Clinical Cancer Research Research Articles

The PLATON Network: An interactive platform for precision oncology.

TPS1613 Background: To increase the access of patients to precision oncology and personalized medicine, we need not only to undertake molecular profiling but rather we need to interlink patients, physicians and researchers using modern technological opportunities, increasing the likelihood of providing new therapies to patients with suitable targets. The PLATON Network (NCT05489250, IKF-T008) addresses these important issues. Methods: The PLATON Network (PLATON) is an interactive structure aiming at improving personalized medicine for all tumor entities (starting with upper GI tumors). The goal of the PLATON Network is to provide a platform for connecting medical practitioners, researchers and patients to personalized cancer treatments. The platform combines comprehensive molecular profiling, data on active clinical trials, remote data access with networking solutions, implemented substudies and associated educational and discussion forums. The main elements of PLATON are: a Platform-study design, an interactive Cloud-based WebApp, Networking, a Molecular Pathology Case Discussion Board, an educational forum, and a BioDataBank. The network will be composed of a global network of cancer centers and cancer specialists who can submit genomic data of their patients to PLATON. The WebApp allows members and associated scientists to view each other's current patients' clinical and molecular data and get into contact with the treating physicians or identify patients for ongoing biomarker-driven clinical trials using advanced algorithms. The PLATON Network also offers molecular testing via Foundation CDx and CDx Liquid for standardized NGS testing and functions as an umbrella for substudies within the platform design. PLATON enrolls patients during first line treatment and collects information on routine clinical data (baseline data, medical history, histopathology reports, treatment decisions, etc.). During follow up, all anti tumor therapy lines, tumor response and survival data are recorded. Importantly, quality of life data is captured monthly under therapy (with EORTC QLQ-30,-BIL21, -HCC18, -PAN26, -STO22 and EQ-5D-5L) and at further follow up (with EQ-5D-5L). So far, 110 cancer centers have joined the PLATON network. Over 200 patients with upper GI tumors received comprehensive molecular profiling and 162 cases were reviewed and discussed in the Molecular Pathology Case Discussion Board. Five sub-projects/-studies have been initiated under the umbrella of PLATON. The educational forum is in the planning stage. PLATON is conducted by the Institute of Clinical Cancer Research (IKF) in Frankfurt with the supervision of an independent scientific steering committee.

Engaging European society at the forefront of cancer research and care: How discussions at the 5th Gago Conference on European Science policy led to the Heidelberg Manifesto

European cancer research stakeholders met in October 2022 in Heidelberg, Germany, at the 5th Gago conference on European Cancer Policy, to discuss the current cancer research and cancer care policy landscape in Europe. Meeting participants highlighted gaps in the existing European programmes focusing on cancer research, including Europe's Beating Cancer Plan (EBCP), the Mission on Cancer (MoC), Understanding Cancer (UNCAN.eu), and the joint action CRANE, and put forward the next priorities, in the form of the Heidelberg Manifesto for cancer research. This meeting report presents all discussions that shed light on how infrastructures can be effectively shaped for translational, prevention, clinical and outcomes cancer research, with a focus on implementation and sustainability and while engaging patients and the public. In addition, we summarize recommendations on how to introduce frameworks for the digitalization of European cancer research. Finally, we discuss what structures, commitment, and resources are needed to establish a collaborative cancer research environment in Europe to achieve the scale required for innovation.

A High Parameter Flow Cytometric Assay to Identify Human Myeloid Derived Suppressive Cells

Abstract The concept of myeloid derived suppressive cells (MDSCs) has emerged in recent years as a group of myeloid cells that pocess potent immunosuppressive activity. These cells expand under pathologic conditions and suppress the immune functions of T cells, dendritic cells, macrophages, and natural killer cells. They have been shown to be involved in the pathological states of cancer, autoimmune diseases, and infections, such as COVID-19. MDSCs are subset into PMN (polymorphonuclear)- and M (monocytic)-MDSCs. Phenotypic markers of MDSCs have been elucidated in recent years. Here Cytek® developed a 14-color, 16-marker, single-tube flow cytometric assay to analyzed MDSCs. The panel includes markers to exclude lymphoid lineage cells, and markers to identify PMN-MDSC and M-MDSC populations, such as CD15, CD14, CD16, CD66b, CD11b and HLA-DR. In addition, PMN- and M-MDSC specific expression markers such as Lox-1, CXCR-1, DR5 are also included. Fresh whole blood samples were stained with erythrocyte lyse wash method and the samples were analyzed on a Cytek® Aurora or 3-laser Northern Light TMinstrument. The panel performance was evaluated on blood samples collected in EDTA, Heparin, ACD, and Cytochex blood tubes as well as peripheral blood mononuclear cell (PBMC) samples. Assay precision was assessed by testing on 12 donor samples in triplicates on three consecutive days. Targeted cell populations are well identified in peripheral blood and PBMC samples with good resolution and assay precision with %CV less than 25% for all cell populations of interests. This 14-color 16-marker preoptimized flow cytometric assay can be used in clinical research and drug discovery in cancer, autoimmune diseases, infections and other inflammatory diseases.

Practical strategies for creating diversity, equity, inclusion, and access in cancer clinical research: DRIVE.

Practical strategies for creating diversity, equity, inclusion, and access in cancer clinical research: DRIVE.

Delivery of Doxorubicin by Ferric Ion-Modified Mesoporous Polydopamine Nanoparticles and Anticancer Activity against HCT-116 Cells In Vitro

In clinical cancer research, photothermal therapy is one of the most effective ways to increase sensitivity to chemotherapy. Here, we present a simple and effective method for developing a nanotherapeutic agent for chemotherapy combined with photothermal therapy. The nanotherapeutic agent mesoporous polydopamine-Fe(III)-doxorubicin-hyaluronic acid (MPDA-Fe(III)-DOX-HA) was composed of mesoporous polydopamine modified by ferric ions and loaded with the anticancer drug doxorubicin (DOX), as well as an outer layer coating of hyaluronic acid. The pore size of the mesoporous polydopamine was larger than that of the common polydopamine nanoparticles, and the particle size of MPDA-Fe(III)-DOX-HA nanoparticles was 179 ± 19 nm. With the presence of ferric ions, the heat generation effect of the MPDA-Fe(III)-DOX-HA nanoparticles in the near-infrared light at 808 nm was enhanced. In addition, the experimental findings revealed that the active targeting of hyaluronic acid to tumor cells mitigated the toxicity of DOX on normal cells. Furthermore, under 808 nm illumination, the MPDA-Fe(III)-DOX-HA nanoparticles demonstrated potent cytotoxicity to HCT-116 cells, indicating a good anti-tumor effect in vitro. Therefore, the system developed in this work merits further investigation as a potential nanotherapeutic platform for photothermal treatment of cancer.

Abstract 1942: Effectiveness of community outreach/engagement and faith-based strategies among African American & African Nationals to increase cancer clinical trials participation using a culturally tailored educational manual

Abstract Background: The importance of diversity in clinical trials is vital to ensure treatments and medications work and respond well for everyone. In contrast to other ethnic groups, AAs are disproportionately affected by various types of cancers in the U.S., such as prostate & pancreatic cancer, and have higher cancer mortality rates. Yet AA participation in cancer clinical trials remains extremely low. Black/African Americans make up 13.4% of the US population and have a clinical trial enrollment rate of less than 5%. In comparison, White/Caucasians make up about 67% of the US population and have a 75% enrollment rate in clinical trials and the Asian community makes up less than 6% of US population and have a 15% participation rate in clinical trials. Reported factors that have influenced Black/African American clinical trials enrollment rates are little awareness of clinical trials, religious beliefs, and access to health care barriers. Improving clinical trial participation among African Americans/African Nationals (AA/AN) is essential to reduce cancer health disparities because it gives opportunity to increased access to breakthrough cancer therapies and treatments. Methods: To address these disparities, we composed an AA/AN Clinical Trials manual to be distributed among these populations living in Los Angeles County (LAC). The AA/AN manual modules review: 1) Intro to Clinical Trials 2) Demographics 3) Types of clinical trials 4) Phases of clinical trials 5) Safety of clinical trials 6) The role of faith among AA communities and 7) Life during and after clinical trials. There is also a Call to Action to share the manual information with friends and family, to talk with one’s primary care physician and get screened, and to participate in clinical trials. The manual was culturally and linguistically adapted to deliver lay messages on clinical trials as needed, using graphs, infographics, and educational videos featuring clinical trials cancer researchers and experts. Results: 90 Churches in Los Angeles County serving AA/AN communities have been provided with avirtual copy of the Clinical Trials manual to be disseminated among their communities. Additionally, have participated in 7 major community health events in LAC to outreach and engage African American community members at which we have distributed 822 hard copy clinical trials manuals between November of 2021 and November of 2022. Conclusion: Involvement of faith-based communities in outreach and engagement strategies mayincrease cancer clinical trials participation among African American communities. The utilization of culturally sensitive and adapted educational materials may increase access to information on clinical trials and contribute to tackle clinical trials enrollment barriers affecting underserved minorities. Citation Format: Lourdes A. Baezconde-Garbanati, Carolina Aristizabal, Eduardo Ibarra, Cynthia Quince. Effectiveness of community outreach/engagement and faith-based strategies among African American & African Nationals to increase cancer clinical trials participation using a culturally tailored educational manual [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1942.

Abstract 2295: Utility of circulating tumor DNA in lung cancer clinical research and practice: systematic review and meta-analysis

Abstract Background: Circulating tumor DNA (ctDNA) has been increasingly used in the clinical care of patients with cancer. This systematic review summarized current data on the utility of ctDNA in lung cancer clinical research and practice and provides insights for integrating ctDNA into drug development and patient care. Methods: The Embase database was used to identify clinical research articles of ctDNA in lung cancer from 2015 to 2020. ctDNA clinical utilities were reviewed and summarized into 3 areas: early diagnosis, prognostication, and monitoring disease progression/treatment response. Associations of ctDNA with progression-free survival (PFS) and overall survival (OS) were estimated in the embedded meta-analysis. Pooled estimates were calculated using fixed-effect or random-effect models depending on study heterogeneity. Results: After screening and review, 111 studies were included. ctDNA testing has been increasing in recent years, with 54.1% of the selected studies published in 2019 or 2020. 73.0% of the studies were conducted in patients with advanced/metastatic disease; 79.3% included patients with non-small cell lung cancer (NSCLC). ctDNA was used mainly for prognostication (76.6%), demonstrating that the presence of ctDNA is associated with poor prognosis. In the meta-analyses, overall ctDNA detection/positivity was associated with shorter PFS (n=622; HR=2.34; 95% CI, 1.90-2.89) and OS (n=723; HR=2.33; 95% CI, 1.91-2.85). Studies focused specifically on EGFR mutations in ctDNA reported similar prognostication results. Heterogeneity by stage, histological type, and ctDNA measurement timing were evaluated and showed no significant impact on these pooled estimates. ctDNA clearance/decrease during treatment was associated with a lower risk of progression (n=552; HR=0.24; 95% CI, 0.19-0.31) and death (n=669; HR=0.40; 95% CI, 0.27-0.60). Few studies evaluated the utility of ctDNA in lung cancer for diagnosis or monitoring tumor progression across the treatment spectrum. Conclusions: Recent studies demonstrated the clinical value of ctDNA in lung cancer prognostication/monitoring, primarily in advanced NSCLC. Large, multicenter clinical trials and real-world longitudinal data sets are needed to validate these findings, and prospective trials are required to address challenges related to integrating ctDNA testing into clinical practice. Citation Format: Solange Peters, Page Abrahamson, Nicholas Ballew, Linda Kalilani, Kelesitse Phiri, Kelly Bell, Alexander Slowley, Maglalena Zajac, Erin Hofstatter, Alexander Stojadinovic, Angela Silvestro, Zebin Wang, Amine Aziez, Xuezheng Sun. Utility of circulating tumor DNA in lung cancer clinical research and practice: systematic review and meta-analysis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 2295.

Abstract 6695: Utility of circulating tumor DNA in breast cancer clinical research and practice: systematic review and meta-analysis

Abstract Background: Circulating tumor DNA (ctDNA) has been increasingly used in the clinical care of patients with cancer. This systematic review summarizes current data on the utility of ctDNA in breast cancer clinical research and practice and provides insights for integrating ctDNA into drug development and patient treatment. Methods: The Embase database was used to identify original clinical research articles of ctDNA in breast cancer published from 2015 to 2020. ctDNA clinical utilities were reviewed and summarized, focusing on 3 areas: early diagnosis, prognostication, and monitoring disease progression/treatment response. Associations of ctDNA with disease-free survival (DFS) and overall survival (OS) were estimated in the embedded meta-analysis. Pooled estimates were calculated using fixed-effect or random-effect models depending on study heterogeneity. Results: After screening and review, 72 articles were included. ctDNA studies have increased in recent years, with 59.7% of included articles published in 2019 or 2020. Overall, 61.1% of the studies were in patients with advanced stage/metastatic cancer; 45.8% were restricted to patients with specific cancer subtypes. ctDNA was minimally used in diagnosis; it was predominantly used in clinical outcome prediction with differences by stage. In patients with early-stage disease, the meta-analyses found that overall ctDNA detection/positivity was associated with shorter DFS (n=697; HR, 5.37; 95% CI, 2.94-9.80) and OS (n=238; HR, 4.60; 95% CI, 2.56-8.26). Specific gene mutations in ctDNA were mainly assessed in patients with advanced/metastatic disease, with mutations of ERBB, ESR1, and TP53 linked to shorter DFS in the meta-analyses (P<0.05). Moreover, current studies provided evidence that ctDNA reflects the dynamics of breast tumors in the patient treatment journey, acting as a biomarker to monitor tumor evolution and drug resistance. Conclusions: Recent studies demonstrate ctDNA application in breast cancer prognostication/monitoring, suggesting an important role in patient stratification, molecular relapse identification, and personalized treatment. Large, multicenter clinical trials and real-world longitudinal data sets are needed to validate findings and to address challenges related to ctDNA to improve clinical utility and to integrate ctDNA testing into clinical practice and drug development. Citation Format: Xuezheng Sun, Nicholas Ballew, Linda Kalilani, Kelesitse Phiri, Kelly Bell, Alexander Slowly, Magdalena Zajac, Erin Hofstatter, Angela Silvestro, Zebin Wang, Jeanne Schilder. Utility of circulating tumor DNA in breast cancer clinical research and practice: systematic review and meta-analysis. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 6695.

Abstract 1941: Barriers and effective interventions to engage Latinas' participation in breast cancer clinical trials

Abstract Breast cancer is the most diagnosed cancer among Latina women and is the leading cause of cancer-related death among Latinas (16.6%). While The Latino population is one of the fastest-growing populations in the US, they are severely underrepresented in clinical trials. Latinos make up 17% of the population but only 1% of clinical trial participants. Of clinical trials published covering 2001-2010, Latinos’ enrollment constituted only 2.2% of accrued participants. The percentage of Latino participants narrows down when we separate by gender. The goal of this study is to examine the prevalence of breast cancer-related barriers among Latinas and to determine the extent to which these barriers might influence Latinas enrolling in breast cancer clinical trials. If language and religion are the reason Latinas enroll less in breast cancer clinical trials, then increasing the availability of translated materials and a priest of a Catholic Church advertising the breast cancer studies will increase the enrollment rate of Latinas. Semi-constructed interviews were conducted with two Latino organizations to understand current barriers Latina’s face within the medical field. Based on these findings, I conducted an intervention at Our Lady of Tepeyac Church consisting of an information booth, making an announcement regarding Research Study 9127, and having bilingual Latinas available to give out more information while helping them enroll in Research Study 9127. At the end of the church intervention, 33 Latinas were enrolled in Research Study 9127, seeing a 550% increase in Latinas participating in Research Study 9127. Latinx women remain severely underrepresented in breast cancer clinical trials, thus limiting the generalizability of cancer clinical research, but interventions across churches would lead to improvements in general cancer knowledge, breast cancer screening practices, and intentions to enroll in clinical trials. This study can inform efforts to increase clinical trial participation in Latinas by highlighting important motivators to participation specific to Latinas and informing future interventions aimed at encouraging participation in clinical trials in a culturally sensitive and effective way. Citation Format: Monica J. Padilla, Gregory Karczmar. Barriers and effective interventions to engage Latinas' participation in breast cancer clinical trials [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1941.

Completion and publication of clinical trials in a cooperative group: a cohort study of trials of the Swiss Group for Clinical Cancer Research (SAKK)

BackgroundPremature trial discontinuation and non-publication of trial results are still major issues negatively affecting reliable evidence generation.ObjectivesTo investigate trial completion and publication rate of cancer trials conducted within the Swiss...

Defining the role of real-world data in cancer clinical research: The position of the European Organisation for Research and Treatment of Cancer

The emergence of the precision medicine paradigm in oncology has led to increasing interest in the integration of real-world data (RWD) into cancer clinical research. As sources of real-world evidence (RWE), such data could potentially help address the uncertainties that surround the adoption of novel anticancer therapies into the clinic following their investigation in clinical trials. At present, RWE-generating studies which investigate antitumour interventions seem to primarily focus on collecting and analysing observational RWD, typically forgoing the use of randomisation despite its methodological benefits. This is appropriate in situations where randomised controlled trials (RCTs) are not feasible and non-randomised RWD analyses can offer valuable insights. Nevertheless, depending on how they are designed, RCTs have the potential to produce strong and actionable RWE themselves. The choice of which methodology to employ for RWD studies should be guided by the nature of the research question they are intended to answer. Here, we attempt to define some of the questions that do not necessarily require the conduct of RCTs. Moreover, we outline the strategy of the European Organisation for Research and Treatment of Cancer (EORTC) to contribute to the generation of robust and high-quality RWE by prioritising the execution of pragmatic trials and studies set up according to the trials-within-cohorts approach. If treatment allocation cannot be left up to random chance due to practical or ethical concerns, the EORTC will consider undertaking observational RWD research based on the target trial principle. New EORTC-sponsored RCTs may also feature concurrent prospective cohorts composed of off-trial patients.

Advancing wide implementation of precision oncology: A liquid nitrogen-free snap freezer preserves molecular profiles of biological samples.

In precision oncology, tumor molecular profiles guide selection of therapy. Standardized snap freezing of tissue biospecimens is necessary to ensure reproducible, high-quality samples that preserve tumor biology for adequate molecular profiling. Quenching in liquid nitrogen (LN2 ) is the golden standard method, but LN2 has several limitations. We developed a LN2 -independent snap freezer with adjustable cold sink temperature. To benchmark this device against the golden standard, we compared molecular profiles of biospecimens. Cancer cell lines and core needle normal tissue biopsies from five patients' liver resection specimens were used to compare mass spectrometry (MS)-based global phosphoproteomic and RNA sequencing profiles and RNA integrity obtained by both freezing methods. Unsupervised cluster analysis of phosphoproteomic and transcriptomic profiles of snap freezer versus LN2 -frozen K562 samples and liver biopsies showed no separation based on freezing method (with Pearson's r 0.96 (range 0.92-0.98) and >0.99 for K562 profiles, respectively), while samples with +2h bench-time formed a separate cluster. RNA integrity was also similar for both snap freezing methods. Molecular profiles of liver biopsies were clearly identified per individual patient regardless of the applied freezing method. Two to 25 s freezing time variations did not induce profiling differences in HCT116 samples. The novel snap freezer preserves high-quality biospecimen and allows identification of individual patients' molecular profiles, while overcoming important limitations of the use of LN2 . This snap freezer may provide a useful tool in clinical cancer research and practice, enabling a wider implementation of (multi-)omics analyses for precision oncology.

Advances and prospects of drug clinical research in colorectal cancer in 2022.

Colorectal cancer (CRC) is the third most common cancer and the second leading cause of cancer death worldwide. Clinical research results have provided more treatment opportunities for CRC patients, showing that an optimal combination of existing drugs and new drugs is needed to mitigate the burden of this disease. In this review, we have summarized recent advances in drug clinical research for CRC in 2022, including chemotherapy, targeted therapy, and immunotherapy, to find opportunities for substantial improvements in drug discovery and clinical development methods.

Editorial: Clinical cancer research in vulnerable populations

Editorial: Clinical cancer research in vulnerable populations

Abstract OT2-15-01: COntinue the SaMe systemic therapy after local ablative therapy for Oligoprogression in metastatic breast cancer - the COSMO study

Abstract Background Patients with metastatic breast cancer (MBC) are usually treated with palliative systemic therapy until progression or unacceptable toxicity. When progression occurs, clinicians typically switch to the next line of systemic therapy. However, this strategy might be suboptimal in case of mixed response or oligoprogression. Oligoprogression refers to a situation in which inter-lesion heterogeneity causes one or few metastatic lesions to progress while the vast majority of the metastatic burden responds to the treatment. Locally ablative treatment of the progressive lesion(s) with radiotherapy, resection or radiofrequency ablation may enable continuation of otherwise effective systemic treatment. Solid data to support this approach, however, is lacking at this moment. Study design The COSMO study is an investigator-initiated single-arm phase 2 study. It is intended to be a multicenter study. Eligibility criteria Patients with MBC and oligoprogression, defined as 1-2 progressive lesions while the majority of the metastatic burden remains stable or in remission, are eligible. Current systemic therapy must be 1st or 2nd line and patients must have responded to this systemic therapy for at least six months prior to the occurence of oligoprogression. The aberrant lesion must be amenable to locally ablative therapy. All eligibility criteria may be found in table 1: eligibility criteria. Aim To investigate efficacy of local ablation of aberrant lesions combined with continuation of the same systemic therapy in patients with oligoprogression of MBC. Primary endpoint: Progression-free survival rate at six months (PFS-6). Secondary endpoints: - PFS - Overall survival - Time to next line of systemic therapy Primary and secondary endpoints will also be stratified by localization of progressive lesion and BC subtype (ER+/HER2- vs. HER2+ vs. TN). - Local control rate of lesion treated with LAT at 12 months - Complications due to LAT - Quality of life - Incidence of visceral crisis Exploratory endpoints: - Biomarkers, including receptor (ER/PR/HER2), PD-L1 and gene expression patterns in biopsies from progressive and responding lesions - Prognostic value of ctDNA at oligoprogression and during the course of treatment Statistical methods An A’hern design was chosen to conduct this study. As null-hypothesis (H0), PFS-6 rate ≤ 25% is set. The alternative hypothesis (H1) is PFS-6-rate ≥ 40%. Hypotheses were set to meet criteria for clinical significance, as stated by experts in the field. Setting one-sided α = 0.05 and a desirable power=95%, 107 evaluable patients are needed. To account for 10% of the patients to be unevaluable, 118 included patients are needed. An early stopping rule for safety is applicable: if out of the first 45 patients ≥4 of these patients have developed visceral crisis, the study will be closed early. Accrual Start: July 2022 Target: 118 patients Estimated accrual time: 2-3 years Further information Corresponding author: c.almekinders@nki.nl Clinicaltrials.gov identifier: NCT05301881 This study is funded by the Maarten van der Weijden foundation. This study was developed during the 21st EORTC/ESMO/AACR workshop on methods in clinical cancer research (MCCR). Table 1. Eligibility criteria. Citation Format: Cornelia AM Almekinders, Tessa G Steenbruggen, Ingrid A. Mandjes, Marta Lopez-Yurda, Monique EMM Bos, Terry G Wiersma, Gabe S. Sonke. COntinue the SaMe systemic therapy after local ablative therapy for Oligoprogression in metastatic breast cancer - the COSMO study [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr OT2-15-01.

Abstract P3-04-07: Safety and artifact testing of a nitinol breast biopsy clip in an ultra-high resolution magnetic resonance imaging (MRI) environment

Abstract Background: The lack of safety clearance of several metallic breast implants in 7T(Tesla) poses a significant hurdle to standard clinical breast cancer care and research from reaping the benefits of ultra-high resolution MR imaging. A breast biopsy clip (Ultracor Twirl, Becton, Dickinson and Company, Vernon Hills, IL) composed of nitinol, was tested for safety and artifact susceptibility clearance in a 7T MRI scanner, using standardized procedures. This clearance is significant in henceforth allowing patients with this implant to be scanned in now FDA approved ultra-high-field MRI scanners of 7T or less for clinical and research purposes. Methods: Tests for magnetic susceptibility (torque and translational attraction), MRI-related heating, and artifacts were conducted as per standardized protocols. The torque and translational attraction tests evaluated the effects of magnetic force by the MRI to cause the clip to move and twist respectively. The heating test was conducted with customized MR parameters of short TR (repetition time) and maximum echo-train length, designed to induce temperature change. The artifact test using T1 weighted spin and gradient echo imaging sequences, evaluated potential localized signal loss that may result in misrepresentation of the imaged area. This may occur due to the presence of the metallic clip in the MR environment. Results: The torque and translational attraction tests respectively indicated that the MR environment did not induce any movement in the clip in eight orientations, with a deflection angle of 0 degrees. Results of the heating test indicated no significant temperature change of the clip. A temperature change of less than 0.45C° was observed in the phantom gel in both the absence and presence of the clip, which is well within the safety threshold (< 1°C). Results of the artifact test indicated a very small artifact, with the largest artifact cross-sectional area appearing on gradient echo images. Conclusion: These cumulative results indicate that the Ultracor Twirl breast biopsy clip is safe for imaging patients at 7T. Citation Format: William Dong, Kanchna Ramchandran, Adam Galloy, Marco A. Nino, Marla Kleingartner, Madhavan L. Raghavan, Sneha Phadke, Vincent A. Magnotta. Safety and artifact testing of a nitinol breast biopsy clip in an ultra-high resolution magnetic resonance imaging (MRI) environment [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P3-04-07.

Abstract OT2-21-01: Assessing Response to neoadjuvant Taxotere and TrAstuzumab in Nigerian women with HER2-positive breast cancer (ARETTA)

Abstract Background: Populations of African ancestry are underrepresented in global oncology clinical trials resulting in paucity of data on safety and efficacy of cancer medicines in vulnerable Black populations. The ARETTA clinical trial was initiated by the Nigerian Breast Cancer Study Team in partnership with the University of Chicago Comprehensive Cancer Center to build local capacity for biomarker informed clinical trials and translational breast cancer research. ARETTA is a pragmatic single-arm, phase II clinical trial to optimize therapy and determine the safety and efficacy of neoadjuvant taxotere and trastuzumab in women with HER2-positive breast cancer. The study sought to 1) determine the pathological complete response (pCR) rate of patients with early stage breast cancer to neoadjuvant docetaxel and subcutaneous trastusumab 2) develop the capacity of investigators in Nigeria to improve quality of care through participation in oncology clinical trials using upgraded facilities and trained personnel and 3) determine accrual rate and retention of participants. Methods: Inclusion criteria include treatment naïve women aged 18 years to 70 years with HER-2 positive breast cancer stages II-IIIC (AJCC). Eligible participants receive four cycles of docetaxel 75mg/m2 and trastuzumab every 3 weeks. Those with incomplete clinical response by breast ultrasound volume measurements receive 3 additional cycles of chemotherapy; cyclophosphamide 600mg/m2, epirubicin 90mg/m2 and 5-fluorouracil 600mg/m2 every 3 weeks before re-evaluation for surgery. All participants receive a fixed dose of sub-cutaneous Herceptin (600mg) every 3 weeks (total of 18 doses). The primary endpoint is pCR rate. Secondary objectives are to evaluate invasive disease-free survival (iDFS), the pattern of response and mechanisms of resistance to treatment based on genomic markers, the pharmacokinetics of Herceptin SC, quality of life, and adverse event rates, including cardiac toxicity. Planned enrollment is 47 evaluable patients, which will provide 90% power to test the null hypothesis that the pCR rate is 20% versus a 40% alternative (one-sided alpha=0.05). More protocol details can be found at ClinicalTRial.gov NCT03879577 and JCO Glob Oncol2020 doi: 10.1200/GO.20.00043 Progress: The study has met its primary endpoint and will be closed to accrual by the time of the meeting. Results will be submitting as Late Breaking before the meeting Citation Format: Atara Ntekim, Adenike Adeniji-Sofoluwe, Abiola Ibraheem, Anthonia Sowunmi, Ayorinde Folasire, Thomas Olajide, Olalekan Olasehinde, Akinwunmi Komolafe, AbdulRazzak Lawal, Foluso Omodele, Ayodele Sanni, Mustapha Ajani, Olayinka Kotila, Sharifat Folorunsho, Tonyin Aniagwu, Adewumi Alabi, Abiodun Popoola, Chioma Asuzu, Adetola Daramola, Chinedum Babalola, Theodore Karrison, Fatimah Abdulkareem, Olufunmilayo I. Olopade. Assessing Response to neoadjuvant Taxotere and TrAstuzumab in Nigerian women with HER2-positive breast cancer (ARETTA) [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr OT2-21-01.

Abstract P6-09-03: Examining recollections of Black women with breast cancer who participated in clinical trials: A grounded practical theory study of patient-provider communication

Abstract Introduction: The presence of strong barriers to research participation for Black and Brown women is indisputable. However, existing evidence clearly supports the possibility of equal levels of participation among members of minoritized populations in past breast cancer clinical trials, demonstrating that while these participation barriers do undoubtedly exist, they are not always insurmountable. A main implication of this current study is that researchers should take greater strides to remove the onus of recruitment responsibility from racialized population members, and instead leave it with the providers, investigators, and health care teams who hold enough power to make change. Purpose: This project takes a grounded practical theory (GPT) approach to engage with Black women who have been diagnosed with breast cancer and have participated in a breast cancer clinical trial and explores their recollections of conversations with their providers. GPT focuses on reconstructing particular communication practices, highlighting both the important procedural role of communication in practice and its ability to present intricate complications that echo society’s norms and values. The aim of this work is to investigate and analyze those patient-provider conversations to try to illuminate how providers can better engage these women in ways that will positively influence their perceptions of breast cancer clinical trial participation. Methods: The current study was part of a larger project examining the recruitment of Black women to breast cancer clinical trials. Fourteen women (N=14) from six different states in the U.S., all of whom self-identified as Black, Black American, or African American, agreed to be interviewed as part of a larger study. All participants had participated or were currently participating in a breast cancer clinical trial. The interviews yielded a wealth of interesting and potentially important additional data about Black female breast cancer patients and their communication experiences with their providers. Employing grounded practical theory as a framework helped increase insight into the patient-provider communication needs of Black women who have participated in a breast cancer clinical trial. Results: Findings were summarized into four categories: 1) the participants held differing perspectives and personal impressions toward their providers; 2) the women reflect on their individual breast cancer journeys through richly described incidences, describing searching for, and finding trials on their own, or being guided by healthcare providers who suggested a clinical trial for them; 3) each participant’s shared details of their unique communication relationship with medical and research providers; and 4) the cultural aspects of participants’ patient-provider communication, focusing primarily on their expressions of faith. These findings have important implications for health communication scholars, healthcare providers, and breast cancer clinical trial research principal investigators and team members. Conclusion: As opposed to the conclusion that one may draw from most published explanations of poor minority accrual to clinical trials, which appear to put the blame on the minoritized population members themselves, the current work outlines the actions and non-actions of many providers, and suggests that adjusting to approaches that demonstrate more encouragement and acceptance of their patients might result in better clinical trial participation outcomes from these group members. Citation Format: Precious Okoruwa, Katherine E. Ridley-Merriweather. Examining recollections of Black women with breast cancer who participated in clinical trials: A grounded practical theory study of patient-provider communication [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P6-09-03.

Abstract P6-14-02: Hope for OTHERS – An organ donation program for metastatic breast cancer research

Abstract Background: Previous studies have shown that rapid autopsies (RA) provide a unique opportunity for tissue collection from patients who succumb to the disease. Because cancer patients are unable to donate their organs to other people, this program provides the patient an opportunity to leave a legacy by donating their body to research. These donations are vital for advancing breast cancer research. The UPMC/Pitt RA group revamped an existing program in 2018 through the formation of a larger multidisciplinary team that includes breast cancer laboratory and clinical researchers, pathologists, nurses, bioinformaticians, and tissue bankers. Because recruitment to the RA program was a challenge, we recently added patient advocates to the team to provide their essential perspective, and a dedicated research coordinator who serves as an ambassador for the program. Methods: Autopsy is performed by the Autopsy and Forensic Pathology Center of Excellence/Decedent Affairs Service of UPMC. Samples are banked in the Pitt Biospecimen Core (PBC), in addition to immediate processing including preparing of samples for sequencing and growing of organoids in the laboratory. Immunohistochemical (IHC) analysis is performed by UPMC/Magee Pathology. Results: The research coordinator quickly became an integral part of the program and closely interacts with care providers, patients and their families, pathologists on call, and manages interactions with transport services. Five breast cancer advocates have been instrumental in advising on additional changes to the program. The advocates attend regular team meetings and have formulated patient considerations for the the RA program, including appropriate and sensitive recruitment of patients, the role of physicians in decision making by the patient, registration for more than one RA program, potential issues with transporting a body across state lines and more. The advocates also developed the name for the program - “Hope for OTHERS” with Others standing for “Our Tissue Helping Enhance Research & Science”. As of June 2022, the team has completed 26 autopsies, and an additional 20 patients have consented to the program. The completed autopsies include patients with breast tumors representing different molecular and histological classes, ethnicities, and genders. The average disease-free survival and overall survival of patients that underwent autopsy was 81.6 and 127.8 months, respectively. Most patients passed outside the hospital (86%), with 62% in home hospice and 24% in inpatient hospice. Average time between death and start and end of autopsy was 4.56 hrs and 7.09 hours, respectively. The most common metastatic sites from which specimens are collected are liver, lung and lymph nodes. Per patient we collect on average specimens from 4 different organs. In addition to the metastatic lesions, we have access to primary tumor tissue and liquid biopsies obtained during the breast cancer disease progression for 44% and 73% of the patients, respectively. For a subset of the patients, tissue has been grown as patient-derived organoids or xenograft models. Preliminary IHC and sequencing analysis has provided insight into inter- and intra-patient and intra-tumor heterogeneity. Further molecular studies are ongoing. Conclusion In summary, over the last 5+ years, we have established a successful post-mortem tissue collection program, by addressing a series of barriers through the formation and work of a multi-disciplinary well-coordinated team. We are currently expanding our omics studies using state-of-the-art technologies to improve understanding how intra- and inter-tumor heterogeneity play a role in the clinical course of advanced breast cancer, to increase diversity of the patients enrolled in the RA program, and to support the successful implementation of other RA programs nationwide and worldwide. Citation Format: Steffi Oesterreich, Lori Miller, Margaret Q. Rosenzweig, Tanner L. Bartholow, Megan Yates, Ashuvinee Elangovan, Laura Savariau, Allison N. Casey, Nolan Priedigkeit, Kai Ding, Abdalla Wedn, Jie Bin Liu, Daniel D. Brown, Tara Hyder, Geoffrey Pecar, Neil Carleton, Humberto Trejo Bittar, Daniel Geisler, Oscar Lopez-Nunez, Amanda M. Clark, Alan Wells, Partha Roy, Shannon Puhalla, Naomi Howard, Christine Needles, Susan Trent, Stephanie Walker, Christine Hodgdon, Rohit Bhargava, Jennifer M. Atkinson, Adrian V. Lee. Hope for OTHERS – An organ donation program for metastatic breast cancer research [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P6-14-02.

Abstract P4-01-25: Safety analysis after 11 years of follow-up of the randomized phase III trial SAKK22/99: upfront chemotherapy in advanced HER2 positive breast cancer

Abstract P4-01-25: Safety analysis after 11 years of follow-up of the randomized phase III trial SAKK22/99: upfront chemotherapy in advanced HER2 positive breast cancer