Early-stage Cancer Patients Research Articles

An enzymatic reaction-based SERS saliva analysis microporous array chip for chiral differentiation and high-throughput detection of D-amino acids.

ARaman-active boronate modified surface-enhanced Raman scattering (SERS) microporous array chip based on the enzymatic reaction was constructed for reliable, sensitive, and quantitative monitoring of D-Proline (D-Pro) and D-Alanine (D-Ala) in saliva. Initially, 3-mercaptophenylboronic acid (3-MPBA) was bonded to Au-coated Si nanocrown arrays (Au/SiNCA) via Au-S bonding. Following this, H2O2 obtained from D-amino acid oxidase (DAAO)-specific catalyzed D-amino acids (D-AAs) further reduced 3-MPBA to 3-hydroxythiophenol (3-HTP) with a new Raman peak at 882cm-1. Meanwhile, the original characteristic peak at 998cm-1 remained unchanged. Therefore, the I882/I998 ratio increased with increasing content ofD-AAs in the sample to be tested, allowing D-AAs to be quantitatively detected. TheAu/SiNCA with large-area periodic crown structure prepared provided numerous, uniform "hot spots," and the microporous array chip with 16 detection units was employed as the platform for SERS analysis, realizing high-throughput, high sensitivity, high specificity and high-reliability quantitative detection of D-AAs (D-Pro and D-Ala). The limits of detection (LOD) were down to 10.1µM and 13.7µM throughout the linear range of 20-500µM. The good results of the saliva detection suggested that this SERS sensor could rapidly differentiate between early-stage gastric cancer patients and healthy individuals.

Nomogram to Predict Nodal Recurrence-Free Survival in Early Oral Squamous Cell Carcinoma.

This study aimed to develop and internally validate a prognostic nomogram for predicting nodal recurrence-free survival (NRFS) in patients with early-stage oral squamous cell carcinoma (OSCC) with clinically negative neck lymph nodes. The management of early-stage oral cancer patients with clinically negative neck lymph nodes (cN0) remains controversial, especially concerning the need for elective neck dissection. Data from a single institution spanning 2010 to 2020 were utilized to develop and evaluate the nomogram. The nomogram was constructed using multivariable Cox regression and LASSO regression analyses to identify independent risk factors for lymph node metastasis. Internal validation was performed using bootstrap resampling to assess the nomogram's predictive accuracy. A total of 930 cN0 patients with T1 and T2 stage OSCC were randomly divided into training and validation cohorts (8:2 ratio). Independent risk factors for lymph node metastasis included tumor pathological grade (well: reference, moderate/poor: OR 1.69), cT (cT1: reference, cT2: OR 2.01), history of drinking (never: reference, current/former: OR 1.72), and depth of invasion (0 mm < DOI ≤ 5 mm: reference, 5 mm < DOI ≤ 10 mm: OR 1.31). The nomogram, incorporating these variables, demonstrated good predictive accuracy with a C-index of 0.67 (95% CI: 0.58-0.76) in the validation set. In both training and validation groups, the nomogram effectively stratified patients into low-risk and high-risk groups for occult cervical nodal metastases (p < 0.05). The nomogram enables risk stratification and improved identification of occult cervical nodal metastases in clinically node-negative OSCC patients by incorporating tumor-specific and patient-specific risk factors.

203 (PB191): Molecular biomarker testing in Slovenian non-small cell lung cancer patients in early and late stages of the disease

203 (PB191): Molecular biomarker testing in Slovenian non-small cell lung cancer patients in early and late stages of the disease

1665P Awareness of illness, psychological difficulties, and resources across life ages in early stage and metastatic cancer patients

1665P Awareness of illness, psychological difficulties, and resources across life ages in early stage and metastatic cancer patients

Live-Cell Invasive Phenotyping Uncovers ALK2 as a Therapeutic Target in LKB1-Mutant Lung Cancer.

The acquisition of invasive properties is a prerequisite for tumor progression and metastasis. Molecular subtypes of KRAS-driven lung cancer exhibit distinct modes of invasion that contribute to unique growth properties and therapeutic susceptibilities. Despite this, pre-clinical strategies designed to exploit growth within the context of invasion are lacking. To address this, we designed an experimental system to screen for targetable signaling pathways linked to active early 3D invasion phenotypes in different molecular subtypes of KRAS-driven lung adenocarcinoma (LUAD). Combined live-cell imaging of human bronchial epithelial cells in a 3D invasion matrix and transcriptomic profiling identified mutant LKB1-specific upregulation of BMP6. LKB1 loss increased BMP6 signaling, which induced the canonical iron regulatory hormone hepcidin. Intact LKB1 was necessary to maintain BMP6 signaling homeostasis and restrict ALK2/BMP6-fueled growth. Pre-clinical studies in a Kras/Lkb1-mutant syngeneic mouse model and in a xenograft model showed potent growth suppression by inhibiting the ALK2/BMP6 signaling axis with single agent inhibitors that are currently in clinical trials. Lastly, BMP6 expression was elevated in LKB1-mutant early-stage lung cancer patient tumors. These results are consistent with a model where LKB1 acts as a 'brake' to iron regulated growth and suggest that ALK2 inhibition can be used for patients with LKB1-mutant tumors.

A pilot study on ultra-sensitive circulating tumor DNA detection with a novel methylation amplifier probe in colorectal cancer.

10547 Background: Liquid biopsy is extensively researched for detecting cancer-related methylation markers. However, detecting ultra-low methylation signals in liquid biopsies is extremely challenging. In early-stage cancer patients, less than 1% of circulating cell-free DNA (cfDNA) is tumor tissue-derived DNA (ctDNA), presenting a low signal-to-noise ratio for effective tumor marker detection. Methods: Here, we introduce Methylation Amplifier Probe for Low-signal Enrichment (MAPLE), a method for designing ultra-short hybrid capture probes (25-55 nt). By reducing the length of the probes, MAPLE enhances their intolerance to DNA base mismatches, thereby significantly improving their ability to specifically bind and enrich the targeted methylation haplotypes. A panel consisting of 13,218 CRC-related methylation haplotypes was constructed for validation. 42 samples from patients with cancer and 43 gender/age matched control samples were processed for the panel validation. All the DNA samples underwent bisulfite conversion, library preparation and parallelly hybridized with two capture panels composed with conventional probes (120 nt) or the MAPLE probes, demonstrating its effectiveness in increasing cancer signal-to-noise ratio in the final NGS data. Results: With MAPLE, in the final NGS data, ratio of CRC-related methylation haplotypes reads (signal) in patient’s plasma samples increased from 7% (conventional) to 28% (MAPLE). At 20M total raw reads (1000x sequencing depth), the MAPLE panel detects over four times the targeted haplotype fragments compared to the conventional panel. For a cohort including 42 patients (I-III:24, IV:18) with CRC and 43 gender/age matched controls, the MAPLE panel aided by a machine-learning classifier detected patients with a sensitivity of 0.83 and a specificity of 0.95. Conclusions: This pilot study highlights the potential of ultra-short probes in capturing cancer-related methylation haplotypes, advancing towards an early detection test for pan-cancer.

Organic small molecule catalytic PET-RAFT electrochemical signal amplification strategy for miRNA-21 detection

Quantitative detection of the cancer-associated biomarker miRNA-21 is essential for the prevention and treatment of early-stage cancer patients. In the early diagnosis of cancer, due to the low concentration of miRNA in the organism, it is necessary to develop a fast, simple, highly sensitive and specific method using signal amplification techniques. Herein, a photo-induced electron/energy transfer reversible addition-fragmentation chain transfer polymerization signal amplification electrochemical biosensor was developed. Peptide nucleic acid was used as the recognition probe for miRNA-21 and the chain transfer agent (4-cyano-4-(dodecylsulfonylsulfanylthiocarbonyl)sulfonylpentanoic acid) bearing a carboxylic acid group was successfully conjugated with a phosphate group in the presence of ZrOCl2 to form the phosphate-Zr(IV)-carboxylic acid complex. Subsequently, the polymerization of the monomer (ferrocenylmethyl methacrylate) was achieved by blue light irradiation in the presence of erythrosin B (higher triple quantum yield) and triethanolamine (increases electron transfer rate). With this sophisticated signal amplification biosensing platform, low detection limit of 12.4 aM was achieved for miRNA-21. The biosensor reduces costs and simplifies experimentation while ensuring high sensitivity and selectivity. Meanwhile, the biosensor exhibits excellent anti-interference ability in serum samples and has great potential for practical applications in the early prevention of cancer.

Tumor necrosis serves as an important pathological characteristic of stage I-II colon cancer.

The long-term prognosis of colon cancer patients remains little changed with relatively high mortality and morbidity. Since the most widely used prognostic parameter TNM staging system is less satisfactory in predicting prognosis in early-stage cancers, numerous clinicopathological factors, including tumor necrosis, have been proposed for prognosis stratification, but substantial evidences are still lacking for early-stage colon cancer. In the retrospective study, a total of eligible 173 stage I-II colon cancer patients, who received tumor radical resection and lymphadenectomy in the local hospital between January 1, 2010, and December 31, 2018, were enrolled for analyzing the prognostic role of tumor necrosis. The primary endpoints included 5-year overall survival (OS) and progression-free survival (PFS). The median follow-up of enrolled early-stage colon cancer patients was 58.3 months. The 2-year and 5-year OS rates were 88.3% and 68.2%, respectively, and the 2-year and 5-year PFS rates were 85.6% and 62.7%, respectively. Seventy-eight patients (45.1%) were diagnosed with tumor necrosis by pathological examination. Demographic analysis revealed a significant association of tumor necrosis with larger tumor size and a marginal association with vascular invasion. Kaplan-Meier survival curves demonstrated that tumor necrosis was associated with worse OS (log-rank P = 0.003) and PFS (log-rank P = 0.002). The independent unfavorable prognostic effect of tumor necrosis was further validated in univariate and multivariate Cox regression analysis (hazard ratio = 1.91 (1.52-2.40), P = 0.004). The current study confirmed the independent prognostic role of tumor necrosis from pathological review in early-stage colon cancer patients. This pathological criterion promises to help in identifying high-risk subgroup from early-stage colon cancer patients, who may benefit from strict follow-up and adjuvant therapy.

Empowerment-Led Guided Self-Help Intervention for Symptom Burden in Breast Cancer Women Treated With Ovarian Function Suppression: A Randomized Trial Protocol.

Ovarian function suppression (OFS) treatment causes breast cancer patients' estrogens to fall rapidly to postmenopausal levels, and the 5-year treatment duration and 28-day treatment cycles place a heavy physical and psychological symptom burden on them, which in turn directly or indirectly affects the survival benefit. Managing symptom burden early in treatment is critical, but OFS-related studies have yet to be seen. Self-management is essential for patients' symptom burden. However, self-help management is hampered by patients' lack of knowledge, skills, motivation, etc. Guided self-help intervention (GSH) provides a feasible approach. Empowerment theory is a promising theoretical framework to guide self-management. A prospective two-arm parallel randomized controlled single-blind clinical trial will be conducted to investigate the effect of symptom burden GSH based on empowerment theory in breast cancer patients in the early stages of OFS treatment. A block randomization method is used to allocate 144 patients to either the control or intervention group. The program is conducted according to the OFS return-to-hospital treatment cycle. The intervention group will receive a total of two rounds and five sessions of empowering GSH, lasting at least 15 weeks in total; the control group will receive only usual nursing care. Symptom burden and related metrics will be assessed at baseline and 1, 3, and 6 months after OFS treatment, and changes between and within groups will be explored. This paper adhered to the SPIRIT and CONSORT guidelines. These results will help to validate the GSH in symptom burden management for breast cancer patients in OFS treatment early stages. It enriches its symptom burden management research and may provide implications for the whole cycle of OFS treatment patients.

Outcomes after fertility-sparing surgery of early-stage ovarian cancer: A nationwide population-based study.

Fertility-sparing surgery (FSS) is an alternative choice of young patients who have not completed their family planning and still have fertility needs. The aims of this study were to compare the outcomes of early-stage epithelial ovarian cancer (EOC) patients undergoing FSS and radical comprehensive staging surgery (RCS), and the suitability of FSS. A total of 1297 patients aged between 20 and 44 years with newly diagnosed early-stage EOC were recruited from the Taiwan Cancer Registry database between 2009 and 2017. Site-specific surgery codes were used to distinguish patients in FSS group or RCS group. Cancer-specific survival (CSS) was evaluated using Kaplan-Meier method with log-rank test and Cox regression model. There were 401 and 896 patients in FSS and RCS group. Patients in FSS group were with younger age and mostly had Stage I disease. In contrast, patients in RCS group were older. There were more Stage II, high-grade (Grade 3) disease, and adjuvant chemotherapy in RCS group. Stage and tumor grade were two independent factors correlating with CSS and the type of surgery showed no effect on CSS (HR: 1.09, 95% CI: 0.66-1.77, p = 0.73) in multivariable analysis. In multivariable analysis, the clear cell carcinoma group who underwent FSS demonstrated better CSS compared to those in the RCS group (HR: 0.28, 95% CI: 0.06-0.82, p = 0.04). A total of 17 women who underwent FSS developed second malignancies of the uterine corpus or contralateral ovary. FSS can be a safe alternative procedure in selected young patients of Stage I EOC who have fertility desire. Endometrial biopsy before or during FSS and regular surveillance to detect recurrence are mandatory for ovarian cancer patients undergoing FSS.

Exosomal LINC00853 promotes progression of gastric cancer via the MAP17/PDZK1/AKT signaling pathway

Although rare, there is ongoing research into biomarkers that predict the onset and recurrence of gastric cancer, particularly focusing on substances found in exosomes. Long non-coding RNAs (lncRNAs) have garnered attention for their potential in diagnosing gastric cancer.This study investigates the role of lncRNAs in gastric cancer, focusing on their presence in exosomes as potential biomarkers for the disease's onset and recurrence. We utilized the ArrayStar Human LncRNA array 2.0 to analyze lncRNA expression in tissues from early-stage gastric cancer patients. Our analysis highlighted LINC00853, which was significantly upregulated in cancer tissues and implicated in promoting epithelial-mesenchymal transition via the MAP17/PDZK1/AKT pathway. Functional studies on AGS and MKN74 gastric cancer cell lines demonstrated that LINC00853 facilitates cell proliferation, invasion, and migration. Additionally, RNA immunoprecipitation and electrophoretic mobility shift assays confirmed LINC00853 interaction with MAP17. Importantly, LINC00853 was also detected in exosomes from both patient samples and cell lines, and its downregulation led to decreased tumorigenicity in AGS cells. These findings suggest that both cellular and exosomal LINC00853 contribute to gastric cancer pathogenesis and may serve as valuable biomarkers for the disease.

Abstract 5060: Role of molecular driver mutations in recurrence of early stage laryngeal cancer following narrow field definitive radiotherapy

Abstract PURPOSE/OBJECTIVES Recurrent early-stage laryngeal cancer poses profound clinical and prognostic dilemmas. The primary endpoint of this study was to identify patient exome differences between early-stage laryngeal cancer patients who responded or rapidly progressed following definitive, narrow field radiotherapy. Our study offers the first exploration of mutation patterns in early-stage laryngeal head and neck squamous cell carcinoma (HNSCC) patients receiving curative radiation therapy. MATERIALS/METHODS We identified 36 early-stage laryngeal (T1 = 8, T1a = 4, T1b = 2, T1c = 1, T2 = 20, NA =1) HNSCC patients from the University of Kansas Medical Center treated with definitive narrow field radiotherapy to 63-70 Gray (gy) dose. Whole exome sequencing was performed in all patients. Patients were stratified into “responders” (never failed, N=14) and “non-responders” (recurrence &amp;lt;12 months, N=21). Most non-responder patients with local recurrence underwent total salvage laryngectomy (TSL, N=18). All patients underwent whole exome sequencing. The Genome Analysis Toolkit (GATK) was used for pre-processing and functional annotation of variants. Cancer driver genes were detected for each group using the OncodriveCLUST algorithm. Differentially mutated genes were assessed using Fisher’s exact or exact McNemar’s test at P &amp;lt; 0.05. Tumor mutational burden (TMB) comparisons employed the Wilcoxon rank-sum test with the same threshold. For pathway analysis in Reactome and Ingenuity, a P &amp;lt; 0.1 was used for exploratory significance. RESULTS Mutation analysis identified distinct cancer driver genes between responders, (N=3), non-responders (N=36), and post-TSL (N=4). Among 75 genes with significant pre-treatment mutation differences between responders and non-responders, KCNT2 and AGAP6 were exclusively mutated in non-responders (OR=0, P=0.005 and OR=0, P=0.027, respectively), ADAMTS7 was solely mutated in responders (OR=inf, P=0.019), and PLEC showed more mutations in responders (OR=11.6, P=0.006). Pathway analysis showed these genes were involved in the RND2 GTPase cycle, protein O-glycosylation related diseases, and apoptotic pathways. Post-treatment analysis indicated an enrichment of mutations in apoptosis regulation pathways, with genes like PLEC being more frequently mutated in responders than in non-responders or TSL patients. In addition, we observed in non-responders that they trended towards higher median pre-treatment TMB compared to responders (7.98 vs 6.16, P=0.072). There was no significant difference in TMB between TSL patients and responders or non-responders pre-treatment. CONCLUSION Our analysis reveals distinct mutation patterns in early-stage laryngeal cancer patients by response to radiotherapy and the potential role of these mutated genes in apoptosis related pathways. Citation Format: Aaron Segura, Emily Nissen, Chris Lominska, Ryan Morse, Deri Morgan, Prakash Neupane, Dong Pei, Devin Koestler, Randall Kimple, Umamaheswar Duvvuri, Kevin Sykes, Sufi Thomas, Rohit Nallani, Lisa Shnayder, Kiran Kakarala, Emrullah Yilmaz, Andres Bur. Role of molecular driver mutations in recurrence of early stage laryngeal cancer following narrow field definitive radiotherapy [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 5060.

Abstract 2566: Molecular characteristic profile in early colorectal cancer with V600E and non-V600E BRAF mutations

Abstract Background: The BRAF V600E mutation in colorectal cancer (CRC) is a significant indicator of poor prognosis, especially in tumors exhibiting microsatellite instability (MSI). It is more common on the right side of the colon but can occur anywhere within the colon. Although other BRAF mutations existed, current research primarily focused on BRAF V600E. Most clinical data sets were centered on advanced colorectal cancer. There was limited understanding of the molecular characteristics of early-stage colorectal cancer patients with BRAF mutations, which impacted postoperative prognosis management, including refining adjuvant therapy regimens. Therefore, we analyzed the molecular characteristics of early-stage CRC surgical patients. Methods: Tumor tissue from 767 early-stage CRC patients diagnosed between 2021 to 2022 in China were analyzed using NGS (panel on 733 gene) to validate the mutation characteristics. Tumor specimens were tested for the BRAF mutation and MSI status. Result: Among 767 early CRC cases tested, BRAF mutations accounted for 6.52% (50/767), with 62% (31/50) being BRAF V600E, followed by 14% (7/50) for BRAF D594G. Notably, there were two cases of fusion variations, TRIM24-BRAF, and one case of BRAF copy gain. Among the BRAF mutation population, 11 cases were MSI-H, with 8 of them being BRAF V600E/MSI-H. Only one MSH-H patient had a germline mutation in the MLH1 gene, with a concurrent mutation in BRAF K601T.Interestingly, when comparing the mutation profiles of the BRAF V600E population with those of the non-V600E BRAF mutation population, we found distinct co-mutated genes despite both being BRAF mutations. In the BRAF V600E group, the top three frequently mutated genes were TP53 (52%), RNF43 (32%), and SMAD4 (32%). Additionally, the BRAF V600E/MSI-H subgroup presented a distinct mutation profile, with minimal occurrences of TP53 and SMAD4 mutations. In the non-V600E BRAF mutation group, the top three frequently mutated genes were TP53 (84%), APC (63%), and KRAS (32%). Conclusions: In examining the mutation profile characteristics of early colorectal cancer with BRAF mutations, the proportion of BRAF V600E/MSI-H appeared to have been lower than that reported in advanced cases. Furthermore, in terms of the frequency of co-mutated genes, it seemed that BRAF V600E had exhibited a higher malignant driving mutation effect as a single gene, while non-V600E mutations had required more cooperative tumor suppressor genes or oncogenes. Analyzing the molecular characteristics of early colorectal cancer patients with V600E and non-V600E BRAF mutations could help improve postoperative management and further our understanding of tumor progression. Citation Format: Zhang Quan An. Molecular characteristic profile in early colorectal cancer with V600E and non-V600E BRAF mutations [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 2566.

Abstract 737: Arrays of 3D ECM-embedded fibroblast clusters for characterization of ECM remodeling by primary cancer associated fibroblasts and for evaluation of drugs attenuating fibrotic ECM remodeling

Abstract Chronic fibrosis can lead to organ failure and is also associated with cancer, where the tumor is interpreted as a chronic wound, and the fibrotic tumor environment drives disease progression. Fibrosis occurs in an inflammatory environment where macrophages are activated, and fibroblasts transdifferentiate into myofibroblasts. Activated macrophages stimulate the myofibroblasts to produce excessive amounts of collagen-rich ECM. Changes in proteolytic activity and high contractile forces that myofibroblasts apply onto their tissue environment, further lead to extensive remodeling of the healthy tissue matrix into a scar matrix. Similar activity is displayed by cancer-associated fibroblasts (CAFs) in tumors. Intervening with the excessive ECM remodeling by activated fibroblasts represents a candidate therapeutic strategy to normalize the architecture of fibrotic and malignant tissues. We developed a screening platform using an assay based on automated image guided injection of clusters of fibroblasts in wells of multi-well plates preloaded with a collagen-rich ECM network. The identical x-y-z position, spacing, and size of the ECM-embedded fibroblast clusters in each well facilitates automated real time confocal microscopy and quantitative image analysis algorithms. We use this setup for automated quantitative analysis of ECM remodeling activity of CAFs obtained from early-stage colorectal cancer patients. We find that CAFs from these early-stage lesions display increased ECM remodeling capacity as compared to patient matched normal fibroblasts. We then use the same setup to screen a series of compounds for their ability to attenuate ECM remodeling triggered by TGFb-activated primary human fibroblasts. We detect known and novel pathways, and we identify small molecule inhibitors with a promising efficacy versus toxicity profile. Lastly, we detect a previously unknown concentration-dependent side effect of ALK5 inhibitors that leads to the identification of a novel profibrotic pathway and indicates that caution is warranted for the clinical application of ALK5 inhibitors. Citation Format: Erik H. J. Danen. Arrays of 3D ECM-embedded fibroblast clusters for characterization of ECM remodeling by primary cancer associated fibroblasts and for evaluation of drugs attenuating fibrotic ECM remodeling [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 737.

Abstract 2420: Evaluating circulating tumor DNA (ctDNA) as a prognostic biomarker utilizing a tissue-free epigenomic assay in early-stage triple negative breast cancer (TNBC)

Abstract Background: ctDNA has shown promise as a prognostic biomarker in early-stage solid tumors. Current breast cancer clinical guidelines do not recommend routine screening for metastatic disease outside of clinical features suggestive of disease recurrence. The detection of ctDNA may be a useful biomarker for the management of early-stage cancer patients to identify patients who are at high risk of recurrence. Methods: Patients with stage II or III TNBC undergoing neoadjuvant docetaxel and carboplatin chemotherapy on a clinical trial (NCT02124902) followed by surgery were included in this study. Blood samples were prospectively collected prior to, during, and after completion of neoadjuvant chemotherapy, post-surgery, and throughout pre-specified surveillance time points (every 6 months for 5 years). Plasma samples were analyzed using Guardant Reveal powered by Infinity, a tissue-free, multiomic assay that interrogates differentially methylated regions of DNA using an applied bioinformatics filter optimized to detect breast cancer DNA from non-cancerous cell-free DNA and estimate quantitative tumor fraction. Samples were sequenced and resulted blinded to the patients’ clinical data. Results: A total of 120 patients with evaluable plasma samples were included in this study. At baseline prior to chemotherapy, ctDNA was detected in 75% (54/72) of patients. Baseline ctDNA detection was higher in node-positive cancers (100%; 29/29) versus node-negative cancers (58%; 25/43; p&amp;lt;0.0001). ctDNA quantity was higher in node-positive cancers (p&amp;lt;0.0001), and in stage III versus stage II disease (p=0.0179). During surveillance follow-up, the sensitivity for detecting any distant metastatic recurrence was 71% (5/7). Among patients with samples drawn within one year of recurrence, the sensitivity for detecting distant recurrence was 83% (5/6) with a sample-level specificity of 98% (186/190) and a patient-level specificity of 94% (63/67). ctDNA detection prior to recurrence had a median lead time of 5.0 months (range, 4.6-5.6). Notably, the detection of ctDNA during follow-up was associated with worse recurrence-free (HR 23.3, 95% CI 2.70-201, p&amp;lt;0.0001) and distant-recurrence free survival (HR 29.3, 95% CI 1.86-461, p&amp;lt;0.0001). Conclusions: ctDNA is detected with a tissue-free MRD assay with high sensitivity and specificity for distant recurrence in early-stage TNBC. Furthermore, the presence of ctDNA during follow-up is a prognostic indicator. Additional prospective studies are needed to assess the clinical utility of ctDNA monitoring in early-stage TNBC. Citation Format: Foluso O. Ademuyiwa, Cynthia X. Ma, Katherine Weilbaecher, Rama Suresh, Lindsay Peterson, Ron Bose, Nusayba Bagegni, Caron E. Rigden, Ashley Frith, Katherine Clifton, Andrew Davis, Derek Dustin, Mingyang Cai. Evaluating circulating tumor DNA (ctDNA) as a prognostic biomarker utilizing a tissue-free epigenomic assay in early-stage triple negative breast cancer (TNBC) [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 2420.

Exploring non-curative endoscopic submucosal dissection: Current treatment optimization and future indication expansion.

The increasing popularity of endoscopic submucosal dissection (ESD) as a treatment for early gastric cancer has highlighted the importance of quality assessment in achieving curative resections. This article emphasizes the significance of evaluating ESD quality, not only for curative cases but also for non-curative ones. Postoperative assessment relies on the endoscopic curability (eCura) classification, but management strategies for eCuraC-1 tumour with a positive horizontal margin are unclear. Current research primarily focuses on comparing additional surgical procedures in high-risk patients, while studies specifically targeting eCuraC-1 patients are limited. Exploring management strategies and follow-up outcomes for such cases could provide valuable insights. Furthermore, the application of molecular imaging using near-infrared fluorescent tracers holds promise for precise tumour diagnosis and navigation, potentially impacting the management of early-stage gastric cancer patients. Advancing research in these areas is essential for improving the overall efficacy of endoscopic techniques and refining treatment indications.

Endoscopic resection vs. endoscopic resection plus chemoradiation for T1 stage colorectal cancer: a real-world retrospective cohort study.

Early-stage colorectal cancer (CRC) patients treated with either endoscopic resection (ER) alone or combined ER with chemoradiotherapy (CRT) have unknown survival rates. A national descriptive epidemiological study was conducted to compare the long-term survival of patients with T1 stage CRC with or without the two different treatment options. Our study identified the records of patients with T1-stage CRC between 2010 and 2018 by searching the Surveillance, Epidemiology, and End Results (SEER) database. Long-term survival was compared using Kaplan-Meier methods and Cox proportional hazard models based on patient demographic and cancer parameters. After propensity score matching (PSM), 825 T1-stage CRC patients were finally enrolled in this study, with 718 patients treated with ER and 107 patients treated with ER + CRT. The overall survival (OS) and cancer specific survival (CSS) rates were similar between the two treatment options (OS: P=0.47; CSS: P=0.28). According to subgroup analysis, older patients and patients with rectal tumor locations exhibited significantly higher OS and CSS rates in the ER + CRT group than in the ER group (OS: P<0.0001; CSS: P<0.0001). The findings from the SEER database showed that OS and CSS rates were similar between the ER and ER + CRT treated groups. Older patients and patients with rectal cancer benefited the most from ER + CRT treatment.

A pancancer analysis of the clinical and genomic characteristics of multiple primary cancers

Multiple primary cancer (MPC) denotes individuals with two or more malignant tumors occurring simultaneously or successively. Herein, a total of 11,000 pancancer patients in TCGA database (1993–2013) were divided into MPC or non-MPC groups based on their history of other malignant tumors. The incidence of MPC has risen to 8.5–13.1% since 2000. Elderly individuals, males, early-stage cancer patients, and African Americans and Caucasians are identified as independent risk factors (p < 0.0001). Non-MPC patients exhibit significantly longer overall survival (OS) and disease-free survival (DFS) (p = 0.0038 and p = 0.0014). Age (p < 0.001) and tumor staging at initial diagnosis (p < 0.001) contribute to this difference. In our center, MPC was identified in 380 out of 801 tumor events based on SEER criteria. The peak occurrence of secondary primary was about 1–5 years after the first primary tumor, with a second small peak around 10–15 years. Multiple tumors commonly occur in the same organ (e.g., breast and lung), constituting 12.6%. Certain cancer types, notably skin cutaneous melanoma (SKCM), exhibit significantly higher tumor mutational burden (TMB) in the MPC group (17.31 vs. 6.55 mutations/MB, p < 0.001), with high TMB associated with improved survival (p < 0.001). High TMB in MPC may serve as a predictor for potential immunotherapy application.

Factors influencing quality of life in early-stage upper gastrointestinal cancer patients in Nanchong city: a qualitative study.

To identify the determinants of quality of life (QoL) among early-stage upper gastrointestinal cancer (UGIC) patients in Nanchong City to inform the development of targeted treatment plans. In this retrospective study, 642 patients diagnosed with UGIC were included. A phenomenological approach was employed, involving in-depth face-to-face interviews to explore patients' real-life experiences with QoL, with an emphasis on spiritual and psychological aspects. Data analysis followed Colaizzi's seven-step method. Statistical analyses included one-way Analysis of Variance (ANOVA), t-tests, binary logistic regression, and Pearson correlation tests. QoL was significantly reduced in patients with early-stage GI cancer (P<0.001), with prevalent symptoms of anxiety and depression necessitating focused psychological interventions and enhanced medical care. Influential factors on QoL included income, health insurance coverage, illness duration, and levels of anxiety and depression (P<0.001). A strong negative correlation was observed between QoL scores and both the Hamilton Anxiety Scale (r=-0.7808, P<0.001) and the Hamilton Depression Rating Scale (r=-0.7493, P<0.001). This study underscores the substantial impact of anxiety and depression on the QoL of patients with early-stage UGIC. The findings provide a theoretical basis for implementing comprehensive long-term care strategies.

Preoperative and pre-chemotherapy CA-125 levels in high-risk early-stage ovarian cancer – An NRG/GOG study

ObjectivesTo determine clinical significance of preoperative and pre-chemotherapy CA-125 in high-risk early-stage epithelial ovarian cancer patients. MethodsAll patients with stage IA/IB and grade 3, stage IC, clear cell, or completed resected stage II cancer were enrolled in a phase III trial and treated with chemotherapy. Kaplan-Meier method and Cox proportional hazards model were used for statistical analyses. Results427 patients with high-risk early-stage ovarian cancer were enrolled. Of 213 patients with preoperative CA-125 data, 79% had elevated CA-125. Median preoperative CA-125 level was 103 U/mL. Patients with ≤10, 11–15, and > 15 cm tumors had median preoperative CA-125 levels of 62, 131 and 158 U/mL, respectively (p = 0.002). For the 350 patients with data for pre-chemotherapy CA-125 level, 69% had elevated pre-chemotherapy CA-125 above 35 U/mL with median value of 65 U/mL. However, age, race, stage, cell type and grade of disease were not correlated with CA-125 levels before and after surgery. On multivariate analysis, elevated pre-chemotherapy CA-125 independently predicted worse recurrence-free survival (HR = 2.13, 95% CI: 1.23–3.69; p = 0.007) and overall survival (HR = 1.99, 95% CI: 1.10–3.59; p = 0.022) after adjusting for age, stage, cell type and grade of disease. Compared to those with normal CA-125, patients with elevated pre-chemotherapy CA-125 had lower recurrence-free survival (RFS, 87% vs. 75%; p = 0.007) and overall survival (OS, 88% vs. 82%; p = 0.02). However, preoperative CA-125 was not prognostic of RFS (p = 0.699) or OS (p = 0.701). ConclusionsPreoperative CA-125 was elevated in nearly 80% of high-risk early-stage ovarian cancer patients. Pre-chemotherapy CA-125 was associated with recurrence-free and overall survival; however, preoperative CA-125 was not prognostic.