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10520 Background: PATHFINDER (NCT04241796) was a prospective, interventional return of results study that enrolled 6,662 participants (pts) from 7 US institutions to assess clinical implementation of a blood-based multi-cancer early detection (MCED) test. Test results for those with a cancer signal detected also included a cancer signal origin prediction designed to help guide diagnostic evaluations. We analyzed whether the diagnostic evaluations in PATHFINDER were appropriately directed by cancer signal origin predictions, assessed the residual risk of cancer after negative initial evaluation, and examined the role of whole-body imaging (WBI, defined as PET/CT or CT chest/abdomen/pelvis) in diagnostic evaluation. Methods: Analysis included pts with a cancer signal detected result from the two different versions of an MCED test evaluated in PATHFINDER. Prespecified criteria blinded to study results were used to define expected diagnostic evaluations by cancer signal origin prediction. These criteria were then used to judge concordance between cancer signal origin predictions and the diagnostic evaluation actually performed. Definitive cancer or no cancer diagnosis (cancer status at end of study [EOS]) was assessed at 12 months after enrollment (EOS). Results: 39 pts had cancer signal detected results by both test versions. Diagnostic evaluations were consistent with cancer signal origin in 30/39 (77%) cases. Diagnostic resolution was achieved in 32/39 (82%) pts after initial evaluation, while 7/39 (18%) required additional workup. 25 of the 32 (78%) pts who achieved diagnostic resolution after initial evaluation had a cancer signal origin-guided workup. Additional evaluation of the 7 pts not achieving initial diagnostic resolution was based on persistent clinical suspicion of cancer due to prior cancer history (n = 1) or abnormal/equivocal findings on initial evaluation (n = 6). Additional workup led to diagnostic resolution in all 7 cases (3 with cancer and 4 with no cancer confirmed at EOS). WBI was ordered in 27 cases, of whom 9 had a prior cancer history, 10 had non-localizing cancer signal origin (hematologic or indeterminate), and 1 had both. WBI was equivocal or had no impact on diagnostic resolution in 8/27 (30%) cases. Conclusions: Most cases resulted in diagnostic resolution after cancer signal origin-directed diagnostic workup. In pts with a cancer history and negative initial evaluations, and those with equivocal initial evaluations, there was still a risk of cancer, suggesting the need for additional evaluation. WBI was used mostly in those with a cancer history or non-localizing cancer signal origins, and had no impact on diagnosis in almost one-third of pts. Clinical trial information: NCT04241796 .

5094 Background: In prior studies, basal vs. luminal differentiation portends differential response to a) androgen suppression (AS) duration for high-risk prostate cancer (PCa) (NRG-GU-TS006) and b) docetaxel chemotherapy (CT) and AS for metastatic hormone-sensitive disease (CHAARTED). In NRG-GU-TS006, basal tumors appeared to benefit the most from longer duration of AS while those with luminal subtype did not whereas, in CHAARTED, luminal subtype had greater benefit from addition of CT. Herein, we examined basal-luminal subtyping to predict differential response to the addition of CT in the setting of high-risk PCa treated with AS and definitive radiotherapy (AS + RT) in NRG/RTOG 0521. Methods: Per pre-specified and approved NCI analysis plan (Navigator #1061), we obtained available NRG biobank biopsy specimens from patients enrolled on the NRG/RTOG 0521 phase III trial, which randomized patients to AS + RT +/- CT. The highest-grade tumors were profiled on clinical-grade whole-transcriptome arrays (Veracyte, San Diego, CA). Basal-luminal subtypes were generated using a 215-gene PCa subtyping classifier (PSC), a second generation PAM50 basal-luminal model. Treatment effects in Luminal Proliferating (LP) and non-LP subtypes were examined with Cox (for overall survival, OS, and metastasis-free survival, MFS) and Fine & Gray (for distant metastasis, DM) multivariable (MVA) models adjusted for age and trial risk stratification, as well as with restricted mean survival times (RMST). Results: Of 183 samples available for analysis (91 from control and 92 from the CT arm), 52 (28%) were classified as LP subtype. Median follow-up for OS was 9.9 years. No significant differences in clinical or pathological variables were observed between LP and non-LP subtypes. In MVA, we did not detect any significant LP subtype-by-CT treatment interaction but observed evidence of non-proportional hazards (Grambsch-Therneau test, p<0.05). In unselected patients, 5- and 10-year RMST difference between the arms was 0.9 (95% CI [-1.5, 3.4], p=0.46) and 5.7 (95% CI [-2.5, 13.9], p=0.17) months of OS. Stratifying by tumor subtype, at 5 years the RMST difference in months was 3.8 (95% CI [0.3, 7.2], p=0.03) for LP and -0.2 ([-3.4, 2.9], p=0.89) for non-LP. The RMST difference in months at 10-years was 13.7 (95% CI [-0.2, 27.5], p=0.053) for LP and 2.5 ([-7.6, 12.5], p=0.63) for non-LP. Conclusions: In pre-treatment biopsy samples from a Phase 3 trial cohort of localized high-risk men, luminal-basal subtyping of tumors demonstrated differential response to docetaxel CT. Similar to results from the CHAARTED trial of metastatic disease, LP tumors may derive greater benefit from addition of CT. Validation of these findings may enable effective earlier use of CT in men with PCa.

1592 Background: While ongoing efforts to decrease opioid use have dramatically altered the prescribing landscape, the impact on patients with cancer is not well understood. We examined trends in new and persistent opioid use in opioid-naïve older patients with and without cancer in the United States. Methods: This retrospective cohort study used SEER-Medicare linked data for patients with solid tumors malignancies diagnosed from 2012 through 2017, and a random sample of patients without cancer. We included patients who did not receive opioids for 3 months prior to the diagnosis or randomly assigned index date. We identified new opioid use (claim in 0-90 days after diagnosis/index date), early persistent opioid use (claims in days 0-90 and 91-180), and long-term persistent opioid use (claims in days 0-90 and 91-180 and months 13-15). Further analysis focused on 4 clinical strata: non-cancer, metastatic cancer, cancer treated with surgery alone, and cancer treated with surgery plus chemotherapy and/or radiotherapy ("surgery+"). We calculated relative changes in the predicted probability of opioid use from 2012 to 2017 based on a logit model adjusted for patient demographics. Results: We identified 238,470 eligible patients with cancer (mean age 76.3 years). Among patients with cancer, 46.4% had new opioid use; use was higher among those receiving surgery+ (70.6%), those treated with surgery alone (58.8%) and those with metastatic cancer (50.0%), compared to patients without cancer (6.9%). From 2012 to 2017, the predicted probability of new opioid use declined in all groups, with lower relative decline in the cancer subgroups (6.8% surgery+; 9.5% surgery alone; 10.2% metastatic cancer) compared to the non-cancer comparator (24.7%). For instance, in patients with metastatic cancer, predicted probability of new use decreased from 52.4 to 47.1% (10.2%) vs. 8.0 to 6.0% (24.7%) in patients without cancer. Relative decline in predicted probability of long-term persistent opioid use was lower in the surgical cancer strata (44.2% surgery+; 46.1% surgery alone) vs. the non-cancer comparator (54.0%). Conclusions: While opioid use remains common in patients with cancer, new and persistent opioid use declined over time in all patients, though with steeper relative declines in non-cancer compared to cancer populations. Our study suggests important but tempered effects of the changing opioid climate on patients with cancer.[Table: see text]

The need for adequate good quality sleep to optimally function is well known. Over years, various physical, psychological, biological, and social factors have been investigated to understand their impact on sleep. However, understanding the etiological processes that are involved in causing sleep disturbances (SD) as impacted by stressful phases such as pandemics has not been well studied. Many such etiological and management strategies have surfaced during the latest “coronavirus disease of 2019 (COVID-19) pandemic. The occurrence of these SD in the infected and uninfected individuals poses a need to investigate factors linked to such occurrence during this phase. Some of such factors include stressful practices such as social distancing, masking, vaccines, and medications availability, changes in routines, and lifestyles. As the status of infection improved, a collective term for all the prolonged effects of COVID-19 after the resolution of the primary infection called the post-COVID-19 syndrome (PCS) surfaced. Apart from impacting sleep during the infectious phase, the aftereffects of this virus left an even greater impact during the PCS. Various mechanisms have been hypothesized to be linked to such SD during the PCS, but the available data are inconclusive. Further, the varied patterns of incidence of these SDs differed by many factors, such as age, gender, and geographical location, making clinical management even more challenging. This review elucidates the impact of coronavirus 2 (SARS-CoV-2) (COVID) disease on sleep health during the various phases of the COVID-19 pandemic. We also investigate different causal relationships, management strategies, and knowledge gaps related to SD during the COVID-19 pandemic.

ImportanceA safe and effective treatment for recurrent Clostridioides difficile infection (CDI) is urgently needed. Antibiotics kill toxin-producing bacteria but do not repair the disrupted microbiome, which promotes spore germination and infection recurrence.ObjectivesTo evaluate the safety and rate of CDI recurrence after administration of investigational microbiome therapeutic SER-109 through 24 weeks.Design, Setting, and ParticipantsThis phase 3, single-arm, open-label trial (ECOSPOR IV) was conducted at 72 US and Canadian outpatient sites from October 2017 to April 2022. Adults aged 18 years or older with recurrent CDI were enrolled in 2 cohorts: (1) rollover patients from the ECOSPOR III trial who had CDI recurrence diagnosed by toxin enzyme immunoassay (EIA) and (2) patients with at least 1 CDI recurrence (diagnosed by polymerase chain reaction [PCR] or toxin EIA), inclusive of their acute infection at study entry.InterventionsSER-109 given orally as 4 capsules daily for 3 days following symptom resolution after antibiotic treatment for CDI.Main Outcomes and MeasuresThe main outcomes were safety, measured as the rate of treatment-emergent adverse events (TEAEs) in all patients receiving any amount of SER-109, and cumulative rates of recurrent CDI (toxin-positive diarrhea requiring treatment) through week 24 in the intent-to-treat population.ResultsOf 351 patients screened, 263 were enrolled (180 [68.4%] female; mean [SD] age, 64.0 [15.7] years); 29 were in cohort 1 and 234 in cohort 2. Seventy-seven patients (29.3%) were enrolled with their first CDI recurrence. Overall, 141 patients (53.6%) had TEAEs, which were mostly mild to moderate and gastrointestinal. There were 8 deaths (3.0%) and 33 patients (12.5%) with serious TEAEs; none were considered treatment related by the investigators. Overall, 23 patients (8.7%; 95% CI, 5.6%-12.8%) had recurrent CDI at week 8 (4 of 29 [13.8%; 95% CI, 3.9%-31.7%] in cohort 1 and 19 of 234 [8.1%; 95% CI, 5.0%-12.4%] in cohort 2), and recurrent CDI rates remained low through 24 weeks (36 patients [13.7%; 95% CI, 9.8%-18.4%]). At week 8, recurrent CDI rates in patients with a first recurrence were similarly low (5 of 77 [6.5%; 95% CI, 2.1%-14.5%]) as in patients with 2 or more recurrences (18 of 186 [9.7%; 95% CI, 5.8%-14.9%]). Analyses by select baseline characteristics showed consistently low recurrent CDI rates in patients younger than 65 years vs 65 years or older (5 of 126 [4.0%; 95% CI, 1.3%-9.0%] vs 18 of 137 [13.1%; 95% CI, 8.0%-20.0%]) and patients enrolled based on positive PCR results (3 of 69 [4.3%; 95% CI, 0.9%-12.2%]) vs those with positive toxin EIA results (20 of 192 [10.4%; 95% CI, 6.5%-15.6%]).Conclusions and RelevanceIn this trial, oral SER-109 was well tolerated in a patient population with recurrent CDI and prevalent comorbidities. The rate of recurrent CDI was low regardless of the number of prior recurrences, demographics, or diagnostic approach, supporting the beneficial impact of SER-109 for patients with CDI.Trial RegistrationClinicalTrials.gov identifier: NCT03183141

Background Uncontrolled blood pressure (BP) remains a leading cause of death in the United States. The American Medical Association developed a quality improvement program to improve BP control, but it is unclear how to efficiently implement this program at scale across multiple health systems. Methods and Results We conducted BP MAP (Blood Pressure Measure Accurately, Act Rapidly, and Partner With Patients), a comparative effectiveness trial with clinic‐level randomization to compare 2 scalable versions of the quality improvement program: Full Support (with support from quality improvement expert) and Self‐Guided (using only online materials). Outcomes were clinic‐level BP control (<140/90 mm Hg) and other BP‐related process metrics calculated using electronic health record data. Difference‐in‐differences were used to compare changes in outcomes from baseline to 6 months, between intervention arms, and to a nonrandomized Usual Care arm composed of 18 health systems. A total of 24 safety‐net clinics in 9 different health systems underwent randomization and then simultaneous implementation. BP control increased from 56.7% to 59.1% in the Full Support arm, and 62.0% to 63.1% in the Self‐Guided arm, whereas BP control dropped slightly from 61.3% to 60.9% in the Usual Care arm. The between‐group differences‐in‐differences were not statistically significant (Full Support versus Self‐Guided=+1.2% [95% CI, −3.2% to 5.6%], P =0.59; Full Support versus Usual Care=+3.2% [−0.5% to 6.9%], P =0.09; Self‐Guided versus Usual Care=+2.0% [−0.4% to 4.5%], P =0.10). Conclusions In this randomized trial, 2 methods of implementing a quality improvement intervention in 24 safety net clinics led to modest improvements in BP control that were not statistically significant. Registration URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03818659.

Clinical trial participants do not reflect the racial and ethnic diversity of people with cancer. ASCO and the Association of Community Cancer Centers collaborated on a quality improvement study to enhance racial and ethnic equity, diversity, and inclusion (EDI) in cancer clinical trials. The groups conducted a pilot study to examine the feasibility, utility, and face validity of a two-part clinical trial site self-assessment to enable diverse types of research sites in the United States to (1) review internal data to assess racial and ethnic disparities in screening and enrollment and (2) review their policies, programs, procedures to identify opportunities and strategies to improve EDI. Overall, 81% of 62 participating sites were satisfied with the assessment; 82% identified opportunities for improvement; and 63% identified specific strategies and 74% thought the assessment had potential to help their site increase EDI. The assessment increased awareness about performance (82%) and helped identify specific strategies (63%) to increase EDI in trials. Although most sites (65%) were able to provide some data on the number of patients that consented, only two sites were able to provide all requested trial screening, offering, and enrollment data by race and ethnicity. Documenting and evaluating such data are critical steps toward improving EDI and are key to identifying and addressing disparities more broadly. ASCO and Association of Community Cancer Centers will partner with sites to better understand their processes and the feasibility of collecting screening, offering, and enrollment data in systematic and automated ways.

6530 Background: Only a small fraction of patients with cancer participate in treatment trials. Patients identifying as members of racial and ethnic minority groups are consistently underrepresented in these trials. A recent systematic review reported that patients, regardless of race and ethnicity, are willing to enroll in trials if asked to participate by their treating clinician. Prospective and longitudinal data and metrics at the site- and clinician-level are necessary to understand whether patients are equitably considered for clinical trials. Methods: ASCO and Association of Community Cancer Centers (ACCC) developed a self-assessment for trial sites to record and gauge the number of patients across races and ethnicities screened, offered, and enrolled into clinical trials. Research sites, from across the US, were recruited through an open call to apply to participate in the ASCO-ACCC Pilot Project. There were 65 sites assigned to this pilot study, which tested the feasibility and utility of the site assessment. Sites were asked to enter 2019 and 2020 aggregate data for each step along the clinical trial enrollment continuum by select races and ethnicities (Black, Hispanic/Latinx, White) and overall. Results: 62 of 65 sites completed the study and represented a range of settings and practice types (61% academic, 26% hospital/health system, 13% independent). Only 2 sites (3%) were able to provide the data requested at each enrollment step in the assessment (table). Sites that collected the data did not do so routinely (table) and most had to compile data through multiple sources and/or manual extraction (40-100% across enrollment steps). Sites with missing data reported they did not collect data at all (36-64% across enrollment steps), did not collect data in a systematic way (0-29% across enrollment steps), or stated it would be too burdensome to manually review charts to extract data (12-29% across enrollment steps). Conclusions: Data collection and routine evaluation of participation metrics, by race and ethnicity, are necessary to assess and monitor equity and diversity in clinical trials. Most sites in this study did not collect, or routinely collect, data for screening, offering, and consenting patients to clinical trials. Without these data, sites are unable to evaluate and monitor whether their patients have equitable access to clinical trials or establish strategies to address any inequities. ASCO and ACCC will continue to partner with sites to better understand their processes and the feasibility of collecting such data in a systematic and automated way, such as through electronic health record systems. [Table: see text]

A concerted commitment across research stakeholders is necessary to increase equity, diversity, and inclusion (EDI) and address barriers to cancer clinical trial recruitment and participation. Racial and ethnic diversity among trial participants is key to understanding intrinsic and extrinsic factors that may affect patient response to cancer treatments. This ASCO and Association of Community Cancer Centers (ACCC) Research Statement presents specific recommendations and strategies for the research community to improve EDI in cancer clinical trials. There are six overarching recommendations: (1) clinical trials are an integral component of high-quality cancer care, and every person with cancer should have the opportunity to participate; (2) trial sponsors and investigators should design and implement trials with a focus on reducing barriers and enhancing EDI, and work with sites to conduct trials in ways that increase participation of under-represented populations; (3) trial sponsors, researchers, and sites should form long-standing partnerships with patients, patient advocacy groups, and community leaders and groups; (4) anyone designing or conducting trials should complete recurring education, training, and evaluation to demonstrate and maintain cross-cultural competencies, mitigation of bias, effective communication, and a commitment to achieving EDI; (5) research stakeholders should invest in programs and policies that increase EDI in trials and in the research workforce; and (6) research stakeholders should collect and publish aggregate data on racial and ethnic diversity of trial participants when reporting results of trials, programs, and interventions to increase EDI. The recommendations are intended to serve as a guide for the research community to improve participation rates among people from racial and ethnic minority populations historically under-represented in cancer clinical trials. ASCO and ACCC will work at all levels to advance the recommendations in this publication.

AbstractBackgroundLike other chronic, inflammatory skin disorders, hidradenitis suppurativa (HS) is increasingly recognized to be associated with various medical disorders.ObjectiveUsing the Rochester Epidemiology Project (REP), we sought to conduct the first American population‐based study examining the association between HS and various comorbid conditions.MethodsFrom the REP database, we identified patients diagnosed with HS from 2003 through 2018 who were residents of Olmsted County, Minnesota, USA, along with age‐ and gender‐matched controls. The frequency of a wide variety of comorbid conditions was compared between the groups.ResultsA total of 1160 patients with HS were identified during the study period. Compared with age‐ and gender‐matched controls, patients with HS had a significantly higher frequency of several medical conditions, including depression, anxiety, hyperlipidemia, acne conglobata, dissecting cellulitis, pilonidal cysts, polycystic ovary syndrome, diabetes, chronic kidney disease, psoriasis, atopic dermatitis, obesity, and disordered substance use, among others.LimitationsOur study was limited by its retrospective design.ConclusionsProviders caring for patients with HS should consider these results, along with those of similar studies, and obtain a thorough history, comprehensive physical examination, and, potentially, laboratory testing and referral to other specialists.