Univariate Analysis Research Articles

Prognostic value of tumor regression grade (TRG) in patients with gastric/gastroesophageal junction cancer treated by peri-operative chemotherapy and surgery: A single-center experience (Institut Mutualiste Montsouris, Paris, France).

486 Background: Management of locally advanced gastric and gastroesophageal junction (GOJ) cancer relies on peri-operative chemotherapy and radical surgery. Response to neoadjuvant chemotherapy can be evaluated by Mandard Tumor Regression Grade (TRG) performed on the removed specimens. The aim of this study was to investigate the prognostic value of TRG, in terms of post-surgical disease-free survival (DFS) and overall survival (OS). Methods: Retrospective analysis of all consecutive patients (Jan 2010 to Dec 2021) who underwent oncological gastrectomy for gastric or GOJ adenocarcinoma after neoadjuvant chemotherapy was performed. TRG was evaluated according to Mandard classification, ranging from 1 (complete pathological response) to 5 (absence of response), TRG 1-2 being considered as “good responders” and TRG 3-5 as “bad responders”. Univariate and multivariate analysis were performed for DFS and OS. Results: One hundred and ninety-nine patients were included, 157 treated with FOLFOX and 42 with FOLFOX + Taxanes (either FLOT or FOLFOX + Abraxane). TRG 1-2 was observed in 30% in patients (pts) treated with FOLFOX and 24% in pts treated with FOLFOX + Taxanes. With a median follow-up over 5 years (yrs), median DFS and OS were not reached (DFS rates at 3, 5 and 10yrs of 66.5%, 64.1% and 55.7%, respectively; OS rates at 3, 5 and 10yrs of 75.6%, 66.8% and 60.4%, respectively). In univariate analysis, TRG 1-2 was significantly associated with favorable outcome compared to TRG 3-5 in terms of DFS (HR 2.4, p-value 0.0056) and OS (HR 2.6, p-value 0.0061), as well as ECOG at diagnosis (0 vs. 1), ypT stage (yp T0-2 vs. yp T3-4), ypN stage (ypN- vs. ypN+), tumor localization (antrum + body vs. cardia + esophagus), and lymphatic, vascular and peri nervous embolisms (negative vs. positive) for both DFS and OS. However, in multivariate analysis (selection backward Cox-model), only ypT stage and vascular embolisms for DFS, and ypT and ypN stages for OS were found to be independent prognostic factors. Conclusions: Although TRG is a prognostic factor in patients with gastric or GOJ cancer, it does not appear as an independent factor for DFS and OS in this series of 199 pts. These results raise the issue of “good responder” definition, especially for TRG 3. Prognostic impact of TRG needs to be investigated for patients treated with combination of immune checkpoint inhibitors and chemotherapy in neoadjuvant regimens.

Histopathological growth patterns of gastric cancer liver metastasis and their association with patient prognosis.

484 Background: The histopathological growth patterns (HGPs) of liver metastasis reflect the complicated and varied interactions between tumor cells and the host microenvironment. We studied HGPs of gastric cancer liver metastasis (GCLM) and sought to predict them using radiomic and clinical variables. Methods: Hepatectomy was performed in 62 patients with GCLM at our university hospital between 2011 and 2021. HGPs were evaluated according to international consensus guidelines, and were classified as either desmoplastic HGP (dHGP) or non-dHGP. CD4, CD8, VEGF and CD31 were analyzed by immunohistochemistry. Eight hundred and fifty-one radiomics features were extracted from CT portal venous phase images and the optimal radiomics signature was determined by univariate analysis and LASSO regression. Multivariable regression analyses and ROC curves were used to assess the predictive performance of HGPs with a radiomic and clinical combined model. Results: Among 62 patients, 14 were categorized as dHGP, and 48 as non-dHGP. Non-dHGP vs. d-HGP was associated with higher tumor N stage and CEA level, and with decreased CD8 + T cells, and lower VEGF and CD31 expression. HGP status was independently associated with patient cancer-specific survival (CSS) (P＜0.05) multivariately.Analysis of percent relative contribution revealed that HGP ranked first for CSS (35.9%), ahead of T (28.9%) and N (28.9%) stage. A model with combined radiomic and clinical features demonstrated robust performance with area under the curve (AUC) values of 0.993 and 0.933 in the training and validation sets, respectively. Conclusions: Non-invasive determination of radiomic and clinical features was shown to predict HGPs types. Compared to dHGP, GCLM with non-dHGP exhibited significantly lower immune cell infiltration and decreased angiogenesis. Among features examined in GCLM, HGP was the most robust for prognostication. Univariate and multivariate analysis of prognostic factors for cancer-specific survival. Characteristics Univariate analysis Multivariate rergression analysis HR (95%CI) P HR (95%CI) P Gender ( Women vs Men ) 1.13(0.61-2.09) 0.71 Age ( >60years vs ≤60years) 1.08(0.60-1.70) 0.98 HGP ( non-desmoplastic HGP vs desmoplastic HGP ) 3.63(1.78-7.41) 0.00 3.48(1.37-8.88) 0.01 T stage ( T3-T4 vs T1-T2 ) 2.03(1.08-3.80) 0.03 2.29(1.15-4.58) 0.02 N stage ( N1-N3 vs N0 ) 3.46(1.66-7.23) 0.00 2.54(1.17-5.56) 0.02 CEA ( >5ng/ml vs ≤5ng/ml ) 2.37(1.25-4.48) 0.01 1.56(0.70-3.48) 0.27

Value and Kinetics of Virological Markers in the Natural Course of Chronic Hepatitis D Virus Infection.

Chronic hepatitis D virus (HDV) infection can cause severe liver disease. With new treatment options available, it is important to identify patients at risk for liver-related complications. We aimed to investigate kinetics and predictive values of novel virological and immunological markers in the natural course of chronic HDV infection. HBcrAg, HBV RNA and quantitative anti-HBc were analysed in samples from HDV-infected patients at three consecutive time points. Results were linked to clinical outcome by univariable and multivariable analyses. Primary endpoint was the composite endpoint of any liver-related event. Samples from 190 individual patients were analysed with a median clinical follow-up time of 2.69 (IQR 1.13-6.51) years. The majority of patients had cirrhosis (98/190, 52%), and the primary endpoint occurred in 33% (62/190). In univariable analysis, age, cirrhosis, lower quantitative anti-HBc, higher ratio of HBcrAg/anti-HBc and detectable HDV RNA were associated with the primary endpoint. In multivariable analysis, only the presence of liver cirrhosis (HR 7.74, p < 0.001) and age (1.06, p < 0.001) remained independently associated with the primary endpoint. Kinetics of virological parameters during follow-up were similar between the groups. Quantitative anti-HBc was significantly lower in patients with liver cirrhosis (687 (IQR 188-3388) IU/ml vs. 309 (IQR 82-924) IU/ml, p < 0.0004), and lower levels were independently associated with the development of the primary endpoint (HR 1.0, p = 0.014). In chronic HDV infection, neither baseline values nor kinetics of HBV RNA, HBcrAg and anti-HBc were independently associated with clinical outcome, while stage of liver disease and age were predictors of liver-related events.

Risk of peritoneal recurrence following laparoscopic versus open surgery for stage II or III colorectal cancer (JCOG2310A): An integrated analysis of three phase III randomized controlled trials.

161 Background: Peritoneal recurrence in colorectal cancer (CRC) has long been a concern. Although studies have examined the higher risk of peritoneal recurrence following laparoscopic (LAP) compared with open (OP) surgery, the issue remains unresolved, largely due to the heterogeneity of existing data and the limited number of observed peritoneal recurrence events, preventing any definitive conclusions. This study aimed to evaluate whether LAP for pStage II/III CRC presents a potential risk factor for peritoneal recurrence compared with OP. Methods: Data from three phase III trials (JCOG0404, JCOG0910, JCOG1006) were extracted from an ancillary research database (JCOG2310A). From this cohort, patients with pStage II or III CRC who underwent curative surgery were included, and the incidence of peritoneal recurrence was compared between LAP and OP. A multivariate analysis was conducted to adjust covariates between the two groups. The primary outcome was the cumulative incidence of peritoneal recurrence, and the secondary outcome was recurrence in specific high-risk subgroups identified through a univariate analysis. Results: From 3061 patients (OP: 1734; LAP: 1327), pT4 (25% vs. 17%), pStage III (65% vs. 83%), and right-sided tumor (63% vs. 70%) were different between OP and LAP, respectively. With a median follow-up for peritoneal recurrence of 6.2 years, the 5-year cumulative incidence of peritoneal recurrence was 2.8% in the OP group and 2.9% in the LAP group (hazard ratio (HR): 0.940, 95% confidence interval (CI): 0.621-1.425 in the univariate analysis, and HR: 1.086, 95% CI: 0.683-1.727 in the multivariate analysis. The univariate analysis identified pT4, pN2, pStage III, right-sided tumor, poorly differentiated (por/sig/muc), and ECOG-PS 1 as risk factors for peritoneal recurrence. No significant difference was observed in the subgroups (see table). An exploratory propensity score matching analysis with 1066 patients in each group also showed no difference between the groups (the 5-year cumulative incidence of peritoneal recurrence was 2.8% in the OP group and 3.0% in the LAP group [HR: 1.002, 95% CI: 0.625-1.607]). Conclusions: This study revealed that LAP was not a risk factor regarding peritoneal recurrence following curative surgery for Stage II/III CRC. Subgroup analysis of cumulative incidence of peritoneal recurrence. OutcomeMeasures Subgroups pT4 pN2 pStage III Right-sided Poorly differentiated ECOG PS 1 N(OP vs. LAP) 428 vs. 229 274 vs. 184 1133 vs. 1105 635 vs. 403 122 vs. 66 56 vs. 25 Event(OP vs. LAP) 31 vs. 23 13 vs. 10 45 vs. 32 28 vs. 18 10 vs. 2 7 vs. 2 5-year peritoneal recurrence rate (OP vs. LAP)(%) 6.8 vs. 10.1 4.8 vs. 5.4 3.6 vs. 2.9 4.1 vs. 4.5 7.5 vs. 3.0 9.1 vs. 8.0 HR (95% CI) 1.403(0.819-2.402) 1.144(0.503-2.603) 0.725(0.461-1.139) 1.014(0.562-1.829) 0.372(0.081-1.699) 0.609(0.130-2.862)

The role of sequential PET/CT imaging to predict complete response after definitive chemoradiotherapy for locally advanced squamous cell carcinoma of the anal canal.

12 Background: The standard treatment for locally advanced squamous cell carcinoma of the anal canal (SCCAC) is definitive radiotherapy (RT) with concurrent chemotherapy (CRT), with excellent outcomes. Nevertheless, rates of locoregional failure of 10% to 30% have been reported. Due to the narrow therapeutic window between time-dependent response to RT and prompt salvage surgery, the definition of a surveillance strategy after radical CRT is challenging. In particular the contribution of 18-FDG PET/CT is not clearly established. The purpose of this study was to evaluate the effectiveness of follow-up MR and 18-FDG PET/CT to predict response to CRT in patients with SCCAC. Methods: We analyzed a cohort of consecutive patients who received definitive RT/CRT from January 2019 to February 2024. After completion of therapy, radiologic (rCR) and metabolic complete response (mCR) was assessed with pelvic MR (RECIST v.1.0) and 18-FDG PET/CT at 3 ad 6 months respectively. Local Control (LC) was defined as time from the end of CRT to local failure or last follow-up. Univariate analysis (UVA) was performed to identify variables associated with outcome using the log rank test. Sensitivity and Specificity analysis was performed to assess the correlation between rCR/mCR and LC. Results: A total of 67 patients (median age 67 years, range 44-83) were included. All patients completed RT, and 52 received concurrent CRT. Baseline and surveillance MR and 18-FDG PET/CT were available for 49 patients. After a median follow-up of 28 months, 12 patients experienced disease progression (PD) (10 local; 2 distant), resulting to salvage surgery in 10 cases after biopsy. At 3 years, LC rate was 78%. At UVA, only mCR was correlated with LC (3-year LC 90% versus 59%, p=0,0137; HR 0,01660, IC 95% 0,03-0,84). For prediction of LC, accuracy of mCR at 6 months was 83.7% versus 62.5% for rCR. Specificity/Sensitivity analysis is summarized in the table. Conclusions: 18FDG PET/CT at 6 months may identify patients with a higher likelihood of developing complete tumor regression following CRT. Further data is needed to confirm the appropriate surveillance strategy for patient undergoing CRT in clinical practice. Specificity and sensitivity analysis. Sensitivity Specificity Positive Predictive Value Negative Predictive Value mCR 83.3% 84.0% 92.6% 68.7% rCR 25.0% 70.0% 14.0% 82%

The role of stereotactic radiotherapy in brain metastases from gastrointestinal cancer.

181 Background: The incidence of brain metastases from Gastrointestinal primary tumors (GI-BMs) is approximately of 6%. Appropriate management of these patients, who often presents at advanced disease stage, is poorly defined. Stereotactic Radiotherapy (SRT) could be proposed to improve symptoms and extend disease control. The aim of this study is to assess the impact of SRT in this population. Methods: Data from consecutive patients treated for GI-BMs with SRT from March 2015 to March 2024 were retrospectively collected. Dose was expressed as Equivalent Dose in 2Gy Fractions (EQD2). lntra-Cranial Control (IC) and Overall Survival (OS) were calculated from date of SRT to event (intracranial relapse and death respectively) or last follow-up. Results: Fifty-four patients (median age 68 years, range 46-84) accounting for 98 GI-BMs were included. Primary tumors were colorectal and gastro-oesophageal adenocarcinoma in 37 (68.5%) and 17 (31.5%) patients respectively. Eighteen (33%) patients presented with a single GI-BM. Extra-cranial disease was present in 41 (76%) patients, including unresected/relapsing primary tumor in 9 (17%) cases. Detection of BMs occurred at diagnosis in 8 (15%) patients, as first site of relapse in 27 (50%) or as progression of known metastatic disease in 19 (35%) patients. Before SRT, surgery and/or WBRT were performed in 10 (19%) and 5 (9%) patients respectively. For each SRT course a median of 1 (range 1-5) GI-BMs was treated. Dose regimens consisted of 12-30 Gy in 1-5 fractions, to a median EQD2 of 50 Gy 10 (range 22-68). A second SRT course for out-of-field intracranial progression was performed in 7 patients (13%). First- and further chemotherapy lines were administered in 39 (72%) and 15 (28%) patients respectively. IC rate was 88% at 6 months and 70% at 1 year. At univariate analysis (UVA) no variables were correlated with IC. Median OS was 11 months (IC 95% 9-16), 6-months and 1-year OS rate was respectively 76% and 48%. Only systemic treatment beyond first line was correlated with OS at UVA (4 versus 15 months, p=0.02). Two (4%) patients developed mild symptomatic radionecrosis. Conclusions: Onset of GI-BMs can occur at any stage of disease. Despite poor overall outcome, selected patients may benefit from SRT to improve IC, particularly in association with first-line systemic treatment. Multiple SRT courses can be delivered in case of further intracranial recurrence. Symptomatic radionecrosis may occur in less than 5% of cases.

Association between adjuvant component of perioperative chemotherapy and survival outcomes in resected gastric cancer (GC).

378 Background: Perioperative chemotherapy is the standard of care for resectable GC but many patients do not proceed to or complete adjuvant chemotherapy (AC). It remains unclear whether AC following neoadjuvant chemotherapy (NAC) improves survival. Methods: Patients with GC who received NAC and underwent curative-intent gastrectomy from 2006-2022 were identified from an institutional database. Patients with mismatch repair-deficient/microsatellite instability-high tumors, GEJ tumors, M1 disease, neoadjuvant radiotherapy, total neoadjuvant intent treatment, incomplete NAC (&lt;66% of planned cycles), and incomplete data were excluded. A lymph node ratio (LNR) risk cutoff was determined using maximally selected rank statistics. Kaplan-Meier analysis with log-rank tests were used to compare overall survival (OS) and disease-free survival (DFS). Cox proportional hazards regression models were used to identify independent predictors of OS and DFS. All analyses were performed in R statistical software. Results: Of 340 patients included, 264 (78%) received AC. Most common reasons for incomplete AC were postoperative complications (20%), poor performance status (16%), minimal pathologic response to NAC (14%), patient choice (14%), and NAC toxicity (9%). Median follow-up was 6.4 years. In the overall cohort, there was no significant difference in OS (median 10 vs. 8.3 years; p=0.14) or DFS (7.0 vs. 7.5 years; p=0.12) between AC and non-AC groups. In node-negative (ypN-) patients (n=170), there was no association between receipt of AC and OS (12 vs. 10 years; p=0.6) or DFS (12 vs. 10 years; p=0.8). On univariable analysis, lack of AC receipt was not associated with shorter OS (p=0.3) or DFS (p=0.4). In the node-positive (ypN+) cohort (n=170), AC receipt was associated with significantly longer DFS (4.8 vs. 2.7 years; p=0.031) but not OS (5.5 vs. 2.8 years; p=0.071). However, on multivariate analysis, AC only showed a non-significant trend towards longer DFS (HR 0.77 [95% CI 0.49-1.19]; p=0.20). High-risk patients based on LNR (LNR&gt;0.0684; n=112) who received AC (n=87; 78%) had longer OS (p=0.033) and DFS (p=0.014). No such differences were observed in the low risk LNR subgroup (LNR&lt;0.0684; n=227). Conclusions: Following NAC, AC was not associated with improved survival in patients with ypN- GC. The association between AC and survival in ypN+ GC remains unclear but LNR may be used to identify patients with ypN+ disease who may benefit from AC. These observations require prospective validation but may have implications for clinical care and future trial design.

Definitive local therapy in solitary liver metastatic anal squamous cell carcinoma.

5 Background: Metastatic anal squamous cell carcinoma is rare and associated with a poor prognosis. There is limited evidence on the impact of local interventions on survival outcomes in patients with metastatic disease. We aimed to evaluate the survival of patients with liver-only metastatic anal cancer following definitive local management of liver lesions. Methods: This is a single-institution retrospective cohort study of patients with liver-limited metastatic anal cancer who underwent curative-intent local therapy. Clinical characteristics were collected and analyzed. The Kaplan-Meier method was used to calculate disease-free survival (DFS) and overall survival (OS). Prognostic factors associated with DFS and OS were assessed using Cox-proportional hazards models. Results: Twenty-five patients were included, median age was 59 years, and 92% were female. None of the patients had known HIV infection, 92% had HPV-positive disease and 76% had metachronous liver metastases following locoregional disease. All patients received chemoradiation for the primary lesion Unilobar hepatic involvement was present in 76% of the patients, with 56% having a single metastatic lesion. Pre-intervention systemic therapy was provided to 52% of the patients, including 8 who received carboplatin and paclitaxel, with a median duration of 3 months and ORR of 69%. Definitive treatment of metastatic disease included surgical resection (60%), non-surgical interventions (20%), and multimodal therapy (20%). All patients had viable tumor in the pathological specimen. With a median follow-up of 22 months, median DFS was 7.3 months, and median OS was 51.3 months. An ECOG performance status of 2, poorly differentiated histology, and extrahepatic recurrence were identified as significant prognostic factors in the univariate analysis, but not in the multivariate analysis. Conclusions: Our results demonstrate potential for long-term survival in liver-limited metastatic anal squamous cell carcinoma amenable to local therapeutic intervention combined with systemic therapy. These findings warrant further prospective study of local therapy in oligometastatic anal cancer. Characteristics N=25 (%) Median number of liver metastases (range), lesions- 1- 2-3- &gt;3 1 (1-20)14 (56)8 (32)3 (12) Median maximal diameter of liver metastases (range), cm 3 (0.9-11.9) Best response of liver metastases to chemotherapy (N=13)- Complete response- Partial response- Stable disease- Progressive disease 2 (15)7 (54)3 (23)1 (8) Surgical procedure (N=20)- Right/left hemi-hepatectomy- Segmentectomy- Wedge resection 4 (20)14 (70)2 (10) Non-surgical procedure (N=10)- Local ablation- Radiotherapy- Other 5 (50)3 (30)2 (20) Hepatic surgical margins (N=20)- Positive margins- Close margins (&lt;1mm)- Negative margins 02 (10)18 (90) Recurrent disease- Yeso Intrahepatico Extrahepatic- No 20 (80)14 (70)6 (30)5 (20)

Impact of sirtuin genes expression on first-line treatment outcomes in patients (pts) with metastatic colorectal cancer (mCRC) enrolled in CALGB/SWOG 80405 (Alliance).

269 Background: Sirtuins (SIRT1-7) are class III histone deacetylases with different roles in CRC as tumor suppressive and oncogenic, mainly influencing proliferation, migration, invasion, DNA damage and chemoresistance. In the present study, we explored the association between tumor gene expression of sirtuins and first-line treatment outcomes in mCRC pts. Methods: We evaluated the impact of the tumor gene expression of sirtuin genes ( SIRT1 -7) on treatment outcomes (overall survival: OS; progression free survival: PFS) in 433 pts enrolled in the randomized, phase III CALGB/SWOG 80405 (NCT00265850) trial. RNA extracted from FFPE tumor samples was sequenced using the HiSeq 2500 (Illumina). Subgroup analyses were based on treatment (bevacizumab [bev] (N = 226) vs. cetuximab [cet] (N = 207)). For each gene, expression was divided into tertiles of high, medium and low. The associations between tumor gene expression and outcomes (PFS and OS) were assessed using log-rank test in univariate analysis. Multivariable Cox proportional hazards regression model was used to compute hazard ratios (HR) and 95% confidence intervals while adjusting for baseline characteristics. Treatment-gene interactions were analyzed using the likelihood ratio test. Results: Of the seven genes analyzed, SIRT3 high was associated with both longer PFS (HR: 0.59 [95% CI: 0.46-0.74], P &lt; 0.001) and OS (HR:0.64 [95% CI: 0.50-0.83], P = 0.002) overall. Treatment-gene interaction testing found significant interactions for SIRT1 and SIRT5 with PFS ( P values: 0.021 and 0.016, respectively) and OS ( P values: 0.038 and 0.014, respectively) with targeted therapies (bev vs. cet). Multivariate analysis showed SIRT1 high associated with longer PFS (HR: 0.62 [95% CI: 0.42-0.89], P = 0.014) and OS (HR: 0.59 [95% CI: 0.40-0.89], P = 0.036) in cet-treated pts; in contrast with shorter observed PFS (HR: 1.38 [95% CI: 0.96-1.99], P = 0.22) and OS (HR: 1.31 [95% CI: 0.90-1.93], P = 0.23) in bev-treated pts. SIRT5 high showed similar results and associated with longer PFS (HR: 0.64 [95% CI: 0.45-0.91], P = 0.039) and OS (HR: 0.57 [95% CI: 0.39-0.83], P = 0.013) in cet-treated pts, with no similar associations in bev-treated pts. Conclusions: Our results highlight a potential role for SIRT3 as prognostic and, SIRT1 and SIRT5 as predictive biomarkers for first-line treatment in mCRC, with differential effects based on targeted agents. Significant interaction favored cet treatment in SIRT1 high and SIRT5 high tumors. However, previous reports suggest an opposite role of SIRT5 that has been linked to chemotherapy and/or cet resistance in CRC via the inactivation of succinate dehydrogenase complex subunit A. Therefore, further studies are warranted to dissect the mechanism behind the interaction of SIRT5 with cetuximab activity and establish the potential of targeting SIRT1/5 in CRC.

Long-term survival outcomes of atezolizumab plus bevacizumab treatment in patients with advanced hepatocellular carcinoma.

600 Background: Immunotherapy combinations such as atezolizumab plus bevacizumab (Atezo-Bev) or STRIDE have been established as standard therapies for patients with advanced hepatocellular carcinoma (HCC). After dual immunotherapy treatment, durable responders and long-term survivors had been reported. However, the longevity of such outcomes following Atezo-Bev treatment remains to be evaluated. Methods: We analyzed medical records of four medical centers in Taiwan for patients with Child-Pugh class A liver reserve who received first-line Atezo-Bev treatment for advanced HCC from January 2018 to May 2021, to evaluate their survival outcomes after a long-term follow-up. Results: We enrolled 54 patients, predominantly male (90.7%) with the median age of 65 years. The main hepatitis etiology was viral hepatitis (92.6%), including 68.5% chronic hepatitis B. After a median follow-up of 61.9 months, the median overall survival (OS) was 21.0 months (95% confidence interval 10.4 – 31.6 months). The 3-year, 4-year and 5-year OS rate was 36.4%, 25.7% and 25.7%, respectively. For patients with tumor response (N = 19, 34.5%) or disease control (N = 44, 80.0%), the 3-year, 4-year, and 5-year OS rates are listed at Table 1. In univariate analysis, younger age (≤ 70 years), absence of intrahepatic tumor, lack of macrovascular invasion (MVI), and ALBI grade 1 were associated with an OS &gt; 3 years. In multivariate analysis, after adjusting sex, viral hepatitis, MVI, extrahepatic spread, and initial alpha-fetoprotein &gt; 400 ng/ml, the absence of intrahepatic tumor (Odds ratio [OR] = 5.36, p = 0.047) and ALBI grade 1 (vs grade 2, OR = 10.02, p = 0.037) remained independent predictors for OS &gt; 3 years. Conclusions: In patients with advanced HCC, Atezo-Bev treatment led to a notable proportion achieving long-term survival, especially in patients with good response to the treatment. Absence of intrahepatic tumors and preserved liver function are predictive of prolonged survival. 3-year, 4-year and 5-year OS rate of patients who receive Atezo-Bev treatment, stratified by treatment response. Landmark survival OS rate (%) by treatment response Disease control Responder 3 years 35.6 52.2 4 years 30.3 52.2 5 years 30.3 47.7 Responder: patients who achieved a best response of complete response or partial response after treatment with Atezo-Bev. Disease control: includes responders and patients who achieved a best response of stable disease following Atezo-Bev treatment.

Diagnostic Yield and Therapeutic Implications of Vascular Imaging in Acute Ischemic Stroke: Prospective and Consecutive Study of Small Vessel versus Large Vessel Ischemia.

To evaluate patients acute cerebral ischemia in order to assess for factors which may help to differentiate patients with small vessel involvement from those with large vessel involvement in an effort to determine diagnostic yield of vascular imaging. We prospectively and consecutively evaluated all acute ischemic stroke patients at our medical center from May 16, 2021 to December 10, 2021. Distinction between small vessel and large vessel involvement was based upon clinical presentation, the results of brain imaging and either computed tomographic angiography, in the vast majority, or magnetic resonance angiography. Patient demographics and risk factors for stroke as well as therapeutic intervention was assessed. Of the 90 patients studied, 59 had large vessel ischemia (66%) with 26 (44%) having large vessel occlusion and one had symptomatic high-grade middle cerebral artery stenosis. Conversely, none of the 31 patients with small vessel presentation (34%) had large vessel occlusion or high-grade stenosis. In addition, 19 out of 59 (32%) large vessel patients compared to 2 of 31 (6%) of the small vessel patients had atrial fibrillation identified as a potential mechanism with a p-value of 0.01 by univariate analysis and 0.17 by multivariate analysis. The routine use of vascular imaging in acute ischemic stroke is of very low yield in small vessel presentation with the presence of potential cardiogenic emboli is also relatively low. Efforts at accelerated identification of a small vessel mechanism, to avoid unnecessary testing, should provide significant value from both a patient management and cost standpoint.

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.

Investigating the real-world outcomes of single- versus multi-agent preoperative chemoradiotherapy for locally advanced rectal cancer: NCDB analysis from 2004-2020.

61 Background: Fluorouracil-based chemoradiotherapy is the standard initial treatment for locally advanced rectal cancer, demonstrating improved pathological response and reduced local recurrences compared to radiation alone. Fluorouracil-based chemo-radiation therapy has no impact on distant recurrences. Oxaliplatin was tested in addition to fluorouracil-based chemo-radiotherapy in clinical trials to improve pathological complete response (pCR), distant recurrence-free survival, and overall survival. The trial results are conflicting. In this study, we aim to compare single-agent (SA) versus multi-agent (MA) chemotherapy using real-world data from the National Cancer Database (NCDB). Methods: The NCDB was used to identify 39,667 patients with rectal cancer who received concurrent chemoradiotherapy between 2004 and 2020. We compared patients who received SA chemotherapy with those who received MA concurrent chemotherapy. The primary outcomes of interest were overall survival and pCR. The groups were compared using univariate analysis and Cox proportional hazard models to adjust for potential confounding factors. Results: Of 39,667 patients with rectal cancer, 24,452 received single-agent (SA) chemotherapy and 14,215 received multi-agent (MA) chemotherapy. Patients in the SA group were of advanced age, had a greater number of comorbidities (as calculated by the Charleson-Dayo score), were treated within community facilities, had a higher income status, were covered by government insurance, were situated on the east coast, and had lower educational attainment compared to those in the MA group (p&lt;0.05). SA group had higher T4 and N1 disease, however MA group had more N2 disease. Upon survival analysis, patient in MA group had higher survival (41.2 vs 38.9 months, p=0.005), however pCR was significantly higher in SA group (10.4% vs 6.4%, p&lt;0.001). Conclusions: MA chemoradiotherapy for rectal cancer improves survival, with the SA regimen showing enhanced complete pathological response. Differences in baseline characteristics may explain the outcomes. While MA chemotherapy offers modest overall survival benefits, potential toxicity needs to be considered and confirmed in future studies. Comparison between single agent vs multi-agent chemo-radiotherapy group. Outcome Single-agent chemotherapy Multiagent chemotherapy Chi Squared p-value No readmission within 30 days of surgical discharge 22,727 (89.3 %) 12,921 (90.9 %) &lt;0.001 30-day mortality after surgery 360 (1.5 %) 59 (0.5 %) &lt;0.001 90-day mortality after surgery 716 (3.0 %) 158 (1.3%) &lt;0.001 Median duration of surgical admission 6.0 5.0 &lt;0.001 Median survival-vital = deceased (months) 38.9 41.2 0.005 Median survival-vital = alive (months) 66.9 52.0 &lt;0.001 Pathological complete response (pCR) 2,644 (10.4%) 904 (6.4%) &lt;0.001

Sex disparities in outcome of medication-assisted therapy of opioid use disorder: Nationally representative outpatient clinic data.

The opioid epidemic causes massive morbidity, and males have substantially greater overdose mortality rates than females. It is unclear whether there are sex-related disparities at different stages in the trajectory of opioid use disorders (OUD), from large samples in the community. To determine sex disparities in non-medical opioid use (NMOU) at the end of treatment with medications for opioid use disorder (MOUD), using national data. Observational study of outpatient MOUD programs in the "Treatment episode data set-discharges" (TEDS-D) for 2019. Persons aged ≥ 18 in their first treatment episode, in outpatient MOUD-based therapy for heroin or other opioids (N = 10,065). The binary outcome was presence/absence of NMOU in the month prior to discharge. In univariate analyses, males had higher odds of NMOU compared to females (odds ratio=1.22; p = 6.84 ×10-5 after Bonferroni correction). A multivariable logistic regression detected a relatively small male>female odds ratio of 1.14 (p = 0.0039), surviving adjustment for demographic variables and social determinants of health. Several specific conditions were revealed in which males had greater odds of NMOU compared to females (e.g., if they were in the white racial category, and were not of hispanic ethnicity). Also, using by smoking, inhalation or injection routes (versus oral) was associated with greater odds of NMOU, irrespective of sex. This national community sample shows that males overall have greater odds of NMOU in their first treatment episode with MOUD, a potential indicator of more unfavorable outcomes. Further analyses should examine the underpinnings of this disparity, including clinical severity features.

Optimal duration of neoadjuvant chemotherapy prior to CRS±HIPEC for colorectal cancer: An assessment of survival and postoperative outcomes.

188 Background: Cytoreductive surgery (CRS) with or without heated intraperitoneal chemotherapy (HIPEC) represents a viable treatment option for select patients with colorectal cancer peritoneal metastases. Given high recurrence rates after surgery, it is common practice to administer neoadjuvant chemotherapy (NAC). The optimal duration, however, when considering oncologic value and postoperative outcomes, is not known. Methods: A single institution database (2009-2024) of colorectal cancer patients that underwent CRS±HIPEC was reviewed. Patients with colorectal cancer undergoing CRS±HIPEC for curative intent (completeness of cytoreduction 0 or 1) with known NAC duration were included. Analysis was stratified by NAC duration of 0-3 months or greater than 3 months. Co-primary outcomes were recurrence free survival (RFS) and overall survival (OS). Secondary outcomes included clinically significant complications, defined as Grade 3 or greater adverse events based on Common Terminology Criteria for Adverse Events Version 5.0. Results: From 2009-2024, 108 patients underwent CRS±HIPEC for colorectal cancer. Final analysis included 84 patients that underwent curative intent surgery and had a known duration of NAC ( &gt; 3 months NAC: 55 patients, 0-3 months NAC: 29 patients). Median peritoneal cancer index (PCI) score was similar between the two cohorts ( &gt; 3 months: median PCI 11 versus (vs) 0-3 months: median PCI 12; p = 0.42). Recurrence-free survival was 9 months for the entire cohort and not significantly different based on duration of NAC ( &gt; 3 months: 8 months vs 0-3 months: 15 months, p = 0.14). Overall survival was also similar between both cohorts ( &gt; 3 months: 26 months vs 0-3 months: 37 months; p = 0.11). On univariate analysis, &gt; 3 months of NAC was associated with an increased rate of complications of any severity ( &gt; 3 months: 83.6% vs 0-3 months: 55.2%; p = 0.01), clinically significant complications ( &gt; 3 months: 54.5% vs 0-3 months: 31.0%; p = 0.07), and increased median length of stay ( &gt; 3 months: 10 days vs 0-3 months: 8 days; p = 0.01). When controlling for other perioperative variables on multivariable analysis, &gt; 3 months of NAC trended towards an increased risk of clinically significant complications (HR 1.76, 95% CI 0.59-5.30; p = 0.32). Conclusions: Even with a similar disease burden, as measured by PCI, an extended duration of neoadjuvant chemotherapy prior to CRS±HIPEC does not appear to be associated with any improved recurrence-free or overall survival. Conversely, postoperative outcomes are worse with higher complication rates and increased length of stay. Thus, despite high recurrence rates after CRS±HIPEC for this disease, it still appears that in well selected patients, an extended duration of neoadjuvant chemotherapy may not be the best treatment strategy.

Explainable machine learning and online calculators to predict heart failure mortality in intensive care units.

This study aims to develop explainable machine learning models and clinical tools for predicting mortality in patients in the intensive care unit (ICU) with heart failure (HF). Patients diagnosed with HF who experienced their first ICU stay lasting between 24h and 28days were selected from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database. The primary outcome was all-cause mortality within 28days. Data analysis was performed using Python and R, with feature selection conducted via least absolute shrinkage and selection operator (LASSO) regression. Fifteen models were evaluated, and the most effective model was rendered explainable through the Shapley additive explanations (SHAP) approach. A nomogram was developed based on logistic regression to facilitate interpretation. For external validation, the eICU database was utilized. After selection, the study included 2343 records, with 1808 surviving and 535 deceased patients. The median age of the study population was 70.00, with ~3/5 males (60.31%). The median length of stay in the ICU was 6.00days. The median age of the survival group was younger than the non-survival group (69.00 vs. 73.00), and non-survival patients spent longer time in the ICU. Seventy-five features were initially selected, including basic information, vital signs, laboratory tests, haemodynamics and oxygen status. LASSO regression determined the shrinkage parameter α=0.020, and 44 features were chosen for model construction. The linear discriminant analysis (LDA) model showed the best performance, and the accuracy reached 0.8354 in the training cohort and 0.8563 in the testing cohort. It showed satisfying area under the curve (AUC), recall, precision, F1 score, Cohen's kappa score and Matthew's correlation coefficient. The concordance index (c-index) reached 0.7972 in the training cohort and 0.8125 in the testing cohort. In external validation, the LDA model achieved approximately 0.9 in accuracy, precision, recall and F1 score, with an AUC of 0.79. Univariable analysis was performed in the training cohort. Features that differed significantly between the survival and non-survival groups were subjected to multiple logistic regression. The nomogram built on multiple logistic regression included 14 features and demonstrated excellent performance. The AUC of the nomogram is 0.852 in the training cohort, 0.855 in the internal validation cohort and 0.770 in the external validation cohort. The calibration curve showed good consistency. The study developed an LDA and a nomogram model for predicting mortality in HF patients in the ICU. The SHAP approach was employed to elucidate the LDA model, enhancing its utility for clinicians. These models were made accessible online for clinical application.

Spontaneous breathing trial in the weaning process from mechanical ventilation in pediatrics: outcome and predictive factors.

Introduction. spontaneous breathing trial (SBT) in weaning from pediatric invasive mechanical ventilation (IMV) is an endorsed practice, its positivity is based on clinical parameters; however, its results could be better documented. Objective. To describe the results of the SBT in the IMV weaning process. Population and methods. Retrospective analysis. Patients with ≥48 h in IMV from March 1, 2022 to January 31, 2024. Results. A total of493 SBT were analyzed in 304 patients; 71% (348) were positive, and 87% (302) resulted in successful extubations. The causes of negative SBT were increased work of breathing (70%), respiratory rate (57%), and heart rate (27%). In univariate analysis, respiratory distress as the reason for admission, peak inspiratory pressure before SBT and T-tube use, were predictors of negative SBT. In multivariate analysis, this association persisted for admission for respiratory cause, the higher programmed respiratory rate in IMV, as the T-tube modality. Those with negative SBT stayed more days in IMV (9 [7-12] vs. 7 [4-10]) and in PICU (11 [9-15] vs. 9 [7-12]). Conclusion. Positive SBT predicted successful extubation in a high percentage of cases. Respiratory distress on admission, higher programmed respiratory rate, and a higher proportion of T-tube mode were negative predictors of the test. Negative SBT was associated with more extended stays in IMV and PICU.

Potential for reduction of radiation dose in the assessment of the lead orientation in directional deep brain stimulation electrodes.

Directional deep brain stimulation (dDBS) relies on electrodes steering the stimulation field in a specific direction. Post implantation, however, the intended and real orientation of the lead frequently deviates e.g. due to torque of the electrode. The orientation is assessed by postoperative imaging such as C-arm cone-beam CT (CBCT) using 3D rotational fluoroscopy and multi-slice CT (MSCT). The objective is to determine the effect of different X-ray systems such as CBCT and MSCT, and scan acquisition parameters on effective radiation doses. We retrospectively investigated the dose area product (DAP) and dose length product (DLP) of patients who underwent both CBCT and MSCT after dDBS surgery. These metrics were then converted into the effective dose by established conversion coefficients. For CBCT, the feasible dose optimization by collimation was virtually assessed. Univariate analysis was performed to determine differences. Among 88 patients median effective dose was 0.20±0.07mSv in CBCT and 2.11±0.33mSv in MSCT (p<0.001). The field of view (FOV) in CBCT can be collimated in craniocaudal orientation by 33.6% and mediolaterally by 60.8%. This optimized collimation implies an effective dose reduction of 76% (p<0.001). Comparison of the effective dose of MSCT vs. CBCT revealed a significant dose reduction by 90.3% (p<0.001), whereas optimal collimation by 97.7% (p<0.001). For assessment of dDBS orientation, CBCT had significantly lower radiation doses compared to MSCT. Optimized collimation in CBCT allows for a further substantial dose reduction. Moreover, the proposed approach is applicable on other neuroimaging procedures such as 3D visualization of treated intracranial aneurysm.

Analysis of Outcomes and Factors Influencing Community-Acquired Pressure Injury: A Retrospective Review of 413 Patients.

The purpose of this study was to analyze the outcomes and influencing factors of patients with community-acquired pressure injuries (CAPIs) and provide insights for clinical practice. Retrospective cohort study. We reviewed medical records of 413 patients with a total of 522 CAPIs. Patients with CAPIs who were hospitalized at Mianyang Central Hospital, Sichuan Province, China, between December 2021 and December 2022. Depending on CAPI outcome at the time of discharge, the patients were split into "improvement" and "no improvement" groups. Factors influencing CAPI outcomes were examined using univariate analysis followed by multivariate analysis (logistic regression). A majority of patients (n=324, 78.5%) showed improvement, and 89 (21.5%) showed no improvement. Logistic regression analysis showed statistically significant associations between CAPI outcomes and Braden Scale for Pressure Sore Risk scores, Barthel Index for Activities of Daily living scores, along with serum albumin, hemoglobin, interleukin-6, and C-reactive protein levels. The outcomes of patients with CAPIs were influenced by the Braden score, the Barthel score, serum albumin and hemoglobin levels, as well as inflammatory markers, including interleukin-6 and C-reactive protein. To effectively treat and care for patients with CAPIs, nurses should develop customized nursing interventions based on the unique characteristics of patients.

Predictors of Hospital Readmission, Institutionalization, and Mortality in Geriatric Rehabilitation Following Hospitalization According to Admission Reason.

Older adults following an inpatient geriatric rehabilitation (GR) program commonly experience adverse health outcomes such as hospital readmission, institutionalization, and mortality. Although several studies have explored factors related to these outcomes, the influence of admission reason on the predictive factors of adverse health outcomes in the rehabilitation process remains unclear. Therefore, this study aimed to identify predictive factors for adverse health outcomes in inpatients attending GR according to their admission reason. This retrospective study included patients with orthogeriatric (OG) conditions and patients with hospital-associated deconditioning (HAD) admitted to GR after an acute hospitalization between 2016 and 2020. Patients were evaluated by a comprehensive geriatric assessment at admission, including sociodemographic data, social resources, clinical data, cognitive, functional and nutritional status, and physical performance measurements. Adverse health outcomes were collected (hospital readmission, institutionalization, and mortality). Univariate analyses and multivariate backward binary logistic regressions were used to determine predictive factors. In this study, 290 patients were admitted for OG conditions, and 122 patients were admitted due to HAD. In patients with OG conditions, lower Mini-Mental State Examination (MMSE) predicted institutionalization and mortality. Lower Mini Nutritional Assessment-Short Form predicted institutionalization, whereas lower Barthel Index and lower Tinetti-Performance-Oriented Mobility Assessment scores were associated with higher mortality. In patients with HAD, higher age-adjusted comorbidity index predicted hospital readmission and mortality, and lower Short Physical Performance Battery scores predicted institutionalization and mortality. Finally, lower MMSE scores, worse values in Older Americans Resources and Services Scale and male gender were associated with a higher risk of institutionalization. Predictive factors for hospital readmission, institutionalization, and mortality in patients with OG conditions and HAD during GR were different. Some of those predictors, such as nutritional status and physical performance, are modifiable. Understanding predictive factors for adverse outcomes, and how these factors differ by admission diagnosis, improves our ability to identify patients most at risk. Early identification of these patients could assist with prevention efforts and lead to a reduction of negative outcomes.