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Frequency of surveillance CT scan ordering in patients with stage II/III colorectal cancer.

106 Background: Patients with stage II/III colorectal cancer (CRC) undergo surveillance CT scans to detect early asymptomatic oligometastatic spread, which can be treated with curative intent. However, randomized clinical trials show no difference in 5-year mortality in those that undergo low intensity surveillance (annual) compared a higher intensity strategy (every 6 months). In Ontario, the Program in Evidence-Based Care (PEBC), Ontario Health (Cancer Care Ontario) guidelines recommend surveillance CT scan for patients with stage II/III CRC every 12 months. We aimed to determine the frequency at which clinicians in our Ontario-based hospital system ordered surveillance CT scans for patients with stage II/III CRC. Methods: This single centre retrospective cohort study included all patients that underwent surgical resection for CRC from April 1, 2018 – March 31, 2019 at our academic tertiary care centre in Ontario, Canada. We excluded patients that were followed at an outside hospital, had stage IV disease, had disease recurrence, had a concurrent neoplasm, or did not have CRC. The primary outcome was the proportion of surveillance CT scans completed 10+ months after the previous scan. We also described sociodemographic and medical characteristics of included patients. Follow-up was until August 2023. Results: We included 200 patients. The median age was 62 years (IQR: 52-70), 48% (N=96) were female, the rectum was the most commonly involved disease site (43%, N=86), 38% (N=76) had stage III disease, and 54% (N=107) received adjuvant chemotherapy. A total of 1286 scans were ordered during the study period. Of these, 67% (N=860) were ordered as surveillance. Of these, 18% (n=155) were completed 10 months or longer from the previous scan. The median time interval between surveillance scans was 6.6 months (IQR: 5.9-7.9). Approximately 20% (n=137 of 630) of surveillance scans ordered by general surgeons were completed 10 months or longer from the previous scan, whereas only 9% (n=18 of 205) of scans ordered by medical oncologists were completed 10 months or longer from the previous scan. Less than 1% of surveillance scans (n=3) identified new metastatic disease. Conclusions: The minority of surveillance CT scans ordered in patients with stage II/III CRC in our hospital were timed in concordance with Ontario-based guidelines. Future studies should seek to standardize ordering habits such that they align with best practices.

Permeable and Durable Liquid‐Metal Fiber Mat as Implantable Physiological Electrodes with Long‐Term Biocompatibility

Abstract Implantable physiological electrodes provide unprecedented opportunities for real‐time and uninterrupted monitoring of biological signals. Most implantable electronics adopt thin‐film substrates with low permeability that severely hampers tissue metabolism, impeding their long‐term biocompatibility. Recent innovations have seen the advent of permeable electronics through the strategic modification of liquid metals (LMs) onto porous substrates. However, the durability of these electronics is limited by the inherent poor wettability of LMs, particularly within the intricate 3D skeleton of the porous substrate. Herein, the study reports a spatial wettability tuning strategy that solves the wettability issue of LMs within the porous substrates, enabling the LM physiological electrodes with high durability and long‐term biocompatibility. The study demonstrates the use of the electrodes as implantable neural interface to realize in vivo acquisition of electrocardiograph and electrocorticogram signals with long‐term biocompatibility and high signal‐to‐noise ratio. This work demonstrates a promising direction for rational design of durable implantable bioelectronics with long‐term biocompatibility.

Clinical outcomes of stereotactic body radiation therapy to the liver.

565 Background: Stereotactic body radiation therapy (SBRT) can accurately and effectively target liver lesions with an ablative dose. However, prior studies suggest that SBRT directed at tumors near the central hepatobiliary tract may lead to downstream toxicity including biliary stricture and impaired liver function. This study aims to evaluate clinical outcomes and hepatobiliary toxicities associated with SBRT to the liver. Methods: This retrospective study reviews 177 patients who received CT- or MR-guided SBRT to the liver at Dana-Farber Cancer Institute and Brigham and Women’s Hospital from 2010 to 2024. Patient demographics, treatment characteristics, and clinical outcomes were extracted from electronic medical records. Local control, regional control, and overall survival were assessed using Kaplan-Meier methods. Toxicity was evaluated by tracking the incidence of biliary stricture requiring intervention and Child-Pugh (CP) scores pre- and post-SBRT. Results: Of the 177 patients, 47 (26.6%) had primary disease and 130 (73.4%) had metastatic disease, with a median follow-up of 58.7 months. Among those with primary disease, 9 (19.1%) had post-SBRT local progression (median time to progression not reached, 95% CI: 47.3, NA) and 26 (55.3%) had regional progression (median time to progression of 20.5 months, 95% CI: 6.5, 58.1). Of patients with metastatic disease, 44 (33.8%) had local progression (median time to progression of 40.2 months, 95% CI: 23.0, NA) and 96 (73.8%) had regional progression (median time to progression of 5.9 months, 95% CI: 4.8, 9.3). Median overall survival post-SBRT was 34.6 months for primary disease (95% CI: 20.2, 57.7) and 23.6 months for metastatic disease (95% CI: 19.0, 28.8). 18 patients (10.1%) later developed biliary stricture requiring intervention (12.8% of primary disease and 9.2% of metastatic disease). Of the 119 patients with CP scores available, 59 patients (49.6%) had a maximum post-SBRT CP score increase of 2 or more (55.0% of primary disease, 46.8% of metastatic disease). Conclusions: This study demonstrates that SBRT is an effective treatment option for local control in the liver, with better survival and progression outcomes for primary disease compared to metastatic disease. Among potential post-SBRT toxicities, initial analysis indicates frequent increase in CP score and low incidence of biliary stricture requiring intervention. An ongoing analysis will explore whether the dose to central bile ducts correlates with late strictures and toxicities.

The role of artificial intelligence in colorectal cancer and polyp detection: A systematic review.

47 Background: Colorectal cancer (CRC) remains a leading cause of cancer-related mortality worldwide. Early detection and accurate diagnosis are essential for improving survival rates and optimizing therapeutic strategies. Recently, artificial intelligence (AI) technologies, such as machine learning algorithms, convolutional neural networks (CNNs), and computer-assisted diagnostic (CAD) systems, have significantly enhanced traditional diagnostic tools like colonoscopy and histopathology. This systematic review evaluates the current role of AI in CRC management, focusing on diagnostic improvements, predictive modeling, and outcome prediction. Methods: A comprehensive literature review was conducted using PubMed, Google Scholar, and MEDLINE using MeSH term to identify studies utilizing AI in CRC diagnosis and management, with a focus on diagnostic imaging, histopathological analysis, and predictive modeling. Studies were evaluated for the accuracy of AI-driven diagnostic systems and the predictive performance of AI models in clinical outcomes. Results: Out of 147 studies identified, 37 met the eligibility criteria for this review. AI tools such as CNNs, CAD systems, and EndoBRAIN showed high accuracy in CRC detection and polyp classification. Kudo et al. (2020) reported 98% CRC detection accuracy using EndoBRAIN. Blanes-Vidal et al. (2019) achieved 96.4% accuracy in polyp detection via DCNN. Additionally, Wang et al. (2019, 2020) demonstrated improved Adenoma Detection Rates (ADR) of 34.1% and 29.1%, respectively, using AI over traditional methods. For outcome prediction, AI models, including CNNs, predicted patient prognosis with reasonable accuracy, as highlighted by Skrede et al. (2020) with 76% accuracy in prognosis prediction. Conclusions: The systematic review and analysis of AI-assisted diagnostic modalities in colorectal cancer and polyp detection reveal promising results, with most models demonstrating high sensitivity, specificity, and accuracy. CNN-based models and CAD systems, in particular, show strong potential for improving detection rates and clinical outcomes in CRC screening. The studies included in this review demonstrate that AI can enhance diagnostic precision, particularly in identifying polyps and predicting clinical outcomes, with high validation rates. However, more external validation and long-term clinical studies are needed to fully establish the robustness of these AI tools in routine clinical practice.

Comparative efficacy of TAS-102 and chemotherapy rechallenge in the third-line setting and beyond in patients with advanced colorectal cancer: A retrospective study.

78 Background: The optimal approach to third line therapy for patients with metastatic colorectal cancer remains a subject of debate. Options include Trifluridine/Tipiracil (TAS-102), TAS-102 with bevacizumab, regorafenib, chemotherapy rechallenge with or without an anti-EGFR agent, or fruquintinib. This study aims to evaluate the efficacy of standard of care TAS-102, TAS-102 with bevacizumab, or regorafenib versus chemotherapy rechallenge in patients with metastatic colorectal cancer in the third line setting and beyond. Methods: We conducted a retrospective analysis of patients with metastatic colorectal cancer who received either TAS-102 with or without bevacizumab, regorafenib or chemotherapy rechallenge with or without an anti-EGFR agent between 2018 and 2023, at the Ministry of National Guard for Health Affairs in Riyadh, Saudi Arabia. Patients received such agents in the third line setting and beyond. Results: A total of 75 patients were included in this study, with 39 patients receiving TAS-102 with or without bevacizumab, or regorafenib, and 36 receiving chemotherapy rechallenge. The median patient age was 58 years (range 28-81), with the majority being males at 55%. Among the chemotherapy rechallenge group, 31% were treated with cetuximab and 6% had panitumumab rechallenge, some of which were guided by cell free DNA liquid biopsy testing. In the other group, 66% received regorafenib, 26% TAS-102 alone, and 8% TAS-102 with bevacizumab. At the time of analysis, 56% of patients had passed away. Median overall survival for patients who received TAS-102 with our without bevacizumab, and regorafenib in the third line setting was found to be 13.1 months. Whereas for patients who received chemotherapy rechallenge, their median overall survival was 19.5 months. Conclusions: Patients with metastatic colorectal cancer who received chemotherapy rechallenge in the third line setting survived longer compared with patients who received TAS-102 with or without bevacizumab, or regorafenib.

The role and regulation of integrins in cell migration and invasion

Long-course chemoradiation vs short-course radiation in total neoadjuvant therapy for rectal cancer: Propensity score case-matched analysis.

156 Background: Short-course radiotherapy (Short-TNT) is not widely used in the United States as part of total neoadjuvant therapy (TNT) for rectal cancer, due to concerns for lower tumor regression, increased local recurrence, and poorer quality of surgical specimens compared to long-course chemoradiotherapy (Long-TNT). However, there have been few studies that directly compared outcomes of Long-TNT versus Short-TNT. This study aimed to evaluate outcomes of Short-TNT versus Long-TNT. Methods: Consecutive patients with stage II-III rectal cancer who underwent TNT at an NCI-designated comprehensive cancer center from 2019 to 2022 were identified. Outcomes after Short-TNT and Long-TNT were compared using 1:1 propensity score matching. Results: Among 318 patients, 170 (85 Short-TNT, 85 Long-TNT) were eligible for the matched analysis (Table). The median follow-up was 31 months. The two groups were similar in tumor distance from anal verge (5cm vs. 6cm), clinical stage (stage III: 90.6% vs. 89.4%), radiologic high-risk features, and treatment sequence (induction chemotherapy: 30.5% vs. 28.2%). The Long-TNT was associate with a higher proportion of nonoperative management (38.8% vs. 24.7%, p=0.03). A local regrowth rate with long-TNT was not lower than short-TNT (39.4% vs. 28.6%, p=0.42). There were no differences in rates of clinical complete plus near-complete response (52.9% vs. 52.9%, p=1.00), overall complete response (pathologic plus sustained clinical complete response; 32.2% vs. 29.9%, p=0.74), and surgical outcomes including retrieved lymph nodes number (19 vs. 22, p=0.27), sphincter preservation (46.2% vs. 62.5%, p=0.10), distal margin (3cm vs. 3.5cm, p=0.77), CRM+ (83.8% vs. 3.1%, p=0.42) and postoperative complications (overall: 34.6% vs. 25.0%, p=0.14; ≥Grade3: 5.8% vs. 9.4%, p=0.60). Conclusions: Short-TNT had a comparable overall complete response rate with equivalent surgical outcomes to Long-TNT. Short-TNT should be revisited in the US as a viable alternative TNT strategy both for nonoperative management and for treatment of locally advanced rectal cancer. Propensity score case-matched analysis. Outcomes Total (n=170) Long-TNT (n=85) Short-TNT (n=85) p value Clinical complete/near complete response, number (%) 90 (52.9) 45 (52.9) 45 (52.9) 1.00 Non-operative management, number (%) 54 (31.8) 33 (38.8) 21 (24.7) 0.03 Overall complete response, number (%)* 54 (31.0) 26 (30.6) 28 (32.9) 0.74 Surgical outcomes Surgery (n=116) Surgery after Long-TNT (n=52) Surgery after Short-TNT (n=64) Sphincter-preserving surgery, number (%) 64 (55.2) 24 (46.2) 40 (62.5) 0.10 Circumferential resection margin +, number (%) 4 (3.4) 2 (3.8) 2 (3.1) 0.42 Distal margin, cm (range) 3.4 (0.1-12) 3 (0.2-6.5) 3.5 (0.1-12) 0.77 Major complications (≥Grade3), number (%) 9 (7.8) 3 (5.8) 6 (9.4) 0.60 *Pathologic + sustained clinical complete response.

Liposomal irinotecan + 5-fluorouracil + leucovorin + bevacizumab as second-line therapy in metastatic colorectal cancer (IRIS): A multi-center, single-arm, prospective, phase II study.

195 Background: In patients with advanced colorectal cancer (CRC), the recommended second-line treatment following first-line therapy with oxaliplatin-based regimens is irinotecan-based therapy. Liposomal irinotecan, a novel formulation of traditional irinotecan, has demonstrated potential to enhance efficacy while minimizing toxicity. This study aims to investigate the efficacy and safety of liposomal irinotecan in combination with 5-FU/LV and bevacizumab as a second-line treatment option for metastatic CRC. Methods: This is a multi-center, single-arm, prospective, phase II study. Patients with metastatic CRC who received oxaliplatin-based chemotherapy as first-line treatment were enrolled to receive liposomal irinotecan + 5-fluorouracil + leucovorin + bevacizumab regimen until disease progression and/or unacceptable toxicity. The primary endpoint is objective response rate (ORR), secondary endpoints include disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and safety. Results: A total of 50 patients were enrolled from Jan 2024 to Jul 2024 across 6 sites in China. The median age was 56.5 years (range: 30.0-76.0), with 58.0% male and 36.0% ECOG 0. Among the patients, 38.0% had left-sided colon cancer, 24.0% had right-sided colon cancer, and 38.0% had rectal cancer. As of Sept 14, 2024, 39 patients had at least one tumor assessment and 19 patients were still on treatment. ORR and DCR were 20.5% (8/39, 95% CI: 9.3%-36.5%) and 84.6% (33/39, 95% CI: 69.5%-94.1%), respectively. Eleven patients had disease progression and 5 patients died, and the median PFS and OS were not reached. The relative dose intensity of liposomal irinotecan and 5-fluorouracil were 92.8% (range: 23.6%-109.6%) and 89.5% (range: 13.3%-116.8%), respectively. During treatment, 43 (86.0%) patients had at least one adverse event (AE) and 24 (48.0%) had grade 3-4 AE. Most common (≥ 10%) grade 3-4 AEs were neutropenia (20.0%), leukocytopenia (16.0%) and diarrhea (10.0%). No unexpected toxicities observed in this study. Conclusions: These preliminary results reveled that liposomal irinotecan + 5-fluorouracil + leucovorin + bevacizumab after oxaliplatin-based treatment for metastatic CRC was well tolerated with encouraging clinical activity, which warrants further follow up. Clinical trial information: NCT06184698 .

Observational study of the extent of lymph node metastasis among patients who underwent pancreatoduodenectomy for non-ampullary duodenal cancer using the National Clinical Database in Japan.

798 Background: Non-ampullary duodenal cancer (NPDC) is a rare cancer that occurs in 0.3% of all cancers of the gastrointestinal tract. The first Japanese guidelines for this entity were published in 2021, and resection by pancreatoduodenectomy was weakly recommended as a standard treatment. Although presence of regional lymph node metastasis was identified as a prognostic factor among patients who underwent resection with curative intent, the recommendation concerning the optimal extent of lymphadenectomy based on big data was lacking. Methods: We conducted an observational study of patients who underwent pancreatoduodenectomy for NPDC between 2018 and 2021 in Japan, using the National Clinical Data (NCD) database. The NCD database is web-based, is linked with the board certification systems of several domestic surgical societies and covers >95% of the operations carried out by surgeons at 5,728 institutions in Japan. All cases of pancreatoduodenectomy for NPSC were retrieved from the NCD database after rigorously checking appropriateness of the patient selection, and surgeons in charge of these patients were invited by e-mails to fill in some additional data for this study during a time slot of Oct 2022 ~March 2023. Data thus obtained were the analyzed with particular focus on the incidence of metastases to each lymph node station, stratified by the tumor location in relation to the papilla. In addition, safety of surgery was compared between high-volume (institutions conducting ≥30 major hepatobiliary-pancreatic surgery) and low-volume (<30) hospitals. The study was funded in part by the Japanese Ministry of Health, Labor and Welfare as a project to create guidelines for rare cancers. Results: Data of 881 patients from 600 institutions were obtained for the analysis. Male constituted 68% and the median age was 70 years. The depth of invasion and presence of nodal metastasis were significant prognostic factors. The median number of lymph node retrieval was similar between the high-volume and low-volume hospitals (19: 95%CI 12~27 versus 18: 95% CI 11~25). Distribution of metastatic nodes depended on the location of tumor. Incidence of nodal metastasis exceeded 10% in lymph node station Nos. 5, 6, 7, 8 and 9 in cancers located on the oral side of the papilla. Thus, stomach-conserving pancreatoduodenectomy was considered appropriate only for cancers located distal to the papilla. The incidences of Grade IIIb~IVb complications (4% versus 7.1%), Grade V complications (0.4% versus 1.9%), and mortality within 30 days (0.4% versus 2.6%) were lower in high-volume hospitals. Conclusions: Stomach-preserving pancreatoduodenectomy is recommended only for NDPC located distal to the papilla. Centralization of surgery may be desirable.

Self‐Adaptive Dielectrics with Tunable Nonlinear Electrical Conductivity via Virus‐Like Structures Composed of Metal Particles

AbstractSelf‐adaptive dielectrics (SADs), with the characteristics of rapid charge dissipation in electric field distortion, is regarded as the future material for package insulation of advanced electronic devices. The current landscape of SADs is incapable to achieve tunable nonlinear electrical conductivity and threshold field strength due to the inherent Schottky barrier, significantly limiting the application scenarios of SADs. Here, a strategy is reported to construct a stepped Schottky barrier through virus‐like structures, which are composed of subminiature metal particles and semiconductor microspheres. It is found that the metal particles can serve as the capture center to attract the free charge in the matrix, precisely instructing the charge transfer pathway. The barriers between metal particles and semiconductor filler, flexibly controlled by the composition of metal particles, endow with extra source of nonlinear conductivity. Under the optimal composition and size of metal particles, SADs exhibit prominent nonlinear electrical conductivity and reliable adaptive charge release characteristics under pulsed electric field. The work pioneers a breakthrough by overcoming the constraint that SADs are previously limited to the inherent Schottky barrier of semiconductor materials and enabling the unprecedented controllability and flexibility of nonlinear electrical characteristics by metal particles, contributing a distinctive perspective to the development of SADs.

Genomic alterations in circulating tumor DNA (ctDNA) and response to telisotuzumab adizutecan (ABBV-400) treatment in patients (pts) with colorectal cancer (CRC).

258 Background: Telisotuzumab adizutecan is an antibody-drug conjugate comprising the c-Met–targeting antibody telisotuzumab conjugated to a topoisomerase 1 inhibitor payload, adizutecan. A phase 1 trial (NCT05029882) in advanced solid tumors reported higher response rates in pts with CRC and high c-Met expression. We present an analysis of responses based on genomic alterations in ctDNA. Methods: Pts with CRC that is refractory to standard treatment were enrolled. Telisotuzumab adizutecan was given IV Q3W. ctDNA was isolated from baseline (BL) and cycle 3, day 1 plasma samples and analyzed with the GuardantINFINITY assay. Circulating tumor fraction (cTF) was estimated on the basis of variant allele frequency of somatic mutations in a 74-gene panel and methylation signals across targeted regions of the GuardantINFINITY methylation panel. Molecular response (MR) was defined as 50% decrease in cTF from BL. Radiographic response (RR) was assessed by RECIST v1.1. Results: Overall, 113 pts had both BL ctDNA and RR data. Confirmed ORR was 18% (20/113). The most prevalent gene alterations included TP53 (75%), APC (68%), and KRAS (66%) mut; PTPRT (56%), ASXL1 (53%), and FLT1 (52%) amp; SMAD4 (44%) and TP53 (43%) deletions; and MET (4%), BRAF , FGFR3, and NRG1 (all 3%) fusions. The Table shows RRs in pts with specific CRC biomarkers, and MR using the 2 panels with corresponding clinical outcomes. RRs were seen in pts with positive plasma samples at BL for TMB, RAS, BRAF, and HER2. MRs were detected in 64% and 65% of pts using the 74-gene and methylation panel, respectively. ORR was higher in pts with MR (35%) than without MR (8%) using the 74-gene, and 35% vs 0% using the methylation panel, respectively. Median PFS (mPFS) was longer in pts with MR. Conclusions: Telisotuzumab adizutecan has promising efficacy. RRs were seen in CRC pts with heterogeneous genomic profiles, including pts positive for actionable biomarkers in the metastatic setting. More pts with MR experienced RRs and benefited from treatment. Clinical trial information: NCT05029882 . Pts with ctDNA and radiographic response data(N=113) Radiographic cPR, n/N (%) 20/113 (18) Genomic alteration TMB a high ( ≥ 20 mut/Mb) KRAS mut KRAS G12C mut BRAF mut b HER2 amp cPR, n/N (%) Pos 11/48 (23) 11/73 (15) 1/5 (20) 4/14 (29) 2/9 (22) Neg 9/51 (18) 9/40 (23) 19/108 (18) 16/99 (16) 18/104 (17) MR, n/N (%) 74-gene panel 42/66 (64) Methylation panel 48/74 (65) ORR, n/N (%) MR pos 15/42 (36) MR neg 2/24 (8) MR pos 17/48 (35) MR neg 0/26 (0) mPFS, mo (95% CI) Events (n/N) 6.1 (5.3, 6.9)28/42 3.5 (2.6, 4.3)21/24 5.9 (5.3, 6.8)31/48 3.5 (2.7, 4.1)23/26 MR in pts with SD, n/N (%) 74-gene panel 27/45 (60) Methylation panel 31/53 (58) mPFS, mo (95% CI)Events (n/N) MR pos 5.3 (4.5, 5.9)21/27 MR neg 3.9 (2.8, 4.3)16/18 MR pos 5.3 (4.5, 5.9)23/31 MR neg 4 (2.8, 4.4)19/22 a 14 pts not evaluable for TMB. Threshold determined by Guardant. b 1 pt had V600E mutation. mo, months; neg, negative; pos, positive.

Nivolumab plus ipilimumab (N+I) in patients (pts) with pancreatic cancer (PC) with <i>BRCA1/2</i> mutation (mut): Results from the Targeted Agent and Profiling Utilization Registry (TAPUR) study.

715 Background: TAPUR is a phase II basket study evaluating antitumor activity of commercially available targeted agents in pts with advanced cancers with genomic alterations. Results from a cohort of pts with PC with BRCA1/2 mut treated with N+I are reported. Methods: Eligible pts had measurable disease, ECOG performance status (PS) 0-2, adequate organ function, and no standard treatment (tx) options or prior immune checkpoint inhibitor tx. PD-L1 expression testing was not required. Genomic testing was performed in CLIA-certified, CAP-accredited site-selected labs. Most genomic tests did not distinguish between germline or somatic mut. Pts received I at 3 mg/kg every 3 weeks (wks) for 4 doses with N at 1 mg/kg IV every 3 wks for 4 doses. N alone was then continued at 240 mg every 2 wks or 480 mg every 4 wks until disease progression. Primary endpoint was disease control (DC) per investigator defined as complete (CR) or partial (PR) response per RECIST v. 1.1, or stable disease of at least 16 wks duration (SD16+). CR is based on radiographic assessment. CA 19-9 levels were not collected. Simon 2-stage design tested null DC rate of 15% vs. 35% (power = 0.85; α = 0.10). If ≥2 of 10 pts in stage 1 have DC, 18 more pts are enrolled; otherwise, the cohort is closed. If ≥7 of 28 pts have DC, the null DC rate is rejected. Secondary endpoints were objective response (OR), progression-free survival (PFS), overall survival (OS), duration of response (DOR) and SD, and safety. DOR is defined as time from pt’s first documented OR to progressive disease. Results: 32 pts with PC with BRCA1 (n=8), BRCA2 (n=22) or both BRCA1/2 (n=2) were enrolled between October 2017 and March 2023. 4 pts were not evaluable for efficacy. Pts had adenocarcinoma (n=29), acinar cell carcinoma (n=2), and poorly differentiated carcinoma (n=1). Table shows demographics and outcomes. 1 CR, 3 PR and 4 SD16+ were observed for a DC rate of 31% (90% CI, 18 to 100) and OR rate of 14% (95% CI, 4 to 33). The pt with CR had a BRCA1 mut, the pts with PR had BRCA1 (n=1) and BRCA2 (n=2) muts, and the pts with SD16+ had BRCA1 (n=2) and BRCA2 (n=2) muts. The null DC rate was rejected (p=0.04). The pt with CR remains on tx with a DOR of 311 wks as of May 2024. 15 pts received prior tx with olaparib and 1 of those pts had SD16+ on this study. 17 pts had ≥1 drug-related grade 3-4 adverse event (AE) or serious AE. All were consistent with N+I labels except generalized muscle weakness and lymphopenia. Conclusions: N+I shows antitumor activity in pts with PC with BRCA1/2 mut and warrants further study. Clinical trial information: NCT02693535 . Demographics (N=32) and efficacy outcomes (n=28). Median (Med) age, years (range) 66 (37-80) ECOG PS, % 0-12 31 (97)1 (3) Prior systemic regimens, % 0-2≥3 10 (31)22 (69) DC rate, % (OR and SD16+) (90% CI) 31 (18, 100) OR rate, % (95% CI) 14 (4, 33) Med PFS, wks (95% CI) 9 (7, 16) Med OS, wks (95% CI) 34 (14, 46)

Survival benefits of asymptomatic primary tumor resection after bevacizumab plus FOLFIRI as first-line therapy for patients with metastatic colorectal cancer with synchronous unresectable metastasis.

56 Background: Metastatic colorectal cancer (mCRC) poses a clinical challenge and requires a combination of systemic therapy and conversion surgery. Although first-line chemotherapy and target therapy are considered the standard treatments for mCRC, the role of primary tumor resection (PTR) in asymptomatic synchronous mCRC with unresectable metastatic lesion after initial therapy remains relatively underexplored. Methods: A retrospective observational study was conducted from January 2015 to January 2021, involving 74 patients with synchronous mCRC who received bevacizumab plus FOLFIRI as first-line systemic therapy. All 74 patients had unresectable metastatic lesions confirmed through multidisciplinary team (MDT) discussion. Patients' characteristics, PTR data, and radiotherapy (RT) and overall survival (OS) outcomes were analyzed. The patients were categorized into a "PTR" group and a "No PTR" group and then further stratified into IVA, IVB, and IVC subgroups based on the initial mCRC stage. Additionally, four subgroups - namely "PTR(+)/RT(+)", "PTR(+)/RT(-)", "PTR(-)/RT(+)", and "PTR(-)/RT(-)" were formed to assess the combined effects of PTR and RT. Results: The median OS for all the patients was 23.8 months (20.5 - 27.1 months). The "PTR" group exhibited a significantly higher median OS of 25.9 months (21.3 - 30.5 months) compared with 21.4 months (15.8 - 27.1 months) in the "No PTR" group ( P = 0.048). Subgroup analyses revealed a trend of improved survival with PTR in patients with stage IVA and IVB; however, the results were not statistically significant ( P = 0.116 and 0.493, respectively). A subgroup analysis of PTR and RT combinations revealed no significant difference in median OS rates. Conclusions: For asymptomatic mCRC with synchronous unresectable distant metastasis. PTR following first-line therapy with bevacizumab plus FOLFIRI can provide a survival benefit, particularly in stage IVA/IVB patients compared with stage IVC patients. Additionally, RT for primary tumor did not provide an additional OS benefit in mCRC with unresectable metastasis. A prospective randomized trial with a larger sample size is essential to further elucidate the role of PTR in this context.

High‐Efficiency Intrinsically Thermoplastic Semiconducting Polymer with Excellent Strain‐Tolerance Capacity for Flexible Ultra‐Deep‐Blue Polymer Light‐Emitting Diodes

Abstract Complex internal stresses that appear in flexible thin‐film electronic devices under long‐term deformation operation are associated with incompatible mechanical properties of the multiple layers, which potentially cause intralayer fracture and separation. These defects may result in device instability, performance loss, and failure. Herein, a thermoplastic functional strategy is proposed for manufacturing high‐performance stretchable semiconducting polymers with excellent strain‐tolerance capacities for flexible electronic devices. Internal plasticization is used to obtain a thermoplastic light‐emitting polymer (N2) that can suppress intralayer tensile fracture and compressive separation to enhance the deformation stability of flexible thin‐film optoelectronic devices, enabling outstanding energy dissipation capacity under stress. The thermoplastic films exhibit stable and efficient ultra‐deep‐blue emission with a high efficiency of ≈90% and chromaticity coordinates of (0.16, 0.04). Moreover, the N2‐based rigid and flexible polymer light‐emitting diodes (PLEDs) exhibit stable ultra‐deep‐blue electroluminescence properties with high EQEs of ≈2.4% and 1.9%, respectively. Compared with devices based on brittle PODPF, flexible PLEDs based on thermoplastic films effectively suppress performance degradation after hundreds of cycles of bending fatigue, even under extremely rigid conditions. Introducing intrinsically thermoplastic semiconducting polymers in flexible electronic devices can thus substantially enhance their operational stability under deformation.

Retreatment with immune checkpoint inhibitors (ICIs) for patients with advanced gastric cancer: A retrospective, real-world study.

343 Background: Immunotherapy combined with chemotherapy has become the standard first-line treatment for advanced gastric cancer and is recommended by multiple guidelines and consensuses. After the first line immunotherapy, there is still controversy over whether immune inhibitors can continue to be used across lines after progression. Methods: This is a single-center, retrospective, observational, real-world study. We collected clinical information of patients with advanced gastric cancer hospitalized at the First Affiliated Hospital of Zhengzhou University from January 2018 to July 2024. All patients received combination therapy with ICIs inhibitors for at least 2 cycles in the first-line and at least 2 cycles of ICI inhibitor-based therapy in the second-line after first-line progression. The efficacy and safety of treatment were evaluated, including overall survival (OS), progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), the progression pattern of retreatment with immune checkpoint inhibitor, grade 3-5 treatment-related adverse events (TRAEs), and immune-related adverse events (irAEs). Cox regression model was used to investigate the influence of multiple factors on survival. Results: We included 217 patients with a median age of 59.0 (18-84) years, of which 70.0% were male. The median OS and PFS were 9.8 (95% CI 8.8-10.8) months and 4.6 (95% CI 4.0-5.3) months. The ORR and DCR were 22.7% (95% CI 17.1-29.0) and 56.2% (95% CI 49.0-63.1). For the second-line treatment regimens, there were 87 (40.1%) patients and 130 (59.9%) patients received immunotherapy combined with chemotherapy (I+C) and immunotherapy combined with chemotherapy and anti-angiogenic drugs(I+C+A) respectively. The median OS was 9.3 (95% CI 8.5-10.1) months and 11.5 (95% CI 9.3-13.7) months, p=0.032. The median PFS was 4.2 (95% CI 3.1-5.3) months and 5.2 (95% CI 4.3-6.1) months, p=0.082. Cox regression model analysis showed that ECOG 0-1, PFS≥6 months in the first-line treatment, second-line regimen (I+C+A), and second-line medication &gt; 3 cycles were independent prognostic factors for OS in the second-line treatment. The incidence of grade ≥3 TRAEs was 20.7%, and the incidence of irAEs was 6.5%. No treatment-related deaths occurred. Conclusions: This real-world study results showed that retreatment with immune checkpoint inhibitors had promising clinical benefit for patients with advanced gastric cancer and manageable safety. Efficacy of different groups. 　 n mOS（m） mPFS（m） ORR（%） DCR（%） ITT 217 9.8 4.6 22.7 56.2 ECOG 0-1 180 9.8 4.7 19.5 56.8 2 37 8.6 4.0 38.2 52.9 1-Line PFS ＜3m 61 5.5 2.2 1.7 17.2 ≥3m 156 11.7 6.0 31.0 71.7 ＜6m 136 7.4 3.2 2.4 38.7 ≥6m 81 15.1 8.0 54.4 83.5 Second-line treatment I+C 87 9.3 4.2 16.9 54.2 I+C+A 130 11.5 5.2 26.7 57.5 Second-line treatment cycle ≤3 97 7.4 2.9 4.8 31.0 　 ＞3 120 13.1 6.2 35.3 73.9

A method for classifying colorectal cancer and gastric/esophageal cancer using blood-based testing.

52 Background: Identifying the cancer signal of origin is of great value in the clinical use of blood-based cancer testing, especially in those tests that have potential to assess for more than one cancer type. Thus, an approach that can accurately identify cancer signal of origin in order to guide subsequent diagnostic workup is impactful to the adoption of this new technology. Here, we report feasibility data using the DNA methylation signature of plasma cell-free DNA to differentiate between colorectal cancer (CRC) and gastric/esophageal cancer (GEC) types. Methods: We developed an algorithm to distinguish between CRC and GEC based on the DNA methylation signature of plasma cell-free DNA molecules from more than 3,000 differentially methylated regions. First, a regression model (a multi-cancer classifier) was trained to identify the samples with sufficient tumor derived methylation signal using 6,822 cancer samples of 24 cancer types and the samples from 4,423 cancer-free individuals. A second regression model (a CRC/GEC classifier) was trained to distinguish CRC from GEC cases on the samples with positive calls from the multi-cancer classifier. The second model was trained on methylation signals from advanced stage CRC samples, advanced stage GEC samples (including esophageal, gastroesophageal, and gastric cancers), and samples from cancer-free individuals. Results: The multi-cancer classifier identified 92% (2,954/3,204) of CRC and GEC samples as positive at 90% target specificity, including 93% (2,086/2,253) of CRC samples and 91% (868/951) of gastric/esophageal cancer samples. The performance of the CRC/GEC classifier is evaluated through 10-fold cross validation on these 3,204 cancer samples, where in each fold, an additional 6,298 samples from cancer-free individuals were also used in training. Among the 2,954 CRC and GEC samples detected by the multi-cancer classifier, 2,698 (91%) were accurately classified by the CRC/GEC classifier. Among the detected CRC samples, 91% (1,907/2,086) were correctly classified as CRC. Similarly, 91% (791/868) of the detected GEC samples were correctly classified. The precision of the CRC/GE prediction was also assessed and 91% (2,698/2,954) of the detected cancer samples were correctly classified. Of the 1,984 detected cancer samples predicted as CRC, 96% (1,907/1,984) were true CRC samples. Of the 970 detected cancer samples classified as GEC, 82% (791/970) were correct. Conclusions: This assay with high sensitivity and accurate CRC/GEC classification can effectively guide subsequent diagnostic workups following a positive result, maximizing potential clinical utility. Ongoing work will continue further refinements.

A protocol for pretreatment testing for antibodies to galactose-alpha-1,3-galactose to mitigate the risk of cetuximab hypersensitivity reactions.

115 Background: Cetuximab has been shown to improve survival in patients with KRAS wildtype metastatic colorectal cancer. However, high rates of hypersensitivity reactions (HSRs) limit its use, with HSR rates up to 10-20%. A major driver of cetuximab HSR is from pre-formed antibody response to galactose-1,3-alpha-galactose (alpha-gal). Evidence from retrospective studies supports alpha-gal pre-screening in this setting. We are the first to report on the impact of prospective alpha-gal antibody screening on cetuximab HSR. Methods: Records were reviewed across three medical oncology centres that have adopted alpha-gal antibody screening measures. Data for patients with metastatic colorectal cancer treated with cetuximab were retrieved. All centres assessed alpha-gal antibody status using the ImmunoCAP ELISA assay. Due to lack of a shared screening approach across study sites, a pre-determined protocol was retrospectively applied to all cases. This protocol allowed cetuximab administration if alpha-gal levels were ≤0.1 kUA/L, but prohibited it if alpha-gal levels were &gt;0.1 kUA/L in favour of panitumumab administration. Patients were allocated to either the Protocol Applied or Protocol Not Applied cohorts based on protocol requirements being met. The primary outcome between these patient groups was the incidence of cetuximab HSRs. Results: Of 254 assessable patients, 39 underwent the pre-treatment screening protocol. Of the Protocol Applied group, 3% (n=1/38) experienced a cetuximab HSR compared to 16% (n=35/215) in the Protocol Not Applied group (Odds ratio (OR) 7.16; 95% CI 1.13–299.61, p =0.02). Patients with alpha-gal antibody titres &gt;0.1 kUA/L were more likely to experience a cetuximab HSR (OR 69.71; 95% CI 5.18–4296.81, p =0.0001). Conclusions: Pre-treatment screening for alpha-gal antibodies significantly reduces the incidence of cetuximab HSRs. A testing threshold of 0.1 kUA/L is effective in identifying patients at risk. Implementing this protocol can improve the safety of cetuximab therapy in high-risk populations.

Phytochlorin‐Based Sonosensitizers Combined with Free‐Field Ultrasound for Immune‐Sonodynamic Cancer Therapy

AbstractPhytochlorins, a class of plant‐derived tetrapyrroles, show great potential as sonosensitizers in sonodynamic therapy (SDT). The development of new phytochlorin‐based sonosensitizers has significantly improved SDT, yet the absence of specialized sonodynamic systems limits their clinical translation. Herein, a dedicated ultrasound system along with a detailed step‐by‐step sonodynamic process from in vitro to in vivo is developed to activate phytochlorin‐based sonosensitizers. Compared to standing‐wave ultrasound, free‐field ultrasound maintains stable acoustic pressure amplitudes and minimizes mechanical damage to cell membranes. In vitro experiments demonstrate that free‐field ultrasound effectively activates naturally occurring phytochlorin, reducing the cavitation threshold for reactive oxygen species production and triggering immunogenic cell death. Furthermore, the intravenously injectable phytochlorin‐based sonosensitizer (C34) enhances sonodynamic efficiency by reducing interfacial tension. Driven by in vivo free‐field ultrasound, C34 effectively inhibits tumor growth in an orthotopic murine breast cancer model and elicits an immune response, preventing tumor metastasis. The reliable protocol provided by the free‐field ultrasound system facilitates the activation of phytochlorin‐based sonosensitizers while simultaneously stimulating the immune system, highlighting the potential of immune‐sonodynamic therapy.

Comprehensive landscape of FGFR variations and prognosis revelance in colorectal cancer from circulating tumor DNA and tissue gene analyses in 2083 patients.

278 Background: FGFR genomic alterations have been identified, and several FGFR inhibitors are approved for various malignancies, including bladder and cholangiocarcinoma. However, limited studies have shown FGFR alterations and their prognostic impact in colorectal cancer (CRC). Methods: This retrospective analysis involved tissue and blood samples from a single-institute cohort (The Sixth Affiliated Hospital of Sun Yat-sen University) of stage I-IV CRC patients from 2014 to 2024. FGFR genomic alterations were analyzed using tissue NGS and plasma ctDNA. Disease-free survival (DFS) for stages I-III and progression-free survival (PFS) for stage IV were compared between FGFR-altered and negative CRC patients, matched in a 1:2 ratio. Validation of genomic alterations and their prognostic impact was conducted using cBioPortal and TCGA data. Results: FGFR alterations were found in 7.89% of 608 tissue samples and 10.95% of 2083 ctDNA samples. The most frequent alteration was FGFR1 amplification in all cohorts, along with FGFR2 p.R165W and FGFR3 p.A634T mutations in ctDNA. FGFR alterations correlated with younger age, left-sided colon tumors, adenocarcinomas, poor differentiation, advanced TNM staging, and multi-organ metastasis. Prognostic analysis showed a higher proportion of FGFR alterations in stage IV patients (66.23% vs. 59.14%), lower rates of no evidence of disease (NED) (6.62% vs. 17.68%), and significantly shorter PFS (median 17 vs. 20 months, HR 2.184, p=0.007). In stages I-III, FGFR-altered patients also had a lower NED rate (79.22% vs. 82.19%) and significantly shorter DFS (median 13 vs. 29 months, HR 2.833, p=0.002). Among frequent alterations, FGFR1 amplification was significantly associated with poor prognosis (PFS 17 vs. 20 months, HR 2.221, p=0.014; DFS 13 vs. 29 months, HR 2.964, p=0.002), while others showed no significant correlation. In stage IV patients receiving bevacizumab, FGFR1 alteration was linked to significantly shorter PFS (p=0.0021). KEGG analysis indicated FGFR1 was associated with angiogenesis pathways. FGFR alteration profiles and prognostic outcomes were consistent across tissue samples, ctDNA analyses, and databases. Conclusions: Our study outlines the genomic landscape and prognostic significance of FGFR in CRC, highlighting FGFR1 amplification as the dominant alteration. FGFR alterations were associated with poorer outcomes, as reflected in lower NED rates and shorter DFS and PFS. FGFR1 amplification was notably linked to reduced DFS and PFS, and it correlated with shorter PFS in patients receiving bevacizumab, indicating a potential link to resistance against bevacizumab. ctDNA n=2083 Tissue genen=608 cBioPortal Databasen=6998 FGFR Total 228/10.95% 48/7.89% 528/8.0% FGFR1 76/3.65% 29/4.77% 264/4.0% FGFR2 78/3.74% 10/1.64% 125/1.9% FGFR3 104/4.99% 10/1.64% 139/2.1%

Effect of dose adjustments on overall survival (OS) in patients with metastatic pancreatic ductal adenocarcinoma (mPDAC) treated with NALIRIFOX: A post hoc analysis of NAPOLI 3.

716 Background: NALIRIFOX is approved by the US Food &amp; Drug Administration and European Medicines Agency for the first-line treatment of adults (no upper age limit) with mPDAC. Approval was based on the results of NAPOLI 3 (NCT04083235), in which NALIRIFOX demonstrated significant improvements in OS (primary outcome) and progression-free survival compared with nab-paclitaxel plus gemcitabine. In this exploratory post-hoc analysis of NAPOLI 3, we examined the impact of NALIRIFOX dose adjustments on OS in patients treated in North America. Methods: Patients (N = 770) with confirmed untreated mPDAC were randomized (1:1) to receive liposomal irinotecan 50 mg/m 2 + oxaliplatin 60 mg/m 2 + leucovorin 400 mg/m 2 + 5-fluorouracil 2400 mg/m 2 (NALIRIFOX) on days 1 and 15 of a 28-day cycle or nab-paclitaxel 125 mg/m 2 and gemcitabine 1000 mg/m 2 on days 1, 8 and 15 of a 28-day cycle. In this analysis, liposomal irinotecan dose reductions, delays, and exposure were examined descriptively in patients who received NALIRIFOX at centers in North America. OS was evaluated using Kaplan–Meier methods; no statistical tests were performed. Results: Overall, 120 patients were randomized to receive NALIRIFOX at centers in North America (intention-to-treat [ITT] population) and 112 received treatment (safety population). Dose adjustments (dose reductions and dose delays) occurred in a higher proportion of patients presenting with longer OS. Patients with the longest duration of liposomal irinotecan exposure and highest cumulative dose had the longest OS. Conclusions: This finding suggests that tolerability-guided dose modification of liposomal irinotecan does not adversely affect efficacy outcomes and suggests a path forward to further optimize the OS of patients with mPDAC receiving NALIRIFOX. Clinical trial information: NCT04083235 .