Extrapulmonary neuroendocrine carcinomas (EP-NECs) are a heterogeneous group of rare tumors with poor clinical outcomes. These patients have limited treatment options after progressing on first-line platinum-based chemotherapy. Although dual immune checkpoint inhibitors (ICIs) with anti-CTLA-4 and anti-PD-1 blockade have significantly improved outcomes for several solid tumors, they demonstrated modest activity for EP-NECs with 9–26% response rates and low survival rates. Preliminary data demonstrated that NP-101 (Nigella sativa formulation) enhances T-cell infiltration and is synergistic with dual ICPIs in NECs’ cellular models. This pilot study evaluated the tolerability and efficacy of NP-101 plus nivolumab and ipilimumab in patients with metastatic EP-NECs refractory to first-line platinum-based chemotherapy. This is a single-arm pilot study (NCTNCT05262556) in which patients with metastatic EP-NECs received NP-101 (oral capsules), 3,000 mg daily, plus ICPIs (intravenous nivolumab 3 mg/kg and ipilimumab 1 mg/kg) every 3 weeks for four cycles. Nonprogressors received NP-101 (3,000 mg daily), plus biweekly maintenance of nivolumab (240 mg), and then completed 24 weeks of treatment. Treatment-related adverse events (TR-AEs) were characterized according to CTCAE v4.03. The response rate was estimated according to Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1. The Kaplan–Meir method was used to estimate median PFS and OS. Twelve patients received ≥1 dose of NP-101 and nivolumab plus ipilimumab. There were no dose-limiting toxicities (DLTs). Grade 1/2 TR-AEs occurred in 100% (12/12) of patients. The most common G1/2 TR-AEs included the following: fatigue (75%), nausea (41.7%), pruritus (41.7%), muscle weakness (33.3%), vomiting (25%), rash (25%), and abdominal pain (25%). Eight patients (66%) experienced grade 3/4 TR-AEs, including rash (33.3%), nausea (16.7%), vomiting (16.7%), and transaminitis (16.7%). No treatment-related grade 5 toxicities or deaths were recorded. The objective response rate was 41.7% (2/12 (16%) complete response (CR) + 3/12 (25%) partial response (PR); 95% CI: 15.2–72.3%) for all patients and 50% (2/8 CR + 2/8 PR, 95% CI: 0.16–0.84) for patients with NEC of gastrointestinal origin. The median duration of response was 7.5 months. As for the median progression-free survival, it was 5.7 months, and the median overall survival (OS) was 10.5 months with a median follow-up of 10.4 months. The combination of NP-101 plus dual ICPIs (nivolumab and ipilimumab) was safe and well tolerated with preliminary evidence of antineoplastic activity. Currently, a randomized phase II clinical trial evaluating the combination is under development.

Purpose/Objective(s) We sought to test the utility of an advanced cone beam computed tomography (CBCT) solution on a C-arm Linac to precisely formulate prostate treatment plans directly from CBCT scans, thereby obviating the necessity for initial simulation or any subsequent resimulation. Materials/Methods Five patients undergoing prostate radiotherapy were imaged on a HyperSight CBCT (hCBCT) on a c-arm linear accelerator as part of a prospective imaging clinical trial (NCT05975619). Each patient had a treatment planning CT (TPCT) and a study hCBCT protocol scan at 140 kVp, followed by the reconstruction of each CBCT using three methods: FDK (Feldkamp-Davis-Kress), iCBCT (iterative CBCT), and iCBCT-MAR (Metal Artifact Reduction) for comparative analyses. Subsequent steps involved registering the CBCT images to TPCTs for alignment, and contouring targets and critical, in-field organs-at-risk (OARS; rectum, bladder) upon the iCBCT-MAR. Contours were edited exclusively on the iCBCT-MAR and then copied to registered FKS, iCBCT, and TPCT images without adjustment so there would be no difference in contour structures across all registered image sets. This was followed by plan reoptimization such that each CBCT reconstruction type had its own plan. Each of the three CBCT-derived plans per patient were then recalculated on respective TPCTs without modifications, and without reoptimization, to evaluate dose differences. Mean and standard deviation for the percent differences for the CTV, PTV, maximum, and mean doses to the OARs were calculated. Results Three CBCT-based plans that met all clinical goals were successfully created for all 5 patients using each reconstruction type as a primary dataset for each patient. Dose comparisons (in % difference from TPCT recalculation) are shown in Table 1 for each of the reconstructions. Target coverage and bladder metrics had lower differences between CBCT and TPCT compared to the rectum structure. 16 of the 18 (88.9%) metrics were within 5% of dose difference. A single OAR objective exceeded constraint on an iCBCT-MAR plan after recalculation on the TPCT (>98% of all OAR objectives met in all scenarios). Conclusion Our preliminary findings suggest that dose calculation relying solely on CBCT images as the primary dataset results in acceptable and dosimetrically minimal dose differences for the majority of evaluable structures, thus potentially enabling CBCT only treatment planning across all reconstruction types.

e15521 Background: The rising incidence of young-onset colorectal cancers (YO-CRC) in individuals < 50 years old is alarming. Despite the updated USPSTF recommended age for CRC screening ( < 45) in 2021, disparities in receiving proper care for YO-CRC remained largely under addressed. We sought to identify modifiable disparities to be addressed with future interventions for patients with YO-rectal cancer (YO-RC). Methods: We analyzed a cohort of patients with newly diagnosed YO-RC from 2001 to 2023 at a large academic center in Northeast Ohio. Demographic data included sex, race, age, smoking status, and poverty index. A retrospective chart review was completed to assess diagnosis date and time from symptom onset to diagnosis. Access to guideline-concordant care was assessed via clinic visits with specialty providers in medical oncology, radiation oncology, colorectal surgery, genetics, and onco-fertility. Chi-square testing and Cox regression modeling was used for statistical analyses. Results: We identified 83 patients with YO-RC, 52% female (n = 43) and 48% male (n = 40), of which 76% were White (n = 63), 21% Black (n = 17), 2% Hispanic (n = 2), and 1% Asian (n = 1). Median age at diagnosis was 44 years (IQR[39-49]). Non-White (NW) patients had a greater delay from symptom onset to diagnosis compared to White (W) patients, with an average time of 6.9mo vs 1.3mo (p < 0.00001). Colonoscopy completion rates after symptom onset for NW and W patients at 2-months was 11% vs 81% and 33% vs 98% at 4-months (p < 0.0001, respectively). Rate of access to specialty care once diagnosed was not statistically significant for either groups, but there is a lower percentage of all YO-RC patients who accessed onco-fertility (13%, n = 11) or genetics services (46%, n = 38). The median 1-year overall survival was 50% for NW patients vs 85.7% for W patients, which was statically significant on univariate analysis (p = 0.04), but not on multivariate analysis. Conclusions: We found significant disparities for YO-RC from symptom onset to diagnosis with longer delays noted in NW patients. Such delays in diagnosis may lead to higher staging upon presentation and impact survival. Once a diagnosis was made, access to specialty oncology care rates was similar across groups. This study encourages further evaluation and consideration of socioeconomic factors and care access patterns to address disparities in diagnosis, access, and treatment of YO-CRC. [Table: see text]

Purpose/Objective(s) Celiac plexus SBRT (CP-RT 25Gy/1fx) is an effective method of palliative pain relief for patients suffering from celiac axis tumor invasion. Standard complex/SBRT radiotherapy (RT) workflows for simulation and planning delay time to pain relief during end-of-life care. We propose a sim free, direct-to-unit (DTU) adaptive radiotherapy (ART) approach, using a diagnostic CT (dxCT) pre-plan and online adaptation for final plan construction to enable same-day radiation oncology consult and CP-RT. We aimed to demonstrate that hCBCT imaging enables this DTU, adaptive CP-RT workflow in silico with acceptable plan quality. Materials/Methods Five patients with abdominal malignancies were imaged on a HyperSight CBCT (hCBCT) solution on a c-arm linear accelerator as part of a prospective imaging clinical trial. Next, existing patient-specific dxCTs were used to generate CP-RT pre-plans. A radiation oncologist contoured initial pre-plan organ-at-risk (OARs; stomach, duodenum, small and large bowel, liver, kidneys, spinal cord) and targets. The CP-RT target (PTV25Gy) was defined as a 5mm ant-left/right rind around the aorta from the level of T12 to L2. An additional 5mm isotropic expansion was used to create the PTV20Gy. A semi-automated ART planning template developed for CP-RT was then applied. After pre-plan construction, to simulate a sim-free, DTU workflow, hCBCTs were injected into a CT-guided ART emulator environment as the primary dataset, with contours propagated from the registered dxCT. Contours were updated as needed to reflect the treatment anatomy and positioning. A standard online ART workflow was utilized for predicted and final adaptive plan calculation. Dosimetric statistics for each clinical goal were compared between predicted and final plans. Results DTU adaptive CP-RT plans were successfully created for all 5 patients and met all clinical goals. Table 1 shows comparative PTV coverage and OAR sparing of predicted and final ART plans. Without adaptation, predicted plans were infeasible for clinical use; 3/5 patients had non deliverable predicted plans. In contrast, all ART plans were clinically deliverable and met clinical goals. Conclusion DTU ART for CP-RT is dosimetrically feasible. Adaptation is a critical component for DTU CP-RT to achieve deliverable plans. This approach could reduce treatment delay for cancer-related celiac pain. A prospective pilot clinical trial is in development.

Purpose/Objective(s) At present, rural residents are less likely to receive radiotherapy due in part to the high travel burden required for daily treatment visits to a distant facility. This burden could be reduced by bringing mobile radiation oncology (MRO) units installed on trucks to remote areas with high cancer rates. However, due to the lack of precedence in this approach, this could be a high-risk venture for a healthcare network. Therefore, we developed a digital twin Agent-Based Model (ABM) simulation using systems engineering, opinion dynamic theory, and targeted survey data to guide and simulate the implementation of an MRO. Materials/Methods ABMs are defined as having a bottom-up modeling approach where individual agents (such as patients or physicians) are governed by “rules-of-engagement.” In our ABM, agent interactions were defined by patient and physician preferences to utilize MRO from collected survey data. General public cancer population data was collected from public health resources and data for rate of radiation therapy and rate of referral within our network was captured to model the current state of our cancer network. The MRO Linac would visit two separate geographic locations over a two-week period. In our ABM, each patient is initiated with an MRO preference and cancer type. A patient then interacts with physicians (such as a consult) and family where their intent to utilize MRO is updated via opinion dynamic models e.g., Continuous Opinion Discrete Action and the Relative Agreement Algorithm. The patient’s preference to pursue MRO is calculated via the Theory of Planned Behavior. Three separate methods of MRO implementation strategy were tested by influencing the agents within the model. A grass-roots approach (GRA) by improving patient attitude towards MRO, a community physician focus approach (CA) by improving physicians’ attitude towards MRO, and a main-hub physician focus (HA). Rates of MRO usage and impact on network patient volume were evaluated. Results In a 2-year period, the GRA treated an average of 106.3±21.5 patients. The CA treated an average of 115.9±22.6 patients and HA treated an average of 132.3±29.1 patients. Although numerically higher, HA was not statistically higher than the other approaches. To demonstrate patient benefit, HA reduced patient travel by an average of 15.2±11.6 miles. HA had the highest utilization rates for both patients and physicians whereas CA did not improve utilization rate for the main-hub physicians. This may be due to the low spoke-to-spoke interactions within our network which may limit influencing power. All intervention strategies resulted in a 23.9% average reduction in patient volume at a facility closer to the MRO. Conclusion An ABM was successfully developed that could test potential intervention strategies in high-risk scenarios for healthcare technology deployment. MRO has potential to reduce patient travel burden and increase access to care.

Purpose/Objective(s) Racial and ethnic minority populations are underrepresented in cancer clinical trials, with significant barriers more pronounced in these groups. The United States Food and Drug Administration (FDA) recommends the inclusion of underrepresented racial and ethnic populations and provides a standardized approach for collecting and reporting race and ethnicity data. This study aims to evaluate compliance with this recommendation and the distribution of national accrual among different race/ethnicity groups in early phase radiation oncology clinical trials. Materials/Methods We searched the clinicaltrials.gov database for registered interventional clinical trials over a 10-year period, including those started on or after January 1, 2014, and completed by January 1, 2024. The intervention for all included trials was ‘radiation therapy’ without further specification. Other inclusion criteria were adult age >18 years, study phase = ‘early phase 1’ or ‘phase 1’, study type = ‘interventional’, funder type = ‘NIH’ or ‘industry’, and trial location = ‘United States’. The data were screened to remove irrelevant information before analysis. Participants were recategorized as: non-Hispanic black (NHB), non-Hispanic white (NHW), Asian, Hispanic, and Others. Data were reported using descriptive statistics, with confidence intervals (Cis) for rates calculated using the binomial exact distribution and a significance level set at <0.05. Results Out of 215 clinical trials that met the search criteria, 172 were related to radiation oncology interventions. Of these, 105 (61.4%) were completed before January 1, 2024 (the rest were terminated or withdrawn). Results for 86 (81.9%; 95% CI 73.2-88.7) clinical trials were published; of these, 39 (45.3%; 95% CI 34.6-56.4) were in peer-reviewed journals and 47 (54.6%; 95% CI 43.5-65.4) were only published as abstracts at scientific meetings. Of the 86 published clinical trials, only 16 (18.6%; 95% CI 11.0-28.4) reported the racial distribution of study participants per FDA recommendations. Of the 432 subjects enrolled in these 16 studies, 213 (49.3%; 95% CI 44.5-54.1) were male and 219 (50.7%; 95% CI 45.9-55.5) were female. The racial/ethnic distribution was as follows: 32 (7.4%; 95% CI 5.1-10.3) NHB, 317 (73.4%; 95% CI 68.9-77.5) NHW, 11 (2.5%; 95% CI 1.3-4.5) Hispanic, 7 (1.6%; 95% CI 0.6-3.3) Asian, and 65 (15.0%; 95% CI 11.8-18.8) Others. Conclusion Less than 20% of early phase clinical trials in radiation oncology complied with the FDA’s recommendations for the collection and reporting of race and ethnicity data. Moreover, the lack of racial and ethnic diversity in early phase radiation oncology clinical trials has persisted over the past decade, necessitating immediate interventions to address this disparity.

In this patient population which included a large portion of patients with ECOG of 2 or greater and those deemed MI, a 5-fraction SMART regimen yielded durable long-term LC. The impact of increasing duration of induction chemotherapy underlies the importance of patient selection and improved understanding of tumor-specific biology when selecting patient's with locally advanced pancreatic cancer for aggressive local therapy.

These data demonstrate sART led to a significant decrease in dose to GI OARs, particularly for prescription dose or greater, even after accounting for intra-fractional bowel motion. While both the PI and the PA violated the V33 luminal GI OAR constraint in approximately ½ of pTx-CBCTs, the fraction of OARs receiving at least 50 Gy was significantly higher when overlaying the PI compared to the PA. While no G3 toxicities were reported in this small cohort, further studies are needed to characterize if the increased dose to GI OARs over the expected dose is clinically significant.

The results show that more plans are needed to improve the KBP model. This initial model was used to create a standardized clinical protocol in the TPS in order to continue adding plans to the KBP model database. This approach ensures that we obtain consistent plan quality and standardize our planning. The manual planning objectives achieved: CONCLUSION: The experience using the TPS to standardize our treatment planning process achieved good consistency in our planning objectives. This approach will help create KBP models according to our own clinic-specific requirements. Future work will be made to compare our LMIC KBP models with those made at a HIC academic radiotherapy center.

Despite different prescriptions, guidelines and demographics of cancer patients between two institutions in a HIC and LMIC, this work demonstrates that KB planning can be used to generate better and more consistent VMAT plans versus manually created plans. In addition, KB planning has the potential to greatly increase planning efficiency higher efficiency and help address the shortage of medical physicists and dosimetrists in LMICs.

Purpose/Objective(s) We recently deployed CT-guided stereotactic body radiation therapy (SBRT) using an O-ring gantry linear accelerator with an artificial intelligence-enhanced treatment planning system capable of online adaptive radiotherapy. The intrafraction motion management solution for this system gates based on optical monitoring of the patient's skin surface. This system has not yet been clinically validated. Therefore, we prospectively evaluated the feasibility of surface-guided optical gating in a Phase I clinical trial for patients with mobile, upper abdominal or lower thoracic malignancies treated with SBRT on this machine. Materials/Methods Ten patients were planned for accrual to this study. Eligible patients were medically fit for SBRT, had at least one abdominal or thoracic disease site suitable for treatment, and were capable of breath hold for at least 17 seconds, the minimum duration of the on-board volumetric cone-beam CT. The trial protocol stipulated a treatment prescription in five fractions. Daily adaptation was at the discretion of the daily treating physician. MD arrival, re-contour, re-plan, delivery, and total fraction times were recorded. Results Eight patients enrolled and were eligible for evaluation at the time of this submission. Forty of 41 fractions (98%) were successfully delivered. One patient tolerated only partial delivery of his first fraction because of pain, but the remaining dose was successfully delivered in a sixth fraction. Twenty-seven fractions (53%) were adapted online, motivated by improving target coverage (7%), meeting organ constraints (33%), or both (44%). The median total fraction time was 80 minutes (IQR 66 – 96). Conclusion Skin surface-guided optical gating proved feasible in nearly all attempted fractions for respiratory gating of upper abdominal and lower thoracic tumors. This methodology is now being incorporated for SBRT on this platform off-trial.