Shahab, Sarim Hassan

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)