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Oriented Molecular Dipole‐Enabled Modulation of NiO<i>_x</i>/Perovskite Interface for Pb‐Sn Mixed Inorganic Perovskite Solar Cells

AbstractNickel oxide (NiOx) is considered as a potential hole transport material in the fabrication of lead‐tin (Pb‐Sn) perovskite solar cells (PSCs) for tandem applications. However, the energy level mismatch and unfavorable redox reactions between Ni≥3+ species and Sn2+ at the NiOx/perovskite interface pose challenges. Herein, high‐performance Pb‐Sn‐based inorganic PSCs are demonstrated by modulating the NiOx/perovskite interface with a multifunctional 4‐aminobenzenesulfonic acid (4‐ABSA) interlayer. The 4‐ABSA interlayer induces the formation of an oriented dipole moment directed from NiOx to perovskite, effectively elevating the valance band maximum of the NiOx film, thus balancing the energy level difference and promoting charge carrier extraction of the device. Moreover, the 4‐ABSA molecules interact with both NiOx and perovskite, suppressing the reaction of highly active Ni≥3+ species with perovskites while regulating perovskite crystallization. This results in perovskite films with reduced defect density and enlarged grains. Consequently, a remarkable device efficiency of 17.4% is obtained, representing the highest reported value for Pb‐Sn‐based inorganic PSCs thus far. Furthermore, the 4‐ABSA interlayer enhances the UV‐radiation and operational stability of the resulting devices, maintaining over 80% and 90% of the initial efficiency after 240 h of UV‐light exposure and 480 h of 1 sun illumination, respectively.

Gastric cancer patient insights: Patient-reported outcomes and real-world perspectives from the gastric cancer patient community.

362 Background: According to the National Cancer Institute Surveillance, Epidemiology, and End Results Program, an estimated 26,890 patients in the United States will be diagnosed with gastric (stomach) cancer in 2024. Estimated deaths from the disease in 2024 will reach 10,880, with a five-year relative survival rate of 36%. Understanding the need for increased gastric cancer education and awareness, the GI Cancers Alliance created a 12-month series of engagement opportunities to better understand and listen to the gastric cancer patient voice and perspectives. Methods: Our 12-month patient-reported outcomes (PRO) research (September 2023 – August 2024) included an online survey, in person and virtual focus groups, and personalized follow-up interviews. 651 gastric cancer patients and survivors participated in these engagement opportunities, with 89% of participants asking for follow-up personalized interviews. One of our program goals was to reach and interact with patients who often experience barriers in receiving quality cancer care. Our PRO research provided an opportunity to amplify the patient voice and lived experience by engaging patients in medically underserved communities, rural and urban populations, diverse ethnic communities, and patients receiving care in community-based and federally funded oncology centers, and charity (indigent) care. Results: Overarching results from our study suggest that while advances have been made, health equity, racial disparities and barriers in cancer care remain a challenge. 651 patient participants (43% male, 54% female, 3% non-binary) identified their race/ethnicity as: 24% Black/African American, 22% Hispanic, 21% Multiracial, Non-Hispanic/White 19%, Asian/Pacific Islander 7%, Native American 2%, and 5% Other. 69% of patients reported that their clinician did not suggest biomarker testing, nor discuss the role of biomarkers to help make informed treatment decisions. 68% of patients were concerned that they lacked knowledge and options to make informed decisions regarding their treatment. 64% of patients reported they suffered from mental health concerns ranging from severe depression, feelings of hopelessness and anxiety; 63% of patients struggled to afford nutritious food to meet their changing dietary needs, especially post-surgery. Conclusions: Our PRO research underscores the need for increased education and outreach for gastric cancer patient communities experiencing barriers to high quality cancer prevention, early detection, and treatment. By partnering with our 100+ advocacy partner organizations, we will continue to amplify the gastric cancer patient voice by establishing new programming, initiatives, and enhanced outreach addressing the challenges and barriers to quality cancer care for all patients.

A Multicenter Open-Label Randomized Phase II Study of Osimertinib With and Without Ramucirumab in Tyrosine Kinase Inhibitor–Naïve <i>EGFR</i> -Mutant Metastatic Non–Small Cell Lung Cancer (RAMOSE trial)

PURPOSE Preclinical studies demonstrated that dual inhibition of epidermal growth factor receptor (EGFR) and vascular endothelial growth factor (VEGF) pathways delay the emergence of resistance to EGFR tyrosine kinase inhibitors (TKIs), and in trials with first-generation EGFR TKIs, the combination of EGFR VEGF pathway inhibitors prolonged progression-free survival (PFS). METHODS The RAMOSE trial (ClinicalTrials.gov identifier: NCT03909334 , HCRN LUN-18-335) is a randomized, open-label multicenter phase II study comparing osimertinib with ramucirumab (arm A) to osimertinib (arm B) for initial treatment of metastatic EGFR -mutant non–small cell lung cancer (NSCLC) with 2:1 random assignment. The primary end point is PFS for evaluable patients; secondary end points include objective response rates (ORRs), disease control rate (DCR), overall survival, and safety. The stratification criteria were EGFR mutation type and the presence of CNS metastasis. RESULTS At data cutoff on August 29, 2023, 160 patients consented, 147 patients received treatment, and 139 patients were evaluable with at least one scan. In this preplanned interim analysis, the median follow-up was 16.6 months. Among the evaluable patients, 57 PFS events occurred. The median PFS was 24.8 (A) versus 15.6 (B) months (hazard ratio, 0.55 [95% CI, 0.32 to 0.93]; log-rank P = .023), 12-month PFS rate was 76.7% (A) versus 61.9% (B; P = .026). No significant difference was observed in the ORRs and DCRs between arms. Any-grade (G) adverse events (AEs) occurred in 100% (A) and 98% (B) of patients, with no G5 treatment-related AE (TRAE), one G4 TRAE (hyponatremia, A), and 53% (A) versus 41% (B) G3 TRAEs. AE-related discontinuation occurred in 13 patients (9.7% in A and 8.7% in B). The safety profile was in line with known safety of each drug. CONCLUSION Ramucirumab plus osimertinib significantly prolonged PFS compared with osimertinib alone in patients with TKI-naïve EGFR -mutant NSCLC. The combination is safe and well tolerated.

Molecular characteristics of early-onset versus average-onset gastroesophageal adenocarcinoma.

496 Background: Incidence of early-onset gastroesophageal adenocarcinoma (eoGEA, ages &lt;50 years) has been increasing in the United States since the 1990s, the etiology of which is still unclear, and limited data exists on molecular drivers. This study evaluates somatic and germline profiles in eoGEA compared to average-onset GEA (aoGEA, ages≥ 50 years). Methods: This is a retrospective, cross-sectional study utilizing data from de-identified records of GEA (esophageal, gastroesophageal junction and gastric adenocarcinomas) patients who underwent somatic NGS testing via the Tempus xT assay (595-648 gene DNA panel) from 12/2017 to 07/2024. This assay assesses somatic tumor mutations (including SNVs, Indels, CNVs, and select SVs), MSI, TMB, and incidentally detected germline SNVs and small indels in matched normal tissue. Clinical characteristics and immunotherapy markers were compared between eoGEA and aoGEA by Wilcoxon Rank Sum or Chi-squared test. Somatic and germline mutations were compared between two age groups with false discovery rate adjustments. Results: We compared the demographic, clinical, and molecular features of a total of 5863 patients with eoGEA (n=785, median age 43) and aoGEA (n=5078, median age 68). Over 80% of patients were diagnosed with stage IV disease. The eoGEA group had a higher proportion of females, non-white, and Hispanic or Latino patients compared to the aoGEA group (p&lt;0.001). Prevalence of MSI-H/ dMMR, and TMB-H was lower in eoGEA vs aoGEA (p&lt;0.001), while PD-L1 expression was similar. Prevalence of somatic CDH1 , CDKN2A , and TP53 SNVs, and FGFR2 and KRAS CNAs were higher in eoGEA vs aoGEA (q&lt;0.001). In a subset of 3286 patients with tumor/normal match testing (eoGEA=464 and aoGEA=2822), eoGEA also had a higher prevalence of germline CDH1 mutations (q&lt;0.001). Conclusions: eoGEA has a unique somatic and germline mutation profile compared to aoGEA; further study evaluating the molecular landscape including epigenetic changes could shed light on underlying mechanisms responsible for the rising incidence of eoGEA. eoGEA (n=785) aoGEA (n=5078) p-value/q-value* Baseline characteristics Median age at diagnosis (IQR) 43 (38, 47) 68 (61,74) &lt;0.001 Gender: male 509 (65%) 3798 (75%) &lt;0.001 Race (white) 280 (69%) 2347 (80%) &lt;0.001 Ethnicity (not hispanic or latino) 206 (60%) 1768 (86% &lt;0.001 Stage IV 495 (85%) 2883 (81%) 0.073 Immunologic markers TMB ≥ 10 25 (3.2%) 519(10%) &lt;0.001 MSI-H 13 (1.7%) 261 (5.1%) &lt;0.001 dMMR 7 (2.2%) 120 (5.9%) 0.007 Somatic mutations profiles * CDH1 126 (16%) 334 (6.6%) &lt;0.001 TP53 515 (66%) 3764 (74%) &lt;0.001 CDKN2A 101 (13%) 1011 (20%) &lt;0.001 KRAS 92 (12%) 931 (18%) &lt;0.001 NOTCH1 12 (1.5%) 228 (4.5%) 0.002 Germline mutation profiles * eoGEA (N=464) aoGEA (N= 2,822) Overall prevalence 46 (9.9%) 207 (7.3%) CDH1 10 (2.2%) 8 (0.3%) 0.001 TP53 3 (0.6%) 0 (0%) 0.039 BRCA2 2 (0.4%) 38 (1.3%) 0.6 BRIP1 4 (0.9%) 10 (0.4%) 0.6

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Association between sarcopenia components and depressed mood varies by sex among community-dwelling older adults from the Korean Frailty and Aging Cohort Study

Resonantly Enhanced Hybrid Wannier–Mott–Frenkel Excitons in Organic–Inorganic Van Der Waals Heterostructures

Abstract Hybrid excitons formed via resonant hybridization in 2D material heterostructures feature both large optical and electrical dipoles, providing a promising platform for many‐body exciton physics and correlated electronic states. However, hybrid excitons at organic–inorganic interface combining the advantages of both Wannier–Mott and Frenkel excitons remain elusive. Here, hybrid excitons are reported in the copper phthalocyanine/molybdenum diselenide (CuPc/MoSe 2 ) heterostructure (HS) featuring strong molecular orientation dependence by low‐temperature photoluminescence and absorption spectroscopy. The hybrid Wannier–Mott–Frenkel excitons exhibit a large oscillator strength and display signatures of the Frenkel excitons in CuPc and the Wannier–Mott excitons in MoSe 2 simultaneously through the delocalized electrons. The density functional theory (DFT) calculations further confirm the strong hybridization between the lowest unoccupied molecular orbital (LUMO) of CuPc and the conduction band minimum (CBM) of MoSe 2 . The out‐of‐plane molecular orientation is further employed to tune the hybridization strength and tailor the hybrid exciton states. The results reveal the hybrid excitons at the CuPc/MoSe 2 interface with tunability by molecular orientation, suggesting that the organic–inorganic HS constitutes a promising platform for many‐body exciton physics such as exciton condensation and optoelectrical applications.

Impact of COVID-19 pandemic on critically ill patients with colon cancer: A population-level study.

297 Background: The COVID-19 pandemic strained healthcare systems and disrupted pre-pandemic levels and trends in the short-term mortality of colon cancer hospitalizations. Colon cancer is the fourth most diagnosed cancer in the US and Texas. The impact on short term mortality in Texas in the years since the COVID-19 pandemic have not been explored. Methods: We used publicly available, deidentified, and state-wide data to conduct a population-base cohort study of hospitalizations aged ≥ 18 years admitted to intensive care units at acute care hospitals in Texas during 2016-2022 with a diagnosis of colon cancer. Hospitalizations transferred to another acute care hospital were excluded from the study. Colon cancer was identified using ICD-10-CM codes C18x and C20 selected from Clinical Classification Software Refined category NEO015: Gastrointestinal cancers - colorectal. Short-term mortality was defined as in-hospital mortality or discharge to a hospice. The response variables are pre-pandemic time trend, level change, change in time trend, and final time trend. The primary analysis method was interrupted time series analysis (ITSA) based on multilevel-multivariable logistic regression with results reported as average marginal effects per quarter (AME) and 95% confidence intervals (95% CI) in changes to the absolute probability of mortality. The matched pairs t-test was applied to ITSA and counterfactual predicted probabilities to further elucidate the impact of the COVID-19 pandemic. Sensitivity analyses was performed for hospitalizations aged ≥ 65 years and for hospitalizations without a diagnosis of COVID-19. Results: A total of 49,007 hospitalizations were included in the study of which 21,995 (44.9%) occurred after the beginning of the pandemic. Unadjusted short-term mortality was lower in the pre-pandemic period compared to the post-pandemic period (18.1% vs 20.1%). On adjusted analysis, the post-pandemic period remained associated with higher mortality rates. The pre-pandemic short-term mortality time trend was negative (AME -0.19%/quarter, 95% CI [-0.28% to -0.10%], p = 0.0001). The change in time trend was positive (AME 0.39%/quarter, 95% CI [0.23% to 0.55%], p &lt; 0.0001) and the change in level was also positive (AME 1.25%, 95% CI [0.0.04% to 2.47%], p = 0.0436). The final time trend was significant and positive (AME 0.20%/quarter, 95% CI [0.07% to 0.33%], p = 0.0023). The point estimate and 95% CI for the difference between ITSA predicted and counterfactual predicted probabilities of mortality was 3.45% (3.41% to 3.48%). Similar results were observed on sensitivity analyses. Conclusions: Since the onset of the pandemic there was a 2% increase in the absolute probability of short-term mortality and a change from negative to positive time trend in short-term mortality. The average impact of the COVID-19 pandemic on the absolute probability of short-term mortality is estimated at over 3%.

Total neoadjuvant therapy with FOLFOX plus bevacizumab and short-course radiotherapy for Ras mutant, high-risk, locally advanced rectal cancer: The TRAINER trial.

133 Background: Total neoadjuvant therapy (TNT) intensified by the combination of targeted therapy or immunotherapy is warranted to achieve satisfying local and systemic control for high-risk locally advanced rectal cancer (LARC). Our study aimed to explore the efficacy and safety of a FOLFOX-based TNT regimen plus bevacizumab and short-course radiotherapy (SCRT) in Ras-mutant high-risk LARC patients. Methods: In this single-arm, single-center, phase II trial, LARC patients with at least one risk factor (cT3c-4, mesorectal fascia positive, cN2, lateral lymph node involvement, and extramural venous invasion positive) were recruited and only Ras-mutant patients were included. Four cycles of FOLFOX plus bevacizumab were arranged as induction chemotherapy followed by SCRT (25Gy/5Fx) and two cycles of FOLFOX as consolidation chemotherapy. Surgery was performed 8 weeks after completion of radiotherapy. After surgery, high-risk stage III patients (T4 or N2) were recommended to receive an extra 6 cycles of FOLFOX as adjuvant chemotherapy, while low-risk stage III patients were scheduled for regular follow-up. Patients with clinical complete response(cCR) were allowed to choose the “Watch &amp; Wait” (W&amp;W) strategy instead of surgery. The primary endpoint was the complete response (CR) rate, defined as the total rate of cCR plus pathological complete response (pCR). Secondary endpoints included adverse events of TNT, postoperative complications, 2-year disease-free survival, and overall survival. Results: Between April 2, 2021, and March 12, 2024, 47 of 51 enrolled patients were eligible for treatment. All patients completed the prescribed TNT cycles, and six (12.8%) of them had dose reduction. The CR was achieved in 18 (38.3%) patients, including 14 (29.8%) pCR. No grade IV-V toxicity was observed and the incidence of grade III toxicities was 34.0%. Four patients (8.5%) achieved cCR and chose the W&amp;W strategy. The other 43 patients underwent curative surgery and anal preservation was achieved in 39 (90.7%) patients. Seven patients (16.3%) experienced postoperative complications, including four (9.3%) cases of anastomotic leakage. Conclusions: The intensified TNT regimen combined with bevacizumab achieved a satisfying CR rate with acceptable toxicities and complications for Ras-mutant high-risk LARC patients. Long-term survival data of this cohort are needed to validate the efficacy of this regimen further. Clinical trial information: NCT04923620 .

Clinical outcomes of hypofractionated radiotherapy (5x5 Gy) with a simultaneous integrated boost (5x6 Gy) in locally advanced rectal cancer.

60 Background: Hypofractionated RT (5x5 Gy) with or without subsequent chemotherapy is a standard of care used at the National Institute of Oncology, Warsaw, Poland, as a preoperative treatment for locally advanced rectal cancer. To maximize the chance of achieving a complete response (CR), when surgery is not planned or when there are clinically involved lymph nodes located outside the standard TME field, RT can be augmented with a simultaneous integrated boost (SIB) delivering 5x6 Gy. This report aims to evaluate the clinical outcomes of hypofractionated RT with a SIB in rectal cancer. Methods: From Dec 2018 to Sep 2022, 78 consecutive pts with a median age of 67 years (range 36–89 years), received hypofractionated RT utilizing the SIB-VMAT technique. The radiation dose fractionation was 5x5 Gy to the rectum, mesorectum and elective lymph nodes and a SIB to the GTV for a total dose of 30 Gy. Results: 30 pts (38.5%) received a SIB for the rectal tumor, of which 15 pts (19.2%) were deemed unfit for surgery, 10 pts (12.8%) refused surgical treatment, 3 pts (3.8%) had an oligometastatic disease, and 2 pts (2.6%) had an advanced primary tumor. 48 pts (61.5%) received a SIB to the clinically involved lymph nodes located outside the standard TME field. All 78 pts completed RT as planned without interruptions or dose modifications and with an acceptable toxicity profile. There was a 26.9% (n = 21) incidence of G2 toxicities (diarrhea, proctitis, skin toxicity, cystitis or lumbosacral plexus neuropathy) and a 3.8% (n = 3) incidence of G3 toxicities (diarrhea or proctitis). After a median follow-up of 917 days (range 33–1927 days), an assessment of response was conducted in 68 cases. In 94.1% (n = 64) there was no progression at the site irradiated to a dose of 30 Gy. After completion of RT, mr-TRG was evaluated in 28 pts. In 46.4% (n = 13) mr-TRG 1-2 (cCR) was achieved. Of the 24 pts qualified for the watch and wait strategy, 17 had follow-up. Of this group, 64.7% (n = 11) remained progression-free, and 11 pts had an adequate evaluation for cCR (imaging and endoscopy), resulting in a 63.6% (n = 7) rate of cCR. 43 pts underwent surgery, of which 97.7% (n = 42) had R0 resection. In 41 cases pathological TRG was assessed according to AJCC or Ryan, of which 41.4% (n = 17) achieved TRG 0-1 (pCR). In 40 cases the operated pts had no initial metastatic spread, among them 67.5% (n = 27) remain disease-free. 67 pts reported disease-related symptoms before RT. After treatment, 89.6% (n = 60) of those pts achieved symptomatic improvement in either rectal bleeding, bowel frequency, or pain control. Conclusions: Hypofractionated RT with SIB-VMAT delivering a dose of 30 Gy/25 Gy/5 fractions provides good local control and is a safe and viable option for both young and elderly patients who will not undergo surgery and for patients with involved lymph nodes located outside the standard TME field to maximize the chance of achieving CR.

Application of chokeberry biochar as a modified additive to the vegetable lubricants: the tribological and rheological properties

Cost-effectiveness of blood-based colorectal cancer screening: A simulation model incorporating real-world longitudinal adherence.

93 Background: Colorectal cancer (CRC) is a predominant cause of cancer-related mortality worldwide. Regular screening improves outcomes. However, despite there being many U.S. Preventive Services Task Force (USPSTF) recommended CRC screening options, many people elect not to use any of them. Most cost-effectiveness models assume perfect (100%) adherence initially and over time (longitudinally), which is implausible as approximately one-third of eligible individuals are not up to date with CRC screening. Our study evaluates the cost-effectiveness of Shield, an FDA-approved blood-based CRC test, while incorporating real-world adherence. Methods: The CAN-SCREEN (Colorectal cANcer SCReening Economics and adherENce) model is a validated, discrete-event simulation model designed to evaluate the clinical and economic outcomes of CRC screening strategies under real-world adherence scenarios. We simulated individual lifetime outcomes for a cohort of 10,000 people beginning screening at age 45, running 4,000 trials per cohort. We conducted a cost-effectiveness analysis using the CAN-SCREEN model, and compared the Shield blood-based test administered every three years to no screening. Costs were calculated from a healthcare perspective and adjusted to 2023 US dollars. Shield was considered cost-effective if the incremental cost-effectiveness ratio (ICER) was below $100,000 per quality-adjusted life-year (QALY) gained. The analysis also assessed the maximum price Shield could maintain while remaining cost-effective. Results: Compared to no screening, Shield increased the number of QALYs by 154 per 1,000 individuals and raised costs by $7.5 million per 1,000 individuals at its commercial test cost. With an incremental cost of $48,662 per QALY gained, Shield was found to be cost-effective relative to no screening at $100,000 cost per QALY willingness-to-pay threshold. Furthermore, the unit cost of Shield can be as high as $3,241 and $4,942 to be considered cost-effective at $100,000 and $150,000 per QALY gained, respectively. Conclusions: This study used the CAN-SCREEN model to compare Shield, an FDA-approved blood-based CRC screening test, against no screening, finding that Shield is cost-effective. With about one-third of the U.S. population not up to date on CRC screening, Shield's noninvasive approach offers a promising, cost-effective solution to increase adherence and reduce CRC mortality. Economic outcomes of Shield against no screening using CAN-SCREEN model. Intervention Test Unit Cost QALYs/Person Cost ($)/Person Cost ($)/QALY Gained vs No screening No Intervention - 15.269 $6,312.18 - Shield $1,495 15.423 $13,786.72 $48,662 Shield $3,241 15.423 $21,672.34 $100,000.00 Shield $4,942 15.423 $29,352.42 $150,000.00

Safety and efficacy of first-line nivolumab plus chemotherapy for HER2-negative advanced gastric cancer in real-world patients: Updated analysis.

341 Background: Based on the results of CheckMate-649 and ATTRACTION-4, nivolumab plus chemotherapy is the new standard of care as first-line treatment for patients with HER2-negative advanced gastric cancer (AGC) regardless of PD-L1 combined positive score (CPS) status in Japan. This study aimed to evaluate the safety and efficacy of this regimen in real-world patients with HER2-negative AGC with a longer follow-up. Methods: In this single-institutional retrospective study, patients with HER2-negative AGC who were treated with first-line nivolumab plus chemotherapy between September 2021 and April 2024 were consecutively enrolled and evaluated. Early tumor shrinkage (ETS) was defined as ≥20% tumor reduction at 8 ± 2 weeks. Results: Of 151 patients, median age was 66 years (range, 27–83); 58% were male; 81% had diffuse-type histology; the peritoneal metastasis was seen in 60%; PD-L1 CPS of &lt;1, 1≤/&lt;5, 5≤ was 30%/41%/29%; deficient mismatch repair and/or high microsatellite instability was 7%. At a median follow-up of 14.2 months, the median overall survival (OS) and progression-free survival (PFS) were 21.7 months (95% confidence interval [CI] 14.4–26.2) and 7.7 months (6.4–9.6), respectively. The median OS according to CPS subgroups (&lt;1, 1≤/&lt;5, 5≤) were 21.7 / not reached (NR) /25.0 months, respectively (log-rank P = 0.55). In patients with measurable lesions at baseline according to RECIST ver 1.1, the objective response rate and disease control rate were 62% and 87%, respectively, with a complete response rate of 10%. In the exploratory analysis by ETS, both median PFS and OS were significantly longer in the ETS group compared to the non-ETS group (PFS, NR vs. 6.2 months; hazard ratio [HR] 0.35; 95% CI 0.17–0.68; P = 0.001) (OS, 25.0 vs. 11.7 months; HR 0.44; 95% CI 0.20–0.93; P = 0.03). The immune-related adverse events (irAEs) of any grade were observed in 26% (grade 3–4 irAEs 12%), whereas no treatment-related death was documented. Conclusions: The updated analysis suggests that first-line nivolumab plus chemotherapy provides benefit in real-world patients with HER2-negative AGC regardless of PD-L1 status, and suggests that the magnitude of ETS may predict a significant impact on the duration of survival.

Comparative restricted mean survival time (RMST) analysis of survival in advanced hepatocellular carcinoma (aHCC) from pivotal phase III trials: IMbrave-150, ORIENT-32, CARES-310, HIMALAYA, and CM-9DW.

597 Background: In advanced hepatocellular carcinoma (aHCC), the evaluation of overall survival (OS) and progression-free survival (PFS) through restricted mean survival time (RMST) provides a nuanced understanding of treatment efficacy. The RMST analysis serves as a valuable complement to the hazard ratio (HR) analysis, offering insights into the average survival time over a specified period. This study compares RMST analyses of OS at 24 and 36 months, and PFS at 12 and 18 months, across five pivotal phase III trials: IMbrave-150, ORIENT-32, CARES-310, HIMALAYA, and CM-9DW. Methods: Data from the experimental arms of the five phase III trials were analyzed. The RMST was calculated using the area under the Kaplan-Meier survival curves up to the specified time points. Specifically, OS was evaluated at 24 and 36 months, and PFS at 12 and 18 months. The RMST provides an estimate of the average time that patients survive (for OS) or remain progression-free (for PFS) within a specific timeframe. Kaplan-Meier survival curves were digitized if not available in raw form, and the area under the curve (AUC) was computed using numerical integration methods. RMST values were extracted from the AUC for the specified periods. This approach accounts for censored data and provides a robust comparison of survival times across different treatment groups. Results: The results for OS RMST at 24 and 36 months and PFS RMST at 12 and 18 months are summarized in the table. Conclusions: Angiogenesis inhibitor + immune checkpoint inhibitor combinations (Atezolizumab + Bevacizumab; Sintilimab + IBI305) provide the most favorable RMST outcomes in terms of OS and PFS. Restricted mean survival time (RMST) comparison of OS and PFS (months). aHCC 1L Phase III Trials Treatment Arm OS 24m OS 36m PFS 12m PFS 18m IMbrave-150 1, 2 Atezolizumab + Bevacizumab 17.50 22.79 9.69 13.29 ORIENT-32 3 Sinitilimab + IBI305 17.01 21.09 9.18 12.54 CARES-310 4 Camrelizumab + Rivoracenib 16.34 19.75 9.29 12.14 HIMALAYA 5, 6 Tremelimumab + Durvalumab 15.36 18.76 8.95 12.02 CM-9DW 7, 8 Nivolumab + Ipilimumab 15.87 20.08 8.74 11.78 1 Finn et al. N Engl J Med 2020;382:1894-905; 2 Cheng et al. J Hepatol 2022;76:862-873; 3 Ren et al. Lancet Oncol 2021;22:977–90; 4 Qin et al. Lancet 2023;402:1133–46; 5 Abou-Alfa et al. NEJM Evid 2022;1(8):EVIDoa2100070; 6 Sangro et al. Ann Oncol 2024;35:448-457; 7 Galle et al. J Clin Oncol 2024;42(suppl 17):abstr LBA4008; 8 Decaens et al. Ann Oncol 2024;35:S657.

Atractylenolide I prevents acute liver failure in mouse by regulating M1 macrophage polarization

Lenvatinib plus hepatic arterial infusion chemotherapy of oxaliplatin, fluorouracil, and leucovorin versus lenvatinib alone for advanced hepatocellular carcinoma.

580 Background: Lenvatinib stands out as a first-line therapy for individuals with advanced hepatocellular carcinoma (HCC). Concurrently, hepatic arterial infusion chemotherapy comprising oxaliplatin, fluorouracil, and leucovorin (FOLFOX-HAIC) has emerged as a potential option for those with advanced HCC. It is necessary to investigate the efficacy and safety of lenvatinib plus FOLFOX-HAIC (lenvaHAIC) for advanced HCC in real-world situations. Methods: In this retrospective analysis, 127 consecutive patients underwent lenvaHAIC, while 184 patients received lenvatinib alone as first-line treatment at six Chinese academic centers between January 2019 and June 2022. Following 1:1 propensity-score matching, we established paired cohorts (113 patients in each group) for evaluating survival. Overall survival (OS), progression-free survival (PFS), objective response rate (ORR) evaluated by RECIST 1.1 and mRECIST criteria, and safety profiles were compared between the two groups. Results: The lenvaHAIC group exhibited significantly prolonged median PFS and OS than the lenvatinib group (PFS: 12.3 vs. 6.2 months; OS: 25.6 vs. 12.3 months; P &lt; .001 for each). In the propensity-score matched cohorts (113 pairs), both PFS and OS were notably extended in the lenvaHAIC group compared with those in the lenvatinib group (P &lt; .001). Multivariate analysis identified lenvaHAIC treatment as an independent factor for improved PFS (hazard ratio [HR] 0.45; P &lt; .001) and OS (HR 0.38; P &lt; .001). Grade 3-4 adverse events, including nausea, vomiting, diarrhea, thrombocytopenia, and neutropenia, were more prevalent in the lenvaHAIC group. Conclusions: LenvaHAIC may be a promising treatment in patients with advanced hepatocellular carcinoma, demonstrating enhanced OS, PFS, and ORR and an acceptable safety profile.

Positive homologous recombination signature (HRDsig+) and the genomic landscape of intrahepatic cholangiocarcinoma (iCCA).

627 Background: Defective DNA repair has not been a major focus in iCCA clinical research. In this comprehensive genomic profiling (CGP) study, we queried whether the presence of a scar-based HRDsig biomarker could identify a subset of patients with unique genomic alterations (GA) and potential for responsiveness to PARP inhibitor-based treatment regimens. Methods: 6,271 cases of clinically advanced iCCA underwent hybrid capture based CGP to evaluate all classes of GA. Microsatellite instability (MSI) status, tumor mutation burden (TMB) levels, genomic ancestry and genomic trinucleotide signatures were determined from the sequencing data. HRDsig status was calculated using a broad set of genome-wide copy number features (PMID 37769224). PD-L1 was determined by IHC using the Dako 22C3 tumor proportional score (TPS). Results were compared using the Fisher exact system with the Benjamini-Hochberg procedure. Results: 288 (4.6%) of the sequenced iCCA featured an HRDsig+ status. Gender distribution (46-49% male) and median age (67 years) were similar in both HRDsig+ and HRDsig- iCCA. More pathogenic GA per tumor were found in HRDsig+ vs HRDsig- iCCA (5 vs 4; P&lt;0.0001). Genomic ancestry distribution was similar; European ancestry ranged from 73% to 76% in the two cohorts. The APOBEC signature was uncommon but slightly more frequent in the HRDSig+ cases (1.7% vs 0.4%; P=.034). MSI High status was slightly more frequent in the HRDsig- group (1.8% vs 0.0%; P=0.034). Median TMB was higher in the HRDsig+ cases (3.6 vs 1.2 mut/Mb; P&lt;0.0001) as was the frequency of TMB &gt; 10 mut/Mb (9.1% vs 3.5%; P&lt;0.0001). PD-L1 expression was similar with low level (1-49% TPS) ranging from 19% to 23% in the 2 groups. As anticipated, GA in genes associated with HRD including BRCA1 (6.6% vs 0.8%; P&lt;0.0001), BRCA2 (25.0% vs 1.3%; P&lt;0.0001), PALB2 (8.7% vs 0.3%; P&lt;0.0001), and ATM (6.3% vs 3.4%; P=0.033) were all more frequent in the HRDsig+ iCCA. In contrast, GA in genes associated with iCCA targeted therapies were less frequent in the HRDsig+ cases including FGFR2 (8.0% vs 12.5%; P=0.033), IDH1 (3.5% vs 14.0%; P&lt;0.0001) and ERBB2 (3.5% vs 5.7%; NS). In the HRDsig- group, 83.3%/74.1% of BRCA1 / BRCA2 mutated iCCA were mono-allelic likely non-driver GA respectively. MTOR pathway activating GA were more frequent in the HRDsig+ cases including PTEN (7.3% vs 3.3%; P=0.003) and NF1 (8.0% vs 2.8%; P&lt;0.0001). MTAP deletion, an emerging iCCA target, was more frequent in the HRDsig+ iCCA (23.3% vs 16.9%; P=0.024). Conclusions: Nearly 5% of advanced iCCA feature HRDsig positive status which is associated with both significant differences in the frequencies of therapy associated genomic targets and the potential for introducing PARP inhibitors for these patients. HRDsig- iCCAN = 5983 HRDsig+ iCCAN = 288 P-value ATM 3.4% 6.3% 0.033 BRCA1 0.8% (83.3% mono-allelic) 6.6% &lt;.0001 BRCA2 1.3% (74.1% mono-allelic) 25.0% &lt;.0001 PALB2 0.3% 8.7% &lt;.0001

Neoadjuvant SHR-1701 (a bifunctional anti-PD-L1/TGF-βRII agent) combined with chemoradiotherapy for resectable locally advanced esophageal squamous cell carcinoma (ESCC): A phase II trial.

410 Background: Neoadjuvant chemotherapy or chemoradiotherapy followed by surgery is the standard of care for resectable locally advanced ESCC. SHR-1701, a new bifunctional fusion protein composed of a monoclonal antibody against PD-L1 fused with the extracellular domain of TGF-β receptor II, may enhance antitumor activity in combination with neoadjuvant standard therapies in ESCC patients (pts). The aim of this phase II trial is to determine the safety and efficacy of neoadjuvant chemoradiotherapy plus SHR-1701 followed by esophagectomy in pts with locally advanced resectable ESCC. Methods: Pts with resectable thoracic ESCC, diagnosed as clinical stage of cT1b-cT2N+M0 or cT3-cT4aNxM0 per AJCC 8th were eligible. Preoperative therapy included SHR-1701 (30 mg/kg every 3 weeks for 2 cycles), albumin paclitaxel (50 mg/m 2 , once a week for 5 weeks), carboplatin (AUC=2, once a week for 5 weeks) and radiotherapy (41.4Gy in 23 fractions). Following esophagectomy, pts received SHR-1701 up to 1 year. The primary endpoint was pathological complete response (pCR) rate in the per-protocol population. Secondary endpoints included R0 resection rate, major pathological response (MPR) rate, disease free survival (DFS) and safety. Results: Between Dec. 2021 and Feb. 2023, 43 pts were screened and 41 met the inclusion criteria, among whom the clinical stage I, II, III, and IVa at baseline were 1 (2.4%), 8 (19.5%), 31 (75.6%), and 1 (2.4%), respectively. All 41 pts received neoadjuvant SHR-1701 combined with chemoradiotherapy. As of Mar. 2024, 30 pts underwent surgery, and all achieved R0 resection. There was no in-hospital and postoperative 30-day mortality. 9 (30.0%) pts achieved pCR in both primary tumor and lymph nodes (ypT0N0), and 12 (40.0%) pts had complete pathological response of the primary tumor with residual disease in lymph nodes alone (ypT0N+). Treatment-related adverse events (TRAEs) occurred in all pts, and most of TRAEs were grade 1-2. Notable toxicity included pneumonitis (31.7%) and anastomotic leak (12.2%). Conclusions: The addition of SHR-1701 to neoadjuvant chemoradiotherapy in ESCC demonstrated promising efficacy with acceptable toxicity, and might be a promising approach for neoadjuvant treatment. Clinical trial information: ChiCTR2000041562.

Association between Healthy Eating Index-2020, alternative Mediterranean Diet scores, and gastrointestinal cancer risk in NHANES 2005–2018

Phase II study of organ preservation (OP) in node-negative (NN) low rectal cancer (RC): Updated clinical and patient reported outcomes (PROs).

148 Background: Total mesorectal excision (TME) is a highly effective treatment for rectal cancer (RC) but is associated with significant morbidity and mortality. Organ preservation (OP) approaches for locally advanced RC have been successful but not well studied for node-negative (NN) low RC. The objective of this investigator-initiated trial (IIT) is to determine the feasibility of performing successful local excision (LE) after neoadjuvant chemotherapy (CTX) in NN low RC. Methods: With IRB approval, patients (pts) with clinical stage T1-3, N0 low rectal adenocarcinomas (&lt;6 cm from anal verge) were included in this single arm phase II IIT. Pts received 6 cycles of FOLFOX (5-FU bolus 400 mg/m2 and infusion 2400 mg/m2, Leucovorin 400 mg/m2, Oxaliplatin 85 mg/m2). Those with evidence of a response underwent LE (transanal excision) 6-12 weeks later. To target occult nodal metastases and reduce in-bowel recurrences, LE was followed by chemoradiotherapy ([CXRT] capecitabine 825 mg/m2 and long course RT to 54 Gy). The primary endpoint was the proportion of pts with successful LE after neoadjuvant CTX (NCT03548961). Results: Nineteen pts with low RC were enrolled; nine were female, and the mean age at diagnosis was 65 years. T stage was as follows: T1- 1(5%), T2 - 11(58%), T3 - 7(36%). Eighteen (95%) pts completed at least 5 cycles of neoadjuvant Ctx and 16/19 (84%) underwent LE. Negative margins were achieved in 79% (15/19), meeting our primary endpoint (p &lt; 0.001). Ten (53%) were downstaged, and complete pathological response was achieved in 5/16 (31%) of pts who underwent LE. Four (21%) pts (all T2 stage) did not meet the primary endpoint (3 with inadequate response to CTX and 1 with LE and positive margins). Of these, three were salvaged (2 with CXRT; 1 with TME), and one died of infection (unrelated complication). All 16 who underwent LE completed CXRT. Of the 15 pts with successful OP at a median follow-up of 25.5 months, no local recurrences have been reported and 1 pt with lung nodules below the threshold for metastases at study entry ultimately developed clear lung metastases. Median DFS was not reached. Patient reported outcomes (PRO) assessment revealed a slight decline in physical health scores after neoadjuvant CTX but improved to baseline at follow-up. No decline was seen in mental health scores. Symptom specific QOL (sexual and bowel function) and long-term survival data will be presented. Conclusions: Neoadjuvant CTX and LE allows for OP in NN low RC and results in a margin negative LE in over three fourths of pts with durable long term local control and preserved QOL. Ongoing trials are investigating an OP approach in NN RC (NCT03259035). Our approach adds to the mounting evidence and will provide early data of the benefit of adjuvant chemoradiation to target occult nodes in this setting. Clinical trial information: NCT03548961 .