Prognosis For Overall Survival Research Articles

A Comprehensive Pan-Cancer Analysis of the Mitochondrial Uncoupling Protein UCP2, with a Focus on Sex and Gender-Related Aspects.

Mitochondrial uncoupling protein 2 (UCP2) plays a crucial role in regulating oxidative stress and cellular metabolism, positioning it as an important subject in oncological research. The involvement of UCP2 in cancer is complex and context-dependent, suggesting it as a potential therapeutic target. In this study, we aimed to perform a comprehensive pan-cancer analysis of UCP2, with a particular focus on gender-related malignancies such as breast (BRCA), prostate (PRAD), ovarian (OV), and testicular tumors (TGCT). We analyzed UCP2 expression in The Cancer Genome Atlas (TCGA), examining correlations with prognosis, tumor mutational burden (TMB), microsatellite instability (MSI), immune cell infiltration, immune checkpoint genes, genes involved in steroidogenesis, sex hormone receptor genes, and drug sensitivity. Significant variability in UCP2 expression was observed across cancer types. UCP2 levels were elevated in BRCA and OV but reduced in PRAD and TGCT. High UCP2 expression was associated with a better prognosis in OV and poorer overall survival in PRAD. Furthermore, UCP2 correlated with TMB and MSI in OV, TGCT, and BRCA. UCP2 expression was also linked to immune cell infiltration, immune checkpoint genes, steroidogenic genes, and sex hormone receptor genes, with variable effects depending on cancer type and gender. Additionally, UCP2 also demonstrated sensitivity to specific anticancer drugs. Our findings highlight the interplay between UCP2, immune and hormonal pathways, and drug responseand reveal potential opportunities for new therapeutic combinations, especially in gender-related cancers.

Prognostic and clinicopathological value of the controlling nutritional status (CONUT) score in patients with head and neck cancer: a meta-analysis

BackgroundThe efficiency of controlling nutritional status (CONUT) score in detecting the prognosis of head and neck cancer (HNC) patients has been investigated in some works, but no consistent findings are obtained. Therefore, this work focused on evaluating the precise prognostic role of CONUT for HNC patients through meta-analysis.MethodsThe effect of CONUT on predicting the prognosis of HNC patients was evaluated through calculating combined hazard ratios (HRs) as well as 95% confidence intervals (CIs). The correlations of CONUT with clinicopathological features of HNC patients were investigated through combined odds ratios (ORs) and 95%CIs. This study used the random-effects model in the case of significant heterogeneity; or else, we selected the fixed-effects model.ResultsThere were eight articles involving 1,478 patients enrolled for the current meta-analysis. We adopted the fixed-effects model for OS and DFS analysis because of the non-significant heterogeneity. As demonstrated by our combined findings, high CONUT score could significantly predict the poor overall survival (OS) (HR = 1.94, 95%CI = 1.55–2.44, p < 0.001) and disease-free survival (DFS) (HR = 1.93, 95%CI = 1.45–2.56, p < 0.001) of HNC. In addition, higher CONUT score was significantly connected to T3-T4 stage (OR = 3.21, 95%CI = 1.94–5.31, p < 0.001) and N1-N3 stage (OR = 3.10, 95%CI = 1.74–5.53, p < 0.001).ConclusionAccording to findings in the present meta-analysis, high CONUT score significantly predicted the prognosis of OS and DFS for HNC patients. Higher CONUT score was also correlated to larger tumor size and LN metastasis in HNC. Due to it is a cost-effective and easily available parameter, CONUT could serve as promising prognostic biomarker for HNC.

Prognostic value of the "dynamic" R2-ISS in patients with multiple myeloma undergoing anti-CD38 antibody-based triplet therapies.

To retrospectively analyze whether the second revision of the international staging system (R2-ISS) influenced prognosis at treatment initiation in patients with multiple myeloma (MM) receiving anti-CD38 antibody-based triplet treatments. High-risk chromosomal abnormalities were examined from diagnosis to treatment initiation and considered positive if detected once. R2-ISS was recalculated at the initiation of treatment and defined as "dynamic R2-ISS." Data from 150 patients who underwent the defined treatments were analyzed. The median progression-free survival (PFS) was 19.5months, and the median overall survival (OS) was 36.5months. Dynamic R2-ISS significantly stratified prognoses for both PFS and OS. The median PFS for patients with dynamic R2-ISS IV was 3.3months, and the median OS was 11.7months, indicating extremely poor outcomes. Although the Revised International Staging System (R-ISS) calculated at the initiation of treatment significantly stratified treatment outcomes, the patients classified as R-ISS could be further stratified by R2-ISS to provide better prognostic information. Dynamic R2-ISS showed potential as a prognostic tool in patients with MM who are treated with anti-CD38 antibody-based triplet therapies.

Integrative analysis reveals the potential prognostic roles and immunological values of unc-5 netrin receptor A (UNC5A) in glioma

BackgroundUNC5A had been reported to play crucial roles in multiple cancers. However, little was known about the associations among UNC5A and glioma. Therefore, we first combined scRNA-seq, proteomics, as well as bulk RNA-seq in order to investigate UNC5A’s functions in gliomas.MethodsOnline databases provided scRNA-seq, proteomics, as well as bulk RNA-seq data on UNC5A in gliomas. The following procedures were conducted in order: QRT-PCR, Norman chart, gene set enrichment analysis (GSEA), and univariate/multifactor Cox regression analyses. We further explored the associations among UNC5A and tumor immunity.ResultsBy comparing gliomas with normal tissues, the TCGA dataset showed a significantly reduced expression of UNC5A, which was also confirmed by GSE50161, GSE4290, and QRT-PCR findings (p < 0.05). In both the TCGA and CGGA datasets, gliomas patients with low-UNC5A expression would have poorer overall survival (OS) prognoses (p < 0.05). ScRNA-seq analysis by the CancerSEA online website presented that UNC5A had a low expression in various glioma clusters and significantly associated with six functional states. Moreover, UNC5A might be a reliable independent biomarker of OS in gliomas patients (p < 0.05). Based on the results of GSEA, UNC5A might be connected to three significant pathways in gliomas. We also successfully created a Norman chart to assess the OS prognoses of these patients. Additionally, in aspects of tumor immunity, the infiltration levels of immune cells in LGG, the immune cell pathways, tumor immune microenvironment, as well as immune checkpoints in both LGG and GBM were revealed to be significantly influenced by UNC5A (p < 0.05).ConclusionsUNC5A was found to have prognostic and immunological significance in gliomas, offering patients with gliomas new treatment options.

Cerebrospinal fluid cytology: A theragnostic and prognostic tool- Experience from a tertiary cancer care centre in central India

: CSF examination is the gold standard for diagnosing leptomeningeal metastases. Malignant cells may access the subarachnoid space by hematogenous dissemination, spreading directly from parenchymal brain lesions, or spreading along the spinal cord or cranial nerves. Cytological detection of malignant cells in CSF is still a crucial decision point for systemic and intrathecal chemotherapy, and it has prognostic significance even with improvements in biochemical analysis and CNS imaging. Over the course of two years, a total of 397 patients—regardless of gender and age—were investigated. There were sixty-four cases with involvement of the central nervous system documented, comprising 42 hematologic malignancies and 22 solid tumors. Cell centrifugation (Cytospin) method were used to prepare smears and cell blocks where prepared, as feasible and indicated. : A cytological analysis of the cerebrospinal fluid showed that metastatic tumors were much more prevalent than primary central nervous system tumours. Lung tumors were the most frequent primary site in our analysis, with breast, gastrointestinal, and female genital tract malignancies following closely behind. CNS involvement has been reported in patients with Lymphoma (DLBCL) and Leukemia (most commonly ALL, but also AML and JMML) among hematological malignancies. Two cases of Retinoblastoma and one each of Medulloblastoma and an Atypical teratoid/rhabdoid tumor were observed in the pediatric age group.: Cerebrospinal fluid cytology is a simple and useful method, used as a primary diagnostic method in the evaluation of leptomeningeal metastases. This helps in the early detection of secondary CNS lesions and allows for timely intervention, prognosis, and prediction of overall survival.

Construction of the prognostic nomogram and treatment recommendation in patients with mixed endometrial carcinoma treated with hysterectomy.

The study aimed to identify the independent prognostic factors of mixed endometrial carcinoma (MEC) patients treated with hysterectomy and to explore the optimal treatment modalities for overall survival (OS) and cancer-specific survival (CSS). Using the Surveillance, Epidemiology, and End Results (SEER) database, a total of 12,848 MEC patients treated with hysterectomy were screened out. Independent prognostic factors were identified by Cox regression analysis and used to construct the nomogram. The concordance index (C-index) of OS and CSS were 0.807 and 0.834 in the training set. Validation of the nomogram revealed that the receiver operating curve (ROC) maintained good discrimination, the decision curve analysis (DCA) had a high net benefit rate, and the calibration curves showed high consistency. Patients were grouped by the nomogram formula and the number of positive regional lymph nodes (NPR-Lymph node) to evaluate the therapeutic outcomes of chemotherapy, radiotherapy, neoadjuvant treatment and lymph node operation. Survival analysis revealed that chemotherapy could improve the prognosis for OS and CSS in the high-risk group and in the group with NPR-Lymph node counts above 1 (P < 0.05). Radiotherapy was associated with better OS and CSS in the intermediate-risk and high-risk groups, and in the group with NPR-Lymph node counts above 0 (P < 0.05). Lymphadenectomy was found to prolong OS and CSS in the high-risk group (P < 0.05), while neoadjuvant treatment did not prolong OS and CSS in any group. Thus, in this study, the nomogram for MEC patients treated with hysterectomy was successfully built and validated which could effectively predict the prognosis and identify at-risk population to guide clinical decision-making. The NPR-Lymph node was identified as a potentially strong prognostic indicator with good clinical value.

Prognostic significance of hemoglobin, albumin, lymphocyte, and platelet (HALP) score in breast cancer: a propensity score-matching study

BackgroundThe hemoglobin-albumin-lymphocyte-platelet (HALP) score functions as a comprehensive index that assesses the systemic inflammatory response, nutritional, and immune status. This study aimed to explore the relationship between preoperative HALP score and the prognosis of BC patients and to develop predictive nomograms.MethodsClinicopathological data were collected for BC patients who underwent mastectomy between December 2010 and April 2014 from Sun Yat-sen University Cancer Center. The optimal cutoff value for HALP was determined by maximally selected rank statistics for overall survival data. Propensity score matching (PSM) was applied to develop comparable cohorts of high-HALP group and low-HALP group. Kaplan–Meier curves and Cox regression analyses were performed to determine the impact of HALP on BC patients. Prognostic nomograms were developed based on the multivariate Cox regression method. Then, the concordance index (C-index), calibration plots, and decision curves analysis (DCA) were applied to evaluate the prognostic performance of the nomograms.ResultsA total of 1,856 patients were included as the primary cohort, and 1,470 patients were matched and considered as the PSM cohort. In the primary cohort, the 5-year overall survival (OS) and progression-free survival (PFS) rates for high-HALP group (≥ 47.89) and low-HALP group (< 47.89) were 94.4% vs. 91.0% (P = 0.005) and 87.8% vs. 82.1% (P = 0.005), respectively. Similar results were observed in PSM cohort (5-year OS, 94.3% vs. 90.8%, P = 0.015; 5-year PFS, 87.5% vs. 83.2%, P = 0.036). Notably, multivariate Cox regression analysis in the PSM cohort showed that HALP could independently predict BC patient prognosis in both OS (HR: 0.596, 95%CI [0.405–0.875], P = 0.008) and PFS (HR: 0.707, 95%CI [0.538–0.930], P = 0.013). OS and PFS nomograms showed excellent predictive performance with the C-indexes of 0.783 and 0.720, respectively. The calibration plots and DCA also indicated the good predictability of the nomograms. Finally, subgroup analysis further demonstrated a favorable impact of HALP on both OS and PFS.ConclusionPreoperative HALP score can be used as a reliable independent predictor of OS and PFS in BC patients, and the nomograms may provide a personalized treatment strategy.

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.

Impact of race/ethnicity on the MammaPrint genomic assay risk and prognosis in early breast cancer (EBC): A National Cancer Database (NCDB) analysis.

564 Background: The 21-gene Oncotype DX Recurrence Score (RS) and 70-gene MammaPrint (MP) assays provide prognostic information for distant recurrence and are used to guide chemotherapy use in hormone receptor (HR)-positive, HER2-negative EBC. Previous reports have demonstrated that Black women with low genomic risk (RS 0-25) have a higher recurrence risk than White women in the TAILORx (PMID: 32986828) and RxPONDER trials (SABCS 2023, abstract GS1-01), and that Black race was associated with worse overall survival (OS) in multivariate models including RS in the NCDB registry (PMID: 33649322).The goal of this study was to evaluate the impact of race/ethnicity on MP risk distribution and prognostic information provided by the MP assay in the NCDB cohort. Methods: Women with HR-positive EBC with tumor size up to 5 centimeters (T1-T2), 0-3 involved lymph nodes (LNs, N0-N1), diagnosed between 2009-2018, and who had available information on MP testing and OS in the NCDB 2019 dataset were identified. Patients (pt) were stratified by MP result of high or low risk. T-tests and chi-square tests were used to compare pt characteristics, while log-rank tests assessed differences in OS between the high- and low-risk MP groups, as well as across different racial/ethnic categories. Results: 6096 eligible women were included of whom 41.0% (N=2502) were MP high-risk and 59.0% (N=3594) MP low-risk. Overall, 82.7% of pts were Non-Hispanic White (NHW), 8.7% Non-Hispanic Black (NHB), 4.7% Hispanic (H), and the remainder other/unknown (O). A higher proportion of H and NHB pts had high MP results, p&lt;0.0001. The MP high-risk group had a greater proportion of pts &lt;/= 50 years (p=0.0013) and larger tumors (p&lt;0.0001) and higher grade (p&lt;0.0001), but not LN positive (p=0.7649). The 5-year OS rates (and 95% Confidence Intervals) for the MP high and low-risk groups were 92.6% (91.6% - 93.7%) and 96.6% (95.9% - 97.2%), respectively, p&lt;0.0001. There were no differences in OS based on race/ethnicity in the low-risk group with 5-year OS rates of 98.4% (96.1%-100%), 95.9% (93.3% - 98.6%), 96.4% (95.7% - 97.1%), and 99.2% (97.7% - 100%) for H, NHB, NHW and O, respectively, p=0.34. Similarly, in MP high-risk, race/ethnicity did not impact prognosis with OS rates of 92.6% (88.2% - 97.1%), 90.8% (87.2% - 94.5%), 92.8% (91.7% - 94.1%), and 95.8% (91.2% - 100%) for H, NHB, NHW and O groups, respectively, p=0.45. There was no significant interaction between race and MP for OS when accounting for age, tumor grade, tumor size, and LN status, p=0.75. Conclusions: NHB and H women were more likely to have high-risk MP results compared with NHW women in this NCDB cohort, although race/ethnicity did not impact prognosis for 5-year OS in either MP risk group. Limitations of this analysis include absence of information on recurrence and short follow up, as about one-half of recurrences in HR-positive EBC occur after 5 years.

Long-term efficacy of high-dose imatinib in Hispanic patients without access to second-generation tyrosine kinase inhibitors treated in LATAM centers.

6512 Background: Treatment for patients with chronic myeloid leukemia (CML) had a benchmark with the introduction of imatinib, a tyrosine kinase inhibitor (TKI). Nevertheless, resistance due to genetic mutations in the BCR::ABL1 kinase receptor remains relatively common for many patients, leading to failure, lack of response, or suboptimal response. Ideally, to bypass genetic resistance, guidelines recommend switching to a second-generation TKI, but for many developing countries, socioeconomic barriers hinder the possibility of switching medication. Despite this scenario, scarce information is available to evaluate the clinical prognosis of these patients. Methods: We conducted a retrospective cohort analysis to compare the overall mortality of patients with CML who developed a suboptimal response to standard-dose imatinib and were treated with either high-dose imatinib or a second-generation TKI. We created a marginal structural model with inverse probability weighting and stabilized weights and depicted the survival curves and median using the Kaplan-Meier estimator. Our primary outcome was overall survival (OS) at 150 months, defined as the number of deaths once patients had reached treatment response based on parameters of the European Leukemia Net Guidelines for CML. Our secondary outcomes were disease-free survival (DFS) at 150 months, defined as the number of months after patients achieved either major molecular response or deep molecular response, and adverse events that included gastrointestinal, dermatologic, hematologic, and others. Results: The cohort included 148 patients, of which 32 received high-dose imatinib and 116 a second-generation TKI. While we found no difference in the 150-month risk in both OS and DFS (Table), patients receiving second-generation TKI had an increase in median survival of OS ( p-value = 0.009). No difference was found in the median survival of DFS ( p-value = 0.55). No difference was found in either hematologic, gastrointestinal, dermatologic, or other adverse events (p-values of 0.39, 0.94, 0.24, and 0.33, respectively). Conclusions: Ideally, patients who develop a suboptimal response to imatinib should be switched to a second-generation TKI. However, If impossible, our findings suggest that patients treated with high-dose imatinib have a similar OS and DFS prognosis to those receiving a second-generation TKI. [Table: see text]

Clinical characteristics and prognosis of patients with newly diagnosed primary central nervous system lymphoma: a multicentre retrospective analysis.

Bruton's tyrosine kinase inhibitors (BTKi) exhibit superior efficacy in relapsed/refractory primary central nervous system lymphoma (PCNSL), but few studies have evaluated patients with newly diagnosed PCNSL, and even fewer studies have evaluated differences in efficacy between treatment with BTKi and traditional chemotherapy. This study retrospectively analyzed the clinical characteristics of 86 patients with PCNSL and identified predictors of poor prognosis for overall survival (OS). After excluding patients who only received palliative care, 82 patients were evaluated for efficacy and survival. According to the induction regimen, patients were divided into the traditional chemotherapy, BTKi combination therapy, and radiotherapy groups; the objective response rates (ORR) of the three groups were 71.4%, 96.2%, and 71.4% (P = 0.037), respectively. Both median progression-free survival and median duration of remission showed statistically significant differences (P = 0.019 and P = 0.030, respectively). The median OS of the BTKi-containing therapy group was also longer than that of the traditional chemotherapy group (not reached versus 47.8 (32.5-63.1) months, P = 0.038).Seventy-one patients who achieved an ORR were further analyzed, and achieved an ORR after four cycles of treatment and maintenance therapy had prolonged OS (P = 0.003 and P = 0.043, respectively). In conclusion, survival, and prognosis of patients with newly diagnosed PCNSL are influenced by the treatment regimen, with the BTKi-containing regimen showing great potential.

Clinical calculator based on CT and clinicopathologic characteristics predicts short-term prognosis following resection of microsatellite-stabilized diffuse gastric cancer.

Although microsatellite stability/Epithelial-mesenchymal transition (MSS/EMT) subtypes have been reported in multiple cancer prognosis studies, strong confounding factors between MSS/EMT (usually with Lauren's diffuse phenotype) and diffuse gastric cancer (GC) may obscure the independent prognostic value of diffuse GC. Additionally, recent studies suggest a strong correlation between mural stratification based on CT and diffuse GC. This study aims to investigate potential prognostic factors of MSS diffuse GC using mural stratification and to develop a risk assessment model. This retrospective study included 131 patients with MSS diffuse GC who underwent radical surgery. Univariate and multivariate Cox proportional hazards regression analysis was used to identify model predictors and construct a nomogram for overall survival (OS) and recurrence-free survival (RFS) risks. The model's performance was evaluated using ROC, accuracy, and C-index. Internal validation of the model was conducted using the bootstrap resampling method. Among 131 cases, 60 cases (45.8%) exhibited grade 2 mural stratification, which correlated with a poorer tumor prognosis and a more invasive phenotype. Furthermore, a nomogram for predicting OS and RFS prognosis was established based on multivariate results (age, extranodal invasion, mural stratification, and/or P53). The nomogram demonstrated excellent performance, with an AUC of 0.859 (95% CI 0.794-0.924) for OS and 0.859 (95% CI 0.789-0.929) for RFS. Internal validation using 1000 bootstrap samples yielded AUC values of 0.845 and 0.846 for OS and RFS, respectively. Grade 2 mural stratification based on CT imaging revealed a more aggressive invasive phenotype, characterized by increased LN metastasis, higher rates of peritoneal metastasis, and a poorer short-term prognosis. Furthermore, the CT phenotype-based nomogram demonstrates favorable discrimination and calibration, enabling convenient individual short-term prognostic evaluation following resection of MSS diffuse GC.

Abstract PO3-17-02: Analysis of clinical benefit in the real world of HER2-positive metastatic breast cancer following the development of anti-HER2 therapeutics over the past 20 years

Abstract Analysis of clinical benefit in the real world of HER2-positive metastatic breast cancer following the development of anti-HER2 therapeutics over the past 20 years Ahrong Ham1, Sewon Lee1, Jungmin Jo1, Soo Ji Hong2, Ji Eun Lee2, Haena Lee2, Sungchan Gwark2, Jeongshin An2, Hyun Goo Kim2, Jun Woo Lee2, Joohyun Woo2, Woosung Lim2, Byung-In Moon2, Sei Hyun Ahn2, Hye Ah Lee3, Kyoung Eun Lee1 1 Division of Hematology and Oncology, Department of Internal Medicine, Ewha Womans University Mokdong hospital, Ewha Womans University College of Medicine, Seoul, Republic of Korea 2 Department of Surgery, Ewha Womans University Mokdong hospital, Ewha Womans University College of Medicine, Seoul, Republic of Korea 3 Clinical Trial Center, Ewha Womans University Mokdong hospital, Ewha Womans University College of Medicine, Seoul, Republic of Korea Purpose: Over the last two decades, treatment landscapes for human epidermal growth factor receptor 2 (HER2) positive metastatic breast cancer (MBC) have shown remarkable growth with the development of drugs targeting HER2. The standard of care for HER2+ MBC has continued to change with the ongoing development of new anti-HER2 therapies. We aimed to provide a comprehensive analysis of HER2-targeted therapies, clinical characteristics, and treatment outcomes in real-world practice of HER2+ MBC patients over the past 20 years. Methods: Patients who received palliative chemotherapy with HER2+ MBC between 2000 and 2022 were analyzed. We derived cohorts of two groups with or without anti-HER2 containing therapies. Patients receiving multiple anti-HER2 therapies throughout the entire period of treatment were further analyzed according to treatment regimen. The progression-free survival for palliative first-line (PFS1), and overall survival (OS) were compared between groups. A multivariate Cox regression model was used to investigate predictors of survival outcome in HER2+ MBC. Results: A total of 185 patients were analyzed. Median age was 49 years (IQR, 42-56 years). 47 patients (25.4%) were initially diagnosed with de novo stage IV disease. Visceral metastases were found in 95 patients (51.4%). The median PFS1 was 3.9 months (without anti-HER2 therapy) versus 15.6 months (with anti-HER2 therapy) between two groups (P&amp;lt; 0.001). Likewise, the median OS was significantly improved in anti-HER2 therapy group (34.0 months vs. 70.5 months, P=0.010). As a result of confirming the difference in OS according to the type of anti-HER2 therapies during the entire period of treatment by correspondence analysis, significant improvement was found when two or three types of anti-HER2 were used (without anti-HER2 vs. 2 types of anti-HER2, P=0.009; without anti-HER2 vs. 3 types of anti-HER2, P=0.010). Interestingly, when analyzed by treatment regimen, trastuzumab (H) + pertuzumab (P), HP + TDM-1, and H + TDM-1 significantly improved OS over regimens without anti-HER2 (without anti-HER2 vs. HP, P=0.009; without anti-HER2 vs. HP + TDM-1, P=0.013; without anti-HER2 vs. H + TDM-1, P=0.028, respectively). HP + TDM-1 therapies significantly improved survival rate compared to H single containing regimen (P=0.029). Based on our multiple Cox regression model, visceral metastasis was a significant poor OS prognostic factor and two and three types of anti-HER2 therapies were associated better OS prognosis (visceral metastasis: HR=2.40, P=0.003; 2 types of ant-HER2: HR=0.29, P=0.001; 3 types of anti-HER2: HR=0.22, P=0.018, respectively). Conclusions: Anti-HER2 therapies significantly improved PFS1 and OS. Continuing treatment by changing anti-HER2 therapies may act as a better prognostic factor. Further prospective studies are required. Citation Format: Ahrong Ham, Sewon Lee, Jungmin Jo, Soo Ji Hong, Ji Eun Lee, Haena Lee, Sungchan Gwark, Jeongshin An, Hyun-Goo Kim, Jun Woo Lee, Joohyun Woo, Woosung Lim, Byung-In Moon, Sei Hyun Ahn, Hye Ah Lee, Kyoung Eun Lee. Analysis of clinical benefit in the real world of HER2-positive metastatic breast cancer following the development of anti-HER2 therapeutics over the past 20 years [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-17-02.

Limited resection is comparable to lobectomy for tumor size ≤ 2 cm pulmonary invasive mucinous adenocarcinoma

ObjectivesInvasive mucinous adenocarcinoma (IMA) has a rare incidence with better prognosis than nonmucinous adenocarcinoma. We aimed to investigate the prognosis between limited resection and lobectomy for patients with clinical stage IA IMA ≤ 2 cm.MethodsData were taken from two cohorts: In Shanghai Pulmonary Hospital (SPH) corhort, we identified 403 patients with clinical stage IA IMA who underwent surgery. In the SEER corhort, 480 patients with stage T1 IMA who after surgery were included. Recurrence-free survival (RFS) for SPH corhort, lung cancer–specific survival (LCSS) for the SEER corhort and overall survival (OS) for both corhort were compared between patients undergoing lobectomy and limited resection by Log-rank and Cox proportional hazard regression model.ResultsIn SPH corhort, patients who underwent limited resection had equivalent prognosis than those underwent lobectomy (5-year RFS: 79.3% versus. 82.6%, p = 0.116; 5-year OS: 86.2% versus. 88.3%, p = 0.235). However, patients with IMA > 2 to 3 cm had worse prognosis than those with IMA ≤ 2 cm (5-year RFS: 73.7% versus. 86.1%, p = 0.007). In the analysis of IMA > 2 to 3 cm subgroup, multivariate analysis showed that limited resection was an independent risk factor of RFS (hazard ratio, 2.417; 95% confidence interval, 1.157–5.049; p = 0.019), while OS (p = 0.122) was not significantly different between two groups. For IMA ≤ 2 cm, limited resection was not a risk factor of RFS (p = 0. 953) and OS (p = 0.552). In the SEER corhort, IMA ≤ 2 cm subgroup, limited resection was equivalent prognosis in LCSS (p = 0.703) and OS (p = 0.830).ConclusionsLimited resection could be a potential surgical option which comparable to lobectomy in patients with clinical stage IA IMA ≤ 2 cm.

MRI radiomics in head and neck cancer from reproducibility to combined approaches

The clinical applicability of radiomics in oncology depends on its transferability to real-world settings. However, the absence of standardized radiomics pipelines combined with methodological variability and insufficient reporting may hamper the reproducibility of radiomic analyses, impeding its translation to clinics. This study aimed to identify and replicate published, reproducible radiomic signatures based on magnetic resonance imaging (MRI), for prognosis of overall survival in head and neck squamous cell carcinoma (HNSCC) patients. Seven signatures were identified and reproduced on 58 HNSCC patients from the DB2Decide Project. The analysis focused on: assessing the signatures’ reproducibility and replicating them by addressing the insufficient reporting; evaluating their relationship and performances; and proposing a cluster-based approach to combine radiomic signatures, enhancing the prognostic performance. The analysis revealed key insights: (1) despite the signatures were based on different features, high correlations among signatures and features suggested consistency in the description of lesion properties; (2) although the uncertainties in reproducing the signatures, they exhibited a moderate prognostic capability on an external dataset; (3) clustering approaches improved prognostic performance compared to individual signatures. Thus, transparent methodology not only facilitates replication on external datasets but also advances the field, refining prognostic models for potential personalized medicine applications.

Exploring The Prognostic Significance of SET-Domain Containing 2 (SETD2) Expression in Advanced and Castrate-Resistant Prostate Cancer.

SET-domain containing 2 (SETD2) is a histone methyltransferase and an epigenetic modifier with oncogenic functionality. In the current study, we investigated the potential prognostic role of SETD2 in prostate cancer. A cohort of 202 patients' samples was assembled on tissue microarrays (TMAs) containing incidental, advanced, and castrate-resistant CRPCa cases. Our data showed significant elevated SETD2 expression in advanced and castrate-resistant disease (CRPCa) compared to incidental cases (2.53 ± 0.58 and 2.21 ± 0.63 vs. 1.9 ± 0.68; p < 0.001, respectively). Interestingly, the mean intensity of SETD2 expression in deceased vs. alive patients was also significantly different (2.31 ± 0.66 vs. 2 ± 0.68; p = 0.003, respectively). Overall, high SETD2 expression was found to be considered high risk and was significantly associated with poor prognosis and worse overall survival (OS) (HR 1.80; 95% CI: 1.28-2.53, p = 0.001) and lower cause specific survival (CSS) (HR 3.14; 95% CI: 1.94-5.08, p < 0.0001). Moreover, combining high-intensity SETD2 with PTEN loss resulted in lower OS (HR 2.12; 95% CI: 1.22-3.69, p = 0.008) and unfavorable CSS (HR 3.74; 95% CI: 1.67-8.34, p = 0.001). Additionally, high SETD2 intensity with ERG positive expression showed worse prognosis for both OS (HR 1.99, 95% CI 0.87-4.59; p = 0.015) and CSS (HR 2.14, 95% CI 0.98-4.68, p = 0.058). We also investigated the protein expression database TCPA, and our results showed that high SETD2 expression is associated with a poor prognosis. Finally, we performed TCGA PRAD gene set enrichment analysis (GSEA) data for SETD2 overexpression, and our data revealed a potential association with pathways involved in tumor progression such as the AMPK signaling pathway, the cAMP signaling pathway, and the PI3K-Akt signaling pathway, which are potentially associated with tumor progression, chemoresistance, and a poor prognosis.

Lymphovascular invasion is associated with poor long-term outcomes in patients with pT1N0-3 or pT2-3N0 remnant gastric cancer: a retrospective cohort study

BackgroundLymphovascular invasion (LVI) is a poor prognostic factor in various malignancies. However, its prognostic effect in remnant gastric cancer (RGC) remains unclear. We examined the correlation between LVI and disease prognosis in patients with T1N0-3 or T2-3N0 RGC in whom adjuvant chemotherapy was not indicated and a treatment strategy was not established.MethodsWe retrospectively analyzed patients with T1N0-3 and T2-3N0 RGC who underwent curative surgery at the Kyoto Prefectural University of Medicine between 1997 and 2019 and at the Kyoto Chubu Medical Center between 2009 and 2019.ResultsFifteen of 38 patients (39.5%) with RGC were positive for LVI. Patients with LVI had a significantly poorer prognosis for both overall survival ([OS]: P = 0.006) and recurrence-free survival ([RFS]: P = 0.001) than those without LVI. Multivariate analyses using the Cox proportional hazards model revealed LVI as an independent prognostic factor affecting OS (P = 0.024; hazard ratio 8.27, 95% confidence interval:1.285–161.6) and RFS (P = 0.013; hazard ratio 8.98, 95% confidence interval:1.513–171.2).ConclusionsLVI is a prognostic factor for patients with T1N0-3 or T2-3N0 RGC. Evaluating LVI may be useful for determining treatment strategies for RGC.

RNA splicing regulator EIF3D regulates the tumor microenvironment through immunogene-related alternative splicing in head and neck squamous cell carcinoma.

Study finds that eukaryotic translation initiation factor 3 subunit D (EIF3D) may play an important role in aberrant alternative splicing (AS) events in tumors. AS possesses a pivotal role in both tumour progression and the constitution of the tumour microenvironment (TME). Regrettably, our current understanding of AS remains circumscribed especially in the context of immunogene-related alternative splicing (IGAS) profiles within Head and Neck Squamous Cell Carcinoma (HNSC). In this study, we comprehensively analyzed the function and mechanism of action of EIF3D by bioinformatics analysis combined with in vitro cellular experiments, and found that high expression of EIF3D in HNSC was associated with poor prognosis of overall survival (OS) and progression-free survival (PFS). The EIF3D low expression group had a higher degree of immune infiltration and better efficacy against PD1 and CTLA4 immunotherapy compared to the EIF3D high expression group. TCGA SpliceSeq analysis illustrated that EIF3D influenced differentially spliced alternative splicing (DSAS) events involving 105 differentially expressed immunogenes (DEIGs). We observed an induction of apoptosis and a suppression of cell proliferation, migration, and invasion in EIF3D knock-down FaDu cells. RNA-seq analysis unveiled that 531 genes exhibited differential expression following EIF3D knockdown in FaDu cells. These include 52 DEIGs. Furthermore, EIF3D knockdown influenced the patterns of 1923 alternative splicing events (ASEs), encompassing 129 IGASs. This study identified an RNA splicing regulator and revealed its regulatory role in IGAS and the TME of HNSC, suggesting that EIF3D may be a potential target for predicting HNSC prognosis and immunotherapeutic response.

Abstract 5066: Integrating spatial and single cell transcriptomics to identify and characterise biologically driven subgroups in invasive lobular carcinoma

Abstract Background: Invasive lobular carcinoma (ILC) is the second most common histological breast cancer subtype; however, little is known about its tumor microenvironment (TME). Here, we aimed to identify and to characterise ILC subgroups based on TME heterogeneity by combining spatial transcriptomics (ST) and single cell RNA-sequencing (scRNA-seq). Methods: We performed ST (Visium 10x Genomics) on frozen tumor samples from 41 primary hormone receptor positive (HR+), HER2-negative (HER2-) ILCs. Information coming from the morphological annotation of ST slides and the gene expression-based clustering of ST spots was integrated and used as input for a patient level classification (using intNMF algorithm). Subgroups of patients were annotated using morphology, gene set enrichment analysis and ST deconvolution based on scRNA-seq data (CARD software). SCAN-B bulk RNA-seq dataset was used as validation set (HR+, HER2- ILC samples, n = 853). Results: Four subgroups of patients were identified: proliferative (P, n = 12, enriched in tumor cells and proliferation-related pathways), normal-stroma enriched (NSE, n = 10, enriched in fibroblasts, stroma-related pathways and showing an higher level of colocalization between invasive and in situ carcinoma), metabolic (M, n = 9, enriched in metabolic related-pathways) and metabolic-immune enriched (MIE, n = 10, enriched in adipocytes, metabolic and immune-related pathways). Deconvolution of ST spots with single cell data revealed matching results with morphology (in terms of cell types). We observed an enrichment of myofibroblasts in NSE, an enrichment of cancer epithelial in P and, interestingly, an enrichment of endothelial cells in M subgroup (fdr &amp;lt; 0.25). MIE was characterized by perivascular like-endothelial cells and myeloid cells (monocytes and macrophages, fdr &amp;lt; 0.25). Of note, at the level of the ST slide, myeloid cells in MIE subgroup were more present in the adipose tissue compartment (fdr &amp;lt; 0.25) compared to the rest of the slide. NSE subgroup showed a trend for association with better prognosis. Gene signature-based assignment identified the same four subgroups in SCAN-B: GSEA analysis and comparisons among the four subgroups showed matching results between our dataset and SCAN-B. Of note, in SCAN-B, we observed differences in prognosis among the subgroups, with NSE showing better, M and MIE intermediate and P worse prognosis for overall survival and relapse free interval (p &amp;lt; 0.01). Conclusions: Four subgroups of ILC based on TME heterogeneity and showing differences in prognosis were identified and validated in external cohort. Of note, two of these groups were related to metabolism, highlighting the value of such process in ILC biology. Importantly, myeloid cells were the predominant immune cell types in ILC, and they showed a specific compartmentalization inside the TME. Further validation is needed. Citation Format: Matteo Serra, Andreas Papagiannis, Mattia Rediti, Frederic Lifrange, Nicola Occelli, Laetitia Collet, Delphine Vincent, Ghizlane Rouas, Danai Fimereli, Ligia Craciun, Denis Larsimont, David Venet, Miikka Vikkula, Francois P. Duhoux, Françoise Rothé, Christos Sotiriou. Integrating spatial and single cell transcriptomics to identify and characterise biologically driven subgroups in invasive lobular carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 5066.

Abstract 5397: Characteristics of cancer associated fibroblasts isolated from refractory colorectal cancer using RNA sequence

Abstract Primary tumor location of colorectal cancers (CRCs) is emerging as an important prognostic factor owing to distinct biological features. In fact, the patients with right-side CRCs (R-CRCs), in which primary tumors were resected in our department and followed by systemic chemotherapy, have a poorer prognosis in 2-year overall survival and progression-free survival than those with left-side CRCs (L-CRCs). Furthermore, cancer-associated fibroblasts (CAFs) promote tumor malignancy, but the precise transcriptional mechanisms regulating the acquisition of the CAF phenotype are not well understood. Here, we isolated the CAFs and normal counterparts from 10 CRCs which were performed radical resection, including 5 L-CRCs and 5 R-CRCs, and analyzed transcriptomic profile of CAFs by RNA-sequencing. Gene Set Enrichment Analysis (GSEA) was performed and inflammatory signatures, such as "HALLMARK IL2 STAT5 SIGNALING"(NOM p-value&amp;lt;0.001, FDR q-value=0.146), "HALLMARK IL6 JAK STAT3 SIGNALING"(NOM p-value=0.014, FDR q-value=0.162), "HALLMARK INTERFERON GAMMA RESPONSE"(NOM p-value=0.032, FDR q-value=0.1726), were enriched in the CAFs isolated from R-CRCs (R-CAFs). In addition to sidedness of CRCs, based on gene expression profiles from bulk tumors, CRCs were classified into four consensus molecular subtypes (CMS1-4). Among them, The fibrotic CMS4 subtype portends poor relapse-free survival. We identified 4 CMS4-CRCs, which have the characteristics of stromal activation and the worst prognosis among other CRCs. GSEA showed that the signature of "HALLMARK TNFA_SIGNALING_VIA_NFKB" (NOM p-value=0.023 FDR q-value=0.207), "HALLMARK GLYCOLYSIS" (NOM p-value=0.036 FDR q-value=0.239) were upregulated in the CAFs isolated from CMS4-CRCs. These results indicated that CAFs isolated from refractory CRCs have unique phenotypes and the elucidation of these mechanisms might lead to a promising treatment for refractory CRCs. Citation Format: Hiroaki Kasashima, Yasuhiro Fukui, Ken Yonemitsu, Kisyu Kitayama, Yuichiro Miki, Mami Yoshii, Tatsunari Fukuoka, Tatsuro Tamura, Masatsune Shibutani, Takahiro Toyokawa, Shigeru Ree, Masakazu Yashiro, Kiyoshi Maeda. Characteristics of cancer associated fibroblasts isolated from refractory colorectal cancer using RNA sequence [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 5397.