Carbohydrate Antigen Research Articles

Treatment patterns and survival outcomes in patients with non-metastatic early-onset pancreatic cancer.

The incidence of patients with early-onset pancreatic cancer (EOPC; age ≤ 50 years at diagnosis) is on the rise, placing a heavy burden on individuals, families, and society. The role of combination therapy including surgery, radiotherapy, and chemotherapy in non-metastatic EOPC is not well-defined. To investigate the treatment patterns and survival outcomes in patients with non-metastatic EOPC. A total of 277 patients with non-metastatic EOPC who were treated at our institution between 2017 and 2021 were investigated retrospectively. Overall survival (OS), disease-free survival, and progression-free survival were estimated using the Kaplan-Meier method. Univariate and multivariate analyses with the Cox proportional hazards model were used to identify prognostic factors. With a median follow-up time of 34.6 months, the 1-year, 2-year, and 3-year OS rates for the entire cohort were 84.3%, 51.5%, and 27.6%, respectively. The median OS of patients with localized disease who received surgery alone and adjuvant therapy (AT) were 21.2 months and 28.8 months, respectively (P = 0.007). The median OS of patients with locally advanced disease who received radiotherapy-based combination therapy (RCT), surgery after neoadjuvant therapy (NAT), and chemotherapy were 28.5 months, 25.6 months, and 14.0 months, respectively (P = 0.002). The median OS after regional recurrence were 16.0 months, 13.4 months, and 8.9 months in the RCT, chemotherapy, and supportive therapy groups, respectively (P = 0.035). Multivariate analysis demonstrated that carbohydrate antigen 19-9 level, pathological grade, T-stage, N-stage, and resection were independent prognostic factors for non-metastatic EOPC. AT improves postoperative survival in localized patients. Surgery after NAT and RCT are the preferred therapeutic options for patients with locally advanced EOPC.

Prognostic usefulness of the C-reactive protein-albumin-lymphocyte (CALLY) index as a novel biomarker in patients undergoing colorectal cancer surgery

BackgroundThe C-reactive protein (CRP)–albumin–lymphocyte (CALLY) index is a novel immuno-nutritional biomarker based on the levels of CRP, serum albumin, and lymphocyte count. This study examined the prognostic value of the CALLY index in patients with colorectal cancer undergoing curative surgery. MethodsBetween 2010 and 2017, 578 patients with stage II-III colorectal cancer who underwent curative resection were enrolled. The CALLY index was defined as (albumin × lymphocyte)/(CRP × 104). We investigated the association of the CALLY index with disease-free survival (DFS) and overall survival (OS). ResultsThe cutoff value of the CALLY index was determined to be 2. Of the 578 patients, 175 (30%) had a preoperative CALLY index <2. In multivariate analysis, the pre-operative carcinoembryonic antigen (CEA) level (p = 0.003), cell differentiation (p = 0.045), venous invasion (p = 0.036), Tumor-Node-Metastasis stage (p < 0.001), and CALLY index score <2 (p = 0.006) were independent predictors of DFS. Meanwhile, preoperative carbohydrate antigen (CA)19-9 levels (p = 0.019), lymphatic invasion (p = 0.018), preoperative platelet (p = 0.037), and CALLY index score <2 (p = 0.007) were independent predictors of OS. ConclusionThe CALLY index may be an independent prognostic biomarker for long-term outcomes in patients with colorectal cancer.

Recurrent Intrahepatic Cholangiocarcinoma: A 10-Point Score to Predict Post-Recurrence Survival and Guide Treatment of Recurrence.

Although up to 50-70% of patients with intrahepatic cholangiocarcinoma (ICC) recur following resection, data to predict post-recurrence survival (PRS) and guide treatment of recurrence are limited. Patients who underwent resection of ICC between 2000 and 2020 were identified from an international, multi-institutional database. Data on primary disease as well as laboratory and radiologic data on recurrent disease were collected. Factors associated with PRS were examined and a novel scoring system to predict PRS (PRS score) was developed and internallyvalidated. Among 986 individuals who underwent resection for ICC, 588 (59.6%) patients developed recurrence at a median follow up of 20.3months. Among patients who experienced a recurrence, 97 (16.5%) underwent re-resection/ablation for recurrent ICC; 88 (15.0%) and 403 (68.5%) patients received intra-arterial treatment or systemic chemotherapy/supportive therapy, respectively. Patient American Society of Anesthesiologists (ASA) class > 2 (1 point), primary tumor N1/Nx status (1 point), primary R1 resection margin (1 point), primary tumor G3/G4 grade(1 point), carbohydrate antigen (CA) 19-9 > 37 UI/mL (2 points) at recurrenceand carcinoembryonic antigen (CEA) > 5ng/mL (2 points) at recurrence, as well as recurrent bilateral disease (1 point) and early recurrence (1 point) were included in thePRS score. The PRS score successfully stratified patients relative to PRS and demonstrated strong discriminatory ability (C-index 0.70, 95% confidence interval 0.68-0.72). While a PRS score of 0-3 was associated with a 3-year PRS of 62.5% following resection/ablation for recurrent ICC, a PRS score > 3 was associated with a low 3-year PRS of 35.5% (p = 0.03). The PRS score demonstrated strong discriminatory ability to predict PRS among patients who had developed recurrencefollowing initial resection of ICC. The PRS score may be a useful tool to guide treatment among patients with recurrent ICC.

Abstract 3937: Investigating the role of fibulin 3 in pancreatic tumorigenesis

Abstract Pancreatic ductal adenocarcinoma (PDA) is a highly lethal malignancy with a five-year survival rate of less than 11%, making it one of the deadliest cancers. Notably, 95% of PDA cases exhibit KRAS mutations, contributing to highly dysregulated cell signaling networks. Despite extensive research into the interplay of various oncogenic pathways in pancreatic tumorigenesis, targeted therapies against these signaling networks have displayed modest efficacy, with most patients rapidly developing therapeutic resistance. Recent studies highlight the significance of the carbohydrate antigen 19-9 (CA19-9) as a functional biomarker linked to disease progression and resistance. However, understanding the detailed functions of CA19-9-modified proteins in PDA has been limited due to the lack of adequate models for synthesizing CA19-9. To address this challenge, we have developed unique mouse and 3D organoid culture models capable of producing CA19-9. CA19-9 elevation in mice with KRAS-mutations results in an aggressive PDA phenotype through increased tumor proliferation and microenvironment (TME) remodeling. Furthermore, our research has identified Fibulin 3 (FBLN3), an extracellular matrix glycoprotein, as a secreted, CA19-9-modified protein that stimulates tumorigenesis. In this study, we found that FBLN3 not only facilitates tumor proliferation but also drives epithelial-mesenchymal transition (EMT) and promotes STAT3 pathways activation in the CA19-9pos, KRAS-mutant PDA organoids. Additionally, in both CA19-9pos, KRAS-mutant PDA mouse models and human PDA, FBLN3 is expressed by cancer-associated fibroblasts (CAFs), suggesting its role in TME remodeling. These findings have significant implications for providing novel insights into PDA biology and paracrine signaling mechanisms, identifying FBLN3 as a potential therapeutic target for the improved treatment of this devastating disease. Citation Format: Hyemin Song, Jasper Hsu, Xiaoxue Lin, Satoshi Ogawa, Vasiliki Pantazopoulou, Kristina Peck, Chelsea Bottomley, Shira Okhovat, McKenna Stamp, Kassidy Curtis, Jeffrey D. Esko, Dannielle D. Engle. Investigating the role of fibulin 3 in pancreatic tumorigenesis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3937.

Abstract 6037: Copper-67 as a next-generation radioconjugate warhead for cancer therapy

Abstract Background and Purpose: Antibody drug conjugates (ADCs) have shown promise as cancer treatments. However, the efficacy of ADCs has been limited in solid tumors and can come with significant toxicities. Radioconjugates utilize various radionuclides that are chelated and can be conjugated to small molecules, peptides and antibodies. We propose Targeted Copper Theranostics (TCTs) which use copper-64 to image tumors and beta-emitting copper-67 to irradiate and kill cancer cells using various molecular targets of oncological relevance. We have evaluated the efficacy of copper-67 based therapy in three formats; peptides, antibodies, and pre-targeting of antibody conjugates in relevant tumor mouse models. Benefits of copper-67 [half-life, 61.8 h; 100% β- energy in the range of 0.18-0.56 MeV] include high purity, high specific activity, manufacturing in a centralized distribution model at high yields on electron accelerators, and half-life suitable to various targeting formats. Copper-64 and copper-67 provide multiple logistical benefits relative to other radionuclides including Ga-68, F-18 and Lu-177. Methods: We evaluated three tumor-targeting moieties conjugated to a sarcophagine bifunctional chelator (SAR), including: a peptide dimer targeting prostate specific membrane antigen (SAR-bisPSMA); an antibody 5B1, targeting the PDAC-specific biomarker carbohydrate antigen-19-9 (CA19-9); and a Tz-TCO IDEEA huA33 antibody/sarcophagine tetrazine conjugate targeting transmembrane glycoprotein A33. Various doses were administered of [67Cu]Cu-SAR-bisPSMA in LNCAP xenografts; [67Cu]Cu-SAR-5B1 (~10 μg) in FC1245 Ft2Ab PDAC tumor-bearing C57BL/6 mice; and [67Cu]Cu-MeCOSAR-Tz in athymic nude mice bearing A33 antigen-expressing SW1222 human colorectal carcinoma xenografts 72 hours after administration of huA33-TCO. Results: Administration of either 7.5, 15 or 30 MBq of [67Cu]Cu-SAR-bisPSMA increased overall survival relative to the control group. Similarly, after administration of 4, 11, 18 MBq of [67Cu]Cu-5B1, treated groups enhanced overall survival to 32 days compared to control (14 days). Pre-targeting using ~18.5, 37.0 or 55.5 MBq or fractionated dosing of two 27.8 MBq doses of [67Cu]Cu-MeCOSAR-Tz showed efficient tumor growth reduction with enhanced overall survival for treated mice pre-administered huA33-TCO, from 68 days to &amp;gt;200 days (dose dependent) compared to control (21 days). Conclusion: We report the inhibition of tumor growth with minimal radiotoxicity and each format demonstrated significantly improved overall survival compared to controls. Collectively our results demonstrated that TCTs using the sarcophagine chelator with copper-67 are effective radioconjugates across multiple formats with an acceptable safety profile. Copper-67-based TCTs are being translated in multiple theranostic clinical trials in the USA and Australia. Citation Format: Matt Harris, Kurt Gehlsen, Lachlan McInnes, Jason Lewis. Copper-67 as a next-generation radioconjugate warhead for cancer therapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6037.

Abstract 6038: Copper-67 based targeted radiotherapy primes immunologically cold PDAC for immunotherapy

Abstract Background and Purpose: Immune checkpoint therapy (ICT) has revolutionized cancer treatment however efficacy remains dismal for some cancers, including pancreatic cancers. Strategies to enhance immune responses include combining ICT with other existing cancer therapies. Targeted radiotherapy (TRT) uses a radiolabeled cancer-targeting vector, allowing for systematic delivery of specific radiation to all tumor sites while minimizing radiation exposure to healthy tissues. We propose Targeted Copper Theranostics (TCTs) as a TRT, utilizing copper-67 to irradiate and prime immunologically “cold” pancreatic adenocarcinoma (PDAC) and evaluate the efficacy of copper-67-based TRT-ICT combination therapy. Methods: We evaluated two tumor-targeting vectors conjugated to a sarcophagine macrobicyclic chelator (SAR), an antibody—5B1, targeting the PDAC-specific biomarker carbohydrate antigen-19-9 (CA19-9), and a peptide RGD, targeting the αvβ3 integrin receptor, which is highly expressed in some PDAC tumors. We administrated ~1.1 MBq of [64Cu]Cu-SAR-bisRGD (~0.1 μg) or [64Cu]Cu-SAR-5B1 (~10 μg) to FC1245 Ft2Ab PDAC (a murine PDAC cell line expressing CA19-9) tumor-bearing C57BL/6 mice and performed biodistribution studies at 1 and 4 h for [64Cu]Cu-SAR-bisRGD-injected mice and at 24 and 48 h for [64Cu]Cu-5B1-injected mice. [67Cu]Cu-SAR-bisRGD- and [67Cu]Cu-SAR-5B1-based dose escalation studies and the combination of a copper-67-based TRT and ICT were performed to evaluate therapeutic efficacy of copper-67-based TRT and potential synergistic effects of combination therapy. Results: Tumor uptake of [64Cu]Cu-SAR-bisRGD is ~5 %ID/g at 4h-post injection, and tumor uptake of [64Cu]Cu-SAR-5B1 is ~55 %ID/g 24h-post injection. In dose escalation studies, administration of ~11, 22, and 37 MBq of [67Cu]Cu-SAR-bisRGD (~1 μg) or administration of ~4, 11, 18 MBq of [67Cu]Cu-5B1(~150 μg) improved overall survival to 25 or 32 days respectively, compared to the control cohort (14 days). Based on weekly whole-blood analyses, no significant radiotoxicity was observed in mice receiving various doses of TRTs. The combination of 11 MBq of either [67Cu]Cu-SAR-bisRGD or [67Cu]Cu-SAR-5B1 in combination with either antiPD-L1/PD1 or antiCTLA4, improved overall survival by ~7 days compared to ICT-treated control groups. Conclusion: Biodistribution studies demonstrated relatively high tumor specific uptake for [64Cu]Cu-SAR-bisRGD and [64Cu]Cu-SAR-5B1. Dose escalation study results suggest copper-67-based TRT could effectively inhibit tumor growth with minimal radiotoxicity. The combination of TRT with ICTs improved overall survival compared to single-ICT-treated control groups. Collectively, our results strongly support the hypothesis that TRT with [67Cu]Cu-SAR-bisRGD or [67Cu]Cu-SAR-5B1 could prime immunologically “cold” pancreatic adenocarcinoma (PDAC) to be responsive to ICTs. Citation Format: Yi Rao, Tara Viray, Kurt Gehlsen, Matt Harris, Lachlan McInnes, Olufolake Majekodunmi, Jason Lewis. Copper-67 based targeted radiotherapy primes immunologically cold PDAC for immunotherapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6038.

Abstract 3125: TCX-101, a novel antibody-drug conjugate targeting a tumor-associated carbohydrate antigen for the treatment of solid tumors

Abstract Tumor-associated carbohydrate antigens (TACAs) are short oligosaccharides expressed on the surface of cancer cells and play key roles in cellular communication, immune evasion, apoptosis and metastasis. TACAs are therefore interesting targets for antibody-based therapies in cancer. We have generated an antibody (TCX-101) against a TACA structure with improved binding affinity compared to other monoclonal antibodies (mAbs) against the same target as shown by surface plasmon resonance (~ 10x superior KD), as well as high level of specificity against glycan species related to the target, as accessed by glycan array, flow cytometry, and immunocytochemistry or immunofluorescence. Immunohistochemistry studies on fresh-frozen tissue microarrays showed high expression of the target in various solid tumors (e.g. gastrointestinal, lung, and breast) and only low expression in normal tissues. In vitro, TCX-101 has ~ 4x higher maximum binding, ~ 2x faster binding kinetics, ~ 4x faster cellular internalization and induces ~ 2x higher antibody-dependent cellular cytotoxicity than a reference antibody. Monomethyl auristatin E (MMAE) was used in a drug-antibody ratio (DAR) of 4 to generate an antibody-drug conjugate (ADC). This ADC was effective in in vitro toxicity assays against murine B16 melanoma cells induced to express the target (measurable effect on WT cells), as well as human breast cancer MCF7 WT cells (~ 25x less activity on target-knockout MCF7 cells, Table 1). When tested in vivo, TCX-101 was highly effective in two different xenograft mouse models (B16, MCF7) with more than 95% tumor growth inhibition compared to vehicle, and no signs of toxicity (no weight loss, no histophatological findings). A fully humanized version of TCX-101 with improved binding properties (EC50 6.27 nM vs. 8.13 nM) was generated and will be evaluated in further in vivo experiments. In conclusion, TCX-101 is a promising ADC for the treatment of various solid tumors. IC50 [nM] TCX-101-MMAE 4 DAR B16 KI 7.64 B16 WT no killing observed MCF7 WT 1.97 MCF7 KO 45.97 Citation Format: Fausto G. Gomes, Francesco Muraca, Gustavo M. Schmidt Garcia Moreira, Kathrin Rösch, Maria Bräutigam, Peter Sondermann, Matthias Ocker. TCX-101, a novel antibody-drug conjugate targeting a tumor-associated carbohydrate antigen for the treatment of solid tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3125.

Abstract 7289: PancreaAlert: Intelligent nanoengineered biosensor for pancreatic cancer

Abstract Introduction: Pancreatic cancer accounts for 3% of cancer cases and 7% of cancer deaths in the United States. It is currently in the third position with respect to cancer-related deaths, and it is expected to move to second place as of 2040. This is mainly due to its diagnosis in the later stage. If detected in the first or second stage surgery can be performed thus increasing the patient’s survival rate. The current methods of diagnosis cannot do early stage or asymptomatic detection. So, detecting cancer-specific biomarkers can aid in the prognosis. Serum protein-based biomarkers carbohydrate antigen CA242, CA19-9, and carcinoembryonic antigen CEA are specific to pancreatic cancer. Thus, in this preliminary study, we aim to develop a nanoengineered electrochemical biosensor combined with machine learning to detect pancreatic cancer-specific biomarkers CA242, CA19-9, and CEA. Methodology: Nanoengineering the biosensor: The gold working electrode of the gold- biosensor (DRP-250AT) was coated with graphene oxide nano colloidal solution and kept in UV overnight for the graphene oxide nanosheet to crosslink with the working electrode. Detection of biomarkers using an electrochemical biosensor: First, a Crosslinker (DSP) was added to ethanol cleaned biosensor to bind the analytes. Following that antibody specific to each biomarker were added to the biosensors. The addition of TBS superblock prevented non-specific binding. Then different concentrations of biomarkers were added, and the corresponding sensor was subjected to various electrochemical analyses such as electrochemical impedance spectroscopy and voltammetry. SEM-EDAX analysis: The antigen-antibody binding on the biosensor's surface was confirmed. Automation and machine learning: Python code was developed to automate the analysis process and machine learning models (support vector machine and neural network) were used to classify the concentrations into various risk levels. The sensitivity of the developed tool was high when compared with conventional methods like ELISA and confocal microscopy. Results: From the electrochemical studies we found that with increasing concentration of biomarkers, there was a trend in output parameters: capacitance, resistance, impedance and area under the curve. By analyzing this trend, the concentrations of biomarkers can be detected. Using this data as input the machine learning model (accuracy greater than 80%) classified the concentrations into risk levels (normal, low risk, and high risk). Significance: Nanoengineering with graphene oxide nanosheets enhances the sensitivity of electrochemical biosensors. Automation and machine learning models help in the analysis of large datasets produced by this sensor. Overall, this device aids in the prognosis of pancreatic cancer. Our preliminary results are encouraging but more thorough research is required to make this diagnostic tool a working application. Citation Format: Meenal Karunanidhi, Hemalatha Kanniyappan, Edith Zhan, Ruth Mathew, Yani Sun, Junyi Wu, Yan Yan, Gnanasekar Munirathinum, Mathew T. Mathew. PancreaAlert: Intelligent nanoengineered biosensor for pancreatic cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 7289.

Abstract 2613: Treatment of solid tumors with antibody drug conjugates targeting aberrant O-glycoproteins

Abstract The lack of antibodies with sufficient cancer selectivity is currently limiting the treatment of solid tumors by immunotherapies. Many solid tumors display aberrant glycosylation that results in the expression of tumor-associated carbohydrate antigens (TACAs) distinct from healthy tissues. Targeting aberrantly glycosylated glycopeptide epitopes provides the cancer selectivity needed for immunotherapy of solid tumors. However, only a few such glycopeptide epitopes have been targeted to date. We have developed a strategy to predict, design, and produce cancer-specific antibodies targeting novel O-glycoprotein epitopes with exquisite cancer specificity. Our mAbs avoid on-target off-tumor toxicity due to the specificity of aberrant glycosylation, and cover a broad range of cancer indications, including breast, lung, colon, pancreatic, and ovarian cancer. Additionally, our antibodies can be used as an IHC companion diagnostic and can be functionalized across a number of modalities, including next-generation CAR-T, T-cell bispecifics, and antibody-drug-conjugates (ADCs).Here, we present two novel antibodies, GO-08 and GO-013, selectively targeting cancer-specific Tn-glycosylated proteins in a site-specific manner with low nanomolar affinities. GO-008 and GO-013 were collectively shown to be highly cancer-selective by immunohistochemistry of sections from a large array of different squamous and adenocarcinomas, including triple-negative breast cancer, lung cancer, gastric cancer, ovarian cancer, pancreatic, and colorectal cancer. The two antibodies were functionalized utilizing ConjuAllTM technology, conjugating the microtubule disrupting payload MMAE via a site-specific beta-glucuronidase cleavable linker. ConjuAllTM functions as a plasma stable, tumor labile linkage, and due to the minimal expression pattern of beta-glucuronidase in healthy tissues, reduces both off- and on-target toxicity due to the minimization of release of free payload in non-tumor tissues. The ADCs based on GO-08 and GO-013 (LCB45A and LCB22A) demonstrated target-specific cytotoxicity invitro and in vivo with tumor elimination in breast and lung PDX models. GO-013 conjugated to MMAE (LCB22A) was well tolerated in cynomolgus monkey toxicity studies. Moreover, the ADCs selectively kill target cells in a human mixed organotypic cancer model without affecting healthy cells, indicating tolerability and safety. The combination of specificity of TACA targeting to differentiate ADC binding from healthy tissue and ConjuAll’s tumor selective payload release promises to enable an excellent anti-cancer therapy. Citation Format: Aaron C. Groen, Nisha Shrestha, Boris Klebanov, Byeongjun Yu, BeomYong Lee, Chul-Woong Chung, Changsik Park, Mikkel K. Aasted, Sally Dabelsteen, Hans H. Wandall. Treatment of solid tumors with antibody drug conjugates targeting aberrant O-glycoproteins [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2613.

A unique case of a typical pancreatic ductal adenocarcinoma that initially presented with a cystic component but underwent morphological changes.

A 66-year-old man was initially suspected of having a microcystic serous cystic neoplasm based on magnetic resonance imaging findings of a multifocal mass measuring 46mm in the pancreatic head, with a cystic component showing a high signal on T2-weighted images. The tumor marker levels were within normal limits. However, contrast-enhanced computed tomography revealed thick cyst walls with delayed staining, which was atypical for serous cystic neoplasms; therefore, the patient was followed up closely. Twenty-two months later, the delayed contrast area was enlarged, carbohydrate antigen 19-9 levels were elevated, and 18 F-fluorodeoxyglucose-positron emission tomography revealed increased accumulation, indicating a potentially malignant lesion. Pancreatoduodenectomy was performed and histopathological examination confirmed the diagnosis of normal-type pancreatic carcinoma with predominantly poorly differentiated cells. Based on the pathological findings and a literature review, it is highly likely that this case represents pancreatic ductal adenocarcinoma with a cystic structure from the beginning. While distinguishing pancreatic ductal adenocarcinoma from other pancreatic cystic tumors, such as serous cystic neoplasms, is critical owing to differing treatments and prognoses, caution is warranted as they may exhibit similar imaging features, as observed in our patient.

Tumor Size Combined With CA-19 Level Improves Prediction of Survival of Patients With Pancreatic Adenocarcinoma Undergoing Perioperative Chemotherapy and Resection.

Five-year survival in pancreatic adenocarcinoma is less than 20%. While previous studies have postulated that a carbohydrate antigen 19-9 (CA19-9) threshold could predict outcome of resection, the role for CA19-9 in decision-making remains unclear. This study aims to assess whether CA19-9 levels combined with tumor size improve prediction of post-resection survival. A retrospective analysis was conducted on 109 patients with pancreatic adenocarcinoma who underwent perioperative chemotherapy followed by resection. The primary outcome of mortality was, divided into short (<1year) or prolonged (>2years). Univariate and multivariable analyses compared the tumor size-adjusted CA19-9 between the outcome groups. Twenty-seven (24.78%) and eighty-two (75.23%) patients were in the short survival and prolonged-survival groups, respectively. The mean CA19-9 was significantly greater in the short vs prolonged group (P < .001). Analyzing CA19-9 level by tumor size, the association of high CA19-9 and short survival was significant for small (≤2cm) and large tumor (>4cm), but not for intermediate-size tumors (2-4cm). Adjusting for preoperative variable did not change this association. CA 19-9 in combination with tumor size better identifies patients with prolonged post-resection survival. This prediction is most accurate in patients with either small (≤2cms) or large (>4cms) tumors compared to intermediate-size tumors.

Clinical value of circulating tumour cells in evaluating the efficacy of continuous hepatic arterial infusion among colorectal cancer patients

Few studies have been conducted to evaluate the efficacy of HAIC using circulating tumour cells (CTCs). In this study, a total of 100 patients who received HAIC treatment and CTC detection were selected. The results showed that after HAIC treatment, the levels of CTC, carbohydrate antigen 19-9 (CA19-9) and carcinoembryonic antigen (CEA) decreased. Postoperative progression-free survival (PFS) rates between patients with positive and negative preoperative CTC results, and for CA19-9, CEA were significantly different. The positive rate of CTCs was 61% before chemotherapy and 23% after chemotherapy, and the correlation coefficient between the two was 0.385. Those whose CTC values increased after chemotherapy had shorter PFS rates. CTCs are an independent predictor of recurrence. Patients with CTC-positive results are more susceptible to recurrence. The CTC count in peripheral blood has a close bearing on the postoperative chemotherapy efficacy of patients with CRC and affects patients’ PFS.

A Quest for Survival: A Review of the Early Biomarkers of Pancreatic Cancer and the Most Effective Approaches at Present.

Pancreatic cancer (PC) is the most lethal type of cancer; it has the lowest 5-year survival rate among all other types of cancers. More than half of PC cases are diagnosed at an advanced stage due to PC's insidious and non-specific symptoms. Surgery remains the most efficacious treatment option currently available, but only 10-20% of PC cases are resectable upon diagnosis. As of now, the sole biomarker approved by the United States Food and Drug Administration (US-FDA) for PC is carbohydrate antigen 19-9 (CA19-9); however, its use is limited for early diagnosis. An increasing number of studies have investigated a combination of biomarkers. Lately, there has been considerable interest in the application of a liquid biopsy, including the utilization of microRNAs (miRNAs), circulating tumor DNA (ctDNA), and circulating tumor cells (CTCs). Screening for PC is indicated for high-risk patients; studies on new diagnostic models combined with biomarkers for early detection have also shown promising results in terms of the ability of these models and biomarkers to aid clinicians in deciding on whether to start screening. This review seeks to provide a concise overview of the advancements in relation to existing biomarkers and explore novel strategies for the early detection of PC.

Clinical value of combined detection of Carcinoembryonic Antigen and CA125 in the diagnosis of non-small cell lung cancer combined with Malignant Pleural Effusion.

To investigate the clinical value of combined detection of carcinoembryonic antigen(CEA) and CA125 in the diagnosis of non-small cell lung cancer(NSCLC) combined with malignant pleural effusion. This was retrospective research. Fifty-six NSCLC patients combined with malignant pleural effusion in Baoding No.1 Hospital, China, from January 2020 to January 2022 were recruited as the malignant group, and another 56 NSCLC patients combined with pleural effusion in the same period were recruited as the benign group. Pleural effusion and serum specimens were collected from both groups and their carcinoembryonic antigen (CEA), carbohydrate antigen 125(CA125) and SP70 antigen levels were measured respectively. The differences in index levels between the two groups were compared, and the value of the index in diagnosing NSCLC combined with malignant pleural effusion was analyzed. The positive rates of CEA, CA125 and SP70 antigen in pleural effusion were higher in the malignant group than in the benign group (p>0.05); The positive rates of CEA and CA125 in the malignant group were higher than those in the benign group (p>0.05), with no statistically significant difference between the two groups in the positive rates of SP70 antigen (p>0.05). ROC curve analysis revealed the value of serum CEA and CA12 in the diagnosis of NSCLC combined with malignant pleural effusion, while serum SP70 antigen had no diagnostic value (p>0.05). The combined detection of CEA, CA125 and SP70 antigen boasts a higher diagnostic value for NSCLC-mediated pleural effusion, with higher diagnostic value than the combined detection of serum indexes.

The inflammation score predicts the prognosis of gastric cancer patients undergoing Da Vinci robot surgery.

Neutrophil-to-lymphocyte ratio (NLR), calculated from peripheral blood immune-inflammatory cell counts, is considered a predictor of survival in various cancers. Nevertheless, there is a lack of research into the predictive value of NLR specifically in gastric cancer patients following surgery using the Da Vinci robot. Investigate the objectives of this research, confirm the positive predictive value of NLR in the prognosis of gastric cancer patients undergoing Da Vinci robotic-assisted surgery by comparing its prognostic ability with other inflammation markers and tumor biomarkers. In this retrospective analysis, information from 128 individuals diagnosed with gastric cancer and treated with da Vinci robot-assisted surgery was examined. The study examined various markers in the peripheral blood, including neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), lymphocyte/monocyte ratio (LMR), systemic immune-inflammatory index (SII) prognostic nutrition index (PNI), cancer antigen 125 (CA125), carbohydrate antigen 19-9 (CA19-9), carbohydrate antigen 72-4 (CA72-4), carcinoembryonic antigen (CEA) and alpha-fetoprotein (AFP).To ascertain the prognostic ability and optimal cutoff values of each parameter, operating characteristic curves and the area under the curve were utilized in the analysis. For evaluation of independent prognostic factors, we utilized Kaplan-Meier curves and multifactorial Cox analysis. The variables from the multifactorial Cox analysis were used to construct a nomogram. NLR, LMR, CEA, AFP, primary location, largest tumor size and TNM stage were all found to be significant predictive elements for overall survival (OS). Multivariate Cox identified NLR (P = 0.005), LMR (P = 0.03) and AFP (P = 0.007) as the only separate predictive variables among hematological indicators. The nomogram built using NLR demonstrates excellent predictive performance at 1 year (AUC = 0.778), 3 years (AUC = 0.773), and 5 years (AUC = 0.781). Cross-validation demonstrates that this model has favorable predictive performance and discriminative ability. NLR is an uncomplicated yet potent marker for forecasting the survival result of individuals with gastric cancer following da Vinci robotic surgery, and it possesses considerable predictive significance. The nomogram based on NLR provides patients with a visual and accurate prognosis prediction.

Is multidisciplinary treatment effective for invasive intraductal papillary mucinous carcinoma?

Surgical resection is standard treatment for invasive intraductal papillary mucinous carcinoma (IPMC); however, impact of multidisciplinary treatment on survival including postoperative adjuvant therapy (AT), neoadjuvant therapy (NAT), and treatment for recurrent lesions is unclear. We investigated the effectiveness of multidisciplinary treatment in prolonging survival of patients with invasive IPMC. This retrospective multi-institutional study included 1183 patients with invasive IPMC undergoing surgery at 40 academic institutions. We analyzed the effects of AT, NAT, and treatment for recurrence on survival of patients with invasive IPMC. Completion of the planned postoperative AT for 6 months improved the overall survival (OS), disease-specific survival (DSS), and recurrence-free survival (RFS) of patients with stage IIB and stage III resected invasive IPMC, elevated preoperative carbohydrate antigen 19-9 level, lymphovascular invasion, perineural invasion, serosal invasion, and lymph node metastasis on un-matched and matched analyses. Of the patients with borderline resectable (BR) invasive IPMC, the OS (p = 0.001), DSS (p = 0.001), and RFS (p = 0.001) of patients undergoing NAT was longer than that of those without on the matched analysis. Of the 484 invasive IPMC patients (40.9%) who developed recurrence after surgery, the OS of 365 patients who received any treatment for recurrence was longer than that of those without treatment (40.6 vs. 22.4 months, p < 0.001). Postoperative AT might benefit selected patients with invasive IPMC, especially those at high risk of poor survival. NAT might improve the survivability of BR invasive IPMC. Any treatment for recurrence after surgery for invasive IPMC might improve survival.

Combining prognostic value of serum carbohydrate antigen 19-9 and tumor size reduction ratio in pancreatic ductal adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is a common cancer with increasing morbidity and mortality due to changes of social environment. To evaluate the significance of serum carbohydrate antigen 19-9 (CA19-9) and tumor size changes pre- and post-neoadjuvant therapy (NAT). This retrospective study was conducted at the Chongqing Key Laboratory of Translational Research for Cancer Metastasis and Individualized Treatment, Chongqing University Cancer Hospital. This study specifically assessed CA19-9 levels and tumor size before and after NAT. A total of 156 patients who completed NAT and subsequently underwent tumor resection were included in this study. The average age was 65.4 ± 10.6 years and 72 (46.2%) patients were female. Before survival analysis, we defined the post-NAT serum CA19-9 level/pre-NAT serum CA19-9 level as the CA19-9 ratio (CR). The patients were divided into three groups: CR < 0.5, CR > 0.5 and < 1 and CR > 1. With regard to tumor size measured by both computed tomography and magnetic resonance imaging, we defined the post-NAT tumor size/pre-NAT tumor size as the tumor size ratio (TR). The patients were then divided into three groups: TR < 0.5, TR > 0.5 and < 1 and TR > 1. Based on these groups divided according to CR and TR, we performed both overall survival (OS) and disease-free survival (DFS) analyses. Log-rank tests showed that both OS and DFS were significantly different among the groups according to CR and TR (P < 0.05). CR and TR after NAT were associated with increased odds of achieving a complete or near-complete pathologic response. Moreover, CR (hazard ratio: 1.721, 95%CI: 1.373-3.762; P = 0.006), and TR (hazard ratio: 1.435, 95%CI: 1.275-4.363; P = 0.014) were identified as independent factors associated with OS. This study demonstrated that post-NAT serum CA19-9 level/pre-NAT serum CA19-9 level and post-NAT tumor size/pre-NAT tumor size were independent factors associated with OS in patients with PDAC who received NAT and subsequent surgical resection.

Serum ITIH5 as a novel diagnostic biomarker in cholangiocarcinoma.

Cholangiocarcinoma often remains undetected until advanced stages due to the lack of reliable diagnostic markers. Our goal was to identify a unique secretory protein for cholangiocarcinoma diagnosis and differentiation from other malignancies, benign hepatobiliary diseases, and chronic liver conditions. We conducted bulk RNA-seq analysis to identify genes specifically upregulated in cholangiocarcinoma but not in most other cancers, benign hepatobiliary diseases, and chronic liver diseases focusing on exocrine protein-encoding genes. Single-cell RNA sequencing examined subcellular distribution. Immunohistochemistry and enzyme-linked immunosorbent assays assessed tissue and serum expression. Diagnostic performance was evaluated via receiver-operating characteristic (ROC) analysis. Inter-alpha-trypsin inhibitor heavy chain family member five (ITIH5), a gene encoding an extracellular protein, is notably upregulated in cholangiocarcinoma. This elevation is not observed in most other cancer types, benign hepatobiliary diseases, or chronic liver disorders. It is specifically expressed by malignant cholangiocytes. ITIH5 expression in cholangiocarcinoma tissues exceeded that in nontumorous bile duct, hepatocellular carcinoma, and nontumorous hepatic tissues. Serum ITIH5 levels were elevated in cholangiocarcinoma compared with controls (hepatocellular carcinoma, benign diseases, chronic hepatitis B, and healthy individuals). ITIH5 yielded areas under the ROC curve (AUCs) from 0.839 to 0.851 distinguishing cholangiocarcinoma from controls. Combining ITIH5 with carbohydrate antigen 19-9 (CA19-9) enhanced CA19-9's diagnostic effectiveness. In conclusion, serum ITIH5 may serve as a novel noninvasive cholangiocarcinoma diagnostic marker.

EVA1A, a novel and promising prognostic biomarker in colorectal cancer.

The purpose of this study was to investigate the potential of EVA1A as a prognostic biomarker for Colorectal cancer (CRC). The study utilized public databases to analyze the difference in Evala mRNA expression between CRC tumor tissues and adjacent normal tissues. Additionallymunohistochemical staining was performed on 90 paired tissue samples to detect EVA1A expression. The relationship between EVA1A and clinicopathological features was examined, and a Kaplan-Meier survival analysis was conducted. Univariate and multivariate Cox analyses were employed to identify prognostic factors affecting the overall survival (OS) of CRC patients. The analysis revealed a significant increase in Evala mRNA expression in CRC tumor cells compared to normal controls from public databases (P< 0.05). Immunohistochemical staining further confirmed a significant upregulation of EVA1A expression in CRC tissues (P< 0.05). High EVA1A expression was associated with age, pathological M stage, total tumor stage, and Carbohydrate antigen CA19-9 (CA19-9). Kaplan-Meier analysis demonstrated a significant association between high EVA1A expression and poor OS. Univariate and multivariate analysis identified EVA1A as an independent risk factor for CRC prognosis. The study suggests that EVA1A is increased in CRC tumor tissues and may serve as a potential biomarker for poor prognosis in CRC.

Benign Brenner tumor of the ovary: two-dimensional and contrast-enhanced ultrasound features-a retrospective study from a single center.

Benign Brenner tumor (BBT) is a rare ovarian tumor, and there are few discrete reports about its manifestation in an ultrasound. This study sought to investigate the two-dimensional (2D) and contrast-enhanced ultrasound (CEUS) features of this entity. This is a retrospective single-center study. The clinical manifestations, laboratory examination, and ultrasound data of 25 female patients with BBT were confirmed by pathology when they underwent 2D and/or CEUS examination at Ningbo First Hospital from January 2012 to June 2023. The ultrasound findings of the patients were analyzed using the terminology of the International Organization for the Analysis of Ovarian Tumor and were read by two senior sonographers who reached an agreement. Among the all 25 patients, most of them were unilateral, and only one patient was bilateral. Thus, 26 lesions were found: 44.0% (11/25) were in the left and 52.0% (13/25) were in the right. Moreover, 53.84% (14/26) were solid lesions, 15.38% (4/26) were mixed lesions, and 26.92% (7/26) were cystic lesions. Among the solid-type patients, 42.85% (6/14) of the cases were with calcification. Upon laboratory examination, 12.0% (3/25) of the patients had high carbohydrate antigen 125 (CA-125) level, and 19.04% (4/21) of the patients had an elevated carbohydrate antigen724 (CA-724) level in the serum tumor markers. In the hormone test, 14.28% (3/21) were found to have a high postmenopausal estrogen level and 14.28%(3/21) were found to have a high level of follicle-stimulating hormone (FSH). One patient with complex manifestations and three with solid manifestations were examined by CEUS to observe the microcirculation perfusion of the tumor. One with solid and cystic separation was rapidly hyperenhanced and cleared, and the filling subsided faster than the uterus. The postoperative pathological diagnosis was benign Brenner tumor with mucinous cystadenoma. The other three cases were solid adnexal lesions, which showed isoenhancement on CEUS and disappeared slowly, synchronizing with the uterus. The CEUS results were considered as benign tumors and confirmed by pathology. BBT can show ovarian cystic, mixed cystic and solid type, and solid echo in 2D ultrasound. Unilateral ovarian fibrosis with punctate calcification is an important feature of BBT in 2D ultrasound. However, for solid adnexal masses and mixed cystic and solid masses with unclear diagnosis, if CEUS shows isoenhancement or hyperenhancement, the possibility of BBT cannot be excluded.