Biliary Cancer Research Articles

Biliary Track Cancer Retrospective Analysis of Last 10 Years

Biliary Track Cancer Retrospective Analysis of Last 10 Years

Percutaneous transhepatic cholangiography: An effective option for endo-biliary radiofrequency ablation before stent insertion in unresectable biliary cancer?

Biliary cancer is a highly aggressive disease that is typically diagnosed at advanced stages when surgical removal is no longer an option. In these cases, palliative care and mechanical widening of the blocked biliary system are preferred. The insertion of a stent is often necessary to prevent the recurrence of blockages caused by cancer progression. Prior to stent placement, endo-biliary radiofrequency ablation (EB-RFA) appears to result in longer-lasting stent effectiveness without increasing the risk of severe complications. However, its impact on overall survival is not yet clear. Additionally, while endoscopic retrograde cholangiopancreatography is the most common method for performing EB-RFA, percutaneous transhepatic cholangiodrainage seems to be a safe and potentially more efficient alternative, particularly for long, angulated, or significantly narrowed bile ducts.

Application of irreversible electroporation ablation in oncology - a narrative review

Irreversible electroporation-IRE is an innovative cancer treatment method that can selectively destroy cancer cells without damaging surrounding tissues. It is a safe and effective alternative to traditional methods, with the patient faster recover potential and spare critical body structures such as blood vessels and nerves.In surgical oncology, the IRE treatment technique is used especially in cases where other methods are not possible or have limited effectiveness. The method is proving to be seen as an effective local treatment with good clinical results and limited side effects in prostate, biliary, pancreatic, kidney and liver cancers.

Trajectory Analysis of Healthcare Use Before and After Gastrointestinal Cancer Surgery.

Frailty correlates with worse post-operative outcomes and higher surgical costs, but the long-term impact on healthcare utilization remains ill-defined. We sought to evaluate patterns of healthcare utilization pre- and post-surgery among patients with gastrointestinal cancer and characterize the association with frailty. Data on patients who underwent surgical resection for liver, biliary, pancreatic, colon and rectal cancer were obtained from the 2005-2020 SEER-Medicare database. Frailty was assessed using the claims-based frailty index. Group-based trajectory modelling identified clusters of patients with discrete patterns of healthcare utilization. Multivariable regression was performed to predict cluster membership based on preoperative factors, including frailty. Among 66,684 beneficiaries, four distinct utilization trajectories based on data from 12 months before and after surgery were identified. Following a surge in utilization during the month of surgery, most patients reverted to pre-surgery baseline utilization (low: n=6588, 9.9%; moderate: n=17,627, 26.4%; high: n=29,850, 44.8%). However, a notable trajectory involving 12,619 (18.9%) patients was identified, wherein surgery precipitated a transition from a "low" pre-surgery utilization state to a "high" utilization state post-surgery. Frail patients were more likely to be among those individuals who transitioned to high utilizers (low: 4.2% vs. vs. transition: 12.6% vs. high: 7.5%; p<0.001). On multivariable analysis incorporating preoperative variables, frailty was associated with high group trajectory membership (ref: least and moderate; highest: OR 4.90, 95%CI 4.49-5.35; p<0.001). Patients with gastrointestinal cancer demonstrated distinct clusters of healthcare utilization after surgical resection. Preoperative predictive models may help differentiate different health care utilization trajectories to help tailor care for patients in the postoperative period.

Usefulness of multigene liquid biopsy of bile for identifying driver genes of biliary duct cancers.

Liquid biopsy (LB) is an essential tool for obtaining tumor-derived materials with minimum invasion. Bile has been shown to contain much higher free nucleic acid levels than blood plasma and can be collected through endoscopic procedures. Therefore, bile possesses high potential as a source of tumor derived cell-free DNA (cfDNA) for bile duct cancers. In this study, we show that a multigene panel for plasma LB can also be applied to bile cfDNA for comparing driver gene mutation detection in other sources (plasma and tumor tissues of the corresponding patients). We collected cfDNA samples from the bile of 24 biliary tract cancer cases. These included 17 cholangiocarcinomas, three ampullary carcinoma, two pancreatic cancers, one intraductal papillary mucinous carcinoma, and one insulinoma. Seventeen plasma samples were obtained from the corresponding patients before surgical resection and subjected to the LiquidPlex multigene panel LB system. We applied a machine learning approach to classify possible tumor-derived variants among the prefiltered variant calls by a LiquidPlex analytical package with high fidelity. Among the 17 cholangiocarcinomas, we could detect cancer driver mutations in the bile of 10 cases using the LiquidPlex system. Of the biliary tract cancer cases examined with this method, 13 (54%) and 4 (17%) resulted in positive cancer driver mutation detection in the bile and plasma cfDNAs, respectively. These results suggest that bile is a more reliable source for LB than plasma for multigene panel analyses of biliary tract cancers.

S2312 Beyond Gastric Cancer: Evaluating the Risks of Biliary, Hepatic, and Colorectal Cancer Post-H. pyloriInfection

S2312 Beyond Gastric Cancer: Evaluating the Risks of Biliary, Hepatic, and Colorectal Cancer Post-H. pyloriInfection

Metabolic dysfunction‐associated steatotic liver disease and MetALD increases the risk of liver cancer and gastrointestinal cancer: A nationwide cohort study

SummaryBackgroundThe new nomenclature of metabolic dysfunction‐associated steatotic liver disease (MASLD) substituting nonalcoholic fatty liver disease was proposed along with a new category of MASLD with increased alcohol intake (MetALD).AimsWe aimed to explore the cancer risk by MASLD and MetALD.MethodsThis nationwide cohort study included 3,596,709 participants who underwent a health check‐up in 2011 in South Korea. Steatotic liver disease (SLD) was defined as a fatty liver index ≥30. Participants were categorized into four exclusive groups: MASLD, MetALD, other combination aetiology and no SLD. The subdistribution hazard ratio (SHR) was calculated using the Fine–Gray model after adjusting other variables.ResultsDuring the 33.9 million person‐years of follow‐up, 285,845 participants (7.9%) developed cancers. Compared with no SLD, MASLD, MetALD and other combination aetiology had an increased risk of all cancer. Liver cancer risk escalated from no SLD to MASLD (SHR, 1.16; 95% CI, 1.12–1.21), MetALD (SHR, 2.06; 95% CI, 1.92–2.20) and other combination aetiology (SHR, 8.16; 95% CI, 7.69–8.67). Gastrointestinal cancers including oesophagus, stomach, colorectal, biliary and pancreas cancers increased in MASLD (SHR, 1.13; 95% CI, 1.11–1.15), MetALD (SHR, 1.17; 95% CI, 1.14–1.21) and other combination aetiology (SHR, 1.09; 95% CI, 1.05–1.13). A modest increase in lung cancer and hormone‐sensitive cancer was observed with MASLD.ConclusionsThis study showed that MASLD and MetALD are associated with an increased risk of cancer, particularly liver and gastrointestinal cancers. The findings build new evidence for the clinical outcomes of MetALD while highlighting the importance of managing alcohol intake properly in MASLD and MetALD.

The HALP score as a prognostic factor in metastatic biliary cancer.

Biliary tract cancers are serious diseases and new biomarkers may be useful for the optimal management and prediction of these cases. This study aimed to evaluate the prognostic significance of the hemoglobin, albumin, lymphocyte, and platelet (HALP) score, a novel composite marker, in patients with metastatic biliary tract cancer. Patients with biliary tract cancers were analyzed retrospectively. Laboratory values, patient and disease characteristics, and survival rates were evaluated. The diagnostic impact of the HALP score was assessed with regression analyses. The study included 106 individuals with metastatic biliary tract cancer. Based on the median HALP score, ≥ 2.22 was considered a high score and < 2.22 was considered low. The overall average survival time was found to be 11.4months. Patients with low HALP scores had median overall survival of 9.5months, while those with high HALP scores had median overall survival of 15.9months. In multivariate analysis, Eastern Cooperative Oncology Group performance status, CA19-9 level, and HALP score remained significant predictors of overall survival. The HALP score appears to be a useful prognostic marker in patients with metastatic biliary tract cancer.

Safety of pressurized intraperitoneal aerosolized chemotherapy in biliary cancer patients with peritoneal metastases.

Biliary tract cancers are a rare diagnosis with a rising incidence. Up to 20% of patients have peritoneal metastases, resulting in symptoms of ascites, abdominal pain and potential bowel obstruction. A standard of care systemic treatment comprises gemcitabine, cisplatin and durvalumab (gem/cis/durva). However, the clinical benefit among patients with peritoneal metastases remains unknown. Pressurized intraperitoneal aerosolized chemotherapy (PIPAC) delivers chemotherapy directly to the peritoneal space, which could potentially improve efficacy with minimal systemic toxicity. We describe the design of a Phase I study investigating PIPAC with nab-paclitaxel plus systemic gem/cis/durva among biliary tract cancer patients with peritoneal metastases who have not received prior systemic treatment. The primary end point is safety of PIPAC with nab-paclitaxel in combination with systemic gem/cis/durva.Clinical Trial Registration: NCT05285358 (ClinicalTrials.gov).

Efficacy of durvalumab plus chemotherapy in advanced biliary duct cancer and biomarkers exploration

BackgroundThe anti-PD-L1 antibody durvalumab has been approved for use in first-line advanced biliary duct cancer (ABC). So far, predictive biomarkers of efficacy are lacking.MethodsABC patients who underwent gemcitabine-based chemotherapy with or without durvalumab were retrospectively enrolled, and their baseline clinical pathological indices were retrieved from medical records. Overall (OS) and progression free survival (PFS) were calculated and analyzed. The levels of peripheral biomarkers from 48 patients were detected with assay kits including enzyme-linked immunosorbent assay. Genomic alterations in 27 patients whose tumor tissues were available were depicted via targeted next-generation sequencing.ResultsA total of 186 ABC patients met the inclusion criteria between January 2020 and December 2022 were finally enrolled in this study. Of these, 93 patients received chemotherapy with durvalumab and the rest received chemotherapy alone. Durvalumab plus chemotherapy demonstrated significant improvements in PFS (6.77 vs. 4.99 months; hazard ratio 0.65 [95% CI 0.48–0.88]; P = 0.005), but not OS (14.29 vs. 13.24 months; hazard ratio 0.91 [95% CI 0.62–1.32]; P = 0.608) vs. chemotherapy alone in previously untreated ABC patients. The objective response rate (ORR) in patients receiving chemotherapy with and without durvalumab was 19.1% and 7.8%, respectively. Pretreatment sPD-L1, CSF1R and OPG were identified as significant prognosis predictors in patients receiving durvalumab. ADGRB3 and RNF43 mutations were enriched in patients who responded to chemotherapy plus durvalumab and correlated with superior survival.ConclusionThis retrospective real-world study confirmed the clinical benefit of durvalumab plus chemotherapy in treatment-naïve ABC patients. Peripheral sPD-L1 and CSF1R are promising prognostic biomarkers for this therapeutic strategy. Presence of ADGRB3 or RNF43 mutations could improve the stratification of immunotherapy outcomes, but further studies are warranted to explore the underlying mechanisms.

Investigation of a Serine Protease Inhibitor Active in the Infectious Stage of the Human Liver Fluke Opisthorchis viverrini.

Serine protease inhibitors (serpins) participate in the regulation of inflammation, blood coagulation, and complement activation in humans. This research aimed to identify and characterize such inhibitors of the human liver fluke Opisthorchis viverrini. Parasite proteins that might contribute to the modulation of host physiology are of particular interest, especially as chronic opisthorchiasis increases the risk of developing biliary cancer. BLAST was used to find hypothetical serpins predicted from the parasite genome data. RNA extraction and reverse transcriptase PCR were used to isolate a serpin cDNA and to determine developmental transcript abundance. The evolutionary relation to other trematode serpins was revealed by phylogenetic analysis. Recombinant serpin was expressed in Escherichia coli and used to test the immunoreactivity of human opisthorchiasis sera and the inhibition of human serine proteases. A substantial serpin family with high sequence divergence among the members was found in the genus Opisthorchis. A serpin, different from previously analyzed trematode serpins, was cloned. The transcript was only detected in metacercariae and newly excysted juveniles. Human opisthorchiasis sera showed statistically significant reactivity to recombinant serpin. The serpin caused moderate inhibition of thrombin and low inhibition of kallikrein and chymotrypsin. This parasite serpin could be further evaluated as a diagnostic tool for early infection. Kallikrein and thrombin are involved in fibrinolysis; therefore, further research should explore the effects of the parasite serpin on this process.

Clinical outcome of patients hospitalized for pancreatic-biliary malignancy with comorbid acute decompensated heart failure: An analysis from National Inpatient Sample (NIS).

81 Background: Recent data suggest an association between cardiovascular disease burden and biliary cancer patients. However, the outcomes of hospitalized patients for biliary-pancreatic malignancy with concurrent acute decompensated heart failure (ADHF) are not well understood. Therefore, our objective is to assess the impact of ADHF on patients hospitalized for biliary-pancreatic malignancy. Methods: We used the 2020 U.S. National Inpatient Sample (NIS) to study patients hospitalized for biliary tract and pancreatic malignancy with concurrent acute decompensated heart failure (ADHF) identified by ICD-10 CM codes. Adjusted odds ratios (aORs) for predefined outcomes were determined via multivariable logistic and linear regression analyses. The primary outcome examined was inpatient mortality, while secondary outcomes included complications related to various body systems. Results: We identified 43,009 patients with a primary discharge diagnosis of biliary tract and pancreatic cancer. The mean age was 68.5 years; 49.4% were female. Caucasians accounted for 68%, followed by Hispanics (13%). Of these, 6.27% (3,699/43,009) had a concurrent diagnosis of heart failure. In the survey's multivariable logistic and linear regression analysis, accounting for patient and hospital confounding factors, ADHF demonstrated significant associations with higher in-hospital mortality (aOR 1.63; 95% CI 1.09, 2.44, p = 0.015). In addition, a significant association between ADHF and various adverse in-hospital outcome was observed including prolonged mean length of stay (Beta 1.45; 95% CI 0.67, 2.24, p &lt; 0.001), increased mean total hospital cost (Beta 3,757; 95% CI: 2,641, 36,630, p = 0.024), elevated risk of shock (aOR 2.75; 95% CI: 1.77, 4.26, p &lt; 0.001), higher risk of sepsis (aOR 1.71, 95% CI: 1.09, 2.68, p = 0.018), increased risk of acute respiratory failure (aOR 3.18, 95% CI: 2.25, 4.51, p &lt; 0.001), and heightened risk of acute kidney injury (aOR 1.57; 95% CI: 1.24, 1.99, p &lt; 0.001). Conclusions: Among patients hospitalized for biliary-pancreatic malignancy, concurrent ADHF is linked to increased mortality risk and various in-hospital adverse complications. Additional long-term studies are required for a comprehensive understanding of this association.

The Impact of Biliary Injury on the Recurrence of Biliary Cancer and Benign Disease after Liver Transplantation: Risk Factors and Mechanisms.

Liver transplantation is known to generate significant inflammation in the entire organ based on the metabolic profile and the tissue's ability to recover from the ischemia-reperfusion injury (IRI). This cascade contributes to post-transplant complications, affecting both the synthetic liver function (immediate) and the scar development in the biliary tree. The new occurrence of biliary strictures, and the recurrence of malignant and benign liver diseases, such as cholangiocarcinoma (CCA) and primary sclerosing cholangitis (PSC), are direct consequences linked to this inflammation. The accumulation of toxic metabolites, such as succinate, causes undirected electron flows, triggering the releases of reactive oxygen species (ROS) from a severely dysfunctional mitochondrial complex 1. This initiates the inflammatory IRI cascade, with subsequent ischemic biliary stricturing, and the upregulation of pro-tumorigenic signaling. Such inflammation is both local and systemic, promoting an immunocompromised status that can lead to the recurrence of underlying liver disease, both malignant and benign in nature. The traditional treatment for CCA was resection, when possible, followed by cytotoxic chemotherapy. Liver transplant oncology is increasingly recognized as a potentially curative approach for patients with intrahepatic (iCCA) and perihilar (pCCA) cholangiocarcinoma. The link between IRI and disease recurrence is increasingly recognized in transplant oncology for hepatocellular carcinoma. However, smaller numbers have prevented similar analyses for CCA. The mechanistic link may be even more critical in this disease, as IRI causes the most profound damage to the intrahepatic bile ducts. This article reviews the underlying mechanisms associated with biliary inflammation and biliary pathology after liver transplantation. One main focus is on the link between transplant-related IRI-associated inflammation and the recurrence of cholangiocarcinoma and benign liver diseases of the biliary tree. Risk factors and protective strategies are highlighted.

Differences in cancer rates among adults born between 1920 and 1990 in the USA: an analysis of population-based cancer registry data

Trends in cancer incidence in recent birth cohorts largely reflect changes in exposures during early life and foreshadow the future disease burden. Herein, we examined cancer incidence and mortality trends, by birth cohort, for 34 types of cancer in the USA. In this analysis, we obtained incidence data for 34 types of cancer and mortality data for 25 types of cancer for individuals aged 25-84 years for the period Jan 1, 2000, to Dec 31, 2019 from the North American Association of Central Cancer Registries and the US National Center for Health Statistics, respectively. We calculated birth cohort-specific incidence rate ratios (IRRs) and mortality rate ratios (MRRs), adjusted for age and period effects, by nominal birth cohort, separated by 5 year intervals, from 1920 to 1990. We extracted data for 23 654 000 patients diagnosed with 34 types of cancer and 7 348 137 deaths from 25 cancers for the period Jan 1, 2000, to Dec 31, 2019. We found that IRRs increased with each successive birth cohort born since approximately 1920 for eight of 34 cancers (pcohort<0·050). Notably, the incidence rate was approximately two-to-three times higher in the 1990 birth cohort than in the 1955 birth cohort for small intestine (IRR 3·56 [95% CI 2·96-4·27]), kidney and renal pelvis (2·92 [2·50-3·42]), and pancreatic (2·61 [2·22-3·07]) cancers in both male and female individuals; and for liver and intrahepatic bile duct cancer in female individuals (2·05 [1·23-3·44]). Additionally, the IRRs increased in younger cohorts, after a decline in older birth cohorts, for nine of the remaining cancers (pcohort<0·050): oestrogen-receptor-positive breast cancer, uterine corpus cancer, colorectal cancer, non-cardia gastric cancer, gallbladder and other biliary cancer, ovarian cancer, testicular cancer, anal cancer in male individuals, and Kaposi sarcoma in male individuals. Across cancer types, the incidence rate in the 1990 birth cohort ranged from 12% (IRR1990 vs 1975 1·12 [95% CI 1·03-1·21] for ovarian cancer) to 169% (IRR1990 vs 1930 2·69 [2·34-3·08] for uterine corpus cancer) higher than the rate in the birth cohort with the lowest incidence rate. The MRRs increased in successively younger birth cohorts alongside IRRs for liver and intrahepatic bile duct cancer in female individuals, uterine corpus, gallbladder and other biliary, testicular, and colorectal cancers, while MRRs declined or stabilised in younger birth cohorts for most cancers types. 17 of 34 cancers had an increasing incidence in younger birth cohorts, including nine that previously had declining incidence in older birth cohorts. These findings add to growing evidence of increased cancer risk in younger generations, highlighting the need to identify and tackle underlying risk factors. American Cancer Society.

Effectiveness of palliative photodynamic therapy for unresectable biliary cancer. Systematic review and meta-analysis

A systematic review and meta-analysis was aimed to assess the effectiveness of palliative photodynamic therapy for unresectable malignant tumors of the biliary system in order to justify the feasibility of including photodynamic therapy (PDT) in the complex treatment of this category of patients. Publications in the databases PubMed Central, the bibliographic database of scientifi citations of the RSCI, and the Cochrane library were considered. Heterogeneity was assessed graphically using forest plots and statistically using tau2 and I2 statistics. A meta-analysis of 5-year survival revealed a statistically signifiantly longer pooled estimate of the survival period in groups where PDT was used – 339±161 days (95% CI 25-710; p &lt; 0.001) compared to groups where PDT was not used – 83±16 days (95% CI 33-100; p &lt; 0.001). Heterogeneity among studies was found to be statistically insignifiant (I2 = 29%, p = 0.23). A meta-analysis of the risk difference for adverse events revealed a statistically signifiantly lower risk (-0.2306; 95% CI -0.3917-0.0696; p = 0.005) of adverse events after PDT compared with the comparison group. Heterogeneity among studies was found to be statistically insignifiant (I2 = 0%, p = 0.35). There were no signifiant publication biases in either meta-analysis. The presented meta-analysis demonstrated that PDT may be the method of choice in the palliative complex treatment of patients with unresectable cholangicarcinomas, increasing the ˝ve-year survival of patients along with the absence of increased risks of postoperative complications in comparison with other methods of palliative surgical treatment.

Second line chemotherapy for advanced biliary cancer: FOLFOX versus FOLFIRI: Analysis of retrospective and prospective data

Aim. To evaluate the efficacy and toxicity of second-line polychemotherapy according to FOLFOX or FOLFIRI regimen in patients with biliary tract tumours after progression during first-line chemotherapy (CT). Materials and methods. The study is based on the analysis of retrospective and prospective data on the examination and treatment of 94 patients with biliary cancer of grades T1-4N0-2M0-1 followed-up and treated at the N.N. Blokhin National Medical Research Center of Oncology from 2015 to 2023. All patients were divided into 2 groups: Group 1 (FOLFOX, n=47) and Group 2 (FOLFIRI, n=47). In Group 1, patients received the recommended FOLFOX second-line CT regimen. Patients in Group 2 received FOLFIRI regimen. The endpoints were overall survival (OS) and incidence of grade 3-4 adverse events. Results. The study included 94 patients. In the FOLFOX group, the median OS was 13.0 months (1-year OS was 57.8±7.4%); for the FOLFIRI group, the median OS was 12.3 months (1-year OS was 54.4±7.3%). The toxicity profiles of FOLFOX and FOLFIRI were acceptable and consistent with those reported for the regimens. According to the grade 3–4 toxicity data, diarrhea was significantly more common in the FOLFIRI group (p=0.014), and neurotoxicity was more common in the FOLFOX group (p=0.006). During the second-line CT, the frequency of grade 1–4 toxicities in the groups did not differ: 18 (38.3%) events in the FOLFOX group and 19 (40.0%) events in the FOLFIRI group. Conclusion. Our results of evaluating the efficacy and toxicity of the second-line polychemotherapy regimens show that the FOLFOX and FOLFIRI CT regimens have equal efficacy in patients with advanced biliary tract cancer with a good performance according to the ECOG scale, who previously received the first-line therapy with a combination of gemcitabine with a platinum agent (cisplatin or oxaliplatin); also, our data demonstrate similar toxicity profiles of these regimens.

Palliative Interventions in Advanced Cholangiocarcinoma

AbstractPatients with advanced cholangiocarcinoma have poor prognosis and often experience severe tumor-related symptoms. Malignant biliary obstruction and cancer pain are common complications associated with advanced cholangiocarcinoma. We review percutaneous palliative interventions that can improve quality of life for these patients.

Pathophysiological features of acute liver failure caused by cholestasis [

Acute liver failure is a syndrome that occurs in 20-59% of patients with liver pathology and is one of the main causes of death in 40% of patients with mechanical jaundice of benign origin and in more than 70% of cases of tumor obstruction of the biliary tract and cancer of caput pancreas. In most cases, the syndrome is a consequence of acute liver damage (viral or drug-induced). Still, it can occur with longterm obstructive jaundice, be the first manifestation of Wilson’s disease, autoimmune chronic hepatitis, or superinfection of the hepatitis D virus against the background of chronic hepatitis B. The aim of the work was to study the pathophysiological features of the development of acute liver failure in patients with bile outflow disorders. The pathogenesis of acute liver failure caused by cholestasis is based on the damage and death of hepatocytes due to impaired blood circulation in the liver, as well as the toxic effect on the parenchyma of both the etiological factors themselves and their metabolites. The first week from the onset of symptoms is very important and usually accompanied by a systemic inflammatory response syndrome with significant consequences. At the same time, the main factors influencing the results of treatment of patients at different points in time are the combination of the critical functional reserve of the liver and the nature and severity of liver damage. In the case of the development of a systemic inflammatory response syndrome, there is a further increase in inflammation, which has a systemic nature and leads to the failure of other organs. Under these circumstances, understanding the pathophysiological features of the course of acute liver failure makes it possible to carry out the necessary diagnostic measures on time and offer appropriate therapy.

Effect of immune checkpoint inhibitor administration timing on survival outcomes in advanced biliary tract cancers: A single-center propensity score matching analysis.

e16186 Background: Circadian rhythms in the immune system and anti-tumor immune responses have not received adequate attention in terms of their impact on cancer immunotherapy. Recent advances in immune checkpoint inhibitors (ICIs) have marked a significant breakthrough in the treatment of advanced biliary tract cancer (BTC), but not all patients benefit from this therapy. Our study aimed to investigate whether the timing of ICI administration affects the treatment outcomes in BTC patients. Methods: We included patients with advanced BTC patients at West China Hospital of Sichuan University who received at least two ICI treatments from October 2019 to May 2023, with follow-up until December 2023. The primary outcome was overall survival (OS), with secondary outcomes including progression-free survival (PFS), objective response rate (ORR), and adverse event incidence. Propensity score matching (1:2 ratio, nearest-neighbor caliper width of 0.1) and COX regression were used to analyze the relationship between the proportion of ICI administrations after 16:30 and both OS and PFS, while the Chi-square test was used to compare the ORR and adverse event rates between groups. Results: A total of 207 patients were eligible for analysis. Before matching, 37 patients had more than 20% of their ICI administrations after 16:30, and 170 had less than 20%. After matching, 34 patients receiving more than 20% of ICIs after 16:30 were compared with 65 who did not. The former group showed significantly shorter OS (median 10 months [95%CI: 8-14 months] vs. 17 months [95%CI: 12-20 months], HR = 2.067 [95%CI: 1.226-3.485, P = 0.00645]) and PFS (median 5 months [95%CI: 4-7 months] vs. 9 months [95%CI: 8-12 months], HR = 2.093 [95%CI: 1.315-3.331, P = 0.00183]), with these results remaining robust after multivariate Cox regression analysis. No significant difference in ORR (χ^2 = 2.287, p = 0.131) was observed. Safety analysis showed no difference in the incidence of adverse events, including Grade 3/4 adverse events, immune-related adverse events, and medication discontinuation due to adverse events (all p &gt; 0.050). Sensitivity analyses in patients receiving at least three ICI treatments revealed similar results. Conclusions: The timing of ICI administration influences the efficacy of immunotherapy in advanced biliary cancer, with administrations before 16:30 associated with better survival outcomes. Further research with larger sample sizes and prospective studies is needed to validate these findings.

Clinical validation of Northstar response: A novel methylated ctDNA therapy response monitoring assay in patients with advanced gastrointestinal cancers.

e16000 Background: Circulating tumor DNA (ctDNA) offers a non-invasive method to comprehensively assess tumors. While most assays for therapy response monitoring rely on variant allele frequencies, methylated ctDNA has shown promise. However, accuracy has been limited by quantification precision. The CLIA-approved Northstar Response assay quantifies over 550 hyper-methylated loci and has demonstrated a 10-fold increase in detection signal over tissue-informed assays. Methods: We present an interim analysis from an ongoing prospective, observational study designed to assess the clinical validity of Northstar Response as a tool to monitor therapeutic response without prior tumor tissue. Our study aims to include 100 advanced GI cancer patients undergoing systemic therapies for advanced disease. Serial ctDNA measurements are collected at baseline, approximately every 30 days post-treatment initiation, and with imaging assessments. The primary endpoint is concordance between ctDNA and RECISTv1.1 criteria for disease response until progression or death. Results: Baseline ctDNA characteristics were examined from 44 patients, with 23 undergoing at least two longitudinal blood collections and subsequent imaging. The median age in this cohort was 65.5 years, with a male predominance (70.5%) and a majority identifying as White (79.5%). Cancers included esophageal (18.2%), hepatocellular (29.5%), biliary (15.9%) and colorectal (15.9%), among others. A majority (59.1%) had both primary and metastatic lesions. Baseline methylation scores ranged from 280 in biliary cancers to 100,000 in colorectal cancers. Those on second-line treatments had lower scores than first or third-line therapies. Methylation scores decreased in patients responding to treatment, indicating that these scores have the potential to serve as indicators of therapeutic efficacy. Conclusions: Baseline methylation scores differ across GI tumor types, disease burdens, and treatment lines, reflecting the complexity of using methylation as a biomarker. Northstar Response has shown initial promise in monitoring therapy response in GI cancers. More mature data, which will further elucidate the assay's clinical utility, will be presented at the meeting.