Citations

e13893 Background: For individuals with CNS tumors who have experience difficulties with in-person (IP) evaluations due to disease-related neurologic disability or the costs associated with travel, telehealth (TH) offers a convenient and timely alternative for accessing specialized neuro-oncology care. We report our institution’s experience with telehealth utilization in neuro-oncology. Methods: We conducted a retrospective review of patients who had at least one neuro-oncology telehealth visit between August 2021 and May 2024 at Mayo Clinic in Rochester, Minnesota. Reasons for visits, outcomes of appointments, acute care utilization following visits was reviewed. Results: A total of 660 patients who had at least one TH visit between August 2021 and May 2024 were included in the analysis. Median age was 56 (range 20-98), 49% were female, and 92% were white. Most patients resided in the US Midwest (84%), followed by the South (8%), West (5%), Northeast (1%), and US Territories (< 1%). Less than two percent were international patients. The most common primary visit diagnosis was glioblastoma (GBM, 26%), followed by astrocytoma, IDH-mutant (17%), meningioma (17%), oligodendroglioma, IDH-mutant, 1p/19q codeleted (7%). Of 6657 visits reviewed, 2745 (41%) were conducted via TH. Telehealth visits served various purposes, including consultation for newly diagnosed tumors or abnormal MRIs (n = 26), second opinion for an established tumor diagnosis (n = 119), discussion about clinical trial participation (n = 108), tumor-related treatment discussions (n = 719), chemotherapy education (n = 161), new symptom assessment (n = 117), symptom management (n = 366), and tumor surveillance (n = 1694). Outcomes from telehealth visits included enrollment in clinical trials (n = 28), proceeding with tumor-directed surgery (n = 46), initiation of radiation therapy (n = 88), starting or changing systemic therapy (n = 377), continuing existing systemic therapy (n = 932), transition to supportive care (n = 45), tumor diagnostic workup (n = 28), continuation of tumor surveillance (n = 1254). Acute care utilization, defined as an emergency department visit or hospitalization within one month of an appointment, was the same following telehealth visits compared to in-person visits (6.9% for IP vs 5% for TH, p = 0.507). Conclusions: Our findings demonstrate that telehealth can effectively support all aspects of neuro-oncology care, ranging from initial diagnosis discussions to systemic therapy management and transitions to supportive care. Telehealth offers a convenient and accessible method of care delivery option for patients faced with neurologic illness. Additionally, THs do not lead to increased acute care utilization compared to IP evaluations.

e13890 Background: Many oncology practices have reported continued use of telemedicine since onset of the COVID-19 pandemic. However, the future sustainability of telemedicine within oncology practices remains unclear, particularly because federal policies that enabled adoption in response to the public health emergency (PHE) have not been made permanent. Understanding similarities and differences in telemedicine utilization at high-volume oncology centers is crucial for shaping evidence-based policy that enables equitable access to oncology care across varying geographies. Methods: This is a cross-sectional, year-over-year, retrospective cohort analysis of trends in telemedicine utilization across all medical oncology clinical appointments conducted among adult patients (age >18) from January 2019 to December 2023 at Stanford Medicine Cancer Center (SM) – comprising multiple campuses in the California Bay Area – and the Mayo Clinic Comprehensive Cancer Center (MC) – a multiregional cancer practice with tertiary referral campuses in Minnesota, Florida, and Arizona, as well as community-based clinics throughout the Upper Midwest. Results: Both institutions exhibited a similar trend in telemedicine adoption over time. This was characterized by an initial surge in utilization following the PHE declaration in March 2020, followed by sustained utilization rates from 2021 to 2023. However, telemedicine use as a proportion of the overall practice differed significantly between institutions. At SM, the rate of telemedicine visits as a proportion of overall clinical practice was 60.3% (49,136/ 81,502) in 2021, 59.9% (52,247/ 87,215) in 2022, and 57.2% (55,007/ 96,163) in 2023. At MC, the proportion of telemedicine utilization was 12.8% in 2021 (23,873/186,086), 14.7% in 2022 (28,985/196,777), and 14.0% in 2023 (30,208/215,941). Deployment in the setting of new versus return visits also differed between institutions. In 2023, telemedicine accounted for 53.7% (6,440/11,998) of new and 57.7% (48,567/84,165) of return visits at SM, compared to 15.5% (3,359/21,728) and 13.8% (26,849/194,213) at MC. Additionally, while video visits were the predominant modality used to conduct telemedicine visits at both institutions from 2021 onward, in 2023 phone visits still made up 17.9% (5,394/30,208) of all telemedicine visits at MC, compared to just 5.4% (2,990/55,007) at SM. Conclusions: Stanford Medicine and Mayo Clinic exhibited a pattern of initial growth of telemedicine adoption in 2020, followed by sustained utilization from 2021-2023. We observed unique differences in the overall proportion, visit type deployment, and modality of telemedicine utilization between institutions. However, this study confirms telemedicine visits have remained a fixture of medical oncology care for many patients at these institutions since the COVID-19 pandemic.

e23345 Background: Telemedicine enables patients to attend visits remotely and is associated with shorter wait times (i.e. scheduling-to-appointment duration). However, its impact on patient–clinic distance and wait times for new patients in high-volume surgical oncology centers remains unclear. In these centers, where appointment availability and travel distance significantly influence care decisions, understanding telemedicine’s impact on access is essential as federal policies supporting telemedicine continue to be under legislative review. To address this, we examined the relationship between new patient visit modality, distance, and wait time across demographics, providing insights to guide policy makers, and clinical practice. Methods: We extracted visit data from a multispecialty surgical oncology center in Northern California from 2019 to 2023 and used linear models with fixed effects for clinician and patient characteristics to assess the association of NPV modality with distance and wait times. We calculated distance using geodesic measurements between residential ZIP codes and care sites and derived median household income and education levels from the American Community Survey. Results: There were 10596 NPVs in 2019, and 13982 in 2023, conducted by 78 and 100 clinicians respectively. The proportion of NPV visits conducted by telemedicine increased from 0% to 28% during this period. From 2021–2023, NPVs conducted by telemedicine were more likely to fall outside the center’s 2019 catchment area (80th percentile of distance) with an adjusted odds ratio of 1.89 (95% CI 1.62, 2.21). Wait times for telemedicine NPVs was 3.0 days shorter (95% CI [2.0, 3.9]) than in-person visits. Compared to the reduction in wait times for patients aged 45–65 (2.8 days, 95% CI [1.8, 3.8]), those 80 and older had a smaller reduction (1.9 days, 95% CI [0.9, 2.8]), while patients aged 65–79 had a greater reduction (3.4 days, 95% CI [2.4, 4.5]). This effect did not significantly vary by sex, race, ethnicity, education, income, or insurance status. Conclusions: At this multispecialty surgical oncology center, new patients seen via telemedicine were more likely to reside outside the center’s traditional catchment area and had shorter wait times, with these differences varying by demographic characteristics. Strategic telemedicine integration tailored to patient needs could enhance access by reducing wait times and expanding specialized surgical oncology care to patients across broader geographic distances.

TPS4616 Background: Osseous metastases (OM) occur in approximately 30% patients with advanced RCC. Despite therapeutic advances, OM are associated with poor survival and risk of symptomatic skeletal events (SSEs). Cabozantinib targets multiple tyrosine kinases, including vascular endothelial growth factor (VEGF) receptors and MET (Mesenchymal-Epithelial Transition factor), which are overexpressed in OM, contributing to cabozantinib’s enhanced bone activity. Radium-223, an alpha-emitting bone-seeking radioisotope, prolongs survival in men with metastatic castration-resistant prostate cancer to the bone. Building on this therapeutic approach targeting OM, our pilot study of radium-223 with VEGF inhibition in RCC with OM has also shown safety, improvement in circulating bone turnover markers, and early efficacy (McKay et al, CCR 2018). To address the unmet need to improve SSE rates and outcomes in RCC and OM, we designed a study investigating cabozantinib with or without radium-223 in patients with RCC with OM (NCT04071223). Methods: This is an open-label, multicenter randomized phase-2 study. Key inclusion criteria include metastatic RCC of any histology with ≥1 OM, at least 1 OM without prior radiation, any number of prior therapies, and Karnofsky performance status ≥ 60%. Use of a bone protecting agent is required unless contraindicated. Patients are randomized 1:1 to cabozantinib with (Arm A) or without (Arm B) radium-223. The starting dose of cabozantinib for Arm A is 40 mg by mouth daily to be escalated to 60 mg daily after cycle 1 (1 cycle = 28 days) if no persistent grade 2 or grade ≥3 toxicity. Radium-223 is administered at a fixed dose of 1.49 microcurie/kg IV every 28 days x 6 doses. The starting dose for cabozantinib in Arm B is 60 mg daily. The primary endpoint is SSE-free survival. Secondary endpoints include safety, progression-free survival, overall survival, time to first SSE, objective response rate, time to subsequent anti-cancer therapies, quality of life (QoL) measures, and correlative analyses including liquid biopsy and tumor tissue analysis. The study is designed to have 85% power to detect an improvement in 6-month SSE-free survival rate from 65% to 78% with one-sided α = 0.05 significance. To ensure 124 evaluable patients, target accrual is 134 (67 per arm). The group-sequential design includes a safety run-in and an interim analysis for futility when 50% of the expected number of events have been observed. The safety run-in, performed in the first 12 patients randomized to combination therapy, did not demonstrate dose limiting toxicities. Final data analysis will occur when 99 events have been observed. The study was activated in July 2020 and accrual is ongoing throughout the National Clinical Trials Network (NCTN). Continued site participation and enrollment are essential to evaluate this therapeutic strategy. Clinical trial information: NCT04071223 .

TPS4630 Background: Bacillus Calmette-Guérin (BCG) is the standard first-line therapy for patients with high-risk non–muscle-invasive bladder cancer (NMIBC) with carcinoma in situ (CIS) ± papillary tumors; however, patients whose disease is unresponsive to BCG therapy are unlikely to benefit from further courses of BCG. Bladder-preserving treatment options for patients with BCG-unresponsive NMIBC with CIS ± Ta/T1 include intravesical gene therapy (nadofaragene firadenovec-vncg), intravesical chemotherapy (gemcitabine and docetaxel), and immunotherapy (intravenous pembrolizumab and intravesical nogapendekin alfa inbakicept-pmln). In a pivotal phase 3 study, 53.4% of participants (55/103) with BCG-unresponsive NMIBC with CIS ± Ta/T1 achieved a complete response (CR) within 3 months of a single instillation of nadofaragene firadenovec, and of them, 45.5% (25/55) maintained a CR at 12 months. Nadofaragene firadenovec in combination with chemotherapy or immunotherapy may further improve clinical efficacy. ABLE-22 (NCT06545955) is an interventional study evaluating the safety and efficacy of nadofaragene firadenovec alone or in combination with chemotherapy (gemcitabine and docetaxel) or immunotherapy (pembrolizumab) in participants with high-risk BCG-unresponsive NMIBC. Participants not responding at month 3 will be offered reinduction. Methods: ABLE-22 will include approximately 40 to 75 sites across the United States and Canada; sites in Asia, Australia, and Europe may be included. Participants (anticipated N = 150) will be randomly assigned 1:1:1 to receive nadofaragene firadenovec (n = 50), nadofaragene firadenovec plus gemcitabine and docetaxel (n = 50), or nadofaragene firadenovec plus pembrolizumab (n = 50). Adults aged ≥18 years with documented NMIBC with CIS ± Ta/T1 that is unresponsive to ≥2 courses of BCG therapy within the last 12 months are eligible to enroll. The primary endpoint is CR (defined as absence of low- and high-grade NMIBC) at months 3 or 6, as participants with persistent NMIBC (any CIS, low-grade Ta, and > 3 cm or multifocal high-grade Ta) will be offered reinduction once, at month 3. Secondary endpoints include durability of CR, incidence of muscle-invasive progression, cystectomy-free survival, pathologic staging, overall survival, and safety. Durability of CR will be followed up to month 36 (assessed quarterly for the first 24 months); all other secondary endpoints will be assessed up to and including month 36. Exploratory endpoints include changes in expression of potential biomarkers in blood and urine. Results from this investigational, randomized, multicenter, open-label study evaluating the safety and efficacy of nadofaragene firadenovec alone or in combination with chemotherapy or immunotherapy are expected July 2028. Clinical trial information: NCT06545955 .

3145 Background: SnoRNAs are non-coding RNAs that primarily guide the chemical modification of ribosomal RNA. Emerging evidence suggests snoRNAs play critical roles in cancer, including CRC, by regulating cell proliferation, apoptosis and tumor progression. Aberrant snoRNA expression has been linked to CRC development and poor prognosis, offering potential as diagnostic biomarkers and therapeutic targets. We investigated whether the tumor expression levels of 3 types of snoRNAs (SCARNA, SNORA, SNORD) affect treatment response in pts enrolled in CALGB/SWOG 80405 (NCT00265850). Methods: 433 mCRC pts treated with bevacizumab (bev, n = 226) or cetuximab (cet, n = 207) in combination with first-line chemotherapy were analyzed. RNA was isolated from FFPE tumor samples and sequenced on the HiSeq 2500 (Illumina). 422 snoRNAs were evaluated (23 SCARNA, 140 SNORA, 259 SNORD). Overall survival (OS) and progression-free survival (PFS) were compared across tertiles of gene expression (high [H], medium [M], low [L]) by multivariable Cox proportional hazards models adjusted for age, sex, ECOG performance status, tumor side, number of metastatic sites, KRAS , CMS subtypes, and treatment. Interaction tests for the predictive effect (bev vs cet) were performed. P -values were corrected for multiple testing using the Benjamini-Hochberg approach ( q < 0.05). Results: Only SCARNA21 achieved statistical significance for OS after false discovery rate (FDR) adjustment. Tumors with H levels of SCARNA21 had shorter survival compared to tumors with M or L expression (median OS 24.4 vs 32.4 vs 33.9 months, respectively; P = 0.0015, q = 0.033), independent of treatment. No snoRNAs achieved FDR significance for PFS. However, several snoRNAs showed significant treatment interactions with biologic agents. SCARNA6-H and SCARNA5-H tumors had longer PFS and OS when treated with cet, but shorter PFS and OS when treated with bev, compared to the M and L expression groups (PFS interaction q = 0.0067 and 0.045, respectively; OS interaction q = 0.022 and 0.034, respectively). SCARNA7 also showed significant treatment interaction for OS, favoring cet in the H expression group ( q = 0.018); the opposite was observed for SNORA63B, SNORA63D, SNORA35B, and SNORA36C ( q = 0.027, 0.027, 0.027 and 0.047, respectively). No significant results were observed for any of the tested SNORDs. Conclusions: SnoRNAs dysregulation affects key pathways such as cell cycle control and immune evasion, making them promising players in CRC biology. Our study highlights the prognostic and predictive potential of specific snoRNAs in mCRC. Notably, high SCARNA21 expression was linked to shorter OS, while SCARNA5 and 6 showed predictive value for treatment response, indicating their potential for guiding treatment decisions. Further validation is needed to confirm these findings, and mechanistic studies are warranted.

3128 Background: LncRNAs have emerged as key regulators of cancer progression and therapeutic responses. In CRC, several lncRNAs have been implicated in modulating tumor growth, metastasis and treatment resistance by interacting with critical tumorigenic pathways. Here, we investigate the potential prognostic and predictive value of lncRNA expression in patients (pts) with mCRC enrolled in CALGB/SWOG 80405 (NCT00265850) trial. Methods: We analyzed 433 mCRC pts treated with either bevacizumab (bev, n = 226) or cetuximab (cet, n = 207) plus first-line chemotherapy. Tumor RNA expression (Illumina HiSeq 2500) of 13 candidate lncRNAs (SNHG11, HOTAIR, FGF14-AS2, H19, YWHAE, NEAT1, MIR100HG, UCA1, LINC00973, SLCO4A1-AS1, POU5F1P4, MALAT1, HCG18) was explored. Median overall survival (mOS) and progression-free survival (mPFS) in months (mo) were compared between pts grouped by tertiles (low [L] vs medium [M] vs high [H]) of gene expression. Likelihood ratio tests, hazard ratios and 95% confidence intervals were computed from multivariable Cox proportional hazards models, adjusting for age, sex, ECOG PS, tumor location, number of metastatic sites, KRAS , Consensus Molecular Subtypes (CMS), and treatment. Results: Overall, SNHG11 was strongly associated with OS and PFS after adjusting for multiple tests (Benjamini-Hochberg False Discovery Rate < 0.05). High SNHG11 expression (H group, n = 144) was associated with improved mPFS (H: 14.3 vs M: 11.2 vs L: 8.3 mo; p = 0.038) and mOS (H: 39.6 vs M: 31.1 vs L: 20.5 mo; p = 0.033) in the combined treatment analysis. Among cet-treated pts, SNHG11-H showed a numerically longer mPFS (H: 14.2 vs M: 11.1 vs L: 7.6 mo; p = 0.19) and significantly longer mOS (H: 41.1 vs M: 32.4 vs L: 14.3 mo; p = 0.012). In contrast, no statistically significant OS or PFS differences were observed in bev-treated pts. SNHG11-H tumors had a significant OS benefit from cet compared to bev (mOS 41.1 vs 36.5 mo, respectively; p = 0.016), with a nominally significant treatment interaction observed for OS (p = 0.030). No significant differences were observed in the L or M expression groups. Additional analyses showed that SNHG11 expression was high in the CMS2 (canonical) subtype and substantially lower in CMS1 (immune). Conclusions: LncRNA SNHG11 plays a significant role in CRC progression and metastasis via tumorigenic pathways, including c-Myc and HIF-1α. Moreover, elevated circulating SNHG11 levels show promise as a non-invasive biomarker for early CRC detection. In CALGB/SWOG 80405, high SNHG11 expression correlated with improved PFS and OS, particularly in cet-treated pts, supporting its role as a prognostic and predictive biomarker. Its strong association with CMS2 aligns with its reported involvement in c-Myc-driven pathways. Further validation is needed to confirm the clinical utility of this biomarker and elucidate underlying mechanisms.

High-grade gliomas, like glioblastoma multiforme (GBM), are the most common malignant brain tumors in adults and are treated with the chemotherapy drug temozolomide (TMZ). In humans, a retrospective analysis of patients’ overall survival suggests that morning dosing may confer a benefit over evening dosing. Circadian variation in O6-methylguanine-DNA methyltransferase (MGMT) gene expression and promoter methylation has been implicated in increased tumor cell sensitivity to TMZ in the morning. Although patient compliance with timed oral administration of TMZ was high in a prospective trial, it is not known whether differences in daily sleep patterns of patients impact the biological time of drug administration or overall survival. Using wrist actigraphy collected from 10 high-grade glioma patients, we quantified the moment of oral TMZ delivery in terms of wall clock time and internal biological time during the months after surgical tumor resection. We found that variation of daily rhythms within and between individuals caused dosing times to vary more in their internal biological time than wall clock time so that, for example, some doses taken by patients assigned for the evening (2000 h) were closer to the patient’s internal biological morning. We conclude that wrist actigraphy provides a reliable and non-invasive estimate of personal circadian time that could improve efficacy and precision of TMZ delivery. These findings may inform personalized circadian medicine and optimized times for TMZ delivery in the clinic.

Importance Nontraumatic subarachnoid hemorrhage (SAH) represents the third most common stroke type with unique etiologies, risk factors, diagnostics, and treatments. Nevertheless, epidemiological studies often cluster SAH with other stroke types leaving its distinct burden estimates obscure. Objective To estimate the worldwide burden of SAH. Design, Setting, and Participants Based on the repeated cross-sectional Global Burden of Disease (GBD) 2021 study, the global burden of SAH in 1990 to 2021 was estimated. Moreover, the SAH burden was compared with other diseases, and its associations with 14 individual risk factors were investigated with available data in the GBD 2021 study. The GBD study included the burden estimates of nontraumatic SAH among all ages in 204 countries and territories between 1990 and 2021. Exposures SAH and 14 modifiable risk factors. Main Outcomes and Measures Absolute numbers and age-standardized rates with 95% uncertainty intervals (UIs) of SAH incidence, prevalence, mortality, and disability-adjusted life-years (DALYs) as well as risk factor–specific population attributable fractions (PAFs). Results In 2021, the global age-standardized SAH incidence was 8.3 (95% UI, 7.3-9.5), prevalence was 92.2 (95% UI, 84.1-100.6), mortality was 4.2 (95% UI, 3.7-4.8), and DALY rate was 125.2 (95% UI, 110.5-142.6) per 100 000 people. The highest burden estimates were found in Latin America, the Caribbean, Oceania, and high-income Asia Pacific. Although the absolute number of SAH cases increased, especially in regions with a low sociodemographic index, all age-standardized burden rates decreased between 1990 and 2021: the incidence by 28.8% (95% UI, 25.7%-31.6%), prevalence by 16.1% (95% UI, 14.8%-17.7%), mortality by 56.1% (95% UI, 40.7%-64.3%), and DALY rate by 54.6% (95% UI, 42.8%-61.9%). Of 300 diseases, SAH ranked as the 36th most common cause of death and 59th most common cause of DALY in the world. Of all worldwide SAH-related DALYs, 71.6% (95% UI, 63.8%-78.6%) were associated with the 14 modeled risk factors of which high systolic blood pressure (population attributable fraction [PAF] = 51.6%; 95% UI, 38.0%-62.6%) and smoking (PAF = 14.4%; 95% UI, 12.4%-16.5%) had the highest attribution. Conclusions and Relevance Although the global age-standardized burden rates of SAH more than halved over the last 3 decades, SAH remained one of the most common cardiovascular and neurological causes of death and disabilities in the world, with increasing absolute case numbers. These findings suggest evidence for the potential health benefits of proactive public health planning and resource allocation toward the prevention of SAH.