. Results: 317 total Veterans were enrolled in concurrent care hospice (96) and traditional hospice (221) from Oct 2017 to July 2021. 72% of Veterans in concurrent care (69/96) died at home compared to only 57% in traditional hospice (125/221) with the remainder dying in an institution; this result was statistically significant by Chi-square analysis (p = 0.01). Median LOS in hospice was 62 days for concurrent care and 26 days for traditional hospice. Conclusions: This project demonstrates that concurrent care hospice is significantly associated with Veterans being able to die in their own home. Concurrent care was also correlated with longer median LOS in hospice, suggesting greater duration of support services provided to patients and families.
Impact of COVID-19 on referrals to outpatient palliative care for patients with advanced cancer in a safety-net health system.
Authors: DiMartino Lisa , Merrill Vincent , Hogan Timothy P. , Skinner Celette Sugg , Sadeghi Navid , Roche-Green Alva , Hong Arthur S.
Published: June 2024

e24071

Background: Medically underserved adults with cancer experience challenges with access to care and tend to present at later disease stage. Amidst the complex needs of safety-net patients, the value of early palliative care (PC) services can go unrecognized. Few studies have examined PC referral patterns in the outpatient setting among advanced cancer patients within a safety-net system, and none has studied how or whether referrals have evolved since the most acute stages of the COVID-19 pandemic. This study examined PC referrals for cancer patients seen as outpatients in the urban safety-net primary provider of cancer care for uninsured individuals in Dallas, TX, and assessed changes from before to after the acute pandemic phase. Methods: We used tumor registry records linked to outpatient PC referral data from the safety-net health system’s electronic health record from January 1, 2018 to July 31, 2023. The primary outcome was a binary indicator for receipt of PC referral among patients diagnosed with advanced-stage solid tumor cancer. Using a multivariate logistic regression model, we evaluated whether our independent variable – a binary indicator for pre-pandemic (January 1, 2018 to February 28, 2020) and post-pandemic (March 1, 2020 to July 31, 2023) time periods – was associated with PC referrals. We included age, sex, race/ethnicity, cancer type, preferred language, and insurance as covariates. Results: Among 1,590 eligible patients (mean age 58.1, range: 21-94), 44% were female and 75% were non-White. Diagnoses included lung (20%), gastrointestinal (17%), colorectal (14%), breast (9%), prostate (9%), head/neck (9%), pancreatic (8%), gynecologic (6%), and other (8%) cancers. Across both time periods, a total of 785 (49%) of patients received a PC referral. Whereas 53% of the 754 patients in the pre-pandemic cohort received a PC referral, 46% of the 836 in the post-pandemic cohort received a referral. In the adjusted regression model, pre-pandemic patients were 1.26 times more likely to have a PC referral than post-pandemic patients (95% CI, 1.02-1.56). Referrals varied by cancer type across both time periods – compared to breast cancer patients, gynecologic cancer patients had lower odds of PC referral (aOR, 0.19; 95% CI, 0.10-0.36) and pancreatic cancer patients had higher odds of PC referral (aOR, 2.93; 95% CI, 1.71-5.00). Conclusions: Our analysis showed that referrals declined during the COVID-19 pandemic and revealed differing underlying patterns of PC referral along disease groups. Understanding pre-existing referral patterns and lasting practice changes post-pandemic can support clinicians to integrate PC and improve cancer outcomes. Findings can be used to develop interventions, such as clinical triggers, to improve PC delivery for underserved cancer patients.
Feasibility of hydromorphone PCA 10-day simple mode home management of patients in severe pain: A prospective multicenter study.
Authors: Zhao Kelei , Han Yu , Li Chunqing , Zhang Guifang , He Junling , Chang Wei , Yin Haiqing , Cui Yuelong , Dong Yanhu , Yao Yibo , Chen Guorong , Wang Pei , Tang Dongxia , Dong Hua , Zhang Qiang , Li Bo , Zhang Min , Ji Yinghua , Lu Ping
Published: June 2024

e24072

Background: Pain is a common symptom affecting patients with cancer. In clinical practice patients with advanced refractory cancer pain often face multiple anti-tumor treatments and prefer treatment at home or in community clinics versus hospitalization; thus, pain relief and drug management are challenging. Patient-controlled analgesia (PCA) is an essential component of analgesic treatment. However, difficulties associated with PCA configuration, unified pump configuration mode, and tube blockage may limit its use by both doctors and patients, negatively affecting large-scale promotion of PCA technology in hospitals and at home. In this study we optimized PCA parameters to resolve problems around cumbersome operation and tube blockage, thereby increasing pump utility and feasibility. We refer to this mode as the "10-day simple mode." The study objective is to evaluate the analgesic effect of the "10-day simple mode" of hydromorphone PCA and to explore its home-based convenience and use. Methods: A total of 100 patients with refractory cancer pain were included in this study. The pump configuration mode was divided into two stages. The first (titration) stage was: hydromorphone + normal saline with a total volume of 24 ml and pump speed of 1.0 ml/h. The second (maintenance) stage was: hydromorphone + normal saline with a total volume of 288 ml and pump speed of 1.2 ml/h with PCA of 2.4 ml. During the maintenance stage, if pain control was unsatisfactory the background dose was increased based on the number of PCA presses in the previous 24 hours. Patients' numeric rating scale (NRS) scores, quality of life scores, and adverse reactions were recorded before and after treatment. Results: Patients' average NRS score before treatment was 7.4 (7-10). Average time to successful titration was 49.6 minutes (35.6-56.9) and 40.7% of patients achieved successful titration within 30 minutes. After titration, the average NRS score was 3.2 (0-6). There was a statistically significant difference in NRS scores before and after titration (p < 0.05). During maintenance, 56.0% of patients experienced breakthrough pain on day 1, when the average NRS score was 5.2. As background dosing continued breakthrough pain and average NRS score gradually decreased (p < 0.05). Quality of life scores and patient satisfaction measured before and after 10 days of PCA pump use showed significant improvement (p < 0.001). Conclusions: For patients with refractory cancer pain, the hydromorphone PCA "10-day simple mode" produces good analgesic effect, is easy to manage, and suitable for patients seeking home-based pain relief. These results warrant further clinical study. Clinical trial information: NCT05744089 .
Preclinical development of ATR04-484, an auxotrophic strain of Staphylococcus epidermidis, for the topical treatment of epidermal growth factor receptor (EGFR) inhibitor-induced dermal toxicity.
Authors: Whitfill Travis M. , Mootien Sara , Leger Roger
Published: June 2024

e24074

Background: Agents targeting the EGFR-mediated signaling pathway are commonly used for the treatment of advanced lung, pancreatic, colorectal, and head and neck cancers. Significant dermal toxicities, which occur in up to 90% of patients treated with EGFR inhibitors (EGFRis) and other therapies inhibiting downstream signaling pathways, may be disruptive to a patient’s quality of life and adherence to therapy. Inhibition of the EGFR pathway may suppress host defenses and lead to opportunistic pathogenic colonization or infection. EGFRi-induced dermal toxicity is associated with elevated levels of Staphylococcus aureus and IL-36γ. ATR04-484 is a topical ointment containing S. epidermidis strain SE484, isolated from a healthy human volunteer that was selected for its ability to inhibit S. aureus and IL-36γ . Methods: Reconstructed human epidermis (RHE) and ex vivo pig skin were used to measure the effect of ATR04-484 on S. aureus in therapeutic and prophylactic settings with S. aureus added prior to or after ATR04-484, respectively. To evaluate the anti-inflammatory effects of ATR04-484, IL-36γ levels were measured on untreated RHE and RHE treated with erlotinib alone or in combination with ATR04-484. 104 colony-forming units (CFU) of methicillin-resistant (MRSA) or methicillin-sensitive (MSSA) S. aureus were used. Toxicology was assessed by measuring cell viability in three in vitro toxicology assays: the eye irritant potential was tested on 3D reconstituted human cornea-like epithelium (RhCE), the skin irritant potential of the strain in the ointment was assessed on 3D RHE, and the skin corrosive potential was evaluated on RHE. Results: ATR04-484 comparably inhibited growth of both MRSA and MSSA in therapeutic and prophylactic settings. In a therapeutic setting, ATR04-484 inhibited MRSA growth by 1 log (90%) compared to untreated MRSA in both RHE and pig skin. In a prophylactic setting, ATR04-484 inhibited MRSA growth by approximately 5 logs on RHE and 2 logs on pig skin. Additionally, application of ATR04-484 reduced IL-36γ to a level comparable to untreated RHE. The effect was dose-dependent; application of 109CFU/cm2 of ATR04-484 showed more potent IL-36γ reduction compared to 108 CFU/cm2. The three toxicology assays indicate that ATR04-484 does not cause irritation or corrosion. Conclusions: In these preclinical studies, ATR-04-484 showed a promising preclinical profile for the treatment of EGFRi-induced dermal toxicity by significantly reducing S. aureus growth, completely ameliorating IL-36γ levels, and showing no safety concerns.
Quality of life in patients with malignant wounds treated at a wound care clinic.
Authors: Chen Anna , Dusza Stephen W. , Bromberg Jacqueline , Chandarlapaty Sarat , Goldfarb Shari Beth , Sanford Rachel Ann , Markova Alina
Published: June 2024

e24075

Background: Malignant wounds can present in up to 14.5% of patients with advanced cancer, significantly reducing quality of life (QoL). Patients with chronic leg ulcers experienced improved QoL, as determined by a reduction in Skindex-16 score after treatment at a dedicated wound care clinic. We sought to assess the effect of wound care clinics on QoL in patients with malignant wounds. Objectives: To describe the baseline QoL, physical symptoms, and treatment modalities that affect QoL in patients with malignant wounds. To assess changes in QoL over time of patients attending a wound care clinic. Methods: This retrospective study included 36 patients seen from 1/1/2016 - 4/1/2023 at a wound care clinic at an oncologic hospital with at least one completed Skindex-16 questionnaire, which is a validated measure of the effects of skin diseases on QoL. Data were extracted from the electronic medical record. Descriptive statistics, graphical methods, and random effects models for change were used to describe the patient population and the QoL measures over time. Results: Of the 36 patients who completed at least one Skindex-16 questionnaire, 69% were female, and 50% developed malignant wounds from metastatic breast cancer, 22.2% from cutaneous squamous cell carcinoma, and 27.8% from various malignancies such as sarcoma. Most patients had advanced cancer; 9.7% were stage II, 41.9% stage III, and 48.4% stage IV. At the initial visit, patients had drainage associated with their wound 86.1% of the time, odor 47.2%, bleeding 63.9%, pain 69.4%, and itch 50% of the time. Patients were treated with dressings 100% of the time, and 88.2% of patients received topical treatment for odor, 73.9% received topical treatment for bleeding, 55.6% topical itch treatment, 44% topical pain treatment, 36% gabapentin, and 24% received an opioid. The median baseline Skindex-16 score was 59.5, falling into the “extremely severe” category, with a median score of 17.5, 21, and 23 for the symptom, emotion, and function domains, respectively. Nineteen patients completed an additional Skindex-16 questionnaire at follow up visits (visit two 52.8%, visit three 33.3%, visit four 19.4%, visit five or greater 13.9%). Compared to the median Skindex-16 score at baseline, there was a 34.5% improvement at visit two, 45.4% at visit three, 73.1% at visit four, and 83.2% improvement in QoL at visit five or more. Conclusions: Malignant wounds severely reduce patients’ quality of life; however, patients experienced significantly improved quality of life after being treated at dedicated wound clinics.
Effect of lactobacillus rhamnosus DY801 on methionine metabolism and Th17 cells in the treatment of acute radiochemotherapy induced bowel injury.
Authors: Yu Lu , Chen Zhenhui , Fan Hongying , Ding Yi
Published: June 2024

e24099

Background: Radiation and chemotherapy are important treatments for patients with pelvic malignant tumors, and they will inevitably lead to the occurrence of radiochemotherapy-induced intestinal injury. Acute radiochemotherapy-induced intestinal injury reduces the quality of life and treatment compliance of patients, which ultimately affects overall survival. However, at present, the treatment of acute intestinal injury is limited. Therefore, alleviating acute radiochemotherapy-induced intestinal injury is an important scientific problem to be solved urgently in tumor treatment. Methods: The stool samples of patients before and after treatment were analyzed by 16S rRNA sequencing to explore the intestinal bacteria associated with radiochemotherapy-induced intestinal injury. The changes in intestinal bacteria and metabolism related to radiochemotherapy-induced intestinal injury were explored through mice in vivo experiments, metagenomics, and non-target metabolomics analysis. New strains of Lactobacillus were obtained from fresh human fecal samples. The molecular mechanism of the therapeutic effect of Lactobacillus rhamnosus DY801 was explored through in vivo experiments, RNA-sequencing, Crispr/cas9 gene knockout, immunohistochemistry, flow cytometry, LC/MS, and western blot. Results: 16S rRNA sequencing of stool samples from patients before and after treatment suggested that the abundance of Lactobacillus and Bacteroides decreased after radiotherapy and chemotherapy. In vivo experiments in mice showed that the decrease in abundance of Lactobacillus and Bacteroides, the decrease of methionine metabolism, and the increase of activated Th17 cells were related to the severity of radiochemotherapy-induced intestinal injury. Ten new strains of Lactobacillus were isolated, cultured, and identified from the feces of matched normal people. Among them, Lactobacillus rhamnosus DY801 had a resistance to acid and bile salt, and has the strongest ability to treat radiochemotherapy-induced intestinal injury. In vivo and in vitro experiments suggest that Lactobacillus rhamnosus DY801 inhibited the proinflammatory Th17 cells through methionine, a production of metB gene, and significantly improve acute intestinal injury. Conclusions: Lactobacillus rhamnosus DY801 regulated methionine metabolism and inhibited Th17 cells in the treatment of the acute radiochemotherapy-induced intestinal injury.
Beyond the “teachable moment”: Smoking cessation during cancer treatment remains challenging despite high motivation to quit.
Authors: Rieth Katherine , Cupertino Ana Paula , Kadambi Sindhuja G , Janelsins Michelle Christine , Morrow Gary R. , Peppone Luke Joseph
Published: June 2024

e24141

Background: Continued smoking throughout cancer treatment, including surgery, is associated with treatment-related complications and a higher total symptom burden during treatment. This can lead to interruptions and delays in therapy that can compromise treatment efficacy and survival. Approximately 1 in 3 patients smoke at or around time of cancer diagnosis. Despite this “teachable moment” for smoking cessation, at least half of patients with cancer are unsuccessful in their attempts, and relapse rates for post-surgical cancer patients are high. Better understanding of quit motivation among these patients can help guide tobacco treatment interventions in the post-operative and adjuvant treatment time periods. Methods: This is an analysis of a longitudinal nationwide multicenter study of 1003 patients through the University of Rochester Cancer Center NCI Community Oncology Research Program (URCC NCORP) that assessed treatment type, treatment-related symptoms, smoking status, and motivation to quit smoking for patients with a new diagnosis of cancer. Patients supplied demographic and clinical information at enrollment with assessments at two weeks pre- adjuvant treatment, post adjuvant treatment, and 6 months. Chi-square, multinomial logistic regression, and ANOVA were used to analyze the difference between smokers and nonsmokers, and those with previous surgical treatment. Results: The majority of patients had surgery as part of their cancer treatment (n = 718, 71.6%). Of these (n = 222, 30.9%) had a diagnosis of a tobacco-associated cancer, which was associated with smoking status at pre-treatment (p < 0.05). For those with previous surgery, n = 90 (68.7%, p < 0.001) were current smokers before starting adjuvant treatment. Post-surgical patients who smoke had both higher total symptom burden ( M= 23.7 vs M= 17.0; p < 0.05) and higher symptom severity ( M =1.97 vs M= 1.42; p < 0.001) pre-adjuvant treatment and at 6 month follow up [( M =31.3 vs M= 22.2; p < 0.05);( M= 2.6 vs M= 1.8; p < 0.05)] compared to post-surgical patients who were not smokers. Motivation to quit was sustained among current smokers between the pre- and post- adjuvant treatment periods (p < 0.001), as well as for those that had previous surgery (p < 0.05). Despite motivation to quit among 64.4% of current smokers with previous surgery, 15.4% reported being able to quit by post-adjuvant treatment with 50% relapsing to smoking at 6-month follow up. Conclusions: For patients that continue to smoke after surgical treatment, cessation rates are much lower than motivation to quit with high rates of relapse. Early intervention around the time of surgery presents an ideal opportunity to optimize the “teachable moment” by providing longitudinal tobacco treatment as part of cancer care to improve treatment-related symptoms, as well as overall survival.
TACTIVE-K: Phase 1b/2 study of vepdegestrant, a proteolysis targeting chimera (PROTAC) estrogen receptor (ER) degrader, in combination with PF-07220060, a cyclin-dependent kinase (CDK)4 inhibitor, in ER+/human epidermal growth factor receptor 2 (HER2)- advanced breast cancer.
Authors: Telli Melinda L. , Gawryletz Chelsea D. , Wei Mei , Patnaik Amita , Lu Dongrui R. , Mazzoletti Marco , Valota Olga , Parmar Swapnil S , Tan Weiwei , Mukohara Toru
Published: June 2024

TPS1131

Background: Vepdegestrant (ARV-471) is an investigational, orally administered PROTAC ER degrader. Initial results from a phase 1b cohort of a first-in-human phase 1/2 study (NCT04072952) showed that vepdegestrant, in combination with the CDK4/6 inhibitor palbociclib, had robust clinical activity (clinical benefit rate [CBR]: 63.0%) in heavily pretreated patients (pts) with ER+/HER2- advanced breast cancer. PF-07220060 is an investigational CDK4-selective inhibitor, which in contrast to CDK4/6 inhibitors, spares CDK6 blockade and demonstrates less neutropenia in in vivo models. A first-in-human phase 1/2a study (NCT04557449) demonstrated promising antitumor activity with PF-07220060 in pts with advanced solid tumors with a CBR of 52.4%. Preclinical tumor models have shown that vepdegestrant + PF-07220060 effectively suppresses tumor growth to a greater extent than either agent alone. This open-label, multicenter phase 1b/2 study (NCT06206837) will evaluate the combination of vepdegestrant + PF-07220060 in pts ≥18 y with confirmed ER+/HER2- advanced breast cancer. Methods: The phase 1b portion will use an escalation/de-escalation approach to determine the recommended phase 2 dose (RP2D) of the combination of vepdegestrant and PF-07220060. The phase 2 portion will further evaluate the preliminary antitumor activity, safety, and pharmacokinetics (PK) of the combination at the RP2D. Pts (N≈65) will receive vepdegestrant orally once daily continuously and PF-07220060 orally twice daily continuously. The primary endpoint of the phase 1b portion is the number of pts with dose-limiting toxicities; secondary endpoints are antitumor activity (objective response rate [ORR], duration of response [DOR], CBR), progression-free survival (PFS), safety, and PK. The primary endpoint of the phase 2 portion is ORR; secondary endpoints are antitumor activity (DOR, CBR), PFS, safety, plasma concentrations of study drugs, and changes in circulating tumor DNA. Previously presented at ESMO Breast Cancer 2024, FPN: 264TiP, M Telli, et al. Reused with permission. Clinical trial information: NCT06206837 .
Innovation of the first-line strategy optimized as abemaciclib with endocrine therapy based on the ESR1mutation of ctDNA for patients with HR-positive HER2-negative advanced metastatic breast cancer (JBCRG-M08; AMBER study).
Authors: Yoshinami Tetsuhiro , Sasada Shinsuke , Nishimura Meiko , Iwase Madoka , Oshiro Chiya , Terata Kaori , Ishihara Mikiya , Bando Hiroko , Tanabe Masahiko , Yoshimoto Nobuyasu , Akiyoshi Sayuri , Takada Masahiro , Ishiguro Hiroshi , Saji Shigehira , Morita Satoshi , Masuda Norikazu
Published: June 2024

TPS1134

Background: Aromatase inhibitor (AI) + CDK4/6 inhibitor (CDK4/6i) has been established as a standard of care of 1st line treatment for hormone receptor (HR)-positive/HER2-negative advanced metastatic breast cancer (AMBC). ESR1 mutations are considered to be one of the causes of acquiring resistance against the AI +CDK4/6i. PADA-1 trial showed that replacing AI with fulvestrant (FUL) as a partner of palbociclib (PAL) at occurrence of some ESR1 mutations improved progression-free survival (PFS) and PFS2, suggesting PAL should be used based on the strategy of selecting endocrine agents according to ESR1 mutation status by ctDNA analysis. On the other hand, we don’t know if this strategy is effective in the case of abemaciclib (ABM), another CDK4/6i established as the standard of care for AMBC. We are conducting a study to make evidence on this clinical question. Methods: This multicenter, single-arm phase II study is designed to evaluate the efficacy and safety of the strategy to replace AI with FUL for detectable ESR1 mutations in combination with ABM. Key eligibility criteria include patients receiving AI+ABM for at least 6 months as first-line treatment for HR-positive/ HER2-negative AMBC without progressive disease (PD). While continuing AI+ABM, ctDNA analysis will be performed at approximately 3, 9, 15 months from enrollment. If ESR1 mutation is identified at any point and non-PD is confirmed by CT, FUL+ABM will be initiated instead of AI+ABM. In patients with ESR1 mutations completely cleared by ctDNA analysis 6 months after the start of FUL+ABM, AI+ABM will be resumed (Re-AI+ABM arm); the Re-AI+ABM arm is intended to investigate whether the discontinuation of FUL will allow clones with ESR1 mutations to proliferate again. Primary endpoint is 2-year PFS rate in full analysis set. Key secondary endpoints include 2-year PFS rate by treatment sequences, and rate of disappearance of ESR1mutations in ctDNA with FUL+ABM. Plasma-SeqSensei Breast Cancer IVD Kit, which can simultaneously detect mutations in a wide range of six genes including ESR1, as well as PIK3CA, AKT1, ERBB2, KRAS, and TP53, is used for ctDNA analysis in this study. Based on PFS data in MONARCH3 study, the threshold and expected value of the 2-year PFS rate were estimated to be 45% and 55%, respectively, and target sample size was calculated as 160 patients. Patient enrollment started in December 2022 and run through December 2024; as of December 2023, 54 patients have been enrolled. Clinical trial information: 051220133.
Phase I/II study of stereotactic radiation and sacituzumab govitecan with zimberelimab in the management of metastatic triple negative breast cancer with brain metastases.
Authors: Ahmed Kamran A. , Kim Youngchul , DeJesus Michelle , Oliver Daniel Eli , Mills Matthew , Nair Rajesh , Armaghani Avan J. , Costa Ricardo L , Lee Kimberley T , Loftus Loretta S. , O'Connor Tracey L. , Soliman Hatem Hussein , Soyano Muller Aixa Elena , Vogelbaum Michael A. , Forsyth Peter A. J. , Arrington John , Rosa Marilin , Yu Michael , Han Hyo S.
Published: June 2024

TPS1140

Background: Patients with triple negative breast cancer (TNBC) are at a high risk to develop brain metastases. The prognosis and quality of life for triple negative brain-metastatic breast cancer remains very poor. Treatment options are limited and improvement in efficacy is needed. Sacituzumab govitecan (SG) has shown blood brain barrier (BBB) penetration in preclinical and clinical settings with anti-tumor activity in the phase III ASCENT Trial (NCT02574455). Radiotherapy can open the BBB and has been shown to be safe in combination with anti-PD-1 therapy in our previous trial (NCT03807765). Therefore, combining radiation with the anti-PD-1 monoclonal antibody, zimberelimab, and SG may provide a synergistic anti-tumor approach. We hypothesize the use of SG and zimberelimab with stereotactic radiosurgery (SRS) among patients with metastatic TNBC with brain metastases will be safe and improve progression free survival compared to treatment with SG alone. Methods: The study is designed as a single-arm, nonrandomized, open-label, phase I/II trial of SG and zimberelimab with SRS among patients with metastatic TNBC with brain metastases. The primary endpoint will be neurologic toxicity defined by CTCAE v5 criteria (phase I) and 12 month PFS (phase II). TNBC patients ≥ 18 years old with ≤ 15 brain metastases with at least one measurable lesion ≥ 0.5 cm per RANO-BM criteria will be enrolled. Treatment will be initiated with SRS followed 1 week later by SG on days 1 and 8 (10 mg/kg) with zimberelimab on day 1 (360 mg IV) repeated every 3 weeks. Follow-up imaging response assessments will be conducted at q9 week intervals. An interim analysis will be performed after 21 patients are enrolled. An additional 10 patients will be enrolled if interim futility criteria are not met. Clinical trial information: NCT06238921 .
Dose/Exposure Relationship of Exercise and Distant Recurrence in Primary Breast Cancer
Authors: Soldato Davide , Michiels Stefan , Havas Julie , Di Meglio Antonio , Pagliuca Martina , Franzoi Maria Alice , Pistilli Barbara , Iyengar Neil M. , Cottu Paul , Lerebours Florence , Coutant Charles , Bertaut Aurélie , Tredan Oliver , Vanlemmens Laurence , Jouannaud Christelle , Hrab Iona , Everhard Sibille , Martin Anne-Laure , André Fabrice , Vaz-Luis Ines , Jones Lee W.
Published: June 2024

PURPOSE

Postdiagnosis exercise is associated with lower breast cancer (BC) mortality but its link with risk of recurrence is less clear. We investigated the impact and dose-response relationship of exercise and recurrence in patients with primary BC.

METHODS

Multicenter prospective cohort analysis among 10,359 patients with primary BC from 26 centers in France between 2012 and 2018 enrolled in the CANcer TOxicities study, with follow-up through October 2021. Exercise exposure was assessed using the Global Physical Activity Questionnaire-16, quantified in standardized metabolic equivalent of task–hours per week (MET-h/wk). We examined the dose/exposure response of pretreatment exercise on distant recurrence-free interval (DRFI) for all patients and stratified by clinical subtype and menopausal status using inverse probability treatment weighted multivariable Cox models to estimate hazard ratios (HRs).

RESULTS

For the overall cohort, the relationship between exercise and DRFI was nonlinear: increasing exercise ≥ 5 MET-h/wk was associated with an inverse linear reduction in DRFI events up to approximately 25 MET-h/wk; increasing exercise over this threshold did not provide any additional DRFI benefit. Compared with <5 MET-h/wk, the adjusted HR for DRFI was 0.82 (95% CI, 0.61 to 1.00) for ≥ 5 MET-h/wk. Stratification by subtype revealed the hormone receptor–/human epidermal growth factor receptor 2– (HR–/HER2–; HR, 0.59 [95% CI, 0.38 to 0.92]) and HR–/HER2+ (HR, 0.37 [95% CI, 0.14 to 0.96]) subtypes were preferentially responsive to exercise. The benefit of exercise was observed especially in the premenopausal population.

CONCLUSION

Postdiagnosis/pretreatment exercise is associated with lower risk of DRFI events in a nonlinear fashion in primary BC; exercise has different impact on DRFI as a function of subtype and menopausal status.
Challenges in Diagnosing and Managing the Spectrum of Primary Aldosteronism
Authors: Yang Jun , McCarthy Josephine , Shah Sonali S , Ng Elisabeth , Shen Jimmy , Libianto Renata , Fuller Peter J
Published: June 2024

Primary aldosteronism, characterized by the dysregulated production of aldosterone from 1 or both adrenal glands, is the most common endocrine cause of hypertension. It confers a high risk of cardiovascular, renal, and metabolic complications that can be ameliorated with targeted medical therapy or surgery. Diagnosis can be achieved with a positive screening test (elevated aldosterone to renin ratio) followed by confirmatory testing (saline, captopril, fludrocortisone, or oral salt challenges) and subtyping (adrenal imaging and adrenal vein sampling). However, the diagnostic pathway may be complicated by interfering medications, intraindividual variations, and concurrent autonomous cortisol secretion. Furthermore, once diagnosed, careful follow-up is needed to ensure that treatment targets are reached and adverse effects, or even recurrence, are promptly addressed. These challenges will be illustrated in a series of case studies drawn from our endocrine hypertension clinic. We will offer guidance on strategies to facilitate an accurate and timely diagnosis of primary aldosteronism together with a discussion of treatment targets which should be achieved for optimal patient outcomes.
Neuropsychological Test Performance Differentiates Subgroups of Individuals With Adult Moyamoya Disease: A Cross-Sectional Clinical Study
Authors: DeDios-Stern Samantha L. , Gotra Milena Y. , Resch Zachary J. , Jennette Kyle J. , Amin-Hanjani Sepideh , Charbel Fady T. , Alaraj Ali , Testai Fernando D. , Thulborn Keith R. , Vargas Alejandro , Pliskin Neil H. , Soble Jason R.
Published: June 2024

BACKGROUND AND OBJECTIVES:

Moyamoya disease (MMD) is a rare noninflammatory disorder involving progressive intracranial vasculopathy and impaired cerebral blood flow in the anterior circulation, resulting in stroke and cognitive impairment. We aimed to characterize cognitive impairment and the possible predictive value of sociodemographic and clinical characteristics of adults with MMD.

METHODS:

This cross-sectional study examined neurocognitive performance in a group of 42 consecutive adult patients (mean age = 40.52 years; 69% female) referred for a presurgical neuropsychological evaluation. Neuropsychological functioning was assessed with a comprehensive battery, and cognitive dysfunction was defined as 1.5 SDs below the mean. Neurocognitive performance correlated with clinical/demographic characteristics and disease markers.

RESULTS:

Most patients (91%) had a history of stroke, and 45% had cognitive deficits, most notably on measures of attention/speed (48%), executive functioning (47%), visuoconstruction (41%), and memory (31%-54%). Only higher educational attainment and poor collateral blood flow in the right hemisphere differentiated cognitively impaired (n = 19) and intact groups (n = 23), and MMD-related characteristics (eg, disease duration, stroke history) did not differentiate the 2 groups.

CONCLUSION:

Consistent with previous work, frontal-subcortical cognitive deficits (eg, deficits in mental speed, attention, executive functioning) were found in nearly half of patients with MMD and better cognitive performance was associated with factors related to cognitive reserve. Angiographic metrics of disease burden (eg, Suzuki rating, collateral flow) and hemodynamic reserve were not consistently associated with poorer cognitive outcomes, suggesting that cognition is a crucial independent factor to assess in MMD and has relevance for treatment planning and functional status.
Staying in the Game: Interventions for Managing Achilles Tendinopathy in the In-Season Athlete
Authors: Dyrek Paige , Tsitsilianos Nicholas , McInnis Kelly C. , Tenforde Adam S. , Borg-Stein Joanne
Published: June 2024

Achilles tendinopathy is a common overuse injury that is traditionally managed with activity modification and a progressive eccentric strengthening program. This narrative review describes the available evidence for adjunctive procedural interventions in the management of midportion and insertional AT, specifically in the athletic population. Safety and efficacy data from available literature on extracorporeal shockwave therapy, platelet-rich plasma, high-volume injectate with or without tendon scraping, and percutaneous needle tenotomy are used to propose an algorithm for treatment of Achilles tendinopathy for the in-season athlete.
Analysis of Common Exercise Modalities in Improving Athletic Performance in Older Adults: A Narrative Review
Authors: Nguyen Chantal , Kaufman Matthew , Vallejo Adrian , DeParis Sarah , Friedlander Anne , Frehlich Levi , Fredericson Michael
Published: June 2024

Exercise leads to robust cardiovascular, musculoskeletal, and psychological benefits that improve quality of life and longevity for older adults, but accompanying improvements in athletic parameters are less well explored. The aim of this review is to summarize some of the most common exercise modalities, namely, Pilates, martial arts (tai chi, Japanese-style karate, hard martial arts), locomotion (brisk walking/jogging and running), Masters sports, resistance training, and high-intensity interval training, in improving athletic performance for older adults. Regular participation in these activities can have robust yet unique impacts on physical performance that prolong exercise participation. In particular, this review will explore benefits in cardiorespiratory fitness, power, strength, flexibility, and balance, thereby hopefully improving endurance, exercise adherence, and overall fall risk. A narrative literature review was performed to explore benefits, pitfalls, and recommendations for some of the most popular exercise modalities for older adults.
Hope and Healing: Black Colleges and the Future of American Democracy
Authors: Betsey Charles
Published: June 2024

Charles Betsey of Howard University reviews “Hope and Healing: Black Colleges and the Future of American Democracy” by John Silvanus Wilson Jr. The EconLit abstract of this book begins: “Discusses historically Black colleges and universities (HBCUs) in the context of the larger history of American higher education, highlighting what HBCUs have done and what non-HBCUs have failed to do to actualize democracy.”
The safety and efficacy of spray cryotherapy after endoscopic sinus surgery in chronic rhinosinusitis: A systematic review of randomized controlled trials
Authors: Taha Mohammad J. J. , Falah Obaida , Abuawwad Mohammad T. , Sara Ayham R. , Aljariri Adham A. , Nashwan Abdulqadir J. , Abuawwad Ibrahim T. , Taha Ahmad J. , Elhakim Abdullah A. , Akili Majed
Published: June 2024

Background Chronic rhinosinusitis (CRS) is a condition that affects 5–12% of the general population. Endoscopic sinus surgery (ESS) is the preferred treatment because of its few adverse effects and highest success rates. The most common post-operative consequences include synechia, nasal blockage, and disease recurrence. Spray cryotherapy is a novel therapeutic approach with promising outcomes for the treatment of upper airway disorders. This review aimed to investigate the effects of spray cryotherapy (SCT) following ESS in patients with chronic rhinosinusitis. Methods Six electronic databases were searched for randomized clinical trials (RCTs). The selected trials were evaluated for methodological quality, and data were extracted by two independent reviewers. The Cochrane risk-of-bias tool was used to assess the quality of evidence. Results Three RCTs with 85 patients were included in the final analysis. SCT was related to -16 and -77 reductions in Lund-McKay and SNOT-22 scores after 36 weeks of follow-up, in contrast to a placebo, which showed -10.4, -65. Regarding the side effects of SCT, no adverse effects were reported, and visual assessments showed no pain, visual field loss, or any other ocular complications. Conclusions SCT is a new treatment modality after endoscopic sinus surgery that shows an effective post-operative management strategy with better post-operative scales (Lund-McKay, SNOT-22, POSE, and Lund-Kennedy) and less edema, obstruction, crusting, and inflammation with minimal or no side effects. However, further research with longer follow-ups, a larger sample size, and subjective assessment is needed to assess any possible long-term side effects.