bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ancillary treatment referrals and visits after breast cancer surgery in a sociodemographically diverse population.
Authors: Chan Vernice Hui Yan , Heller Danielle R. , Berger Elizabeth Rapp , Capozza Scott , Greenup Rachel Adams , Sanft Tara B. 
Published: June 2022

1533 Background: Ancillary therapies by rehabilitative, palliative, and survivorship specialists mitigate breast cancer surgery's physical and emotional effects. Existing data suggest that patients from disadvantaged backgrounds may be less likely to receive such care. We investigated provider referrals and patient visits at a high-volume urban cancer center to identify associated sociodemographic factors and characterize which populations may not be maximally benefiting from ancillary services. Methods: Data was culled from electronic health records of surgically-treated breast cancer patients at Yale-New Haven Health System between 2010-2017. Post-operative provider referrals to Physical/Occupational Therapy, Palliative Medicine, and Survivorship Program were evaluated for associations with demographic and disease variables in univariable and multivariable logistic regression analyses. Patient utilization of referrals, defined as attending at least one consultation, were analysed similarly. Results: Among 5,496 patients identified, 2,288 (41.6%) were referred for ancillary treatments and 1,572 (28.6%) attended at least one consultation. Provider referrals were highest among patients of Hispanic and Black ancestry (57.5% and 54.9%, respectively), no health insurance (57.6%), lowest percentage high school degree for zip code (50.5%), and lowest median income for zip code (50.7%). These associations remained significant in multivariable analysis [all p<0.050]. In contrast, referral utilization was greatest among patients with private insurance (70.7%), highest percentage high school degree (72.8%), and highest median household income (72.2%), in addition to Hispanic ethnicity (73.5%). In multivariable analysis, highest median household income (OR 1.45, p = 0.019) and Hispanic ethnicity (OR 1.50, p = 0.048) remained associated. Conclusions: In a large urban health system serving a diverse population, traditional markers of poor healthcare access were positively associated with provider referral for ancillary services after breast cancer surgery. However, referral did not translate to utilization, suggesting that access remains a critical barrier to therapies that target post-operative morbidity and elevate quality of life.[Table: see text]
Impact of cancer diagnosis, stage, and systemic therapies on immunogenicity after COVID-19 vaccination in patients with cancer: A systematic review and meta-analysis.
Authors: Nader Marta Guilherme , Spilleboudt Chloe , Martins-Branco Diogo , Tecic Vuger Ana , Debien Veronique , Ameye Lieveke , Brandão Mariana , Punie Kevin , Loizidou Angela , Willard-Gallo Karen , Awada Ahmad , Piccart-Gebhart Martine J. , de Azambuja Evandro 
Published: June 2022

1537 Background: Patients (pts) with cancer are at increased risk of severe COVID-19. Both underlying malignancy and anti-cancer treatments influence the immune system, potentially impacting the level of vaccine protection achieved. Methods: A systematic literature search of PubMed, Embase, CENTRAL and conference proceedings (ASCO annual meetings and ESMO congress) up to 28/09/21, was conducted to identify studies reporting anti-SARS-CoV-2 spike protein immunoglobulin G seroconversion rates (SR) at any time point after complete COVID-19 immunization (mRNA- or adenoviral-based vaccines) in cancer pts. Complete immunization was defined as 1 dose of JNJ-78436735 vaccine or 2 doses of BNT162b2, mRNA-1273 or ChAdOx1 nCoV-19 vaccines. Subgroup analyses were performed to examine the impact of cancer diagnosis, disease stage, and anticancer therapies on the SR. Overall effects were pooled using random-effects models and reported as pooled SR with 95% confidence intervals (CI). Results: Of 1,548 identified records, 64 studies were included in this analysis reporting data from 10,511 subjects. The Table shows the SR in the overall population and specific subgroups. In pts with solid malignancies (SM), disease stage and primary site did not significantly impact the SR. In pts with hematologic malignancies (HM), SR were significantly lower in pts with chronic lymphocytic leukemia (CLL) and non-Hodgkin lymphoma (NHL) compared to acute lymphoblastic leukemia (ALL), Hodgkin lymphoma (HL), and multiple myeloma (MM). Concerning the impact of cancer therapies on SR, pts with SM undergoing chemotherapy had numerically lower SR (N = 1,234, SR 87%, CI 81-92) compared to those treated with immune checkpoint inhibitors (N = 574, SR 94%, CI 88-97) or endocrine therapy (N = 326, SR 94%, CI 86-97) with or without another targeted therapy. Pts with HM treated with anti-CD20 therapy (within the last 12 months: N = 360, SR 7%, CI 2-20; or more than 12m: N = 175, SR 59%, CI 35-80), immune-modulating agents (BTK or BCL2 inhibitors) (N = 462, SR 47%, CI 32-64%) or other immunotherapies (anti-CD19/CART or anti-CD38) (N = 293, SR 37%, CI 23-53) had lower SR compared to pts treated with autologous (N = 353, SR 77%, CI 67-85) or allogenic stem cell transplantation (N = 509, SR 77%, CI 68-84). Conclusions: SR varies between cancer types and anticancer therapies with some cancer pts having low protection against COVID-19 even after complete vaccination. [Table: see text]
Characteristics associated with functional resilience versus functional decline among adult patients with advanced non–small cell lung cancer.
Authors: Tang Joy , Janse Sarah A. , Carbone David Paul , Shields Peter G. , Wong Melisa L. , Arrato Nicole A , Andersen Barbara L. , Presley Carolyn J 
Published: June 2022

1538 Background: As more treatment options become available for advanced non-small cell lung cancer (NSCLC), oncologists still have difficulty predicting functional resiliency versus functional disability throughout treatment. Functional resiliency refers to the ability to recover baseline functional status in the face of an intervening health care event. This study aims to identify characteristics associated with resilience among adults with advanced NSCLC. Methods: In a prospective cohort of participants with newly diagnosed stage IV NSCLC, resilience was evaluated based on three functional disability items in the EQ-5D-5L (modified: mEQ-5D-5L) through 12 months of follow-up compared to baseline scores. This included patients treated with chemotherapy, immunotherapy, targeted agents and no treatment. Participants were classified into four groups: functional decline, maintenance, resilient, or variable. Resilience was determined based on improvement in disability scores, with a 1-point increase in functional status score representing a 0.5 standard deviation change on the mEQ-5D-5L. Patient characteristics included demographics, comorbidities, ECOG performance status, presence of brain or bone metastases, mood (GAD-7, PHQ-9), and lung cancer-specific symptoms (QLQ-LC13). Treatment toxicity and toxicity grades were also recorded. Differences between groups were determined through Fisher’s exact test or ANOVA. Results: Among 207 participants, 87 (42.0%) maintained functional status, 78 (37.7%) experienced functional decline, 22 (10.6%) were classified as resilient and 20 (9.7%) were variable. Characteristics associated with higher resilience (p < 0.1) included being employed (p = 0.02) and living in a metro setting (p = 0.10). Characteristics not associated with resilience included age, education level, smoking status, presence of brain metastases, ECOG performance status, or psychological symptoms. Approximately half the participants (n = 105, 50.7%) who received treatment experienced toxicities. One third (33.8%) experienced ≥ grade 3 toxicities. There was no significant association between toxicity grade and resilience grouping. Conclusions: Characteristics associated with functional resilience included employment status and living setting. At least half of adults with advanced NSCLC experience treatment-related toxicities. It is important to determine characteristics of resilience to better understand which patients will tolerate cancer treatments.
Enabling community-led integrated women health care models for women cancers screening and early detection through EMPOWER (Enabling and Motivating Partnerships Owned by Women who Engage and Reclaim their lives) project.
Authors: Nyongo Dorothy Ogada , Wambua Jacqueline 
Published: June 2022

1541 Background: With the growing burden of Women cancers in East Africa, integrating cancer screening and prevention to optimize horizontal care delivery models is a paramount approach to strengthening women-centered and cost-effective primary healthcare. EMPOWER is a unique partnership with the government of Kenya, County referral hospitals, County First Ladies Association, International Cancer Institute, Patient organizations and Roche Kenya to demonstrate integrated cancer prevention and treatment within primary healthcare shared across the Kenyan Health system. Methods: EMPOWER clinics were launched with over 300 community health workers (including women living with disabilities) and HCPs were identified and trained to provide facility and community-based screening and early detection for breast cancer, cervical cancer, hypertension and diabetes through an integrated health systems strengthening approach. Mentorship was provided to HCPs through routinely held joint screenings and clinics, weekly Tumor Boards, Teleclinics, Telemedicine and Digital Pathology platforms. In addition, training support was provided through virtual preceptorships, skills-training workshops, hub-and-spoke oncological services provision and robust patient navigation. Results: 14 EMPOWER clinics have been launched across Kenya to increase community awareness of breast, cervical, and NCDs, strengthen capacity to deliver integrated Women cancer management services in County health clinics. In Kenya out of 25,502 people screened, 13,192 were screened for breast cancer with 97 abnormal findings identified; 10,349 screened for cervical cancer with 200 abnormal cervical screenings identified and 1,664 screened for prostate cancer with 32 abnormal findings. In addition, an integrated approach in Non Communicable Disease (NCD) care, diabetes and hypertension screening; 4,298 screened for diabetes and 6,116 screened for hypertension. All those diagnosed with cancers were linked to existing cancer care delivery systems and continuous support offered through the strengthened health care systems. Prostate cancer was added as more men turned up for screening events. Conclusions: This model is replicable and scalable across LMIC and recently the model inspired health providers’ from Tanzania and Nigeria to adopt the same for women’s cancers. EMPOWER has demonstrated a scalable care model in Kenya contributing to investments in pathology training and clinical treatment to improve challenges in referrals and updating guidelines to enable multi-disease tissue testing and handling and treatment with Standard of Care.
Improving first-in-human and window-of-opportunity informed consent forms through participant feedback.
Authors: Avinger Anna , Sibold Hannah Claire , Campbell Gavin Paul , Abernethy Eli Rowe , Bourgeois John , McClary Tekiah , Blee Shannon M. , Dixon Margie D. , Harvey R. Donald , Pentz Rebecca D. 
Published: June 2022

1562 Background: Although patient advocates have created templates for standard consent forms, assessing patient preferences for First in Human (FIH) and Window of Opportunity (WO) trials consents is important given their unique risks. FIH trials are the first time a drug is tested in humans. In WO trials, treatment naïve patients receive a therapeutic agent in the window of time between diagnosis and standard of care (SOC) surgery. Our goal was to determine patient-preferred presentation of important information in FIH and WO consent forms. Methods: The study consisted of two phases: (1) analysis of consents for FIH and WO oncology trials open at a cancer center between 2019 and 2022; (2) interview patients who had reviewed consents for FIH or WO trials during the consent process. FIH consents were analyzed for the location(s) of information stating that the study drug has not been tested in humans (FIH info). The WO consents were analyzed for the location(s) of information stating the risk that trial may delay SOC surgery (WO info). Participants were asked about their preferred placement of the information in their own trial’s consent form and whether the consent was clear. Interviews were audio-recorded and double coded. Consent form analysis was compared to patients’ preferences. Results: 25 consents [20 FIH; 5 WO] were analyzed. 19/20 FIH consent forms included FIH info, and 4/5 WO consent forms included WO info. 42 patients were approached [19 FIH; 23 WO]; 34 [17 FIH; 17 WO] participated. 12/17 (71%) WO participants thought that the trial explanation in the consent form was clear. Conversely, only 9/17 (53%) FIH participants found it clear. Conclusions: Patients preferred that the important FIH and WO information be placed early in the consent, though exactly where varied. 82% of FIH participants wanted FIH information in the purpose, while only 19% of WO participants clearly preferred that WO information be in the purpose, and 41% preferred WO information to remain in the risks section. Using consent templates that reflect patient preferences accurately is essential for ethical informed consent; however, a one-size fits all approach may not accurately capture patient preferences, so multiple templates may be necessary. [Table: see text]
Phase 1 trial of TIM-3 inhibitor cobolimab monotherapy and in combination with PD-1 inhibitors nivolumab or dostarlimab (AMBER).
Authors: Falchook Gerald Steven , Ribas Antoni , Davar Diwakar , Eroglu Zeynep , Wang Judy S. , Luke Jason J. , Hamilton Erika P. , Di Pace Brian , Wang Tianli , Ghosh Srimoyee , Dhar Arindam , Borgovan Theo , Waszak Angela , LoRusso Patricia 
Published: June 2022

2504 Background: TIM-3 expressed on tumor-infiltrating T cells is associated with T-cell suppression. AMBER (NCT02817633) is evaluating cobolimab (TSR-022/GSK4069889) monotherapy and with PD-1 inhibitors in advanced solid tumors. Methods: Multi-center, open-label study conducted with the following escalation arm (Parts 1A–C primary analysis reported here): (1A) cobolimab (IV Q2W) monotherapy at 7 doses (6 weight-based [0.03–10 mg/kg] and 1 flat [1200 mg] dose); (1B) cobolimab (1 mg/kg) + nivolumab (3 mg/kg IV Q2W); and (1C) cobolimab (100, 300, or 900 mg) + dostarlimab (500 mg IV Q3W). Primary endpoints were safety, tolerability, and recommended phase 2 dose (RP2D, monotherapy and combination). Results: 104 patients (pts) were included: 1A (n=46), 1B (n=7), or 1C (n=55); 4 pts from 1A crossed over to 1C (included in 1A and 1C safety and efficacy analyses). Most common cancers were non-small cell lung cancer (NSCLC) and melanoma (1A), NSCLC (1B), and NSCLC, skin, and peritoneal mesothelioma (1C). In 1A, 30.4% had ≥5 lines (L) of prior therapy; 42.9% had 3L in 1B; 33.3% had 2L in 1C. Treatment-related treatment-emergent adverse events (TR-TEAE) occurred in 67.4% (1A), 85.7% (1B), and 67.3% (1C); most commonly in 1A (n≥4) fatigue (13.0%) and nausea (8.7%); 1B (n≥3) diarrhea (57.1%) and nausea and vomiting (42.9% each); and 1C (n≥8) fatigue (20.0%) and rash (14.5%). Grade (Gr)≥3 TR-TEAEs occurred in 4.3% (1A), 28.6% (1B), and 14.5% (1C). There were no Gr5 TR-TEAEs or TR-TEAEs leading to dose delay. Serious TR-TEAEs occurred in 2.2% (1A), 0% (1B), and 12.7% (1C). TR-TEAEs led to discontinuation in 2.2% (1A), 28.6% (1B), and 9.0% (1C). Dose limiting toxicities (DLTs) occurred in 3.0% (1/33) in 1A (Gr3 lipase increased [10 mg/kg]); 40.0% (2/5) in 1B (Gr3 diarrhea and ALT and AST elevation); and 0% in 1C. Cobolimab serum exposure increased in a dose proportional manner at the therapeutic dose range. Preliminary mean terminal phase t1/2 ranged from 2.5–5.8 days for 0.03–0.3 mg/kg and 6.9–10.2 days for 1–10 mg/kg doses (1A), 6.9 days for 1B, and 9.5–12.3 days for 1C. Conclusions: Cobolimab + dostarlimab was well tolerated and showed preliminary anti-tumor activity, warranting further investigation of the RP2D + docetaxel in a randomized, phase 2 study. Funding: GSK (213348). Clinical trial information: NCT02817633. [Table: see text]
A phase 1 trial of the bifunctional EGFR/TGFβ fusion protein BCA101 alone and in combination with pembrolizumab in patients with advanced solid tumors.
Authors: Bedard Philippe L. , Hernando-Calvo Alberto , Carvajal Richard D. , Morris Van K. , Paik Paul K. , Zandberg Dan Paul , Kaczmar John M. , Niculescu Liviu , Bohr David , Reiners Ralf , Gharakhani Elham , Salazar Rachel , Bilic Sanela , Hanna Glenn J. 
Published: June 2022

2513 Background: BCA101 is a first-in-class bifunctional fusion protein consisting of an anti-EGFR monoclonal antibody (mAb) and TGFβ receptor 2 extracellular domain (TGFβRII-ECD). Herein, we report the safety, pharmacokinetic (PK), pharmacodynamic (PD), and preliminary efficacy data of BCA101 as monotherapy and in combination with pembrolizumab among patients (pts) with advanced solid tumors refractory to standard therapies. Methods: Pts received BCA101 as a single agent (SA) or in combination with pembrolizumab at escalating doses in a parallel 3+3 design starting at 64 mg intravenously (IV) weekly (qw); and at 240 mg IV qw with pembrolizumab 200 mg IV q3w. Primary endpoint: safety and tolerability (CTCAE v5.0); dose limiting toxicity (DLT) period: 21 days. Secondary endpoints: overall response rate (ORR), PK/PD profile, progression-free survival (PFS), and changes in plasma and intra-tumoral TGFβ signaling assessed by SMAD2 phosphorylation. Results: As of 08-Feb-2022, 60 pts have received BCA101 (part A). Forty-five pts (colorectal, n=14; pancreatic, n=7; head and neck squamous cell carcinoma [HNSCC], n=6) received SA BCA101 at doses up to 1500 mg IV weekly. Fifteen subjects (SCC of the anal canal [SCAC], n=8; HNSCC, n=7) received BCA101 doses ranging from 240 to 1500 mg IV qw in combination with pembrolizumab. Maximum tolerated dose has not been reached. Common adverse events (AEs) attributed to BCA101 include rash (70%), fatigue (23%), pruritis and epistaxis (17% each); all grade (G)2 or less. One DLT was observed at the 1250 mg SA dose (G3 anemia, hematuria). No drug-related G4 AEs or deaths were observed. At data cutoff, best response in the SA arm was stable disease (SD) in 15/39 (39%) evaluable pts. In combination, partial response (PR) was observed in 3/11 (27%) evaluable pts (2 in SCAC, 1 in HNSCC) and a disease control rate (DCR) of 9/11 (82%). Two of 3 responders have been on study >4 months; including 1 confirmed PR in a HNSCC pt refractory to anti-PD-1 therapy and cetuximab. Saturation of the EGFR target was observed at BCA101 doses ≥750 mg. Dose proportional increase in Cmax and AUC were observed with doses of BCA101 750-1500 mg. Prolonged neutralization of plasma TGFβ1 was achieved at all doses ≥500 mg. Among paired tumor biopsies (n=23), pSMAD2 reduction up to 62% was observed at doses ≥500 mg. Conclusions: BCA101 is well tolerated and clinically active as a SA and in combination with PD-1 blockade with a predictable PK/PD profile. A recommended dose of 1500 mg both as SA and in combination has advanced to the part B expansion phase for pts with HNSCC, SCAC, and cutaneous SCC. Clinical trial information: NCT04429542.
Predictors of severe CRS in longitudinal CAR T-cell clinical trial data.
Authors: Strait Caleb , Aptekar Jacob , Kattan Michael W. , Agarwal Vibhu 
Published: June 2022

2540 Background: Cytokine release syndrome (CRS) is a life-threatening toxicity of chimeric antigen receptor (CAR) T-cell therapy and there is a limited understanding of its risk factors. Known markers of severe CRS lack specificity or require central lab facilities, making them unsuitable for safety surveillance during trials. Using data from anti-CD19 CAR-T trials from the Medidata Enterprise Data Store (MEDS) we analyzed laboratory tests with repeated measurements to identify differences in trends that persist across a variety of study designs, sponsors and indications. Our aim was to capture the dynamic response to lymphodepletion (LD) and CAR-T infusion events in the time course values of laboratory markers and compare these in the severe CRS (grade 3 and higher) and non severe CRS groups. Methods: Subjects in the anti-CD19 CAR-T trials obtained from MEDS had relapsed or refractory disease in one of the following: B Acute Lymphoblastic Leukemia (B-ALL), Mantle Cell Lymphoma (MCL), Non-Hodgkin Lymphoma (NHL) and Diffuse Large B-cell Lymphoma (DLBCL). Laboratory markers with repeated measurements across all studies were included in the analysis. Response to LD, CAR-T infusion and the onset of hematologic recovery was modeled with piecewise linear splines with knots at the boundaries of the pre LD (-18d to LD), the LD - infusion and post infusion (1d to 6d and 6d to 18d) intervals using linear mixed effects regression. Results: The dataset consisted of 542 patients: 24.1% B-ALL, 44.4% NHL, 16.8% MCL, 14.6% DLBCL; mean age 54.8 (SE = 0.021) years, 67.7% males. 27.3% had CRS 3+ with a median time-to-event of 4.5 days. Average rates of change (units per day) for the severe CRS subjects in the pre LD, LD-infusion and post infusion intervals relative to the rest are shown (table). None of the markers had a significant relative rate of change prior to LD. The average change in Albumin, Platelets and Hematocrit was consistently lower in severe CRS patients. Conclusions: Longitudinal laboratory marker data may be used to derive predictors of severe CRS in patients undergoing anti-CD19 CAR-T therapy. While some of the laboratory markers discussed above corroborate earlier findings, modeling the pre and post infusion kinetics can yield novel markers with improved precision in severe CRS prediction and better patient safety. [Table: see text]