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Effects of tumor treating fields (TTFields) with FOLFIRINOX on BRCA WT pancreatic cancer cells.

753 Background: Pancreatic cancer remains one of the most aggressive malignancies, frequently diagnosed at the locally advanced or metastatic stage. In the advanced setting, first-line chemotherapy options include gemcitabine with nab-paclitaxel or FOLFIRINOX, a combination regimen of fluorouracil, oxaliplatin, irinotecan and leucovorin. The FOLFIRINOX regimen is however associated with greater toxicity and is hence used only in patients with good performance status. BRCA-mutated tumors seem to be more sensitive to FOLFIRINOX due to the DNA-damaging, platinum-based component of this treatment regimen. Tumor Treating Fields (TTFields) are electric fields that disrupt cellular processes crucial for cancer cell viability that have shown efficacy in preclinical pancreatic cancer models; and, in various cancer types, have been shown to reduce expression of proteins from the BRCA-dependent DNA repair pathway. The current study examined the potential use of TTFields for sensitization of BRCA wild-type pancreatic cancer cells to treatment with FOLFIRINOX. Methods: Human pancreatic BRCA wild-type cancer cells BxPC3 and AsPC1 were treated with TTFields (150 kHz; 0.7 and 1 V/cm RMS, respectively), using the inovitro device. FOLFIRINOX was administered to the cells at increasing concentrations, with or without co-treatment with TTFields. After 72h of treatment, cell count, colony formation, and apoptosis were measured. For mechanistical insight, gene and protein expression were evaluated following 24, 48, or 72h of TTFields treatment. Results: TTFields application to the pancreatic cells together with FOLFIRINOX elevated the cytotoxic, clonogenic and apoptotic effects induced by FOLFIRINOX or TTFields alone. RNA sequencing data revealed that TTFields downregulated DNA damage repair, DNA replication, and cell cycle related processes. Specifically, real-time PCR and Western blot analysis demonstrated reduced expression of several central players in the BRCA DNA damage repair pathway. Conclusions: TTFields application together with FOLFIRINOX in pancreatic cancer cells lacking background BRCA mutations exhibits potential improvement relative to FOLFIRINOX alone, that may be rationalized based on downregulation of key DNA repair pathways. Future studies should explore the possibility of reducing FOLFIRINOX treatment dose, potentially alleviating FOLFIRINOX-related toxicity.

Tracking metal pollution from illegal gold mining: a health risk assessment in Edfu, Egypt

Abstract Over the past decade, there has been an increase in small-scale gold mining in the arid southern region of Egypt. Miners extract ore from the Eastern Desert and transport it to Nile Valley farms, where ample water facilitates the processing. In Edfu, Egypt, the lack of economic opportunities prompted resource-constrained farmers to transform their agricultural lands into gold mines. The study utilized a multifaceted approach that integrated various methodologies, including remote sensing technologies, field surveys, chemical analyses, and statistical methods. The study aimed to assess the concentrations of carcinogenic agents and determine the potential human health risks associated with these agents in soil and fish samples collected within the city boundaries. The study examined correlations between various heavy metals (HMs), such as Ni, Pb, Cd, Cr, Cu, and Hg, in Soilsamples collected in 2020 and 2022. The results revealed direct proportional relationships among specific HMs. The Index of Geoaccumulation (Igeo) and Pollution Load Index (PLI) revealed significantly elevated values in both years, indicating potential environmental degradation. Although no carcinogenic hazards were identified, non-carcinogenic risks related to ingestion were observed for both adults and children exposed to mercury (Hg), copper (Cu), and arsenic (As). Contamination Factor (CF) values were also significantly high. Ecological risks were observed in both Soiland water, as well as in Nile Tilapia samples. Hazard Quotients (HQ) calculated for Nile Tilapia indicated potential risks for both adults and children, particularly associated with elevated arsenic (As) levels. This transformation elicited concerns regarding environmental and health implications, leading us to undertake a thorough investigation.

Regulation of sod1 mRNA and protein abundance by zinc in fission yeast is dependent on the CCR4-NOT complex

A multicenter, open-label study investigating RP2 oncolytic immunotherapy in combination with second-line systemic atezolizumab plus bevacizumab in patients with locally advanced unresectable or metastatic hepatocellular carcinoma (HCC).

TPS649 Background: Despite advances in unresectable HCC treatment, long-term survival rates remain poor. The combination of atezolizumab (Atezo) plus bevacizumab (Bev) is approved as frontline therapy for advanced HCC, but only a minority of patients (pts) respond, and secondary resistance usually occurs within months. HCC has an immune-suppressed tumor microenvironment (TME) mediated by the expression of immune checkpoint signals and angiogenesis pathways, which may contribute to therapeutic resistance. RP2 is an enhanced potency oncolytic herpes simplex virus type 1 (HSV-1) that expresses GM-CSF, a fusogenic glycoprotein (GALV-GP-R–), and an anti–CTLA-4 antibody-like molecule. RP2 showed preliminary clinical activity alone or combined with anti–PD-1 in a phase 1 study in pts with advanced solid tumors. The direct oncolytic effect coupled with immune stimulation by RP2 in the TME is intended to provide systemic antitumor activity and synergize with anti–PD-1/PD-L1 agents, such as Atezo. Preclinical data have demonstrated improved distribution of oncolytic HSV within tumors when administered with Bev, supporting the clinical combination of RP2 with Bev. This study will evaluate the safety and efficacy of RP2 combined with Atezo plus Bev as second-line systemic therapy for unresectable advanced HCC (NCT05733598). Methods: This is an open-label, single arm, phase 2 trial. Up to 30 pts will be enrolled and receive RP2 in combination with Atezo plus Bev. Key inclusion criteria include advanced unresectable HCC with ≥1 measurable tumor of ≥1 cm in longest diameter, Child-Pugh class A, an Eastern Cooperative Oncology Group performance status of 0 to 1, and progression on 1 prior systemic treatment, which must have included a PD-1/PD-L1–directed agent. Key exclusion criteria include untreated/incompletely treated esophageal and/or gastric varices with bleeding or at high risk for bleeding and macroscopic invasion of the tumor into any major blood vessel(s) and/or main bile ducts. Pts will receive intratumoral RP2 Q2W for 4 doses, then Q3W for up to 4 doses. Bev will be given at 10 mg/kg Q2W starting with the first dose of RP2, then at 15 mg/kg Q3W starting with cycle 4; Atezo will be given at 840 mg Q2W for cycles 2 and 3, then at 1200 mg Q3W starting with cycle 4. Pts will receive treatment until confirmed progressive disease, loss of clinical benefit, or unacceptable toxicity. The primary endpoint is overall response rate (ORR), defined as the proportion of pts achieving a best overall response of complete response or partial response per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 as modified for this study. Secondary endpoints include safety, ORR using HCC-modified RECIST, duration of response, complete response rate, and progression-free survival. Clinical trial information: NCT05733598 .

Patient body fat and AI ensemble technique and the influence on false-positive rate in AI second observer for colorectal cancer detection.

216 Background: Colorectal cancer (CRC) is the second leading cause of cancer-related deaths. We previously found that delayed diagnosis due to lack of radiological identification results in significantly worse outcome for patients. We had developed a rudimentary, AI second observer which demonstrated potential for detecting CRC on routine CT abdomen/pelvis (CTAP). However, the AI algorithm detected many false positives. In this study, we analyzed the data using TCIA as test cases and evaluated whether patient peritoneal fat content influenced the false positive rate. This could serve as a guide for future training of AI second observer to minimize false positive detection. Methods: 2D U-Net convolutional neural network (CNN) containing 31 million trainable parameters was trained with 58 CRC CT images from Banner MD Anderson (AZ) and MD Anderson Cancer Center (TX) (51 used for training and 7 for validation) and 59 normal CT scans from Banner MD Anderson Cancer Center. 18 of the 25 CRC cases from public domain data (The Cancer Genome Atlas) were used to evaluate the performance of the models (5 had no identifiable cancer and 2 were rejected for having no contrast). The CRC was segmented using ITK-SNAP open-source software (v. 3.8). To apply the deep ensemble approach, five CNN models were trained independently with random initialization using the same U-Net architect and the same training data. Given a testing CT scan, each of the five trained CNN models was applied to produce tumor segmentation for the testing CT scan. The tumor segmentation results produced by the trained CNN models were then fused using a simple majority voting rule (up to 2 voters) to produce consensus tumor segmentation results. The segmentation was analyzed for the number and location of false positives per case. The peritoneal fat content was classified at the level of aortic bifurcation by the distance of fat between adjacent small bowel loops (≤ or > 1 cm). Chi-square test was performed testing fat volume and number of voters as the intervention. Results: Our results showed that the higher volume of peritoneal fat (> 1 cm, N=6) decreases the rate of false positive compared with low volume (≤ 1 cm, N=12, p=0.013). When comparing between having one voter and two voter ensemble using low fat volume data, two voter ensemble also decreased the number of false positives but not statistically significant (p=0.286). Conclusions: Our results show that AI-based second observer generates more false positives when patients have lower peritoneal fat volume; this implies that future training may require higher percentage of cases with low peritoneal fat to improve second observer precision. Our analysis also showed that increasing the number of voter in the ensemble also decrease the number of false positives per case.

Cetuximab every second week in combination with daily encorafenib in patients with BRAF V600E mutated metastatic colorectal cancer: Interim analysis from NEW BEACON.

153 Background: Weekly administered cetuximab in combination with the BRAF inhibitor encorafenib has improved survival in pre-treated patients (pts) with BRAF V600E mutated (BRAFmut) metastatic colorectal cancer (mCRC), with a median progression free survival (PFS) of 4.3 months in the BEACON study. It is now standard-of-care in the second line treatment. However, a regimen with cetuximab administered every second week may demonstrate comparable efficacy and is more convenient for the pts. Thus, we initiated the NEW BEACON study investigating cetuximab given every second week together with daily encorafenib. Details on the rationale and aims of the study have previously been published (doi: 10.1186/s12885-022-10420-x.). Methods: NEW BEACON is an open-label, single-arm, multicenter, phase II study including pts with pre-treated BRAFmut mCRC. The primary end point is 2 months PFS rate. We report here the result of a pre-specified interim analysis after treatment of the first 19 included pts. We collected fresh tumor tissues for comprehensive molecular profiling in order to explore features associated with response and resistance. Baseline genomic variants will be reported. Results: From February 2021 to February 2024 20 pts were included in the study. 1 patient never started study treatment due to rapid disease progression. At the data cut-off date 19 pts had initiated study treatment. The 2 months PFS rate was 89% (17/19 pts). We had tumor tissue for molecular profiling available from 12 pts. Pathogenic variants in TP53 were the most frequently detected co-mutations at baseline in 83% of pts (10/12 pts). Available preliminary safety, efficacy, and survival data and more extensive genomic data will be presented at the meeting. Conclusions: The preliminary PFS data from pts with BRAFmut mCRC treated with cetuximab every second week together with daily encorafenib is promising demonstrating a 2 months PFS rate of 89%. This is similar to what was reported from the BEACON study (2 months PFS rate of 84%). Loss-of-function mutations in tumor suppressor genes were frequently detected as co-mutations at baseline. Clinical trial information: EudraCT: 2020-003283-10 .

Efficacy, safety and DNA methylation analysis of cadonilimab combined with taxane and cisplatin as first-line treatment for advanced esophageal squamous cell carcinoma (ESCC): Updated results from an open-label, multicenter phase II trial (AK104-IIT-014).

463 Background: Immune checkpoint inhibitors combined with chemotherapy had become the first-line standard treatment for advanced ESCC and cadonilimab, as a bispecific antibody simultaneously targeting PD-1 and CTLA-4, may further boost anti-tumor activity with a satisfied safety profile. Here, we present the updated data for the safety and efficacy of cadonilimab combination therapy as the first-line treatment in advanced ESCC. The correlation between DNA methylation and clinical response was also investigated. Methods: Treatment-naïve patients (pts) with unresectable locally advanced or metastatic ESCC were enrolled. Cadonilimab (10mg/kg, iv, d1, q3w) combined with paclitaxel or nab-paclitaxel (175 mg/m 2 , iv, d1, q3w) and cisplatin (65 to 75 mg/m 2 , iv, d1, q3w) were administrated for up to 6 cycles, then Cadonilimab (10mg/kg, iv, d1, q3w) monotherapy continued as maintenance until progressive disease or unacceptable toxicity, with a maximum of 24 months. The primary endpoint was objective response rate (ORR). Secondary endpoints were progression-free survival (PFS), overall survival (OS), disease control rate (DCR) and safety. Plasma cell-free DNA samples were collected before and after treatment and prepared for methylation level sequencing. Results: As of September 20, 2024, 43 pts were enrolled with a median age of 61 years (range 44-75), 81.4% were male, 39.5% had PD-L1 CPS≥10 and 95.3% had metastatic diseases. All pts were evaluable for safety and efficacy. The ORR was 81.4% (95%Cl: 66.1%-91.1%) and DCR was 97.7% (95%Cl: 86.2%-99.9%). The median PFS (mPFS) was 7.05 months (mo) (95%Cl: 5.86-8.24) and OS analysis was immature. In the PD-L1 CPS≥10 pts, the ORR was 100.0% (95%Cl: 77.1%-100.0%) and mPFS was 7.05 mo (95%Cl: 5.19-8.91). In the PD-L1 CPS＜10 pts, the ORR was 77.3% (95%Cl: 54.2%-91.3%) and mPFS was 7.05 mo (95%Cl: 5.87-8.24). Six hyper-methylated CpG sites, EPTIN9、PKNOX2、DLEU7、SOX7、CNRIP1 and LINC00554 might be the candidate biomarkers as the mean pretreatment methylation levels were significantly higher in the PR pts than those in the non-PR pts (p=7.8×10 -7 ). Grade 3-4 treatment-related adverse events (TRAEs) were reported in 44.2% (19/43) pts, mainly including neutropenia (25.6%), leukopenia (9.3%) and hyponatremia (7.0%). The infusion-related reactions (IRR) occurred in 14.0% (6/43) and grade ≥3 IRR occurred in 4.7% (2/43) pts. 7 pts discontinued cadonilimab administration due to TRAEs. Conclusions: The updated results suggested that bispecific antibody cadonilimab combined with taxane and cisplatin as first-line treatment continued to show encouraging anti-tumor activity and manageable safety in pts with advanced ESCC. DNA methylation level might be a potential biomarker for guiding patient outcomes. Clinical trial information: NCT05522894 .

The effectiveness of orthodontic treatment with clear aligners in different thicknesses

Bending stiffness of Toxoplasma gondii actin filaments

Impact of neoadjuvant radiation therapy modalities on post-surgical lymphopenia in operable pancreatic cancer.

710 Background: Recent advances in therapeutic vaccines show promise for KRAS -mutated pancreatic cancer (PC), with ongoing clinical trials exploring their potential further. Lymphocytes are essential in generating vaccine-induced immune response. Patients who develop lymphopenia following neoadjuvant radiation therapy (RT) are frequently excluded from these vaccine trials. We aimed to assess how different modalities of neoadjuvant RT impact the severity and incidence of lymphopenia. Methods: We identified patients with PC who received neoadjuvant therapy including RT followed by surgery at our institution between March 2009 and June 2024. Patients were stratified by the type of RT they received: conventional long-course chemo-RT (LCRT) with 50.4 Gy over 28 fractions (Fr), short-course chemo-RT (SCRT) with 36 Gy over 15 Fr, and stereotactic body RT (SBRT) with 30 Gy over 5 Fr. The absolute lymphocyte count (ALC, 10 3 cells/µL) was compared at various timepoints: baseline, during RT, 6-weeks after surgery (post-op), and every 3-month interval up to 1 year post-op. Moderate lymphopenia was defined as ALC <1.0 and severe lymphopenia as ALC <0.5. Results: Among the 627 patients included in the study, 522 had baseline pre-RT ALC data available for analysis. There was no difference in baseline ALC among the different RT groups (Table). During RT, patients receiving LCRT experienced a higher incidence of severe lymphopenia (86.1%; median ALC (mALC) nadir 0.28) compared to SCRT (41.9%; mALC nadir 0.50) or SBRT (20.0%; mALC nadir 0.72, p<0001). No difference in the mALC or rates of lymphopenia was observed beyond 6 weeks post-op. Notably, 53% of the patients experienced lymphopenia for as long as 1 year after surgery. Conclusions: LCRT resulted in more severe lymphopenia compared to SCRT or SBRT during RT, but this difference in severity diminished 6 weeks after surgery. Alternatives in treatment sequencing for operable pancreatic cancer can have profound effects on patterns of disease recurrence. When applying multiple treatments in series, toxicities such as lymphopenia may impact receipt of therapy. Techniques to mitigate such toxicities, while maximizing response, will be important to consider. Absolute lymphocyte count (ALC, 10 3 cells/µL) at different time point. Patients with baseline ALC LCRT (n=454) SCRT (n=34) SBRT (n=34) P-value Baseline ALC, median (IQR) 1.48 (0.74) 1.27 (0.94) 1.51 (0.74) 0.74 6-week lymphopenia, n (%) No Moderate Severe 173 (37)219 (46)79 (17) 13/27 (48)11/27 (41)3/27 (11) 18/35 (51)16/35 (46)1/35 (3) 0.10 1-year lymphopenia, n (%) No Moderate Severe 101/217 (47)90/217 (41)26/217 (12) 3/8 (37)5/8 (63)0/8 (0) 9/13 (69)1/13 (8)3/13 (23) 0.054

A prospective multi-site translational study investigating the association of gut microbiome (GM) diversity with pathological complete response (pCR) after neoadjuvant treatment in early stage rectal and esophageal cancer.

TPS849 Background: The diversity of the GM is defined as the number and relative abundance distribution of distinct types of microorganisms colonizing within the gut. Studies have suggested that dysbiosis of the GM confers a predisposition to certain malignancies and impacts response to immunomodulating therapies. The influence of the GM diversity on the pathological response after neoadjuvant chemotherapy and radiotherapy is unclear. Some studies have suggested that the GM may offer predictive biomarkers for response to chemoradiation in rectal cancer. Other studies in early-stage rectal cancer patients indicated an association between GM diversity and pathological outcomes following neo-adjuvant therapy (NAT). We hypothesize that a more diverse GM constitution at baseline leads to an improved pathological response at the time of definitive surgery. Methods: We designed a cross-institutional translational study investigating the impact of the GM diversity on the efficacy of NAT in GI cancers by assessing its association with pathological response. The study population includes patients with early-stage rectal or esophageal cancer due to commence NAT (including chemotherapy and chemoradiation) who are planned for definitive surgery. Exclusion criteria includes prior allogenic tissue/solid organ transplantation and prior receipt of anti-cancer therapy. The study assessments include fecal sampling of the GM prior to NAT, upon completion and again six months post completion of therapy. Fecal samples are analysed by 16S RNA sequencing. Pathological response will be examined at time of surgery and patients will be classified as responders (complete pathological response) or non-responders. The primary endpoint of the study is to examine the association between the GM diversity and pathological response. Exploratory analysis will include the assessment of the association between cf-DNA and the GM diversity as well as an assessment of the association between cf-DNA at baseline and pCR. Species richness (Alpha Diversity) will be analysed using the Shannon diversity index and Jaccard similarity index will be used to calculate beta diversity. Following planned study recruitment, classification and clustering analysis will be performed with Principal Component Analysis (PCA) and Random Forest analysis. Logistic regression analysis adjusting for potential confounding factors will be employed to assess the primary endpoint of the association between GM and complete pCR in the final statistical analysis. Adjusted odds ratios (OR) and 95% confidence intervals will be presented. This trial accrued 11 patients between May 2023 and Sept 2024. Out of the 11 patients enrolled, 9 patients have undergone their planned surgery. We are expecting to have 30 patients accrued prior to Jan 2025.

A retrospective study of colorectal cancer CT imaging features involving microsatellite instability.

265 Background: This study aimed to identify correlations between CT imaging characteristics accessible to the radiologist with microsatellite instability (MSI) status among colorectal cancer. Noninvasive identification of MSI status can decrease time to treatment if pathology can be bypassed. Methods: 109 colorectal cancer patients were identified retrospectively from 2011 to 2018 with an average age of 61 years (58 male, 51 female) and had MSI pathological assessment. These subjects all had CT abdomen and pelvis obtained at the time of initial diagnosis. Imaging features of both the primary and metastatic lesions were assessed. Primary lesion features included: location, size, stage, attenuation compared to the liver, growth pattern, tumor margin, primary mass area, and the presence/absence of mesenteric infiltration. Metastatic lesion features included: size, attenuation relative to liver, and enhancement pattern. Patient age, sex, and tumor staging were obtained from patient medical records. Statistical analysis was performed using various methods, including chi-square, Mann-Whitney and Kruskal-Wallis tests. Results: 5 tumor characteristics displayed a statistically significant relationship with MSI status. MSI-H lesions were more likely to be clinical Stage 2, and MSI-L lesions were more likely to be Clinical Stage 3 (p=0.012). Tumors with distant metastasis were more likely MSI-L versus regional metastasis were more likely MSI-H (p<0.001). Primary mass area was larger in the MSI-H than MSI-L group (p<0.001). Tumors in the left colon are more likely to be MSI-L versus CRC tumors in the right colon are more likely to be MSI-H (p<0.001). MSI-H tumors had a lower primary tumor Hounsfield Unit standard deviation (SD) than MSI-L tumors (p=0.002). The remaining features were not statistically significant. For primary lesion, these include mesenteric infiltration (p=0.189), tumor margin (p=1.000), enhancement pattern (p=0.498), growth pattern (p=0.127), tumor CT density (p=0.162), and liver density (p=0.105). Enhancement of metastasis also had no difference (p=0.376). Conclusions: Multiple CT imaging characteristics were predictive of MSI classification in CRC tumors, holding potential clinical relevance that can help guide individualized therapy. While these results were statistically significant, more research must be done to validate these findings and to derive useful nomograms.

Adherence to the multi-target stool DNA test in the US Hispanic population from 2016-2024.

100 Background: With colorectal cancer (CRC) as the second most common cause of cancer-related mortality in the US, adherence to CRC screening is a vital component to alleviating the cancer burden. Statistics show that only 52% of Hispanic or Latino individuals ≥45 years were up-to-date with CRC screening in 2021. A guideline-recommended, at-home CRC screening option, such as the multi-target stool DNA test (mt-sDNA), could be an efficient modality for screening average-risk individuals. Using a large national claims database, we examined CRC screening adherence with mt-sDNA in the US Hispanic population. Methods: Data was sourced from a database of over 165 million individuals linked with Exact Sciences Laboratories data. Hispanic persons who received mt-sDNA orders and resided in the US were retrospectively identified from 2016 to 2024. The analyses included persons who were ≥45 years of age, new to mt-sDNA and average risk for CRC during the 12-month pre-index period. Primary outcome of interest was adherence, which was defined as the mt-sDNA kit return rate within 365-days from shipment. All patients received a mailed letter along with digital outreach through the accompanying patient navigation program, according to their communication preference. The modes of digital outreach included: SMS, email, or both. Baseline demographics collected included age, sex, ordering provider, residential geography, payor, and outreach preference. Adjusted analyses were used to examine effects of covariates on adherence. Results: A total of 447,968 mt-sDNA orders were shipped during the study period and the overall adherence rate was 62.5%. Average time to test return was 28.5 days. Women comprised the majority of the cohort (59.9%), resided mostly in the Southern US (46.9%), aged 50-64 (60.9%), resided in a metropolitan area (91.2%), and received their mt-sDNA order from their primary care provider (62.7%). Across evaluated age groups, adherence was above 60% for all: ages 45-49 [60.5%]; 50-64 [62.6%], 65-75 [62.6%]), and ≥ 76 years [66.8]. By payor, Medicare-insured patients demonstrated the highest adherence (65.5%). Digital SMS was the preferred contact method (51.2%), and those opting for SMS + Email had the highest adherence rate (64.2%). Of provider specialties, individuals having their tests ordered by GIs produced the shortest time to adherence (23.2 days). Regression analyses revealed that older age (≥ 76 years), living in a rural area, and receiving fully or partially digital outreach were associated with increased mt-sDNA adherence. Conclusions: This large, national analysis reveals high mt-sDNA adherence amongst Hispanic individuals in the US, despite reports of low national CRC screening rates in this population. These data support the important role of mt-sDNA in facilitating screening engagement, while emphasizing the importance of preference-based navigation in facilitating screening test completion.

Harnessing the biology of regulatory T cells to treat disease

Insights into neuromyelitis optica spectrum disorder and pregnancy from a single-center study in Thailand

CBX2 promotes cervical cancer cell proliferation and resistance to DNA-damaging treatment via maintaining cancer stemness

Trends and disparities in palliative care utilization among patients with anal cancer: A ten-year retrospective study.

2 Background: Anal cancer patients often experience high symptom burden and psychosocial distress. Early integration of palliative care (PC) in their management can improve health-related quality of life. We examined the trends and predictors of PC utilization among hospitalized anal cancer patients in the US. Methods: A retrospective longitudinal study using the NIS database (2010-2019) was conducted. Using joinpoint regression and multivariable logistic regression, trends and factors associated with PC receipt were assessed. Results: The overall prevalence of PC utilization in the cohort of about 70,000 admissions with anal cancer was 6.9%. PC consultations increased from 3,372 to 11,081 per 100,000 anal cancer hospitalization (p-trend <0.001) with an average annual percentage change of 12.8%. Individuals ≥ 60 years with anal cancer had lower odds (Adjusted odds ratio (AOR): 0.81; 95% CI: 0.68-0.97) of receiving PC compared to their counterparts < 60 years. Patients in the second (AOR: 1.31; 95% CI: 1.05-1.62), and fourth (AOR: 1.29; 95% CI: 1.01–1.64) median household national income quartiles had about 30% greater likelihood of utilizing PC relative to those in the first income quartile. Patients in teaching hospitals had 40% higher likelihood (AOR: 1.40; 95% CI: 1.14-1.71) of PC in comparison to patients in non-teaching hospitals. Relative to patients who had a routine discharge home or with self-care, those discharged to facilities or with home health care were five-fold more likely (AOR: 5.04; 95% CI: 4.09-6.20) to receive PC. Those who died during hospitalization were also more likely to utilize PC (AOR: 33.9; 95% CI: 24.9-46.1). Other factors associated with PC receipt were non-elective admissions and higher Comorbidity burden. Conclusions: Though the trends in PC utilization have improved over the years, it remains suboptimal. Older patients were less likely to receive PC. Targeted interventions are needed to narrow the identified disparities for optimal utilization of PC in this patient population. Factors predicting the use of palliative care among hospitalized anal cancer patients. a Unadjusted Odds Ratio (95% CI) Adjusted Odds Ratio (95% CI) Age “60 years and above “vs “Less than 60” 0.98 (0.86-1.12) 0.81 (0.68-0.97) Hospital region South vs Northeast 1.04 (0.84-1.29) 1.33 (1.04-1.69) West vs Northeast 1.28 (1.02-1.61) 1.39 (1.06-1.82) Hospital Teaching Status Teaching vs Nonteaching 1.36 (1.16-1.60) 1.40 (1.14-1.71) Patient disposition Transfer to facility/home health care vs Routine discharge 4.98 (4.14-5.99) 5.04 (4.09-6.20) Died vs Routine discharge 39.4 (30.2-51.4) 33.9 (24.9-46.1) Admission type Non-elective vs Elective 2.97 (2.39-3.68) 2.91 (2.28-3.70) Median Household income national quartiles Quartile 2 vs Quartile 1 1.07 (0.90-1.29) 1.31 (1.05-1.62) Quartile 4 vs Quartile 1 1.17 (0.96-1.42) 1.29 (1.01-1.64) a CI = confidence intervals.

Clinical outcome of radiofrequency ablation in elderly hepatocellular carcinoma patients over 80 years old.

603 Background: The SURF trial showed the efficacy and safety of radiofrequency ablation(RFA). However, patients over 80 years old were excluded from the study. Aims: To evaluate clinical outcomes of RFA for largest hepatocellular carcinoma (HCC) diameter ≤3 cm, and ≤3 HCC nodules in patients over 80 years. Methods: Patients who underwent RFA at our institution for initial treatment of largest HCC diameter ≤3 cm, and ≤3 HCC nodules from January 2011 to December 2023. Treatment outcome and prognosis were examined in the elderly group for cases 80 years or older and in the non-elderly group for cases under 80 years. The Cox proportional hazards model was used to analyze the factors associated with treatment outcome and prognosis. Results: Of the 518 eligible patients, 136 patients were 80 years or older. Median overall Survival (OS) was 80 (95%CI 60-96) vs. 123 (95%CI 101-NA) months (p=0.021) in the elderly vs. nonelderly group. The median recurrence-free survival was 16 (95%CI 14-22) vs. 26 (95%CI 19-30) months (p=0.023), better in the non-elderly group, Interestingly, for liver disease-related deaths, median OS was 97 (95% CI 80-NA) vs. NR (95% CI NA-NA) months (p=0.62) in the elderly vs. non-elderly group. In the multivariate analysis, factors associated with OS were ALBI grade 2 or 3 (HR 1.67, 95%CI 1.07-2.60), DCP ≥ 40mAU/ml (HR 2.08, 95%CI 1.42-3.05), persistent HCV infection (HCV non-SVR) (HR 5.45, 95%CI 3.07-9.67), nonviral liver disease (HR 4.18, 95%CI 2.31-7.55). HCC recurrence was significantly associated with male (HR 1.51, 95%CI 1.18-1.94), elderly group (HR 1.46,95%CI 1.10-1.95), PT ≥80% (HR 0.69, 95%CI 0.53-0.91), DCP ≥40mAU/ml (HR 1.37, 95%CI 1.07-1.76), and HCV non-SVR (HR 1.73, 95%CI 1.35-2.21). The factors associated with liver disease-related death were ALBI grade 2 or 3 (HR 2.16, 95% CI 1.25-3.73), DCP ≥ 40mAU/ml (HR 2.34, 95% CI 1.48-3.70) and HCV non-SVR (HR 2.22, 95% CI 1.39-3.56). Conclusions: In RFA for diameter ≤3 cm, and ≤3 HCC nodules, over 80 years was not a significant factor associated with OS or liver disease-related death. The results support that RFA would be a promising treatment option for HCC patients over 80 years.

End-of-life (EOL) outcomes and healthcare utilization for patients with hepatocellular carcinoma (HCC) who received immune checkpoint inhibition (ICI).

560 Background: ICI is standard of care treatment for advanced HCC. EOL outcomes for patients with HCC who receive ICI prior to death are unknown. We examine relationships between EOL outcomes, healthcare utilization, and receipt of ICI for patients with advanced HCC referred to our tertiary center. Methods: Patients with advanced HCC evaluated at our center on or after January 1, 2020 and who died by March 29, 2024 were included. Patients were identified using diagnostic codes for liver cancer and HCC, and subsequently verified by manual review of the electronic health record. Demographic data, Child-Pugh (CP) status, and treatment history were collected. Primary EOL outcomes include: documentation of advance directives and goals of care (GOC) conversations, location of death, palliative care referral, hospice referral, days in hospice, and code status. Secondary healthcare utilization outcomes include: systemic therapy receipt, emergency department (ED) visits, hospitalization, and intensive care unit (ICU) admissions within 14, 30, and 90 days of death. Outcomes were stratified by ICI or non-ICI as last therapy received and p-values were derived using Pearson’s chi-square test for equality of proportions. Results: Of 221 evaluated patients, 71 died and met criteria for analysis. Baseline characteristics include mean age 64.1 years, 70.8% male, 71.8% received systemic treatment (median 1 line, range [1-7]), 54.1% CPA, 37.5% CPB, and 8.3% CPC at the time of last treatment. No statistically significant differences in primary EOL outcomes were detected when stratified by receipt of ICI or non-ICI as last therapy. Median days enrolled in hospice were not statistically significant between groups (24.5 days [non-ICI] vs 10 days [ICI]; p = 0.39). A higher proportion of patients who received ICI as last therapy had increased healthcare utilization across all outcomes (see Table). Conclusions: Patients with advanced HCC receiving ICI as their last treatment before death compared to those receiving non-ICI had similar EOL outcomes but higher healthcare utilization. This may be due to increased real-world use of ICI in CPB patients. Further investigation into risk stratification to predict high healthcare utilizers could guide decision-making and conversations around ongoing use of ICI, particularly near the EOL. Healthcare utilization outcomes stratified by receipt of ICI. Outcome Before Death n = 71 90 days 30 days 14 days Therapy within Total: Last therapy ICI 33/71 (46.5%)69.7% 18/71 (25.4%)66.7% 6/71 (8.5%)33.3% ED visit Total: Last therapy ICI 29/71 (40.8%)58.6% 27/71 (38.0%)55.6% 22/71 (30.1%)59.1% Hospitalization Total: Last therapy ICI 32/71 (45.1%)59.4% 30/71 (42.3%)56.6% 29/71 (40.8%)58.6% ICU admission Total: Last therapy ICI 6/71 (8.5%)66.7% 6/71 (8.5%)66.7% 6/71 (8.5%)66.7%

Association of social deprivation and colon cancer mortality: A population-based analysis.

25 Background: Colon cancer mortality is largely influenced by social factors, with higher rates seen in deprived areas. The Social Deprivation Index (SDI) measures factors like poverty, education, and unemployment, which have been linked to poor health outcomes. This study examines the relationship between county level social deprivation and colon cancer mortality in Texas. Methods: We conducted a population-based cohort study of colon cancer deaths in Texas. We queried the National Cancer Institute Surveillance, Epidemiology and End Results Program for county level colon cancer deaths in Texas over the most recent available year, 2021. We calculated age-adjusted mortality rates (AAMRs) per 100,000 population using the direct standardization method based on the age group weights from the 2000 standard US population. Confidence intervals for AAMR were derived by estimating the standard error as the AAMR divided by square root of number of mortalities. The SDI by county was linked to mortality rate using Federal Information Processing Standards (FIPS) codes. The significance of the difference between two AAMR was evaluated by determining if the intersection of 95% confidence intervals was empty. The association between SDI and AAMR was tested using both unweighted and weighted Spearman correlation with county population as weight. Results are reported and Spearman correlation and 95% confidence interval (ρ [95% CI]). Sensitivity analysis was performed by considering only the individual components of the SDI. Subgroup analyses included age group, sex, urban counties, rural counties, and race/ethnicity groups. Results: A total of 3,800 colon cancer mortalities were identified in 2023. The statewide AAMR was 12.5 (95% CI 12.1 to 12.9). Out of 254 counties, 29 (11.4%) had an SDI ≤ 25, 61 (24.0%) had 26 ≤ SDI ≤ 50, 87 (34.3%) had SDI 51 ≤ SDI ≤ 75, and 77 (30.3%) had 76 ≤ SDI ≤ 100. Total population in counties with SDI ≥ 76 was 15,106,726 (51.1%) with AAMR 12.959 (12.379 to 13.538). In contrast, the population in counties with SDI ≤ 25 was 4,771,473 (16.1%) with significantly lower mortality (AAMR 9.752 [95% CI 8.879 to 10.625]). The population weighted Spearman correlation between county level SDI and AAMR was positive (ρ = 0.339 [95% CI 0.209 – 0.514]). The unweighted Spearman correlation between county level SDI and AAMR was also positive (ρ = 0.178 [95% CI 0.089 – 0.238]). Households with no vehicle, poverty, and unemployment were most correlated with AAMR while renter occupied housing had no association. The correlation of county level SDI and AAMR were similar for rural counties, urban counties, males, females, Whites, Hispanics and Blacks. Conclusions: This study reveals a significant positive correlation between higher SDI and increased colon cancer mortality at the county level in Texas. The findings highlight the need for targeted public health interventions in deprived areas to reduce mortality and address disparities.