Worse Overall Survival Research Articles

Polymorphisms in immunosuppression-related genes are associated with AML

BackgroundAcute myeloid leukemia (AML) is a hematologic malignancy with poor overall survival (OS). The immunosuppressive microenvironment significantly impacts AML development and chemoresistance. Despite new immunotherapeutic strategies entering standard clinical care for various tumors, progress in AML remains poor. Multi-omics analyses, such as single-cell transcriptomics, have revealed many potential new targets to improve AML prognosis from an immunological perspective.MethodsDNA from 307 AML patients and 316 healthy individuals were extracted. We detected nine single nucleotide polymorphisms (SNPs) in five immunosuppression-related genes (CIITA, CD200, CD163, MRC1 and LILRB4) in these samples. SNP genotyping was performed on the MassARRAY platform. We then analyzed the relationship between these SNPs and AML susceptibility, treatment response, and prognosis.ResultsOur findings indicated that rs4883263 in the CD163 gene is a protective factor for AML susceptibility and chromosomal karyotype abnormalities. Additionally, rs4883263 in CD163 was related to low PLT count at diagnosis, while rs2272022 in CD200 was protective against low PLT count. rs4780335 in CIITA was associated with high WBC count at diagnosis and worse OS. Furthermore, rs1048801 in LILRB4 was linked to worse AML treatment response, lower OS, and may be an independent prognostic risk factor for AML. Lastly, expressions of CD163, CIITA, LILRB4, and CD200 were higher in AML patients than that in normal controls.ConclusionsOur findings on SNP associations in AML immunosuppression-related genes provide important reference points for predicting treatment outcomes in AML patients.

Prognostic value of Glasgow prognostic score in hematological malignancies: a systematic review and meta-analysis.

The Glasgow prognostic score (GPS) is used to predict the prognosis of several cancers. This first systematic review and meta-analysis evaluated the role of GPS in predicting overall survival (OS) and progression-free survival (PFS) in patients with hematological malignancies. Embase, PubMed, CENTRAL, Scopus, and Google Scholar were screened for studies evaluating the prognostic role of GPS in hematological malignancies. Twelve studies were eligible. Meta-analysis showed that patients with GPS of ≥1 and ≥2 had worse OS than those with GPS of 0. We noted that both GPS scores of ≥1 and ≥2 were associated with significantly poor PFS in patients with hematological malignancies. Results remained robust on sensitivity analysis. GPS can be used as a predictor of OS and PFS in patients with hematological malignancies. High GPS scores can lead to a twofold higher risk of poor OS and PFS.

HLA class I supertypes and HLA class I alleles influence the outcome after allogeneic hematopoietic stem cell transplant from unrelated matched donor.

This retrospective study analyses the impact HLA heterozygosity, supertypes, and alleles have on incidence of graft versus host disease (GvHD), relapse, overall survival (OS), disease-free survival (DFS) and transplant-related mortality (TRM) after HSCT. The study included patients who underwent HSCT, typed at allele resolution level for HLA-A, -B, -C, -DRB1, -DQB1, and -DPB1 loci. The analysis performed on the entire patient cohort (N=232) showed that HLA-B07 supertype positive patients demonstrated decreased incidence of relapse, better OS and DFS in comparison to those negative for HLA-B07 supertype. Further, a higher incidence of TRM was observed among patients positive for HLA-B27 supertype. Significant association of the HLA-A*02:01 allele presence with decreased incidence of GvHD was found. The occurrence of HLA-A*11:01 allele was associated with a worse OS, DFS and a higher rate of TRM. The analysis of the subgroup of patients with AML or MDS (N=148) showed an association of HLA-A24 supertype with a worse OS. The HLA-B07 supertype positive patients demonstrated a lower incidence of relapse and a better DFS. A decline in OS and a higher TRM rate were observed among patients positive for HLA-B27 supertype. The presence of HLA-A*11:01 allele was indicative of a worse OS, DFS and a higher rate of TRM. The associations of HLA and HSCT clinical outcome parameters found in this study justify further investigation of this matter.

Prognostic significance of serum complement activation, neutrophil extracellular traps and extracellular DNA in newly diagnosed epithelial ovarian cancer.

We observed that the tumor microenvironment (TME) in metastatic epithelial ovarian cancer (EOC) and in other solid tumors can reprogram normal neutrophils to acquire a complement-dependent suppressor phenotype characterized by inhibition of stimulated T cell activation. This study aims to evaluate whether serum markers of neutrophil activation and complement at diagnosis of EOC would be associated with clinical outcomes. We conducted a two-center prospective study of patients with newly diagnosed EOC (N=188). Blood and ascites fluid were collected at diagnosis for biomarker analysis. Patients were evaluated for progression-free survival (PFS) and overall survival (OS). The median OS was 47months (95% CI: 34-58) and the median PFS was 12months (95% CI: 11-15). Pre-treatment serum levels of genomic DNA (gDNA), markers of neutrophil degranulation (myeloperoxidase [MPO]) and neutrophil extracellular traps (NETs) (citrullinated histone H3 [CitH3]), and complement activation (C3b/c) were each associated with worse OS in univariate analysis. In multivariate analyses controlling for age, stage, and optimal debulking, serum gDNA, MPO, and CitH3 remained associated with worse OS, while C3b/c levels were not. In an exploratory analysis, the largest magnitude of difference in 2-year OS occurred in patients with low C3b/c and low CitH3 compared to all other patients (87% vs 46% survival, respectively). In ascites fluid, increased factor H, a negative regulator of complement activation, was associated with improved OS in univariate analysis. These results point to serum gDNA, NETs, and complement activation as potential prognostic biomarkers in patients with newly diagnosed EOC.

The role of immunotherapy for real-world patients with HER2-negative advanced gastric cancer between 2011-2023.

404 Background: Although the appearance of immunotherapy has apparently brought benefits for all patients (pts) with advanced gastric cancer (AGC), the magnitude of the benefit in real-world pts with HER2-negative AGC has not been fully investigated. Methods: We conducted a retrospective study on pts with HER2-negative AGC who received first-line platinum-based chemotherapy between 2011 and 2023. We evaluated the clinical outcomes across different periods of immunotherapy approval in Japan: Group A (pre-immunotherapy approval): 2011-2017, Group B (approved for third-line treatment or later): 2018-2021, and Group C (approved for first-line treatment): 2022-2023. Results: A total of 949 pts were enrolled (A: n = 477; B: n = 344; C: n = 128). Patient's characteristics were comparable except for the proportion of those with age ≥75 years (P = 0.002), prior gastrectomy (P = 0.03), and liver metastases (P < 0.001). The median overall survival (OS) was 16.2, 15.2, and 21.3 months in group A, B, and C, respectively, with no significant difference between groups (log-rank P = 0.50). Pts who had received first-line immunotherapy plus chemotherapy (n = 173) showed significantly improved OS compared with pts without having received any immunotherapy-containing treatment at 2011-2017 (n = 382) (hazard ratio [HR], 0.78; 95% confidence interval [CI], 0.61-0.99; P = 0.04). In the multivariate analysis, the use of immunotherapy at first-line treatment was not significantly associated with worse OS, whereas the use of immunotherapy at any lines was prognostic (HR, 0.54; 95% CI, 0.41-0.71; P < 0.0001). The proportion of pts who had received any second-line treatment was comparable among groups: 76%, 80%, and 71%, respectively. Conclusions: Our study suggests that the immunotherapy might partially have an impact on the survival improvement of real-world pts with HER2-negative AGC, which calls for the need for appropriate treatment strategies, including other agents.

Midterm outcomes of aortobifemoral bypass, axillobifemoral bypass and covered endovascular reconstruction of aortic bifurcation.

Aortobifemoral bypass (ABFB) is the gold-standard procedure for aortoiliac occlusive disease (AIOD). Axillobifemoral bypass (AxBFB) has been alternatively used for revascularization in patients who are deemed high risk for ABFB. However, in the endovascular era, covered endovascular reconstruction of aortic bifurcation (CEARB) is being used frequently in high- and standard-risk patients with AIOD. We aimed to compare the midterm outcomes of ABFB, AxBFB, and CERAB in the Vascular Quality Initiative (VQI)-Medicare-Linked database. All patients with AIOD who underwent aortoiliac reconstruction by ABFB, AxBFB or CERAB during 2013-2019 in VQI-Medicare-Linked database were included. The primary outcome was amputation-free survival (AFS). The secondary outcomes were overall survival (OS), limb salvage (LS), and freedom from reintervention (FFR). Outcomes were assessed at one- and three-years. Kaplan-Meier estimates and Cox regression were used for the analyses. Three cohorts of patients undergoing ABFB (N=1,906, 60.4%), AxBFB (N=1,077, 34.1%) and CERAB (N=173, 5.5%) were studied. The patients in AxBFB and CERAB cohorts were older than the ABFB cohort and were more likely to have comorbidities compared to their ABFB counterparts. Three-year AFS was 79.4%, 54.6%, 71.1% in ABFB, AxBFB and CERAB cohorts, respectively (P<.001). After adjusting for potential confounders, AxBFB was associated with higher hazards of major amputation/death compared to ABFB at three-year (adjusted Hazard Ratio[aHR]=1.89, 95% Confidence Interval [CI], 1.61-2.23; P<.001) but CERAB was not (aHR=1.27, 95% CI, 0.84-1.91; P=0.251). AxBFB was also associated with higher hazards of major amputation compared to ABFB at three-year (aHR=1.74, 95% CI, 1.05-2.90; P=0.032) but CERAB was not (aHR=2.14, 95% CI, 0.73-6.31; P=0.166). On the other hand, CERAB was associated with increased hazards of three-year reintervention (aHR=1.75, 95% CI, 1.16-2.64; P=0.007) compared to ABFB. CERAB was also associated with lower hazards of major amputation/death at one-year compared to AxBFB (aHR=0.62, 95% CI, 0.38-0.99; P=0.048) but not at three-year. We found that CERAB is comparable to ABFB in terms of OS, LS and AFS, albeit with substantial increase in reintervention rate at three years. AxBFB had worse OS, LS and AFS compared to ABFB. CERAB was associated with higher AFS compared to AxBFB at one-year. This national contemporary study supports the use of CERAB as a safe and durable alternative to ABFB and AxBFB. However, further prospective studies are necessary to confirm our findings.

A comparison of real-world outcomes by mismatch repair status in patients with stage II/III rectal cancer in the Netherlands.

260 Background: A subset of rectal tumours (~3–5%) have mismatch repair deficiency (dMMR); the remaining are classified as MMR proficient (pMMR). A recent trial for stage II/III dMMR rectal cancer (RC) showed that 6 months of neoadjuvant treatment with dostarlimab, a programmed cell death protein 1 inhibitor, induced a 100% clinical complete response rate and allowed for organ preservation. Using real-world data from the Netherlands, a dMMR patient cohort was compared to a matched pMMR cohort to assess if clinical outcomes differed, even after matching for baseline characteristics. Methods: Utilizing data from the Netherlands Cancer Registry, this retrospective analysis assessed patients with stage II/III RC treated from 2015–2022 with known MMR status. The dMMR cohort was matched 1:2 to a cohort of pMMR patients on age, year of diagnosis, tumour clinical (cT) stage, and node clinical (cN) stage. Event-free survival (EFS; defined as first occurrence of locoregional failure, distant metastasis, a new primary colorectal tumour, or death from any cause) and overall survival (OS) were compared using Kaplan-Meier methodology and a univariable Cox model. Results: Among the 7939 patients included, 184 (2.3%) had dMMR tumours. After matching and a loss of 8 dMMR patients due to ineligibility, 176 dMMR patients were compared to 363 pMMR patients. Matching successfully removed differences in age, cT, and cN stage; however, dMMR patients continued to have more BRAF mutants (p=0.014), more poorly differentiated tumours (p&lt;0.001) and more variation in histology (p=0.01). dMMR patients had a statistically significant lower risk of experiencing an event (hazard ratio [HR] 0.54 [95% confidence interval (CI) 0.38–0.77], p&lt;0.001), with a 3-year EFS of 79.6% (95% CI 73.7–86.1) compared to pMMR patients (64.7% [95% CI 59.8–70.1]). For OS, there was no significant difference between the dMMR and pMMR cohorts (HR 0.73 [95% CI 0.47–1.16], p=0.181); however, within the small group of patients with an event, OS at 1 year for dMMR patients was 68.4% (95% CI 55.1–84.9) compared to 93.5% (95% CI 89.5–97.7) for pMMR patients (p=0.001). Conclusions: dMMR RC is rare, and tumour characteristics differ from those of patients with pMMR tumours (1). After controlling for clinical stage and age, this study suggests dMMR patients have improved EFS compared to pMMR patients. There is no significant difference in OS between groups but dMMR patients with an event have worse OS than pMMR patients, highlighting an additional need to prevent recurrence of disease within dMMR patients.1. Lunenberg, R et al. Poster presented at ESMO Congress (Presentation 569P), 13-17 Sept 2024, Barcelona, Spain.

Plasma shallow whole-genome sequencing profiling in patients with RAS WT metastatic colorectal cancer (mCRC) undergoing first-line anti-EGFR therapy.

214 Background: Acquired resistance (AR) to first-line (1L) chemotherapy (CT) + anti-EGFR inhibitors is a major challenge in the management of RAS WT mCRC patients (pts). While AR in later lines has been explained with point mutations in the EGFR pathway, its real mechanisms in 1L remain poorly understood. Tumor molecular biology can be dynamically studied through circulating tumor DNA (ctDNA) analysis, a real-time, non-invasive approach to detect AR. In this context, we conducted the multicenter prospective PLATFORM-B study, which enrolled 100 RAS WT mCRC pts receiving 1L CT + cetuximab across 15 Spanish Medical Oncology Departments, alongside 30 RAS MUT pts (control) treated with 1L CT + bevacizumab. Peripheral blood samples have been collected at baseline (BL), week 8, and disease progression (PD). Next-generation sequencing analysis (Ion S5 system) of ctDNA at PD revealed AR mutations in only 10% of pts, suggesting that alterations in the EGFR pathway may only partially explain AR in 1L. Therefore, we conducted shallow whole-genome sequencing (shWGS) to further characterize genomic profiles possibly related with novel mechanisms of AR. Methods: Baseline and PD samples with sufficient remaining plasma were considered for this analysis. shWGS was performed with a coverage ranging 0.5X to 2.0X and analyzed using ichorCNA pipeline to evaluate various genomic characteristics such as copy number alterations (CNA), tumor fraction (TF), subclonal fraction (SF), and ploidy. Molecular results were correlated to clinical-pathological features and outcomes. Results: Overall, 35 mCRC pts (27 RAS WT and 8 RAS MUT ) were included in the study. At BL ( N = 26), median TF (mTF) was 0.19, median ploidy 2, median SC fraction 0.5, median SC genome fraction 0.21, and median subclonal CNA fraction 0.41. At PD ( N = 33), mTF was 0.08, median ploidy 2, median SC fraction 0.5, median SC genome fraction 0.17, and median subclonal CNA fraction 0.38. Of all the features analyzed, only the TF showed potential prognostic value. At BL, pts with TF levels above the median had poorer overall survival (OS) compared to those with lower levels, approaching statistical significance ( P = .055). At PD, higher TF levels were statistically significantly associated with worse OS ( P = .02). No meaningful differences between the RAS WT and RAS MUT groups were observed. Specific variations in CNA, TF, SF, or ploidy under treatment are being correlated to clinical data to seek for predictive value. Conclusions: This preliminary analysis of the PLATFORM-B using shWGS showed the prognostic value of TF. Further analyses are undergoing to better understand the molecular landscape of acquired resistance to 1L anti-EGFR-based therapy in RAS WT mCRC pts.

Molecular characteristics and prognostic impact of GNAS mutations in colorectal cancer: An international collaborative study between United States and Japan.

48 Background: GNAS (Guanine nucleotide-binding protein, alpha stimulating) encodes the alpha subunit of the stimulatory G protein, and gain of function mutations in this gene have been previously identified, especially those located at the R201 codon. Although GNAS R201C/H has been associated with mucinous histology and poor response to chemotherapy in appendiceal cancer, the impact of GNAS mutations in colorectal cancer (CRC) remains unclear. Methods: We conducted a comparative, integrative analysis of GNAS mutations in CRC using two cohorts: MD Anderson Cancer Center (MDA) across all stages (N=5,249) and the GALAXY study involving only resectable disease (UMIN000039205, N=2,599). We assessed the correlation between GNAS pathogenic mutations and microsatellite stability, CRC sidedness, co-mutations, and survival outcomes. The Chi-squared test was used for categorical variables, and the log-rank test for overall survival (OS) and disease-free survival (DFS). Results: In the MDA and GALAXY cohorts, GNAS mutations were identified in 107 (2.0%) and 61 (2.4%) patients, respectively. Prevalence of GNAS mutations was higher in right sided tumors (MDA: 3.8% vs. 1.3%, GALAXY: 6.2% vs 2.8%, p&lt;0.01 for both cohorts) and microsatellite instability-high (MSI-H) tumors (MDA: 6.5% vs. 1.8%, GALAXY: 16.5% vs. 1.4%, p&lt;0.01 for both cohorts). There was not an association of GNAS mutations with stage in either cohort. GNAS was significantly enriched for co-mutation with KRAS in the MDA cohort (OR=3.26, P&lt;0.01), similar to prior observations in appendix cancer, but was not significantly associated with KRAS mutations in the GALAXY cohort (OR=1.35, P=0.3). GNAS mutations were mutually exclusive with TP53 in both cohorts (MDA: OR=0.58, P=0.026; GALAXY: OR=0.21, P&lt;0.01). With regards to survival, in the MDA cohort, GNAS mutant tumors had a trend towards worse OS in the overall population (20 mo vs. 33 mo, HR=1.27, 95% CI=0.61-1, P=0.085). The survival impact of GNAS mutations was greatest in metastatic patients (Stage IV: 19 mo vs. 38 mo, HR=1.49, 95% CI=0.47-0.94, P=0.021 vs. Stage I-III: HR=1.35, 95% CI=0.46-1.2, P=0.22). The GALAXY cohort showed no significant association between GNAS mutations and DFS (HR=1.05, 95% CI=0.6-1.8, P=0.9). In both cohorts, GNAS mutations had a worse prognosis in left-sided CRC (MDA: HR for OS = 1.45, P = 0.091; GALAXY: HR for DFS=2.15, P=0.09) with no significant effect observed in right-sided CRC (MDA: HR for OS=0.91, P=0.68; GALAXY: HR for DFS=0.65, P=0.3). Conclusions: Our findings highlighted the intricate role of GNAS mutations in CRC, demonstrating its higher prevalence in MSI-H and right-sided colon, significant association with KRAS mutations, and divergent prognostic impacts based on tumor sidedness. Further research is needed to elucidate the mechanisms behind the worsened survival in left-sided GNAS- mutated CRC.

Immunotherapy outcomes in dMMR/MSI-H and/or TMB-H metastatic colorectal cancer (CRC) with peritoneal metastases (PM).

163 Background: CRC with PM has a poor prognosis and limited treatment options. Immunotherapy has shown promise in improving outcomes for patients with microsatellite instability-high (MSI-H), mismatch repair-deficient (dMMR), and high tumor mutational burden (TMB-H) tumors. However the peritoneal niche has a unique microenvironment, which can influence the effectiveness of immune check point inhibitors (ICIs). We assessed the impact of ICI on progression-free survival (PFS) and overall survival (OS) in CRC patients (pts) and PM, considering key clinical and molecular characteristics. Methods: A retrospective review aiming to identify CRC pts with MSI-H/dMMR and PM treated with immunotherapy between 2015 and 2023 was performed. Data collected included pt demographics, tumor characteristics, and treatment details. Responses were evaluated using RECIST v1.1 criteria. Results: 37 pts were included, 9 (24%) had Lynch syndrome. The median age of diagnosis was 61 years and most pts were females (65%). Most pts had MSI-H/dMMR tumors, while one pt was treated based on ultra-hypermutated phenotype (TMB 202) and POLE mutation. Among those with available TMB data, the median TMB was 52 mutations/Mb (0-202). Common mutations were PMS2 (51%), MLH1 (38%), MSH6 (16.2%), and MSH2 (16.2%). Right-sided tumors were in 54%, mucinous histology in 62%, and ascites in 54%. Pts received a median of 11 cycles of ICI (2-52). Pembrolizumab was the most frequently used ICI (78%), while Nivolumab was used either alone (11%) or in combination with Ipilimumab (11%). Median PFS in our cohort was 7.8 months and median OS was 29.9 months. The disease control rate (DCR) was 81%, with an objective response rate (ORR) of 51.3% (9 complete responses, 12 partial responses). At the time of data collection, 30% of pts were off systemic therapy and 5-FU-based chemotherapy combined with a biologic agent was the most common subsequent treatment in 32% who had PD. Univariate analysis showed no significant differences in PFS or OS based on tumor sidedness, isolated PM, liver metastases, mucinous vs. non mucinous histology or BRAF / RAS status (WT vs mutant). Malignant ascites was associated with worse OS(HR 0.3; p= 0.03). Conclusions: Treatment with ICIs in pts with MSI-H/dMMR and/or TMB-H CRC and PM improved disease control in CRC pts with PM, however, as compared to historical controls for patients with MSI-H/d-MMR disease treated with ICI, this group showed less favorable outcomes. Malignant ascites was associated with poorer overall survival. Further research of the immune response and tumor microenvironment in the peritoneal cavity is warranted.

Abdominal myosteatosis measured with computed tomography predicts poor outcomes in patients with glioblastoma.

Alterations in cellular metabolism affect cancer survival and can manifest in metrics of body composition. We investigated the effects of various body composition metrics on survival in patients with glioblastoma (GBM). We retrospectively analyzed patients who had an abdominal and pelvic computed tomography (CT) scan performed within 1 month of diagnosis of GBM (178 participants, 102 males, 76 females, median age: 62.1 years). Volumetric body composition metrics were derived using automated CT segmentation of adipose tissue, skeletal muscle, and aortic calcification from L1 to L5. Univariable and multivariable Cox proportional hazards models were performed separately in males and females using known predictors of GBM overall survival (OS) as covariates. A sex-specific composite score of predisposing and protective factors was constructed using the relative importance of each metric in GBM OS. Higher skeletal muscle volume and lower skeletal muscle fat fraction were associated with better OS in the entire dataset. A robust and independent effect on GBM OS was seen specifically for fraction of inter/intramuscular adipose tissue to total adipose tissue after correction for known survival predictors and comorbidities. Worse OS was observed with increased abdominal aortic calcification volume in both sexes. There was a significant difference in GBM OS among participants stratified into quartiles based on sex-specific composite predisposing and protective scores. The relationship between body composition and GBM OS provides an actionable advancement toward precision medicine in GBM management, as lifestyle and dietary regimens can alter body composition and metabolism and from there GBM survival.

Choice of Adjuvant Radiotherapy Facility in Sinonasal Squamous Cell Carcinoma.

Undergoing surgery and adjuvant radiotherapy (aRT) at the same facility has been associated with higher overall survival (OS) in head and neck squamous cell carcinoma. Our study investigates whether undergoing surgery and aRT at the same academic facility is associated with higher OS compared with separate facilities in sinonasal squamous cell carcinoma (SNSCC). The 2006 to 2017 National Cancer Database was queried for patients with SNSCC undergoing surgery at an academic facility followed by aRT with or without adjuvant chemotherapy. Multivariable binary logistic and Cox proportional hazards regression models were implemented. Of 419 patients satisfying inclusion criteria, 299 (71.4%) underwent surgery and aRT at the same academic facility. Residence in a less populated area (adjusted odds ratio [aOR] 1.75, 95% confidence interval [CI] 1.02-2.99, p = 0.042) and surgical facility case volume (aOR 2.51, 95% CI 1.21-5.21, p = 0.014) were associated with undergoing surgery and aRT at different facilities on multivariable logistic regression adjusting for patient demographics, clinicopathologic features, and adjuvant therapy (p < 0.05). Five-year OS was higher among patients undergoing surgery and aRT at the same academic facility (64% vs. 55%, p = 0.039). Undergoing surgery and aRT at different facilities remained associated with worse OS on multivariable Cox regression (aHR 1.90, 95% CI 1.09-3.32, p = 0.023). Undergoing surgery and aRT at the same academic facility is associated with higher OS in SNSCC. Academic physicians should carefully consider the recommendation of aRT treatment facility based on the level of benefit that the patient may derive from coordinated multidisciplinary care. 3 Laryngoscope, 135:705-715, 2025.

Impact of comorbidity on survival in cancer patients receiving immune checkpoint inhibitors.

Immunotherapy efficacy in elderly patients with comorbidities and poor performance status is not well understood. More knowledge on this topic is needed to identify subgroups that will benefit from immunotherapy. We aimed to evaluate the effect of comorbidity burden in patients receiving immunotherapy. Patients older than 18 years of age and diagnosed with various malignancies, followed up in our tertiary cancer center were screened. Patients treated with immunotherapy were included in this study. We used to Charlson Comorbidity Index (CCI) to evaluate patients' comorbidity burden. The primary outcome was overall survival (OS). Hazard ratio (HR) with confidence interval (CI) was evaluated in multivariable analysis. A total number of 197 patients were included. The median age was 62 years. Patients were grouped based on CCI scores: CCI-low (≤ 8) and CCI-high (> 8). One-hundred and seven patients (54.9%) had metastatic disease at the time of diagnosis. Most frequently used immunotherapy agent was nivolumab (n = 124, 62.9%), followed by pembrolizumab (n = 36, 18.3%). The median OS was shorter in the CCI-high group than in the CCI-low group (10.6 vs. 21.2 months, p = 0.002) In multivariable analysis, treatment with anti-CTLA4 (HR: 1.85, 95% CI 1.07-3.20, p = 0.028), ECOG performance status (2-4 vs. 0-1) (HR: 2.17; 95% CI 1.25-3.75; p = 0.005), and higher CCI scores (CCI-high vs. CCI-low) (HR: 1.97; 95% CI 1.3-3.0; p = 0.001) were independently associated with worse OS. Comorbidity burden and performance status independently predict survival outcomes in immunotherapy-treated cancer patients. Comprehensive comorbidity assessment is essential for optimizing treatment and improving patient outcomes.

Neutrophil-to-lymphocyte ratio as a prognostic factor in patients with castration-resistant prostate cancer treated with docetaxel-based chemotherapy: a meta-analysis

BackgroundIn recent years, many studies have illustrated that the neutrophil-to-lymphocyte ratio (NLR) is a prognostic factor of metastatic castration-resistant prostate cancer (mCRPC), but their conclusions are controversial. The aim of this study was to assess the prognostic value of the NLR in patients with mCRPC treated with docetaxel-based chemotherapy.MethodsDatabase searches were conducted in PubMed, EMBASE and the Cochrane Library to retrieve relevant published English-language literature up to 20 February 2023. RevMan 5.4.1 was used to summarize the hazard ratio (HR) and its 95% confidence interval (CI) for overall survival (OS) and progression-free survival (PFS) with subgroup analysis. Finally, Stata software was adopted for sensitivity analysis, and Egger’s test was used to calculate the results of stability to determine whether there was publication bias.ResultsA total of 1,983 mCRPC patients from 14 retrospective cohort studies were included in this meta-analysis. The combined results showed that elevated NLR was significantly associated with worse OS (HR = 1.86, 95% CI: 1.55–2.23, P < 0.00001) and PFS (HR = 1.96 (95% CI: 1.52–2.53), P < 0.00001) in patients with mCRPC treated with docetaxel-based therapy. For subgroup analysis of high NLR, studies performed in Asia and cutoff value > 3 were associated with poorer OS, while cutoff values > 3 were associated with poorer PFS.ConclusionOur results suggest that the neutrophil-to-lymphocyte ratio may be a prognostic factor in patients with mCPRC with docetaxel-based chemotherapy.

HER2 expression and pathway status in male breast cancer patients: results of an integrated analysis among 6,150 patients

The role of human epidermal growth factor 2 (HER2) in male breast cancer (MBC) is poorly defined. A comprehensive description of HER2 status was conducted. A total of 6,015 MBC patients from 45 studies and 135 MBC patients with sequencing data were identified. HER2 positive rates and hazard ratios (HR) for overall survival (OS) were combined using Metaprop. The prevalence of HER2 + MBC was 10.0% (95% CI: 8.0-13.0%). Subgroup analyses showed that 7% (95% CI: 2.0-14.0%) had HER2 + protein overexpression. 10% of MBC patients had HER2 + overexpression and/or gene amplification. Asian MBC patients had the highest HER2 + incidence of 17% (95% CI: 12.0-22.0%). The prevalence of HER2 positive MBC fluctuated widely from 2001 to 2015 and then stabilized at 10%. HER2 positivity was significantly correlated with worse OS than negative ones (HR = 1.92, 1.47–2.51). The proportion of HER2 + MBC was inconsistent with the results for the intrinsic HER2-enriched subtype. Altered genes in HER2 + MBC, such as ERBB2, AGO2, RECQL4, and CLTC, were not detected in HER2-MBC. Genomic analysis revealed differences between the patients with HER2 + MBC and those with HER2 + FBC. The percentage of HER2 + MBC was slightly lower than that of women. Multiple approaches may be needed to jointly assess HER2 status in MBC.

Association of hepatitis B virus DNA levels with efficacy and safety and the impact of antiviral therapy on prognosis in liver cancer patients receiving immune checkpoint inhibitors therapy: a systematic review and meta-analysis.

The current evidence regarding the relationship between baseline hepatitis B virus (HBV) DNA levels and survival outcomes in liver cancer patients receiving immune checkpoint inhibitors (ICIs) remains inconsistent. Therefore, this review was intended to explore the impact of the baseline HBV-DNA level on the efficacy and safety of ICIs in patients with liver cancer. Relevant studies were identified through a comprehensive search in PubMed, EMBASE, Cochrane Library, and Web of Science up to August 1, 2024. The outcomes were hazard ratios (HRs) for overall survival (OS) and progression-free survival (PFS), as well as odds ratios (ORs) for objective response rate (ORR), disease control rate (DCR) and HBV reactivation (HBVr). Subgroup analysis, publication bias, and sensitivity analysis were conducted with STATA 14.0. This meta-analysis comprised 17 articles involving a total of 2,130 patients. The pooled results demonstrated that high HBV DNA was associated with a worse OS (HR = 1.48 95% CI 1.11-1.96). Further subgroup analysis showed that there was no difference in OS between the high HBV DNA group and low HBV DNA group when all patients received antiviral treatment. No associations between baseline HBV DNA and PFS (HR = 1.08, 95% CI 0.90-1.29), ORR (OR = 0.91, 95% CI 0.65-1.28), or DCR (OR = 0.83, 95% CI 0.58-1.20) were observed. The risk of HBVr in the high HBV DNA group was lower than that in the low HBV DNA group (OR = 0.30, 95% CI 0.15-0.58), especially among patients who received antiviral therapy (OR = 0.42, 95% CI 0.18-0.98). High HBV DNA was associated with worse OS, but not with PFS, ORR, or DCR in liver cancer patients receiving ICIs. When patients were simultaneously treated with antiviral treatment, elevated HBV DNA level had no unfavorable impact on the efficacy of ICIs. Furthermore, the risk of HBVr in the high HBV-DNA group was lower than that in the low HBV DNA group. More prospective studies with larger sample sizes are essential to confirm the results.

Evaluating survival outcomes and treatment recommendations in resectable gastric cancer

No consensus exists on the optimal therapy for resectable gastric cancer (GC) and gastroesophageal junction (GEJ) tumors, including the effectiveness of chemoradiotherapy versus perioperative chemotherapy (PC). Our study aimed to compare overall survival (OS) outcomes associated with the recommended treatment modalities for GC and GEJ tumors and evaluate treatment trends from 2010 to 2020. A national registry cohort identified patients with ≥ cT2 nonmetastatic GC and GEJ cancer. Treatment modalities were classified as neoadjuvant chemotherapy (NC), neoadjuvant chemoradiotherapy (NCR), PC, adjuvant chemotherapy (AC), and adjuvant chemoradiation (ACR). Kaplan-Meier curve and multivariable Cox regression models evaluated factors associated with OS. A cohort of 7665 patients were included. Patients who received PC had the highest OS (median 86.80 months, 95% CI 73.40-NE), while chemoradiotherapy in the neoadjuvant and adjuvant settings had worse OS than PC and NC (NCR median 47.15 months, 95% CI 44.58–52.27, and ACR median 52.67 months, 95%CI 42.78–63.93). The Cox proportional hazards model showed that NCR and NC had worse survival than PC (HR 1.74, 95% CI 1.50–2.02, p < 0.001 and HR 1.26, 95% CI 1.10–1.44, p = 0.0008, respectively). Additionally, the most utilized modality during 2020 was NC (35.8%), followed by PC (28.0%) and NCR (24.9%). The utilization of PC and NC had the most substantial rise between 2010 and 2020, increasing by 11.0%. The study demonstrates the association of PC with improved OS outcomes for nonmetastatic GC and GEJ tumors. Therapies combining radiation with chemotherapy and extended lymph node dissection correlated with a worse prognosis compared to PC and NC. Despite the association with improved outcomes, national data reveals low utilization rates for PC.

Baseline PSMA PET/CT parameters predict overall survival and treatment response in metastatic castration-resistant prostate cancer patients.

Metastatic castration-resistant prostate cancer (mCRPC) is a heterogeneous disease with varying survival outcomes. This study investigated whether baseline PSMA PET/CT parameters are associated with survival and treatment response. Sixty mCRPC patients underwent [18F]PSMA-1007 PET/CT before treatment with androgen receptor-targeted agents (ARTAs) or chemotherapy. Intensity-based parameters, volumetric parameters, metastatic sites and DmaxVox (distance between the two outermost voxels) from baseline PSMA PET/CT were collected, as well as age, Gleason score and laboratory parameters. Cox regression analysis evaluated their prognostic value for overall survival (OS). Additionally, a preliminary lesion-level analysis was done (n = 241 lesions) with lesion location and twelve radiomic features selected from previous literature. Logistic regression evaluated their association with PSMA PET/CT-based lesion progression after 3-4 months of treatment. Total tumour volume (PSMA-TV) (HR = 1.41 per doubling [1.17-1.70]), total lesion uptake (TL-PSMA) (HR = 1.40 per doubling [1.16-1.69]) and DmaxVox (HR = 1.31 per 10 cm increase [1.07-1.62]) were prognostic for OS, each independent of baseline PSA level (HR = 0.82 per doubling [0.68-0.98]), haemoglobin level (HR = 0.68 per mmol/L increase [0.49-0.95]) and line of treatment. On lesion-level, location (prostate vs bone OR = 0.23 [0.06-0.83]) and SUVmean (OR = 1.72 per doubling [1.08-2.75]) were independent prognostic markers for lesion progression, morphological and texture-based radiomic features were not. Baseline PSMA PET/CT scans have prognostic value in mCRPC patients and can potentially aid in treatment decision-making. DmaxVox can serve as a simpler alternative to PSMA-TV when automated segmentation software is not available. When combined with PSMA-TV, lower PSA levels indicated worse OS, which may be a marker of tumour dedifferentiation. Further research is needed to validate these models in larger patient cohorts. Question mCRPC is a highly heterogeneous disease, requiring good prognostic markers. Findings PSMA-TV was the best independent prognostic marker for OS; maximum distance between lesions (DmaxVox) can be used as a simpler alternative. Clinical relevance Baseline PSMA PET/CT parameters representing tumour burden were independently associated with OS in mCRPC patients, providing prognosticinsights for clinical decision-making. Although PSMA-TV was the best prognostic marker, DmaxVox can serve as an easier to obtain alternative.

Prognostic significance of right subdiaphragmatic washing cytology in patients with endometrial cancer

Cancer cells in the right subdiaphragmatic lavage may reflect peritoneal dissemination, but its prognostic significance is unknown. This study investigated recurrence-free survival (RFS), overall survival (OS), and recurrence patterns in patients with curatively resected endometrial cancer by cytology collection site. Peritoneal cytology was collected at the beginning of surgery by washing the pelvic and right subdiaphragmatic cavity separately. The analysis included 465 patients with the median follow-up duration of 121 months. Of these, 62 (13%) patients had positive pelvic cytology and 22 (5%) patients had positive right subdiaphragmatic cytology. Patients positive for right subdiaphragmatic cytology were all positive for pelvic cytology, showing the worst RFS and OS among the study population. Multivariate analyses showed positive right subdiaphragmatic cytology, not pelvic cytology, significantly correlated with shorter RFS and OS when adjusted for clinicopathological factors. Patients with both pelvic and right subdiaphragmatic positive cytology had significantly higher peritoneal recurrence rates than those negative at both sites. However, patients with only positive pelvic cytology showed no significant difference in the recurrence rate. Our results suggest that the prognostic significance of peritoneal cytology may differ depending on the collection site in endometrial cancer and provide new insights to select patients for adjuvant therapy.

Construction of a prognostic model for gastric cancer based on immune infiltration and microenvironment, and exploration of MEF2C gene function

BackgroundAdvanced gastric cancer (GC) exhibits a high recurrence rate and a dismal prognosis. Myocyte enhancer factor 2c (MEF2C) was found to contribute to the development of various types of cancer. Therefore, our aim is to develop a prognostic model that predicts the prognosis of GC patients and initially explore the role of MEF2C in immunotherapy for GC.MethodsTranscriptome sequence data of GC was obtained from The Cancer Genome Atlas (TCGA), the Gene Expression Omnibus (GEO) and PRJEB25780 cohort for subsequent immune infiltration analysis, immune microenvironment analysis, consensus clustering analysis and feature selection for definition and classification of gene M and N. Principal component analysis (PCA) modeling was performed based on gene M and N for the calculation of immune checkpoint inhibitor (ICI) Score. Then, a Nomogram was constructed and evaluated for predicting the prognosis of GC patients, based on univariate and multivariate Cox regression. Functional enrichment analysis was performed to initially investigate the potential biological mechanisms. Through Genomics of Drug Sensitivity in Cancer (GDSC) dataset, the estimated IC50 values of several chemotherapeutic drugs were calculated. Tumor-related transcription factors (TFs) were retrieved from the Cistrome Cancer database and utilized our model to screen these TFs, and weighted correlation network analysis (WGCNA) was performed to identify transcription factors strongly associated with immunotherapy in GC. Finally, 10 patients with advanced GC were enrolled from Sun Yat-sen University Cancer Center, including paired tumor tissues, paracancerous tissues and peritoneal metastases, for preparing sequencing library, in order to perform external validation.ResultsLower ICI Score was correlated with improved prognosis in both the training and validation cohorts. First, lower mutant-allele tumor heterogeneity (MATH) was associated with lower ICI Score, and those GC patients with lower MATH and lower ICI Score had the best prognosis. Second, regardless of the T or N staging, the low ICI Score group had significantly higher overall survival (OS) compared to the high ICI Score group. For its mechanisms, consistently, for Camptothecin, Doxorubicin, Mitomycin, Docetaxel, Cisplatin, Vinblastine, Sorafenib and Paclitaxel, all of the IC50 values were significantly lower in the low ICI Score group compared to the high ICI Score group. As a result, based on univariate and multivariate Cox regression, ICI Score was considered to be an independent prognostic factor for GC. And our Nomogram showed good agreement between predicted and actual probabilities. Based on CIBERSORT deconvolution analysis, there was difference of immune cell composition found between high and low ICI Score groups, probably affecting the efficacy of immunotherapy. Then, MEF2C, a tumor-related transcription factor, was screened out by WGCNA analysis. Higher MEF2C expression is significantly correlated with a worse OS. Moreover, its higher expression is also negatively correlated with tumor mutation burden (TMB) and microsatellite instability (MSI), but positively correlated with several immunosuppressive molecules, indicating MEF2C may exert its influence on tumor development by upregulating immunosuppressive molecules. Finally, based on transcriptome sequencing data on 10 paired tumor tissues from Sun Yat-sen University Cancer Center, MEF2C expression was significantly lower in paracancerous tissues compared to tumor tissues and peritoneal metastases, and it was also lower in tumor tissues compared to peritoneal metastases, indicating a potential positive association between MEF2C expression and tumor invasiveness.ConclusionsOur prognostic model can effectively predict outcomes and facilitate stratification GC patients, offering valuable insights for clinical decision-making. The identified transcription factor MEF2C can serve as a biomarker for assessing the efficacy of immunotherapy for GC.