Tumor Size Research Articles

Clinical Significance and Pathogenic Mechanisms of Long Non-Coding RNA TRPM2-AS in Cancers.

Long non-coding RNAs (lncRNAs) are known to play vital roles in human cancers. LncRNA TRPM2-AS has been found to be upregulated in various types of cancers. The elevated levels of TRPM2-AS are associated with important clinicopathological parameters such as tumor size, tumor stage, and lymph node metastasis, revealing that TRPM2-AS could be a potential target for cancer diagnosis, prognosis and treatment. Moreover, TRPM2-AS is involved in regulating the cell proliferation, migration, invasion, apoptosis, drug or radio resistance by serving as a competing endogenous RNA, directly bounding to proteins and regulating multiple signaling pathways. In this review, we comprehensively summarize the latest knowledge on the aberrant expression of TRPM2-AS, the relationship between TRPM2-AS and clinical features, and the detailed mechanisms of potential functions of TRPM2-AS in various cancer types. The current study highlights the potential of TRPM2-AS as a prognostic and therapeutic target in cancers.

PER3 suppresses tumor metastasis of oral squamous cell carcinoma by promoting HIF-1α degradation.

The low expression of period circadian regulator 3 (PER3) in head and neck squamous cell carcinoma is closely correlated with tumor size and invasion depth. Hypoxia-inducible factor 1 subunit alpha (HIF-1α) regulates epithelial-mesenchymal transition (EMT) transcription factors, activates EMT, and promotes tumor metastasis. Here, we investigated the role and molecular mechanism of PER3 in regulating HIF-1α and metastasis in oral squamous cell carcinoma (OSCC) by using bioinformatics analyses and in vitro and in vivo experiments. PER3 expression was decreased in OSCC, and PER3 expression was significantly negatively correlated with T stage, N stage, clinical classification, and survival time. PER3 overexpression inhibited, while PER3 knockdown prompted EMT and metastasis of OSCC cells. HIF-1α reversed the effects of alterations in PER3 expression on OSCC metastasis. Mechanistically, PER3 bound to HIF-1α via the Per-ARNT-Sim 1 domain and promoted its ubiquitination degradation. Hypermethylation at CpG site cg12258811 of PER3 promoter inhibited PER3 expression and prognosis of OSCC. Decitabine combined with LW6 upregulated PER3, downregulated HIF-1α, and inhibited lymph node metastasis of OSCC in nude mice. Our findings reveal the role and mechanism of HIF-1α regulation by PER3 and support the potential clinical application of targeting PER3 in treating OSCC metastasis.

Adjuvant therapy with somatostatin analogs for recurrent gastric neuroendocrine tumors type 1.

665 Background: Neuroendocrine gastric tumors (gNETs) type 1 are associated with chronic autoimmune atrophic gastritis, hypergastrinemia and usually have multifocal lesions and high frequency of recurrence (up to 70% for 2 years). Somatostatin analogs (SA) showed promising data in neoadjuvant setting with 84% of complete responses in a small retrospective trial. The aim of this study was to evaluate the efficacy of adjuvant treatment with SA for recurrent gNETs type 1. Methods: This retrospective, single-center study included patients (pts) with recurrent gNETs who received adjuvant treatment with SA. Recruitment of pts was carried out from 2012 to February 2024. Results: The study included 35 pts, 33 females and 2 males. Endoscopic mucosal resection (EMR) was performed in 34 cases (97.1%), gastric resection in 1 (2.9%). The median of previous EMR was 2 (1-6) procedures. Most of the pts have multifocal lesions – 28 (80%), the median of lesions is 5. The median tumor size – 6 mm, tumor size >10 mm was observed in 2 cases (5.7%), one of them had N+. The median of ki67 was 3,5% (1-10%), grade 1 (G) - 14 (40%) and G2 - 21 (60%). All pts received adjuvant therapy with SA, 33 (94.3%)long-active releasing octreotide30 mg and 2 (5.7%) lanreotide 120 mg every 4 weeks. The time of SA therapy was <12 months in 23 cases (65.7%) and ≥12 months in 12 (34.3%). The median of follow-up was 30.5 months. The median disease-free survival (DFS) was not reached (95% CI, 67-NR). We compared median DFS after previous EMR (DFS1) without adjuvant SA and DFS after EMR with adjuvant SA (DFS2). The DFS2 was significantly higher – median of DFS1 was 8.8 months (95% CI, 2.7-14.9) not reached (95% CI, 67-NR, p<0.01) . Adjuvant treatment with SA ≥12 months was associated with improved DFS compared to <12 months – not reached (95% CI, 58.1-NR) versus 61 months (95% CI, 26.2-96.2, p=0.05). Adjuvant SA reduced gastrin levels after a year of therapy by ≥50% from baseline in 13 cases (37.1%). Conclusions: Adjuvant treatment with SA significantly improved DFS and should be considered for recurrent and multifocal gNETs type 1. Duration of therapy ≥12 months was significantly associated with improvement in DFS compared with shorter duration of therapy.

ERα, HER-2, pan-RAS, p53, and aromatase expression in spontaneous malignant canine mammary tumors: Prognostic relevance and association with clinicohistological parameters.

The interlacing interaction between proto-oncoproteins and tumor-suppressing proteins in malignant canine mammary tumors (mCMT) microenvironment remains largely unexplored. The present study intended to decipher the i) association between the intratumoral expression of ERα, HER-2, pan-RAS, p53 and aromatase, ii) their relationship with the clinicohistological parameters and serum sex hormones, and iii) their prognostic relevance in mCMT. Tumor samples from animals with mCMT (n=27) were subjected to histopathology and immunohistochemistry for ERα, HER-2, pan-RAS, p53, and aromatase. Serum estradiol and progesterone levels from dogs with mCMT and healthy dogs (n=10) were estimated using chemiluminescence immunoassay. Kaplan-Meier analysis (log-rank test), univariable and multivariable Cox regression, and Mann-Whitney U test were employed for statistical analysis. The expression of aromatase, ERα, pan-RAS, p53, and HER-2 were detected in 100%, 88%, 67%, 12% and 11% of mCMT cases, respectively. Serum estradiol and progesterone were significantly higher in mCMT-affiliated patients than healthy dogs. Also, a positive association of ERα expression with aromatase (stromal component) and HER2 expression in mCMT patients was detected. Furthermore, intratumoral aromatase expression and p53 overexpression were correlated with tumor size and angiogenesis, respectively. No relationship was detected between other tumor markers, serum steroid hormones and clinicohistological parameters. P53 overexpression was associated with poor survival in mCMT patients. Overexpression of aromatase and p53 overexpression has clinical relevance in mCMT, and an intratumoral ERα expression is positively associated with HER-2 expression and aromatase production by stromal components.

Immunohistochemical Analysis of a1-Acid Glycoprotein and Tumor Associated Macrophages in Clear Cell Renal Cell Carcinoma.

α1-Acid glycoprotein (AGP), also known as orosomucoid, is an acute-phase protein that has been found increased in plasma of cancer patients. This study investigates the role of AGP expression in clear cell renal cell carcinoma (ccRCC) and its association with clinical outcomes. We investigated the correlation between AGP levels and the prognosis of ccRCC through an analysis of The Cancer Genome Atlas (TCGA) database. To examine AGP expression and its clinicopathological associations, immunostaining was performed on paraffin-embedded tissue samples of 92 ccRCC cases. AGP expression was found to be higher in RCC cell lines compared to normal renal epithelial cells. Analysis of the TCGA dataset showed that patients with AGP gene expression had significantly worse overall survival. However, AGP expression was not correlated with age, sex, or cancer stage. A mouse monoclonal antibody against AGP was generated. This antibody reacted with human and mouse hepatocytes, but not in AGP-deficient mice. From 92 examined ccRCC cases, AGP protein expression was detected in 89 cases, with only 3 being negative. AGP expression levels did not correlate with clinicopathological factors, such as age, tumor size, or nuclear grade. CD14, a receptor of AGP, was found to be expressed in Iba1-positive monocytes and tumor-associated macrophages (TAMs) but not in other cell types like lymphocytes or cancer cells. No significant correlation was found between AGP expression and the number of Iba1-positive cells in ccRCC tissues. Iba1-positive cells were correlated with Fuhrman grade, and patients with ≥30% Iba1-positive cells were, on average, significantly younger and had more aggressive tumor. AGP expression is linked to poorer survival in ccRCC, but its association with immune cell infiltration (via Iba1-positive cells) is unclear.

Evaluation of the impact of lymph node ratio on survival in patients with pancreatic cancer undergoing neoadjuvant therapy.

702 Background: Pancreatic cancer continues to have a dismal prognosis despite improvements in surgical care. Resection status and lymph node status continues to be key factors impacting prognosis. There remains significant debate on the utility of increasing nodal harvest in patients undergoing surgery, while others report an improvement in survival. We sought to evaluate the impact of lymph node positivity to lymph nodes resected in patients with pancreatic cancer undergoing resection. Methods: Utilizing the National Cancer Database, we identified patients diagnosed with pancreatic cancer who underwent neoadjuvant chemotherapy (NCT) or neoadjuvant chemoradiation (NCR) followed by resection. We then stratified by nodal status and calculated a LN+/LNR (lymph node resected) ratio. Pearson’s Chi-square test was used to compare categorical variables. Survival analysis was estimated by the Kaplan-Meier method and associated log-rank test. Propensity score matching (PSM) was completed for variables of age, sex, tumor size, LN removed, LN positive, pathogenic T- stage and N-stage, grade, 30- and 90-day mortality, R0 resection, facility volume, response, adjuvant therapy, and LNR. Significance was considered at p-value ≤0.05. Results: We identified 4117 patients with a median age of 65 (25-90). There were 2323 patients who underwent NCT and 1794 who underwent NCR. The median LN resected in the NCT was 18 vs 15 in the NCR, p<0.001. However, there were more LN+ in the NCT vs NCR, 2.1 vs 0.9, p<0.001. The R0 resection rates were lower in the NCT vs NCR 81% vs 86%, p<0.001. Additionally, complete response rates were higher amongst the NCR, 9.2% vs 4.7%, p<0.001. Lymph node ratios were consistently higher in the NCT cohorts among all ratio strata, p<0.001. Patients with pN+ disease had a median and 5-year survival of 26.4mo and 17% compared to their pN- counterparts at 38.8mo and 36%, p<0.001. Patients treated with NCT demonstrating a LNR of 0.01-0.1 had median and 5-year survival of 32.8 and 27%, LNR 0.11-0.4 (25.5mo and 12%), and LNR>0.4 (19.1mo and 10%), p<0.001. Patients treated with NCR demonstrating a LNR of 0.01-0.1 had median and 5-year survival of 29.1 and 21%, LNR 0.11-0.4 (25.8mo and 17%), and LNR>0.4 (21.3mo and 5%), p<0.001. PSM confirmed a higher LNR in the NCT cohort compared to NCR, p<0.001, however survival was also longer in these patients among the LNR 0.01-0.1, and 0.11-0.4, p<0.001. Conclusions: Lymph node status in patients with pancreatic cancer continues to be a significant prognostic indicator of survival. Moreover, lymph node ratio may be a more accurate predicter of survival in patients undergoing neoadjuvant chemotherapy and neoadjuvant chemoradiation.

Machine learning–based liquid biomarker analysis from the NEONAX trial for response prediction to perioperative (PO) and adjuvant (A) gemcitabine/nab-paclitaxel in resectable PDAC (rPDAC).

755 Background: The phase II NEONAX trial examined PO and A gemcitabine/nab-paclitaxel (G/nP) efficacy for rPDAC pts with a comprehensive biomarker program. This translational study aimed at identifying liquid biomarker for early prediction of G/nP success in each treatment group (PO and A) and for the combined group using machine learning (ML). Methods: Pts from both study arms were stratified into groups based on Short- or Long-DFS ( n=80 pts total; PO n=42 pts; A n=38 pts). Blood plasma from selected G/nP naïve pts was analyzed by multiplexed ELISA (mELISA, 80-Plex ProcartaPlex Human Immune Response) and mass spectrometry (MS; feature list generation) and clinical data were acquired for each patient. For ML pts were divided into training (80%) and validation (20%) datasets. The Weka-based algorithm WrapperSubsetEval (WSE) with 8 different classifiers was used for feature selection. The best performing (highest accuracy, best ROC-AUC, minimal signature) classifier with the corresponding feature panel was selected by a 10x10-fold cross-validation (CV). Respective panels for all features combined as compared to clinical features and Ca19-9 blood levels were tested for performance via CV and bootstrap aggregating for training and validation datasets (10x with replacement). Results: The feature generation process generated 579 features from G/nP-naive pts (mELISA: 80; clinical data: 99; MS: 400). For response prediction of the whole rPDAC group to G/nP (S-/L-DFS), the ML-based flow identified a panel of 8 proteins from MS (SERPINA1, C1QB, KRT1, C4B, UBB, VCAM1, HPD, LYZ) and 3 proteins from mELISA (Galectin3, IL34, CCL4) combined with a logistic regression classifier. The predictive panel with the best performance for determining PO G/nP success was established using a kernel logistic regression classifier and included 2 proteins from mELISA (CXCL2, IL17A), 4 proteins from MS (C3, IGLV3-25, HLA-B, SHBG), and 2 clinical data (WHO grade, Na/Mg blood level ratio). The best performing biomarker for predicting success in A included 2 clinical data (tumor size at staging, hematocrit) and 1 protein from mELISA (IL22) and was established with a random forest classifier. All panels represented minimal feature signatures (rPDAC: 11; PO: 8; A; 3) and showed a high performance with ROC-AUC (training) > 0.90, ROC-AUC (CV) > 0.85, and ROC-AUC (validation) > 0.90. All panels described were superior compared to similar predictive signatures (with corresponding ML classifiers) for all clinical data or Ca19-9 blood levels. Conclusions: We show that minimal liquid biomarker signatures for early prediction of G/nP success in the NEONAX trial based on mELISA, MS and clinical data can be established by ML. The study shows the potential of ML for biomarker panel development and the value of mELISA/MS for generation of feature lists to use in ML. Clinical trial information: NCT02047513 .

Prognostic factors for gastric cancer patients with positive peritoneal cytology who underwent upfront surgery.

400 Background: Positive peritoneal cytology (CY1) is classified as Stage IV disease, the standard treatment for which is systemic chemotherapy. However, CY1 is often diagnosed after surgery in patients for whom staging laparoscopy is not indicated. In addition, the treatment strategy for patients with CY1 diagnosed during surgery is controversial. The Japanese guidelines recommend upfront surgery followed by adjuvant chemotherapy for patients diagnosed with CY1 during surgery. To identify patients with CY1 who are most likely to benefit from upfront surgery, we investigated prognostic factors in patients with CY1 who underwent upfront surgery. Methods: A total of 169 gastric cancer patients diagnosed as P0CY1 during or after surgery who underwent R1 resection other than positive resection margins were included. The diagnosis of CY1 was obtained by staging laparoscopy or during laparotomy in 69 patients and after surgery in 87 patients. Fourteen patients were initially diagnosed as CY0 by staging laparoscopy but were rediagnosed as CY1 after surgery. The clinicopathological factors of overall survival (OS) and progression-free survival (PFS) were investigated. Prognostic factors were identified using Cox regression models. Results: The median patient age was 72 years, and there were 108 males. The histological type was undifferentiated type in all of 102 patients. The macroscopic types were 0 in 10) patients 1 in 3, 2 in 27 3 in 84 and 4 in 45). cT grades and cN grades were cT1 in 3, cT2 in 7, cT3 in 12, cT4 in 147, cN0 in 65cN1 in 30), cN2 in 46 and cN3 in 28. The median OS and PFS were 25.1 months and 14.6 months, with 5-year OS rate and PFS rate of 30% and 23%, respectively. A multivariate analysis for OS identified macroscopic type 0-2, Charlson Comorbidity Index<3, and adjuvant chemotherapy as independent prognostic factors. Similarly, macroscopic type 0-2, tumor size <80 mm, and adjuvant chemotherapy were identified as independent prognostic factors for PFS. In a subgroup analysis of patients who received adjuvant chemotherapy, macroscopic type 0-2 was the only independent prognostic factor for PFS. The 5-year PFS rate in patients with macroscopic type 0-2 was 42%. Conclusions: Patients with macroscopic type 0-2 who are suitable for adjuvant chemotherapy may have benefit from upfront surgery, even if peritoneal cytology is positive.

Rates and risk factors for recurrence of hepatocellular carcinoma after initial complete remission in response to transcatheter arterial chemoembolization: A systematic review and meta-analysis.

612 Background: Transcatheter arterial chemoembolization (TACE) is used for palliative treatment of patients with inoperable hepatocellular carcinoma (HCC). Despite remarkable initial remission rates, frequent recurrences of HCC after TACE have resulted in questionable survival benefit. Our investigation aimed to study the rates and risk factors for HCC recurrence following remission after TACE. Methods: Comprehensive search of 5 databases (EMBASE, Web of Science, PubMed, CINAHL, ClinicalTrials.gov) was conducted to yield 4263 studies, which were screened based on prespecified inclusion and exclusion criteria. Outcomes assessed were total recurrence rate; 6-month, 1, 2, and 3-year cumulative recurrence rates; and 1 and 3-year survival rates for patients with and without recurrence. Meta-analysis was conducted by the random-effects model and heterogeneity was assessed by the I 2 statistic and 95% prediction interval. Systematic review of risk factors for recurrence was performed. Results: Twelve studies and 1,152 patients who underwent complete remission in response to TACE were included. The pooled rate of total recurrence was 60% (95% CI 53-67%). The pooled 6-month, 1-year, 2-year, and 3-year cumulative recurrence rates were 26% (95% CI 18-33%), 33% (95% CI 22-43%), 49% (95% CI 34-64%), and 62% (95% CI 53-71%), respectively. The pooled 1-year survival rates for patients with and without recurrence were 94% (95% CI 89-99%) and 99% (95% CI 99-100%), respectively. The pooled 3-year survival rates for patients with and without recurrence were 61% (95% CI 31-90%) and 91% (95% CI 81-100%). Heterogeneity was considerable based on the 95% prediction interval. Predominant risk factors for recurrence were larger tumor size, multinodularity, portal vein thrombosis, and higher AFP levels. Conclusions: HCC frequently recurs after initial remission achieved through TACE, with differences in survival rates between patients with and without recurrence. Identifying high-risk patients based on tumor size, multinodularity, portal vein thrombosis, and AFP levels could improve long-term outcomes.

Prognostic models for progression-free survival in atypical meningioma: Comparison of machine learning-based approach and the COX model in an Asian multicenter study.

Atypical meningiomas are prevalent intracranial tumors with varied prognoses and recurrence rates. The role of adjuvant radiotherapy (ART) in atypical meningiomas remains debated. This study aimed to develop and validate a prognostic model incorporating machine learning techniques and clinical factors to predict progression-free survival (PFS) in patients with atypical meningiomas and assess the impact of ART. A retrospective review of 669 patients from five institutions in Korea and China was conducted. Cox proportional hazards, gradient boosting machine, and random survival forest models were employed for comparative analysis, utilizing both internal and external validation sets. Model performance was assessed using Harrell's concordance index and permutation feature importance. Of 581 eligible patients, age, post-operative platelet count, performance status, Simpson grade, and ART were identified as significant prognostic factors across all models. In the ART subgroup, age and tumor size were the top prognostic indicators. The Cox model outperformed other methods, achieving a training C-index of 0.73 (95 % CI: 0.72-0.73) and an external validation C-index of 0.74 (95 % CI: 0.73-0.74). The model effectively stratified patients into risk categories, revealing a differential impact of ART: low-risk patients in the active surveillance group showed a 5.6 % improvement in 5-year PFS with predicted ART addition, compared to a 15.9 % improvement in the high-risk group. This multicenter study offers a validated prognostic model for atypical meningiomas, highlighting the need for tailored treatment plans. The model's ability to stratify patients into risk categories for PFS provides a valuable tool for clinical decision-making, potentially optimizing patient outcomes.

Prediction model establishment of prognosis factors for distant metastasis of hepatocellular carcinoma based on the SEER database.

Distant metastasis in hepatocellular carcinoma (HCC) is an important indicator of poor patient prognosis. Identifying patients who are at high risk of metastasis early on is essential for creating personalized treatment plans, yet currently, there is a scarcity of effective predictive tools. To investigate the effects of different factors on distant metastasis in HCC patients and to establish a clinical prediction model for predicting distant metastasis in HCC patients. Our study retrospectively examined 22,318 patients diagnosed with confirmed HCC from the SEER database. Prognostic factors for developing distant metastases in HCC patients were identified by univariate and multivariate logistic regression analyses. Utilizing data from a multivariate logistic regression analysis, we created a nomogram. Its predictive precision was evaluated by analyzing the calibration curve, the area under the curve (AUC) of the receiver operating characteristic curve, decision curve assessment (DCA), and Kaplan-Meier (KM) curve analysis of overall survival. Finally,the nomogram was visualized with an online calculator. We identified six independent prognostic factors: ethnicity, marital status, tumor size, survival time, surgery, and radiotherapy. The nomogram constructed from these six factors showed good calibration, discrimination, and clinical application value after calibration curve analysis, receiver operating characteristic curve analysis and DCA curve analysis. Besides, KaplanMeier survival curves also demonstrated that this nomogram had predictive accuracy. In this research, a nomogram model was created to accurately predict distant metastasis risk in patients with HCC. This study provides guidance for optimizing individual therapies and making better clinical decisions.

Systematic literature review (SLR) of prognostic factors (PFs) in locally advanced rectal cancer (LARC) and mismatch repair deficient (dMMR)/microsatellite instability-high (MSI-H) rectal cancer (RC).

303 Background: Innovative immunotherapies arebeing developed to improve clinical outcomes in patients (pts) withdMMR/MSI-H LARC who respond poorly to the current standard of care. A comprehensive overview of PFs in dMMR/MSI-H LARC may provide insight into the natural history of this disease to inform clinical study design and pt risk stratification. Methods: Systematic searches of bibliographic databases (EMBASE, MEDLINE, Cochrane; 2013–2023) and congress websites (2021–2023) were conducted to identify PFs for tumor response and survival outcomes in adult pts with LARC (SLR1) and dMMR/MSI-H RC (SLR2). Given the expected high volume of evidence, SLR1 was limited to large observational studies (≥1000 pts) and clinical trials (≥100 pts); SLR2 had no such limits. Results: 95 of 2307 publications met the inclusion criteria for SLR1. Of the PFs reported in ≥20 studies, older age, more lymph node involvement or fewer nodes assessed, higher T-stage or larger tumor size, higher histologic grade, and more comorbidities were most frequently significantly associated with poorer patient prognosis (Table). 3 of 289 publications met the inclusion criteria for SLR2. Neoadjuvant chemoradiation therapy (CRT) compared to chemotherapy (CT) was associated with statistically significant worse disease-free survival (DFS) and distant metastasis-free survival (DMFS), while T- or N-stage, age, and sex did not significantly impact these outcomes. Low vs middle tumor localization was also associated with worse DMFS. Stage III and IV disease were associated with worse RC-specific survival, while surgical procedure (segmental vs extended) showed no difference in overall survival (OS). The addition of neoadjuvant CRT or adjuvant CRT/CT to surgery alone had no impact on OS but was associated with worse DFS. Conclusions: Evidence regarding PFs in dMMR/MSI-H RC is scarce and may limit its interpretability, highlighting the need for further research that may be informed by the PFs identified from SLR1. The results from these SLRs may be helpful for optimizing patient management and treatment decision making, and to further contextualize RC clinical trials. PFs reported in ≥20 studies with ≥75% of studies reporting significant results in pts with LARC. PF Studies reporting PF (n) Studies reporting significant* impact of PF on prognosis (%) Poorer prognosis group Top 2 most frequently reported outcomes Age 59 81.4 Older OS, DFS Lymph node involvement/assessment 55 78.2 Yes or higher N stage OS, DFS T-stage or tumor size 53 79.2 Higher or larger OS, DFS Histologic grade 37 75.7 Higher OS, pathological complete response (pCR) Comorbidities 23 87.0 More OS, pCR *p-value <0.05 was considered significant as reported in the identified studies.

Outcomes of simultaneous, adaptive, MRI-guided liver SBRT in patients with heavily pretreated colorectal cancer and four or more liver metastases.

160 Background: About one-third of colorectal cancer (CRC) patients (pts) develop metastases, most commonly in the liver (CRLM). Ablative treatment of multiple liver lesions is difficult and often not done with conventional CT-based radiation therapy, but feasible with MRI-guided adaptive radiation. This study reviews our experience treating pts with high burden CRLM using MRI-guided stereotactic body radiation therapy (MRgRT). Methods: This study identified pts with 4 or more CRLM treated with MRgRT between 7/2019 and 4/2024, all of whom had progressive disease during or after standard-of-care therapy. Ablative radiation was delivered to all sites of disease with no concurrent systemic therapy. All with Child-Pugh score 5-6 (class A) liver function. Local control was defined as no progression in any treated lesion on a per-patient basis. Descriptive statistics summarized the data. A Cox proportional hazards model was used to identify predictors of survival, while the Kaplan-Meier method was used to estimate survival functions. Statistical analysis was performed using SPSS. Results: Seventeen pts with 110 lesions were included, with a median follow-up of 10.7 months (range, 1.7–36.9). The majority (n=15) received systemic therapy in the year before MRgRT. The median number of prior lines of systemic therapy was 2 (range, 1–5). Eight pts (47.1%) had nodal and/or lung progression in addition to CRLM, and 4 pts (23.5%) had at least one prior course of MRgRT. A median of 6 liver lesions (range, 4–11) were prescribed a median dose of 60 Gy (range, 60–80), each delivered in 5 fractions. Median total gross tumor volume per pt was 23.8 cm 3 (range, 0.97–60.1). Seventy-four fractions were available for radiation delivery analysis, of which 55 (74.3%) were adapted. At least one target was modified in 51 (92.7%) of the adapted fractions. Acute toxicity occurred in 7 pts, all with self-limited fatigue and nausea. Progression in Child-Pugh classification from A to B occurred in three pts 3-6 months post-MRgRT. Late toxicity occurred in 1 patient with mild, possibly radiation-related peripheral biliary dilation. Two pts developed malignant biliary strictures. Per-patient local control was 50.8% and 34.8% at 1 and 2 years, respectively, while liver control was 28.7% at 2 years. Six-month systemic therapy-free survival was 31.9%. Two-year overall survival (OS) was 43.9%, with a median of 17.1 months (range, 8.6–25.7). The size of the largest tumor correlated with OS (HR 1.23, p=0.014). Conclusions: In this small series of CRC pts with 4+ CRLM, MRgRT is well-tolerated and shows promise as astrategy to consolidate disease and delay the immediate need for systemic therapy changes. Patient selection is critical to identify those most likely to benefit, though the overall impact on survival and disease trajectory remains uncertain.

Utility of circulating tumor DNA in patients with unresectable pancreatic cancer using a patient-specific panel: ARTEMIS-PC study.

684 Background: Circulating tumor DNA (ctDNA) analysis has proven to be a highly accurate method for assessing treatment efficacy and detecting molecular residual disease (MRD) in cancer patients, outperforming tumor markers and imaging modalities. However, the ctDNA detection rate is reported to be low, and its utility remains unclear in pancreatic cancer (PC). We conducted the prospective “ARTEMIS-PC” study to evaluate the utility of a personalized, tumor-informed MRD assay in patients with unresectable PC. Methods: Eligible patients had histopathologically confirmed unresectable PC, were previously untreated, and had disease measurable per Response Evaluation Criteria in Solid Tumors v1.1. A patient-specific tumor-informed assay (Invitae Personalized Cancer Monitoring) was used for the detection of ctDNA. Blood samples were collected at structured pre- and post-systemic therapy timepoints. Results: A total of 99 patients were eligible for the ARTEMIS-PC study, and personalized panels were successfully created for 92 patients. The median age of patients was 70 years (range 45-81 years), with 43/92 being female. Thirty patients were stage III, and 62 stage IV. Median size of the primary tumor was 38 mm (range 13-100 mm). MRD positivity at enrollment was 88.0%, with 73.3% in stage III patients, and 95.2% in stage Ⅳ (p=0.007). During follow-up, ctDNA clearance was achieved in 33 patients (40.7%). ctDNA clearance was associated with a significantly higher objective response rate (61.5% vs. 17.6%, p=0.001) and disease control rate (100% vs. 64.7%, p=0.002) compared to those who did not achieve clearance. Patients who achieved ctDNA clearance had significantly longer progression-free survival (PFS) than those who did not (9.0 vs. 3.5 months, hazard ratio 0.2, p<0.001). The predictive performance of select biomarkers (variant allele frequency [VAF], CEA, CA19-9) was evaluated using area under the curve (AUC) for treatment response and disease control. For disease control, VAF showed superior predictive performance with AUCs of 0.84 at enrollment and 0.97 at both Week 4 and Week 8, compared to CEA (AUCs: 0.65, 0.73, 0.60) and CA19-9 (AUCs: 0.51, 0.57, 0.56). The predictive performance for treatment response was lower than AUC 0.75 for any of the biomarkers. Among patients who were MRD negative before treatment or became negative during follow-up (n=44), 45.5% (n=20) subsequently turned MRD positive. Of these, disease progression was confirmed by CT in 14 patients. The median time from MRD turning positive to CT-confirmed progressive disease was 88.5 days (range: -28 to 385 days). Conclusions: ctDNA clearance is a useful predictor of improved objective response, disease control, and PFS, with VAF emerging as the more accurate biomarker for disease control, underscoring its potential utility in treatment monitoring in patients with unresectable PC. Clinical trial information: UMIN000043561 .

Conversion therapy strategy: A novel GPC3-targeted multimodal organic phototheranostics platform for mid-late-stage hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is typically diagnosed at intermediate to advanced stage, making surgical treatment unfeasible. Conversion therapy aims to reduce tumor stage, improve hepatic resection feasibility, and lower recurrence rates. Since traditional therapies are often accompanied by uncertainty of efficacy, there is an urgent need to explore new treatment strategies. Near-infrared phototheranostics technology provides a new way for HCC diagnosis and treatment by its excellent optical properties. However, complex preparation and poor biocompatibility of phototheranostics probes limit clinical application. In this study, we developed a fluorescence/magnetic resonance dual-modality imaging (FLI/MRI) as well as photothermal/photodynamic therapy (PTT/PDT) GPC3-targeted multifunctional phototheranostics probe, IR820-GPC3-Gd NPs (IGD NPs), to improve the efficiency of conversion therapy for HCC. The IGD NPs were simply prepared with the IR820 as the core. Conjugating the HCC-specific targeting molecule GPC3 peptide and the MRI agent DOTA-Gd through click chemistry. IGD NPs target HCC cells through GPC3, releasing heat and reactive oxygen species (ROS) under noninvasive 808nm laser irradiation to reduce tumor size and achieve downstaging. High-sensitivity FLI/MRI precisely delineates tumor boundaries, providing real-time surgical navigation and prognosis assessment. This novel probe offers a feasible and effective treatment option for advanced HCC.

Molecular and pathological landscape of the AT-rich interaction domain 1A (ARID1A) mutation in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related deaths worldwide, with complex etiological factors and a diverse genetic landscape. Among the critical genetic mutations in HCC, the AT-rich interaction domain 1 A (ARID1A) gene, a key component of the SWI/SNF chromatin remodeling complex, stands out due to its significant role in both tumor suppression and oncogenesis. This review comprehensively examines the molecular and pathological impacts of ARID1A mutations in HCC. ARID1A mutations, which occur in approximately 7.9 % of HCC cases, predominantly involve truncating mutations leading to loss of function. These mutations are associated with various aggressive cancer features, including larger tumor size, higher rates of metastasis, and poor prognosis. The dual role of ARID1A in HCC is context-dependent, acting as a tumor suppressor by regulating cell cycle control, DNA damage repair, and gene expression, while also displaying oncogenic properties in specific contexts by promoting early tumorigenesis through oxidative stress pathways. Understanding the molecular mechanisms of ARID1A, including its interactions with key cellular pathways such as PI3K/AKT/mTOR, β-catenin, and PD-L1, provides insights into its complex role in HCC pathogenesis. Furthermore, ARID1A's impact on cancer stem cell maintenance, metabolic reprogramming, and immune evasion underscores its potential as a therapeutic target. This review highlights the need for context-specific therapeutic strategies targeting ARID1A, which could lead to more effective treatments for HCC, addressing both its tumor-suppressive and oncogenic activities.

Immunotherapy engagement in pancreatic adenocarcinoma: Provisional results of iLSTA study— Durvalumab, LSTA1 (certepetide), gemcitabine, and nab-paclitaxel for locally advanced pancreatic ductal adenocarcinoma.

746 Background: Pancreatic ductal adenocarcinoma (PDAC) is characterised by a dense, extracellular matrix-rich stroma, which creates a physical barrier against drug penetration. Evidence suggests that the iRGD peptide, LSTA-1, can increase the penetration of anti-cancer drugs to tumours through selective targeting of tumour endothelial cell receptors. Additionally, LSTA-1 administration promotes CD8+ immune cell tumour infiltration, potentially enabling immunotherapy as a treatment modality. iLSTA examined safety, tolerability and effect of the combination. Methods: Participants diagnosed with locally advanced PDAC were divided into 3 cohorts in a 1:1:4 ratio. Cohort 1 (n=5) received gemcitabine (1000mg/m 2 ), nab-paclitaxel (125mg/m 2 ), placebo LSTA-1 (3.2mg/kg) and placebo durvalumab (750mg). Cohort 2 (n=5) received gemcitabine, nab-paclitaxel, active and placebo LSTA-1, and placebo durvalumab. Cohort 3 (n=20) received gemcitabine, nab-paclitaxel, LSTA-1 and durvalumab. Tissue biopsies via endoscopic ultrasound were obtained pre-treatment and between weeks 12 and 16 for analysis of tumour infiltrating lymphocytes (TILs). Patient tumour sizes were assessed every 8 weeks using radiological imaging according to RECIST v1.1, and serum CA19-9 levels were analysed monthly. Results: 6/17 patients showed significant RECIST partial response after 2 cycles of treatment (5 patients in cohort 3), with the remaining 11 patients exhibiting stable disease. After 4 cycles of treatment, 10/17 patients demonstrated partial response (9 patients in cohort 3). Of the remaining 7 patients, 6 demonstrated stable disease, and 1 patient (cohort 2) exhibited a RECIST complete response. 13/17 patients who completed 4 treatment cycles showed a decrease in CA19-9 levels. 6 patients demonstrated >90% reduction in CA19-9 (5 in cohort 3), with the remaining 7 patients showing a >50% reduction in CA19-9 levels (5 in cohort 3). 12 patients underwent repeat biopsies 12-16 weeks post-treatment to assess TILs. 10 patients showed immune cell infiltration (5% to 50% stroma infiltration), 2 had no tumour found (Cohort 3). The combination was safe with no unexpected toxicities. Conclusions: The preliminary results of this study suggest that the combination of gemcitabine and nab-paclitaxel with LSTA-1 and durvalumab is safe and potentially induces tumour infiltrating lymphocytes and RECIST response in locally advanced pancreatic adenocarcinomas. Clinical trial information: ACTRN12623000223639 .

Management of vestibular schwannoma during pregnancy: A systematic review.

This systematic review evaluates the management strategies for vestibular schwannoma (acoustic neuroma) during pregnancy, a rare but significant clinical condition, by synthesizing findings from case reports. A comprehensive literature search was conducted across PubMed, Embase, Cochrane Library, Scopus, and Web of Science databases. Relevant case reports were included based on predefined inclusion and exclusion criteria. Data were extracted on patient demographics, tumor characteristics, clinical symptoms, management strategies, and outcomes. Thirty-seven cases were included, with a mean patient age of 28.72 years and a mean gestational age at diagnosis of 26.63 weeks. Hearing loss was the most common symptom (92.3%), followed by facial numbness (53.8%) and headache (41%). Tumor sizes ranged from 2.0 to 6.5 cm, with larger tumors associated with increased neurological symptoms. Surgical intervention was performed post-delivery in 78.9% of cases, while 21.1% underwent surgery during pregnancy. Seizures showed a statistically significant difference with the timing of surgery, with one case occurring during pregnancy and none post-delivery (p = 0.05). Most cases were managed conservatively, with surgery deferred until postpartum unless neurological decline or tumor growth warranted earlier intervention. The management of vestibular schwannoma during pregnancy requires a multidisciplinary approach, balancing maternal and fetal health. Conservative management is generally preferred, with surgical intervention reserved for cases with significant symptoms. Hormonal changes during pregnancy may exacerbate tumor growth, underscoring the need for early diagnosis and careful monitoring. Further research is needed to optimize management guidelines and improve outcomes.

Remote organ cancer induces kidney injury, inflammation, and fibrosis and adversely alters renal function.

Approximately 30% of the patients with cancer experience kidney complications, which hinder optimal cancer management, imposing a burden on patients' quality of life and the healthcare system. The etiology of kidney complications in patients with cancer is often attributed to oncological therapies. However, the direct impact of cancer on kidney health is underestimated. Our previous study demonstrated that metastatic lung cancer adversely alters the kidney and exacerbates chemotherapy-induced nephrotoxicity, indicating lung cancer-kidney crosstalk. The current study examines whether this phenomenon is specific to the employed cancer model. Female and male mice of various strains were injected with different cell lines of remote organ cancer, and their kidney tissues were analyzed for toxicity and fibrosis. The impact of cancer on the kidney varied by cancer type. Breast cancer and specific subtypes of lung cancer, including KRAS- and epidermal growth factor receptor (EGFR)-mutant cancer, pathologically altered kidney physiology and function in a manner dependent on the metastatic potential of the cell line. This was independent of mouse strain, sex, and cancer cell line origin. Moreover, tumor DNA was not detected in the renal tissue, excluding metastases to the kidney as a causative factor for the observed pathological alterations. Lewis lung carcinoma and B16 melanoma did not cause nephrotoxicity, regardless of the tumor size. Our results confirm cancer-kidney crosstalk in specific cancer types. In the era of precision medicine, further research is essential to identify at-risk oncology populations, enabling early detection and management of renal complications.NEW & NOTEWORTHY Patients with cancer frequently experience kidney complications, often attributed to antineoplastic therapies. This emphasis on therapy-induced nephrotoxicity has led to the underestimation of the impact of cancer on the kidney. Our study demonstrates that distant organ cancer is sufficient to induce nephrotoxicity, highlighting the existence of cancer-kidney crosstalk. Our findings underscore a gap in our understanding of renal complications in patients with cancer and provide a rationale for identifying the underlying mechanisms for the development of nephroprotective agents.

Characteristics of optic canal invasion in the large midline non-tuberculum sellae anterior skull base meningiomas and the surgical outcomes

ObjectiveThere is a lack of available data regarding the incidence and characteristics of optic canal invasion (OCI) in large midline non-tuberculum sellae anterior skull base meningiomas (NTSAM), specifically those originating predominantly from the olfactory groove and planum sphenoidale. This study aims to describe the incidence and characteristics of OCI as well as clinical and visual outcomes following extensive tumor resection with optic canal exploration in intra-optic canal tumor removal. In addition, the predictive performance of OCI by preoperative magnetic resonance imaging (MRI) is investigated.Materials and methodsFrom 2016 to 2024, we retrospectively reviewed 24 patients with large midline NTSAM who underwent extensive tumor resection in our institution. The OCI was evaluated and compared between preoperative MRI and intraoperative findings. The OCI was classified as follows. Type 1 represented no invasion, type 2 represented secondary invasion, type 3 represented partial wall invasion (two subtypes), and type 4 represented invasion into the superior-medial-inferior walls of the optic canal. Visual functions were assessed before and after surgery.ResultsAmong 24 patients, a mean tumor size of 57.2 mm (range 39.0–79.0). The OCI was observed intraoperatively in 22 cases (91.7%), with 19 cases exhibiting bilateral OCI. Among the 48 optic canals in the 24 patients, 18 (37.5%) were type 4, 12 (25.0%) were type 3-inferomedial, 9 (18.8%) were type 3-superomedial, and 2 (4.2%) were type 2, where 7 (14.6%) optic canals were without OCI. A significant correlation was observed between intraoperative OCI and the tumors that exhibited involvement of the tuberculum sellae (TS) on MRI (p < 0.001). For patients with visual impairment, the vision in 27 of 38 (71.1%) eye sides showed improvement following the surgery. There was 1 (4.2%) case of tumor recurrence at the mean follow-up time of 27.3 months (range 4–73 months).ConclusionsA high incidence of OCI was observed in the large midline NTSAM. The identification of TS involvement on MRI can serve as a strong predictor of OCI. Therefore, optic canal exploration to remove the optic canal invasion during the surgical removal of these particular tumors should be contemplated to attain radical tumor resection to enhance the possibility of improving visual function and reduce the risk of recurrence.