bluuebunny/crossref_metadata_2025_split huggingface dataset:
Designing and implementing an evidence-based and longitudinal implicit bias training curriculum for school of medicine members and healthcare providers.
Authors: Hamel Lauren M. , Robinson Leah M. , Chamblee Marquita , Dougherty David W. , Sood Beena 
Published: June 2022

e24136 Background: Implicit bias negatively influences decisions and communication in oncology care, and may also lead to disparities in cancer treatment and outcomes. The School of Medicine (SOM) at Wayne State University (WSU), based in the diverse yet segregated city of Detroit, Michigan, has faced the consequences of bias. Fortunately, within SOM/WSU, expertise on the problem of and solutions to implicit bias have flourished. We leveraged that expertise to design and implement a comprehensive and longitudinal implicit bias curriculum for SOM members and healthcare providers, including hematology/oncology faculty, providers, and trainees. We designed the curriculum to satisfy State of Michigan implicit bias training requirements for all healthcare providers. To date, we have implemented two modules. Prior to the second module, we received IRB-approval to recruit curriculum participants as study participants and tested effectiveness. Methods: The curriculum is comprised of 1½ hour modules offered every three months. Topics include how implicit bias influences clinical communication with a focus on the oncology care context, how structural racism influences health policy, among others. To evaluate, we utilize Kirkpatrick’s Four-Level Training Evaluation Model, to assess outcomes at 4 levels: 1. reaction, 2. learning, 3. behavior change and 4. long-term results. After obtaining passive consent from participants, we gathered effectiveness data at Levels 1 and 2. Results: We implemented two modules (How Patient and Physician Race-Based Attitudes Influence Clinical Communication & Structural Racism 101: Basic Training for Doctors) in 2021 via Zoom. More than 160 people attended each module with many participants representing oncology-focused hospitals and academic departments. All participants received a certificate of participation as a part of the state requirements for implicit bias training, and CME credit. For Session 2 we asked participants to respond to a survey before (n = 106) and after (n = 35) the session assessing Levels 1 and 2. Participant evaluations (Level 1) were very positive, with many participants noting that they plan to put what they have learned into practice immediately. A common critique was the desire for more topics and more time to discuss. Findings show increased knowledge (Level 2) of structural racism (pre: 92% vs. post: 97%); spatial racism (pre: 87% vs. post: 91%); and how racism influences health policy (pre: 80% vs post: 86%). Conclusions: We successfully implemented a longitudinal implicit bias curriculum for SOM members and healthcare providers. Next steps include continuing to implement and assess the curriculum, and collecting data at Levels 3 and 4. This type of curriculum could be an important tool to decrease bias in cancer care and improve cancer care equity.
Adjusting the TMIST study design to accommodate slower than expected accrual: ECOG-ACRIN EA1151.
Authors: Pisano Etta , Gatsonis Constantine , Schnall Mitchell D. , Yaffe Martin , Troester Melissa A. , Gareen Ilana F. , Collins Laura C. , Curtis Amarinthia , Cole Elodia B , Cormack Jean , Steingrimsson Jon , Carlos Ruth C , Miller Kathy , Comstock Christopher 
Published: June 2022

TPS10614 Background: The ECOG-ACRIN Tomosynthesis Mammographic Imaging Screening Trial (TMIST), which opened in 2017, is a randomized trial designed to assess whether Tomosynthesis Mammography (TM) should replace Digital Mammography (DM) for breast cancer screening. It is hypothesized that women assigned to TM for 3-5 screening rounds will have fewer advanced breast cancers than the women assigned to DM. Advanced cancers are those that have distant metastases or positive nodes, are invasive tumors greater than or equal to 2.0 cm in size, or are invasive tumors greater than 1.0 cm in size that are triple negative or HER 2+. The initially planned enrollment of 164,946 women was due to be completed by the end of 2020, with follow-up concluded by 2025. There were substantial challenges in meeting this timeline, including the organizational and funding structure of the NCI National Clinical Trials Network which is dependent upon sites using their existing staffing resources (not always readily available at the time of study activation). This led to longer than anticipated start of enrollment for most interested sites and lower than anticipated annual enrollment per participating site based ultimately on the staffing support that could be allocated to manage TMIST. In addition, research staffing shortages and periodic research operations closures due to COVID-19 have also impacted enrolling TMIST sites, though unevenly, since the start of the pandemic. Enrollment plateaued at approximately 2,100 subjects per month by the end of 2020. With that accrual rate expected, the trial design was modified to reduce the sample size so that the study could be completed by 2027. Methods: With the approval of the NCI CIRB, we changed how the primary endpoint measure for TMIST is assessed from the number of advanced cancers that occur by 4.5 years after randomization to the time from randomization to occurrence of advanced cancers. All advanced cancers occurring within 7 years of randomization are now included and all participants followed for at least three years. In addition, the power of the study of the study was modified from 0.9 to 0.85, while the originally assumed effect size at 4.5 years was retained These changes allowed a reduction of sample size to 128,905, with subject recruitment projected to end in 2024. As of February 14, 2022, there are 125 sites open, 114 in the U.S. and 11 in other countries, with an additional 31 sites planning to open. As of February 14, 2022, a total of 63,845 women have been enrolled in the trial worldwide at 115 sites, with 20% of US participants self-identifying as belonging to minority racial and ethnic groups and 70% consenting to optional blood and/or buccal cell collection. Clinical trial information: NCT03233191.
A randomized phase III study assessing the efficacy of liquid biopsy in early diagnosis of recurrence and second malignancies in lung cancer survivors.
Authors: Raoof Sana , Gomez Daniel Richard 
Published: June 2022

TPS10617 Background: Lung cancer survivors are highly enriched for extensive smoking histories and have an increased risk of subsequent primary cancers, including those of the larynx, mouth and throat, esophagus, pancreas, bladder, thyroid, stomach, small intestine, colon, rectum, and kidney. Guideline-concordant surveillance after definitive treatment for lung cancer consists of periodic chest CT scans, which do not visualize the majority of second malignancies that this population ultimately develops. Disadvantaged and minority patients are diagnosed with recurrence and second primary cancers at later stages due to reduced compliance with survivorship surveillance. To address these issues, we propose utilizing multi-cancer early detection (MCED) liquid biopsies. MCED liquid biopsies are part of a rapidly growing field of research that assesses parallel cancer screening for multiple cancer types with point of care blood, urine, or saliva sampling. We selected a methylation-based screening liquid biopsy for multiple reasons: 1) it has the highest PPV and specificity of any test clinically validated in the multi-cancer detection setting thus far, 2) it produces a tissue of origin, allowing for targeted workup of positive findings, and 3) it requires only a single test, which we believe will minimize attrition among vulnerable populations with decreased access to healthcare. We designed a 9,000-patient prospective, multi-institutional randomized clinical trial to assess the efficacy of liquid biopsy in early diagnosis of recurrence and second malignancies in lung cancer survivors. To ensure over 25% of participants are of minority status, we have recruited multiple community hospitals to the study in partnership with Memorial Sloan Kettering Cancer Center. Patients included in this study are survivors of non-metastatic non- small cell lung cancer, status-post definitive treatment (surgery or radiation) with no evidence of disease for at least one year. Participants will be randomized 1:1 to standard surveillance or standard surveillance plus six-monthly methylation-based liquid biopsy tests over a two-year study period, and strict guidelines on follow-up of positive liquid biopsy testing will be provided to reduce harms from false positives or over-diagnosis. Methods: The primary endpoint of this study is the incidence of late stage cancer (distant recurrence or new primary cancer of stage III/IV). Secondary endpoints include cancer-specific mortality, eligibility for definitive interventions once cancer is diagnosed, and utilization of liquid biopsy versus standard of care scans. This is the first randomized controlled trial of screening liquid biopsy in a survivorship population and the first trial utilizing liquid biopsy in a large minority population.
Longitudinal immunological responses of COVID-19 vaccination in patients with solid tumors on active treatment: A pilot study.
Authors: Cao Lifen , Kopp Shelby Rose , Rayman Patricia A. , Mallat Naji , Leyfman Yan , Martin James Michael , Selfridge Jennifer Eva , Diaz-Montero C. Marcela , Montero Alberto J. 
Published: June 2022

TPS10618 Background: Coronavirus disease 2019 (COVID-19), caused by betacoronavirus SARS-CoV-2, is associated with an increased risk of severe infection or death in cancer patients compared to the general population. The CANVAX trial recently demonstrated that short term immune responses to SARS-CoV-2 vaccines are modestly impaired in patients with cancer— particularly those who receive myelosuppressive chemotherapy. Because little is known regarding longitudinal antibody or T-cell responses in cancer patients who receive cytotoxic chemotherapy or non-myelosuppressive targeted systemic therapy, the aim of this longitudinal study is to assess immune B and T cell responses to SARS-CoV-2 over a 12-month period in solid tumor patients who receive chemotherapy or non-immunosuppressive therapy compared to healthy individuals without cancer. Methods: This is an ongoing prospective non-interventional clinical trial (NCT05238467). Approximately 100 patients will be enrolled into three different arms. Accrual began in May 2021 and 37 patients have been enrolled. Eligible patients must not have prior COVID-19 infection < 6 months from study enrollment and have a diagnosis of a solid tumor (breast, genitourinary, or gastrointestinal cancers), who either: received myelosuppressive chemotherapy within 60 days prior to initial or booster COVID vaccination, or who started on chemotherapy within 30 to 60 days after the initial or booster COVID vaccination (Arm A); or received non-immunosuppressive treatments (Arm B); or have no history of cancer or prior history of cancer but beyond 12 months from completion of curative cancer treatment (Arm C, control cohort). Whole blood will be collected in accordance with standard operating procedures. Blood samples analyzed for the presence of antibodies against the major antigenic components of SARS-CoV-2 including the spike glycoprotein (S), receptor binding domain (R) and nucleocapsid phosphoprotein (N). Antibody levels will be quantified utilizing quantitative ELISA. T-cell responses will also be quantified. The primary endpoint is seroprotection rate with an antibody titer protective (1:40) at any point: baseline, 2, 6, and 12 months. The secondary endpoint is to evaluate differences in longitudinal immunological responses to SARS-CoV-2 over a 12-month period. The difference of the seroprotection rate among 3 cohorts of participants will be examined using chi-square test. Moreover, the effect of treatment (chemotherapy, endocrine, TKIs) on seroprotection will be estimated using multivariable logistic regression controlling the effects of confounders, such as age, gender and cancer type. COVID antibody titers measured over time (baseline, 8 weeks, 6, 9, 12 months after the second vaccination) will be analyzed using mixed-effect models. Clinical trial information: NCT05238467.
postMONARCH: A phase 3 study of abemaciclib plus fulvestrant versus placebo plus fulvestrant in patients with HR+, HER2-, metastatic breast cancer following progression on a CDK4 & 6 inhibitor and endocrine therapy.
Authors: Kalinsky Kevin , Layman Rachel M. , Kaufman Peter A. , Graff Stephanie L. , Bianchini Giampaolo , Martin Miguel , Zhou Yanhong , Knoderer Holly , Litchfield Lacey , Wander Seth Andrew 
Published: June 2022

TPS1117 Background: The use of cyclin dependent kinase 4 and 6 (CDK4 & 6) inhibitors plus endocrine therapy (ET) has transformed the management of hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer (ABC). However, most patients will experience disease progression. Identification of treatment options following progression is an unmet medical need. Additionally, as CDK4 & 6 inhibitors are now being deployed in the adjuvant setting, determination of optimal therapy following metastatic relapse is an important question. In patients with disease progression following a CDK4 & 6 inhibitor-based regimen, continuing CDK4 & 6 inhibition with abemaciclib while switching the ET backbone may provide benefit and delay the need for cytotoxic chemotherapy. Abemaciclib is an oral, selective, and potent CDK4 & 6 inhibitor administered continuously and approved as monotherapy or with ET for treatment of HR+, HER2- ABC. Abemaciclib has also been approved with ET for the adjuvant treatment of HR+, HER2-, node-positive, early breast cancer at high risk of recurrence and a Ki-67 score ≥20%. Fulvestrant is a selective ER degrader (SERD) approved for treatment of HR+, HER2- ABC. The postMONARCH study investigates whether abemaciclib plus fulvestrant will improve outcomes in patients with HR+, HER2- ABC after disease relapse or progression after adjuvant or first-line treatment with a CDK4 & 6 inhibitor plus ET. Methods: postMONARCH is a Phase 3, global, multicenter, randomized, double-blind, placebo-controlled study in patients with HR+, HER2- ABC and with disease progression on treatment with a prior CDK4 & 6 inhibitor plus an aromatase inhibitor as initial therapy for ABC or recurrence on/after treatment with a CDK4 & 6 inhibitor plus ET in the adjuvant setting. Eligible patients are randomized 1:1 to receive abemaciclib 150 mg twice daily or placebo, plus fulvestrant. Stratification factors include geography, presence of visceral metastasis, and duration of prior CDK4 & 6 inhibitor-based regimen. The study is powered at 80% with a cumulative Type I error of 0.025 to detect the superiority of abemaciclib plus fulvestrant versus placebo plus fulvestrant in terms of investigator-assessed progression free survival. Key secondary endpoints include overall survival, PFS by blinded independent central review, objective response rate, safety, patient-reported outcomes, and pharmacokinetics. This study opened in Jan 2022, plans for approximately 122 centers in 18 countries, and anticipates enrolling ̃350 patients. Clinical trial information: NCT05169567.
KEYNOTE-B49: A phase 3, randomized, double-blind, placebo-controlled study of pembrolizumab plus chemotherapy in patients with HR+/HER2- locally recurrent inoperable or metastatic breast cancer.
Authors: Rugo Hope S. , Sohn Joohyuk , Jerez Gilarranz Yolanda , Gonzalez-Cortijo Lucia , Sonnenblick Amir , Sabanathan Dhanusha , Korbenfeld Ernesto Pablo , Egle Daniel , Poirier Brigitte , Zagouri Flora , Matikas Alexios , Aksoy Sercan , Demirci Umut , Ramos-Elias Pier , Im Seock-Ah , Cardoso Fatima , Jia Liyi , Baccan Carlos , Tryfonidis Konstantinos , Schmid Peter 
Published: June 2022

TPS1118 Background: HR+/HER2− advanced breast cancer that progresses on endocrine therapy is treated with chemotherapy (chemo). The phase 1b KEYNOTE-028 trial showed durable activity with pembrolizumab (pembro) monotherapy in previously treated HR+/HER2−, PD-L1–positive (combined positive score [CPS] ≥1) advanced breast cancer. KEYNOTE-B49 (NCT04895358) is a phase 3, randomized, double-blind study of pembro + chemo vs placebo (pbo) + chemo in centrally assessed PD-L1–positive, HR+/HER2− locally recurrent inoperable or metastatic breast cancer (mBC) after progression on prior endocrine therapy. Methods: ∼800 patients (pts) with HR+/HER2− locally recurrent inoperable or mBC who are candidates for chemo (no prior chemo for metastatic disease) with PD-L1 CPS ≥1 and documented progression on prior endocrine therapy will be enrolled. Prior endocrine therapy comprises ≥2 lines (≥1 in combination with a CDK4/6 inhibitor) in the metastatic setting or 1 line with CDK4/6 inhibitor treatment for mBC in pts who had a relapse within 24 mo of primary surgery. Pts without prior CDK4/6 inhibitor treatment may enroll if they had progressed within 6 mo of starting endocrine therapy for metastatic disease and had previously relapsed within 24 mo of primary tumor surgery while on adjuvant endocrine therapy. Pts are randomized 1:1 to receive pembro 200 mg IV or pbo Q3W, each in combination with investigator’s choice of chemo: paclitaxel 90 mg/m2 IV on days 1, 8, and 15 Q4W; nab-paclitaxel 100 mg/m2 IV on days 1, 8, and 15 Q4W; liposomal doxorubicin 50 mg/m2 IV on day 1 Q4W; or capecitabine 1000 mg/m2 PO BID on days 1–14 Q3W. Randomization is stratified by tumor PD-L1 (CPS 1–9 vs ≥10), presence of visceral metastases (yes vs no), and chemo on-study (taxanes vs liposomal doxorubicin vs capecitabine). Treatment is continued until disease progression, unacceptable toxicity, withdrawal, or, for pembro/pbo, completion of 35 cycles (̃2 years); chemo can be continued per investigator discretion. Tumor PD-L1 status is determined centrally using the PD-L1 IHC 22C3 pharmDx assay (Agilent Technologies; Carpinteria, CA, USA). Radiologic assessments are performed Q9W for 54 wk and then Q12W thereafter. AEs occurring from randomization until 30 d after treatment discontinuation (90 d for serious AEs) are graded per NCI-CTCAE v 5.0. Primary endpoints are PFS per RECIST v1.1 by BICR and OS in pts with PD-L1 CPS ≥10 and ≥1 tumors, separately. Enrollment is ongoing at 204 international sites. Clinical trial information: NCT04895358.
Neoadjuvant survivin-targeted immunotherapy maveropepimut-S (MVP-S) to increase Th1 immune response in Ki67-high hormone receptor-positive (HR+) early-stage breast cancer (ESBC).
Authors: Stanton Sasha E. , MacDonald Lisa Diana , Mellinger Staci L. , Moxon Nicole , Kelly Tracy , Hirsch Heather Anne , Fiset Stephan , Young Kristina Hoot , Page David B. 
Published: June 2022

TPS1119 Background: HR+ ESBC is associated with suboptimal pathologic complete response rate (pCR, ̃10%) following neoadjuvant cytotoxic chemotherapy. Neoadjuvant anti-endocrine therapy with aromatase inhibitors (AI) may serve as an effective alternative. Efficacy can be gauged using the surrogate Ki67 cell proliferation histologic marker. Patients with poor Ki67 response (defined as Ki67 > 10%) following neoadjuvant AI exhibit poor prognosis and therapeutic resistance to both anti-endocrine therapy and chemotherapy. In a genomic analysis among Ki67-high HR+ tumors, we identified 8-fold upregulation of BIRC5 (survivin), a gene that regulates apoptosis and the cell cycle and that is associated with poor clinical outcome. Maveropepimut-S (MVP-S, previously named DPX-Survivac) leverages the non-aqueous, lipid-based DPX delivery platform to educate a specific and persistent T cell-based immune response to 5 HLA-restricted peptides from Survivin, a cancer-associated protein commonly upregulated in several cancers. Treatment with MVP-S and intermittent, low-dose cyclophosphamide (CPA) has shown tumor infiltration of survivin-specific T cells. Previous clinical trials have shown that MVP-S is well-tolerated, immunogenic, and could lead to clinical response in several cancer indications. Further exploration of the regimen in breast cancer could extend the application of this immunotherapy for this unmet medical need. Methods: NCT04895761 is phase I trial evaluating the safety and immunologic effects of neoadjuvant MVP-S plus letrozole (arm A, n = 6), with/without tumor-directed MR-guided radiotherapy (arm B, n = 6), or intermittent low-dose cyclophosphamide or CPA (arm C, n = 6). Postmenopausal patients with T1c+ HR+HER2- breast cancer with Ki67 > 10% will receive two doses of MVP-S and 7 weeks of neoadjuvant letrozole prior to surgery (all arms), whereas arm B will be treated additionally with concurrent 10Gy x 2 tumor boost radiation to facilitate immunogenic cell death, and arm C (n = 6) will be treated additionally with intermittent low-dose CPA (50mg BID) to facilitate regulatory T cell depletion. The primary objective is safety. Biomarker objectives are to evaluate for each treatment arm: 1) systemic type I survivin-specific immune response, as measured by IFN-γ ELISPOT; 2) changes in immune environment by GeoMx digital spatial genomic profiling; 3) and changes in tumor infiltrating lymphocytes (TILs) and Ki67. These data will be used to identify the most immunogenic MVP-S combination therapy for study in phase II trial powered to assess clinical outcome (pCR). Clinical trial information: NCT04895761.