Browse Articles

Association between cardiometabolic index and hypertension among US adults from NHANES 1999–2020

Disorder within order: Identification of the disordered loop of STAS domain as the inhibitory domain in SLC26A9 chloride channel

PD-1 inhibitor (sintilimab) and fruquintinib plus SOX as conversion therapy for initially unresectable gastric/gastroesophageal junction adenocarcinoma (GC/GEJC): Updated results from a single-arm, phase 2 clinical trial.

406 Background: The evidence of conversion therapy for unresectable GC/GEJC is limited. Previously, preliminary results of the ongoing open-label, phase 2 study (NCT05177068) have showed promising R0 surgical conversion rate (62.1%), R0 resection rate (100%) and acceptable tolerability in unresectable GC/GEJC with sintilimab and fruquintinib plus SOX (ASCO 2024). Here we present updated results with longer follow-up duration, including more enrolled patients. Methods: Eligible patients were administered fruquintinib (4mg/d, po, qd, d1-14), sintilimab (200mg, iv, d1), oxaliplatin (130 mg/m 2 , iv, d1) and S-1 (40-60mg based on BSA, po, bid, d1-14) every 3 weeks for 3 or 6 cycles. One more cycle of sintilimab plus SOX was given before resection. Patients were assessed for tumor response and surgical feasibility by radiologic imaging & MDT every 3 cycles. Primary endpoint was R0 resection rate. Secondary endpoints included pathological response, ORR, PFS, OS, and safety. Results: As of July 30, 2024, 42 pts (37 males/5 females) with a median age of 64 years (range: 43–76), 71% ECOG PS1, 55% GEJC were enrolled. Nine (21.4%) of the 42 pts had distant metastasis and five (11.9%) pts had more than one unresectable factors. The most common unresectable factors were extensive or bulky lymph nodes 54.8% (23), liver metastasis 11.9% (5), peritoneal metastasis 4.8% (2), para-aortic lymph node metastasis 2.4% (1), and local progression 38.1% (16). Of 35 evaluable pts, ORR was 68.6% and DCR was 97.1%. Among the 29 pts who had completed surgical conversion, the R0 resection rate was 100% (29/29) and R0 surgical conversion rate was 82.9% (29/35). 10.3% (3/29) pts achieved pathological complete response (pCR), and 20.7% (6/29) pts reached tumor regression grade (TRG) 0-1. Additionally, the pathological response rate (pRR) according to JCGC (≥ Grade 1b) was 93.1% (27/29). Seven pts (16.7%) had grade 3 treatment-emergent adverse events, including 4 cases of anemia, 2 cases of neutrophil count decreased, and 1 case of each (lymphocyte count decreased, gastrointestinal hemorrhage, diarrhea, and immune-related pneumonitis). No severe surgery-related complication was observed. Conclusions: Fruquintinib combined with sintilimab and SOX yielded very high R0 conversion rate and R0 resection rate with a manageable safety profile in unresectable GC/GEJC, representing a potential and feasible conversion therapy regimen for this population. Survival data will continue to be followed up. Clinical trial information: NCT05177068 .

Outcomes of surveillance in patients with intraductal papillary mucinous neoplasms (IPMNs) who tested negative for high-risk mutations (HRMs) in next-generation sequencing (NGS).

704 Background: HRMs in NGS have demonstrated high sensitivity and specificity for predicting advanced neoplasia in patients with IPMNs. However, the outcomes of surveillance in patients who tested negative for these HRMs have not been investigated in prior studies. This study aimed to identify the predictors of progression in patients with negative NGS results for HRMs. Methods: We conducted a retrospective review of prospectively collected data from patients who underwent NGS testing between 2016 and 2023 in our pancreatic cancer prevention program. Patients without IPMNs (i.e., negative for KRAS/GNAS), with HRMs, and those without at least one follow-up imaging post-NGS were excluded from the study. Progression was defined as the development of new or additional worrisome features or high-risk stigmata (per Kyoto guidelines), or advanced neoplasia (HGD/PDAC) following NGS testing. A Cox proportional hazards regression model was used to identify predictors of progression. Results: A total of 543 patients underwent NGS testing during the study period, of which 210 patients met the inclusion criteria. The median follow-up duration was 22 months (IQR = 12-36). Of these, 72 patients developed progression following NGS testing. A total of 11 patients underwent surgical resection, and 5 of them had HGD. Factors predictive of progression included a history of smoking (HR = 1.74; 95% CI = 1.06 - 2.86), larger cyst size (HR = 1.09; 95% CI = 1.03 - 1.16), and the presence of a dilated main pancreatic duct (MPD) (HR = 2.56; 95% CI = 1.5 - 4.4) prior to NGS testing. The median time to progression for patients with worrisome features was 33 months, compared to 59 months for those without worrisome features at baseline. Similarly, the median time to progression for patients with cysts ≥ 2 cm was 38 months, compared to 57 months for those with cysts < 2 cm. Conclusions: Patients who test negative for high-risk mutations in NGS are not exempt from the risk of progression. Any smoking history and presence of any worrisome features before NGS testing showed to be independent predictors of disease progression. For patients with smoking history, worrisome features or cysts ≥ 2 cm, frequent surveillance should be recommended following NGS testing. Results of Cox proportional hazards regression model for identifying the predictors of progression. Variables Hazards ratio (HR) 95% Confidence Interval P-value Age 0.99 0.96 – 1.01 0.257 Male sex 1.02 0.62 – 1.7 0.93 White race 1.07 0.63 – 0.83 0.8 Family history of pancreatic cancer 0.6 0.26 – 1.36 0.22 Personal history of other cancers 0.95 0.56 – 1.62 0.86 Diabetes 1.22 0.72 – 2.05 0.46 Any history of smoking 1.74 1.06 – 2.86 0.03* Pre-NGS cyst size (cm) 1.09 1.03 – 1.16 0.006* Pre-NGS dilated main pancreatic duct (≥5mm) 2.56 1.5 – 4.4 0.001* Pre-NGS presence of mural nodules 0.32 0.04 – 2.37 0.26 *Significant p-value.

An organ-preserving strategy in patients with esophageal squamous cell carcinoma treated with immunochemotherapy.

424 Background: This study evaluated the strategy of dose-dense chemotherapy plus a PD-1 inhibitor with selective organ-preservation in patients with advanced esophageal squamous cell carcinoma (ESCC). Methods: Patients with locally advanced or metastatic (confined to the supraclavicular lymph nodes) ESCC were enrolled to receive treatment with a PD-1 inhibitor plus albumin bound-paclitaxel, cisplatin and 5-FU every two weeks. After six cycles of treatment, patients with clinical complete response (cCR) confirmed by computed tomography (CT), endoscopy and biopsy underwent an organ-preserving strategy with continuation of immunochemotherapy. The primary endpoint was cCR rate in the intention-to-treat population. A post hoc analysis was also conducted in patients with advanced ESCC who had a best response of CR after immunochemotherapy from three prospective studies we previously reported. Consecutive patients who had not received esophagectomy prior to immunochemotherapy, and had durable CR as confirmed by imaging, endoscopy with or without biopsy were identified to provide supporting evidence for the organ-preserving strategy. Results: A total of twenty patients were enrolled. At data cut-off (September 12, 2024), eight patients fulfilled the criteria of cCR (40%), while six patients actually adopted the organ-preserving strategy. 75% of the patients experienced ≥ grade 3 treatment-related adverse events (TRAEs), most commonly neutropenia and leukopenia. All TRAEs were managed with appropriate medical care. In the post hoc analysis, out of 71 patients who had a best response of CR to immunochemotherapy in three previous trials, sixteen consecutive patients who had not received esophagectomy before immunochemotherapy, and remained CR assessed with CT at data cut-off were identified. Although endoscopy was not mandatory during follow-up, twelve patients underwent endoscopic exams, and none of them had suspected tumor with endoscopic visualization. Biopsies were taken for eight patients, and were all negative for tumor. The median follow-up for these twelve patients reached 42.7 months, suggesting a long-term disease-free survival after immunochemotherapy. Conclusions: Dose-dense nab-paclitaxel, cisplatin and 5-FU combined with a PD-1 inhibitor showed encouraging cCR rate and manageable safety, making organ-preservation a possible subsequent approach in patients with advanced ESCC. Clinical trial information: ChiCTR2300072992.

Chemoimmunotherapy plus radiotherapy in advanced esophageal squamous-cell carcinoma.

437 Background: Chemotherapy plus Immune checkpoint inhibitors (ICIs) have improved survival outcomes of patients with advanced or metastatic esophageal squamous-cell carcinoma in both first- and second-line settings. However, the benefit of additional radiotherapy for the residual esophageal lesion after chemo-immunotherapy remains unclear. Methods: We conducted a one-arm, three-center, open label study involving patients who were treatment naïve, radiological and histological confirmed advanced or metastatic squamous-cell esophageal carcinoma. Enrolled patients were expected the survival time was three months or longer; and ECOG performance status score was 0 or 1. In induction phase, patients received four cycles of TP regimen chemotherapy (docetaxel, 75/mg 2 , iv on day 1 and cisplatin, 75mg/m 2 , iv on day 1) combined with PD-1 inhibitor (sintilimab, 200mg intravenous infusion on day 1) every 21 days. Patients who finished four cycles of chemo-immunotherapy with stable disease (SD) or partial response (PR) were initiated 50Gy/25f irradiation for residual tumors. 3-4weeks after radiotherapy, maintenance sintilimab therapy was administered every 21 days for another 31 cycles or until disease progression or intolerable toxicity. Results: Total of 39 patients were enrolled in this study, 30 of them could be evaluated in efficiency and toxicities. All of them were male and were squamous-cell carcinoma in histology. 12/30 (40.0%) patients were in stage III, and 18/30 (60.0%) were in stage IV. 29/30 (96.7%) patients completed four cycles chemo-immunotherapy, the complete response (CR) rate was 6.7% (2/30), the partial response (PR) rate was 53.3% (16/30) and disease control rate (DCR) was 86.7% (26/30). The median depth of response (DpR) was 34.5% for chemoimmunotherapy and was 64.0% after radiotherapy. The progression-free survival (PFS) was 16.4 months and the overall survival (OS) was not reached. The most common grade 3 or worse adverse event was neutropenia and occurred in 3 (10.0%) patients. Conclusions: Four cycles sintilimab plus cisplatin and docetaxel followed by radiotherapy for residual tumors and maintained sintilimab had high response rate, prolonged PFS and tolerable toxicities as first line treatment in patients with advanced or metastatic esophageal squamous-cell carcinoma. Longer OS is promising and more patients enrolled in this study is needed in future. Clinical trial information: NCT06138028 . Clinicopathological features and patient factors. Factors No. of patients (n=30) (%) Gender 　 Male 30 (100.0) Female 0 (0) Age (year) 　 < 65 27 (43.3) ≥ 65 17 (56.7) PD-L1 (CPS) 　 < 5 9 (30.0) ≥ 5 21 (70.0) Clinical Stage 　 III 12 (40.0) IV 18 (60.0) Metastatic Pattern 　 Regional lymph node 12 (40.0) Cervical & Supraclavicular 4 (13.3) Abdomen 5 (16.7) Lung 6 (20.0)

Biomass production and silage quality of ensiled BRS Capiaçu elephant grass at different regrowth ages and residue heights

Substrate and inhibitor specificity of Plasmodium nucleoside transporters ENT1 orthologs

Outcomes of patients with peritoneal-limited metastatic gastric cancer (PLGC) undergoing bidirectional (BD) chemotherapy cytoreductive surgery (CRS) with heated intraperitoneal chemotherapy (HIPEC).

328 Background: The prognosis of PLGC patients (pts) is poor with standard systemic therapy. PLGC pts who undergo CRS after BD chemotherapy (chemo) demonstrate prolonged survival. We retrospectively analysed the outcomes of pts who underwent BD chemo followed by CRS and HIPEC in a single institution, stratifying by peritoneal carcinomatosis index (PCI) and chemo regimen. Methods: PLGC pts who received BD chemo between January 2016 to September 2023 were enrolled and consented for data collection. BD chemo was either 3 weekly paclitaxel (PTX) (50mg/m2), S-1 (80mg/m2) and IP PTX (20mg/m2) or capecitabine (2g/m2), oxaliplatin (100mg/m2) (CAPOX) and IP PTX (40mg/m2). HIPEC utilised cisplatin 50mg/m2 at 40 for 60 minutes. Trastuzumab and nivolumab were given selectively. Pts without radiological progression after 24 weeks of BD chemo, with PCI7 and potential for complete resection underwent CRS including D2 gastrectomy and HIPEC. Post-resection, BD chemo was stopped. Survival was analysed by Kaplan Meier curves, adverse events (AEs) by CTCAE v5.0 and response by independent radiological review. Results: 34 pts were enrolled with median follow-up of 26.9 months (m). Median (range) age was 51 (17 – 79) and median PCI 12 (0-29). 52.9% were female, 8.8% had Cy1 only disease and 38% had prior gastrectomy. 3 out of 6 pts with evaluable disease had partial response. Median progression-free survival and overall survival (mOS) was 9.1m and 16.5m respectively. 7 pts (20.6%) underwent CRS with median (range) PCI of 1 (0-15.0). mOS in CRS vs non-CRS pts was 23.8m vs 14.6m (p=0.4); PCI <7 vs PCI ≥7 was 23.8m vs 14.6m (p=0.63); and CAPOX vs S1/PTX systemic chemotherapy was 23.9m vs 14.6m (p=0.29) respectively. Peritoneal cytology negativity increased from 25.8% to 86.4% after BD chemo. Peritoneal lesions biopsied post-BD chemo showed no tumour cells in 64% of cases. There was no treatment-related mortality. 1 pt had IP port removal due to complications. The commonest grade 3 AE was neutropenia (14.7%). Biomarker analysis is currently being performed. Conclusions: BD chemo CRS HIPEC was well tolerated with longer survival in patients undergoing CRS. Evaluation of tumour using PCI post-BD chemo may be sub-optimal.

Treatment preferences in advanced pancreatic ductal adenocarcinoma (PDAC) from qualitative patient (PT), caregiver (CG), and oncologist (OC) interviews.

712 Background: Most treatment regimens for patients with PDAC focus on extending survival while managing symptoms and maintaining quality of life (QoL). Here we report insights from PT, CG, and OC interviews on PDAC treatment preferences. Methods: A targeted literature review of 7 quantitative/preference and 12 qualitative/patient-reported outcome studies was used to develop semi-structured interview guides. Single 60-minute interviews of US PTs with stage 4 PDAC, CGs, and OCs with ≥5 years’ experience treating PDAC were undertaken virtually by staff from March to April 2024. Interviews had 5 sections: background/clinical experience (OC only); key treatment benefits and risks to avoid (ranked by importance); treatment convenience; and 2 hypothetical treatment preference questions. Participants completed a sociodemographic and clinical questionnaire. Interviews were recorded with permission, transcribed, and analyzed with ATLAS.ti v8+. Results: Ten PTs, CGs, and OCs completed interviews (N=30 total), including 4 PT/CG dyads. Mean PT age was 56.8 (standard deviation [SD] 12.15) years; 6 were men and 4 did not have CGs. Mean CG age was 51.1 (SD 14.2) years; 9 were women and 7 cared for their partners. OCs had mean 18.5 (SD 6.9) years’ clinical experience and 10 were men. Top-ranked treatment benefits were increased overall survival (OS) (6 PTs [60%], 8 CGs [80%], 7 OCs [70%]); improved QoL (6 PTs [60%], 5 CGs [50%], 7 OCs [70%]); stopping disease progression (5 PTs [50%], 3 CGs [30%], 7 OCs [70%]), and increased life expectancy (7 PTs [70%], 5 CGs [50%], 3 OCs [30%]). PTs’ top 3-ranked side effects to avoid included fatigue (n=4 [40%]), nausea (n=4 [40%]), and vomiting (n=3 [30%]). CGs ranked trouble remembering (n=4 [40%]), neutropenia (n=4 [40%]), and neuropathy (n=3 [30%]) in the top 3, while OCs ranked vomiting (n=5 [50%]), neuropathy [n=5 [50%]), and neutropenia (n=4 [40%]) highest. Most PTs/CGs were indifferent to ≥1 infusion/visit and infusion duration. In the first hypothetical treatment preference question, the treatment with higher efficacy but higher side effect risk and longer infusion time was preferred by 80% of PTs/CGs and 70% of OCs. In the second hypothetical treatment question, treatments had the same efficacy; 90% of PTs/CGs/OCs preferred the treatment with shorter infusion time and lower risk of gastrointestinal side effects and hypersensitivity reactions, despite higher risk of severe hypokalemia and severe neutropenia. Conclusions: OS and QoL were ranked as similarly important by participants, suggesting that extending survival is insufficient without acceptable QoL. Avoiding side effects was important to all participants, though PTs, CGs, and OCs ranked specific risks with differing importance. More studies are needed to quantify tradeoffs between treatment efficacy and side effects in the care of patients with advanced PDAC.

CK2 expression gastrointestinal cancer: Exploring clinical characteristics and cancer genetics.

834 Background: The expression of protein kinase CK2 subunits (CSNK2A1, CSNK2A2, CSNK2A3, and CSNK2B) in gastrointestinal cancers has not been fully characterized. In this study, we seek to evaluate how changes in CK2 subunit expression are associated with GI cancer clinical characteristics and genetics. Methods: Data analysis was performed with data from The Cancer Genome Atlas (TCGA). R version 4.2.2 was used for analysis. We provide an analysis of several cancer cohorts looking at CK2 subunit expression, as well as cancer mutations, copy number alterations, and clinical characteristics. Results: From the TCGA datasets containing mRNA expression data, we assessed hepatocellular carcinoma (n=361), colorectal adenocarcinoma (n=339), gastric adenocarcinoma (n=306) and diffuse type gastric adenocarcinoma (n=69), pancreatic adenocarcinoma (n=169), esophageal adenocarcinoma (n=89) and squamous cell carcinoma (n=95), and cholangiocarcinoma (n=36). We explored associations between CK2 subunit expression and GI cancer-specific known driver mutations, of which we report the following significant findings (p < 0.05 for all). Mutations in TP53 were associated with increased expression of CSNK2A1 in hepatocellular carcinoma and stomach adenocarcinoma, increased CSNK2A2 in colorectal adenocarcinoma, and CSNK2B in colorectal adenocarcinoma, pancreatic adenocarcinoma, and stomach adenocarcinoma. Mutations in KRAS were associated with increased expression of CSNK2A1 and CSNK2B in pancreatic adenocarcinoma. Mutations in BRAF were associated with decreased expression of CSNK2A2 and CSNK2B in colorectal adenocarcinoma. We also noted significant changes in CSNK2 subunit expression when looking at mutations and copy number alterations in signaling pathways such as Wnt, NOTCH, PI3K, TGFβ, and more. We also explored associations between CK2 subunit expression and GI cancer clinical characteristics, of which we report the following significant findings (p < 0.05 for all). In colorectal adenocarcinoma, increased CSNK2A2 expression was associated with lymph node invasion and advanced clinical stage. In hepatocellular carcinoma, increased CSNK2A1 and CSNK2A3 expression was associated with greater tumor grade, tumor size, and more advanced clinical staging. Increased CSNK2A2 expression was associated with greater tumor size, more advanced clinical staging, and vascular invasion. Increased CS2NKB expression was associated with increased tumor grade, size, and vascular invasion. In pancreatic adenocarcinoma, increased CSNK2A3 expression was associated with a worse response to the first treatment course. Conclusions: Our results suggest that changes in protein kinase CK2 expression are associated with different cancer clinical characteristics as well as cancer-specific mutations and signaling pathways.

Beamion BCGC-1: A phase Ib/II trial of the HER2-selective tyrosine kinase inhibitor (TKI) zongertinib (BI 1810631) + trastuzumab deruxtecan (T-DXd) or trastuzumab emtansine (T-DM1) for patients with metastatic breast cancer (mBC) and metastatic gastric, gastroesophageal junction, or esophageal adenocarcinoma (mGEAC).

TPS509 Background: Approximately 15% of mGEAC tumors overexpress HER2. Currently, the HER2-targeted antibody-drug conjugate (ADC), T-DXd, is approved in mGEAC as a second-line or later-line treatment option following the failure of prior trastuzumab-containing therapy. Zongertinib (BI 1810631) is a novel, orally administered HER2-selective TKI that spares EGFR. In a Phase I trial (NCT04886804), zongertinib showed encouraging tolerability and efficacy in patients with HER2 aberration-positive advanced solid tumors, including mGEAC. Beamion BCGC-1 (NCT06324357) is a Phase Ib/II dose escalation/optimization trial investigating zongertinib plus T-DXd or T-DM1 in patients with HER2+ mGEAC or mBC. Here we focus on the mGEAC cohorts, in which patients will receive zongertinib in combination with T-DXd. Methods: Across the whole trial, approximately 240 patients will be enrolled from approximately 48 sites in 6 countries. In the mGEAC cohorts, approximately 80 patients with histologically/cytologically confirmed locally advanced/metastatic, unresectable, HER2-positive, pre-treated mGEAC will be enrolled. All patients must have investigator-assessed progression and documented HER2-positive disease (overexpressed and/or amplified; confirmed by immunohistochemistry and in situ hybridization). In Phase Ib, approximately 20 patients will receive escalating doses of zongertinib plus a fixed approved dose of T-DXd (6.4 mg/kg, once every 21 days). Dose escalation will be guided by a Bayesian Logistic Regression Model, with overdose control. In Phase Ib, the primary endpoint is the occurrence of dose-limiting toxicities (DLTs) during the maximum tolerated dose evaluation period (first 21-day cycle); secondary endpoints include objective response (RECIST v1.1), DLTs during the on-treatment period and pharmacokinetics. In Phase II, up to 60 patients with mGEAC will be randomized 1:1 to receive one of two zongertinib dose levels (dose levels informed by Phase Ib), plus a fixed approved dose of T-DXd. In Phase II, the primary endpoint is objective response; secondary endpoints include progression-free survival, disease control, treatment-emergent adverse events leading to dose reduction, pharmacokinetics and patient-reported outcomes. Patients will remain on treatment until disease progression, undue toxicity or any other protocol-defined stopping criterion. Enrollment is ongoing. Clinical trial information: NCT06324357 .

Assessing hazard prediction and risk calibration skills in experienced and novice e-scooter riders

Abstract Less experienced e-scooter riders often exhibit risky riding behaviours. Despite this, no studies have examined how riders calibrate risk, respond to hazardous situations, and the impact of riding experience on these skills. To address this, this study assessed hazard prediction and risk calibration in e-scooter riders via bespoke video-based tests featuring real e-scooter footage filmed from the rider’s perspective. The first experiment assessed the ability of e-scooter riders to predict hazardous riding scenarios. The second experiment evaluated their proneness to engage in risky riding situations. The results indicated that increased riding experience did not improve riders’ hazard prediction skills or reduced their proneness to engage in risky riding. In fact, a higher riding frequency was linked to an increased tendency to engage in risky behaviour in certain scenarios. The results highlight that the typically short duration of e-scooter trips may limit riders’ exposure to a variety of hazards, hindering their ability to develop effective risk calibration skills. The observed high propensity to engage in risky riding scenarios, combined with average hazard prediction scores, emphasizes the need for targeted rider training focused on vigilance and risk awareness.

SF3B1 thermostability as an assay for splicing inhibitor interactions

Biomarkers of response in patients with gastric/gastroesophageal junction adenocarcinoma (GEA) treated with telisotuzumab adizutecan.

490 Background: c-Met protein (MET protein) overexpression (OE) and MET amplification (amp) occur in several cancer types, including GEA, and are associated with poor prognosis. The c-Met–directed antibody-drug conjugate telisotuzumab adizutecan (ABBV-400) is being assessed in advanced solid tumors in an ongoing, first-in-human study (NCT05029882). Results showed promising antitumor activity and a tolerable safety profile in GEA (Strickler et al. ESMO 2024, 1439P). Here, we present our analysis on associations between c-Met OE, MET amp, and ctDNA-derived molecular response with clinical outcomes. Methods: c-Met expression was evaluated retrospectively in FFPE tissue (archival/fresh) collected at study screening using IHC (SP44 Ab clone) or whole transcriptomic RNA sequencing (Caris). Plasma ctDNA collected at baseline (BL) and cycle 3 day 1 (C3) was analyzed with the GuardantINFINITY assay. Molecular response (MR) was assessed using circulating tumor fraction (cTF), estimated on the basis of ctDNA variant allele frequencies in a 74-gene panel (Guardant360 CDx) and methylation signals (GuardantINFINITY methylome platform). MR was defined as a 50% decrease in cTF from BL. MET amp status was determined retrospectively by the Guardant Health algorithm. Radiographic response was assessed per RECIST v1.1. Results: Clinical data from 42 patients (pts) with advanced GEA were included in this biomarker analysis. There was a negative correlation between c-Met expression and tumor size change from BL (R=-0.59). Of 42 pts, 12 (29%) had tumors with MET amp per ctDNA analysis/local site reports, which was higher than the bioinformatic analysis of real-world data (Caris-ConcertAI linked RWD360 and PT360; ~3%). Concordance between c-Met expression per IHC and RNA was observed (R=0.75, p<10 -6 ). There were 12 responders; 7 (58%) had MET amp, and 5 (42%) did not. Responders had lower ctDNA percentage change from BL vs nonresponders (1.5-fold and 1.6-fold difference based on 74-gene and methylation panel, respectively). Pts with MR had a greater decrease in tumor size from BL vs those without MR. A positive correlation between change in ctDNA levels (BL to C3) and change in tumor size was observed using the 74-gene panel and methylation panel (R=0.73 and 0.69, respectively). Additional biomarker analyses focused on the association between MET and other key biomarkers relevant in GEA will be discussed. Conclusions: In pts with advanced GEA treated with telisotuzumab adizutecan, c-Met OE/ MET amp and ctDNA-based MR were associated with enhanced antitumor activity. Compared with real-world data, MET amp was enriched in this study population. Phase 2 studies will continue to explore c-Met OE and MET amp prevalence and their potential predictive value with other biomarkers in a clinically representative population. Clinical trial information: NCT05029882 .

Non-contrast MRI as a surveillance tool for recurrent hepatocellular carcinoma after curative treatment: A prospective multicenter intra-individual comparison trial.

530 Background: Hepatocellular carcinoma (HCC) often recurs following curative treatment, significantly impacting long-term survival. Contrast-enhanced multiphasic computed tomography (CECT) is widely utilized for HCC recurrence surveillance but carries risks such as radiation exposure and adverse reactions to contrast agents. This prospective multicenter trial aimed to compare the accuracy of non-contrast abbreviated magnetic resonance imaging (NC-MRI) with CECT in detecting late recurrent HCC. Methods: This prospective multicenter intra-individual head-to-head comparison trial (study identifier: NCT05690451, KCT0006395) enrolled participants who had undergone curative treatment for HCC and remained recurrence-free for over two years. Participants underwent three rounds of surveillance at 2–6-month intervals using both CECT and NC-MRI. The primary outcome was the detection accuracy of each modality, compared using the McNemar test. Secondary outcomes included detection sensitivity and specificity. Results: A total of 203 participants underwent 528 rounds of paired CECT and NC-MRI, detecting recurrent HCC in 22 participants (10.8%). Among these cases, 21 showed intrahepatic recurrent HCC with a median tumor size of 1.3 cm, and one exhibited aortocaval lymph node metastasis. NC-MRI demonstrated a detection accuracy of 96.6% (196/203), significantly higher than CECT's 91.6% (186/203) (P=0.006). NC-MRI also exhibited significantly higher sensitivity in detecting recurrent HCC compared to CECT (77.3% [17/22] vs. 36.4% [8/22]; P=0.012), while specificity did not differ significantly between NC-MRI and CECT (98.9% [179/181] vs. 98.3% [178/181]; P=0.999). Conclusions: NC-MRI showed significantly higher sensitivity and accuracy in detecting recurrent HCC among patients who had been disease-free for more than two years after curative treatment, establishing it as the preferred surveillance modality for late recurrence. Clinical trial information: NCT05690451 . Contrast enhanced CT Non-contrast MRI Difference, % (95% CI) P-value Estimates, % (n/N) 95% CI, % Estimates, % (n/N) 95% CI, % Accuracy 91.6% (186/203) 87.8-95.5 96.6% (196/203) 94.0-99.1 4.9 (1.7, 8.2) 0.006 Sensitivity 36.4% (8/22) 14.5-58.2 77.3% (17/22) 58.3-96.3 40.9 (16.8, 65.0) 0.012 Specificity 98.3% (178/181) 96.5-100 98.9% (179/181) 97.4-100 0.6 (-0.5, 1.6) 0.999

Erratum: A Phase II Study of Acalabrutinib, Venetoclax, and Obinutuzumab (AVO) in a Treatment-Naive CLL Population Enriched for High-Risk Disease

Impact of synchronous vs metachronous primary tumor resection on prognosis of BRAF-V600E mutant metastatic colorectal cancer (mCRC).

304 Background: The goal of this study is to evaluate if resection of the primary tumor in synchronous versus metachronous metastatic disease predicts survival of BRAF-V600E mCRC in the era prior to combination BRAF/EGFR inhibitors. Methods: This is a retrospective study of patients treated at the Ottawa Hospital Cancer Centre with BRAF-V600E mutation mCRC who did not receive combination BRAF/anti-EGFR therapy, diagnosed with colorectal cancer prior to March 31, 2021. Demographic, clinical, pathologic and cancer characteristics were abstracted from electronic medical records. Outcomes of interest included median duration of therapy and overall survival (OS). Results: 71 patients were included with a median age of 70 years:, 37 (52%) were females, 49 (69%)had right-sided tumors and 19 (27%) were mismatch repair deficient (dMMR). The primary tumor was unresected in 22 (30%) and resected in 49 (70%), completely resected in 44 (62%), and partially resected in 5 (7%) patients. Overall, median OS was 12.9 months 95% CI (8.4, 19) with 17 months 95% CI (11, —) mOS in patients with resected primary and 6.3 95% CI (4.8, 15) months in patients with unresected primary, HR 2.48 95% CI (1.42, 4.32), p=0.001. In univariate analysis: signet ring cell (p=0.007), good performance status (p<0.001), distant lymph nodes (p<0.001), peritoneal metastasis (p=0.008), metasetectomy (p=0.002), Charlston Comorbidity Index (p=0.003) were significant prognostic factors. Synchronous versus metachronous primary tumour was not a significant prognostic factor. Conclusions: Real world data confirms that patients with BRAF-V600E mutant mCRC have poor clinical outcomes. Our analysis suggests that resection of the primary tumor did not seem to impact on survival of BRAF-V600E mutant mCRC patients. This suggests that prognosis is dictated by the systemic disease and not complications of the primary tumour itself. Of the patients with unresected primary tumour (n=21), 6 were synchronous. Metastatic status Primary Tumor Resected Primary Tumor unresected Total Synchronous 23 22 45 Metachronous 26 0 26 Total 49 22 71

2024 FDA approvals exceed average number but have lower sales projections

Copper and iron as unique trace elements linked to fibromyalgia risk