bluuebunny/crossref_metadata_2025_split huggingface dataset:
“More than conquerors”: A qualitative analysis of war metaphors for patients with cancer.
Authors: Bodd Monica Himaani , Daniels Nikki C. , Amonoo Hermioni L. , Tate Tyler P. , Herring Kris W. , LeBlanc Thomas William 
Published: June 2022

e24134 Background: Limited research suggests that war metaphors may be harmful for patients with cancer. For instance, it has been claimed that the use of war metaphors is associated with increased anxiety and depression, as well as poor coping for patients with cancer. However, little is known about how patients use and perceive these metaphors. Metaphors, which are intrinsic to the human conceptual system, help articulate patients’ experiences and needs. In this study, we explored patient narratives of illness metaphors in cancer, focusing particularly on war metaphors. Methods: Fifteen patients diagnosed with various stages of lung, colorectal or breast cancer completed semi-structured qualitative interviews about their use of metaphors after their cancer diagnoses. Interviews explored war metaphors in the context of treatment decisions, aggressiveness of care, and quality of life. Patients were also provided with a curated list of metaphors and asked about their use and experience thereof. Transcribed interviews were organized and analyzed by descriptive content analysis using NVivo software. Results: The most used metaphor categories were: 1) nature (e.g., journey, season); 2) militaristic (e.g., battle, victory, fight); and 3) uncertainty (e.g., mystery, puzzle). War metaphors were frequently referenced in patients’ support communities rather than in hospital or clinician encounters. Next, all patients with non-metastatic disease (n = 7) used war metaphors to describe their illness experience. Among all patients who used metaphorical language to describe their experience (n = 14), the only ones who did not use war metaphors (n = 2) had metastatic disease; these patients found war metaphors to be unhelpful due to their sense of having no control over the outcome. Lastly, participants reported that war metaphors served the following purposes in their illness experience with cancer: 1) promoted perseverance in the face of adversity, 2) expressed optimism, and 3) allowed them to relate cancer to previous life challenges. Conclusions: The hypothesis that war metaphors are invariably counterproductive for patients appears to be misguided. Metaphors of fighting, victory and battle worked both to empower and harm patients in this study, depending on the individual patient and their prognosis. While more prospective studies with robust sample sizes are needed to elucidate the role of metaphors in the lived experience of patients with cancer, our patients suggest the need to individualize, acknowledge and explore these metaphors for cancer populations.
Change in breast cancer risk perception related to perceived COVID-19 risk: A WISDOM sub-population analysis.
Authors: Huang Tina Qing , Baxter-King Ryan , Naeim Arash , Rudkin Aaron , Vavreck Lynn , Sepucha Karen , Sabacan Leah P. , Esserman Laura , Wenger Neil ,   WISDOM Study and Athena Investigators
Published: June 2022

e24135 Background: Obstacles to access to care due to the perceptions of the risk posed by COVID-19 have led to unprecedented disruptions in cancer care. Yet, little is understood about whether perceived COVID-19 risk influences perceptions of cancer risk. We examined how COVID-19 risk perception was associated with perceptions of breast cancer risk over one year of the pandemic among women enrolled in the WISDOM study, a PCORI-funded pragmatic trial testing risk-based cancer screening that began before the pandemic. Methods: We conducted four longitudinal surveys among the 13,002 women enrolled in the WISDOM study from May - December 2020. Responses from 8,285 women are eligible for inclusion in this analysis leading to a total sample size of 16,859 survey responses. Surveys were conducted online and asked women’s perceived lifetime chance of developing breast cancer (0-100%). COVID-19 risk perception was reported on a 5-point scale from Very Low to Very High. We computed the difference between breast cancer risk perception at each COVID-19 survey to pre-COVID breast cancer risk perception, measured as a secondary aim of the WISDOM study, and compared that to COVID-19 risk perception at each time point. Results: Across the four survey waves, most women perceived low COVID risk: 29% very low, 42% moderately low, 23% neither high nor low and 6% high or very high. Overall, breast cancer risk perception declined for those with very low COVID-19 risk perception and rose for women in the highest levels of COVID-19 risk perception. However, changes in breast cancer risk perception associated with COVID risk perception were small. For example, in survey wave 4, breast cancer risk change was -2.4% very low, -1.4% low, 2.5% not high or low and 3.1% high or very high. (Table). Conclusions: Among women participating in a pragmatic trial testing risk-based cancer screening, COVID risk perception had a small relationship with change in breast cancer risk perception. Change in breast cancer risk perception paralleled COVID-19 risk perception. This calls for exploration of the underpinnings of these risk changes and may have implications for changes in cancer screening behavior related to COVID-19.[Table: see text]
Depression trajectories among women undergoing chemotherapy.
Authors: Suskin Johanna A. , Paul Steven M , Stuckey Ashley , Miaskowski Christine , Dunn Laura B. 
Published: June 2022

e24144 Background: Depressive symptoms are common among women undergoing chemotherapy (CTX) for breast or gynecological cancer. Many studies have examined the prevalence of depressive symptoms (usually at the beginning or end of CTX). However, given that CTX unfolds over a number of cycles, there is a need to better understand patterns of change in depressive symptoms over the course of treatment, and to identify factors that may predispose individuals to worse symptom trajectories. The purpose of this study, among women who underwent CTX for breast or gynecological cancer, was to evaluate for interindividual differences in depressive symptoms over the course of two cycles of CTX, and to identify characteristics associated with both initial levels (i.e., at the beginning of the study) and trajectories of depressive symptoms. Methods: Patients undergoing CTX for breast (n = 530) or gynecologic (n = 233) cancer completed the Center for Epidemiological Studies-Depression (CES-D) questionnaire six times over two treatment cycles. Patient-reported measures were used to assess demographic, clinical, symptom, stress, and coping characteristics at enrollment. Using hierarchical linear modeling (HLM), we evaluated characteristics associated with initial levels and trajectories of depressive symptoms. Results: One demographic (marital status) and two clinical (number of comorbidities, functional status) characteristics predicted interindividual differences in initial levels of depressive symptoms. One demographic (education) and one clinical (MAX-2 score, a CTX toxicity metric) characteristic were associated with interindividual differences in depressive symptom trajectories. Several symptom characteristics predicted interindividual differences in initial levels (i.e., morning fatigue), trajectories (i.e., initial level of depression), or both initial levels and trajectories (i.e., sleep disturbance, attentional function) of depressive symptoms. Two stress-related variables (i.e., perceived stress, cancer-related distress) predicted interindividual differences in both initial levels and trajectories of depressive symptoms. Several coping variables predicted interindividual differences in initial levels (i.e., behavioral disengagement), trajectories (i.e., venting), or both initial levels and trajectories (i.e., self-blame) of depressive symptoms. Conclusions: The range of demographic, clinical, symptom, stress and coping characteristics associated with interindividual differences in depressive symptoms underscores the importance of evaluating risk and protective factors. These factors may serve as useful markers for both screening and intervention to address depressive symptoms during CTX.
Phase 2 study to evaluate palbociclib in combination with irinotecan and temozolomide in pediatric patients with recurrent or refractory Ewing sarcoma.
Authors: Laetsch Theodore Willis , Janeway Katherine A. , Hawkins Douglas S. , Juszczak-Kosela Katarzyna , Muscal Jodi Ann , Collier Anderson B. 
Published: June 2022

TPS11583 Background: Palbociclib (PD-0332991) is a highly selective, reversible, small molecule inhibitor of cyclin-dependent kinases (CDK) 4 and 6, administered orally. Functional dependence of Ewing Sarcoma (EWS) cell lines and tumor xenografts on Cyclin D1/CDK4 via genetic knockdown has shown both Cyclin D1 and CDK4 as critical dependencies for EWS cell line proliferation. The phase 1 portion of the study established the recommended Phase 2 dose (RP2D) with two chemotherapy backbones in children with solid tumors. The Phase 2 portion of the study now enrolls patients with EWS. The primary objective of this portion of the study is to determine whether the addition of palbociclib to irinotecan (IRN) and temozolomide (TMZ) will prolong event-free survival (EFS) of pediatric and young adult patients with recurrent or refractory EWS. Methods: Patients with recurrent or refractory EWS are randomized 2:1 to receive either palbociclib in combination with IRN and TMZ or IRN and TMZ alone. Randomization is stratified by type and time of disease recurrence (primary refractory or 1st recurrence <2 years vs. 1st recurrence ≥2 years or 2nd or greater recurrence). The primary efficacy endpoint is EFS per investigator assessment. Secondary efficacy endpoints include objective response, progression-free survival and overall survival. An interim futility analysis will be conducted to allow for early stopping of the study due to futility/no signal of activity based on the primary endpoint of EFS. Safety and planned interim efficacy data will be assessed by an Independent Data Monitoring Committee (DMC). Key eligibility criteria include: recurrent or refractory EWS with evaluable disease, no known bone marrow metastases, histopathological confirmation of EWSR1-ETS or FUS-ETS rearrangement or availability of formalin fixed paraffin embedded (FFPE) tumor tissue sample for central testing, age ≥2 and <21 years at the time of study entry. Treatment intervention: Patients randomized to palbociclib with IRN and TMZ treatment arm will receive palbociclib at the RP2D of 75 mg/m2 orally (either as a capsule or oral solution) once daily on Days 1-14 of each 21-day treatment cycle. TMZ will be administered orally once daily at 100 mg/m2 on Days 1-5 (intravenously (IV) if patient cannot swallow the TMZ capsule). IRN will be administered IV at 50 mg/m2 on Days 1-5. Patients randomized to the chemotherapy only treatment arm will receive IRN and TMZ at the same doses on Days 1-5 of the 21-day treatment cycle. Treatment will continue until disease progression, patient and/or legal guardian refusal, unacceptable toxicity , or up to 24 months of treatment, whichever occurs first. The Phase 2 enrolment has been initiated and 1/75 patients has been enrolled as of Jan 2022. Clinical trial information: NCT03709680.
A phase II study, with a safety lead-in, to evaluate ATX-101, a peptide drug targeting PCNA, in advanced dedifferentiated liposarcoma and leiomyosarcoma.
Authors: Bose Sminu , Ingham Matthew , Singh-Kandah Shahnaz V. , Magana Wendy , Schwartz Gary K. 
Published: June 2022

TPS11587 Background: Soft tissue sarcoma (STS) is a heterogeneous malignancy of mesenchymal origin; leiomyosarcoma (LMS) and liposarcoma (LPS), two of the most common adult STS, are treated with first-line chemotherapy with objective response rates (ORRs) of 15-20%. There is an urgent need for novel therapeutics. ATX-101 is a small peptide comprised of a novel human AlkB homolog 2 proliferating cell nuclear antigen (PCNA) interacting motif termed APIM coupled to cellular and nuclear delivery domains. Via APIM, PCNA interacts with many cellular proteins important in the cellular stress and DNA damage responses, as well as intracellular signaling, apoptosis, metabolism, and anti-tumor immunity. In preclinical studies, ATX-101 demonstrated single-agent activity and potentiated other cytotoxic and targeted agents across multiple cancer models in vitro and in vivo, including LMS and LPS. In a phase I safety and pharmacokinetic study in solid tumors, ATX-101 was well tolerated and demonstrated prolonged disease stabilization in patients (pts) with heavily pretreated malignancies. This study will evaluate preliminary efficacy and further establish the safety profile of ATX-101 in advanced LMS and LPS. Methods: This is a single-arm, open-label, Simon 2-stage, phase II clinical trial of ATX-101 in pts with advanced LMS and LPS. Eligible pts have ECOG PS ≤2, progression on ≥1 prior line of therapy and disease measurable by RECIST v1.1 and amenable to image-guided biopsy. Pts receive ATX-101 60 mg/m2 IV weekly in continuous 21-day cycles. The 1° endpoint is progression free rate at 12 weeks (PFR12). A Simon 2-stage design is used to evaluate for improvement in PFR12 of ≤ 30% (null hypothesis) versus ≥ 55% (alternative hypothesis). The design calls for 34 pts with a safety lead-in among the first 10 pts enrolled. If 15/34 meet the PFR12 endpoint, the treatment is promising. This design yields 85% power and 1-sided type I error of 5%. 2° endpoints include progression free survival, ORR, and safety. 10 pts undergo tumor biopsies pre-treatment and during cycle 2. Tissue is used for correlative analysis interrogating ATX-101’s effects on the immune microenvironment through multiplex immunohistochemistry, DNA damage response through whole exome sequencing/RNAseq to evaluate for alterations in HR pathway component genes, and intracellular signaling pathways by Western blot for AKT/mTOR components. The study opened to accrual 12/2021. Clinical trial information: NCT05116683.
A phase 1b lead-in to a randomized phase 2 trial of lurbinectedin plus doxorubicin in leiomyosarcoma (LMS).
Authors: Cote Gregory Michael , Choy Edwin , Thornton Katherine Anne , Mazzola Emanuele , Bouberhan Sara , Merriam Priscilla , Wagner Andrew J. , Morgan Jeffrey A. , Haddox Candace L. , Oza Jay , Demetri George D. , George Suzanne 
Published: June 2022

TPS11592 Background: Single agent or combination chemotherapy regimens, typically including doxorubicin or gemcitabine, represent standard of care options for first- and second-line therapy in patients (pts) with metastatic LMS. However, response rates (ORR) and progression-free (PFS)/overall survival (OS) remain poor. Lurbinectedin (PharmaMar S.A. and Jazz Pharmaceuticals) uniquely binds DNA, inducing DNA double strand breaks leading to apoptosis and delaying progression through phase S/G2 of the cell cycle. Lurbinectedin is a novel structural analog of trabectedin with improved toxicity profile, potency, and pharmacokinetics. In a prior pilot study, we showed that the combination of lurbinectedin and doxorubicin (L+D) was safe, with early signs of clinical activity, particularly in LMS. Thus, we designed this investigator-initiated/investigator-sponsored phase 1b lead-in to optimize doses of L+D, to be followed by a randomized (1:1) phase 2 study of L+D versus doxorubicin monotherapy in anthracycline-naïve LMS. Methods: Pts age > 18 years with locally advanced or metastatic, unresectable LMS (non-GIST soft-tissue sarcoma histologies allowed in Phase 1b), without prior anthracycline or lurbinectedin/trabectedin, ECOG PS < 3, measurable disease by RECIST 1.1, and normal organ function, are eligible. Phase 1b dosing will include a fixed dose of lurbinectedin and two dose levels of doxorubicin. The Phase 1b lead-in follows a standard 3+3 design where dose escalation will occur if 0/3 or 1/6 patients experience a dose-limiting toxicity (DLT). Tumor assessments are conducted every two cycles. Once the recommended phase 2 dose (RP2D) is confirmed, Phase 2 will be initiated. Fifty pts will be randomized 1:1 including doxorubicin +/- lurbinectedin. Randomization will be stratified by uterine v. non-uterine origin of LMS. Pts progressing on single agent doxorubicin will be allowed to cross over to lurbinectedin monotherapy. The Phase 2 primary endpoint is PFS. Secondary endpoints include disease control rate, ORR, OS, PFS2 (for doxorubicin monotherapy patients who cross to lurbinectedin monotherapy). Archival tumor, germline DNA, and ctDNA will be collected for correlative studies exploring genomic markers of sensitivity/resistance. We will provide respective point estimate along with 90% confidence interval for each of the arms. Log-rank test will be performed to test the difference in survival (both PFS and OS) between groups. Regression analyses of survival data will be based on the Cox proportional hazards model. The first pt in dose-level 1 of the Phase 1b lead-in was enrolled in February 2022. Clinical trial information: NCT05099666.
Screening for high frequency malignant disease (SHIELD).
Authors: NGUYEN HA , Raymond Victoria M. , Vento-Gaudens Erika , Marino Enrique , Lang Kathryn , Eagle Craig 
Published: June 2022

TPS1602 Background: Implementation of asymptomatic cancer screening has yielded positive impacts on global cancer mortality rates. However, significant screening adherence gaps exist. A blood-based multi-cancer screening test with clinically significant performance in cancers where early detection and intervention can save lives, can address adherence gaps, especially by reducing access barriers inherent to current screening options. Effective evaluation of such a test in screen relevant populations requires studies designed to enroll individuals across multiple cancer types, taking into account prevalence rates for the cancers being evaluated, allowing for overlapping screen-eligible populations, and ensuring representation of individuals from diverse ethnicities and geographies. Methods: SHIELD (Screening for High Frequency Malignant Disease; NCT# 05117840) is a prospective, observational, multi-center basket study ongoing in the United States and Europe uniquely designed to recruit individuals across multiple cancer types. The study’s primary objective is to evaluate the performance of a blood-based multi-cancer screening test (GuardantLUNAR-2, Guardant Health, USA) to detect cancer in screen-relevant individuals as compared to the reference standard cancer screening modality. The study will recruit eligible individuals into multiple separate cohorts with specified pathways for cancer screening. Within each cohort, eligible individuals consent to whole blood collection within 90-days of the standard of care screening method. Clinical diagnoses, including the diagnosis of cancer, are made per standard of care. Primary outcomes are sensitivity, specificity, negative predictive value, and positive predictive value of the test as compared to the standard of care screening modality. Secondary outcome is the number of screen-detected cancers, early- (stage I/II) and late-stage (stage III/IV), per 1000 screened individuals. Follow-up continues for 24 months with outcomes collected at one and two-years to investigate the possibility of incidental non-screen relevant cancer cases and interval screen-relevant cancer cases that had not reached clinical threshold for detection at initial screening. Additional cancer specific follow-up is designed per cohort. The first cohort to enroll screen-eligible individuals, cohort A, is focused on those who meet guideline criteria for lung cancer screening with low dose CT. Additional cancer-risk cohorts will begin enrolling as the study expands and are designated cohort B, C, etc. Cohort A: Eligibility criteria are aligned with lung cancer screening guidelines – age 50-80 years with > 20 pack-year smoking history who are current smokers or have quit < 15 years prior, without a cancer history, preinvasive lung lesions, or current treatment for pneumonia. Cohort A enrollment, targeting 9,000 subjects over 24 months at up to 120 global sites, began in January 2022. Clinical trial information: NCT05117840.
A phase Ia/Ib study of intrathecal deferoxamine in patients with leptomeningeal metastases.
Authors: Wilcox Jessica , Modelevsky Lisa R. , Thomas Tiffany , Cremers Serge , Young Robert J. , Reiner Anne S. , Panageas Katherine , Yu Helena Alexandra , Boire Adrienne Ann 
Published: June 2022

TPS2074 Background: Leptomeningeal metastases (LM) represent an aggressive form of advanced cancer with few durable therapeutic options. One of the principal barriers in treating LM is the paucity of knowledge on cancer cell survival and proliferation within the nutrient-sparse cerebrospinal fluid (CSF). Single-cell RNA sequencing of patient-derived CSF has identified that cancer cells in the spinal fluid employ the single iron-binding transporter and receptor system, lipocalin-2/SLC22A17, to gather sparse iron to sustain their metabolic needs. This phenotype is recapitulated in preclinical mouse models of LM. Depletion of CSF iron via intracisternal administration of deferoxamine, a parenteral iron chelator, dramatically reduced LM growth and significantly prolonged survival in preclinical models. Exploiting LM iron dependency using intrathecal deferoxamine (IT-DFO) represents a novel therapeutic approach for patients with LM. Methods: This is a prospective, open-label, single center phase Ia dose escalation study of IT-DFO in patients with LM from any solid tumor malignancy to determine the maximum tolerated dose (MTD) and recommended phase II dose (RP2D), followed by a phase Ib dose expansion of IT-DFO at the RP2D in patients with LM from non-small-cell lung cancer (NSCLC). Eligibility criteria include newly diagnosed or recurrent LM identified by magnetic resonance imaging (MRI), positive CSF cytology, and/or elevated CSF circulating tumor cells (CTCs), age ≥ 18 years, Karnofsky Performance Status ≥ 60, and life expectancy ≥ 8 weeks. All patients will receive IT-DFO in 28-day cycles at a frequency of twice weekly (cycle 1), once weekly (cycle 2), and once every two weeks (cycle 3+). Patients will be monitored for LM progression by neurological examination, neuraxial MRI, and CSF cytology as per modified Response Assessment in Neuro-Oncology LM criteria. Phase Ia will involve a modified accelerated titration over 9 dosing cohorts (IT-DFO dose range 10mg to 495mg) with monitoring for dose-limiting toxicities until the MTD is reached. Phase Ib will further explore the safety of IT-DFO at the RP2D in 20 patients with NSCLC LM. Secondary objectives include the determination of pharmacokinetic and pharmacodynamic properties of IT-DFO and its metabolite, ferrioxamine, in the CSF and serum (phase Ia/Ib), and efficacy outcomes (phase Ib) including LM-objective response rate, LM-clinical benefit rate, LM-duration of response, LM-progression-free survival, and overall survival. Exploratory analyses will prospectively correlate CSF CTC enumeration with treatment response and characterize the impact of IT-DFO on cancer cell metabolism, resistance pathways, and the CSF immune microenvironment. Clinical trial information: NCT05184816.