Utah Cancer Specialists

Routine preoperative echocardiograms (ECHOs) are frequently obtained in patients undergoing minimally invasive repair of pectus excavatum (MIRPE), but the benefit and necessity of preoperative screening remain debated. In this study, we sought to quantify the proportion of preoperative ECHOs that had clinically significant findings. We conducted a retrospective review of 255 patients who underwent MIRPE at a single pediatric referral center from 2018 to 2023. Demographics, cardiopulmonary symptoms, connective tissue disorder evaluations, and ECHO findings were collected. ECHO results were categorized as incidental or significant based on whether they warranted cardiology referral or follow-up imaging. Chest CTs were reviewed in patients with ascending aortic dilation to assess for concordant findings. The cohort had a mean age of 15.5 years, a mean BMI of 18.8 kg/m, and was predominantly male (83 %) and White (97.6 %). Most patients had no known history or evaluation for connective tissue disorders (96 %) and had not undergone genetic testing (97 %). Cardiopulmonary symptoms were common (80 % reported exertional shortness of breath), but most ECHO findings were incidental. However, 14 patients (5.5 %) had significant findings, including Aortic root dilation (n = 5), bicuspid aortic valve (n = 4; one with prior coarctation), mitral valve cleft (n = 1), mitral valve prolapse (n = 1), persistent ductus arteriosus (n = 1), coronary fistula (n = 1), and dysplastic tricuspid valve (n = 1). One patient had two significant anomalies. These findings prompted cardiology referral or intervention in 13 of 14 patients (93 %). Several anomalies (e.g., bicuspid valves, PDA, fistula) would not have been detected on standard non-contrast chest CT. Although most preoperative ECHO findings in MIRPE patients were incidental, over 5 % revealed clinically significant cardiac anomalies that would have been missed on screening non-contrast CT. These results suggest routine preoperative echocardiography may be more valuable than previously assumed in this population. Retrospective review. Level III.

BackgroundAdherence to cancer screening is important for cancer survivors because they are at high risk of subsequent cancer diagnoses or recurrence. We assessed adherence to breast, cervical, and colorectal cancer‐(CRC)‐screening guidelines and evaluated demographic disparities among a population‐based sample of survivors.MethodsA representative sample of Utah survivors diagnosed from 2012–2018 with any reportable invasive cancer was selected from central cancer registry records for a survey about survivorship needs. We estimated the proportion of eligible survivors adhering to U.S. Preventive Services Task Force screening guidelines and calculated risk ratios and 95% confidence intervals. Analyses were age‐adjusted and weighted to account for sample design and nonresponse.ResultsAnd 1421 survivors completed the survey (57.2% response rate). Screening adherence was 74.4% for breast, 69.4% for cervical, and 79.7% for CRC. Rural residents were more likely to adhere to breast cancer screening than urban residents (86.1% vs. 72.7%; adjusted RR = 1.19, CI = 1.05, 1.36). Higher educational attainment was associated with increased adherence to cervical and colorectal cancer screening. Younger age was associated with greater adherence to cervical cancer screening (p = 0.006) but lower adherence to CRC screening (p = 0.003). CRC screening adherence was lower among the uninsured and those without a primary care provider (45.6%) compared to those with a regular provider (83.0%; adjusted RR = 0.57, CI = 0.42, 0.79).ConclusionsSurveys based on samples from central cancer registries can provide population estimates to inform cancer control. Findings demonstrate work is needed to ensure all Utah cancer survivors obtain recommended cancer screenings. Efforts should focus particularly on increasing uptake of breast and cervical cancer screening and reducing demographic disparities in CRC screening.PrecisDespite high risk for subsequent cancer diagnosis, Utah cancer survivors are not all obtaining recommended breast, cervical, and colorectal cancer screenings. This presents a significant healthcare gap.

While the primary role of central cancer registries in the United States is to provide vital information needed for cancer surveillance and control, these registries can also be leveraged for population-based epidemiologic studies of cancer survivors. This study was undertaken to assess the feasibility of using the NCI's Surveillance, Epidemiology, and End Results (SEER) Program registries to rapidly identify, recruit, and enroll individuals for survivor research studies and to assess their willingness to engage in a variety of research activities. In 2016 and 2017, six SEER registries recruited both recently diagnosed and longer-term survivors with early age-onset multiple myeloma or colorectal, breast, prostate, or ovarian cancer. Potential participants were asked to complete a survey, providing data on demographics, health, and their willingness to participate in various aspects of research studies. Response rates across the registries ranged from 24.9% to 46.9%, with sample sizes of 115 to 239 enrolled by each registry over a 12- to 18-month period. Among the 992 total respondents, 90% answered that they would be willing to fill out a survey for a future research study, 91% reported that they would donate a biospecimen of some type, and approximately 82% reported that they would consent to have their medical records accessed for research. This study demonstrated the feasibility of leveraging SEER registries to recruit a geographically and racially diverse group of cancer survivors. Central cancer registries are a source of high-quality data that can be utilized to conduct population-based cancer survivor studies.

Rural areas of the U.S. experience disproportionate colorectal cancer (CRC) death compared to urban areas. The authors aimed to analyze differences in CRC survival between rural and urban Utah men and investigate potential prognostic factors for survival among these men. A cohort of Utah men diagnosed with CRC between 1997 and 2013 was identified from the Utah Cancer Registry. Survival and prognostic factors were analyzed via 5-year CRC survival and Cox proportional hazards models, stratified by rural/urban residence. Among 4,660 men diagnosed with CRC, 15.3% were living in rural Utah. Compared with urban men, rural CRC patients were diagnosed at older ages and in different anatomic subsites; more were overweight, and current smokers. Differences in stage and treatment were not apparent between rural and urban CRC patients. Compared with urban counterparts, rural men experienced a lower CRC survival (Hazard Ratio 0.55, 95% CI 0.53, 0.58 vs. 0.58, 95% CI 0.56, 0.59). Race and cancer treatment influenced CRC survival among men living in both urban and rural areas. Factors of CRC survival varied greatly among urban and rural men in Utah. The influence of social and environmental conditions on health behaviors and outcomes merits further exploration.

2583 Background: First-generation BRAF inhibitors (BRAFi) show high response rates and prolonged survival in some BRAFV600-mutant cancers; however, paradoxical activation of the RAF/MEK/ERK pathway promotes resistance and development of skin malignancies. PLX8394 is a next-generation, orally available small-molecule BRAFi that does not induce the RAF/MEK/ERK paradoxical activation and blocks signaling from both monomeric BRAFV600 and dimeric BRAFnon-V600 protein. Methods: This is a phase 1/2 study of PLX8394 and cobicistat (cstat,150mg), a CYP3A4 inhibitor used to enhance PLX8394 exposure, to determine the safety, tolerability in subjects with refractory solid tumors (phase 1) and RECIST response rate in BRAFV600 and dimer-dependent, RAS-independent BRAFnon-V600 mutant patients (phase 2). A hot-melt extrusion (HME) formulation of PLX8394 was used for this study. Results are reported as of January 8, 2018. Results: Phase 1: The RP2D was 900mg BID + cstat (Proc AACR-NCI-EORTC 2017, abst B176). A single DLT of reversible grade (G) 3 transaminitis occurred in a subject treated with PLX8394 900mg BID + cstat. Cstat co-administration resulted in a 2-3-fold increase in PLX8394 systemic exposure. Of 13 evaluable BRAFV600-mutated subjects, 3 (23%) achieved partial responses [colorectal cancer (42%), glioma (65%); both BRAFi naïve, and ovarian cancer (62%) previously treated with 3 lines of BRAF/MEKi]. Phase 2: Of 18 patients enrolled, 13 had BRAFV600 mutation [melanoma (n = 5), colorectal (n = 4), glioblastoma (n = 2), thyroid (n = 2)] and 5 BRAFnon-V600 mutation [pancreatic (n = 2), and prostate, thyroid, and colorectal (each n = 1)]. No prior MAPK pathway inhibitors were permitted for non-melanoma subjects. G≥3 AEs included G3 transaminitis and hyperbilirubinemia in one patient. Of 10 evaluable patients, 3 (30%, all with BRAFV600 mutations) had stable disease (+7%, -10%, -14%, respectively). Efficacy and exploratory biomarker analysis including transcriptome and ctDNA analysis is on-going. Conclusions: PLX8394 + cstat has been well tolerated and shows promising activity in refractory solid tumors with BRAF mutations. This work was sponsored by Plexxikon Inc. Clinical trial information: NCT02428712.

Cancer disparities in rural and frontier communities are an important issue in Utah because much of Utah is sparsely populated. The aims of this study were to investigate whether there are differences in the cancer incidence and 5‐year survival rates in Utah by metropolitan/rural residence and to investigate disparities in distributions of cancer risk factors. We used cancer registry records to identify patients diagnosed with a first primary cancer in Utah between 2004 and 2008. We estimated 5‐year survival and incidence rates. The Cox proportional hazards model was used to estimate hazard ratios (HRs) for the risk of death. There were 32,498 (86.9%) patients with cancer who lived in metropolitan counties and 4906 (13.1%) patients with cancer who lived in rural counties at the time of cancer diagnosis. Patients with cancer from rural counties were more likely to be older, American Indian/Alaskan Native, non‐Hispanic, male, and diagnosed at higher stage. Rural residents had a five‐year relative survival that was 5.2% lower than metropolitan residents and a 10% increase in risk of death (HR = 1.10, 95% CI = 1.03, 1.18) after adjustment for multiple factors. Overall, the cancer incidence rates in rural counties were lower by 11.9 per 100,000 per year (449.2 in rural counties vs. 461.1 in metropolitan counties). Cancer patients living in rural counties of Utah had different demographic characteristics as well as differences in incidence and survival rates. Further studies with individual‐level data are necessary to investigate the reasons behind these differences in cancer incidence and survival to reduce disparities.

Introduction: INCB050465 is a potent, selective PI3Kδ inhibitor (≥19,000-fold selectivity for PI3Kδ vs other isoforms), which has demonstrated linear pharmacokinetics (PK) and achieved exposure levels several-fold greater than the IC90 for PI3Kδ inhibition at the recommended phase 2 dose (ASH 2016; Abstract 4195). Here, we report emerging safety and efficacy results from pts receiving INCB050465 monotherapy for r/r B-cell malignancies in an ongoing phase 1/2 study (NCT02018861). Methods: Eligible pts (≥18 y) had ECOG PS ≤2 (≤1 during dose escalation), normal liver and kidney function, and no autologous HSCT within 3 months or allogeneic HSCT within 6 months of screening. The protocol was initiated with a single-pt cohort, treated with oral INCB050465 5 mg QD. Subsequent cohorts used a 3 + 3 design and evaluated doses of 10–45 mg QD. Based on PK/PD, the 20 and 30 mg QD cohorts were expanded. Responses were assessed Q9W using Lugano Classification or International Working Group on Chronic Lymphocytic Lymphoma (CLL) criteria. Results: As of the data cut-off (Nov 1, 2016), 52 pts were treated (median age, 65 y [range, 30–88]; disease subtypes: diffuse large B-cell lymphoma [DLBCL; n = 14], follicular lymphoma [FL; n = 10], Hodgkin lymphoma [HL; n = 9], marginal zone lymphoma [MZL; n = 8], CLL [n = 6], mantle cell lymphoma [MCL; n = 5]). Approximately 62% of pts had ≥3 prior systemic regimens; 31% had prior HSCT. Median duration of therapy was 3.3 months (range, 0.6–13.4); no DLTs were identified. Approximately 67% of pts discontinued therapy, most commonly for disease progression (31%) and AEs (25%). Approximately 33% of pts had dose interruption; 4% had reduction. Most common nonhematologic AEs (all grade [Gr]; Gr ≥3) were nausea (38%; 0%), diarrhea (31%; 6%), and vomiting (25%; 0%). Gr ≥3 hematologic AEs included neutropenia (21%), lymphopenia (17%), thrombocytopenia (10%), and anemia (4%). Approximately 40% of pts had serious AEs, most frequently colitis, diarrhea, and hypotension (all n = 3). A total of 1 pt had Gr 3 pneumonitis; none had Pneumocystis jiroveciipneumonia (PJP) or Gr ≥2 elevated transaminase. Objective responses (OR) occurred at all doses (Table), except 5 mg QD; 90% of the ORs were observed at the 9-week disease assessment. Conclusion: INCB050465 demonstrated manageable toxicities with no clinically meaningful transaminitis or PJP. OR rates were generally high and most responses (90%) were observed at the 9-week disease assessment. Different dosing regimens/schedules, long-term safety, and disease-specific cohorts are being evaluated. a7 pts were not evaluable for response because they had not reached a postbaseline assessment as of the data cutoff date. bRadiologic/metabolic. c1 patient with MCL and 3 with CLL had previously received ibrutinib; among these 4 pts, 1 objective response (partial response in CLL) was observed in this study. Keywords: B-cell lymphoma; non-Hodgkin lymphoma (NHL); PI3K/AKT/mTOR.

7530 Background: INCB050465 is a selective PI3Kδ inhibitor with no preclinical hepatotoxicity at clinically relevant doses. We report emerging safety and efficacy data from a phase 1/2 study of INCB050465 in patients (pts) with r/r B-cell malignancies (NCT02018861). Methods: The protocol was initiated with a single patient cohort, treated with INCB050465 5 mg QD PO. Subsequent cohorts used a 3+3 design and evaluated doses of 10–45 mg QD. Based on PK/PD, the 20 and 30 mg QD cohorts were expanded. Responses were assessed Q9W by the Lugano Classification or International Working Group on Chronic Lymphocytic Lymphoma (CLL) criteria. Results: As of the data cutoff (Nov 1, 2016), 52 pts were treated (median age, 65 y [range, 30–88]; baseline tumors: diffuse large B-cell lymphoma [DLBCL], n=14; follicular lymphoma [FL], n=10; Hodgkin lymphoma [HL], n=9; marginal zone lymphoma [MZL], n=8; CLL, n=6; mantle cell lymphoma [MCL], n=5; 62% had >3 prior systemic regimens). Median duration of therapy was 3.3 mo (range, 0.6–13.4); no DLTs were identified. 67% of pts discontinued therapy (disease progression, 31%; AEs, 25%); 33% had dose interruption; 4% had reduction. Most common nonhematologic AEs (all grade [Gr]; Gr ≥3): nausea (38%; 0%), diarrhea (31%; 6%), vomiting (25%; 0%); Gr ≥3 hematologic AEs: neutropenia (21%), lymphopenia (17%), thrombocytopenia (10%), anemia (4%). 40% of pts had serious AEs, most frequently colitis, diarrhea, hypotension (all n=3). 1 pt had Gr 3 pneumonitis; none had Pneumocystis jirovecii pneumonia (PJP) or Gr ≥2 elevated transaminase. Objective responses (ORs) occurred at all doses (Table), except 5 mg QD; 90% were observed at first assessment. Conclusions: INCB050465 demonstrated manageable toxicities with no clinically meaningful transaminitis/PJP. OR rates were generally high, with 90% observed at first assessment. Different dosing regimens/schedules, long-term safety, and disease-specific cohorts are being evaluated. Clinical trial information: NCT02018861. [Table: see text]