Tumor Size Research Articles

Comparison of submucosal and subserosal approach in ICG-guided laparoscopic lymphadenectomy in gastric cancer patients: long-term outcomes of a phase 3 randomized clinical trial

Background Previous studies have demonstrated similar short-term efficacy between subserosal (SSA) and submucosal (SMA) approaches for ICG injection in gastric cancer (GC). This study aims to compare the long-term oncological outcomes of these two injection methods for lymph node (LN) tracing in ICG-guided laparoscopic gastrectomy. Materials and methods This study was a phase 3, open-label, randomized clinical trial (FUGES-019). A total of 266 patients with resectable gastric adenocarcinoma (cT1-4a, N0/ +, M0) were enrolled. We report predefined long-term secondary outcomes, including three-year actual overall survival (OS), three-year actual disease-free survival (DFS), and recurrence patterns. Results Of the 266 participants, 259 patients were included in the per-protocol analysis; 129 in the SSA group and 130 in the SMA group. The actual OS in the SSA group (87.6%) was comparable to that in the SMA group (90.8%, P = 0.41), as were the 3-year actual DFS rates (SSA: 82.9% vs. SMA: 88.5%, Log-rank P = 0.19). Per-protocol analysis confirmed the equivalence of the SSA compared with the SMA. The most common type of recurrence was multiple site metastasis (11 of 259[4.24%]), with no differences in recurrence types across cancer stages. Further stratified analysis based on pT, pN staging, tumor size, and BMI showed no significant differences between the two groups. Conclusion The 3-year outcomes of the FUGES-019 trial confirm the equivalence of SSA and SMA in ICG-guided laparoscopic lymphadenectomy for GC, supporting the previous short-term findings. The subserosal approach can be recommended for ICG administration based on clinical considerations.

Evolving Indications for Liver Transplantation for Hepatocellular Carcinoma Following the Milan Criteria

Background/Objectives: Since their introduction in the 1990s, the Milan criteria have been the gold standard of indication for liver transplantation (LT) in patients with hepatocellular carcinoma (HCC). Nevertheless, several institutions have reported wider indication criteria for LT with comparable survival outcomes. Methods: This paper summarizes the recent indications for LT for HCC through a literature review. Results: There are several criteria expanding the Milan criteria, which can be subdivided into the “based on tumor number and size only”, “based on tumor number and size plus tumor markers”, and “based on tumor differentiation” groups, with the outcomes being comparable to those of patients included within the Milan criteria. Besides the tumor size and number, which are included in the Milan criteria, recent criteria included biomarkers and tumor differentiation. Several retrospective studies have reported microvascular invasion (MVI) as a significant risk factor for postoperative recurrence, highlighting the importance of preoperatively predicting MVI. Several studies attempted to identify preoperative predictive factors for MVI using tumor markers or preoperative imaging findings. Patients with HCC who are LT candidates are often treated while on the waiting list to prevent the progression of HCC or to reduce the measurable disease burden of HCC. The expanding repertoire of chemotherapeutic regiments suitable for patients with HCC should be further investigated. Conclusions: There are several criteria expanding Milan criteria, with the outcomes being comparable to those of patients included within the Milan criteria.

Prognostic impact of tumor size on cancer-specific survival for postoperative WHO grade II oligodendroglioma: a SEER-based study

BackgroundWHO grade II oligodendroglioma (OG/II) is a rare primary brain tumor with various outcomes. Our study aims to investigate prognostic factors for postoperative OG/II patients and then evaluate the instructional value of tumor size.MethodsWe retrospectively studied the cases from the Surveillance, Epidemiology, and End Results (SEER) database. Univariate and multivariate Cox analyses and Kaplan-Meier survival curves were used to identify and assess prognostic factors. The optimal cut-off value of tumor size was determined by X-tile analysis and verified by multivariate analyses. Subsequently, Subgroup analyses were performed based on tumor size.Result676 OG/II patients were enrolled in our study. Multivariate Cox analyses revealed that age > 60 (HR 3.52), male (HR 1.48), total resection (HR 0.38), and tumor size (HR 2.04) were independent factors in predicting cancer-specific survival (CCS). The optimal cut-off value for tumor size was 60 mm. Patients with tumor size less than 60 mm, age > 60 (HR 3.82), and radiation (HR 1.58) were associated with worse CSS, while total resection (HR 0.35) was associated with better CSS. Lastly, a tumor size-based nomogram was established objectively and accurately.ConclusionOur study identified four crucial prognostic factors related to CSS in postoperative OG/II patients: age, sex, the extent of recession, and tumor size. A tumor size of 60 mm was an optimal cut-off point for dividing patients into low and high-risk groups. Patients in the low-risk group may not benefit from extended resection and radiation. Tumor size can be a valuable factor for making therapeutic schedules.

Prognostic evaluation of non-muscle invasive bladder cancer with P-CRP and its nomogram

PurposeTo investigate the impact of the product of preoperative platelet count and C-reactive protein (P-CRP) on the postoperative prognosis of patients with non-muscle invasive bladder cancer (NMIBC), and to construct a Nomogram to predict the recurrence-free survival (RFS) of NMIBC patients based on pathological data.MethodsA retrospective analysis was conducted on the clinical data of 164 NMIBC patients who underwent transurethral resection of bladder tumors (TURBT) at the Second Affiliated Hospital of University of South China from January 2013 to December 2019. The endpoint of the study was the RFS. Kaplan-Meier (KM) method and Cox regression were used for analysis to identify independent factors affecting RFS. Then, the Nomogram was used to visualize the results of the multivariate analysis that were statistically significant and related to the RFS of NMIBC patients. Finally, the predictive ability of the model was evaluated using the concordance index (C-index) and calibration curves.ResultsBefore the end of the follow-up, the RFS was 88.3% at 1 year, 75.5% at 2 years, and 58.5% at 3 years. KM curves showed that P-CRP (HR=0.357, 95% CI: 0.204-0.625, P<0.001), number of tumors (HR=2.658, 95% CI: 1.572-4.494, P<0.001), tumor size (HR=2.271, 95% CI: 1.377-3.745, P=0.001), T stage of the tumor (HR=2.026, 95% CI: 1.233-3.329, P=0.005), and tumor G grade (G2: HR=1.615, 95% CI: 0.48-5.433, G3: HR=3.361, 95% CI: 1.022-11.054) were independent factors affecting the RFS of NMIBC patients after TURBT. The Nomogram could estimate the risk of tumor recurrence at 1, 2, and 3 years postoperatively. The Nomogram model incorporating P-CRP parameters had a higher predictive accuracy than the classic model that only included EORTC risk group parameters.ConclusionPreoperative P-CRP has a certain impact on the RFS of NMIBC patients after TURBT. The Nomogram incorporating P-CRP, number of tumors, tumor size, T stage, and tumor pathological grading can better predict the postoperative recurrence risk of NMIBC patients.

A comparative study of surgery versus radiation therapy on the risk of cardiovascular disease mortality in patients with early-stage non-small cell lung cancer

Objective: Non-small cell lung cancer (NSCLC) lung cancer continues to be a substantial issue in public health, and cardiovascular disease (CVD) is also an important cause of death in NSCLC patients. There is a lack of studies comparing the effects of surgery and radiation therapy on the risk of CVD-mortality in patients with early-stage NSCLC. This study planned to compare the effects of surgery alone and radiation therapy alone on the risk of CVD-mortality in patients with early-stage NSCLC. Methods: In this cohort study, the data of 32896 participants with NSCLC at stage I or stage II in 2010-2015 were retrieved from the surveillance, epidemiology, and end results (SEER) database. The primary endpoint of this study was CVD mortality, indicating patients died of CVDs and the follow-up was ended in 2020. Univariable Cox regression model was applied to identify covariates. The associations of surgery or radiation therapy with CVD-mortality in in patients with early-stage NSCLC were evaluated via univariable and multivariable Cox regression models and Fine-Gray competitive risk model. Hazards ratio (HR) and confidence interval (CI) were computed. Results: The median follow-up time was 48.00 (17.00, 60.00) months. There were 854 (6.45%) participants died of CVD in the radiation therapy group and 729 (5.35%) participants died of CVD in the surgery group. After adjusting for confounding factors, the elevated risk of CVD mortality in patients with early-stage NSCLC was observed in patients receiving radiation therapy compared to those receiving surgery (HR=2.33, 95%CI: 2.02-2.69). In the competing risk model, the risk of CVD mortality in patients with early-stage NSCLC was also increased in patients receiving radiation therapy (HR=1.37, 95%CI: 1.2.6-1.55). In the PSM group, the risk of CVD mortality in patients with early-stage NSCLC was also increased in patients who underwent radiation therapy (HR=2.62, 95%CI: 2.12-3.24). Subgroup analysis also revealed that radiation therapy was correlated with increased risk of CVD mortality in NSCLC patients with tumor size ≥50 mm or <50 mm, the original primary site in the left or right, histologic types of squamous cell NSCLC or adenocarcinoma NSCLC, stage I and II, and patients ≥ 65 years or < 65 years. Conclusions: Radiation therapy was associated with elevated risk of CVD mortality compared to surgery in patients with early-stage NSCLC.

Myxoid liposarcoma: treatment outcomes, metastatic pattern and volumetric analysis.

Myxoid liposarcoma (MLPS) is arare subtype of soft tissue sarcoma. This entity has aspecific clinical behavior, characterized with adistinct pattern of hematogenous spread, as well as with aunique radiosensitivity and chemosensitivity. Oncologic results, metastatic patterns and treatment response after multimodal therapy were evaluated in aunicentric patient cohort. Patients with myxoid liposarcoma were retrospectively analyzed in asingle institution analysis (n = 31). Oncologic outcomes were evaluated in 28patients with localized MLPS treated with multimodal therapy in curative intent. Metastatic pattern was analyzed in additional 3patients with initially metastatic disease. In patients treated with concomitant MR-guided hyperthermia in the preoperative setting (n = 7), tumor size response was evaluated longitudinally during radio(-chemo)therapy in thermometry MRIs and before surgery (based on preoperative imaging). The median follow-up was 4.1 ± 1.0years. The most common anatomic localization was the lower extremity (78.6%). The 5‑year rates for oncologic outcomes in 28patients treated in curative intent were 91.7% (± 8.0%) for overall survival (OS), 77.4% (± 11.0%) for local control (LC), 60.1% (± 10.6%) for distant metastasis-free survival (DMFS) and 55.4% (± 11.1%) for disease free survival (DFS). Excellent 5‑year LC (94.7 ± 5.1%) was demonstrated for the cohort excluding 5patients treated for local recurrences. Most patients had good pathologic response (< 10% vital tumor tissue) following neoadjuvant treatment (82.4%, 14/17). However, this did not correlate with oncologic outcomes. Aspecific pattern of distant metastases has been observed, with predilection for soft tissues as the most common metastatic site. Furthermore, no isolated pulmonary metastases were observed. The MR analysis demonstrated asignificant tumor size reduction (≥ 25%) of the initial tumor volume in 85.7% (n = 6/7) patients. No local recurrences and no distant metastases were observed in patients with significant MR size reduction. Sequential MRIs during preoperative radiotherapy of myxoid liposarcoma show distinct patterns of the known size reduction of this specific subentity. Our analysis of metastatic patterns demonstrate mostly soft tissue metastases, no patient experienced isolated pulmonary metastases.

Lesion Conspicuity in Contrast-Enhanced Mammography: A Retrospective Analysis of Tumor Characteristics

Background/Objectives: The aim of this study is to evaluate the impact of tumor characteristics on lesion conspicuity in contrast-enhanced mammography (CEM) and identify factors associated with different levels of conspicuity. Methods: In this retrospective study, we analyzed 552 patients with breast cancer who underwent CEM. Lesion conspicuity was categorized into three levels: 1 (low), 2 (moderate), and 3 (high). Tumor characteristics included age, histological subtype, hormone receptor status, HER2 status, Ki67 index, tumor grade, and molecular subtype. Univariate and multivariate analyses were conducted to assess associations between lesion conspicuity and these factors. Results: Of the 552 cases, the majority showed mass enhancement (78.1%), followed by non-mass enhancement (NME) (16.8%), and a combination of mass and NME (4.0%). Lesion conspicuity was significantly associated with enhancement type on CEM (p &lt; 0.001). High conspicuity (score 3) was predominantly observed in masses (84.8%) compared to NME (7.6%). Larger tumor dimensions (median 20 mm) were also associated with higher conspicuity (p &lt; 0.001). Molecular subtypes differed significantly in conspicuity, with Luminal A tumors showing lower conspicuity compared to HER2-positive and triple-negative breast cancers (p = 0.025). In multivariate analysis, lesion conspicuity was strongly associated with enhancement type (p &lt; 0.001) and tumor dimensions (p &lt; 0.001), while histological subtype and molecular characteristics had no significant independent impact. Conclusions: Lesion conspicuity in CEM is primarily influenced by the type of enhancement and tumor size. Mass-forming lesions, particularly larger ones, are more conspicuous, while NME tends to result in lower conspicuity. These findings suggest that enhancement patterns and tumor dimensions are key factors to consider when interpreting CEM in breast cancer diagnosis.

Gasless single-incision transaxillary endoscopic total thyroidectomy versus conventional open thyroidectomy in patients with papillary thyroid carcinoma based on propensity score matching: a case-control study.

In a previous study, we proposed a modified technique for gasless transaxillary endoscopic total thyroidectomy (ETT) for patients with bilateral papillary thyroid carcinoma (PTC) using a single incision. Whether this method shows non-inferiority to the conventional open approach (COT) remains unclear. This study aims to investigate the safety and feasibility of ETT compared to COT in patients with PTC. We retrospectively analyzed the medical records of cT1-2 PTC patients who underwent total thyroidectomy between April 2020 and December 2022. All patients were diagnosed with bilateral PTC and categorized into ETT and COT groups based on the type of surgery. Propensity score matching (PSM) using nine clinicopathological characteristics was employed to compare the technical safety and short-term oncologic outcomes of ETT and COT, generating 45 pairs of matched patients to reduce potential selection bias. This study was followed by STROBE guideline. After PSM, 90 patients who underwent ETT (n = 45) or COT (n = 45) were included. Age, sex, tumor size, BMI, Hashimoto's thyroiditis, multifocality, extrathyroidal extension, T-stage, and central compartment lymph node metastasis were not different between both groups. Both groups showed similar surgical outcomes, including lymph node yield, complications, and total medical costs. A few patients in each group experienced transient complications, all of which resolved within 6months. No patients had permanent complications. Compared to COT, ETT with a modified technique offers excellent safety and acceptable short-term oncological outcomes in a selected cohort of patients with bilateral papillary thyroid carcinoma. ETT is a safe and feasible alternative to COT.

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

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

Cabergoline-induced NDFIP1 upregulation in pituitary neuroendocrine tumor cells activates mTOR signaling and contributes to cabergoline resistance.

To investigate the molecular mechanisms underlying resistance to dopamine agonists (DA). LC-MS/MS analysis was performed on rat pituitary neuroendocrine tumors (PitNET) cell line GH3 to identify differentially expressed proteins induced by cabergoline (CAB) treatment. A total of 180 human PITNET samples were subjected to transcriptome analysis. Immunohistochemistry (IHC) was conducted on 29 tumor samples to validate NDFIP1 alteration. A xenograft mouse model was established by subcutaneously injecting GH3 cells, with or without NDFIP1 overexpression, into nude mice to investigate tumor growth. PitNET cell lines were treated with CAB. Cell proliferation was assessed using the CCK-8, and protein expression levels were examined through Western blot analysis. CAB treatment upregulated FDFT1 and NDFIP1 protein expression in GH3 cells, with NDFIP1 showing a significant positive correlation with tumor size, as confirmed by IHC results. MMQ and GH3 cells overexpressing NDFIP1 exhibited enhanced viability and reduced sensitivity to CAB. In vivo experiments demonstrated that subcutaneous injection of NDFIP1-overexpressing GH3 cells led to enhanced tumor growth compared to parental GH3 cells. Although the total levels of PTEN remained unaltered, NDFIP1 overexpression induced PTEN nuclear translocation, potentially activating the mTOR pathway. This was supported by increased phosphorylation of key mTOR pathway components, including p-AKT and p-4EBP1, in cells overexpressing NDFIP1. CAB treatment induces the upregulation of NDFIP1 in PitNET cells, which correlates with tumor size and contributes to reduced CAB sensitivity, potentially through activation of the mTOR pathway. NDFIP1 as a potential therapeutic target for overcoming DA resistance in PitNET patients.

Development of a modified nutritional index model based on nutritional status and sarcopenia to predict long-term survival and chemotherapy benefits in elderly patients with advanced gastric cancer

BackgroundElderly patients with advanced gastric cancer have poor prognoses. This study aims to develop a prediction model for long-term survival after radical surgery and to identify patients who may benefit from chemotherapy. MethodsData from 555 elderly patients with advanced gastric cancer admitted to two medical centers from 2009 to 2018 were retrospectively analyzed. Sarcopenia was combined with the Controlling Nutritional Status (CONUT) score to create a modified nutritional index (mCONUT). Cox regression analyses were used to develop a novel nomogram prediction model (mCNS) that combined mCONUT, pN, and tumor size, and its performance was further verified both internally and externally. ResultsMultivariate Cox analysis revealed that tumor size, pN, and mCONUT were independent prognostic risk factors for overall survival (OS). The mCNS model showed good fit and high predictive value (AUC: training set 0.711; validation set 0.707), outperforming the pTNM model (p<0.05). To further investigate the association between the model and adjuvant chemotherapy, we categorized the model into two risk groups : a high-risk group and a low-risk group. Further analysis revealed that, in the low-risk group, the OS and recurrence-free survival(RFS) for patients receiving adjuvant chemotherapy was significantly better than that of those who did not receive chemotherapy (p=0.047,p=0.019). In the high-risk group, this result was not observed (p=0.120, p=0.053). ConclusionThe mCNS model has high predictive value in predicting long-term survival of elderly patients with advanced gastric cancer. Patients with mCNS-L were able to benefit from chemotherapy after laparoscopic radical gastrectomy.

P53 status combined with MRI findings for prognosis prediction of single hepatocellular carcinoma

ObjectTo develop and validate a nomogram for predicting recurrence in individuals suffering single hepatocellular carcinoma (HCC) after curative hepatectomy. Material and methodsA retrospective analysis was conducted on 189 patients with single HCC undergoing curative resection in our center were randomized into training and validation cohorts. P53 status was determined using immunohistochemistry. Clinical data, such as age, and gender were collected. MRI findings, such as tumor size, intratumoral arteries, the presence of peritumoral enhancement and intratumoral necrosis were also recorded. Nomograms were established based on the predictors selected in the training cohort, and receiver operating characteristic (ROC) curve analyses were used to compare the predictive ability among single predictors and nomogram model. The Kaplan-Meier method were used to assess the impact of each predictor and nomogram model on HCC recurrence. The results were validated in the validation cohort. ResultsMultivariate Cox regression analysis showed that P53 (P < 0.001), tumor size (P = 0.009), and intratumoral artery (P = 0.026) were the independent risk factors for HCC recurrence. The nomogram model demonstrated favorable C-index of 0.740 (95 %CI:0.653–0.826) and 0.767 (95 %CI: 0.633–0.900) in the training and validation cohorts, and the area under the curve was 0.740 and 0.752, which was better than the performance of P53 and MR factors alone. Calibration curves indicated a good agreement between observed actual outcomes and predicted values. Kaplan-Meier curves indicated that nomogram model was powerful in discrimination and clinical usefulness. ConclusionsThe integrated nomogram combining P53 status and MRI findings can be a valuable prognostic tool for predicting postoperative recurrence of single HCC.

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

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

Optimal cut-off value for lymph node harvesting in colon cancer based on tumor stage and sidedness: A retrospective analysis of a Japanese nationwide cohort.

149 Background: The presence of fewer than 12 harvested lymph nodes (LN) is currently considered a risk factor in stage II colon cancer (CC). However, this cut-off value does not take into consideration the biological differences associated with tumor sidedness. Moreover, the applicability of this cut-off value to stage III CC is unknown. Methods: Patients with pathological stage II/III CC who underwent curative surgical resection were assessed using data from the Japanese Society for Cancer of the Colon and Rectum database (2001–2015). The optimal cut-off value of harvested LN was evaluated by analyzing all cut-off values (i.e., 3–40), taking into account the point estimate of the hazard ratio (HR) and lower limit of the 95% confidence interval (CI), according to the tumor stage (II/III) and sidedness (right/left). A Cox proportional hazards model was used to investigate the impact of the number of harvested LN on overall survival, adjusting for age, sex, T stage, histology, size of tumor, sidedness, adjuvant chemotherapy and extent of colon resection. Multivariate analysis was also conducted. Results: From the data, 4249 (left/right; 3248/1001) and 3549 (left/right; 2798/751) patients with stage II and III CC, respectively, were identified. The median number of harvested LN was identical between stage II (18, interquartile range [IQR] (12–15)) and III (18, IQR (13–25)). However, this number was higher in right-sided CC (21, IQR (14–31)) versus left-sided CC (17, IQR (12–24)). In stage II, the conventional cut-off value (i.e., 12 LN) was identified as a prognostic factor in the multivariate analysis (HR 1.45; 95% CI: 1.20–1.75; p&lt;0.001). Nevertheless, the prognostic impact of the number of harvested LN was stronger when the optimal cut-off value was set to 7 (HR 1.88; 95% CI: 1.44–2.44; p&lt;0.001). In stage III, the optimal cut-off value was 12 (HR 1.88; 95% CI: 1.44–2.44; p&lt;0.001). When evaluated based on tumor sidedness, the optimal cut-off value differed, especially for stage III. Data are shown in the table. Similar results were obtained following the exclusion of the extent of bowel resection as variable in Multivariate analysis. Conclusions: While the presence of 12 harvested LNs remains a valid prognostic factor, the optimal cut-off value can be further evaluated based on tumor stage and sidedness. Stage II Stage III All Left Right All Left Right Cut-off value 12 12 12 12 12 12 N(&gt;cut-off/&lt;cut-off) 3209/1040 2371/877 838/163 2814/735 2181/617 633/118 HR(&gt;cut-off/&lt;cut-off)(95% CI) 1.45 (1.20-1.75) 1.49 (1.20-1.84) 1.31 (0.85-2.02) 1.30 (1.09-1.55) 1.27 (1.05-1.54) 1.43 (0.97-2.13) P value &lt;0.001 &lt;0.001 0.216 &lt;0.003 0.015 0.073 Cut-off value 7 7 10 20 13 N(&gt;cut-off/&lt;cut off) 3930/319 2977/271 889/112 1200/1598 609/142 HR(&gt;cut-off/&lt;cut-off)(95% CI) 1.88 (1.44-2.44) 2.07 (1.56-2.74) 1.39 (0.84-2.27) 1.35 (1.13-1.60) 1.59 (1.11-2.28) P value &lt;0.001 &lt;0.001 0.198 &lt;0.001 0.011

Use of nucleotyping and tumor stroma ratio to predict prognosis in patients with resected intestinal-type gastric cancer.

483 Background: Heterogeneity exists in recurrence and survival among patients with intestinal-type gastric cancer (IGC). Nucleotyping is the alterations in chromatin organization. We sought to identify the prognostic utility of nucleotyping, tumor stroma ratio (TSR) and DNA ploidy in these patients. Methods: Radical resection of gastric carcinoma (&gt; 15 LNs removed) was performed in 283 patients (stage I, n=73; stage II, n=102; stage III, n=108) at our university hospital between 2010 and 2018. Automated image cytometry tools were used to quantitatively measure nucleotyping, TSR and DNA ploidy. Cutpoints of nucleotyping and TSR were 0.044 and 50%, respectively. Associations of these features with clinicopathological characteristics, time-to-recurrence (TTR) and cancer specific survival (CSS) were analyzed by univariate and multivariate analysis. Results: Among 283 patients, chromatin heterogeneity, high TSR and non-diploid were significantly associated with larger tumor size, higher T and N stage, and poorer TTR and CSS at 5 years. In a Cox multivariable analysis, nucleotyping and TSR were independently associated with TTR and CSS (P＜0.05) (Table). The top three contributors to TTR were N stage (33.9%), nucleotying (29.7%) and TSR (25.5%). The top three contributors to CSS were N stage (35.6%), nucleotying (29.7%) and TSR (18.0%). As a combined variable, the percent relative contribution of nucleotyping and TSR ranked first for TTR and CSS (56.0%, 50.0%), ahead of N stage (33.4%, 34.6%) and TILs (8.4%, 10.6%). Conclusions: Nucleotyping and TSR were each significantly and independently associated with TTR and CSS, and their combined variable was more strongly prognostic than either alone. Cox multivariable analysis of TTR and CSS. Features TTR HR (95%CI) TTR P value CSS HR (95%CI) CSS P value Tumor size (&gt;3cm vs ≤3cm) 1.10 (0.48-2.54) 0.83 0.77 (0.35-1.70) 0.56 T stage (T3-T4 vs T1-T2) 1.07 (0.46-2.49) 0.87 1.41 (0.53-3.76) 0.49 N stage (N2N3 vs N0N1) 2.84 (1.39-5.78) &lt;0.01 7.69 (3.37-17.55) &lt;0.01 Adjuvant Therapy (with vs without) 1.32 (0.72-2.40) 0.37 0.85 (0.48-1.52) 0.59 TB (high vs low) 1.29 (0.62-2.69) 0.50 1.61 (0.85-3.07) 0.15 TILs（low vs high） 1.73 (0.96-3.13) 0.07 1.90 (1.06-3.40) 0.03 Nucleotyping (Chromatin heterogeneous vs Chromatin homogeneous) 2.19 (1.21-3.99) 0.01 3.44 (1.96-6.03) &lt;0.01 TSR (high vs low) 2.12 (1.16-3.82) 0.01 2.51 (1.43-4.41) &lt;0.01 DNA ploidy (Non-diploid vs Diploid) 1.20 (0.55-2.63) 0.65 0.98 (0.44-2.15) 0.95 1 TTR, time-to-recurrence; 2 CSS, cancer specific survival.

Prognostic factors in T1 high-grade urothelial carcinoma of the bladder with lymphovascular invasion: a retrospective cohort study.

To evaluate the long-term treatment outcomes of T1 high-grade (T1HG) urothelial carcinoma (UCB) with lymphovascular invasion (LVI). We retrospectively analyzed the data of 70 patients of T1HG UCB with LVI who were treated at the Second Hospital of Tianjin Medical University between 2009 and 2019. The log rank test and Cox regression analyses were performed to identify factors that predict the recurrence and survival of these "highest risk" group of non-muscle invasive bladder cancer (NMIBC). With a median follow-up of 46.0months (range 2-151), the 5-year overall survival (OS), cancer-specific survival (CSS), recurrence-free survival (RFS) and progression-free survival (PFS) rates were 65%, 78%, 28% and 56% after trans-urethral resection of bladder tumor (TURBT), and 35%, 48%, 35% and 35% after radical cystectomy (RC), respectively. Treatment modality (tumor burden) was and independent predictor of OS (Hazard ratios (HRs) 2.176, 95% confidence intervals (CIs) 1.021-4.637, p = 0.044) and CSS (HRs 3.675, CIs 1.311-10.297, p = 0.013), and was weakly associated with RFS (HRs 0.560, CIs 0.281-1.114, p = 0.099). A history of urothelial carcinoma of the bladder (H.UCB) was an independent predictor of RFS (HRs 2.246, CIs 1.102-4.579, p = 0.026) and PFS (HRs 2.259, CIs 1.036-4.927, p = 0.041). Tumor size was an independent predictor of RFS (HRs 2.093, CIs 1.054-4.159, p = 0.035). In T1HG UCB with LVI, tumor burden was a significant predictor of survival. Radical cystectomy should be individualized and not universally recommended. Recurrent T1HG UCB with LVI potentially represents a sign of progression, and RC regardless of tumor burden might be a reasonable alternative for this subgroup of patients.

Transdural location as a predictor of recurrence in spinal cord meningiomas.

Spinal cord meningiomas are typically benign, rare tumors that pose clinical challenges owing to their location and potential for spinal cord compression. This study aimed to assess the radiological features of spinal cord meningiomas and the key factors associated with their recurrence. We conducted a retrospective, single-institution study on 67 patients with pathologically confirmed spinal cord meningiomas who were surgically treated between January 2016 and December 2023. Radiological features, such as tumor size, en plaque growth, tumor signal intensity, and anatomical location, were assessed using preoperative magnetic resonance imaging. Clinical outcomes were evaluated using univariate and multivariate logistic regression analyses to identify risk factors for recurrence. Of the 67 patients, six (9.0%) experienced a recurrence during a mean follow-up of 31.8months. Results of univariate analysis suggested that a younger age, high World Health Organization grade, en plaque growth, and transdural location were significantly associated with tumor recurrence (p<0.05). Multivariate analysis confirmed that a younger age (p=0.027) and transdural growth (p=0.006) were significant independent predictors of recurrence. Our study identified younger age and transdural tumor location as significant risk factors for spinal cord meningioma recurrence. A total resection is the primary surgical goal; however, tumors with complex anatomical presentations, especially those exhibiting transdural growth, pose significant challenges. The findings highlight the importance of developing tailored surgical approaches and intensifying postoperative surveillance in high-risk patients to reduce the recurrence likelihood.

Comparing the Accuracy and Reliability of ABC/2 and Planimetry for Vestibular Schwannoma Volume Assessment.

Vestibular schwannoma (VS) is a common intracranial tumor that affects patients' quality of life. Reliable imaging techniques for tumor volume assessment are essential for guiding management decisions. The study aimed to compare the ABC/2 method to the gold standard planimetry method for volumetric assessment of VS. A retrospective review was conducted on patients with VS diagnosed between 2007 and 2022 at Yale New Haven Hospital. Both ABC/2 and planimetry methods were used for tumor volume assessment, and their correlations were evaluated. Among 140 patients, the mean tumor volumes using the planimetry and ABC/2 methods were 1307.99 ± 142.13 and 1482.76 ± 165.75 mm3, respectively. A strong correlation was observed between the methods (r = 0.99, p < 0.0001). For patients who underwent follow-up scans, the ABC/2 method accurately detected tumor volume changes over time. Subgroup analysis based on tumor size also displayed a significant positive correlation across all size categories. The ABC/2 method demonstrates a high correlation with the planimetry method for VS volume assessment and can be a reliable, less time-intensive alternative in clinical settings. However, it generally overestimates tumor volume compared to planimetry. Subgroup-specific correction formulae were provided to enhance the accuracy of ABC/2-derived measurements. Future studies may explore the integration of these methods for improved clinical decision making.

Performance of a blood-based screening test for the early detection of colorectal cancer.

232 Background: While the clinical benefit of highly sensitive screening tools for colorectal cancer (CRC) has been established, adherence rates remain low. The convenience and familiarity of blood-based testing may reduce disease burden through greater access and compliance to regular and recommended asymptomatic screening. We report on preliminary findings from a minimally invasive blood-based early cancer detection (ECD) screening test for CRC. Methods: Plasma samples from healthy individuals and CRC patients sourced from biobanks were included. A targeted panel composed of differentially methylated genomic regions was developed. Using an independent cohort of plasma samples, a machine-learning model was trained to classify patient samples into cancer-free and CRC based on observed differential methylation patterns in circulating cell-free DNA (cfDNA). The assay performance was calculated based on concordance with clinical diagnosis (CRC, cancer-free). Results: The test set included 440 individuals: 127 with a confirmed CRC diagnosis (47% stage I/II, mean age 65±12 years, male 46%) and 313 without cancer (mean age 56±10 years, male 41%). Overall sensitivity was 95% (95% CI: 88-100%), and specificity was 91% (95% CI: 84-98%). Among patients with stage I disease, sensitivity was 92% overall, and 88% in screen-detected individuals. Sensitivity was 100% (n=14/14) in microsatellite-high tumors and 95% (n=107/113) in microsatellite-stable tumors. Multivariate analysis demonstrated associations between methylation signal and tumor size, cancer stage, and sex. Compared with a tumor-informed, variant-based circulating tumor DNA (ctDNA) test (Signatera), we observed a PPA (positive percent agreement) of 100%. Moreover, the differentially methylated allele fraction (DMAF) across target regions strongly correlated with variant allele frequencies (VAFs) from the tumor-informed test (Spearman’s correlation coefficient, 0.85). Conclusions: Using epigenetic markers specific for CRC, we developed a sensitive and specific blood-based test to detect cfDNA from early-stage and asymptomatic disease. The methylation signal strongly correlated with ctDNA VAFs from a clinically validated tumor-informed test and increased with cancer stage and disease burden. This test could serve as a means to increase patient adherence rates for CRC screening, thereby improving patient outcomes.

Development and validation of a prognostic prediction model for elderly gastric cancer patients based on oxidative stress biochemical markers

BackgroundThe potential of the application of artificial intelligence and biochemical markers of oxidative stress to predict the prognosis of older patients with gastric cancer (GC) remains unclear.MethodsThis retrospective multicenter study included consecutive patients with GC aged ≥ 65 years treated between January 2012 and April 2018. The patients were allocated into three cohorts (training, internal, and external validation). The GC-Integrated Oxidative Stress Score (GIOSS) was developed using Cox regression to correlate biochemical markers with patient prognosis. Predictive models for five-year overall survival (OS) were constructed using random forest (RF), decision tree (DT), and support vector machine (SVM) methods, and validated using area under the curve (AUC) and calibration plots. The SHapley Additive exPlanations (SHAP) method was used for model interpretation.ResultsThis study included a total of 1,859 older patients. The results demonstrated that a low GIOSS was a predictor of poor prognosis. RF was the most efficient method, with AUCs of 0.999, 0.869, and 0.796 in the training, internal validation, and external validation sets, respectively. The DT and SVM models showed low AUC values. Calibration and decision curve analyses demonstrated the considerable clinical usefulness of the RF model. The SHAP results identified pN, pT, perineural invasion, tumor size, and GIOSS as key predictive features. An online web calculator was constructed based on the best model.ConclusionsIncorporating the GIOSS, the RF model effectively predicts postoperative OS in older patients with GC and is a robust prognostic tool. Our findings emphasize the importance of oxidative stress in cancer prognosis and provide a pathway for improved management of GC.Trial registrationRetrospectively registered at ClinicalTrials.gov (trial registration number: NCT06208046, date of registration: 2024–05-01).