Okuno, Scott H.

ABSTRACT Purpose This study assesses the association between colorectal cancer (CRC) screening and a validated, housing-based measure of individual-level socioeconomic status (SES, called HOUSES hereafter) within rural communities and determines whether HOUSES-integrated geospatial analysis can be used to tailor interventions. Methods We used CRC screening data from a subset of Mayo Clinic Midwest patients living in cities without ready access to routine care in the Mayo Clinic Health System in 2019 to represent rural communities. At the individual level, we assessed the association between CRC screening rates and the HOUSES index, adjusting for age, sex, race/ethnicity, comorbidity, distance from home address to clinic, and area deprivation index, using a multilevel mixed-effects logistic regression model. Additionally, we conducted geospatial analysis to examine the correlation between hotspots of 1) lower CRC screening rates and 2) lower SES of the subject population (HOUSES quartile 1). Findings Among 34,489 individuals (median age 64.0 years, 52.4% female), those with the lowest SES (HOUSES Q1) had 37% lower odds of being CRC screening adherent than those with the highest SES (HOUSES Q4) (adj. OR [95% CI]: 0.63 [0.58-0.69]). In the 14 identified HOUSES Q1 hotspots, there was a significant correlation in counts of HOUSES Q1 and low CRC screening (correlation coefficient=0.81). Conclusion Lower SES was significantly associated with lower CRC screening among rural populations. HOUSES-enabled geospatial analysis identified geographic hotspots with lower CRC screening rates for targeted interventions to address disparities in CRC screening in rural communities. HOUSES may be a useful digital tool for cancer preventive care and research.

Abstract Objective To evaluate the clinical value of breast MRI in radiation-associated angiosarcoma of the breast (RAASB) for assessing disease extent at diagnosis and after neoadjuvant therapy compared with clinical examination and surgical pathology. Methods This IRB-approved retrospective study included 25 patients with breast MRIs between1995 and 2020. MRI estimated disease extent was compared to clinical exam and surgical pathology. MRI findings were evaluated for additional disease and impact on clinical management. Agreement between MRI and clinical assessment of disease was evaluated using Cohen’s kappa statistic. Results Baseline MRI demonstrated moderate agreement with clinical disease extent (Cohen’s κ = 0.44; 95% CI, 0.14-0.75). Thirteen of 24 (54%) of MRIs reflected clinical exam, 4/24 (17%) MRIs underestimated disease, and 5/24 (21%) MRIs overestimated disease. Baseline MRI changed surgical management in 4/24 (17%). In 8 patients who proceeded directly to surgery, MRI reflected pathology in 6/8 (75%). In 10 patients with post-neoadjuvant MRI, 4/10 (40%) pathology and MRI extent were similar, 5/10 (50%) MRI overestimated disease, and 1/10 (10%) MRI underestimated disease. Conclusion MRI has clinical value in assessing RAASB with the potential for significantly altering surgical management. In this small cohort, post-neoadjuvant MRI demonstrated limited additional clinical value. Larger studies are needed to define the optimal role and timing of post-neoadjuvant MRI. Advances in knowledge Baseline MRI detected additional disease not identified on initial clinical exam in 5/24 (21%) and changed surgical management in 4/24 (17%). Although baseline MRI demonstrated moderate agreement with clinical examination, post-neoadjuvant MRI frequently overestimated residual disease when compared with final pathology.

TPS11592 Background: Epithelioid hemangioendothelioma (EHE) is an ultra-rare vascular sarcoma with about 120 cases diagnosed in the US per year. Although it is commonly considered an indolent disease, in its aggressive form clinical outcomes are poor. Molecularly, EHE is characterized by the presence of oncogenic fusions with HIPPO pathway effectors TAZ or YAP; TAZ-CAMTA1 or YAP-TFE3. YAP/TAZ are modulators of mTORC1 in preclinical models, suggesting that mTOR inhibition may be an effective treatment mechanism for EHE. Nab-sirolimus is albumin bound sirolimus, which achieves higher intratumoral accumulation compared to oral sirolimus and has demonstrated increased antitumor activity in preclinical cancer models compared to the oral mTOR inhibitors sirolimus and everolimus. This is an open label, multi-center, single arm, phase II clinical trial with a two-stage design, testing nab-sirolimus for progressing or symptomatic EHE. The primary objective is to determine ORR of nab-sirolimus in patients with EHE who require systemic treatment. We hypothesize that nab-sirolimus will have significant clinical efficacy for EHE as measured by the primary endpoint of objective response rate, as well as by secondary outcomes including progression free survival benefit over historical controls and by improvement in patient reported outcomes (PROs). If positive, this trial could lead to a new standard of care for treating EHE. Methods: This is a single arm, multi-center, phase 2 study with a two-stage design. Key inclusion criteria include histologically or cytologically confirmed EHE that is either progressing or clinically symptomatic, not a candidate for curative intent surgery, and requires systemic therapy in the opinion of the investigator, radiographically evaluable disease by RECIST v1.1, age ≥18 years, ECOG performance status ≤ 2, and adequate end organ function. With a Simon two-stage optimal design with one sided alpha 0.10, power 90%, assuming a historical control ORR 5% to detect an ORR of 20% (alternative hypothesis), 12 patients will be included in the first stage. If there is ≥ 1 response, an additional 25 patients will be enrolled to a total of 37 patients. ≥ 4 responses are needed for a significant result. The total planned accrual is 41 patients to account for unevaluable patients who may be enrolled, 10% above the required evaluable patients. Planned post hoc subgroup analyses will include outcomes by fusion type and presence of serosal effusions at the time of study enrollment. The trial is registered at clinicaltrials.gov NCT07104331. Clinical trial information: NCT07104331 .

We previously reported initial results of the pivotal phase II trial of atezolizumab for patients with alveolar soft part sarcoma (ASPS; ClinicalTrials.gov identifier: NCT03141684 ). Here, we report on three additional years of observation. Fifty-three patients with ASPS received atezolizumab. Median duration of response increased to 37.0 months. Objective response rate (ORR) and median progression-free survival (mPFS) remained essentially as previously reported (35.8% [95% CI, 23.1 to 50.2] and 20.8 months [IQR, 7.6-not reached], respectively). ASPSCR1::TFE3 fusion type was determined for 47/53 patients; ORR and mPFS were higher among the 41 patients expressing type 1 (43.9% [95% CI, 28.5 to 60.2] and 28.3 months [IQR, 9.2-not reached], respectively) than the six patients expressing type 2 (0% [95% CI, 0 to 45.9] and 7.5 months [IQR, 3.9-not reached], respectively, PFS HR, 3.2 [95% CI, 1.01 to 10.2]). Eleven patients chose a per-protocol drug holiday (range, 3.5-26.4 months) after ≥2 years of treatment; two experienced disease progression during the holiday. Nine eligible patients elected to receive bevacizumab plus atezolizumab after progressing on monotherapy; ORR was 0% and mPFS was 18.5 months (IQR, 7.9-21.1) in this small cohort. Long-term results support using atezolizumab to treat ASPS, even for several years; a drug holiday with careful monitoring may be an option for some patients.

Background: Localized soft tissue sarcoma (STS) is primarily treated with surgical resection with or without radiotherapy (RT), while the role of chemotherapy (CT) as a radiosensitizer remains unclear. We report our single-institution experience with combined chemoradiotherapy (CCRT) in treating localized STS. Methods: We conducted a retrospective analysis of patients with localized STS treated at Mayo Clinic with mitomycin, cisplatin, and doxorubicin (MitoAP) concurrently with RT between 1/1/85 and 12/12/19. Results: We identified 179 patients (median age 58 years; median tumor size 9.5 cm), with 83.8% of tumors located in the extremities or trunk. Among them, 77.1% received perioperative CT in addition to CCRT, with 95% of those treated in the neoadjuvant setting. Median RT dose was 50 Gray. The 5-year disease-specific survival (DSS) was 77.9% (95% confidence interval, CI: 70.8–83.4%). The addition of perioperative CT to CCRT was associated with improved DSS compared with CCRT alone (p = 0.01, Hazard Ratio, HR: 0.48, 95% CI: 0.27–0.85). Median post-CCRT tumor viability was 30% and did not differ by CT use (p = 0.39), but varied significantly by histology (p < 0.001). Conclusions: Our institutional protocol utilizing two cycles of MitoAP with RT was well tolerated. DSS in our cohort was similar to historical data using perioperative RT alone, suggesting no clear benefit from CCRT. However, the majority of patients in our cohort were classified as high risk, which may have attenuated a potential survival benefit in the absence of appropriate comparative controls. Furthermore, additional perioperative CT to CCRT was associated with improved DSS and differential histology-specific responses in tumor viability, suggesting that a more aggressive neoadjuvant and perioperative approach may be beneficial in selected patients.

Abstract Introduction: The National Cancer Institute estimated almost 317,000 new breast cancer and over 13,000 new cervical cancer cases in 2025. While the National Breast and Cervical Cancer Early Detection Program has served millions of women over the past two decades, inequities in cancer screening, subsequently delayed diagnosis, and timely and appropriate treatment remain a public health challenge in the United States. Despite the substantial impact of social determinants of health (SDOH) on cancer screening, few studies have accounted for SDOH at the individual level when assessing breast and cervical cancer screening adherence. The primary objective of this study is to examine whether the individual-level SDOH, measured using HOUsing-based SocioEconomic Status (HOUSES) index, is associated with breast and cervical cancer screening non-adherence (not current on respective USPSTF recommendations for age and frequency). Methods: In this retrospective study, patients were identified as those receiving primary care in the Mayo Clinic Health System and Mayo Clinic (Rochester, MN). The Midwest Quality Metrics panel was then used to assess patients due for screening for breast or cervical cancer in July 2023. The HOUSES, using home address and publicly available data on the residence which measures and categorizes housing status into quartiles, was obtained using the electronic health records (EHRs)-linkable patient-level information. Logistic regression analyses were conducted, controlling for Census block group-level adverse social exposome from the Area Deprivation Index, age, and comorbidities. Results are presented as odds ratios (OR) with corresponding 95% confidence intervals (CI). Results: For breast cancer, among 128,462 eligible patients, 20.1% (n= 25,857) were non-adherent. Compared to the highest HOUSES quartile (Q4), lower HOUSES groups showed significantly higher odds of non-adherence: Q3 OR=1.20 (95% CI=1.15, 1.25), Q2 OR=1.45; (95% CI=1.40, 1.53), and Q1 OR=1.90 (95% CI=1.81, 1.99). For cervical cancer, among 175,712 eligible patients, 29.9% (n=52,533) were non-adherent. Compared to the highest HOUSES quartile (Q4), lower HOUSES groups showed significantly higher odds of non-adherence: Q3 OR=1.07 (95% CI=1.03, 1.10), Q2 OR=1.16; (95% CI=1.12, 1.20), and Q1 OR=1.36 (95% CI=1.31, 1.41). Conclusions: A clinically meaningful association between the HOUSES index and cancer screening adherence was observed. A lower HOUSES index was associated with higher odds of non-adherence for both breast and cervical cancer screening, even after accounting for neighborhood-level risk, age, and comorbidities. Incorporating HOUSES into EHRs can be a practical “screening-for-screening” tool that enables close monitoring of higher-risk patients without additional burden of surveys. Citation Format: Eunice Y. Park, Madison Beenken, Dave Watson, Chung Il Wi, Tufia Haddad, Gladys Asiedu, Karla BALLMAN, James R. Cerhan, Carolyn Flock, Brian Lynch, Folakemi T. Odedina, Scott H. Okuno, Young J Juhn, . HOUSES as a screening tool for cancer screening: Patient-level housing-based socioeconomic status and breast and cervical cancer screening adherence [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 7599.

Background: Myxofibrosarcomas are notoriously highly infiltrative soft-tissue sarcomas, making negative surgical margins difficult to obtain. Recently, vacuum-assisted closure (VAC) is used to delay wound closure until a negative margin has been achieved; however, this can delay care and increase costs. Our institution has historically performed single-stage resections with intraoperative frozen margin analysis and reconstruction in these patients. The purpose of this study is to report the outcomes of this technique. Methods: We reviewed 112 patients (62 males, mean age 70 ± 14 years) with superficial myxofibrosarcoma. Eighty-eight patients received preoperative radiation. All patients underwent surgical resection with intraoperative frozen margin analysis, and the planned reconstruction was performed in a single anesthetic. Results: The 10-year local recurrence-free survival was 90%; positive intraoperative frozen section (HR 7.44, p = 0.004) and final permanent margins (HR 8.53, p = 0.007) were associated with local recurrence. Intraoperative margins were negative in 103 (92%) of patients, 1 of which was positive on final permanent section. There were nine cases of microscopically positive margins, of which seven underwent immediate re-excision to a negative margin. The accuracy of frozen margin assessment for myxofibrosarcoma was between 92.92 and 98.23%. All patients underwent reconstruction at the time of resection, with 19% needing an additional procedure, most commonly due to a wound complication (12%). Conclusions: Multidisciplinary single-stage excision with intraoperative frozen margin assessment and soft-tissue reconstruction yields low rates of local recurrence in patients with superficial myxofibrosarcoma.

TPS11580 Background: Gastrointestinal stromal tumor (GIST) is the most common sarcoma of the gastrointestinal tract. KIT and platelet-derived growth factor receptor α ( PDGFRA ) mutations remain the key oncogenic drivers in the majority of patients with advanced GIST, with acquired secondary drug-resistant mutations contributing to the heterogeneity and complexity of the disease. The diversity of these resistance mutations allows escape from standard-of-care tyrosine kinase inhibitor (TKI) therapy, creating an unmet need for novel therapies that inhibit all clinically relevant GIST-driving mutations. DCC-3009 is an investigational, highly potent, and selective switch-control KIT and PDGFRA inhibitor designed to act against known clinically relevant primary and secondary GIST-driving mutations while limiting off-target effects. Preclinical data showed that DCC-3009 has strong antitumor effects in xenograft models driven by resistant KIT mutations, optimized solubility and oral bioavailability, and low risk of cytochrome P450 inhibition. Here, we describe an ongoing phase 1/2 study evaluating DCC-3009 as a monotherapy in patients with advanced GIST. Methods: This study is a multicohort, open-label, phase 1/2 trial evaluating the safety, tolerability, and efficacy of DCC-3009 in patients with advanced GIST (NCT06630234). This trial uses a modular approach, with each module defined according to the therapy (DCC-3009 alone or in combination with other anticancer agents) and divided into 2 parts (dose escalation and dose expansion). For inclusion in the DCC-3009 monotherapy dose escalation, adult patients (≥18 years) must have histologically or cytologically confirmed advanced GIST with documented KIT or PDGFRA mutation and progression on or intolerance to at least 1 approved TKI regimen in the advanced setting (imatinib if KIT -mutant). Patients must have at least 1 measurable lesion per modified Response Evaluation Criteria in Solid Tumors version 1.1 (mRECIST v1.1) and an Eastern Cooperative Oncology Group Performance Status of 0 or 1 at screening. Exclusion criteria include receiving systemic anticancer therapy (encompassing investigational agents) within 14 days or less than 5 half-lives, radiotherapy within 14 days prior to first dose of study drug, prior or concurrent malignancy requiring treatment or expected to need treatment for active cancer, known allergy or hypersensitivity to the study drug components or any of its excipients, and impaired oral absorption or malabsorption syndrome. Enrolled patients across monotherapy dose escalation will receive DCC-3009 orally in 28-day cycles. The primary outcome measures for monotherapy dose escalation include safety assessment. Secondary outcome measures include objective response rate, duration of response, and progression-free survival by mRECIST v1.1, as well as overall survival and pharmacokinetics. Clinical trial information: NCT06630234 .

TPS11579 Background: Gastrointestinal stromal tumors (GIST) are commonly driven by mutations in the receptor tyrosine kinase KIT . Resistance to approved tyrosine kinase inhibitors (TKIs) arises from additional KIT mutations in the ATP-binding pocket (AP) and activation loop (AL). No single approved TKI broadly suppresses all resistant clones, and overlapping VEGFR inhibition and toxicity limits TKI combinations. The type I TKI bezuclastinib (“BEZ,” CGT9486) inhibits KIT AL resistance mutations, does not inhibit VEGFR, and has complimentary activity with sunitinib (“SUN,” inhibitor of KIT AP resistance mutations). The first-in-human study (PLX121-01) and ongoing Peak trial (NCT05208047) evaluated BEZ+SUN showing promising safety and efficacy in GIST. SARC044 investigates BEZ+SUN in patients (pts) with SUN-resistant, KIT-mutant GIST, and correlatives aim to determine mechanisms of response and resistance (NCT06208748). Methods: SARC044 is a multi-center, open label, single-arm phase II trial enrolling up to 40 adult pts with KIT exon 9 or 11-mutant GIST resistant to imatinib and SUN. After TKI washout (baseline, “b/l”), pts initiate BEZ 600 mg daily for 2 weeks, then add SUN 37.5 mg daily, taking both drugs continuously (28-day cycles) until mRECISTv1.1 progression or unmanageable toxicity. Response evaluations (RE) are performed every 8 weeks (wk) through 15 months (mo) on study, then every 12 wk. Circulating tumor DNA (ctDNA) is collected at b/l, cycle 1 day 15 (C1D15), C2D1, C3D1, and progression. Targeted exome sequencing (TES) of ctDNA will track primary/resistant KIT mutation dynamics across therapy. 18 FDG PET/CTs are performed in 20 pts at b/l, C1D15, and C2D1, which guide a biopsy of a resistant tumor. TES, allele-specific and long-read PCR (to detect AP+AL mutation phasing), and immunoblotting (evaluating KIT pathway activation) will be performed on tissue. EORTC QLQ-C30 surveys collect pt-reported outcomes (PRO) at b/l, on treatment, and at progression. The primary endpoint is median progression-free survival (mPFS) and secondary endpoints include overall survival at 1 and 2 years, clinical benefit rate at 16 wk, adverse event rate, PRO, and KIT mutation profile in ctDNA and tissue. 35 evaluable pts achieves 83% power (p<0.05, one-sided) in a one-sample log-rank test to detect a mPFS of 6.5 mo vs 4 mo (historic control). Expected accrual is 12 mo across 4 sites in the United States with ~36 mo to study completion. Clinical trial information: NCT06208748 .

Abstract Purpose: Soft-tissue sarcomas are rare malignancies with poor prognosis and limited systemic treatment options. We conducted a phase II study to assess the efficacy and safety of trabectedin and olaparib in patients with advanced disease. Patients and Methods: Patients with soft-tissue sarcoma who received ≥1 prior therapy were recruited into two cohorts. Cohort 1 included leiomyosarcoma and liposarcoma; cohort 2 included other histologies. All patients received trabectedin (1.1 mg/m2 24-hour infusion every 21 days) and olaparib (150 mg twice daily continuously). The study was conducted using a Simon minimax two-stage design with a primary endpoint of objective response (OR) rate per RECIST 1.1. Results: Twenty-nine (cohort 1, 16; cohort 2, 13) patients enrolled; one patient in cohort 2 was not evaluable. There were no confirmed ORs in cohort 1; the best response was stable disease in 12 (75%) patients and progressive disease in four (25%). Two partial responses were observed in cohort 2 (n = 12). The most common adverse events were fatigue (75%), neutropenia (75%), anemia (68%), and thrombocytopenia (68%). The median progression-free survival and overall survival for all patients were 3.5 (95% confidence interval, 3.3–8.2) and 13.2 months (95% confidence interval, 10.3–20.9), respectively. Next-generation sequencing of 17 tumors revealed multiple abnormalities, most commonly in TP53, RB1, and ATRX. Conclusions: Trabectedin plus olaparib conferred high rates of toxicity and failed to demonstrate ORs in leiomyosarcoma and liposarcoma. Preliminary evidence of clinical benefit in two patients in cohort 2 suggests potential value of either or both drugs in other sarcomas.