Clinical Trials In Colorectal Cancer Research Articles

S303 Assessing Enrollment Disparities by Demographics in Colorectal Cancer Clinical Trials Across the United States

S303 Assessing Enrollment Disparities by Demographics in Colorectal Cancer Clinical Trials Across the United States

Evaluation of completeness of commonly used data elements for clinical trial eligibility criteria using a registry-enhanced data collection process: Results from patients with non-small cell lung cancer (NSCLC) and colorectal cancer (CRC) at three community oncology practices.

346 Background: Data elements required for clinical trial eligibility assessments are often unstandardized and incomplete in EHR making clinical research participant identification a challenging and biased process. Moreover, the absence of new patient records and disease codes results in monitoring large patient populations until records are completed. These issues can lead to missed opportunities for timely patient identification. N-Power Medicine (NPM) developed a registry-enhanced oncology network platform for unbiased, and real-time quality data collection. We report from this platform on completeness rates of key variables for eligibility assessment in NSCLC and CRC clinical trials. Methods: NPM’s platform consists of 3 parts: patient registry (Kaleido), onsite and remote staff to consent patients and ensure data completeness, quality and standardization, and technology to structure and process the data. Patients with NSCLC and CRC from 3 community oncology practices across different US regions were enrolled in Kaleido and visited the clinic between February and May 2024. Data for 11 key variables were abstracted. To minimize the need for extensive monitoring until a diagnosis was confirmed, we developed a machine learning (ML) model for lung cancer using non-C34 ICD10 codes to construct multiple classes of tunable predictive models. Results: A total of 728 (NSCLC=281, CRC=447) patients were evaluated. The male-to-female ratio was 1 for NSCLC and 1.3 for CRC and 90% of NSCLC and 68% of CRC patients were over 60 years of age. The platform achieved 99% completeness for critical data points such as diagnosis date, histology, metastatic status, recent systemic anti-cancer treatments, ECOG performance status and other cancer diagnoses with diagnosis date. 47% of NSCLC and 43% of CRC patients had metastatic disease at the time of evaluation. Over 90% of patients with metastasis had their current therapy line and relevant genomic test results successfully documented. Imaging-based cancer status completeness was 95% for NSCLC and 89% for CRC. The ML model would identify over 50% of all patients that would eventually receive a lung cancer diagnosis, with over 80% specificity up to 3 weeks before a diagnosis. Conclusions: NPM’s platform demonstrated high completeness rates for the majority of essential data elements, improving the inclusion of all eligible patients in clinical trials. The predictive ML model shows promise in identifying suitable patients before an ICD10 code is assigned, reducing the need for extensive monitoring and ensuring timely completeness of necessary assessments for eligibility. Importantly, these advancements were achieved without adding financial or resource burdens to clinical workflows.

Cancer Trial Eligibility and Therapy Modifications for Individuals With Duffy Null–Associated Neutrophil Count

Absolute neutrophil counts (ANCs) are used to determine cancer clinical trial (CCT) eligibility and systemic anticancer therapy (SACT) dose modifications. Duffy null-associated ANC (DANC) is a nonpathologic phenotype associated with lower ANC and most frequently seen in individuals with African and Middle Eastern ancestry. It is unclear whether CCTs exclude or SACT regimens modify doses for individuals with ANC within the DANC reference range. To investigate CCT exclusions and SACT dose modifications for ANC within the DANC reference range. This cross-sectional study of contemporary CCTs and SACT regimens included adult, interventional, phase 3 CCTs for the 5 most prevalent cancers in the US and United Kingdom (prostate, breast, melanoma, colorectal, and lung cancers) testing SACTs with start dates between November 1, 2021, and November 1, 2023, and that were registered on ClinicalTrials.gov. Preferred curative-intent SACT regimens were listed in National Comprehensive Cancer Network guidelines. Cancer clinical trial exclusions and SACT regimen modifications. Proportions of CCTs that exclude and SACT regimens that modify doses for individuals with an ANC within the DANC reference range. For CCTs, 289 of 382 trials (75.7%) were eligible, of which 221 (76.5% [95% CI, 71.1%-81.2%]) excluded patients with ANC values within the DANC reference range. Colorectal CCTs had the highest (38 of 44 [86.4% (95% CI, 72.6%-94.8%)]) and prostate CCTs had the lowest (11 of 23 [47.8% (95% CI, 26.8%-69.4%)]) proportions of exclusions. Of CCTs testing cytotoxic chemotherapy, 116 of 142 (81.7% [95% CI, 74.3%-87.7%]) had exclusions; 93 of 123 (75.6% [95% CI, 67.0%-82.9%]) CCTs testing targeted therapies alone and 12 of 24 (50.0% [95% CI, 29.1%-70.9%]) testing hormonal therapies alone had exclusions. Among the 113 US- and UK-based trials, exclusions were present in 89 (78.8% [95% CI, 70.1%-85.9%]). Of 71 SACT regimens, 38 (53.5% [95% CI, 41.3%-65.5%]) included dose modifications for ANC values within the DANC reference range. Lung cancer regimens had the highest (23 of 31 [74.2% (95% CI, 55.4%-88.1%)]) and prostate cancer had the lowest (0 of 12 [0 (95% CI, 0%-26.4%)]) proportions of modifications. Regimens including chemotherapy had modifications in 32 of 44 (72.7% [95% CI, 57.2%-85.0%]); 11 of 20 (55.0% [95% CI, 31.5%-76.9%]) of targeted therapy regimens and 0 of 16 (0% [95% CI, 0%-20.6%]) of hormonal therapy regimens had modifications. Among regimens including chemotherapy and/or targeted therapy, modifications were present in 38 of 55 (69.1% [95% CI, 49.7%-73.2%]). In this cross-sectional study, substantial proportions of CCTs excluded and SACT regimens modified doses for patients with ANCs in the DANC reference range. These practices structurally discriminate against patients of African and Middle Eastern ancestry. While determining optimal SACT dose modifications requires further study, CCT exclusion criteria should be revised.

Global Landscape of Phase III Interventional Clinical Trials in Colorectal Cancer

Global Landscape of Phase III Interventional Clinical Trials in Colorectal Cancer

A Bayesian semiparametric mixed effects proportional hazards model for clustered partly interval-censored data

Clustered partly interval-censored survival data naturally arise from many medical and epidemiological studies. We propose a Bayesian semiparametric approach for fitting a mixed effects proportional hazards (PH) model to clustered partly interval-censored data. The proposed method allows for not only a random intercept as most frailty models do for clustered survival data, but also random effects of covariates. We assume a normal prior for each random intercept/random effect, seeing the instability of a gamma prior for a frailty in this situation. Simulation studies with data generated from both mixed effects PH model and mixed effects accelerated failure times model are conducted, to evaluate the performance of the proposed method and compare it with the three methods currently available in the literature. The application of the proposed approach is illustrated through analyzing the progression-free survival data derived from a phase III metastatic colorectal cancer clinical trial.

Clinical Impact of Exosomes in Colorectal Cancer Metastasis.

Cancer is a complex deadly disease that has caused a global health crisis in recent epochs. Colorectal cancer (CRC) is the third most common malignant gastrointestinal disease. It has led to high mortality due to early diagnostic failure. Extracellular vesicles (EVs) come with promising solutions for CRC. Exosomes (a subpopulation of EVs) play a vital role as signaling molecules in CRC tumor microenvironment. It is secreted from all active cells. Exosome-based molecular transport (DNA, RNA, proteins, lipids, etc.) transforms the recipient cell's nature. In CRC, tumor cell-derived exosomes (TEXs) regulate multiple events of CRC development and progression such as immunogenic suppression, angiogenesis, epithelial-mesenchymal transitions (EMT), physical changes in the extracellular matrix (ECM), and metastasis. Biofluid-circulated tumor-derived exosomes (TEXs) are a potential tool for CRC liquid biopsy. Exosome-based colorectal cancer detection creates a great impact in CRC biomarker research. The exosome-associated CRC theranostics approach is a state-of-the-art method. In this review, we address the CRC and exosomes complex associated with cancer development and progression, the impact of exosomes on CRC screening (diagnostic and prognostic biomarkers), and also highlight several exosomes with CRC clinical trials, as well as future directions of exosome-based CRC research. Hopefully, it will encourage several researchers to develop a potential exosome-based theranostic tool to fight CRC.

Colorectal Cancer Clinical Trial Summit: Devising solutions and interventions.

e15603 Background: Only 5% of adult cancer patients enroll in cancer clinical trials; however, approximately 70% are willing to participate. The numerous gaps between patient willingness and trial participation rates suggest that enrollment in clinical trials can be challenging. The Colorectal Cancer Alliance Clinical Trial Think Tank Summit brought together multidisciplinary voices to propose solutions and tailor interventions to increase participation in colorectal cancer (CRC) clinical trials and save lives. Methods: An expert advisory committee supported the planning of the Summit by collating existing knowledge and best practices from across the field. The Alliance collected patient perspectives through interviews and aligned around three critical themes for change in CRC clinical trials. The Summit created a forum for thoughtful and strategic discussions with expert speakers and sessions to explore thematic solutions. Results: The advisory committee’s research activities and discussion identified strategic solutions across the following themes: 1. Marketing & Messaging Trust in Clinical Trials; 2. Fostering Readiness for Community-Based Cancer Research, and 3. Clinical Trial Patient Navigation. There was consensus that cancer patients and the public need to be educated on the importance of clinical trial access and dispel myths about clinical trials. Messaging must be culturally competent, creating quality standards for trial awareness and participation for utilization in a marketing campaign.  Summit participants discussed barriers to clinical trial enrollment at the institutional, structural, provider, and patient levels. Collaborations with industry sponsors and partnering with community oncology programs are necessary for designing and conducting research serving the understudied and underserved.   Participants identified that navigators are crucial for decentralized clinical trials and are a key element for improving clinical trial efficiency and the patient experience. Developing and launching a centralized clinical trial navigator pilot program is necessary to ensure that navigators are knowledgeable about recruiting CRC clinical trials nationally. Conclusions: Clinical trials are essential to advancing new treatments. To extend clinical research into the community, standardized messaging is needed that dispels myths about clinical trials and highlights positive trial outcomes. By improving our overall messaging, collaboration, education, and access to resources, we can accelerate CRC clinical trial participation to improve outcomes and research answers.

Source of funding and enrollment disparity in cancer clinical trials.

6559 Background: Recent findings that Black and Hispanic patients were significantly underrepresented in industry-sponsored prostate cancer trials warrant a detailed investigation across cancer types to assess the association between funding source and enrollment disparities. Methods: Phase II/III clinical trials in prostate, breast, colorectal, and lung cancers reporting age, gender, race/ethnicity, and reporting NIH or industry as the funding source were considered eligible for inclusion. For age, and gender analysis, all trials were considered eligible. For race/ethnicity analysis, trials recruiting from the United States (US) were considered eligible. Enrollment-incidence ratios (EIR) comparing trial proportion from age/gender or racial/ethnic subgroups against global cancer incidence in the corresponding group (from Global Burden of Disease) or US-population-based incidence in the corresponding racial/ethnic subgroup (from SEER 22), were computed. Trial-level EIRs were pooled using a random-effects model and subsequently stratified by funding source. A univariate meta-regression was conducted to assess the temporal changes in EIR by each funding category. Results: Of 42,390 studies initially identified, 2234 trials (1989-2021) met the eligibility criteria. Regarding age, 361 (16%) trials reported age categories by 65 years threshold. Of 698 trials recruiting from the US, 498 (71%) reported race, and 198 (28%) reported ethnicity. Regarding representation, older adults were under-represented (EIR: 0.66; 95% CI: 0.62-0.70) in the industry but not in NIH-sponsored clinical trials (0.79; 0.62-1.00). Regarding gender, no significant disparity was observed regarding the enrollment of men and women in colorectal and lung cancer clinical trials. In terms of race, there was a greater under-representation of Black patients in industry sponsored trials (0.29; 0.26-0.32) as compared to NIH-sponsored clinical trials (0.65; 0.57-0.74) [Pint <0.01]. Asian patients were significantly overrepresented in industry sponsored trials (3.17; 2.69-3.74) but not in NIH sponsored clinical trials (1.43; 0.85-2.41) [Pint <0.01]. Hispanic patients were significantly under-represented in both, industry (0.27; 0.22-0.34) and NIH-sponsored clinical trials (0.35; 0.22-0.55) [Pint 0.32]. Secondary analyses including trials recruiting exclusively from the US, and analyses by specific cancer types showed consistent results. Recruitment of older adults, men, and Black patients is decreasing over time. Conclusions: There is a consistent under-representation of older adults in industry-sponsored, and of Black and Hispanic patients in both industry-sponsored and NIH-sponsored clinical trials. The under-representation of Black patients is likely to be greater in industry-sponsored trials, which has worsened over the last three decades.

Toxicity reporting consistency and subjective minimizing language use in colorectal cancer (CRC) and pancreatic cancer (PaC) clinical trials: A systematic review of phase III randomized controlled trials (RCTs) presented at ASCO between 2012-2022.

1567 Background: Objective and complete toxicity reporting in clinical trials is critical for patient-centered shared decision-making. Conference abstracts inform initial impressions of practice-changing treatments. Methods: We performed a systematic review of all abstracts of CRC and PaC phase 3 RCTs presented at ASCO annual meetings between 2012 – 2022; long-term follow-up, supportive care, and solely non-pharmacological studies were excluded. Objective minimization of adverse event (AE) reporting was defined as absent and/or incomplete reporting of cumulative grade 3-5 CTCAE (common terminology criteria for AE). We also assessed the use of subjective minimizing language (Chin-Yee et al ASH 2022), defined as use of “acceptable,” “tolerable”, “manageable”, “favorable” (primary minimization terms), or “feasible”, “safe”, “patients did well”, “limited” (secondary minimization terms), terms that falsely imply patients deemed the therapy as such. Presence/absence of PRO or QOL data was also assessed. Results: 63 RCTs met entry criteria (42 CRC, 21 PaC), detailed in Table. Most trials studied chemotherapy +/- other drugs (52; 83%). 17% of all abstracts did not provide any information on AE. Quantitative data on AEs were reported by 38 (60%) of abstracts. However, serious AE reporting was frequently absent (Table), with some trials reporting only specific toxicities (e.g. cytopenias) instead of cumulative CTCAE. Only 7 (11%) of abstracts noted the occurrence or absence of fatal AE. Any subjective-minimizing language was used in 15 (24%) abstracts. Notably, none of the abstracts using subjective-minimizing language provided information on fatal AE rates, nor reported on the patient perspective via QOL or PRO. Average grade ≥ 3 AE in the experimental arm were similar in abstracts with vs without minimizing language (44% vs 45%). Conclusions: Our systematic review of ph 3 RCTs in GI oncology presented at ASCO annual meetings reveals that subjective minimizing language is often used to describe serious toxicities, and without formally assessing the patient voice. Serious AE reporting is frequently absent or incomplete.[Table: see text]

Twitterchats as a means to educate patients with CRC and caregivers and stimulate collaborations.

255 Background: During the COVID-19 pandemic, Twitter has been instrumental in accelerating knowledge dissemination and forging collaborations within the medical community and amongst patient advocates. Tweetchats within Twitter are scheduled conversations on a specific topic. In oncology, Tweetchats have been used by cancer advocates to spread awareness and for patient and caregiver education. A colorectal cancer (CRC) specific tweetchat did not previously exist. This abstract describes the creation, and experiences with a CRC specific tweetchat. Methods: The #CRCTrialsChat tweetchat was created by a patient advocate for colorectal cancer patients, caregivers and clinicians to meet and exchange clinical trial-related information. Two gastrointestinal (GI) medical oncologists and two radiation oncologists were enlisted as moderators. The topic for each session is chosen by the patient advocate, who creates an outline and divides the content, which is designed to last a one hour session. The idea is to create engaging, technical, but easy to understand content. Each moderator then works on the answers to their assigned section, which is edited to fit tweet character limit. Sessions may also have guest moderators with expertise on a specific topic. Through tweeting, moderators answer specific questions that come up during the session and later. Results: To date, we have had four sessions covering the following topics: Clinical trial basics, CRC Updates from ASCO22, ClinicalTrialFinders and BRAF-mutated tumors. The content created has been simple and engaging, the format has functioned smoothly, and the reach of #CRCTrialsChat has been steadily increasing. After the most recent session on BRAF in September 2022, the @CRCTrialsChat has 281 followers, 17K impressions and 14.6K profile visits, a reflection of its excellent content. From a clinician perspective, this is a great format to interact with colleagues, discuss enrolling trials and also become familiar with using Twitter. Conclusions: A CRC clinical trial focused tweetchat is an engaging way to deliver trial-related content to an audience of clinicians, patients and caregivers. The current format appears to be an effective way to create and disseminate information. Future sessions will focus on ctDNA, molecular markers such as KRAS and HER2, and rectal cancer trials. Our hope is that #CRCTrialsChat will stimulate continued patient and clinician engagement, increase awareness of clinical trials, enhance trial participation and initiate patient-centric research and collaborations.

404P A quantitative synthesis of disparities in the inclusion of younger adults and racial/ethnic minorities in colorectal cancer clinical trials

Colorectal cancer (CRC) incidence in younger adults has been rising for unclear reasons, and clinical outcomes also differ across racial/ethnic subpopulations. We analyzed all trials for age disparity and trials recruiting from the US for racial/ethnic disparity from primary reports of CRC randomized controlled trials (1990-2021). We calculated enrollment-incidence ratios (EIR), which compare trial enrollment from an age or racial/ethnic subgroup against global estimates of incidence in the corresponding age subgroup (from Global Burden of Disease) or US-population-based incidence in the corresponding racial/ethnic subgroup (from SEER 21). Individual-trial EIRs were pooled using random-effects meta-analyses. Meta-regression was used to explore associations between key trial characteristics and EIR, as well as trends in EIR over the last three decades. Of 411 global trials, 139 trials (33.8%) reported the number of patients within pre-defined age subgroups/categories; among these, patients were most frequently reported as above/below 65 years of age (n = 86; 20.9%). Only 12 trials (2.9%) reported the number of participants younger than 50 years, while even fewer reported the number of participants younger than 45 or 40 years (n = 8; 1.9%). 78 trials (19.0%) reported a subgroup analysis by age. Of 37 US trials, 19 trials (51.4%) reported race and 5 (13.5%) reported ethnicity, with only 2 (5.4 %) reporting data on all 5 U.S. racial categories. Patients aged >65 years were significantly underrepresented (EIR: 0.85 [95% CI: 0.78 - 0.94]). Asians were under-enrolled (EIR: 0.44 [95% CI: 0.36 - 0.52]), as well as Black (EIR: 0.57 [95% CI: 0.49 - 0.66]) and Hispanic patients (EIR: 0.51 [95% CI: 0.39 - 0.67]) with the inclusion of larger, international trials. There were no significant changes in the degree of disparity over the last three decades. Despite rising incidence of CRC in younger adults, clinical trials show infrequent reporting of this age group. Racial ethnic/minorities are significantly underrepresented in colorectal clinical trials based on their share of colorectal cancer incidence.

337P Prediction of poor response to oxaliplatin by an RNA signature derived and validated in colorectal cancer clinical trials

Colorectal cancer (CRC) is usually treated with oxaliplatin-based regimens in stages II, III and IV as standard of care. However, no predictive oxaliplatin biomarker has ever been fully validated despite intensive research. Here we aimed to discover a biomarker of early progression on oxaliplatin based chemotherapy with potential use in the clinic to guide therapy selection.

Cancer treatment vaccine: DNA vaccines in treating prostate cancer and colorectal cancer

Therapeutic DNA cancer vaccines are now widely regarded as a potential technique for stimulating the immune system's response to cancer. Several clinical experiments involving plasmid DNA vaccines have already the induction of a wide and targeted immune response. Unfortunately, due to the tumor's immunosuppressive mechanisms, these vaccinations often showed very modest therapeutic results in clinical trials. This paper looks at how DNA vaccines for prostate cancer are progressing, as well as colorectal cancer clinical trials. This paper also examines the rationale for various treatment combinations and antigen selection strategies being developed to circumvent the limits of the cancer DNA vaccine. This paper focuses on the most promising discoveries as well as major concerns that must be addressed before therapeutic cancer DNA vaccines may be approved as part of standard cancer care for prostate cancer and colorectal cancer.

Bayesian design of clinical trials using joint models for recurrent and terminating events.

Joint models for recurrent event and terminating event data are increasingly used for the analysis of clinical trials. However, few methods have been proposed for designing clinical trials using these models. In this article, we develop a Bayesian clinical trial design methodology focused on evaluating the effect of an investigational product (IP) on both recurrent event and terminating event processes considered as multiple primary endpoints, using a multifrailty joint model. Dependence between the recurrent and terminating event processes is accounted for using a shared frailty. Inferences for the multiple primary outcomes are based on posterior model probabilities corresponding to mutually exclusive hypotheses regarding the benefit of IP with respect to the recurrent and terminating event processes. We propose an approach for sample size determination to ensure the trial design has a high power and a well-controlled type I error rate, with both operating characteristics defined from a Bayesian perspective. We also consider a generalization of the proposed parametric model that uses a nonparametric mixture of Dirichlet processes to model the frailty distributions and compare its performance to the proposed approach. We demonstrate the methodology by designing a colorectal cancer clinical trial with a goal of demonstrating that the IP causes a favorable effect on at least one of the two outcomes but no harm on either.

Abstract PO-224: Disproportional representation of racial and ethnic minorities in colorectal cancer clinical trials

Abstract Introduction: Despite overall decreasing rates of colorectal cancer, significant disparities in mortality disproportionately impact racial and ethnic minorities. Ancestral differences in tumor biology may affect how patients respond to cancer therapeutics, potentially impacting treatment efficacy. Underrepresentation in clinical trials may perpetuate disparities in colorectal cancer in racial and ethnic minorities. We aim to determine the representation of racial and ethnic minority patients in colorectal cancer clinical trials and to explore how reporting and representation has changed over time. Methods: A database analysis was performed of ClinicalTrials.gov from 2008-2021 of all colorectal, colon and rectal cancers. Trials were excluded if results were not reported, studies were performed outside the US or in other cancer types. Representation was determined using an enrollment fraction (EF), the proportion of trial participants adjusted for prevalence of colorectal cancer for each racial and ethnic subgroup. Wilcoxon rank sum and Kruskal-Wallis tests were used to determine whether the distribution of EF ratios among subgroup trials differed from 1. Results: 255 colorectal cancer clinical trials were analyzed, including 253,135 participants. Overall, gender was reported 98.8% of the time, whereas race was reported in 44.7% of trials and ethnicity was reported in 29.4% of trials. Though data reporting on race and ethnicity have improved over time, rates of reporting remain poor in 2021 (race 68.2%, ethnicity 45.5%). Black (EF 0.7), Asian (EF 0.3), American Indian and Alaskan Native (EF 0.0) and Hispanic (EF 0.4) patients remain underrepresented when compared to US rates of colorectal cancer (p<0.0001). Conclusions: Non-White and Hispanic patients with colorectal cancer are underrepresented in colorectal cancer clinical trials. Though reporting of patient race and ethnicity continue to increase, there are opportunities for further improvement. Equitable representation of racial and ethnic minorities in colorectal cancer clinical trials facilitates the understanding of biologic responses to cancer therapeutics and has the potential to improve cancer health disparities. Citation Format: Kelly M. Herremans, Andrea N. Riner, Katherine Y. Tossas, Shreya Raman, Stephen P. Sharp, Jose G. Trevino. Disproportional representation of racial and ethnic minorities in colorectal cancer clinical trials [abstract]. In: Proceedings of the AACR Virtual Conference: 14th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2021 Oct 6-8. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr PO-224.

Disparities and trends in the participation of minorities, women, and the elderly in breast, colorectal, lung, and prostate cancer clinical trials.

This study was done to determine the representation of minorities, women, and the elderly in National Cancer Institute (NCI) clinical trials. This is an analysis in the NCI Clinical Data Update System. Patients were evaluated in breast, colorectal, lung, and prostate cancer trials from 2000 to 2019. Representation in a trial was determined by race/ethnicity, sex, and age. Secondarily, the change in trial participation by multivariable analysis by comparing years 2000 through 2004 to 2015 through 2019 was evaluated. The cohort included 242,720 participants: 197,320 Non-Hispanic White (81.3%), 21,190 Black (8.7%), 11,587 Hispanic (4.8%), and 6880 Asian/Pacific Islander (2.8%). Black and Hispanic patients were underrepresented for colorectal (odds ratio [OR], 0.58; 95% confidence interval [CI], 0.50-0.67; P < .001 and OR, 0.74; 95% CI, 0.64-0.87; P < .001, respectively), lung (OR, 0.83; 95% CI, 0.76-0.91; P < .001 and 0.66; 95% CI, 0.57-0.77; P < .001, respectively), and prostate cancer trials (OR, 0.85; 95% CI, 0.79-0.92; P < .001 and OR, 0.58; 95% CI, 0.51-0.66; P < .001) between 2015 and 2019. The odds of participation in 2015 to 2019 increased among Black patients in breast (OR, 2.19; 95% CI, 2.07-%2.32; P < .001), lung (OR, 1.54; 95% CI, 1.38-1.73; P < .001), and prostate cancer trials (OR, 1.14; 95% CI, 1.04-1.26; P < .001). The odds of participation in a trial among Hispanic patients increased for breast (OR, 3.32; 95% CI, 3.09-3.56; P < .001), colorectal (OR, 2.46; 95% CI, 2.04-2.96; P < .001), lung (OR, 3.88; 95% CI, 3.20-4.69; P < .001), and prostate cancer (OR, 1.70; 95% CI, 1.42-2.04; P = .005). This study identified that Black and Hispanic patients remain underrepresented in trials, but in recent years, participation has increased. These findings indicate that minority participation has increased over time, but further efforts are needed.

A Bayesian semiparametric accelerate failure time mixture cure model.

The accelerated failure time mixture cure (AFTMC) model is widely used for survival data when a portion of patients can be cured. In this paper, a Bayesian semiparametric method is proposed to obtain the estimation of parameters and density distribution for both the cure probability and the survival distribution of the uncured patients in the AFTMC model. Specifically, the baseline error distribution of the uncured patients is nonparametrically modeled by a mixture of Dirichlet process. Based on the stick-breaking formulation of the Dirichlet process, the techniques of retrospective and slice sampling, an efficient and easy-to-implement Gibbs sampler is developed for the posterior calculation. The proposed approach can be easily implemented in commonly used statistical softwares, and its performance is comparable to fully parametric method via comprehensive simulation studies. Besides, the proposed approach is adopted to the analysis of a colorectal cancer clinical trial data.

Diversity and Inclusion in Pancreatic Cancer Clinical Trials

Diversity and Inclusion in Pancreatic Cancer Clinical Trials

An analysis of the rates of discontinuation and non-publication of colorectal cancer clinical trials.

Non-publication and premature discontinuation for clinical trials pose an ethical dilemma for trial participants, patients, clinicians, and researchers, as well as the general public as these studies receive significant public funding that may be further contributing to research waste. Here, we investigate the rate of trial discontinuation and non-publication among CRC trials using ClinicalTrials.gov. We performed an advanced search on ClinicalTrials.gov pertaining to the treatment of CRC using the keyword colorectal cancer. For each clinical trial, links to the publication provided by ClinicalTrials.gov were searched and verified to be correct. If a publication was unable to be found using the methods above, we attempted to contact the lead investigator via email for the reason for non-publication. Of the 123 (123/428, 28.7%) discontinued trials, a reason for discontinuation was provided for 57 (57/123, 46.3%) trials. Of the 305 (305/428, 71.3%) completed trials, 244 (244/305, 80.0%) had a verifiable publication, while 61 (61/305, 20.0%) did not publish their findings or were unable to be located. We found that more than one-quarter of trials were prematurely ended, and almost one-third of completed trials did not publish their findings. Subjecting trial participants to potentially harmful treatments and interventions that fail to complete or publish study findings have the potential to undermine the patient-provider relationship, as well as public confidence in government-sponsored clinical trials.

The clinical features of polymerase proof-reading associated polyposis (PPAP) and recommendations for patient management

Pathogenic germline exonuclease domain (ED) variants of POLE and POLD1 cause the Mendelian dominant condition polymerase proof-reading associated polyposis (PPAP). We aimed to describe the clinical features of all PPAP patients with probably pathogenic variants. We identified patients with a variants mapping to the EDs of POLE or POLD1 from cancer genetics clinics, a colorectal cancer (CRC) clinical trial, and systematic review of the literature. We used multiple evidence sources to separate ED variants into those with strong evidence of pathogenicity and those of uncertain importance. We performed quantitative analysis of the risk of CRC, colorectal adenomas, endometrial cancer or any cancer in the former group. 132 individuals carried a probably pathogenic ED variant (105 POLE, 27 POLD1). The earliest malignancy was colorectal cancer at 14. The most common tumour types were colorectal, followed by endometrial in POLD1 heterozygotes and duodenal in POLE heterozygotes. POLD1-mutant cases were at a significantly higher risk of endometrial cancer than POLE heterozygotes. Five individuals with a POLE pathogenic variant, but none with a POLD1 pathogenic variant, developed ovarian cancer. Nine patients with POLE pathogenic variants and one with a POLD1 pathogenic variant developed brain tumours. Our data provide important evidence for PPAP management. Colonoscopic surveillance is recommended from age 14 and upper-gastrointestinal surveillance from age 25. The management of other tumour risks remains uncertain, but surveillance should be considered. In the absence of strong genotype–phenotype associations, these recommendations should apply to all PPAP patients.