Citations

AbstractSecure messaging platforms were designed to optimize healthcare communication by providing asynchronous, bidirectional, Health Insurance Portability and Accountability Act‐compliant text messaging options. Proponents argue that these platforms streamline workflows, foster coordination across multidisciplinary teams, and improve patient safety. However, critics highlight their potential to disrupt workflows through overwhelming message volumes and task interruptions, increased risk for miscommunication, and possible detrimental impacts on patient care. While secure messaging shows promise for modernizing hospital communication, it requires institutional guidelines and thoughtful use to mitigate inefficiencies and risks.

Abstract Background Magnetic Resonance‐guided Radiation Therapy (MRgRT) systems are increasingly used in clinical practice, necessitating a dedicated dosimetry protocol to address the challenges posed by the presence of strong magnetic fields. Purpose AAPM TG351 introduces a reference dosimetry protocol for external beam MRgRT systems, aligning with AAPM TG51 reports and incorporating elements from the IAEA TRS398 code of practice. Methods The protocol offers practical guidance on beam quality and dosimetry setup in the presence of strong magnetic fields. It reviews relevant literature to identify reference‐class chambers suitable for external beam MRgRT systems and determines their beam quality conversion and other relevant correction factors through a detailed analysis of available data and associated uncertainties. Results AAPM TG351 offers a comprehensive dosimetry protocol for external beam MRgRT systems, addressing the unique challenges posed by the presence of magnetic fields. It includes detailed guidance for measurement setups, a list of reference‐class chambers appropriate for reference dosimetry in MRgRT systems, and updated beam quality conversion and correction factors. Additionally, the protocol presents an in‐depth analysis of the uncertainty budget, identifying key contributors and providing strategies to minimize uncertainties, thereby enhancing clinical accuracy and reliability. Conclusions This protocol provides a practical, evidence‐based reference for medical physicists conducting reference dosimetry in external beam MRgRT systems.

e18064 Background: Cell-free circulating tumor DNA (ctDNA)-based test has emerged as a promising tool in informing treatment modification in solid tumors. The clinical applications of ctDNA in head and neck squamous cell carcinoma (HNSCC) has been explored and here we report the clinical utilities of ctDNA in disease monitoring in HNSCC. Methods: HNSCC patients treated at our institution with available ctDNA test (Signatera) results between 2022 and 2024 were identified. Clinical information including disease site, stage and imaging results were collected and analyzed. Results: A total of 59 patients were identified. 21 (36%) patients had P16 + oropharyngeal cancer, 16 (27%) had oral cavity cancer, 9 (15%) patients had laryngeal cancer, 7 (12%) had P16-oropharyngeal cancer, 6 (10%) had perinasal sinus, hypopharyngeal or nasopharyngeal cancers. At the time of ctDNA test, 22 (36%) patients completed curative-intent treatment and had no radiographic evidence of disease (NED), 16 (26%) patients were treatment-naïve and had local/regional (LR) disease only, and 22 (36%) patients completed definitive treatment and developed radiographic evidence of LR recurrence or distant (D) metastatic disease. ctDNA was detectable in less than half (44%) of the treatment-naïve patients and the detection rate was even lower (14%) in the subgroup of p16+ oropharyngeal cancer. However, among patients with LR recurrent and distant metastatic disease, majority (77%) had positive ctDNA. ctDNA was undetectable in most of the patients (80%) who completed definitive treatment and were NED radiographically. Among the 3 patients who had detectable ctDNA, 2 were subsequently found to have recurrent disease on images and 1 is still on surveillance (table). Conclusions: Positive ctDNA was detected in most of the HNSCC with LR recurrent or distant metastatic disease, supporting its potential role in treatment response monitoring in this group of patients. Detectable ctDNA preceded radiographic evidence of recurrent disease in a small number of patients, suggesting the possibility of minimal residual disease detection using ctDNA in a subgroup of patients. Treatment history S/P definitive treatment Treatment naive S/P definitive treatment Radiographic evidence of disease (patient number) No (21) Yes (16; LR only) Yes (21; LR only: 10, distant: 11) ctDNA negative 18 9 4 ctDNA positive 3 (recurrence confirmed on subsequent imaging in 2 patients) 7 17

e18031 Background: HPV+ OPSCC has better outcomes than HPV negative OPSCC but more distant metastatic potential. ICM in HPV+ OPSCC are rare. Data regarding risk factors, clinical presentation and outcomes after ICM diagnosis is limited. This study describes clinical characteristics and outcomes of patients (pts) with HPV+ OPSCC who develop ICM. Methods: Retrospective analysis of pts with HPV+ OPSCC and ICM between 2010 - 2024. Demographic, clinicopathologic, and survival data was collected. Skull base recurrences were excluded. Univariate and multivariate analyses used Cox proportional hazard models; continuous variables binarized by receiver operator curves. Survival assessed via Kaplan-Meier method; reported as median (95% CI). Calculations use BlueSky (v10.3.1). Results: Among 1,999 pts with HPV+ OPSCC, 16 (0.8%) had ICM. Pt characteristics and treatment are summarized in Table 1. Primary tumor sites were base of tongue (56%), tonsil (38%), and unknown (13%). Most pts (n=8, 50%) presented with stage IV disease (6 extracranial metastasis (ECM), 1 ICM only, 1 both). Frontal and parietal lobes were the most frequent ICM sites. Neurological symptoms were present in 10 (62%) pts; ICM was incidentally found in 6 (38%) pts. Median overall survival (mOS) from initial diagnosis was 34 months (21 – not reached) and median time from diagnosis to ICM was 24 months (range 1-112). mOS following ICM detection was 10.9 months (4 -18). On multivariate analysis, only surgical resection (hazard ratio [HR] 0.03, p<0.01) and radiotherapy (HR 0.01, p<0.02) were independently associated with post-ICM survival. With median follow up of 100 months, 14 pts (88%) had died; 2 (12%) were alive. Conclusions: ICM from HPV+ OPSCC are rare but devastating with a mOS <1 year from detection. Most pts were symptomatic, had de novo metastatic disease, and had other sites of metastases. Surgical resection and radiation were associated with improved OS. Multicenter efforts to investigate predictors, multiomic sequencing and identification of pt subsets who may benefit from ICM screening are warranted. Baseline characteristics of Pts with ICM in HPV+ OPSCC. Variable Summary statistics (n=16) Median age (range) 58 (34-71) Male 14 (88%) Smoking history 10 (60%) Clinical stage at diagnosis Stage I: 4 (25%) Stage II: 2 (12.5%) Stage III: 2 (12.5%) Stage IV: 8 (50%) Symptoms at ICM diagnosis Incidental: 6 (38%)Neurological: 10 (62%) Seizure (n=3) Motor/Sensory symptoms (n=3) Altered mental status (n=2) Cognitive symptoms (n=1) Dizziness (n=1) ICM site Frontal lobe: 7 (44%) Parietal lobe: 7 (44%) Occipital lobe: 4 (25%) Temporal lobe: 2 (13%) Cerebellum: 2 (13%) Concurrent ECM Bone: 11 (69%) Lung: 9 (56%) Lymph node: 6 (38%) Liver: 5 (31%) Kidney: 1 (6%) Cranial nerve: 1 (6%) Treatment after ICM Radiotherapy: 15 (94%) Chemotherapy: 10 (63%) Immunotherapy: 9 (56%) Surgery: 8 (50%)

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.

e13167 Background: Abemaciclib represents a significant therapeutic advancement in the treatment of advanced metastatic breast cancer. As a selective protein-dependant kinase 4 and 6 (CDK4/6) inhibitor, it acts as a growth blocker. This study aims to evaluate the efficacy and safety of abemaciclib in combination with endocrine therapy for patients with metastatic breast cancer. Methods: We conducted an electronic search on December 27, 2024 using PubMed, Scopus, and the Cochrane database. Our inclusion criteria involved only randomized clinical trials evaluating the efficacy and safety of abemaciclib in combination to endocrine therapy in advanced breast cancer. Our primary outcomes were progression-free survival, overall response rate, overall survival, and grade 3 or 4 adverse effects. The hazard, odds, and risk ratios with 95% confidence intervals were used to determine the effect size. A random-effects model was applied. Results: Out of the 1,648 articles screened, only seven papers from five clinical trials met our inclusion criteria, comprising a total of 2,362 patients. Progression-free survival was significantly improved with abemaciclib in combination with endocrine therapy compared to endocrine therapy alone (hazard ratio: 0.58; 95% CI: 0.51–0.65; p < 0.001). Moreover, abemaciclib improved overall survival (hazard ratio: 0.78; 95% CI: 0.66–0.91; p = 0.002). Additionally, the overall response rate was higher with abemaciclib plus endocrine therapy compared to endocrine therapy alone (odds ratio: 2.75; 95% CI: 1.98–3.80; p < 0.001). However, grade three or higher adverse events were significantly more common in the abemaciclib group (risk ratio: 2.62; 95% CI: 2.30–2.99; p < 0.001). Conclusions: Abemaciclib combined with endocrine therapy is an effective treatment option for patients with HR-positive, HER2- negative advanced breast cancer. This combination significantly improves progression-free survival, overall survival, and response rate, making it a valuable therapeutic option in breast cancer. However, higher adverse events were observed in the abemaciclib group.

e13162 Background: BRCA1/2 mutations impair homologous recombination repair, forcing cancer cells to rely on alternative DNA repair pathways, such as those mediated by poly(ADP-ribose) polymerase (PARP). PARP inhibitors (PARPis), like iniparib, olaparib, talazoparib, niraparib, and veliparib, exploit this dependency, inducing lethality in cells of BRCA-mutated, HER2-negative breast cancers (BRCAm, HER2-BC). Only 2 PARPis, talazoparib and olaparib, are FDA-approved for BRCAm, HER2-BC. However, the treatment with the highest efficacy remains unclear. We conducted a network meta-analysis (NMA) of randomised controlled trials (RCTs) to compare the efficacy of PARPis in treating BRCAm, HER2-BC. Methods: We systematically searched PubMed, Cochrane CENTRAL, SCOPUS, and ClinicalTrials.gov (up to December 2024) for randomized controlled trials (RCTs) following PRISMA-NMA guidelines. Primary outcome was overall survival(OS), with hazard ratios (HRs) and 95% confidence intervals (CIs). Secondary outcome was progression-free survival (PFS). Survival times were converted to HRs under the assumption of exponential distribution. Standard of care (SOC) was defined as taxane/anthracycline-based regimens with additional platinum-based chemotherapy. Physician's choice chemotherapy (PCT) included capecitabine, eribulin, gemcitabine, or vinorelbine. A frequentist approach with random-effects modeling was used to pool estimates, and P-scores ranked treatment efficacy. Heterogeneity and inconsistency were assessed using τ², I², and Q-statistics. Analyses were conducted in R version 4.4.1. Results: 8 studies including 4432 participants incorporating 8 pairwise comparisons and 7 treatments were analyzed for OS. Compared to SOC (reference), HRs of OS were significantly reduced with talazoparib+SOC (HR = 0.49, 95% CI: 0.32–0.74; P = 0.64), olaparib+SOC (HR = 0.46, 95% CI: 0.36–0.59; P = 0.69), niraparib+SOC (HR = 0.44, 95% CI: 0.26–0.76; P = 0.76), and veliparib+SOC (HR = 0.38, 95% CI: 0.29–0.48; P = 0.91). No heterogeneity or inconsistency was detected (τ² = 0; I² = 0; Q = 1.27, p = 0.53). For PFS, iniparib/gemcitabine, talazoparib, olaparib, and niraparib showed significant reduction in HR with increasing order of P-scores, in combination with SOC. Conclusions: Veliparib combined with SOC showed the highest OS improvement, while niraparib ranked highest for PFS, followed by talazoparib and olaparib. Further trials are needed to confirm these findings and refine treatment strategies for BRCAm, HER2-BC.

e13154 Background: Triple-negative breast cancer (TNBC) is a less common but highly aggressive subtype of breast cancer with poor prognosis and limited therapeutic options. Despite advancements in oncology, significant survival disparities persist among racial, histologic, and socio-demographic groups. This study investigates these disparities and identifies factors contributing to unequal outcomes, providing actionable insights for improving care. Methods: Data on TNBC cases from 2000 to 2021 were extracted from the Surveillance, Epidemiology, and End Results (SEER) database, encompassing 17 registries and 76,265 patients. Patients were categorized by stage, marital status, age, race, and histology. Kaplan-Meier survival analysis was used to estimate median survival with 95% confidence intervals (CI), and the log-rank test assessed differences across groups. Cox proportional hazards regression determined the magnitude of disparities. A p-value < 0.05 was considered statistically significant. Results: Among the 76,265 patients analyzed, those with distant-stage disease had the poorest median survival (51 months; 95% CI: 46–60), compared to localized-stage patients (128 months; 95% CI: 127–129). The youngest cohort (15–19 years) exhibited the lowest survival (43 months), while individuals aged 80–84 had a median survival of 79 months (95% CI: 76–84). South Asians, particularly Pakistani individuals, had the shortest survival among racial groups (83 months). Single patients had lower survival (116 months) compared to married or divorced individuals. Histologically, median survival was 113 months (95% CI: 103–120) for epithelial neoplasms and 78 months for mucoepidermoid neoplasms. All observed differences were statistically significant (p < 0.05). Conclusions: Localized-stage TNBC, individuals aged 40–44, and patients from White or Black racial groups exhibited better survival outcomes, as did those with cystic, mucinous, or serous histologies compared to epithelial neoplasms. Addressing these disparities through tailored treatment strategies and improved access to care is critical. Limitations of this study include the lack of treatment-level data and the potential influence of unmeasured confounders. Stage Marital Status Age Group at Diagnosis Distant Localized Single Divorced 15-19 40-44 80-84 Median Survival(LCL-UCL) 51(46-60) 128(127-129) 116(114-118) 127(124-129) 43(14-NA) 132(130-135) 79(76-84) Neoplasm Histology Race Epithelial Muco-epidermoid Cystic, Mucinous& Serous Pakistani OtherAsian Black White Median Survival(LCL-UCL) 113 (103-120) 78(63-NA) 142(123-NA) 83 (63-NA) 97(91-108) 123 (121-125) 126 (125-127) LCL= Lower Confidence Limit, UCL= Upper Confidence Limit.

e13124 Background: Bria-IMT, an allogeneic whole-cell cancer vaccine (SV-BR-1-GM), was administered w/ an anti PD1 checkpoint inhibitor (CPI) to evaluate its safety and efficacy in advanced/metastatic breast cancer (MBC). SV-BR-1-GM breast cancer cells were engineered to directly stimulate anti-tumor immunity through expression of tumor associated antigens and secretion of GM-CSF to enhance endogenous dendritic cell activation. Addition of a CPI potentiates SV-BR-1-GM action by overcoming the immune suppressive tumor microenvironment and may have a differential impact vs monotherapy SV-BR-1-GM. Methods: In this exploratory analysis of the Phase 1 + randomized Phase 2, HLA matching status was assessed to explore potential correlations w/ clinical outcomes. Pts were stratified by overall HLA match by Class I or II (0 vs ≥1 matches), formulation and MBC subtype to assess objective response rate (ORR), clinical benefit rate (CBR), progression free survival (PFS), and overall survival (OS). Partial HLA matching (≥1 Class I and ≥1 Class II allele) was also analyzed. Results: In the total pt population, the ORR was 10%, CBR 56%, PFS 3.2 months and OS 9.9 months. In those pts treated w/ the phase 3 formulation, ORR was 15%, CBR 63%, PFS 3.6 months and OS 13.4 months. Using available HLA data (n = 52), 25% had 0, 34.6% 1, 32.6% 2, and 8% ≥3 matches. While OS and PFS were greater (Undefined vs 8.5 mos ; p = .02) in pts without an HLA match compared w/ those w/ ≥1 match (see Table), ORR and CBR were similar. This was also the case for pts who had 0 HLA Class I matches vs those w/ ≥1 Class I match (15.6 vs 7.2 mos; p = .002). ORR, CBR, PFS and OS were generally similar for pts who had 0 Class II HLA matches vs those w/ ≥1 match. Pts who matched at least at 1 Class I and 1 Class II allele had a higher ORR and CBR than those who matched at a single Class I or a single Class II allele although PFS and OS were similar between the groups. Similar observations were seen for pts treated w/ the phase 3 formulation. Conclusions: Matching at Class I seemed to decrease PFS & OS, but did not have a similar effect on ORR and CBR. Both matched and non matched pts demonstrated favorable OS and response rates. These findings support further investigation into specific mechanisms and the clinical significance of HLA matching in immunotherapy response. A randomized phase 3 trial is ongoing comparing Bria-IMT vs treatment of physician's choice (NCT06072612). Clinical trial information: NCT03328026 . n (Evaluable) % of Cohort Best ORR Best CBR PFS OS Full Cohort 52 (41) 10% 56% 3.2 9.9 No Match (Overall) 13 (10) 25% 20% 60% 4.2 Undefined Any Match (Overall) 39 (31) 75% 6% 55% 3 8.5 MHC Class I No Match / Any Match 27 (20) / 25 (21) 52% / 48% 10% /10% 55% /57% 3.5 / 2.7 15.6 / 7.23 MHC Class II Any Match 27 (19) 52% 11% 63% 3.2 11.4 MHC Class I&II Match 13 (9) 25% 22% 77% 2.8 8.6 Phase 3 Formulation (N=35) 35 (27) 15% 63% 3.57 13.43 No Match (Phase 3 Formulation) 11 (9) 31% 22% 67% 5.6 Undefined MHC Class I&II Match (Phase 3 Formulation) 11 (7) 31% 29% 71% 2.7 7.23

e13121 Background: Metastatic breast cancer remains a major clinical challenge, characterized by poor prognosis and limited therapeutic options. The incidence of metastatic female breast cancer increased from 5.8 to 7.9 per 100,000 females from 2001 to 2021. The Hippo pathway effector YAP1 plays a critical role in driving tumor growth and metastasis in many cancers including breast but little is known about the gene-specific changes that occur when breast cancers have metastasized. This study aimed to investigate the extent of genomic alterations, including copy number alterations (CNAs) and mutations, in YAP1 and its downstream genes in metastatic breast cancer compared to nonmetastatic breast cancer. Methods: Genomic data for the YAP1 gene and its downstream target genes (CTGF, Cyr61, MCL-1, TOP2A, FOSL2, and ANKRD1) were obtained from cBioPortal. This included mutation data and CNA data, considering both amplifications and deletions as CNA events. The chi-square test was performed using GraphPad Prism 10 to compare the frequencies of mutations and CNAs between metastatic and non-metastatic breast cancer cases. Results: A total of 2390 samples of metastatic breast cancer and 9289 samples of non-metastatic breast cancer were analyzed for mutations. Among them, a significantly higher percentage of mutations in the YAP1 (P ≤ 0.0001), ANKRD1 (P ≤ 0.0001), MCL-1 (P ≤ 0.0001), and TOP2A (P ≤ 0.0001) genes was observed in metastatic breast cancer compared to non-metastatic breast cancer. Evaluating CNAs in 2197 cases in the metastatic breast cancer group compared to 9289 cases in the non-metastatic breast cancer group demonstrated a significantly higher frequency of CNAs in the YAP1 ( P ≤ 0.0001), Cyr61 (P ≤ 0.0001), CTGF ( P ≤ 0.0001), ANKRD1 ( P ≤ 0.0001), TOP2A (P ≤ 0.0001) and FOSL2 (P ≤ 0.0001) genes among metastatic breast cancer. Conclusions: This study revealed significant genomic alterations in the YAP1 gene and its downstream genes in metastatic breast cancer. These findings highlight the importance of the YAP1 pathway in breast cancer metastasis and suggest that targeting this pathway may have therapeutic potential for primary and metastatic breast cancer. Frequency of mutations and copy number alterations (CNAs) in metastatic vs. non-metastatic breast cancer. Gene Metastatic Breast Cancer Mutation Frequency (%) Non-Metastatic Breast Cancer Mutation Frequency (%) P-value Metastatic Breast Cancer CNA Frequency (%) Non-Metastatic Breast Cancer CNA Frequency (%) P-value YAP1 0.75 0.17 <0.0001 5.1 1.18 <0.0001 CTGF 0.13 0.18 0.781 5.42 0.65 <0.0001 Cyr61 0.17 0.16 0.999 3.9 0.65 <0.0001 MCL-1 0.63 0.11 <0.0001 10.74 11.93 0.121 ANKRD1 1.17 0.09 <0.0001 1.96 0.25 <0.0001 TOP2A 0.96 0.18 <0.0001 8.06 3.6 <0.0001 FOSL2 0.17 0.1 0.317 3.64 0.62 <0.0001