Prognostic Factors For Survival Research Articles

A comparison of the clinicopathological features and genetic alterations in stage II/III gastric cancer with no recurrence, early recurrence and late recurrence after curative surgery

Background: Few studies have explored the genetic changes and clinicopathological features of stage II/III gastric cancer (GC) patients with no tumor recurrence, early recurrence, or late recurrence after curative surgery. Methods: In this study, 376 patients who underwent curative surgery for stage II/III GC were analyzed. The clinical and genetic features of patients with no recurrence, early recurrence (<2 years), and late recurrence (≥2 years) were compared. Results: Among the 376 patients, 155 experienced tumor recurrence, including 116 with early recurrence and 39 with late recurrence. Patients with early recurrence had larger tumors, fewer superficial tumors, increased lymphovascular invasion, advanced T and N categories, higher TNM stages, and poorer 5-year survival (3.4% vs. 38.5% vs. 63.5%, p<0.001) than those with late recurrence or no recurrence. For intestinal-type GC, patients with early recurrence had more MSI-H tumors than those with late recurrence or no recurrence. For diffuse-type or node-positive GC, patients with early recurrence had more PIK3CA amplifications than did those with late recurrence or with no recurrence. Peritoneal dissemination and lung metastasis were associated with PIK3CA amplifications, whereas liver metastasis was associated with larger numbers of MSI-H tumors and PI3K/Akt pathway mutations. Multivariate analysis revealed that age, tumor recurrence, and pathological T and N categories were independent prognostic factors for both overall survival and disease-free survival. Conclusion: Distinct clinical features and genetic alterations were observed in specific groups of stage II/III GC patients with differences in time to recurrence and recurrence patterns, and targeted therapy and immunotherapy may benefit these groups of patients.

Effect of endometriosis on prognosis of ovarian clear cell carcinoma: a 10-year retrospective study

IntroductionEndometriosis is considered as a precancerous lesion for OCCC; however its prognostic significance remains controversial. This study aims to evaluate the prognostic significance of endometriosis in patients with ovarian clear cell carcinoma (OCCC) and analyze the impact of other clinical pathological features on prognosis. Additionally, we also assess the role of laparoscopic surgery and chemotherapy in OCCC, hoping to provide evidence for improving the clinical diagnosis and treatment of OCCC.MethodsA retrospective analysis was conducted on medical records of 105 OCCC patients diagnosed and treated at the Gynecologic Cancer Center of Hubei Cancer Hospital in China from 2013 to 2022. Based on the presence or absence of endometriosis, OCCC patients were divided into two groups: a group with ovarian endometriosis consisting of 44 cases (41.9%) (EC-positive group) and a group without ovarian endometriosis consisting of 61 cases (58.1%)(EC-negative group). Clinical pathological characteristics, progression-free survival (PFS), and overall survival (OS) were compared between the two groups.ResultsThere were no statistically significant differences between the two groups in terms of age, CA125, tumor size, FIGO stage, adjuvant chemotherapy regimen, or chemotherapy efficacy (P>0.05). Residual tumor after surgery, staging, site invasion involvement, presence of ascites, positive cytology in ascitic fluid, lymph node metastasis, and chemotherapy efficacy were predictive factors for recurrence among patients with statistical significance (P<0.10); chemotherapy efficacy remained as independent predictors for recurrence (P<0.05); staging and chemotherapy efficacy remained as independent predictors for survival (P<0.05). There was no statistically significant difference observed between both groups regarding OS or PFS.ConclusionIn this study, co-existing endometriosis was not a prognostic factor for survival in patients with OCCC. The most important predictors of OS and PFS were FIGO stage and chemotherapy sensitivity. The intrinsic link between endometriosis and OCCC requires larger, better-designed prospective studies to draw more definitive conclusions.

Outcomes of patients with acute myeloid leukemia and bone marrow fibrosis.

The outcomes of patients with acute myeloid leukemia (AML) and bone marrow fibrosis (MF) are not well defined. The study objectives were to evaluate the degrees of MF in AML, and corresponding response rates and outcomes. We performed a retrospective review of 2302 patients with AML. We annotated the clinical and molecular characteristics, response to therapy, and survival outcomes of patients with bone marrow fibrosis. Overall, 492 patients (21.4%) had a reported microscopic evaluation of MF: 344 (69.9%) had MF grade 0-1 and 148 (30.1%) had MF grade 2-3. Patients with MF 2-3 had a higher proportion of complex cytogenetics (39.2% vs. 24.7%, p = 0.002) JAK2 mutations (25.7% vs. 18%, p = 0.07) and lower proportion of IDH2 (16.9% vs. 25.9%, p = 0.03) and CEBPA (15.5% vs. 27.6%, p = 0.006) mutations. 64% were treated with low-intensity chemotherapy (LIT) and 36.1% with intensive chemotherapy (IT). The complete remission (CR)/CR with incomplete count recovery (CRi) rates were 63.5% with IC versus 37.9% with LIT (p = 0.007). In patients aged 60 or older 4-week mortality was 12.5% with IC vs. 9.3% with LIT (p = 0.8). The median overall survival (OS) was 14.2 with MF 0-1 versus 7.5 months with MF 2-3 (p < 0.005). In patients aged 60 or older with MF 2-3 median OS was 6.5 months with IT versus 7.0 months with LIT (p = 0.19). In a multivariate analysis, grade 2-3 MF (HR 2.0, 95%CI 1.59-2.51) was the strongest prognostic factor for survival. In summary, grade 2-3 MF in AML is associated with worse outcomes.

Peripheral Eosinophil Count May Be the Prognostic Factor for Overall Survival in Patients with Pancreatic Ductal Adenocarcinoma Undergoing Surgical Treatment

(1) Background: The importance of total eosinophil count in peripheral blood (EOS) as a type 2 inflammation marker is known to be fundamental in asthma, chronic sinusitis, and vasculitis. In cancer, despite their questionable antiproliferative effect, their role remains unclear. Our purpose was to describe the relationship between baseline blood EOS and overall survival (OS) in pancreatic ductal adenocarcinoma (PDAC) patients. (2) Methods: We retrospectively analyzed data from 137 adult patients who underwent surgical treatment for pancreatic ductal adenocarcinoma (PDAC) between the years 2012 and 2019. Patients with no recent history of systemic steroid use and without intraoperative metastases were included. Patients were categorized into two groups based on EOS (≥0.1 G/l and &lt;0.1 G/l). Survival outcomes were analyzed using Cox proportional hazards regression models. (3) Results: According to EOS and PDAC stage, median OS values were as follows: in stage I–III, EOS ≥ 0.1 G/l group: 14.5 months, in stage I–III, EOS &lt; 0.1 G/l group: 8.0 months, in stage IV, EOS ≥ 0.1 G/l group: 7.0 months, and in stage IV, EOS &lt; 0.1 G/l group: 5.0 months. EOS &lt; 0.1 G/l (vs. ≥0.1 G/l) was an independent prognostic factor for OS in both the uni- and multivariate Cox regression, respectively (HR = 1.48, p = 0.035 and HR = 1.57, p = 0.021). (4) Conclusions: Peripheral eosinophilia seems to be a potential independent prognostic factor. Further studies are necessary to confirm this hypothesis, since our findings suggest that type 2 inflammation may be the factor directly or indirectly lengthening the survival of patients with PDAC.

Predictors of nodal upstaging in clinical N1 nonsmall cell lung cancer.

Surgical resection followed by adjuvant chemotherapy is currently the first choice for the treatment of clinical N1 (cN1) non-small cell lung cancer (NSCLC). However, diagnosing cN1 correctly can be difficult, even with current imaging diagnostic technologies. We aimed to analyze the diagnostic accuracy of preoperative nodal status and the predictive factors for nodal upstaging of cN1-NSCLC. Patients receiving surgery for cN1-NSCLC in 2010 (n=1040) were enrolled in the Japanese Joint Committee of Lung Cancer Registry Database. We investigated the diagnostic accuracy of cN1, predictive factors for nodal upstaging, and prognostic factors for overall survival (OS) and recurrence-free survival (RFS). The 5-year OS and RFS for all patients were 58.2% and 42.7%, respectively. The postoperative pathological nodal status included N0 (36.6%), N1 (39.7%), N2 (23.6%), and N3 (0.1%). In multivariate analysis, younger age (P=.005), no history of smoking (P=.006), and adenocarcinoma (P<.001) were significant predictive factors for nodal upstaging. Older age (P<.001) and higher clinical T (cT) factor (P<.001) were significant indicators for worse OS, while older age (P=.02), higher cT factor (P=.019), high carcinoembryonic antigen value (P=.002), and adenocarcinoma (P=.008) were significant indicators for worse RFS. The diagnostic accuracy of cN1 in this study was ~40%. No history of smoking and adenocarcinoma were significant predictors for nodal upstaging. Although younger age was a significant predictor for nodal upstaging, it was a significant factor for better prognosis.

Prognostic Factors of Long-Term Survival and Conditional Survival Analysis in MPM Patients Treated with CRS+HIPEC: A Retrospective Study of Two Centers.

This study was designed to explore the survival benefit factors of malignant peritoneal mesothelioma (MPM) patients after cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC) and to make dynamic survival prediction by conditional survival (CS). Data of 212 patients with MPM who underwent CRS+HIPEC were retrospectively analyzed. Patients were divided into long-term survival (LTS) group (≥48.0 months) and short-term survival (STS) group (≤16.0 months) according to OS. Conditional survival is the probability of surviving y years after already survived for x years. Univariate and multivariate analyses were performed to explore the favorable factors of LTS. Conditional survival and Kaplan-Meier were applied to assess the postoperative survival probability. Ninety patients were enrolled: 53 (58.9%) were LTS, and 37 (41.1%) were STS. Univariate analysis revealed 14 meaningful factors (P < 0.05): age, surgery history, Karnofsky performance status, pathological types, tumor vascular emboli, lymphatic metastasis, Ki-67 index, preoperative CA125 level, peritoneal cancer index (PCI), completeness of cytoreduction, bleeding, red blood cell (RBC) transfusion, ascites, and severe adverse events (SAEs). Multivariate analysis identified that PCI ≤ 20, less RBC transfusion and no SAEs were independent prognostic factors for LTS. Five-year CS increased from 27% at 0 years to 84% at 4 years with the increasing number of survival years. The survival curve flattens at postoperative 5 years. The key factors in CRS+HIPEC for MPM patients to achieve LTS are lower tumor burden, less intraoperative RBC transfusion, and prevention of SAEs. Malignant peritoneal mesothelioma patients demonstrated a substantial increase in CS over time. Some patients may achieve clinical cure 5 years after surgery.

The prognostic importance of glioblastoma size and shape.

Extent of resection, MGMT promoter methylation status, age, functional level, and residual tumor volume are established prognostic factors for overall survival in glioblastoma patients. Preoperative tumor volume has also been investigated, but the results have been inconclusive. We hypothesized that the surface area and the shape were more representative of the tumor's infiltrative capacities, and thus, the purpose of this study was to assess the prognostic value of tumor size and shape in patients with glioblastoma. In total, 271 patients with primary, unifocal glioblastoma were included from two centers in Norway and Sweden, respectively. All tumors were automatically segmented on preoperative MRI scans and manually validated. Tumor volume was used as a measurement of size, whereas sphericity index and area-to-volume ratio defined the shape complexity of the tumor. Contact surface area of the tumor was considered a measurement of both size and shape. Multivariable Cox proportional hazards models were used to assess the prognostic value of the respective tumor measurements, with previously established prognostic factors as covariates. There were no associations between preoperative tumor volume and overall survival. Contact surface area (HR = 1.013, p = 0.002) and sphericity index (HR = 2.223, p = 0.001) were both significant independent prognostic factors for survival in the multivariable Cox models. Contact surface area was also associated with MGMT promoter methylation (p = 0.039) and extent of resection (p = 0.017). Tumor shape complexity appears to be an independent prognostic factor in glioblastoma patients and may also be associated with MGMT promoter methylation status and extent of surgical resection.

Survival status and prognostic factors analysis in patients with hereditary hemorrhagic telangiectasia-associated pulmonary arterial hypertension

Objective: To analyze the survival status and prognostic factors of patients with hereditary hemorrhagic telangiectasia-associated pulmonary arterial hypertension (HHT-PAH). Methods: This prospective study included patients diagnosed with HHT-PAH at the Fuwai Hospital of the Chinese Academy of Medical Sciences and Guangdong General Hospital from August 2009 to December 2019. Patients were followed up every 6 months±2 weeks, with all-cause mortality as the study endpoint. Multivariate Cox proportional hazards regression mode was used to further screen and validate the prognostic factors. Survival curves were plotted using the Kaplan-Meier method, and the log-rank test was used to compare the survival time differences between patients with and without hepatic arteriovenous malformations. Results: A total of 18 HHT-PAH patients were included, with 14 females (77.8%) and a median age [M (Q1, Q3)] of 39 (32, 45) years. The median follow-up time was 129 (51, 156) months. During the follow-up period, 12 patients (66.7%) died, with a median survival time of 70 (32, 123) months. The 1-year, 3-year, 5-year, and 10-year survival rates were 100.0%, 70.8%(95%CI: 52.3%-96.0%), 53.1%(95%CI: 34.0%-83.0%), and 26.6%(95%CI: 10.6%-66.4%), respectively. HHT-PAH patients with hepatic arteriovenous malformations had a shorter median survival time than those without hepatic arteriovenous malformations [31.0 months (95%CI: 16.6-45.4 months) vs 84.0 months (95%CI: 54.4-113.6 months), P=0.024]. Cox proportional hazards regression analysis showed that hepatic arteriovenous malformation (HR=4.493, 95%CI: 1.064-18.978) was a risk factor for all-cause mortality in HHT-PAH patients. Conclusions: The 10-year survival rate of HHT-PAH patients is poor. The presence of hepatic arteriovenous malformations is a risk factor for mortality in HHT-PAH patients.

Inflammatory markers correlate with lymphocytes infiltrating and predict immunotherapy prognosis for esophageal cancer.

Aim: To investigate the prognostic value of inflammatory markers in esophageal squamous cell carcinoma (ESCC) patients treated with immune checkpoint inhibitors (ICIs).Materials & methods: The infiltration of CD3+ and CD8+ T cells in tissue microarraysfrom 180 patients who underwent radical esophagectomy was detected using immunohistochemistry. A separate cohort of 351 patients with metastatic/recurrent or unresectable ESCC treated with ICIs was enrolled for further investigation. The overall survivaldifference among groups was assessed using Kaplan-Meier analysis. Cox proportional hazards models were employed to investigate the prognostic impact of the inflammatory markers, along with other factors.Results: Decreased inflammation was found to be associated with increased CD3+ and CD8+ T-cell infiltration and a better prognosis. Then, the value of inflammatory markers in predicting survival in 351 ESCC patients receiving immunotherapy was validated. Ultimately, the systemic immune-inflammation index was identified as an independent prognostic factor for overall survival. Additionally, the patients with no distant organ metastasis, or treated by first-line immunotherapy combined with concurrent chemoradiotherapy can considerably prolong survival.Conclusion: Inflammation is associated with the level of tumor infiltrating lymphocytes and that the systemic immune-inflammation index is an effective prognostic predictor for ESCC patients treated with ICIs.

Comment on ‘exploring prognostic factors for survival in patients with advanced pancreatic cancer undergoing PD-1 inhibitor immunotherapy’

Comment on ‘exploring prognostic factors for survival in patients with advanced pancreatic cancer undergoing PD-1 inhibitor immunotherapy’

NCOG-35. IDENTIFYING PROGNOSTIC FACTORS IN PEDIATRIC DIFFUSE MIDLINE GLIOMAS, H3 K27-ALTERED

Abstract INTRODUCTION Diffuse midline gliomas, H3 K27-altered (DMG) are rare, grade 4 tumors localized to the diencephalon, brainstem, and cervical spine. DMGs, characterized by a K27M missense mutation in histone H3, often cannot be safely resected and predominantly present with poor outcomes in children. Few prognostic factors for DMGs have been identified and/or need to be further elucidated, including adolescent age of onset, re-irradiation status, and tumor molecular profile (i.e., PIK3CA mutation). Herein, we describe the clinical outcomes of DMG patients at our institution. METHODS Pediatric patients (&amp;lt;18 y/o) between 2015 and 2023 with biopsy-proven DMG were reviewed. Demographic, treatment, and tumor characteristics (histologic and molecular) were recorded. Adolescent-onset DMGs were defined as patients ≥10 y/o at diagnosis and early-onset DMGs were defined as patients &amp;lt;10 y/o. Progression free survival (PFS) and overall survival (OS) were calculated according to the Kaplan Meier-method. Multivariate regression analyses were performed. RESULTS Twenty-one patients were included (median age=9 y/o). Early-onset DMGs (n=13) progressed significantly earlier and experienced significantly greater mortality than adolescent-onset DMGs (n=8); PFS and OS at 12 months was 7.7% and 23% for early-onset DMGs and 50% and 87.5% for adolescent-onset DMGs (PFS: p&amp;lt;0.01, OS: p&amp;lt;0.02). Patients that received re-irradiation for progressive disease (n=9, mean=84Gy) had an OS of 75% at 12 months, which was significantly greater than an OS of 23% at 12 months (p&amp;lt;0.05) for patients that received no re-irradiation (n=12, mean=53Gy). PIK3CA mutation status was identified as an independent predictor of survival, with PIK3CA-mutant DMGs (n=7) having a median survival of 4.1 months versus 9.7 months for PIK3CA-WT DMGs. CONCLUSION We describe a pediatric cohort that presents several possible prognostic factors of survival in DMGs. Our findings on adolescent age of onset, if further corroborated, has the potential to inform the design and enrollment of DMG clinical trials.

CTNI-13. 18-FET-PET ENHANCED DIAGNOSIS OF PSEUDOPROGRESSION IN GLIOBLASTOMA IS AN INDEPENDENT PROGNOSTIC FACTOR FOR OVERALL SURVIVAL

Abstract INTRODUCTION Detecting pseudoprogression (PSP) in glioblastoma during first-line treatment remains challenging and has significant clinical implications for patient management. The detection of PSP has been shown feasible using FET-PET. The prognostic impact of FET-PET diagnosed PSP on overall survival is still uncertain, as retrospective studies provide limited insights due to the substantial differences in the distribution of prognostic factors between tumor progression (TP) and PSP groups. This study aims to address these uncertainties by leveraging advanced analysis techniques. METHODS Patients with newly diagnosed glioblastoma (WHO 2021) who underwent chemoradiation and contrast-enhanced MRI suspected for TP and subsequent FET-PET scan at Essen University Hospital were retrospectively evaluated. The modified Response Assessment in Neuro-Oncology (RANO) criteria were used to diagnose PSP. FET-PET analysis included mean (TBRmean) and maximum tumor-to-brain ratios (TBRmax). The two groups (TP/PSP) were balanced using a propensity score analysis including age at diagnosis, extent of resection, Karnofsky-Performance-Status Scale (KPS) and MGMT methylation status. Overall survival was predicted using Kaplan-Meier and multivariate analysis as well as conventional FET-PET parameters, PET/MRI volumetry, and FET/MRI-derived radiomics. An independent cohort was used for validation. RESULTS Out of the 165 patients analysed in this study, 38 were diagnosed with PSP. Following balancing analysis, our study cohort consisted of 40 patients (20 TP/20 PSP). Patients with PSP had a significantly longer mean overall survival (mOS) compared to those with TP (mOS TP 20.24 months; mOS PSP 33.25 months; p=0.0023). The multivariate Cox-Regression analysis confirmed PSP as a significant prognostic marker for overall survival (p=0.0153). Confirmation of these results on an independent validation cohort is pending and will be presented at the meeting. CONCLUSION This study shows that PSP is an independent prognostic factor for overall survival in newly diagnosed glioblastoma patients.

Efficacy of durvalumab plus tremelimumab treatment for unresectable hepatocellular carcinoma in immunotherapy era clinical practice.

Since the development of tremelimumab plus durvalumab (Dur/Tre) for unresectable hepatocellular carcinoma (uHCC), it has been used as not only an initial but also later line treatment in clinical practice. This study aimed to elucidate clinical prognostic factors for progression-free survival (PFS) in Dur/Tre treatment cases. Enrolled were 183 uHCC patients treated with Dur/Tre from 2023 to May 2024 (median age, 74years; male patients, 152; Child-Pugh class A:B, 150:33; Barcelona Clinic Liver Cancer stage B:C,59:124; initial line use, 64). Clinical factors with prognostic influence on PFS in these patients were retrospectively evaluated. The median observation period was 7.2months (interquartile range, 3.2-10.4). History of atezolizumab plus bevacizumab (Atz/Bev) treatment was the only significant prognostic factor for PFS at introduction of Dur/Tre in multivariate analysis (hazard ratio 2.040, p=0.028) (median PFS: without vs. with=5.6 vs. 2.7months, p<0.001). Although immune-mediated adverse events (imAE) occurrence was only significant in univariate analysis, when objective response and disease control rates were examined according to imAE positivity (any grade) at the time of analysis, those were noted in 14.4% and 39.2%, respectively, of patients without imAE, while in patients with imAE (any grade), they were noted in 18.2% and 56.1%, respectively (p=0.523 and p=0.038, respectively). History of Atz/Bev treatment may be an independent clinical factor for poor PFS at Dur/Tre introduction.

CNSC-42. PROGNOSTIC VALUE OF INTERLEUKIN-6 IN PATIENTS WITH GLIOBLASTOMA

Abstract Interleukin-6 (IL-6), a pro-inflammatory cytokine, has been implicated in the invasiveness and progression of glioma. However, the association between serum IL-6 levels at specific time points during treatment and patient prognosis remains unclear. This study was aimed to investigate the prognostic value of IL-6 measured at milestones in the treatment of patients with glioblastoma. Between January 2021 and December 2022, consecutive patients with newly diagnosed glioblastoma were enrolled. Serum IL-6 concentrations were measured at different time points, including preoperative, pre- and post-radiation period, and two-month intervals thereafter. Patients with incomplete data were excluded, and increase of IL-6 values due to the overlapping with systemic infection were also excluded from the analysis. During the study period, 26 patients and 270 IL-6 levels at different time points were evaluated. The median follow-up time was 11 months. Tumor progression was evident in 19 patients (73.1%) and 13 patients (50%) were expired. Preoperative and pre-radiation IL-6 values were available in 20 and 23 patients with the median 5.25 and 4.5 pg/mL, respectively. With the cut-off value of pre-radiation IL-6 at 4.5 pg/mL, high IL-6 group showed significantly worse progression-free survival and overall survival than low IL-6 group (p = 0.027 and 0.008, respectively). However, IL-6 levels at other milestone were not related to the patient prognosis. Serum IL-6 elevation in pre-radiation period is an unfavorable prognostic factor in tumor progression and patient survival. Further research is necessary to validate the prognostic role of IL-6 and explore the underlying mechanisms.

CTNI-65. DETERMINANTS OF LONG-TERM SURVIVAL IN PATIENTS WITH IDH-MUTANT GLIOMAS

Abstract BACKGROUND Survival times of patients with IDH-mutant gliomas is variable and can extend to decades. Many studies only provide progression-free rather than overall survival times and prognostic factors remain ill-defined. Here we explored clinical disease characteristics of long-term survivors within a large cohort of patients with extended follow-up. METHODS This single-center, retrospective analysis included 114 patients with IDH-mutant glioma that either died due to tumor-related causes or survived at least 15 years after first diagnosis. Patient characteristics, outcomes, and prognostic factors were stratified by short- (&amp;lt; 15 years) versus long-term (≥ 15 years) survival. Initial diagnosis was (re-)classified according to the WHO 2016 classification. Uni- and multivariate analyses were performed. RESULTS Overall, 66 patients (58%) were diagnosed with astrocytoma and 48 patients (42%) with oligodendroglioma. Median follow-up of the survivors was 16.6 years (range 15-28.9). 62 tumor-related deaths (54%) had been reported at database closure. Patients that died before reaching 15 years survival time had been diagnosed with astrocytoma in 41 (72%) and oligodendroglioma in 16 cases (28%). The long-term survivor cohort comprised 25 patients (44%) with astrocytoma and 32 patients (56%) with oligodendroglioma. Long-term survival was associated with grade 2 histology (p &amp;lt; 0.01), smaller tumor volumes (p &amp;lt; 0.01), and lack of contrast enhancement (p = 0.02). 41 long-term survivors (72%) were initially monitored by a wait-and-scan strategy as opposed to 16 patients (28%) in the cohort of short-term survival (p&amp;lt;0.01). In patients with oligodendroglioma, a higher KPS was associated with longer survival (HR 0.25; 95% CI 0.02-0.67; p = 0.05). Tumor resection (HR 0.43; 95% CI 0.22-0.86; p = 0.02) and wait-and-scan strategies (HR 0.34; 95% CI 0.14-0.79; p = 0.01) were associated with longer survival in patients with astrocytoma. CONCLUSION Tumor resection followed by a wait-and-scan strategy may yield excellent survival times, especially in patients with IDH-mutant grade 2 astrocytoma. Age appears not be an important predictor for survival in patients with IDH-mutant gliomas.

CNSC-45. EXTRINSIC ELECTRICAL MODULATION IMPACTS GLIOBLASTOMA TUMOR GROWTH BY DISRUPTING ITS INTERCELLULAR COMMUNICATION

Abstract Glioblastoma (GBM) is an incurable primary malignant neoplasm of the central nervous system. GBM as an electrically active neoplasm diffusely colonizes healthy brain tissues, disrupting the neurotransmission balance and causing glioma-related epilepsy (GRE) in up to 50% of patients. Interestingly, GRE is an independent favorable prognostic factor for survival in GBM. The therapeutic induction of seizure may have a previously unexplored oncologic value in GBM. We have previously reported in CT-2A-bearing mice subjected to daily extrinsic electrical modulation (EEM) diminished tumor progression and increased overall survival relative to sham-treated mice, but the mechanism by which EEM produces its anti-tumor effect remains uncertain. Therefore, GBM-bearing mice (CT-2A cells xenografted into 5-7 weeks old C57BL/6 female mice, n=5/group) received either a single EEM of 2.0 millicoulombs (mC) or sham treatment. The mice were terminated at 3 hours, 24 hours, 4, 7, and 10 days post-EEM, and tumors and contralateral brain cortex were analyzed using bulk RNA-sequencing and Sequential immunofluorescence (SeqIFTM). SeqIFTM revealed how EEM activates neuronal activity via cFOS expression and induces tumor-specific cell damage through cleaved caspase-3 expression, without affecting healthy brain tissue. Furthermore, RNA-seq performed post-EEM revealed gene expression changes of not only synapse organization markers but also of several tumor-tumor and tumor-neuron connectivity key markers, such as growth-associated protein 43 (GAP43), neuroligin-3 (NLGN3), and glutamate receptors such as GRIA4 and GRIN1 between others. However, the expression of these markers diminished significantly 96h after-EEM, indicating a reduction in intercellular electrical communication by the inhibition of the neoplasm cells electrical integration with neuronal circuits by downregulating glutamatergic receptor expression, blocking the synapse-forming protein NLGN3, and the network-connecting protein GAP43. Taken together, our findings reveal how by the disruption of these critical interactions within the tumor microenvironment though EEM impacts on GBM growth making it more susceptible to therapeutic interventions.

Clinical findings and prognostic factors for immediate survival in 33 dogs undergoing surgery for biliary peritonitis.

To report demographics, clinical signs, physical examination, diagnostic test results, surgical findings, and prognostic factors for in-hospital postoperative mortality following biliary peritonitis surgery in dogs. Retrospective, multi-institutional cohort study. Thirty-three client-owned dogs. The medical records of dogs that underwent surgery for biliary peritonitis between 2015 and 2021 were reviewed. Dogs were included if they had a definitive diagnosis of biliary peritonitis and a surgery report. Information on demographics, clinical signs and duration, physical examination findings, laboratory and diagnostic imaging results, surgery, perioperative medical treatment, and complications for each patient was obtained. Statistical analyses were performed to identify risk factors that affected survival. Cholecystectomy was the procedure most frequently performed (31/33, 94%). The overall mortality rate was 36% (12/33). Survival was affected negatively by hyperbilirubinemia (p = .049), administration of vasopressors (p = .002), renal dysfunction (p = .008), and number of postoperative complications (p = .005). A mortality rate of 50% was observed in dogs with a total bilirubin level greater than 60.5 μmol/L. There was no difference in mortality rate between septic and nonseptic biliary effusions. New prognostic factors associated with in-hospital postoperative mortality in dogs treated surgically for biliary peritonitis were identified, while others that had been reported previously were confirmed. A preoperative bilirubin threshold value associated with a 50% mortality was identified. Additional information that could help to predict survival in dogs with biliary peritonitis has been provided. However, further research is warranted.

Sinonasal Mucosal Melanoma Survival Outcomes, Recurrence Patterns, and Prognostic Factors: A Systematic Literature Review and Meta-analysis of Publications after 2000

Abstract Background Sinonasal mucosal melanoma (SNMM) comprises &lt;1% of all head and neck cancers but has one of the highest 5-year mortalities. Methods A systematic review and analysis using PRISMA (Preferred Reporting Items for Systematic Reviews and Meta- Analyses) guidelines was conducted on SNMM survival, recurrence, and prognostic factors. Results A total of 2,379 abstracts were reviewed resulting in 90 studies describing 3347 SNMM patients. Patients were 49.65% male and 66.5 years old. Surgery plus radiation therapy, followed by surgery only, then radiation only were the most common treatments. Chemotherapy and immunotherapy were used in 418 patients and 101 respectively. The 2-, 3-, and 5-year overall survivals are 55.97, 40.09, and 30.35%, respectively. The 5-year disease-free survival and disease-specific survival are 25.56 and 38.04%. The 5-year local, regional, and distant recurrence-free survivals are 42.35, 81.64, and 44.65%. Mean survival after diagnosis was 26.99 months. Local (n = 650), regional (n = 226), and distant (n = 723) failure presented after 19.36, 6.35, and 12.42 months. Sites of metastasis were lung, liver, bone, brain, skin, kidney, and adrenal glands. Distant metastases, disease in the paranasal sinuses, and higher stage were noted to have worse survival outcomes. Positive margins did not significantly impact overall survival in 11/12 studies. Conclusion Overall survival over 20 years has remained poor with 70% of patients deceased in 5 years. About half of patients will develop distant failure and will thereafter rapidly decline. These data indicate need for advances in treatment of SNMM and new efforts with targeted immunotherapy offer a promising avenue toward improving survival outcomes.

BAIAP2L2 promotes the malignancy of hepatocellular carcinoma via GABPB1-mediated reactive oxygen species imbalance.

Hepatocellular carcinoma (HCC) is a common type of cancer worldwide and ranks as the fourth leading cause of cancer-related deaths. This research investigation identified an upregulation of BAI1-associated protein 2-like 2 (BAIAP2L2) in HCC tissues, which was found to be an independent prognostic factor for overall survival in HCC patients. BAIAP2L2 was observed to enhance cell proliferation, metastasis, stemness, cell cycle progression, and inhibit apoptosis in HCC. Mechanistically, NFκB1 was found to stimulate BAIAP2L2 transcription by directly binding to its promoter region. BAIAP2L2 interacts with GABPB1 to inhibit its ubiquitin-mediated degradation and promote its nuclear translocation. BAIAP2L2 inhibits the levels of reactive oxygen species (ROS) by regulating GABPB1, thereby promoting cancer properties in HCC and reducing the sensitivity of HCC to lenvatinib. In summary, this study elucidates the role and underlying mechanism of BAIAP2L2 in HCC, providing a potential biomarker and therapeutic target for this disease.

Combination of grade and spread through air spaces (STAS) predicts recurrence in early stage lung adenocarcinoma: a retrospective cohort study.

Adenocarcinomas, a common subtype of lung cancer, exhibit diverse histological patterns. In 2020, The International Association for the Study of Lung Cancer (IASLC) introduced a grading system emphasizing high-grade components, which has shown prognostic value. Spread through air spaces (STAS) is recognized as a prognostic feature increasing the risk of recurrence in lung cancer. This study evaluates the combination of STAS status and the IASLC-grading system in surgically resected Stage I lung adenocarcinomas. This study is a retrospective analysis of 123 patients with Stage I lung adenocarcinoma who underwent lobectomy between 2011 and 2019. Histological patterns were assessed according to the IASLC criteria, and STAS status was documented. Patients were categorized based on their IASLC Grade and STAS status. Statistical analyses included Kaplan-Meier survival estimates, Cox proportional hazards models, and comparisons using Chi-square and t-tests. The cohort comprised 43 females and 80 males with a mean age of 61.8 ± 7.6years. STAS positivity was noted in 52.8% of patients. STAS positivity correlated significantly with Grade 3 tumors (p < 0.001). The 5-year recurrence-free survival was significantly lower in STAS-positive patients (70.7% vs. 88.7%, p = 0.026). Patients with Grade 3 and STAS positivity had significantly lower recurrence-free survival compared to other groups (p = 0.002). Grade 3 and STAS positivity were independent predictors of poor recurrence-free survival in multivariate analysis. IASLC Grade 3 tumors and STAS positivity are independent prognostic factors for poor recurrence-free survival in Stage I lung adenocarcinomas. Adjuvant treatment strategies should be considered for patients with these characteristics to improve outcomes.