Sawaira, FNU

e18060 Background: Intensity-modulated proton therapy (IMPT) has been gaining popularity as a method of treating locally advanced HPV positive oropharyngeal squamous cell carcinoma (OPSCC) due to the ability to reduce the amount of normal tissue that is exposed to radiation but whether or not it will result in better clinical outcomes when compared to intensity-modulated photon radiotherapy (IMRT), is still unknown. We performed a meta-analysis to evaluate the effects of IMPT on both cancer related toxicities and outcomes in comparison to IMRT for patients diagnosed with locally advanced HPV positive OPSCC. Methods: We evaluated all comparative studies that examined the use of IMPT vs. IMRT in stage III-IV HPV positive OPSCC. Using random-effects models, we estimated pooled relative risks (RRs) with 95% CIs for each study's measure of association. The primary outcomes of interest were: weight loss; gastrostomy tube insertion; xerostomia; dysphagia; mucositis; fatigue; locoregional recurrence; and OS. Statistical heterogeneity was assessed via I². Results: In total, there were 4 studies that involved 912 patients. As per these studies, a greater number of patients experienced clinically relevant weight loss when receiving IMPT than when receiving IMRT (RR 1.63, 95% CI 1.17–2.27; p= .004; I²= 0%). Additionally, a comparison of six studies which included a total of 1143 patients indicated that gastrostomy tubes are inserted more often after IMPT (RR 2.9, 95% CI 1.8 – 4.6; p<.00001; I²= 0%). No statistically or clinically significant differences were found regarding other side effects from treatments. In terms of cancer recurrence, there was a greater rate of loco-regional recurrence for those patients who received IMPT as compared to IMRT (RR 1.58, 95% CI 1.26- 1.97; p< .0001; I²= 0%) in three studies which included a total of 592 patients. However, no statistical difference in overall survival was identified between IMPT and IMRT (RR 1.06, 95% CI 0.87- 1.29; p=.56), even though there was significant variability (I²= 87%) in three studies which included a total of 747 patients. Conclusions: In locally advanced HPV positive OPSCC, there were no differences in toxicity profiles from IMPT compared to IMRT, and there were increased rates of weight loss, gastrostomy tube placement, and locoregional recurrence from IMPT compared to IMRT, without any observed survival advantage. This highlights the need for future prospective randomized trials to clarify the role of IMPT in the management of locally advanced HPV positive OPSCC.

e16229 Background: Liver cancer is a leading cause of cancer-related mortality worldwide, with rising incidence linked to metabolic disorders. Conditions such as obesity, diabetes mellitus, and metabolic syndrome contribute substantially to non-viral liver carcinogenesis. However, long-term temporal trends and mortality disparities among adults with metabolic disorders in the United States remain incompletely characterized. Methods: Mortality data for liver cancer among adults with metabolic disorders were obtained from the centers for disease control and prevention (CDC) mortality database. Adults aged 25 years and older were included and age-adjusted mortality rates (AAMRs) per 100,000 were calculated. Temporal trends were evaluated using joinpoint regression and average annual percent change (AAPC) with 95% confidence intervals. Results: From 1999–2023, AAMR for liver cancer in adults with metabolic disorders rose from 0.17 to 0.65 per 100,000 in the U.S., with an overall AAPC of 5.95% [95% CI 5.2–6.7]. Men had higher absolute mortality (0.25→0.93; AAPC 5.68%), while women showed a sharper recent rise (0.11→0.41; AAPC 7.08%), peaking at 11.86% annually after 2016. Hispanic/Latino (0.27→0.89; AAPC 6.73%) and Black populations (0.15→0.75; AAPC 6.15%) experienced steady increases, whereas White mortality accelerated post-2011 (AAPC 9.37%). Regionally, the West had highest rates, the South showed highest growth, and Northeast/Midwest had sharp recent increases. Rural mortality overtook urban by 2020 (0.50 vs. 0.48). Most deaths occurred in medical facilities (48.2%) or home (33.1%), with highest state rates in Hawaii (0.56), Texas (0.47), and Rhode Island (0.47). Conclusions: Mortality from liver cancer in adults with metabolic disorders rose sharply in the U.S. since 1999, with accelerating trends and marked disparities by sex, race/ethnicity, region, and urbanization. These findings highlight an urgent need for targeted metabolic risk reduction and equity-focused prevention strategies. Trends in Age-Adjusted Mortality Rates (AAMR) from 1999 to 2023 by demographic and geographic variables. Variable AAMR 1999 (per 100,000) AAMR 2023 (per 100,000) AAPC (95% CI) Overall 0.16 0.64 5.94* (5.22 – 6.67) Males 0.25 0.92 5.67* (4.82 – 6.5) Females 0.11 0.40 7.08* (5.79 – 8.38) White 0.16 0.63 6.12* (5.41 – 6.82) Black 0.15 0.75 6.15* (5.11 – 7.19) Hispanic or Latino 0.27 0.89 6.73* (5.98 – 7.48) Variable AAMR 1999 (per 100,000) AAMR 2020 (per 100,000) AAPC (95% CI) Urban 0.16 0.47 5.38* (4.43 – 6.33) Rural 0.19 0.50 5.73* (4.48 – 6.99) AAPC denotes the average annual percent change; * indicates p < 0.05.

e16157 Background: Liver cancer mortality remains a major public health burden in the United States despite advances in prevention and treatment. Psychoactive substance use disorder (PSUD) is an increasingly prevalent comorbidity; however, national trends and disparities in liver cancer mortality among adults with PSUD remain poorly characterized. Methods: We conducted a retrospective analysis of liver cancer-related deaths among U.S. adults aged 25 years and older with PSUD from 1999 to 2023 using Centers of Disease Control (CDC) Wide Ranging Online Data for Epidemiological Research (WONDER) mortality database. Age-adjusted mortality rates (AAMRs) were calculated per 100,000 population and stratified by census region, state, urban–rural status, sex, and race/ethnicity. Temporal trends were assessed using Joinpoint regression to estimate average annual percent change (AAPC). Statistical significance was determined using p-value (<0.05). Results: Overall liver cancer related AAMR per 100,000 among adults with PSUD significantly increased from 0.15 in 1999 to 1.02 in 2023 (AAPC: 7.47; 95% CI: 6.33 to 8.61; p < 0.000001). The overall mortality burden was higher in males. However, females experienced larger rises in mortality (AAPC: 10.03; 95% CI: 8.85 to 11.24; p < 0.000001) as compared to males (AAPC: 7.30; 95% CI: 5.78 to 8.84; p < 0.000001). Marked racial disparities were observed, with non-Hispanic Black and non-Hispanic White individuals experiencing the highest mortality rates with persistent increases over time, while Hispanic/Latino populations exhibited modest and variable trends. A substantial geographic variability was observed, with the greatest increases in the Midwest and the South. State-level analysis revealed higher mortality rate in Oregon (1.27) followed by Washington (1.12) and Texas (1.06) respectively. Both rural and urban areas experienced a sharp rise in mortality with AAPC being slightly higher in rural areas (AAPC: 10.34) as compared to urban areas (AAPC: 9.67). Conclusions: Liver cancer mortality among U.S. adults with PSUD has risen markedly over the past two decades, with substantial demographic and geographic disparities. These findings highlight the need for integrated liver cancer screening and substance use disorder interventions targeting high-risk populations. Variables AAMR (95% CI) in 2023 AAPC (95% CI) Overall 1.02 (0.98 –1.05) 1999-2023: 7.47* (6.33 – 8.61) Female 0.42 (0.39 – 0.46) 1999-2023: 10.03* (8.85 – 11.24) Men 1.69 (1.62 –1.76) 1999-2023: 7.30* (5.78 – 8.84) White 1.05 (1.0 –1.09) 1999-2023: 9.52* (8.08 – 10.98) Black / African Americans 1.22 (1.09 – 1.35) 1999-2023: 6.59* (5.50 – 7.68) Hispanics / Latinos 0.75 (0.65 – 0.84) 1999-2023: 1.26 (-1.01 – 3.60) AAMR (95% CI) in 2020 AAPC (95% CI) Rural 1.51 (1.39 – 1.62) 1999-2020: 10.34* (5.05 – 15.90) Urban 0.92 (0.82 – 0.95) 1999-2020: 9.67* (7.32 – 12.06)

e16027 Background: Postoperative oral intake after esophagectomy has traditionally been delayed due to concerns about anastomotic leakage. Although Enhanced Recovery After Surgery (ERAS) pathways increasingly support early feeding, its safety remains debated. This study compared early versus delayed oral feeding following esophagectomy for esophageal cancer. Methods: PubMed, Embase, and Scopus were systematically searched through October 2025 for randomized controlled trials evaluating early oral feeding (postoperative days 0–3) versus delayed feeding (postoperative day ≥5) after esophagectomy. Primary outcomes were anastomotic leakage and pneumonia. Secondary outcomes included postoperative complications, gastrointestinal recovery, length of hospital stay, healthcare costs, and quality of life. Pooled risk ratios (RRs), mean differences (MDs), or standardized mean differences (SMDs) with 95% confidence intervals were calculated using Review Manager 5.4. Results: Thirteen trials involving 1,468 patients were included. Early oral feeding was not associated with increased anastomotic leakage (RR: 0.89, 95% CI: 0.55–1.45; I² = 0%) and showed consistent safety across surgical approaches and anastomotic sites. The incidence of pneumonia was significantly reduced (RR: 0.66, 95% CI: 0.47–0.92; p = 0.01). Early feeding accelerated gastrointestinal recovery, including earlier first bowel movement (MD: −0.50 days, p < 0.00001) and passage of flatus (MD: −0.61 days, p = 0.0006). Hospital stay was shortened (MD: −1.89 days, p = 0.002), with lower medical costs (SMD: −1.19, p = 0.009). Quality-of-life measures improved, including global health status, dysphagia, pain, and swallowing function. Conclusions: Early oral feeding after esophagectomy appears safe and beneficial, reducing pulmonary complications and enhancing postoperative recovery. Further high-quality multicenter trials are needed to confirm these findings.

e16024 Background: Patients with advanced esophageal squamous cell carcinoma (ESCC) continue to have poor outcomes with chemotherapy alone. The addition of PD-L1 inhibitors to first-line chemotherapy has shown encouraging results in individual trials, but the overall magnitude and consistency of benefit across key clinical endpoints have not been fully clarified. To better understand the effects of PD-L1 inhibitors used in combination with chemotherapy, we performed a systematic review and meta-analysis to compare the efficacy and safety of PD-L1-based combination therapies to chemotherapy alone in patients with advanced or metastatic ESCC. Methods: A systematic search of PubMed, Embase, and Scopus identified randomized controlled trials comparing PD-L1 inhibitor plus chemotherapy versus chemotherapy alone in patients with advanced or metastatic ESCC. Three eligible studies met inclusion criteria. We calculated pooled hazard ratios (HRs) for overall survival (OS) and progression-free survival (PFS); and pooled risk ratios (RRs) for objective response rate (ORR) and Grade 3-5 treatment-related adverse events (TRAEs) using random effects models. We quantified the heterogeneity among studies using the I² test. Results: Across three randomized trials, the addition of a PD-L1 inhibitor to chemotherapy resulted in a statistically significant and highly consistent survival advantage. OS was longer with combination therapy (HR 0.67, 95% CI 0.60–0.76; p < 0.00001), representing a 33% reduction in the risk of death, with no heterogeneity across studies (I² = 0%). Similarly, PFS was prolonged with combination therapy (HR 0.61, 95% CI 0.55–0.68; p < 0.00001; I² = 0%), corresponding to a 39% reduction in the risk of disease progression or death. Tumor responses occurred at higher frequencies in patients who received PD-L1 inhibitor-based therapy than in patients who received chemotherapy alone (RR = 1.49, 95% CI = 1.35-1.63; p < .00001; I² = 0%). The increased efficacy observed with combination therapy was not accompanied by an increase in severe toxicities. The rates of Grade 3-5 TRAEs were similar between the two groups (RR = 1.06, 95% CI = 0.99-1.13; p = 0.09; I² = 0%). Conclusions: Based on evidence from three randomized trials, the addition of PD-L1 inhibitors to standard chemotherapy improves both survival and response rates in patients with advanced ESCC without an increase in severe treatment related adverse events. Therefore, PD-L1-based combination therapies represent a promising new therapeutic option for patients with advanced ESCC.

e16023 Background: Stroke is an underrecognized cause of death among patients with gastric cancer. While overall cancer mortality has improved, less is known about long-term trends and disparities in stroke-related deaths. We examined national patterns in stroke mortality among gastric cancer patients from 1999 to 2023. Methods: U.S. national mortality data were used to calculate age-adjusted mortality rates (AAMR) per 100,000. Joinpoint regression identified temporal changes and estimated annual percent change (APC) and average annual percent change (AAPC). Analyses were stratified by age, sex, race and ethnicity, census region, and urbanization. Results: Between 1999 and 2023, an overall decline in stroke-related mortality was noted with AAMR falling from 167.29 to 111.35 per 100,000 people (AAPC −1.70%, 95% CI −1.9 to −1.5). The decline was greatest between 2002 and 2009 (−5.28% per year) after which it began to plateau until it rose significantly between 2018 and 2021 (APC 6.56%) followed by a decline after 2021 (−3.63%). Older adults had the highest level of stroke related mortality, and therefore the greatest reduction over time (from 756.36 to 479.63) with a total reduction of −36.6% yet they saw a significant increase in mortality between 2018 and 2021. Middle aged patients had little overall improvement and demonstrated the steepest recent increase (APC 8.46%). Younger patients concluded the study period at rates similar to those seen in 1999. Men demonstrated a greater incidence of stroke related mortality compared to women (118.67 vs 104.15 in 2023) with similar trends over time. Racial disparities were present with Black patients showing the highest stroke related mortality in all years (from 242.47 to 156.26) and the largest recent increase (APC 7.37%). Regionally, the South and rural areas carried the highest mortality burden; however, all geographic areas demonstrated an identical increase between 2018 and 2021. Conclusions: Although stroke-related mortality among gastric cancer patients has declined over two decades, recent nationwide increases highlight ongoing vulnerability and persistent disparities. Targeted integration of cardiovascular risk assessment and stroke prevention into gastric cancer care may help sustain progress and reduce inequities. Group (Category A / Category B) AAMR 1999 (A / B) AAMR 2023 (A / B) Recent Surge Trend 2018–2021 (APC) Overall 167.3 111.4 +6.6%* Sex (Male / Female) 181.5 / 156.2 118.7 / 104.2 +6.8%* / +6.2%* Race (NH White / NH Black) 160.4 / 242.5 108.2 / 158.4 +6.3%* / +7.4%* Race (Hispanic / Asian) 140.3 / 153.6 97.7 / 80.0 +6.9%* / +5.2%* Age (Young / Middle) 6.7 / 47.7 6.7 / 42.3 +7.8%* / +8.5%* Age (Old 65+) 756.4 479.6 +6.2%* Region (Northeast / Midwest) 141.5 / 172.0 82.7 / 115.3 +4.4%* / +6.7%* Region (South / West) 177.5 / 171.4 125.7 / 107.2 +6.9%* / +6.2%* An asterisk (*) indicates that the APC is statistically significant (p < 0.05).