bluuebunny/crossref_metadata_2025_split huggingface dataset:
CLRM-07. INCREASING EFFICIENCY IN EARLY PHASE MULTICENTER IMAGING BIOMARKER TRIALS: EMERGING STRATEGIES FROM THE GABLE (GLIOBLASTOMA ACCELERATED BIOMARKER LEARNING ENVIRONMENT) TRIAL
Authors: Barboriak Daniel , Steingrimsson Jon , Gatsonis Constantine , Schiff David , Kleinberg Lawrence 
Published: September 2021

Abstract
Validated biomarkers that more accurately predict prognosis and/or measure disease burden in patients with high-grade gliomas would help triage which treatment strategies are most promising for evaluation in Phase III multicenter trials. Multicenter trials to evaluate imaging biomarkers in this group face particular challenges; these trials have historically been slow to accrue and have not recently succeeded in validating new imaging biomarkers useful in treatment development. Due to variability in image acquisition protocols, scanner hardware, image analysis, and interpretive schemes, promising results obtained in single centers are poor predictors of success in the multicenter setting. Multicenter preliminary data to support further evaluation of imaging biomarkers is rarely available. The need for more efficient trial designs that bring multicenter data earlier into the process of biomarker development has become increasingly clear. In this presentation, the planning process within ECOG-ACRIN’s Brain Tumor Working Group for a platform multicenter trial called GABLE (Glioblastoma Accelerated Biomarker Learning Environment trial) designed to evaluate biomarkers for distinguishing pseudoprogression from true progression in patients with newly diagnosed GBM is described. In our planning process, it was determined that efficiencies can be gained from evaluating multiple biomarker types in parallel rather than serially; in the context of the proposed trial, not only conventional imaging biomarkers but plasma biomarkers and radiomic biomarkers can be evaluated simultaneously. Patient tolerance limits the feasibility of evaluating multiple non-standard-of-care imaging biomarkers in parallel. For this group of biomarkers, a “fast-switching” serial evaluation strategy using multiple interim analyses was developed to triage out biomarkers unlikely to succeed in identifying patient groups with clinically significant differences in median survival. For biomarker triage, an endpoint of event-free survival (events of either death or NANO progression) was proposed. Simulations were used to evaluate alpha and beta error using this evaluation strategy.
CLRM-14. OPEN-LABEL, MULTINATIONAL, MULTICENTER, PHASE 3B/4 STUDY OF TRASTUZUMAB DERUXTECAN (T-DXD) IN PATIENTS WITH OR WITHOUT BASELINE BRAIN METASTASIS (BM) WITH PREVIOUSLY TREATED ADVANCED/METASTATIC HUMAN EPIDERMAL GROWTH FACTOR RECEPTOR 2–POSITIVE BREAST CANCER (HER2+ BC): DESTINY-BREAST12
Authors: Lin Nancy U , Ciruelos Eva , Jerusalem Guy , Müller Volkmar , Niikura Naoki , Viale Giuseppe , Oscroft Emma , Anand Shawn , Walker Graham , Harbeck Nadia 
Published: September 2021

Abstract

BACKGROUND
Despite treatment advances, up to 50% of patients with advanced HER2+ BC develop BM (Zimmer. Cancer Rep. 2020). Patients with HER2+ BC with BM have a worse prognosis than patients without BM. In DESTINY-Breast01, T-DXd demonstrated efficacy in the overall population and preliminary efficacy in a subgroup with stable BM, with a confirmed objective response rate (ORR) of 61.4% and an extracranial confirmed ORR by independent central review (ICR) of 58.3%, median progression-free survival (PFS) of 19.4 and 18.1 mo, and median duration of response (DOR) of 20.8 and 16.9 mo (Modi. Cancer Res. 2021; Jerusalem. Ann Oncol. 2020). Here we describe a trial evaluating T-DXd in patients with previously treated advanced/metastatic HER2+ BC ±BM.

DESIGN
DESTINY-Breast12 (NCT04739761) is an open-label, multicenter, international (86 sites in the US, Europe, Australia, and Japan), phase 3b/4 study assessing T-DXd 5.4 mg/kg q3w efficacy and safety in patients with previously treated advanced/metastatic HER2+ BC ±BM that progressed with ≥1 prior anti-HER2–based regimen and received ≤2 lines of therapy in the metastatic setting (excluding patients with prior tucatinib). Patients (n=250/cohort) will be enrolled in cohort 1 (−BM at baseline) or 2 (+BM at baseline). BM must be untreated and not needing immediate local therapy or previously treated and stable or progressing. Primary endpoints are ORR (cohort 1) and PFS (cohort 2) (both by RECIST version 1.1 per ICR). Secondary endpoints are OS, DOR, time to progression, duration of subsequent therapy, PFS2, safety, and changes in symptoms, functioning, and QOL in both cohorts; incidence of new symptomatic CNS metastasis (CNSM) in cohort 1; and ORR and CNS ORR by RECIST 1.1 per ICR, CNS PFS and DOR, and time to new CNSM in cohort 2. This is an encore; the original presentation will be at The European Society for Medical Oncology 2021.
IMMU-02. PHASE I/II STUDY OF LASER INTERSTITIAL THERMOTHERAPY (LITT) COMBINED WITH CHECKPOINT INHIBITOR FOR RECURRENT GLIOBLASTOMA (RGBM): PRELIMINARY RESULTS
Authors: Sloan Andrew , Buerki Robin , Murphy Christopher 
Published: September 2021

Abstract

BACKGROUND
Recurrent glioblastoma (rGBM) has poor response rate and survival. Laser Interstitial Thermotherapy (LITT), a minimally invasive approach, improves survival but is not curative alone. Previous studies of LITT suggested the possibility of an abscopal effect. Indeed, GBM are known to harbor elevated levels of immunosuppressive cells such as Treg, M2 macrophages and MDSC both in the tumor microenvironment as well as in the systemic circulation. Checkpoint inhibition (CPI) immunotherapy has proven highly effective for some solid tumors. CPI in newly diagnosed GBM demonstrated safety in phase I trials (NRG BN-002). Further, preclinical studies targeting PD-1 with concurrent RT appears to be synergistic and improve survival. We hypothesized that LITT would block tumor-induced immunosuppression and introduce tumor neoantigens. However, there was no data regarding safety of pembrolizumab combined with LITT. We thus conducted a phase I/II study of LITT + pembrolizumab starting at three times relative to LITT.

METHODS
This is a three armed Phase I/II study based on timing of pembrolizumab (200 mg q 21 days) relative to LITT at 35d or 14d post-op, or 7d pre-op, with an expansion cohort phase II arm conducted at the earliest tolerated time of CPI administration. Adults with proven supratentorial rGBM with KPS &gt;=70 and &lt;= 2mg/d of dexamethasone were eligible.

RESULTS
Arm 1-2 of the phase I trial demonstrated no SAEs grade II or greater, but limited evidence of response. Arm 3 (neoadjuvant) pembrolizumab appears to be equally safe and has been expanded to phase II, demonstrating at least two CR among the first 3 patients (66.6%) with &gt;= 9 month follow-up and patients remain clinically stable at 10 and 15 months post-op.

CONCLUSIONS
Neoadjuvant pembrolizumab combined with LITT for rGBM appears to be safe in this phase I trial, and demonstrates early evidence of response. The phase II trial is ongoing.
NEIM-02. TRIAL IN PROGRESS: A MULTICENTER PHASE 3 STUDY TO ESTABLISH THE DIAGNOSTIC PERFORMANCE OF 18F-FLUCICLOVINE PET IN DETECTING RECURRENT BRAIN METASTASES AFTER RADIATION THERAPY (REVELATE)
Authors: Chao Samuel T , Chaglassian Alain , Tainer Nancy , Teoh Eugene J 
Published: September 2021

Abstract

BACKGROUND
Brain metastases occur in up to 40% of patients with cancer and are associated with poor prognosis and considerable levels of recurrence. Consequently, close follow-up with serial brain MRI is performed post-treatment to monitor for recurrent disease. Although conventional MRI (CE-T1-weighted and FLAIR/T2-weighted) is the recommended follow-up modality, it has poor specificity with limited ability to differentiate between true disease recurrence and treatment-related changes such as radiation necrosis. Therefore, alternative imaging options are sought in order to help physicians confidently diagnose treatment-related changes and thus reliably stratify the risk of continuation of a therapeutic regimen, especially given the morbidity associated with current treatments. Amino acid PET imaging agent, 18F-fluciclovine, has increased uptake in brain tumors relative to normal tissue and may be useful for detecting recurrent brain metastases.

METHODS
NCT04410133 is a prospective, open-label, single-arm, single-dose (185 MBq ±20%) study with a primary objective to confirm the diagnostic performance of 18F-fluciclovine PET (read with conventional MRI for anatomical reference) for detection of recurrent brain metastases where MRI is equivocal. Approximately 150 subjects with solid tumor brain metastases who have undergone radiation therapy will be enrolled in this multicenter trial (~18 US sites) if they have a lesion considered equivocal on MRI that requires further confirmatory diagnostic procedures such as biopsy/neurosurgical intervention or clinical follow-up. Subjects will undergo 18F-fluciclovine PET &lt;42 days after the equivocal MRI and 1–21 days pre-biopsy/neurosurgical intervention. Clinical follow-up will occur for 6m post-18F-fluciclovine PET. Secondary objectives include evaluation of subject- and lesion-level 18F-fluciclovine negative and positive percent agreement (equivalent to specificity and sensitivity, respectively) for recurrent brain metastases, inter-reader and intra-reader agreement, and safety evaluations. Enrolment began in October 2020 and the trial is open at the time of submission.
NEIM-05. [GA68]DOTATATE PET/MRI-BASED RADIOSURGICAL RESPONSE ASESSMENT IN MENINGIOMA
Authors: Ivanidze Jana , Kim Sean , Roytman Michelle , Ramakrishna Rohan , Pannullo Susan , Schwartz Theodore , Osborne Joseph , Magge Rajiv , Lin Eaton , Knisely Jonathan 
Published: September 2021

Abstract

PURPOSE
Postoperative PET/MRI with [68Ga]-DOTATATE can differentiate residual meningioma from postsurgical change, aid in target delineation, and portend a more favorable dosimetry with decreased PTV and organ-at-risk dose. Our purpose was to demonstrate utility of DOTATATE PET/MR for radiosurgical treatment (RT) response assessment in meningiomas.

METHODS
Patients underwent postoperative radiation treatment planning using DOTATATE PET/MRI as part of our IRB-approved prospective trial. Both DOTATATE PET and gadolinium-enhanced T1 weighted MR imaging were incorporated in RT-planning. All patients underwent follow-up DOTATATE PET/MRI at 6-12 months following completion of radiosurgery. Maximum absolute standardized uptake value (SUV) and SUV ratio (SUVR) of lesion/ superior sagittal sinus SUV were obtained. RANO criteria were applied to determine significance of change in size. Statistical analyses were performed using paired t-tests.

RESULTS
13 patients (15% WHO-I, 54% WHO-II, 23% WHO-III, 8% WHO grade unknown) were followed postoperatively with pre- and post-RT DOTATATE PET/MRI. 29 meningiomas were treated. 46% (6/13) of subjects received SBRT and 54% (7/13) received SRS. Post-RT DOTATATE PET/MRI demonstrated a 46.4% SUV decrease (p-value = 0.0001) and a 60.8% SUVR decrease (p-value &lt; 0.0001). Of 21 measurable lesions, the size product decreased by 21%; while this decrease was statistically significant (p-value = 0.0008), it was below the 25% decrease defined as clinically significant by RANO guidelines. To date, all patients remain stable radiographically without evidence of recurrence (mean follow-up post RT: 14 months; range: 6-24 months).

CONCLUSIONS
DOTATATE PET SUV and SUVR demonstrated marked, significant decrease post radiosurgery. Lesion size decrease was statistically significant but not clinically significant by RANO criteria. DOTATATE PET/MR thus represents a promising approach to aid in response assessment for radiosurgically treated meningiomas. Longer-term follow-up is needed to determine the correlation between the degree of post-RT SUV and/or SUVR decrease and progression-free-survival.
SYST-01. MULTICENTER INVESTIGATOR-INITIATED PHASE 2 STUDY OF E7090 IN SUBJECTS WITH ADVANCED OR RECURRENT SOLID TUMORS WITH FIBROBLAST GROWTH FACTOR RECEPTOR (FGFR) GENE ALTERATION: FORTUNE STUDY
Authors: Takahashi Masamichi , Chiba Yohei , Sudo Kazuki , Kojima Yuki , Okuma Hitomi , Kohsaka Shinji , Ichimura Masahiko , Okita Natsuko , Nakamura Kenichi , Machida Ryunosuke , Kinoshita Ichiro , Takahashi Masanobu , Matsubara Junichi , Kusaba Hitoshi , Yonemori Kan 
Published: September 2021

Abstract

Background
Genetic alterations of FGFRs are known to play an important role in the proliferation, survival, and migration of cancer cells as well as tumor angiogenesis and drug resistance. E7090 is an orally available selective tyrosine kinase inhibitor for FGFR1-3. A global Phase 2 study of E7090 in subjects with unresectable advanced or metastatic cholangiocarcinoma harboring FGFR2 gene fusion is ongoing (NCT04238715). We recently reported FGFR alterations that are highly sensitive to E7090 using a high-throughput functional evaluation method called MANO method (Nakamura et al. npj Precision Oncology, in press), narrowing down the most promising FGFR alteration targets. Here, we designed a single-arm, open-label, investigator-initiated multicenter Phase 2 basket study to evaluate the efficacy and safety of E7090 in subjects with advanced or recurrent solid tumors harboring FGFR gene alterations, focusing on alterations identified by MANO method, as a sub-study under the nationwide large registry for rare cancers in Japan (MASTER KEY Project).

Methods
The key eligibility criteria are: 1) Histologically confirmed metastatic or locally advanced solid tumor; 2) Ineffective to or intolerant to first line treatment, or for which standard treatment is no longer available; and 3) Confirmed FGFR gene alterations via next-generation sequencing assays that are reimbursed by insurance. Subjects will receive E7090 140 mg orally once daily until disease progression or development of unacceptable toxicity. The primary endpoint is objective response rate (ORR) by independent central review (RECIST v1.1), and the secondary endpoints include ORR by investigator assessment, progression-free survival, overall survival, disease control rate, safety, duration of response, and time to response. For primary brain tumors, RANO criteria is also applied in assessment of response. The study enrolls approximately 45 subjects. (Clinical Trial Registry: jRCT2031210043)
Setting the Stage for Emerging Adulthood Sexuality
Authors: Cary Kyla M , Reese-Weber Marla 
Published: September 2021

Abstract
This chapter explores the ways in which sexuality development during adolescence sets the stage for sexuality development in emerging adulthood. Sexual experiences and perceptions constructed within adolescence set in motion trajectories that will continue into emerging adult development. This chapter discusses the implications of adolescent experiences with sexual activity, sexual risk, parent–adolescent relationships, and trauma on the development of sexuality in emerging adulthood, while keeping in mind the diverse experiences of adolescents of varying identities. This is followed by implications and suggestions for future research. Understanding the connections between adolescent and emerging adult sexuality can provide a more nuanced view of sexuality development in emerging adulthood.
Method Tutorial
Authors: Wood Erica P. , Cook Stephanie H 
Published: September 2021

Abstract
Retention of emerging adult sexual minority men (SMM) in longitudinal studies including biospecimens collection is often poor. To date, very few methodological examinations exist pertaining to strategies that may increase retention among potentially difficult-to-reach populations, including emerging adult SMM. This chapter describes a multifaceted financial incentive (FI) structure utilized in two daily diary study designs. First, the chapter discusses why typical FI structures may be insufficient for retaining emerging adult SMM in intensive longitudinal study designs due to factors such as increased participant burden. Second, it details two FI approaches utilized in two 5-day daily diary studies examining stress physiology and health behaviors among emerging adult SMM in the Midwest and the Northeast. Last, it discusses how the differing FI structures impacted participation and retention across the two studies. The chapter concludes by providing future directions to researchers who seek to employ intensive longitudinal study designs in emerging adult populations.
Sexuality in Emerging Adulthood
Authors: Killoren Sarah E. 
Published: September 2021

Abstract
Emerging adults’ relationships with parents and other family members are important for their sexuality development. Primarily, research on the roles of family members focuses on parents. Communication with parents, support from parents, and parents’ behaviors have both direct and indirect implications for emerging adults’ sexual values and behaviors. Furthermore, studies show that there are similarities and differences in how parents are influential on emerging adults’ sexuality based on gender, sexual minority status, race and ethnicity, and religious beliefs and practices. Although limited, there is evidence that family members other than parents, such as siblings and extended family, are important for emerging adults’ sexuality, particularly for certain cultural groups. The findings reviewed in this chapter have implications for practitioners working with families. Directions for future research are recommended.
Sexuality and Mental Health in Emerging Adulthood
Authors: Maheux Anne J , Choukas-Bradley Sophia 
Published: September 2021

Abstract
Sexual experience is considered an important developmental milestone for emerging adults. Whereas some sexual experiences incur benefits, others are associated with negative mental health outcomes. This chapter first describes the cultural context in which emerging adults experience their sexuality, including sexualized media, sexual scripts, hookup culture, and technology, and the impact of these contextual forces on emerging adults’ psychological well-being. The mental health effects of sexual behaviors are also discussed as they relate to various relational contexts, including committed romantic relationships, casual “hookups,” and ongoing casual relationships (e.g., “friends with benefits”), with an emphasis on the disproportionate negative outcomes for women and the limited empirical research on the impact of these experiences on racial and sexual minority individuals. The chapter further discusses the mental health outcomes affecting emerging adults with sexual and gender minority identities. The chapter concludes with important directions for future work, including longitudinal studies and greater attention to intersectionality.
Mistrusting Authorities in an Unstable World
Authors: Vermeulen Karla 
Published: September 2021

Abstract
The chapter “Mistrusting Authorities in an Unstable World” examines how members of Generation Disaster engage with the political system today, having grown up in a post-9/11, wartime climate when many felt lied to or misrepresented by politicians and other authorities. That was followed by the extreme divisiveness of U.S. politics in general during their adolescence and as they moved into emerging adulthood. While some have chosen to disengage entirely, others have been moved to protest, vote at record levels, and generally continue the tradition of trying to recapture power from older people they feel aren’t representing them adequately. The importance of civic engagement as a marker of adulthood, and the history of social movements in the United States, are also discussed.
Pornography and Body Image
Authors: Rothman Emily F. 
Published: September 2021

Abstract
There is a concern that the bodies that are shown to us in sexually explicit media are changing what we think is beautiful, are making us anxious and depressed, and even are pushing us to engage in self-harmful behavior. This chapter provides theoretical explanations for why pornography images could impair health and reviews studies that have investigated this question. The chapter covers findings related to pubic hair removal, labiaplasty, vulva acceptance, men’s genital dissatisfaction, satisfaction with body shape and size, self-esteem and self-confidence, and expectations of partners’ bodies. The chapter concludes that pornography likely harms some people’s self-image, and for a minority of those who are harmed, it drives them to extreme behaviors and has mental health consequences. For the majority, pornography either has no effect, improves how they feel about their bodies, or underscores the body-related attitudes that they have already acquired from non-sexually-explicit media.
Visually Verifying the Corporeal Christ
Authors: Wilson Brittany E. 
Published: September 2021

Abstract
This chapter approaches the question of God becoming manifest in human flesh from the perspective of Jesus’s own embodied fleshliness. After surveying early Christian views of Jesus’s humanity, the chapter focuses on the ways in which Luke uses visual verification to demonstrate that Jesus is an embodied human. From his birth to his resurrection, Luke uses the sense of sight, as well as touch, as a means to prove Jesus’s humanity and even his fleshliness (a move that may point ahead to future docetic debates). In this way, Luke’s account of Jesus’s embodiment goes beyond any biblical account of God’s embodiment, for God is never explicitly depicted in terms of “flesh.” But if one understands that God can become manifest in human form, and specifically Jesus’s form, then God’s form in fact finds its most concrete expression in the flesh-and-bone body of Jesus.
Information Resolution and Subnational Capital Markets
Authors: Martell Christine R. , Moldogaziev Tima T. , Espinosa Salvador 
Published: September 2021

Abstract
This book theorizes that information is a critical factor for subnational government (SNG) capital market formation and development. It empirically tests the stated relationship between information resolution institutions and mechanisms of information resolution on SNG borrowing. Based on empirical results, analyses of underlying fundamentals of city credit quality, and the study of contexts of information resolution reforms, the book recommends policy measures for central governments, regional and local governments, and financial sector firms to build capital markets for subnational borrowing. As subnational governments across the globe, especially cities, bear increasing pressures to provide critical capital infrastructure, responsibilities for the provision of local infrastructure resulting from decentralization efforts and population demands, the need for a wider array of internal and external resources, including bond market alternatives, become a priority. With information resolution, access to capital market financing becomes a feasible option of regional and local government finance. The evidence reported in this book demonstrates that SNG access to capital market financing depends on credit contractibility, which is the nation’s capacity of information resolution. The bases of credit contractibility are transparency of credit information, depth of credit information, dissemination, and regulatory quality. Evidence also shows that the informational content of underlying credit quality is a significant covariate of city-level borrowing and debt composition. Based on empirical findings and focusing on cities, the book argues that SNGs can and should strengthen their agency vis-à-vis the public and financial sector actors, in an environment where global capital is increasingly intertwined with the provision of critical infrastructure finance. Agency is necessary for city policymakers not only to achieve their key governance tasks efficiently, but do so effectively and equitably, consistent with the demands of the citizenry.