bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bevacizumab combined with platinum-based chemotherapy in patients with primary or relapsed ovarian cancer: Meta-analysis and literature review.
Authors: Abodunrin Faith , Tauseef Abubakar , Silberstein Peter T. 
Published: June 2022

5582 Background: Epithelial ovarian cancer has the highest mortality rates among all gynecological malignancies and is the fifth leading cause of cancer-related deaths in females. Previously, the treatment of ovarian cancers included cytoreductive surgery in combination with platinum-based chemotherapy. While this treatment regimen initially resulted in a good response, most of the patients subsequently relapsed. Given the role of Vascular Endothelial Growth factor (VEGF) and angiogenesis in the progression of ovarian cancer, VEGF inhibitors such as Bevacizumab were considered in the treatment of advanced or relapsed ovarian cancer patients. We conducted a meta-analysis to compare the efficacy of Bevacizumab with platinum-based chemotherapy to platinum-based chemotherapy. Methods: A thorough systematic literature review identified five eligible studies reporting the efficacy of bevacizumab with platinum-based chemotherapy in the treatment of advanced or recurrent Ovarian cancer as compared to control group receiving platinum-based chemotherapy alone. These studies were randomized Phase III clinical trials, one of which was recently published in 2021. Summary estimates of the clinical endpoints were calculated with risk ratio (RR) and 95% confidence intervals using the random-effects model. Heterogeneity between studies was examined with COCHRAN’S Q based 12 statistics. The primary endpoint was progression free survival at 12 months while secondary endpoints were overall survival and certain adverse effects. Results: Our pooled analysis from the five studies included 4,648 patients. 2,641 were in the Bevacizumab and platinum-based treatment group while 2007 patients in sole-platinum based chemotherapy group. There was a statistically significant difference in primary outcome of progression free survival at 12 months was noted (RR = 1.56 (95% CI: 1.09 to 2.24; p = 0.020). 33,4% of patients in the treatment group as compared to 22.9% observed in the control group attained PFS at 12 months. The secondary outcome of overall survival at 12 months was seen in 76.7% patients in treatment group as compared to 73.02% observed in control group. This was no statistically significant difference in this case (RR = 1.04 (95% CI: 0.96 to 1.12; p = 0.34). Adverse effects including hypertension, proteinuria, arterial and venous thromboembolism, posterior reversible leukoencephalopathy syndrome occurred more frequently in the treatment group. Conclusions: Results from our meta-analysis support the superiority of Bevacizumab with platinum-based chemotherapy over platinum-based chemotherapy with regards to PFS. However, the OS benefit remains questionable.
Survival outcomes for dostarlimab and real-world (RW) treatment (tx) paradigms in post-platinum patients (pts) with advanced/recurrent (A/R) endometrial cancer (EC): The GARNET trial versus an external control arm from the Flatiron Health database.
Authors: Coleman Robert L. , Shen Qin , Goulden Scott , Mathews Cara Amanda , Hunger Matthias , Pahwa Ankit , Schade Rene 
Published: June 2022

5593 Background: There are limited treatment options for pts with A/R EC progressing on or after platinum-based chemotherapy (PBCT) and their prognosis is poor. This study compared the efficacy of the anti-programmed death (PD)-1 antibody dostarlimab evaluated in the single-arm, Phase I GARNET trial with current RW tx. Overall survival (OS) of pts with A/R mismatch repair deficient (dMMR)/microsatellite instability-high (MSI-H) EC receiving dostarlimab in Cohort A1 of the GARNET trial was compared with an equivalent RW cohort receiving non-anti-PD-(ligand [L])1 tx. Methods: The dostarlimab arm was the GARNET (Cohort A1) dMMR/MSI-H EC safety population. For the external control arm, a RW cohort was constructed using the Flatiron Health database and aligning eligibility criteria with those for GARNET, including pts with A/R EC, Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤1, who had received ≤2 lines of chemotherapy (≥1 line PBCT) and no anti-PD-(L)1 therapy. GARNET pts who received anti-PD-(L)1 therapy following dostarlimab (n=5/129) were excluded. Inverse probability of tx weighting (IPTW) was performed based on propensity scores constructed from key prognostic factors identified by literature review and clinical experts. With IPTW, Kaplan–Meier curves were created, OS rates estimated, and adjusted hazard ratios (HR) estimated by a Cox regression model. MMR/MSI status, only partially available in Flatiron and considered not significantly prognostic for OS as per a recent meta-analyses, was not included in the IPTW. Results: Baseline characteristics for GARNET (N=124) and RW (N=185) after IPTW are shown in the Table. Dostarlimab was associated with a 44% lower risk of death compared with RW tx (OS HR [95% confidence interval {CI}] 0.56 [0.385–0.812]; p=0.002) (see Tablefor median OS). Survival rates (95% CI) were higher for dostarlimab than RW tx at 12 months (mos) (72% [57%–82%] vs 51% [43%–59%]), 18 mos (57% [41%–70%] vs 40% [32%–48%]), and 24 mos (53% [37%–67%] vs 34% [26%–42%]). Conclusions: These results indicate that pts with A/R EC receiving dostarlimab in the GARNET trial had significantly lower risk of death than those receiving current non-anti-PD-(L)1 tx in the RW.[Table: see text]
Biomarker associations of immune checkpoint inhibitor versus chemotherapy effectiveness in first-line metastatic endometrial carcinomas: A real-world study.
Authors: Santin Alessandro , Graf Ryon , Shah Kunal J. , Kelly Andrew David , Danziger Natalie , Lin Douglas I. , Oxnard Geoffrey R. , Elvin Julia Andrea 
Published: June 2022

5596 Background: Limited evidence exists comparing outcomes of single-agent anti-PD1 immune checkpoint inhibitors (ICPI) vs. chemotherapy in the 1st line among metastatic endometrial carcinoma (mEC) patients. dMMR, MSI status, and Tumor Mutational Burden (TMB) have been characterized as predictive biomarkers of ICPI response in many solid tumors, including mEC. We sought to evaluate ICPI vs. chemotherapy effectiveness in 1st line mEC, stratified by TMB ≥ 10 mut/MB and MSI as assessed by next-generation sequencing. Methods: Following a prespecified analysis plan, this study used the nationwide (̃280 US cancer clinics) de-identified, EHR-derived, Flatiron Health-Foundation Medicine mEC clinico-genomic database (FH-FMI CGDB), with tissue CGP between 1/2011 - 6/2021. Cohort inclusion criteria: recurrent mEC patients with stage I-III at original diagnosis, 1st line ICPI or platinum chemotherapy treatment with TMB and MSI assessments available. Adjusted hazard ratios (aHR) from multivariable Cox proportional hazard models were utilized for time to next treatment (TTNT) and overall survival (OS) comparisons between 1L chemotherapy and 1L ICPI from start of 1L treatment stratified by TMB (≥ 10 vs. < 10) and adjusted for ECOG, BMI, and stage at diagnosis. Results: Among the 1st line cohort, patients received either Chemotherapy (n = 139, 87%) or first-line ICPI (n = 20, 13%). While the overlap between the TMB ≥ 10 (n = 46) population and MSI-H (n = 39) populations was high, with 38/46 (83%) of TMB ≥ 10 classified as MSI-H and 38/39 (97%) of MSI-H with a TMB ≥ 10, there were also 8 (17%) TMB ≥ 10 patients who were MSS. TMB ≥ 10 was associated with more favorable TTNT (aHR: 0.11 [0.03 - 0.44]) and OS (aHR: 0.1 [0.01 - 0.82]) on single-agent ICPIs vs. chemotherapy; however, TMB < 10 patients exhibited no observed differences in TTNT (aHR: 1.66 [0.79 - 3.48]) or OS (aHR: 1.79 [0.66 - 4.8]) between treatments. MSI-H pts were associated with more favorable TTNT (aHR: 0.1 [0.02 - 0.39]) and OS (aHR: 0.1 [0.01 - 0.86]) on single-agent ICPIs over chemotherapy; however, MSS pts did not observe differences in TTNT (aHR: 1.5 [0.65 - 3.5]) or OS (aHR: 2.14 [0.63 - 7.26]) between ICPI vs. chemotherapy. Conclusions: Recurrent 1st line mEC patients with TMB ≥ 10 and/or MSI-H exhibit more favorable outcomes on single-agent ICPI than standard chemotherapy in real-world settings. These findings warrant prospective randomized validation. Future studies should assess the utility of a combined biomarker approach across TMB and MSI status to identify the broadest group of patients who might benefit from ICPI.
Disparity between Ki67 measurements and tumor gene expression tests in patients with hormone-sensitive early breast cancer from the OPTIMA preliminary trial.
Authors: Stein Robert C. , Marshall Andrea , Bayani Jane , Makris Andreas , MacPherson Iain R. , Hughes-Davies Luke , Sobol Monika , Piper Tammy , Dotchin Georgina , Higgins Helen , Shaaban Abeer , Pinder Sarah E. , Dunn Janet , Bartlett John ,   OPTIMA Trial Management Group
Published: June 2022

567 Background: Tumor gene expression tests are increasingly used in breast cancer management. The Ki67 biomarker has been proposed as an inexpensive alternative for making chemotherapy decisions, has demonstrated utility for determination of endocrine therapy responsiveness and is included in the FDA license for adjuvant abemaciclib. We have compared Ki67 measurements with tumor gene expression test results for patients included in the OPTIMA prelim trial. Methods: We compared Ki67 %staining with the results of Oncotype DX, Prosigna and MammaPrint performed by the test vendor. Ki67 was determined in a single laboratory on triplicate tissue micro-arrays using quantitative image analysis including a 10% manual quality control check. We used kappa statistics to measure agreement between tests, divided into groups using the pre-defined test score boundaries for high vs. not high risk. Results: Data were available for 259 patients. Using ≥20% staining to define a high Ki67 score, kappa values (95% CI) for agreement with Prosigna were: 0.39 (0.28-0.49); Oncotype DX: 0.27 (0.18-0.36); and MammaPrint: 0.38 (0.27-0.49). Kappa values <0.2 are conventionally interpreted as showing slight agreement and 0.21-0.4 as fair agreement. A detailed breakdown of the comparisons of Ki67 with Prosigna and Oncotype DX is tabulated. Conclusions: Agreement between Ki67 and tumor gene expression tests is limited. Therefore, Ki67 values cannot accurately be used to reflect any of the molecular scores assessed here, all of which are well validated prognostic biomarkers. The use of Ki67 to determine suitability for adjuvant chemotherapy requires validation before it can replace the existing tests. Tumor gene expression tests may prove superior to Ki67 for the identification of patients likely to benefit from adjuvant abemaciclib. OPTIMA prelim is registered as ISRCTN42400492 and funded by the UK NIHR Health Technology Assessment Programme, award number 10/34/01. Clinical trial information: ISRCTN42400492. [Table: see text]
Distribution of breast cancer molecular subtypes within receptor classifications: Lessons from the I-SPY2 Trial and FLEX Registry.
Authors: Cha Jaeyoon , Warner Paige , Hiatt Robert , Gomez Scarlett Lin , van 't Veer Laura , Stover-Fiscalini Allison , Borowsky Alexander , Symmans W. Fraser Fraser , Wolf Denise M. , Yau Christina , Yee Douglas , DeMichele Angela , Berry Donald A. , Esserman Laura , Audeh William M. , Modh Shraddha ,   I-SPY2 Consortium
Published: June 2022

592 Background: Expression-based molecular subtypes of breast cancer (BC) predict tumor behavior and therapeutic response. Subtype distributions by age and sociodemographics can inform strategies for BC screening, treatment, and prognosis. The conventional approach, adopted by NCI’s Surveillance, Epidemiology, and End Results (SEER) Program, uses HR and HER2 to label: “triple negative” (HR-HER2-), “HER2-enriched” (HR-HER2+), “luminal A” (HR+HER2-), and “luminal B” (HR+HER2+). However, immunohistochemical (IHC)-based receptor labels may not reflect clinically and epidemiologically relevant molecular subtypes that share the same nomenclature, e.g., luminal B. Methods: We compared IHC labels by HR/HER2 to molecular subtypes by MammaPrint (MP) and BluePrint (BP) for patients in the phase II neoadjuvant I-SPY2 TRIAL for high-risk, stage II-III BC (NCT01042379, n = 981) and in the multicenter, prospective FLEX Registry for stage I-III BC (NCT03053193, n = 5,679). Results: IHC labels were discordant with MP/BP in 52% of I-SPY2 and 43% of FLEX cases (Table 1). HR-HER2- had the highest concordance with basal-type (99% in I-SPY2, 88% in FLEX). HR+ labels had the least agreement with MP/BP: HR+HER2- tumors were molecularly luminal B and basal in 71% and 29% of I-SPY2 and 40% and 4% of FLEX cases, respectively. HR+HER2+ tumors were molecularly luminal A and HER2-type in 10% and 60% of I-SPY2 and 15% and 36% of FLEX cases, respectively. Of molecularly luminal B cases, only 14% in I-SPY2 and 7% in FLEX were HR+HER2+. Conclusions: IHC markers collected by population-based registries (SEER) enable BC surveillance. However, IHC labels cannot be used as surrogates for molecular subtypes by MP/BP, especially for luminal B tumors. Given the unmet need to improve management of luminal B BC, we anticipate the growing importance of molecular subtyping to inform treatment and epidemiological research. We propose that the BC research community work with SEER to update its IHC labels to avoid overlap with molecular subtype nomenclature and incorporate such modern classifications when available. [Table: see text]
Racial and ethnic disparities in adherence and reported symptoms during routine collection of patient-reported outcomes (PROs).
Authors: Takvorian Samuel U , Wu Yaxin , Gabriel Peter Edward , Iocolano Michelle , Bekelman Justin E. , Shulman Lawrence N. , Parikh Ravi Bharat 
Published: June 2022

6510 Background: Routine collection of PROs for patients with cancer is an evidence-based practice and critical component of high-quality cancer care, but real-world adherence and reporting patterns are poorly understood. We examined differences in PRO adherence and reported symptoms by race and ethnicity. Methods: We conducted a retrospective cross-sectional study using de-identified electronic health record data from a National Cancer Institute Comprehensive Cancer Center. Participants included adults seen in follow-up at one of two medical oncology practices (1 academic, 1 community) from June 2019 to February 2020, during which two validated PRO instruments (NCI PRO-CTCAE and PROMIS Global v1.2) were routinely administered electronically via portal or tablet at return visits. Adherence was defined for each participant as the proportion of visits in which a PRO questionnaire was completed within 30 days. Using ordinary least squares regression, we modeled patient adherence as a function of race/ethnicity and adjusted for age, sex, insurance, median area income, ECOG performance status, cancer type, cancer stage, visit site, and number of visits during the study. Among study participants completing at least one PRO questionnaire, we modeled reported symptoms from the first questionnaire using a similar approach. Results: From June 2019 to February 2020, there were 29,726 patients (mean [SD] age 60.8 [15.1] years; 18,045 [60.7%] female) seen across 111,262 medical oncology visits. Of these patients, 19,971 (67.2%) completed at least one PRO questionnaire. Adjusted mean PRO adherence and reported symptoms varied by race/ethnicity, with Black and Hispanic patients reporting significantly higher symptom burden than White patients (Table). Conclusions: In this large cohort reflecting real-world PRO collection patterns, Black and Hispanic patients were less likely than White patients to complete PRO questionnaires, but more likely to report more severe symptoms. There is urgent need to ensure equitable PRO access and implementation and to address greater reported symptom burden among minority patients. [Table: see text]
Parental informed consent comprehension in childhood cancer clinical trials: Associations with social determinants of health.
Authors: Aristizabal Paula , Nataraj Shilpa , Perdomo Bianca , Martinez Elena , Nodora Jesse , Thornburg Courtney D 
Published: June 2022

6512 Background: Adequate informed consent (IC) comprehension is an ethical right prior to participation in clinical trials. Research investigating IC comprehension and associations with social determinants of health (SDoH) is lacking. We assessed whether SDoH and related contextual factors were associated with parental IC comprehension in therapeutic childhood cancer clinical trials. Methods: We prospectively enrolled parents of children with newly-diagnosed cancer. Univariable and multivariable regression were used to assess whether objective IC comprehension and related domains ( Purpose/Procedures/Randomization, Risks/Benefits, Alternatives, and Voluntariness) were associated with SDoH (ethnicity, marital status, language, education attainment, employment, insurance, socio-economic status, health literacy [HL]) and contextual factors (cancer type, voluntariness, satisfaction with IC). Results: Of 223 parents included, 112 (50%) were Hispanic and 38% of Hispanics were monolingual Spanish-speaking. In adjusted multivariable analyses, limited HL was significantly associated with lower overall IC comprehension (β = -7.22; 95% CI, -10.9 to -3.59; P < 0.001) and lower comprehension of Purpose/Procedures/Randomization (β = -7.53; 95% CI, -11.3 to -3.73; P < 0.001), Risks/Benefits (β = -8.14; 95% CI, -15.5 to -0.772; P = 0.031), and Alternatives (β = -17.0; 95% CI, -30.5 to -3.57; P = 0.013). Preferred Spanish language of written/verbal medical information was significantly associated with lower comprehension of Purpose/Procedures/Randomization (β = -8.50; 95% CI, -15.1 to -1.89; P = 0.012) and Voluntariness (β = -20.1; 95% CI, -34.9 to -5.33; P = 0.008). Lower satisfaction with informed consent (β = 0.988; 95% CI, 0.460 to 1.52; P < 0.001) and single marital status (β = -4.42; 95% CI, -7.81 to -1.02; P = 0.011) were significantly associated with lower IC comprehension. Conclusions: Among parents of children with newly diagnosed cancer who provided consent for their child’s participation in a therapeutic clinical trial, limited HL was consistently associated with lower IC comprehension in all domains analyzed, except for Voluntariness. Spanish language preference for medical information was associated with lower comprehension of two domains; and lower satisfaction was associated with lower overall IC comprehension. These findings suggests that parents with limited HL, limited English-proficiency, and lower satisfaction may not fully comprehend the IC and thereby not truly make informed decisions. Our findings highlight the potential role of language-concordant interventions tailored to the participant’s HL level in order to ultimately improve IC comprehension and contribute to a reduction of disparities in clinical trial participation and promote equitable translation of discoveries and treatments to underserved groups.
Analysis of patient (pt) withdrawal of consent using 11,993 pts from 58 alliance for clinical trials in oncology trials.
Authors: Mandrekar Sumithra J. , Hillman Shauna L , Strand Carrie , Zahrieh David , George Suzanne , Jatoi Aminah 
Published: June 2022

6513 Background: Pt recruitment receives well-deserved attention, but pt retention is also important for trial interpretability and generalizability. We report on trends and predictive factors for withdrawal of pt consent, defined as pt cessation from trial participation for reasons not mandated in the protocol. Methods: Alliance phase II/III trials that enrolled pts during 2013 – 2019 were included. All pts had ≥2 years (yrs) of follow-up. Primary outcome was withdrawn consent (yes; no) within 2 yrs of enrollment. Pt factors included year of enrollment, age, race, ethnicity, and gender. Trial factors included randomization, use of placebo, and use of radiation. Univariable (Uni) and full multivariable (MV) logistic regression models (including all factors from Uni setting) with a Bonferroni p-value correction (p <.004 considered significant) were used. Results: Median age was 62 yrs, with 67% female, 82% White, 9% Black or African American, and 7% Hispanic. 52% of trials were phase II, 5% II/III and 43% III. Common (> 10%) trial categories included 22% experimental therapeutics or rare tumors, 12% gastrointestinal, 12% genitourinary, 12% neuro-oncology and 10% symptom intervention. 78% of trials were randomized, 22% placebo-controlled and 14% used radiation. 1060 (9%) pts withdrew consent within 2 yr of enrollment (range,5.7% -9.8%) during 2013-2019. In Uni models, all trial and pt factors significantly predicted pt withdrawal except age, race, and gender (See table). In MV models, pts of Hispanic origin, and >75 yrs were more likely to withdraw. Trials using radiation had less likelihood of pt withdrawal. Placebo-controlled randomized trials had higher likelihood of withdrawal. Conclusions: Both trial and pt factors contribute to higher rates of pt withdrawal from clinical trials. Understanding these factors will enable investigators to focus on pt education and optimization of trial design to improve pt retention and the overall clinical trial plan. Support: U10CA180821, U10CA180882 [Table: see text]