Prognostic Impact Research Articles

The prognostic impact of substantial lymphovascular space invasion in women with node negative FIGO stage I uterine carcinoma

ObjectiveSubstantial lymphovascular space invasion (LVSI) is an important predictor of lymph node (LN) involvement in women with endometrial carcinoma. We studied the prognostic significance of substantial LVSI in patients with 2009-FIGO stage-I uterine endometrioid adenocarcinoma (EC) who all had pathologic negative nodal evaluation (PNNE). MethodsPathologic specimens were retrieved and LVSI was quantified (focal or substantial) in women with stage-I EC who had a hysterectomy and PNNE. In addition to multivariate analysis (MVA), recurrence-free (RFS), disease-specific (DSS), and overall (OS) survival was compared between women with focal vs. substantial LVSI. Results1052 patients were identified with a median follow-up of 9.7 years. 358 women (34%) received adjuvant radiotherapy. 907 patients (86.2%) had no LVSI, 87 (8.3%) had focal, and 58 (5.5%) had substantial LVSI. Five-year RFS was 93.3% (95% CI: 91.5–95.1), 76.8% (95% CI: 67.2–87.7) and 79.1% (95% CI: 67.6–95.3) for no, focal, and substantial LVSI(p < 0.0001). There was no statistically significant difference in 5-year RFS, DSS, OS, and in the patterns of initial recurrence between women with focal vs substantial LVSI. On MVA with propensity score matching, substantial LVSI was not independently associated with any survival endpoint compared to focal LVSI, albeit both were detrimental when compared to no LVSI. Age ≥ 60 years and higher grade were predictors of worse RFS, DSS, and OS. Additionally, comorbidity burden was an independent predictor for OS. ConclusionsOur results suggest that substantial LVSI does not predict worse survival endpoints or different recurrence patterns in women with stage-I EC with PNNE when compared to focal LVSI.

BRAF-V600E mutations in plasma and peripheral blood mononuclear cells correlate with prognosis of pediatric Langerhans cell histiocytosis treated with first-line therapy.

The clinical relevance of BRAF-V600E alleles in peripheral blood mononuclear cells (PBMCs) and the prognostic impact of the mutants in cell-free (cf) and PBMC DNAs of Langerhans cell histiocytosis (LCH) have not been fully clarified in pediatric LCH. We retrospectively determined the levels of BRAF-V600E mutation in paired plasma and PBMC samples at the time of diagnosis of LCH. Subsequently, we performed a separate or combined analysis of the clinical and prognostic impact of the mutants. We assessed BRAF-V600E mutation in peripheral blood from 94 patients of childhood LCH. Our data showed that cfBRAF-V600E was related to young age, multiple-system (MS) disease, involvements of organs with high risk, increased risk of relapse, and worse progression-free survival (PFS) of patients. We also observed that the presence of BRAF-V600E in PBMCs at baseline was significantly associated with MS LCH with risk organ involvement, younger age, and disease progression or relapse. The coexisting of plasma(+)/PBMC(+) identified 36.2% of the patients with the worst outcome, and the hazard ratio was more significant than either of the two alone or neither, indicating that combined analysis of the mutation in plasma and PBMCs was more accurate to predict relapse than evaluation of either one. Concurrent assessment of BRAF-V600E mutation in plasma and PBMCs significantly impacted the prognosis of children with LCH. Further prospective studies with larger cohorts need to validate the results of this study.

Management of Refractory/Resistant Herpes Simplex Virus Infections in Haematopoietic Stem Cell Transplantation Recipients: A Literature Review.

Herpes simplex virus (HSV) infections in allogeneic haematopoietic stem cell transplantation (HSCT) recipients pose significant challenges, with higher incidence, severity, and risk of emergence of resistance to antivirals due to impaired T-cell mediated immunity. This literature review focuses on acyclovir-refractory/resistant HSV infections in HSCT recipients. The review addresses the efficacy of antiviral prophylaxis, the incidence of acyclovir-refractory/resistant HSV infections, and the identification of risk factors and potential prognostic impact associated with those infections. Additionally, alternative therapeutic options are discussed. While acyclovir prophylaxis demonstrates a significant benefit in reducing HSV infections in HSCT recipients and, in some cases, overall mortality, concerns arise about the emergence of drug-resistant HSV strains. Our systematic review reports a median incidence of acyclovir-resistant HSV infections of 16.1%, with an increasing trend in recent years. Despite limitations in available studies, potential risk factors of emergence of HSV resistance to acyclovir include human leucocyte antigen (HLA) mismatches, myeloid neoplasms and acute leukaemias, and graft-versus-host disease (GVHD). Limited evidences suggest a potentially poorer prognosis for allogeneic HSCT recipients with acyclovir-refractory/resistant HSV infection. Alternative therapeutic approaches, such as foscarnet, cidofovir, topical cidofovir, optimised acyclovir dosing, and helicase-primase inhibitors offer promising options but require further investigations. Overall, larger studies are needed to refine preventive and therapeutic strategies for acyclovir-refractory/resistant HSV infections in allogeneic HSCT recipients and to identify those at higher risk.

Prognostic Impact of Each Item of the SARC-F Questionnaire in Patients Undergoing Major Surgery for Urologic Cancer

Prognostic Impact of Each Item of the SARC-F Questionnaire in Patients Undergoing Major Surgery for Urologic Cancer

Lymphocyte recovery after bendamustine therapy in patients with mantle cell lymphoma. Results of a retrospective analysis and prognostic impact in the CAR-T era.

Bendamustine in combination with rituximab (BR) or with rituximab and cytarabine (R-BAC) is the standard first-line immunochemotherapy in mantle cell lymphoma (MCL) for elderly patients and patients ineligible for intensive regimens or autologous transplantation. As bendamustine causes prolonged lymphopenia and the literature lacks evidence of its persistence in patients with MCL, this retrospective analysis aims to estimate the lymphocyte recovery time, also in view of potential immunotherapy with CAR-T cells. Data were collected from 44 consecutive MCL patients who received bendamustine (BR or R-BAC) as first-line therapy at the Hematology Unit of Sapienza University Hospital between May 2011 and April 2022. Twenty patients (45%) were treated with R-BAC and 24 (55%) with BR. At baseline, the median lymphocyte count was 1795/µl (range: 370-11730/µL). One month after the end of therapy, it was 450/µl (range: 50-3300/µl) and 3 months after 768/µl (range: 260-1650/µl). After 6 and 9 months, we observed a gradual increase in median lymphocyte count of 900/µl (range: 370-2560/µl and 130-2770/µl, respectively). After 12 months median lymphocyte count was 1256/µl (range: 240-4140/µl). Median lymphocyte count at 1, 3, 6, and 9 months post-treatment was significantly lower than baseline but showed recovery by the 12 months. This finding is crucial for MCL patients considering CAR-T cell therapy, suggesting a minimum 9-month interval between bendamustine administration and leukapheresis.

Post-hoc analysis of clinicopathological factors affecting lateral lymph node metastasis based on STELLAR study for rectal cancer.

In post-hoc analyses of phaseIII randomized controlled study(STELLAR), to analyzethe prognostic impact oflateral pelvic lymph node (LPLN)metastasis in locally advanced rectal cancer (LARC). LPLN metastasis was defined as a short diameter > 7 mm on magnetic resonance imaging (MRI).The studyincluded 591 patients with LARC.All patients received neoadjuvant (chemo)radiotherapy combined withradical resection. Among 591 patients, 99 (16.8 %) were diagnosed with LPLN metastasis, mostly with unilateral metastasis (79.8 %), with internal iliac lymph node metastasis being more common (81.8 %).Significant differences were found among with and without LPLN metastasis in rectal segmentation (P=0.001),N disease (P<0.001), mesenteric LN metastasis or not (P=0.030). The median follow-up timewas 34.0 months, three-year disease-free survival (DFS),overall survival (OS), andmetastasis-free survival (MFS)were significantly lower in LPLN metastaticgroup than those in LPLN non-metastaticgroup (51.4 % vs. 68.2 %, P<0.001; 71.8 % vs. 84.2 %, P=0.006; 60.8 % vs. 80.1 %,P<0.001), respectively; while there were no significant differences in locoregional recurrence(11.4 % vs. 8.5 %, P=0.564). Multivariate analysis found that LPLN metastasis was an independent prognostic factor affecting DFS (P=0.005), OS (P=0.036),MFS (P=0.001).No significantly survival benefit was observed for the short-term radiotherapy based total neoadjuvant therapy compared to long-term concurrent chemoradiotherapy. LPLN metastasis observed byMRI should be considered in LARC patients, especially in populations with lowrectal cancer, N2 disease, and mesenteric LN metastasis. LPLN metastasis diagnosed by MRI is a significant and independent risk factor and is associated with worse DFS, OS, MFS.

Prognostic impact of lymph node invasion levels in patients with bladder cancer undergoing radical cystectomy and pelvic lymphadenectomy

Prognostic impact of lymph node invasion levels in patients with bladder cancer undergoing radical cystectomy and pelvic lymphadenectomy

Impact of BMI and Body Composition on First-line Systemic Treatment for Unresectable Hepatocellular Carcinoma.

The effects of body mass index (BMI) and body composition on the outcomes of systemic treatment for unresectable hepatocellular carcinoma (uHCC) remain unclear. In this retrospective study, patients with uHCC treated with lenvatinib (LEN) or atezolizumab+bevacizumab, were classified into high- (≥25 kg/m2) and low- (<25 kg/m2) BMI groups and evaluated for prognosis. Prognostic impact of body composition was also evaluated. Patients with a high BMI had lower skeletal mass index (SMI), subcutaneous adipose tissue index (SATI), and visceral adipose tissue index (VATI) compared to those in the low-BMI cohort. The baseline Child-Pugh scores and Barcelona Clinic Liver Cancer stages were comparable between the two cohorts. The overall survival (OS) was better in the high BMI group compared to the low BMI group (median, 913 vs. 484 days; p=0.008). SMI had a strong influence on OS. Additionally, low BMI, VATI, SATI, and visceral-to-subcutaneous fat ratio (VSR) in the LEN treatment group were associated with shorter progression-free survival (PFS). Following systemic treatment for uHCC, patients with low BMI have a poor prognosis. Among anthropometric factors, low SMI is associated with poor OS. In the LEN treatment group, low VATI may impact PFS negatively.

Risk factors for and prognostic impact of lateral pelvic lymph node metastasis in patients with rectal neuroendocrine tumors: a single-center retrospective analysis of 214 cases with radical resection.

Lateral pelvic lymph node (LPLN) metastasis of rectal neuroendocrine tumors (NETs) is rare, with unknown oncological features. We investigated the oncological impact of LPLN metastasis in patients with rectal NETs. This study included 214 patients with rectal NETs who underwent curative surgery. We evaluated their clinicopathological characteristics and short- and long-term outcomes. LPLN dissection was performed in 15 patients with LPLN swelling ≥ 7mm (preoperative imaging); 12 patients had LPLN metastases, 6 of whom had LPLN metastases without mesorectal lymph node metastases (skip metastasis). The short-term outcomes were similar between the groups with and without LPLN dissection. The median follow-up period was 59.4months, and patients with LPLN metastasis showed significantly shorter disease-free and overall survival rates than those without metastasis. Among 199 patients who did not undergo LPLN dissection, only 1 had LPLN recurrence. In a univariate analysis, tumor depth, tumor grade, and LPLN metastasis were associated with the overall survival. In the multivariate analysis, only LPLN metastasis was an independent predictor of the overall survival. LPLN metastasis is a poor prognostic factor for patients with rectal NETs. LPLN enlargement can be considered an indication for dissection, owing to its high rate of metastasis and associated poor prognosis.

Prognostic Impact of Human Lymphocyte Antigen (HLA) Class I Expression in Patients With Breast Cancer.

Various biomarkers are utilized in the field of breast cancer. Human lymphocyte antigen (HLA) class I molecules have a critical role in cancer immune surveillance. Therefore, this study aimed to assess the HLA class I expression and analyze the correlation with clinicopathologic factors in breast cancer. We investigated the clinical pathology archives of 150 consecutive patients with breast cancer who underwent a curative operation at the Sapporo Medical University, Japan, from January 2012 to December 2014. Immunohistochemical staining was used to evaluate HLA class I expression and CD8-positive T cell infiltration. The Pearson χ2 test was used to assess HLA class I expression level and clinicopathological parameters. The Kaplan-Meier method was used to evaluate survival and the log-rank test to analyze the differences between survival curves. Patients with dull/negative HLA class I had significantly poor disease-free survival (DFS) compared with those with positive HLA class I (p=0.0073). Univariate analyses revealed that pT, pN, positive lymphatic invasion, and dull/negative HLA class I were significantly associated with DFS. Multivariate analyses revealed dull/negative HLA class I as an independent poor prognostic factor (hazard ratio=2.75, 95% confidence interval=1.30-5.80, p=0.008). HLA class I expression level may have a very sensitive prognostic effect on patients with breast cancer.

Inflammatory Burden Index Prognostic Impact in Patients With Gastric Cancer After Gastrectomy: A Propensity Score-matched Analysis.

The Inflammatory Burden Index (IBI) has been reported as a novel prognostic indicator in several cancers and diseases. However, research on the IBI in patients with gastric cancer (GC) after gastrectomy is insufficient. This study investigated the utility of the preoperative IBI as a prognostic indicator in patients with GC. This retrospective study enrolled 459 patients undergoing gastrectomy for GC between 2013 and 2017 at the Kanagawa Cancer Center, Kanagawa, Japan. The IBI was calculated from preoperative blood test data. We evaluated the relationship between the preoperative IBI and clinicopathologic factors, overall survival (OS), and recurrence-free survival (RFS) after gastrectomy for GC, using propensity score matched analysis. Regarding the association between IBI and clinicopathologic features, the high-IBI group was significantly older and had more lymphatic invasion and more progressive pT status than the low-IBI group before propensity score-matched analysis. OS and RFS after curative surgery were significantly lower in patients with a high IBI than in those with a low IBI (77.5% vs. 86.1%; p=0.02 and 74.3% vs. 85.1%; p=0.03, respectively). Multivariate analysis identified high IBI as an independent predictor of both OS and RFS. Preoperative IBI may serve as a valuable prognostic indicator for patients undergoing curative gastrectomy for GC.

Prognostic impact of cytogenetic abnormalities by FISH in AL amyloidosis with daratumumab-based frontline therapy.

We performed an international retrospective cohort study to investigate the prognostic impact of cytogenetic abnormalities by FISH in 283 patients with AL amyloidosis treated with frontline daratumumab-bortezomib-cyclophosphamide-dexamethasone (Dara-VCD) or Dara-VD. The cytogenetic subgroups of interest were t(11;14), gain/amp(1q) [hereafter, +1q], hyperdiploidy, deletion(13q), del(17p), and myeloma high-risk (HR) translocations (t[4;14], t[14;16], or t[14;20]). The endpoints of interest were rate of hematologic complete response (heme CR), very good partial response or better (≥VGPR), and hematologic event-free survival (Heme EFS). The incidence of abnormalities was following: t(11;14)-53.4%; deletion (13q)-28.9%; +1q-22.3%; hyperdiploidy-19.4%; HR translocations-6.6%; and deletion(17p)-4.5%. The heme-CR rate by cytogenetic subgroups were: t(11;14) vs no t(11;14)-45.2% vs 41.8% (p=0.597); del(13q) vs no del(13q)-46.8% vs 42.8% (p=0.594); +1q vs no +1q-30.2% vs 47.9% (p=0.022); hyperdiploidy vs no hyperdiploidy-39.5% vs 44.9% (p=0.541); HR translocations vs none: 45.5% vs 43.1% (p=0.877); and del(17p) vs no del(17p)-50.0% vs 42.9% respectively (p=0.658). Similarly, +1q was the only subgroup with a significantly lower ≥VGPR rate (64.2% vs 79.0%; p=0.033). At a median follow-up of 19.8 months, the median heme-EFS was 49.6 months (95% CI, 24.7-not reached [NR]), and the 2-year OS was 80.98% (95% CI, 75.6-85.4). The presence of+1q was significantly associated with worse heme-EFS on multivariate analysis (HR 2.06, 95% CI, 1.14-3.71; p=0.017). Notably, there was no adverse prognostic impact of t(11;14) on heme EFS or OS. In conclusion, +1q is associated with worse outcome in the daratumumab-era. Clinical trials testing novel immunotherapies frontline should be enriched in +1q to further improve outcomes in this subgroup.

Identification of DNA methylation-regulated WEE1 with potential implications in prognosis and immunotherapy for low-grade glioma.

WEE1 is a critical kinase in the DNA damage response pathway and has been shown to be effective in treating serous uterine cancer. However, its role in gliomas, specifically low-grade glioma (LGG), remains unclear. The impact of DNA methylation on WEE1 expression and its correlation with the immune landscape in gliomas also need further investigation. This study used data from The Cancer Genome Atlas (TCGA), Chinese Glioma Genome Atlas (CGGA), and Gene Expression Omnibus (GEO) and utilized various bioinformatics tools to analyze gene expression, survival, gene correlation, immune score, immune infiltration, genomic alterations, tumor mutation burden, microsatellite instability, clinical characteristics of glioma patients, WEE1 DNA methylation, prognostic analysis, single-cell gene expression distribution in glioma tissue samples, and immunotherapy response prediction based on WEE1 expression. WEE1 was upregulated in LGG and glioblastoma (GBM), but it had a more significant prognostic impact in LGG compared to other cancers. High WEE1 expression was associated with poorer prognosis in LGG, particularly when combined with wild-type IDH. The WEE1 inhibitor MK-1775 effectively inhibited the proliferation and migration of LGG cell lines, which were more sensitive to WEE1 inhibition. DNA methylation negatively regulated WEE1, and high DNA hypermethylation of WEE1 was associated with better prognosis in LGG than in GBM. Combining WEE1 inhibition and DNA methyltransferase inhibition showed a synergistic effect. Additionally, downregulation of WEE1 had favorable predictive value in immunotherapy response. Co-expression network analysis identified key genes involved in WEE1-mediated regulation of immune landscape, differentiation, and metastasis in LGG. Our study shows that WEE1 is a promising indicator for targeted therapy and prognosis evaluation. Notably, significant differences were observed in the role of WEE1 between LGG and GBM. Further investigation into WEE1 inhibition, either in combination with DNA methyltransferase inhibition or immunotherapy, is warranted in the context of LGG.

Prognostic impact of body composition in hepatocellular carcinoma patients with immunotherapy

Objective This study aims to examine the possible relationship between body composition parameters, sarcopenia, and clinical outcomes in hepatocellular carcinoma (HCC) patients who received immune checkpoint inhibitor (ICI) treatment. Methods Three online databases, including Embase, PubMed, and the Cochrane Library, were thoroughly searched for literature describing the relationship between body composition parameters, sarcopenia, and outcomes of ICI-treated HCC patients from the start of each database to 21 January 2024. The Newcastle-Ottawa Scale was used to rate the quality of the studies. The assessed outcomes included hazard ratio (HR) for OS and PFS, as well as odds ratio (OR) for ORR and DCR. Results This analysis included a total of 15 articles with a combined patient cohort of 1543 individuals. The results demonstrated that HCC patients with low skeletal muscle index (SMI) had significantly inferior OS (HR: 1.68, p < 0.001), PFS (HR: 1.45, p < 0.001), ORR (OR: 0.64, p = 0.044), and DCR (OR: 0.58, p = 0.009) compared to those with high SMI. The presence of sarcopenia in HCC patients was significantly related to poorer OS (HR: 1.63, p < 0.001) and PFS (HR: 1.48, p < 0.001), as well as a lower ORR (OR: 0.64, p = 0.020) and DCR (OR: 0.58, p = 0.007) in comparison to those without sarcopenia. Subgroup analysis demonstrated that these findings were consistent with the multivariate analysis. Moreover, high subcutaneous adipose index (SAI) levels were associated with better OS (HR: 0.46, p = 0.001) and PFS (HR: 0.68, p = 0.021) than those with low SAI levels. Conclusion The presence of sarcopenia and low SMI in HCC patients undergoing treatment with ICIs was found to be related to inferior treatment response and reduced long-term effectiveness.

Prognostic value of electroanatomic-guided endomyocardial biopsy in patients with myocarditis, arrhythmogenic cardiomyopathy and non dilated left ventricular cardiomyopathy

A wide variety of non-invasive and invasive techniques for SCD risk stratification in non ischemic cardiomyopathy (NICM) have been proposed, including left ventricular (LV) ejection fraction, QRS duration, late gadolinium enhancement (LGE) on cardiac magnetic resonance (CMR) and invasive electrophysiologic study with or without three-dimensional electroanatomic mapping (3D-EAM), to identify and characterize the arrhythmogenic substrate. There is still no clear consensus on the risk stratification in this clinical setting.The aim of our study is to characterize the 3D-EAM substrate in patients with the same clinical presentation of unexplained complex VAs and NICM using CMR, three-dimensional electranatomic mapping (3D-EAM) in association with endomyocardial biopsy (EMB) and genetic screening, as a more precise and early diagnostic assessment may provide important subsequent prognostic impact. The study was designed as a prospective multi-center observational evaluation and the patient follow-up was scheduled at 6 months interval. We enrolled 125 patients distinct into four different group by complete diagnostic work-up: myocarditis, non-dilated left ventricular cardiomyopathy, arrhythmogenic cardiomyopathy and control group. The four groups were compared in terms of clinical, imaging and 3D-EAM data. At multivariate analysis sustained VT/VF on admission [HR: 3.64 (1.79–7.4), p < 0.001], total bipolar scar area of left and right ventricle detected by 3D-EAM [HR: 2.24 (1.13–4.49), p = 0.02], histological diagnosis of myocarditis by 3D-EAM guided endomyocardial biopsy (EBM) [HR: 2.79 (1.04–7.44), p = 0.01] were independent predictors of complex VAs or death at follow-up. 3D-EAM guided EMB represent not only a valid diagnostic tool to identify the arrhythmogenic substrate in patients with NICM and ventricular arrhythmic phenotype but also an important predictor of complex Vas at long term follow-up.

Prognostic impact of pulmonary dysfunction in older gastric cancer patients.

The influence of pulmonary dysfunction on postoperative outcomes in older patients with gastric cancer was assessed. In this retrospective study, 352 older patients (age ≥ 75years) with gastric cancer who underwent preoperative spirometry and curative gastrectomy were enrolled. Of these patients, 200 underwent laparoscopic gastrectomy. Restrictive and obstructive pulmonary dysfunction were defined as percentage of vital capacity (%VC) < 80% and percent of forced expiratory volume in one second (FEV1.0%) < 70%, respectively. Twenty-six (7.3%) and 123 (34.9%) exhibited restrictive and obstructive pulmonary dysfunction, respectively. The low-%VC group showed a higher incidence of postoperative pneumonia (p = 0.018) while the low-FEV1.0% group did not (p = 0.677). Multivariate analysis identified a decreased %VC as a significant risk factor for postoperative pneumonia. However, this association was not observed in patients who underwent laparoscopic gastrectomy. Concerning the long-term outcomes, restrictive dysfunction was a significant prognostic factor in older patients with gastric cancer who underwent either laparotomy or laparoscopy, whereas obstructive dysfunction did not. Restrictive pulmonary dysfunction increased the risk of postoperative pneumonia and had a negative prognostic effect in older patients with gastric cancer, whereas obstructive pulmonary dysfunction did not.

Prognostic Impact and Clinical Features of Spread through Air Spaces in Operated Lung Cancer: Real-World Analysis.

Background and Objectives: Lung cancer is the leading cause of cancer-related deaths. Spread through air spaces (STAS) is an adverse prognostic factor that has become increasingly known in recent years. This study aims to investigate the impact of STAS presence on overall survival (OS) and disease-free survival (DFS) in patients with surgically resected stage IA-IIIA lung cancer and to identify clinicopathological features associated with STAS. Materials and Methods: This research involved 311 lung cancer surgery patients. The relationship between the presence of STAS in the patients' surgical pathology and OS and DFS values was examined. Clinicopathological features associated with the presence of STAS were determined. Results: There were 103 (33%) STAS-positive patients. Adenocarcinoma histological subtype, perineural invasion (PNI), and lymphovascular invasion (LVI) were significantly correlated with being STAS positive. STAS significantly predicted DFS and OS. One-year and five-year DFS rates were significantly lower in the STAS-positive group compared to the STAS-negative group (65% vs. 88%, 29% vs. 62%, respectively, p ≤ 0.001). Similarly, one-year and five-year OS rates were significantly lower in the STAS-positive group compared to the STAS-negative group (92% vs. 94%, 54% vs. 88%, respectively, p ≤ 0.001). In multivariate analysis, STAS was found to be an independent prognostic factor for both DFS and OS (HR: 3.2 (95%CI: 2.1-4.8) and 3.1 (95%CI: 1.7-5.5), p < 0.001 and <0.001, respectively). Conclusions: In our study, STAS was found to be an independent prognostic biomarker in operated stage IA-IIIA lung cancer patients. It may be a beneficial pathological biomarker in predicting the survival of patients and managing their treatments.

Prognostic impact of myosteatosis on survival with immune checkpoint inhibitors: A systematic review and meta-analysis

Myosteatosis has emerged as a promising prognostic biomarker for survival outcomes in patients with advanced cancer. However, recent research has yielded conflicting results on the association between myosteatosis and survival in patients treated with immune checkpoint inhibitors (ICIs). Therefore, we performed this systematic review and meta-analysis to evaluate the association between myosteatosis and survival outcomes in patients treated with ICIs. We conducted a systematic review using Pubmed, Web of Science, and Scopus databases for studies published until June 10, 2024. This protocol was registered in the PROSPERO database (Registration Number: CRD42023466337). We performed the meta-analyses with the generic inverse-variance method with a random effects model. Eleven studies involving 1362 patients were included. The pooled analysis showed that patients with myosteatosis had a significantly higher risk of death compared to patients without myosteatosis (HR: 1.61, 95% CI: 1.23-2.12, p<0.001). Subgroup analysis revealed this association was stronger in melanoma patients (HR: 2.07, 95% CI: 1.09-3.94, p=0.030). Furthermore, patients with myosteatosis had an increased risk of progression or death than those without myosteatosis (HR: 1.31, 95% CI: 1.05-1.64, p=0.020). Myosteatosis is associated with a higher risk of death in ICI-treated patients. Further research in larger cohorts is needed to standardize the definition of myosteatosis as well as the true mechanistic association between myosteatosis and survival in patients treated with ICIs.

The prognostic impact of Progesteron-receptor expression in surgical intracranial meningioma on performance status and quality of life. A single-center observational study

The relationship between meningiomas and gonadal steroid hormones has been the subject of debate, and there is limited understanding of the connection between patient, tumor characteristics, and progesterone receptor (PGR) status. This retrospective observational study aims to explore the prognostic correlation between PGR+ and PGR- meningiomas in terms of various clinical, radiological, and surgical predictors. The analysis included 270 patients, divided into two groups: Group A (PGR-, 194 patients), and Group B (PGR+, 76 patients). The analysis showed no significant differences in terms of age, sex, clinical debut, post-surgical complications, total resection, and grading between the two groups. However, a significant difference was observed in the mean Karnofsky performance status (KPS) at all stages of follow-up. Peritumoral edema measured in preoperative MRI significantly influences the value of KPS in both preoperative (ANOVA, p= 0.05) and postoperative evaluation (Post-operative ANOVA, p= 0.014) only in the Group A. In the multivariate analysis, there are no significant factors related to the clinical, biological, and surgical parameters previously examined for each measurement time (p = 0.826). The study found that PGR+ meningioma patients tend to have better postoperative recovery and earlier clinical debut without any association with age prevalence or grading.

Therapeutic indications for antibody-drug conjugates estimated from HER2 and p53 expressions in endometrial carcinoma

ObjectiveWhile human epidermal growth factor receptor 2 (HER2) is upregulated in endometrial carcinoma—especially in the p53 aberrant type— conventional anti-HER2 therapy is not typically used for this cancer type. Recently, HER2-targeted antibody-drug conjugates have shown antitumor effects against HER2 low-expressing cancers. Therefore, we analyzed the clinicopathological characteristics of HER2-positive endometrial carcinomas including those with low expression, as well as the prognostic significance of p53 and HER2 co-expression. MethodsImmunohistochemistry for HER2 and p53 was performed in 530 patients with endometrial carcinoma; 124 cases (23%) were HER2-positive. ResultsOf the HER2-positive cases, >50% were 1+. A high prevalence of HER2 expression was observed in serous (64%), clear-cell (73%), and mixed (64%) carcinomas. Notably, 19% of endometrioid carcinomas were HER2-positive. HER2 positivity was significantly associated with age ≥60 years, high-grade histological subtype, deep myometrium invasion, stage III/IV, recurrence, and death. Univariate analysis showed that HER2-positive cases had reduced progression-free survival (PFS) (p = 0.007) and overall survival (OS) (p = 0.012). However, after adjusting for stage, HER2 positivity was not associated with survival. In the early stage, co-expression of HER2-positive and p53 aberrant types was associated with shorter PFS (p < 0.001) and OS (p < 0.001) compared with at least one negative result. Multivariate analysis of PFS showed HER2 and p53 co-expression (hazard ratio, 1.891; 95% confidence interval, 1.183–5.971, p = 0.008) as an independent prognostic factor. ConclusionsThis study presents detailed clinicopathological characteristics and the prognostic impact of HER2-positivity in endometrial carcinomas. HER2-targeted antibody-drug conjugate therapy may be broadly applicable to endometrial carcinoma.