Community Oncology Research Articles

Abstract 6296: Biomarkers associated with atherosclerosis-related cardiovascular dysfunction in cancer survivors treated with anthracyclines

Abstract Introduction: Cancer survival has increased in part due to treatment advances. However, anthracycline chemotherapy increases cardiovascular (CV) morbidity risk, including atherosclerotic CV disease (ASCVD). Among those receiving anthracyclines, it is yet unclear who is at greatest risk of ASCVD, a major cause of CV mortality. Elucidating pathophysiologic processes involved in the development ASCVD could shed light on strategies to identify those at risk. Methods: Analyses were performed on 279 lymphoma and breast cancer survivors enrolled in the PREVENT study [clinical trial WF-98213) through Wake Forest NCI Community Oncology Research Base (NCORP) and Alliance (A221501)]. CV dysfunction was measured via cardiac MRI (cMRI) at baseline (pre-treatment) and 6-months post-diagnosis to ascertain aortic distensibility and wall thickness in the descending aorta. Biomarkers were measured at baseline and 6-months and were log-transformed to base 2. Multiple linear regression was used to determine associations between biomarker and outcome at 6 months, adjusted for baseline biomarker and cMRI outcome, age, race, sex, body mass index, and smoking history. Results: The mean age (SD) of cancer survivors 49 (12) years; 92% were women. The mean aortic distensibility and mean wall thickness at baseline was 0.002 (0.0014) and 2.99 (0.41), respectively. Table 1 shows the associations between biomarkers and aortic distensibility and wall thickness of the descending aorta. After adjustment for confounders, Arginine, CRP, MPO, and ornithine were associated with 6-month aortic distensibility, and the HDL and SDMA were associated with aortic wall thickness. Conclusions: The findings of this study suggest that biomarkers in oxidative stress and inflammatory pathways may be involved in pathophysiology of ASCVD among cancer survivors receiving anthracyclines. These results require further study in larger cohorts to better define mechanistic pathways involved. Association of Biomarkers with Atherosclerosis-Related Cardiovascular Dysfunction Citation Format: Kerryn W. Reding, Alexi Vasbinder, Nathaniel O'Connell, Biniyam Demissei, Warren Szewczyk, Richard Cheng, Amy Ladd, Alexander Lucas, Juergen Meyer, Stephen Bowen, Fadi Salloum, Ralph D'Agostino, Glenn Lesser, Kathryn Weaver, Bonnie Ky, W. H. Wilson Tang, W. Gregory Hundley. Biomarkers associated with atherosclerosis-related cardiovascular dysfunction in cancer survivors treated with anthracyclines [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6296.

Abstract 927: Real-world (RW) biomarker characteristics and clinical outcomes in pre-treated non-MSI-H/dMMR metastatic colorectal cancer (mCRC) patients

Abstract Introduction: Given sparse RW evidence, we assessed biomarker characteristics & clinical outcomes in community oncology practices among pre-treated non-MSI-H/dMMR mCRC patients. Methods: This retrospective cohort study used structured & chart review data from iKnowMed, The US Oncology Network electronic health record data & included non-MSI-H/dMMR adult mCRC patients pre-treated with standard of care (SoC) chemo who initiated subsequent systemic anticancer treatment (SACT), best supportive care (BSC) or neither from 1/1/2016 - 12/31/2021. Index date for SACT users was the regimen start date post SoC chemo & for patients on BSC & no SACT/BSC, it was last chemo administration date. Patients were followed from index date until 8/31/2022 for overall survival (OS) & real-world progression-free survival (rwPFS). KM analyses assessed outcomes, overall & stratified by treatment, RAS status & metastasis sites. Results: Of mCRC patients with >2 visits, 70.9% received MSI/MMR testing. In 292 eligible chart review patients, 69.5% received SACT in pre-treated setting (regorafenib 14.8%, trifluridine/tipiracil (TAS-102) 12.3%, other 72.9%), 28.8% received BSC & 1.7% neither. 76.7% reported KRAS/NRAS testing with 60.7% wild-type & 39.3% mutant. Common metastasis sites were liver-only (44.2%), liver & lung (10.3%) & lung-only (8.9%). Median (range) duration of follow-up was 5.2 (2.7, 10.0) months for regorafenib, 5.3 (2.5, 8.6) for TAS-102 & 10.7 (5.3, 18.0) for the other treatments group. Median OS was 7.4 (95% CI: 5.8, 8.8) months & median rwPFS was 3.5 (95% CI: 3.2, 4.3) months (outcomes data in Table). Conclusions: 29.1% pre-treated, mCRC patients did not receive guideline recommended MSI/MMR testing, highlighting the need to improve testing. Outcomes varied by treatment, RAS status, & metastatic sites. The modest RW clinical benefit for SoC regorafenib & TAS-102, was consistent with trials & other RW studies; all highlighting an unmet need. Cohorts Median (95% CI) OS (months) Median (95% CI) rwPFS1 (months) Overall 7.4 (5.8, 8.8) 3.5 (3.2, 4.3) Regorafenib 5.6 (3.1, 9.7) 2.4 (1.8, 3.0) TAS-102 5.9 (3.4, 8.6) 3.0 (2.1, 3.4) Other SACT2 12.8 (9.8, 17.2) 4.9 (3.7, 5.8) BSC 2.4 (1.8, 3.2) - RAS mutation Wild-type 8.6 (6.6, 11.5) 4.0 (3.3, 4.9) Mutant 5.4 (3.4, 9.5) 3.2 (2.1, 4.6) Metastatic sites Liver only 8.0 (5.7, 11.7) 3.9 (3.0, 4.9) Lung only 17.0 (7.8, 35.6) 7.9 (3.3, 10.5) Liver & lung only 5.4 (2.4, 7.2) 3.5 (2.1, 5.4) Other 6.7 (4.1, 9.4) 3.2 (2.7, 3.9) Abbreviation: CI: confidence interval, TAS-102: trifluridine/tipiracil, OS: overall survival, rwPFS: real-world progression-free survival, SACT: systemic anticancer treatment 1Overall rwPFS was calculated among patients receiving subsequent SACT only (n = 203) 2Top 2 “other SACT” included irinotecan- or oxaliplatin-based treatment Citation Format: Mayur M. Amonkar, Sneha Sura, Kaushal Desai, Rishi Jain, Zhimei Liu, Nicole Niehoff, Thomas W. Wilson, Gregory Patton, David Cosgrove. Real-world (RW) biomarker characteristics and clinical outcomes in pre-treated non-MSI-H/dMMR metastatic colorectal cancer (mCRC) patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 927.

Abstract 6476: Solving the real-world data challenge: A hybrid resourcing model to curate RWD at scale

Abstract Introduction: As cancer treatments become more complex, the need for structured real-world data (RWD) to support clinical research is critical. However, researchers often lack resources to curate data in-house. Organizations are challenged with timely data curation at the quality and scale needed for real world applications. Methods: As members of the AACR Project GENIE (Genomics Evidence Neoplasia Information Exchange) Biopharma Collaborative (BPC), Memorial Sloan Kettering Cancer Center (MSK) and Dana-Farber Cancer Institute (DFCI) partnered with Vasta Global, an Omega Healthcare company, to build a model for curating RWD at scale, allowing for cost-effective RWD curation while leveraging expert resources and best practices. The approach includes managing a hybrid onshore and offshore team with clear communication and recurring check-ins, cross-training curators on different EHRs to reallocate Vasta Global resources and maintain project pace, building program-specific clinical data curation training, establishing QA and delivery methods, standardizing data curation, assigning productivity standards, aligning data quality practices and benchmarks, and developing data visualizations and analytics to show progress and insights. Results: In Phase 1 of the AACR GENIE BPC, data was curated from four sites: MSK, DFCI, Vanderbilt Ingram Cancer Center (VICC) in Nashville, and Princess Margaret Cancer Centre, University Health Network (UHN) in Toronto. During Phase 1, MSK and DFCI, with Vasta Global’s assistance, delivered high-quality RWD for 6,475 patients (NSCLC = 1,591; CRC = 1,264; Bladder = 639; Breast = 957; Pancreas 989; and Prostate = 1,035). All data for these cohorts will be publicly available by Spring 2024 in the AACR Project GENIE cBioPortal. MSK and DFCI generated usable and fit-for-purpose RWD to help advance oncology clinical decision-making and data sharing. Conclusion: Accelerating RWD curation will empower the oncology community to leverage data-driven insights and advance treatment opportunities for cancer patients. Working alongside lead sites, a partner like Vasta Global enables researchers to leverage extensive expertise in the BPC data model, allowing for consistency and scalability of the BPC program. In this hybrid model, research partners can curate RWD in a cost-effective way, while remaining focused on core research responsibilities. Citation Format: Julia Rudolph, Kenneth L. Kehl, Melanie Bernstein. Solving the real-world data challenge: A hybrid resourcing model to curate RWD at scale [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6476.

Outcomes for pembrolizumab stratified by pemetrexed maintenance post pembrolizumab-platinum-pemetrexed induction in metastatic non-small-cell lung cancer.

Aim: We assessed treatment patterns and outcomes in patients with metastatic nonsquamous non-small-cell lung cancer (mNSCLC) who initiated first-line pembrolizumab-platinum-pemetrexed (induction) in US community oncology settings. Methods: Patients initiating induction were retrospectively identified. Patients continuing pembrolizumab afterward underwent chart review. Clinical outcomes were described by maintenance pemetrexed exposure after inverse probability of treatment weighting (IPTW). Results: Median induction pembrolizumab and pemetrexed durations were 5.1 and 4.2months. Among patients continuing pembrolizumab after induction, 64% received maintenance pemetrexed. Common discontinuation reasons for induction pemetrexed were completion of planned therapy (79%) and partial response (68%) and progressive disease (38%) and toxicity (29%) for maintenance pemetrexed. After IPTW, median overall survival and real-world progression-free survival were longer in patients continuing pembrolizumab with versus without maintenance pemetrexed (20.3 vs 12.0months and 10.3 vs 5.8months, respectively). Conclusion: Patient characteristics and planned treatment decisions affect maintenance pemetrexed utilization in the community oncology setting.

Optimizing presurgical education for patients with head and neck cancer receiving laryngectomy and free flap surgery: A qualitative study.

There has been limited study of oncology professionals' perspectives on optimizing delivery of presurgical education for individuals with head and neck cancer (HNC). Therefore, we assessed oncology professionals' perspectives about presurgical education for laryngectomy and free flap surgeries, which have a significant impact on patients' quality of life. Interviews were conducted with 27 oncology professionals from an NCI-designated Comprehensive Cancer Center and a community oncology setting. Participants identified six recommendations to improve presurgical education: (1) establishing preoperative consultations with allied health professionals; (2) educating patients and providers on the concept of team-based care; (3) optimizing education through multimodal strategies; (4) connecting patients with other HNC surgical patients; (5) preparing caregivers for their role; and (6) educating patients on insurance navigation. Study findings demonstrate gaps in the timing, content, and mode of delivery for presurgical education and suggest strategies for further evaluation in future studies.

Genome-matched treatments and patient outcomes in the Maine Cancer Genomics Initiative (MCGI)

Genomic tumor testing (GTT) is an emerging technology aimed at identifying variants in tumors that can be targeted with genomically matched drugs. Due to limited resources, rural patients receiving care in community oncology settings may be less likely to benefit from GTT. We analyzed GTT results and observational clinical outcomes data from patients enrolled in the Maine Cancer Genomics Initiative (MCGI), which provided access to GTTs; clinician educational resources; and genomic tumor boards in community practices in a predominantly rural state. 1603 adult cancer patients completed enrollment; 1258 had at least one potentially actionable variant identified. 206 (16.4%) patients received a total of 240 genome matched treatments, of those treatments, 64% were FDA-approved in the tumor type, 27% FDA-approved in a different tumor type and 9% were given on a clinical trial. Using Inverse Probability of Treatment Weighting to adjust for baseline characteristics, a Cox proportional hazards model demonstrated that patients who received genome matched treatment were 31% less likely to die within 1 year compared to those who did not receive genome matched treatment (HR: 0.69; 95% CI: 0.52–0.90; p-value: 0.006). Overall, GTT through this initiative resulted in levels of genome matched treatment that were similar to other initiatives, however, clinical trials represented a smaller share of treatments than previously reported, and "off-label" treatments represented a greater share. Although this was an observational study, we found evidence for a potential 1-year survival benefit for patients who received genome matched treatments. These findings suggest that when disseminated and implemented with a supportive infrastructure, GTT may benefit cancer patients in rural community oncology settings, with further work remaining on providing genome-matched clinical trials.

Frontline pembrolizumab monotherapy for metastatic non-small cell lung cancer with PD-L1 expression ≥50%: real-world outcomes in a US community oncology setting.

This study investigated real-world time on treatment (rwToT) and overall survival (OS) for patients with metastatic non-small cell lung cancer (mNSCLC) who initiated first-line (1L) pembrolizumab monotherapy. We also explored discontinuation reasons and subsequent treatments, stratified by number of cycles among those who completed ≥17 cycles of 1L pembrolizumab. Patients with mNSCLC without actionable genetic aberrations, Eastern Cooperative Oncology Group performance status (ECOG PS) 0-2 and unknown, and PD-L1 TPS ≥ 50% starting 1L pembrolizumab monotherapy between 24-Oct-2016 and 31-Dec-2018 within The US Oncology Network were identified retrospectively and evaluated using structured data, with a data cutoff of 30-Sep-2021. Patient characteristics and disposition were summarized using descriptive statistics. OS and rwToT were evaluated using Kaplan-Meier method for all ECOG PS and PS 0-1. A subgroup of patients who completed ≥17 cycles were evaluated using supplemental chart review data to discern reasons for discontinuation. Of the 505 patients with mNSCLC with PD-L1 TPS ≥50%, 61% had ECOG PS 0-1, 23% had ECOG PS 2, and 65% had nonsquamous histology. Median rwToT and OS of pembrolizumab were 7.0 (95% CI, 6.0-8.4) months and 24.5 (95% CI, 20.1-29.3) months, respectively. In the subgroup with ECOG PS 0-1, they were 7.6 months (95% CI, 6.2-9.2) and 28.8 months (95% CI, 22.4-37.5), respectively. Of the 103 patients who completed ≥17 cycles, 57 (55.3%) patients received 17 - 34 cycles and 46 (44.7%) patients received ≥35 cycles. Approximately 7.7% of the study population received pembrolizumab beyond 35 cycles. Most common reasons for discontinuation were disease progression (38.6%) and toxicity (19.3%) among patients who received 17-34 cycles of pembrolizumab, and disease progression (13.0%) and completion of therapy (10.9%) among patients who received ≥35 cycles. Consistent with findings from KEYNOTE-024 and other real-world studies, this study demonstrates the long-term effectiveness of pembrolizumab monotherapy as 1L treatment for mNSCLC with PD-L1 TPS ≥50%. Among patients who completed ≥17 cycles, nearly half completed ≥35 cycles. Disease progression and toxicity were the most common reasons for discontinuation among patients who received 17-34 cycles of pembrolizumab. Reasons for discontinuation beyond 35 cycles need further exploration.

95P Understanding the real-world (RW) impact of time between treatment regimens on clinical outcomes in patients with metastatic NSCLC previously treated with immunotherapy (IO) in the US community oncology setting

95P Understanding the real-world (RW) impact of time between treatment regimens on clinical outcomes in patients with metastatic NSCLC previously treated with immunotherapy (IO) in the US community oncology setting

270 Radiologic diagnosis of Extranodal Extension (ENE) in patients with HPV-positive oropharyngeal cancer: consensus diagnosis and influence on prognosis

Tumor often progresses through the weakest part of any surrounding tissues. The extent of tumor invasion depends on: a. Aggressiveness of the tumor cells (e.g. number and invasive character of stem cells), b. robustness of the surrounding tissues and their composition (e.g. vessels), and c. time to allow the tumor to proliferate. The lymph node (LN) capsule comprises dense connective tissue stroma and collagenous fibers, and is a natural barrier that generally prevents further tumor progression. Permeation of tumor through the nodal capsule into surrounding tissues is termed “extranodal extension”. The idiosyncratic and inconsistent mechanism of ENE is imprecisely understood, but it is thought to be due to either tumor cell proliferation that outpaces the capacity of nodal capsular expansion (“ruptures” the LN capsule), or factors within the tumor or tumor microenvironment that facilitate the “breach” of the capsule. The latter might explain ENE in small LNs, or a “neglected” tumor (lengthy intranodal tumor growth with eventual “rupture” through an expanded nodal capsule). Several biomarkers (e.g. podoplanin) that are often associated with tumor aggressiveness have been reported to have a high expression in ENE+ LN. ENE represents a spectrum of tumor nodal invasion. The early sign of ENE can only be visible under the microscope (pathologic ENE); when ENE progresses further, the radiographic signal changes become apparent, making it visible on imaging (iENE). Most advanced ENE causes emergence of clinical surrogates (e.g. peau d'orange, or a “fixed” nodal mass), rendering it detectable by regular clinical examination (ENEc). iENE has been reported to be one of the strongest anatomic prognostic factors for overall survival (mainly due to increased risk of distant metastasis) in HPV-positive oropharyngeal carcinoma (HPV+ OPC), and is able to identify a subgroup of stage I disease with poor prognosis. Several deintensification trials (NRG-HN002, ORATOR, ORATOR2, E3311) have excluded HPV+ OPC with some form of iENE from trial enrolment. Several authors have proposed that iENE be included in future clinical N classification for HPV+ OPC. However, adoption of iENE in clinical care remains challenging because it is not a well-defined radiologic feature among the radiology community. Various definitions / descriptions of iENE have been used in literature. There is also insufficient awareness of the prognostic importance of this parameter in head and neck oncology community. The international iENE Expert Panel was convened under the HNCIG comprised expert internationally renowned neuroradiologists and clinicians. Several rounds of Delphi process were conducted to consolidate iENE definition. The consensus recommendations on the terminology and diagnostic criteria for iENE were generated. The experts in the consensus process recognized the following as criteria for the diagnosis of iENE: clear evidence of irregular or indistinct nodal margin/border; extension into perinodal fat; extension into adjacent structures, and conglomerate/matted/coalescent nodes. These recommendations have been endorsed by 19 national organisations, representing 34 countries. With increased awareness and consolidated definition as well as training, iENE could become an important baseline factor for risk stratification and staging in HPV+ OPC.

Therapy for Stage IV Non-Small Cell Lung Cancer Without Driver Alterations: ASCO Living Guideline, Version 2023.3.

To provide evidence-based recommendations for patients with stage IV non-small cell lung cancer (NSCLC) without driver alterations. This ASCO living guideline offers continually updated recommendations based on an ongoing systematic review of randomized clinical trials (RCTs), with the latest time frame spanning February to October 2023. An Expert Panel of medical oncology, pulmonary, community oncology, research methodology, and advocacy experts were convened. The literature search included systematic reviews, meta-analyses, and randomized controlled trials. Outcomes of interest include efficacy and safety. Expert Panel members used available evidence and informal consensus to develop evidence-based guideline recommendations. This guideline consolidates all previous updates and reflects the body of evidence informing this guideline topic. Ten new RCTs were identified in the latest search of the literature to date. Evidence-based recommendations were updated to address first, second, and subsequent treatment options for patients without driver alterations.Additional information is available at www.asco.org/living-guidelines.

Therapy for Stage IV Non-Small Cell Lung Cancer With Driver Alterations: ASCO Living Guideline, Version 2023.3.

To provide evidence-based recommendations for patients with stage IV non-small cell lung cancer with driver alterations. This ASCO living guideline offers continually updated recommendations based on an ongoing systematic review of randomized clinical trials (RCTs), with the latest time frame spanning February to October 2023. An Expert Panel of medical oncology, pulmonary, community oncology, research methodology, and advocacy experts were convened. The literature search included systematic reviews, meta-analyses, and randomized controlled trials. Outcomes of interest include efficacy and safety. Expert Panel members used available evidence and informal consensus to develop evidence-based guideline recommendations. This guideline consolidates all previous updates and reflects the body of evidence informing this guideline topic. Eight new RCTs were identified in the latest search of the literature to date. Evidence-based recommendations were updated to address first, second, and subsequent treatment options for patients based on targetable driver alterations.Additional information is available at www.asco.org/living-guidelines.

Defining Practice Capacity for Cancer Care Delivery to Adolescents and Young Adults in the Community Setting: 2022 Landscape Assessment Results.

Background: Adolescents and young adults (AYAs) commonly receive cancer care in the community setting, but the availability of treatment options, resources, and support services for this population is not well known. The National Cancer Institute Community Oncology Research Program (NCORP) funds a network of practices whose mission is to increase access to cancer care and clinical trials in the community setting. We describe our interdisciplinary methodological approach to identify and characterize NCORP practices where AYAs receive cancer care. Methods: NCORP practices completed a cross-sectional Landscape Assessment to describe resources and practice characteristics. We established an interdisciplinary team of stakeholders to analyze the Landscape Assessment data relating to AYAs. Through an iterative process, we assessed NCORP practice responses to questions assessing AYA cancer care capacity, determined a threshold to define practices treating AYAs, and characterized these practices. Results: We determined that practices provide cancer care to AYAs if the following criteria were met: (1) endorsed having an AYA program (n = 20), (2) AYAs comprised ≥5% of annual cancer cases (n = 55), or (3) the practice treated ≥50 AYA cancer cases annually (n = 70). Of 271 NCORP practices, 100 (37%) met any criteria, whereas 87 (32%) did not; 84 (31%) could not be classified due to missing or unknown data. Conclusion: Using an interdisciplinary process, we define practices that treat AYAs in the community. We posit a uniform approach to examine resources and practice capacity for AYAs receiving cancer care across the United States to guide future AYA-focused cancer care delivery research development.

Radiotherapy statements of the 18th St.Gallen International Breast Cancer Consensus Conference-aGerman expert perspective.

To summarize the radiotherapy-relevant statements of the 18th St.Gallen Breast Cancer Consensus Conference and interpret the findings in light of German guideline recommendations. Statements and voting results from the 18th St.Gallen International Breast Cancer Consensus Conference were collected and analyzed according to their relevance for the radiation oncology community. The voting results were discussed in two hybrid meetings among the authors of this manuscript on March 18 and 19, 2023, in light of the German S3 guideline and the 2023 version of the Arbeitsgemeinschaft Gynäkologische Onkologie (AGO) guidelines. There was ahigh level of agreement between the radiotherapy-related statements of the 18th St.Gallen International Breast Cancer Consensus Conference and the German S3 and AGO guidelines. Discrepancies include the impact of number of lymph node metastases for the indication for postmastectomy radiotherapy.

SWOG S1820: A pilot randomized trial of the Altering Intake, Managing Bowel Symptoms Interventionin Survivors of Rectal Cancer.

Survivors of rectal cancer experience persistent bowel dysfunction after treatments. Dietary interventions may be an effective approach for symptom management and posttreatment diet quality. SWOG S1820 was a pilot randomized trial of the Altering Intake, Managing Symptoms in Rectal Cancer (AIMS-RC) intervention for bowel dysfunction in survivors of rectal cancer. Ninety-three posttreatment survivors were randomized to the AIMS-RC group (N=47) or the Healthy Living Education attention control group (N=46) after informed consent and completion of a prerandomization run-in. Outcome measures were completed at baseline and at 18 and 26weeks postrandomization. The primary end point was total bowel function score, and exploratory end points included low anterior resection syndrome (LARS) score, quality of life, dietary quality, motivation, self-efficacy, and positive/negative affect. Most participants were White and college educated, with a mean age of 55.2years and median time since surgery of 13.1months. There were no statistically significant differences in total bowel function score by group, with the AIMS-RC group demonstrating statistically significant improvements in the exploratory end points of LARS (p=.01) and the frequency subscale of the bowel function index (p=.03). The AIMS-RC group reported significantly higher acceptability of the study. SWOG S1820 did not provide evidence of benefit from the AIMS-RC intervention relative to the attention control. Select secondary end points did demonstrate improvements. The study was highly feasible and acceptable for participants in the National Cancer Institute Community Oncology Research Program. Findings provide strong support for further refinement and effectiveness testing of the AIMS-RC intervention.

Increasing diversity in clinical trials: demographic trends at the National Cancer Institute, 2005-2020.

We described participant demographics for National Cancer Institute (NCI) clinical trials at the clinical center (NCI-CC participants) of the National Institutes of Health to identify enrollment disparities. We analyzed NCI-CC data from 2005 to 2020, calculated enrollment fractions, compared with the US cancer population represented by the Surveillance, Epidemiology, and End Results cancer incidence data (2018) and the Cancer in North America database (2018), and compared further with clinical trial disparities data from the NCI Community Oncology Research Program and National Clinical Trials Network (2005-2019), and from ClinicalTrials.gov (2003-2016). NCI-CC (38 531 participants) had higher enrollment fractions for older adults (8.5%), male (5.6%), non-Hispanic (5.1%), and Black or African American (5.3%) participants; lower women proportion across race and ethnicity; and fewer female sex-specific cancer (6.8%) than male sex-specific cancer (11.7%) participants. NCI-CC had lower median age than Surveillance, Epidemiology, and End Results (54.0 vs 65.4); more Black or African American participants (12.0% vs 11.1%); and fewer women (41.7% vs 49.5%), White (76.1% vs 80.5%), Asian or Pacific Islander (4.6% vs 6.0%), American Indian or Alaska Native (0.3% vs 0.5%), and Hispanic participants (7.1% vs 13%). NCI-CC had more Black or African American and Asian or Pacific Islander participants; fewer Hispanic participants than the NCI Community Oncology Research Program and National Clinical Trials Network; more Black or African American and Hispanic participants; fewer Asian or Pacific Islander participants than ClinicalTrials.gov data. Improvement was noted for NCI-CC (older adults, Black or African American, Asian or Pacific Islander, Hispanic participants). We found lower representation of older adults, women, Asian or Pacific Islander, American Indian or Alaska Native, and Hispanic participants vs the US cancer population and higher representation of Black or African American vs US cancer population and oncology clinical trials. Multifaceted efforts are underway to reduce disparities in cancer clinical trials at the NCI-CC.

Artificial Intelligence-Based Treatment Decisions: A New Era for NSCLC.

Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related mortality among women and men, in developed countries, despite the public health interventions including tobacco-free campaigns, screening and early detection methods, recent therapeutic advances, and ongoing intense research on novel antineoplastic modalities. Targeting oncogenic driver mutations and immune checkpoint inhibition has indeed revolutionized NSCLC treatment, yet there still remains the unmet need for robust and standardized predictive biomarkers to accurately inform clinical decisions. Artificial intelligence (AI) represents the computer-based science concerned with large datasets for complex problem-solving. Its concept has brought a paradigm shift in oncology considering its immense potential for improved diagnosis, treatment guidance, and prognosis. In this review, we present the current state of AI-driven applications on NSCLC management, with a particular focus on radiomics and pathomics, and critically discuss both the existing limitations and future directions in this field. The thoracic oncology community should not be discouraged by the likely long road of AI implementation into daily clinical practice, as its transformative impact on personalized treatment approaches is undeniable.

A strategy to implement the American College of Sports Medicine's Exercise is Medicine® (EIM) initiative in a community oncology clinic.

Despite proven benefits, few cancer patients exercise during chemotherapy. The American College of Sports Medicine's Exercise is Medicine® (EIM) initiative describes a model to integrate exercise into oncology care, based upon assessing patients' ability to exercise safely, advising on exercise benefits, and referring patients to exercise. We developed and tested a strategy to implement EIM in a community-based oncology clinic, to assess-advise-refer 20 patients undergoing chemotherapy to a 3-month online exercise class, and measured implementation outcomes. Using a community-based provider participation in research (CBPPR) model, researchers and staff co-designed and tested a 4-level implementation strategy, with a goal of assessing-advising-referring 20 cancer patients to exercise. Surveys and interviews were conducted with 12 (100%) staff at baseline and post-implementation on acceptability/appropriateness/feasibility, perceptions of individual implementation roles, and organizational strengths/conditions. Data were analyzed using correlations, t-tests, and content analysis. The proposed strategy was revised in collaboration with staff who requested assistance for recruitment and data collection. EIM was successfully implemented with 41 (92%) patients assessed, 37 (90%) advised, and 22 (60%) referred to exercise classes. Barriers to implementation were staff shortages and time constraints; facilitators included research team supports. Staff's perceived organizational strengths were positively correlated with exercise promotion acceptability, appropriateness, and feasibility. There were no statistically significant changes in implementation outcomes (acceptability/appropriateness/feasibility) post-implementation. Using a collaborative model, EIM was successfully implemented in a community oncology clinic; however, the clinic required significant support from the research team. Adaptations to the EIM process may be required to improve implementation outcomes.

Fractal calculus in tumor growth simulations: The proof is in the pudding

Mathematical modeling in oncology has a long history. Recently, mathematical models and their predictions have made inroads into prospective clinical trials with encouraging results. The goal of many such modeling efforts is to make predictions, either to clinician's choice therapy or into “optimal” therapy – often for individual patients. The mathematical oncology community rightfully puts great hope into predictive modeling and mechanistic digital twins – but with this great opportunity comes great responsibility. Mathematical models need to be rigorously calibrated and validated, and their predictive performance ascertained, before conclusions about predictions into the unknown can be drawn. The recent article “Modeling tumor growth using fractal calculus: Insights into tumor dynamics” (Golmankhaneh et al., 2023), applied fractal calculus to tumor growth data. In this short commentary, I raise concerns about the study design and interpretation. In its current form, this study is poised to put cancer patients at risk if interpreted as concluded by the authors.

HRR testing and PARPi utilization among patients with metastatic castration resistant prostate cancer treated in the real-world setting.

91 Background: HRR mutations (HRRm) have prognostic value in metastatic castration-resistant prostate cancer (mCRPC). Treatment with poly (ADP-ribose) polymerase inhibitors (PARPi) has shown better outcomes among patients with HRR mutations. This study aimed to understand the HRR testing rates among mCRPC patients and utilization of PARPi(s) among HRRm mCRPC patients treated in the real world. Methods: A random sample of 480 mCRPC patients from the Integra Connect PrecisionQ de-identified database were included in this retrospective observational analysis with additional information supplemented by curation. The database contains ~80% community oncology and ~20% academic practices with over 2 million cancer patients across 500 sites of care. Eligible male patients were those aged ≥18 years, diagnosed with mCRPC, and who received treatment between 2020 and 2023. HRR testing rates and utilization of PARPi use were assessed and presented for this study. Results: The mean (SD) age of 480 mCRPC patients was 76.9 (8.3) years; 78.3 % reported being White, 7.9% as African American, 1% as Asian, and 12.7% as Other. Most of the patients reported a payer type of Medicare/Medicaid (69.2%) followed by 15.6% Commercial and 15.2% as Self-Pay/Other. Testing for HRR was reported in 235 (48.9%) of the mCRPC patients and 59 (25.1%) of those patients were HRRm. The mean (SD) age of 59 HRRm mCRPC patients was 77.1 (7.2) years; 88.1% were white, 6.8% African/American, and 5.1% Other. Payer type was reported as being Medicare/Medicaid in 72.9% followed by 18.6% Commercial and 8.5% as Self-Pay/Other. BRCA and ATM mutations were reported among 22/59 (37.2%) and 15/59 (25.4%) patients, respectively. Among the 59 HRRm mCRPC patients, 53 (90%) were noted to have received prior NHA (novel hormone agents) while only 36/53 (67.9%) were noted to have received PARPi. Conclusions: Fewer than half of those patients with mCRPC were tested for HRR. This highlights the lack of testing among those receiving care in a real-world setting. The underutilization of PARPi in these patients is a missed potential opportunity for improving their outcomes.

Abstract A007: Picturing progression: A new role of whole slide imaging in comprehensive clinical genomic datasets

Abstract Introduction: Real world data is needed to understand cancer evolution based on changing standards of care. While Next Generation Sequencing (NGS) is the preferred standard for confirmatory testing of mutational status, its use varies tremendously across settings and countries, with the most influential variable being cost. In this research, we examined the utility of Whole Slide Images (WSI) as a discrete data type to predict mutational and other statuses to inform assessments of clinical progression. This could include initial mutational status or the evolution of resistance to a specific treatment and the emergence of a new driver mutation. Experimental Procedures: We have curated datasets from 4000 NSCLC and 2000 CRC patients with clinically tested WES, WTS and WSI tumors with deeply curated longitudinal clinical electronic medical records were compiled through a partnership between ConcertAI and Caris Life Science. This de-identified clinical dataset is drawn from a diverse range of U.S. community and academic oncology practices. The practice patterns reflect the real-world variability of treatment and utilization of molecular testing. Additional stratification was performed based on lines of therapy and evidence of clinical progression for patients with information available. Results: Features from whole slide H&E images were extracted and compared between subcohorts of interest. We demonstrated the correlation of the WSI features with TMB, MSI-H, molecular variants, differential gene expression and PD-L1 IHC of these cohorts within the context human interpretable features (HIFs) of whole slide images. Conclusion: The availability of whole slide images (WSI) is a dimensionality requirement for real world longitudinal comprehensive clinical datasets. Digital images should be considered as a key deliverable of clinical genomic datasets and have the potential to inform treatment selection and outcomes. In settings where NGS is not the standard of care, WSI could be used to predict the value of a test for treatment decisions or determination of prospective clinical trial eligibility. Where the cost of NGS is fundamentally prohibitive, such as less developed economies, WSI is a much lower cost modality that could have very high utility in guiding treatment decisions with better predicted outcomes. In all cases WSI imaging could be used to assess potential status or acquired resistance and the evolution of a new driver mutation. All critical in the decision to continue or discontinue a specific treatment. Citation Format: Elizabeth G. Sweeney, Yawei J. Wang, Jacob Picard, Jim Abraham, Eghbal Amidi, Michael R. Rossi, Sergey Klimov, Claudio D'Ambrosio, Ming Chen, Jeff Elton, George Sledge. Picturing progression: A new role of whole slide imaging in comprehensive clinical genomic datasets [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Translating Cancer Evolution and Data Science: The Next Frontier; 2023 Dec 3-6; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(3 Suppl_2):Abstract nr A007.