Cancer Clinical Studies Research Articles

Microorganisms and Breast Cancer: An In-Depth Analysis of Clinical Studies.

Breast cancer is a multifactorial disease that affects millions of women worldwide. Recent work has shown intriguing connections between microorganisms and breast cancer, which might have implications for prevention and treatment. This article analyzed 117 relevant breast cancer clinical studies listed on ClinicalTrials.gov selected using a bespoke set of 38 search terms focused on bacteria, viruses, and fungi. This was supplemented with 20 studies found from a search of PubMed. The resulting 137 studies were described by their characteristics such as geographic distribution, interventions used, start date and status, etc. The studies were then collated into thematic groups for a descriptive analysis to identify knowledge gaps and emerging trends.

Efficacy and safety of molecularly targeted agents and immune checkpoint inhibitors for unresectable or recurrent/metastatic oral cancer in Japan

Background/purposeFor unresectable recurrent/metastatic head and neck cancer, pembrolizumab alone or pembrolizumab combined with cisplatin and 5-fluorouracil is the first-line therapy, depending on the PD-L1 combined positive score (CPS). However, this is based on clinical studies of head and neck cancer, and few similar studies have been conducted on oral cancer alone. This study aimed to investigate the current status of pharmacotherapy for unresectable, recurrent, or metastatic oral cancer. Materials and methodsPatients with unresectable or recurrent/metastatic oral cancer who received cetuximab, nivolumab, or pembrolizumab as first-line treatment were reviewed. Overall survival (OS), progression-free survival (PFS), PFS 2 (PFS2), overall response rate (ORR), disease control rate (DCR), and immune-related adverse events were obtained from medical records. ResultsA total of 155 patients were enrolled from six hospitals. The ORR in the nivolumab, pembrolizumab, and cetuximab groups was 17.2 %, 4.2 %, and 21.6 %, respectively, and the DCR was 37.9 %, 41.7 %, and 58.8 %, respectively. Median OS in nivolumab, pembrolizumab, and cetuximab groups was 10.3, 9.5, and 11.1 months, respectively. No significant differences were observed in survival among the three groups. The small number of cases and the retrospective nature of the study precluded the determination of the more effective first-line treatment among the three drugs. ConclusionThe current statuses of nivolumab, pembrolizumab, and cetuximab in unresectable recurrent metastatic oral cancer was reported.

Wavelet scattering networks in deep learning for discovering protein markers in a cohort of Swedish rectal cancer patients.

Cancer biomarkers play a pivotal role in the diagnosis, prognosis, and treatment response prediction of the disease. In this study, we analyzed the expression levels of RhoB and DNp73 proteins in rectal cancer, as captured in immunohistochemical images, to predict the 5-year survival time of two patient groups: one with preoperative radiotherapy and one without. The utilization of deep convolutional neural networks in medical research, particularly in clinical cancer studies, has been gaining substantial attention. This success primarily stems from their ability to extract intricate image features that prove invaluable in machine learning. Another innovative method for extracting features at multiple levels is the wavelet-scattering network. Our study combines the strengths of these two convolution-based approaches to robustly extract image features related to protein expression. The efficacy of our approach was evaluated across various tissue types, including tumor, biopsy, metastasis, and adjacent normal tissue. Statistical assessments demonstrated exceptional performance across a range of metrics, including prediction accuracy, classification accuracy, precision, and the area under the receiver operating characteristic curve. These results underscore the potential of dual convolutional learning to assist clinical researchers in the timely validation and discovery of cancer biomarkers.

Radiomics in the Diagnosis of Gastric Cancer: Current Status and Future Perspectives.

Gastric cancer is a malignant cancerous lesion with high morbidity and mortality. Preoperative diagnosis of gastric cancer is challenging owing to the presentation of atypical symptoms and the diversity of occurrence of focal gastric lesions. Therefore, an endoscopic biopsy is used to diagnose gastric cancer in combination with imaging examination for a comprehensive evaluation of the local tumor range (T), lymph node status (N), and distant metastasis (M). The resolution of imaging examinations has significantly improved with the technological advancement in this sector. However, imaging examinations can barely provide valuable information. In clinical practice, an examination method that can provide information on the biological behavior of the tumor is critical to strategizing the treatment plan. Artificial intelligence (AI) allows for such an inspection procedure by reflecting the histological features of lesions using quantitative information extracted from images. Currently, AI is widely employed across various medical fields, especially in the processing of medical images. The basic application process of radiomics has been described in this study, and its role in clinical studies of gastric cancer has been discussed.

Are sex and gender considered in head and neck cancer clinical studies?

We analyzed the inclusion of sex and/or gender (S/G) in Head and Neck Cancer (HNC) clinical studies, through inspecting ClinicalTrials.gov (AACT) and the mention of Human Papilloma Virus (HPV) on a specific subgroup, namely oral cavity, larynx and oropharynx. Only 5% of HNC studies mention S/G as a planned analytical variable. Proportionally more observational studies treated S/G as an analytical variable than interventional studies (10% vs 5%, P-value ≤ 0.001), 8% of studies that mentioned S/G involved more than 100 subjects while 4% less than 100 (P-value ≤ 0.001). In randomized protocols, S/G was mentioned more in studies with a planned sample of more than 100 patients and including HPV status (P-value < 0.05). Small controlled studies have lower mention of S/G as an analytical variable than uncontrolled studies (4% and 10%, respectively among studies with less than 100 subjects). Significantly greater mention of S/G as an analytical variable is observed in controlled and randomized studies with a sample size greater than 100 subjects. HPV was mentioned in only 18% of oral cavity-larynx-oropharynx studies. Interventional studies do not regularly account for S/G during HNC study design. Thus, although fundamental, in studies concerning HNC the S/G variable is often not considered. In trials published in scientific journals (P-value = 0.01) and in more recent clinical trials (P-value = 0.002), S/G is taken more into account suggesting an increasing awareness on its importance. However, the need to systematically include S/G in study design clearly emerges, to better highlight sex-related differences in disease incidence and prognosis and best imbue science and medicine with the proper biological and cultural differences.

Suppression of MUC1-Overexpressing Tumors by a Novel MUC1/CD3 Bispecific Antibody.

Mucin1 (MUC1) is abnormally glycosylated and overexpressed in a variety of epithelial cancers and plays a critical role in tumor progression. MUC1 has received remark attention as an oncogenic molecule and is considered a valuable tumor target for immunotherapy, while many monoclonal antibodies (mAbs) targeting MUC1-positive cancers in clinical studies lack satisfactory results. It would be highly desirable to develop an effective therapy against MUC1-expressing cancers. In this study, we constructed a novel T cell-engaging bispecific antibody (BsAb) targeting MUC1 and CD3 with the Fab-ScFv-IgG format. A high quality of MUC1-CD3 BsAb can be acquired through a standard method. Our study suggested that this BsAb could specifically bind to MUC1- and CD3-positive cells and efficiently enhance T cell activation, cytokine release, and cytotoxicity. Furthermore, our study demonstrated that this BsAb could potently redirect T cells to eliminate MUC1-expressing tumor cells in vitro and significantly suppress MUC1-positive tumor growth in a xenograft mouse model. Thus, T cell-engaging MUC1/CD3 BsAb could be an effective therapeutic approach to combat MUC1-positive tumors and our MUC1/CD3 BsAb could be a promising candidate in clinical applications for the treatment of MUC1-positive cancer patients.

DNAzyme-Amplified Cascade Catalytic Hairpin Assembly Nanosystem for Sensitive MicroRNA Imaging in Living Cells.

Sensitive imaging of microRNAs (miRNAs) in living cells is significant for accurate cancer clinical diagnosis and prognosis research studies, but it is challenged by inefficient intracellular delivery, instability of nucleic acid probes, and limited amplification efficiency. Herein, we engineered a DNAzyme-amplified cascade catalytic hairpin assembly (CHA)-based nanosystem (DCC) that overcomes these challenges and improves the imaging sensitivity. This enzyme-free amplification nanosystem is based on the sequential activation of DNAzyme amplification and CHA. MnO2 nanosheets were used as nanocarriers for the delivery of nucleic acid probes, which can resist the degradation by nucleases and supply Mn2+ for the DNAzyme reaction. After entering into living cells, the MnO2 nanosheets can be decomposed by intracellular glutathione (GSH) and release the loaded nucleic acid probes. In the presence of target miRNA, the locking strand (L) was hybridized with target miRNA, and the DNAzyme was released, which then cleaved the substrate hairpin (H1). This cleavage reaction resulted in the formation of a trigger sequence (TS) that can activate CHA and recover the fluorescence readout. Meanwhile, the DNAzyme was released from the cleaved H1 and bound to other H1 for new rounds of DNAzyme-based amplification. The TS was also released from CHA and involved in the new cycle of CHA. By this DCC nanosystem, low-abundance target miRNA can activate many DNAzyme and generate numerous TS for CHA, resulting in sensitive and selective analysis of miRNAs with a limit of detection of 5.4 pM, which is 18-fold lower than that of the traditional CHA system. This stable, sensitive, and selective nanosystem holds great potential for miRNA analysis, clinical diagnosis, and other related biomedical applications.

Functional Impact of Protein–RNA Variation in Clinical Cancer Analyses

Comprehensive molecular characterization of tumors aims to uncover cancer vulnerabilities, drug resistance mechanisms, and biomarkers. Identification of cancer drivers was suggested as the basis for patient-tailored therapy, and transcriptomic analyses were proposed to reveal the phenotypic outcome of cancer mutations. With the maturation of the proteomic field, studies of protein–RNA discrepancies suggested that RNA analyses are insufficient to predict cellular functions. In this article we discuss the importance of direct mRNA–protein comparisons in clinical cancer studies. We make use of the large amount of data generated by the Clinical Proteomic Tumor Analysis Consortium, which includes protein and mRNA expression analyses from the exact same samples. Analysis of protein–RNA correlations showed marked differences among cancer types, and highlighted the protein–RNA similarities and discrepancies among functional pathways and drug targets. Additionally, unsupervised clustering of the data based on protein or RNA showed substantial differences in tumor classification and the cellular processes that differentiate between clusters. These analyses show the difficulty to predict protein levels from mRNAs, and the critical role of protein analyses for phenotypic tumor characterization.

Intermittent fasting interventions to leverage metabolic and circadian mechanisms for cancer treatment and supportive care outcomes.

Intermittent fasting entails restricting food intake during specific times of day, days of the week, religious practice, or surrounding clinically important events. Herein, the metabolic and circadian rhythm mechanisms underlying the proposed benefits of intermittent fasting for the cancer population are described. We summarize epidemiological, preclinical, and clinical studies in cancer published between January 2020 and August 2022 and propose avenues for future research. An outstanding concern regarding the use of intermittent fasting among cancer patients is that fasting often results in caloric restriction, which can put patients already prone to malnutrition, cachexia, or sarcopenia at risk. Although clinical trials do not yet provide sufficient data to support the general use of intermittent fasting in clinical practice, this summary may be useful for patients, caregivers, and clinicians who are exploring intermittent fasting as part of their cancer journey for clinical outcomes and symptom management.

Anti-Cancer Effects of Artesunate in Human 3D Tumor Models of Different Complexity.

The anti-malaria drug Artesunate (ART) shows strong anti-cancer effects in vitro; however, it shows only marginal treatment results in clinical cancer studies. In this study, ART was tested in preclinical 3D cancer models of increasing complexity using clinically relevant peak plasma concentrations to obtain further information for translation into clinical use. ART reduced cell viability in HCT-116 and HT-29 derived cancer spheroids (p < 0.001). HCT-116 spheroids responded dose-dependently, while HT-29 spheroids were affected more strongly by ART than by cytostatics (p < 0.001). HCT-116 spheroids were chemo-sensitized by ART (p < 0.001). In patient-derived cancer spheroids (PDCS), ART led to inhibition of cell viability in 84.62% of the 39 samples tested, with a mean inhibitory effect of 13.87%. Viability reduction of ART was 2-fold weaker than cytostatic monotherapies (p = 0.028). Meanwhile, tumor-stimulation of up to 16.30% was observed in six (15.38%) PDCS-models. In 15 PDCS samples, ART modulated chemotherapies in combined testing, eight of which showed chemo-stimulation (maximum of 36.90%) and seven chemo-inhibition (up to 16.95%). These results demonstrate that ART's anti-cancer efficacy depends on the complexity of the tumor model used. This emphasizes that cancer treatment with ART should be evaluated before treatment of the individual patient to ensure its benefits and prevent unwanted effects.

Abstract 308: Low molecular weight cyclin E deregulates DNA replication and damage repair to promote genomic instability in breast cancer

Abstract Background: Low molecular weight cyclin E (LMW-E) are oncogenic forms of cyclin E that are post translationally generated from the full-length cyclin E1 (FL-cycE). LMW-E is detected in breast cancer cells and tumor tissues, but not in normal mammary epithelial cells or adjacent normal tissues. Unlike FL-cycE, LMW-E drives mammary epithelial cell transformation in human cells and spontaneous mammary tumor formation in transgenic mouse models, but the oncogenic mechanisms of LMW-E and its unique function(s) independent of FL-cycE are not fully understood. It is currently assumed that LMW-E drives the tumorigenic process by promoting G1/S cell cycle transition and accelerating mitotic exit. Biochemical features such as longer protein half-life, higher affinity to its kinase partner CDK2, and resistance to endogenous CDK inhibitors such as p21 and p27 all promote the tumorigenic ability of LMW-E. Clinical studies in breast cancer reveal that overexpression of LMW-E predicts recurrence and poor survival in breast cancer patients independent of molecular subtype, Ki67 status, nodal status, or tumor grade, suggesting LMW-E may drive breast cancer development independent of its role in cell proliferation. In the current study, we tested the hypothesis that LMW-E promotes genomic instability by deregulating DNA replication and damage repair. Results: We generated immortalized pre-cancerous human mammary epithelial cells (hMECs) to express doxycycline inducible LMW-E or FL-cycE in CCNE1 knock-out background. We found that FL-cycE overexpression led to DNA replication stress and DNA damage accumulation, resulting in reduced cell viability. LMW-E overexpression, on the other hand, promoted cell survival under replication stress, resulting in persistent genomic instability. RNA-sequencing results showed LMW-E but not FL-cycE overexpression enhanced DNA replication and damage repair pathways. Molecularly, LMW-E interacted with and facilitated pre-replication complex assembly. LMW-E also mediated DNA repair by upregulating RAD51 and C17orf53, showing a dominant repairing effect over DNA damage induced by FL-cycE. Moreover, targeting the replication stress response pathway ATR-CHK1-RAD51 with small molecule inhibitors significantly decreased viability of LMW-E overexpressing hMECs and breast cancer cells. Lastly, we showed that positive LMW-E status was associated with genomic instability in tumors from a cohort of 725 patients diagnosed with early-stage breast cancer, further supporting our hypothesis that LMW-E promotes genomic instability to fuel breast cancer development. Conclusions: Collectively, our findings delineated a novel role for LMW-E in breast tumorigenesis mediated by replication stress tolerance and genomic instability, providing novel therapeutic strategies for LMW-E overexpressing breast cancers. Citation Format: Mi Li, Spiridon Tsavachidis, Fuchenchu Wang, Tuyen Bui, Tuyen D. Nguyen, Linjie Luo, Asha S. Multani, Melissa L. Bondy, Kelly K. Hunt, Khandan Keyomarsi. Low molecular weight cyclin E deregulates DNA replication and damage repair to promote genomic instability in breast cancer [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 308.

Kernelized multiview signed graph learning for single-cell RNA sequencing data

BackgroundCharacterizing the topology of gene regulatory networks (GRNs) is a fundamental problem in systems biology. The advent of single cell technologies has made it possible to construct GRNs at finer resolutions than bulk and microarray datasets. However, cellular heterogeneity and sparsity of the single cell datasets render void the application of regular Gaussian assumptions for constructing GRNs. Additionally, most GRN reconstruction approaches estimate a single network for the entire data. This could cause potential loss of information when single cell datasets are generated from multiple treatment conditions/disease states.ResultsTo better characterize single cell GRNs under different but related conditions, we propose the joint estimation of multiple networks using multiple signed graph learning (scMSGL). The proposed method is based on recently developed graph signal processing (GSP) based graph learning, where GRNs and gene expressions are modeled as signed graphs and graph signals, respectively. scMSGL learns multiple GRNs by optimizing the total variation of gene expressions with respect to GRNs while ensuring that the learned GRNs are similar to each other through regularization with respect to a learned signed consensus graph. We further kernelize scMSGL with the kernel selected to suit the structure of single cell data.ConclusionsscMSGL is shown to have superior performance over existing state of the art methods in GRN recovery on simulated datasets. Furthermore, scMSGL successfully identifies well-established regulators in a mouse embryonic stem cell differentiation study and a cancer clinical study of medulloblastoma.

Neoadjuvant immunotherapy in colorectal cancer beyond immune checkpoint inhibitors: emerging from bench to bedside.

Colorectal cancer (CRC) is the second most frequent cancer in both men and women, and of concern increasing in the younger population. Despite the progress in treatment, still up to half of CRC patients will develop metastasis. Immunotherapy consists of an arsenal of different managements that in many aspects has revolutionized cancer therapy. Monoclonal antibodies, chimeric antigen receptor (CAR) T-cell receptor gene modified T-cells and immunization and/or vaccination are different immunotherapies used in cancer treatment. Large trials in metastatic CRC, such as CheckMate 142 and KEYNOTE-177, have proven the efficacy of immune checkpoint inhibitors (ICI). The ICI drugs, targeting the cytotoxic T-lymphocyte associated protein 4 (CTLA-4), programmed cell death protein 1 (PD-1) and programmed death-ligand 1 (PD-L1) are now part of first-line treatment of dMMR/MSI-H metastatic CRC. However, ICIs are gaining a novel role in management of primary operable CRC after preliminary results from early-phase clinical studies in both colon and rectal cancer. Neoadjuvant ICI in operable colon and rectal cancer is hence becoming a clinical reality, while not quite yet adopted as a routine use. However, with some answers comes more questions and challenges. In this review article we aim to give an overview over different modes of immunotherapy to treat cancer with an emphasis on ICIs and their relevance to CRC, describe some of the progresses made in immunotherapy overall, with potential mechanisms, some of the concerns and, some highlight for the way forward.

Abstract P6-04-09: Variations in diagnostic practice of Ki67 scoring suggest standard guidelines needed for pathological assessment: survey results of global Ki67 testing methods

Abstract BACKGROUND The cell proliferation biomarker Ki67 is expressed during every phase of the cell cycle and has long been used as a diagnostic tool for cancer prognosis, especially for hormone receptor positive breast cancer (HR+ BC). More recently, Ki67 has emerged as a companion diagnostic to select patients for the medicines targeting high risk HR+ BC. We report survey results of local Ki67 immunohistochemistry (IHC) testing practices across 99 pathology labs in 11 countries supporting clinical trial sites in 2020-2021 for the coopERA Breast Cancer clinical study in neoadjuvant HR+ BC (NCT04436744). METHODS The survey was disseminated to pathology labs across five continents to assess local Ki67 IHC staining, analysis, and scoring methodologies. Metrics included pre-analytical considerations (e.g. sample type and requirements) and analytical considerations (e.g. test validation status, antibody, scoring methods, reporting). RESULTS All pathology labs reported requiring formalin-fixed, paraffin-embedded (FFPE) tissue for local Ki67 testing with 89% using sections with thickness of 2-5 microns. For the Ki67 test, the majority (65%) reported using an in vitro diagnostic assay, 23% used a validated test, and 8% utilized a research-use-only assay. Ki67 antibody selection varied among the labs with 46% using the MIB-1 mouse monoclonal (Dako Agilent), followed by 33% using the 30-9 rabbit monoclonal (Ventana) and 12% reporting the SP6 rabbit monoclonal (Thermo Fisher). A majority (65%) reported using single pathologist visual assessment for scoring, and 17% reported using two or more pathologists. Use of automated digital image analysis (ADIA) was reported by 18% of labs, either alone or in combination with pathologist visual assessment. A significant portion (75%) reported using the International Ki67 in Breast Cancer Working Group (IKWG) recommendations, whereas 7% reported using only digital image analysis (e.g. Ventana Virtuoso). A minority (7%) indicated neither and instead described variations of “eyeball” or “hot spot” visual estimates. Most labs (65%) reported counting at least 500 cells with 15% of these counting more than 1000 cells. Remaining labs (30%) counted less than 500 or no cells. Predominantly, 85% reported counting cells in at least 3 or more high power fields. Most labs (96%) report Ki67 scores as a percentage of positive nuclei and the remaining minority reported using other methods (e.g. ranges [&amp;lt; 10%, 10-20%, etc.] or H-score [0-300]). CONCLUSIONS The survey results suggest high global variability of local Ki67 testing practices with the highest variability observed in the test validation status, Ki67 clone, and scoring methods. Despite efforts by the IKWG to harmonize and increase the clinical validity of Ki67 as a biomarker, many labs indicating IKWG compliance had survey answers that were discordant with the specific guidelines set forth by the working group. Taking into account the totality of all answers provided by each respondent, only 51% of the surveyed labs fully conformed to the IKWG recommendations. Moreover, a small fraction conducts global estimations without specific cell counting or use “hot spot” scoring methods, despite the high variability and low reproducibility of these scores both intra- and inter-lab. This study demonstrates the benefits of using a central assay in clinical studies to reduce the variability of local Ki67 results in identifying high risk HR+ BC patients and suggests more work is needed to streamline the analytical practices of local Ki67 methodologies, which may directly impact clinical decisions such as the use of neoadjuvant therapies in HR+ BC. Citation Format: Heather M. Moore, Wendy W. Lin, Tharu M. Fernando, Celine Lopez, Emma Kent, Karine Ellouk, Jennifer M. Giltnane. Variations in diagnostic practice of Ki67 scoring suggest standard guidelines needed for pathological assessment: survey results of global Ki67 testing methods [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 P6-04-09.

Current status and future perspectives of bispecific antibodies in the treatment of lung cancer.

Monoclonal antibodies have been successfully incorporated into the current therapeutical landscape of lung cancer in the last decades. Recently, with technological advances, bispecific antibodies (bsAbs) have also shown robust efficacy in the treatment of malignant cancers, including lung cancer. These antibodies target two independent epitopes or antigens and have been extensively explored in translational and clinical studies in lung cancer. Here, we outline the mechanisms of action of bsAbs, related clinical data, ongoing clinical trials, and potent novel compounds of various types of bsAbs in clinical studies, especially in lung cancer. We also propose future directions for the clinical development of bsAbs, which might bring a new era of treatment for patients with lung cancer.

Causal relationship between gut microbiota and cancers: a two-sample Mendelian randomisation study

BackgroundEvidence from observational studies and clinical trials suggests that the gut microbiota is associated with cancer. However, the causal association between gut microbiota and cancer remains to be determined.MethodsWe first identified two sets of gut microbiota based on phylum, class, order, family, and genus level information, and cancer data were obtained from the IEU Open GWAS project. We then performed two-sample Mendelian randomisation (MR) to determine whether the gut microbiota is causally associated with eight cancer types. Furthermore, we performed a bi-directional MR analysis to examine the direction of the causal relations.ResultsWe identified 11 causal relationships between genetic liability in the gut microbiome and cancer, including those involving the genus Bifidobacterium. We found 17 strong associations between genetic liability in the gut microbiome and cancer. Moreover, we found 24 associations between genetic liability in the gut microbiome and cancer using multiple datasets.ConclusionsOur MR analysis revealed that the gut microbiota was causally associated with cancers and may be useful in providing new insights for further mechanistic and clinical studies of microbiota-mediated cancer.

Survival in Black and non-Black patients with metastatic prostate cancer.

101 Background: In the general population, Black men have greater incidence, lower five-year survival, and higher mortality due to prostate cancer when compared to white men. However, in clinical trials and studies of metastatic castrate resistant prostate cancer (mCRPC) in the Veterans Health Affairs (VHA) that excluded chemotherapy, Black men have longer overall survival (OS). We sought to analyze outcomes of Black men treated with androgen receptor targeting agents (ARTAs) abiraterone (AA) and enzalutamide (ENZ) in the VHA. Methods: Patients initially treated with AA or ENZ for mCRPC from May 2011 to June 2017 were identified within the VHA. Racial cohorts of Black and non-Black were determined from patient charts. ANOVA, Kaplan-Meier, and Cox proportional hazards modeling were used to assess the association between overall survival and covariates, including treatment, age, Charlson Comorbidity Index, body-mass index, PSA, year of treatment, prior docetaxel therapy, hemoglobin, creatinine clearance, bilirubin, and albumin at start of treatment. Results: Of 11,027 patients treated for mCRPC with ARTAs, 2550 (23.1%) were identified as Black. Black patients were significantly younger (72.6 vs. 75.8 years, p&lt;0.001), had higher median PSA (60.3 vs. 37.0, p&lt;0.001) and higher Charlson comorbidity index (4.5 vs. 3.9, p&lt;0.001) with lower mean BMI (27.7 vs. 28.4, p&lt;0.001) and higher rates of cardiovascular disease (62.0% vs. 59.8%, p=0.044) and diabetes (45.8% vs. 34.1%, p&lt;0.001). Docetaxel was given more frequently to Black veterans both prior to ARTA (24.7% vs. 16.9%, p&lt;0.001) and at any time (43.1% vs. 31.3%, p&lt;0.001). Black men had a median 2.0 months longer OS than non-Black men (22.0 vs. 20.0, p&lt;0.001) and decreased mortality in unadjusted models (HR 0.89, 95% CI 0.85-0.94) and multivariable models (aHR 0.76, 95% CI 0.72-0.80). Black veterans had longer OS with ENZ compared to AA (24.5 vs. 21.3 months, p&lt;0.001) and decreased mortality (HR 0.83, 95% CI 0.75-0.92) in unadjusted models. However, there was no difference in OS between ENZ and AA in neither multivariable models in all Black men (aHR 0.95, 95% CI 0.85-1.05) nor Black men with cardiovascular disease or diabetes (n=1912, aHR 0.91, 95% CI 0.80-1.03). Conclusions: In the VHA, which provides more equitable access to care, Black men have longer OS with ARTAs compared to non-Black men and increased use of chemotherapy. Importantly, Black men are significantly younger (&gt;3 years) when treated for mCRPC, with higher PSA, and higher rates of comorbid diseases.

NSABP C-14: CORRECT-MRD II—Second colorectal cancer clinical validation study to predict recurrence using a circulating tumor DNA assay to detect minimal residual disease.

TPS284 Background: Detectable ctDNA after resection of early-stage solid tumors has been associated with very high risk of recurrence, suggesting ctDNA is evidence of minimal residual disease (MRD). Several studies are ongoing to investigate the role of ctDNA in the optimal management of pts with colorectal cancer using different assay technologies. Methods: This is a prospective, observational, multicenter study in the United States and Canada of 750 patients who have undergone complete surgical resection for stage II or III colorectal cancer, who have FFPE tissue available from the primary resection sufficient for a novel bespoke MRD assay and are willing to provide serial whole blood specimens for ctDNA analysis. Participants are asked to provide study specimens after definitive surgical resection, pre-recurrence follow-up, and clinical recurrence (if applicable). Recently amended eligibility criteria include inclusion of rectal cancer patients who have completed neo-adjuvant therapy and surgical resection, as well as enrollment of all stage II and III patients regardless of microsatellite stability status. The Oncotype Colon Recurrence Score will be assessed on all patients from their surgical specimen if criteria are met for this testing. ctDNA will be analyzed with an NGS-based tumor-informed MRD assay that identifies somatic genomic alterations from DNA derived from the patient’s tumor tissue, subtracts germline variants, and detects a selected subset of tumor-specific (bespoke) ctDNA in their blood. All primary tumor specimens will undergo full exome and transcriptome sequencing using the Oncomap ExTra assay. If there is evidence of disease recurrence, the metastatic tissue will also undergo Oncomap ExTra testing, which will be shared with participants. The primary objective is to validate the association of post-definitive therapy and pre-recurrence follow-up ctDNA positivity with recurrence-free interval (RFI). Further objectives are to assess the: sensitivity and specificity of ctDNA positivity for subsequent clinical recurrence; contribution of post-surgery baseline, post-adjuvant therapy, and pre-recurrence follow-up ctDNA results on RFI; time from positive ctDNA to clinical recurrence in participants who had a positive ctDNA result; and compare the Oncotype Colon Recurrence Score estimate of 3-year recurrence risk with the observed 3-year recurrence rate. The primary analysis will use a Cox proportional hazards regression applied to the RFI with ctDNA result (positive or negative) measured at post-surgical baseline (or end of adjuvant therapy if used) and serially after that as a single, time-dependent covariate. Protocol#: NSABP C-14 / ES 16-002. Support: NSABP Foundation, ExactSciences Clinical trial information: 05210283 .

Factors contributing to discordance between clinical and pathological staging of operable non-small cell lung cancer

Background: Clinical staging of non-small cell lung cancer (NSCLC) by CT and PET, with or without endobronchial ultrasound-guided transbronchial needle aspiration of lymph nodes (EBUS-TBNA), is essential for prognostication and to direct treatment. Our study investigated the accuracy of clinical staging compared to definitive pathological staging. Methods: Retrospective audit of clinical and pathological staging of all surgical lung cancer cases 2016–present (484 cases). Results: Discordance of clinical and pathological TNM staging (excluding sub-staging) was identified in 93 (25.9%) cases where complete data was available. This included clinical understaging in 61 (17%) and N2 disease in 20 (5.6%) cases. EBUS-TBNA was performed in 14 of the cases with N2 disease, and in five of these cases, involvement of N2 nodes detected post-surgery had been called benign at EBUS-TBNA. Factors contributing to clinical understaging may include delays between clinical staging studies and surgery [CT: median 110 days (IQR 82.5-151), PET: 81 days (59–119), EBUS-TBNA 62 days (43–95)], with significantly longer delays evident during the COVID-19 pandemic. Conclusions: Improved technical quality of lung cancer clinical staging studies and hospital management workflows will potentially increase concordance between clinical and pathological staging of operable NSCLC, improving outcomes for early stage disease. My contribution to this work has focused on the 2022 cases, analysis of which has elucidated the impact of COVID-19 on the lung cancer staging process in comparison to pre-COVID results.

"There's not enough studies": Views of black breast and ovarian cancer patients on research participation.

Black breast and ovarian cancer patients are underrepresented in clinical cancer trials disproportionate to the prevalence of these cancers in Black females. Historically, lower enrollment has been attributed to individualized factors, including medical mistrust, but more recently structural factors, including systemic racism, have received additional scrutiny. We interviewed Black women with a personal or family history of breast and ovarian cancer to understand their views and experiences related to research participation. Qualitative interviews were conducted via telephone or video conference and transcribed verbatim. Transcripts were qualitatively analyzed for iterative themes related to the offer and participation in cancer clinical trials and research studies, impact on cancer care, and recommendations to increase enrollment of Black patients. Sixty-one Black women completed an interview. Participants expressed that Black women are underrepresented in cancer research, and that this negatively impacted their own care. Many cited past historical abuses, including the Tuskegee syphilis trial, as a potential factor for lower enrollment but suggested that lower enrollment was better understood in the context of the entirety of their healthcare experiences, including present-day examples of patient mistreatment or dismissal. Participants suggested that proactive community engagement, transparency, and increased representation of Black research team members were strategies likely to foster trust and bolster research participation. Medical mistrust is only a partial factor in the lower participation of Black patients in cancer research. Researchers should implement the strategies identified by our participants to promote diverse enrollment and ensure that Black patients are included in future therapeutic advances.