Merrell, Kenneth W.

PURPOSE Cancer care capacity in sub-Saharan Africa (SSA) is constrained by late diagnosis and limited treatment access. Few funding mechanisms support innovative, locally led programs to address these challenges. A collaborative initiative was developed to strengthen oncology care through quality improvement (QI) projects. MATERIALS AND METHODS The program was developed by Global Bridges Oncology (GBO) at Mayo Clinic, Pfizer Global Medical Grants, and the African Organisation for Research and Training in Cancer. A committee composed primarily of African oncology experts guided the process. An RFP was disseminated across SSA in English, French, and Portuguese, inviting applications to improve diagnostic and therapeutic cancer care. Applications underwent a structured, two-stage review, with GBO providing technical support, expert guidance, and training resources. RESULTS The RFP generated 218 applications reflecting strong demand for oncology QI funding in SSA. After review, 17 projects representing 10 African countries were selected and awarded $1.1 million USD. Funded initiatives reflected four themes: oncology training and clinical practice improvements, early detection and accurate diagnostics, pediatric cancer care, and oncology nursing and palliative medicine. As of March 2026, 11 (65%) of 17 projects are complete, with 4,565 health care professionals engaged through direct training, conference dissemination, system adoption, and sensitization activities, and program-supported services were delivered to more than 47,300 patients. CONCLUSION This initiative demonstrates the feasibility of a competitive, regionally guided grant program to strengthen cancer care capacity. Early implementation outcomes, including measurable improvements in diagnostic delay, treatment adherence, and care network expansion, confirm that locally led QI initiatives can generate meaningful results across diverse institutional settings. By centering African leadership and supporting diverse QI projects, it advances equitable access to funding, capacity building, and sustainability planning.

Background/Objectives: We performed a systematic review of preclinical literature on the use of high-LET particle therapy, DDRi, and/or immunotherapy specifically in pMMR colorectal cancer. Methods: A systematic review of the literature published between 2014 and 2025 was conducted across major databases. Studies were included if they examined particle radiotherapy (e.g., proton, alpha, and carbon) or X-ray radiation either alone or in combination with DDRi and/or immune checkpoint inhibitors (ICIs) in pMMR colorectal cancer models. Results: In total, 131 studies met the inclusion criteria, including 70 preclinical studies. These studies consistently demonstrate that high-LET radiation amplifies immunogenic cell death, increases cGAS-STING pathway activation, and enhances tumor antigen presentation, thereby fostering greater immune infiltration and systemic antitumor responses. Concurrent irradiation with DDRi enhances persistent DNA damage and cytosolic DNA accumulation. In murine models, high-LET therapies show excellent local control, with manageable toxicity profiles. Combination regimens with ICIs exhibit improved local control and elicit systemic antitumor immune responses. Conclusions: High-LET particle radiation and/or the use of concurrent DDRi with ICI have significant preclinical evidence of immunostimulatory effects in pMMR rectal adenocarcinoma and increased response rates to immunotherapy. The clinical evidence will be reviewed in the companion manuscript.

Background/Objectives: We performed a systematic review of the current clinical and preclinical literature on the use of particle therapy, DDRi, and/or immunotherapy, specifically for pMMR colorectal cancer. Methods: A systematic review of the literature published between 2014 and 2025 was conducted across major databases. Studies were included if they examined particle radiotherapy (e.g., proton, alpha, carbon) either alone or in combination with DDRi and/or immune checkpoint inhibitors (ICI), or X-ray radiotherapy (XRT) in combination with DDRi/ICI. Results: In total, 133 studies met the inclusion criteria, including 62 clinical studies. Clinically, particle therapies show excellent local control and normal tissue sparing, with manageable toxicity profiles. Trials with any form of radiation and DDRi are few, potentially owing to toxicity concerns. ICI combinations showed promising efficacy with XRT, with no randomized trials comparing them to particle radiation. Conclusions: Particle radiation and/or DDRi have significant preclinical evidence of immunostimulatory effects in pMMR rectal adenocarcinoma and increase response rates to immunotherapy (presented in the companion manuscript). Despite strong preclinical evidence and rationale, clinical trials including all three modalities are scarce. Existing evidence suggests a potential benefit based on extrapolation from photon-based studies and supports prospective evaluation with careful attention to treatment-related toxicity, which remains a concern.

BACKGROUND: Cardiac radioablation is emerging as a treatment modality for refractory ventricular tachycardia. This study aimed to evaluate the effects of radiation on the coronary arteries in a swine model of proton beam cardiac radioablation. METHODS: Eighteen swine underwent single-fraction 30 to 40 Gy pencil-beam scanning proton therapy targeting the left ventricle and were euthanized 12 to 40 weeks later. Treatment planning was performed without restricting the dose to the coronary arteries. The maximum point dose (D max ) to the epicardial coronary arteries was calculated. In secondary analyses, the mean (D mean ) and minimum dose received by the highest irradiated 0.01 cm 3 (D 0.01 ) of each coronary artery were also calculated. Coronary artery segments were harvested from the D max sites for histological analysis, and the D max was correlated with stenosis severity. RESULTS: Ninety-six coronary arteries were analyzed. No stenoses were observed by computed tomography imaging preirradiation. By histological analysis posteuthanasia, 25/96 (26%) coronaries sampled at their D max sites had ≥75% stenosis. The median D max was 4.7 Gy for the <75% stenosis group and 29.7 Gy for the ≥75% stenosis group ( P <0.001). The AUC-ROC for the association between D max and stenosis ≥75% was 92.2%. A D max value of 20.1 Gy best predicted stenosis ≥75%, with sensitivity 92.3% and specificity 87.1%. The AUC-ROCs for the associations of D mean and D 0.01 with stenosis ≥75% were 84.8% and 91.6%, respectively. In histopathologic analysis, intimal hyperplasia was the most common coronary artery abnormality at the D max sites, and it was present in 61.5% of all arteries and in 93.9% of arteries with D max ≥20 Gy. CONCLUSIONS: In this preclinical model of proton beam cardiac radioablation, coronary stenoses occurred in a dose-dependent manner, with D max showing the closest correlation with stenosis ≥75%. These data provide for the first time a framework for dose constraint considerations for the coronary arteries during treatment planning for cardiac radioablation and thoracic malignancy radiation.

Background: Cardiac radioablation (CRA) is emerging as a treatment modality for refractory ventricular tachycardia (VT). This study aimed to evaluate the effects of radiation on the coronary arteries in a swine model of proton beam CRA. Methods: Eighteen domestic swine underwent 30–40 Gy pencil-beam scanning proton therapy in a single-fraction targeting the left ventricle with no attempt to spare coronary arteries and were euthanized 12-40 weeks later. Contrast-enhanced cardiac computed tomography (CT) was performed at baseline for treatment planning and at study end. Using dose-volume histograms, the maximum point (D max ), mean (D mean ) doses and the minimal doses received by the highest irradiated volumes of 0.01 cc (D 0.01cc ) for the left main, left anterior descending, circumflex, and right coronary artery, as well as the large diagonal and obtuse marginal branches were calculated. The D max location for each artery was mapped from the baseline planning CT onto the follow-up CT using deformable registration. Coronary artery segments were harvested from the D max sites for histological analysis. Receiver operating characteristic (ROC) analysis was performed to identify dose thresholds for predicting histologically severe coronary stenoses (≥75%). Results: Ninety-six coronary artery segments were analyzed. No stenoses were observed by CT imaging before irradiation. By histological analysis post-euthanasia, 25/96 (26%) coronary segments sampled at the Dmax site per artery had ≥75% stenosis. The median D max was 4.7 Gy for the <75% stenosis group and 29.7 Gy for the ≥75% stenosis group (p<0.001). The AUC-ROC for the association between D max and severe stenosis was 92.2%. A D max value of 20.1 Gy in a single fraction best predicted severe stenosis, with sensitivity of 92.3% and specificity of 87.1%. The AUC-ROC for the association between severe stenosis versus D mean and D 0.01cc was 84.8% and 91.6%, respectively. Based on histopathologic analysis, intimal hyperplasia was the most common coronary artery abnormality at the D max sites. Conclusion: In this pre-clinical model of proton beam CRA, coronary stenoses occurred in a dose-dependent manner, with D max being a better dosimetric predictor of stenosis than D mean and D 0.01cc . These data provide for the first time radiation dose constraint information for the epicardial coronary arteries that can be considered in treatment planning for CRA and radiation for thoracic malignancies.

Objectives: For locally advanced rectal adenocarcinoma (R-ACA), a nonoperative management (NOM) approach has emerged as a guideline-supported treatment option. However, the variables associated with NOM receipt are unknown. Methods: Utilizing the National Cancer Database, we performed a retrospective cohort study of adults with stage 1 to 3 R-ACA managed with curative intent from 2004 to 2018. The primary outcome was the proportion of patients receiving NOM versus surgery. The secondary outcome was survival among NOM patients. Results: A total of 128,297 patients were included. In all, 115,888 (90.3%) received surgery and 12,409 (9.7%) received NOM. Receipt of NOM was associated with age above 70, Charlson-Deyo score of 0, race (Black, Asian or Pacific Islander, or other vs. White), insurance status, geographical region, treatment in a community facility, year of diagnosis (2012-2018 vs. 2004-2011), tumor grade 1 versus ≥ 2, clinical T-stage ≥ 2, and clinical N1 or N2 versus N0. In the NOM cohort, poorer overall survival was associated with age 70 and above, male sex, Charlson-Deyo score ≥ 1, insurance status, geographical region, rural urban density versus metro/urban, treatment in a community facility, year of diagnosis (2004-2011 vs. 2012-2018), clinical T4 versus T1, clinical N1 or N2 versus N0, grade 3 versus 1, treatment with a radiotherapy dose <45 Gy versus 45 to 54 Gy, and omission of chemotherapy. Conclusions: Several demographic factors and social determinants of health were associated with receipt of NOM and overall survival. With the increasing utilization of NOM, it will be important to understand the drivers of treatment decisions and influences on access to the desired treatment approach.

OBJECTIVE Spinal stereotactic radiosurgery (SSRS) is an established treatment modality for spinal metastatic disease. A common complication of SSRS is postradiation pathologic fracture. The authors evaluated the risk of pathologic fracture in sacral SSRS. METHODS All patients receiving SSRS in 1 to 5 fractions to 1 or more sacral levels between 2011 and 2020 at participating institutions were included. Demographic, histological, anatomical, and outcome data were obtained from electronic medical records. Data were analyzed using SPSS version 28. RESULTS Of 67 total patients, 50 (74.6%) were men and 17 (25.4%) were women. The most common tumor histologies were prostate adenocarcinoma (n = 16 [23.9%]) and renal cell carcinoma (n = 12 [17.9%]). Median (range) age at treatment was 63 (8–87) years. The mean ± SD (range) number of levels treated was 1.5 ± 0.7 (1–4) levels. Mean ± SD (range) bone density at S1 was 208.0 ± 74.4 (−3.0 to 443.3) Hounsfield units (HUs). Median (range) follow-up was 16.6 (1.5–132) months, median ± SD (range) overall survival was 24 ± 21.0 (1.7–83.3) months, and the 1-year local control rate was 83.6%. Fourteen patients (20.9%) experienced fracture within the radiation field. There was no association between fracture and patient sex (p = 0.32), age (p = 0.40), S1 HU (p = 0.28), tumor location according to Denis classification (p = 0.87), presence of pain (p = 0.66), single versus multifraction radiation (p = 0.44), or number of levels treated (p = 0.52). Patients experiencing in-field progression were more likely to experience fracture (61.5% vs 10.2%, p < 0.001), and patients experiencing fracture had a higher average Spine Instability Neoplastic Score than patients without fracture (5.7 vs 4.3, p = 0.049). Only local control remained as a factor associated with sacral fracture in the multivariate analysis. Of the patients experiencing fracture, 10 (71.4%) were symptomatic and 3 of those (30.0%) underwent post-SSRS surgical intervention. CONCLUSIONS Pathologic fracture may occur after sacral SSRS in a significant number of patients and is significantly associated with failure of local control.

e18017 Background: Head and neck (H&N) cancers affect the oral cavity, pharynx, larynx, salivary glands, nasal cavity, and sinuses. In Sub-Saharan Africa (SSA), the true burden of H&N cancers remains unclear, with available estimates suggesting approximately 47,000 new cases and 26,000 deaths annually. Limited cancer datasets hinder understanding of disease patterns and outcomes. This study explores patient characteristics, treatments, and outcomes to guide regional cancer control efforts. Methods: A cancer dataset was created and implemented at 4 leading teaching hospitals in Ghana, Kenya, Ethiopia, and Rwanda to systematically collect data on patient demographics, disease characteristics, and treatment patterns. Established through competitive grant funding, the primary objective of the database was to assess the indirect impact of the COVID-19 pandemic on cancer care. The dataset includes all cancer patients seen in consultation and/or treated between 2016 and 2023. In this study, a subset of patients diagnosed with H&N cancers was analyzed using descriptive statistics to assess clinical characteristics, treatments modalities, and patients' outcomes. Results: A total of 1,023 patients with H&N cancer were included in the analysis. The median age at diagnosis was 54 yrs (IQR 41-66), with 37% (n= 374) of the cohort being female. A total of 55% (n= 549) had no health insurance coverage. Of those with staging data, majority presented with advanced disease (89%) on presentation. Regarding treatment modality, 16% (n= 157) underwent surgery, 27% (n=279) received radiotherapy (RT), 14% (n= 143) received chemotherapy (CT), and 56% (n= 572) received no cancer therapy. Of those who received CT the timing was neoadjuvant (12%), concurrent with RT (22%), adjuvant after surgery (8.9%) or as palliative treatment (57%). Platinum-based agents (94%) were the most common CT, followed by Taxol-based (31%), and 5FU-based agents (27%). Regarding RT, planning was performed using 2D (55%) and 3D (45%) techniques. The median delivered dose was 60 Gy in 30 fractions. At a median follow up of 43 months, 1.6% were disease free, 10% (n= 103) were alive, 5.9% (n= 60) were confirmed dead, and 84% (n= 848) were lost to follow up. Conclusions: This study identifies key challenges in managing H&N cancers in SSA, including late-stage presentation, limited access to advanced treatment modalities, and a high lost to follow-up rate (84%). The reliance on older RT techniques such as 2D planning and the limited use of surgery highlight gaps in infrastructure and resource availability. Limited health insurance coverage suggests potential financial barriers to care and disparities in treatment access. Addressing these challenges will require greater investment in cancer care, expansion of the oncology workforce, and improvements in healthcare infrastructure to support better patient outcomes in the region.

e14551 Background: Extracellular vesicles (EVs) are microscopic particles released by all cell types with a distinct fingerprint reflecting the cell of origin. In patients with prostate cancer, PSMA+EVs have been associated with clinical outcomes. In this study, we investigated tumor-derived EVs (tdEVs) using the tumor-specific CD326 marker as a novel biomarker for pancreas ductal adenocarcinoma (PDAC). Methods: The study included patients with localized PDAC treated on a prospective phase 2 clinical trial evaluating a 15-fraction chemoradiation (CRT) regimen. Blood samples were obtained after induction chemotherapy (C) (prior to CRT) and in follow-up. 20 healthy controls were included. High-resolution flow cytometry enumerated levels of fluorescent antibody labelled tumor-specific CD326 (EpCAM)-positive EVs. All samples were de-identified and randomly coded. The technologist responsible for EV analysis was blinded to patient information and clinical data. Each sample was run in triplicate. Flow cytometry data was analyzed with custom-built software to automatically determine and apply gates and generate reports with scatter plots and EV concentrations for each combination of markers and data summaries. Results: tdEV data were analyzed from 70 patients with pre-CRT samples. Patients had mean age 66 years (9.0 standard deviation), with 60% ECOG 0, 43% borderline resectable and 48% locally advanced. Patients had a median 8 cycles of C prior to CRT, and 70% proceeded to surgery after CRT. 2-year overall survival (OS) was 54%. Patient samples showed elevated total CD326 EVs compared to the healthy controls (p = 0.0005). Furthermore, patient CD326 EVs revealed two distinct subpopulations: small (120-1,000nm) and large (1,000-3,000nm) size CD326 EVs. No large CD326 subpopulation was found in healthy donor samples. Higher pre-CRT levels of total CD326 and large CD326 EVs were associated with decreased progression-free survival (PFS) (hazard ratio (HR) = 2.38, p = 0.013 and HR = 2.017, p = 0.021) on multivariable models with surgical resection. Resection was associated with increased PFS (p < 0.0001), and the interaction terms did not meet significance (p = 0.083 and p = 0.21). No differences in pre-CRT total or large CD326 EVs were identified between patients with or without surgical resection (p = 0.72 and p = 0.83). CA19-9 levels were not predictive of clinical outcomes in this trial and showed no association with EV levels. Conclusions: We present an association between clinical outcomes and tdEVs in PDAC, highlighting their potential as a novel, independent biomarker. If validated, tdEVs may offer an opportunity to personalize care and improve risk stratification.

e17511 Background: Cervical cancer is a significant public health concern in Sub-Saharan Africa (SSA), where it remains the leading cause of cancer-related mortality among women. SSA has the highest global incidence and mortality rates, with an estimated 110,300 new cases and 76,700 deaths in 2020. Despite this burden, data on patient characteristics and treatment outcomes remain limited. This study aims to address these gaps by analyzing current treatment patterns and outcomes for cervical cancer in SSA. Methods: A cancer dataset was established at 4 major teaching hospitals in Ghana, Kenya, Ethiopia, and Rwanda to capture data on patient demographics, disease characteristics, and treatment modalities. The dataset encompasses all cancer patients seen between 2016-2023, with over 9,000 cases collected to date. The primary objective of the dataset was to assess impact of COVID-19 pandemic on cancer care in SSA. This study conducted a retrospective analysis of cervical cancer cases within the dataset utilizing descriptive metrics. Results: A total of 2,326 patients were analyzed, with a median age at diagnosis of 56 y (48–65) and 53% having health insurance. The majority had squamous cell carcinoma (87%) and presented with locally advanced disease (FIGO stages IIB–IVA, 88%). Treatment primarily consisted of concurrent chemoradiotherapy (CRT, 34%) or radiotherapy (RT) alone (30%), while smaller proportions received chemotherapy (CT) alone (1.2%) or surgery (1.3%). A total of 33% of patients received no cancer therapy. Among 1,524 patients treated with RT, 1,180 received external beam RT with a median dose of 46 Gy in 23 fractions, using 2D planning in 60% and 3D planning in 40% of cases. Additionally, 25 patients underwent brachytherapy, with 58% receiving low-dose-rate and 42% high-dose-rate treatments. Of 1,011 patients treated with CT, 85% (n=844) completed the intended course, with a median of 4 cycles, primarily delivered concurrently with RT (95%). Only a few received CT as adjuvant (4.8%), neoadjuvant (1.6%), or palliative (3.4%) therapy. Platinum-based regimens were most common, with 43% receiving platinum monotherapy and 5% receiving platinum-taxane combinations. By the end of treatment, 27% (n=633) achieved disease-free status. After a median follow-up of 47 months (range,37–55), 42% were alive, 7% had died, and 53% were lost to follow-up with unknown vital status. Conclusions: This study reveals significant challenges in management and follow-up of cervical cancer in SSA. Most patients were diagnosed at advanced stages, with 32% receiving no treatment and 53% of treated patients lost to follow-up. These findings highlight barriers to early diagnosis, treatment access, and continuity of care. Addressing these issues requires expanding early diagnostic services, increasing vaccination coverage, strengthening healthcare infrastructure, and improving patient retention.