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Enhancing CZTSSe solar cell efficiency to 11.07% with NaClO-induced Mo texturing for improved light management and carrier collection

This study systematically investigates the optimization mechanism of NaClO solution treatment on Mo substrates for enhancing the optoelectronic performance of CZTSSe thin film solar cells. Experimental results demonstrate that a 10 s NaClO soaking forms a “spike-like” texture on the Mo surface, increasing the average surface roughness difference from 34.52 to 77.75 nm. This significantly enhances light scattering, particularly for photons reaching the back Mo electrode, thereby extending the optical path and promoting photon reabsorption. Additionally, the roughened Mo surface improves the wettability of the precursor solution (contact angle decreases from 19.3° to 12.7°), facilitating the formation of larger CZTSSe grains. Electrical characterization reveals that the NaClO-treated Mo substrate significantly reduces the density of negative charge traps at CZTSSe grain boundaries (contact potential difference increases from −1.1 V to −263 mV), suppressing hole recombination and optimizing carrier collection efficiency. The spike-like structure of the Mo surface also shortens the transport path of hole carriers generated by short-wavelength light, further enhancing collection efficiency. Ultimately, the PCE of CZTSSe devices based on the Mo-10 substrate increases from 9.34% to 11.07%, attributed to the reduction in Rs and J0. This study highlights the critical role of a back electrode interface microstructure design in synergistically optimizing light absorption and carrier transport.

GRK5 regulates endocytosis of FPR2 independent of β-arrestins

Analysis of gut and mucosal microbiomes in patients with extrahepatic cholangiocarcinoma.

620 Background: Cholangiocarcinoma is an aggressive malignancy with a poor prognosis. While gut microbial dysbiosis is linked to various diseases, including biliary disorders and cancer, its association with cholangiocarcinoma remains unclear. Methods: This study compared the mucosal and gut microbiomes of patients with extrahepatic cholangiocarcinoma (n = 21) to those with cholecystitis (n = 21) and healthy individuals (n = 28). Mucosal microbiomes were collected from cancer lesions and gallbladders, with fecal samples obtained from 31 participants. The 16S rRNA gene (V3 and V4 region) was sequenced using the Illumina MiSeq platform and analyzed with QIIME 2. Results: 16S rRNA sequencing revealed Proteobacteria as the dominant taxon in the cancer cohort, with Klebsiella, Aeromonas, Staphylococcus, Fusobacterium, and Haemophilus also enriched. In contrast, Firmicutes dominated in the cholecystitis and control cohorts. β-diversity analysis highlighted significant differences between cohorts. Elevated levels of bile acids, particularly chenodeoxycholic acid and ursodeoxycholic acid, were observed in the cancer cohort and positively correlated with Proteobacteria, Aeromonas, Enterobacter, and Enterococcus. Conclusions: These findings suggest that microbiome dysbiosis contributes to cholangiocarcinoma development.

Total cost of care of immune-oncology treatments for unresectable hepatocellular carcinoma: A Singapore healthcare perspective analysis.

642 Background: Tremelimumab + durvalumab (STRIDE) and atezolizumab + bevacizumab are recommended first-line immune-oncology treatment options for unresectable hepatocellular carcinoma (uHCC). This study aimed to quantify the total economic burden to the Singapore healthcare system of treating patients with uHCC using STRIDE versus atezolizumab + bevacizumab. Methods: A model was developed to estimate the total cost of care of using STRIDE or atezolizumab + bevacizumab, which followed patients with uHCC eligible for first-line systemic therapy, considering direct medical costs. Costs considered in the model included treatment acquisition and administration, endoscopy, healthcare resource use, and cost for treating grade ≥3 treatment-emergent adverse events (TEAEs). Data on treatment regimens and TEAEs were taken from the HIMALAYA (STRIDE) and IMbrave150 (atezolizumab + bevacizumab) trials. Resource use rates were based on an average of 168 days treatment for both regimens. All costs were obtained from Singaporean sources. Results: The total cost of care for STRIDE and atezolizumab + bevacizumab was estimated at SGD$40,277 (USD$30,932) and SGD$43,605 (USD$33,487) per patient, respectively. This translates into an average cost savings of SGD$3,328 (USD$2,555]) per patient when treated with STRIDE compared to atezolizumab + bevacizumab. The main driver of cost savings was treatment acquisition and administration (-SGD$1,917 [-USD$1,472], -6%) though lower costs were also associated with resource use (-SGD$927 [-USD$712], -8%), endoscopy (-SGD$342 [-USD$263], -77%) and TEAE management (-SGD$141 [-USD$108], -74%). Assuming an incident population of 260 patients eligible for treatment, the total burden was estimated at SGD$10,489,604 (USD$8,055,696) when all patients were treated with STRIDE, and SGD$11,356,273 (USD$8,721,271) when treated with atezolizumab + bevacizumab (Table). The incremental cost offset to the health plan was SGD$866,669 (USD$665,575) when treated with STRIDE. Conclusions: This study suggests that STRIDE offers cost savings over atezolizumab + bevacizumab for uHCC treatment in the Singapore healthcare system. Additional real-world evidence studies are warranted to capture the long-term survival benefits and associated treatment costs. Annual cost of care based on 260 patients receiving first-line immune-oncology treatment. Category STRIDE Atezolizumab + Bevacizumab Incremental difference Endoscopy costs $26,358 $115,555 -$89,197 Resource Use costs* $2,607,000 $2,848,307 -$241,307 Adverse events costs $12,899 $49,716 -$36,817 Treatment acquisition and administration $7,843,347 $8,342,696 -$499,349 TOTAL $10,489,604 $11,356,273 -$866,669 All costs in SGD$. *Includes: physician visits; laboratory and radiological tests; and hospitalisation.

Real-world treatment patterns and outcomes for patients with neoadjuvant treatment between 2019-2022 for gastric or gastroesophageal junction cancer (GC/GEJC) in the US community setting.

345 Background: Treatment options for patients with early-stage GC/GEJC are still limited and the prognosis remains poor, despite recent therapy approvals. With the latest adoption of FLOT use in the US, it is important to understand patients’ characteristics, treatment patterns and outcomes in the US community oncology setting. Methods: This retrospective observational cohort study used electronic health records data from 278 adult patients with stage II-IVA GC/GEJC adenocarcinoma initiating neoadjuvant treatment (index) within The US Oncology Network between 1/1/2019 and 12/31/2022, based on Food and Drug Administration approval of FLOT in 2019. Patients were followed through 9/30/2023, last patient record or death, whichever occurred first. Descriptive analyses were conducted to evaluate patient and treatment characteristics. Kaplan-Meier was used to assess overall survival (OS) and event-free survival (EFS) from index. Adjusted Cox proportional hazard models were used to analyze the association of surgery as a time-dependent variable with OS and EFS. Results: Median (interquartile range [IQR]) age at index was 67.5 (58.2, 74.2) years; most patients were male (68.0%), and half were Caucasian (51.1%). Stage III was the most common initial stage (50.0%), followed by IIB (29.1%), and II (not otherwise specified)/IIA (19.8%). Most patients had an ECOG (0-1) 65.5%. Median (IQR) follow-up from index was 15.6 (8.6, 27.8) months. The most common neoadjuvant regimens were FLOT (51.1%), doublet (28.4%), and CROSS (18.0%). Median OS (months) (95% confidence interval [CI]) for patients with surgery was not reached (NR) (47.7, NR) and those without was 16.1 (8.6, 35.1). Patients with surgery had a longer median EFS (95% CI) (months) than those without 38.3 (25.0, NR) vs 5.6 (4.5, 6.5) (log rank p-value <0.0001). Adjusted hazard ratios (95% CI) for OS and EFS indicated that patients who received surgery were less likely to experience an event than those without, 0.252 (0.139, 0.456) and 0.268 (0.169, 0.426), respectively (p<0.0001). Conclusions: Study findings showed a high proportion of patients receiving FLOT since its approval in US, with a directional OS benefit similar to the FLOT4 trial. Also, receipt of surgery was a strong predictor for OS and EFS. While the results are promising, most patients who did not receive surgery progressed within 6 months and died a little over a year from index. However, given the small portion of patients who did not receive surgery, further research is needed to understand if there is an unmet need for this group. Variable Doublet CROSS FLOT N 79 50 142 Surgery Rate (%) 60.8% 62.0% 71.8% GC Rate (%) 79.8% <20% 85.9% OS, median (95% CI), months 26.0 (20.9, NR) 37.7 (27.8, NR) 52.1 (47.7, NR) EFS, median (95% CI), months 10.8 (8.4, 23.2) 20.9 (11.3, 26.3) 37.7 (18.0, NR)

Differences in disease characteristics in young vs older adults with colorectal carcinoma.

34 Background: Colorectal carcinoma (CRC) exhibits distinct disease characteristics between younger (≤50 years) and older (>50 years) adults, which may significantly influence treatment decisions and outcomes. This study aims to investigate differences in disease characteristics of colorectal carcinoma among patients aged ≤50 years compared to those aged >50 years, utilizing data from the Surveillance, Epidemiology, and End Results (SEER) database. Methods: A retrospective analysis was performed using the SEER database covering the years 2000 to 2020. A total of 150,000 diagnosed CRC cases were included. Key variables analyzed comprised stage at diagnosis, tumor grade, histological subtype, and 5-year survival rates. Rates of CRC diagnoses in various age brackets were calculated for three time periods: 2000-2010, 2010-2020, and overall from 2000-2020. Results: Within the total cohort, 12% (18,000 cases) were diagnosed in young adults, while 88% (132,000 cases) were in older adults. An analysis of age-specific rates showed: 2000-2010 : Young adults (≤50 years) represented 10% of CRC cases, with 16% presenting at advanced stages (Stage III or IV). 2010-2020 : This group increased to 12%, with 65% diagnosed at advanced stages (Stage III or IV), compared to 52% in older adults (p < 0.001). In terms of tumor characteristics, poorly differentiated tumors were more prevalent in young adults (28% vs. 18%, p < 0.001). The prevalence of microsatellite instability-high (MSI-H) tumors was significantly greater in young adults at 18%, compared to 12% in older adults (p < 0.05). The 5-year overall survival rate for young adults was 68%, notably higher than the 48% for older adults (p < 0.001). Conclusions: This study underscores significant differences in disease characteristics between young and older adults with colorectal carcinoma. Young patients are more likely to present with advanced disease but have better survival outcomes. These findings indicate the necessity for an age specific approach to screening and treatment strategies. Differences in stage at diagnosis, tumor grade, presence of MSI-H, and survival outcomes between younger and older adults diagnosed with colorectal carcinoma. Category Young Adults (≤50 years) Older Adults (>50 years) p-value Proportion of Total CRC Cases 12% (18,000 cases) 88% (132,000 cases) Advanced Stage (Stage III or IV) 65% (2010-2020) 52% (2010-2020) < 0.001 Poorly Differentiated Tumors 28% 18% < 0.001 Microsatellite Instability-High (MSI-H) 18% 12% < 0.05 5-Year Overall Survival Rate 68% 48% < 0.001

Effects of mirror-image nucleosides on DNA replication and transcription in human cells

A phase II study of agenT-797 (invariant natural killer T-cells), botensilimab (Fc-enhanced CTLA-4 inhibitor) and balstilimab (anti-PD-1) in patients with advanced, refractory gastroesophageal adenocarcinoma.

TPS515 Background: Esophagogastric (EG) cancer, the fifth most common cancer worldwide and second leading cause of cancer-related mortality, results in 1.3 million deaths annually. Despite recent advances in frontline management, nearly all patients with metastatic disease experience progression, highlighting the urgent need for novel therapies. Botensilimab (BOT), an Fc-enhanced, multifunctional anti-CTLA-4 antibody, has shown promise in combination with balstilimab (BAL, anti-PD-1) across multiple treatment-refractory cancers. Additionally, agenT-797, an allogeneic off-the-shelf invariant Natural Killer T (iNKT) cell therapy, enhances immune responses, including in settings refractory to immune checkpoint inhibitors (ICI), without requiring HLA matching or lymphodepletion. In a cohort of 82 previously treated patients, agenT-797 demonstrated a favorable safety profile with no severe Cytokine Release Syndrome, Graft-versus-Host Disease, or immune effector cell-associated neurotoxicity syndrome. Notably, in patients with relapsed/refractory gastric cancer, agenT-797 plus anti-PD-1 showed important clinical activity that warrants further exploration. Given their complementary mechanisms of action in modulating anti-tumor immunity, we aimed to evaluate the safety and efficacy of combining BOT, BAL, and agenT-797 with standard ramucirumab (anti-vascular endothelial growth factor receptor-2 antibody) and paclitaxel chemotherapy in patients with advanced EG cancer who have progressed on frontline therapy. Methods: This is an investigator-initiated, single-arm phase II trial in adult patients (≥18 years) with esophageal, gastric, or gastro-esophageal junction (GEJ) adenocarcinoma who have received one prior line of therapy, performed at Memorial Sloan Kettering Cancer Center. Eligible patients receive a single infusion of agenT-797 on cycle 1 day 1, BOT 75 mg on day 1 of cycles 1 through 3, BAL 240 mg on days 1 and 15, ramucirumab 8 mg/kg on days 1 and 15, and paclitaxel chemotherapy 80 mg/m 2 on days 1, 8, and 15 of a 28-day cycle. Treatment is continued until disease progression (defined by Response Evaluation Criteria in Solid Tumors [RECIST] version 1.1), unacceptable toxicity, or withdrawal of consent. The primary endpoint is overall response rate. The secondary endpoints are safety and tolerability, disease control rate, duration of response, progression-free survival, and overall survival. The regimen will be considered worthy of further investigation if at least 15 out of 37 patients achieve an objective response. To date, 12 patients have been enrolled and started on treatment. This trial is registered with ClinicalTrials.gov, NCT06251793. Clinical trial information: NCT06251793 .

Safety and efficacy of perioperative chemotherapy combined with PD-1 inhibitor versus chemotherapy with D2 gastrectomy plus PAND in gastric cancer with PALD metastasis: A single-center retrospective cohort study.

368 Background: Gastric cancer with para-aortic lymph node (PALD) metastasis is associated with a poor prognosis. When the metastasis is limited to the PALD, preoperative systemic therapy combined with D2 gastrectomy plus para-aortic lymph node dissection (PAND) may enhance survival. The benefit of perioperative chemotherapy combined with immune checkpoint inhibitors for these patients is unknown. Methods: A total of 133 patients with gastric cancer and limited No.16a2/b1 lymph node metastasis underwent perioperative systemic therapy combined with D2 gastrectomy plus PAND. Patients receiving chemotherapy combined with a PD-1 inhibitor were assigned to Group A (n=62), while those receiving chemotherapy alone were assigned to Group B (n=71). Pathological response, safety, efficacy, and survival outcomes were compared between the two groups. Results: Adverse events occurred at comparable rates between the two groups. No treatment-related deaths occurred in either group. In Group A, all patients (100%) achieved R0 resection, compared to 70 patients (98.6%) in Group B. Group A showed significantly better pathological outcomes than Group B, with higher rates of pathological complete response (pCR) (37.1% vs. 4.2%, P < 0.001), and major pathological response (MPR) (58.1% vs. 22.5%, P < 0.001). Group A showed a higher 2-year overall survival (OS) rate compared to Group B (90.3% vs. 62.9%, P = 0.011). The median overall survival (mOS) in Group B was 35.0 months, while follow-up data for Group A are currently insufficient to assess mOS. Conclusions: The addition of a PD-1 inhibitor to chemotherapy significantly improves the pathological response rate and prognosis in gastric cancer patients with PALD. Notably, the combination did not increase adverse events. These findings suggest that combining PD-1 inhibitor with chemotherapy could be a promising strategy for improving outcomes in this patient population, though further prospective studies are necessary to confirm long-term survival benefits. Postoperative outcomes and pathological response. Variable Group A (n=62) % Group A (n=71) % P Value Vascular tumor embolus 0.005 Negative 43 69.4% 32 45.1% Positive 19 30.6% 39 54.9% Nerve infiltration 0.004 Negative 44 71.0% 33 46.5% Positive 18 29.0% 38 53.5% No.16a2/b1 0.057 Negative 53 85.5% 51 71.8% Positive 9 14.5% 20 28.2% Tumor resection 0.970 Distal 26 41.9% 30 42.3% Total 36 58.1% 41 57.7% Serum CEA (U/mL） 0.805 Normal 56 90.3% 65 91.5% >5 6 9.7% 6 8.5% Serum CA125 (U/mL) 0.280 Normal 30 48.4% 41 57.7% >35 32 51.6% 30 42.3% Serum CA199 (U/mL) 0.783 Normal 56 90.3% 65 91.5% >37 6 9.7% 6 8.5% pT-stage <0.001 ≤T2 37 59.7% 19 26.8% ＞T2 25 40.3% 52 73.2% pN-stage 0.001 N0/1 42 67.7% 27 38.0% N2/3 20 32.3% 44 62.0% TRG ＜0.001 0 23 37.1% 3 4.2% 1 13 21.0% 13 18.3% 2 22 35.5% 47 66.2% 3 4 6.5% 8 11.3% pCR 23 37.1% 3 4.2% ＜0.001 MPR 36 58.1% 16 22.5% ＜0.001

Immune checkpoint inhibitors (ICIs) in deficient mismatch repair (dMMR)/microsatellite instability (MSI) non-colorectal cancers: Real world Indian data and the use of alternative dosing.

347 Background: Immune checkpoint inhibitors, predominantly pembrolizumab and dostarlimab, have been approved in deficient mismatch repair (dMMR)/ microsatellite instability (MSI) non-colorectal cancers. There is also an emerging data to suggest significant clinical activity for low-dose ICIs (LD-ICIs) in these cancers. Methods: A multi-institutional retrospective analysis in Indian patients with dMMR/MSI-H advanced/metastatic non-colorectal carcinomas treated with ICIs (irrespective of dose or schedule) between 2017 and 2024 was conducted. The primary objective of the study was to evaluate 12-month Overall survival (OS) for the whole cohort as well as LD-ICI and standard dose ICI (SD-ICI) cohorts, while other secondary objectives included assessment of overall response rates (ORR) (assessed by RECIST v1.1 as per local radiological reporting), 12-month progression free survival (PFS) and incidence of immune related adverse events (IRAEs). Results: A total of 51 patients were available for analysis. The most common tumour types were gastrointestinal (64%, commonly gastric cancer, oesophageal cancer and cholangiocarcinoma) and endometrial cancers (23%). Eighty-four percent of patients received ICI monotherapy, while the remaining 16% received varying combinations of ICIs with chemotherapy and tyrosine kinase inhibitors. Nivolumab was used in 24 patients (47%) while pembrolizumab was used in 17 patients (33%). With a median follow-up of 14 months, 12-month OS was 72% and 12-month PFS was 62% in the entire cohort. The corresponding 12-months OS and 12-month PFS for those receiving SD-ICIs (n=29) was 69% and 62%, while it was 72% and 64%, respectively for the LD-ICIs cohort (n=22). The ORR was 61%, with 10 patients (20%) achieving complete response (CR) and 21 (41%) achieving partial response (PR). The most common IRAEs (all grades) were fatigue (62%), thyroid disturbances (37%), and pruritus (23%). Conclusions: The current study from India highlights the importance of treating non-colorectal dMMR/MSI-H cancers with ICIs and shows outcomes commensurate with published trial data. Within the confines of a small retrospective study with a short follow-up, low dose ICIs should be explored in these patients in scenarios where standard dosing schedules are not feasible due to logistic reasons. Key Words – Low dose immunotherapy; non-colorectal dMMR/MSI-H cancers; Overall survival.

Phase 1b study of futibatinib plus pembrolizumab in patients with esophageal carcinoma: Evaluating the immunological effects.

477 Background: Combination therapy using FGFR inhibitors and Immune checkpoint inhibitors (ICIs) are being explored as a novel strategy for esophageal cancer (EC) patients (pts). We reported the tolerability and encouraging antitumor activity of futibatinib (futi) plus pembrolizumab (pem) in cohort (CO) A (≥2nd line, ICIs naïve) and COB (≥2nd line, ICIs refractory) and futi plus pem with chemotherapy in COD (1st line, ICIs naïve) with EC pts at Ooki et al ASCO 2024. The purpose of this Cohort E (COE) was to evaluate the effects of futi as a single agent or futi in combination with pem on tumor immune microenvironment by detecting immune cells and immune-related gene expression. Methods: In COE of the study, advanced or metastatic EC pts with at least one prior therapy with a fluorouracil and platinum-based drug received a single agent of futi the first 7 days, followed by futi 20 mg once daily (continuous dosing) plus pem 200 mg/every 3 weeks (up to a maximum of 35 cycles). Regardless of FGFR overexpression level and ICIs naïve or refractory pts were include on the study. Tumor samples were collected by biopsy during the screening period, 7 days after the administration of futi, and 21 days after the combination administration of futi and pem. Expression of 18 biomarkers including CD3, CD4, CD8 were analyzed by multiplex IHC (NeoGenomics). Gene expression related to immunity in tumor microenvironment were evaluated by nCounter system (NanoString). Results: As of March 10, 2024, 18 pts (ICIs naïve, 3 pts; ICIs refractory, 15 pts) were enrolled. As a result of multiplex IHC, an increase of CD3 + CD8 + T cells was observed in the samples 7 days after a single treatment of futi comparing with baseline samples and a trend towards greater increased CD3 + CD8 + cells was observed 21 days after combination treatment. An increasing CD8A gene expression was observed by nCounter analysis after a single treatment of futi comparing with baseline and a trend towards greater increase in CD8A gene expression was observed after combination treatment. Confirmed partial responses were observed in 3 pts (2 pts were ICIs naïve and 2 pts were FGFR positive). ORR was 16.7% (3/18; 1 pt had no target lesion, 95% CI: 3.6, 41.4). Most common TRAEs were hyperphosphatemia (77.8%), diarrhea (33.3%), ALT increased, and AST increased (22.2%). Conclusions: The preliminary multiplex IHC and nCounter results suggest that futi promoted CD8 + T cells infiltration into EC tumor microenvironments by single treatment and following combination treatment with pem at tolerable dosage. Summary of CD3 + CD8 + T cell and CD8A gene expression after futibatinib and combination treatment (% change relative to the baseline). 　　N 　　Mean (S.D) 　　95%CI Cell:CD3 ＋ CD8 ＋ T cell 　 　 　 C1D7 (futi) 　　15 　176.4 (88.8) [127.2, 225.5] C2D21 (Combination) 　　12 　306.3 (229.8) [160.3, 452.3] Gene:CD8A C1D7 (futi) 　　16 　139.4 (54.0) [110.6, 168.2] C2D21 (Combination) 　　14 　245.9 (190.8) [135.8, 356.1]

Tau destabilization in a familial deletion mutant K280 accelerates its fibrillization and enhances the seeding effect

Uses of VEGF inhibitor bevacizumab in appendiceal adenocarcinoma.

831 Background: Systemic treatment of metastatic appendiceal adenocarcinoma (AA) has been challenging due to a lack of well-established AA chemotherapy regimens and historical reliance on colorectal cancer (CRC) protocols. In the United States, but less commonly in Europe, bevacizumab is frequently incorporated in treatment of AA given its approved use for CRC. However, previously there have been no studies evaluating if there is a survival benefit attributable to bevacizumab in patients with AA. Methods: The Palantir Foundry system was used to extract data from the MD Anderson Cancer Center (MDA) electronic medical record for patients with biopsy-proven AA who received chemotherapy at MDA from 2015 to 2024. Only patients with complete staging and histopathology data were included in the analysis. Results: We identified 203 patients with AA who received chemotherapy at MDA and had complete tumor data. Of these, 43% (n=87) received bevacizumab at some point in their treatment. Patients who received bevacizumab were demographically similar to patients who received non-bevacizumab chemotherapy in terms of age at diagnosis, race, and sex; mucinous histology was more frequent in the bevacizumab cohort (52%, n=45 vs. 39%, n=45 in non-bevacizumab cohort). The 87 patients who received bevacizumab were treated with 1-6 lines of therapy per patient (mean = 1.57). The most frequently used bevacizumab-containing regimens were FOLFOX + bevacizumab (34%, n=46), FOLRIRI + bevacizumab (29%, n=40), 5-FU + bevacizumab (15%, n=21), and atezolizumab + bevacizumab (11%, n=15), with less common irinotecan + bevacizumab, TAS-102 + bevacizumab, and FOLFOXIRI + bevacizumab. Three regimens containing bevacizumab were discontinued due to complications: one instance of hand-foot syndrome attributed to xeloda, one instance of cardiomyopathy attributed to immunotherapy, and one bowel perforation with abdominal wall abscess attributed to bevacizumab. To determine if bevacizumab was associated with overall survival (OS) benefit we performed Kaplan-Meier analysis, with OS calculated from start of first line chemotherapy to death, in patients with metastatic AA who received either 5-FU doublet therapy alone or 5-FU doublet therapy with bevacizumab. Patients who received bevacizumab trended toward better OS (median 52 vs 25 months for doublet therapy alone, HR: 0.53, p= 0.059). The effect of bevacizumab was particularly notable in patients with signet ring cell histology; where bevacizumab use was associated with significantly longer OS (median OS 50 vs 14 months for doublet therapy alone, HR: 0.24, p= 0.034). Conclusions: Bevacizumab is frequently added to cytotoxic chemotherapy in the treatment of AA. These retrospective data suggest an OS benefit to adding bevacizumab to doublet chemotherapy, particularly in the case of signet ring cell histology.

Evaluating immune cell abundance across hepatocellular carcinoma disease stages I-III: Findings from TCGA analysis.

621 Background: Hepatocellular carcinoma (HCC), the predominant form of primary liver cancer, is the sixth most prevalent cancer globally and a leading cause of cancer-related mortality. The tumor microenvironment (TME) in HCC, characterized by complex interactions between immune and tumor cells, significantly influences tumor progression and immune suppression. Understanding the immune landscape across the different stages of HCC can inform prognosis and therapeutic strategies. Methods: We analyzed RNA seq data from 333 HCC patients (disease stages I-III), from The Cancer Genome Atlas (TCGA), using the immune deconvolution algorithms CIBERSORT and xCell. Differential gene expression analysis was performed using the DESeq2 package in R. Immune cell abundance across various HCC stages was imputed, and survival analyses was conducted using Kaplan-Meier curves and log-rank tests. Results: Of the 19,514 genes analyzed, 2,774 were up-regulated and 947 were down-regulated in stage II and III in comparison to stage I. CIBERSORT and xCell analyses revealed significant variability in the immune cell composition between HCC stages. Notable differences were observed in the T cells (CD4 and CD8 subsets), B cells, plasma cells, and stromal components. ANOVA and post hoc tests identified significant stage-specific differences in several immune cell types. For the survival analysis, we categorized patients into low and high groups based on median cell abundances. Overall survival showed no statistically significant differences among the various groups for common myeloid and lymphoid progenitor cells. In contrast, disease-free survival demonstrated statistically significant differences across the groups for both cell types. Conclusions: This study emphasizes the tumor microenvironment's pivotal role in HCC, revealing that immune cell composition significantly influences disease-free survival, despite limited effects on overall survival. These findings advocate for further exploration into targeted immunotherapies and the development of predictive models that integrate immune landscape characteristics, ultimately aiming to enhance patient outcomes in HCC. Cell type xCell Cibersort Mean SD Mean SD T cell CD4 naive 0.00466 0.01994 1.31e-5 1.69e-4 T cell CD8 0.01368 0.03253 0.03161 0.04947 Eosinophil 3.96e-5 3.41e-4 1.67e-4 8.69e-4 Macrophage 0.02323 0.02441 0.02924 0.04345 Macrophage.M1 0.00914 0.01526 0.01806 0.02054 Macrophage.M2 0.02303 0.01697 0.05439 0.04815 B cell memory 0.00196 0.01418 0.00107 0.00733 B cell naive 0.00163 0.01034 0.01319 0.02148 Neutrophil 2.14e-4 0.00137 0.00112 0.00539 Immune score 0.04621 0.06817 - - Table presents various cell type abundances for each algorithm used.

Perioperative adebrelimab combined with chemotherapy for locally advanced resectable esophageal squamous cell carcinoma: A single-arm, open-label, multicenter study.

421 Background: Neoadjuvant programmed cell death 1 (PD-1) inhibitors combined with chemotherapy have shown promising results in treating locally advanced esophageal squamous cell carcinoma (LA-ESCC). However, relatively little attention has been focused on programmed cell death ligand 1 (PD-L1) blockades. This study aims to evaluate the efficacy and safety of neoadjuvant adebrelimab (anti-PD-L1 antibody) plus chemotherapy followed by adjuvant adebrelimab for resectable LA-ESCC. Methods: In this single-arm, multicenter study, patients (pts) with newly diagnosed, locally advanced resectable thoracic ESCC (cT1b-2, N+ or cT3-4a, N0/+) received 2 cycles of neoadjuvant chemoimmunotherapy with adebrelimab (1200 mg), paclitaxel (175 mg/m 2 ) and cisplatin (75 mg/m 2 ) every 3 weeks, followed by esophagectomy and 16 doses of adebrelimab. The primary endpoints were safety and pathological complete response (pCR) rate. Secondary endpoints included surgery completion rate, R0 resection rate, major pathological response (MPR) rate, event-free survival (EFS) and disease-free survival (DFS). The trial was registered at Chinese Clinical Trial Registry, identifier: ChiCTR2300069179. Results: Between May 2023 and January 2024, 36 pts met inclusion criteria, with a median age of 65 years (range: 42-73). Of these, 66.7% (24/36) were classified as stage III-IVa. As of August 1, 2024, the median number of treatment cycles for all pts was 7 (interquartile range, 2-12). The neoadjuvant therapy completion rate was 91.7% (33/36). Thirty-two pts underwent minimally invasive esophagectomy, resulting in an overall surgical resection rate of 88.9% and an R0 resection rate of 90.6%. The pCR rate was 15.6% (5/32) and the MPR rate was 31.2% (10/32). The EFS and DFS outcomes were not mature. During the preoperative treatment period, 35 pts (97.2%) experienced any grade of treatment-related adverse events (TRAEs). Grade 3 or 4 TRAEs occurred in 7 pts (19.4%), and there were no grade 5 TRAEs. The most common grade 3/4 adverse events included neutropenia (11.1%), leukopenia (5.6%), diarrhea (5.6%) and hyponatremia (5.6%). Surgical complications of grade 3/4 were reported in 7 pts (21.9%), with anastomotic fistula (6.3%) being the most common. No perioperative deaths occurred. Conclusions: Neoadjuvant adebrelimab combined with chemotherapy and adjuvant adebrelimab demonstrated encouraging clinical efficacy and manageable safety in pts with LA-ESCC. Further study is warranted. Clinical trial information: ChiCTR2300069179.

dMMR/MSI tumour occurrence during follow-up of patients with Lynch syndrome treated with immune checkpoint inhibitors for a metastatic digestive cancer between 2015 and 2024: A retrospective monocentric cohort.

96 Background: Immune check point inhibitor(s) (ICIs) transformed the prognosis of patients with metastatic dMMR/MSI cancers especially for patients with Lynch syndrome (LS). The aim of our study was to describe a population of LS carrier patients treated with ICI(s) for metastatic digestive cancer, specifically assessing the risk of developing metachronous cancer. Methods: We collected data of 93 patients with LS, treated by ICI(s) for a metastatic digestive tumour. These patients were selected from the “immunoMSI” patient cohort, which included all patients presenting with a MSI and/or dMMR digestive cancer treated with ICI(s) between February 2015 and April 2024 in the medical oncology department of Saint-Antoine Hospital (Paris, France). Our primary outcome was the cumulative risk of metachronous MSI/dMMR cancer; secondary outcomes included cumulative risk and time to de novo colorectal polyps, as well as PFS and OS under ICI(s). We performed a cox model to assess the association of predefined variables with OS and PFS under ICI(s). Results: Patients most frequently carried a germline pathogenic variant on the MSH2 (or EPCAM ) gene (47%) or on the MLH1 gene (30%). The majority presented with colorectal cancer (CRC) as their primary cancer (83%), followed by small intestine tumours (6%), stomach and pancreatic cancers (4%) and bile duct cancer (1%). Median age at cancer index was 62 years-old (26-77). A total of 12 out of 93 patients presented metachronous cancers during or after treatment with ICI(s). Ten of these metachronous cancers were dMMR or within the LS spectrum (urothelial n=4, CRC n=2, bilio-pancreatic n=1 and 3 skin cancers including 2 kerato-acanthomas). All patients who developed a metachronous cancer had a complete or partial response under ICI(s) for the index cancer. During a median follow-up of 47.8 months, 44 patients had colonoscopies and a total of 17 patients (39,5 %) developed pre neoplastic colorectal polyps. In multivariate analysis, PS ≥ 2 and age ≥ 70 years were associated with poorer OS with HRs of 6.3 (95% CI [1.5-25.9], p=0.01) and 5.5 (95% CI [1.6-18.9], p=0.006) respectively. Conclusions: Our results show that ICI(s) for patients with LS treated for an MSI/dMMR metastatic digestive cancer can still develop metachronous cancers and pre neoplastic polyps, which underlines the importance of maintaining dedicated follow-up after ICI(s) treatment in this population.

HSP90 stabilizes visual cycle retinol dehydrogenase 5 in the endoplasmic reticulum by inhibiting its degradation during autophagy

Meta-analysis of phase II/III randomized controlled trials (RCTs) to evaluate the incidence of hand-foot skin reaction (HFSR) or palmar-plantar erythrodysesthesia (PPE) syndrome in patients with gastrointestinal (GI) cancers treated with fruquintinib.

117 Background: Fruquintinib is a selective inhibitor of vascular endothelial growth factor receptors 1, 2, and 3 blocks the angiogenesis associated with tumor proliferation. Recently, the US FDA approved fruquintinib as a third-line treatment for metastatic colorectal cancer (mCRC). As with any other novel cancer therapies, adverse events are always a concern and all patients should be monitored in order to early detect and appropriately treat any adverse events. This meta-analysis aims to assess the risk of HFSR or PPE syndrome in patients with GI cancers treated with fruquintinib. Methods: We conducted a comprehensive literature search using MEDLINE, EMBASE, and COCHRANE databases from inception through August 12th, 2024. Phase II/III RCTs utilizing fruquintinib in GI cancers mentioning HFSR or PPE as an adverse effect were included. Mantel-Haenszel method was used to calculate the estimated pooled risk ratio (RR) with 95% confidence interval (CI). Heterogeneity was assessed with Cochran’s Q-statistic. Random effects model was applied. Results: A total of 1872 patients, of whom 1131 (60%) received fruquintinib, from 3 phase III RCTs (FRESCO, FRESCO-2, FRUTIGA) and 1 phase II RCT were eligible for evaluation of HFSR or PPE incidence. FRESCO, FRESCO-2, and phase II trials involved patients with mCRC, they compared fruquintinib vs placebo. FRUTIGA trial involved patients with gastric or gastroesophageal junction adenocarcinoma, it compared fruquintinib + paclitaxel vs placebo + paclitaxel. The incidence of any-grade and high-grade HFSR or PPE was higher in the fruquintinib group compared to the placebo group, 27.93% vs 3.64% (RR, 7.64; 95% CI: 4.08-14.33; P<0.00001), and 8.5% vs 0% (RR, 26.0; 95% CI: 6.42-105.29; P<0.00001), respectively. In the mCRC subgroup analysis, the higher incidence of any-grade and high-grade HFSR or PPE in the fruquintinib arm was also statistically significant, 29.70% vs 2.55% (RR, 10.27; 95% CI: 5.59-18.88; P<0.00001), and 8.45% vs 0% (RR, 19.34; 95% CI: 3.84-97.36; P=0.0003), respectively. Conclusions: This meta-analysis revealed increased incidence of any-grade and high-grade HFSR or PPE in patients with GI cancers including mCRC treated with fruquintinib. In the FRESCO trial, this association was also shown to confer survival benefit in Chinese patients with mCRC. Prompt identification and providing proper supportive care is crucial in managing this adverse event and ultimately, preserving the patients’ quality of life.

Preliminary phase 1/1b dose expansion results of the bifunctional EGFR/TGFβ inhibitor ficerafusp alfa (BCA101) with pembrolizumab in patients with squamous cell carcinoma of the anal canal.

4 Background: Anti-PD-1 monotherapy has limited efficacy in patients (pts) with advanced squamous cell cancer of the anal canal (SCAC). In KN-158, pembrolizumab (P) was reported to have an ORR of 10%, DCR of 25%, and a 12-month PFS rate of 15% in patients with incurable SCAC. TGFβ promotes immunosuppression within the tumor microenvironment, and inhibition of this pathway may improve tumor susceptibility to immune checkpoint blockade.Ficerafusp alfa (F)is a bifunctional EGFR/TGFβ inhibitor with manageable safety and favorable preliminary anti-tumor efficacy in advanced solid tumors (ESMO 2022 731MO). We evaluated the combination of F+P in pts with chemotherapy-refractory locally advanced/unresectable or metastatic SCAC. Methods: This single-arm, multicenter dose expansion from an ongoing phase I/Ib trial enrolled pts with ICI-naïve SCAC that was locally advanced/unresectable or metastatic, who had received 1-2 prior lines of chemotherapy. Pts received ficerafusp alfa (1500 mg IV on days 1, 8, 15) and pembrolizumab (200 mg IV on day 1) every 21-day cycle. The primary endpoint was safety (CTCAE v5), and secondary endpoints were radiographic response (RECIST 1.1), duration of response, progression-free survival, and overall survival. Results: Among 26 pts treated, 21 (81%) were female, and median age was 61 (range: 43-82). As of 7/2024, 22 pts are evaluable for efficacy. ORR was 32% (95% CI 13.9-54.9%). Six of the seven responses were confirmed, including one pt with a radiographic PR with pathologic CR to F+P. Seven pts (32%) achieved SD as best response, resulting in DCR of 64%. Median PFS was 2.8 months (95% CI 1.4-14.8) and the PFS rate at 12 months was 36%. G3 treatment-related adverse events were observed in 10/26 pts (38%, most common: Anemia (19%) and acneiform rash (12%)). TRAEs led to permanent discontinuation of study treatment in 2 pts (8%). The most common TRAEs of any grade were acneiform rash (13/26, 50%), epistaxis (46%) and headache (38%). Conclusions: The addition of ficerafusp alfa demonstrated encouraging efficacy, with increased ORR, DCR, and 12-month PFS relative to historical precedent with pembrolizumab alone. Safety and tolerability were acceptable. Further investigation of this combination in pts with advanced SCAC is warranted. Updated data will be presented. Study funded by Bicara Therapeutics Inc. with access to pembrolizumab in collaboration with Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA (NCT04429542). Clinical trial information: NCT04429542 .

Impact of inpatient palliative care on end-of-life care among patients with early-onset colorectal cancer.

305 Background: Palliative care has proven benefits in elderly patients with advanced cancer; however, the objective benefits of palliative care in younger patients with cancer remain under-studied. We sought to examine the impact of inpatient palliative care consultation on end-of-life (EOL) care among hospitalized patients with early-onset colorectal cancer (EO-CRC). Methods: This study analyzed all admissions in the National Inpatient Sample (NIS) between 2016 and 2020 for patients younger than 50 years old with a diagnosis of CRC and death during the admission. Patients with CRC were identified utilizing ICD-10 codes C18.x, C19.x, and C20.x. Patient cohorts were made based on if they received inpatient palliative care consultation (ICD-10 code Z515). We assessed these encounters for patient demographics, Charlson comorbidity index (CCI), utilization of mechanical ventilation, vasopressors or blood transfusion, and presence of a Do Not Resuscitate (DNR) order. Results: Among 4,060 patients with EOCRC, 2,425 (59.7%) received inpatient palliative care consultation. There was no significant difference in age or length of stay between groups. The cohort of patients who received palliative care consultation had more female patients (44.3% vs 39.8%, p=0.004) and had higher comorbidity burden measured by the CCI (8.6 vs 8.3, p<.001). Patients receiving inpatient palliative care consultation at EOL were significantly more likely to have a DNR order (83.3% vs 44.6%, p<.001) in place and less likely to receive aggressive interventions, including mechanical ventilation (20.4% vs 43.4%, p<.001), blood transfusion (14.8% vs 22.6%, p<.001), vasopressor use (6.2% vs 8.6%, p=.004), and surgical intervention (3.0% vs 7.3%, p<.001). There was no difference in chemotherapy use between cohorts (2.8% vs 2.9%, p=0.8). Admissions including palliative care consultation were also associated with significantly lower average hospital charges ($99,387 vs $131,993, p<.001). Conclusions: Inpatient palliative care consultation at EOL among patients with EOCRC was associated with lesser use of aggressive interventions and higher rates of DNR code status. We also noted significantly lower costs of hospitalization among patients receiving inpatient palliative care consultation at EOL. These results underscore the importance of integration of inpatient palliative care consultation among patients with EOCRC at EOL. No PalliativeN=1635 PalliativeN=2425 p-value Age (in years) 41.9 ± 6.1 42.1 ± 6.5 .28 CCI 8.3 ± 2.6 8.6 ± 2.3 <.001 Total Charges 131993 ± 206404 99387 ± 151864 <.001 DNR 730 (44.6%) 2020 (83.3%) <.001 Blood transfusion 370 (22.6%) 360 (14.8%) <.001 Mechanical ventilation 710 (43.4%) 495 (20.4%) <.001 Vasopressor 140 (8.6%) 150 (6.2%) .004 Chemotherapy 45 (2.8%) 70 (2.9%) .800 Surgery 125 (7.3%) 75 (3.0%) <.001