Survival Outcomes In Patients Research Articles

CD151-enriched migrasomes mediate hepatocellular carcinoma invasion by conditioning cancer cells and promoting angiogenesis

BackgroundThe tetraspanin family plays a pivotal role in the genesis of migrasomes, and Tetraspanin CD151 is also implicated in neovascularization within tumorous contexts. Nevertheless, research pertaining to the involvement of CD151 in hepatocellular carcinoma (HCC) neovascularization and its association with migrasomes remains inadequate.MethodsTo investigate the correlation between CD151 and migrasome marker TSPAN4 in liver cancer, we conducted database analysis using clinical data from HCC patients. Expression levels of CD151 were assessed in HCC tissues and correlated with patient survival outcomes. In vitro experiments were performed using HCC cell lines to evaluate the impact of CD151 expression on migrasome formation and cellular invasiveness. Cell lines with altered CD151 expression levels were utilized to study migrasome generation and in vitro invasion capabilities. Additionally, migrasome function was explored through cellular aggregation assays and phagocytosis studies. Subsequent VEGF level analysis and tissue chip experiments further confirmed the role of CD151 in mediating migrasome involvement in angiogenesis and cellular signal transduction.ResultsOur study revealed a significant correlation between CD151 expression and migrasome marker TSPAN4 in liver cancer, based on database analysis of clinical samples. High expression levels of CD151 were closely associated with poor survival outcomes in HCC patients. Experimentally, decreased CD151 expression led to reduced migrasome generation and diminished in vitro invasion capabilities, resulting in attenuated in vivo metastatic potential. Migrasomes were demonstrated to facilitate cellular aggregation and phagocytosis, thereby promoting cellular invasiveness. Furthermore, VEGF-enriched migrasomes were implicated in signaling and angiogenesis, accelerating HCC progression.ConclusionsIn summary, our findings support the notion that elevated CD151 expression promotes migrasome formation, and migrasomes play a pivotal role in the invasiveness and angiogenesis of liver cancer cells, thereby facilitating HCC progression. This finding implies that migrasomes generated by elevated CD151 expression may constitute a promising high-priority target for anti-angiogenic therapy in HCC, offering crucial insights for the in-depth exploration of migrasome function and a renewed comprehension of the mechanism underlying liver cancer metastasis.

ZEB family is a prognostic biomarker and correlates with anoikis and immune infiltration in kidney renal clear cell carcinoma

BackgroundZinc finger E-box binding homEeobox 1 (ZEB1) and ZEB2 are two anoikis-related transcription factors. The mRNA expressions of these two genes are significantly increased in kidney renal clear cell carcinoma (KIRC), which are associated with poor survival. Meanwhile, the mechanisms and clinical significance of ZEB1 and ZEB2 upregulation in KIRC remain unknown.MethodsThrough the Cancer Genome Atlas (TCGA) database and Gene Expression Omnibus (GEO) database, expression profiles, prognostic value and receiver operating characteristic curves (ROCs) of ZEB1 and ZEB2 were evaluated. The correlations of ZEB1 and ZEB2 with anoikis were further assessed in TCGA-KIRC database. Next, miRTarBase, miRDB, and TargetScan were used to predict microRNAs targeting ZEB1 and ZEB2, and TCGA-KIRC database was utilized to discern differences in microRNAs and establish the association between microRNAs and ZEBs. TCGA, TIMER, TISIDB, and TISCH were used to analyze tumor immune infiltration.ResultsIt was found that ZEB1 and ZEB2 expression were related with histologic grade in KIRC patient. Kaplan-Meier survival analyses showed that KIRC patients with low ZEB1 or ZEB2 levels had a significantly lower survival rate. Meanwhile, ZEB1 and ZEB2 are closely related to anoikis and are regulated by microRNAs. We constructed a risk model using univariate Cox and LASSO regression analyses to identify two microRNAs (hsa-miR-130b-3p and hsa-miR-138-5p). Furthermore, ZEB1 and ZEB2 regulate immune cell invasion in KIRC tumor microenvironments.ConclusionsAnoikis, cytotoxic immune cell infiltration, and patient survival outcomes were correlated with ZEB1 and ZEB2 mRNA upregulation in KIRC. ZEB1 and ZEB2 are regulated by microRNAs.

Potential Survival Benefit of Upfront Surgery for Lung Tumors Unconfirmed but Highly Suspicious for Stage I Lung Cancer.

Patients with early-stage lung tumors that are highly suspicious for malignancy typically undergo a preoperative diagnostic workup, primarily through bronchoscopy or transthoracic biopsy. Those without a preoperative diagnosis may alternatively be treated with upfront surgery, contingent upon the potential for intraoperative diagnosis. Previous studies have yielded conflicting results regarding the impact of upfront surgery on the survival of these patients. Our study aimed to elucidate the effect of upfront surgery on the survival outcomes of patients undergoing surgery for early-stage lung cancer without a preoperative diagnosis. We analyzed the survival rate of 158 consecutive patients who underwent pulmonary resection for stage I lung cancer, either with or without a preoperative diagnosis. A total of 86 patients (54%) underwent upfront surgery. This approach positively impacted both disease-free survival (p=0.031) and overall survival (p=0.017). However, no significant differences were observed across subgroups based on sex, smoking status, forced expiratory volume in 1 second, histologic tumor size, or histologic subtype. Univariate analysis identified upfront surgery (p=0.020), age (p=0.002), maximum standardized uptake value (SUVmax) exceeding 7 (p=0.001), and histological tumor size greater than 20 mm (p=0.009) as independent predictors. However, multivariate analysis indicated that only SUVmax greater than 7 (p=0.011) was a significant predictor of unfavorable survival. Upfront surgery does not appear to confer a survival advantage in patients with stage I lung cancer undergoing surgical intervention.

Integrated Bioinformatic Analysis Reveals the Oncogenic, Survival, and Prognostic Characteristics of TPX2 in Hepatocellular Carcinoma.

Targeting protein for Xenopus kinesin-like protein 2 (TPX2), a well-known mitotic protein, has been linked to carcinogenesis in several cancers. This study investigated the role of TPX2 in hepatocellular carcinoma (HCC) from various aspects using bioinformatic analyses. TPX2 expression and its prognostic value in pan-cancers were analyzed using SangerBox. TPX2 expression and its association with prognosis, immune infiltration, tumor mutations, and signaling pathways in HCC were analyzed using UALCAN, BoxKaplan-Meier Plotter, GEPIA, Human Protein Atlas, TIMER 2.0, and SangerBox. Genes co-expressed with TPX2 in HCC were analyzed using the HCCDB database, followed by functional enrichment using SangerBox. Clinical predictive models were established based on TPX2 and its co-expressed genes using the ACLBI database. TPX2 expression significantly increased in pan-cancers and was associated with survival in nearly half of the cancer types. High TPX2 expression has been linked to poor survival outcomes in patients with HCC. TPX2 expression was positively correlated with abundant infiltration of immune cells (including B cells, CD4 + /CD8 + T cells, macrophages, neutrophils, and dendritic cells), TP53 mutation, and carcinogenesis-related pathways, such as the PI3K/AKT/mTOR pathway, cellular response to hypoxia, and tumor proliferation signature. Nineteen genes were found to be co-expressed with TPX2 in HCC, and these genes showed close positive correlations and were mainly implicated in cell cycle-related functions. A prognostic model established using TPX2 and its expressed genes could stratify HCC patients into high- and low-risk groups, with a significantly shorter survival time in high-risk groups. The prognostic model performed well in predicting 1-, 3-, and 5-year survival of patients with HCC, with areas under the curve of 0.801, 0.725, and 0.711, respectively. TPX2 functions as an oncogene in HCC, and its high expression is detrimental to the survival of patients with HCC. Thus, TPX2 may be a prognostic biomarker and potential therapeutic target for HCC.

Gustave Roussy Immune score as a prognostic biomarker in patients with platinum-refractory metastatic urothelial carcinoma treated with pembrolizumab: YUSHIMA study.

This study aimed to investigate the prognostic value of the Gustave Roussy Immune score (GRIm-score) in platinum-refractory metastatic urothelial carcinoma (UC) treated with pembrolizumab. This multicenter retrospective study (YUSHIMA study) evaluated 331 patients with metastatic UC treated with pembrolizumab after platinum-based chemotherapy between January 2018 and June 2023 at 13 institutions. We collected pretreatment variables, including the GRIm-score based on serum albumin, lactate dehydrogenase, and neutrophil-to-lymphocyte ratio. The patients were divided into low and high GRIm-score groups. Prognostic factors for overall survival (OS) and progression-free survival (PFS) were determined using the multivariate Cox proportional hazard model. During the median follow-up period of 7.3months, 278 (84%) patients showed disease progression, and 223 (67%) died from any cause. Multivariate analysis revealed that the high GRIm-score group was an independent and significant adverse prognostic factor of both OS and PFS (hazard ratio, 1.65 and 1.82, respectively; both p < 0.001) along with Eastern Cooperative Oncology Group Performance Status of ≥ 2 (both p < 0.001), presence of visceral metastasis (both p < 0.001), and hemoglobin of < 9.2g/dL (p = 0.030 and p = 0.038). C-reactive protein of > 42mg/L was a significant prognostic factor for OS (p = 0.001). The GRIm-score is an independent prognostic marker for survival outcomes in patients with platinum-refractory metastatic UC treated with pembrolizumab.

Sex and survival outcomes in patients with renal cell carcinoma receiving first-line immune-based combinations

BackgroundThere is an ongoing debate as to whether sex could be associated with immune checkpoint inhibitor (ICI) benefit. Existing literature data reveal contradictory results, and data on first-line immune combinations are lacking.MethodThis was a real-world, multicenter, international, observational study to determine the sex effects on the clinical outcomes in metastatic renal cell carcinoma (mRCC) patients treated with immuno-oncology combinations as first-line therapy.ResultsA total of 1827 mRCC patients from 71 cancer centers in 21 countries were included. The median OS was 38.7 months (95% CI 32.7–44.2) in the overall study population: 40.0 months (95% CI 32.7–51.6) in males and 38.7 months (95% CI 26.4–41.0) in females (p = 0.202). The median OS was higher in males vs. females in patients aged 18-49y (36.9 months, 95% CI 29.0–51.6, vs. 24.8 months, 95% CI 16.8–40.4, p = 0.426, with + 19% of 2y-OS rate, 72% vs. 53%, p = 0.006), in the clear cell histology subgroup (44.2 months, 95% CI 35.8–55.7, vs. 38.7 months, 95% CI 26.0–41.0, p = 0.047), and in patients with sarcomatoid differentiation (34.4 months, 95% CI 26.4–59.0, vs. 15.3 months, 95% CI 8.9–41.0, p < 0.001). Sex female was an independent negative prognostic factor in the sarcomatoid population (HR 1.72, 95% CI 1.15 − 2.57, p = 0.008).ConclusionsAlthough the female’s innate and adaptive immunity has been observed to be more active than the male’s, women in the subgroup of clear cell histology, sarcomatoid differentiation, and those under 50 years of age showed shorter OS than males.

Comparative analysis through propensity score matching in thyroid cancer: unveiling the impact of multiple malignancies.

The incidence of thyroid cancer is on the rise worldwide, with childhood exposure to radiation being the sole acknowledged catalyst for its emergence. Nonetheless, numerous other factors that may pose risks are awaiting thorough examination and validation. This retrospective study aims to explore the malignancies linked to thyroid cancer and contrast the survival rates of those afflicted with a solitary tumor versus those with multiple primary neoplasms (MPN). This retrospective study examined data from King Hussein Cancer Center (KHCC), Jordan. Among 563 patients diagnosed with thyroid cancer, 30 patients had thyroid malignancy as part of MPN. For a 1:3 propensity score-matched analysis, 90 patients with only a primary thyroid malignancy were also enrolled. Hematologic and breast malignancies were among the most frequent observed cancers alongside thyroid neoplasm. Patients who had MPN were diagnosed at older age, had higher body mass index and presented with higher thyroglobulin antibody levels (p < 0.05 for each). Additionally, MPN patient displayed a stronger family history for cancers (p= 0.002). A median follow-up duration of 135 months unveiled that MPN patients faced a worse 5-year survival compared to their counterparts with a singular neoplasm (87% vs 100% respectively; p < 0.01). However, no distinction emerged in the 5-year event-free survival between these two groups. MPN correlates with a significantly altered survival outcome of thyroid cancer patients. The diagnosis of thyroid carcinoma at an older age, accompanied by elevated initial thyroglobulin antibody levels and a notable familial predisposition, may raise concerns about the potential occurrence of synchronous or metachronous tumors.

Diversifying the anthracycline class of anti-cancer drugs identifies aclarubicin for superior survival of acute myeloid leukemia patients

The efficacy of anthracycline-based chemotherapeutics, which include doxorubicin and its structural relatives daunorubicin and idarubicin, remains almost unmatched in oncology, despite a side effect profile including cumulative dose-dependent cardiotoxicity, therapy-related malignancies and infertility. Detoxifying anthracyclines while preserving their anti-neoplastic effects is arguably a major unmet need in modern oncology, as cardiovascular complications that limit anti-cancer treatment are a leading cause of morbidity and mortality among the 17 million cancer survivors in the U.S. In this study, we examined different clinically relevant anthracycline drugs for a series of features including mode of action (chromatin and DNA damage), bio-distribution, anti-tumor efficacy and cardiotoxicity in pre-clinical models and patients. The different anthracycline drugs have surprisingly individual efficacy and toxicity profiles. In particular, aclarubicin stands out in pre-clinical models and clinical studies, as it potently kills cancer cells, lacks cardiotoxicity, and can be safely administered even after the maximum cumulative dose of either doxorubicin or idarubicin has been reached. Retrospective analysis of aclarubicin used as second-line treatment for relapsed/refractory AML patients showed survival effects similar to its use in first line, leading to a notable 23% increase in 5-year overall survival compared to other intensive chemotherapies. Considering individual anthracyclines as distinct entities unveils new treatment options, such as the identification of aclarubicin, which significantly improves the survival outcomes of AML patients while mitigating the treatment-limiting side-effects. Building upon these findings, an international multicenter Phase III prospective study is prepared, to integrate aclarubicin into the treatment of relapsed/refractory AML patients.

Immune-related adverse events and their effects on survival outcomes in patients with non-small cell lung cancer treated with immune checkpoint inhibitors: a systematic review and meta-analysis.

The use of immune checkpoint inhibitors (ICIs) has become the standard of care for non-small cell lung cancer. The purpose of this study was to systematically review the literature to determine whether the occurrence of immune-related adverse events (irAEs) following the use of ICIs predicts different clinical outcomes in non-small cell lung cancer (NSCLC). Relevant studies from the time of database creation to July 20, 2023, were systematically searched to explore the differences in clinical outcomes in patients with advanced NSCLC with or without irAEs. The outcome indicators included the occurrence of irAEs, progression-free survival (PFS), and overall survival (OS). 25 studies met the inclusion criteria. Of these studies, 22 reported the effect on OS, and 19 reported the effect on PFS. The results showed that for patients with NSCLC, the occurrence of irAEs after receiving immunotherapy showed a statistically significant benefit over the absence of irAEs for OS (HR=0.55,95% CI=0.46-0.65) and PFS (HR=0.55 95% CI=0.48-0.64), but severe irAEs (grades 3-5) were associated with worse OS (HR=1.05, 95% CI=0.87-1.27). Compared with gastrointestinal, lung, and hepatitis, irAEs of the skin and endocrine system tend to predict better OS and PFS. The occurrence of irAEs, especially mild and early irAEs, indicates better OS and PFS in patients with NSCLC treated with ICIs, irrespective of patient characteristics, type of ICIs, and irAEs. However, Grade 3 or higher toxicities resulted in worse OS. https://www.crd.york.ac.uk/prospero/, identifier CRD42023409444.

The impact of gender on survival outcomes in patients with small intestinal stromal tumors: a comprehensive analysis using the SEER database.

Small intestinal stromal tumors (SISTs) are a rare type of mesenchymal tumor. Gender is known to influence the incidence and prognosis of various tumors, but its role on the survival of SISTs at the population level remains unclear. Therefore, we aim to explore the relationship between gender and the prognosis of SISTs using the Surveillance, Epidemiology, and End Results (SEER) database. Data on SISTs patients from 2000 to 2019 were derived from the SEER database. Multiple imputation was used to address missing data. Kaplan-Meier analyses and Cox proportional hazard models were applied to evaluate the impact of demographic and clinical characteristics on overall survival (OS) and cancer-specific survival (CSS). A total of 3513 patients with SISTs were analyzed, including 1921 males and 1592 females. Kaplan-Meier analysis coupled with log-rank testing demonstrated a significantly higher mortality rate among male patients compared to females (P < 0.001). Notably, female patients exhibited superior OS (hazard ratio [HR] 0.808, 95% confidence interval [CI] 0.724-0.902, P < 0.001) and CSS (HR 0.801, 95% CI 0.692-0.927, P = 0.003) compared to male patients. While the mean 1-year CSS rates were comparable between genders (95.3% for males vs. 96.0% for females, P = 0.332), male patients consistently showed lower mean survival rates at 3-, 5-, and 10-year intervals. Surgical intervention significantly boosted 5-year OS and CSS rates in both male and female patients (P < 0.001). Multivariate Cox regression analysis identified age, sex, grade, TNM stage, surgery, and mitotic rate as independent risk factors for OS and CSS in patients with SISTs. Our findings suggest that male patients with SISTs have a higher risk of mortality compared to female patients, indicating that gender may serve as a predictive indicator for survival in this patient population.

Risk factors for secondary thyroid cancer in patients with breast cancer: a propensity‑matched SEER analysis

With the rapid development of imaging technology and comprehensive treatment in modern medicine, the early diagnosis rate of breast cancer is constantly improving, and the prognosis is also improving; As breast cancer patients survive longer, the risk of developing second primary cancers increases. Since both breast and thyroid are Hormone receptor sensitive organs, which are regulated by hypothalamus pituitary target gland endocrine axis, changes in body endocrine status may lead to the occurrence of these two diseases in succession or simultaneously. This study extracted clinical data and survival outcomes of breast cancer patients registered in the Surveillance, Epidemiology and End Results (SEER) database between 2010 and 2019. After matching the case and controls with propensity scores, the selected patients were randomly split into training and test datasets at a ratio of 7:3. Univariate and multivariate COX proportional regression analysis is used to determine independent risk factors for secondary thyroid cancer and construct a column chart prediction model. Age, ethnicity, whether radiotherapy, tumor primary location, N stage, M stage were identified by Cox regression as independent factors affecting secondary thyroid cancer in patients with breast cancer patients, and a risk factor nomogram was established to predict patients’ 3 and 5 year survival probabilities. The AUC values for 3 and 5 years in the training set were 0.713, 0.707, and the c-index was 0.693 (95% CI 0.67144, 0.71456), and the AUC values for 3 and 5 years in the validation set were 0.681, 0.681, and the c-index was 0.673 (95% CI 0.64164, 0.70436), respectively.

Comprehensive analysis of stereotactic Radiosurgery outcomes in triple-negative breast cancer patients with brain metastases: The influence of immunotherapy and prognostic factors

IntroductionBreast cancer stands as the second most common solid tumors with a propensity for brain metastasis. Among metastatic breast cancer cases, the brain metastasis incidence ranges from 10 % to 30 %, with triple-negative breast cancer (TNBC) displaying a heightened risk and poorer prognosis. SRS has emerged as an effective local treatment modality for brain metastases; however, data on its outcomes specifically in pure triple-negative subtype remain scarce. MethodWe retrospectively reviewed the electronic medical records of all brain metastasis (BM) TNBC patients treated with SRS. Patient, tumour characteristics and treatment details data were collected. This retrospective cohort study aimed to evaluate local control (LC), distant brain metastasis free survival (DBMFS), and overall survival (OS) outcomes in TNBC patients undergoing SRS for brain metastases while identifying potential prognostic factors. ResultForty-three patients with TNBC and brain metastases treated with SRS between January 2017 and 2023 were included. The study found rates of LC (99 % at 1 year) and DBMFS (76 % at 1 year) after SRS, with brain metastasis count (p = 0,003) and systemic treatment modality (p = 0,001) being significant predictors of DBMFS. The median OS following SRS was 19.5 months, with neurological deficit (p = 0.003) and systemic treatment modality (p = 0.019) identified as significant predictors of OS. ConclusionSRS demonstrates favourable outcomes in terms of local control and distant brain metastasis-free survival in TNBC. Neurological deficit and systemic treatment significantly influence overall survival, emphasizing the importance of personalized treatment approaches and (magnetic resonance imaging) MRI surveillance based on these factors.

Association of body composition and systemic inflammation for patients with locally advanced cervical cancer following concurrent chemoradiotherapy.

Systemic inflammation and body composition are associated with survival outcomes of cancer patients. This study aimed to examine the combined prognostic value of systemic inflammatory markers and body composition parameters in patients with locally advanced cervical cancer (LACC). Patients who underwent concurrent chemoradiotherapy (CCRT) for LACC at a tertiary referral teaching hospital between January 2010 and January 2018 were enrolled. A predictive model was established based on systemic immune-inflammation index (SII) and computer tomography-derived visceral fat-to-muscle ratio (vFMR). Overall survival (OS) and progression-free survival (PFS) were assessed using the Kaplan-Meier method and Cox regression models. The model performance was assessed using discrimination, calibration, and clinical usefulness. In total, 212 patients were enrolled. The SII and vFMR were closely related, and both independently predicted survival (P < 0.05). A predictive model was established based on the above biomarkers and included three subgroups: high-risk [both high SII (>828) and high vFMR (>1.1)], middle-risk (either high SII or high vFMR), and low-risk (neither high SII nor high vFMR). The 3-year OS (PFS) rates for low-, middle-, and high-risk patients were 90.5% (86.0%), 73.9% (58.4%), and 46.8% (36.1%), respectively (P < 0.05). This model demonstrated satisfactory predictive accuracy (area under the curve values for predicting 3-year OS and PFS were 0.704 and 0.718, respectively), good fit (Hosmer-Lemeshow tests: P > 0.05), and clinical usefulness. Systemic inflammatory markers combined with body composition parameters could independently predict the prognosis of patients with LACC, highlighting the utilization of commonly collected indicators in decision-making processes. The SII and vFMR, as well as their composite indices, were promising prognostic factors in patients with LACC who received definitive CCRT. Future studies are needed to explore novel therapies to improve the outcomes in high-risk patients.

Prognostic value of FGFR2 alterations in patients with iCCA undergoing surgery or systemic treatments: A meta-analysis.

Over recent years, there has been a notable rise in the incidence of intrahepatic cholangiocarcinoma (iCCA), which presents a significant challenge in treatment due to its complex disease characteristics and prognosis. Notably, the identification of fibroblast growth factor receptor 2 (FGFR2) fusion/rearrangement, a potential oncogenic driver primarily observed in iCCA, raises questions about its impact on the prognostic outcomes of patients undergoing surgical intervention or other therapeutic approaches. A comprehensive search from inception to July 2023 was conducted across PubMed, Embase, Web of Science, and the Cochrane Library databases. The objective was to identify relevant publications comparing the prognosis of FGFR2 alterations and no FGFR2 alterations groups among patients with iCCA undergoing surgical resection or other systemic therapies. The primary outcome indicators, specifically Overall Survival (OS) and Disease-Free Survival (DFS), were estimated using Hazard Ratios (HRs) with 95% confidence intervals (CIs), and statistical significance was defined as p < .05. Study quality was assessed using the Newcastle-Ottawa Quality Assessment Scale. Statistical analyses were performed using Review Manager 5.4 software and Stata, version 12.0. Six studies, involving 1314 patients (FGFR2 alterations group n = 173 and no FGFR2 alterations group n = 1141), were included in the meta-analysis. The analysis revealed that the FGFR2 alterations group exhibited a significantly better OS prognosis compared to the no FGFR2 alterations group, with a fixed-effects combined effect size HR = 1.31, 95%CI = 1.001-1.715, p = .049. Furthermore, meta-regression and subgroup analysis showed that the length of the follow-up period did not introduce heterogeneity into the results. This finding indicates the stability and reliability of the study outcomes. The current study provides compelling evidence that FGFR2 alterations are frequently associated with improved survival outcomes for patients with iCCA undergoing surgical resection or other systemic treatments. Additionally, the study suggests that FGFR2 holds promise as a safe and dependable therapeutic target for managing metastatic, locally advanced or unresectable iCCA. This study offers a novel perspective in the realm of targeted therapy for iCCA, presenting a new and innovative approach to its treatment.

The Prognostic Role of Prognostic Nutritional Index and Controlling Nutritional Status in Predicting Survival in Older Adults with Oncological Disease: A Systematic Review

The increase in new cancer diagnoses in the elderly calls for new, accessible, and easy-to-use prognostic tools that contribute to lowering the burden of the disease. Recognising the importance of inflammation and nutritional status in the progression of the disease, the purpose of this systematic review was to synthesise the evidence on the prognostic role of Prognostic Nutritional Index (PNI) and Controlling Nutritional Status (CONUT) in predicting survival of older adult cancer patients. A comprehensive search was conducted in PubMed and Web of Science Core Collection databases until 22 February 2024. The articles included in this review (n = 38) examined the relationships of PNI and CONUT with survival outcomes in elderly cancer patients. Despite high heterogeneity between the studies, most concluded that low PNI values are associated with poor overall survival (OS), particularly in gastric cancer patients. Most studies did not find an association between PNI and cancer-specific survival, progression-free survival, disease-free survival, recurrence-free survival, and mortality. Results regarding the prognostic role of CONUT in predicting survival were inconclusive. This study suggests that PNI could be used to predict OS in elderly cancer patients, while more studies are needed to assess the prognostic role of CONUT.

Predicting prostate adenocarcinoma patients’ survival and immune signature: a novel risk model based on telomere-related genes

Alterations in telomeres constitute some of the earliest occurrences in the tumourigenesis of prostate adenocarcinoma (PRAD) and persist throughout the progression of the tumour. While the activity of telomerase and the length of telomeres have been demonstrated to correlate with the prognosis of PRAD, the prognostic potential of telomere-related genes (TRGs) in this disease remains unexplored. Utilising mRNA expression data from the Cancer Genome Atlas (TCGA), we devised a risk model and a nomogram to predict the survival outcomes of patients with PRAD. Subsequently, our investigations extended to the relationship between the risk model and immune cell infiltration, sensitivity to chemotherapeutic drugs, and specific signalling pathways. The risk model we developed is predicated on seven key TRGs, and immunohistochemistry results revealed significant differential expression of three TRGs in tumours and paracancerous tissues. Based on the risk scores, PRAD patients were stratified into high-risk and low-risk cohorts. The Receiver operating characteristics (ROC) and Kaplan–Meier survival analyses corroborated the exceptional predictive performance of our novel risk model. Multivariate Cox regression analysis indicated that the risk score was an independent risk factor associated with Overall Survival (OS) and was significantly associated with T and N stages of PRAD patients. Notably, the high-risk group exhibited a greater response to chemotherapy and immunosuppression compared to the low-risk group, offering potential guidance for treatment strategies for high-risk patients. In conclusion, our new risk model, based on TRGs, serves as a reliable prognostic indicator for PRAD. The model holds significant value in guiding the selection of immunotherapy and chemotherapy in the clinical management of PRAD patients.

Short-term and long-term survival outcomes in patients with invasive lobular carcinoma vs. invasive ductal carcinoma of the breast.

e12564 Background: Invasive lobular carcinoma (ILC) accounts for 10% of all invasive breast cancer and has distinct histological and biological features compared to the most common breast cancer histological subtype, invasive ductal carcinoma (IDC). ILC is more endocrine sensitive and chemotherapy resistant than IDC and has a different metastatic pattern. There is lack of conclusive data on the differences in survival outcomes between ILC and IDC. We aimed to assess the short-term and long-term survival outcomes in patients with ILC and IDC in a large population database. Methods: This is a retrospective, population-based study using data from the Surveillance, Epidemiology, and End Results database. We included women &gt; 18 years with stage I-III ILC or IDC diagnosed from 1992-2020. Multivariable logistic regression was used to assess factors associated with different treatment modalities in patients with IDC vs. ILC. We estimated breast cancer-specific survival (BCSS) using Kaplan-Meier methods and their survival rates were compared using the log-rank test. We analyzed BCSS at different time points using a cox regression model with time-varying coefficients. Results: 343,397 patients with IDC and 39,859 patients with ILC were included in this study. Patients with ILC were older (63.0 ± 12.5 years vs. 59.2 ± 13.5 years, p&lt;0.001). There were more non-Hispanic white patients with ILC vs. IDC (76% vs. 67%, p&lt;0.001). Patients with ILC had more advanced disease: more stage III disease (16% vs. 11%, p&lt;0.001), more T3-T4 disease (15% vs. 6%, p&lt;0.001), and more N2-N3 disease (12% vs. 9%, p&lt;0.001). Patients with ILC also had a higher frequency of hormone receptor positive disease (97% vs. 81%, p&lt;0.001). Fewer patients with ILC had grade 3-4 tumors (9% vs. 36%, p&lt;0.001). Our multivariate analysis showed that compared to patients with IDC, patients with ILC were more likely to undergo mastectomy (OR=1.85, p &lt; 0.001) and radiation (OR=1.20, p&lt;0.001), but less likely to receive chemotherapy (OR= 0.92, p&lt;0.001). After adjusting for clinicopathological features, treatment modalities, and socioeconomic variables; compared to patients with IDC, patients with ILC had better BCSS in the first five years (HR=0.71, p &lt;0.001), but worse BCSS in later years (HR=1.30, p&lt;0.001 in year 6-10; HR=1.75, p&lt;0.001 in year 11-15; HR=2.17, p&lt;0.001 in year 16-20). Annual hazard models show that IDC peaked at recurrence in the first 5 years after diagnoses, and the hazard rate declines gradually after that. ILC peaked at recurrence in the first 5 years after diagnosis with minimal decrease in hazard rates after that. Conclusions: BCSS of patients with ILC is better in early years but worse in later years compared to patients with IDC. Future studies are needed to identify predictors of late relapses in ILC, and novel therapeutic strategies are required for these patients.

Predictors of survival outcome of TAS102 combined with bevacizumab compared to TAS102 alone in Saudi patients with metastatic colorectal cancer beyond second line of systemic therapy.

e15545 Background: Significant proportion of metastatic colorectal cancer (mCRC) patients receive systemic therapy beyond second line. This study aims to assess predictors of survival outcome in patients treated with TAS 102/bevacizumab compared to TAS102 alone beyond 2nd line. Methods: In this retrospective study, we assessed patients with mCRC treated with TAS102/bevacizumab or TAS102 alone beyond second line in 4 institutes in Saudi Arabia from January 2020 to December 2022. We checked progression-free survival (PFS) and overall survival (OS) of the study group and we assessed different parameters that may affect the survival outcomes. Results: We included 68 patients in this analysis (39 treated with TAS102/bevacizumab, 29 with TAS102 alone) with a median follow up of 20 months. Noteworthy, 39.7% of patients received treatment in third line (56.4% vs. 17.2%, respectively, p = 0.001) and 48.5% developed neutropenia with first cycle (51.3% vs. 44.8%, p = 0.59). Time from stage IV diagnosis to study treatment (TTAS102) was &gt; 18 months in 56.4% vs. 44.8 %, respectively, p = 0.34. The two treatment arms were balanced for other parameters including site of primary tumour, tumour stage at diagnosis. Median PFS was significantly higher with TAS102/Bevacizumab compared to TAS102 alone (5 vs 3 months, HR = 0.59, 95% CI 0.35-0.98, p = 0.043). Similarly, median OS was significantly improved with TAS102/bevacizumab (15 vs 8 months, HR = 0.55, 95% CI: 0.30-0.98. p = 0.034). After adjustment of line of study treatment, TTAS102 and number of metastatic sites, PFS and OS were significantly improved with TAS102/bevacizumab compared to TAS102 alone (PFS: HR = 0.48, 95% CI: 0.26-0.89, p = 0.021), (OS: HR = 0.54, 95% CI: 0.26-0.91, p = 0.034). Survival outcomes were higher with TAS102/bevacizumab compared to TAS102 in patients with TTAS102 &gt; 18 months (PFS: 5 vs. 3 months, HR = 0.27, 95% CI: 0.12-0.62, p = 0.002), (OS: 22 vs. 6 months, HR = 0.28, 95% CI: 0.11-0.68, p = 0.005) and in patients with neutropenia with first cycle (PFS: 6 vs 3 months, HR = 0.45, 95% CI: 0.21-0.98, p = 0.043), (OS: 26 vs 8 months, HR = 0.33, 95% CI: 0.13-0.81, p = 0. 0.016). No difference in survival outcomes in patients with TTAS102≤ 18 months and those with no neutropenia with first cycle. Conclusions: TAS102 with bevacizumab is associated with improved PFS and OS beyond 2nd line compared to TAS 102 alone especially in patients with longer TTAS102 and first cycle neutropenia.

Correlating survival outcomes in patients with advanced prostate cancer with novel hyperpolarized 13C MRI metabolic imaging biomarkers.

e15059 Background: Hyperpolarized 13C (HP 13C) MRI is a novel molecular imaging approach that detects aberrant aerobic metabolism, namely elevated rates of pyruvate-to-lactate conversion (kPL), in patients with advanced malignancies. Higher kPL has been shown to correlate with higher tumor grade among patients with localized prostate cancer (PC). This research sought to evaluate the correlation between kPL and clinical outcome measures in patients with advanced PC. Methods: Patients with metastatic or locally advanced PC (castration sensitive or resistant) were prospectively enrolled at our institution and underwent HP 13C MRI of one or more target lesions identified on prior conventional imaging. Voxelwise kPL values were computed in MATLAB using an inputless two site exchange model. kPL,median was defined as the median kPL value per-patient across all target lesions; kPL,kurtosis measured the tailedness of the kPL distribution per-patient. We retrospectively analyzed progression free survival (PFS) and overall survival (OS) in subgroups divided by metabolic activity below versus above cut-point (kPL,median &lt;0.017 s-1 and ≥ 0.017s-1, respectively). Survival statistics were calculated using the Cox PH model. Results: Sixteen patients (6 with castration-sensitive and 10 with castration-resistant PC) were accrued. With a median follow-up of 22.0 months from the date of MRI, the lower-kPL subgroup had significantly longer median PFS (11.2 vs 0.5 months; p&lt;0.01) and OS (NR vs 18.4 months; p&lt;0.05) compared to the higher-kPL subgroup. By comparison, baseline serum PSA (PFS: p=0.19, OS: p=0.41) and LDH (PFS: p=0.60, OS: p=0.34) did not demonstrate a significant association with clinical outcomes. There was a strong negative correlation between kPL,kurtosis and OS (r = -0.75), and moderate negative correlations between kPL,median and OS (r = -0.45) as well as kPL,max with both PFS (r = -0.48) and OS (r = -0.54). There was no significant kPL,median difference between castration-sensitive and resistant subgroups (0.015±0.011 vs 0.016±0.006 s-1, p&gt;0.8). Conclusions: HP 13C MRI-derived non-invasive metabolic biomarker kPL,median significantly correlated with clinical outcome measures in a retrospective analysis of patients with advanced PC, outperforming established serological prognostic markers PSA and LDH. Limitations include our small sample size, retrospective design, and heterogeneous patient population. Nevertheless, these encouraging preliminary results support further investigation of HP 13C MRI as a prognostic and/or predictive PC biomarker in multi-center prospective imaging trials. [Table: see text]

Trends in survival in solid malignancies with synchronous brain metastases: A population-based study.

e23299 Background: Brain metastasis in solid malignancies at diagnosis has a poor prognosis. Improvements in the treatment of solid malignancies and advancements in neuroimaging techniques have led to increased incidence of brain metastases. In our study, we examined survival outcomes in patients diagnosed with brain metastasis at the time of diagnosis of primary malignancy at four different sites in the year groups 2010 to 2014 and 2015 to 2020. Methods: Surveillance, Epidemiology, and End Results (SEER) Program 17 registry (November 2022 submission) database was analyzed for four primary sites of cancer based on their high propensity to develop brain metastases- lung and/or bronchus, breast, kidney and/or renal pelvis, and melanoma. Patients diagnosed with malignancy during autopsy or via death certificate and patients with incomplete survival data were excluded. R 4.3.1 software was used for all the analyses. Kaplan-Meier method was used for 2-year survival rate and overall survival analyses. Cox regression analysis was used for hazard ratios (HR). Results: A total of 29,056 and 37,437 cases were identified across the four cancer groups during the period 2010-2014 (Group 1) and 2015-2020 (Group 2), respectively. Lung and/or bronchus tumors comprised the majority of the cases (n = 58,324). 14,811 patients in Group 1 and 18,703 patients in Group 2 received chemotherapy. 8,741 patients in Group 1 and 12,533 patients in Group 2 received radiotherapy. In all the cancers combined, the median survival time in Group 1 was 4 months, and in Group 2 was 5 months. Patients in Group 2 had significantly better survival outcomes than Group 1 (HR:0.81, 95% CI:0.78-0.83, p &lt; 0.001). Table 1 outlines the 2-year survival rates with overall survival p-value. Conclusions: Modest improvement in survival was found in patients diagnosed with synchronous brain metastases during 2015-2020 compared to patients diagnosed in 2010-2014. This slight improvement could be attributed to the improved systemic therapies for cancer, like immunotherapy, as well as advanced local therapy options for brain metastases, although the data for immunotherapy use is unavailable in the SEER database. Overall, the prognosis of synchronous brain metastases remains poor in both groups. Further studies and brain metastases inclusive clinical trials are warranted to improve outcomes in this population. [Table: see text]